Glaucoma Surgery
Number: 0484
Table Of Contents
PolicyApplicable CPT / HCPCS / ICD-10 Codes
Background
References
Policy
Scope of Policy
This Clinical Policy Bulletin addresses glaucoma surgery.
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Medical Necessity
Aetna considers the following glaucoma treatments as medically necessary (unless otherwise stated):
- Laser trabeculoplasty as first-line treatment of primary open angle glaucoma;
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Food and Drug Administration (FDA)-approved aqueous drainage/shunt implants for the treatment of members with refractory primary open-angle glaucoma when first-line drugs (e.g., latanoprost or timolol), and second-line drugs (e.g., brimonidine or dorzolamide) have failed to control intra-ocular pressure (IOP). Currently available implants include:
- Ahmed glaucoma implant
- Baerveldt seton
- Ex-PRESS mini glaucoma shunt
- Glaucoma pressure regulator
- Krupin-Denver valve implant
- Molteno implant
- Schocket shunt;
- One or two iStent Trabecular Micro-Bypass Stents per eye for the treatment of adults with mild or moderate open-angle glaucoma and a cataract when the individual is currently being treated with an ocular hypotensive medication and the procedure is being performed in conjunction with cataract surgery;
- Hydrus Microstent for the treatment of adults with mild or moderate open-angle glaucoma and a cataract when the individual is currently being treated with an ocular hypotensive medication and the procedure is being performed in conjunction with cataract surgery;
- XEN Glaucoma Treatment System for the management of refractory glaucoma, including cases where previous surgical treatment has failed, cases of primary open angle glaucoma, and pseudoexfoliative or pigmentary glaucoma with open angles that are unresponsive to maximum tolerated medical therapy;
Aetna considers replacement of the Xen gel stent not medically necessary. - Adjunctive use of anti-fibrotic agents (e.g., mitomycin C) for use with the Ex-PRESS mini glaucoma shunt. However, adjunctive use of anti-fibrotic agents (e.g., mitomycin C) or systemic corticosteroids with other shunt implants is considered experimental, investigational, or unproven because there are no advantages to the adjunctive use of these agents with currently available shunts;
- Goniotomy or ab interno trabeculotomy for treatment of:
- Pediatric or congenital glaucoma
- Primary congenital glaucoma In infants aged 3-12 months; as first-line therapy in cases wherein cornea allows satisfactory visualization of angle;
- Juvenile open-angle glaucoma (JOAG), including in adolescents;
- Open-angle glaucoma secondary to uveitis;
- Open angle glaucoma, including normal tension glaucoma, performed as a standalone procedure or combined with cataract surgery, when either of the following criteria are met:
- Intraocular pressure (IOP) does not decrease with medication therapy; or
- Member is unable to comply with therapy (e.g., lacks manual dexterity, caregiver unavailabe, dementia or other cognitive dysfunction);
- Any of the following trabecular meshwork tissue cutting and/or removing devices (e.g., Gonioscopy-assisted transluminal trabeculotomy [GATT], iAccess Precision Blade, Kahook Dual Blade [KDB], SION Surgical Instrument, Trabectome) are considered medically necessary for goniotomy or ab interno trabeculotomy;
- Goniotomy or ab interno trabeculotomy for all other indications, such as ocular hypertension and angle-closure glaucoma, is considered experimental, investigational, or unproven because their clinical value for other indications has not been established.
Note: Goniotomy refers to incision and/or excision of the trabecular meshwork (TM) for at least 3 or more clock hours to create an opening into Schlemm's canal via an internal approach through the anterior chamber. Trabeculotomy involves an external approach, using a deep scleral incision to access Schlemm's canal and then rotating a probe into the anterior chamber to open the TM. Goniotomy (CPT code 65820) should not be coded in addition to other angle surgeries, stent insertions or Schlemm canal implants or if the incision into the trabecular meshwork is minimal or simply incidental to another procedure. Performing multiple goniopunctures with or without excision of tissue does not meet the CPT description for a true goniotomy (CMS, 2025).
- Pediatric or congenital glaucoma
- Ab interno canaloplasty (e.g., iTrack, OMNI Surgical System, Streamline Surgical System) for the treatment of mild-to-moderate open angle glaucoma including low or normal-tension glaucoma, and pseudoexfoliative glaucoma, when any of the following criteria are met:
- The member is on glaucoma medical therapy; or
- Member is unable to comply with therapy (e.g., lacks manual dexterity, caregiver unavailable, dementia or other cognitive dysfunction); or
- With failed glaucoma surgery in contralateral eye;
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Experimental, Investigational, or Unproven
The following glaucoma treatments are considered experimental, investigational, or unproven because the effectiveness of these approaches has not been established (not an all-inclusive list):
- Artificial intelligence-based applications for the diagnosis, management, and progression detection of glaucoma;
- Beta radiation for the treatment of glaucoma;
- Cataract surgery combined with ab interno canaloplasty (e.g., OMNI Surgical System) and micro-trabecular bypass stent surgery (e.g., iStent or iStent inject) for the treatment of open-angle glaucoma;
- iStent G3 Supra;
- Excimer laser trabeculostomy for the treatment of glaucoma;
- Femtosecond laser image-guided high-precision trabeculotomy (FLIGHT) for the treatment of glaucoma;
- iStent Trabecular Micro-Bypass Stent System is considered contraindicated for persons with primary angle-closure glaucoma, secondary angle-closure glaucoma (including neovascular glaucoma), retrobulbar tumor, thyroid eye disease, Sturge-Weber Syndrome or any other type of condition that may cause elevated episcleral venous pressure;
- Hydrus Microstent is considered contraindicated for persons with birth defects of the anterior chamber angle of the eye, primary angle-closure glaucoma, secondary angle-closure glaucoma (including neovascular glaucoma), malignant glaucoma, traumatic glaucoma, and uveitic glaucoma;
- Intra-operative optical coherence tomography in glaucoma surgery;
- Minimally Invasive Nasal Trabeculostomy (MINT) (Sanoculis);
- More than 1 Hydrus Microstent per eye;
- More than 2 iStents per eye;
- Standalone iStent Infinite or iStent Infinite combined with cataract surgery for the treatment of open-angle glaucoma.
- Transorbital electrical stimulation for the treatment of open-angle glaucoma.
Background
Glaucoma is an irreversible group of conditions/diseases involving death of the nerve cells in front of the optic nerve. It was once thought that glaucoma was generally due to increased intraocular pressure (IOP); however, the condition is also found in individuals with normal or low eye pressure. Therefore, diagnosis of glaucoma does not rely on increased IOP and may be related to optic nerve damage. Glaucoma is one of the leading causes of blindness with loss of peripheral vision being a hallmark sign of glaucoma.
The majority (about 90 %) of patients with glaucoma have primary open-angle glaucoma (POAG) that is defined as a chronic condition in which the IOP is elevated beyond a level compatible with the continued health and function of the eye, with a gonioscopically open angle, and a decreased facility of outflow. It is a slow progressive, insidious optic neuropathy. Primary open-angle glaucoma is also known as chronic open-angle glaucoma and chronic simple glaucoma. Another form of glaucoma is acute angle-closure glaucoma (AACG), which occurs as a dramatic, violent attack with closure of the entire angle. In contrast to POAG, AACG manifests with symptoms of blurred vision with colored halos around lights, pain, redness, and often nausea and vomiting related to the pain. In AACG, the IOP can rise precipitously to more than 50 mm Hg.
Medication, in the form of eye drops, pills or both, is the most common early treatment for glaucoma. There are numerous medications available for treating glaucoma; all of which must be taken regularly. If medication fails, other interventions may be recommended.
Acute angle-closure glaucoma is treated with oral or intravenous carbonic anhydrase inhibitors (e.g., acetazolamide), topical beta-blockers (e.g. timolol), and miotics (e.g., pilocarpine) to induce miosis. If pharmacotherapies fail, laser iridotomy can be performed to create an opening in the peripheral iris to relieve pupillary block.
Primary open-angle glaucoma is usually treated with ophthalmic medications. The first-line drugs include timolol (a non-specific beta blocker) and latanoprost (a prostaglandin F2a agonist). The second-line drugs entail brimonidine (an alpha agonist) and dorzolamide (a topical carbonic anhydrase inhibitor). The third-line drugs include apraclonidine (an alpha agonist), pilocarpine (a cholinergic agonist), acetazolamide (an oral carbonic anhydrase inhibitor), and epinephrine (a non-specific adrenergic agonist). In a randomized controlled study, Doi et al (2005) concluded that the combination of bimatoprost and latanoprost in POAG increases IOP and should not be considered as a therapeutic option.
- the mechanical theory,
- the cellular (biologic) theory, and
- the cell division theory.
Since both lasers are applied to the same tissue and produce similar results, they most likely produce their effects in comparable ways. These researchers also described the results of several studies comparing these devices. Most show them to be equally effective at lowering IOP; however, there are a few circumstances when selective laser trabeculoplasty may be a better option than argon laser trabeculoplasty. The authors concluded that argon laser and selective laser trabeculoplasty are safe and effective procedures for lowering IOP. They noted that results of ongoing clinical trials will help further define their role in the management of patients with OAG.
The American Optometric Association's guideline on care of the patient with OAG (AOA, 2002; reviewed 2007) listed argon laser trabeculoplasty as an alternative to drug therapy for the management of patients with POAG. The Singapore Ministry of Health's guideline on glaucoma stated that laser trabeculoplasty may be used as an adjunct to medical therapy. Furthermore, the American Academy of Ophthalmology (AAO)'s guideline on POAG (2005) stated that laser trabeculoplasty is an appropriate initial therapeutic alternative (e.g., patients with memory problems or are intolerant to the medication).
- full-thickness fistulas (e.g., thermal sclerostomy),
- partial-thickness fistulas (e.g., trabeculectomy),
- tubes and setons (e.g., Molteno implant, Krupin-Denver valve implant, or Ahmed glaucoma implant), and
- cyclodestructive procedures (e.g., cyclophotocoagulation or cyclocryotherapy).
Trabeculectomy is a surgical procedure used in the treatment of glaucoma to relieve intraocular pressure by removing part of the eye's trabecular meshwork and adjacent structures; the most common glaucoma surgery performed, it allows drainage of aqueous humor from within the eye to underneath the conjunctiva where it is absorbed.
The term aqueous drainage device refers to a broad class of tools used to facilitate aqueous flow out of the anterior chamber to control IOP. They may also be referred to as glaucoma drainage devices, tubes or shunts and may be valved or nonvalved. Such drainage devices may be placed in individuals with advanced disease in whom medical and laser therapies are inadequate and who have an underlying diagnosis that increases the risk of failure of conventional surgery. Examples of U.S. Food and Drug Administration (FDA) approved standard aqueous drainage devices include Ahmed glaucoma valve, Baerveldt seton, Schocket shunt, Krupin-Denver valve implant, Molteno implant, and the Glaucoma pressure regulator. These aqueous drainage/shunt devices are implanted to reduce IOP in the anterior chamber of the eye. The basic design of these devices is similar – a silicone tube shunts aqueous humor from the anterior chamber to a fibrous capsule surrounding a synthetic plate or band positioned at the equatorial region of the globe. The capsule serves as a reservoir for aqueous drainage. Many studies have demonstrated that these devices are comparable and are effective in treating patients with POAG.
Guidelines from the AAO (2003) stated that "[t]he use of drainage devices (such as those described by Molteno, Ahmed, Krupin, Baerveldt, and others) is generally reserved for patients who have failed filtering surgery with antimetabolites or for patients whose conjunctiva is so scarred from previous surgery that filtering surgery with antimetabolites is at high risk for failure."
In a report on aqueous shunts in glaucoma by the AAO, Minckler et al (2008) provided an evidence-based summary of commercially available aqueous shunts currently used in substantial numbers (Ahmed [New World Medical, Inc., Rancho Cucamonga, CA], Baerveldt [Advanced Medical Optics, Inc., Santa Ana, CA], Krupin [Eagle Vision, Inc, Memphis, TN], Molteno [Molteno Ophthalmic Ltd., Dunedin, New Zealand]) to control IOP in various glaucomas. A total of 17 previously published randomized trials, 1 prospective non-randomized comparative trial, 1 retrospective case-control study, 2 comprehensive literature reviews, and published English language, non-comparative case series and case reports were reviewed and graded for methodologic quality. Aqueous shunts are used primarily after failure of medical, laser, and conventional filtering surgery to treat glaucoma and have been successful in controlling IOP in a variety of glaucomas. The principal long-term complication of anterior chamber tubes is corneal endothelial failure. The most shunt-specific delayed complication is erosion of the tube through overlying conjunctiva. There is a low incidence of this occurring with all shunts currently available, and it occurs most frequently within a few millimeters of the corneo-scleral junction after anterior chamber insertion. Erosion of the equatorial plate through the conjunctival surface occurs less frequently. Clinical failure of the various devices over time occurs at a rate of approximately 10 % per year, which is approximately the same as the failure rate for trabeculectomy. The authors concluded that based on level I evidence, aqueous shunts seem to have benefits (IOP control, duration of benefit) comparable with those of trabeculectomy in the management of complex glaucomas (phakic or pseudophakic eyes after prior failed trabeculectomies). Level I evidence indicates that there are no advantages to the adjunctive use of anti-fibrotic agents or systemic corticosteroids with currently available shunts. Too few high-quality direct comparisons of various available shunts have been published to assess the relative efficacy or complication rates of specific devices beyond the implication that larger-surface-area explants provide more enduring and better IOP control. Long-term follow-up and comparative studies are encouraged.
A review by the AAO (Minckler et al, 2008) concluded that Level I evidence indicates that there are no advantages to the adjunctive use of antifibrotic agents with currently available shunts. The AAO assessment stated that two of three randomized controlled trials concluded that antifibrotic agents have no beneficial long-term outcome effect when used with aqueous shunts (citing Cantor, et al., 1998, Costa, et al., 2004). The AAO assessment stated that, among published randomized controlled trials, only the study of Duan, et al. (2003) concluded that adjunctive mitomycin C was helpful to promote bleb formation and duration. The AAO assessment noted that, as pointed out in the Cochrane Review on aqueous shunts (citing Minckler, et al., 2006), this study had several methodologic flaws. The AAO assessment (Minckler, et al., 2008) concluded: "Thus, there is sufficient level I evidence that demonstrates no benefit in using antifibrotic agents as adjuncts to aqueous shunt procedures." This conclusion was reaffirmed in an AAO Preferred Practice Pattern on primary open-angle glaucoma (AAO, 2010).
The ExPress glaucoma filtration device, a stainless steel nonvalved shunt, is inserted through a conjunctival flap to drain aqueous from the anterior chamber without removal of any scleral or iris tissue. Optinol (Kansas City, KS) introduced the Ex-PRESS mini glaucoma shunt in an attempt to simplify the glaucoma drainage device implantation. This device is a single-piece, stainless steel, translimbal implant that is placed using an inserter. Although its ease of implantation is greatly desired, its long-term efficacy and risk of complications have yet to be determined. The Ex-PRESS mini glaucoma shunt is a 400-micron diameter tube made from implantable stainless steel that is less than 3 mm long, and is loaded on a specially designed disposable inserter. The device reduces IOP by diverting excess aqueous humor from the anterior chamber to a subconjunctival bleb. The Ex-PRESS shunt has an advantage over conventional filtering surgery in that it is minimally invasive. Originally, the Ex-PRESS was designed for a direct limbus insertion through the irido-corneal angle under a conjunctival flap to drain aqueous from the anterior chamber to the subconjunctival space. However, because of long-term complications, including conjunctival erosions, hypotony, tube dislocation, conjunctival scarring or fibrosis within the tube, the device was re-designed. The new device is inserted via an external approach in the superficial scleral flap through the trabeculum into the anterior chamber.
In a multi-center study evaluating the safety and effectiveness of the Ex-PRESS R-50 mini glaucoma shunt, researchers found the device effective in reducing IOP. The success rate of the Ex-PRESS in lowering IOP to less than 21 mm Hg was 69 % after 1 year without medications. This represented a 30 to 40 % IOP reduction. The overall average number of glaucoma medications dropped significantly from 1.65 to 0.38 at 1 year (Optonol, Inc., 2002).
In a retrospective comparative series of 100 eyes, Maris et al (2007) compared the Ex-PRESS mini implant (Model R 50) placed under a partial-thickness scleral flap with standard trabeculectomy. Success was defined as IOP greater than or equal to 5 mm Hg and less than or equal to 21 mm Hg, with or without glaucoma medications, without further glaucoma surgery or removal of implant. Early post-operative hypotony was defined as IOP less than 5 mm Hg during the first post-operative week. The average follow-up was 10.8 months (range of 3.5 to 18) for the Ex-PRESS group and 11.2 months (range of 3 to 15) for the trabeculectomy group. Although the mean IOP was significantly higher in the early post-operative period in the Ex-PRESS group compared with the trabeculectomy group, the reduction of IOP was similar in both groups after 3 months. The number of post-operative glaucoma medications in both groups was not significantly different. Kaplan-Meier survival curve analysis showed no significant difference in the success between the 2 groups (p = 0.594). Early post-operative hypotony and choroidal effusion were significantly more frequent after trabeculectomy compared with the Ex-PRESS implant under scleral flap (p < 0.001). The authors concluded that the Ex-PRESS implant under a scleral flap had similar IOP lowering efficacy with a lower rate of early hypotony compared with trabeculectomy.
Chen and colleagues (2014) evaluated the safety and effectiveness of Ex-PRESS implantation (Ex-PRESS) compared to trabeculectomy in the treatment of patients with OAG. A comprehensive literature search using the Cochrane Methodology Register to identify randomized controlled clinical trials (RCCTs) comparing Ex-PRESS to trabeculectomy in patients with OAG. Efficacy estimates were measured by weighted mean difference (WMD) for the percentage IOP reduction (IOPR%) from baseline to end-point, and odds ratios (OR) for the complete success rate and post-operative interventions. Safety estimates were measured by OR for post-operative complications. Statistical analysis was performed using the RevMan 5.1 software. A total of 4 RCCTs were selected for this meta-analysis, including 215 eyes of 200 patients (110 eyes in the Ex-PRESS group, 105 eyes in the trabeculectomy group). There was no significant difference between Ex-PRESS and trabeculectomy in the IOPR%. The pooled OR comparing Ex-PRESS to trabeculectomy for the complete success rate at 1 year after surgery were in favor of Ex-PRESS. The Ex-PRESS procedure was found to be associated with lower number of post-operative interventions and with a significantly lower frequency of hyphema than trabeculectomy, whereas other complications did not differ statistically. The authors concluded that in OAG, Ex-PRESS and trabeculectomy provided similar IOP control, but Ex-PRESS was more likely to achieve complete success, with fewer post-operative interventions. Complication rates were similar for the 2 types of surgery, except for a lower frequency of hyphema in the Ex-PRESS group.
An AAO's technology assessment on "Novel glaucoma procedures" (Francis et al, 2011) noted that the disadvantages of FUGO Blade TCF are that it is an external filtration procedure with bleb formation, risk of over-filtration, and hypotony.
Trabectome is the name of the device and procedure during which a strip of tissue along the edge of the iris is removed in an attempt to reestablish normal pressure and drainage in affected eyes.
In a retrospective, cohort study, Jea and colleagues (2012) compared the effect of ab interno trabeculectomy with trabeculectomy. A total of 115 patients who underwent ab interno trabeculectomy (study group) were compared with 102 patients who underwent trabeculectomy with intra-operative mitomycin as an initial surgical procedure (trabeculectomy group). Inclusion criteria were open-angle glaucoma, aged greater than or equal to 40 years, and uncontrolled on maximally tolerated medical therapy. Exclusion criterion was concurrent surgery. Clinical variables were collected from patient medical records. Main outcome measures included IOP and Cox proportional hazard ratio (HR) and Kaplan-Meier survival analyses with failure defined as IOP greater than 21 mmHg or less than 20 % reduction below baseline on 2 consecutive follow-up visits after 1 month; IOP less than or equal to 5 mmHg on 2 consecutive follow-up visits after 1 month; additional glaucoma surgery; or loss of light perception vision. Secondary outcome measures included number of glaucoma medications and occurrence of complications. Mean follow-up was 27.3 and 25.5 months for the study and trabeculectomy groups, respectively. Intra-ocular pressure decreased from 28.1 +/- 8.6 mmHg at baseline to 15.9 +/- 4.5 mmHg (43.5 % reduction) at month 24 in the study group, and from 26.3 +/- 10.9 mmHg at baseline to 10.2 +/- 4.1 mmHg (61.3 % reduction) at month 24 in the trabeculectomy group. The success rates at 2 years were 22.4 % and 76.1 % in the study and trabeculectomy groups, respectively (p < 0.001). Younger age (p = 0.037; adjusted HR, 0.98 per year; 95 % confidence interval [CI]: 0.97 to 0.99) and lower baseline IOP (p = 0.016; adjusted HR, 0.96 per 1 mmHg; 95 % CI: 0.92 to 0.99) were significant risk factors for failure in the multi-variate analysis of the study group. With the exception of hyphema, the occurrence of post-operative complications was more frequent in the trabeculectomy group (p < 0.001). More additional glaucoma procedures were performed after ab interno trabeculectomy (43.5 %) than after trabeculectomy (10.8 %, p < 0.001). The authors concluded that ab interno trabeculectomy has a lower success rate than trabeculectomy.
Furthermore, a Cochrane review on "Medical versus surgical interventions for open angle glaucoma" (Burr et al, 2012), and a U.S. Preventive Services Task Force's review on "Comparative effectiveness of treatments for open-angle glaucoma" (Boland et al, 2013), as well as an UpToDate review on "Open-angle glaucoma: Treatment" (Jacobs, 2013) mentioned trabeculectomy, but not ab interno trabeculectomy.
Bussel et al (2015) evaluated outcomes of ab interno trabeculectomy (AIT) with the trabectome following failed trabeculectomy. The indication for AIT was IOP above target on maximally tolerated therapy, and for phaco-AIT a visually significant cataract and need to lower IOP or glaucoma medications. Outcomes included IOP, medications, complications, secondary procedures and success, defined as IOP of less than 21 mm Hg and a greater than 20 % reduction from baseline without further surgery. Exclusion criteria were trabeculectomy less than 3 months prior to AIT or follow-up under 1 year. A total of 73 eyes of 73 patients with 1 year follow-up were identified. At 1 year, mean IOP in AIT significantly decreased by 28 % from 23.7 ± 5.5 mm Hg, and medications from 2.8 ± 1.2 to 2 ± 1.3 (n = 58). In phaco-AIT, the mean IOP decreased 19 % from 20 ± 5.9 mm Hg and medications from 2.5 ± 1.5 to 1.6 ± 1.4 (n = 15). Transient hypotony occurred in 7 %, and further surgery was necessary in 18 %. For AIT and phaco-AIT, the 1-year cumulative probability of success was 81 % and 87 %, respectively. The authors concluded that both AIT and phaco-AIT showed a reduction in IOP and medication use after 1 year, suggesting that AIT with or without cataract surgery is a safe and effective option following failed trabeculectomy.
Kaplowitz et al (2016) analyzed all of the PubMed publications on AIT with the Trabectome to determine the reduction in IOP and medications following the procedure. For IOP outcomes, PubMed was searched for "trabectome", "ab interno trabeculotomy" and "ab interno trabeculectomy" and all available papers retrieved. The meta-analysis used a random-effects model to achieve conservative estimates and assess statistical heterogeneity. To investigate complications, these researchers included all abstracts from the American Glaucoma Society, AAO, American Society of Cataract and Refractive Surgery and the Association for Research in Vision and Ophthalmology. The overall arithmetic mean baseline IOP for stand-alone Trabectome was 26.71 ± 1.34 mm Hg and decreased by 10.5 ± 1.9 mm Hg (39 % decrease) on 0.99 ± 0.54 fewer medications. Defining success as IOP less than or equal to 21 with a 20 % decrease while avoiding re-operation, the overall average success rate after 2 years was 46 ± 34 %. For combined phacoemulsification-Trabectome, the baseline IOP of 21 ± 1.31 mm Hg decreased by 6.24 ± 1.98 mm Hg (27 % decrease) on 0.76 ± 0.35 fewer medications. The success rate using the same definition at 2 years was 85 ± 7%. The weighted mean IOP difference from baseline to study end-point was 9.77 mm Hg (95 % CI: 8.90 to 10.64) stand-alone and 6.04 mm Hg (95 % CI: 4.95 to 7.13) for combined cases. Despite heterogeneity, meta-analysis showed significant and consistent decrease in IOP and medications from baseline to end-point in AIT and phaco-AIT. The rate of visually threatening complications was less than 1 %. On average, trabectome lowered the IOP by approximately 31 % to a final IOP near 15 mm Hg while decreasing the number of medications by less than 1, with a low rate of serious complications. After 2 years, the overall average success rate is 66 %.
- ab interno trabeculectomy with the Trabectome, and
- implantation of the Ex-PRESS shunt.
Ab interno trabeculectomy (Trabectome) achieves a sustained 30 % reduction in IOP by focally ablating and cauterizing the trabecular meshwork/inner wall of Schlemm's canal. It has a remarkable safety profile with respect to early hypotonous or infectious complications as it does not generate a bleb, but it can be associated with early post-operative IOP spikes that may necessitate additional glaucoma surgery. The Ex-PRESS shunt is more commonly implanted under a partial thickness scleral flap, and appears to have similar efficacy to standard trabeculectomy offering some advantages with respect to the rate of early complications related to hypotony. The authors concluded that penetrating glaucoma surgery will continue to evolve. The findings of randomized clinical trials will determine the exact role of these surgical techniques in the glaucoma surgical armamentarium.
In a review on the use of novel devices for control of IOP, Minckler and Hill (2009) noted that Trabectome, Glaukos iStent, iScience (canaloplasty), and SOLX (suprachoroidal shunt) are newly developed surgical technologies for the treatment of OAG. These new approaches to angle surgery have been demonstrated in preliminary case series to safely lower IOP in the mid-teens with far fewer complications than expected with trabeculectomy and without anti-fibrotics. Trabectome and iStent are relatively non-invasive, aim to improve access of aqueous to collector channels and do not preclude subsequent standard surgery. SOLX potentially offers an adjustable aqueous outflow from the anterior chamber into the suprachoroidal space.
An AAO's technology assessment on "Novel glaucoma procedures" (Francis et al, 2011) noted that the SOLX gold shunt is limited to investigational use in the U.S. The disadvantages of the SOLX gold shunt are the presence of a permanent implant in the anterior chamber and suprachoroidal space with the risk of erosion or exposure, and that the mechanism of action is not well-delineated. The assessment also stated that randomized controlled trials (RCTs) are needed to ascertain the effectiveness of procedures (including FUGO Blade goniotomy, iStent, and the SOLX gold shunt) compared with trabeculectomy, with one another, and with phacoemulsification alone (in the case of combined procedures).
In a Cochrane review, Kirwan and colleagues (2009) evaluated the effectiveness of beta radiation during glaucoma surgery (trabeculectomy). These investigators searched the Cochrane Central Register of Controlled Trials (CENTRAL) in The Cochrane Library (which includes the Cochrane Eyes and Vision Group Trials Register) (Issue 4 2008), MEDLINE (January 1966 to October 2008) and EMBASE (January 1980 to October 2008). The databases were last searched on 24 October 2008. They included randomized controlled trials comparing trabeculectomy with beta radiation to trabeculectomy without beta radiation. Data on surgical failure (IOP greater than 21 mm Hg), IOP, and adverse effects of glaucoma surgery were collected. Data were pooled using a fixed-effect model. These researchers found 4 trials that randomized 551 people to trabeculectomy with beta irradiation versus trabeculectomy alone – 2 studies were in Caucasian people (n = 126), 1 study in black African people (n = 320), and 1 study in Chinese people (n = 105). People who had trabeculectomy with beta irradiation had a lower risk of surgical failure compared to people who had trabeculectomy alone (pooled risk ratio (RR) 0.23 (95 % confidence interval [CI]: 0.14 to 0.40). Beta irradiation was associated with an increased risk of cataract (RR 2.89, 95 % CI: 1.39 to 6.0). The authors concluded that trabeculectomy with beta irradiation has a lower risk of surgical failure compared to trabeculectomy alone. They stated that a trial of beta irradiation versus anti-metabolite is needed.
Iridotomy, iridectomy or iridoplasty may be necessary for angle-closure glaucoma. Current guidelines (AAO, 2010) describe the indication for laser peripheral iridoplasty in the treatment of acute angle closure crisis (AACC) when laser iridotomy is not possible or if the AACC cannot be medically broken. Iridectomy involves surgical removal of part of the iris of the eye. Iridoplasty is a procedure using laser energy to shrink the peripheral iris; also called gonioplasty. Iridotomy is a surgical procedure in which a laser is used to cut into the iris.
However, there is insufficient evidence for the use of laser peripheral iridoplasty in the nonacute setting. In a Cochrane review, Ng and colleagues (2012) evaluated the effectiveness of laser peripheral iridoplasty in the treatment of narrow angles (i.e., primary angle-closure suspect), primary angle-closure (PAC) or primary angle-closure glaucoma (PACG) in non-acute situations when compared with any other intervention. In this review, angle-closure will refer to patients with narrow angles (PACs), PAC and PACG. These investigators searched CENTRAL (which contains the Cochrane Eyes and Vision Group Trials Register) (The Cochrane Library 2011, Issue 12), MEDLINE (January 1950 to January 2012), EMBASE (January 1980 to January 2012), Latin American and Caribbean Literature on Health Sciences (LILACS) (January 1982 to January 2012), the metaRegister of Controlled Trials (mRCT), ClinicalTrials.gov and the WHO International Clinical Trials Registry Platform (ICTRP). There were no date or language restrictions in the electronic searches for trials. The electronic databases were last searched on January 5, 2012. These researchers included only RCTs in this review. Patients with narrow angles, PAC or PACG were eligible. They excluded studies that included only patients with acute presentations, using laser peripheral iridoplasty to break acute crisis. No analysis was carried out as only 1 trial (n = 158) was included in the review. The trial reported laser peripheral iridoplasty as an adjunct to laser peripheral iridotomy compared to iridotomy alone. The study reported no superiority in using iridoplasty as an adjunct to iridotomy for IOP, number of medications or need for surgery. The authors concluded that there is currently no strong evidence for laser peripheral iridoplasty's use in treating angle-closure.
On behalf of the AAO, Francis and colleagues (2011) reviewed the published literature and summarized clinically relevant information about novel, or emerging, surgical techniques for the treatment of open-angle glaucoma and described the devices and procedures in proper context of the appropriate patient population, theoretic effects, advantages, and disadvantages. Devices and procedures that have FDA clearance or are currently in phase III clinical trials in the United States were included: the Fugo blade (Medisurg Ltd., Norristown, PA), Ex-PRESS mini glaucoma shunt (Alcon, Inc., Hunenberg, Switzerland), SOLX Gold Shunt (SOLX Ltd., Boston, MA), excimer laser trabeculotomy (AIDA, Glautec AG, Nurnberg, Germany), canaloplasty (iScience Interventional Corp., Menlo Park, CA), trabeculotomy by internal approach (Trabectome, NeoMedix, Inc., Tustin, CA), and trabecular micro-bypass stent (iStent, Glaukos Corporation, Laguna Hills, CA). Literature searches of the PubMed and the Cochrane Library databases were conducted up to October 2009 with no date or language restrictions. These searches retrieved 192 citations, of which 23 were deemed topically relevant and rated for quality of evidence by the panel methodologist. All studies but 1, which was rated as level II evidence, were rated as level III evidence. All of the devices studied showed a statistically significant reduction in IOP and, in some cases, glaucoma medication use. The success and failure definitions varied among studies, as did the calculated rates. Various types and rates of complications were reported depending on the surgical technique. On the basis of the review of the literature and mechanism of action, the authors also summarized theoretic advantages and disadvantages of each surgery. The authors concluded that the novel glaucoma surgeries studied all show some promise as alternative treatments to lower IOP in the treatment of open-angle glaucoma. It is not possible to conclude whether these novel procedures are superior, equal to, or inferior to surgery such as trabeculectomy or to one another. The studies provide the basis for future comparative or randomized trials of existing glaucoma surgical techniques and other novel procedures.
The iStent (trabecular bypass device or microbypass implant) is a small heparin-coated, titanium implant, placed into Schlemm’s canal, intended to restore more normal fluid drainage and reduce IOP in individuals who are also undergoing cataract surgery. Schlemm’s Canal is a circular channel in the eye that collects aqueous humor from the anterior chamber and delivers it into the bloodstream. CyPass Micro-Stent is a small drainage device inserted under goinioscopic view through a clear corneal incision using a retractable guidewire. Once in place, it is designed to directly connect the anterior chamber to the suprachoroidal space (between the sclera and choroid) to increase uveoscleral outflow, thereby purportedly decreasing IOP. The iStent G3 Supra is a third generation iStent device under development and is similar in design to the CyPass Micro-Stent. The device is inserted under goinioscopic view through a clear corneal incision into the suprachoroidal space and is proposed for use alone or at the time of cataract surgery.
On June 25, 2012, the FDA approved the iStent Trabecular Micro-Bypass Stent System, Model GTS100R/L. This is the first device approved for use in combination with cataract surgery to reduce IOP in adult patients with mild or moderate open-angle glaucoma and a cataract who are currently being treated with medication to reduce IOP. The iStent, an anterior segment aqueous drainage device, is a small (approximately 1 mm by 0.5 mm) L-shaped titanium device that is inserted into the trabecular meshwork through the cornea and is designed to create a bypass between the anterior chamber and Schlemm's canal for aqueous humor to flow directly into the canal toward the episcleral drainage system.
In a prospective, non-randomized, interventional case-series study, Buchacra et al (2011) evaluated the mid-term safety and effectiveness of the iStent glaucoma device in patients with secondary open-angle glaucoma. A total of 10 patients with secondary open-angle glaucoma (traumatic, steroid, pseudoexfoliative, and pigmentary glaucoma) of recent onset who underwent ab interno implantation iStent were included in this analysis. Patients were assessed following the procedure on days 1, 7, and 15 and months 1, 3, 6, and 12, and examinations included visual acuity, IOP measurement using Goldmann tonometry, number of glaucoma medications, and complications. Wilcoxon rank-test for data with abnormal distribution was used for the analysis of IOP and glaucoma medications at baseline versus 3, 6, and 12 months following the procedure. The mean baseline IOP was 26.5 ± 7.9 (range of 18 to 40) mm Hg, and significantly decreased in 10.4 ± 9.2 mm Hg at 3 months (p < 0.05), in 7.4 ± 4.9 mm Hg at 6 months (p < 0.05), and in 6.6 ± 5.4 mm Hg at 12 months (p < 0.05) following iStent implantation. The mean number of hypotensive medications at baseline was 2.9 ± 0.7 (range of 2 to 4). Statistically significant reductions in the number of medications of 1.1 ± 1.1 were observed at 3 months (p < 0.05), 1.0 ± 0.7 at 6 months (p < 0.05), and 1.1 ± 0.6 at 12 months (p < 0.05). No significant changes in visual acuity were noted. The most common complications comprised mild hyphema in 7 eyes and transient IOP greater than or equal to 30 mm Hg in 3 eyes on post-operative day 1. Obstruction of the lumen of the stent with a blood clot was seen in 3 eyes, and all instances resolved spontaneously. The authors concluded that the iStent is a safe and effective treatment option in patients with secondary open-angle glaucoma, and reduces the topical treatment burden in one hypotensive medication.
Francis and Winarko (2012) stated that in POAG, the site of greatest resistance to aqueous outflow is thought to be the trabecular meshwork. Augmentation of the conventional (trabecular) outflow pathway would facilitate physiologic outflow and subsequently lower IOP. Ab interno Schlemm's canal surgery including 2 novel surgical modalities, Trabectome (trabeculotomy internal approach) and Trabecular Micro-bypass Stent (iStent), is designed to reduce IOP by this approach. In contrast to external filtration surgeries such as trabeculectomy and aqueous tube shunt, these procedures are categorized as internal filtration surgeries and are both performed from an internal approach via gonioscopic guidance. Published results suggest that these surgical procedures are both safe and efficacious for the treatment of open-angle glaucoma.
Augustinus and Zeyen (2012) reviewed the different aspects that influence the choice and sequence of surgical treatment in patients with co-existing open-angle glaucoma and cataract. The effect of phaco-emulsification on IOP and on a pre-existing bleb was discussed and phaco-trabeculectomy and trabeculectomy were compared. Moreover, the most recent surgical pressure lowering techniques in combination with phaco-emulsification were reviewed: iStent, Trabectome, Hydrus, Cypass and Canaloplasty. Medline database was used to search for relevant, recent articles. The authors concluded that a sustained IOP decrease of 1.5 mm Hg can be expected after a phaco-emulsification in patients with open-angle glaucoma. The higher the pre-operative pressure, the greater the IOP lowering will be. A phaco-emulsification on a trabeculectomized eye will often lead to reduced bleb function and an IOP rise of on average 2 mm Hg after 12 months. Compared to a trabeculectomy, phaco-trabeculectomy will have a less IOP lowering effect and a higher complication rate. iStent and Trabectome combined with phaco-emulsification can decrease the IOP with 3 to 5 mm Hg, with a low complication rate. The combination of Cypass and Hydrus with phaco-surgery may have a more significant IOP lowering effect but long-term results are not yet published. Combining Canaloplasty with phaco-emulsification is a more challenging surgery but if a tension suture can be placed, an IOP decrease around 10 mm Hg might be expected.
In a prospective, non-comparative, uncontrolled, non-randomized, interventional case series study, Arriola-Villalobos and associates (2012) evaluated the long-term safety and effectiveness of combined cataract surgery and Glaukos iStent implantation for co-existent open-angle glaucoma and cataract. Subjects older than 18 years with co-existent uncontrolled mild or moderate open-angle glaucoma (including pseudoexfoliative and pigmentary) and cataract underwent phaco-emulsification and intra-ocular lens implantation along with ab-interno gonioscopically guided implantation of 1 Glaukos iStent. The variables recorded during a minimum of 3 years of follow-up were: IOP, number of anti-glaucoma medications and best-corrected visual acuity (BCVA). The 19 patients enrolled were 58 to 88 years old (mean age of 74.6 ± 8.44 years). Mean follow-up was 53.68 ± 9.26 months. Mean IOP was reduced from 19.42 ± 1.89 mm Hg to 16.26 ± 4.23 mm Hg (p = 0.002) at the end of follow-up, indicating a 16.33 % decrease in IOP. The mean number of pressure-lowering medications used by the patients fell from 1.32 ± 0.48 to 0.84 ± 0.89 (p = 0.046). In 42 % of patients, no anti-glaucoma medications were used at the end of follow-up. Mean BCVA significantly improved from 0.29 ± 0.13 to 0.62 ± 0.3 (p < 0.001). No complications of surgery were observed. The authors concluded that combined cataract surgery and Glaukos iStent implantation seems to be an effective and safe procedure to treat co-existent open-angle glaucoma and cataract.
In a prospective randomized controlled multi-center (29 sites) clinical trial, Craven et al (2012) evaluated the long-term safety and effectiveness of a single trabecular micro-bypass stent with concomitant cataract surgery versus cataract surgery alone for mild-to-moderate open-angle glaucoma. Eyes with mild-to-moderate glaucoma with an unmedicated IOP of 22 mm Hg or higher and 36 mm Hg or lower were randomly assigned to have cataract surgery with iStent trabecular micro-bypass stent implantation (stent group) or cataract surgery alone (control group). Patients were followed for 24 months post-operatively. The incidence of adverse events was low in both groups through 24 months of follow-up. At 24 months, the proportion of patients with an IOP of 21 mm Hg or lower without ocular hypotensive medications was significantly higher in the stent group than in the control group (p = 0.036). Overall, the mean IOP was stable between 12 months and 24 months (17.0 mm Hg ± 2.8 [SD] and 17.1 ± 2.9 mm Hg, respectively) in the stent group but increased (17.0 ± 3.1 mm Hg to 17.8 ± 3.3 mm Hg, respectively) in the control group. Ocular hypotensive medication was statistically significantly lower in the stent group at 12 months; it was also lower at 24 months, although the difference was no longer statistically significant. The authors concluded that patients with combined single trabecular micro-bypass stent and cataract surgery had significantly better IOP control on no medication through 24 months than patients having cataract surgery alone. Both groups had a similar favorable long-term safety profile.
Drug-eluting punctual plugs made of resorbable material are inserted into the lacrimal punctum (tear duct) and purportedly emit sustained release medications for a 30 - 60 day period until degrading and exiting via the nasolacrimal system. These devices are currently being studied but have not received FDA approval.
Ocular Therapeutics is currently conducting clinical trials regarding the insertion of a drug-eluting implant, including punctual dilation and implant removal when performed, into the lacrimal canaliculus. The clinical trials are investigating the use of dexamethasone intracanalicular plugs for the treatment of post-operative inflammation and pain and travoprost intracanalicular plugs for reduction of intraocular pressure in patients with glaucoma or ocular hypertension. Ocular Therapeutix recently announced that the American Medical Association (AMA) approved a Category III CPT code for the insertion of a drug-eluting implant which could be used in clinical trials to establish use and provide a mechanism for reimbursement for insertion of these intracanalicular plugs following FDA approval.
Munoz-Negrete et al (2015) evaluated the safety and effectiveness of non-penetrating deep sclerectomy (NPDS) in 3 consecutive eyes with pre-existing and uncontrolled glaucoma after Descemet stripping with automated endothelial keratoplasty (DSAEK). Non-penetrating deep sclerectomy with intra-scleral implant and topical adjunctive intra-operative mitomycin C (0.2 mg/ml 1 minute) was performed. Intra-ocular pressure and number of glaucoma medication were registered before and after NPDS with at least 1-year follow-up. Intra-operative and post-operative complications were also registered. Before NPDS, IOP was 18 mm Hg in 1 patient and 32 mm Hg in the other 2 patients. Four anti-glaucoma drugs were used in 2 cases and 3 in the other one. At 1 year after NPDS, all the patients had an IOP less than or equal to 18 mm Hg. Two patients required post-operative anti-glaucoma medications (1 drug in 1 case and 2 drugs in the other one). Neodymium-doped yttrium aluminum garnet laser goniopuncture was needed in 2 patients and it had to be repeated in 1 of them. No complications related to NPDS were observed. A corneal graft rejection was observed 5 months after NPDS in 1 case that resolved without sequelae with intensive corticosteroid eye-drop therapy. The authors concluded that NPDS could be a safe and successful alternative to conventional filtration surgery after DSAEK in eyes with uncontrolled glaucoma. They stated that larger series and a longer follow-up would be needed to set the actual role of surgery in DSAEK patients.
An UpToDate review on "Open-angle glaucoma: Treatment" (Jacobs, 2016) states that "Filtration surgery not uncommonly fails due to excessive scar tissue formation. There are reports of the use of adjuncts before, during, or after surgery, such as beta irradiation and antimetabolites (5-fluorouracil and mitomycin C), to increase the rate of surgical success. There is great variation in use and choice of adjuncts worldwide, and adjuncts can be associated with a higher complication rate. For example, beta irradiation at the time of trabeculectomy can minimize scar tissue formation and increase the likelihood that surgery will effectively lower the IOP, but increases the risk of cataract formation".
Two iStents for the Treatment of Open-Angle Glaucoma
Myers and associates (2018) evaluated long-term outcomes of 2 trabecular micro-bypass stents, 1 suprachoroidal stent, and post-operative prostaglandin in eyes with refractory OAG. Prospective, ongoing 5-year study of 80 eligible subjects (70 with 4-year follow-up) with OAG and IOP of greater than or equal to 18 mmHg after prior trabeculectomy and while taking 1 to 3 glaucoma medications. Subjects received 2 iStent trabecular micro-bypass stents, 1 iStent Supra suprachoroidal stent, and post-operative travoprost. Post-operative IOP was measured with medication and annually following medication wash-outs. Performance was measured by the proportion of eyes with greater than or equal to 20 % IOP reduction on 1 medication (the protocol-specified prostaglandin) versus pre-operative medicated IOP (primary outcome); and the proportion of eyes with post-operative IOP of less than or equal to 15 and less than or equal to 18 mmHg on 1 medication (secondary outcome). Additional clinical and safety data included medications, visual field, pachymetry, gonioscopy, AEs, VA, and slit-lamp and fundus examinations. Pre-operatively, mean medicated IOP was 22.0 ± 3.1 mmHg on 1.2 ± 0.4 medications, and mean unmedicated IOP was 26.4 ± 2.4 mmHg. Post-operatively, among eyes without later cataract surgery, mean medicated IOP at all visits through 48 months was less than or equal to 13.7 mmHg (greater than or equal to 37 % reduction), and annual unmedicated IOP was less than or equal to 18.4 mmHg (reductions of greater than or equal to 30 % versus pre-operative unmedicated IOP and greater than or equal; to 16 % versus pre-operative medicated IOP). At all post-operative visits among eyes without additional surgery or medication, greater than or equal to 91 % of eyes had greater than or equal to 20 % IOP reduction on 1 medication versus pre-operative medicated IOP. At month 48, 97 and 98 % of eyes achieved IOP of less than or equal to 15 and less than or equal to 18 mmHg, respectively, on 1 medication; 6 eyes required additional medication, no eyes required additional glaucoma surgery, and safety measurements were favorable throughout follow-up. The authors concluded that IOP control was achieved safely with 2 trabecular micro-bypass stents, 1 suprachoroidal stent, and post-operative prostaglandin; this micro-invasive, ab interno approach introduced a possible new treatment option for refractory disease.
