Anterior Segment Scanning Computerized Ophthalmic Diagnostic Imaging

Number: 0749

Table Of Contents

Policy

Scope of Policy

This Clinical Policy Bulletin addresses anterior segment scanning computerized ophthalmic diagnostic imaging.

1. Experimental, Investigational, or Unproven

   The following interventions are considered experimental, investigational, or unproven because the effectiveness of these approaches has not been established:

   1. Anterior segment optical coherence tomography (OCT) for all indications including the following (not an all-inclusive list) because its clinical value has not been established:
      1. Assessment of Haab striae;
      2. Characterization of the ocular surface changes associated with ocular graft-versus-host disease;
      3. Detection of glaucoma;
      4. Diagnosis of Descemet membrane detachment during cataract surgery;
      5. Diagnosis / management of pigmentary dispersion syndrome;
      6. Evaluation of anterior segment morphology of hyperopia;
      7. Evaluation of belantamab-associated superficial keratopathy;
      8. Evaluation of benign reactive lymphoid hyperplasia;
      9. Evaluation of blebs after filtering surgery;
      10. Evaluation of conjunctival amyloidosis;
      11. Evaluation of conjunctival hyperemia;
      12. Evaluation of conjunctival lymphoma;
      13. Evaluation of corneal and conjunctival tumors;
      14. Evaluation of ocular surface squamous neoplasia;
      15. Evaluation of post-operative opacification of intra-ocular lens;
      16. Evaluation of strabismus;
      17. Evaluation of the proximal lacrimal system;
      18. Identification of fungal infections with endophthalmitis after cataract surgery;
      19. Imaging of extra-ocular rectus muscle insertions for pre-operative planning;
      20. Management of Wilson disease;
      21. Prediction of post-operative outcomes following trabeculectomy;
      22. Quantification of corneal haziness.
   2. Anterior segment imaging (ciliary body, cornea, iris and lens) using the following techniques because of insufficient evidence of its effectiveness:
      1. Pentacam;
      2. Scanning laser ophthalmoscopy (SLO), also called confocal laser scanning ophthalmoscopy;
      3. Scanning laser polarimetry (SLP), also called confocal scanning laser polarimetry.

2. Policy Limitations and Exclusions

   Note: Aetna members may not be eligible under the Plan for anterior segment (ciliary body, cornea, iris and lens) imaging using the Pentacam for any indication relating to refractive eye surgeries (eg, LASIK, laser eye surgery, etc.). Refractive eye surgeries are generally excluded by contract; therefore, any imaging done in conjunction with this type of procedure would not be covered if the surgery itself is not a covered benefit.

3. Related Policies

   • CPB 0344 - Optic Nerve and Retinal Imaging Methods

Background

Scanning computerized ophthalmic diagnostic imaging (SCODI) may be used as a diagnostic measure for eye conditions and includes the following technologies:

Optical coherence tomography (OCT) is a noninvasive, transpupillary, retinal imaging technology, which uses near-infrared light to produce high-resolution cross-sectional images. It is suggested for diagnostic use as an alternative to standard excisional biopsy and to guide interventional procedures.

Scanning laser ophthalmoscopy (SLO), also called confocal laser scanning ophthalmoscopy, is a method of examining the eye using confocal laser scanning microscopy (stereoscopic videographic digitized imaging) to make quantitative topographic measurements of the optic nerve head and surrounding retina. This may be done with either reflection or fluorescence. Targeted tissues can be viewed in 3-dimensional (3D) high-resolution planes running parallel to the line of sight.

Scanning laser polarimetry, also called confocal scanning laser polarimetry, measures change in the linear polarization (retardation) of light. It uses both a scanning laser ophthalmoscope and a polarimeter (an optical device to measure linear polarization change) to measure the thickness of the nerve fiber layer of the retina. The confocal scanning laser polarimeter is essentially a confocal scanning laser ophthalmoscope with an additional polarization modulator, a cornea polarization compensator and a polarization detection unit. 

The Oculus Pentacam system is a multifunctional tool that images the cornea and anterior segment using a rotating Scheimpflug camera and a monochromatic light source (blue LED at 475 nm) that rotate together around the optical axis of the eye. There are five evaluation modes: Scheimpflug tomography, pachymetry (including adjustment for intraocular pressure), 3D anterior chamber analysis (chamber depth, angle and volume, including a manual measuring function for any location in the anterior chamber), densitometry of the lens and corneal topography (including anterior and posterior corneal surface as well as keratometry).

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 (2014) 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.

Chen and colleagues (2013) compared the differences in the ACD measured by AS-OCT and UBM.  All studies pertaining to ACD measured by AS-OCT and UBM were collected from online databases.  The assessment of methodological quality and data extraction from the included studies were performed independently by 2 reviewers for meta-analysis.  A total of 8 studies involving 710 eyes were included in the analysis.  The difference of ACD measurements between AS-OCT and UBM was not statistically significant in the overall patients included for analysis (SMD = 0.19, 95 % CI: 0.00 to 0.39]) or in the patients with primary angle-closed glaucoma (SMD = 0.02, 95 %CI: -0.04 to 0.19).  The authors concluded that the ACD measurements do not differ significantly between AS-OCT and UBM.  Moreover, they stated that due to the relatively small number of the included studies and the patients involved, this conclusion needs further confirmation by high-quality studies involving larger sample sizes.

On behalf of the AAO, Smith et al (2013) evaluated the published literature pertaining to the association between anterior segment imaging and gonioscopy and determined if such imaging aids in the diagnosis of PAC.  Literature searches of the PubMed and Cochrane Library databases were last conducted on July 6, 2011.  The searches yielded 371 unique citations.  Members of the Ophthalmic Technology Assessment Committee Glaucoma Panel reviewed the titles and abstracts of these articles and selected 134 of possible clinical significance for further review.  The panel reviewed the full text of these articles and identified 79 studies meeting the inclusion criteria, for which the panel methodologist assigned a level of evidence based on a standardized grading scheme adopted by the AAO -- 3, 70, and 6 studies were rated as providing level I, II, and III evidence, respectively.  Quantitative and qualitative parameters defined from UBM, AS-OCT, Scheimpflug photography, and the scanning peripheral anterior chamber depth analyzer (SPAC) demonstrated a strong association with the results of gonioscopy.  There was substantial variability in the type of information obtained from each imaging method.  Imaging of structures posterior to the iris is possible only with UBM.  Direct imaging of the ACA was possible using UBM and OCT.  The ability to acquire OCT images in a completely dark environment allowed greater sensitivity in detecting eyes with appositional angle closure.  Non-contact imaging using OCT, Scheimpflug photography, or SPAC made these methods more attractive for large-scale PAC screening than contact imaging using UBM.  The authors concluded that although there is evidence suggesting that anterior segment imaging provides useful information in the evaluation of PAC, none of these imaging methods provides sufficient information about the ACA anatomy to be considered a substitute for gonioscopy.  Moreover, they stated that longitudinal studies are needed to validate the diagnostic significance of the parameters measured by these instruments for prospectively identifying individuals at risk for PAC.

Piotrowiak and colleagues (2014) evaluated anterior segment spectral OCT (AS-SOCT) for assessing the lens-to-cornea fit of rigid gas-permeable (RGP) lenses.  The results were verified with the fluorescein pattern method, considered the criterion standard for RGP lens alignment evaluations.  A total of 26 eyes of 14 patients were enrolled in the study.  Initial base curve radius (BCR) of each RGP lens was determined on the basis of keratometry readings.  The fluorescein pattern and AS-SOCT tomograms were evaluated, starting with an alignment fit, and subsequently, with BCR reductions in increments of 0.1 mm, up to 3 consecutive changes; AS-SOCT examination was performed with the use of RTVue (Optovue, CA).  The average BCR for alignment fits, defined according to the fluorescein pattern, was 7.8 mm (SD = 0.26).  Repeatability of the measurements was 18.2 %.  Base curve radius reductions of 0.1, 0.2, and 0.3 mm resulted in average apical clearances detected with AS-SOCT of 12.38 (SD = 9.91, p < 0.05), 28.79 (SD = 15.39, p < 0.05), and 33.25 (SD = 10.60, p > 0.05), respectively.  The authors concluded that BCR steepening of 0.1 mm or more led to measurable changes in lens-to-cornea fits.  Although AS-SOCT represents a new method of assessing lens-to-cornea fit, apical clearance detection with current commercial technology showed lower sensitivity than the fluorescein pattern assessment.

