Vitrectomy

Number: 0393

Policy

Aetna considers vitrectomy medically necessary for the following conditions:

• Macular hole repair
• Proliferative retinopathy
• Rapidly progressing infectious endophthalmitis
• Retinal detachments secondary to vitreous strands
• RPE65 mutation-associated retinal dystrophy (for administration of voretigene neparvovec-rzyl (Luxturna) (see CPB 927 - Luxturna (Voretigene Neparvovec-rzyl)).
• Traumatic penetrating ocular injury
• Vitreous loss incident to cataract surgery
• Vitreous opacities due to vitreous hemorrhage or other causes
• Vitreous retraction.

Aetna considers the vitrectomy face support device (post-vitrectomy face-down support system) medically necessary for members who have undergone vitrectomy surgery, and who are required to maintain a face down position in the post-operative period.

Aetna considers monitoring of intra-ocular pressure during vitrectomy surgery experimental and investigational because of a lack of evidence that such monitoring improves clinical outcomes.

Aetna considers prophylactic pars plana vitrectomy for acute retinal necrosis experimental and investigational because the effectiveness of this approach has not been established.

Background

Vitrectomy is the surgical removal of the vitreous (transparent gel that fills the eye from the iris to the retina). Vitrectomy may be necessary for the following conditions (CMS, 2006): vitreous loss incident to cataract surgery, vitreous opacities due to vitreous hemorrhage or other causes, retinal detachments secondary to vitreous strands, proliferative retinopathy, and vitreous retraction.

Vitrectomy may be indicated for complications of diabetic retinopathy, including vitreous hemorrhage and retinal detachment.  It may also be indicated for persons with traumatic penetrating ocular injury, non-diabetic vitreous hemorrhage, rapidly progressing infectious endophthalmitis, and cataract extractions complicated by a vitreous loss or an underlying inflammatory condition.

Wide fluctuations in intra-ocular pressure (IOP) have been documented during vitrectomy in animal models.  Such fluctuations in IOP are posited to have potential adverse effects on retinal and optic nerve function and visual acuity recovery, especially for patients with compromised retinal or optic nerve blood flow and decreased ocular perfusion pressure.

An indirect method of monitoring IOP during vitrectomy surgery has been developed (Armoor Ophthalmics, Houston, TX), which involves placing disposable blood pressure transducers into the line tubing used for vitrectomy infusion.  Moorhead et al (2005) reported on a clinical study in which this indirect method of IOP measurement was compared to direct measurement during vitrectomy procedures in 10 patients.  Intra-ocular pressure was directly measured by inserting a catheter pressure transducer by an extra pars plana incision directly into the vitreous.  During various maneuvers of vitrectomy, including air-fluid exchange and gas-forced fusion, pressure measurements were taken simultaneously from the indwelling pressure transducer and the disposable blood pressure sensors in the infusion line.  The directly measured IOP varied between 0 and 120 mm Hg during vitrectomy.  The investigators reported in each case how indirectly measured IOP during fluid flow, calculated from infusion line pressures, correlated with the directly measured IOP.  The investigators commented that the variation in pressures encountered during these vitrectomy surgeries weree similar to measurements reported during cataract surgery.  The investigators stated that it is likely that pressure variations documented in this study may be detrimental, but the physiological significance of these findings requires further study.

Following vitrectomy surgery (e.g., repair of macular hole, retinal detachment), face-down positioning may be required for several weeks to maximize retinal tamponade and, subsequently, hole closure or retinal attachment.  The vitrectomy face-down positioning system (also known as a vitrectomy chair or a vitrectomy support system) is a device that may be appropriate in selected cases to assist the patient in maintaining a face down position.  The rental of a vitrectomy face support may be necessary for up to 6 weeks after vitrectomy surgery.

Ishikawa et al (2009) evaluated the safety and effectiveness of intra-vitreal injection of bevacizumab (IVB) advanced to vitrectomy for severe proliferative diabetic retinopathy (PDR).  A total of 8 eyes of 6 patients (33 to 64 years old, all male subjects) with severe PDR were investigated.  An intra-vitreal injection of 1.25 mg bevacizumab was carried out 3 to 30 days before planned vitrectomy.  All cases showed minimum bleeding during surgical dissection of fibro-vascular membrane.  Two cases receiving bevacizumab 7 days before the surgery showed strong fibrosis and adhesion of fibro-vascular membrane, resulted in some surgical complications.  The cases having IVB for shorter time did not show extensive fibrosis.  The authors concluded that pre-treatment of bevacizumab is likely effective in the vitrectomy for severe PDR.  The appropriate timing of vitrectomy after bevacizumab injection should be further evaluated.