In a prospective, randomized, single-masked, concurrently controlled, multi-center clinical trial, Samuelson and colleagues (2019) examined the safety and effectiveness of the iStent inject Trabecular Micro-Bypass System (Glaukos Corporation, San Clemente, CA) in combination with cataract surgery in subjects with mild-to-moderate POAG. Subject were individuals with eyes with mild-to-moderate POAG and pre-operative IOP of less than or equal to 24 mmHg on 1 to 3 medications, unmedicated diurnal IOP (DIOP) 21 to 36 mmHg, and cataract requiring surgery. After uncomplicated cataract surgery, eyes were randomized 3:1 intra-operatively to ab interno implantation of iStent inject (Model G2-M-IS; treatment group, n = 387) or no stent implantation (control group, n = 118). Subjects were followed through 2 years post-operatively. Annual wash-out of ocular hypotensive medication was performed. Effectiveness end-points were greater than or equal to 20 % reduction from baseline in month 24 unmedicated DIOP and change in unmedicated month 24 DIOP from baseline. Safety measures included best spectacle-corrected visual acuity (BSCVA), slit-lamp and fundus examinations, gonioscopy, pachymetry, specular microscopy, visual fields, complications, and AEs. The groups were well balanced pre-operatively, including medicated IOP (17.5 mmHg in both groups) and unmedicated DIOP (24.8 ± 3.3 mmHg versus 24.5 ± 3.1 mmHg in the treatment and control groups, respectively, p = 0.33). At 24 months, 75.8 % of treatment eyes versus 61.9 % of control eyes experienced greater than or equal to 20 % reduction from baseline in unmedicated DIOP (p = 0.005), and mean reduction in unmedicated DIOP from baseline was greater in treatment eyes (7.0 ± 4.0 mmHg) than in control eyes (5.4 ± 3.7 mmHg; p < 0.001). Of the responders, 84 % of treatment eyes and 67 % of control eyes were not receiving ocular hypotensive medication at 23 months. Furthermore, 63.2 % of treatment eyes versus 50.0 % of control eyes had month 24 medication-free DIOP of less than or equal to 18 mmHg (difference 13.2 %; 95 % CI: 2.9 to 23.4). The overall safety profile of the treatment group was favorable and similar to that in the control group throughout the 2-year follow-up. The authors concluded that clinically and statistically greater reductions in IOP without medication were achieved after iStent inject implantation with cataract surgery versus cataract surgery alone, with excellent safety through 2 years.
Ab Interno Kahook Dual Blade Trabeculectomy for the Treatment of Primary Congenital Glaucoma
Harvey and Schmitz (2020) noted that primary congenital glaucoma is a rare ocular disorder that is responsible for 0.01 % to 0.04 % of total blindness worldwide. The goal of congenital glaucoma management is to allow for proper development of the immature visual system by controlling IOP. Medical therapy usually provides a supportive role to temporarily reduce IOP, however, patients typically require irido-corneal angle surgery to facilitate aqueous humor outflow. These researchers described the use of minimally invasive ab interno Kahook dual blade trabeculectomy for the treatment of primary congenital glaucoma. The subject was a 13-month old infant with bilateral primary congenital glaucoma due to a loss of function TEK mutation. He had bilateral findings of elevated IOP, buphthalmos, Haab's striae, photophobia, and myopia. Over the course of 6 weeks, 3 ab interno trabeculectomies with a Kahook dual blade were performed in the patient's left eye and 1 in the patient's right eye. After 3 months, IOP while receiving pressure reducing ophthalmic drops bilaterally reduced from 43 to 21 mmHg in the right eye after a single surgery and from 44 to 34 mmHg in the left eye after 3 surgeries, eventually requiring glaucoma drainage implant placement. There were no complications. The authors concluded that ab interno Kahook dual blade trabeculectomy is a minimally invasive and potentially successful procedure for the treatment of congenital glaucoma. These researchers stated that the safety profile of minimally invasive glaucoma surgery warrants consideration for congenital glaucoma patients, as they usually require irido-corneal angle surgery because pharmacologic therapy is usually inadequate. These preliminary findings need to be validated by further investigation.
Ab Interno Supraciliary Microstent Surgery for the Treatment of Open-Angle Glaucoma
Sandhu and colleagues (2021) noted that glaucoma is the leading cause of global irreversible blindness, often associated with elevated IOP. Where medical or laser treatment has failed or is not tolerated, surgery is often required. Minimally-invasive surgical approaches have been developed in recent years to reduce IOP with lower surgical risks. Supraciliary microstent surgery for the treatment of OAG is one such approach. In a Cochrane review, these investigators examined the safety and effectiveness of supraciliary microstent surgery for the treatment of OAG, and compared with standard medical, laser or surgical treatments. They searched the Cochrane Central Register of Controlled Trials (CENTRAL; which contains the Cochrane Eyes and Vision Trials Register; 2020, Issue 8); Ovid Medline; Ovid Embase; the ISRCTN registry; ClinicalTrials.gov and the WHO ICTRP. The date of the search was August 27, 2020. These investigators searched for RCTs of supraciliary microstent surgery, alone or with cataract surgery, compared to other surgical treatments (cataract surgery alone, other minimally invasive glaucoma device techniques, trabeculectomy), laser treatment or medical treatment. Two review authors independently screened titles and abstracts from the database search to identify studies that met the selection criteria. Data extraction, analysis, and evaluation of risk of bias from selected studies was carried out independently and according to standard Cochrane methodology. One study met the inclusion criteria of this review, examining the safety and effectiveness of the Cypass supraciliary microstent surgery for the treatment of OAG, comparing phacoemulsification + supraciliary microstent surgery with phacoemulsification alone over 24 months. This study comprised 505 eyes of 505 participants with both OAG and cataract, 374 randomized to the phacoemulsification + microstent group. In this study, the perceived risk of bias from random sequence generation, allocation concealment and selective reporting was low. However, these researchers considered the study to be at high risk of performance bias as surgeons/investigators were unmasked. Attrition bias was unclear, with 448/505 participants contributing to per protocol analysis. Insertion of a Cypass supraciliary microstent combined with phacoemulsification probably increased the proportion of participants who were medication-free (not using eye-drops) at 24 months compared with phacoemulsification alone (85 % versus 59 %, RR 1.27, 95 % CI: 1.09 to 1.49, moderate-certainty evidence). There was high-certainty evidence that a greater improvement in mean IOP occurs in the phacoemulsification + microstent group - mean (SD) change in IOP from baseline of -5.4 (3.9) mmHg in the phacoemulsification group, compared to -7.4 (4.4) mmHg in the phacoemulsification + microstent group at 24 months (MD -2.0 mmHg, 95 % CI: -2.85 to -1.15). There was moderate-certainty evidence that insertion of a microstent was probably associated with a greater reduction in use of IOP-lowering drops (mean reduction of 0.7 medications in the phacoemulsification group, compared to a mean reduction of 1.2 medications in the phacoemulsification + microstent group). Insertion of a microstent during phacoemulsification may reduce the requirement for further glaucoma intervention to control IOP at a later stage compared to phacoemulsification alone (RR 0.26, 95 % CI: 0.07 to 1.04, low-certainty evidence). There was no evidence relating to the rate of visual field progression, or proportion of participants whose visual field loss progressed in this study. There was moderate-certainty evidence showing little or no difference in the proportion of participants experiencing post-operative complications over 24 months between participants in the microstent group compared to those who received phacoemulsification alone (RR 1.1, 95 % CI: 0.8 to 1.4). Five-year post-approval data regarding the safety of the Cypass supraciliary microstent showed increased endothelial cell loss, associated with the position of the microstent in the anterior chamber. There were no reported health-related QOL (HR-QOL) outcomes in the included study. The authors concluded that data from this single RCT showed superiority of supraciliary microstent surgery when combined with phacoemulsification compared to phacoemulsification alone in achieving medication-free control of OAG. However, there are long-term safety concerns with the device used in this trial, relating to the observed significant loss of corneal endothelial cells at 5 years following device implantation. At the time of this review, this device has been withdrawn from the market. This review has found that few high-quality studies exist comparing supraciliary microstent surgery to standard medical, laser or surgical glaucoma treatments. This should be addressed by further appropriately designed RCTs with sufficient long-term follow-up to ensure robust safety data are obtained. Consideration of health-related QOL outcomes should also feature in trial design.
Ab Interno Trabecular Bypass Surgery with Trabectome for Open-Angle Glaucoma
Hu and colleagues (2021) noted that glaucoma is the leading cause of irreversible blindness. Minimally invasive surgical techniques, such as ab interno trabecular bypass surgery, have been introduced to prevent glaucoma from progressing. In light of the potential benefits for patients with OAG and the widespread uptake of the technique, it is important to examine the evidence of treatment with ab interno trabecular bypass surgery with Trabectome. These investigators searched the Cochrane Central Register of Controlled Trials (CENTRAL; which contains the Cochrane Eyes and Vision Trials Register; 2020, Issue 7); Ovid Medline; Ovid Embase; the ISRCTN registry; ClinicalTrials.gov and the WHO ICTRP. The date of the search was July 17, 2020. They searched for RCTs of ab interno trabecular bypass surgery with Trabectome compared to other surgical treatments (other minimally invasive glaucoma device techniques, trabeculectomy), laser treatment, or medical treatment. These researchers also included trials in which these devices were combined with phacoemulsification compared to phacoemulsification in combination with other glaucoma surgery or alone. They used the standard methodological procedures expected by Cochrane. The primary outcome was proportion of subjects who were medication-free (not using eye-drops). Secondary outcomes included mean change in IOP, proportion of subjects who needed further glaucoma surgery, mean change in QOL, proportion of subjects who achieved an IOP of 21 mmHg or less, 17 mmHg or less, or 14 mmHg or less and rate of visual field progression. Adverse effects were the proportion of subjects experiencing intra- and post-operative complications. All outcomes were measured in the short-term (6 to 18 months), medium-term (18 to 36 months), and long-term (36 months or longer). In this update, these researchers included 1 RCT which had previously been identified as an ongoing study in the 2016 publication. This trial was a single-center, single-surgeon RCT set in Canada with 19 subjects; they were adults who had OAG, open angles, and had inadequately controlled IOP that needed surgical intervention. The study was terminated before the intended sample size was reached due to slow recruitment and increasing lack of clinical equipoise over time. This reduced the power of the study to detect clinically important effects. These investigators evaluated the trial as being at high risk of attrition, reporting, and other potential sources of biases. The risks of performance and detection bias are unclear. The intervention group of 10 individuals had Trabectome ab interno trabeculotomy combined with cataract extraction (phaco-AIT) and the comparator group of 9 individuals had trabeculectomy with mitomycin C combined with cataract extraction (phaco-Trab), 1 of whom was lost to follow-up; 7 of 10 subjects in the phaco-AIT group and 4 of 8 in the phaco-Trab group were medication-free (not using eye-drops) at 12 months (OR 2.33, 95 % CI: 0.34 to 16.2; very low-certainty evidence). At 12 months, the mean change in IOP was worse for phaco-AIT than for phaco-Trab, but this evidence was very uncertain (MD 3.70 mmHg, 95 % CI: -1.44 to 8.84; very low-certainty evidence) in the phaco-AIT group, as was the difference in the mean number of IOP-lowering eye-drops taken per day (MD -0.41, 95 % CI: -1.22 to 0.40; very low-certainty evidence). Only 1 subject in the phaco-AIT group needed further glaucoma surgery. The study protocol declared that QOL and visual field progression were measured, but they were not reported. All 8 subjects with complete data in the phaco-Trab group and 8 of 10 in the phaco-AIT had at least 1 early or late post-operative complication (e.g., day 1 IOP spike, hypotony, choroidal effusion, bleb leak or encapsulation, uveitis, or peripheral anterior synechiae). The evidence was very low-certainty due to high risk of bias for several domains for this study and for large imprecision of all estimates. These researchers also identified 1 ongoing study, identified from the International Clinical Trials Registry Platform (ICTRP): an open, multi-center, RCT comparing Trabectome to ab interno trabeculectomy using microhook. The study investigators plan to recruit 120 adults between 20 and 90 years of age. The primary outcome is duration of treatment success; and secondary outcomes include post-operative IOP, number of anti-glaucoma medications, and AEs. The authors concluded that there is currently no high-quality evidence for the outcomes of ab interno trabecular bypass surgery with Trabectome for OAG. These researchers stated that properly designed RCTs are needed to examine the long-term safety and efficacy of this technique.
Ab Interno Trabeculectomy with the Dual Blade in Juvenile Open-Angle Glaucoma
Khouri and colleagues (2021) introduced the use of the Kahook Dual Blade in the treatment of juvenile OAG. A 14-year old boy was presented with juvenile OAG in the left eye. Ab interno trabeculectomy was performed using a dual-blade device; IOP was reduced from 28 to 15 mmHg in the left eye after 18 months. There were no complications. The authors concluded that dual blade ab interno trabeculectomy is a promising alternate to goniotomy in the treatment of juvenile OAG.
Ahmed, Ex-PRESS, or Trabeculectomy for the Treatment of Primary and Secondary Glaucoma
In a systematic review and network meta-analysis, Zhang and colleagues (2022) compared the effectiveness of Ahmed, Ex-PRESS, and trabeculectomy to provide a reference for determining surgical schemes for glaucoma patients undergoing external drainage surgery in clinical practice. These investigators carried out a literature search for studies on the treatment of primary and secondary glaucoma with 3 types of external drainage surgery (Ahmed, Ex-PRESS, and trabeculectomy). As of April 24, 2021, 7 electronic databases were searched for RCTs comparing any 2 of Ahmed, Ex-PRESS, and trabeculectomy in the treatment of glaucoma. The Cochrane tool was also adopted to examine the risk of bias in these trials. The RR with 95 % CI, and WMD were determined and compared indirectly using R software. A total of 14 RCTs were included in this study, involving 866 eyes of 808 patients. As for the IOP after 3 months, trabeculectomy did not contribute to better improvement than Ahmed (WMD = 0.014; 95 % CI: -0.14 to 0.18) and Ex-PRESS (WMD = 0.014; 95 % CI: -0.072 to 0.097). However, there was a significant difference in the IOP 1 year between trabeculectomy and Ex-PRESS (WMD = 0.097; 95 % CI: 0.0080 to 0.18), with the latter achieving a favorable improvement effect. Meanwhile, the complete success (CS) of trabeculectomy was significantly lower than that of Ex-PRESS (RR = 0.73; 95 % CI: 0.57 to 0.93). In addition, Ex-PRESS was superior to Ahmed (WMD = -0.48; 95 % CI: -0.89 to -0.084) in terms of a decreased number of post-operative medications. The authors concluded that for glaucoma patients who are required to receive external drainage surgery, Ex-PRESS could achieve a significant effect on the IOP 1 year and CS, as well as a marked decrease in the number of post-operative medications used, compared with the other 2 types of surgery. In terms of the effectiveness at least 1 year after surgery, Ex-PRESS should be one of the preferred methods for external drainage.
Anti-Inflammatory Treatment on the Effectiveness of Selective Laser Trabeculoplasty
Chen and colleagues (2021) noted that selective laser trabeculoplasty (SLT) can lower IOP in cases of OAG. Several studies had examined the effectiveness of anti-inflammatory treatment to relieve discomfort following SLT; however, whether such treatments affect the response of SLT remains uncertain. These investigators systematically searched PubMed, Embase, Web of Science, and Cochrane Library for relevant studies published before March 31, 2021. The major outcomes were the effectiveness of post-SLT anti-inflammatory treatment on IOP reduction, incidence of discomfort, and anterior chamber inflammation compared with those of placebo agents. A total of 5 RCTs with 235 eyes receiving anti-inflammatory treatment and 170 eyes receiving placebo agents were included in the meta-analysis. Compared with placebo, no significant differences were present in IOP reduction effects upon using topical non-steroidal anti-inflammatory drugs (NSAIDs) or steroid post-SLT. The results were consistent from 1 to 6 months during follow-up. Furthermore, anti-inflammatory treatment had no significant effects on pain or discomfort or the presence of anterior chamber cells 1 hour to 1 week following SLT. The authors concluded that topical anti-inflammatory treatment following SLT for patients with glaucoma neither significantly affected IOP reduction nor remarkably relieved clinical discomfort and anterior chamber inflammation. These investigators stated that regular use of post-SLT anti-inflammatory treatment may be unnecessary.
Artificial Intelligence in Diagnosis, Management, and Progression Detection of Glaucoma
Zhu et al (2024) stated that glaucoma comprises a group of progressive optic neuropathies requiring early detection and lifelong treatment to preserve vision. Artificial intelligence (AI) technologies are now showing transformative potential across the spectrum of clinical glaucoma care. These investigators examined current capabilities, future outlooks, and practical translation considerations. For enhanced screening, algorithms analyzing retinal photographs and machine learning (ML) models synthesizing risk factors can identify high-risk patients needing diagnostic work-up and close follow-up. To augment definitive diagnosis, deep learning techniques detect characteristic glaucomatous patterns by interpreting results from OCT, VF testing, fundus photography, and other ocular imaging. AI-powered platforms also enable continuous monitoring, with algorithms that analyze longitudinal data alerting physicians regarding rapid disease progression. By integrating predictive analytics with patient-specific parameters, AI can also guide precision medicine for individualized glaucoma treatment selections. Advances in robotic surgery and computer-based guidance revealed AI's potential to improve surgical outcomes as well as surgical training. Beyond the clinic, AI chatbots and reminder systems could provide patient education and counseling to promote medication adherence. However, thoughtful approaches to clinical integration, usability, diversity, and ethical implications remain critical to successfully implementing these emerging technologies. The authors concluded that the future of AI in glaucoma care hinges on overcoming challenges related to dataset diversity, algorithmic bias, and the standardization of disease definitions. By addressing these issues, AI can significantly enhance glaucoma diagnosis, monitoring, and management, offering more personalized and effective care for a globally diverse patient population. These researchers stated that continued research and development in this field promises to not only improve patient outcomes but also to revolutionize the approach to managing this complex and prevalent eye disease.
The authors stated that a significant challenge in AI’s application to glaucoma is the absence of a universally accepted definition for the disease’s diagnosis and progression. High inter-provider variability in glaucoma diagnosis complicates the evaluation of algorithm outputs. Each imaging modality, whether OCT or VFs, comes with its unique set of challenges, from high costs to subjectivity influenced by patient factors. Hybrid models, which require paired data from different imaging modalities, face barriers in data collection, and the risk of over-fitting. In addition, as glaucoma severity intensifies, patients often struggle with medication adherence due to deteriorating vision, emphasizing the need for tools like AI-powered smartphone apps. However, as new tools emerge, research must also focus on evaluating patient engagement, treatment adherence, and follow-up to ensure that these innovations truly benefit the patients they aim to serve.
These researchers stated that in addition to the technical and ethical challenges already discussed, the clinical adoption of AI in glaucoma treatment faces several crucial hurdles. These include regulatory complexities surrounding AI applications in healthcare, which require rigorous scrutiny to ensure effectiveness and patient safety. Issues of patient privacy and data security are crucial, especially considering the sensitive nature of medical data. The question of data ownership, especially in the context of patient-generated data, raises significant legal and ethical considerations. Moreover, the matter of liability in cases of mis-diagnosis or treatment errors involving AI systems remains an area of active debate and legal evolution. Addressing these challenges is essential for the responsible and effective integration of AI in clinical settings.
Cataract Surgery Combined with Ab Interno Canaloplasty and Micro-Trabecular Bypass Stent Surgery for the Treatment of Open-Angle Glaucoma
In a retrospective, 2-center, case-series study, Porter et al (2024) examined the effectiveness of canaloplasty via an ab-interno technique using the combined with micro-trabecular bypass stent surgery with the Hydrus Microstent following cataract surgery (CE) in patients with POAG. This trial included 51 POAG eyes that underwent phacoemulsification followed by canaloplasty combined with micro-trabecular bypass stent surgery. Eyes were categorized according to IOP and disease severity. A subgroup of patients on 3+ medications at baseline was included. Primary end-points included the mean IOP and mean number of medications at 12 months, 24 months and at the last follow-up. Baseline IOP (mmHg) and number of medications were 19.1 ± 4.0 and 2.3 ± 1.2 and reduced to 13.9 ± 2.6 (p < 0.001) and 1.2 ± 1.4 (p < 0.001) at 12 months, 13.7 ± 2.0 and 1.5 ± 1.5 (p < 0.001, p = 0.008, respectively) at 24 months (n = 31) and 14.4 ± 3.2 and 2.1 ± 1.5 (p < 0.001, p = 0.5, respectively) at 36 months. In the uncontrolled group (n = 27), baseline IOP and number of medications were 21.9 ± 3.1 and 1.9 ± 1.3 and reduced to 14.6 ± 4.2 (p = 0.006) and 1.7 ± 1.6 (p = 0.821) at 36 months post-operatively. Baseline IOP and number of medications of severe patients (n = 12) were 19.0 ± 4.8 and 1.9 ± 1.1. IOP reduced to 12.8 ± 2.4 (p = 0.005) at 12 months while the number of medications did not show any statistically significant change: 1.9 ± 1.6 (p = 0.4). No eyes underwent additional glaucoma surgery in the study period. The authors concluded that canaloplasty combined with micro-trabecular bypass stent surgery following cataract extraction shoed effectiveness in reducing IOP and medication burden up to 24 months post-operatively. IOP reduction was also sustained up to 36 months post-operatively. Moreover, these researchers stated that further investigations are needed to examine the integration of multiple MIGS within a single surgery and their role in addressing various underlying causes of elevated IOP; and these studies should include evaluation of the cost-effectiveness of combining MIGS procedures and identification of the most suitable candidates for such approaches. The authors stated that the drawbacks of this trial included the modest sample size, the retrospective design, the lack of randomization, as well as the lack of comparison with a control group.
Combined Glaucoma and Cataract Surgery
Zhang and colleagues (2015) stated that cataract and glaucoma are leading causes of blindness worldwide, and their co-existence is common in elderly people. Glaucoma surgery can accelerate cataract progression, and performing both surgeries may increase the rate of post-operative complications and compromise the success of either surgery. However, cataract surgery may independently lower intra-ocular pressure (IOP), which may allow for greater IOP control among patients with co-existing cataract and glaucoma. The decision between undergoing combined glaucoma and cataract surgery versus cataract surgery alone is complex. Therefore, it is important to compare the effectiveness of these 2 interventions to aid clinicians and patients in choosing the better treatment approach. In a Cochrane review, these investigators evaluated the relative safety and effectiveness of combined surgery versus cataract surgery (phacoemulsification) alone for co-existing cataract and glaucoma. The secondary objectives included cost-analyses for different surgical techniques for co-existing cataract and glaucoma. These investigators searched CENTRAL (which contains the Cochrane Eyes and Vision Group Trials Register) (2014, Issue 10), Ovid MEDLINE, Ovid MEDLINE In-Process and Other Non-Indexed Citations, Ovid MEDLINE Daily, Ovid OLDMEDLINE (January 1946 to October 2014), EMBASE (January 1980 to October 2014), PubMed (January 1948 to October 2014), Latin American and Caribbean Health Sciences Literature Database (LILACS) (January 1982 to October 2014), the metaRegister of Controlled Trials (mRCT), ClinicalTrials.gov, and the World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP). They did not use any date or language restrictions in the electronic searches for trials. They last searched the electronic databases on October 3, 2014. They checked the reference lists of the included trials to identify further relevant trials. These researchers used the Science Citation Index to search for references to publications that cited the studies included in the review. They also contacted investigators and experts in the field to identify additional trials. The authors included RCTs of participants who had open-angle, pseudoexfoliative, or pigmentary glaucoma and age-related cataract. The comparison of interest was combined cataract surgery (phacoemulsification) and any type of glaucoma surgery versus cataract surgery (phacoemulsification) alone. Two review authors independently assessed study eligibility, collected data, and judged risk of bias for included studies. They used standard methodological procedures expected by the Cochrane Collaboration. These investigators included 9 RCTs, with a total of 655 participants (657 eyes), and follow-up periods ranging from 12 to 30 months; 7 trials were conducted in Europe, 1 in Canada and South Africa, and 1 in the United States. These researchers graded the overall quality of the evidence as low due to observed inconsistency in study results, imprecision in effect estimates, and risks of bias in the included studies. Glaucoma surgery type varied among the studies: 3 studies used trabeculectomy, 3 studies used iStent implants, 1 study used trabeculotomy, and 2 studies used trabecular aspiration. All of these studies found a statistically significant greater decrease in mean IOP post-operatively in the combined surgery group compared with cataract surgery alone; the MD was -1.62 mmHg (95 % CI: -2.61 to -0.64; 489 eyes) among 6 studies with data at 1 year follow-up. No study reported the proportion of participants with a reduction in the number of medications used after surgery, but 2 studies found the mean number of medications used post-operatively at 1 year was about 1 less in the combined surgery group than the cataract surgery alone group (MD -0.69, 95 % CI: -1.28 to -0.10; 301 eyes); 5 studies showed that participants in the combined surgery group were about 50 % less likely compared with the cataract surgery alone group to use 1 or more IOP-lowering medications 1 year post-operatively (RR 0.47, 95 % CI: 0.28 to 0.80; 453 eyes). None of the studies reported the mean change in visual acuity or visual fields. However, 6 studies reported no significant differences in visual acuity and 2 studies reported no significant differences in visual fields between the 2 intervention groups post-operatively (data not analyzable). The effect of combined surgery versus cataract surgery alone on the need for re-operation to control IOP at 1 year was uncertain (RR 1.13, 95 % CI: 0.15 to 8.25; 382 eyes). Also uncertain was whether eyes in the combined surgery group required more interventions for surgical complications than those in the cataract surgery alone group (RR 1.06, 95 % CI: 0.34 to 3.35; 382 eyes). No study reported any vision-related quality of life data or cost outcome. Complications were reported at 12 months (2 studies), 12 to 18 months (1 study), and 2 years (4 studies) after surgery. Due to the small number of events reported across studies and treatment groups, the difference between groups was uncertain for all reported adverse events. The authors concluded that there is low quality evidence that combined cataract and glaucoma surgery may result in better IOP control at 1 year compared with cataract surgery alone. The evidence was uncertain in terms of complications from the surgeries. Furthermore, this Cochrane review has highlighted the lack of data regarding important measures of the patient experience, such as visual field tests, quality of life measurements, and economic outcomes after surgery, and long-term outcomes (5 years or more). They stated that additional high-quality RCTs measuring clinically meaningful and patient-important outcomes are needed to provide evidence to support treatment recommendations.
CyPass Micro-Stent
Saheb and Ahmed (2012) noted that there is an increasing interest and availability of micro-invasive glaucoma surgery (MIGS) procedures. It is important that this increase is supported by sound, peer-reviewed evidence. These researchers defined MIGS, reviewed relevant publications in the period of annual review and discussed future directions. The results of the pivotal trial comparing iStent combined with phaco-emulsification to phacoemulsification alone showed a significantly higher percentage of patients with unmedicated IOP of less than or equal to 21 mm Hg, and a comparable safety profile. Initial results were published regarding a second-generation micro-bypass stent (iStent inject, Glaukos Corporation, Laguna Hills, CA), a canalicular scaffold (Hydrus, Ivantis Inc., Irvine, CA) and an ab interno suprachoroidal micro-stent (CyPass, Transcend Medical, Menlo Park, CA), showing a decrease in mean post-operative IOP. Phaco-Trabectome (Ab interno trabeculectomy Trabectome, NeoMedix Inc., Tustin, CA) was compared to phaco-trabeculectomy and showed less IOP reduction, less post-operative complications, and a similar success rate. Similar success rates were found with the comparison of excimer laser trabeculostomy (ELT, AIDA, Glautec AG, Nurnberg, Germany) and selective laser trabeculoplasty. A number of publications reviewed the importance of the location of implantable devices, intra-operative gonioscopy, cost-effectiveness and quality-of-life studies, and randomized clinical trials. The authors concluded that MIGS procedures offer reduction in IOP, decrease in dependence on glaucoma medications and an excellent safety profile. Their role within the glaucoma treatment algorithm continues to be clarified and differs from the role of more invasive glaucoma surgeries such as trabeculectomy or glaucoma drainage devices.
Saheb and associates (2014) evaluated the supra-ciliary space (SCS) with anterior segment optical coherence tomography (OCT) imaging after CyPass Micro-Stent implantation. The SCS was imaged with OCT after micro-stent implantation at 1, 6 months, and 1 year. Images were graded on a scale of 0 to 4 for morphological features indicative of fluid presence within, or drainage through, the SCS. A total of 35 patients underwent ab-interno micro-stent implantation. Mean age was 68.6 ± 10.2 years. Baseline mean IOP was 21.9 ± 6.1 mm Hg on average of 3.0 topical medications. At 1 month, the fluid space grade was greater than or equal to 1 for 96 % (24/25) of patients for tenting, 79 % (15/19) for fluid posterior to the micro-stent, and 89 % (8/9) for fluid surrounding the micro-stent. The mean (composite) score for all features was 2.5 ± 0.99. The majority of patients maintained aqueous fluid through 12 months. The authors concluded that OCT imaging provided adequate visualization of the angle, the SCS and aqueous fluid drainage after implantation of a suprachoroidal micro-stent into the SCS.
The drawbacks of this study included its retrospective nature and short-term follow-up (12 months). Furthermore, while standardized for the purposes of this study, the grading of OCT images did not follow a validated systematic approach due to the lack of such grading scales. There is a paucity of OCT grading systems in general, and none available for the SCS. The authors used the size of the micro-stent as a standard measure, since its size was consistent across all subjects and independent of OCT software or print-outs. The individual measuring the images was masked as to the post-operative time of the image, however, there may have been a bias toward larger measures when the micro-stent was fully visible. Finally, images were not available for all subjects, with a gradual decrease in available images at later time-points. There could have been some selection bias in this study for imaging of patients with poorer post-operative outcomes. This bias needs to be considered as researchers evaluate the grades of the available images, especially at later time-points.
In a multi-center, prospective, consecutive case-series study, Hoh and co-workers (2014) evaluated through 2 post-operative years the clinical outcomes associated with a novel SCS micro-stent for the surgical treatment of OAG when implanted in conjunction with cataract surgery. A total of 136 subjects (136 eyes) with OAG and requiring cataract surgery with 24-month post-operative data were included. A combined phacoemulsification procedure, with intra-ocular lens insertion and CyPass Micro-Stent implantation into the SCS of the study eye, was performed. At baseline, all subjects were on glaucoma medication with either uncontrolled IOP (greater than or equal to 21 mmHg, Cohort 1, n = 51) or controlled IOP (less than 21 mmHg, Cohort 2, n = 85). Glaucoma medications were stopped post-operatively, but could be re-started if needed, at the investigator's discretion. Device-related adverse events (AEs), post-operative IOP, best corrected distance visual acuity (BCDVA), and number of IOP-lowering medications were recorded. The micro-stent was successfully implanted in all eyes. At 24 months, 82 subjects remained in the study. No sight-threatening AEs occurred. The most common AEs were transient hypotony (15.4 %) and micro-stent obstruction (8.8 %), typically due to iris tissue over-growth; 15 subjects (11 %) required secondary incisional glaucoma surgery. For Cohort 1 (n = 23), mean ± SD IOP was 15.8 ± 3.8 mmHg after 24 months (change, -37 % ± 19 %). Mean IOP decrease from baseline was statistically significant (p < 0.0001) at months 6, 12, and 24. For Cohort 2 (n = 59), mean ± SD IOP at 24 months was 16.1 ± 3.2 mmHg (change, 0 % ± 28 %). Mean decrease from baseline was statistically significant at months 6 (p = 0.0188) and 12 (p = 0.0356). At 24 months, the mean ± SD number of medications was 1.0 ± 1.1 in Cohort 1 and 1.1 ± 1.1 in Cohort 2. Mean decrease from baseline medication use was statistically significant at months 6 (p < 0.001), 12 (p < 0.001), and 24 (p = 0.0265) in Cohort 1, and at months 6, 12, and 24 (all p < 0.0001) in Cohort 2. The authors concluded that CyPass Micro-Stent implantation, in combination with cataract surgery, was associated with minimal complications while substantially lowering IOP and/or use of IOP-lowering medications.
In a multi-center RCT, Void and colleagues (2016) evaluated 2-year safety and effectiveness of SCS micro-stenting for treating mild-to-moderate POAG in patients undergoing cataract surgery. Subjects were enrolled beginning July 2011, with study completion in March 2015. Subjects had POAG with mean diurnal un-medicated IOP 21 to 33 mmHg and were undergoing phacoemulsification cataract surgery. After completing cataract surgery, subjects were intra-operatively randomized to phacoemulsification only (control) or SCS micro-stenting with phacoemulsification (micro-stent) groups (1:3 ratio). Micro-stent implantation via an ab interno approach to the SCS allowed concomitant cataract and glaucoma surgery. Outcome measures included percentage of subjects achieving greater than or equal to 20 % un-medicated diurnal IOP lowering versus baseline, mean IOP change and glaucoma medication use, and ocular AE incidence through 24 months. Of 505 subjects, 131 were randomized to the control group and 374 were randomized to the micro-stent group. Baseline mean IOPs in the control and micro-stent groups were similar: 24.5 ± 3.0 and 24.4 ± 2.8 mmHg, respectively (p > 0.05); mean medications were 1.3 ± 1.0 and 1.4 ± 0.9, respectively (p > 0.05). There was early and sustained IOP reduction, with 60 % of controls versus 77 % of micro-stent subjects achieving greater than or equal to 20 % un-medicated IOP lowering versus baseline at 24 months (p = 0.001; per-protocol analysis). Mean IOP reduction was a decrease of 7.4 mmHg for the micro-stent group versus a decrease of 5.4 mmHg in controls (p < 0.001), with 85 % of micro-stent subjects not requiring IOP medications at 24 months. Mean 24-month medication use was 67 % lower in micro-stent subjects (p < 0.001); 59 % of control versus 85 % of micro-stent subjects were medication free. Mean medication use in controls decreased from 1.3 ± 1.0 drugs at baseline to 0.7 ± 0.9 and 0.6 ± 0.8 drugs at 12 and 24 months, respectively, and in the micro-stent group from 1.4 ± 0.9 to 0.2 ± 0.6 drugs at both 12 and 24 months (p < 0.001 for reductions in both groups at both follow-ups versus baseline). No vision-threatening micro-stent-related AEs occurred; VA was high in both groups through 24 months; greater than 98 % of all subjects achieved 20/40 BCVA or better. The authors concluded that the findings of this RCT demonstrated safe and sustained 2-year reduction in IOP and glaucoma medication use after micro-stent surgical treatment for mild-to-moderate POAG.
The authors stated that findings from this study were generalizable to men and women aged over 45 years, with Shaffer grade greater than or equal to 3 POAG and baseline un-medicated IOP 21 to 33 mmHg, and demographics typical of the enrolled US subpopulation. They noted that the Latino/Hispanic ethnicity category constituted only 4 % of the cohort and may be under-represented. These investigators also noted that another drawback of this study was that the principal investigator at each study site was not masked to treatment randomization during patient follow-up examinations.
The AAO Preferred Practice Pattern Glaucoma Panel (Prum et al, 2015) stated that "Several other glaucoma surgeries exist as alternatives to trabeculectomy and aqueous shunt implantation. The precise role of these procedures in the surgical management of glaucoma remains to be determined". Trabecular micro-bypass stent (or iStent) is listed as one of these procedures.
McCartney and Phagura (2020) stated that microinvasive glaucoma surgery and its associated devices remain a field of continued interest and innovation in the management of patients with glaucoma. While a range of outflow optimization devices have been designed, the safety and efficacy of these devices remains to be proven, especially in the long-term. These investigators presented the 1st reported case of bilateral hypertensive crisis associated with CyPass Micro-stent insertion 2 months post-operation and its resultant management. The authors concluded that despite the recall of the CyPass Micro-stent, further clinical experience in the use of these and similar stents is needed. These researchers presented possible hypotheses explaining this phenomenon, the most likely being sudden closure of the suprachoroidal space.
Drug-Eluting Implant into Lacrimal Canaliculus During Routine Cataract Removal
An UpToDate review on “Cataract in adults” (Jacobs, 2021) does not mention the use of drug-eluting implant as a management option.
Drug-Eluting Ocular Insert
Bhagav et al (2011) stated that pathology of eye, especially in the case of glaucoma, requires optimal therapeutically effective concentration of the drug in the ocular tissues for prolonged period of time with decreased dosing frequency and improved patient compliance. In the present study, brimonidine tartrate (BRT) ocular inserts were designed based on hydrophilic and/or inert/zwitterionic polymer matrix to design muco-adhesive and extended release ocular inserts. Designed inserts were evaluated for their physicochemical properties such as crushing strength/hardness, friability, drug content and muco-adhesion, and erosion and in-vitro drug release characteristics. The selected optimized formulations were compared with marketed preparation for in-vivo ocular irritation in healthy rabbits and for in-vivo pharmacodynamic efficacy on alpha-chymotrypsin-induced glaucomatous rabbits. The developed formulations showed good physicochemical properties and muco-adhesive strength, and a good correlation was seen between rate of erosion or swelling with drug release rate in case of formulations with higher proportion of polyethylene oxide (PEO). Modulation of drug release was achieved by incorporating Eudragit in PEO matrix. Addition of Eudragit resulted in shifting of drug release mechanism from erosion-controlled to diffusion-controlled mechanism. The authors concluded that in-vivo ocular irritation studies confirmed the absence of any irritation upon administration in rabbits; and intra-ocular pressure (IOP) measurement studies showed an improved IOP-lowering ability of ocular insert of BRT in comparison to eye drops.
Franca et al (2014) developed and evaluated a novel sustained-release drug delivery system of bimatoprost (BIM). Chitosan polymeric inserts were prepared using the solvent casting method and characterized by swelling studies, infrared spectroscopy, differential scanning calorimetry, drug content, scanning electron microscopy and in-vitro drug release. Bio-distribution of 99mTc-BIM eye drops and 99mTc-BIM-loaded inserts, after ocular administration in Wistar rats, was accessed by ex-vivo radiation counting. The inserts were evaluated for their therapeutic efficacy in glaucomatous Wistar rats. Glaucoma was induced by weekly intra-cameral injection of hyaluronic acid. BIM-loaded inserts (equivalent to 9.0 µg BIM) were administered once into conjunctival sac, after ocular hypertension (OHT) confirmation. BIM eye drop was topically instilled in a second group of glaucomatous rats for 15 days, while placebo inserts were administered once in a third group. An untreated glaucomatous group was used as control; IOP was monitored for 4 consecutive weeks after treatment began. At the end of the experiment, retinal ganglion cells and optic nerve head cupping were evaluated in the histological eye sections. Characterization results revealed that the drug physically interacted, but did not chemically react with the polymeric matrix. Inserts released continually BIM in-vitro during 8 hours. Bio-distribution studies showed that the amount of 99mTc-BIM that remained in the eye was significantly lower after eye drop instillation than after chitosan insert implantation. BIM-loaded inserts lowered IOP for 4 weeks, after 1 application, while IOP values remained significantly high for the placebo and untreated groups. Eye drops were only effective during the daily treatment period; IOP results were reflected in retinal ganglion cells counting and optic nerve head cupping damage. The authors concluded that BIM-loaded inserts provided sustained release of BIM and appeared to be a promising system for glaucoma management.
In a phase II, parallel-arm, multi-center, double-masked, randomized controlled trial (RCT), Brandt et al (2016) compared topical BIM ocular insert with twice-daily timolol (TIM) eye drops in patients with open-angle glaucoma (OAG) or OHT treated for 6 months. A total of 130 adult OAG or OHT patients were included in this study. Eligible patients were randomized 1:1 to receive a BIM insert plus artificial tears twice-daily or a placebo insert plus TIM (0.5 % solution) twice-daily for 6 months after a screening wash-out period. Diurnal IOP measurements (at 0, 2, and 8 hours) were obtained at baseline; weeks 2, 6, and 12; and months 4, 5, and 6. Key eligibility included wash-out IOP of 23 mmHg or more at time 0, IOP of 20 mmHg or more at 2 and 8 hours, and IOP of 34 mmHg or less at all time-points; no prior incisional surgery for OAG or OHT; and no known non-responders to prostaglandins. The primary efficacy end-point examined the difference in mean change from baseline in diurnal IOPs (point estimate, 95 % CI] across 9 co-primary end-points at weeks 2, 6, and 12 comparing the BIM-arm with the TIM-arm using a non-inferiority margin of 1.5 mmHg. Secondary end-points were diurnal IOP measurements at months 4, 5, and 6 and adverse events (AEs). A mean reduction from baseline IOP of -3.2 to -6.4 mmHg was observed for the BIM group compared with -4.2 to -6.4 mmHg for the TIM group over 6 months. The study met the non-inferiority definition at 2 of 9 time-points but was under-powered for the observed treatment effect. Adverse events were consistent with BIM or TIM exposure; no unexpected ocular AEs were observed. Primary retention rate of the insert was 88.5 % of patients at 6 months. The authors concluded that clinically relevant reduction in mean IOP was observed over 6 months with a BIM ocular insert and appeared to be safe and well-tolerated. They stated that the topically applied BIM insert may provide an alternative to daily eye drops to improve adherence, consistency of delivery, and reduction of elevated IOP.
Excimer Laser Trabeculostomy
Durr and colleagues (2020) state that excimer laser trabeculostomy (ELT) is a microinvasive glaucoma surgery (MIGS) that creates multiple laser channels through the trabecular meshwork using a cold laser system, which minimizes tissue fibrosis and aids in bypassing the main area of resistance to aqueous outflow. These researchers examined the available evidence regarding ELT in terms of efficacy and reviewed the safety profile of the procedure. Studies screened had to show clear inclusion and exclusion criteria as well as well-defined outcome measures. PubMed, Medline, Embase and the Cochrane Controlled Trial Database were searched. Preferred Reporting Items of Systematic Reviews (PRISMA) guidelines were used to evaluate for study quality and for any bias. A total of 64 articles were initially identified with 18 meeting preliminary screening criteria. A total of 8 studies met inclusion criteria and 2 additional non-referenced publications were also included: 1 RCT, 4 prospective case-series studies and 5 retrospective studies. Overall studies showed moderate IOP lowering of between 20 % and 40 % from baseline without medication washout and mostly a decrease in glaucoma medications with few complications. The authors concluded that current available evidence showed an IOP-lowering effect from ELT alone or in combination with cataract surgery with encouraging results across different studies and patient populations, notably without washout IOP, and a favorable safety profile. Multiple studies, albeit with small sample sizes and variable loss to follow-up, have shown a long-lasting response up to 8 years after the initial surgery. The potential advantages of this procedure are less scarring than results from traditional thermal lasers, repeatability in different quadrants, ease of use, no device left in the angle and, with lower hyphema risks compared to ablative procedures, potentially less secondary synechia to the angle. Moreover, these researchers stated that the procedure also appears to have a favorable safety profile with few intra-operative or post-operative risks; however, like any new technology, more studies are needed to better characterize ELT and further substantiate these promising findings. These investigators noted that drawbacks to these studies included the lack of controls and washout IOP.
Furthermore, an UpToDate review on “Open-angle glaucoma: Treatment” (Jacobs, 2021) does not mention excimer laser trabeculostomy as a therapeutic option.
Excimer Laser Trabeculotomy
Lavia and associates (2017) noted that micro-invasive glaucoma surgery (MIGS) have been developed as a surgical alternative for glaucomatous patients. These researchers analyzed the change in intraocular pressure (IOP) and glaucoma medications using different MIGS devices (Trabectome, iStent, excimer laser trabeculotomy (ELT), iStent Supra, CyPass, XEN, Hydrus, Fugo Blade, Ab interno canaloplasty, Goniscopy-assisted transluminal trabeculotomy) as a solo procedure or in association with phaco-emulsification; RCTs and non-RCTs (non-randomized comparative studies, non-randomized study of intervention [NRS], and before-after studies) were included. Studies with at least 1 year of follow-up in patients affected by POAG, pseudo-exfoliative glaucoma or pigmentary glaucoma were considered. Risk of bias assessment was carried out using the Cochrane Risk of Bias and the ROBINS-I tools. The main outcome was the effect of MIGS devices compared to medical therapy, cataract surgery, other glaucoma surgeries and other MIGS on both IOP and use of glaucoma medications 12 months after surgery. Outcomes measures were the mean difference in the change of IOP and glaucoma medication compared to baseline at 1 and 2 years and all ocular AEs. Over a total of 3,069 studies, 9 RCTs and 21 case-series studies with a total of 2,928 eyes were included. Main concerns regarding the risk of bias in RCTs were lack of blinding, allocation concealment and attrition bias while in non-RCTs they were represented by patients' selection, masking of participants and co-intervention management. Limited evidence was found based on both RCTs and non RCTs that compared MIGS surgery with medical therapy or other MIGS. In before-after series, MIGS surgery appeared effective in lowering both IOP and glaucoma drug use. MIGS showed a good safety profile: IOP spikes were the most frequent complications and no cases of infection or BCVA loss due to glaucoma were reported. The authors concluded that although MIGS appeared effective in lowering IOP and glaucoma medication and showed good safety profile, this evidence was mainly derived from non-comparative studies and further, good quality RCTs are needed. They stated that future research should be comparative, ideally randomized, including patients and alternative treatments that are relevant to clinical settings.