Maram et al (2015) evaluated the reproducibility of ACA measurements obtained by the Zeiss Visante AS-OCT.  A total of 20 eyes from 20 normal subjects with open ACAs were studied.  The ACA was imaged using the Visante AS-OCT.  The angle-opening distance (AOD 500, AOD 750), trabercular iris space area (TISA 500, TISA 750) and scleral spur angle (SS angle) at the inferior angle location were measured.  All the subjects underwent imaging in a darkened room (1 foot candles measured at the eye).  Images were graded in a masked fashion by certified Doheny Image Reading Center graders.  For intra-grader reproducibility assessments, images were re-graded by the same grader 1 week later after random sorting of images.  For inter-grader assessments, a 2nd masked grader independently reviewed the images.  Intra-class correlation coefficients (ICC) were used to assess reproducibility. Inferior angle measurements of AOD (500, 750), TISA (500, 750) and SS angle for 20 normal eyes were calculated.  The intra-observer ICC calculations showed excellent reproducibility for all measurements (AOD 500 = 0.95, AOD 750 = 0.97, TISA 500 = 0.93, TISA 750 = 0.94, SS = 0.96; p < 0.001 for all).  The inter-observer ICC calculations showed lower reproducibility for all measurements (AOD 500 = 0.71, p < 0.001; AOD 750 = 0.82, p < 0.001; TISA 500 = 0.49, p = 0.08; TISA 750 = 0.61, p = 0.02; SS = 0.75).  The authors concluded that determination of ACA measurements was possible with the time-domain AS-OCT, but only modest inter-observer reproducibility was found even among experienced graders.

In a single-center, prospective clinical study, Yamazaki et al (2014) investigated in-vivo corneal changes of radial keratoneuritis in early-stage acanthamoeba keratitis (AK) using AS-OCT.  A total of 4 eyes (4 patients with a mean age of 28.5 years) with early-stage AK showing radial keratoneuritis were included in this study.  Definitive diagnosis was made by confirmation of AK cysts using in-vivo confocal microscopy and culture.  Anterior-segment OCT examination was performed on the initial visit and at follow-up visits paying special attention to radial keratoneuritis.  Selected AS-OCT images of the cornea were evaluated qualitatively for the shape and degree of light reflection of abnormal neurons.  With the use of AS-OCT, these researchers successfully obtained high-resolution images of putative radial keratoneuritis in all patients as highly reflective bands or lines in the corneal stroma.  The depth and width of the highly reflective bands/lines varied from case to case (anterior stroma to mid-stroma, from 20 to 200 μm).  Some lines ran obliquely from the deep peripheral stroma toward the anterior stroma, and some were located at different depths (subepithelial and mid-stroma) and ran relatively parallel to the corneal layers.  After appropriate treatment, radial keratoneuritis was resolved by both slit-lamp biomicroscopy and AS-OCT in all patients.  The authors concluded that high-resolution Fourier-domain AS-OCT provides novel and detailed visual information of radial keratoneuritis in patients with early-stage AK.  They stated that visualization of radial keratoneuritis by AS-OCT may be a useful adjunct to the diagnosis and follow-up of early-stage AK.

In a prospective, single-center, consecutive case-series study, Ehlers et al (2014) evaluated the feasibility, safety, and utility of intra-operative OCT for use during ophthalmic surgery. Intra-operative scanning was performed with a microscope-mounted spectral-domain OCT system. Disease-specific or procedure-specific imaging protocols (e.g., scan type, pattern, size, orientation, density) were used for anterior and posterior segment applications. A surgeon feedback form was recorded as part of the study protocol to answer specific questions regarding intra-operative OCT utility immediately after the surgical procedure was completed. During the first 24 months of the PIONEER study, 531 eyes were enrolled (275 anterior segment cases and 256 posterior segment surgical cases). Intra-operative OCT imaging was obtained in 518 of 531 eyes (98 %). Surgeon feedback indicated that intra-operative OCT informed surgical decision-making and altered surgeon understanding of underlying tissue configurations in 69 of 144 lamellar keratoplasty cases (48 %) and 63 of 146 membrane peeling procedures (43 %). The most common anterior segment surgical procedure was Descemet stripping automated endothelial keratoplasty (DSAEK, n = 135). Vitrectomy with membrane peeling was the most common procedure for posterior segment surgery (n = 154). The median time that surgery was paused to perform intra-operative OCT was 4.9 minutes per scan session. No adverse events were specifically attributed to intra-operative OCT scanning during the procedure. The authors concluded that intra-operative OCT is feasible for numerous anterior and posterior segment ophthalmic surgical procedures. A microscope-mounted intra-operative OCT system provided efficient imaging during operative procedures. The information gained from intra-operative OCT may impact surgical decision-making in a high frequency of both anterior and posterior segment cases. The clinical value of intra-operative OCT for both anterior and posterior segment ophthalmic surgical procedures has yet to be determined.

In a cross-sectional, observational study, Ang and colleagues (2015) evaluated the application of an OCT angiography (OCTA) system adapted for the assessment of anterior segment vasculature. Consecutive subjects with normal eyes on slit-lamp clinical examination and patients with abnormal corneal neovascularization were included in this study. All scans were performed using a commercially available AngioVue OCTA system (Optovue, Inc., Fremont, CA) using an anterior segment lens adapter and the split-spectrum amplitude decorrelation angiography algorithm. Each subject underwent scans from 4 quadrants (superior, inferior, nasal, and temporal) in each eye by 2 trained, independent operators. Analysis of signal strength, image quality, and reproducibility of corneal vascular measurements were performed. In this study of 20 normal subjects (10 men, 10 women; mean age of 25.3 ± 7.8 years), these researchers found good repeatability (κ coefficient, 0.76) for image quality score and good inter-observer agreement for vasculature measurements (intra-class coefficient, 0.94). After optimization of the angiography scan protocol, vascular measurements within the regions of interest were compared in the superior versus inferior quadrants (mean vascular loops of 3.34 ± 1.16 versus 3.12 ± 0.90 [p = 0.768]; segment-to-loop ratio of 4.18 ± 0.71 versus 4.32 ± 0.87 [p = 0.129]; fractal dimension [Df] value of 1.78 ± 0.06 versus 1.78 ± 0.06 [p = 0.94]; vascular loop area, 25.9 ± 14.5 versus 25.9 ± 10.7 × 10-3 mm2 [p = 0.21]) and nasal versus temporal quadrant (mean vascular loops of 2.89 ± 0.98 versus 3.57 ± 0.99 [p < 0.001]; segment-to-loop ratio of 3.94 ± 0.69 versus 4.55 ± 0.78 [p = 0.897]; Df value of 1.78 ± 0.06 versus 1.77 ± 0.06 [p = 0.14]; vascular loop area of 29.7 ± 15.7 versus 22.1 ± 7.1 × 10-3 mm2 [p = 0.38]. These investigators then used the established OCTA scanning protocol to visualize abnormal vasculature successfully in 5 patients with various corneal pathologic features, including graft-associated neovascularization, post-herpetic keratitis scarring, lipid keratopathy, and limbal stem cell deficiency. The authors concluded that this preliminary study described a method for acquiring OCTA images of the cornea and limbal vasculature with substantial consistency. They stated that this technique may be useful for the objective evaluation of corneal neovascularization in the future.

In a prospective, observational study, Kojima et al (2015) evaluated time-dependent post-trabeculectomy changes in filtering bleb parameters using 3-D AS-OCT. Patients with open-angle glaucoma who underwent uncombined fornix-based trabeculectomy between January 1, 2012, and October 31, 2012, were included. A total of 29 eyes were enrolled, 23 of which were followed-up for 1 year without additional glaucoma surgical procedures; 3 required additional glaucoma surgery. The primary end-points were changes in bleb parameters including the position and width of the filtration openings on the scleral flap, the total bleb height, fluid-filled cavity height, bleb wall thickness, and bleb wall intensity, which were measured using 3-D AS-OCT. The secondary end-points were post-surgical intra-ocular pressure (IOP) measured 0.5, 3, 6, and 12 months after trabeculectomy, and the effects of aqueous cytokine levels on the bleb parameters. These researchers observed increased total bleb height (0.82 to 1.25 mm; difference: 95 % CI: 0.10 to 0.75; p = 0.01), bleb wall thickness (0.46 to 0.61 mm; difference: 95 % CI: 0.02 to 0.28; p = 0.03), and distance from the top of the scleral flap to the filtration opening (1.69 to 2.16 mm; difference: 95 % CI: 0.28 to 0.70; p < 0.001), as well as decreased width of the filtration opening (2.08 to 1.12 mm; difference: 95 % CI: -1.75 to -0.49; p = 0.002) between 0.5 and 12 months post-trabeculectomy. The filtration openings tended to close from the fornix side of the scleral flap during the wound healing process. Moreover, the width of the filtration opening at 0.5 months post-trabeculectomy correlated with the IOP at 12 months (p = 0.02). The aqueous humor level of monocyte chemo-attractant protein-1 was correlated with the width of the filtration opening at 3 and 6 months post-trabeculectomy. The authors concluded that the width of the filtration opening at 0.5 months post-trabeculectomy correlated with the IOP at 12 months. The width of the filtration opening at the early stage may be a prognostic factor for long-term IOP control. They stated that large-scale studies with longer follow-up periods are needed.