In a review on diabetic retinopathy (DR), Cheung et al (2010) noted that although anti-vascular endothelial growth factor (VEGF) therapy has promising clinical applications for the management of DR, its long-term safety in patients with diabetes has not yet been established.  Local adverse events of IVB include cataract formation, infection, retinal detachment, vitreous hemorrhage, as well as potential loss of neural retinal cells.  Furthermore, a significant portion of anti-VEGF agents injected into the eye could pass into the systemic circulation.  Thus, systemic inhibition of angiogenesis is a potential risk.  Also, although clinical trials on the use of intra-vitreal anti-VEGF therapy for the treatment of age-related macular degeneration generally show low (0.6 to 1.2 %) rates of stroke, this risk could be increased in patients with DR because of pre-existing diabetes-related vascular disease.

Nicholson and Schachat (2010) stated that many observational and pre-clinical studies have implicated VEGF in the pathogenesis of DR, and recent successes with anti-VEGF therapy for age-related macular degeneration have prompted research into the application of anti-VEGF drugs to DR.  These investigators reviewed the numerous early studies that suggest an important potential role for anti-VEGF agents in the management of DR.  The authors concluded that for diabetic macular edema, phase II trials of intra-vitreal pegaptanib and intra-vitreal ranibizumab have shown short-term benefit in visual acuity.  Intra-vitreal bevacizumab also has been shown to have beneficial short-term effects on both visual acuity and retinal thickness.  For PDR, early studies suggest that IVB temporarily decreases leakage from diabetic neovascular lesions, but this treatment may be associated with tractional retinal detachment.  Furthermore, several studies indicate that bevacizumab is likely to prove a helpful adjunct to diabetic pars plana vitrectomy for tractional retinal detachment.  Finally, 3 small series suggest a potential beneficial effect of a single dose of bevacizumab to prevent worsening of diabetic macular edema (DME) after cataract surgery.  The authors noted that use of anti-VEGF medications for any of these indications is off-label.  Despite promising early reports on the safety of these medications, the results of large, controlled trials to substantiate the safety and efficacy of anti-VEGF drugs for diabetic retinopathy are eagerly awaited.

In a prospective, comparative case series, El-Sabagh and colleagues (2011) evaluated the effects of intervals between pre-operative IVB and surgery on the components of removed diabetic fibro-vascular proliferative membranes.  A total of 52 eyes of 49 patients with active diabetic fibro-vascular proliferation with complications necessitating vitrectomy were included in this study.  Participant eyes that had IVB were divided into 8 groups in which vitreo-retinal surgery was performed at days 1, 3, 5, 7, 10, 15, 20, and 30 post-injection.  A group of eyes with the same diagnosis and surgical intervention without IVB injection was used for comparison.  In all eyes, proliferative membrane specimens obtained during vitrectomy were sent for histopathologic examination using hematoxylin-eosin stain, immunohistochemistry (CD34 and smooth muscle actin), and Masson's trichrome stain.  Main outcome measure was comparative analysis of different components of the fibro-vascular proliferation (CD34, smooth muscle actin, and collagen) among the study groups.  Pan-endothelial marker CD34 expression levels starting from day 5 post-injection were significantly less than in the control group (p < 0.001), with minimum expression (1+) in all specimens removed at or after day 30 post-injection.  Positive staining for smooth muscle actin was barely detected in the control eyes at day 1, and consistently intense at day 15 and beyond (p < 0.001).  The expression level of trichrome staining was significantly high at day 10, compared with control eyes (p < 0.001), and continued to increase at subsequent surgical time points.  The author concluded that a pro-fibrotic switch was observed in diabetic fibro-vascular proliferation after IVB, and these findings suggest that at approximately 10 days post-IVB the vascular component of proliferation is markedly reduced, whereas the contractile components (smooth muscle actin and collagen) are not yet abundant.  Moreover, the authors noted that their histologic findings are in agreement with many published clinical findings and might be predictive of an optimal time interval for the pre-operative use of adjunctive IVB, which makes surgery more successful with less intra-operative bleeding and complications; thus resulting in better visual outcomes.  However, such favorable outcomes need validation from large-scale clinical studies.