Excimer laser trabeculotomy (ELT) is a minimally invasive procedure used to lower the intraocular pressure (IOP) via a photo-ablative laser that is applied to the trabecular meshwork of the eye. The trabecular meshwork is one of the main outflow barriers in glaucoma, and the goal of ELT treatment aims to increase the outflow of the aqueous humor. However, there are limited number of studies examining mostly relatively small sample sizes with midterm follow-up available in published peer-reviewed literature. Thus, Deubel et al (2021) present the analysis of a large ELT cohort in a long-term follow-up. The authors conducted a retrospective cohort study of recorded data from 580 patients who underwent ELT (using the XeCl Excimer Laser AIDA via clear cornea incisions) or combined ELT with cataract surgery at a single-center institution in Germany from November 2000 until March 2011. A total of 512 patients with primary open angle glaucoma (POAG), pseudoexfoliation glaucoma (PEX), and ocular hypertension (OHT) were included in the analysis. At every follow-up examination, the usage of IOP-lowering medication and the IOP were recorded. Failure criteria were defined as the need for another surgical glaucoma procedure, when the IOP was not 21 mmHg or less and a reduction of 20% from the baseline was not achieved with (qualified success) or without (absolute success) additional medication. Statistical analysis was done using Kaplan-Meier analysis and Cox regression. Four hundred twenty-eight patients underwent combined cataract and ELT surgery, and 84 underwent solitary ELT surgery. After a median follow-up time of 656 days, 87% (combined surgery) and 66% (ELT) of the patients did not have to undergo another IOP-lowering intervention; 47/31% were classified as a qualified success and 31/11% as a complete success. The IOP-lowering medication, however, could not be significantly reduced within that time period. The authors concluded that ELT is a feasible minimally invasive procedure to lower the IOP on a mid- to long-term basis, especially when combined with cataract surgery. However, over the long term, IOP-lowering medication could not be reduced.
Fornix-Based Versus Limbal-Based Conjunctival Trabeculectomy Flaps for Glaucoma
Theventhiran and colleagues (2021) stated that glaucoma is one of the leading, but largely preventable causes of blindness. It is usually managed first medically with topical IOP-lowering drops or by laser trabeculoplasty. In cases where such treatment fails, glaucoma-filtering surgery such as trabeculectomy, is commonly considered. Surgeons can differ in their technique when carrying out trabeculectomy, for example, the choice of the type of the conjunctival flap (fornix- or limbal-based). In a fornix-based flap, the surgical wound is performed at the corneal limbus; while in a limbal-based flap, the incision is further away. Many studies compared fornix- and limbal-based trabeculectomy with respect to outcomes and complications. In a Cochrane review, these investigators compared the effectiveness of fornix- versus limbal-based conjunctival flaps in trabeculectomy for adult glaucoma, with a specific focus on IOP control and complication rates (adverse effects). They searched the Cochrane Central Register of Controlled Trials (CENTRAL; which contains the Cochrane Eyes and Vision Trials Register; 2021, Issue 3); Ovid Medline; Ovid Embase; the ISRCTN registry; ClinicalTrials.gov and the WHO ICTRP. The date of the search was March 23, 2021. There were no restrictions to language or year of publication. These researchers included RCTs comparing the benefits and complications of fornix- versus limbal-based trabeculectomy for glaucoma, irrespective of glaucoma type, publication status, and language. They excluded studies on children less than 18 years of age, since wound healing is different in this age group and the rate of bleb scarring post-operatively is high. These investigators used standard methodological procedures as per Cochrane criteria. They did not identify any new eligible studies for this review update. As presented in the original review, these researchers included 6 trials with a total of 361 participants; 2 studies were conducted in the U.S., and 1 each in Germany, Greece, India, and Saudi Arabia. The participants of 4 trials had OAG; 1 study included participants with primary OAG or primary closed-angle glaucoma, and 1 study did not specify the type of glaucoma; 3 studies used a combined procedure (phacotrabeculectomy). Trabeculectomy with mitomycin C (MMC) was carried out in 4 studies, and trabeculectomy with 5-fluorouracil (5-FU) was conducted in only 1 study. None of the included trials reported trabeculectomy failure at 24 months. Only 1 trial reported the failure rate of trabeculectomy as a late complication. Failure was higher among participants randomized to the limbal-based surgery: 1/50 eyes failed trabeculectomy in the fornix group compared with 3/50 in the limbal group (Peto OR 0.36, 95 % CI: 0.05 to 2.61)); thus, these researchers were very uncertain as to the relative effect of the 2 procedures on failure rate; 4 studies including 252 participants provided measures of mean IOP at 12 months. In the fornix-based surgeries, mean IOP ranged from 12.5 to 15.5 mmHg and similar results were noted in limbal-based surgeries with mean IOP ranging from 11.7 to 15.1 mmHg without significant difference. Mean difference was 0.44 mmHg (95 % CI: -0.45 to 1.33; 247 eyes) and 0.86 mmHg, (95 % CI: -0.52 to 2.24; 139 eyes) at 12 and 24 months of follow-up, respectively. Neither of these pooled analyses showed a statistically significant difference in IOP between groups (moderate certainty evidence); 1 trial reported number of anti-glaucoma medications at 24 months of follow-up with no difference noted between surgical groups. However, 3 trials reported the mean number of anti-glaucoma medications at 12 months of follow-up without significant difference in the mean number of post-operative IOP-lowering medications between the 2 surgical techniques. Mean difference was 0.02, (95 % CI: -0.15 to 0.19) at 12 months of follow-up (high certainty evidence). Because of the small numbers of events and total participants, the risk of many reported AEs was uncertain and those that were found to be statistically significant may have been due to chance. For risk of bias assessment: although all 6 trials were randomized, selection bias was mostly unclear, with unclear random sequence generation in 4 of the 6 studies and unclear allocation concealment in 5 of the 6 studies. Attrition bias was encountered in only 1 trial, which also suffered from reporting bias. All other trials had an unclear risk of reporting bias as there was no access to study protocols. All included trials were judged to have high risk of detection bias due to lack of masking of the outcomes. These researchers noted that trabeculectomy is quite a standard procedure and unlikely to induce bias due to surgeon “performance”, hence performance bias was not evaluated. The authors concluded that the main result of this review was that there was uncertainty as to the difference between fornix- and limbal-based trabeculectomy surgeries due to the small number of events and CIs that crossed the null hypothesis. This also applied to post-operative complications, but without any impact on long-term failure rate between the 2 surgical techniques.
Gonioscopy-Assisted Transluminal Trabeculotomy (GATT)
Gonioscopy-assisted transluminal trabeculotomy (GATT) is a minimally invasive, ab interno surgical procedure for treating open-angle glaucoma. It involves accessing Schlemm’s canal through a small corneal incision under gonioscopic visualization, then threading a microcatheter or suture circumferentially through the canal to incise the trabecular meshwork (TM) along its full 360-degree length. This approach aims to restores physiologic aqueous outflow without creating a filtering bleb or disturbing the conjunctiva.
In a retrospective, non-comparative cases-series study, Grover et al (2014) introduced a minimally invasive, ab interno approach to a circumferential 360-degree trabeculotomy and reported the preliminary results. A total of 85 eyes of 85 consecutive patients with uncontrolled OAG and underwent gonioscopy-assisted transluminal trabeculotomy (GATT) for whom there was at least 6 months of follow-up data were included in this analysis. These investigators performed retrospective chart review of patients who underwent GATT by 4 of the authors between October 2011 and October 2012. The surgery was performed in adults with various OAG. Main outcome measures included (IOP, glaucoma medications, visual acuity, and intra-operative as well as post-operative complications. Eighty-five patients with an age range of 24 to 88 years underwent GATT with at least 6 months of follow-up. In 57 patients with POAG, the IOP decreased by 7.7 mm Hg (standard deviation [SD], 6.2 mm Hg; 30.0 % [SD, 22.7 %]) with an average decrease in glaucoma medications of 0.9 (SD, 1.3) at 6 months. In this group, the IOP decreased by 11.1 mm Hg (SD, 6.1 mm Hg; 39.8 % [SD, 16.0 %]) with 1.1 fewer glaucoma medications at 12 months. In the secondary glaucoma group of 28 patients, IOP decreased by 17.2 mm Hg (SD, 10.8 mm Hg; 52.7 % [SD, 15.8 %]) with an average of 2.2 fewer glaucoma medications at 6 months. In this group, the IOP decreased by 19.9 mm Hg (SD, 10.2 mm Hg; 56.8 % [SD, 17.4 %]) with an average of 1.9 fewer medications (SD, 2.1) at 12 months. Treatment was considered to have failed in 9 % (8/85) of patients because of the need for further glaucoma surgery. The cumulative proportion of failure at 1 year ranged from 0.1 to 0.32, depending on the group. Lens status or concurrent cataract surgery did not have a statistically significant effect on IOP in eyes that underwent GATT at either 6 or 12 months (p > 0.35). The most common complication was transient hyphema, seen in 30 % of patients at the 1-week visit. The authors concluded that the preliminary results and safety profile for GATT, a minimally invasive circumferential trabeculotomy, are promising and at least equivalent to previously published results for ab externo trabeculotomy.
Gonioscopy-Assisted Transluminal Trabeculotomy (GATT) for the Treatment of Juvenile-Onset Open Angle Glaucoma
In a retrospective, case-series study, Wang et al (2021) reported the outcomes of GATT for the treatment of juvenile-onset primary OAG (JOAG). This study included JOAG patients who underwent GATT with follow-up period of up to 18 months; IOP, number of glaucoma medications and success rate were compared between eyes with and without prior glaucoma surgery, and between mild-to-moderate and severe cases defined based on Humphrey Visual Field mean deviation. A total of 59 eyes of 48 patients were included. Overall, IOP was reduced from 26.5 ± 9.0 mmHg on 3.7 ± 0.9 medications pre-operatively to 14.7 ± 3.0 mmHg on 0.7 ± 1.2 medications at 12 months and to 14.1 ± 2.3 mmHg on 0.4 ± 0.8 medications at 18 months post-operatively (p < 0.001). The complete and qualified success rates were 70.8 % and 81.2 % at 12 months, and 58.6 % and 81.2 % at 18 months, respectively. Eyes with and without prior glaucoma surgery did not differ significantly in terms of post-operative IOP, glaucoma medication, and success rate. Furthermore, GATT was effective for both mild-to-moderate and severe cases; the latter achieved a surgical success of 79.1 %. The authors concluded that GATT was effective for JOAG. In particular, this case-series study suggested that GATT is promising in treating severe JOAG and those with prior glaucoma surgery. These researchers stated that further investigations are needed to determine the long-term success of GATT in the treatment of patients with JOAG.
The authors stated that this trial had several drawbacks. First, it was a retrospective study. Some cases did not undergo AS-OCT within the 1st week after surgery; therefore, these investigators may have under-estimated the frequency of transient ciliochoroidal detachment. There was also no grading for macro-hyphema; thus, these researchers could not determine the association between surgical failure and macro-hyphema. Second, this study was limited by the short follow-up duration (up to 18 months). Third, this trial had a relatively small sample size (n = 48 patients).
In a prospective, case-series study, Shi et al (2022) identified risk factors for surgical failure after GATT in JOAG. GATT was the initial surgery in 70 eyes of 70 patients with JOAG. Surgical success was defined as a post-operative IOP of 21 mm Hg or less with at least a 20 % reduction from pre-operative IOP, with or without the use of anti-glaucoma medication (qualified and complete success, respectively) at each post-operative visit. IOP spike was defined as IOP of greater than 30 mm Hg and an increase of at least 10 mm Hg from IOP before the spike, and then reduced to 21 mm Hg or less. The median age at the time of surgery was 19.3 years (range of 4.9 to 37.5 years) with a visual field mean deviation of -17.4 ± 10.6 dB. Mean IOP decreased from 31.3 ± 9.5 mm Hg pre-operatively to 15.8 ± 2.7 at 12 months post-operatively. The complete and qualified success rates were 74.3 % and 91.4 %, respectively. An IOP spike occurred in 52 eyes (74 %), with a median spike duration of 3.5 days (range of 1 to 21 days). Longer duration of IOP spike (p = 0.009) and older age at the time of surgery (p = 0.025) were both associated with worse surgical outcomes. Advanced disease was associated with prolonged IOP spike (p = 0.007). The authors concluded that GATT provided excellent outcomes in patients with severe JOAG. Older age and longer duration of post-operative IOP spike were risk factors for failure. Severe cases were more likely to have longer durations of IOP spike. Frequent IOP monitoring during the early post-operative period is needed to detect IOP spikes in these patients.
The authors stated that this study had several drawbacks. First, only single baseline pre-operative IOP was recorded, which may have resulted in variation on IOP analysis. Furthermore, Snellen acuity instead of EDTRS acuity was used for vision measurement. Although logMAR conversion from Snellen acuity has been applied broadly, converting a categorical Snellen acuity measurement to a continuous logMAR could cause bias because there are no detailed data between any 2 lines of the Snellen acuity, and the measurement between the lines of Snellen acuity is not equally incremental. Second, post-operative follow-up was only 12 months. Although the angle configuration remained stable through this time-point, it was possible that further changes in aqueous humor flow patterns, collector channel entrances, and the deep scleral plexus after GATT may affect longer-term outcomes. Third, the generally advanced stage glaucoma observed in this study group might add bias; however, many patients with JOAG have greater field defects and visual disability at presentation. Fourth, only Chinese patients were included in this trial; thus, generalization of these findings to other ethnicities may be limited.
In a retrospective, case-series study, Wang et al (2023) examined the safety and effectiveness of GATT in the treatment of patients with OAG who had failed prior incisional glaucoma surgery. This trial included OAG patients aged 18 years or older who underwent GATT with previous failed glaucoma incision surgery. Main outcome measures included IOP, the number of glaucoma medications, surgical success rate, and occurrence of complications. Success was defined as an IOP of 21 mmHg or less and a reduction of IOP by 20 % or more from baseline with (qualified success) or without (complete success) glaucoma medications. For eyes with pre-operative IOP of less than 21 mmHg on 3 or 4 glaucoma medications, post-operative IOP of 18 mmHg or less without any glaucoma medications was also defined as complete success. A total of 44 eyes of 35 patients (21 with JOAG and 14 with adult-onset POAG) with a median age of 38 years were included in this study. The proportion of eyes with 1 prior incisional glaucoma surgery was 79.5 %, and the others had 2 prior surgeries. IOP decreased from 27.4 ± 8.8 mm Hg on 3.6 ± 0.7 medications pre-operatively to 15.3 ± 2.7 mm Hg on 0.5 ± 0.9 medications at the 24-month visit (p < 0.001). The mean IOP and the number of glaucoma medications at each follow-up visit were lower than the baseline (all p < 0.001). At 24 months post-operatively, 82.1 % of the eyes had IOP of 18 mmHg or less (versus 15.9 % pre-operatively, p < 0.001), 56.4 % reached IOP of 15 mmHg or less (versus 4.6 % pre-operatively, p < 0.001), and 15.4 % achieved IOP of 12 mmHg or less (compared to none pre-operatively, p = 0.009). While 95.5 % of eyes took 3 or more medications pre-operatively, 66.7 % did not take glaucoma medication 24 months after GATT. A total of 34 (77.3 %) eyes achieved IOP reduction greater than 20 % on fewer medications. The complete and qualified success rates were 60.9 % and 84.1 %, respectively. No vision-threatening complications occurred. The authors concluded that GATT was safe and effective for the treatment of OAG patients who had prior failed incisional glaucoma surgery. Moreover, these researchers stated that randomized controlled trials (RCTs) with long-term follow-up are needed to better understand the effectiveness of GATT.
The authors stated that this trial was limited by the small sample size and the follow-up period of 24 months. For several patients, both eyes were included in this study, which may have affected interpretation of the results. IOP spike is a common post-operative complications and attracts attention. Since patients in this study were not followed daily until the end of the spike, these researchers could not show the exact duration of IOP spike; further studies are needed to investigate this issue. Moreover, these investigators stated that the limitations universal to retrospective studies such as non-randomization with no control group may also have affected the results; however, this study provided real-world data on the safety and effectiveness of GATT in treating refractory glaucoma.
Gunay et al (2023) reported the successful IOP control in 2 uveitic glaucoma cases secondary to juvenile idiopathic arthritis (JIA) following 360° GATT. Case 1 was a 7-year-old pseudophakic boy with a pre-operative IOP of 38 mmHg; his IOP stabilized at 17 mmHg with 2 topical antiglaucoma medications over 18 months. Case 2 was a 8-year-old aphakic boy with a pre-operative IOP of 42 mmHg; his IOP decreased to 12 mmHg over 15 months. These investigators observed post-operative IOP spike in case 1 that was successfully controlled conservatively. Peripheral anterior synechia formation also occurred in both cases during follow-up. The authors concluded that patients should be vigilant for possible complications after GATT in such cases. As glaucoma surgery success can have a tendency to decline with time in pediatric cases with uveitis-associated glaucoma, the authors believed that further evidence is still needed to shed more light regarding the benefits of GATT technique in complex cases of pediatric secondary glaucoma subtypes like JIAU-induced glaucoma.
Furthermore, an UpToDate review on “Overview of glaucoma in infants and children” (Reynolds and Reynolds, 2025) does not mention gonioscopy-assisted transluminal trabeculotomy (GATT) / minimally invasive glaucoma surgery as a therapeutic option.
Goniotomy and Trabeculotomy
Goniotomy and trabeculotomy are both surgical procedures used to treat glaucoma by improving the outflow of aqueous humor from the eye, thereby lowering intraocular pressure (IOP). While they share similarities, there are key differences in technique and application. Goniotomy refers to incision and/or excision of the trabecular meshwork (TM) with a blade (e.g., Kahook dual blade) or other surgical instrument for at least several clock hours to create an opening into Schlemm's canal from the anterior chamber, via an internal approach through the anterior chamber. Trabeculotomy involves an external approach, using a deep scleral incision to access Schlemm's canal and then rotating a probe into the anterior chamber to open the TM.
In a narrative review regarding surgical management of pediatric glaucoma, Chang et al (2017) emphasize that goniotomy and trabeculotomy are the preferred initial treatments for primary congenital glaucoma.
In a clinical guideline developed by the American Academy of Ophthalmology (AAO), Gedde et al (2021) provided comprehensive, evidence-based recommendations for the diagnosis, monitoring, and treatment of primary open-angle glaucoma (POAG). The guideline emphasizes individualized care based on risk factors such as age, race, family history, intraocular pressure (IOP), and corneal thickness. It recommends regular optic nerve imaging, visual field testing, and gonioscopy to assess angle status. In the section on minimally invasive glaucoma surgery (MIGS), the authors discuss ab interno trabeculectomy, a minimally invasive procedure that removes a portion of the trabecular meshwork and inner wall of Schlemm’s canal to lower intraocular pressure (IOP). Devices such as the trabectome, Kahook dual blade (KDB), and goniotome are used for this purpose. The trabectome uses electrocautery and has shown IOP-lowering effects with minimal complications, especially when combined with cataract surgery, though the specific contribution of each component remains unclear due to a lack of randomized trials. Similarly, KDB and goniotome can be used alone or with phacoemulsification, and retrospective studies suggest modest IOP reduction with low complication rates. One prospective case series showed IOP reduction to the low teens at one year with combined KDB and cataract surgery, but lacked a control group. A retrospective comparison also suggested KDB may outperform the iStent, though prospective, randomized trials are needed to confirm these findings.
In a narrative review, Lim (2022) explored the evolving landscape of glaucoma surgery. The author outlines how traditional procedures like trabeculectomy and glaucoma drainage devices (GDDs) remain the gold standard, but are now complemented by a growing array of newer techniques, including minimally or micro-invasive glaucoma surgeries (MIGS). These newer approaches are categorized by their mechanism -- targeting trabecular, suprachoroidal, or subconjunctival outflow, or reducing aqueous production -- and may be performed via ab-interno or ab-externo routes. Goniotomy, once primarily used in congenital glaucoma, is now applied more broadly in adult cases using modern tools like the Kahook dual blade and OMNI system. This review recommends that procedure selection should be individualized based on glaucoma subtype, disease severity, and patient-specific factors, emphasizing that newer MIGS procedures may be appropriate for mild-to-moderate disease, while traditional filtering surgeries remain preferred for advanced or refractory cases.
In a randomized clinical trial, Lin et al (2025) compared two surgical treatments for advanced primary angle-closure glaucoma (PACG) without cataract: trabeculectomy versus a combination of surgical peripheral iridectomy (SPI), goniosynechialysis (GSL), and goniotomy (GT). The study included 88 patients (88 eyes), with 43 eyes receiving SPI + GSL + GT and 45 eyes undergoing trabeculectomy. The primary endpoint was the reduction in intraocular pressure (IOP) at 12 months. Both groups achieved comparable IOP reductions, with a mean difference of 0.5 mm Hg (P = .55), demonstrating the non-inferiority of the combination procedure. The findings suggest that SPI + GSL + GT may serve as a safer alternative to trabeculectomy in selected patients. However, the study's limitations include a relatively short follow-up period (12 months), exclusion of patients with coexisting cataract, and the need for longer-term data to assess sustained efficacy and safety.
Hydrus Microstent
In a prospective, multi-center, single-masked RCT, Pfeiffer and co-workers (2015) evaluated the safety and effectiveness of the Hydrus Microstent (Ivantis, Inc., Irvine, CA) with concurrent cataract surgery (CS) for reducing IOP in OAG. A total of 100 eyes from 100 patients aged 21 to 80 years with OAG and cataract with IOP of 24 mmHg or less with 4 or fewer hypotensive medications and a washed-out diurnal IOP (DIOP) of 21 to 36 mmHg. On the day of surgery, patients were randomized 1:1 to undergo CS with the microstent or CS alone. Post-operative follow-up was at 1 day, 1 week, and 1, 3, 6, 12, 18, and 24 months. Washout of hypotensive medications was repeated at 12 and 24 months. Response to treatment was defined as a 20 % or more decrease in washed out DIOP at 12 and 24 months of follow-up compared with baseline. Mean DIOP at 12 and 24 months, the proportion of subjects requiring medications at follow-up, and the mean number of medications were analyzed. Safety measures included AEs, change in VA, and slit-lamp observations. The proportion of patients with a 20 % reduction in washed out DIOP was significantly higher in the Hydrus plus CS group at 24 months compared with the CS group (80 % versus 46 %; p = 0.0008). Washed out mean DIOP in the Hydrus plus CS group was significantly lower at 24 months compared with the CS group (16.9 ± 3.3 mmHg versus 19.2 ± 4.7 mmHg; p = 0.0093), and the proportion of patients using no hypotensive medications was significantly higher at 24 months in the Hydrus plus CS group (73 % versus 38 %; p = 0.0008). There were no differences in follow-up VA between groups. The only notable device-related AE was focal peripheral anterior synechiae (1 to 2 mm in length). Otherwise, AE frequency was similar in the 2 groups. The authors concluded that IOP was clinically and statistically significantly lower at 2 years in the Hydrus plus CS group compared with the CS alone group, with no differences in safety.
In a retrospective case-series study, Fea and associates (2017b) examined the safety and efficacy of a new Schlemm canal scaffold microstent (Hydrus) combined with CS in routine clinical practice. Clinical outcomes in patients with POAG who had combined phacoemulsification and microstent implantation were analyzed. Data (IOP, number of glaucoma medications, incidence of complications) were collected pre-operatively and post-operatively through 24 months. A total of 92 eyes were included; 6 patients had previous glaucoma surgeries; 67 patients completed a 2-year follow-up. The mean baseline IOP was 19.4 mm Hg ± 4.4 (SD). The mean IOP was 15.5 ± 2.7 mm Hg at 1 year and 15.7 ± 2.5 mm Hg at 2 years (p < 0.001). The IOP reduction was correlated with the baseline IOP (R2 = 0.72). The mean number of glaucoma medications was 2.1 ± 1.0 pre-operatively, decreasing significantly at 1 year (0.6 ± 1.0) and 2 years (0.7 ± 1.0) (p < 0.001). At 2 years, 64 % of patients were medication-free. In patients with an IOP of 18 mm Hg or higher pre-operatively, the reduction in IOP and in the number of medications was higher; 2 patients required microstent re-positioning intra-operatively; 1 patient was treated with an argon laser for microstent obstruction, and 1 patient had a trabeculectomy at 18 months. The authors concluded that this microstent combined with CS safely and effectively reduced the IOP and medication use in a routine clinical practice setting with results comparable to those in previously published controlled clinical trials.
In a prospective, interventional, case-series study, Fea and colleagues (2017c) compared the reduction of IOP and glaucoma medications following selective laser trabeculoplasty (SLT) versus stand-alone placement of the Hydrus microstent. This trial included a total of 56 eyes (56 patients) with uncontrolled POAG. Patients received either SLT (n = 25) or Hydrus implantation (n = 31) in 2 centers; they were evaluated at baseline and 1, 7 days, 1, 3, 6 and 12 months after surgery. Main outcome measures were IOP and number of glaucoma medications variations inter-groups and intra-groups. There were no significant differences at baseline between groups, but the mean deviation was worse in the Hydrus group (-8.43 ± 6.84 dB, CI: -2.8 to -3.3 versus -3.04 ± 0.65 dB, CI: -6 to -10.8; p < 0.001). After 12 months, there was a significant decrease in IOP and medications in the Hydrus group compared with baseline values. In the SLT group, only the decrease in IOP was significant. There was 3-fold greater reduction in medication use in the Hydrus group compared with SLT (-1.4 ± 0.97 versus -0.5 ± 1.05, p = 0.001); 47 % of patients were medication-free at 12 months in the Hydrus group (4 % in the SLT group). No complications were recorded in the SLT group. In the Hydrus group, 3 patients experienced a temporary reduction of VA post-operatively, and 2 patients had post-operative IOP spikes that resolved within 1 week. The authors concluded that both SLT and Hydrus implantation reduced IOP without serious AEs; and Hydrus implantation led to a significant and further reduction in medication dependence at 12 months.
Al-Mugheiry and co-workers (2017) evaluated learning effects with respect to outcomes of a MIGS inserted during CS in glaucoma patients. This trial was a ingle-surgeon, observational cohort study of 25 consecutive Hydrus microstent insertions, with a minimum follow-up of 12 months. A learning curve analysis was performed by assessing hypotensive effect, AEs, and surgical procedure duration, with respect to consecutive case number. Success was defined with respect to various IOP targets (21, 18, 15 mm Hg) and reduction in required anti-glaucoma medications. Complete success was defined as achieving target IOP without anti-glaucoma therapy. No clinically significant AEs or learning effects were identified, although surgical time reduced with consecutive case number. Mean follow-up was 16.8 months. At final follow-up the mean IOP for all eyes was reduced from 18.1 (± 3.6) mm Hg [and a simulated untreated value of 25.9 (± 5.2) mm Hg] to 15.3 (± 2.2) mm Hg (p = 0.007; p < 0.0001) and the mean number of topical anti-glaucoma medications was reduced from 1.96 (± 0.96) to 0.04 (± 0.20) (p < 0.0001). Complete success (IOP of less than 21 mm Hg, no medications) was 96 % at final follow-up. Complete success (IOP of less than 18 mm Hg, no medications) was 80 % at final follow-up, but only 32 % with a target IOP of less than 15 mm Hg (no medications). The authors concluded that no significant learning curve effects were observed for a trained surgeon with respect to MIGS microstent insertion performed at the time of CS. Adjunctive MIGS surgery was successful in lowering IOP to less than 18 mm Hg and reducing/abolishing the requirement for anti-glaucoma medication in eyes with OAG, but less successful at achieving low IOP levels (less than 15 mm Hg).
In a prospective, multi-center, single-masked, RCT, Samuelson and colleagues (2019) compared CS with implantation of a Schlemm canal microstent with CS alone for the reduction of IOP and medication use after 24 months. Subjects with concomitant POAG, visually significant cataract, and washed-out modified DIOP (MDIOP) between 22 and 34 mmHg were enrolled in this trial. They were randomized 2:1 to receive a single Hydrus microstent in the Schlemm canal or no stent after uncomplicated phacoemulsification. Comprehensive eye examinations were conducted 1 day, 1 week, and 1, 3, 6, 12, 18, and 24 months post-operatively. Medication washout and MDIOP measurement were repeated at 12 and 24 months. The primary and secondary effectiveness end-points were the proportion of subjects demonstrating a 20 % or greater reduction in unmedicated MDIOP and change in mean MDIOP from baseline at 24 months, respectively. Hypotensive medication use was tracked throughout the course of follow-up. Safety measures included the frequency of surgical complications and AEs. A total of 369 eyes were randomized after phacoemulsification to Hydrus microstent (HMS) and 187 to no microstent (NMS). At 24 months, unmedicated MDIOP was reduced by greater than or equal to 20 % in 77.3 % of HMS group eyes and in 57.8 % of NMS group eyes (difference = 19.5 %, 95 % CI: 11.2 % to 27.8 %, p < 0.001). The mean reduction in 24-month unmedicated MDIOP was -7.6±4.1 mmHg (mean ± standard deviation) in the HMS group and -5.3±3.9 mmHg in the NMS group (difference = -2.3 mmHg; 95 % CI: -3.0 to -1.6; p < 0.001). The mean number of medications was reduced from 1.7 ± 0.9 at baseline to 0.3 ± 0.8 at 24 months in the HMS group and from 1.7 ± 0.9 to 0.7 ± 0.9 in the NMS group (difference = -0.4 medications; p < 0.001). There were no serious ocular AEs related to the microstent, and no significant differences in safety parameters between the 2 groups. The authors concluded that this 24-month multi-center RCT demonstrated superior reduction in MDIOP and medication use among subjects with mild-to-moderate POAG who received a Schlemm canal microstent combined with phacoemulsification compared with phacoemulsification alone.
On August 10, 2018, the FDA approved the Hydrus Microstent for use in conjunction with cataract surgery for the reduction of IOP in adult patients with mild-to-moderate POAG.
The Hydrus Microstent should not be used in patients with the following types of glaucoma:
- Angle closure glaucoma
- Malignant glaucoma
- Neovascular glaucoma
- Traumatic glaucoma
- Uveitic glaucoma.
Furthermore, the Hydrus Microstent should not be used in patients with birth defects of the anterior chamber angle of the eye.
In a prospective, multi-center RCT, Ahmed et al (2022) presented the 5-year results of the HORIZON trial comparing cataract surgery (CS) combined with an intra-canalicular Microstent with CS alone. Patients with cataract and POAG treated with 1 or more glaucoma medications, washed-out diurnal intra-ocular pressure (DIOP) of 22 to 34 mmHg, and no prior incisional glaucoma surgery were included in this trial. Eyes were randomized 2:1 to receive a Hydrus Microstent (HMS) or no stent following successful CS. Main outcome measures included IOP, glaucoma medication use, repeat glaucoma surgery, visual acuity (VA), visual field, procedure-related AEs, and corneal endothelial cell counts. A total of 369 eyes were randomized to HMS treatment, and 187 eyes were randomized to CS only. Study groups were well-matched for pre-operative IOP, medication use, washed-out DIOP, and glaucoma severity. Five-year follow-up was completed in 80 % of patients. At 5 years, the HMS group included a higher proportion of eyes with IOP of 18 mmHg or less without medications than the CS group (49.5 % versus 33.8 %; p = 0.003), as well as a greater likelihood of IOP reduction of 20 % or more without medications than the CS group (54.2 % versus 32.8 %; p < 0.001). The number of glaucoma medications was 0.5 ± 0.9 in the HMS group and 0.9 ± 0.9 in the CS group (p < 0.001), and 66 % of eyes in the HMS group were medication-free compared with 46 % in the CS group (p < 0.001). The cumulative risk of incisional glaucoma surgery was lower in the HMS group (2.4 % versus 6.2 %; p = 0.027, log-rank test). No clinical or statistically significant differences were found in the rate of endothelial cell loss (ECL) from 3 to 60 months between the HMS and CS alone groups (p = 0.261). The authors concluded that the addition of a Schlemm's canal Microstent in conjunction with CS was safe, resulted in lowered IOP and medication use, and reduced the need for post-operative incisional glaucoma filtration surgery compared with CS after 5 years. Furthermore, long-term presence of the implant did not affect the corneal endothelium adversely.
The authors stated that the 5-year HORIZON study findings suggested the following: First, combining HMS implantation with phacoemulsification reduced medication dependence and improved the likelihood of remaining drop-free regardless of pre-operative medication count. Second, the percentage of eyes that were medication-free was durable. Third, combining HMS implantation with CS reduced the need for further incisional glaucoma surgery compared with CS alone. Fourth, no clinically significant differences in safety outcomes existed between the HMS and CS groups, including the long-term rate of ECL. By reducing dependency on topical medications and reducing the risk of further glaucoma surgery without introducing significant complications, HMS treatment has a durable and significant impact on QOL of and the long-term consequences faced by patients with early-stage glaucoma.
Intra-Operative Optical Coherence Tomography in Glaucoma Surgery
In a pilot study, Kumar and associates (2015) reported on the use of a spectral-domain OCT (SDOCT) integrated surgical microscope in glaucoma surgery. An SDOCT system was used to interface directly with an ophthalmic surgical microscope, to allow real-time intra-operative SDOCT (iOCT) imaging during glaucoma procedures like phaco-trabeculectomy, Ahmed glaucoma valve (AGV) implantation, gonio-synechiolysis, and bleb needling. The various surgical steps during glaucoma surgeries where iOCT can be of potential help in guiding the surgeon were recorded. High-resolution, cross-sectional images of the relevant structures were achieved with the iOCT system in all procedures. The surgeon could determine the depth of the scleral dissection, the intra-stomal bed, the path of the AGV tube in the eye, the release of peripheral anterior synechiae and the efficacy of needling with respect to breakage of loculations; most of these were technically "blind" procedures, where the outcomes were determined post-operatively. Metallic instruments cast a shadow on tissues below, thereby restricting the use of the device in its current state. The authors concluded that the iOCT system provided high quality, intra-operative, real-time imaging, which could possibly improve the safety and efficacy of the surgical procedures in glaucoma. Moreover, these researchers stated that further studies and modifications to the iOCT are needed to better understand and increase the uptake of this technology in daily practice.
The authors stated that as with every new technology, the iOCT has got limitations. The majority of the limitations of this tool were surgeon- and machine-related. The restricted scanning area and the need to move the scanning zone to target the instrument tip required a rather cumbersome coordination between the surgeon and assistant/technician manning the scanner; re-focusing to the region of interest (ROI) was constantly required to achieve good quality images. Distortion of images during eye or microscope movements also causes motion artefacts. There was a learning curve for focusing and aligning the ROI and the inconvenience of simultaneously looking at both the surgical field and the OCT image simultaneously. The synchronization between the 2 areas under observation had a definite learning curve. The other major limitation was the shadowing effect caused by the metallic instruments currently used, that rendered the underlying tissues invisible. These investigators noted that the integration of real-time in-vivo OCT imaging with the operating microscope is still in its infancy; and improvements in the resolution of the integrated OCT and possible color coding to determine tissue thickness could be other potential areas that need to be addressed. They stated that the iOCT, with further advancements in its technology, could potentially provide the surgeon both quantitative and qualitative, real-time depth and tissue proximity details, thus improving the safety and accuracy of glaucoma surgery.
Ang and colleagues (2020) noted that the application of the OCT in clinical ophthalmology has expanded significantly since its introduction more than 20 years ago. There has been recent growing interest in the application of iOCT. The iOCT's ability to enhance visualization and depth appreciation has the potential to be further exploited in glaucoma surgery, especially with the emergence of minimally invasive glaucoma surgery (MIGS) – to facilitate targeted device placement and fine surgical maneuvers in the angles, the sub-conjunctival layer and the suprachoroidal space. These investigators examined the current literature on the applications of iOCT in glaucoma surgery. A total of 79 studies were identified following a literature search adhering to PRISMA guidelines. After full text evaluation, 10 studies reporting on iOCT use in glaucoma surgery were included. Traditional glaucoma filtering procedures reviewed included trabeculectomy surgery, gonio-synechiolysis, bleb needling and glaucoma drainage device implantation. MIGS procedures reviewed included canaloplasty, trabecular aspiration, ab-interno trabectome and the XEN45 gel stent. iOCT use in ophthalmic surgery is becoming increasingly prevalent and has already been applied in various surgeries and procedures in the field of glaucoma. The authors concluded that with the greater adoption of MIGS, iOCT may further contribute in facilitating surgical techniques and improving outcomes. These researchers stated that while iOCT offers many advantages, there are still limitations to be overcome – iOCT technology continues to evolve to optimize imaging quality and user-experience.
Furthermore, UpToDate reviews on "Open-angle glaucoma: Treatment" (Jacobs, 2020), "Angle-closure glaucoma" (Weizer, 2020), "Primary infantile glaucoma" (Reynolds and Reynolds, 2020a), and "Overview of glaucoma in infants and children" (Reynolds and Reynolds, 2020b) do not mention intra-operative OCT as an adjunctive surgical option.
iStent Infinite
In an open-label, unmasked, single-center study, Katz et al (2018) examined the long-term outcomes following implantation of 1, 2, or 3 trabecular micro-bypass stents in a standalone procedure in eyes of patients with OAG taking ocular hypotensive medication. Prospective randomized ongoing study of 119 subjects (109 with 42-month follow-up) with OAG, pre-operative IOP of 18 to 30 mmHg on 1 to 3 glaucoma medications, and unmedicated (post-washout) IOP of 22 to 38 mmHg were included in this study. Subjects were randomized to receive 1 (n = 38), 2 (n = 41), or 3 (n = 40) iStent trabecular micro-bypass stents in a standalone procedure. Post-operatively, IOP was measured with medication and annually following washout. Data included IOP, medications, gonioscopy, pachymetry, visual field, visual acuity (VA), AEs, and slit-lamp and fundus examinations. Pre-operative mean medicated IOP was 19.8 ± 1.3 mmHg on 1.71 medications in 1-stent eyes, 20.1 ± 1.6 mmHg on 1.76 medications in 2-stent eyes, and 20.4 ± 1.8 mmHg on 1.53 medications in 3-stent eyes. Post-washout IOP before stent implantation was 25.0 ± 1.2, 25.0 ± 1.7, and 25.1 ± 1.9 mmHg in the 3 groups, respectively. Post-operatively, month 42 medicated IOP was 15.0 ± 2.8, 15.7 ± 1.0 and 14.8 ±1 .3 mmHg in the 3 groups, and post-washout IOP (months 36 to 37) was 17.4 ± 0.9, 15.8 ± 1.1 and 14.2 ± 1.5 mmHg, respectively. IOP reduction of 20 % or more without medication was achieved in 89 %, 90 %, and 92 % of 1e-, 2-, and 3-stent eyes, respectively, at month 12; and in 61 %, 91 %, and 91 % of eyes, respectively, at month 42. The need for additional medication remained consistent at months 12 and 42 in multi-stent eyes (4 2-stent eyes and 3 3-stent eyes at both time-points), whereas it increased in 1-stent eyes (4 eyes at month 12 versus 18 eyes at month 42). Safety parameters were favorable in all groups. The authors concluded that the standalone implantation of either single or multiple iStent device(s) produced safe, clinically meaningful IOP and medication reductions through 42 months post-operatively, with incrementally greater and more sustained reductions in multi-stent eyes.
The authors stated that this study had several drawbacks. This trial was an open-label, unmasked, single-center study in a solely Caucasian patient population. Baseline and post-operative IOPs were not measured at multiple time-points, leaving open the possibility of regression to the mean. No standardized cataract grading system nor threshold for completing cataract surgery was employed. One may notice the relatively low values for IOP variance in this study; these appeared consistent with variance in previous studies. Finally, this trial entailed data through 42 months; a future report will be able to examine even longer-term outcomes through study completion at 60 months.
Healey et al (2021) noted that standalone trabecular micro-bypass glaucoma surgery with the iStent devices is associated with clinically relevant reductions in IOP sustained over a reasonably long-term while simultaneously reducing medication burden and a relatively favorable safety profile. While there is a relatively large body of evidence supporting the implantation of the iStent trabecular micro-bypass devices during phacoemulsification in patients with OAG, its effectiveness as a standalone procedure has been less widely reported. In a systematic review and meta-analysis, these investigators examined evaluate the effectiveness of iStent devices (iStent and iStent inject) when performed independently of cataract surgery in patients with OAG. They carried out a systematic review of the literature in August 2019 to identify studies of standalone trabecular micro-bypass glaucoma surgery with iStent devices in patients with OAG. All randomized trials were considered as well as non-randomized studies that included at least 6 months of follow-up or more than 10 eyes. Key effectiveness analyses included post-operative IOP and medication use, which were used to examine WMDs from baseline, and the proportion of eyes free of ocular medication. Post-operative AEs were descriptively summarized. A total of 13 studies were identified including 4 RCTs and 9 non-randomized or single-arm studies providing data for 778 eyes. In eyes implanted with iStent devices, a weighted mean IOP reduction of 31.1 % was observed at 6 to 12 months. In studies reporting longer-term outcomes (36 to 48 months or 60 months), the weighted mean IOP reduction was 30.4 % and 32.9 %, respectively. The pooled weighted mean reduction in IOP from baseline across all studies at 6 to 12 months and 36 to 60 months post-stent implantation was 7.01 mm Hg (95 % CI: 5.91 to 8.11) and 6.59 mm Hg (95 % CI: 5.55 to 7.63), respectively. Medication burden was reduced by approximately 1.0 medication at 6 to 18 months and 1.2 medications at 36 to 60 months. AEs reported in more than 5 % of participants were progression of pre-existing cataract/cataract surgery and loss of BCVA; however, these rates were no different to those reported in comparator medical therapy study arms. The authors concluded that the findings from these studies supported the independent effect of the iStent trabecular bypass devices on IOP and medication burden over a duration of follow-up of up to 5 years.
The authors stated that this study had several drawbacks. First, the control groups from controlled studies were not considered in the primary effectiveness analysis. This was to allow the incorporation of non-randomized studies. In this context, these researchers considered it reasonable to use pre-operative baseline measurements as a proxy for a control arm. Second, medication use at endpoint was not reported consistently in the included studies, which limited the ability to carry out robust statistical meta-analyses. Third, studies were not evaluated for bias and were not excluded for reasons other than inadequate sample size (10 eyes or less) and follow-up (less than 6 months) to allow a comprehensive review of the available evidence. While this resulted in substantial heterogeneity between the included studies in terms of study design, treatment protocols, outcome measures, severity of disease, prior treatment exposure and surgeon experience, it provided a much more inclusive study population that better reflected the patients for whom clinicians need to make treatment decisions.
In a retrospective, single-center study, Guedes et al (2022) compared standalone implantation of multiple (2 to 3) trabecular micro-bypass stents (iStent inject ± iStent) (Multi-Stent group) versus trabeculectomy + mitomycin C (Trab group) in moderate-to-severe OAG. Eligible patients underwent Multi-Stent or Trab surgery from 2018 to 2020 and had at least 3-month follow-up; visual field mean deviation (VF MD) -6 dB or worse; inadequate prior response to maximum medications ± laser procedures; and had trabeculectomy as their next planned intervention. Primary effectiveness, safety-adjusted treatment success, was defined as 20 % or higher IOP reduction on the same or fewer medications, without clinically significant safety events (severe complications, secondary surgeries, re-interventions). Secondary effectiveness included mean IOP and medications; qualified and complete attainment of target IOP (21/18/15/12 mmHg or less and higher than 6 mmHg); health-economic and QOL measures; and 2-versus-3-stent subgroup analysis. The baseline groups (n = 70 Multi-Stent/40 Trab) were similar: mean IOP (21.1 mmHg/22.3 mmHg); medications (2.87/3.10 medications); disease stage (30 %/35 % severe); VF MD (-10.1 dB/-10.4 dB); and mean last follow-up (LFU, 13.1 months/15.7 months) (all differences non-significant). Primary effectiveness: treatment success at LFU was 62.9 % versus 30.0 % in Multi-Stent versus Trab eyes, respectively (p = 0.001). Secondary effectiveness: At LFU in Multi-Stent versus Trab groups, respectively: mean IOP decreased by 31 % to 14.2 mmHg (p < 0.001) versus by 43 % to 12.5 mmHg (p < 0.001); mean medications decreased by 51 % to 1.31 medications (p < 0.001) versus by 84 % to 0.43 medications (p < 0.001). Multi-Stent eyes, compared to Trab eyes, had fewer visits ± re-interventions within 3 months (3.6 versus 6.1, p < 0.001); longer time to 1st re-intervention (12.2 months versus 4.5 months, p = 0.01); fewer total re-interventions (0.26 versus 0.75, p = 0.006); and earlier lifting of post-operative restrictions (12.6 versus 32.1 days, p < 0.001). In 2-versus-3-stent analysis, there was a trend toward more 3-stent eyes achieving target IOP than 2-stent eyes. Visual fields remained stable in both Multi-Stent and Trab eyes. The authors concluded that implanting 2 to 3 trabecular micro-bypass stents was a viable alternative to trabeculectomy for moderate-to-severe OAG, with clinically appropriate IOP/medication reductions and higher safety-adjusted treatment success versus trabeculectomy. They stated that these findings reported a highly favorable risk-benefit balance. They demonstrated that standalone implantation of 2 or 3 trabecular bypass stents (iStent or iStent inject) may be a viable and safe therapeutic option for patients with moderate-to-severe treatment-resistant glaucoma.