An UpToDate review on “Angle-closure glaucoma” (Weizer, 2015) states that “Gonioscopy is the gold-standard method of diagnosing angle-closure …. High definition anterior segment optical coherence tomography is being used as a modality to image the drainage angle and detect eyes at risk for angle-closure. Findings suggest that eyes prone to developing angle-closure do not merely differ anatomically from normal eyes, but may also respond differently to light stimuli”.

Ehlers et al (2015a) assessed the feasibility and effect on surgical decision making of a microscope-integrated intraoperative OCT (iOCT) system. This report highlighted the 1-year results (March 2014 to February 2015) of the RESCAN 700 portion of the DISCOVER (Determination of Feasibility of Intraoperative Spectral Domain Microscope Combined/Integrated OCT Visualization During En Face Retinal and Ophthalmic Surgery) study, a regarding this investigational device. Participants included patients undergoing ophthalmic surgery. Data on clinical characteristics were collected, and iOCT was performed during surgical milestones, as directed by the operating surgeon. A surgeon questionnaire was issued to each surgeon and was completed after each case to evaluate the role of iOCT during surgery and its particular role in select surgical procedures. Main outcome measures included percentage of cases with successful acquisition of iOCT (i.e., feasibility) and percentage of cases in which iOCT altered surgical decision making (i.e., utility). During year 1 of the DISCOVER study, a total of 227 eyes (91 anterior segment cases and 136 posterior segment cases) underwent imaging with the RESCAN 700 system. Successful imaging (e.g., the ability to acquire an OCT image of the tissue of interest) was obtained for 224 of 227 eyes (99 % [95 % CI: 98 % to 100 %]). During lamellar keratoplasty, the iOCT data provided information that altered the surgeon's decision making in 38 % of the cases (e.g., complete graft apposition when the surgeon believed there was interface fluid). In membrane peeling procedures, iOCT information was discordant with the surgeon's impression of membrane peel completeness in 19 % of cases (e.g., lack of residual membrane or presence of occult membrane), thus affecting additional surgical maneuvers. The authors concluded that the DISCOVER study demonstrated the feasibility of real-time iOCT with a microscope-integrated iOCT system for ophthalmic surgery. The information gained from iOCT appeared to allow surgeons to assess subtle details in a unique perspective from standard en face visualization, which can affect surgical decision making some of the time, although the effect of these changes in decision-making on outcomes remains unknown. They stated that a prospective randomized masked trial is needed to confirm these results.

Ehlers et al (2015b) evaluated the feasibility and utility of iOCT during pars plana vitrectomy surgery for dense vitreous hemorrhage. The Prospective Assessment of Intraoperative and Perioperative OCT for Ophthalmic Surgery study examined the utility of iOCT in ophthalmic surgery. Intra-operative scanning was performed with a microscope-mounted spectral domain OCT system. This report was a case-series study of those eyes undergoing pars plana vitrectomy for dense central vitreous hemorrhage that precluded pre-operative OCT assessment. Intra-operative OCT images were qualitatively evaluated for retinal abnormalities that might impact intra-operative or peri-operative management. Clinical variables were collected and assessed. Surgeon assessment of iOCT utility was also evaluated. A total of 23 eyes were identified and included. The etiology for the vitreous hemorrhage was proliferative diabetic retinopathy (19 eyes, 82.6 %), horseshoe retinal tear (1 eye, 4.3 %), retinal vein occlusion with neovascularization (1 eye, 4.3 %), presumed polypoid choroidal vasculopathy (1 eye, 4.3 %), and presumed retinal arterial macro-aneurysm (1 eye, 4.3 %). Intra-operative OCT revealed epi-retinal membrane (14 eyes, 60.9 %), macular edema (14 eyes, 60.9 %), posterior hyaloid traction (1 eye, 4.3 %), and retinal detachment (1 eye, 4.3 %). Surgeon feedback suggested that iOCT impacted surgical decision-making in eyes where membrane peeling was performed. The authors concluded that iOCT during pars plana vitrectomy for vitreous hemorrhage may provide physicians with clinically relevant information that may impact surgical management, peri-operative management, and patient outcomes. The clinical value of intra-operative OCT during pars plana vitrectomy has to be ascertained in well-designed studies.

Chen and Costello (2018) noted that OCT is an ocular imaging technique that can complement the neuro-ophthalmic assessment, and inform the understanding regarding functional consequences of neuro-axonal injury in the afferent visual pathway.  Indeed, OCT has emerged as a surrogate end-point in the diagnosis and follow-up of several demyelinating syndromes of the central nervous system (CNS), including optic neuritis (ON) associated with: multiple sclerosis (MS), neuromyelitis optica spectrum disorder (NMOSD), and anti-myelin oligodendrocyte glycoprotein (MOG) antibodies.  Recent advancements in enhanced depth imaging (EDI) OCT have distinguished this technique as a new gold standard in the diagnosis of optic disc drusen (ODD).  Moreover, OCT may enhance the ability to distinguish cases of papilledema from pseudo-papilledema caused by ODD.  In the setting of idiopathic intracranial hypertension (IIH), OCT has shown benefit in tracking responses to treatment, with respect to reduced retinal nerve fiber layer (RNFL) measures and morphological changes in the angling of Bruch’s membrane.  Longitudinal follow-up of OCT measured ganglion cell-inner plexiform layer thickness may be of particular value in managing IIH patients who have secondary optic atrophy.  Causes of compressive optic neuropathies may be readily diagnosed with OCT, even in the absence of overt visual field defects.  Furthermore, OCT values may offer some prognostic value in predicting post-operative outcomes in these patients.  Finally, OCT can be indispensable in differentiating optic neuropathies from retinal diseases in patients presenting with vision loss, and an unrevealing fundus examination.  The authors highlighted the potential role of OCT, as an ancillary investigation, in the diagnosis and management of various optic nerve disorders.

These researchers stated that OCT has been touted to provide a “window to the brain” as a potential biomarker for neurodegenerative conditions.  Multiple studies have shown RNFL and ganglion cell-inner plexiform (GCIP) layer thinning in patients with Alzheimer’s disease (AD) compared to age matched controls, which were summarized in a meta-analysis by Coppola and colleagues.  In addition, similar findings were observed with Parkinson’s disease and frontotemporal dementia.  Abnormalities in the vascular structure of the retina have also been recently found on OCTA in patients with AD, which supports the hypothesis that vascular abnormalities may be involved in the pathobiology of this disease.  While OCT appeared to have a promising role in the diagnosis and prognostication of patients suspected of having neurodegenerative conditions, future longitudinal studies are needed  to determine its usefulness in clinical practice.

Key points: OCT future directions and new applications:

• OCTA allows visualization of the capillary network in the retina
• Decreased peri-papillary capillary density has been seen in all forms of chronic optic neuropathy
• Swept source OCT uses faster scan rates and a longer wave-length than spectral domain OCT, which allows improved imaging of the deeper structures of optic nerve and choroid
• OCT is a promising biomarker for neurodegenerative disorders.

The authors stated that the applications for OCT are countless and its role is constantly expanding, including its use as a potential biomarker for neurodegenerative conditions.  As OCT technology continues to advance, it will undoubtedly augment the ability to diagnose and better understand the pathophysiology of optic nerve diseases in the future.

