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Background
In optical coherence tomography (OCT), low coherence near-infrared light is split into a probe and a reference beam. The probe beam is directed at the tissues while the reference beam is sent to a moving reference mirror. The probe light beam is reflected from tissues according to their distance, thickness, and refractive index, and is then combined with the beam reflected from the moving reference mirror. When the path lengths of the two light beams coincide (known as constructive interference), this provides a measure of the depth and reflectivity of the tissue that is analogous to an ultrasound A scan at a single point. A computer then corrects for axial eye movement artifacts and constructs a 2-dimensional B mode image from successive longitudinal scans in the transverse direction. A map of the tissue is then generated based on the different reflective properties of its components, resulting in a real-time cross-sectional histological view of the tissue (AHFMR, 2003).
Optical coherence tomography (OCT) of the posterior segment of the eye has been used for screening, diagnosis, and management of glaucoma and other retinal diseases (AHFMR, 2003; NHSC, 2002).
Optical coherence tomography is also being studied as a method of evaluating the anterior segment of the eye (e.g., the cornea, iris, anterior chamber and the central portion of the lens). Primary angle closure glaucoma is a common cause of visual loss. Currently, gonioscopy is the standard method for evaluating the anatomy of the anterior segment of the eye. Anterior segment OCT (AS-OCT), with its rapid, non-contact, and high-resolution image acquisition, appears to be a promising tool for the assessment of the anterior chamber angle (ACA) configuration, including changes induced by illumination and laser peripheral iridotomy. It has the potential for use as a rapid screening tool for detection of occludable angles.
The Visante OCT (Carl Zeiss Meditec, Dublin, CA) is a non-contact, high-resolution tomographic and biomicroscopic device that received marketing clearance through the U.S. Food and Drug Administration (FDA) 510(k) process in 2005, listing the Stratus OCT and Orbscan II as predicate devices. It is indicated for the in vivo imaging and measurement of ocular structures in the anterior segment such as corneal and laser in situ keratomileusis (LASIK) flap thickness (FDA, 2005). Since Visante OCT is a non-invasive procedure that can be conducted by a technician, it has been proposed that this device may provide a rapid diagnostic and screening tool for the detection of angle closure in glaucoma. Also being investigated is the possibility that the 0.8 micron wavelength Stratus OCT may provide sufficient detail for routine clinical assessment of the ACA in glaucoma patients. Radhakrishnan et al (2005) stated that ongoing clinical trials should aid to evaluate the effectiveness of AS-OCT especially in the setting of detection of occludable angles.
In a prospective observational case series, Nolan and colleagues (2007) evaluated AS-OCT as a qualitative method for imaging the ACA and ascertained its ability to detect primary angle closure when compared with gonioscopy in Asians. A total of 203 subjects with diagnoses of primary angle closure, primary open-angle glaucoma, ocular hypertension, or cataract were recruited. Both eyes (if eligible) of each patient were included in the study. Exclusion criteria were pseudophakia or previous glaucoma surgery. Images of the nasal, temporal, and inferior angles were obtained with AS-OCT in dark and then light conditions. Gonioscopic angle width was graded using the Spaeth classification for each quadrant in low lighting conditions. Angle closure was defined by AS-OCT as contact between the peripheral iris and angle wall anterior to the scleral spur and by gonioscopy as a Spaeth grade of 0 degree (posterior trabecular meshwork not visible). Comparison of the two methods in detecting angle closure was done by eye and by individual. Sensitivities and specificities of AS-OCT were calculated using gonioscopy as the reference standard. Complete data were available for 342 eyes of 200 patients. Of the patients, 70.9 % had a clinical diagnosis of treated or untreated primary angle closure. Angle closure in greater than or equal to 1 quadrants was detected by AS-OCT in 142 (71 %) patients (228 [66.7 %] eyes) and by gonioscopy in 99 (49.5 %) patients (152 [44.4 %] eyes). The inferior angle was closed more frequently than the nasal or temporal quadrants using both AS-OCT and gonioscopy. When performed under dark conditions, AS-OCT identified 98 % of those subjects found to have angle closure on gonioscopy (95 % confidence interval [CI]: 92.2 to 99.6) and led to the characterization of 44.6 % of those found to have open angles on gonioscopy to have angle closure as well. With gonioscopy as the reference standard, specificity of AS-OCT in the dark was 55.4 % (95 % CI: 45.2 to 65.2) for detecting individuals with angle closure. The authors concluded that AS-OCT is a rapid non-contact method for imaging angle structures. It is highly sensitive in detecting angle closure when compared with gonioscopy.
It should be noted that evaluation of the diagnostic performance of the Visante OCT should depend on demonstration of an improvement in clinical outcomes. Although the resolution of the images and the ease of use might be considered advantageous, available evidence is insufficient to ascertain if the use of OCT can improve detection and management of patients at risk of developing primary angle closure glaucoma.
In a prospective observational study, Kalev-Landoy and colleagues (2007) assessed the ability of OCT to visualize the ACA in patients with different angle configurations. The anterior segments of 26 eyes of 26 patients were imaged using the Zeiss Stratus OCT, model 3000. Imaging of the anterior segment was achieved by adjusting the focusing control on the Stratus OCT. A total of 16 patients had abnormal angle configurations including narrow or closed angles and plateau irides, and 10 had normal angle configurations as determined by prior full ophthalmic examination, including slit-lamp biomicroscopy and gonioscopy. In all cases, OCT provided high-resolution information regarding iris configuration. The ACA itself was clearly visualized in patients with narrow or closed angles, but not in patients with open angles. The authors concluded that the Stratus OCT offers a non-contact, convenient and rapid method for assessing the configuration of the anterior chamber. Despite its limitations, it may be of help during the routine clinical assessment and treatment of patients with glaucoma, particularly when gonioscopy is not possible or difficult to interpret.
In a population-based, cross-sectional study, Zhao and associates (2007) compared the measurement of the central corneal thickness (CCT) by Visante OCT with ultrasound pachymetry (USP). Subjects were part of a study of 3,280 Malay subjects aged 40 to 80 years. Ultrasound pachymetry of CCT was performed on all participants and approximately 10 % underwent further evaluation with AS-OCT. A total of 285 subjects were included, with a mean age of 57.9 (+/- 10.8) years. Central corneal thickness as measured by USP was highly correlated with the equivalent AS-OCT reading (the Pearson correlation coefficient = 0.93, p < 0.001). However, Bland-Altman analysis showed that CCT as measured by USP was significantly higher by 16.5 +/- 11.7 microm (limits of agreement -6.1 to 39.1, p < 0.001). The authors concluded that CCT measured by Visante AS-OCT was highly correlated with that from USP. However, CCT readings by Visante OCT were consistently less than that of USP.
Konstantopoulos and co-workers (2007) stated that anterior segment imaging is a rapidly advancing field of ophthalmology. New imaging devices such as rotating Scheimpflug imaging (Pentacam-Scheimpflug) and AS-OCT (Visante OCT and Slit-Lamp OCT) have recently become commercially available. These new devices supplement the more established imaging tools of Orbscan scanning slit topography and ultrasound biomicroscopy. All devices promise quantitative information and qualitative imaging of the cornea and anterior chamber. They provide a quantitative angle estimation by calculating the angle between the iris surface and the posterior corneal surface. Direct angle visualization is feasible with the OCT devices and biomicroscopy; they provide images of the scleral spur, ciliary body, ciliary sulcus and even canal of Schlemm in some eyes. Pentacam-Scheimpflug can measure net corneal power, a feature especially useful for cataract patients having undergone previous corneal surgery. Anterior segment OCT can measure corneal flap depth following LASIK and anterior chamber width prior to phakic intra-ocular lens implantation. The authors noted that the advent of new imaging devices may herald the dawn of a new era for ophthalmic diagnosis.
In an observational, cross-sectional study (n = 70), Li and co-workers (2007) evaluated the agreement of CCT and para-central corneal thickness (PCCT) measurements between USP, Orbscan II, and Visante AS-OCT. Each subject underwent Orbscan II (using an acoustic equivalent correction factor of 0.89), AS-OCT, and USP examination. Bland-Altman plots were used to evaluate agreement between instruments. Main outcome measures were CCT and PCCT measurements by the 3 methods and agreement, as evaluated by 95 % limits of agreement (LOA). The mean measurements of average CCT by USP, Orbscan II, and AS-OCT were 553.5 +/- 30.26 microm, 553.22 +/- 25.47 microm, and 538.79 +/- 26.22 microm, respectively. There was high correlation between instruments: USP with AS-OCT (r = 0.936, p < 0.001), USP with Orbscan II (r = 0.900, p < 0.001) for CCT measurements, and Orbscan II with AS-OCT for average para-central 2- to 5-mm measurements (r = 0.947, p < 0.001). The mean differences (and upper/lower LOA) for CCT measurements were 0.31 +/- 13.34 microm (26.44/-25.83) between USP and Orbscan II, 14.74 +/- 10.84 microm (36.0/-6.51) between USP and AS-OCT, and 14.44 +/- 9.14 microm (32.36/-3.48) between Orbscan II and AS-OCT. The average mean difference (and upper/lower LOA) between Orbscan II and AS-OCT for PCCT 2- to 5-mm corneal thickness measurements was 10.35 +/- 8.67 microm (27.35 +/- 6.65). The authors concluded that AS-OCT under-estimated corneal thickness compared with that measured with USP. Anterior segment-OCT had better agreement with the gold standard USP, as compared with Orbscan II. However, important discrepancies among instruments exist. These researchers stated that clinicians should be aware that measurements of CCT are influenced by the method of measurement and that, although highly correlated, these instruments should not be used inter-changeably for the assessment of corneal thickness.
Ho et al (2007) compared corneal thickness assessment using 4 measurement methods in eyes after LASIK for myopia. A total of 52 consecutive patients (103 eyes) who had LASIK for the correction of myopia had Orbscan II, Visante, Pentacam, and USP 6 months after surgery. Data were analyzed using the paired sample t test, Bland-Altman plots, and linear regression. The mean post-operative corneal thickness measurements by USP, Orbscan (0.89 acoustic factor), Pentacam, and Visante were 438.2 microm +/- 41.18, 435.17 +/- 49.63 microm, 430.66 +/- 40.23 microm, and 426.56 +/- 41.6 microm, respectively. Compared with the USP, Pentacam and Visante measurements significantly under-estimated corneal thickness by a mean of 7.54 +/- 15.06 microm (p < 0.01) and 11.64 +/- 12.87 microm (p < 0.01), respectively. There was no statistically significant difference between USP and Orbscan measurements. The authors concluded that Pentacam and Visante measurements of corneal thickness 6 months after LASIK were significantly less than those obtained using Orbscan and USP, although all 4 measurement methods showed a high correlation with each other.
Radhakrishnan et al (2007) evaluated the reproducibility of ACA measurements obtained using AS-OCT. Patients with suspected glaucoma and those with glaucoma, ocular hypertension, or anatomically narrow angles were recruited for this study. All subjects underwent imaging of the nasal, temporal, and inferior ACA with an AS-OCT prototype under standardized dark and light conditions. For short-term reproducibility analysis, a single observer acquired 2 sets of images followed by a 3rd set of images acquired by a 2nd observer. The interval between sessions was 10 minutes. For long-term reproducibility analysis, a single observer acquired two sets of images at least 24 hours apart. Images were measured using custom software to determine the anterior chamber depth (ACD), angle opening distance at 500 microm (AOD(500)), angle recess area at 500 microm (ARA(500)), and trabecular-iris space area at 500 microm (TISA(500)). The intra-class correlation coefficient (ICC) was calculated as a measure of intra-observer and inter-observer reproducibility. Twenty eyes of 20 patients were analyzed for short-term reproducibility, and 23 eyes of 23 patients were analyzed for long-term reproducibility. Anterior chamber depth measurement demonstrated excellent reproducibility (ICC 0.93 to 1.00) in both dark and light conditions. For the nasal and temporal quadrants, all ACA parameters demonstrated good to excellent short-term (ICC 0.67 to 0.90) and long-term (ICC 0.56 to 0.93) reproducibility in both dark and light conditions. In the inferior quadrant, reproducibility was lower in all categories of analysis and varied from poor to good (ICC 0.31 to 0.73). The authors concluded that AS-OCT allows quantitative assessment of the ACA. The reproducibility of ACA measurements was good to excellent for the nasal and temporal quadrants. The lower reproducibility of measurements in the inferior quadrant may be unique to this prototype due to difficulty in acquiring high-quality images of the inferior angle. These researchers noted that further assessment of the commercially available AS-OCT is needed to clarify this finding.