The authors stated that this study had several drawbacks. First, given the retrospective nature of data collection, it was not possible to perfectly match baseline characteristics of the 2 groups; and these researchers could not rule out the possibility of non-quantifiable patient differences between the 2 groups. Despite this constraint, the groups were well-matched for baseline characteristics, including for the most clinically relevant measures such as pre-operative IOP, medication burden, glaucoma type, disease severity, and visual field. The only data point differing between the groups was lens status, with more pseudo-phakic eyes in the Multi-Stent group than in the Trab group. Second, these investigators acknowledged that their standard protocol for post-operative restrictions was cautious and comprehensive, and that some clinicians may advocate earlier resumption of unrestricted activity. However, the same restrictions were applied to both groups in this study; thus, the significant between-group differences were still meaningful. Third, there were no pre-operative or post-operative medication washouts, as these would not be appropriate in this real-world clinical population. Fourth, visual field outcomes were stable in both groups through up to 24 months post-operative; however, longer monitoring are needed to confirm that patients’ glaucoma remains controlled.
In a prospective, open-label, single-arm, multi-center study, Sarkisian et al (2023) examined the safety and effectiveness of the iStent infinite Trabecular Micro-Bypass System in patients with OAG uncontrolled by prior surgical or medical therapy. Implantation of iStent infinite (3 iStent inject W stents) was carried out as a stand-alone surgical procedure in eyes with OAG uncontrolled by prior incisional or cilio-ablative surgeries or maximum tolerated medical therapy (MTMT). Prospectively declared effectiveness endpoints were proportion of eyes achieving 20 % or greater mean diurnal IOP (MDIOP) reduction from baseline at month 12 on the same or fewer IOP-lowering medication classes (responder endpoint) and mean change in MDIOP from baseline at month 12. Safety parameters included AEs, VA, slit-lamp and fundus examinations, gonioscopy, perimetry, and surgical complications. A total of 72 eyes of 72 patients (mean age of 71.9 years) with pre-operative mean medicated MDIOP of 23.4 ± 2.8 mm Hg on a mean of 3.1 ± 0.9 IOP-lowering medication classes were enrolled: 61 eyes with failed prior surgery/ies (Failed-Surgery subgroup) and 11 eyes uncontrolled on MTMT (MTMT subgroup). A total of 76.1 % of all enrolled patients met the responder endpoint (73.4 % Failed-Surgery, 90.9 % MTMT), with mean reduction (SE) in MDIOP at month 12 of 5.9 (0.6) mm Hg [5.5 (0.7) mm Hg Failed-Surgery subgroup, 8.1 (0.9) mm Hg MTMT subgroup]. For patients on the same or fewer medication(s) as baseline, 53.0 % achieved 30 % or greater MDIOP reduction without surgical interventions/other events. Safety was favorable, with no explants, infection, or device-related interventions or hypotony. The authors concluded that iStent infinite stand-alone surgery achieved clinically significant IOP reduction and favorable safety in patients with OAG uncontrolled by prior therapy.
The authors stated that this study had several drawbacks. This was an open-label, single-arm study, consistent with FDA standards for registration submission for a 510(k) device. Although the follow-up period of 12 months was of relatively short duration, the iStent infinite has the same mechanism of action and treatment approach as the 1st-generation iStent and 2nd-generation iStent inject devices, which have shown consistent durability in maintaining IOP and medication reductions for up to 8 years postoperative. Thus, long-term studies with iStent infinite would be expected to show similarly consistent safety and effectiveness over time. No medication washout was carried out, as this might have placed the enrolled glaucoma patients at undue risk for optic nerve damage. However, this trial design was consistent in this regard with similar studies on patients at high risk for glaucoma progression.
Droste and Newman-Casey (2023) stated that glaucoma remains one of the largest causes of irreversible blindness globally. Traditional treatment guidelines suggest topical glaucoma eye-drop as 1st-line therapy followed by addition of supplementary medications before proceeding to more invasive glaucoma surgeries. Unfortunately, poor glaucoma self-management remains high, resulting in disease progression and blindness. Recent advancements in the field of pharmacotherapies, surgeries, as well as behavioral approaches have taken aim at increasing support for glaucoma self-management. These investigators reviewed the current and emerging approaches towards glaucoma management, with the exception of bleb-based surgical approaches, to examine if they have had an impact on adherence. They carried out literature searches via Medline (PubMed), Embase (Elsevier), Cochrane Library (Wiley), and Preprints from January 1, 2018, to January 26, 2023. The authors concluded that the ability to offer patients a multitude of choices enables patients to tailor their glaucoma treatment to their values and lifestyle. Offering personalized patient education and coaching to support chronic glaucoma self-management would better enable patient engagement in whichever treatment path is chosen. Currently, literature regarding the impact of these new advancements on treatment engagement is lacking; this field is ripe for additional intervention and assessment. Keywords of this review include iStent, and micro invasive glaucoma surgery (MIGS).
Kahake et al (2023) noted that the iStent is one of the minimally invasive glaucoma devices. It can be inserted at the time of phaco-emulsification or as a stand-alone procedure to lower the IOP. In a systematic review and meta-analysis, these investigators compared the effect of iStent insertion at the time of phaco-emulsification with phacoemulsification alone in patients with ocular hypertension or OAG. They searched Embase, Medline (OVID and PubMed), CINAHL, and Cochrane Library for studies published between 2008 and June 2022 (PRISMA 2020 for the checklist). Studies comparing the IOP-lowering effect of iStent with phaco-emulsification versus phaco-emulsification alone were included. The endpoints were IOP reduction (IOPR) and the mean reduction in the number of glaucoma eye-drops. A quality-effects model was used to compare both surgical groups. A total of 10 studies were included, reporting on 1,453 eyes; 853 eyes had the combined iStent and phaco-emulsification, and 600 eyes underwent phaco-emulsification alone. IOPR was higher in the combined surgery at of 4.7 ± 2 mm Hg compared to 2.8 ± 1.9 mm Hg in phaco-emulsification alone. A greater decrease in post-operative eye drops was noted in the combined group having a decrease of 1.2 ± 0.3 eye-drops versus of 0.6 ± 0.6 eye-drops in isolated phaco-emulsification. The quality effect model showed an IOPR WMD of 1.22 mm Hg (CI: -0.43 to 2.87; Q = 315.64; p < 0.01; I2 = 97 %) and decreased eye-drops WMD 0.42 drops (CI: 0.22 to 0.62; Q = 42.6; p < 0.01; I2 = 84 %) between both surgical groups. Subgroup analysis showed that the new generation iStent may be more effective in reducing IOP. The authors concluded that iStent exhibited a synergetic effect with phaco-emulsification. The reduction of IOP and glaucoma eye-drops was higher when iStent is combined with phaco-emulsification compared with isolated phaco-emulsification. Moreover, these researchers stated that further studies are still needed to examine the long-term IOP-lowering effect of iStent, the protective effect on the optic nerve, and how long it may delay the need for future, more invasive, glaucoma surgeries.
The authors stated that this systematic review had several drawbacks. First, the heterogeneity (I2) between studies was found to be high. This could be attributed to both the low number of studies included, as well as the small sample size in these studies. The 2 outcomes (IOP and glaucoma eye-drops) were inter-connected and may increase this heterogeneity. The difference in surgeon skill, geographic location, population, year of conduction of study, number of patients included, and follow-up period were factors that may have contributed to this heterogeneity. Second, these researchers excluded some studies due to missing SD and other values. This may have affected the final outcome of the meta-analysis. Third, the duration of follow-up that was significantly different among studies ranging between 12 months and 51 months. Fourth, visual inspection of funnel plots for both pre- and post-operative IOPR%, and the number of topical medications revealed asymmetry indicating possible publication bias. Furthermore, these investigators stated that other potential biases may be related to industry funding due to the difficulty in obtaining peer-reviewed funding for device trials.
Balas and Mathew (2023) noted that MIGS has emerged as a novel approach in the glaucoma treatment spectrum, offering a range of diverse procedures and devices aimed at lowering IOP. MIGS can be broadly classified into several categories: those that enhance trabecular outflow (Trabectome, iStent, Hydrus Microstent, Kahook Dual Blade, high frequency deep sclerotomy, and gonioscopy-assisted transluminal trabeculotomy), those that augment supra-choroidal outflow (CyPass Microstent and iStent Supra), those that target Schlemm's canal (TRAB360 and the OMNI Surgical System, Streamline, and Ab Interno Canaloplasty), and conjunctival bleb-forming procedures (EX-PRESS Glaucoma Filtration Device, Xen Gel Stent and PreserFlo MicroShunt). MIGS is considered to have a shorter surgical time and fewer severe complications when compared to traditional glaucoma surgeries such as trabeculectomy and glaucoma drainage device implantation (Ahmed, Baerveldt, and Molteno valves). These investigators examined the distinct MIGS devices and procedures, their underlying mechanisms, and clinical outcomes, emphasizing the importance of evaluating the effectiveness and complications of each approach individually. The authors stated that as the field of MIGS continues to evolve, it is important to prioritize high-quality, long-term studies to better understand the safety and effectiveness of these innovative interventions in glaucoma management.
These researchers stated that while MIGS has shown promising results, it is important to recognize that long-term outcomes and the sustainability of IOP control require further investigation. Comparative studies and RCTs will be crucial in establishing the relative safety and effectiveness of MIGS devices and techniques compared to traditional glaucoma surgeries and medical management. Moreover, future research should focus on refining existing technologies and exploring new mechanisms of action to address the diverse etiologies of glaucoma and cater to the specific needs of patients who may not benefit from current MIGS options.
StatPearls’ review on “Minimally invasive glaucoma surgery” (Gurnani and Tripathy, 2023) stated that “MIGS has opened a new door for mild-to-moderate glaucoma management, reducing the medication burden on the patients. Recent studies have provided highly encouraging results, and more large-scale studies with long-term follow-up will be needed to give better insight and understanding of MIGS”.
In a systematic review and network meta-analysis, Sener et al (2024) compared the IOP-lowering effect of different types of surgery available in the literature. PubMed and the Cochrane database were searched. Randomized clinical trials involving surgical interventions for high IOP for PAC or PACG were included. Descriptive statistics and outcomes were extracted. Bayesian NMA was performed to compare the IOP-lowering effect and the change in the number of anti-glaucoma drugs needed between baseline and endpoint, as well as success rates. This NMA included 21 studies with 1,237 eyes with PAC or PACG. Interventions were characterized as phaco-emulsification (phaco), trabeculectomy, goniosynechialysis (GSL) with viscoelastic or blunt device, goniosurgery (GS) (trabeculotomy or goniotomy), micro-bypass stent (iStent), endocyclophotocoagulation (ECPL) or various combinations of these procedures. Phaco+GSL [-1.73 (95 % CI: -3.53 to -0.13)] and phaco+GSL+GS [-3.92 (95 % CI: -6.91 to -1.31)] provided better IOP lowering effects than phaco alone. Phaco+trabeculectomy [-3.11 (95 % CI: -5.82 to -0.44)] was inferior to phaco+GSL+GS. Phaco+trabeculectomy [-0.45 (95 % CI: -0.81 to -0.13)] provided a better outcome in terms of reducing the need for anti-glaucoma drug compared to phaco alone. There were no differences between the other surgeries in terms of reduction of anti-glaucoma drug number and IOP lowering effect. Success rates were similar for all surgical procedures. The authors concluded that phaco+GSL+GS showed the most promising results for lowering IOP. Phaco+trabeculectomy resulted in a significant reduction in the number of anti-glaucoma drugs compared to phaco alone.
In a retrospective, comparative, single-center, case-series study, Morita et al (2024) compared the 12-month post-operative outcomes of iStent and iStent inject W (inject W), and the factors associated with their success in OAG. These investigators examined the medical records of patients who underwent iStent (comprising 1 stent) or inject W (comprising 2 stents) implantation with cataract surgery for POAG and normal tension glaucoma between January 2019 and March 2022. The 12-month post-operative effectiveness outcomes included IOP, glaucoma medications, and survival analysis of the probability of success. "Failure" was defined as any of the following conditions compared to baseline: IOP elevation, increased glaucoma medication, or IOP decline not exceeding 20 % when glaucoma medication scores were comparable, and need for additional glaucoma surgery. The safety outcomes included intra- and post-operative AEs and changes in the BCVA and VF. The study comprised 55 eyes in the iStent, and 105 in the inject W groups. At 12 months, treatment success was achieved in 66.0 % of iStent, and 78.4 % of inject W eyes. The mean IOP was lower, and the percent reduction from baseline was equal in iStent-treated eyes (8.0 % reduction, 14.8 mmHg to 13.7 mmHg, p < 0.01) and inject W-treated eyes (11.9 % reduction, 15.0 mmHg to 13.8 mmHg, p < 0.01) (between-group comparison, p = 0.23). The mean medication burden decreased significantly from 2.5 to 1.1 for iStent (55.0 % reduction, p < 0.01) and 2.9 to 1.7 for iStent inject (46.8 % reduction, p < 0.01), with no significant differences between the 2 groups (p = 0.17). Both devices exhibited excellent safety. The authors concluded that both devices significantly reduced IOP and glaucoma medication 12 months post-operatively. The outcome measures did not differ significantly between the 2 groups, and lower baseline IOP was predictive of surgical failure. Moreover, these researchers stated that a prospective study with a larger population and longer follow-up is needed to validate these findings.
The authors stated that one of the drawbacks of this trial was that it incorporated a retrospective, non-randomized case-series design. These researchers also did not compare their findings with cataract surgery alone. Phaco-emulsification alone also reduces post-operative IOP; however, IOP reduction by phaco-emulsification alone reportedly is less effective in maintaining the post-operative VF, ultimately resulting in progression of VF decay. Previous prospective studies have shown that cataract surgery with iStent or inject versus cataract surgery alone was superior in lowering the IOP and reducing the number of glaucoma medications. A previous study reported that no complications could compromise the visual improvement benefits of cataract surgery. Furthermore, iStent and inject W are cost-effective compared to cataract surgery alone in terms of the patient’s financial burden and healthcare economics. In Japan, inject was superior to cataract surgery alone in terms of cost-effectiveness. Furthermore, MIGS, including the iStent, is said to improve the patient’s QOL. These researchers stated that in the future, they would like to examine the difference in cost-effectiveness and the effect of VF maintenance for iStent and inject W. These investigators noted that the relatively low incidence of complications compared to the overall number of patients could have obfuscated accurate assessment of the differences between the 2 groups. While it is evident that the procedure is relatively safe, a more precise evaluation of significant differences in complications between the 2 groups would require a larger cohort. These researchers noted that eyes in which the iStent and inject W were not inserted correctly intra-operatively were also excluded. The learning curves of both devices and the stability of the surgical technique were also not evaluated. In iStent inject W, the interval between the 2 inserted devices was not standardized at 1 to 3 hours, depending on the case, which may also have affected these findings. The absence of abnormal device positioning or occlusion at each follow-up point was also not confirmed. Furthermore, the pre-operative IOP was lower than previously reported, which may have limited the effectiveness of the iStent and inject W, and prevented accurate evaluation of the difference between the 2 devices. In addition, it is worth noting that this trial did not calculate the sample size, which may have resulted in poor statistical power. These investigators stated that to address this limitation, future studies should consider enhancing the statistical power by increasing the sample size and observing patients over an extended time-period.
Barkander et al. (2025) compare thed 12-month outcomes of cataract surgery alone versus cataract surgery combined with either iStent Inject W or Kahook Dual Blade Glide (KDB) in patients with cataract and ocular hypertension or mild to advanced primary open-angle or pseudoexfoliative glaucoma. This prospective, randomized controlled trial included 120 eyes from 120 patients, randomized into three equal groups, and was conducted at a single center in Sweden. Participants were followed for one year, and the primary endpoints were surgical success, which was defined as either a ≥20% reduction in intraocular pressure (IOP) and/or a reduction of at least one glaucoma medication, and changes in IOP and medication use. Secondary endpoints included achieving specific IOP thresholds and adverse events. Results showed that surgical success was significantly higher in the combined surgery groups (87.5% for both iStent and KDB) compared to cataract surgery alone (52.5%, P < 0.001). While mean IOP reduction was similar across groups (approximately 3 mmHg, P = 0.755), the reduction in medication use was greater in the combined groups (−0.8 and −0.9 medications for iStent and KDB, respectively) compared to cataract surgery alone (−0.4, P = 0.01). More patients in the combined groups became medication-free at 12 months. Adverse events included transient hyphema in 15% of KDB cases and higher rates of early corneal edema in the combined groups, while IOP spikes were more frequent after cataract surgery alone (37.5% vs. 10–15% in combined groups). No serious complications occurred, and visual acuity and visual field outcomes remained stable or improved across all groups. Study limitations included lack of masking, absence of medication washout, small sample size, and baseline differences in medication use, which may have influenced results. Additionally, the study population was homogeneous (all white), limiting generalizability, and the trial was not powered to detect differences in patient-reported outcomes. The investigators concluded that adding iStent or KDB to cataract surgery significantly improves surgical success primarily by reducing medication burden, with similar efficacy between the two devices.
Cheema and Cheema (2024) examined the evolution, current status, and future potential of MIGS in the treatment of glaucoma. MIGS offer a less invasive alternative to traditional glaucoma surgeries, primarily aimed at lowering IOP, minimizing tissue trauma, and providing a safer profile. With the emergence of devices such as the Trabectome, iStent, and others, MIGS have expanded the surgical tool-kit, allowing personalized, patient-centered care. Despite their advantages, MIGS face challenges such as effectiveness in severe cases, long-term data, and accessibility. These researchers stated that ongoing research and technological innovations continue to refine their capabilities and applications, promising to further transform glaucoma management and patient outcomes.
The authors stated that while MIGS represent a significant advancement in glaucoma treatment, they are not without limitations and challenges. First, MIGS are primarily effective in mild-to-moderate glaucoma. Their ability for substantial IOP reduction in severe cases is less significant compared to traditional surgeries such as trabeculectomy or glaucoma drainage devices (GDDs); thus, patients with advanced glaucoma requiring significant IOP reduction may not be ideal candidates for MIGS. Second, there is a notable lack of long-term data on the sustainability of IOP control with MIGS. While most studies reported shorter follow-up periods, traditional surgeries have more extensive long-term data. This gap highlighted the need for further research into the long-term effectiveness of MIGS and the potential necessity for additional surgical interventions. Third, the cost of MIGS devices and surgical fees can be prohibitive, especially in resource-limited settings. Furthermore, the availability of MIGS varies across different regions and healthcare systems. This variation affects the widespread adoption and accessibility of MIGS for all glaucoma patients, posing a challenge to their global implementation. Fourth, selecting the most suitable candidates for MIGS is a complex task, necessitating consideration of the patient's specific type and severity of glaucoma, as well as overall ocular health. The solution entails comprehensive pre-operative evaluation and a tailored approach for each patient, which is essential to maximize the benefits of MIGS. Fifth, integrating MIGS into existing glaucoma treatment paradigms, which include medications, laser therapy, and traditional surgeries, poses a challenge due to the need for a nuanced understanding of their relative benefits and limitations. This challenge can be addressed via continuous education and the development of consensus guidelines, aiding clinicians in making informed decisions regarding incorporating MIGS into comprehensive treatment plans. These researchers stated that as the field of MIGS continues to evolve, addressing these limitations and challenges via research, education, and technological advancement will be critical to optimizing patient outcomes in glaucoma management.
In a prospective, non-randomized, unmasked, longitudinal study, Hengerer et al (2024) examined 7-year safety and effectiveness of 2nd-generation trabecular micro-bypass implantation (iStent inject) either in combination with cataract surgery or as a stand-alone procedure (combined or stand-alone subgroups, respectively) in eyes with OAG. This trial included 125 consecutive iStent inject cases of a single surgeon at a large academic hospital. Patients had considerable pre-operative disease burden, with mean IOP of 23.5 mmHg, 84.8 % of eyes on 2 or more medications, and 38.4 % of eyes with prior glaucoma surgery. IOP, medications, AEs, and secondary surgeries were assessed through 7 years in the overall cohort and in combined (n = 81) and stand-alone (n = 44) subgroups. Over 7-year follow-up, mean IOP decreased by 36.2 % to 40.0 % in overall eyes, 34.1 % to 38.9 % in combined eyes, and 39.5 % to 43.5 % in stand-alone eyes (p < 0.001 at all time-points for all groups). Mean medications decreased by 59.3 % to 71.3 % in overall eyes, 57.9 % to 69.0 % in combined eyes, and 62.1 % to 76.2 % in stand-alone eyes (p < 0.001 at all - in all groups). At last follow-up (mean 77.4 months; 92.8 % of patients with last visit at 6 or 7 years), 83.7 % of overall eyes, 82.3 % of combined eyes, and 86.4 % of stand-alone eyes had achieved 20 % or greater IOP reduction versus pre-operative. At last follow-up versus pre-operative, 100 % of eyes in all groups had the same or lower IOP and 100 % had the same or lower medication regimen. Safety outcomes were favorable, with no filtration surgeries and only 4.84 % of eyes experiencing clinically significant VF loss over 7 years of follow-up. The authors concluded that iStent inject implantation with or without phaco-emulsification resulted in significant and durable 7-year reductions in IOP (approximately 34 % to 44 % reduction) and medications (approximately 58 % to 76 % reduction) while preventing filtering surgery in this cohort of patients with relatively high pre-operative disease burden. Combined and stand-alone cases had similarly favorable safety and effectiveness.
The authors stated that this study had several drawbacks. First, given its real-world nature, the study was non-randomized, and unmasked. Second, the cohort included consecutive patients, which increased generalizability but also may have introduced confounders when calculating outcomes; the 125-patient sample size aided in mitigating against this. No wash-outs were completed, given this would not have been ethical in a real-life clinical practice. Third, all participants were non-Hispanic white and of German nationality; thus, these findings may need to be considered cautiously in other populations. Fourth, as with any population undergoing concomitant phaco-emulsification, in the combined subgroup of this trial, the effect of the stents could not be isolated from that of the cataract extraction. However, post-phaco-emulsification IOP reduction is known to diminish following the first few years post-operatively, and of course would not be expected in stand-alone cases. Therefore, the consistent 7-year IOP reduction in this cohort, as well as the similar reductions observed in the combined and stand-alone subgroups, suggested it is the stents (not the phaco-emulsification) that were producing the effect. Fifth, given the real-world nature of the data, not all data were available at every visit, and not all patients were able to attend all follow-ups. These investigators stated that future research could entail a more in-depth annualized investigation of VF and retinal nerve fiber layer (RNFL) outcomes; subgroup stratifications by glaucoma subtypes, severities, or surgical histories; or inclusion of the iStent inject W (wide-flanged) model or iStent infinite (3-stent) model.
Furthermore, an UpToDate review on “Open-angle glaucoma: Treatment” (Jacobs, 2024) states that “There is a group of interventions emerging called “minimally invasive glaucoma surgery” (MIGS), which offers promise as a less risky approach to surgical control of glaucoma progression. Based on data from Cochrane reviews, some MIGS may afford patients with glaucoma greater medication-free disease control than cataract surgery alone”. However, MIGS is not mentioned in the “Summary and Recommendations” section of this UTD review.
Microcatheter-Assisted Trabeculotomy for the Treatment of Open-Angle Glaucoma
Schreurs et al (2024)noted that trabeculotomy is usually carried out using a rigid probe, allowing for 180° trabeculotomy. More recently, microcatheter-assisted 360° trabeculotomy (MCAT) has demonstrated safe and effective results in pediatric glaucoma cases, especially in primary congenital glaucoma (PCG) and to a lesser extent in JOAG. In this case-series study, these investigators discussed the successful IOP control following iTrack-assisted trabeculotomy in 1 adult with PCG and 2 with JOAG. A total of 4 eyes of 3 adults, aged 50, 28, and 45 years, underwent MCAT for uncontrolled PCG or JOAG, with no prior surgical history. No major complications were observed. Post-operatively, IOP ranging from 11 to 15 mmHg was attained without the need for topical therapy or re-operation during a follow-up period of 12 to 14 months. The authors concluded that the findings of these cases suggested that MCAT was safe and effective for adults with PCG or JOAG requiring surgery. These researchers stated that the relatively short follow-up period was a drawback in this case-series study. They stated that the long-term effectiveness of angle surgery in adults needs further validation. These investigators stated that future research, entailing both pediatric as well as adult patients, will provide more insights into MCAT outcomes compared to traditional trabeculotomy and other surgical techniques; thus, guide the surgical management of PCG and JOAG in adulthood.
The XEN Glaucoma Treatment System (XEN45 Gel Stent and XEN Injector)
In a pilot, non-randomized, prospective clinical trial, Sheybani and colleagues (2015) examined the effect on IOP of implanting a new gelatin stent at the time of cataract surgery in the treatment of OAG. The implantation of 2 models of a gelatin stent (Xen140 and Xen63) was performed at the time of cataract surgery without mitomycin-C. Complete success was defined as a post-operative IOP of less than 18 mm Hg and more than a 20 % reduction in IOP at 12 months without glaucoma medication. Failure was defined as loss of light perception vision or worse, a need for additional glaucoma surgery, or less than a 20 % reduction in the IOP from baseline. The study included 37 eyes of 37 patients. The mean pre-operative IOP was 22.4 mm Hg ± 4.2 (SD) on 2.5 ± 1.4 medication classes. The mean IOP was reduced to 15.4 ± 3.0 mm Hg on 0.9 ± 1.0 medication classes (p < 0.0001) 12 months post-operatively. This resulted in a qualified success of 85.3 % and a complete success rate off medications of 47.1 %. There were no failures. The authors concluded that cataract surgery combined with implantation of the gelatin stent resulted in a significant reduction in IOP in eyes with OAG.
Sheybani and associates (2016) evaluated the IOP-lowering effect of the XEN140 micro-fistula gel stent implant for the surgical treatment of OAG. A total of 49 eyes (49 patients) with an IOP of greater than 18 mm Hg and less than or equal to 35 mm Hg were studied in a prospective non-randomized multi-center cohort trial of the surgical implantation of the XEN140 implant in patients with OAG. Complete success was defined as a post-operative IOP less than or equal to 18 mm Hg with greater than or equal to20 % reduction in IOP at 12 months without any glaucoma medications. Failure was defined as vision loss of light perceptions vision or worse, need for additional glaucoma surgery, or less than 20 % reduction of IOP from baseline. The average age was 64.3 (28.1 to 86.9) years old; 21 eyes had prior failed trabeculectomy with mitomycin C surgery; IOP at 12 months decreased from a mean of 23.1 (± 4.1) mm Hg to 14.7 (± 3.7) mm Hg for a 36.4 % reduction in IOP from baseline. The number of patients at 12 months who achieved an IOP of less than or equal to 18 mm Hg and greater than or equal to 20 % reduction in IOP was 40 (89 %). The number of patients who achieved an IOP of less than or equal to 18 mm Hg and greater than or equal to 20 % reduction in IOP without anti-glaucoma medications was 18 (40 %). The authors concluded that XEN140 gel stent lowered IOP with few complications when implanted for the surgical treatment of OAG.
Dupont and Collignon (2016) noted that POAG is a progressive ocular disease affecting adults and associated with visual field defect. The aim of its treatment is to lower the IOP by means of ocular drops, laser or surgery. To-date, traditional surgical techniques still remain quite invasive, but recent research efforts have been made with a view to develop minimally invasive techniques. The XEN Gel Stent is one of them. It allows a safe and efficient lowering of IOP by creating a sub-conjunctival flow, following an ab interno procedure that highly preserves the architecture of the treated eye.
On November 21, 2016, the FDA cleared the XEN Glaucoma Treatment System for the management of refractory glaucoma, including cases where previous surgical treatment has failed, cases of POAG, and pseudoexfoliative glaucoma (PXG) or pigmentary glaucoma with open angles that are unresponsive to maximum tolerated medical therapy. In the U.S. pivotal trial conducted in refractory glaucoma patients, XEN reduced IOP from a mean medicated baseline of 25.1 (+ 3.7) mmHg to 15.9 (+ 5.2) mmHg at the 12 month visit (n=52). The mean baseline number of IOP-lowering medications was 3.5 (± 1.0) versus an average use of 1.7 (± 1.5) medications at 12 months. The most common postoperative adverse events included BCVA loss of > 2 lines (< 30 days 15.4%; > 30 days 10.8%; 12 months 6.2%), hypotony IOP < 6 mm Hg at any time (24.6%; no clinically significant consequences were associated, no cases of persistent hypotony, and no surgical intervention was required), IOP increase > 10 mm Hg from baseline (21.5%), and needling procedure (32.3%).
XEN Gel Stent is contraindicated in angle-closure glaucoma where angle has not been surgically opened, previous glaucoma shunt/valve or conjunctival scarring/pathologies in the target quadrant, active iris neovascularization, anterior chamber IOL, intraocular silicone oil, and vitreous in the anterior chamber.
XEN Gel Stent complications may include choroidal effusion, hyphema, hypotony, implant migration, implant exposure, wound leak, need for secondary surgical intervention, and intraocular surgery complications. Safety and effectiveness in neovascular, congenital, and infantile glaucoma has not been established. The product labeling recommends avoiding digital pressure following implantation of the XEN Gel Stent to avoid implant damage.
Kerr and associates (2017) stated that recently, many new devices and procedures have been developed to lower IOP in a less invasive and purportedly safer manner than traditional glaucoma surgery. These new devices might encourage an earlier transition to surgery and reduce the long-term commitment to topical glaucoma medications with their associated compliance and intolerance issues. Although often seen as an adjunct to cataract surgery, a growing body of evidence suggested that primary MIGS may be a viable initial treatment option. New studies have shown that primary ab interno trabeculectomy (Trabectome, NeoMedix Inc., Tustin, CA), trabecular micro-bypass stent insertion (iStent and iStent Inject, Glaukos Corporation, Laguna Hills, CA), canalicular scaffolding (Hydrus, Invantis Inc., Irvine CA), the ab interno gel Implant (XEN, Allergan, Dublin, Ireland) or SC stenting (CyPass Micro-Stent, Alcon, Fort Worth, TX) may lower the lowering IOP and/or topical medication burden in phakic or pseudophakic patients with glaucoma. This effect appeared to last at least 12 months, but reliable cost-effectiveness and quality of life (QOL) indicators have not yet been established by investigator-initiated randomized trials of sufficient size and duration.
Richter and Coleman (2016) stated that MIGS aims to provide a medication-sparing, conjunctival-sparing, ab interno approach to IOP reduction for patients with mild-to-moderate glaucoma that is safer than traditional incisional glaucoma surgery. The current approaches include: increasing trabecular outflow (Trabectome, iStent, Hydrus stent, gonioscopy-assisted transluminal trabeculotomy [GATT], Excimer laser trabeculotomy); suprachoroidal shunts (Cypass micro-stent); reducing aqueous production (endocyclophotocoagulation); and subconjunctival filtration (XEN gel stent).
These investigators noted that MIGS technology has the potential to solve a variety of problems in current glaucoma management. These include minimizing patient adherence problems, increasing QOL for patients with ocular toxicity, and potentially reducing lifetime costs of expensive glaucoma medications, all while preserving the conjunctiva if additional, more invasive glaucoma surgeries are necessary in the future. Non-adherence rates in glaucoma have been reported to vary from 24 % to 59 %, and patient reasons for non-adherence include forgetfulness, side effects, lack of affordability, difficulty administering drops, complicated medication schedules, poor understanding of the disease, and poor patient-doctor communication. Moderate-to-severe ocular surface disease is present in 71 % of patients receiving triple-drop therapy, and in these patients, implementing preservative-free alternatives may help but present additional cost and/or logistical insurance coverage barriers. Stein et al recently reported that laser trabeculoplasty is more cost-effective than a prostaglandin analog for newly diagnosed POAG when taking into account realistic patient adherence rates. Meanwhile, Kaplan et al recently reported that both Baerveldt implant and trabeculectomy with mitomycin C are more cost-effective than maximal medical treatment. While there are no data on cost-effectiveness of MIGS yet, if long-term efficacy of MIGS is demonstrated in future clinical studies, MIGS may also prove more cost-effective than medical treatment.
Nonetheless, there are several limitations to the current state of MIGS. These include limited quality and duration of evidence, lack of study standardization, lack of cost-effectiveness data, and incomplete knowledge of ideal patient selection. MIGS evidence is currently limited by the retrospective and non-masked nature in the majority of cases. Directly comparing the evidence of each MIGS type is difficult due to the varied study designs, patient populations, and outcome measures. Long-term outcomes over several years are mostly unknown. In evaluating current MIGS data, because most trials have included cataract surgery, it is important for clinicians to recognize the IOP-lowering ability of cataract surgery alone. According to a recent review by the AAO, cataract surgery results in a small, moderate, and marked reduction in IOP and medications for POAG, PXG, and PACG, respectively. In studies where MIGS surgery has only been reported in combination with cataract surgery, clinicians cannot assume that IOP-lowering abilities will be similar when cataract surgery is not also performed. Additionally, nearly all of the current MIGS procedures have the potential risk of late failure due to scarring, and longer follow-up periods in future studies are needed to determine how the longevity of these MIGS procedures compares to the less than ideal longevity of selective laser trabeculoplasty.
While the current MIGS procedures are generally designed to treat patients with mild-to-moderate OAG, clinicians will need to learn which specific patients will or will not benefit from a particular MIGS procedure. The specific clinical indications that have been learned to-date were discussed under the "Adverse events and clinical considerations" sections for each procedure. In general, the trabecular procedures will not benefit patients with elevated episcleral venous pressure. Patients with a bleeding predisposition are less ideal for GATT and possibly for Trabectome as well. It is also interesting to note that in the trabecular procedures, patients with higher baseline IOPs appeared to demonstrate the greatest IOP-lowering effects. These data are not yet available for the non-trabecular procedures. Future data will also help clinicians to individualize their management strategy for each patient. Advances in aqueous angiography imaging will allow clinicians to localize the most active collector channels pre-operatively, before deciding where to place a particular trabecular stent. Such imaging modalities may also assess the activity of uveo-scleral flow, thus informing placement location for uveo-scleral stents. Perhaps in the future, these diagnostic studies will determine which class of MIGS procedure would be most effective for a particular patient. Because future trials will follow more standardized clinical trial protocols, the ability to select appropriate patients for each MIGS type will become more optimized. Future-generation MIGS devices will aim to surpass current MIGS outcomes, and these devices have the ever-increasing potential to improve the lives of patients with glaucoma worldwide.
Hohberger and co-workers (2017) stated that treatment of glaucoma eyes with irido-corneal endothelial syndrome is complex; MIGS, such as one that implements a novel, micro-invasive device, known as XEN gel stents, has shown promise in surgical glaucoma treatment and offers a new therapeutic option. In a case report, these investigators reported the successful implantation of XEN45 gel stent in a woman with secondary glaucoma due to unilateral irido-corneal endothelial syndrome after descement membrane endothelial keratoplasty (DMEK) operation, and the follow-up were presented. The authors concluded that implantation of XEN gel stents may be a promising option for minimally invasive glaucoma surgery in difficult situations, as low adverse events (AEs), good post-surgery VA and sufficient regulation of IOP can be seen.
Pinto Ferreira and colleagues (2017) noted that MIGS aims to provide a safer and less-invasive means of reducing IOP compared with traditional surgery, with the goal of reducing the need for topical medications. The XEN gel stent is an ab-interno minimally invasive glaucoma surgery device that approaches IOP reduction by creating a sub-conjunctival drainage pathway. As with any new device there is lack of experience and knowledge about its long-term results in terms of effectiveness, technique, and complications. These investigators reported a clinical case of a XEN blood clot internal ostium obstruction and how it was managed. The ab-interno approach with micro-forceps appeared a minimally invasive, safe, and effective procedure.
Vinod and Gedde (2017) reviewed recent studies evaluating the effectiveness and complication profiles of novel glaucoma procedures promoting aqueous outflow. Literature from the 2015 to 2016 review period included abundant data regarding new and emerging glaucoma procedures. Notable findings from recent RCTs include titratability of IOP with multiple trabecular micro-bypass stents (iStent; Glaukos, Laguna Hills, CA) and greater reduction in IOP and medication usage following intra-canalicular scaffolding (Hydrus Microstent; Ivantis Inc., Irvine, CA) combined with phacoemulsification versus phacoemulsification alone. A SC micro-stent (CyPass Micro-Stent; Transcend Medical, Inc., Menlo Park, CA) received approval from the FDA after a pivotal trial demonstrated its safety and effectiveness. Early studies of investigational sub-conjunctival filtering devices (XEN Gel Stent; AqueSys, Inc., Aliso Viejo, CA and InnFocus MicroShunt; InnFocus Inc., Miami, FL) offer promising evidence, but late complications are as yet unknown. The authors concluded that newer glaucoma procedures targeting different aqueous outflow pathways have improved the safety profile of glaucoma surgery while preserving modest effectiveness. Most can be combined with phacoemulsification, allowing for simultaneous treatment of co-morbid cataract and glaucoma. Moreover, they stated that well-designed RCTs with extended follow-up are needed to evaluate the long-term effectiveness and late complications of these novel procedures.
Furthermore, UpToDate reviews on "Open-angle glaucoma: Treatment" (Jacobs, 2017) and "Angle-closure glaucoma" (Weizer, 2017) do not mention stenting as a therapeutic option.
In a prospective 12-month study on patients with POAG, Fea and colleagues (2017a) evaluate the safety and efficacy of the Xen Gel Stent and provided a macroscopic as well as microscopic analyses of bleb morphology. Patients underwent implantation of the XEN Gel Stent (Allergan INC, Dublin, Ireland) either alone or combined with a cataract surgery (CS). Biomicroscopy, in-vivo confocal microscopy (IVCM), and anterior segment-optical coherence tomography (AS-OCT) were used to assess bleb morphology. Safety parameters were AEs, BCVA, visual field, and corneal endothelial cell loss. A post-operative IOP less than or equal to 18 mmHg without or on medications was respectively defined as complete and qualified success while an IOP greater than or equal to 18 mmHg was defined as failure. A total of 12 eyes of 11 patients were evaluated. At 1 year, 5 out of 10 patients available achieved a complete success while 5 were qualified success; AS-OCT showed that bleb wall reflectivity was significantly higher in the failure group; IVCM revealed that stromal density was significantly lower in the success group. No safety issues were recorded. The authors concluded that these findings showed that there were statistically significant reductions in both IOP and medication use following implantation of the XEN Gel Stent in this group of POAG patients, and no safety issues related to the procedure or to the study device were observed. They stated that implantation of the XEN Gel Stent appeared to be a safe and effective procedure for the treatment of POAG. It is unclear whether these results provided clinically significant health outcomes.
The authors noted that this study had several drawbacks. It had a small sample size (n = 12 eyes), had a relatively short follow-up (12 months), and lacked an early post-operative evaluation to more stringently monitor the bleb development. A more standardized approach in bleb evaluation with imaging techniques was also needed. The presence of inflammatory cells, indicators of inflammation, and subsequent fibrosis in the conjunctival epithelium was not methodically investigated; however, it could provide a valuable predictive tool and deserved further investigations. It was also possible that AS-OCT may mis-represent bleb structure and artifacts. These researchers stated that larger scale studies with longer follow-up are needed.
In a prospective, interventional study, Galal and associates (2017) evaluated gel microstent (XEN, AqueSys, Inc.) for treatment of POAG. A total of 13 eyes with POAG underwent XEN implantation with subconjunctival mitomycin-C. Of those eyes, 3 were pseudophakic and 10 underwent simultaneous phacoemulsification and XEN. Patients had uncontrolled IOP, had intolerance to therapy, or had maximal therapy but undergoing cataract extraction. Follow-up visits included IOP, number of medications, vision, and complications and lasted for 1 year. Complete success was defined as IOP reduction greater than or equal to 20 % from pre-operative baseline at 1 year without any glaucoma medications while partial success as IOP reduction of greater than or equal to 20 % at 1 year with medications. IOP dropped from 16 ± 4 mmHg pre-op to 9 ± 5, 11 ± 6, 12 ± 5, 12 ± 4, and 12 ± 3 mmHg at 1 week, 1, 3, 6, and 12 months (p = 0.004, 0.026, 0.034, 0.01, and 0.01, Wilcoxon Signed Ranks) consecutively. BCVA (LogMAR) was 0.33 ± 0.34 and improved to 0.13 ± 0.11 at 1 year. Mean number of medications dropped from 1.9 ± 1 pre-operatively to 0.3 ± 0.49 (p = 0.003) at 1 year; 42 % of eyes achieved complete success and 66 % qualified success. Complications included choroidal detachment in 2 eyes, and implant extrusion in 1 eye, and 2 eyes underwent trabeculectomy. The authors concluded that XEN implant was an effective surgical treatment for POAG, with significant reduction in IOP and glaucoma medications at 1 year follow-up. Moreover, they stated that this new technique needed further assessment for longer follow-up survival.
In a single-arm, open-label, multi-center clinical study, Grover and co-workers (2017) evaluated the IOP-lowering performance and safety of an ab interno gelatin stent (XEN 45 Gel Stent, Allergan plc, Irvine, CA) in refractory glaucoma. Following mitomycin C pre-treatment, the stent was placed ab interno in patients who failed prior filtering/cilio-ablative procedure or had uncontrolled IOP on maximum-tolerated medical therapy, with medicated IOP greater than or equal to 20 and less than or equal to 35 mm Hg and visual field mean deviation less than or equal to -3 dB. Primary performance outcomes: patients (%) achieving greater than or equal to 20 % IOP reduction from baseline on the same or fewer medications and mean IOP change from baseline at month 12. Procedure-related complications and ocular AEs were assessed. A total of 65 patients were implanted (intent-to-treat/safety population). At 12 months, 75.4 % (46/61; observed data) reported greater than or equal to 20 % IOP lowering from baseline on the same or fewer medications. Mean IOP change from baseline was -9.1 mm Hg (95 % CI: -10.7 to -7.5) (n = 52; observed data) at 12 months, excluding patients with missing data (n = 4) and those requiring a glaucoma-related secondary surgical intervention (n = 9). Mean medication count decreased from 3.5 (baseline) to 1.7 (12 months). No intra-operative complications or unexpected post-operative AEs were reported. Most AEs were mild/moderate; common AEs included needling (without sight-threatening complications), non-persistent loss of BCVA, and transient hypotony (requiring no surgical intervention). The authors concluded that the gelatin stent reduced IOP and medication use without raising unexpected safety concerns, offering a minimally invasive surgical option for refractory glaucoma patients.
The authors stated that potential study limitations included the absence of comparator and open-label study design, which could have impacted the outcomes. As mentioned in the key studies of the supra-ciliary microstent and trabecular micro-bypass, however, investigator masking was not feasible with this type of treatment. It was also worth noting that potential effects on the study eye of changes in the fellow eye were not considered. In addition, the study population included less than or equal to 5 % Asian patients and less than or equal to 13 % patients with pseudo-exfoliation, pigmentary, or mixed-mechanism glaucoma. Nonetheless, they stated that these findings were generalizable to men and women with refractory glaucoma characterized by uncontrolled IOP on maximum-tolerated medical therapy and open angles.
Ozal and co-workers (2017) reported follow-up data for patients who underwent XEN45 gel stent implantation. A total of 15 eyes in 15 patients who underwent XEN45 gel stent implantation surgery were examined in the study. All patients were examined pre-operatively and at the following post-operative time points: 1 day; 1 and 2 weeks; and 1, 2, 3, 6, and 12 months; IOP was measured via Goldmann applanation tonometry. Combined surgical procedures (XEN45 + phacoemulsification + intraocular lens) were performed in patients who that had cataracts in addition to glaucoma. The mean IOP values were significantly lower than the pre-operative values at all post-operative visits (p < 0.001). In 2 patients, the IOP exceeded 20 mmHg 12 months after surgery. These IOP increases were controlled by medical therapy, and none of the patients needed another surgical procedure. The authors concluded that the results of this study were promising, and XEN45 gel stent implantation presented a valuable contribution to glaucoma surgery. Using XEN45 gel stents, these investigators reduced IOP and medication use without significant complications in patients with different forms of glaucoma. They believed that this new surgical procedure would play an important role in glaucoma surgery in the future. Moreover, they stated that further studies with greater numbers of patients and longer follow-up periods are needed to clarify certain points.
The authors stated that this study had several drawbacks; in particular, the small number of patients (n = 15) and the lack of control group limited their comparisons. Thus, it has not been evaluated whether the efficacy of XEN45 gel implantation differs between patients according to prior glaucoma surgery. Furthermore, the mild IOP-reducing effect of phacoemulsification alone was not evaluated. In addition, these researchers could not evaluate in which glaucoma type this surgical method is most effective. They noted that clinical trials (NCT02006693, NCT02036541) are ongoing for XEN gel stents; these researchers think that after the results of these studies have been published, new aspects of XEN gel stent implantation will be revealed.
Sng and associates (2018) noted that the XEN-45 implant (a hydrophilic collagen implant that drains aqueous to the subconjunctival space) has not been studied in the context of uveitic glaucoma. In an exploratory, prospective, case-series study, these researchers determined the safety and efficacy of the XEN-45 collagen implant in eyes with uveitic glaucoma. A total of 24 consecutive patients with medically uncontrolled uveitic glaucoma (mean age ± standard deviation [SD] = 45.3 ± 18.1 years) were implanted with the XEN-45 implant. The primary outcome measure was IOP reduction at 12 months as compared to baseline. Secondary outcome measures included ocular hypotensive medication use at 12 months, the requirement for further glaucoma surgery and failure. Intra-operative and post-operative complications were documented. The baseline mean ± SD IOP was 30.5 ± 9.8 mmHg and the mean ± SD number of glaucoma medications required was 3.3 ± 0.8. In 20 eyes (83.3 %) in whom conventional glaucoma surgery was originally perceived to be inevitable, further surgery was not required after XEN-45 implantation. The mean IOP was reduced by 60.2 % from baseline to 12.2 ± 3.1 mmHg and mean medication usage was reduced to 0.4 ± 0.9 at 12 months (both p < 0.001); 1 patient had hypotony persisting beyond 2 months that required surgical revision, and 1 patient developed blebitis. The 12-month cumulative Kaplan-Meier survival probability was 79.2 %. The authors concluded that the XEN-45 implant was effective for the treatment of patients with medically uncontrolled uveitic glaucoma. Moreover, they stated that potentially sight-threatening complications, including bleb-related ocular infection and persistent hypotony, may occur. These researchers noted that these preliminary findings from an exploratory study need to be validated by well-designed studies.
In an international, multi-center, retrospective, interventional cohort study, Schlenker and colleagues (2017) compared the safety, efficacy, and risk factors for failure of standalone ab interno gelatin microstent implantation with mitomycin C (MMC) versus trabeculectomy with MMC. A total of 354 eyes of 293 patients (185 microstent and 169 trabeculectomy) with no prior incisional surgery were included in this trial. Consecutive eyes with uncontrolled glaucoma underwent microstent or trabeculectomy surgery from January 1, 2011 through July 31, 2015 at 4 academic ophthalmology centers. Primary outcome measure was HR of failure, with failure defined as 2 consecutive IOP readings of less than 6 mmHg with vision loss or greater than 17 mmHg without glaucoma medications (complete success) at least 1 month after surgery despite in-clinic interventions (including needling). Secondary outcome measures included IOP thresholds of 6 to 14 mmHg and 6 to 21 mmHg and same thresholds allowing for medications (qualified success), interventions, complications, and re-operations. Baseline characteristics were similar, except more men (56 % versus 43 %), younger patients (average, by 3 years), better pre-operative VA (22 % versus 32 % with 0.4 logarithm of the minimum angle of resolution vision or worse), and more trabeculoplasty (52 % versus 30 %) among microstent eyes. The adjusted HR of failure of the microstent relative to trabeculectomy was 1.2 (95 % CI: 0.7 to 2.0) for complete success and 1.3 (95 % CI: 0.6 to 2.8) for qualified success, and similar for other outcomes. Time to 25 % failure was 11.2 months (95 % CI: 6.9 to 16.1 months) and 10.6 months (95 % CI: 6.8 to 16.2 months) for complete success and 30.3 months (95 % CI: 19.0 to infinity months) and 33.3 months (95 % CI: 25.7 to 46.2 months) for qualified success. Overall, white ethnicity was associated with decreased risk of failure (adjusted HR, 0.49; 95 % CI: 0.25 to 0.96), and diabetes was associated with increased risk of failure (adjusted HR, 4.21; 95 % CI: 2.10 to 8.45). There were 117 and 165 distinct interventions: 43 % and 31 % underwent needling, respectively, and 50 % of trabeculectomy eyes underwent laser suture lysis. There were 22 and 30 distinct complications, although most were transient; 10 % and 5 % underwent re-operation (p = 0.11). The authors concluded that there was no detectable difference in risk of failure and safety profiles between stand-alone ab interno microstent with MMC and trabeculectomy with MMC.
In a retrospective analysis, Hengerer and associates (2017) evaluated the IOP-lowering effects and complication management of an ab interno gel implant for the treatment of patients refractory to anti-glaucoma medication or glaucoma surgery. These investigators examined medical records of 242 consecutive eyes of 146 patients with uncontrolled IOP despite maximum tolerated medical therapy or prior surgical intervention that underwent XEN45 implantation (as sole procedure or in combination with CS) between March 2014 and June 2015. Data included IOP, number of glaucoma medications, the need for additional surgery, needling, and complications. During the study period, mean IOP had decreased by 54.1 % from 32.19 (± 9.1) mm Hg to 14.24 (± 4.0) mm Hg (p = 0.00; Wilcoxon test). The number of anti-glaucoma medications had decreased from a mean of 3.13 ± 1.0 to 0.3 ± 0.7 (p = 0.00; Wilcoxon test). Needling was required between week 1 and months 3 in 27.7 % of all eyes to enhance the outflow. Hypotony (IOP less than 6 mm Hg) was observed in 9 eyes (4.0 %) at 1 month but normalized in all eyes at 12 months post-operatively; 2 eyes experienced hypotony requiring the refill of the anterior chamber. The authors concluded that these findings indicated that the XEN45 gel implant had a favorable safety profile and was an effective therapeutic option for controlling IOP in glaucoma patients with unregulated IOP despite IOP-lowering medical therapy or prior surgical intervention. It offered an effective approach, both as sole procedure and in combination with CS.
In a prospective, non-randomized, clinical study, De Gregorio and co-workers (2018) examined the efficacy in IOP reduction and safety of the smallest gel stent (XEN 45 Gel Stent) micro-incisional glaucoma surgery combined with micro-incisional CS (MICS). A total of 41 eyes of 33 patients with OAG underwent a XEN 45 Gel Stent implantation combined with MICS. Treatment outcomes analyzed included: IOP, medication use, intra- and post-operative complications. At the end of the follow-up, these researchers evaluated the complete success, defined as a post-operative IOP of greater than or equal to 6 and less than or equal to 17 mmHg without glaucoma medications and the qualified success defined as a post-operative IOP greater than or equal to 6 and less than or equal to 17 mmHg, with glaucoma medications. The mean pre-operative IOP was 22.5 ± 3.7 mmHg on 2.5 ± 0.9 medication classes. After 12 months, the mean post-operative IOP was 13.1 ± 2.4 mmHg (mean IOP reduction of 41.82 %) with a mean of 0.4 ± 0.8 medication classes (p < 0.05 for IOP and medications). The complete success rate was achieved in 80.4 % and a qualified success in 97.5 %. There were no major intra- and post-operative complications during the 1st year of follow-up. The authors concluded that this study demonstrated that the smaller diameter XEN 45 gel implant was statistically effective in reducing IOP and medications in glaucoma patients with a low rate of complications. The main drawbacks of this study were its small sample size (n = 33 patients), relatively short-term follow-up (12 months), and its non-randomized design.
In a prospective, interventional study, Mansouri and colleagues (2018) evaluated the safety and efficacy of XEN gel implant as a stand-alone treatment versus combined XEN-phacoemulsification surgery (XEN + CS) in glaucoma patients. A total of 149 eyes (113 patients) with OAG and uncontrolled (IOP despite medical treatment were enrolled at a tertiary glaucoma center and followed-up for a minimum of 1 year. Approximately 2/3 of patients underwent combined XEN + CS, while the remainder had XEN alone surgery. Primary outcome was a 20 % or more decrease in IOP from medicated baseline at 1 year. Mean IOP, mean number of medications at last follow-up, and incidence of AEs were analyzed. Of 149 enrolled eyes, data of 87 (58 %) were available at 1 year. A total of 109 (73.2 %) eyes underwent XEN + CS and 40 (26.8 %) XEN alone surgery. Mean medicated IOP was 20.0 ± 7.1 at baseline and 13.9 ± 4.3 mm Hg at 1 year (p < 0.01), a 31 % IOP reduction. Mean medications dropped from 1.9 ± 1.3 pre-operatively to 0.5 ± 0.8 at 1 year (p < 0.001). In total, 62.1 % of patients achieved a greater than or equal to 20 % IOP reduction; this proportion was higher in the XEN alone group; 57.7 % of eyes achieved complete success (without any anti-glaucoma medications) and 71.1 % qualified success (with or without medications) when IOP of less than 16 mm Hg was considered as the definition of success. In all, 37 % of patients required needling intervention; AEs included bleb revision in 5 eyes, choroidal detachment in 2 eyes, and 2nd glaucoma surgery in 9 eyes. The authors concluded that the XEN gel implant as a stand-alone procedure or combined with CS demonstrated safe and sustained IOP reduction after 1 year. This study had 2 main drawbacks: First, only 58 % (87) of the 149 enrolled eyes were available at 1 year follow-up; and second, follow-up was short-term (1 year).
Widder and colleagues (2018) examined the IOP-lowering potential, the risk profile, and the success rate of the XEN45 Gel Stent. A total of 261 eyes underwent surgery. The mean follow-up time was 8.5 months. The aim of the treatment was to achieve adequate IOP reduction without medication. Therefore, all patients who did not show sufficiently reduced IOP underwent a surgical revision with opening of the conjunctiva. To determinate the success rate, these researchers performed 2 kinds of analysis: the primary success rate – eyes with appropriate IOP control without medication or surgical revision, and overall success rate – 1 surgical revision was allowed; IOP was lowered from 24.3 mmHg (SD 6.6) to 16.8 mmHg (SD 7.6), and the medication score was lowered from 2.6 (SD 1.1) to 0.2 (SD 0.7). Revisional surgery was performed in 80 eyes (34 %). After a 1st revision, IOP was lowered to 14.0 mmHg (SD 5.1), and the medication score was lowered to 0.2 (SD 0.6). The primary success rate was 66 % and the overall success rate 90 %. The primary success rate was higher in pseudophakic eyes (73 %) than in phakic eyes (53% ) or combined surgery (55 %). The authors concluded that the XEN45 Gel Stent had an IOP-lowering potential and few side-effects; pseudophakic eyes appeared to have a better primary prognosis compared to combined surgery or surgery in phakic eyes.
In a prospective, non-randomized, open-label, multi-center, 2-year study, Reitsamer and colleagues (2019) examined the effectiveness of an ab interno subconjunctival gelatin implant (the AqueSys XEN Implant) as primary surgical intervention in reducing IOP and IOP-lowering medication count in medically uncontrolled moderate POAG. Eyes with medicated baseline IOP 18 to 33 mmHg on 1 to 4 topical medications were implanted with (phaco + implant) or without (implant alone) phacoemulsification. Changes in mean IOP and medication count at months 12 (primary outcomes) and 24, clinical success rate (eyes [%] achieving greater than or equal to 20 % IOP reduction from baseline on the same or fewer medications without glaucoma-related secondary surgical intervention), intra-operative complications, and post-operative AEs were assessed. The modified intent-to-treat population included 202 eyes (of 218 implanted). Changes (S.D.) in mean IOP and medication count from baseline were - 6.5 (5.3) mmHg and - 1.7 (1.3) at month 12 and - 6.2 (4.9) mmHg and - 1.5 (1.4) at month 24, respectively (all p < 0.001). Mean medicated baseline IOP was reduced from 21.4 (3.6) to 14.9 (4.5) mmHg at 12 months and 15.2 (4.2) mmHg at 24 months, with similar results in both treatment groups. The clinical success rate was 67.6 % at 12 months and 65.8 % at 24 months. Overall, 51.1 (12 months) and 44.7 % (24 months) of eyes were medication-free. The implant safety profile compared favorably with that published for trabeculectomy and tube shunts. The authors concluded that the gelatin implant effectively reduced IOP and medication needs over 2 years in POAG uncontrolled medically, with an acceptable safety profile.
Minimally Invasive Nasal Trabeculostomy (MINT)
Minimally Invasive Nasal Trabeculostomy (MINT) is a stent-free surgical procedure developed by Sanoculis intended for the reduction of elevated IOP in persons with glaucoma. The system is a powered surgical device, designed to create trabeculostomy openings of about 100 microns diameter each, via an ab-interno approach, directly from the anterior chamber into Schlemm's canal by removing segments of the trabecular meshwork (i.e., an ab-interno nasal trabeculostomy). The ab-interno approach aims to decrease IOP by increasing aqueous outflow through a direct communication from the anterior chamber to the outer wall of Schlemm’s canal and the collector channels. The opening in the nasal trabecular meshwork to the Schlemm’s canal is created by a sterile surgical instrument (the Surgical Device) made of stainless steel and plastic, which is coupled to a rotating system (the Activation Device). The Surgical Device of the Minimally Invasive Nasal Trabeculostomy System consists of a stainless steel micro trephine, covered by a small needle-shaped sleeve with a rotating mechanism behind it. While being rotated, the Surgical Device enters and moves along the trabecular meshwork, removing trabecular meshwork tissue with minimal collateral damage. Mechanical rotation of the Surgical Device is achieved by the rotating system (i.e., Activation Device), which is comprised of: (1) controller which dictates the activation pulse duration, the rotations per minute (RPM) and the forwards and backwards movement of the micro trephine; (2) motor; and (3) footswitch. Evidence for the MINT procedure reported by the manufacturer is from a single-arm clinical study on 66 patients who received the treatment as a standalone procedure (Sanoculis, 2025). The study showed that at a two-year follow-up, patients experienced a significant reduction in their IOP. The procedure is being studied in clinical trials (NCT05638906, NCT06612346).
Transorbital Electrical Stimulation for the Treatment of Open Angle Glaucoma
Schittkowski et al (2025) stated that glaucoma is one of the most common causes of blindness and affects more than 70 million people globally. The disease is characterized by the loss of retinal ganglion cells associated with a progressive optic neuropathy, resulting in an impairment of visual functions. Currently, the only modifiable risk factor is the increase in IOP, and its treatment is to lower IOP by medication, laser treatment, or surgery to avoid disease progression; therefore, new approaches for preventing and reversing vision loss are needed. Several small and 2 multi-center studies have reported that repetitive trans-orbital alternating current stimulation (rtACS) could result in long-lasting visual field improvement. This could open a new and inexpensive therapeutic option for optic atrophy; however, the level of evidence for this approach is still poor, and further investigations are needed. These researchers presented the protocol of a clinical trial (the VIRON Trial) that is designed to prove the effectiveness of rtACS compared with sham stimulation in patients with POAG. The VIRON (Vision Restoration in Optic Neuropathy) Trial is a prospective, randomised, placebo-controlled, double-blind, multi-center study with 3 arms. The primary objective is to examine the effectiveness of rtACS in patients with POAG compared with sham stimulation. The primary outcome is the change in mean defect (MD) in the visual field immediately after 10 sessions of rtACS (days 9, 16, and 23) compared with the values of initial perimetry (days -21 to -14, and 0) after applying electrical stimulation with a classical montage, compared with sham and electrical stimulation using individualized montage. Secondary outcome measures comprise a long-term effect with changes in MD at 24 weeks after stimulation, and data from the National Eye Institute 25-Item Visual Function Questionnaire (NEI VFQ-25) and QOL questionnaire (Short Form 36). The target population are patients with glaucomatous optic atrophy and significant glaucomatous visual field defects (MD of 5-22 dB) due to POAG. After randomization, participants will receive either classical rtACS (group 1), individual rtACS (group 2), or sham stimulation (group 3) in daily 25-min stimulation sessions in 2 series of 5 consecutive days separated by a weekend interval. In group 1, active stimulation will be via the routinely applied montage using 2 electrodes affixed on the right and left side of the head, next to the eyes, with straight-forward fixation. In group 2, the current flow will be individually modeled (MRI-based) to target areas of partial visual field defects by optimizing electrode positions in conjunction with an optimized visual fixation direction. In group 3, sham stimulation will serve as control. The calculated sample size required to achieve a statistical power of 80 % for a relevant effect size and allow for drop-outs is 300 (100 per group). The trial has already begun with the 1st patient in July 2023. The planned recruitment period is 24 months with an estimated end of the study in November 2025 (last patient out). An adjusted extension of the study period is planned. The study data will be published within 6 months following the completion of the study.
VisionGraft Patch Graft for the Treatment of Glaucoma
The AAO Preferred Practice Pattern Glaucoma Committee‘s guideline on “Primary Open Angle Glaucoma” (Gedde et al, 2020) noted that patch allografts of sclera, cornea, or pericardium are commonly used to prevent tube erosion, and a long scleral tunnel may also mitigate this risk.
Viscocanalostomy and Canaloplasty
Glaucoma is an irreversible group of conditions/diseases involving death of the nerve cells in front of the optic nerve. It was once thought that glaucoma was generally due to increased intra-ocular pressure (IOP); however, the condition is also found in individuals with normal or low eye pressure. Therefore, diagnosis of glaucoma does not rely on increased IOP and may be related to optic nerve damage. Glaucoma is one of the leading causes of blindness with loss of peripheral vision being a hallmark sign of glaucoma.
Medication, in the form of eye drops, pills or both, is the most common early treatment for glaucoma. There are numerous medications available for treating glaucoma; all of which must be taken regularly. If medication fails, other interventions may be recommended.
Current standard surgical treatments for glaucoma include trabeculectomy or trabeculoplasty (incisional or laser). Iridotomy, iridectomy or iridoplasty may be necessary for angle-closure glaucoma.
Viscocanalostomy is an ophthalmic surgical procedure that has been developed as an alternative to trabeculectomy. In some cases, viscocanalostomy has been used in conjunction with cataract removal via phaco-emulsification. Viscocanalostomy is similar to canaloplasty in that tissue flaps are cut in the conjunctiva and the sclera. The creation of these flaps exposes a portion of the drainage (Schlemm’s) canal into which a high-viscosity elastic gel is injected. The injected material opens and enlarges the canal to allow increased fluid flow out of the anterior chamber. The tissue flaps are then closed.
Although there are a variety of viscocanalostomy techniques, the procedure basically involves production of superficial and deep scleral flaps, excision of the deep scleral flap to create a scleral reservoir, and unroofing of Schlemm's canal. A high-viscosity viscoelastic, such as sodium hyaluronate, is used to open the canal and create a passage from a scleral reservoir to the canal. The superficial scleral flap is then sutured water tight, trapping the viscoelastic until healing takes place. However, the peer-reviewed published medical literature reveals that viscocanalostomy has only been studied in a relatively small number of patients at a few centers. There are no published peer-reviewed data on long-term outcomes of viscocanalostomized patients, and what few clinical studies have been published directly comparing viscocanalostomy with trabeculectomy show that trabeculectomy is more effective at lowering intra-ocular pressure (IOP).
Randomized controlled multi-center clinical trials directly comparing viscocanalostomy with trabeculectomy are needed before viscocanalostomy can be accepted as an established alternative to trabeculectomy. As one of the leading investigators of viscocanalostomy in North America commented: "As with all glaucoma studies, long term follow-up evaluation will be required to prove its [viscocanalostomy's] real efficacy. In addition, randomized studies which would compare viscocanalostomy and phacoemulsification with other combined glaucoma procedures are also in order" (Henahan, 1998).
In a technology assessment on non-penetrating glaucoma surgery, the American Academy of Ophthalmology (AAO, 2001) stated that non-penetrating glaucoma surgery (viscocanalostomy is one of the 2 major variations of this procedure) has the potential to reduce IOP) while minimizing the risk of post-operative relative hypotony and the complications associated with hypotony. The authors found, however, that the majority of the published literature on non-penetrating glaucoma surgery contains information from case series, which are not randomized and lack a control group. The authors concluded that randomized clinical trials (RCTs) are needed to assess these procedures and to determine their role in the clinical management of glaucoma patients.
The AAO's practice guideline on the management of primary open-angle glaucoma (2005) recognized viscocanalostomy as being a non-penetrating surgery used by some physicians as an alternative to trabeculectomy, but it stated that the precise role of non-penetrating surgeries (i.e., viscocanalostomy and non-penetrating deep sclerectomy) has yet to be determined.
Shaarawy and associates (2003) studied prospectively the success rate and complications of viscocanalostomy in patients with medically uncontrolled primary and secondary open angle glaucoma (n = 57). These investigators concluded that viscocanalostomy appears to be a promising modification of filtering surgery.
Randomized controlled clinical studies comparing viscocanalostomy with trabeculectomy in glaucomatous patients have shown that trabeculectomy is more effective in lowering IOP than viscocanalostomy. In a RCT (n = 20) comparing viscocanalostomy and trabeculectomy for the treatment of patients with open angle glaucoma, Jonescu-Cuypers et al (2001) found that trabeculectomy was more effective than viscocanalostomy in lowering IOP in glaucomatous eyes of such patients. This is in agreement with the finding of Luke et al (2002) who examined the IOP-lowering effectiveness and the post-operative complication profile of viscocanalostomy versus trabeculectomy in a prospective randomized trial (n = 60). The authors concluded that in eyes with open-angle glaucoma, viscocanalostomy is less effective in reducing IOP than standard filtering surgery. However, post-operative complications are less frequent after viscocanalostomy. In a prospective clinical study, Kobayashi and colleagues (2003) compared the IOP-lowering effect and safety of viscocanalostomy and trabeculectomy with mitomycin C in patients with bilateral primary open-angle glaucoma (n = 25). The eyes of each patient were randomly assigned to receive viscocanalostomy in 1 eye and trabeculectomy with mitomycin C in the other eye. The patients were followed-up for 12 months. These researchers reported that trabeculectomy with mitomycin C may be more effective than viscocanalostomy in lowering IOP in patients with primary open-angle glaucoma, while eyes undergoing viscocanalostomy experience a lower incidence of complications, and they stated that further investigation of more cases is needed.
In a single-masked, parallel-group, prospective, randomized 24-month trial, Carassa et al (2003) compared the effectiveness and safety of viscocanalostomy and trabeculectomy in adults with uncontrolled open-angle glaucoma (n = 50). Eyes were assigned randomly to either viscocanalostomy (group 1) or trabeculectomy (group 2) with no intraoperative anti-fibrotics in the study eye. In group 1, no further intervention was allowed, whereas trabeculectomy eyes could receive subconjunctival 5-fluorouracil (5-FU) injections or laser suture lysis after surgery. It was found that viscocanalostomy is an effective IOP-lowering procedure in adults affected by open-angle glaucoma. Trabeculectomy with post-operative 5-FU can probably provides lower IOPs but, with more numerous complications, greater discomfort, and more intensive post-operative management. The authors concluded that large, multi-center controlled studies are needed to define the role of viscocanalostomy in the surgical management of glaucoma.
An assessment prepared for the Cochrane Collaboration comparing surgical and medical management of glaucoma found no studies comparing viscocanalostomy with medical management (Burr et al, 2004). The assessment noted that although viscocanalostomy may have fewer complications than trabeculectomy, viscocanalostomy may have limited effectiveness at lowering IOP.
Guidelines from the Royal College of Ophthalmologists (2004) conclude that "[a]t the present time there is insufficient evidence from prospective studies that these operations [viscocanalostomy and deep sclerectomy] have a lower incidence of long-term complications while maintaining good IOP control to advocate their use in routine glaucoma practice."
In a prospective randomized 1-year study, Kobayashi and Kobayashi (2007) compared the IOP-lowering effect of combined viscocanalostomy and phaco-emulsification and combined trabeculectomy and phaco-emulsification with mitomycin C in eyes with primary open-angle glaucoma. A total of 40 consecutive patients (40 eyes) with primary open-angle glaucoma and cataract were enrolled in this study. Eyes were assigned randomly either to trabeculectomy with mitomycin C or to viscocanalostomy in combination with phaco-emulsification and intra-ocular lens implantation. Mean baseline IOP was 24.0 +/- 2.0 mm Hg in the viscocanalostomy group and 23.7 +/- 2.6 mm Hg in the trabeculectomy group (p = 0.7). Mean post-operative IOP was 13.7 +/- 2.2 mm Hg at 3 months, 14.8 +/- 3.3 mm Hg at 6 months, and 14.9 +/- 3.0 mm Hg at 12 months in the viscocanalostomy group and 12.1 +/- 4.0 mm Hg at 3 months, 13.8 +/- 4.7 mm Hg at 6 months, and 14.1 +/- 4.4 mm Hg at 12 months in the trabeculectomy group. There was no significant difference in the mean IOP between the groups at any time. At 12 months, 17 patients (85 %) in the viscocanalostomy group and 16 patients (80 %) in the trabeculectomy group achieved an IOP of 20 mm Hg or less without medication (p = 0.7). Complications included 2 cases (10 %) of flat/shallow anterior chamber and 4 cases (20 %) of hypotony in the trabeculectomy group, whereas intra-operative micro-perforation of Descemet's membrane occurred in 3 cases (15 %) in the viscocanalostomy group. The authors concluded that there was no significant difference in IOP reduction between viscocanalostomy and trabeculectomy with mitomycin C in combination with phaco-emulsification and intra-ocular lens implantation in patients with primary open-angle glaucoma. They also stated that future study of a large population is needed to verify these observations.
In a long-term, prospective, randomized study, Gilmour et al (2007) compared the lowering effects of viscocanalostomy and trabeculectomy without anti-metabolite on IOP. The results of this study showed that at 40-month follow-up, trabeculectomy was more likely to achieve IOP levels below 18 mm Hg than viscocanalostomy. The study enrolled 21 primary open angle glaucoma patients who underwent trabeculectomy and 22 who underwent viscocanalostomy by a single surgeon familiar with both procedures. The mean pre-operative IOP was 25 mm Hg, and the trabeculectomies were performed without anti-metabolite intra-operatively, although some patients received 5-FU in the post-operative period. The follow-up period was 4 years, and the post-operative treatment was similar in both groups.
Survival analysis suggested that patients who underwent trabeculectomy had a 42 % chance of experiencing lower IOP compared to a 21 % chance in the viscocanalostomy group at 40 months. Success was defined as IOP below 18 mm Hg, and qualified success was IOP below 18 with medications. The trabeculectomy group, however, had more complications, and interventions such as needling and 5-FU injections were needed in the early post-operative period. Although the trabeculectomy group was less likely to need glaucoma medications to control IOP in the post-operative period, IOP with medication was well-controlled in the viscocanalostomy group. Of interest, only 1 patient required gonio-puncture in the viscocanalostomy group compared to other studies in the literature where gonio-puncture was required for around 30 % of patients. It is unclear how this might have influenced the results.
The authors stated that the findings of this study confirmed previous reports that the likelihood of obtaining lower IOP over the long-term with viscocanalostomy is lower than that with a standard trabeculectomy. The re-introduction of canal based surgery in adults has generated intense interest in the glaucoma community to develop new approaches to improve filtration through the trabecular and other pathways. They noted that prospective, randomized, long-term, clinical trials will hopefully provide some insight as to which of these new procedures might be most beneficial to glaucoma patients.
More recently, a glaucoma canaloplasty (enhanced viscocanalostomy) has been introduced, which involves modification of the viscocanalostomy procedure. Canaloplasty uses viscoelastic and a specialized microcatheter (e.g., iScience Surgical Ophthalmic Microcannula, Menlo Park, CA) to forcibly open the Schlemm's canal. The procedure is intended to restore the natural drainage of fluid from the eye, thus reducing IOP in persons with glaucoma.
Canaloplasty is a surgical procedure in which tissue flaps are cut in the conjunctiva and the sclera to expose the drainage area (Schlemm’s canal). Canaloplasty attempts to open the entire drainage area surrounding the anterior chamber (360°) instead of just a portion of it, as in viscocanalostomy below. A very small catheter is placed in the opening and used to inject the high-viscosity elastic gel into the entire drainage area forming a ring around the anterior chamber. A suture loop is left in the canal to help maintain tension and keep the canal open. The canal is expanded by the injection to promote better fluid drainage.
Similar to the viscocanalostomy, canaloplasty is completed under a scleral flap. The canal is identified then intubated with a flexible microcatheter which has a lighted tip to identify its location as it passes through the Schlemm's canal. The microcatheter also has a lumen to allow for the passage of high viscosity sodium hyaluronate for dilation of the canal. Once the cannula has passed the full length (360º through) of the Schlemm's canal, a suture is tied to the cannula and as the cannula is withdrawn the suture is tied off and left in place. The intra-canalicular suture cinches and stretches the trabecular meshwork inwards and permanently opening the Schlemm's canal. The scleral flap is tightly closed as well as the conjunctiva. Before, during and after the surgery, a special ultrasound imaging system is used to help identify the canal and the instrumentation in the canal.
An important difference between viscocanalostomy and canaloplasty is that canaloplasty aims at opening the entire length of the Schlemm's canal, not just one section of it. Canaloplasty is currently under investigation. Several trials are currently underway to further support the benefits and safety of this technique.
Although a relatively new procedure, canaloplasty seems effective in lowering IOP when used in glaucoma patients as an alternative to trabeculectomy. The choice between these procedures relates to the degree of IOP lowering required by a patient as well as the patient's risk factors for complications. Canaloplasty will likely be used most often in earlier stages of glaucoma and in patients in whom bleb infection and leakage would put them at higher risk for infection-associated blindness (endophthalmitis). This procedure may also be indicated in patients who may not need IOP-lowering to the degree that is achievable with trabeculectomy. Canaloplasty and other procedures that lower IOP without creating an aqueous filtering hole in the eye with a conjunctival bleb may have an increasing role in the surgical management of patients with glaucoma because of their potentially improved safety profile.
In an international multi-center prospective study (14 sites in Germany and in the U.S.), Lewis et al (2007) assessed the safety and effectiveness of circumferential visco-dilation and tensioning of the inner wall of Schlemm's canal (canaloplasty) for the treatment of open-angle glaucoma (OAG). Adult patients having glaucoma surgery, patients with qualifying pre-operative IOP of at least 16 mm Hg or higher and open angles were eligible. Evaluation was performed at baseline and 1 day, 1 week, and 1, 3, 6, and 12 months post-operatively. After a non-penetrating dissection technique to expose Schlemm's canal was performed, a flexible microcatheter was used to dilate the full circumference of the canal by injecting sodium hyaluronate 1.4 % during catheterization. A suture loop was placed in the canal to apply tension to the trabecular meshwork. High-resolution ultrasound imaging was used to evaluate Schlemm's canal and anterior segment angle morphology, including distension of the trabecular meshwork caused by the tensioning suture. Data analysis was performed in 2 groups: Group 1, in which patients met all inclusion criteria, and Group 2, made up of Group 1 patients who had successful suture placement. Group 1 comprised 94 patients and Group 2, 74 patients. The mean baseline IOP in Group 1 was 24.7 mm Hg +/- 4.8 (standard deviation [SD]) on a mean of 1.9 +/- 1.0 medications per patient. In Group 2 (patients with sutures), the mean IOP was 16.1 +/- 4.7 mm Hg 3 months post-operatively, 15.6 +/- 4.0 mm Hg at 6 months, and 15.3 +/- 3.8 mm Hg at 1 year. Medication use dropped to a mean of 0.6 +/- 0.9 per patient at 12 months. Suture tensioning was an apparent contributing factor in achieving surgical success. Patients with measurable trabecular meshwork distension from suture tension had a mean IOP of 15.9 +/- 5.2 mm Hg at 6 months and 14.5 +/- 3.0 mm Hg at 12 months. Surgical and post-surgical adverse events were reported in 15 of 94 patients (16 %) and included hyphema (n = 3), elevated IOP greater than 30 mm Hg (n = 3), Descemet's tear (n = 1), hypotony (n = 1), choroidal effusion (n = 1), and exposed closure suture with eyelid edema and erythema epiphora (n = 1); 4 patients were subsequently converted to trabeculectomy. The authors concluded that canaloplasty was a safe and effective procedure to reduce IOP in adult patients with OAG. The major drawbacks of this study included the lack of randomization and a control group, as well as the learning curve associated with performance of the procedure. Other limitations include the small, heterogeneous patient group, short-term follow-up, and the number of patients lost to follow-up.
Shingleton et al (2008) evaluated the safety and effectiveness of canaloplasty combined with clear corneal phaco-emulsification and posterior chamber intraocular lens (IOL) implantation in in treating OAG. This international multi-center prospective study comprised adult patients with OAG having combined glaucoma and cataract surgery. Patients with qualifying treated pre-operative IOP of at least 21 mm Hg or higher and open angles were eligible. Evaluation was performed at baseline and 1 day, 1 week, and 1, 3, 6, and 12 months post-operatively. Intra-operative and post-operative high-resolution ultrasound imaging was used to assess Schlemm canal and anterior segment angle morphology, including distension of the trabecular meshwork due to the tensioning suture. Data from 54 eyes that had combined glaucoma and cataract surgery performed by 11 surgeons at 9 study sites were analyzed for this interim analysis. The mean baseline IOP was 24.4 mm Hg +/- 6.1 (SD) with a mean of 1.5 +/- 1.0 medications per eye. In all eyes, the mean post-operative IOP was 13.6 +/- 3.8 mm Hg at 1 month, 14.2 +/- 3.6 mm Hg at 3 months, 13.0 +/- 2.9 mm Hg at 6 months, and 13.7 +/- 4.4 mm Hg at 12 months. Medication use dropped to a mean of 0.2 +/- 0.4 per patient at 12 months. Surgical complications were reported in 5 eyes (9.3 %) and included hyphema (n = 3, 5.6 %), Descemet tear (n = 1, 1.9 %), and iris prolapse (n = 1, 1.9 %). Transient IOP elevation of more than 30 mm Hg was observed in 4 eyes (7.3 %) 1 day post-operatively. The authors concluded that canaloplasty combined with clear corneal phaco-emulsification and posterior chamber IOL implantation was a safe and effective procedure to reduce IOP in adult patients with OAG.
The National Institute for Health and Clinical Excellence (NICE, 2008) stated that canaloplasty for the treatment of primary OAG should be used only in the context of research or formal prospective data collection. It noted that current evidence on the safety and effectiveness of canaloplasty is inadequate in quality and quantity. Specialist advisors to NICE considered theoretical adverse events to include anterior chamber perforation, tearing of Descemet’s membrane resulting in corneal opacification or retinal damage, intra-ocular inflammation caused by the suture, cataract formation, sustained increases in IOP, hypotony, and bleb formation or suture exposure with endophthalmitis.
In a meta-analysis, Hondur and colleagues (2008) evaluated the effectiveness of non-penetrating glaucoma surgery for OAG with respect to target IOP and severity of glaucoma. Studies encompassing only combined glaucoma and cataract surgery were excluded. Measurement of effectiveness was determined on the basis of achievement of target IOP. Data related to post-operative gonio-puncture and needling with anti-metabolite application were noted. The percentage of cases achieving less than or equal to 21 mm Hg was 48.6 % after primary deep sclerectomy (DS), 68.7 % after DS with implant, 67.1 % after DS with anti-metabolite, 51.1 % after primary viscocanalostomy, and 36.8 % after viscocanalostomy with anti-metabolite or implant. Visual field parameters were almost exclusively not available; whereas cup/disk ratio and target IOP lower than 21 mm Hg were available in very few reports. With lower set IOP targets, the rates of success varied between 35 % and 86 % for DS, and between 10 % and 67 % for viscocanalostomy. The mean follow-up of the studies were mostly in the range of 3 years. The authors concluded that non-penetrating glaucoma surgery seems to provide IOP reduction into the high teens. Its potential to achieve lower target IOPs seems to be low. They stated that longer-term studies, with data related to glaucoma severity and proper target IOPs are needed.
Mendrinos et al (2008) noted that non-penetrating glaucoma surgeries have been developed in recent years in order to improve the safety of conventional filtering procedures. The goal of non-penetrating filtering procedures is to reduce IOP by enhancing the natural aqueous outflow channels, while reducing outflow resistance located in the inner wall of the Schlemm's canal and the juxta-canalicular trabecular meshwork. In the last few years, viscocanalostomy and DS with external trabeculectomy have become the most popular non-penetrating filtering procedures. Both involve removal of a deep scleral flap, the external wall of Schlemm's canal and corneal stroma behind the anterior trabeculum and Descemet's membrane, thus creating an intra-scleral space. The aqueous humour leaves the anterior chamber through the intact trabeculo-Descemet's membrane into the scleral space, from where it will egress into different pathways. The technique is associated with a long learning curve. Published clinical trials comparing non-penetrating glaucoma surgery to full-thickness trabeculectomy have a consensus on the superior safety profile of non-penetrating glaucoma surgery but are not in agreement when it comes to efficacy, where conflicting results have been found.
Lewis and colleagues (2009) assessed 2-year post-surgical safety and efficacy of canaloplasty (circumferential viscodilation and tensioning of the inner wall of Schlemm canal) to treat OAG. This international prospective study comprised adult OAG patients having glaucoma surgery or combined glaucoma-cataract surgery. Qualifying pre-operative IOP was at least 16 mm Hg and historical IOP, at least 21 mm Hg. The full circumference of the canal was viscodilated and a trabecular tensioning suture placed with a micro-catheter. Primary outcome measures included IOP and glaucoma medication use. At 24 months, all 127 eyes (127 patients) had a mean IOP of 16.0 mm Hg +/- 4.2 and mean glaucoma medication use of 0.5 +/- 0.8 (baseline values 23.6 +/- 4.8 mm Hg and 1.9 +/- 0.8 medications). Eyes with canaloplasty alone had a mean IOP of 16.3 +/- 3.7 mm Hg and 0.6 +/- 0.8 medications (baseline values 23.2 +/- 4.0 mm Hg and 2.0 +/- 0.8 medications). Eyes with combined glaucoma-cataract surgery had a mean IOP of 13.4 +/- 4.0 mm Hg and 0.2 +/- 0.4 medications (baseline values 23.1 +/- 5.5 mm Hg and 1.7 +/- 1.0 medications). The IOP and medication use results at all time points were statistically significant versus baseline (p < 0.001). The late post-operative follow-up identified 3 patients with elevated IOP. No other serious ocular or non-ocular complications were reported. The authors concluded that canaloplasty was safe and effective in reducing IOP in adult patients with OAG. These are "interim" results of an ongoing clinical study; the clinical value of canoplasty awaits the completion and final analyses of results.
Griesbacher et al (2010) reported on a prospective study evaluating 32 consecutive eyes that had canaloplasty and at least 1 year of follow-up. The mean pre-operative IOP (with medications) of 27.3 +/- 5.6 mm Hg improved to a mean post-operative IOP (without medications) of 12.8 +/- 1.5 mm Hg at 12 months. The success rate where the IOP reached less than 21, less than 18, and less than 16 mm Hg was 93.8 % (95 % confidence interval [CI]: 0.86 to 1.0), 84.4 % (95 % CI: 0.73 to 0.98), and 74.9 % (95 % CI: 0.61 to 0.92) at 12 months, respectively.
Minckler and Hill (2009) described the rationales and initial clinical outcomes in studies to date on Glaukos iStent, iScience (canaloplasty), Solx (supra-choroidal shunt), and Trabectome, which are newly developed surgical technologies for the treatment of OAG. These new approaches to angle surgery have been demonstrated in preliminary case series to safely lower IOP in the mid-teens with far fewer complications than expected with trabeculectomy and without anti-fibrotics. Trabectome and iStent are relatively non-invasive, aim to improve access of aqueous to collector channels and do not preclude subsequent standard surgery. Canaloplasty, modified from viscocanalostomy, is thought to improve trans-trabecular flow. Solx potentially offers an adjustable aqueous outflow into the supra-choroidal space.
In a prospective and non-randomized study, Chakib and colleagues (2010) evaluated the short-term clinical results and complications of viscocanalostomy. A total of 107 consecutive eyes of 67 patients who underwent viscocanalostomy were analyzed. The surgeon conducted post-operative care. The minimal follow-up was 1 year, with a mean follow-up of 13.1 months (range of 12 to 18 months). The criteria for success were defined as IOP less than 21 mm Hg without treatment. The mean pre-operative IOP was 28.3 mm Hg while the mean post-operative IOP was 5.4 mm Hg on the first day and 10.2 mm Hg at 13 months. The rate of patients who had IOP below 21 mm Hg with or without treatment was 98 % at 13 months. The complete success rate without treatment was 80 % at 13 months. Seven cases of ocular hypotony lasting more than 1 month were noted. The authors concluded that viscocanalostomy is a promising procedure because in the short-term it provides good tonometric results in glaucomatous patients without the complications of trabeculectomy. However, it remains a technique with a learning curve.
Tian and Kaufman (2013) stated that since the inner wall of Schlemm's canal (SC) is directly in contact with the trabecular meshwork (TM) for 360 degrees and the catheter device used in canaloplasty allows viscoelastic to be injected into the entire length of SC, canaloplasty might also be used to perform SC/TM-targeted delivery of transgene vectors for glaucoma gene therapy. This hypothesized new method for transgene delivery may give the transgene access to the entire inner wall of SC and the whole juxta-canalicular region of the TM and allow the transgene to be expressed in both the TM and SC without affecting the cornea, iris and ciliary body. The authors concluded that this strategy might have a greater trabecular outflow resistance-decreasing effect than either the genetic or surgical approach alone.
Aktas et al (2014) noted that SC inner wall is adjacent to the juxta-canalicular TM over their entire circumference. These researchers attempted to transfer reporter and therapeutic genes to these outflow-modulating tissues via canaloplasty surgery in live monkeys. A standard canaloplasty surgical approach was performed in cynomolgus monkeys using flexible canaloplasty catheters, modified for monkey eyes with a 175-μm outer diameter and an LED-lighted tip. A 6-0 prolene suture was used for the exact localization of SC. Trypan blue was injected during catheter withdrawal to document catheter placement within SC and to determine ease of injecting fluid into SC. Before, during, and after the injection, the position of the catheter and the anatomic details were video-captured with an externally positioned non-contact endoscopic imaging system and 50-mHz ultrasound biomicroscopy (UBM). A 360-degree catheterization and injection of dye into SC was achieved. Suture, catheter, and trypan blue were imaged with the endoscope camera system and the catheter was also visualized with UBM. Trypan blue was seen in the SC over 5 clock hours after a 1 clock-hour insertion of the catheter. The authors concluded that a modified canaloplasty catheter device might be used for gene delivery to the SC/TM area without circumferential catheterization. Moreover, they stated that further studies comparing different delivery methods of the vector/transgene into the SC using canaloplasty are needed.
The AAO Preferred Practice Pattern on primary open angle glaucoma (AAO, 2015) states that the precise role of canaloplasty in the management of open-angle glaucoma remains to be determined. The AAO states that "The safety and efficacy of canaloplasty alone and combined with phacoemulsification was described in a nonrandomized multicenter clinical trial through 3 years of follow-up [citing Lewis et al, 2011]. No randomized clinical trial comparing trabeculectomy and canaloplasty exists. A retrospective case series found lower post-operative IOP with trabeculectomy compared with canaloplasty (citing Ayyala et al, 2011)."
An AAO‘s clinical practice guideline on “Primary open-angle glaucoma” (AAO, 2010) as well as an AAO report on “Novel glaucoma procedures” (Francis et al, 2011) did not mention phaco-viscocanalostomy as an therapeutic option. Furthermore, in an UpToDate review on “Open-angle glaucoma: Treatment” (Jacobs, 2014), viscocanalostomy and phaco-viscocanalostomy are not mentioned as therapeutic options.
In a prospective, non-randomized case-series study, Moradian et al (2013) evaluated the safety and effectiveness of viscocanalostomy in the management of medically uncontrollable primary OAG (POAG) in a developing country. A total of 14 consecutive eyes with medically uncontrollable POAG were subjected to viscocanalostomy. The main outcome measure was success rate based on the IOP level achieved post-operatively. The procedure was considered a complete success if IOP was less than 21 mmHg without any anti-glaucoma medication. Qualified success was defined as IOP of less than 21 mmHg with anti-glaucoma medication. All patients had a regular follow-up of at least 12 months. Overall, IOP was reduced from a mean baseline value of 27.9 ± 7.3 mmHg (range of 21 to 40 mmHg) to a mean final value of 16.0 ± 2.7 mmHg (range of 13 to 22 mmHg), which was statistically highly significant (p < 0.005). The mean number of pre-operative anti-glaucoma medications was 3.0 ± 0.4 (range of 2 to 4), which was reduced significantly (p < 0.0001) to 0.3 ± 0.6 (range of 0 to 2) at the last follow-up visit. One year post-operatively, complete success was achieved in 71 % and qualified success was observed in 21.4 % of patients, summing up to an overall success rate of 92.4 %. There were no major complications in any of the patients. The authors concluded that viscocanalostomy could be performed effectively and safely for control of POAG in developing countries. Moreover, they stated that “A larger number of patients and a longer follow-up period are warranted for the further evaluation of this relatively novel procedure in developing countries. In addition, comparing the future surgical cases of the same surgeon would show the learning curve of viscocanalostomy more precisely. However, we believe that the high success rate and low complication rate in these initial 14 cases are highly encouraging to suggest popularization of non-penetrating glaucoma procedures in developing countries”.