Marin et al (2022) notes that AS-OCT constitutes an important imaging modality to examine the anterior eye, which is commonly used in research and clinical practice.  Since its introduction, a range of image analysis methods have been developed to quantify these images using different analysis techniques for various applications.  In a systematic review, these investigators provided an in-depth summary and classified image analysis techniques found in the literature applied to AS-OCT images.  Scopus and Engineering Village databases were searched to retrieve relevant studies up to and including January 2022.  Customized search statements were used along with cross reference and hand search techniques to ensure a complete coverage.  Performance metrics were extracted, analyzed, and compared (when possible).  A total of 3 main application categories were identified: glaucoma assessment, corneal segmentation, and anterior segment biometry.  These 3 categories constituted 66 % of the total studies reported in this review.  Studies were also analyzed by year of publication, and since 2019 deep learning methods were favored over traditional programming or machine learning methodologies.  Overall, the AS-OCT image analysis field is less developed compared to posterior segment OCT imaging.  The authors concluded that this review presented the state of the art in the field of AS-OCT image analysis.  It highlighted the opportunities for future areas of research, such as the expansion of deep learning (DL) methods and the extension to specific clinical areas that have received limited attention including surgical monitoring, contact lenses, and specific clinical conditions such as keratoconus and corneal lesions.

Assessment of Haab Striae

Spierer et al (2015) presented a case series demonstrating the AS-OCT findings of Haab striae in 3 patients with congenital glaucoma. The authors stated that the use of AS-OCT in the assessment of Haab striae in pediatric glaucoma is novel, previously undescribed, and possibly allows differentiation between acute and chronic corneal changes.  These preliminary findings need to be further evaluated in well-designed studies.

Characterization of the Ocular Surface Changes Associated with Ocular Graft-Versus-Host Disease

Li and colleagues (2015) performed AS-OCT imaging of eyelids, tear meniscus, cornea and conjunctiva in subsequent sessions on a patient who has ocular graft-versus-host disease (GVHD) following allogeneic hematopoietic stem cell transplantation (aHSCT).  The OCT results were presented together with those from a normal subject.  OCT imaging is promising in visualizing several ocular GVHD manifestations, such as abnormal meibomian gland orifice (MGO), conjunctival keratinization, conjunctival hyperemia and chemosis, corneal epithelium opacification, thinning and sloughing.  The authors concluded that the promising results of this pilot, case-study showed the capability of AS-OCT in the imaging and monitoring of ocular GVHD, which may be useful in the development of current ocular GVHD staging system and the clinical management for GVHD treatment.  Moreover, these researchers stated that in the future, more pre- and post-aHSCT cases, with or without ocular GVHD ,will be recruited for OCT imaging and statistical analysis to examine the significance between these reported OCT findings and ocular GVHD.

In a prospective, phase-II clinical trial, Sun and associates (2021) identified the ocular surface changes of ocular graft-versus-host disease (GVHD) using AS-OCT and examined the efficacy of disposable bandage soft contact lens (BSCL) treatment in ocular GVHD patients.  This trial included 19 patients who were diagnosed with chronic GVHD based on the NIH criteria and ocular symptoms of NIH eye score 2 or greater.  Disposable BSCL was applied to the GVHD-affected eyes with topical antibiotic coverage.  Ocular examinations, eye symptom surveys, and AS-OCT were performed with signed informed consent.  Patients were followed for 1 to 3 months.  A total of 38 eyes of 19 patients with ocular GVHD underwent BSCL treatment in this study.  AS-OCT scans were carried out in 14 out of 19 patients.  The mean best-corrected visual acuity (BCVA) at enrollment, 2-week, and 4-week visits was 0.180, 0.128, and 0.163 logMAR, respectively; 24 out of 25 eyes (96 %) that initially presented with conjunctival inflammation, 23 out of 30 eyes (76.7 %) that initially presented with punctate epithelial erosion, and 8 out of 15 (53.3 %) eyes that initially presented with filamentous keratopathy showed improvement after wearing BSCL for 2 to 4 weeks.  AS-OCT revealed corneal epithelial irregularity, abnormal meibomian gland orifice, and conjunctival hyperemia, in patients with ocular GVHD.  The authors concluded that BSCL treatment provided significant subjective and objective improvements in ocular GVHD patients.  Meanwhile, these researchers found that AS-OCT could be a promising diagnostic tool to characterize the ocular surface changes associated with ocular GVHD.

The authors stated that 1 drawback of this trial was related to the fact that it was essentially not possible to conduct a double-masked BSCL clinical trial.  Nonetheless, in this study, the ocular symptoms and AS-OCT of trial patients were separately examined by 2 reviewers, and the interpretations of ocular symptoms and AS-OCT were mostly consistent between independent reviewers.  Another drawback was that this study did not include a group of control patients.  However, as the natural course of topical lubricant application to ocular GVHD patients has been extensively characterized, and the safety of BSCL treatment has already been proven, this clinical trial was designed as a single-arm study.

Detection of Glaucoma

In a prospective case-series study, Qian and colleagues (2015) evaluated the role of AS-OCT as a standardized method of imaging Boston type I kerato-prosthesis (KPro) after surgery, particularly in the visualization of iris and angle structures. A total of 20 patients who underwent KPro implantation in 1 eye were included in this study.  Patients underwent AS-OCT imaging before surgery.  After KPro implantation, patients were imaged using the AS single, dual, and quad scans to obtain transverse images of the eye every 15^° over 360^°.  High-resolution, corneal quad, and anterior chamber scans were also obtained.  This imaging protocol allowed juxtaposition and comparison of the same imaging coordinates obtained before surgery and 3, 6, and 12 months after surgery.  Main outcome measures included post-operative visual acuity (VA), glaucoma progression on clinical examination and formal visual field testing, and anatomic angle changes on AS-OCT defined by angle closure, peripheral anterior synechiae (PAS), iris-KPro backplate touch, and graft-host interface changes over time.  Mean follow-up was 18.8 ± 3.2 months.  The average pre-operative VA was 1.9 ± 0.5 logarithm of the minimum angle of resolution.  After surgery, VA improved to 1.0 ± 0.9 at last follow-up (p = 0.002); 14 of 20 patients had glaucoma before surgery.  After surgery, 5 of these patients deteriorated clinically and 1 de-novo diagnosis of glaucoma was made.  On OCT, the average total degrees of angle closure for all patients increased from 158.5 ± 158.9^° before surgery to 205.4 ± 154.0^° after surgery (p = 0.04).  The number of eyes with 360^° of PAS increased from 6 of 20 before surgery to 9 of 20 after surgery.  Iris-backplate touch was demonstrated in 5 of 20 patients, with an average area of involvement of 24.2 ± 36.2^°.  Overall, of the 12 of 20 patients with clear signs of anatomic angle narrowing and synechiae progression on imaging, 3 had glaucoma deterioration detected by clinical examination.  In the other 9 patients, angle changes on OCT were not accompanied by any detectable clinical signs of glaucomatous deterioration.  The authors concluded that AS-OCT can be used to observe anatomic changes after KPro implantation that cannot be detected otherwise.  However, they were unable to demonstrate a correlation between anatomic features and clinical progression.  The major drawbacks of this study were its small sample size and technical limitations.

Desmond and associates (2022) stated that it is currently unclear how AS-OCT fits into clinical practice for detecting angle closure.  In a systematic review and meta-analysis, these researchers compared the accuracy of AS-OCT against gonioscopy in detecting eyes with angle closure.  They carried out a literature search on Medline, Embase, Scopus and the Cochrane Central Register of Controlled Trials to identify studies that examined the diagnostic accuracy of AS-OCT in detecting eyes with angle closure as diagnosed by gonioscopy.  Eligible studies included in the analysis met stringent inclusion criteria determining the sensitivity and specificity of AS-OCT.  The initial search identified 727 studies, of which 23 were included in the final analysis.  These investigators found substantial variation in the parameters being studied and methodologies.  The sensitivity of AS-OCT ranged from 46 % to 100 % (median of 87 %); 21 studies identified parameters that showed sensitivity above 80 %.  The specificity ranged from 55.3 % to 100 % (median of 84 %).  The authors concluded that AS-OCT showed good sensitivity for detecting angle closure.  It may provide an avenue to address high rates of undiagnosed angle closure, such as found in developing Asian countries.  However, AS-OCT is not yet able to replace gonioscopy.  Clinicians should consider whether the diagnostic accuracy of AS-OCT is acceptable for their specific clinical use before adopting it.  These researchers stated that more studies are needed to determine the use of AS-OCT, including longitudinal studies to determine the significance of eyes classified to have closed angles by AS-OCT but open on gonioscopy.