Do and colleagues (2013) noted that cataract formation or acceleration can occur after intra-ocular surgery, especially following vitrectomy.  The underlying problem that led to vitrectomy may limit the benefit from cataract surgery.   In a Cochrane review, these researchers evaluated the safety and effectiveness of surgery for post-vitrectomy cataract with respect to visual acuity, quality of life, and other outcomes.  They searched CENTRAL (which contains the Cochrane Eyes and Vision Group Trials Register) (The Cochrane Library 2013, Issue 4), Ovid MEDLINE, Ovid MEDLINE in-Process and Other Non-Indexed Citations, Ovid MEDLINE Daily Update, Ovid OLDMEDLINE (January 1946 to May 2013), EMBASE (January 1980 to May 2013, Latin American and Caribbean Health Sciences Literature Database (LILACS) (January 1982 to May 2013), PubMed (January 1946 to May 2013), the metaRegister of Controlled Trials (mRCT), ClinicalTrials.gov and the WHO International Clinical Trials Registry Platform (ICTRP). These investigators did not use any date or language restrictions in the electronic searches for trials.  They last searched the electronic databases on May 22, 2013.  They planned to include randomized and quasi-randomized controlled trials (RCTs) comparing cataract surgery with no surgery in adult patients who developed cataract following vitrectomy.  Two authors screened the search results independently according to the standard methodological procedures expected by The Cochrane Collaboration.  They found no randomized or quasi-RCTs comparing cataract surgery with no cataract surgery for patients who developed cataracts following vitrectomy surgery.  The authors concluded that there is no evidence from randomized or quasi-RCTs on which to base clinical recommendations for surgery for post-vitrectomy cataract.  There is a clear need for RCTs to address this evidence gap.  Such trials should stratify participants by their age, the retinal disorder leading to vitrectomy, and the status of the underlying disease process in the contralateral eye.  Outcomes assessed in such trials may include gain of vision on the Early Treatment Diabetic Retinopathy Study (ETDRS) scale, quality of life, and adverse events such as posterior capsular rupture.  Both short-term (6-month) and long-term (1-year or 2-year) outcomes should be examined.

Simunovic et al (2014) performed a meta-analysis of published RCTs regarding the effectiveness of vitrectomy for DME.  These investigators searched PubMed and the Cochrane database for randomized, controlled trials investigating vitrectomy for DME. Structural (foveal thickness) and functional (visual acuity) outcomes were used as the primary outcome measures.  A total of 11 studies met the criteria for inclusion in this review: these studies were heterogeneous in their experimental and control interventions, follow-up period, and eligibility criteria.  Seven studies compared vitrectomy with the natural history of diabetic maculopathy, with laser, or with intra-vitreal corticosteroid injection; 4 studies compared vitrectomy with internal limiting membrane peeling to vitrectomy alone; 1 of the latter 4 studies was the only to investigate vitrectomy in patients with vitreo-macular traction.  Meta-analysis suggested a structural, and possibly functional, superiority of vitrectomy over observation at 6 months.  Vitrectomy also appears superior to laser in terms of structural, but not functional, outcomes at 6 months.  At 12 months, vitrectomy offers no structural benefit and a trend toward inferior functional outcomes when compared with laser.  The authors concluded that there is little evidence to support vitrectomy as an intervention for DME in the absence of epiretinal membrane or vitreo-macular traction.  They noted that although vitrectomy appears to be superior to laser in its effects on retinal structure at 6 months, no such benefit has been proved at 12 months.  Furthermore, there is no evidence to suggest a superiority of vitrectomy over laser in terms of functional outcomes.