In a Cochrane review, Eldaly and colleagues (2014) compared the effectiveness of non-penetrating trabecular surgery with conventional trabeculectomy in people with glaucoma. These investigators searched CENTRAL (which contains the Cochrane Eyes and Vision Group Trials Register) (The Cochrane Library 2013, Issue 8), Ovid MEDLINE, Ovid MEDLINE In-Process and Other Non-Indexed Citations, Ovid MEDLINE Daily, Ovid OLDMEDLINE (January 1946 to September 2013), EMBASE (January 1980 to September 2013), Latin American and Caribbean Literature on Health Sciences (LILACS) (January 1982 to September 2013), the metaRegister of Controlled Trials (mRCT) (www.controlled-trials.com), ClinicalTrials.gov (www.clinicaltrials.gov) and the WHO International Clinical Trials Registry Platform (ICTRP) (www.who.int/ictrp/search/en). They did not use any date or language restrictions in the electronic searches for trials. They last searched the electronic databases on September 27, 2013. This review included relevant RCTs and quasi-RCTs on participants undergoing standard trabeculectomy for OAG compared to non-penetrating surgery, specifically viscocanalostomy or deep sclerectomy, with or without adjunctive measures. Two review authors independently reviewed the titles and abstracts of the search results. They obtained full copies of all potentially eligible studies and assessed each one according to the definitions in the “Criteria for considering studies” section of this review. They used standard methodological procedures expected by The Cochrane Collaboration. These researchers included 5 studies with a total of 311 eyes (247 participants) of which 133 eyes (participants) were quasi-randomized. A total of 160 eyes that had trabeculectomy were compared to 151 eyes that had non-penetrating glaucoma surgery (of which 101 eyes had deep sclerectomy and 50 eyes had viscocanalostomy). The CI for the odds ratio (OR) of success (defined as achieving target eye pressure without eye drops) does not exclude a beneficial effect of either deep sclerectomy or trabeculectomy (OR 0.98, 95 % CI: 0.51 to 1.88). The odds of success in viscocanalostomy participants was lower than in trabeculectomy participants (OR 0.33, 95 % CI: 0.13 to 0.81). These investigators did not combine the different types of non-penetrating surgery because there was evidence of a subgroup difference when examining total success. The OR for achieving target eye pressure with or without eye drops was imprecise and was compatible with a beneficial effect of either trabeculectomy or non-penetrating filtration surgery (NPFS) (OR 0.79, 95 % CI: 0.35 to 1.79). Operative adjuvants were used in both treatment groups; more commonly in the NPFS group compared to the trabeculectomy group, but no clear effect of their use could be determined. Although the studies were too small to provide definitive evidence regarding the relative safety of the surgical procedures, these researchers noted that there were relatively fewer complications with non-filtering surgery compared to trabeculectomy (17 % and 65 %, respectively). Cataract was more commonly reported in the trabeculectomy studies. None of the 5 trials used quality of life measure questionnaires. The methodological quality of the studies was not good. Most studies were at high risk of bias in at least one domain and for many, there was lack of certainty due to incomplete reporting. Adequate sequence generation was noted only in 1 study. Similarly, only 2 studies avoided detection bias. These investigators detected incomplete outcome data in 3 of the included studies. The authors concluded that this review provided some limited evidence that control of IOP is better with trabeculectomy than viscocanalostomy. For deep sclerectomy, they could not draw any useful conclusions. This may reflect surgical difficulties in performing non-penetrating procedures and the need for surgical experience. This review has highlighted the lack of use of quality of life outcomes and the need for higher methodological quality RCTs to address these issues. Since it is unlikely that better IOP control will be offered by NPFS, but that these techniques offer potential gains for patients in terms of quality of life, the authors felt that such a trial is likely to be of a non-inferiority design with quality of life measures.
Ghate and Wang (2015) stated that primary congenital glaucoma (PCG) manifests within the first few years of a child's life and is not associated with any other systemic or ocular abnormalities. Primary congenital glaucoma results in considerable morbidity even in developed countries. Several surgical techniques for treating this condition, and lowering the IOP associated with it, have been described. These investigators compared the safety and effectiveness of different surgical techniques for PCG. They searched CENTRAL (which contains the Cochrane Eyes and Vision Group Trials Register) (The Cochrane Library 2014, Issue 6), Ovid MEDLINE, Ovid MEDLINE In-Process and Other Non-Indexed Citations, Ovid MEDLINE Daily, Ovid OLDMEDLINE (January 1946 to June 2014), EMBASE (January 1980 to June 2014), (January 1982 to June 2014), PubMed (January 1946 to June 2014), the metaRegister of Controlled Trials (mRCT) (www.controlled-trials.com), ClinicalTrials.gov (www.clinicaltrials.gov), the WHO International Clinical Trials Registry Platform (ICTRP) (www.who.int/ictrp/search/en). They did not use any date or language restrictions in the electronic searches for trials. They last searched the electronic databases on June 23, 2014. These researchers included all randomized and quasi-randomized trials in which different types of surgical interventions were compared in children less than 5 years of age with PCG. The authors used standard methodological procedures specified by The Cochrane Collaboration. A total of 6 trials (4 randomized and 2 quasi-randomized) with 102 eyes in 61 children were included in this analysis. Two trials were conducted in the USA and 1 trial each in Egypt, Israel, Lebanon and Saudi Arabia. All trials included children aged younger than 1 year when diagnosed with PCG, and followed them for periods ranging from 6 months to 5 years. No 2 trials compared the same pair of surgical interventions, so these investigators did not perform any meta-analysis. One trial compared trabeculotomy versus goniotomy; a 2nd trial compared combined trabeculectomy-trabeculotomy with mitomycin C versus trabeculectomy-trabeculotomy with mitomycin C and deep sclerectomy; a 3rd trial compared combined trabeculotomy-trabeculectomy versus trabeculotomy; a 4th trial compared 1 goniotomy versus 2 goniotomies; a 5th trial compared trabeculotomy versus viscocanalostomy; and the 6th trial compared surgical goniotomy versus neodymium-YAG laser goniotomy. For IOP change and surgical success (defined by IOP achieved), none of the trials reported a difference between pairs of surgical techniques. However, due to the limited sample size for all trials (average of 10 children per trial), the evidence as to whether a particular surgical technique is effective and which surgical technique is better still remains uncertain. Adverse events, such as choroidal detachment, shallow anterior chamber and hyphema, were reported from 4 trials. None of the trials reported quality of life or economic data. These trials were neither designed nor reported well overall. Two trials were quasi-randomized trials and judged to have high risk of selection bias; 4 trials were at unclear or high risk for performance bias and detection bias; and these researchers judged 1 trial to have high risk of attrition bias due to high proportions of losses to follow-up. Due to poor study design and reporting, the reliability and applicability of evidence remain unclear. The authors concluded that no conclusions could be drawn from the trials included in this review due to paucity of data. They stated that more research is needed to determine which of the many surgeries performed for PCG are effective.
Tan and colleagues (2016) stated that childhood glaucoma is known to be one of the most challenging conditions to manage. Surgical management is more complicated than in adults because of differences in anatomy from adults along with variations in anatomy caused by congenital and developmental anomalies, wide-ranging pathogenetic mechanisms, a more aggressive healing response, and a less predictable post-operative course. Challenges in post-operative examination and management in less co-operative children and the longer life expectancies preempting the need for future surgeries and re-interventions are also contributing factors. Angle surgery is usually the 1st-line treatment in the surgical management of primary congenital glaucoma because it has a relatively good success rate with a low complication rate. After failed angle surgery or in cases of secondary pediatric glaucoma, options such as trabeculectomy, glaucoma drainage devices, or cyclo-destructive procedures can be considered, depending on several factors such as the type of glaucoma, age of the patient, and the severity and prognosis of the disease. Various combinations of these techniques have also been studied, in particular combined trabeculotomy-trabeculectomy, which has been shown to be successful in patients with moderate-to-advanced disease. Newer non-penetrating techniques, such as viscocanalostomy and deep sclerectomy, have been reported in some studies with variable results. The authors concluded that further studies are needed to evaluate these newer surgical techniques, including the use of modern minimally invasive glaucoma surgeries, in this special and diverse group of young patients.
The current UpToDate review on “Open-angle glaucoma: Treatment” (Jacobs, 2016) still does not mention viscocanalostomy and phacoviscocanalostomy as therapeutic options.
Canaloplasty for the Treatment of Uveitic Glaucoma
Lommatzsch and colleagues (2016) noted that glaucoma is a common vision-threatening complication of uveitis. In a pilot study, these investigators examined the outcome of canaloplasty in patients with chronic uveitis and uncontrolled secondary glaucoma. This was a retrospective study of 12 patients with medically uncontrolled secondary glaucoma who underwent canaloplasty (14 treated eyes), with follow-up of greater than or equal to 24 months. The primary outcome measure was complete and qualified (requirement for anti-glaucomatous medication) surgical success rates, as determined by a reduction in IOP and the need for anti-glaucomatous medication. Secondary outcome measures were uveitis activity, best-corrected visual acuity (BCVA), vision-threatening complications, and secondary glaucoma surgery. Canaloplasty resulted in a significant IOP reduction, from a mean pre-operative baseline level of 27.1 ± 12.3 mmHg to a mean of 14.5 ± 4.3 mmHg (p = 0.01) at 24 months. Complete success (limit of 15 mmHg) was achieved in 6 patients and qualified success in 1 patient. However, failure was noted in 5 patients, 2 of whom required additional glaucoma surgery. Topical anti-glaucomatous medications were reduced from 2.7 ± 1.2 (mean ± SD) at baseline to 0.6 ± 1.2 at 24 months (p = 0.007). Uveitis activity did not increase after surgery; BCVA was not reduced; cataract progressed in 2 patients. The authors concluded that at 2-year follow-up, overall success rate was 58 % (IOP less than or equal to 15 with or without medication), and surgery failed in 5 eyes, 2 eyes requiring additional glaucoma surgery. No harmful complications or worsening of uveitis activity were noted. These preliminary findings from a small (n= 12 patients) pilot study need to be validated by well-designed studies.
Canaloplasty for the Treatment of Normal-Tension Glaucoma
The Academy of Ophthalmology’s Preferred Practice Pattern on “Primary open-angle glaucoma” (AAO, 2016) stated that there are benefits to lowering IOP even in persons with normal-tension glaucoma.
Viscocanalostomy / Phacoviscocanalostomy for the Treatment of Glaucoma
In a retrospective study, Qian and colleagues (2017) evaluated the long-term outcome of viscocanalostomy combined with trabeculotomy (VCT) and mitomycin C in the treatment of PCG. A total of 42 eyes of 26 patients with PCG were enrolled; IOP, corneal diameter (mm) and cup/disc (C/D) were measured before and after the surgery respectively. Follow-up period was 30 months. The mean pre-operative IOP was 30.6 ± 7.35 mm Hg. Of the 42 eyes, 2 eyes were required conversion to trabeculectomy for the absence of Schlemm's canal. Of remained 40 eyes, 38 eyes (95 %) achieved successful IOP control. The average post-operative IOP was 11.69 ± 4.18 mm Hg at 12 months. The mean reduction was 18.91 mm Hg (p < 0.0001); 18 (75 %) eyes presented a reduction in corneal diameter, and 25 (62.5 %) eyes presented a C/D ratio reversal after the surgery. There was no serious complication in any patients over the follow-up period. The authors concluded that the findings of this study demonstrated that VCT was safe and effective in controlling infantile glaucoma, and it could be an alternative choice for infantile glaucoma procedure in the future although controlled studies with large subject numbers and long follow-up period are needed.
Ho and associates (2017) evaluated the efficacy of viscocanalostomy/phacoviscocanalostomy (VC/PVC) in lowering IOP in patients with normal tension glaucoma (NTG). These investigators carried out a retrospective electronic database review of patients who underwent VC/PVC for NTG between December 2009 and November 2011 at Stanley eye unit in Abergele Hospital. Goldmann applanation tonometry (GAT) was used for all IOP measurements, which were taken at the time of listing for surgery and at 1 day, 1 week, 1 month, then 3-monthly up to 1 year, then half-yearly up to 3 years post-operatively. Statistical analysis was performed using unpaired t-test. A p value of < 0.05 was accepted as the level of significance. Operations were performed on 94 eyes from 67 patients over the study period. The mean age at the time of surgery was 76.4 years. Pre-operative IOP was 17.75 ± 2.19 mmHg (range of 12 to 21 mmHg); 3 year follow-up showed a mean IOP of 13.41 ± 2.22 mmHg (range of 8 to 18 mmHg). By year 3, a total of 17 patients needed laser gonio-puncture and 25 patients needed anti-glaucoma drops; IOP was reduced by 24.4 % at 3 years post-surgery, which was statistically significant (p < 0.0001). The authors concluded that from these findings, which showed a 24.5 % reduction in IOP at 3 years with 12 % complication rate, they proposed that a logical surgical management for NTG patients would be viscocanalostomy, thereby keeping trabeculectomy as an alternative.
The authors stated that this study had several drawbacks. First, it was a retrospective study. In addition the patients in this study were from a different population, without any control group compared to other studies. This might make interpretation of these findings with other study populations difficult. Post-operative evaluation including tonometry was not masked and therefore subject to observer bias. Second, this study did not consider analysis of phakic versus pseudophakic eyes, as study participants included only 6 phakic eyes within the VC subgroup, compared to 88 pseudophakic eyes either from previous cataract operations or as a result of combined PVC surgeries. These researchers considered the number of phakic eyes to be too low to draw any statistical conclusions with sufficient power. Third, VA was not analyzed in this study. Lastly, visual field analysis in previous papers was performed using various methods, making it difficult to directly compare the visual field analysis from this study.
Viscocanalostomy and Combined Phacoemulsification with Viscocanalostomy in the Treatment of Uveitic Glaucoma
El Salloukh and colleagues (2021) noted that uveitic glaucoma commonly leads to a more intense optic nerve damage than other types of glaucoma, resulting in glaucomatous optic nerves and visual field defects. Anterior uveitis is the most commonly associated risk factor. Surgical intervention is usually indicated when all medical treatment has failed. In a retrospective, case-series study, these investigators reported 5-year results for 16 eyes of uveitic glaucoma managed with viscocanalostomy (VC)/phaco-viscocanalostomy (PVC). All patients were managed surgically with either VC or PVC. Outcomes evaluated included IOP measurement pre-listing, on day 1, year 1 to year 5. Complete success rate was defined as achieving an IOP lower than 21 mmHg or reduced by 30 % without medications, and qualified success was achieved when IOP was lower than 21 mmHg or a reduction in IOP of 30 % with topical medical therapy ± laser gonio-puncture (LGP). If further surgeries were required to reduce IOP due to glaucoma progression, then they were classified as a failure. A total of 16 patients with uveitic glaucoma were reviewed. Complete success was observed in 75 % of patients at year 1, 50 % of patients at year 3 and 19 % of patients in year 5. Conversely, qualified success was achieved in 94 % of patients at year 1, 86 % of patients at year 3 and 75 % of patients at year 5. In the group of patients requiring further surgery, 50 % of patients had previous surgeries, including cataract surgery, trabeculectomy and viscocanalostomy. There was a mean number of 4 pre-operative drops before their primary surgery and a mean drop in eye medications of 1.1 at 5 years follow-up. Success rates were prognostically linked to lower mean number of interventions and lower percentage of previous surgeries. The authors concluded that there remains a significant paucity of information in the utilization of PVC in uveitic glaucoma. The advantage of NPGS includes the lack of entry into the anterior chamber and the avoidance of an iridectomy that may reduce intra-ocular inflammation and post-operative complications. This study showed that non-penetrating surgery was successful in treating advanced uveitic glaucoma.
The authors stated that there are several limiting factors in this study. This was a retrospective case-series study with limited sample size (n = 16 eyes) and the included eyes were heterogeneous based on type of uveitis, type of procedure and lens status. None of the subjects was on immune-modulating medication and this may have affected the success rate. Furthermore, of relevance was that these investigators only had idiopathic uveitis and Fuch’s heterechromic cyclitis (FHC) and hence a direct comparison with other studies (with different uveitic etiology) was not possible. The limited sample size, heterogeneous subjects further reduced the possibility for analytical approach to the data. In addition, these findings were of surgery in a subset of patient with mild form of uveitis and could not be generalized to other types of uveitis.
Gallardo et al (2022a) noted that between 2010 and 2019, the Hispanic demographic increased in the U.S. from 16 % to 18 %. Hispanic ethnicity accounted for 52 % of U.S. population growth over this period. By 2035, Hispanic men will be the largest POAG demographic; by 2050, Hispanics will account for 50 % of POAG. Glaucoma in the Hispanic population is more prevalent than for non-Hispanic Whites with a higher proportion undiagnosed. While the Hispanic demographic is growing there remains much to be learned regarding specific risk factors for OAG in this population and how they may differ between the Hispanic and non-Hispanic White demographics. Population differences may have an effect on response to medical or surgical therapeutics; thus, it is important to understand the safety and effectiveness of glaucoma therapeutics within this significant demographic. Available evidence on the performance of various minimally invasive glaucoma surgeries in the Hispanic population remains relatively sparse. In a single-center, single surgeon study, these investigators reported the 12-month outcomes for canaloplasty followed by trabeculotomy (OMNI Surgical System) in conjunction with cataract surgery in a Hispanic (Northern Mexico/mestizo) OAG population from El Paso (TX). A total of 39 subjects were treated and followed for 12 months (March 2019 to April 2021). Demographics aside from ethnicity were similar to those for the GEMINI study as a whole; mean age and percentage female were 68.3 years, 60 % in GEMINI and 69.2 years, 51 % in this subset. Average [SD} Visual Field Mean Deviation and Pattern Standard Deviation were −3.9 [3.5] dB and 3.2 [2.1] dB compared to −3.7 [3.6] dB and 3.7 [2.6] dB for the GEMINI study as a whole. It was noted that nearly all (39/41, 95 %) of subjects self-reporting as Hispanic in the GEMINI study were included in the present single-center analysis. Before washout, mean IOP was 16.5 (2.8) mmHg on average 2.0 (1.1) medications. Unmedicated mean (SD) DIOP was 22.8 mmHg (2.5) pre-operatively and 14.9 (3.6) at 12 months, (-7.9 mmHg, -35 %, p < 0.001). Most (38/39, 97 %) had an IOP reduction, and 85 % had 20 % or greater reduction. Medications were reduced to 0.15 (0.43, -93 %, p < 0.001). The majority (87 %) of patients needed no medications. There were no SSI; AEs were mild, self-limiting and typical of MIGS combined with cataract surgery; IOP increased 10 mmHg or more at 1 month or longer (2, 5.1 %), mild inflammation (3, 7.6 %), and hyphema 1 mm or greater (1, 2.6 %). The authors concluded that these findings were derived from a single-center, single-surgeon dataset. These researchers stated that results from other centers and confirming studies are needed; longer-term data to establish effect durability would be desirable. However, within the 12 months of follow-up, no SSI was needed; and medication re-introduction was limited to 5 of 39 patients suggesting that the therapeutic effect was not diminishing.
These investigators stated that this trial was a case-series of patients undergoing the OMNI procedure in conjunction with cataract surgery; thus, it was not possible with the current dataset to know the relative contributions of the OMNI procedure and of cataract surgery to the observed IOP lowering. However, a recent systematic review and meta-analysis of 32 studies including 1,826 patients (Armstrong et al, 2017) found that cataract surgery alone could provide a 14 % reduction in IOP at 12 months post-surgery in contrast to the 35 % reduction observed in the present study. The OMNI device is a safe, implant-free MIGS combining trabeculotomy and canaloplasty. The present analysis indicated that the favorable safety and effectiveness for OMNI reported in the broader population (Gallardo et al, 2021) was also observed in Hispanic patients.
Dickerson et al (2024) examined if there was an association between severity of glaucoma and IOP and medication (med) outcomes for patients in the ROMEO (Retrospective, Observational, Multicenter Evaluation of OMNI) Trial, which entailed 11 ophthalmology practices in 8 U.S. states. These investigators carried out post-hoc analysis of all eyes enrolled and treated with ab interno canaloplasty and trabeculotomy in the retrospective, multi-center ROMEO Trial. Eyes were grouped according to visual field mean deviation (MD): mild (MD better than -6 dB), moderate (MD between -6 and -12 dB), advanced (-12 dB or worse). IOP and med outcomes at 12 months were compared across groups. Least squares regression was used to examine the relationship of MD with month-12 IOP. Outcomes for 1st and last MD deciles were compared as a sensitivity analysis. A total of 127 eyes were available for analysis including 79 mild, 42 moderate, 6 advanced. Most eyes had a reduction in IOP at month-12 (70 %) with most at 18 mmHg or less. Percentage IOP reduction was similar across the groups (mild 16.9 %, moderate 18.6 %, and advanced 18.0 %) with mean month-12 IOP between 14 and 16 mmHg. Medications were also reduced in all 3 groups; -0.8 (mild, p < 0.001), -0.55 (moderate, p < 0.05), and -1.0 (advanced, p = 0.139, ns). Regression analysis revealed no relationship between month-12 IOP and MD. Med reductions were observed for all groups with a reduction of 1 or more medications observed in (%, 95 % CI) 69 %, 59 to 79 (mild), 50 %, 35 to 65 (moderate), and 60 %, 21 to 99 (advanced). Secondary interventions tended to have greater incidence with worse MD likely reflecting lower desired IOP targets. The authors concluded that analysis of data from the ROMEO Trial suggested that similar meaningful IOP and med reductions could be expected across the range of disease severity studied. Moreover, these researchers stated that confirmation of these findings through additional studies, with a greater representation of patients with advanced field loss, is needed to determine the role of MIGS in glaucoma patients with advanced disease.
The authors stated that this study had 2 main drawbacks. First, this was a post-hoc analysis of a retrospective study. However, the study included all available eligible patients treated with OMNI; therefore, mitigating the risk of selection bias. Also, this was a multi-center study; thus, mitigating the risk of investigator or center bias. Moreover, a retrospective study of patients treated in actual clinical practice, in the authors’ view, provided data more generalizable to the actual outcomes others may obtain with OMNI. Second, the majority of patients in this study were mild or moderate with a small number of patients having advanced visual field loss, extrapolation of these findings were therefore limited. Nevertheless, these researchers felt confident that for the range of visual field deficits included, the study conclusions were valid.
Corticosteroid-Induced Glaucoma
Brusini and colleagues (2018) presented the mid-term results of canaloplasty in a small cohort of patients with corticosteroid-induced glaucoma (CIG). A total of 9 eyes from 7 patients with various types of CIG in maximum medical therapy underwent canaloplasty. Patients underwent complete ophthalmic examination every 6 months. Success was defined as: post-operative IOP of less than or equal to 21 mmHg and less than or equal to 16 mmHg without ("complete success"), and with/without medical treatment ("qualified success"). The IOP reduction had to be greater than or equal to 20. The number of medications before and after surgery was considered. The follow-up mean period was 32.7 ± 20.8 months (range of 14 to 72 months). The pre-operative mean IOP was 30.7 ± 7.2 mmHg (range of 24 to 45). The mean IOP at 6 and 12-month follow-up was 13.1 ± 2.6 mmHg, and 13.7 ± 1.9 mmHg, respectively. Qualified and complete success at 6 and 12 months was 100 % for both of the 2 definitions. The number of medications used pre-operatively and at the 12-month follow-up was 4.3 ± 0.7, and 0.2 ± 1.0, respectively. No serious complication was observed. The authors concluded that the mid-term results of canaloplasty in patients with CIG appeared to be very promising. They stated that canaloplasty should be considered as a possible alternative to filtering surgery in this form of glaucoma, when medical therapy is not sufficient to maintain the IOP within reasonable limits. Moreover, they stated that the study is currently still underway. New patients with CIG that fit the inclusion criteria are being added and follow-up data of existing patients are being constantly updated to provide long-term results and a larger cohort for the future study. Regarding these patients, multi-centric randomized studies with a larger population, where canaloplasty is compared to gold standard surgery (trabeculectomy), are needed to draw more definite and robust conclusions.
The authors stated that even the results obtained were very promising, it should be remembered that this was a non-randomized study with a small sample of patients (n= 9 eyes) without a control group. Another drawback of this study was that both eyes of 2 patients had been considered. Even if this could be incorrect from a statistical point of view, considering the small number of patients treated, these researchers decided to describe all cases they treated with this surgical procedure.
Stegmann Canal Expander for Canaloplasty
In a non-comparative, prospective study, Grieshaber and colleagues (2017) examined longer-term post-surgical safety and efficacy of a new expander for Schlemm's canal (SC). A total of 42 White patients with medically uncontrolled POAG underwent primary canaloplasty with greater than 2-year follow-up. The bleb-independent procedure comprised catheter-assisted canaloplasty and implantation of 2 Stegmann Canal Expanders to maintain trabecular distension and canal patency over 180°; IOP, glaucoma medication use and complications were assessed. Mean IOP was 26.8 ± 5.6 mmHg pre-surgery, 12.8 ± 1.5 mmHg at 6 months, 13.2 ± 1.2 mmHg at 12 months and 13.3 ± 2.5 mmHg at 24 months (p < 0.001). Rate of complete success, defined as IOP less than or equal to 21, less than or equal to 18, and less than or equal to 16 mmHg and a ≥ 30 % IOP reduction, was 85 % (95 % CI: 0.76 to 0.95), 85 % (0.76 to 0.95) and 82 % (0.70 to 0.96) at 12 months and 83 % (0.73 to 0.94), 80 % (0.70 to 0.92) and 80 % (0.70 to 0.92) at 24 months. Pre-operative factors were not significant predictors of less than or equal to 16 mmHg IOP reduction: IOP (hazard ratio [HR]: 0.68; 95 % CI: 0.44 to 1.04; p = 0.08), mean visual defect (1.06; 0.90 to 1.20; p = 0.47), number of medications (0.59; 0.17 to 2.14; p = 0.42) and age (0.96; 0.87 to 1.13; p = 0.41). Number of medications dropped from 2.8 ± 0.4 pre-surgery to 0.2 ± 0.5 post-surgery (p < 0.001). Mean pre-operative BCVA was 0.19 ± SD 0.21 (range of 0 to 1.6), and logMAR was similar to 0.23 ± 0.16 (range of 0 to 1.6; p = 0.42) after a mean follow-up of 27.4 months. Complications included peripheral Descemet's membrane detachment (7.2 %) and trimming of the expander (4.7 %) during surgery, and transient micro-hyphema (23.8 %) and IOP elevation (7.2 %) post-surgery. The authors concluded that canaloplasty with the Stegmann Canal Expander was a safe and effective procedure to reduce IOP in White patients with moderate-to-advanced POAG; however, comparative, randomized trials are needed to draw final conclusions.
The authors stated that in spite of the promising findings, the results of this study need to be interpreted with caution due to study limitations. First, the study design was un-masked and non‐comparative; thus, it lacked a control group, namely standard canaloplasty. Second, the Stegmann Canal Expander has only been evaluated in White patients with POAG undergoing primary surgery, thus, the results could not be extrapolated to patients of other ethnicity, to eyes with other types of glaucoma, or to eyes with previous surgery, which could have impeded cannulation of SC and implantation of the device. Furthermore, it should be noted that the surgeons in this study had many years of experience with non‐penetrating glaucoma surgery, and thus, the results did not include the long learning curve related to the dissection of the scleral flaps and preparation of the Descemet's membrane window.
Grieshaber (2018) stated that the concept of canaloplasty is to increase aqueous egress through all structures that control the aqueous outflow, such as the trabecular meshwork, SC, and collector channels, by viscomodulation and by placing of a suture stent into the canal. Clinical studies showed canaloplasty to be safe and efficient in lowering the IOP; however, proper knotting of the tensioning suture is technically challenging and even impossible if circumferential cannulation cannot be achieved. Furthermore, protrusion of the suture stent is a potential lifelong risk. The specific design of the Stegmann Canal Expander allows a permanent expansion of the canal and distension of the trabecular meshwork; 2 expanders are implanted on either side of the surgically created ostium of SC to treat half of the circumferential outflow system. The author described the technique step-by-step, provided the clinician with surgical pearls, and highlighted the management of adverse events (AEs). This investigator noted that technically, implantation of the Stegmann Canal Expander was simple and did not require a long learning curve, compared to placing and knotting a tensioning suture. Most issues were related to the 2-flap dissection technique (deep sclerectomy technique) and not to implantation of the Stegmann Canal Expander; and IOP reduction without medications to the low teens could be achieved. The authors concluded that Stegmann Canal Expander is a novel micro-device that has the potential to make canaloplasty a simplified, more controlled, and reproducible surgical procedure.
Furthermore, an UpToDate review on “Open-angle glaucoma: Treatment” (Jacobs, 2019) does not mention canal expander as a management tool.
Combined Phacoemulsification and Viscocanalostomy with Ologen Implant
In a prospective, interventional, randomized clinical study, Gad and colleagues (2019) examined the efficacy of the biodegradable collagen implant Ologen as an adjuvant in phaco-viscocanalostomy in patients with co-existing cataract and POAG. This trial entailed patients with co-existing cataract and glaucoma who were randomized to receive either phaco-viscocanalostomy (Phacovisco group) (39 eyes) or phaco-viscocanalostomy with Ologen implant (OloPhacovisco group) (40 eyes). Follow-up period was 2 years; Nd:YAG laser gonio-puncture was performed in cases where the IOP was elevated above 21 mmHg after discontinuation of corticosteroid eye drops at any follow-up visit. No significant operative or post-operative complications (other than failure) were encountered in either group. At 2 years follow-up, the mean IOP level was statistically significantly decreased in the OloPhacovisco group (p = 0.02) and complete success occurred in 23 eyes (59.0 %) in the Phacovisco group and in 32 eyes (80.0 %) in the OloPhacovisco group. There was a statistically significant higher success rate regarding complete success in patients that received Ologen implant (p = 0.04). The authors concluded that Ologen implant improved the success rate of phaco-viscocanalostomy. Moreover, these researchers stated that larger studies with longer follow-up periods are needed to confirm the safety and efficacy of this device in viscocanalostomy. The main drawbacks of this study were the relatively small sample size (40 eyes in the OloPhacovisco group) and short follow-up period (2 years).
Ab Interno Canaloplasty (ABiC)
In a retrospective, cohort outcome study, Davids and colleagues (2019) examined if the ab interno canaloplasty (ABiC) is a reasonable minimally invasive method to significantly reduce the IOP and number of anti-glaucomatous medications over a certain period of time in adults with POAG. A total of 36 eyes of 28 POAG patients (mean age of 74.8 ± 9.3 years) with an IOP above target pressure were included; ABiC was performed in all subjects as sole procedure in pseudophakic eyes (n = 20) or in combination with cataract surgery in phakic eyes (n = 16); IOP and the number of anti-glaucomatous medications were evaluated pre-operatively, day 1, week 6, month 3, month 6, and month 12. IOP decreased from 19.8 ± 4.1 to 13.8 ± 3 mmHg at 12 months follow-up (n = 21, p < 0.001). The IOP reduction showed significant results at all time-points (1 day p < 0.001; 6 weeks p < 0.001; 3 months p < 0.001; 6 months p = 0.001; and 12 months p < 0.001). Glaucoma therapy was stabilized at 2.1 ± 1.6 number of anti-glaucomatous medications after 12 months post-operatively. There was no significant difference in the number of anti-glaucomatous medication at 12 months follow-up (p = 1.0). No major peri-operative complications were reported. The authors concluded that the ABiC effectively lowered the IOP in POAG in the short-term follow-up of 12 months; however, a reduction of glaucoma therapy could not be attained and should be discussed with the patients before surgery.
Canaloplasty for the Treatment of Pseudo-Exfoliation Glaucoma
Hasanov and Kasimov (2018) examined the safety and efficacy of phaco-canaloplasty in patients with concomitant advanced pseudo-exfoliation glaucoma and cataract. The study included 56 patients (57 eyes) who underwent phaco-canaloplasty guided by Glaucolight microcatheter. All patients were followed up for 48 months. Visual acuity (VA), changes of intra-ocular pressure (IOP), use of glaucoma medications, incidence of complications, as well as post-surgical interventions were examined. Mean pre-operative IOP decreased significantly from 29.8 mmHg (15.8 to 61.6) with a mean of 1.92 (0 to 3) glaucoma drops to 12.9 mmHg (11.0 to 19.6) with a mean of 0.12 (0 to 3) drops, respectively 48 months after phaco-canaloplasty. Mean VA increased from pre-operative 0.15 (0.01 to 0.8) to 0.6 (0.01 to 1.2). The most frequent complications included intra-operative perforation of Descemet's membrane (4 eyes, 7 %) and hyphema (37 eyes, 65 %), IOP spikes (4 eyes, 7 %) and inflammation (4 eyes, 7 %) in the early post-operative period. The authors concluded that phaco-canaloplasty in eyes with concomitant advanced pseudo-exfoliation glaucoma and cataract re-established the natural outflow system and led to significant IOP reduction with minimal risk of intra- and post-operative complications.
Gabai et al (2019) carried out a meta-analysis on the safety and efficacy of trabeculectomy (TE) and non-penetrating glaucoma surgery (NPGS) techniques in patients with primary open-angle glaucoma (POAG), pseudo-exfoliation glaucoma, pigmentary glaucoma, and normal-tension glaucoma. All studies were identified by searching electronic sources (PubMed, Medline, Scopus, and Embase) until February 5, 2018. Primary outcome was mean IOP reduction at 6, 12, and 24 months. Complications, number of anti-glaucomatous medications, and visual outcomes were also evaluated. A total of 21 studies were included; 10 studies compared TE with deep sclerectomy (DS), 5 with viscocanalostomy (VC), 1 study with both DS and VC, and 5 with canaloplasty (CP). TE was superior to DS, VC, and CP in reducing IOP at 6 and 12 months, and to DS at 24 months. When comparing TE to VC and to CP at 24 months, there was no significant difference in IOP reduction. Hypotony, choroidals, anterior chamber shallowing or flattening, and cataract formation or progression were more associated with TE than with NPGSs. TE was more effective in reducing anti-glaucomatous medications than VC and CP. The authors concluded that TE was more effective in reducing IOP; and it presented a higher risk of complications as compared with NPGS, except for hyphema.
Kodomskoi et al (2019) noted that significant IOP reduction was achieved using a novel suture-probe canaloplasty (SPCP) procedure in patients with glaucoma. The effect and low rate of surgical complications were comparable with those of iTrack canaloplasty. Ab externo canaloplasty using the iTrack microcatheter has been established as a safe surgical procedure to treat OAG. These researchers described the results of a novel technique using a cost-efficient suture-probe as an alternative to iTrack canaloplasty and presented 12-month follow-up results. SPCP was carried out on 50 eyes of 50 patients with POAG, pseudo-exfoliation glaucoma, and steroid-induced glaucoma. The mean ± SD pre-operative IOP was 21.9 ± 7.0 mm Hg. A suture-probe was used to dilate Schlemm canal and to place a trabecular tensioning suture. Post-operative results were noted and statistically analyzed on the day of discharge from the clinic, and at 1.5, 3, 6, and 12 months of follow-up. In all eyes, the mean post-operative IOP 12 months after SPCP was 13.7 ± 3.0 mm Hg. The number of medications decreased from 2.8 ± 0.9 to 0.1 ± 0.4, and VA was 0.3 ± 0.3 logMAR. Post-operative course and complications included: hyphema of greater than 1 mm (2 %); micro-hyphema (4 %); bleb leakage (2 %); bleb suture (2 %); laser gonio-puncture (18 %); laser suture lysis (4% ); scleral flap lifting (4 %); and iris incarceration following laser gonio-puncture (4 %). The authors concluded that SPCP was an inexpensive procedure that could achieve significant IOP reduction in patients with glaucoma. The IOP-lowering effect and low rate of surgical complications were very similar to those of iTrack canaloplasty.
Seuthe et al (2021) examined the long-term safety and efficacy of the modified canaloplasty technique with additional supra-choroidal drainage in patients with pseudo-exfoliation glaucoma. This retrospective clinical trial included 131 patients with pseudo-exfoliation glaucoma who underwent canaloplasty with supra-choroidal drainage (scD). A total of 111 of 131 patients underwent the follow-up examination after 48 months. Primary endpoints were the pressure-lowering and drug-sparing effect as well as the success rates. Secondary endpoints were intra- and post-operative complications and the occurrence of secondary surgical interventions. The IOP was reduced by 45.8 % after 12 months (from baseline 23.4 ± 5.1 mmHg to 12.7 ± 2.2 mmHg) and by 45.1 % after 4 years (12.8 ± 2.2 mmHg) (p < .001). The mean number of IOP-lowering medication decreased significantly from 3.4 at baseline to 0.6 after 12 months and to 1.0 after 4 years. The IOP-reducing effect was even stronger in those cases in whom canaloplasty+ scD was combined with cataract surgery (49.4 % after 12 months and 47.6 % after 4 years). No serious complications were observed. The authors concluded that the modified surgery technique of canaloplasty with supra-choroidal drainage was a safe and effective way of reducing IOP in patients with pseudo-exfoliation glaucoma.
Furthermore, an UpToDate review on “Open-angle glaucoma: Epidemiology, clinical presentation, and diagnosis” (Jacobs, 2021) states that “Other possible risk factors for developing open-angle glaucoma include myopia, pseudo-exfoliation, low diastolic perfusion pressure, cardiovascular disease, a history of prior vitreoretinal surgery, and hypothyroidism”.
Canaloplasty and Trabeculotomy Ab Interno with the OMNI System Combined with Cataract Surgery for the Treatment of POAG
Brown et al (2020) stated that micro-catheterization and viscodilation of Schlemm canal or canaloplasty has been shown to reduce intra-ocular pressure (IOP) in open-angle glaucoma (OAG). In separate studies, trabeculotomy carried out with a catheter or a suture has been shown to lower IOP. The OMNI Surgical System was the 1st micro-invasive glaucoma surgery device that enables surgeons to carry out canaloplasty and trabeculotomy in succession with a single instrument. These investigators reported the early results with this multi-modal surgical technology. Eyes with OAG underwent phacoemulsification combined with 180 degrees of canaloplasty, followed by 180 degrees of trabeculotomy using the OMNI device. The pre-operative IOP was determined by the mean value of IOPs from the 2 visits before surgery measured using a Goldmann applanation tonometer. The post-operative IOP was determined by the mean value of IOPs from the last 3 post-operative visits. The pre-operative IOP was used to stratify the eyes into 3 groups. In each group, a paired 1-sample t-test was used to examine if there were statistically significant changes in IOP compared with baseline as a result of the operation. The study evaluated 41 eyes (24 patients). The mean IOP reduction in all eyes was 5.6 ± 4.5 mm Hg (p < .001). The mean follow-up was 4.1 ± 1.9 months. There was a significant correlation between the magnitude of IOP reduction and pre-operative IOP that was best described by a linear relationship (R2 = 0.7, p < .001). In eyes with a pre-operative IOP higher than 22 mm Hg, the mean IOP reduction was 9.6 ± 3.5 mm Hg (p < .001). In eyes with a pre-operative IOP higher than 16 mm Hg, 100 % had a decrease in IOP post-operatively. There were no complications related to cataract surgery. There were 2 cases of hyphema (4 %) that cleared within 1 week. There was no protocol for reducing medication usage post-operatively. The mean number of medications decreased slightly; however, this was not significant. No eye has required secondary glaucoma surgery. The authors concluded that this study found that OMNI combined with phacoemulsification reduced IOP. The magnitude of pressure lowering with OMNI was highly correlated with the pre-operative IOP. This was a similar finding to a previous study of the original iStent. However, the phaco-OMNI surgery had a mean overall IOP reduction of 5.6 mm Hg, whereas the mean phaco-iStent IOP reduction was 3.2 mm Hg.
These investigators stated that the decision to carry out 180 degrees of OMNI in combined surgery was based on the objective of maximizing efficacy while minimizing the extent of surgery and to conduct a smaller rather than a larger procedure. Some surgeons may choose to perform 360 degrees of canaloplasty with 180 degrees of trabeculotomy or some other combination. The extent of trabeculotomy and canaloplasty could be titrated easily depending on the clinical context. Patients in this study generally had mild-to-moderate glaucoma; however, some had more advanced disease. Follow-up was limited (mean of 4.1 months) because the OMNI device has only been available in the U.S. since mid-2018. There was no protocol for reducing medications; however, the level of pressure reduction suggested that some patients may benefit from a reduction in medications. However, longer-term studies are needed to examine the durability of reduction in IOP and the opportunity for decreasing the medication burden. Moreover, these researchers stated that the OMNI device may give surgeons a safe, implant-free micro-invasive glaucoma surgery option for combining trabeculotomy and canaloplasty in a single procedure. Combined with phacoemulsification the device reduced IOP more in eyes with higher pre-operative pressures; thus, eyes with the greatest need for IOP reduction may experience the greatest benefit.
In a retrospective, single-center, consecutive, case-series study, Hughes and Traynor (2020) reported treatment outcomes of ab interno canaloplasty using the Visco360 and Omni system devices as a standalone procedure or combined with cataract surgery in patients with open-angle glaucoma (OAG). A total of 89 eyes of 64 patients aged 43 to 91 with OAG treated with ab interno canaloplasty between January 2018 and September 2019 were included in this trial. Eyes with previous incisional glaucoma surgery and eyes with less than 90 degrees of viscodilation were excluded. Patients underwent ab interno canaloplasty as a stand-alone procedure or in conjunction with cataract surgery. Ab interno canaloplasty was carried out with either the Visco360 or Omni System devices. Treatment consisted of viscodilation without trabeculotomy. Primary outcome measures were mean IOP and mean number of glaucoma medications. Additional analysis included the impact of degrees of treatment on health outcomes. Pre-operative mean IOP was 24.5 ± 8.3; the number of pre-operative glaucoma medications was 2.5 ± 1.3. At 18 months post-operative, the mean IOP was reduced 36 % to 15.8 ± 2.5 (p < 0.001) and glaucoma medications were reduced 32 % to 1.7 ± 1.5 (p < 0.05). Higher pre-operative IOP was significantly correlated with increased IOP lowering. Reduction of mean IOP and medications were not significantly different between standalone ab interno canaloplasty versus cataract surgery/ab interno canaloplasty. Reduction of mean IOP and medications were not significantly different between patients with 180 degrees of treatment vs 360 degrees of treatment. The authors concluded that ab interno canaloplasty reduced IOP and glaucoma medication use in patients with OAG whether as a standalone surgery or in combination with cataract surgery.
The authors stated that study limitations included the relatively small number of standalone surgery eyes. Nevertheless, the standard deviation at 18 months for this group was similar to that for the overall group providing some confidence in the point estimate for the mean. With 72 eyes in the combined with cataract group, the results were reasonably robust. This study was also limited by the weaknesses inherent to retrospective studies including selection bias and variable follow-up. To mitigate against this potential bias, all eligible patients were included with minimal exclusion criteria. Both eyes from a given patient were included in the analysis when each eye met the eligibility criteria; thus, complete independence of all variates was not satisfied. The consequence of this was potential under-estimation of variability in the findings; however, the measured standard deviation for the IOP at baseline was greater than generally observed in published studies (e.g., 3 to 4 mmHg) arguing against such bias. Nevertheless, this potential bias should be considered when interpreting the results. In the authors’ view, the increased number of surgical cases and the consequent greater likelihood of revealing infrequent safety issues more than balanced this weakness. The study did not attempt to explain how ab interno canaloplasty reduced IOP; and there was no further investigation to understand why some eyes were not able to receive a full circum-navigation of 360 degrees.
The retrospective, multicenter ROMEO study evaluated the 12‑month safety and effectiveness of stand‑alone canaloplasty followed by trabeculotomy using the OMNI Surgical System in pseudophakic patients with mild to moderate open‑angle glaucoma (Vold et al., 2021). The primary objective was to assess whether this sequential ab interno procedure could achieve meaningful intraocular pressure (IOP) reduction or maintain IOP control while reducing medication burden in patients undergoing glaucoma surgery without the confounding IOP‑lowering effect of cataract extraction. The study reviewed medical records from 48 pseudophakic eyes treated across 10 U.S. ophthalmology practices. Eligible patients had open‑angle glaucoma, medicated baseline IOP ≤36 mmHg on up to four medications, and at least 12 months of follow‑up. Patients were stratified by baseline IOP into >18 mmHg (Group 1) or ≤18 mmHg (Group 2) to reflect differing treatment goals of pressure reduction versus medication reduction and IOP maintenance. The primary success endpoint was achieving either a ≥20% IOP reduction from baseline or an IOP between 6 and 18 mmHg at 12 months while using the same or fewer medications and without secondary surgical intervention. Secondary outcomes included mean IOP and medication changes, and safety assessments included best‑corrected visual acuity, adverse events, and need for reintervention. As a real‑world study, no medication washout was performed. Overall, 72.9% of patients met the primary success endpoint at 12 months. In Group 1, mean IOP decreased significantly from 21.8 to 15.6 mmHg (approximately 27% reduction), accompanied by a modest but statistically significant reduction in medication use. In Group 2, mean IOP remained stable (15.4 to 13.9 mmHg) while medication burden decreased significantly, with the proportion of medication‑free patients increasing three‑fold. Safety outcomes were consistent with expectations for angle surgery: adverse events were generally mild and transient, including inflammation, IOP spikes, hyphema, and corneal edema, and 10% of patients required secondary surgical intervention over 12 months. Visual acuity remained stable throughout follow‑up. Study limitations include its retrospective, single‑arm design without a control group, absence of standardized medication adjustment protocols, lack of medication washout, and relatively small sample size with only 12‑month follow‑up. These factors limit causal inference and long‑term durability assessment. However, the multicenter “real‑world” design enhances external validity and demonstrates that stand‑alone OMNI canaloplasty and trabeculotomy can provide clinically meaningful IOP control and medication reduction with an acceptable safety profile in pseudophakic patients.
In a retrospective, single-arm, multi-center study (ROMEO study), Hirsch and colleagues (2021) provided safety and effectiveness outcomes 12 months post-surgically for sequential canaloplasty and trabeculotomy with the OMNI System combined with cataract surgery in mild-to-moderate OAG. The trial was carried out in 11 ophthalmology practices and surgery centers located in 8 states (AL, AR, CA, KS, LA, MO, NY, TX). A total of 12 surgeons contributed 81 patients meeting eligibility criteria: OAG, 12-month follow-up, medicated IOP of less than or equal to 36 mmHg on less than or equal to 4 medications pre-operatively. Analysis stratified by baseline (BL) IOP; greater than 18 mmHg (group 1), less than or equal to 18 mmHg (Group 2). Success defined as proportion with greater than or equal to 20 % reduction in IOP, or IOP between 6 and 18 mmHg (inclusive) AND on the same or fewer medications without secondary surgical intervention (SSI). Other endpoints included mean IOP and medications at 12 months; and safety outcomes included BCVA and AEs. Primary success was met by 79 % (Group 1) and 81 % (Group 2). Mean IOP was reduced in Group 1 (21.9 to 15.1 mmHg, p < 0.0001), and remained controlled in Group 2 (14.1 to 13.4 mmHg, p = 0.3177). Medications went from 2.0 ± 1.3 to 1.1 ± 1.1 (Group 1) and from 1.6 ± 1.3 to 0.9 ± 1.2 (Group 2); AEs were typical for cataract or angle surgery: mild inflammation (11 %), IOP spikes (5 %), hyphema (4 %); and 4 patients (5 %) required an SSI. The authors concluded that OMNI system provided effective IOP reduction, sustained IOP control, and meaningful medication reduction for up to 12 months post-operative. The OMNI System provided the ability to perform a circumferential viscodilation and ab interno trabeculotomy. This newly introduced device showed promising preliminary results for the management of moderate and advanced glaucoma; however, limited data are currently available regarding its safety and efficacy because of the short time this device has been marketed.
In a prospective, institution review board (IRB)-approved, multi-center study, Pyfer et al (2021) analyzed diurnal IOP data (9 AM, 12 PM, and 4 PM) from a prospective 12-month trial of the OMNI Surgical System in OAG)patients with the aim of examining the effect of MIGS surgery on the amplitude of the diurnal IOP profile pre- and post-operatively. A total of 15 ophthalmology practices and surgery centers located in 14 states in the U.S. Subjects included patients treated with canaloplasty (360°) and trabeculotomy (180°). Patients had cataract and mild-to-moderate OAG with IOP of less than or equal to 33 mmHg on 0 to 4 hypotensive medications. Post-hoc analysis of diurnal IOP data from the multi-center GEMINI study. Analysis included comparison of IOP pre-operatively and at month 12 for each of the diurnal time-points, 9 AM, 12 PM, and 4 PM, change in magnitude of spread between the maximum IOP and minimum IOP for each patient and the proportions of patients pre-operatively and at month 12 with IOPs at or below 25, 21, 18, and 15 mmHg, average variability (standard deviation [SD] of the 9 AM, 12 PM, and 4 PM IOP) pre-operatively and at month 12. A total of 128 patients included in this analysis. IOP at each diurnal timepoint was significantly lower post-operatively (p < 0.0001). The difference between highest and lowest IOP measurement for each patient averaged 2.8 mmHg pre-operatively (SD 2.4, MAX 14, MIN 0) and 1.8 mmHg (SD 1.7, MAX 10, MIN 0) month 12 (p < 0.00001). The proportion with IOP less than or equal to 25, 21, 18, and 15 mmHg increased 75 % to 97 %, 27 % to 88 %, 1 % to 79 %, and less than 1 % to 56 %, respectively. The average variability was greater at all time-points pre-operatively (p < 0.0001). The authors concluded that the findings of this study demonstrated that eyes with OAG could benefit from an overall decreased IOP and degree of IOP fluctuations for as long as 12 months after surgical treatment with canaloplasty and trabeculotomy. Moreover, these researchers stated that further study with a greater sample size and longer follow-up are needed and ongoing. Study using other minimally (or micro) invasive glaucoma surgery (MIGS) procedures to determine the generalizability of these results are also needed.
The authors stated that this study had several drawbacks. First, analysis of fluctuation was not an a priori objective of the GEMINI study; however, these researchers had employed appropriate statistical analyses including testing for normality and using distribution-free methods where appropriate, controlling for multiplicity using Bonferroni correction, and limiting the data interrogation to focus on intra-patient IOP variability. Second, this study did not address progression; the GEMINI study was not designed to assess progression. Automated perimetry was performed at pre-operative baseline and at month 12 primarily for eligibility and safety reasons; however, there were no AEs for worsening of visual field mean deviation. Third, there was not an untreated control group. Including a “no treatment” or placebo control is problematic for ethical reasons in a 12-month long study such as GEMINI where patients have a progressive and potentially blinding disease. However, the analysis did compare pre-operative with post-operative IOP data for the same patients; effectively each patient serving as their own control. Finally, these findings suggested that MIGS could be effective in controlling IOP fluctuations; however, the data were restricted to eyes treated with canaloplasty and trabeculotomy using the OMNI Surgical System. These investigators did not know if these findings could be generalized to other MIGS procedures and implants.
In a prospective, multi-center, IRB-approved study, Gallardo et al (2021) reported interim 6-month safety and effectiveness outcomes of 360° canaloplasty and 180° trabeculotomy using the OMNI Surgical System concomitantly with phacoemulsification in patients with OAG. This trial included a total of 15 multi-subspecialty ophthalmology practices and surgery centers located in 14 states (Alabama, Arizona, Arkansas, Florida, Georgia, Iowa, Kansas, Montana, Nebraska, North Dakota, Oklahoma, Pennsylvania, Texas, and Wisconsin). Subjects included patients treated with canaloplasty (360°) and trabeculotomy (180°). Eligible patients had cataract and mild-to-moderate OAG with IOP of less than or equal to 33 mmHg on 1 to 4 hypotensive medications. Medication wash-out before baseline diurnal IOP (Goldmann). Effectiveness outcomes included mean IOP and medications. Safety outcomes included AEs, BCVA and SSI. Analysis included descriptive statistics and t-tests evaluating change from baseline. A total of 137 patients were enrolled and treated. Mean diurnal IOP after washout was 23.8 ± 3.1 mmHg at baseline. At month 6, 78 % (104/134) were medication free with IOP of 14.2 mmHg, a mean reduction of 9.0 mmHg (38 %); 100 % (104/104) had a greater than or equal to 20 % reduction in IOP and 86 % (89/104) had IOP greater than or equal to 6 and less than or equal to 18 mmHg. The mean number of medications at screening was 1.8 ± 0.9 and 0.6 ± 1.0 at month 6. AE included transient hyphema (4.6 %) and IOP elevation greater than or equal to 10 mmHg (2 %). There were no AE for loss of BCVA or recurring hyphema. There were no SSI. The authors concluded that canaloplasty followed with trabeculotomy and performed concomitantly with phacoemulsification had favorable intra- and peri-operative safety, significantly reduced IOP and anti-glaucoma medications through 6 months in eyes with mild-to-moderate OAG. Moreover, these researchers stated that full 12-month results of the entire cohort will be reported upon study completion.
In a retrospective, uncontrolled, single-surgeon study, Klabe and Kaymak (2021) reported on the IOP, medication outcomes at 24 months following trabeculotomy/viscodilation using the OMNI Surgical System as a standalone procedure in medically uncontrolled mild-to-moderate OAG. IOP and medication data were collected before surgery and through 24 months. Safety data included adverse events (AEs) and the need for additional surgery. Pre-operative medication washout, Goldmann tonometry as well as number of medications and AEs at each time-point were examined. Primary outcomes included changes in IOP and medications; 2-sided paired t-tests compared values at each follow-up with baseline, significance p = 0.05. Secondary outcomes included proportion of eyes with IOP reduction of greater than or equal to 20 %, on fewer medications, and medication-free at each time-point. This analysis included data from 38 eyes of 27 subjects. Mean (standard deviation [SD]) baseline IOP was 24.6 (3.0) mmHg and through 24 months ranged from 12.6 to 14.9 mmHg (p < 0.0001), representing reductions of 10.0 to 12.0 mmHg. Mean medications were 1.9 (baseline) and through 24 months ranged from 0.0 to 0.5 (70.6 % to 100 % reduction) (p < 0.0001). At month 24, mean IOP was 14.9 mmHg (−10.0 mmHg), and 100 % of eyes achieved IOP reduction greater than 20 % from baseline; mean medication use was 0.5 (−1.4 medications, p < 0.0001), 84.6 % of eyes using greater than 1 fewer medication, and 57.7 % were medication-free. The most common AE was intra-operative hyphema (44.7 %); all resolved spontaneously. There were 2 secondary procedures for IOP control. The authors concluded that the OMNI Surgical System provided clinically relevant and statistically significant reductions in both IOP and medications with an excellent safety profile and should be considered in phakic or pseudophakic eyes with mild-to-moderate OAG requiring IOP or medication reduction, or both.
The authors stated that this study had several drawbacks. It was a retrospective, uncontrolled, single-surgeon study. Moreover, the eye was the unit of analysis and not the patient. As this was a non-comparative, non-hypothesis testing, descriptive study, the main effect (if any) of the lack of independence among variates would be a potential under-estimate of variability. These researchers felt that the inclusion of all available eyes strengthened the safety and effectiveness outcomes reported. It should also be noted that this study included both phakic and pseudophakic eyes, as well as both secondary OAG (pseudo-exfoliative glaucoma [PXF]) and primary OAG (POAG). While sample sizes were too small (n = 27 patients) to permit formal analysis, final mean IOP was similar in phakic and pseudophakic eyes, with no lens-related AEs (aside from transient lens-cornea touch in 1 phakic eye) reported. Likewise, final mean IOP was similar in PXF and POAG suggesting that canaloplasty with trabeculotomy is an effective treatment for IOP reduction in these often more challenging cases. Furthermore, while many minimally invasive glaucoma surgeries (MIGS) studies limited outcomes to IOP and medication parameters, this study also reported functional glaucoma status in all patients followed for 24 months, with no change in the mean visual field mean deviation [VFMD] over the 2-year follow-up period.
Furthermore, an UpToDate review on “Open-angle glaucoma: Treatment” (Jacobs, 2021) states that “All patients with glaucoma should receive treatment upon diagnosis. Pharmacologic therapy, laser therapy (trabeculoplasty), and/or surgery (trabeculectomy) have been shown to lower intraocular pressure (IOP) in randomized trials. However, there are little data on their efficacy in preventing deterioration of vision. A limitation of available evidence is the dual challenge of accounting for ongoing advances in all three therapeutic strategies and assessing a key outcome, visual deterioration, that may take many years to develop”. Moreover, this review does not mention canaloplasty and phacoemulsification as management / therapeutic options.
In a prospective, IRB-approved multi-center study, Gallardo et al (2022) reported the 12-month effectiveness outcomes of 360° canaloplasty and 180° trabeculotomy using the OMNI surgical system in combination with phacoemulsification in patients with mild-moderate open-angle glaucoma (OAG) and visually significant cataract. This trial was carried out in 15 multi-subspecialty ophthalmology practices and surgery centers located in 14 U.S. states. Subjects were patients treated with canaloplasty (360°) and trabeculotomy (180°); eligible patients had cataract and mild-moderate OAG with IOP of less than or equal to 33 mmHg on 1 to 4 hypotensive medications. Unmedicated post-washout mean diurnal IOP (DIOP) was greater than or equal to 21 and less than or equal to 36 mmHg. Medication washout was performed pre-operatively and before month-12 DIOP. Effectiveness outcomes were IOP and IOP lowering medication use. Safety outcomes included AEs and SSIs. Evaluations were carried out at 1, 3, 6, and 12 months. A total of 149 subjects underwent surgery and 120 were included in the final effectiveness analysis. Mean (SD) unmedicated diurnal IOP was reduced from 23.8 (3.1) mmHg at baseline to 15.6 (4.0) at month 12 (-35 %) and medications (before washout) were reduced from 1.8 (0.9) at baseline to 0.4 (0.9) at month 12 (-80 %). At month 12, 84.2 % of eyes achieved IOP reductions of greater than 20 % from baseline, 80 % of eyes were medication-free, and 76 % of eyes achieved IOP between 6 to 18 mmHg inclusive; AEs were uncommon. Most were mild and self-limited including transient hyphema (9 of 149; 6 %) and transient IOP elevations (3 of 149; 2.0 %). No eyes needed SSIs or experienced loss of VA that was attributable to the device or procedure. The authors concluded that canaloplasty and trabeculotomy carried out with the OMNI surgical system at the time of phacoemulsification significantly lowered unmedicated mean DIOP and medication use 12 months post-operatively, with an excellent safety profile. This procedure should be considered for eyes with mild-moderate OAG to reduce IOP, medication burden, or both
The authors stated that the lack of a control group was a drawback that precluded quantifying the contribution of elements from the phacoemulsification and OMNI procedures (as would be possible with a phacoemulsification-only arm) or comparison of OMNI to other MIGS procedures (as would be possible with an active comparator arm). Phacoemulsification alone is known to lower IOP and the need for IOP-lowering medications in glaucomatous eyes. These researchers have tried to mitigate this limitation by designing the statistical analysis plan around the relevant outcomes of phacoemulsification-only groups (which have been remarkably consistent albeit greater than what has been typically reported in other publications) in recent pivotal MIGS trials, specifically powering the study to detect an effect size in excess of that expected by phacoemulsification alone in eyes with mild-moderate OAG. The decision to design this study without a cataract surgery only control group was not made lightly. First, the availability of published data for large cohorts of similarly defined patient populations undergoing phacoemulsification only allowed reasonable estimation of the cataract surgery only treatment effect. Second, in the early 2010ʹs when the pivotal studies for iStent, Hydrus, and CyPass were initiated, the treatment landscape for mild-to-moderate glaucoma in the U.S. was very different. MIGS was a new modality with limited availability and options. Standard treatment was generally medical (drops) or laser (SLT). In contrast, by 2019 when the present study was designed there were several MIGS options available to patients and surgeons with increasing adoption. In this evolving environment, execution of a trial where many patients would be randomized to a “no treatment” (aside from cataract surgery) control would have faced increased unwillingness of patients to participate and would arguably be less ethically sound given the many new therapeutic options available for mild-to-moderate glaucoma.
In a retrospective, observational study, Toneatto et al (2022) examined the effectiveness of ab-interno micro-catheterization and 360° viscodilation of Schlemm's canal (SC) performed with OMNI visco-surgical system in OAG together or not with phacoemulsification. A total of 80 eyes from 73 patients with mild-to-moderate OAG underwent ab- interno SC viscodilation carried out with the OMNI system; 50 eyes (Group 1) underwent only SC viscodilation, while 30 eyes (Group 2) underwent glaucoma surgery + cataract extraction. Primary success endpoint at 12 months was an IOP reduction higher than 25 % from baseline with an absolute value of 18 mmHg or lower, either on the same number or fewer ocular hypotensive medications, without further interventions. Secondary effectiveness endpoints included mean IOP, number of medications and comparison of outcomes between groups. Safety endpoints consisted of BCVA, AEs, and subsequent surgical procedures. Primary success was achieved in 40.0 % and 67.9 % in Groups 1 and 2, respectively. Mean IOP at 12-month follow-up showed a significant reduction in both groups (from 23.0 to 15.6 mmHg, p < 0.001, and from 21.5 to 14.1, p < 0.001, in Groups 1 and 2, respectively). Mean medication number decreased in both groups (from 3.0 to 2.0, p < 0.001 and from 3.4 to 1.9, p < 0.001, in Groups 1 and 2, respectively); AEs included hyphema (2 eyes), mild hypotony (4 eyes), IOP spikes 1 month after surgery (1 eye); 12 eyes (15.0 %) required subsequent surgical procedures. No BCVA reduction was observed. The authors concluded that viscodilation of SC using the OMNI viscosurgical system, with or without cataract extraction, appeared to be a promising surgical procedure to effectively control and reduce IOP with a highly safer profile, even if a high percentage of eyes needed a medical treatment. Moreover, these researchers stated that further studies are needed to report long-term results and complications, and to examine the real advantage of an associated trabeculotomy.
The authors stated that the drawbacks of this trial included the retrospective nature of collected data, the relatively low number of subjects included, the short follow-up period (12 months), and the enrollment of both eyes of the same patient in some cases. Furthermore, not all eyes were naive to prior surgery: 13 had already underwent previous major glaucoma surgery (trabeculectomy and deep sclerectomy). This choice was based on previous studies that have shown that canaloplasty can also be successfully carried out in patients with failed trabeculectomy in which the SC has been left mostly undamaged from previous filtering surgeries. There was no standardized protocol for reducing or increasing medications; however, the medical therapy was adjusted to reach the target IOP on a case-by-case basis. Follow-up was limited to 1 year. Due to the limited number of patients included in this cohort, it was difficult to examine the role and influence of glaucoma types on surgery between the groups. These investigators stated that future prospective studies are currently underway to aid in addressing this issue. In particular, longer-term studies on a larger group of prospectively enrolled patients are needed to evaluate the duration of IOP reduction with this surgical technique.
In a prospective, case-series study, Grabska-Liberek et al (2022) examined clinical outcomes of combined viscodilation of Schlemm's canal and collector channels and 360° trabeculotomy as a standalone procedure or combined with cataract surgery in eyes with mild-to-moderate open-angle glaucoma (OAG). The OMNI glaucoma surgical platform was employed to carry out the procedure either combined with phacoemulsification or as a standalone procedure. Changes from baseline in IOP and IOP-lowering medications were evaluated through the first 12 months of a planned 24-month follow-up period. Among 17 eyes of 15 subjects, mean IOP was reduced from 20.4 mmHg to 12.7-13.7 mmHg through 12 months of follow-up (p < 0.001 at every time-point) and mean medications reduced from 2.5 to 0.1-0.6 (p < 0.001 at every time-point). IOP reductions in eyes undergoing stand-alone surgery were approximately 2 to 4 mmHg greater at each time-point compared to eyes undergoing surgery combined with phacoemulsification; this may be related to a higher baseline IOP in the former eyes (22.1 versus 18.5 mmHg); 6 eyes developed hyphema, of which 3 required wash-out for elevated IOP on the 1st post-operative day; 6 additional eyes had IOP elevations that resolved with medical management. The authors concluded that viscodilation of Schlemm's canal and collector channels paired with ab interno trabeculotomy performed with a single integrated instrument (OMNI), whether as standalone or combined with phacoemulsification, effectively lowered both IOP and the need for IOP-lowering medications through 12 months of follow-up. Moreover, these researchers stated that further study is needed to more robustly characterize outcomes and clarify the optimal use of this procedure. This study is ongoing and 24-month data will be reported when available.
The authors stated that drawbacks of this study included its relatively small sample size (n = 15) as well as the absence of a comparator group. This was a common drawback for studies of many of the minimally invasive glaucoma surgeries (MIGS) procedures, especially those cleared for marketing through the 510(k) equivalence-to-predicate pathway without the requirement for a pivotal trial, in which funding for well-designed and adequately-powered clinical trials is often not available.
In a retrospective, open-label, case-series study, Murphy et al (2022) reported that 12-month safety and effectiveness results for canaloplasty combined with trabeculotomy using the OMNI Surgical System in pseudophakic eyes or combined with cataract surgery in mild-to-moderate OAG. This trial was carried out in 16 centers in 11 U.S. states (AL, AR, CA, CT, KS, LA, MO, NY, SD, TN, TX). A total of 136 eligible patients from 20 surgeons: mild-to-moderate OAG (VFMD) not worse than − 12 dB), 12-month follow-up, pre-operative medicated IOP of greater than 18 mmHg and 36 mmHg or less on 5 medications or less. One eye per patient enrolled. Endpoints included proportion with 20 % or greater reduction in IOP or IOP between 6 and 18 mmHg (inclusive) and on the same or fewer medications without secondary surgical intervention (SSI) (primary success), mean IOP, change in IOP, ocular hypotensive medication use, and proportion of patients with a 20 % or greater reduction in IOP at 12 months. Safety: AE and best corrected visual acuity (BCVA). Primary success was met by 71 %. Mean IOP was reduced (22.3 to 15.9 mmHg, p < 0.0001). Medications went from 1.9 ± 1.3 to 1.3 ± 1.2 (p < 0.001). AE were mild and as expected for angle surgery. The most frequent AE were BCVA loss (6 %), mild inflammation (4 %), IOP elevation (3 %), and clinically significant hyphema (3 %). There were 4 (3 %) SSI. The authors concluded that the OMNI Surgical System provided effective IOP reduction, sustained IOP control, and meaningful medication reduction for up to 12 months post-operative; this trial confirmed and extended the results from the ROMEO Trial.
The authors stated that this trial had several drawbacks. First, eligibility required a pre-operative IOP of greater than 18 mmHg that was measured at 1 visit (mean of 2 repeated measurements). While this could create the risk of regression to the mean it was, in the authors’ view, an acceptable risk that would likely be relevant for only a small fraction of the study population. The alternative of using 2 or more pre-operative visits to obtain a mean pre-operative IOP would likely have been confounded with differences in number and class of medications used, given the generally poor IOP control pre-operatively. Moreover, to be comparable to ROMEO 1, it was important to match eligibility criteria. Second, while there was overlap in investigational sites/surgeons between ROMEO 2 and ROMEO 1, which could arguably account for the consistency of results, ROMEO 2 included 5 new centers with 7 new surgeons who had not participated in the original ROMEO Trial. The new centers and surgeons would certainly have introduced some diversity and variability beyond what was measured. Nevertheless, the overall similarity in outcomes suggested generalizability and robustness. Third, this trial, was limited to 12 months of post-operative follow-up and additional follow-up beyond 12 months would allow better characterization of the durability of the treatment effect. These researchers believed such data would be forthcoming with time. Similar to the original ROMEO study, ROMEO 2 was retrospective. Protocol defined measurement methods (e.g., for IOP), strict surgical procedural guidelines, rules for medication introduction or discontinuation, and washout of IOP-lowering medication before treatment and at the endpoint were commonplace in prospective clinical trials but were not in retrospective studies. While this lack of standardization could be viewed as a weakness, it was in fact a core strength of this study. No 2 ophthalmologists treated glaucoma in exactly the same way. Individual practitioners have different thresholds for surgical intervention, differing ideas regarding IOP targets and treatment escalation, and different ideas regarding when a medication can be discontinued. A prospective “one size fits all” clinical trial could not capture this diversity of practice; thus, generalizability may be limited. However, in a study such as ROMEO or ROMEO 2, this diversity was embraced and the results may in some ways better inform other surgeons of the outcomes they might achieve in their own patients.
In a retrospective, single-center study, Ondrejka et al (2022) examined the long-term safety and effectiveness of canaloplasty in reducing IOP and use of IOP-lowering medications in eyes with OAG. A total of 206 eyes from 130 patients were included. Canaloplasty was carried out using the VISCO360 or OMNI Surgical System as a stand-alone procedure in 22 eyes and concomitantly with cataract extraction (CE) in 185 eyes with chronic OAG insufficiently controlled or intolerant to IOP-lowering medications. The number of hypotensive medications and IOP were recorded at baseline, day 1, week 1, month 1, month 3, and every 3 months thereafter, with the last follow-up visit at 36 ± 6 months post-operatively. Patients were stratified by baseline IOP (Group 1, IOP greater than18 mm Hg; Group 2, IOP 18 mm Hg or lower). Treatment success in Group 1 was defined as a reduction in IOP and the use of IOP-lowering medications; Group 2 success was defined as maintenance of a lower IOP and a reduction in medication use. The pre-operative mean IOP of both groups was 21.1 ± 8.8 mm Hg, with a mean of 2.0 ± 0.9 hypotensive medications. The primary success endpoint was met by 73 % of patients, with a mean IOP reduction in Group 1 (131 eyes; 21.8 to 15.6 mm Hg, p < 0.0001) and a maintenance of IOP control in Group 2 (76 eyes; 15.4 to 13.9 mm Hg, p = 0.24). Medications decreased from 2.2 ± 0.9 to 0.9 ± 1.1 in Group 1 (p = 0.024) and from 1.8 ± 0.8 to 0.7 ± 1.0 in Group 2 (p = 0.003). The authors concluded that canaloplasty carried out using the VISCO360 or OMNI Surgical System was a safe, tissue-preserving, and effective MIGS option that allowed surgeons to perform multiple procedures (canaloplasty and CE) using a clear corneal incision or perform a stand-alone procedure in phakic or pseudophakic eyes. Both devices successfully and consistently performed canaloplasty and achieved statistically significant and clinically meaningful reductions in IOP and the use of medications in adult patients with OAG. Ongoing data collection is expected to better describe the persistence of these real-world outcomes, and further studies are needed to confirm the persistence of benefit of this intervention in patients with OAG.
The authors noted that their findings were based on a retrospective, single-center, case-series study. As both eyes from 1 patient may have been included in the analysis when both met the eligibility criteria, the statistical analysis may be limited in the ability to consistently maintain independent data points. The majority of eyes (89.8 %) included in this analysis received canaloplasty in conjunction with cataract surgery. As cataract is the most common co-morbidity in patients with glaucoma, simultaneous cataract and glaucoma surgery are routine in practice. In such cases, IOP reduction can be attributed to both the procedures. It was noteworthy that, in small subgroup (n = 22) included in this study eyes that underwent a stand-alone canaloplasty, the percentage reduction in IOP was 40 % (from 25.9 to 15.5 mm Hg with a maintained medication burden), which was greater than that observed in the overall cases included in the analysis, the majority of which received OMNI in conjunction with cataract surgery (28 % reduction in IOP with a 62 % reduction in medication burden). The readers should also take into consideration the number of medications used in each group at 36 months. Cataract surgery in patients with glaucoma has been previously observed to achieve an IOP reduction ranging between 0.6 mm Hg and 2.5 mm Hg at 1 year. Moreover, these researchers noted that patient inclusion criteria were purposefully broad to reflect real-world practice. This trial also lacked a control group to compare outcomes more reliably over time with other interventions. Nevertheless, the durable efficacy and favorable safety profile demonstrated after 36 months of follow-up suggested that ab interno canal viscodilation with the VISCO360 or OMNI Surgical System is an attractive and minimally invasive strategy for the treatment of patients with OAG.
The National Institute for Health and Clinical Excellence’s interventional procedures guidance on “Ab interno canaloplasty for open-angle glaucoma” (NICE, 2022) stated that the evidence on the safety of ab interno canaloplasty for OAG shows no major safety concerns. The NICE guidance also noted that the evidence on the effectiveness ab interno canaloplasty for OAG is limited in quality and quantity, especially in the long-term; thus, this procedure should only be used with special arrangements for clinical governance, consent, and audit or research.
In a retrospective, multi-center study (7 multi-subspecialty ophthalmology practices located in AK, CA, KS, LA, MO and NY), Williamson et al (2023) provided extended safety and effectiveness follow-up for eyes treated with circumferential canaloplasty and trabeculotomy (CP+TR) that were included in the 12-month ROMEO study. Eligible eyes had mild-moderate glaucoma and were treated with CP+TR with cataract surgery or as a standalone intervention were included in this analysis. Main outcome measures were mean IOP, mean number of ocular hypotensive medications, mean change in number of medications, proportion of patients with a 20 % or greater reduction in IOP or with IOP of 18 mmHg or less, and proportion of medication-free patients. Safety outcomes were AEs and SSI. A total of 8 surgeons at 7 centers contributed 72 patients stratified by pre-operative IOP: greater than 18 mmHg (Grp1), 18 mmHg or less (Grp2). Mean follow-up of 2.1 years (minimum of 1.4 years, maximum of 3.5 years). 2-year IOP (SD) was 15.6 mmHg (− 6.1 mmHg, − 28 % from baseline) on 1.4 medications (− 0.9, − 39 %) for Grp1 with cataract surgery; 14.7 mmHg (− 7.4 mmHg, − 33 % from baseline) on 1.6 medications (− 0.7, − 15 %) for Grp1 stand-alone, 13.7 mmHg (− 0.6 mmHg, − 4.2 %) on 1.2 medications (− 0.8, − 35 %) for Grp2 with cataract surgery, 13.3 mmHg (− 2.3 mmHg, − 14.7 %) on 1.2 medications (− 1.0, − 46 %) for Grp2 stand-alone. The proportion of patients at 2 years with either a 20 % or greater IOP reduction or IOP between 6 and 18 mmHg and no increase in medication or SSI was 75 % (54 of 72, 95 % CI: 69.9 % to 80.1 %). One-third of patients (24 of 72) were medication-free whereas 9 of 72 were pre-surgical. No device-related AEs during extended follow-up; 6 eyes (8.3 %) required additional surgical or laser intervention for IOP control after 12 months. The authors concluded that CP+TR provided effective IOP control that was sustained for 2 years or more.
The authors stated that this study had several drawbacks. First, it was a retrospective chart review; thus, dependent on data collected in routine medical practice and not for the purpose of research. This meant that there is inherently more variability in the way in which procedures were carried out and data collected than would be the case in a prospective study. It also meant that there was inevitably more missing data, including factors that could influence outcomes that were not recorded. Nevertheless, the study included a relatively large number of patients from multiple research sites and multiple surgeons. These researchers believed that such outcomes did provide a realistic view of the effectiveness of the canaloplasty and trabeculotomy (OSS) in actual clinical practice and, importantly, durability of the treatment effect beyond 12 months. Such information will be of great value to surgeons considering the OSS for use in their practices. Second, the extended follow-up reported included only 7 of the original 11 ROMEO study sites. While the participating sites accounted for 86 % of the enrollment, the potential for unintended bias must be acknowledged. As the non-participating sites were, in general, low enrollers in ROMEO, there was arguably the possibility that higher enrollment sites were more experienced with the OSS, which might have resulted in a bias toward better outcomes reported here. These investigators believed this unlikely based on 2 observations: comparison of outcomes for the first 12 months from the overall ROMEO study population with those for the consistent cohort included in this study found no differences; 12-month mean IOP for the 18 patients at the non-participating sites was essentially identical to the mean for the 111 patients from participating sites (14.4 versus 14.3 mmHg). Third, there was a 35 % lost to follow-up rate at 24 months. While significant loss to follow-up is commonplace in retrospective studies, and it was not possible to ascertain the reasons for loss to follow-up, drop-outs due to AEs and non-response could not be ruled out. However, attrition was not unexpected given the restrictions imposed on routine clinical visits at ophthalmic clinics due to the COVID-19 pandemic.
Combined Gonioscopy-Assisted Transluminal Trabeculotomy (GATT) with Ab Interno Canaloplasty (ABiC) in Conjunction with Phacoemulsification for the Treatment of POAG
In a prospective, interventional, non-comparative, case-series study, Al Habash and colleagues (2020) reported the surgical outcomes of combined gonioscopy-assisted transluminal trabeculotomy (GATT) with ab interno canaloplasty (ABiC) in conjunction with phacoemulsification for the treatment of patients with POAG. This trial included POAG patients who underwent combined GATT and ABiC in conjunction with phacoemulsification performed between January 2018 and August 2018. Main outcome measures include surgical success rate, changes in IOP, number of anti-glaucoma medications, corrected distance visual acuity (CDVA), and complications. These researchers enrolled 19 patients (20 eyes) in this study. The mean age was 61.2 ± 6 years, and all the patients completed a 12-month follow-up. The overall success rate was 100 %. The mean baseline IOP was 19.75 ± 4.68 mmHg, and at 12 months, the mean IOP was 13.30 ± 1.30 mmHg (IOP reduction of 32.7 %). The baseline number of anti-glaucoma medications was 3.4 ± 0.6 (range of 2 to 4 medications), and after 12 months follow-up, the number was reduced to 1.1 ± 1.0 (range of 0 to 2 medications). The CDVA for all 20 eyes was 0.85 ± 0.58 LogMAR at baseline, and 0.16 ± 0.30 LogMAR at 12-month follow-up. Only 6 eyes developed hyphema, which had cleared by the 1st post-operative month, and 3 eyes needed medical treatment for post-operative IOP spikes. The authors concluded that this study, to their knowledge, was the 1st to report on the outcomes of combined GATT with ABiC in conjunction with phacoemulsification for POAG. According to the 12-month results of this trial, the combined procedure appeared to be safe and effective in decreasing the IOP and the number of anti-glaucoma medications in POAG patients. These researchers stated that the drawbacks of this study included the limited number of patients (n = 19) and the lack of long follow-up duration. Furthermore, it was a non-randomized study with no control group. Despite these drawbacks, these investigators believed that combined GATT with ABiC in conjunction with phacoemulsification has the potential to be a great alternative option for the management of POAG, given the favorable efficacy outcomes and high safety profile in all eyes in this study. These researchers recommended that more extensive RCTs be carried out with a longer follow-up in order to examine the long-term outcomes of this procedure in such patient population.
Furthermore, an UpToDate review on “Open-angle glaucoma: Treatment” (Jacobs, 2021) states that “All patients with glaucoma should receive treatment upon diagnosis. Pharmacologic therapy, laser therapy (trabeculoplasty), and/or surgery (trabeculectomy) have been shown to lower intraocular pressure (IOP) in randomized trials. However, there are little data on their efficacy in preventing deterioration of vision. A limitation of available evidence is the dual challenge of accounting for ongoing advances in all three therapeutic strategies and assessing a key outcome, visual deterioration, that may take many years to develop”. Moreover, this review does not mention canaloplasty and phacoemulsification as management / therapeutic options.
Ab Interno Canaloplasty for the Treatment of Primary Open-Angle Glaucoma
In a single-center, case-series study, Korber (2018) examined the effectiveness of ab interno canaloplasty (ABiC) in patients with POAG. This trial included patients with cataract and open-angle glaucoma (combined procedure) and pseudophakic patients (mean age of 76 years; range of 66 to 83 years) with POAG who underwent ABiC using the iTrack 250-μm micro-catheter to circumferentially viscodilate and intubate Schlemm’s canal without placement of a tensioning suture. The primary endpoints were mean IOP and mean number of glaucoma medications at 1, 3, 6, 9, and 12 months post-operatively. A total of 20 patients (20 eyes) were enrolled in this trial. Mean IOP reduced from 18.5 ± 3.44 mm Hg pre-operatively to 14.88 ± 2.82 mm Hg (n = 17), 13.80 ± 2.05 (n = 12), 14.57 ± 2.59 mm Hg (n = 9) and 15.47 ± 2.42 (n = 6) at 1, 3, 6 and 9 months post-operatively. The 12‑month data for 2 patients showed that IOP had reduced from 17 mm Hg pre-operatively to 16 mm Hg in 1 patient and from 20 mm Hg to 13 mm Hg in the other patient. The mean number of medications was reduced from 2.4 pre-operatively to 0.25 at the last follow-up visit. There was 1 reported complication of limited descemetolysis near the limbus by the viscoelastic during the dilatation of Schlemm’s canal. No AEs as a result of the device were reported. The authors concluded that ABiC was straight-forward to perform in this group of patients with minimal complications. Moreover, these researchers stated that although the initial findings from this study showed that ABiC was comparable to conventional canaloplasty in lowering IOP and medication dependency, long-term follow-up in a large patient cohort is needed to confirm the effectiveness of this minimally invasive glaucoma procedure. The authors noted that the drawbacks of this trial included the small study cohort (n = 20); and follow-up data beyond 6 months post-operative were only available for a handful of patients.
Gillmann and Mansouri (2020) noted that the past 10 years has witnessed an unprecedented growth in therapeutic options of glaucoma via the introduction of (MIGS. In a systematic review and meta-analysis, these investigators provided an understanding of the currently available MIGS and examined what data are currently available to guide treatment choice. Out of 2,567 studies identified, a total of 77 were retained for analysis, including 28 comparative studies, and 12 RCTs. Overall, 7,570 eyes were included. When data permitted, the weighted mean difference (WMD) in IOP reduction was calculated for comparison purposes. Weighted mean IOP reductions from all analyzed studies were: 15.3 % (iStent), 29.1 % (iStent inject), 36.2 % (ab interno canaloplasty), 34.4 % (Hydrus), 36.5 % (gonioscopically-assisted transluminal trabeculotomy), 24.0 % (trabectome), 25.1 % (Kahook dual blade), 30.2 % (Cypass), 38.8 % (XEN), and 50.0 % (Preserflo). The authors concluded that one of the advantages of the heterogenous range of available MIGS options is the chance to tailor therapy in an individualized manner; however, high-quality data are needed to make this choice more than an educated guess. Overall, this review confirmed the effectiveness of assessed MIGS compared with stand-alone phacoemulsification; however, it highlighted that only few studies compared different MIGS techniques and even fewer evaluated MIGS against criterion standard treatments. These researchers stated that current evidence, while non-negligible, is mostly limited to heterogenous non-randomized studies and uncontrolled, retrospective comparisons, with few quality RCTs. This resulted in significant variability in studies ’ results and a blurring of the outcomes, and further highlighted the need for carefully designed RCTs. These investigators suggested that future research should be comparative and include relevant comparators, standardized to report key outcome features, long-term follow-up to examine sustainability and late complications.
Balas and Mathew (2023) stated that MIGS has emerged as a novel approach in the therapeutic options for glaucoma, offering a range of diverse procedures and devices aimed at reducing IOP. MIGS can be broadly classified into several categories: those that enhance trabecular out-flow (Trabectome, iStent, Hydrus Microstent, Kahook Dual Blade, high-frequency deep sclerotomy, and gonioscopy-assisted transluminal trabeculotomy), those that augment supra-choroidal out-flow (CyPass Microstent and iStent Supra), those that target Schlemm's canal (TRAB360 and the OMNI Surgical System, Streamline, and ab interno canaloplasty), and conjunctival bleb-forming procedures (EX-PRESS Glaucoma Filtration Device, Xen Gel Stent and PreserFlo MicroShunt). MIGS is considered to have a shorter surgical time and fewer severe complications when compared to traditional glaucoma surgeries such as trabeculectomy and glaucoma drainage device implantation (Ahmed, Baerveldt, and Molteno valves). These investigators examined the distinct MIGS devices and procedures, their underlying mechanisms, and clinical outcomes, emphasizing the importance of evaluating the effectiveness and complications of each approach individually. The authors concluded that as the field of MIGS continues to evolve, it is important to prioritize high-quality, long-term studies to better understand the safety and effectiveness of these innovative interventions in glaucoma management.
Kicinska and Mare (2023) reported the 3-year results of a prospective assessment of 3 modifications of canaloplasty (C): ab externo (ABeC), mini-canaloplasty (miniABeC), and ab interno (ABiC) carried out concomitantly with cataract removal in patients with POAG. A total of 48 patients were randomized for one of the surgeries: ABeC, miniABeC, or ABiC and cataract removal -- 16 eyes for each group. Follow-up examinations were performed on the day of the surgery, on days 1 and 7, after 1, 3, 6 months, and at 1, 2, and 3 years. Complete and qualified success was an IOP of 15 mmHg or less without or with anti-glaucoma eye-drops, respectively. The IOP reduction of 20 % or more was considered an additional success criterion. Within 3 years the probability of qualified success was ABiC and miniABeC – 94 %, ABeC – 100 %, and of complete success ABiC – 75 %, miniABeC – 100 %. At the 3-year follow-up, the median IOP decreased from 22 to 15 mmHg in the ABeC group (p = 0.001), from 22 to 15 mmHg in the miniABeC group 15 (p < 0.001), and from 21 to 15 mmHg in the ABiC group (p = 0.001) compared to the post-washout stage. The IOP dropped by 20 % or more without medications in 56.2 % of patients post-ABiC, 68.8 % post-miniABeC, and 75 % post-ABeC. median number of anti-glaucoma medications dropped in all 3 groups; at the 3-year follow-up, only 1 patient following ABeC, and 4 patients following miniABeC needed treatment; and 1 patient required re-operation and further intensification of topical treatment-post miniABeC. The levels of IOP, CDVA, and success probability at the 36-month follow-up showed no significant difference for individual groups. The authors concluded that after 36 months of observation, all 3 variants were effective in decreasing IOP and medication numbers, with no late complications. The results showed no significant differences while comparing the groups. Among patients after ABiC, a few needed medications; perhaps further observation on larger groups would enhance differences in medicated and un-medicated IOP reduction. These researchers noted that all 3 modifications combined with phacoemulsification could be considered as adequate for individuals with POAG at a mild-to-moderate stage with vision-impairing cataract and no history of trauma to iridocorneal angle, and under the assumption of a patent out-flow system. Moreover, these investigators stated that it needs to be emphasized that this trial was of a preliminary nature and has to be validated with more data from multi-center studies.
The authors stated that the findings of this study should be treated as preliminary in their nature. This trial had several drawbacks, namely, a relatively small sample size (n = 48) and a short observation period. The scarce number of enrollees requires interpreting these results with great caution. In this study, all modifications of C (ABeC, miniABeC, and ABiC) carried out with phacoemulsification gave a satisfactory lowering of IOP, a significant reduction in the number of medications, and an improvement of CDVA as well as visual field (VF) stabilization without complications in Caucasians suffering from mild-to-moderate POAG. Two and three years post-operatively, no differences in median IOP reduction, achieved CDVA, or surgical success were noted. The only complication registered was posterior capsule opacification (PCO), which was rather a consequence of the phacoemulsification procedure and was easily removable. The findings of this study were in line with previously published data on phacoC and initial results of miniABeC. This study also added to the state of the literature on ABiC. Three years after surgery, a few post-ABiC patients needed re-introduction of topical treatment. These investigators stated that further research on a larger sample is needed to confirm this tendency. Perhaps ABiC would be more suitable for patients who are compliant to the use of eye-drops.
A StatPearls’ review on “Minimally invasive glaucoma surgery” (Gurnani and Tripathy, 2023) stated that MIGS has revolutionized glaucoma management over the past few years. It is a relatively new modality of glaucoma management that is gaining popularity as large numbers of surgeons are opting for it. The post-operative outcomes and patient satisfaction rate are good with these procedures. The safety profile and efficacy are also good. The authors stated that MIGS has opened a new door for mild-to-moderate glaucoma management, reducing the medication burden on the patients. Recent studies have provided highly encouraging results, and more large-scale studies with long-term follow-up are needed to provide better insight and understanding of MIGS.
Cheema and Cheema (2024) examined the evolution, current status, and future potential of MIGS, which offer a less invasive alternative to traditional glaucoma surgeries, primarily aimed at reducing IOP, minimizing tissue trauma, and providing a safer profile. With the emergence of devices such as the Trabectome, iStent, and others, MIGS have expanded the surgical armamentarium, allowing personalized, patient-centered care. Despite their advantages, MIGS face challenges such as effectiveness in severe cases, long-term data, and accessibility. The learning curve and the necessity for precise patient selection highlight the need for thorough training in MIGS techniques. The authors stated that ongoing research and technological innovations continue to refine MIGS capabilities and applications, promising to further transform glaucoma management and patient outcomes.
In a retrospective, single-center, consecutive case-series study, Koerber and Ondrejka (2024) examined the long-term effectiveness of iTrack ab-interno canaloplasty for reducing IOP and the number of glaucoma medications in patients with POAG and pseudo-exfoliative glaucoma. Subjects were treated with either ab-interno canaloplasty performed as a stand-alone procedure or combined with cataract surgery and were followed for up to 6 years. iTrack was used to circumferentially catheterize and visco-dilate the Schlemm canal over 360 degrees. Primary effectiveness endpoints included IOP and number of glaucoma medications at 12, 24, 36, 48, 60, and 72 months after surgery. A total of 27 eyes of 22 patients, with a mean age of 76.9 ± 6.3 years, were recruited. Mean IOP was reduced significantly from 19.9 ± 5.2 mm Hg (n = 27) at baseline (no wash-out) to 14.6 ± 3.3 mm Hg at the 6-year follow-up (n = 18; p < 0.001). The number of medications was significantly reduced from 1.9 ± 1 at baseline to 0.9 ± 0.9 at 6 years (n = 18; p = 0.005). At all time-points, there was no statistical difference between POAG (n = 16) and pseudo-exfoliative (n = 11) eyes, nor between stand-alone procedures (n = 4) and those combined with phacoemulsification (n = 23). At 72 months, the mean reduction in IOP was 27 % while 53 % in the number of medications. No serious complications were recorded. The authors concluded that this trial reported a clinically and statistically significant reduction in IOP and number of medications achieved by ab-interno canaloplasty using the iTrack canaloplasty micro-catheter and that these reductions were sustained up to 6 years post-operatively. In addition, these reductions appeared comparable with other MIGS devices. These researchers stated that MIGS appeared to provide long-term sustained effectiveness; however, further studies are needed to confirm the long-term outcomes when canaloplasty is performed in association with cataract removal or as a stand-alone procedure.
The authors stated that the key drawbacks of this study were associated with the retrospective, single-center design, such as the small number of eyes (n = 27), selection bias, the heterogenous nature of the cohort, and loss of follow-up, which is sometimes linked to the elderly nature of the patients.
Schlemm's Canal-Targeting Approaches for the Treatment of Primary Open-Angle Glaucoma (e.g., Ab Interno Canaloplasty, OMNI Surgical System, STREAMLINE Surgical System, and TRAB360 Trabeculotomy System)
In a retrospective, multi-center, case-series study, Areaux et al (2020) reported outcomes and complications of trabeculotomy ab interno using the Trab360 device (Trab360; Sight Sciences, Menlo Park, CA) in eyes with childhood glaucoma. Eyes with childhood glaucoma that underwent Trab360 with at least 3 months follow-up were evaluated. Success was defined as post-operative IOP of less than or equal to 24 mm Hg with or without medications and no additional surgery. A total of 46 eyes of 41 patients were included. Median age at surgery was 12 months (range of 1 to 325 months, mean of 71 months); 54 % prior to 20 months. A total of 48 % were right eyes; 48 % were male. Mean treatment was 290°. Median follow-up was 14.5 months (range of 6 to 34 months, mean of 16.2 months). Median pre-operative IOP was 30 mm Hg (range of 18 to 49 mm Hg, mean of 30.9 mm Hg); median post-operative IOP was 18 mm Hg (range of 5 to 40 mm Hg, mean of 20.3 mm Hg]. Median number of pre-operative glaucoma medications was 2.5 (range of 0 to 5, mean of 2.6); median number post-operatively was 1 (range of 0 to 4, mean of 1.6). Success was achieved in 67.4 % (95 % CI: 51.9 % to 80.0 %) of eyes. Among 40 eyes for which Trab360 was the 1st glaucoma surgery, success rate was 70 % (95 % CI: 53.3 % to 82.9 %). Success was achieved in 81 % (95 % CI: 57.4 % to 93.7 %) of PCG eyes. Among 18 PCG eyes for which Trab360 was the 1st glaucoma surgery, success rate was 83.3 % (95 % CI: 57.7 % to 95.6 %); and 2 eyes (4.3 %) suffered cyclo-dialysis. There were no other significant complications. The authors concluded that Trab360 success resembled literature on other angle surgeries for childhood glaucoma. Good surgical technique and caution in high-risk angles was imperative to avoid cyclo-dialysis. Moreover, these researchers stated that this trial was limited by the imperfections inherent in any retrospective analysis.