Kan and colleagues (2022) stated that minimally invasive glaucoma surgery (MIGS) has gained popularity over the last 10 years.  In a systematic review, these investigators examined the peri-operative and intra-operative application of anterior segment imaging to maximize the safety and efficacy of MIGS.  They carried out a review of the PubMed, Embase and CINAHL databases with inclusion criteria restricted to MIGS that had received FDA premarket approval, FDA 510(k) premarket notification, or were listed as a class 1 device exempt from FDA approval or notification.  A total of 21 manuscripts from 21 unique studies were identified pertaining to MIGS devices including the XEN Gel Stent, Trabectome, iStent Inject, 1st-generation iStent and the Kahook Dual Blade (KDB).  Anterior segment imaging modalities included AS-OCT, UBM, aqueous angiography, OCT volumetric scans and in-vivo confocal microscopy.  Identification and evaluation of aqueous outflow pathways before and after MIGS have potential for improving patient pre-operative patient selection and post-operative outcomes.  Intra-operative imaging potentially provides the resolution needed for good visualization of angle anatomy and accurate evaluation of surgical endpoints in angle-based MIGS.  Anterior segment imaging has been used to identify procedural complications, provide objective information on implant location in relation to surrounding anatomy, evaluate the post-implantation structural impact of MIGS devices and manage bleb failure and scarring.   Moreover, the authors stated that technical difficulties in incorporating imaging modalities into the surgical microscope, variable quality of images and optical interference from ocular structures or surgical instruments are remaining barriers, which discourage the widespread clinical use of this technology.

Diagnosis of Descemet Membrane Detachment During Cataract Surgery

Benatti and colleagues (2017) updated the mechanisms, clinical presentations, diagnoses, and managements of Descemet membrane detachment during cataract surgery.  These investigators stated that the advent of new imaging techniques such as AS-OCT and better comprehension of the clinical and pathological aspects of detachment have improved the diagnosis and treatment of this complication to the extent that the first algorithms and protocols have been proposed.  The authors stated that though infrequent, Descemet membrane detachment is a complication of intra-ocular surgery, including cataract surgery and phacoemulsification.  Since the first systematic description and classification in the literature by Samuels in 1928 and its characterization as a potential sight-threatening condition by Scheie in 1964, plenty of retrospective and anecdotal evidence contribute to uncertainty and debate.  The main controversy still lies in the choice between conservative treatment in hopes of spontaneous re-attachment and surgical treatment in a timely manner to maximize visual recovery.

Diagnosis and Management of Pigmentary Dispersion Syndrome

Birner and colleagues (2014) examined if anterior chamber parameters are risk factors for the development of pigment dispersion syndrome (PDS) and/or for the conversion to pigmentary glaucoma (PG).  This study included a total of 63 eyes from 35 patients with PDS and PG and 65 eyes from 49 unaffected volunteers as the control group.  The following parameters were measured by slit lamp OCT (SL-OCT): ACV and ACD, AOD and TISA at 500 µm and 750 μm from the scleral spur.  Comparisons between the following groups were performed: between the PDS/PG and the control group, between PDS and PG and between male and female patients.  The results of ACV, ACD, AOD and TISA were significantly higher in PDS/PG patients when compared to the control group.  There were no significant differences between PDS and PG.  The gender-specific comparison also showed no significant differences.  The authors concluded that significantly higher anterior chamber parameters were a possible risk factor for development of PDS; however, a higher risk of conversion to PG did not appear to correlate with increased anterior chamber parameters.  The parameters of the anterior chamber were apparently not associated with the male predominance of PDS and PG.

Arifoglu and associates (2017) examined the ganglion cell complex (GCC) and RNFL thickness in PDS and PG with RTVue spectral domain-OCT (SD-OCT).  A total of 102 subjects were enrolled: 29 with PDS, 18 with PG, and 55 normal subjects.  Full ophthalmic examination including visual field analysis was performed; SD-OCT was used to analyze GCC superior, GCC inferior, and average RNFL thickness.  To compare the discrimination capabilities, the areas under the ROC curves were assessed.  Superior GCC, inferior GCC, and RNFL thickness values of patients with PG were statistically significantly lower than those of patients with PDS (p < 0.001) and healthy individuals (p < 0.001 for all).  No statistically significant difference was found between PDS and normal subjects in same parameters (p > 0.05).  The authors concluded that the SD-OCT-derived GCC and RNFL thickness parameters could be useful to discriminate PG from both PDS and normal subjects.

Okafor and co-workers (2017) examined the clinical features and pathogenesis of PDS and PG and provided an update regarding their diagnosis and management.  Newer imaging modalities including US biomicroscopy and AS-OCT facilitate visualization of the iris concavity characteristic of eyes with PDS and PG.  Patients with PG may be distinguished from those with other glaucoma types by the presence of typical symptoms, personality type, and patterns of diurnal IOP fluctuation.  Although laser iridotomy has been shown to alter iris anatomy in PG, it is not proven to slow visual field progression.  Multiple studies have validated the safety and efficacy of filtering surgery in treating PG, with fewer studies published on the role of micro-invasive glaucoma surgery.  The authors concluded that literature from the review period has further defined the unique clinical characteristics of PDS and PG.  Laser surgery has a limited role in the management of these entities, whereas trabeculectomy remains an acceptable 1st-line surgical treatment.  These researchers stated that further studies are needed to define the potential application of the newer micro-invasive glaucoma procedures in PG.

Harpster et al (2019) stated that patients with PDS are frequently encountered in clinical practice.  Iris abnormalities and the absence of key features of PDS could guide the discovery of secondary causes of PG, such as peripheral iris pigment epithelial cysts.  These investigators described a patient initially diagnosed as having primary PG found to have multiple bilateral peripheral iris pigment epithelial cysts causing pigment liberation, focal angle closure, and advanced secondary glaucoma. A 64-year old man presented for follow-up after a recent diagnosis of primary PG in the left eye.  Clinical examination revealed transillumination defects of both irides and a heavily pigmented trabecular meshwork.  A mid-peripheral bulge of the iris was appreciated in the superior temporal quadrant of the left eye.  Gonioscopic evaluation showed that the bulge focally obstructed the angle.  Anterior segment OCT demonstrated a normal iris insertion of both eyes, with the exception of a steepened approach superotemporally in the left eye; US biomicroscopy revealed bilateral small-to-medium-sized peripheral iris pigment epithelial cysts and confirmed a large cyst superotemporally in the left iris.  The authors concluded that this case described a patient with advanced secondary PG from iris pigment epithelial cysts.  The mechanisms of glaucoma were likely 2-fold: First, pigment liberation from the cysts contacting the lens zonules and, to a lesser extent; second, focal angle closure at the site of the large peripheral cyst.  The key features of PG, namely, posterior bowing of the iris, may not be present in secondary pigment dispersion.  This case highlighted the importance of careful evaluation of the iris and angle in making a correct diagnosis.  The choice of topical agent to control IOP while not increasing the size of these cysts is also an important consideration.

Furthermore, the AAO’s webpage on “Pigment Dispersion Syndrome Diagnosis and Treatment” (Porter, 2020) does not mention OCT as a diagnostic tool.  

Evaluation of Anterior Segment Parameters of Hyperopia

Wang et al (2015) examined the feasibility of AS-OCT in evaluating the anterior segment morphology of hyperopia in school-aged children. A total of 320 eyes of 160 school-aged children aged 6 to 12 years were examined with AS-OCT and were divided into 4 groups according to the cycloplegic spherical equivalence of refractive error.  The mentioned 4 groups were:

1. emmetropia group,
2. low hyperopia group,
3. moderate hyperopia group, and
4. high hyperopia group. 

The measurements of central corneal thickness, anterior chamber depth, angle opening distance, trabecular iris space area and scleral angle were compared in pairs among objects in the 4 groups.  The results showed that high hyperopia and moderate hyperopia had shallower anterior chamber depth and narrower anterior chamber angle compared to those in emmetropia group.  The authors concluded that the findings of this study showed that AS-OCT is a non-contact technology that could become a new technology for accessing the anterior segment morphology of hyperopia in school-aged children.

Evaluation of Belantamab-Associated Superficial Keratopathy

Matsumiya and colleagues (2021) described structural changes in corneal epithelium using AS-OCT in 2 patients with relapsed and refractory multiple myeloma (RRMM) who were treated for bilateral belantamab-associated superficial keratopathy (BASK).  The 1^st subject was a 56-year old man who was diagnosed with RRMM and initiated on belantamab mafodotin, presented on Day 42 (3 weeks after the 2nd infusion) with decreased pinhole VA from 20/20 and 20/25 to 20/70 and 20/50 in the right eye and left eye, respectively.  Slit-lamp examination revealed moderate superficial keratopathy with microcystic-like epithelial changes (MECs) in the paracentral cornea in both eyes.  AS-OCT demonstrated increased bilateral heterogeneous signal intensity and hyper-reflective lesions as well as increased thickness in the paracentral corneal epithelium with uninvolved central cornea.  Given bilateral MECs, the 3rd infusion was withheld, and then given on Day 62 after 5 weeks of drug-free interval.  Although MECs had improved on Day 82, pinhole VA remained at 20/50 and 20/40 in the right eye and the left eye.  AS-OCT showed that hyper-reflective lesions mostly resolved and corneal epithelial thickness returned to baseline, despite a slightly increased persisting heterogeneous signal intensity in the peripheral corneal epithelium in both eyes.  The 2^nd subject was a 77-year-old man with RRMM, who was started on belantamab mafodotin infusions.  His pinhole VA decreased from 20/40 and 20/30 at baseline to 20/60 and 20/40 on Day 41 (3 weeks after the 2nd infusion) in the right eye and left eye, respectively.  Slit-lamp examination showed diffuse, moderate MECs in both eyes, which was more severe in the peripheral cornea.  AS-OCT demonstrated increased bilateral heterogeneous signal intensity and hyper-reflective lesions in the corneal epithelium, which were more severe in the right eye along with increased corneal epithelial thickness; thus, belantamab mafodotin was withheld.  The authors concluded that AS-OCT objectively demonstrated structural changes such as signal intensity and thickness alterations with hyper-reflective lesions in the corneal epithelium related to BASK.  Moreover, these researchers stated that AS-OCT might be useful for clinicians to monitor ocular surface adverse events in RRMM patients receiving belantamab mafodotin and to adjust therapeutic plans for the patients.  These researchers stated that AS-OCT may be a useful, complementary, objective imaging modality to evaluate BASK; and future prospective studies will be of importance to elaborate further and confirm these findings.

Evaluation of Benign Reactive Lymphoid Hyperplasia and Conjunctival Amyloidosis, Hyperemia, and Lymphoma

Venkateswaran and colleagues (2019) stated that conjunctival lymphoma, conjunctival amyloidosis, and benign reactive lymphoid hyperplasia (BRLH) are conditions that often have a similar appearance on the ocular surface.  The use of high-resolution anterior segment OCT (HR-OCT) enables clinicians to evaluate distinctive differences in tissue morphology and cellular patterns in various ocular surface conditions.  In this study, these investigators characterized the morphological differences observed in conjunctival lymphoma, conjunctival amyloidosis and BRLH on HR-OCT imaging.  They carried out a retrospective chart review of patients with biopsy proven conjunctival lymphoma, conjunctival amyloidosis and BRLH between 2012 and 2019 at the Bascom Palmer Eye Institute.  Patients were excluded if HR-OCT imaging was not performed on initial presentation.  A total of 34 eyes of 27 patients were identified; 20 eyes had conjunctival lymphoma (16 patients), 8 eyes had conjunctival amyloidosis (6 patients) and 6 eyes had BRLH (5 patients).  All conditions appeared clinically as pink, red or yellow sub-epithelial lesions but had different features on HR-OCT.  In lymphoma, HR-OCT images typically showed homogenous, dark sub-epithelial lesions with smooth borders, containing monomorphic dot-like infiltrates; HR-OCT images of amyloidosis typically showed heterogeneous, dark lesions with irregular borders, often containing hyper-reflective linear infiltrates; HR-OCT images of BRLH showed variable infiltration of the sub-epithelial tissue, at times with homogenous lesions containing dot-like infiltrates like lymphoma and other times with more hyper-reflective, sub-epithelial tissue.  Flow cytometry and gene re-arrangement was needed for final differentiation between BRLH and lymphoma lesions.  The authors concluded that distinctive features on HR-OCT of conjunctival lymphoma, conjunctival amyloidosis and BRLH could help characterize these lesions beyond what is apparent with the clinical examination.  Moreover, these researchers stated that future studies with longitudinal follow-up can further validate this technology's use with more subtle and challenging lesions.

In a prospective, cross-sectional study, Akagi and associates (2019) examined conjunctival and intra-scleral vasculature in glaucoma eyes using anterior segment (AS)-OCT angiography (OCTA) and evaluated the factors contributing to the vessel density in AS-OCTA images.  A total of 34 patients with primary open-angle glaucoma and 20 healthy subjects were included.  A swept-source OCT system was used to obtain AS-OCTA images of the corneal limbus at the nasal and temporal quadrants.  Vessel densities were measured in the superficial (from the conjunctival epithelium to a depth of 200 μm) and deep (from a depth of 200 μm to 1,000 μm) layers.  The vessel density was compared between healthy and glaucoma eyes, and the associations of the vessel density with possible confounding factors were analyzed using uni-variable and multi-variable analyses.  The vessel density was not significantly different between healthy eyes and eyes with glaucoma.  There was a significant association of superficial vessel density with the use of a prostaglandin analog (p = 0.007) and with nasal location (p = 0.016) in eyes with glaucoma.  Deep vessel density was significantly smaller with advancing age (p = 0.029) in healthy eyes and greater with higher IOP (p = 0.021) in eyes with treated glaucoma.  The authors concluded that AS-OCTA images may be useful for objective assessment of conjunctival hyperemia and helpful for understanding the pathophysiology of post-trabecular aqueous humor outflow.

Evaluation of Blebs After Filtering Surgery

In a pilot study, Meziani et al (2016) compared characteristics of functioning blebs (FBs) and non-functioning blebs (NFBs) with en-face spectral-domain OCT. These researchers evaluated 41 blebs of 38 patients after a first-time trabeculectomy.  Eyes were classified into 2 groups: (i) FBs (22 eyes) and (ii) NFBs (19 eyes).  En-face OCT images were analyzed semi-quantitatively for the density of intra-epithelial microcysts (0 to 3), internal fluid-filled cavity (0 to 3), and bleb vascularization (0 to 2).  Presence of conjunctival fibrosis and visualization of the scleral flap were also analyzed.  Functioning blebs showed significantly more intra-epithelial microcysts than did NFBs: the mean grading of microcyst density was 1.86 for FBs and 0.11 for NFBs (p < 0.0001).  None of the FBs was rated 0 and none of the NFBs was rated 2 or 3 for the density of intra-epithelial microcysts.  Non-functioning blebs presented more conjunctival fibrosis than FBs (63 % versus 32 %, p < 0.05).  There was no significant difference between FBs and NFBs for bleb vascularization, visualization of the scleral flap, and presence of sub-epithelial fluid-filled cavities.  There was a direct correlation between post-operative intra-ocular pressure (IOP) and intra-epithelial microcyst density (r = -0.7655, p < 0.0001).  The long-term administration of preserved eye-drops before surgery was associated with fewer intra-epithelial microcysts (r = -0.5436; p = 0.0006).  The authors concluded that FBs were associated with a higher number of intra-epithelial microcysts evaluated with en-face OCT.  A higher density of microcysts was associated with a lower IOP and a shorter duration of preserved topical treatment before surgery.  They stated that en-face OCT provided a simple, non-invasive, and reproducible method to analyze blebs after filtering surgery.  The findings of this pilot study need to be validated by well-designed studies.

Evaluation of Ocular Surface Squamous Neoplasia

In a prospective, cross-sectional study, Singh and colleagues (2018) evaluated the imaging characteristics of intra-epithelial and invasive ocular surface squamous neoplasia (OSSN) on high-resolution AS-OCT.  A total of 17 consecutive patients (10 intra-epithelial and 7 invasive) with histopathologically proven OSSN were included.  All patients underwent slit-lamp imaging and time-domain AS-OCT at pre-marked sites.  Management included standard complete surgical excision with margin clearance and cryotherapy for all cases.  The correlation between imaging characteristics and histopathology sections at the pre-marked sites was analyzed to determine surrogate markers that may help differentiate intra-epithelial from invasive OSSN.  In addition, 3 patients with presumed OSSN underwent serial AS-OCT for surveillance.  All tumors were staged as T3N0M0 except 2 that were staged as T1N0M0 by the 8th Edition of the American Joint Committee on Cancer (AJCC).  Mean age was comparable between the 2 groups (56 years versus 54 years for intra-epithelial and invasive groups, respectively, p = 0.79); ASOCT characteristics included all cases (100 %) showing a hyper-reflective thickened epithelium and abrupt transition between normal and abnormal epithelium; 9 of 10 (90 %) intra-epithelial OSSN showed a clear plane of separation.  A hyper-reflective basal membrane was seen in 60 % of intra-epithelial OSSN, and hypo-reflective zones were seen in 57 % of invasive OSSN.  Mean thickness was 924 and 1,662 µm in intra-epithelial and invasive OSSN, respectively (p = 0.02, Mann-Whitney test).  The authors concluded that a visible clear plane of separation and increased thickness on AS-OCT may serve as surrogate markers of intra-epithelial OSSN and help differentiate it from invasive OSSN.  These preliminary findings need to be validated by well-designed studies.

Venkateswaran and co-workers (2018) stated that the advent of OCT imaging has changed the way ophthalmologists image the ocular surface and anterior segment of the eye.  Its ability to obtain dynamic, high and ultra-high resolution, cross-sectional images of the ocular surface and anterior segment in a non-invasive and rapid manner allows for ease of use.  These investigators focused on the use of AS-OCT, which provides an "optical biopsy" or in-vivo imaging of various ocular surface and corneal pathologies.  The authors concluded that this innovative technology helps assess tissue anatomy and evaluate differences in cellular morphology and patterns to distinguish between divergent anterior segment conditions.  They stated that while there is still room for growth with aspects of this imaging modality, its utility is quite apparent and it is actively emerging as a promising clinical and research tool.

Evaluation of Post-Operative Opacification of Intra-Ocular Lens

Choudhry and associates (2018) noted that post-operative opacification of a hydrophilic acrylic intra-ocular lens (IOL) is an uncommon complication.  These investigators reported on the case of a 57-year old diabetic woman who had undergone phacoemulsification with IOL implantation in her right eye 16 years back presented with diminution of vision in the same eye for 3 years.  Significant IOL opacification was observed clinically and AS-OCT clearly delineated the intra-optic deposits, sparing the haptics, and edges of the optic; IOL explant and exchange was performed leading to restoration of VA to 6/9.  Histochemical evaluation of the IOL confirmed that the hydrophilic acrylic IOL optic had calcium deposits.  The authors concluded that this report described the role of AS-OCT in detecting intra-optic calcification leading to IOL opacification.  The use of this modality for in-vivo evaluation of opacified IOLs may prevent potentially avoidable procedures with their antecedent risks.  A careful follow-up of diabetes patients implanted with hydrophilic acrylic IOLs is also to be emphasized.  These preliminary findings need to be validated by well-designed studies.

Evaluation of the Proximal Lacrimal System

In a prospectively designed, observational study, Singh and colleagues (2017) reported proximal lacrimal system parameters using AS-OCT (Visante) in an apparently normal Asian Indian population with assessment of any correlation between tear meniscus height and punctal diameter.  This study included healthy adults, who volunteered for OCT of their proximal lacrimal system.  Time domain AS-OCT (Visante) images of the punctum and proximal canaliculus were captured using the high resolution corneal scan protocol.  External lacrimal punctal diameter (ELP), internal lacrimal punctal diameter (ILP), vertical canalicular length (VCL) and tear meniscus height (TMH) were calculated.  Statistical analysis was performed using Pearson's correlation test.  This study included 100 normal subjects with mean age of 24.14 years (range of 15 to 38 years).  AS-OCT (Visante) with advantage of deeper penetration was able to image canaliculus in all cases.  The mean TMH, ELP, ILP and VCL were 252.7 ± 67.98 μm, 382.2 ± 103.14μm, 140.7 ± 67.29 μm and 811.8 ± 253.7 μm, respectively, in 100 normal subjects.  No correlation was found between ELP, ILP and TMH (Pearson's Correlation; r = -0.355, p > 0.05 for all).  The authors concluded that AS-OCT (Visante) is a non-invasive and easy to use objective tool for imaging proximal lacrimal system.  Moreover, they stated that further studies are needed to validate normative data and correlate with microscopic findings of lacrimal system.

Evaluation of Strabismus

Chopra and colleagues (2018) noted that binocular OCT has the potential to evaluate and quantify strabismus objectively and in an automated manner.  These investigators examined the use of a binocular OCT prototype to assess the presence and size of strabismus.  A total of 15 participants with strabismus were recruited in 2016 as part of the EASE study from Moorfields Eye Hospital National Health Service Foundation Trust, London, England, and 15 healthy volunteers underwent automated anterior segment imaging using the binocular OCT prototype.  All participants had an orthoptic assessment, including alternating prism cover test (APCT), before undergoing imaging.  Simultaneously acquired pairs of OCT images, captured with 1 eye fixating, were analyzed using ImageJ (National Institutes of Health) to assess the presence and angle of strabismus.  The direction and size of strabismus measured using binocular OCT was compared with that found using APCT.  The median age for participants with strabismus was 55 years (interquartile range [IQR], 33 to 66.5 years) and for the healthy group, 50 years (IQR, 41 to 59 years); 15 participants (50 %) were women, and 25 participants (83.3 %) were white.  The median magnitude of horizontal deviation was 20∆ (IQR, 13 to 35∆) and for vertical deviation, 3∆ (IQR, 0 to 5∆)..  Binocular OCT imaging correctly revealed the type and direction of the deviation in all 15 participants with strabismus, including horizontal and vertical deviations.  The APCT and OCT measurements were strongly correlated for the horizontal (Pearson r = 0.85; 95 % CI: 0.60 to 0.95; p < 0.001) and vertical (r = 0.89; 95 % CI: 0.69 to 0.96; p < 0.001) deviations.  In the healthy cohort, 9 of 15 participants (60 %) had a latent horizontal deviation on APCT results (median magnitude 2∆, range of 2 to 4∆); 6 (40 %) had orthophoria.  Horizontal deviations were observed on OCT imaging results in 12 of the 15 participants (80 %), and a vertical deviation was visible in 1 participant (6.7 %).  The authors concluded that these findings suggested that binocular AS-OCT imaging could provide clinicians with a precise measurement of strabismus.  The prototype could potentially incorporate several binocular vision tests that will provide quantitative data for the assessment, diagnosis, and monitoring of ocular misalignments.

Identification of Fungal Infections with Endophthalmitis after Cataract Surgery

In a case-reports study, Kitahata and associates (2016) reported the use of AS-OCT for characterization of late-onset tunnel fungal infections with endophthalmitis after cataract surgery. A 77-year old female (case 1) and a 76-year old male (case 2) who received cataract surgery 15 and 1 year before their initial visits, respectively, were treated with topical steroids based on a diagnosis of uveitis, because they showed growing white lesions on the upper iris and beneath the cataract scleral wound.  Irrigation of the anterior chambers and removal of the white lesions were performed in each case, and microbiological tests were positive for fungi (case 1, a positive culture of Fusarium sp.; case 2, a filamentous fungus present in a direct smear) in the white lesions.  Both cases were diagnosed as late-onset fungal endophthalmitis after cataract surgery and were treated with topical and systemic anti-fungal agents.  However, the white lesions re-appeared, and the inflammation in the anterior chambers worsened.  Anterior segment optical coherence tomography showed the spread of the white lesions into the scleral incisions from cataract surgery.  De-roofing of the tunnel and sclera-corneal patch grafts were performed in both cases to treat the fungal tunnel infections.  After these treatments, inflammation of both corneas and anterior chambers subsided.  The authors concluded that AS-OCT can be used to identify late-onset fungal tunnel infections with endophthalmitis after cataract surgery.  These preliminary findings need to be validated by well-designed studies.

Imaging of Extra-Ocular Rectus Muscle Insertions for Pre-Operative Planning

Pihlblad and co-workers (2016) evaluated the possibility of determining the insertion distance from the limbus of horizontal and vertical extra-ocular rectus muscles with AS-OCT. The right eyes of 46 patients underwent AS-OCT.  The horizontal and vertical extra-ocular rectus muscle insertion distances from the limbus were measured in a masked fashion by 2 pediatric ophthalmologists.  A total of 42 lateral rectus, 43 medial rectus, 35 inferior rectus, and 40 superior rectus muscles of the right eyes of 46 patients were included.  Insertion to limbus measurements (mean ± SD) were as follows: lateral rectus = mean 6.8 ± 0.7 mm, range = 4.8 to 8.4 mm; medial rectus = mean 5.7 ± 0.8 mm, range = 4.3 to 7.8 mm; inferior rectus = mean 6.0 ± 0.6 mm, range = 4.8 to 7.0 mm; superior rectus = mean 6.8 ± 0.6 mm, range = 5.5 to 8.1 mm.  The intra-observer and inter-observer correlation coefficients for the insertion to limbus measurements of all 4 rectus muscles exceeded 0.75 (excellent correlation).  The authors concluded that the findings of this study showed that AS-OCT is capable of imaging all 4 of the rectus muscle insertions and measuring the insertion to limbus distance, and this study was the second AS-OCT study to image the superior and inferior rectus muscle insertions.  They stated that the insertion to limbus measurements between examiners and on repeat measurements were consistent and reproducible; and the ability to accurately image extra-ocular rectus muscle insertions may have future implications for the pre-operative procedure planning in patients who have had previous surgery.

Evaluation of Corneal and Conjunctival Tumors

The main drawback of this review was that the sample size of most studies was small, often leading to the conclusion that further research is needed.  Also, only a limited amount of tumor types was examined, which made it impossible to extrapolate these findings to all corneal and conjunctival tumors.

Management of Wilson Disease

In a retrospective, case-series study, Sridhar and colleagues (2017) presented AS-OCT as an alternative method of evaluating Kayser-Fleischer (KF) ring in Wilson disease (WD) not only by ophthalmologists but also by other clinicians dealing with WD.  This study included 6 WD patients with KF ring.  Evaluation of KF ring was done by naked eye examination using torch light, slit lamp biomicroscopy (SL), and AS-OCT.  SL examination was done using a narrow slit of the superior cornea; AS-OCT was performed using the Optovue RTvue PremierTM device (Fremont, CA).  AS-OCT revealed KF ring as an intense hyper-reflective band at the level of Descemet membrane (DM).  Color scale of AS-OCT showed KF ring as greenish/greenish yellow/orange yellow/yellowish/red band.  Validation of AS-OCT findings was carried out by a 2nd ophthalmologist, medical gastroenterologist, surgical gastroenterologist, and neurophysician.  After seeing the first observation, they could identify the AS-OCT features in all pictures with ease.  The authors concluded that this was the first observation of KF ring in WD on AS-OCT.  On AS-OCT, KF ring was visualized as intense hyper-reflectivity at the level of DM in the peripheral cornea.  Moreover, they stated that further studies are needed to evaluate the usefulness of AS-OCT in WD management.

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.

Prediction of Post-Operative Outcomes Following Trabeculectomy

Kokubun and associates (2018) examined if AS-OCT can be used to predict post-trabeculectomy bleb outcomes.  These researchers divided 58 eyes of 47 trabeculectomy patients into success or failure groups based on their status at 12 months after surgery.  They then compared various AS-OCT measurement parameters between the 2 groups at 1 and 2 weeks and 1, 3, 6, and 12 months.  They also analyzed the early post-trabeculectomy bleb parameters with multiple logistic regression, step-wise multiple regression, and the receiver operating characteristic (ROC) curve, to evaluate the power of these parameters to predict long-term outcomes; IOP 3 or more months after trabeculectomy was significantly lower in the success group than the failure group (all: p < 0.0016).  Cleft volume was significantly higher 6 or more months after trabeculectomy in the success group than the failure group (p = 0.0027 and < 0.0016).  Reflectivity of the bleb wall was significantly higher in the failure group than the success group at 2 weeks and all later time points (all: p < 0.0016).  Reflectivity of the bleb wall at 2 weeks after trabeculectomy was a risk factor for failure, with an odds ratio (OR) for failure of 2.48 (95 % CI: 1.31 to 4.68, increasing per 10 AU).  The area under the ROC curve for reflectivity of the bleb wall at 2 weeks after trabeculectomy was 0.775 when the cut-off value was set at 122.8, with sensitivity, specificity, and OR of 78.3 %, 80.0 %, and 14.4, respectively.  A step-wise multiple regression analysis showed that reflectivity of the bleb wall at 2 weeks was an independent factor indicating post-operative bleb survival period (β = -0.39, p = 0.007).  The authors concluded that reflectivity of the bleb wall, measured by AS-OCT, may be an early post-trabeculectomy predictor of bleb outcome.  These findings need to be validated by well-designed studies.

Quantification of Corneal Haziness

In an observational, cross-sectional study, Rose and colleagues (2017) quantified normal corneal transparency by AS-OCT by measuring the average pixel intensity.  These researchers analyzed the variation in the average pixel intensity in mild and severe grades of corneal opacities.  This trial included 38 eyes from 19 patients with mild or severe grades of corneal opacities greater than 3 mm and a normal contralateral cornea; AS-OCT was performed centered on the opacity with a 3-mm cruciate protocol.  A similar image was taken of the contralateral clear cornea in the same quadrant.  The average pixel intensity was calculated in a standardized manner using MATLAB software.  The average pixel intensity of the normal cornea was 99.6 ± 10.9 [standard deviation (SD)].  The average pixel intensity of the mild and severe corneal opacities was 115.5 ± 9.1 and 141.1 ± 10.3, respectively.  The differences were statistically significant.  The authors concluded that the findings of this study provided proof of principle evidence to estimate corneal opacification on a nominal scale.  They stated that a follow-up study with a larger sample size is underway to prove this principle in a larger population including leucoma scars.

The authors stated that the drawbacks of this study included the small sample size (n = 19 subjects), no correlation with any specific etiological diagnosis, analysis of only 2 directional scans for a given image, and the lack of comparisons with any other instruments that could measure corneal transparency.

Repair of Cyclodialysis Cleft

Teoh et al (2022) described different imaging modalities used to localize cyclodialysis clefts and direct cyclopexy repair of cyclodialysis clefts.  In a retrospective study, these investigators reviewed the record of a patient with traumatic cyclodialysis cleft who underwent direct cyclopexy.  Pre-operative and post-operative VA and IOP were recorded.  Gonioscopy, UBM and 360° swept-source AS-OCT (SS-ASOCT) were used to localize the cyclodialysis cleft.  The authors concluded that UBM is the current gold standard imaging modality in localization of cyclodialysis clefts, and that SS-ASOCT is potentially useful as alternative imaging modality.

Repeatability and Agreement of Two Swept-Source Optical Coherence Tomographers for Anterior Segment Parameter Measurements

Cheng et al (2022) examined the repeatability and agreement of 2 swept-source optical coherence tomographers for anterior segment parameters in healthy subjects.  These researchers carried out automated mark of scleral spur and angle recess for the CASIA2 and manual mark of scleral spur and angle recess for the Anterion; then the measurement values of the related parameters were automatically generated.  Subjects with pupil diameter (PD) differing by less than 15 % between the 2 devices were included.  PD, lens vault (LV), anterior chamber depth (ACD), angle to angle distance (ATA), anterior chamber width (ACW), anterior chamber angle (ACA), angle opening distance (AOD), and trabecular iris space area (TISA) were measured in the horizontal images with both CASIA2 and Anterion.  Intra-class correlation coefficient (ICC) was employed to examine intra-device repeatability.  Bland-Altman plots were carried out to evaluate the agreement between the 2 devices.  A total of 35 right eyes of 35 subjects were included with a mean age of 25.60 ± 3.00 years.  The CASIA2 showed moderate-to-good intra-device repeatability (ICCs ranged from 0.786 to 0.989) whereas the Anterion showed good intra-device repeatability (ICCs ranged from 0.921 to 0.998) for anterior segment parameters.  Compared with the CASIA2, the Anterion offered larger values of ACA500/750, AOD500/750, and TISA500/750 but smaller values of PD, LV, ACD, ATA, and ACW.  Good agreement for PD, ACD, ATA, and ACW was detected with 95 % limits of agreement of -1.02 to 1.02 mm, -0.11 to 0.14 mm, -0.17 to 0.19 mm, -0.13 to 0.28 mm, respectively.  Poor agreement for LV, ACA500/750, AOD500/750, and TISA500/750 was achieved with the 2 devices.  The authors concluded that Anterion out-performed CASIA2 on intra-device repeatability.  They noted that while agreement was noted for some parameters using manual Anterion and automated CASIA2 approaches, poor agreement of LV and angle parameters indicated that measurements from these OCT devices should not be considered inter-changeable.

References