An UpToDate review on “Diabetic retinopathy: Prevention and treatment” (Fraser and D’Amico, 2015) states that “Vitrectomy may be beneficial in selective cases of clinically significant ME. However, the results of vitrectomy are somewhat variable, ranging from no benefit to visual acuity gains of several lines or more.  Some authors advocate simple removal of the vitreous gel, others recommend additional removal of the thick posterior hyaloid, and still others perform both of these and also remove the internal limiting membrane ("ILM peeling") of the retina itself.  A systematic review of trials assessing a combination of these techniques versus observation or focal photocoagulation reported that vitrectomy may be beneficial in some patients with clinically significant ME, particularly in those with evidence of vitreo-macular traction, although the evidence was weak”.

An American Academy of Ophthalmology Preferred Practice Pattern on Diabetic Retinopathy (2014) stated that vitreous surgery is frequently indicated in patients with traction macular detachment (particularly of recent onset), combined traction–rhegmatogenous retinal detachment, and vitreous hemorrhage precluding panretinal photocoagulation. Patients with vitreous hemorrhage and rubeosis iridis also should be considered for prompt vitrectomy and intraoperative panretinal photocoagulation surgery.

Macular Hole Repair

In a Cochrane review, Spiteri Cornish et al (2014) examined if ILM peeling improves anatomic and functional outcomes of full-thickness macular hole (FTMH) surgery when compared with the no-peeling technique.  Systematic review and individual participant data (IPD) meta-analysis were undertaken under the auspices of the Cochrane Eyes and Vision Group.  Only RCTs were included.  Patients with idiopathic stage 2, 3, and 4 FTMH undergoing vitrectomy with or without ILM peeling were included in this analysis.  Subjects underwent macular hole surgery, including vitrectomy and gas endotamponade with or without ILM peeling.  Primary outcome was best-corrected distance visual acuity (BCdVA) at 6 months post-operatively.  Secondary outcomes were BCdVA at 3 and 12 months; best-corrected near visual acuity (BCnVA) at 3, 6, and 12 months; primary (after a single surgery) and final (after greater than 1 surgery) macular hole closure; need for additional surgical interventions; intra-operative and post-operative complications; patient-reported outcomes (PROs) (EuroQol-5D and Vision Function Questionnaire-25 scores at 6 months); and cost-effectiveness.  A total of 4 RCTs were identified and included in the review.  All RCTs were included in the meta-analysis; IPD were obtained from 3 of the 4 RCTs.  No evidence of a difference in BCdVA at 6 months was detected (mean difference, -0.04; 95 % confidence interval [CI]: -0.12 to 0.03; p = 0.27); however, there was evidence of a difference in BCdVA at 3 months favoring ILM peeling (mean difference, -0.09; 95 % CI: -0.17 to -0.02; p = 0.02).  There was evidence of an effect favoring ILM peeling with regard to primary (odds ratio [OR], 9.27; 95 % CI: 4.98 to 17.24; p < 0.00001) and final macular hole closure (OR, 3.99; 95 % CI: 1.63 to 9.75; p = 0.02) and less requirement for additional surgery (OR, 0.11; 95 % CI: 0.05 to 0.23; p < 0.00001), with no evidence of a difference between groups with regard to intra-operative or postoperative complications or PROs.  The ILM peeling was found to be highly cost-effective.  The authors concluded that available evidence supports ILM peeling as the treatment of choice for patients with idiopathic stage 2, 3, and 4 FTMH.