In a prospective, single-arm, first-in-human case-series study, Lazcano-Gomez et al (2022) examined the clinical outcomes of a novel ab interno minimally invasive procedure with the STREAMLINE Surgical System for creation of incisional goniotomies and canal of Schlemm viscodilation in eyes with mild-to-severe POAG. A total of 20 eyes of 20 subjects with mild-to-severe POAG underwent creation of incisional goniotomies and canal of Schlemm viscodilation following phacoemulsification cataract extraction after washout of all IOP-lowering medications. The angle surgery portion was carried out with a single-use hand-piece tipped with a micro-cannula that creates precise goniotomies via the trabecular meshwork into the canal of Schlemm and delivers a small volume of ophthalmic viscosurgical device directly into the canal via precise catheterization. Outcomes in this interim analysis included mean reduction in IOP and medications through 6 months of follow-up, as well as the proportion of eyes achieving IOP reduction of 20 % or greater from baseline. At month 6, mean IOP reduction of 20 % or greater from baseline was achieved in 89.5 % of eyes (17/19). Mean (SD) medicated IOP at screening was 16.3 (3.6) mmHg and unmedicated baseline IOP (after washout) was 23.5 (2.5) mmHg. Mean IOP was significantly reduced from baseline through 6 months of follow-up to 14.7 (2.4) mmHg (p < 0.001), representing an IOP reduction of 8.8 mmHg (36.9 %). Overall, 57.9 % (11/19) of eyes decreased dependence on IOP-lowering medications by at least 1 medication, and 42.1 % (8/19) were medication-free. Mean medication use was reduced from 2.0 (0.8) at screening to 1.1 (1.1) at 6 months (p < 0.001); 3 eyes had transient IOP spikes treated with topical medications. The authors concluded that the creation of incisional goniotomies and canal of Schlemm viscodilation safely and effectively reduced IOP and the need for IOP-lowering medications by both clinically and statistically significant magnitudes in eyes with mild-to-severe POAG undergoing concomitant phacoemulsification cataract extraction through the first 6 months of follow-up.
The authors stated that the drawbacks of this trial included both small sample size (n = 20) and short-term follow-up 96 months); a larger sample is being collected, and follow-up is planned through 12 months for the full data-set, including assessment of pachymetry and specular microscopy, which will be collected at the final visit and compared to baseline values. Given that this device has been cleared by the FDA and the instrument is available for use, the need to disseminate preliminary outcomes data supports the reporting of this interim analysis. Another drawback was the lack of a phacoemulsification-only control group, as phacoemulsification alone is known to reduce both IOP and the need for IOP-lowering medications in glaucomatous eyes. However, the magnitude of both IOP reduction and medication reduction in this study was significantly greater than would be expected from phacoemulsification alone, supporting the effectiveness of the incisional goniotomy procedure. Furthermore, the IOP outcomes presented in this interim analysis were not assessed after drug washout.
In a prospective analysis, Lazcano-Gomez et al (2023) examined clinical outcomes of transluminal dilation of the canal of Schlemm using the STREAMLINE Surgical System combined with phacoemulsification in eyes of Hispanic patients diagnosed with mild-to-moderate POAG. This study entailed all cases performed and followed-up to 12 months. All eyes underwent medication washout preoperatively. Reduction in IOP from unmedicated baseline, as well as medications from pre-washout baseline, were analyzed at post-operative day 1, week 1, and months 1, 3, 6, 9, and 12. All 37 patients were Hispanic, 83.8 % were women, and mean (SD) age was 66.0 (10.5) years. Mean medicated pre-operative IOP was 16.9 (3.2) mmHg using a mean of 2.1 (0.9) medications, unmedicated baseline IOP (after washout) was 23.2 (2.3) mmHg, and mean IOP at every post-operative study visit was significantly lower (p < 0.0002). Mean IOP from month 1 through the 1st post-operative year ranged from 14.7 to 16.2 mmHg, representing a reduction of 7.0 to 8.5 mmHg (30.7 % to 36.5 %). At month 12, 80 % of all eyes (28/35) and 77.8 % of medication-free eyes (14/18) had IOP reduction of 20 % or more from unmedicated baseline, and 51.4 % of eyes (18/35) were medication-free. Mean medication use was significantly reduced (by 59.9 % to 74.6 %, p < 0.0001) at every post-operative study visit. The only adverse event (AE) occurring in more than 1 eye was high IOP (n = 4) that responded to topical medical therapy; no AEs were attributed to the transluminal dilation procedure. The authors concluded that transluminal dilation of the canal of Schlemm using the STREAMLINE Surgical System combined with phacoemulsification safely and effectively reduced both IOP and dependence on IOP-lowering medications in a Hispanic population diagnosed with POAG and should be considered at the time of phacoemulsification in Hispanic patients who have a need for IOP reduction, medication reduction, or both.
These researchers stated that drawbacks of this study included a relatively small sample size (n = 37), which was appropriate for first-in-human studies. In addition, the study duration was short (up to 1 year) relative to the chronic lifelong nature of glaucoma; however, intermediate-term data are of value to surgeons when selecting from among the various glaucoma procedures available. Furthermore, the inclusion of a single surgeon limited generalizability of results. Another drawback was the lack of a phacoemulsification-only control group, as phacoemulsification alone is known to reduce both IOP and the need for IOP-lowering medications in glaucomatous eyes. However, the reduction in IOP and medications observed at 12 months in this study exceeded what would be expected from phacoemulsification alone, supporting the additive advantage of this combination procedure. Lastly, while baseline IOP was assessed after medication washout, 12-month IOP outcomes were not.
Balas and Mathew (2023) stated that MIGS has emerged as a novel approach in the glaucoma treatment spectrum, offering a range of diverse procedures and devices aimed at reducing IOP. MIGS can be broadly classified into several categories: those that enhance trabecular outflow (Trabectome, iStent, Hydrus Microstent, Kahook Dual Blade, high frequency deep sclerotomy, and gonioscopy-assisted transluminal trabeculotomy), those that augment suprachoroidal outflow (CyPass Microstent and iStent Supra), those that target Schlemm's canal (TRAB360 and the OMNI Surgical System, Streamline, and Ab Interno Canaloplasty), and conjunctival bleb-forming procedures (EX-PRESS Glaucoma Filtration Device, Xen Gel Stent and PreserFlo MicroShunt). MIGS is considered to have a shorter surgical time and fewer severe complications when compared to traditional glaucoma surgeries such as trabeculectomy and glaucoma drainage device implantation (Ahmed, Baerveldt, and Molteno valves). The authors examined the distinct MIGS devices and procedures, their underlying mechanisms, and clinical outcomes, emphasizing the importance of evaluating the effectiveness and complications of each approach individually. These researchers stated that as the field of MIGS continues to evolve, it is important to prioritize high-quality, long-term studies to better understand the safety and effectiveness of these innovative interventions in glaucoma management.
These investigators noted that Streamline (New World Medical) is a MIGS procedure designed to enhance aqueous humor outflow by targeting Schlemm’s canal via canaloplasty, which involves the cannulation and viscodilation of Schlemm’s canal without performing a trabeculotomy. The device consists of a single-use and disposable stainless-steel cutting inner cannula with a polymer outer sleeve, inserted via a clear corneal incision. As the outer cannula retracts, it creates a 150-μm diameter goniotomy while simultaneously delivering approximately 7 μL of viscoelastic material into Schlemm’s canal, effectively dilating the canal and connected collector channels. This dilation facilitates improved aqueous humor outflow and aids in lowering IOP in patients with glaucoma. The Streamline device, composed of biocompatible materials, ensures optimal safety and performance during the procedure and allows for extended goniotomies over multiple clock hours as needed. It received FDA approval in 2021, with various clinical trials underway. An interim analysis of a prospective, non-randomized trial showed a significant reduction in mean IOP and number of medications at the 6-month follow-up (Lazcano-Gomez et al, 2022). It is suitable for both phakic and pseudophakic eyes. Moreover, these investigators stated that further research is needed to examine the long-term safety, effectiveness, and potential complications associated with the Streamline Surgical System, as well as to compare its outcomes to other MIGS procedures.
In a narrative review, Koerber and Ondrejka (2023) examined IOP, glaucoma medication dependence, and safety profile of canaloplasty performed via an ab-interno surgical technique using the iTrack canaloplasty micro-catheter (Nova Eye Medical). These investigators carried out a literature search in March 2022 using Medline and Embase to identify all studies that examined ab-interno canaloplasty using the iTrack, either combined with phacoemulsification or as a stand-alone procedure in POAG. The primary effectiveness outcome was IOP; secondary outcomes were glaucoma medication use as well as safety profile. The search retrieved 170 results, of which 9 studies were included totaling 365 eyes. Both IOP and number of medications were reduced at 12 to 24 months. IOP decreased from 20.0 ± 2.5 mmHg pre-operatively to 13.8 ± 0.6 and 14.0 ± 0.9 at 12 and 24 months, respectively; the number of medications was reduced from 2.5 ± 0.5 pre-operatively to 0.8 ± 0.4 and 0.9 ± 0.6 at 12 and 24 months post-operatively, respectively. Comparable results were observed in the iTrack-alone and iTrack + phaco groups: IOP was reduced from baseline 20.5 ± 1.9 and 19.6 ± 3.0 mmHg to 14.3 ± 1.1 and 13.9 ± 1.1 mmHg 24 months post-operatively, respectively. The authors concluded that the findings of this review suggested that ab-interno canaloplasty as a stand-alone procedure or combined with phacoemulsification using the iTrack resulted in a reduction in IOP and glaucoma medication use up to 24 months post-operatively.
A StatPearls’ review on “Minimally invasive glaucoma surgery” (Gurnani and Tripathy, 2023) stated that MIGS has revolutionized glaucoma management over the past few years. It is a relatively new modality of glaucoma management that is gaining popularity as large numbers of surgeons are opting for it. The post-operative outcomes and patient satisfaction rate are good with these procedures. The safety profile and efficacy are also good. The authors stated that MIGS has opened a new door for mild-to-moderate glaucoma management, reducing the medication burden on the patients. Recent studies have provided highly encouraging results, and more large-scale studies with long-term follow-up are needed to provide better insight and understanding of MIGS.
In a non-randomized, observational study (the GEMINI Trial), Greenwood et al (2023) examined the long-term outcomes of canaloplasty and trabeculotomy combined with cataract surgery in patients with POAG. This trial was carried out in 11 ophthalmology practices in the U.S., the study extended the original 12-month prospective trial to 36 months. It reported significant reductions in IOP and medication usage, with mean unmedicated DIOP decreasing from 23.1 mmHg at baseline to 16.3 mmHg at 36 months. The proportion of patients achieving a 20 % or greater reduction in IOP was 78 % at 36 months, and 74 % of patients were medication-free at this time. Safety outcomes were favorable, with few AEs and only 1 secondary surgical intervention required. However, the study had several drawbacks, including its observational design, lack of a parallel control group, and non-randomized nature. Furthermore, the study's demographic was predominantly White and non-Hispanic, which may affect generalizability. Despite these drawbacks, the study showed sustained IOP and medication reductions over 3 years, suggesting the potential for OMNI to delay more aggressive surgical interventions in mild-to-moderate glaucoma patients.
Goldberg et al (2024) reported interim results of the VENICE Trial, a multi-center RCT comparing STREAMLINE Surgical System (STREAMLINE) canaloplasty with iStent inject W (iStent W) implantation in patients with mild-to-moderate POAG undergoing phacoemulsification. Safety and efficacy analyses involving the first 72 randomized eyes were included in this interim report. Following pre- (screening) and post-medication washout (eligibility) visits, 1 eye per subject was randomized 1:1 to STREAMLINE or iStent W after undergoing uncomplicated phacoemulsification. Participants were evaluated post-operatively at day 1, week 1, month 1, 3, and 6. IOP measurements, number of IOP-lowering medications, and AEs were assessed at each follow-up visit. A total of 72 eyes were randomized; 35 underwent STREAMLINE canaloplasty and 37 were implanted with the iStent W. A total of 70 eyes completed their 6-month follow-up. Both the mean morning post-washout baseline IOP between STREAMLINE 24.86 ± 3.05 mmHg and iStent W 25.16 ± 3.41 mmHg and the mean IOP at 6 months between STREAMLINE eyes 16.52 ± 3.63 mmHg and iStent W eyes 16.08 ± 3.19 mmHg were not statistically significantly different (p = 0.691 and 0.596, respectively). At 6 months, more eyes were on 0 glaucoma medications in the STREAMLINE group (81.8 %) compared to the iStent W group (78.4 %). In medication-free eyes, the mean IOP was reduced from 24.80 ± 2.79 mmHg to 16.00 ± 3.40 mmHg and 24.60 ± 3.18 mmHg to 15.80 ± 2.21 mmHg in the STREAMLINE and iStent W groups, respectively (p = 0.752). Both groups showed reduction in IOP-lowering medications at every visit, compared to pre-washout (screening), with STREAMLINE resulting in numerically fewer medications 0.20 ± 0.48 compared to iStent W 0.40 ± 0.79 at 6 months (p = 0.384); AEs were mild and self-limited. The authors concluded that the VENICE Trial was the 1st RCT involving canaloplasty. These interim findings showed comparable IOP and medication reduction between STREAMLINE canaloplasty and iStent W implantation, when combined with phacoemulsification. These investigators stated that drawbacks of this interim report included the relatively short follow-up period (up to 6 months). This study is ongoing and 12-month results for this cohort will be reported in the future to aid in better understanding the long-term safety and effectiveness for both STREAMLINE canaloplasty and iStent inject W implantation to treat glaucoma when combined with cataract surgery. (Also, it should be noted that this clinical study was sponsored by New World Medical, Rancho Cucamonga, CA).
In a prospective, non-randomized, comparative study, Noh et al (2024) compared outcomes of ab-interno canaloplasty and trabeculotomy of the superior versus inferior angle. This trial was carried out at the Veteran Affairs Hospital (Long Beach, CA). All subjects underwent cataract surgery with IOL implantation combined with ab-interno canaloplasty and trabeculotomy with the OMNI Surgical System (SightSciences, Menlo Park, CA), either superiorly or inferiorly. Pre- and post-operative IOP using Goldmann applanation tonometry and BCVA were obtained and compared using paired t-tests. Subjects were excluded if they had any previous intra-ocular surgery or prior laser trabeculoplasty procedures. A total of 38 eyes from 29 patients were analyze -- 19 eyes were included in the superior group and 19 eyes in the inferior group. Mean pre-operative IOP in the superior group was 17.6 ± 5.2 mmHg and in the inferior group was 17.6 ± 4.6 mmHg (p > 0.99). At 12 months, mean post-operative IOP for the superior group decreased 24 % to 13.3 ± 2.8 mmHg while the inferior group decreased 26 % to 13.1 ± 2.2 mmHg (p = 0.92). Mean pre-operative medications in the superior group were 2.2 ± 1.3 and in the inferior group was 2.4 ± 1.3 (p = 0.88). At 12 months, this decreased to 1.3 ± 1.5 post-operatively in the superior group and 2.2 ± 1.6 post-operatively in the inferior group (p = 0.64). The authors concluded that there was no statistical difference in the effectiveness between superior versus inferior canaloplasty/trabeculotomy with OMNI; thus, surgeons could perform the procedure in the direction that is most comfortable for them without affecting outcomes.
The authors stated that this study had several drawbacks. First, subjects were not randomized pre-operatively to treatment hemispheres to allow for more patients with complete 180 degrees of treatment and to better approximate real-world results as surgeons will often perform the procedure in the most easily managed hemisphere based on patient positioning, individual angle anatomy, and other intra-operative factors. Second, although there was no statistically significant difference between the change in pre- versus post-operative number of medications when comparing the 2 groups, there was only a mild reduction in number of post-operative medications in the inferior group compared to the superior group. These investigators hypothesized that this difference may be due to the fact that the subjects in the inferior treatment group had more moderate stage glaucoma (mean baseline deviation of −7.2 ± 7.3 dB versus −4.8 ± 5.0 dB for the superior group); thus, requiring more medications post-operatively to maintain goal IOP. Third, the patient population was all male, and these results may not be generalizable to female patients. However, these findings were consistent with other studies of OMNI that included both sexes. Fourth, each subject also underwent cataract extraction with IOL implantation at the same time as ab-interno canaloplasty and trabeculotomy; thus, the results may not be applicable to patients undergoing stand-alone procedures. Fifth, these findings were not directly correlated to aqueous angiography in individual eyes to examine if an absolute number of collector channels is a factor in IOP reduction. Sixth, this study only looked at IOP outcomes from post-operative month 6 to 12, and future studies would be strengthened by longer follow-up periods.
In a retrospective, case-control study, Asaoka et al (2024) examined the post-operative changes in the corneal biomechanical properties between solo cataract surgery and solo microhook ab interno trabeculotomy (LOT). This trial included 37 eyes belonging to 26 patients who underwent solo cataract surgery and 37 eyes belonging to 31 patients who underwent solo microhook LOT. These 2 groups were matched according to their pre-operative IOP, axial length, and age. Corneal Visualization Scheimpflug Technology (Corvis ST) was used to obtain 4 biomechanical parameters representing the corneal stiffness or corneal deformation at the highest concavity, including stiffness parameter A1 (SP-A1), stress-strain index (SSI), peak distance (PD), and deflection amplitude max (DefAmpMax). These parameters were compared pre-operatively and 6 months post-operatively, and between the 2 surgical groups. Pre-operatively, the patients' IOP, age, and axial length, as well as their results in 4 Corvis ST parameters, were similar between the 2 groups (p > 0.05). No significant difference was observed in SP-A1; however, PD and DefAmpMax were significantly larger, and SSI was significantly smaller post-operatively in the LOT group than in the cataract group. The authors concluded that corneal stiffness was reduced, and the cornea was more deformed with LOT than cataract surgery.
The authors stated that this trial had several drawbacks. First, the sample size was relatively small, and further validation of the current results in a larger dataset is needed. Second, the retrospective nature of this study: this study’s data were limited to a period of 6 months after the operation. Extended follow-up evaluation would be beneficial in understanding the enduring biomechanical alterations and their consequences on visual outcomes and the advancement of diseases. Third, although this study considered the effects of anti-glaucoma drugs, their possible influence on corneal biomechanics could not be not thoroughly examined because of the relatively small sample size. Therefore, these findings should be considered as initial findings that necessitate further investigations to validate the conclusions. Furthermore, eyes with relatively low IOP were selected in the LOT group. This consideration was needed in the authors’ selection of glaucoma patients, because biomechanical corneal properties are closely associated with IOP, and post-operative changes in the biomechanical corneal properties could not be compared between the 2 surgical groups unless the pre- and post-operative IOP values were matched.
In a retrospective study, Dickerson et al (2024) examined if there was an association between severity of glaucoma and IOP and medication (med) outcomes for patients in the ROMEO (Retrospective, Observational, Multicenter Evaluation of OMNI) Trial, which entailed 11 ophthalmology practices in 8 U.S. states. These investigators carried out post-hoc analysis of all eyes enrolled and treated with ab interno canaloplasty and trabeculotomy in the retrospective, multi-center ROMEO Trial. Eyes were grouped according to visual field mean deviation (MD): mild (MD better than -6 dB), moderate (MD between -6 and -12 dB), advanced (-12 dB or worse). IOP and med outcomes at 12 months were compared across groups. Least squares regression was used to examine the relationship of MD with month-12 IOP. Outcomes for 1st and last MD deciles were compared as a sensitivity analysis. A total of 127 eyes were available for analysis including 79 mild, 42 moderate, 6 advanced. Most eyes had a reduction in IOP at month-12 (70 %) with most at 18 mmHg or less. Percentage IOP reduction was similar across the groups (mild 16.9 %, moderate 18.6 %, and advanced 18.0 %) with mean month-12 IOP between 14 and 16 mmHg. Medications were also reduced in all 3 groups; -0.8 (mild, p < 0.001), -0.55 (moderate, p < 0.05), and -1.0 (advanced, p = 0.139, ns). Regression analysis revealed no relationship between month-12 IOP and MD. Med reductions were observed for all groups with a reduction of 1 or more medications observed in (%, 95 % CI) 69 %, 59 to 79 (mild), 50 %, 35 to 65 (moderate), and 60 %, 21 to 99 (advanced). Secondary interventions tended to have greater incidence with worse MD likely reflecting lower desired IOP targets. The authors concluded that analysis of data from the ROMEO Trial suggested that similar meaningful IOP and med reductions could be expected across the range of disease severity studied. Moreover, these researchers stated that confirmation of these findings through additional studies, with a greater representation of patients with advanced field loss, is needed to determine the role of MIGS in glaucoma patients with advanced disease.
The authors stated that this study had 2 main drawbacks. First, this was a post-hoc analysis of a retrospective study. However, the study included all available eligible patients treated with OMNI; therefore, mitigating the risk of selection bias. Also, this was a multi-center study; thus, mitigating the risk of investigator or center bias. Moreover, a retrospective study of patients treated in actual clinical practice, in the authors’ view, provided data more generalizable to the actual outcomes others may obtain with OMNI. Second, the majority of patients in this study were mild or moderate with a small number of patients having advanced visual field loss, extrapolation of these findings were therefore limited. Nevertheless, these researchers felt confident that for the range of visual field deficits included, the study conclusions were valid.
A retrospective real‑world study by Yadgarov and colleagues (2023) evaluated the long‑term safety and effectiveness of sequential canaloplasty and trabeculotomy using the OMNI Surgical System when performed in combination with cataract surgery in patients with all stages of open‑angle glaucoma (OAG), including mild, moderate, and advanced disease. The primary objective was to assess changes in intraocular pressure (IOP) and glaucoma medication burden through 12 and 24 months postoperatively, with secondary objectives including stage‑specific outcomes, the need for secondary surgical interventions (SSI), and safety outcomes. The investigators conducted a retrospective chart review of 171 consecutive eyes from 171 patients treated at a single center between June 2018 and July 2020. All eyes underwent phacoemulsification with intraocular lens implantation followed by ab interno canaloplasty (at least 180°) and trabeculotomy (at least 90°) using the OMNI device. Patients included those with primary open‑angle glaucoma, pigmentary glaucoma, pseudoexfoliative glaucoma, and previously treated chronic angle‑closure glaucoma with an open angle. Outcomes included mean IOP and number of IOP‑lowering medications at baseline and postoperative time points, analyzed overall and by glaucoma stage, as well as Kaplan–Meier survival analysis for avoidance of SSI over 24 months. Adverse events were also recorded. The study demonstrated statistically significant and sustained reductions in both IOP and medication use through 24 months. Mean IOP decreased from 17.2 mmHg on 1.3 medications at baseline to 14.3 mmHg on 0.8 medications at 12 months and 14.0 mmHg on 0.9 medications at 24 months (p<0.001). Importantly, eyes with advanced glaucoma also showed meaningful IOP reductions, from 17.8 mmHg on 1.6 medications at baseline to 13.6 mmHg at 12 months and 13.0 mmHg at 24 months, although medication use remained higher in advanced disease compared with mild or moderate stages. The cumulative probability of avoiding secondary glaucoma surgery at 24 months was 93.0% overall, with slightly lower survival in advanced glaucoma (88.9%) compared with mild and moderate disease. Adverse events were infrequent, mild, and transient, with low rates of IOP spikes, hyphema, and hypotony, and no permanent sight‑threatening complications reported. The authors noted several limitations, including the retrospective design, lack of a control group, single‑surgeon and single‑center experience, and attrition over time, with fewer patients completing the 24‑month follow‑up. Baseline IOP was relatively low, which may have limited the magnitude of observed IOP reduction, and treatment extent was variable based on intraoperative factors. Despite these limitations, the study provides robust real‑world evidence supporting the safety and effectiveness of combined OMNI‑assisted canaloplasty and trabeculotomy with cataract surgery across the full spectrum of OAG severity.
A multicenter retrospective study by Terveen and colleagues (2023) evaluated the effectiveness and safety of canaloplasty and trabeculotomy using the OMNI Surgical System in patients with open-angle glaucoma (OAG whose disease remained inadequately controlled after prior trabecular microbypass stenting (iStent or iStent inject) and medical therapy. The objective was to assess whether a second, implant-free MIGS procedure could provide meaningful intraocular pressure (IOP) control and reduce the need for traditional filtering surgery in this challenging population. The study included 27 eyes from 27 patients across five U.S. practices, all of whom had pre-OMNI IOP ≥17 mmHg on at least one medication and a minimum of 3 months of follow-up. Outcomes included change in IOP and medication burden, proportions achieving ≥20% IOP reduction or an IOP between 6 and 18 mmHg, cumulative freedom from secondary surgical intervention (SSI), and adverse events. At a mean follow-up of 11 months (maximum 41 months), mean IOP decreased significantly from 22.3 mmHg at baseline to 17.2 mmHg, representing an average reduction of 5.1 mmHg (23%, p<0.001). Forty-one percent of eyes achieved an IOP reduction of at least 20% without additional laser or surgical intervention, and 56% achieved an IOP ≤18 mmHg at last follow-up. Medication use decreased modestly from a mean of 2.2 to 1.8 medications, with approximately 30% of patients becoming medication-free postoperatively. IOP reductions were observed across disease severities and appeared durable over time. Secondary surgical interventions were required in 15% of eyes, all within the first postoperative year; eyes requiring SSI tended to have higher baseline IOP and more advanced visual field loss. The procedure demonstrated a favorable safety profile, as all adverse events were non-serious and transient, with hyphema, transient IOP spikes, and mild best-corrected visual acuity decreases being the most commonly reported events. The authors noted several limitations, including the small sample size, retrospective design, lack of a control or comparator group, and variability in follow-up duration. Additionally, glaucoma severity staging relied primarily on visual field mean deviation from single tests, which may introduce classification imprecision. Despite these limitations, the study provides real-world evidence that sequential use of an implant-free MIGS procedure can offer meaningful IOP reduction and delay more invasive glaucoma surgery in patients whose disease progresses after initial trabecular microbypass stenting.
A systematic literature review by Cantor and colleagues (2023) was conducted to comprehensively evaluate the clinical, humanistic, and economic outcomes associated with minimally invasive glaucoma surgery (MIGS) and selective laser trabeculoplasty (SLT) for adults with mild‑to‑moderate open‑angle glaucoma (OAG), including procedures performed with or without concomitant cataract extraction. The authors aimed to update and consolidate the expanding evidence base for newer MIGS technologies, with particular attention to efficacy, safety, patient‑reported outcomes, and cost implications, recognizing the increasing role of MIGS earlier in the glaucoma treatment paradigm. The review was performed in accordance with PRISMA guidelines and registered with PROSPERO. Systematic searches of MEDLINE, Embase, the Cochrane databases, and ClinicalTrials.gov identified studies published between 2011 and 2021 that evaluated MIGS or SLT compared with other glaucoma treatments in adults with mild‑to‑moderate OAG. Both randomized controlled trials and observational studies were included, provided sample sizes were at least 15 patients. Data extraction covered intraocular pressure (IOP) reduction, medication use, adverse events, health‑related quality of life (HRQoL), patient burden, and economic outcomes, and formal risk‑of‑bias tools were applied according to study design. Out of 2,720 screened records, 81 publications were included, of which 58 reported clinical outcomes. The largest body of evidence was for iStent and iStent inject, followed by the OMNI Surgical System, which accounted for nine publications. OMNI‑specific studies included both standalone ab interno canaloplasty and trabeculotomy and procedures combined with cataract surgery. Across prospective studies, OMNI demonstrated some of the largest and most consistent IOP reductions among MIGS, with percentage reductions ranging from approximately 31% at 6 months to as high as 39% at 12 months, and mean postoperative IOPs typically in the low‑to‑mid teens. Both standalone and combined OMNI procedures were effective in lowering IOP and reducing the need for IOP‑lowering medications, with a substantial proportion of patients becoming medication‑free at 12 months. OMNI was also the only MIGS platform in the review with published data showing a significant reduction in diurnal IOP fluctuation. Across all MIGS and SLT modalities, adverse events were generally mild and transient; notably, OMNI and other implant‑free procedures avoided device‑specific complications such as malposition or obstruction seen with some stent‑based MIGS. Humanistic and economic evidence was limited overall, and while MIGS were generally found to be cost‑effective, particularly when combined with cataract surgery, no dedicated economic analyses specific to OMNI were identified. Key limitations of the evidence base highlighted by the authors included heterogeneity in study designs, patient populations, baseline IOP, outcome definitions, and follow‑up durations, which precluded formal comparative effectiveness analyses between devices. Most included studies had relatively short follow‑up (commonly 12–24 months), limiting assessment of long‑term disease control and visual field outcomes in this chronic condition. The majority of evidence came from non‑randomized or retrospective studies, contributing to moderate‑to‑high risk of bias in many analyses, and data on HRQoL and indirect economic costs were sparse. Despite these limitations, the review concluded that MIGS, and particularly devices such as iStent and OMNI with a comparatively larger evidence base, provide effective and safe IOP reduction in mild‑to‑moderate OAG, with OMNI standing out for its versatility as both a standalone and cataract‑combined procedure and its implant‑free approach.
A systematic evidence review and meta‑analysis by Zhu and colleagues (2025) evaluated the efficacy and safety of the OMNI Surgical System when used as a standalone procedure for ab interno canaloplasty and trabeculotomy in patients with open‑angle glaucoma (OAG). The primary objective was to quantify longitudinal reductions in intraocular pressure (IOP) and topical medication burden following standalone OMNI, addressing a gap in the literature given that most prior MIGS evidence focused on procedures combined with cataract surgery. A secondary aim was to assess the proportion of patients achieving medication freedom and to summarize reported safety outcomes. The authors conducted a PRISMA‑compliant systematic review and meta‑analysis registered with PROSPERO. PubMed, Embase, and Scopus were searched through May 2025 for English‑language clinical studies reporting outcomes of standalone OMNI canaloplasty and trabeculotomy in adults with OAG and baseline IOP >18 mm Hg. Five studies (one prospective case series and four retrospective cohorts) comprising 290 eyes met inclusion criteria. Random‑effects meta‑analyses were performed to estimate mean IOP change at 1 month, 6 months, 1 year, and 2 years, as well as changes in medication use and the proportion of medication‑free patients at 1 year. Study quality was assessed using the NIH before–after tool, and overall certainty of evidence was graded using GRADE. Across all time points, standalone OMNI was associated with statistically significant and clinically meaningful IOP reductions. Mean IOP decreased by 7.40 mm Hg at 1 month, 7.25 mm Hg at 6 months, 7.49 mm Hg at 1 year, and 8.77 mm Hg at 2 years, all with p<0.0001. Medication burden also improved, with a mean reduction of 0.77 topical medications at 1 year and 46.2% of patients medication‑free at that time point. Heterogeneity across studies was high, largely attributable to differences in baseline IOP, surgical extent, lens status, and use of preoperative medication washout. Although adverse events were not pooled quantitatively, reported complications were generally mild and self‑limited, most commonly transient hyphema, IOP spikes, and short‑term inflammation, with no device‑related serious adverse events or vision‑threatening complications reported. Key limitations of this evidence review include the small number of included studies, predominance of retrospective, single‑arm designs without control groups, substantial statistical heterogeneity, and limited follow‑up beyond two years. Medication‑related outcomes were supported by very low‑certainty evidence, and adverse event reporting was inconsistent across studies. Despite these constraints, the review provides the clearest synthesized evidence to date that standalone OMNI offers durable IOP reduction and meaningful medication sparing in appropriately selected OAG patients with elevated baseline IOP, supporting its role as an interventional, medication‑sparing option prior to more invasive glaucoma surgery.
Furthermore, an UpToDate review on “Open-angle glaucoma: Treatment” (Jacobs, 2024) states that “There is a group of interventions emerging called “minimally invasive glаսсoma ѕurgеry” (MIGS), which offers promise as a less risky approach to ѕurgiϲal control of glаսϲomа progression. Based on data from Cochrane reviews, some MIGS may afford patients with glаսϲοma greater medication-free disease control than cataract ѕսrgеrу alone”. Moreover, this UTD review does not mention “canaloplasty”, “OMNI Surgical System”, “STREAMLINE Surgical System”, “trabeculotomy” or “TRAB360 Trabeculotomy System” as a management tool.
In a retrospective study, Matsuo et al (2025) examined the surgical effectiveness of combined cataract surgery with microhook ab-interno trabeculotomy (phaco-µLOT) or iStent trabecular micro-bypass stent (phaco-iStent) in eyes with POAG and pre-operative IOP controlled below 15 mmHg (low-teen IOP). This trial included consecutive patients with POAG and low-teen IOP who underwent phaco-µLOT or phaco-iStent as their initial glaucoma surgery and were followed-up for 1 year post-operatively. Surgical failure was defined as the inability to achieve the following criteria twice in a row: IOP of 6 to 15 mmHg with over 20 % IOP reduction; and IOP of 6 to 12 mmHg with over 20 % IOP reduction. A total of 75 eyes from 75 subjects were included, with 48 in the phaco-µLOT group and 27 in the phaco-iStent group. The mean pre-operative IOP and number of anti-glaucoma medications were 13.1 ± 2.1 mmHg and 3.4 ± 0.9 mmHg in the phaco-µLOT group, and 12.6 ± 2.0 mmHg and 2.5 ± 1.2 mmHg in the phaco-iStent group, respectively. The number of anti-glaucoma medications was significantly lowered to 2.5 ± 0.9 (phaco-µLOT) and 2.0 ± 1.1 (phaco-iStent) at 1-year post-operatively, respectively (all p < 0.05). For criteria A and B, the survival rates were significantly higher in the phaco-µLOT group than in the phaco-iStent group (all p < 0.01). The authors concluded that both phaco-µLOT and phaco-iStent hold promise in reducing the need for anti-glaucoma medications in POAG eyes with low-teen IOP. Phaco-µLOT may be more effective than phaco-iStent in controlling IOP. Moreover, these investigators stated that these procedures should be limited to reducing the number of anti-glaucoma medications used, as they did not significantly lower the post-operative IOP in POAG eyes with low-teen IOP.
In a retrospective study, Mbagwu et al (2025) described the real-world characteristics and outcomes of patients undergoing FDA-approved ab interno minimally invasive glaucoma surgery (MIGS) combined with cataract surgery or cataract surgery alone, using data from the American Academy of Ophthalmology (AAO) IRIS Registry. It included 77,391 patients with glaucomatous disease treated with the OMNI Surgical System, Hydrus, iStent Inject, or cataract surgery alone, over a period from July 1, 2017, to December 31, 2022. The outcomes measured were IOP and IOP-lowering medication usage over 24 months, stratified by baseline IOP. Significant reductions in IOP and medication usage were observed in patients with baseline IOP of greater than 18 mmHg across all cohorts, while those with baseline IOP of 18 mmHg or less showed significant medication reductions without change in IOP. The authors concluded that MIGS combined with cataract surgery and cataract surgery alone resulted in significant and sustained IOP and medication reductions. Moreover, these researchers stated that drawbacks of this trial included the retrospective design, potential selection bias, reliance on electronic health records, which may not capture all relevant clinical data, exclusion of off-label procedures, potential under-reporting of medication use, as well as the inability to match and perform statistical analysis due to low sample sizes in some subgroups.
In a retrospective, cohort study, Radcliffe et al (2025) examined long-term, real-world clinical outcomes of stand-alone canaloplasty and trabeculotomy using the OMNI Surgical System in patients POAG. This trial used the AAO IRIS Registry (Intelligent Research in Sight) data. Patients/eyes in the IRIS Registry with POAG or ocular hypertension with known laterality on or after January 1, 2016 and undergoing stand-alone canaloplasty and trabeculotomy using the OMNI Surgical System with at least 6 months and up to 36 months of post-operative follow-up were included. Eyes were excluded for prior filtration surgery, trabeculoplasty within 90 days of the OMNI procedure, or concomitant cataract surgery. Outcome measures included IOP and glaucoma medication changes post-operatively. A total of 230 eyes in 196 patients were analyzed. Most eyes had moderate (40.0 %) or severe (41.3 %) POAG; two-thirds (153 of 230) were pseudophakic. Fewer than half of procedures (44.4 %) were caried out by glaucoma specialists. Mean baseline IOP was 22.1 (6.4) mmHg and over 36 months of follow-up ranged from 15.1 to 16.7 mmHg (p < 0.0001 at every time-point compared to baseline), with average eye-level reductions of 5.6 to 7.1 mmHg. The mean number of glaucoma medications used at baseline was 2.1 (1.5) and over 36 months ranged from 1.1 to 1.8 medication classes, with statistically significant reductions in utilization through 18 months post-operatively (p ≤ 0.0011) and non-significant at months 24 and 36. Eyes with lower baseline IOP (18 mmHg or less) had reductions in medication use through 36 months, and eyes with higher baseline IOP (greater than 18 mmHg) had statistically significant reductions in IOP through 36 months. The authors concluded that stand-alone canaloplasty and trabeculotomy provided clinically and statistically significant reductions in IOP through up to 36 months post-operatively. Eyes with lower baseline IOP had long-term glaucoma medication reductions and eyes with higher baseline IOP had statistically significant long-term IOP reductions. These researchers stated that based on these findings, stand-alone OMNI surgery appeared to be a reasonable MIGS option for patients with POAG with the objective of IOP reduction, medication reduction, or both. Moreover, they noted that outcomes for specific subgroups in the present analysis including disease severity and lens status (phakic or pseudophakic) will be the subject of a future report.
The authors stated that drawbacks of this study included those applicable to all data-base studies (i.e., surgeon bias, non-randomized) and included issues related to data quality, accuracy of documentation and coding, s well as missing data, among others. Of relevance to the OMNI procedure the extent of treatment (i.e., number of clock hours) was not captured in the IRIS data-base. This trial did include both eyes of a patient where both eyes met eligibility criteria. While this could result in an under-estimation of variability, the number of bilateral cases was relatively low relative to the entire cohort, and these investigators felt that the resultant larger safety data-set more than offset this possibility. Specific to claims data analysis, claims data lack laterality of medication use; thus, this study implemented medication utilization analyses at the patient-level, limiting inference on the effectiveness of surgery in decreasing the medication burden for the specific study eye. However, as the direction and magnitude of medication changes over time were consistent with previous reports, it was reasonable to conclude that these data accurately characterized the expected benefits of OMNI surgery on medication burden. There were a diminishing number of eyes with each successive follow-up time-point; while some of this was attrition (including death, or loss to follow-up), smaller numbers at later time-points were expected at the outset of the study based on the decision to include any eye with a minimum of 6 months of follow-up for an OMNI procedure that occurred between January 2018 and June 2023 coupled with the increasing utilization of OMNI since its 2018 introduction.
Mercieca et al (2025) stated that deep sclerectomy (DS) and canaloplasty provide better IOP control than viscocanalostomy. DS required less glaucoma medications but more interventions to reach target IOP. In a retrospective, multi-center study, these investigators compared real-world outcomes of 3 non-penetrating glaucoma surgery (NPGS) techniques. This trial included consecutive patients undergoing canaloplasty (CP), deep sclerectomy (DS), and viscocanalostomy (VC), across nine European glaucoma units. Four IOP criteria were used to define success at 2-year follow-up: Criterion A -- IOP of 21 mmHg or less and 20 % or greater reduction; Criterion B -- IOP of 18 mmHg or less and 20 % or greater reduction; Criterion C -- IOP of 15 mmHg or less and 25 % or greater reduction; and Criterion D -- IOP of 12 mmHg or less and 30 % or greater reduction. Secondary outcomes included IOP control, BCVA, number of medications over time, risk factors for failure, complications, and post-operative interventions. Success was distinguished as qualified or complete, if reached with or without anti-glaucoma medications, respectively. A total of 600 eyes (545 patients) undergoing stand-alone CP (201 eyes), DS (200 eyes), and VC (199 eyes) were included. Qualified success rates of CP, DS, and VP at 24 months were, respectively: (Criterion A) 85.1 %, 67.6 % and 64.6 %; (Criterion B) 85.1 %, 66.1 % and 58.6 %; (Criterion C) 76.6 %, 55.5 % and 39.0 %; (Criterion D) 27.7 %, 28.5 % and 22.1 %. Success rates were significantly different across the 3 techniques (p = 0.04 or below), except for complete success according to criterion A (p = 0.07). Mean IOP (± SD) reduced from 25.2 (± 6.9), 20.5 (± 6.7), and 22.7 (± 7.2) mmHg pre-operatively to 13.1 (± 3.1), 12.9 (± 4.5), and 14.7 (± 4.6) mmHg at post-operative year 2 in the CP, DS, and VC groups, respectively (p < 0.001 between pre-operative and post-operative time-points for all groups). The authors concluded that all 3 NPGS provided sustained IOP reduction; however, DS and CP provided better success rates and IOP control. Success rates were low for the most stringent cut-offs, suggesting that other techniques such as trabeculectomy may be indicated when a very low target IOP is demanded.
Penetrating Canaloplasty versus Ab Externo Canaloplasty for the Treatment of Primary Open-Angle Glaucoma
In a prospective, single-center RCT, Ye et al (2025) reported the 2-year safety and effectiveness of penetrating canaloplasty versus ab externo canaloplasty for the treatment of POAG. Surgical success, IOP, number of glaucoma medications, and surgical complications were evaluated until 24 months post-operatively. Surgical success was defined as 6 mmHg ≤ IOP ≤ 21 mmHg with an IOP reduction ≥ 20 %, which included qualified success (with or without medications) and complete success (without medications). A total of 52 eyes (45 patients) were randomly assigned to the penetrating canaloplasty group (PCP, n = 26) or the ab externo canaloplasty group (CP, n = 26). The probabilities of qualified success and complete success were 92.3 % and 76.9 %, respectively, in the PCP group; and 64.1 % and 52.1 %, respectively, in the CP group at 24 months (p = 0.013, p = 0.042, log-rank test). The mean IOP decreased from 30.8 ± 10.7 and 28.6 ± 11.8 mmHg to 14.1 ± 3.3 mmHg in the PCP group; and 22.1 ± 13.6 mmHg in the CP group at year 2 (p = 0.007). The PCP group also received fewer medications (0.2 ± 0.5) than did the CP group (0.7 ± 1.2) at year 2 (p = 0.038). Post-operative complication rates were similar, and the most common complications were transient IOP elevation and hyphema in the PCP group (42.3 %, 46.2 %) and the CP group (38.5 %, 23.1 %) (p > 0.05). The authors concluded that compared to ab externo canaloplasty, penetrating canaloplasty exhibited a greater surgical success rate and better IOP reduction with a comparable rate of complications.
Cataract Surgery Combined with Ab Interno Canaloplasty and Micro-Trabecular Bypass Stent Surgery for the Treatment of Open-Angle Glaucoma
In a retrospective, 2-center, case-series study, Porter et al (2025) examined the effectiveness of canaloplasty via an ab-interno technique using the iTrack combined with micro-trabecular bypass stent surgery with the Hydrus Microstent following cataract surgery (CE) in patients with POAG. This trial included 51 POAG eyes that underwent phacoemulsification followed by canaloplasty combined with micro-trabecular bypass stent surgery. Eyes were categorized according to IOP and disease severity. A subgroup of patients on 3+ medications at baseline was included. Primary end-points included the mean IOP and mean number of medications at 12 months, 24 months and at the last follow-up. Baseline IOP (mmHg) and number of medications were 19.1 ± 4.0 and 2.3 ± 1.2 and reduced to 13.9 ± 2.6 (p < 0.001) and 1.2 ± 1.4 (p < 0.001) at 12 months, 13.7 ± 2.0 and 1.5 ± 1.5 (p < 0.001, p = 0.008, respectively) at 24 months (n = 31) and 14.4 ± 3.2 and 2.1 ± 1.5 (p < 0.001, p = 0.5, respectively) at 36 months. In the uncontrolled group (n = 27), baseline IOP and number of medications were 21.9 ± 3.1 and 1.9 ± 1.3 and reduced to 14.6 ± 4.2 (p = 0.006) and 1.7 ± 1.6 (p = 0.821) at 36 months post-operatively. Baseline IOP and number of medications of severe patients (n = 12) were 19.0 ± 4.8 and 1.9 ± 1.1. IOP reduced to 12.8 ± 2.4 (p = 0.005) at 12 months while the number of medications did not show any statistically significant change: 1.9 ± 1.6 (p = 0.4). No eyes underwent additional glaucoma surgery in the study period. The authors concluded that canaloplasty combined with micro-trabecular bypass stent surgery following cataract extraction were effective in reducing IOP and medication burden up to 24 months post-operatively; and IOP reduction was also sustained up to 36 months post-operatively. The combined MIGS procedure was also effective in eyes with uncontrolled glaucoma.
The authors stated that the drawbacks of this trial included the modest sample size (n = 51), the retrospective design, lack of randomization, and lack of comparison with a control group. These researchers stated that future investigations should examine the integration of multiple MIGS within a single surgery and their role in addressing various underlying causes of elevated IOP. This should include examining the cost-effectiveness of combining MIGS procedures and identifying the most suitable candidates for such approaches.
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