The American Optometric Association's guideline on care of the patient with open angle glaucoma (2002) recommended biomicroscopy for the evaluation of anterior and posterior segment ocular structures. Furthermore, the American Academy of Ophthalmology's guidelines on primary open-angle glaucoma as well as primary open angle glaucoma suspect (2005a, 2005b) did not discuss the use of AS-OCT, especially in the physical examination of the anterior segment as well as measurement of CCT.
Anterior segment OCT is also being investigated for other indications such as imaging of trabeculectomy blebs (Singh et al, 2007), diagnosis and management of capsular block syndrome (Lau et al, 2007), diagnosis of residual Descemet's membrane after Descemet's stripping endothelial keratoplasty (Kymionis et al, 2007), as well as visualization of aqueous shunt position and patency (Sarodia et al, 2007). However, there is currently insufficient evidence to support its use for these indications.
Nolan (2008) described the 2 main anterior segment imaging modalities and summarized their applications, strengths and weaknesses. Ultrasound biomicroscopy and more recently AS-OCT are imaging modalities that can be used to obtain 2-D images of the angle and surrounding structures. Ultrasound biomicroscopy has the advantage of being able to illustrate the ciliary body and therefore give clinicians information on non-pupil block mechanisms of primary angle closure and also diagnose other abnormalities such as cyclodialysis clefts. Moreover, AS-OCT is a non-contact and rapid method of imaging the angle and anterior segment that has great potential in the diagnosis and follow-up of patients with angle closure. The author concluded that rapid advances in anterior segment imaging are enlightening clinicians and researchers to the importance in making the diagnosis of primary angle closure, trying to establish underlying causal mechanisms, and evaluating treatments. Although they do not replace conventional angle and anterior segment examination, they hold great potential for the future.
Pekmezci and colleagues (2009) noted that AS-OCT is an alternative method for the assessment of angle width. These investigators evaluated the accuracy of AS-OCT for detecting occludable angles and compared the results of high- and low-resolution images with gonioscopy. Visante AS-OCT (Carl Zeiss Meditec, Dublin, CA) images of 303 eyes (155 patients) presenting between February 1 and July 15, 2007, were retrospectively analyzed. Angle recess area (ARA) and angle opening distances (AOD) at 250, 500, and 750 micron were measured and correlated with the corresponding gonioscopic measurements. Anterior segment OCT parameters showed a non-linear relationship with gonioscopy, ARA having the highest correlation. Correlations between high- and low-resolution images were modest. Cut-off values were 0.180 mm2 (70.3 % sensitivity, 87.4 % specificity) for ARA and 0.264 mm (71.8 % sensitivity, 84.8 % specificity) for AOD at 500 micron. The authors concluded that AS-OCT appears to be a promising screening tool for narrow angles.
In a prospective, observational case series study, Pavlin and colleagues (2009) assessed the utility of AS-OCT in the imaging of anterior segment tumors and compared the images to ultrasound biomicroscopy (UBM). A total of 18 eyes (18 patients) with anterior segment tumors were evaluated at Princess Margaret Hospital. The evaluation included clinical examination, clinical photography, AS-OCT, and UBM. Comparison of images obtained by both methods was done. Anterior segment-OCT imaged small hypo-pigmented tumors with complete penetration. Cysts were incompletely imaged behind the iris pigment epithelium. Highly pigmented tumors, large tumors, and ciliary body tumors were incompletely penetrated. Even without complete penetration, it was possible to differentiate cystic lesions from solid lesions. Ultrasound biomicroscopy penetrated all tumors completely. The authors concluded that AS-OCT can penetrate small hypo-pigmented tumors and supply some information on internal characteristics of other tumors. However, UBM is preferable for clinical anterior tumor assessment and follow-up because of its superior ability to penetrate large tumors, highly pigmented tumors, and ciliary body tumors.