In a Cochrane review, Parravano and colleagues (2015) examined the effects of vitrectomy for idiopathic macular hole on VA.  A secondary objective was to investigate anatomic effects on hole closure and other dimensions of visual function, as well as to report on adverse effects recorded in included studies.  These investigators searched the Cochrane Eyes and Vision Group Trials Register (March 4, 2015), the Cochrane Central Register of Controlled Trials (CENTRAL; 2015, Issue 2), Ovid MEDLINE, Ovid MEDLINE In-Process and Other Non-Indexed Citations, Ovid MEDLINE Daily, Ovid OLDMEDLINE (January 1946 to March 2015), EMBASE (January 1980 to March 2015), Latin American and Caribbean Health Sciences Literature Database (LILACS) (January 1982 to March 2015), the Web of Science Conference Proceedings Citation Index-Science (CPCI-S) (January 1980 to March 2015), the ISRCTN registry (www.isrctn.com/editAdvancedSearch), ClinicalTrials.gov (www.clinicaltrials.gov) and the World Health Organization (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 March 4, 2015.  These researchers included RCTs comparing vitrectomy (with or without ILM peeling) to no treatment (that is observation) for macular holes.  They used standard methodological procedures expected by Cochrane.  Two review authors independently extracted the data.  They estimated best-corrected visual acuity (BCVA) and macular hole closure at 6 to 12 months of follow-up.  A total of 3 studies provided data on the comparison between vitrectomy and observation in eyes with macular hole and VA less than 20/50.  Two studies, conducted in the USA and published in 1996 and 1997, used a similar protocol and included participants with stage II macular hole (42 eyes randomized, 36 analyzed, number of participants not reported) or participants with stage III/IV hole (129 eyes of 120 participants, 115 eyes in analyses).  The 3rd study, conducted in the UK and published in 2004, included 185 eyes of 174 participants with full-thickness macular hole (41 eyes with stage II holes and 74 eyes with stage III/IV holes in analyses).  Studies were of good quality for randomization and allocation concealment, whereas VA measurement was un-masked.  At 6 to 12 months, VA was improved by about 1.5 Snellen lines (-0.16 logMAR, 95 % CI: -0.23 to -0.09 logMAR, 270 eyes, moderate-quality evidence).  The chances of macular hole closure at 6 to 12 months were greatly increased using vitrectomy, yielding an OR of 31.4 (95 % CI: 14.9 to 66.3, 265 eyes, high-quality evidence; raw sum data: 76 % vitrectomy, 11 % observation).  Vitrectomy was beneficial both in smaller (stage II) and in larger (stage III/IV) macular holes.  The largest study reported that cataract surgery was needed in about 50 % of cases at 2 years after operation and that retinal detachment occurred in approximately 5 % of operated eyes.  The authors concluded that vitrectomy is effective in improving VA, resulting in a moderate visual gain, and in achieving hole closure in people with macular hole.

Prophylactic Pars Plana Vitrectomy for the Treatment of Acute Retinal Necrosis

Liu and co-workers (2018) compared the efficacy of pars plana vitrectomy (PPV) at different time-points to treat acute retinal necrosis (ARN) and to investigate the necessity of PPV for ARN.  These researchers carried out a retrospective review of the therapeutic options and outcomes of the ARN patients.  A total of 30 ARN patients (34 eyes) were included in this study.  The eyes were divided into 3 groups depending on the treatment administered.  In the medically treated group, there was no retinal detachment (RD) at the 1st visit.  The routine group patients were treated with systemic anti-viral medications, as well as with intra-vitreal anti-viral injections.  In the early PPV treatment group, there was no RD at the 1st visit.  The early PPV treatment group patients were treated with systemic anti-viral medications and PPV plus silicone oil tamponade and intra-vitreal injection.  In the PPV group, there was RD at the 1st visit.  The PPV group patients were treated with systemic anti-viral medications and PPV plus silicone oil tamponade and intra-vitreal injection.  In the medically treated group, the mean baseline BCVA (logMAR) was 1.38 ± 0.35.  The BCVA was 1.21 ± 0.36 at the last visit for the medically treated group.  In this group, 1 eye (12.5 %) developed RD after 1 month of treatment.  In the early PPV treatment group, the mean BCVA (logMAR) was 1.68 ± 0.26.  The BCVA was 1.83 ± 0.21 at the last visit for the early PPV group.  In this group, 5 eyes (29.4 %) had recurrent RD before silicone oil removal.  In the PPV group, the mean BCVA (logMAR) was 2.0 ± 0.35.  The BCVA was 1.72 ± 0.34 at the last visit for the PPV group.  In this group, 1 eye (11.1 %) had recurrent RD before silicone oil removal.  There were no significant differences among the 3 groups in the baseline BCVA and the BCVA at the last visit (p > 0.05).  There were no significant differences between the early PPV group and the PPV group in the recurrent RD rates (p = 0.38).  The authors concluded that prophylactic PPV showed no difference in recurrent RD rates or better BCVA; thus, prophylactic vitrectomy could not prevent RD nor improve the prognosis of ARN based on these findings.  Moreover, they stated that further studies are needed to ascertain the therapeutic method to decrease the development of PVR.

The above policy is based on the following references: