Comparison between the Recommendations of Glaucoma Specialists and OCT Report Specialists for Further Ophthalmic Evaluation in a Community-Based Screening Study.

PURPOSE: To compare glaucoma referral patterns between glaucoma and OCT report specialists and to determine what influence, if any, a designated OCT reading could have on a glaucoma specialist's judgments. DESIGN: Retrospective, exploratory study. SUBJECTS: We included 483 eyes (243 individuals) from high-risk New York City neighborhoods screened as part of a mobile van glaucoma screening study from July 2017 to October 2017. METHODS: All participants underwent comprehensive testing, including visual acuity, commercial OCT imaging, gonioscopy, intraocular pressure, frequency-doubling testing, and funduscopic assessment. Three glaucoma specialists independently evaluated all the collected data to determine whether a further glaucoma workup referral was recommended. Two OCT report specialists evaluated only the OCT image for each eye using the commercial report as well as a specialized, customized report. In phase II, the glaucoma specialists then re-evaluated a subset of these eyes, this time with an OCT report specialist's judgments made available. MAIN OUTCOME MEASURES: Comparison of glaucoma specialist referrals made by glaucoma specialists versus OCT report specialists. RESULTS: Intergrader agreement between glaucoma specialists was 60% (κ = 0.43) and between report specialists was 95% (κ = 0.77). There was an agreement between a single OCT report specialist and the consensus (2 of 3) of glaucoma specialists in 74% of eyes (κ= 0.32). Of the eyes studied, 25% were referred for further glaucoma evaluation by the glaucoma specialists alone and 1% were referred for further glaucoma workup by only the report specialist. With the addition of the report specialist's judgments, referral pattern changes varied by glaucoma specialist but overall agreement increased to 85% (κ = 0.53). CONCLUSIONS: There was a fair level of agreement regarding glaucoma referral recommendations between glaucoma specialists with access to comprehensive screening data and OCT report specialists with access to only OCT data. Overall agreement increased when the designated OCT evaluation was made available to the glaucoma specialists. These results may aid in the design of future large-scale glaucoma screening studies.

Artificial Intelligence for Glaucoma: Creating and Implementing Artificial Intelligence for Disease Detection and Progression.

On September 3, 2020, the Collaborative Community on Ophthalmic Imaging conducted its first 2-day virtual workshop on the role of artificial intelligence (AI) and related machine learning techniques in the diagnosis and treatment of various ophthalmic conditions. In a session entitled "Artificial Intelligence for Glaucoma," a panel of glaucoma specialists, researchers, industry experts, and patients convened to share current research on the application of AI to commonly used diagnostic modalities, including fundus photography, OCT imaging, standard automated perimetry, and gonioscopy. The conference participants focused on the use of AI as a tool for disease prediction, highlighted its ability to address inequalities, and presented the limitations of and challenges to its clinical application. The panelists' discussion addressed AI and health equities from clinical, societal, and regulatory perspectives.

Virtual Reality and Augmented Reality in Ophthalmology: A Contemporary Prospective.

PURPOSE: Most published systematic reviews have focused on the use of virtual reality (VR)/augmented reality (AR) technology in ophthalmology as it relates to surgical training. To date, this is the first review that investigates the current state of VR/AR technology applied more broadly to the entire field of ophthalmology. METHODS: PubMed, Embase, and CINAHL databases were searched systematically from January 2014 through December 1, 2020. Studies that discussed VR and/or AR as it relates to the field of ophthalmology and provided information on the technology used were considered. Abstracts, non-peer-reviewed literature, review articles, studies that reported only qualitative data, and studies without English translations were excluded. RESULTS: A total of 77 studies were included in this review. Of these, 28 evaluated the use of VR/AR in ophthalmic surgical training/assessment and guidance, 7 in clinical training, 23 in diagnosis/screening, and 19 in treatment/therapy. 15 studies used AR, 61 used VR, and 1 used both. Most studies focused on the validity and usability of novel technologies. CONCLUSIONS: Ophthalmology is a field of medicine that is well suited for the use of VR/AR. However, further longitudinal studies examining the practical feasibility, efficacy, and safety of such novel technologies, the cost-effectiveness, and medical/legal considerations are still needed. We believe that time will indeed foster further technological advances and lead to widespread use of VR/AR in routine ophthalmic practice.

ACUTE ZONAL OCCULT OUTER RETINOPATHY: Structural and Functional Analysis Across the Transition Zone Between Healthy and Diseased Retina.

PURPOSE: To assess structure and function across the transition zone (TZ) between relatively healthy and diseased retina in acute zonal occult outer retinopathy. METHODS: Six patients (6 eyes; age 22-71 years) with acute zonal occult outer retinopathy were studied. Spectral-domain optical coherence tomography, fundus autofluorescence, near-infrared reflectance, color fundus photography, and fundus perimetry were performed and images were registered to each other. The retinal layers of the spectral-domain optical coherence tomography scans were segmented and the thicknesses of two outer retinal layers, that is, the total receptor and outer segment plus layers, and the retinal nerve fiber layer were measured. RESULTS: All eyes showed a TZ on multimodal imaging. On spectral-domain optical coherence tomography, the TZ was in the nasal retina at varying distances from the fovea. For all eyes, it was associated with loss of the ellipsoid zone band, significant thinning of the two outer retinal layers, and in three eyes with thickening of the retinal nerve fiber layer. On fundus autofluorescence, all eyes had a clearly demarcated peripapillary area of abnormal fundus autofluorescence delimited by a border of high autofluorescence; the latter was associated with loss of the ellipsoid zone band and with a change from relatively normal to markedly decreased or nonrecordable visual sensitivity on fundus perimetry. CONCLUSION: The results of multimodal imaging clarified the TZ in acute zonal occult outer retinopathy. The TZ was outlined by a distinct high autofluorescence border that correlated with loss of the ellipsoid zone band on spectral-domain optical coherence tomography. However, in fundus areas that seemed healthy on fundus autofluorescence, thinning of the outer retinal layers and thickening of the retinal nerve fiber layer were observed near the TZ. The TZ was also characterized by a decrease in visual sensitivity.

The 24-2 Visual Field Test Misses Central Macular Damage Confirmed by the 10-2 Visual Field Test and Optical Coherence Tomography.

PURPOSE: To determine the extent to which the 24-2 visual field (VF) misses macular damage confirmed with both 10-2 VF and optical coherence tomography (OCT) tests and to evaluate the patterns of damage missed. METHODS: One hundred forty-one eyes of 141 glaucoma patients or suspects underwent 24-2 VF (mean deviation [MD] better than -6 dB), 10-2 VF, and OCT testing. Retinal nerve fiber layer (RNFL) and retinal ganglion cell plus inner plexiform (RGC+) probability plots were combined with 10-2 VF probability plots. Eyes were classified as "abnormal macula" if abnormal regions on both the 10-2 VF and OCT plots agreed. The number of abnormal eyes missed (i.e., false negatives) was determined for the following 24-2 VF metrics: MD; pattern standard deviation (PSD); glaucoma hemifield test (GHT); cluster criteria (CC); and abnormal points within ± 10°. Eyes that were missed on one or more of the 24-2 metrics were classified by damage type based upon circumpapillary RNFL thickness plots. RESULTS: Fifty-nine (41.8%) eyes were classified as "abnormal macula," and comprised the reference standard. Of the 59, 31 (52.5%) were missed by one or more of the 24-2 metrics. The individual 24-2 metrics missed between 7 (CC) and 20 (MD) eyes. The eyes missed had widespread macular damage, as well as both shallow and deep local defects. CONCLUSIONS: Eyes with macular glaucomatous damage may be classified as normal based on the 24-2 VF alone. TRANSLATIONAL RELEVANCE: To detect macular damage with perimetry, the 10-2 VF test (or a modified 24-2 VF test) is essential.

Reliability of a Manual Procedure for Marking the EZ Endpoint Location in Patients with Retinitis Pigmentosa.

PURPOSE: We developed and evaluated a training procedure for marking the endpoints of the ellipsoid zone (EZ), also known as the inner segment/outer segment (IS/OS) border, on frequency domain optical coherence tomography (fdOCT) scans from patients with retinitis pigmentosa (RP). METHODS: A manual for marking EZ endpoints was developed and used to train 2 inexperienced graders. After training, an experienced grader and the 2 trained graders marked the endpoints on fdOCT horizontal line scans through the macula from 45 patients with RP. They marked the endpoints on these same scans again 1 month later. RESULTS: Intragrader agreement was excellent. The intraclass correlation coefficient (ICC) was 0.99, the average difference of endpoint locations (19.6 µm) was close to 0 µm, and the 95% limits were between -284 and 323 µm, approximately ±1.1°. Intergrader agreement also was excellent. The ICC values were 0.98 (time 1) and 0.97 (time 2), the average difference among graders was close to zero, and the 95% limits of these differences was less than 350 µm, approximately 1.2°, for both test times. CONCLUSIONS: While automated algorithms are becoming increasingly accurate, EZ endpoints still have to be verified manually and corrected when necessary. With training, the inter- and intragrader agreement of manually marked endpoints is excellent. TRANSLATIONAL RELEVANCE: For clinical studies, the EZ endpoints can be marked by hand if a training procedure, including a manual, is used. The endpoint confidence intervals, well under ±2.0°, are considerably smaller than the 6° spacing for the typically used static visual field.

Details of Glaucomatous Damage Are Better Seen on OCT En Face Images Than on OCT Retinal Nerve Fiber Layer Thickness Maps.

PURPOSE: High-resolution images of glaucomatous damage to the retinal nerve fiber layer (RNFL) were obtained with an adaptive optics-scanning light ophthalmoscope (AO-SLO) and used as a basis for comparisons between en face slab images and thickness maps derived from optical coherence tomography (OCT) scans. METHODS: Wide-field (9 × 12 mm) cube scans were obtained with swept-source OCT (DRI-OCT) from six eyes of six patients. All eyes had a deep defect near fixation as seen on a 10-2 visual field test. Optical coherence tomography en face images, based on the average reflectance intensity, were generated (ATL 3D-Suite) from 52-µm slabs just below the vitreal border of the inner limiting membrane. The RNFL thickness maps were generated from the same OCT data. Both were compared with the AO-SLO peripapillary images that were previously obtained. RESULTS: On AO-SLO images, three eyes showed small regions of preserved and/or missing RNFL bundles within the affected region. Details in these regions were seen on the OCT en face images but not on the RNFL thickness maps. In addition, in the healthier hemi-retinas of two eyes, there were darker, arcuate-shaped regions on en face images that corresponded to abnormalities seen on AO-SLO. These were not seen on RNFL thickness maps. CONCLUSIONS: Details of local glaucomatous damage, missing or easily overlooked on traditional OCT RNFL thickness analysis used in clinical OCT reports, were seen on OCT en face images based on the average reflectance intensity. While more work is needed, it is likely that en face slab imaging has a role in the clinical management of glaucoma.

A comparison of structural and functional changes in patients screened for hydroxychloroquine retinopathy.

PURPOSE: The aims of this retrospective study were to compare the results of recommended screening tests for hydroxychloroquine-related retinal toxicity and analyze disparities between the structural and functional findings. METHODS: Thirty-four patients (31 women and 3 men) were included in the study. All were evaluated with standard automated perimetry using the 10-2 and/or 24-2 visual field program (Zeiss, Meditec), multifocal electroretinography (mfERG), spectral-domain optical coherence tomography (SD-OCT), and short-wavelength fundus autofluorescent imaging (SW-FAF). The results for the right eye from each patient were analyzed. Visual fields were classified as normal or abnormal based on pattern deviation plots, and mfERGs based on a comparison of R5 ring ratios to values from 20 controls. The SW-FAF images were examined for areas/rings of abnormal hypo- and/or hyperautofluorescence, and the SD-OCT line scans were classified as abnormal based on visual inspection and thickness measurements of the outer segment plus retinal pigment epithelial layer and total receptor layers compared to mean thicknesses from 35 controls. RESULTS: Fifteen patients had abnormal results on at least one test; however, only two patients had abnormal results on all four tests. Excluding SW-FAF, seven of the 15 had abnormal visual fields, mfERG ring ratios, and SD-OCTs. The remaining eight had either abnormal mfERGs and/or visual fields and normal SD-OCTs. We found no evidence of abnormal SD-OCTs in the presence of normal mfERG and visual field results. CONCLUSIONS: The findings suggest that functional deficits precede structural changes seen on SD-OCT in these patients.

A comparison of progressive loss of the ellipsoid zone (EZ) band in autosomal dominant and x-linked retinitis pigmentosa.

PURPOSE: In patients with retinitis pigmentosa (RP), the inner segment ellipsoid zone (EZ; also known as the inner segment/outer segment [IS/OS] border) is a marker of the usable visual field at a given point in time and of the progression of the disease over time. Here we compare the change in the width per year of the EZ band in patients with autosomal dominant (ad) and x-linked (xl) RP. METHODS: Using optical coherence tomography (OCT), 9-mm horizontal and vertical line scans through the fovea were obtained for one eye of 26 xlRP patients and 33 adRP patients. Scans were repeated on average 2.0 years later (range, 0.6-4.8 years). Using a manual segmentation procedure, the EZ band was delineated and its horizontal width (HW) and vertical width (VW) were determined. RESULTS: The adRP and xlRP patients had similar initial EZ HW (xlRP: 11.8 ± 5.4°, adRP: 12.4 ± 6.3°, P = 0.69) and VW (xlRP: 8.5 ± 4.9°, adRP: 11.4 ± 7.1°, P = 0.09). However, between visits the absolute loss and percent loss of the EZ width per year was significantly greater for xlRP than adRP for both HW (xlRP: 1.0 ± 0.6°/y, 9.6 ± 5.6%/y; adRP: 0.4 ± 0.5°/y, 3.4 ± 5.4%/y; P < 0.001) and VW (xlRP: 0.8 ± 0.8°/y, 9.2 ± 8.9%/y; adRP: 0.3 ± 0.5°/y, 4.2 ± 6.4%/y; P < 0.01). There was a weak correlation between the loss of EZ width per year and the initial width for xlRP (r(2) = 0.17, P = 0.036), but no correlation for adRP (r(2) = 0.004, P = 0.73). The test-retest difference of EZ HW was 0.2 ± 0.5°. CONCLUSIONS: The OCT data here support a faster rate of loss per year in the case of xlRP. (ClinicalTrials.gov number, NCT00100230.).

Quantitative fundus autofluorescence and optical coherence tomography in best vitelliform macular dystrophy.

PURPOSE: Quantitative fundus autofluorescence (qAF), spectral domain optical coherence tomography (SD-OCT) segmentation, and multimodal imaging were performed to elucidate the pathogenesis of Best vitelliform macular dystrophy (BVMD) and to identify abnormalities in lesion versus nonlesion fundus areas. METHODS: Sixteen patients with a clinical diagnosis of BVMD were studied. Autofluorescence images (30°, 488-nm excitation) were acquired with a confocal scanning laser ophthalmoscope equipped with an internal fluorescent reference to account for variable laser power and detector sensitivity. The grey levels (GLs) of each image were calibrated to the reference, zero GL, magnification, and normative optical media density, to yield qAF. Horizontal SD-OCT scans were obtained and retinal layers manually segmented. Additionally, color and near-infrared reflectance (NIR-R) images were registered to AF images. All patients were screened for mutations in BEST1. In three additional BVMD patients, in vivo spectrofluorometric measurements were obtained within the vitelliform lesion. RESULTS: Mean nonlesion qAF was within normal limits for age. Maximum qAF within the lesion was markedly increased compared with controls. By SD-OCT segmentation, outer segment equivalent thickness was increased and outer nuclear layer thickness decreased in the lesion. Changes were also present in a transition zone beyond the lesion border. In subclinical patients, no abnormalities in retinal layer thickness were identified. Fluorescence spectra recorded from the vitelliform lesion were consistent with those of retinal pigment epithelial cell lipofuscin. CONCLUSIONS: Based on qAF, mutations in BEST1 do not cause increased lipofuscin levels in nonlesion fundus areas.

A Comparison of Methods for Tracking Progression in X-Linked Retinitis Pigmentosa Using Frequency Domain OCT.

PURPOSE: To compare the efficacy of frequency domain optical coherence tomography (fdOCT)-derived outer retinal measures in tracking disease progression in x-linked (xl) retinitis pigmentosa (RP) patients. METHODS: Macular volume scans and line scans (Spectralis) were obtained from 27 xlRP patients (15.3 ± 6.4 years) at two visits approximately 2 years apart. Changes in average outer retinal layer thicknesses across the volume scan were compared to changes detected by measures derived from the edge of the inner segment ellipsoid zone (EZ) band, that is, where the EZ band (also known as inner segment/outer segment border) disappears. Repeatability was tested on an independent set of 18 RP patients (43.5 ± 18.0 years). RESULTS: Average outer segment (OS) and outer nuclear layer (ONL) thickness showed marginally significant annual changes (P < 0.05), while total receptor (TR) thickness showed a greater change (P < 0.01). All measures derived from the edge of the EZ band significantly decreased (P < 0.01). Mean ± SD for test-retest differences in horizontal widths was 0.01 ± 0.06 mm. CONCLUSIONS: Measures of the EZ band are more effective in detecting disease progression than are thickness measures. Given the similar effectiveness of line and volume scans, manually marking the EZ band edge on vertical and/or horizontal line scans can be useful in tracking progression. TRANSLATIONAL RELEVANCE: Because disease progression in RP can be relatively slow, annual changes can be difficult to monitor during the course of a clinical trial. Here we suggest a quick, effective, and reliable method for detecting subtle changes.

Transition zones between healthy and diseased retina in choroideremia (CHM) and Stargardt disease (STGD) as compared to retinitis pigmentosa (RP).

PURPOSE: To describe the structural changes across the transition zone (TZ) in choroideremia (CHM) and Stargardt disease (STGD) and to compare these to the TZ in retinitis pigmentosa (RP). METHODS: Frequency-domain (Fd)OCT line scans were obtained from seven patients with CHM, 20 with STGD, and 12 with RP and compared with those of 30 previously studied controls. A computer-aided manual segmentation procedure was used to determine the thicknesses of the outer segment (OS) layer, the outer nuclear layer plus outer plexiform layer (ONL+), the retinal pigment epithelium plus Bruch's membrane (RPE+BM), and the outer retina (OR). RESULTS: The TZ, while consistent within patient groups, showed differences across disease groups. In particular, (1) OS loss occurred before ONL+ loss in CHM and RP, whereas ONL+ loss occurred before OS loss in STGD; (2) ONL+ was preserved over a wider region of the retina in CHM than in RP; (3) RPE+BM remained normal across the RP TZ, but was typically thinned in CHM. In some CHM patients, it was abnormally thin in regions with normal OS and ONL+ thickness. In STGD, RPE+BM was thinned by the end of the TZ; and (4) the disappearances of the IS/OS and OLM were more abrupt in CHM and STGD than in RP. CONCLUSIONS: On fdOCT scans, patients with RP, CHM, and STGD all have a TZ between relatively healthy and severely affected retina. The patterns of changes in the receptor layers are similar within a disease category, but different across categories. The findings suggest that the pattern of progression of each disease is distinct and may offer clues for strategies in the development of future therapies.

The inner segment/outer segment border seen on optical coherence tomography is less intense in patients with diminished cone function.

UNLABELLED: PURPOSE; The integrity of the inner segment ellipsoid (ISe) band, previously called the inner segment/outer segment (IS/OS) border, seen on optical coherence tomography (OCT) scans is of clinical significance. To better understand the influence of cones on the appearance of this band, the intensity of its signal in patients with diminished cone function was examined. METHODS: Horizontal line scans through the fovea of 30 healthy controls, 10 patients with achromatopsia (A), and six with cone dystrophy (CD) were obtained with frequency domain (fd) OCT. The fdOCT borders were segmented with a computer-aided manual technique. The ISe was divided into regions 60.1 µm wide and 19.5 µm deep. The relative ISe intensity of each region was defined as its intensity divided by the intensity of a local region, which extended in depth from the choroid to the retinal ganglion cell/retinal nerve fiber layer. RESULTS: Except for the central fovea, all patients had a clear ISe band across the region studied, ± 3 mm from the foveal center. However, the relative ISe intensity was significantly lower (P < 0.0001) in patients (A: 1.14 ± 0.14; CD: 1.27 ± 0.14), than in controls (1.61 ± 0.16). There were no differences in the relative intensity of the other retinal layers. CONCLUSIONS: Although present, the intensity of this ISe band is lower in patients with diminished cone function than it is in healthy controls. This is consistent with the hypothesis that both rod and cone receptors must be absent or damaged for the ISe band to be missing.

Automated segmentation of outer retinal layers in macular OCT images of patients with retinitis pigmentosa.

To provide a tool for quantifying the effects of retinitis pigmentosa (RP) seen on spectral domain optical coherence tomography images, an automated layer segmentation algorithm was developed. This algorithm, based on dual-gradient information and a shortest path search strategy, delineates the inner limiting membrane and three outer retinal boundaries in optical coherence tomography images from RP patients. In addition, an automated inner segment (IS)/outer segment (OS) contour detection method based on the segmentation results is proposed to quantify the locus of points at which the OS thickness goes to zero in a 3D volume scan. The segmentation algorithm and the IS/OS contour were validated with manual segmentation data. The segmentation and IS/OS contour results on repeated measures showed good within-day repeatability, while the results on data acquired on average 22.5 months afterward demonstrated a possible means to follow disease progression. In particular, the automatically generated IS/OS contour provided a possible objective structural marker for RP progression.

Method for deriving visual field boundaries from OCT scans of patients with retinitis pigmentosa.

The location of the loss of the inner segment (IS)/outer segment (OS) border, as seen with frequency domain optical coherence tomography (fdOCT), was determined on fdOCT scans from patients with retinitis pigmentosa. A comparison to visual field loss supported the hypothesis, based upon previous work, that the point at which the IS/OS border disappears provides a structural marker for the edge of the visual field. Repeat fdOCT measures showed good within day reproducibility, while data obtained on average 22.5 months later showed signs of progression. The IS/OS contour shows promise as a measure for following changes in patients undergoing treatment.