In a cross-sectional study, Mansouri and colleagues (2010) compared the accuracy in measurement of the anterior chamber (AC) angle by AS-OCT and UBM in European patients with suspected primary angle closure (PACS), primary angle closure (PAC), or primary angle-closure glaucoma (PACG). In all, 55 eyes of 33 consecutive patients presenting with PACS, PAC, or PACG were examined with AS-OCT, followed by UBM. The trabecular-iris angle (TIA) was measured in all 4 quadrants. The AOD was measured at 500 mum from the scleral spur. The Bland-Altman method was used for assessing agreement between the 2 methods. The mean (+/- SD) superior TIA was 19.3 +/- 15.8 degrees in AS-OCT and 15.7 +/- 15.0 degrees in UBM (p = 0.50) and inferior TIA was 17.9 +/- 12.9 degrees (AS-OCT) and 16.7 +/- 1 4.1 degrees (UBM) (p = 0.71). The superior AOD(500) was 0.17 +/- 0.16 mm in UBM and 0.21 +/- 0.16 mm in AS-OCT (p = 0.06). Bland-Altman analysis showed a mean SD of +/- 9.4 degrees for superior and inferior TIA and a mean SD of +/- 0.10 mm for superior and inferior AOD(500). This comparative study showed that AS-OCT measurements are significantly correlated with UBM measurements but show poor agreement with each other. The authors do not believe that AS-OCT can replace UBM for the quantitative assessment of the AC angle.
The American Academy of Ophthalmology's preferred practice patterns of primary angle closure (AAO, 2010) stated that there is good evidence showing general agreement between findings on gonioscopy and anterior segment imaging, including UBM and AS-OCT. The AAO noted that these technologies may prove useful in evaluating for secondary causes of angle closure and to elucidate plateau iris.
In a population-based, cross-sectional study, Foo and colleagues (2012) investigated determinants of angle width and derive mathematic models to best predict angle width. A total of 1,067 Chinese subjects aged greater than or equal to 40 years were included in this study. Participants underwent gonioscopy, A-scan biometry, and imaging by AS-OCT (Carl Zeiss Meditec, Dublin, CA). Customized software (Zhongshan Angle Assessment Program, Guangzhou, China) was used to measure AS-OCT parameters. Linear regression modeling was performed with trabecular-iris space area at 750 μm (TISA750) and angle opening distance at 750 μm (AOD750) from the scleral spur as the 2 dependent angle width variables. By using a combination of AS-OCT and biometric parameters, an optimal model that was predictive of angle width was determined by a forward selection regression algorithm. Validation of the results was performed in a separate set of community-based clinic study of 1,293 persons aged greater than or equal to 50 years. Main outcome measures were angle width and biometric parameters. The mean age (standard deviation) of the population-based subjects was 56.9 (8.5) years; and 50.2 % were male. For TISA750, the strongest determinants among AS-OCT and A-scan independent variables were anterior chamber volume (ACV, R(2) = 0.51), followed by anterior chamber area (ACA, R(2) = 0.49) and lens vault (LV, R(2) = 0.47); for AOD750, these were LV (R(2) = 0.56), ACA (R(2) = 0.55), and ACV (R(2) = 0.54). The R(2) values for anterior chamber depth and axial length were 0.39 and 0.27 for TISA750, respectively, and 0.46 and 0.30 for AOD750, respectively. An optimal model consisting of 6 variables (ACV, ACA, LV, anterior chamber width [ACW], iris thickness at 750 μm, and iris area) explained 81.4 % of the variability in TISA750 and 85.5 % of the variability in AOD750. The results of the population-based study were validated in the community-based clinic study, where the strongest determinants of angle width (ACA, ACV, and LV) and the optimal model with 6 variables were similar. The authors concluded that angle width is largely dependent on variations in ACA, ACV, and LV. They stated that a predictive model comprising 6 quantitative AS-OCT parameters explained more than 80 % of the variability of angle width and may have implications for screening for angle closure.
Nguyen and Chopra (2013) stated that the rapid emergence and widespread adoption of OCT has spurred the development of many ophthalmic applications. Spectral domain OCT provides high-resolution in-vivo images of both anterior and posterior segments of the eye. Innovations in AS-OCT aim to improve refractive accuracy and reduce surgical risks. These investigators reviewed the utility of AS-OCT in cataract surgery for pre-operative assessment, intra-operative assistance, and post-operative management to improve surgical outcomes. Recent advances in AS-OCT for pre-operative planning include characterization of dry eye and ocular surface conditions, calculation of intra-ocular lens (IOL) power, delineation of anterior chamber structures, and assessment of risk factors for post-operative complications. Successful intra-operative use of AS-OCT has been described for in-vivo assessment of clear cornea wound architecture and OCT-guided femtosecond laser-assisted cataract surgery. The essential roles of OCT in managing post-operative complications include characterization of maculopathy or corneal wound integrity, assessment of IOL stability or optical changes, and evaluation of laser-assisted in situ keratomileusis flaps after cataract surgery. The authors concluded that in its rapidly evolving state, the utility of OCT in cataract surgery continues to broaden with applications from pre-operative planning, intra-operative image-based treatments, and post-operative care. They advocate the judicious use of OCT, wherever clinically indicated, because routine use may not be clinically necessary or economically feasible for each stage of cataract evaluation and management.
In a cross-sectional study, Nongpiur et al (2013) identified subgroups of PACS based on AS-OCT and biometric parameters. These investigators evaluated 243 PACS subjects in the primary group and 165 subjects in the validation group. Participants underwent gonioscopy and AS-OCT. Customized software was used to measure AS-OCT parameters. An agglomerative hierarchical clustering method was first used to determine the optimum number of parameters to be included in the determination of subgroups. The best number of subgroups was then determined using Akaike Information Criterion (AIC) and Gaussian Mixture Model (GMM) methods. Main outcome measures were subgroups of PACS. The mean age of the subjects was 64.8 years, and 65.02 % were female. After hierarchical clustering, 1 or 2 parameters from each cluster were chosen to ensure representativeness of the parameters and yet keep a minimum of redundancy. The parameters included were iris area, anterior chamber depth (ACD), ACW, and LV. With the use of GMM, the optimal number of subgroups as given by AIC was 3. Subgroup 1 was characterized by a large iris area, subgroup 2 was characterized by a large LV and a shallow ACD, and subgroup 3 was characterized by elements of both subgroups 1 and 2. The results were replicated in a second independent group of 165 PACS subjects. The authors concluded that clustering analysis identified 3 distinct subgroups of PACS subjects based on AS-OCT and biometric parameters. These findings may be relevant for understanding angle-closure pathogenesis and management.
Benitez-Herreros et al (2013) compared AS-OCT, direct visualization, and ultrasound biomicroscopy (UBM) for detecting conjunctival blebs in sutureless sclerotomies after vitrectomy. Conjunctival blebs are formed by sclerotomy leakage due to incompetent closure. Experimental, randomized, and observer-masked study in which 23-gauge vitrectomies were performed in cadaveric pig eyes were used in this analysis. Post-operative conjunctival blebs were assessed by UBM, AS-OCT, and direct visualization. No conjunctival blebs were classified as Grade 0 (G0), thin blebs (less than or equal to 50 % of scleral thickness) as Grade 1 (G1) and thick blebs (greater than 50 % of scleral thickness) as Grade 2 (G2). A total of 50 pig eyes were included in this study. Conjunctival blebs were found in 13.3 % (8 % G1, 5.3 % G2) of the incisions analyzed by UBM, in 20 % (14.7 % G1, 5.3 % G2) of the sclerotomies studied by AS-OCT, and in 7.3 % (2 % G1, 5.3 % G2) of the wounds evaluated by direct visualization. Anterior segment-OCT was the most sensitive method for identifying conjunctival blebs when compared with UBM and direct visualization (p < 0.001). In turn, UBM was better than direct visualization for observing sclerotomy blebs (p = 0.004). The authors concluded that AS-OCT is the most sensitive technique for detecting subclinical blebs (G1) and thus, it may be useful in research for studying the influence that surgical factors and maneuvers may exert on sclerotomy closure capacity after vitrectomy. Moreover, they stated that direct visualization, that is used in routine clinical practice to determine which sclerotomies should be sutured, is useful only to identify thick blebs (G2) after vitrectomy.
In summary, available evidence for AS-OCT is primarily comparison studies between this imaging tool and established methods for measuring anterior segment ocular structures. Currently, there are no data that demonstrate improved outcomes using this technology. Thus, AS-OCT is a promising technology; but its clinical value remains to be ascertained by well-designed studies that show improved outcomes.
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