Search

To evaluate clinical characteristics of eyes in which investigator-determined new-onset exudative age-related macular degeneration (eAMD) developed during the FILLY trial.Post hoc analysis of the phase 2 study of intravitreal pegcetacoplan in geographic atrophy (GA).Patients with GA secondary to age-related macular degeneration (AMD), n = 246.Either 15 mg intravitreal pegcetacoplan or sham given monthly or every other month for 12 months followed by a 6-month off-treatment period.Time of new eAMD onset in the study eye, history of eAMD in the fellow eye, presence of double-layer sign (DLS) on structural OCT in the study eye, changes in retinal anatomic features by structural OCT and fluorescein angiography (FA), and changes in visual acuity.Exudation was reported in 26 study eyes across treatment groups over 18 months. Mean time to eAMD diagnosis was 256 days (range, 31-555 days). Overall, a higher proportion of patients with a baseline history of eAMD in the fellow eye (P = 0.016) and a DLS in the study eye (P = 0.0001) demonstrated eAMD. Among study eyes in which eAMD developed, 18 of 26 (69%) had history of fellow-eye eAMD and 19 of 26 (73.1%) had DLS at baseline, compared with 76 of 217 study eyes (35%; P = 0.0007) and 70 of 215 study eyes (32.5%; P0.0001), respectively, in which eAMD did not develop. All 21 patients with structural OCT imaging at the time of eAMD diagnosis demonstrated subretinal fluid, intraretinal cysts, or both consistent with exudation. Among 17 patients who underwent FA at eAMD diagnosis, 10 showed detectable macular neovascularization (MNV), all occult lesions. Development of eAMD did not have an appreciable impact on visual acuity, and all patients responded to anti-vascular endothelial growth factor (VEGF) therapy.Intravitreal pegcetacoplan slowed the rate of GA growth and was associated with an unexpected dose-dependent increased incidence of eAMD with no temporal clustering of onset. Exudative AMD seemed to be associated with baseline eAMD in the contralateral eye and a DLS, suggestive of nonexudative MNV, in the study eye. The safety profile of pegcetacoplan was acceptable to proceed to phase 3 studies without adjustments to enrollment criteria.

A panel of imaging experts was assembled to review neovascular age-related macular degeneration optical coherence tomography angiography descriptors published to date, and test agreement on use of these terms, which was found to be low. Optical coherence tomography angiography (OCTA) has been used to identify and characterize macular neovascularization (MNV) secondary to age-related macular degeneration (AMD). 1 , 2 , 3 , 4 Many studies have explored OCTA morphological features of MNV that might serve as biomarkers to assess disease activity and response to treatment. 1 , 2 , 3 , 4 , 5 , 6 The proliferation of studies however has resulted in an OCTA terminology that has been variable and inconsistent. To address inconsistency of nomenclature and allow harmonization, a multidisciplinary panel of retinal imaging experts with a history of relevant research contributions to the field was assembled with the purpose of reviewing published terminology and to recommend a reduced list of key terms pertinent to OCTA. The group was called UNICORN, because of its ultimate goal of generating a UNIfied COmmentary of the committee of inteRnational experts on the nomenclature for Neovascular AMD in OCTA. In this report we describe the first steps, which included a review of OCTA descriptors of neovascular AMD (nAMD) published to date, and an exercise that tested agreement of these terms among retinal imaging experts. Prior to the first UNICORN meeting, a non-systematic review of the literature was performed, using the search terms “optical coherence tomography angiography” or “OCT angiography” or “OCT-A”, AND “neovascular macular degeneration” or “neovascular age-related macular degeneration” or “neovascular AMD” or “nAMD” or “wet age-related macular degeneration” or “wet AMD” or “wet ARMD”. A dictionary of OCTA descriptors relating to the features of MNV in AMD was generated and circulated to the panel.

Many studies over the past 20 years have pursued the goal of preventing or deferring progression from early and intermediate age-related macular degeneration (AMD) to advanced AMD. The onset of neovascular AMD has been used as a primary endpoint in some prophylactic clinical trials because it is easy to assess and relatively well-defined. Nevertheless, the use of this endpoint for assessing progression of AMD lacks validation. The aims of this paper are to review the current practice of clinical trials investigating the prevention of progression of early or intermediate AMD to neovascular AMD, so-called prophylactic trials, as well as identify ongoing efforts to standardize endpoints and select the ideal population for such studies.

Purpose To identify optical coherence tomography angiography (OCTA) derived vessel metrics of the macula and optic nerve head (ONH) that predict diabetic retinopathy (DR) disease progression. Design Secondary analysis of clinical trial data Methods This was a sub-analysis of prospectively collected data from 73 subjects that participated in the TIME-2b Study (Aerpio Pharmaceuticals), a multi-center clinical trial for patients with moderate to severe DR treated with AKB-9778 and followed over a 12-month period. Eligible subjects were tested every 3 months with color fundus photography, spectral domain OCT and slit-lamp biomicroscopy. OCTA of the macula and ONH was obtained for a subset of patients enrolled at participating sites. En-face, full-depth retinal projections centered at the macula were analyzed for multiple metrics including foveal avascular zone (FAZ) area and perimeter, non-perfusion area, vessel density (VD) and presence of intraretinal microvascular abnormalities (IRMA). VD of the radial peripapillary capillaries was evaluated in four quadrants surrounding the optic disc for ONH images. Progression was defined as a ≥ 2-step increase in DR severity scale score or development of diabetic macular edema. Results Over a follow-up period of 12 months, 15 of 73 (20.5%) subjects progressed. At pre-treatment baseline, larger FAZ area, presence of IRMA, and reduced peripapillary VD in the superior temporal and inferior temporal regions were significantly associated with increased odds of progression. Conclusions FAZ area and temporal peripapillary VD are predictors of DR progression. OCTA metrics may improve progression risk assessment in DR when compared to established risk factors alone.

Assess epidermolysis bullosa (EB)-related corneal pathology using anterior segment optical coherence tomography (AS-OCT) and correlate imaging with clinical metrics in EB patients versus age-matched controls.EB patients and controls were recruited during an EB conference (July 2018) and at Tufts Medical Center (June-August 2019). Subjects completed a questionnaire, had best corrected visual acuity (BCVA) tested, and underwent AS-OCT scanning. Stromal and epithelial thickness were measured. Depth, length, and type of the three largest lesions were assessed by a masked examiner using a novel pathology grading system. Multivariate analysis of AS-OCT findings and clinical metrics was performed.62 EB patients and 60 age-matched controls were enrolled. Mean BCVA was 1.8 lines worse in patients (p 0.001). Vision loss was associated with increased stromal thickness. Discrete lesions were seen in 60.2% of patient eyes, averaging 1.71 ± 1.75 lesions in patients and 0.14 ± 0.42 in controls (p 0.001). Mean primary lesion depth was 151.88 ± 97.49 μm in patients. Patients showed significant stromal thickening versus controls and lesions were most common in the periphery and inferiorly. Differences in frequency and duration of abrasions and severity of pain were all statistically and clinically significant in patients versus controls (p 0.001).AS-OCT can visualize and quantify differences in the corneas of EB patients compared with age-matched controls. Novel findings include quantification of average depth, length, and severity of discrete lesions, and sparing of the superior quadrant from stromal thickening in EB patients. These results support use of AS-OCT and a questionnaire in clinical trials for new EB therapies.

Purpose To establish a process to evaluate and standardize a state-of-the-art nomenclature for reporting neovascular age-related macular degeneration (AMD) data. Design Consensus meeting. Participants An international panel of retina specialists, imaging and image reading center experts, and ocular pathologists. Methods During several meetings organized under the auspices of the Macula Society, an international study group discussed and codified a set nomenclature framework for classifying the subtypes of neovascular AMD and associated lesion components. Main Outcome Measures A consensus classification of neovascular AMD. Results The study group created a standardized working definition of AMD. The components of neovascular AMD were defined and subclassified. Disease consequences of macular neovascularization were delineated. Conclusions The framework of a consensus nomenclature system, a definition of AMD, and a delineation of the subtypes of neovascular AMD were developed. Establishing a uniform set of definitions will facilitate comparison of diverse patient groups and different studies. The framework presented is modified and updated readily, processes that are anticipated to occur on a periodic basis. The study group suggests that the consensus standards outlined in this article be used in future reported studies of neovascular AMD and clinical practice.

Age-related macular degeneration (AMD) is a major blinding disease, affecting over 14% of the elderly. Risk for AMD is related to age, diet, environment, and genetics. Dietary modulation of AMD risk is a promising treatment modality, but requires appropriate animal models to demonstrate advantages of diet. Mice lacking the antioxidant transcription factor Nrf2 (Nfe2l2) develop age-related retinopathy relevant to human AMD. Here we evaluated the effect of consuming high glycemic (HG) or low glycemic (LG) diets until 18-months of age on development of features relevant to AMD in Nrf2-null mice. Nrf2-null mice that consumed HG diets developed atrophic AMD, characterized by photoreceptor degeneration, retinal pigment epithelium (RPE) atrophy and pigmentary abnormalities, basal laminar deposits, and loss of the choriocapillaris. In contrast, Nrf2-null-mice that consumed LG diets did not develop retinal disease phenotypes. Consumption of HG diets was associated with accumulation of advanced glycation end-products in the RPE and systemically, whereas consumption of the LG diet was associated with increased levels of anti-glycative and anti-oxidative detoxification machinery. Together our data indicate that the Nrf2-null HG mouse is a good model for atrophic AMD studies and that the LG diet can activate protective pathways to prevent AMD, even in a genetically predisposed animal.

Purpose To develop an optical coherence tomography angiography (OCTA)-based framework for quantitatively analyzing the spatial distribution of choriocapillaris (CC) impairment around choroidal neovascularization (CNV) secondary to age-related macular degeneration. Methods In a retrospective, cross-sectional study, 400-kHz swept-source OCTA images from 7 eyes of 6 patients with CNV secondary to age-related macular degeneration were quantitatively analyzed using custom software. A lesion-centered zonal OCTA analysis technique-which portioned the field-of-view into zones relative to CNV boundaries-was developed to quantify the spatial dependence of CC flow deficits. Results Quantitative, lesion-centered zonal analysis of CC OCTA images revealed highest flow-deficit percentages near CNV boundaries, decreasing in zones farther from the boundaries. Optical coherence tomography angiography using shorter (1.5 ms) interscan times revealed more severe flow deficits than OCTA using longer (3.0 ms) interscan times; however, spatial trends were similar for both interscan times. A detailed description of the OCTA processing steps and parameters was provided so as to elucidate their influence on quantitative measurements. Conclusion Impairment of the CC, assessed by flow-deficit percentages, was most prominent closest to CNV boundaries. The lesion-centered zonal analysis technique enabled quantitative CC measurements relative to focal lesions. Understanding how processing steps, imaging/processing parameters, and artifacts can affect quantitative CC measurements is important for longitudinal, OCTA-based studies of disease progression, and treatment response.

Neovascular age-related macular degeneration (AMD) can lead to rapid, irreversible vision loss in untreated eyes. While the pathogenesis of neovascular AMD remains incompletely understood, the choriocapillaris has been hypothesized as the initial site of injury. Due to limitations of dye-based angiography, in vivo imaging of the choriocapillaris has been a longstanding challenge. However, the clinical introduction of optical coherence tomography angiography (OCTA) has enabled researchers and clinicians to noninvasively image the choriocapillaris vasculature, allowing the evaluation of the choriocapillaris in eyes with a variety of pathologies. In this perspective, we review important OCTA-based findings regarding choriocapillaris impairment in neovascular AMD and discuss limitations and future directions of OCTA technologies in the context of this disease.

PURPOSE With the increasing prevalence of diabetes, fast, noninvasive identification of proliferative diabetic retinopathy (PDR) becomes essential. This study evaluated the utility of optical coherence tomography angiography (OCTA) to characterize intraretinal microvascular abnormalities (IRMA) and retinal neovascularization (NV). METHODS Patients with severe non-PDR or PDR were imaged with fluorescein angiography and widefield swept-source OCTA (Zeiss Plex Elite 9000; Carl Zeiss Meditec, Dublin, CA). Regions suspicious for IRMA or retinal NV were identified and the OCTA, including flow overlay on the co-registered structural optical coherence tomography, and fluorescein angiography images were graded by two masked readers. RESULTS Ninety-six foci of irregular vasculature were analyzed, comprised of 70 IRMA and 26 retinal NV lesions from 14 eyes. Compared with fluorescein angiography, OCTA with flow overlay demonstrated specificity of 99% and sensitivity of 92% in identifying IRMA and NV. Neovascularization differed from IRMA on OCTA by demonstrating supraretinal flow breaching the internal limiting membrane and posterior hyaloid (P < 0.001). Intraretinal microvascular abnormalities were distinguished from NV by outpouching of the internal limiting membrane (P = 0.035). Vascular flow was reduced in the presence of fibrosis. CONCLUSION Optical coherence tomography angiography, through flow overlay, has utility to image and differentiate IRMA and NV, which are key features distinguishing severe non-PDR and PDR, respectively. Noninvasive widefield OCTA may be a useful tool to diagnose high-risk diabetic retinopathy eyes.

To evaluate changes in macular vessel density following intravitreal anti-VEGF injection in patients with diabetic macular edema (DME) and proliferative diabetic retinopathy (PDR). In this retrospective case series, optical coherence tomography angiography (OCTA) images from 55 eyes of 35 patients with either DME (46 eyes) or PDR (9 eyes) were included. Macular capillary vessel density at the level of the superficial retinal capillary plexus (SCP), deep retinal capillary plexus (DCP) and total retinal capillary plexus (TCP) before and after anti-VEGF treatment was calculated. Longitudinal changes in vessel density following serial anti-VEGF treatment were analyzed in a subset of eyes. Vessel density in the SCP, DCP or TCP was not found to be significantly different after one, two or three intravitreal injections (p > 0.05 for all time points). Subgroup analysis revealed no significant change in the DME and PDR subgroups (all p > 0.05). Multivariate analysis revealed no effect of type of injected anti-VEGF agent or presence of previous treatment on VD measurements (all p > 0.05). There was no correlation between the anatomic response of DME to treatment and VD measurements. In this study, macular vessel density remained statistically unchanged following up to three intravitreal injections of any anti-VEGF agent. This indicates that there may not be an early effect of anti-VEGF treatment on macular vessel density and its effect on macular perfusion may not be a direct change in microvascular flow.

Copyright 2019 The Authors PURPOSE. To evaluate whether retinal capillary nonperfusion is found predominantly adjacent to arteries or veins in eyes with diabetic retinopathy (DR). METHODS. Sixty-three eyes from 44 patients with proliferative DR (PDR) or non-PDR (NPDR) were included. Images (12 3 12-mm) foveal-centered optical coherence tomography (OCT) angiography (OCTA) images were taken using the Zeiss Plex Elite 9000. In 37 eyes, widefield montages with five fixation points were also obtained. A semiautomatic algorithm that detects nonperfusion in full-retina OCT slabs was developed, and the percentages of capillary nonperfusion within the total image area were calculated. Retinal arteries and veins were manually traced. Based on the shortest distance, nonperfusion pixels were labeled as either arterial-side or venous-side. Arterial-adjacent and venous-adjacent nonperfusion and the A/V ratio (arterial-adjacent nonperfusion divided by venous-adjacent nonperfusion) were quantified. RESULTS. Twenty-two eyes with moderate NPDR, 16 eyes with severe NPDR, and 25 eyes with PDR were scanned. Total nonperfusion area in PDR (median: 8.93%) was greater than in moderate NPDR (3.49%, P < 0.01). Arterial-adjacent nonperfusion was greater than venous-adjacent nonperfusion for all stages of DR (P < 0.001). The median A/V ratios were 1.93 in moderate NPDR, 1.84 in severe NPDR, and 1.78 in PDR. The A/V ratio was negatively correlated with the total nonperfusion area (r ¼ -0.600, P < 0.0001). The results from the widefield montages showed similar patterns. CONCLUSIONS. OCTA images with arteries and veins traced allowed us to estimate the nonperfusion distribution. In DR, smaller nonperfusion tends to be arterial-adjacent, while larger nonperfusion tends toward veins.

Background To evaluate the changes in the mean macular intercapillary area (ICA) from sequential enface optical coherence tomography angiography (OCTA) images following intravitreal anti-vascular endothelial growth factor (VEGF) therapy in initially treatment-naive eyes with diabetic macular oedema (DME). Methods In this multicentre retrospective study, 6 × 6 and 3 × 3 mm customised, total retinal projection enface OCTA images were collected and processed for quantitative assessment of ICA by a customised MATLAB software. Measurements were done in concentric regions centred on the fovea-with the exclusion of foveal avascular zone (FAZ)-in 0.5 mm diameter increments as well as within the intervening rings. Results In this study, 6 × 6 mm OCTA images from 46 eyes of 29 patients, and 3 × 3 mm OCTA images from 23 eyes of 15 patients were included. There was no significant change in mean ICA after treatment in either scan size or in any measurement regions (all p > 0.05). Multivariate analysis revealed that baseline BCVA was significantly correlated with the visual outcome (p = 0.039). Additionally, after correction for age, baseline central retinal thickness (CRT), baseline BCVA, and retinopathy severity, mean ICA in the 1.5 mm circle was found to be a significant predictor of post treatment CRT, (p = 0.006). Conclusions Absence of significant change in mean ICA after a minimum of three intravitreal anti-VEGF injections, may indicate that, in the short term, anti-VEGF injections neither impair nor improve macular perfusion in DME. Baseline BCVA was found to be a robust predictor of functional outcome, while inner mean ICA was a significant predictor for macular thickness outcomes.

PurposeTo describe the differences in a range of quantitative OCT angiography (OCTA) metrics across early stages of diabetic retinopathy (DR), providing robust effect estimates as well as sensitivity and specificity.DesignCross-sectional study with population-based sampling.ParticipantsFour hundred forty-one eyes from 296 individuals: 328 control eyes (no diabetes mellitus [DM] and no DR), 55 eyes with DM and no DR, and 58 eyes with early nonproliferative DR.MethodsMultimodal retinal imaging included color fundus photography, color Optomap ultra-widefield imaging, and spectral-domain OCT (Spectralis OCT2; Heidelberg Engineering GmbH) with the OCTA module. All images were graded for the presence and severity of DR features. OCTA images were assessed manually for inclusion based on quality. Binary OCTA metrics were assessed after 3-dimensional projection artifact removal including from the nerve fiber layer vascular plexus, superficial vascular plexus (SVC), and deep vascular plexus (DVC) by Early Treatment Diabetic Retinopathy Study (ETDRS) grid, foveal avascular zone (FAZ) area, FAZ minimum and maximum diameter, perimeter length, and circularity.Main Outcome MeasuresDiabetes mellitus and DR status and presence or absence of DR in the retinal periphery.ResultsThe reduction in vessel densities in participants with DM and manifest DR compared with control participants tended to be twice that of those with DM, but no DR, compared with control participants. Some evidence of spatial heterogeneity in vessel reductions was found in those yet to develop DR, whereas those with manifest DR had significant reductions across the ETDRS grid. The FAZ perimeter and circularity were impacted most significantly by DM, and those with DR showed decreased multispectral fractal dimensions compared with control participants. Eyes with peripheral DR had reduced vessel density compared with those with DM and no DR only in the superior outer, temporal inner, and temporal outer regions in the DVC and SVC. The area under the receiver operating characteristic curve ranged between 0.48 and 0.73.ConclusionsSignificant differences in OCTA metrics can be found in those with DM before manifest DR using commercially available equipment with minimal image postprocessing. Although diagnostic performance was poor, these metrics may be useful for measuring change over time in clinical trials.

IMPORTANCE: Anti–vascular endothelial growth factor (VEGF) agents may provide a prophylactic effect in high-risk eyes with intermediate dry age-related macular degeneration (AMD) against conversion to exudative AMD (eAMD), lowering the risk of vision loss. OBJECTIVE: To evaluate intravitreal aflibercept injection (IAI) as prophylaxis against the conversion to eAMD in high-risk eyes at 24 months. DESIGN, SETTING, AND PARTICIPANTS: This single-masked, sham-controlled, randomized clinical trial performed at 4 US clinical sites enrolled patients with intermediate AMD in 1 eye (study eye), defined as presence of more than 10 medium drusen (≥63 to

PurposeTo evaluate the various patterns of subretinal fluid (SRF) in eyes with age-related macular degeneration (AMD) in the absence of macular neovascularisation (MNV) and to assess the long-term outcomes in these eyes.MethodsThis retrospective study included only eyes with non-neovascular AMD and associated SRF. Eyes with evidence of MNV were excluded. Spectral-domain optical coherence tomography (SD-OCT) was obtained at baseline and at follow-up, and qualitative and quantitative SD-OCT analysis of macular drusen including drusenoid pigment epithelial detachment (PED) and associated SRF was performed to determine anatomic outcomes.ResultsForty-five eyes (45 patients) were included in this analysis. Mean duration of follow-up was 49.7±36.7 months. SRF exhibited three different morphologies: crest of fluid over the apex of the drusenoid PED, pocket of fluid at the angle of a large druse or in the crypt of confluent drusen or drape of low-lying fluid over confluent drusen. Twenty-seven (60%) of the 45 eyes with fluid displayed collapse of the associated druse or drusenoid PED and 24 (53%) of the 45 eyes developed evidence of complete or incomplete retinal pigment epithelial and outer retinal atrophy.ConclusionNon-neovascular AMD with SRF is an important clinical entity to recognise to avoid unnecessary anti-vascular endothelial growth factor therapy. Clinicians should be aware that SRF can be associated with drusen or drusenoid PED in the absence of MNV and may be the result of retinal pigment epithelial (RPE) decompensation and RPE pump failure.

Optical coherence tomography angiography (OCTA) is a clinically promising modality to image retinal vasculature. For this end, optical coherence tomography (OCT) volumes are repeatedly scanned and intensity changes over time are used to compute OCTA images. Because of patient movement and variations in blood ow, OCTA data are prone to noise.

Purpose To report a case of presumed ocular sarcoidosis initially presenting with features of multiple evanescent white dot syndrome (MEWDS) with atypical optical coherence tomography angiography (OCTA) findings. Observations A 23 year-old woman presented with a unilateral central scotoma, photophobia, and decreased visual acuity after a viral illness. Examination of the right eye revealed multiple round white macular spots and stippled granularity at the fovea. Multimodal imaging with fluorescein angiography (FA), indocyanine green angiography (ICG), fundus autofluorescence (FAF), and optical coherence tomography (OCT) was consistent with a diagnosis of MEWDS. However, OCTA demonstrated choriocapillaris (CC) flow deficits, which is not typical for MEWDS. The clinical course was initially consistent with MEWDS, with spontaneous recovery of symptoms over ensuing months. The patient presented five months later with floaters and a central scotoma. Examination showed panuveitis, and systemic evaluation revealed an elevated angiotensin converting enzyme (ACE) and hilar lymphadenopathy on chest x-ray consistent with presumed sarcoidosis. Conclusions and Importance A case of MEWDS atypically demonstrated CC flow deficits on OCTA and subsequently presented as uveitis secondary to presumed sarcoidosis. Atypical features in MEWDS may be a sign of another disorder masquerading early on as MEWDS and ought to prompt further investigation.

Purpose To evaluate the usefulness of a high-magnification module (HMM) lens to visualize retinal photoreceptors, retinal nerve fiber layer (RNFL), and superficial retinal vasculature in physiologic and pathologic retinal conditions. Design Observational descriptive study. Participants Thirty-two participants with normal and pathologic retina examination results. Methods Normal and pathologic maculae were imaged in vivo using still and video HMM lens modes, with fixation and contrast adjustments to enhance visualization. The HMM images were classified qualitatively based on structures identified as either good (photoreceptors seen), average (photoreceptor mosaic cannot be visualized clearly, retinal vessels and other retinal changes can be seen), or poor (no identifiable structures). Selected eyes were imaged with fundus photography, OCT, OCT angiography, indocyanine green angiography, and fluorescein angiography for comparison with the pathologic maculae. Main Outcomes Measures Description of HMM module-obtained macula images. Results From 32 eyes imaged (16 normal and 16 pathologic retinas), 12 of 16 normal and 11 of 16 pathologic retinas demonstrated at least average image quality, in which retinal vasculature and landmarks could be visualized. The mosaic pattern of hexagonal shapes representing photoreceptors could not be resolved in most pathologic retinas. For the retinas in which the photoreceptor mosaics were visualized (12 of 16 normal and 2 of 16 pathologic retinas), parafoveal mosaic patterns appeared denser with better image quality for all participants compared with foveal photoreceptors. Difficulty in resolving the photoreceptors in the umbo, fovea, and perifovea was encountered, similar to what has been reported with adaptive optics devices. The RNFL was seen as arcuate hyperreflective bundles. Flow was observed in the macular microvasculature. Poorly resolved photoreceptors and scattered hyperreflective foci were correlated with changes in the retinal pigment epithelium in eyes with age-related macular degeneration or central serous chorioretinopathy. Macular striae were seen in eyes with epiretinal membrane. Conclusions In most eyes, regardless of whether retinal pathologic features were present, it was challenging to obtain average quality (or better) images. In the few participants with good-quality imaging, the parafoveal photoreceptor mosaic, vascular flow, and various features of pathologic eyes could be visualized.

Purpose To determine which spectral domain optical coherence tomography biomarkers of idiopathic macular hole (MH) correlate with the postoperative best-corrected visual acuity (BCVA) in anatomically closed MH. Methods Retrospective analysis of spectral domain optical coherence tomography scans of 44 patients presenting with MH followed for a mean of 17 months. Widths of MH aperture, base, and ellipsoid zone disruption were calculated from presenting foveal spectral domain optical coherence tomography B-scans. Macular hole base area and ellipsoid zone disruption area were calculated through the custom in-house software. Results Poorer postoperative BCVA correlated with increased preoperative choroidal hypertransmission (r = 0.503, P = 0.0005), minimum diameter (r = 0.491, P = 0.0007), and base diameter (r = 0.319, P = 0.0348), but not with preoperative ellipsoid zone width (r = 0.199, P = 0.2001). Applying en-face analysis, the BCVA correlated weakly with preoperative ellipsoid zone loss area (r = 0.380, P = 0.013), but not with preoperative MH base area (r = 0.253, P = 0.1058). Conclusion Increased MH minimum diameter, base diameter, base area, and choroidal hypertransmission are correlated with a poorer postoperative BCVA. Ellipsoid zone loss measurements were not consistently correlated with a BCVA. Choroidal hypertransmission width may be an easy-to-visualize predictive imaging biomarker in MH surgery.

Normative databases of optical coherence tomography (OCT) metrics, such as retinal nerve fiber layer (RNFL) and macular thickness, are critical to clinical use of OCT imaging. In order to accurately represent the range of normal variation in patient populations, these normative databases must themselves be adequately diverse. Thus far, diversity in OCT normative databases has largely been defined as racial diversity. However, this has largely been based on self-reported “race,” which is inconsistent and generally not scientifically rigorous as a form of categorization. Moreover, there is a great deal of variation even within any single racial group, suggesting that other drivers of variation, such as geography or socioeconomic status, may be more important metrics for diversity. Finally, race itself is a proxy for the biological variation that must be represented in such samples, and as such racial diversity does not itself inherently equate to adequate biologic diversity. As clinical use of OCT continues to grow, including to international settings, it is increasingly important that normative databases built into OCT systems accurately represent the populations to which they are applied. Race is not an ideal sole or even primary means of assessing sample diversity in this context. In future normative OCT database construction, other forms of diversity should be considered.

Background To compare the anatomical and visual outcomes in eyes with persistent diabetic macular edema (DME) after initial anti-VEGF therapy that were retreated continuously with the same anti-VEGF drug versus those that underwent two successive cycles of medication change in anti-VEGF drugs (double anti-VEGF switch). Methods Retrospective review of eyes with persistent DME after 3 initial consecutive monthly anti-VEGF injections. This cohort was divided into two groups: Group 1 continued to receive the same initial anti-VEGF drug for at least 18 months while group 2 eyes were switched to different anti-VEGF medications twice. Group 1 was further subdivided into: Group 1A composed of eyes with less than 20% reduction in central subfield thickness (CRT) at month 3; and group 1B eyes with greater than or equal to 20% reduction in CRT. The percentage of eyes that achieved greater than 10 letters visual acuity (VA) gain or loss was recorded as the primary end point (through month 18 in group 1 and month 6 after 2nd switch in group 2). Results Group 1A, 1B and group 2 were composed of 24, 18, and 14 eyes respectively. 34.7%, 56.2% and 36.3% of eyes achieved > 10 letters gain, while 4.3%, 6.2% and 27.2% of eyes lost > 10 letters in groups 1A, 1B, and 2, respectively. Analysis of the visual acuity (VA) letter change in this time interval revealed no significant difference between all groups (p = 0.11). Mean VA and CRT measurements at the primary endpoint in all groups were 0.5, 0.39, and 0.47 logMAR (p = 0.44), and 369.7, 279.9, 321 µm, (p = 0.01) respectively. Conclusions There was no difference in the visual outcomes between the two treatment strategies in eyes with persistent DME after 3 consecutive anti-VEGF injections. This may indicate that anti-VEGF switching—even if it is done twice—may have comparable clinical outcomes to sustained treatment with one agent.

Purpose To determine optical coherence tomography signs associated with macular atrophy (MA) in eyes with neovascular age-related macular degeneration and pigment epithelial detachments treated with vascular endothelial growth factor inhibitors. Methods Optical coherence tomography scans from a subgroup of the pigment epithelial detachment cohort of the HARBOR study were analyzed for MA. Two groups were formed based on MA presence/absence at Month 24. Then, optical coherence tomography scans from each baseline visit were graded with standard reading center grading parameters including ellipsoid zone disruption, intraretinal cysts, subretinal fluid, and MA or nascent MA in the study and fellow eyes. Results Twenty-eight eyes from 28 patients were included in the analysis. Fourteen eyes had optical coherence tomography-based MA at Month 24 and 14 did not. Macular atrophy at Month 24 was significantly associated with 1) MA/nascent MA at baseline (P = 0.0136), 2) intraretinal cysts at baseline (P = 0.0048), and 3) collapse of pigment epithelial detachments in the study eye (P = 0.0025). Macular atrophy was not associated with ellipsoid zone disruption or subretinal fluid in the study eye at baseline. Conclusion This study suggests that some optical coherence tomography findings in eyes of patients with neovascular age-related macular degeneration were present before the start of anti-vascular endothelial growth factor therapy and may predict the development of MA.

Optical coherence tomography (OCT) was one of the biggest advances in ophthalmic imaging. Building on that platform, OCT angiography (OCTA) provides depth resolved images of blood flow in the retina and choroid with levels of detail far exceeding that obtained with older forms of imaging. This new modality is challenging because of the need for new equipment and processing techniques, current limitations of imaging capability, and rapid advancements in both imaging and in our understanding of the imaging and applicable pathophysiology of the retina and choroid. These factors lead to a steep learning curve, even for those with a working understanding dye-based ocular angiography. All for a method of imaging that is a little more than 10 years old. This review begins with a historical account of the development of OCTA, and the methods used in OCTA, including signal processing, image generation, and display techniques. This forms the basis to understand what OCTA images show as well as how image artifacts arise. The anatomy and imaging of specific vascular layers of the eye are reviewed. The integration of OCTA in multimodal imaging in the evaluation of retinal vascular occlusive diseases, diabetic retinopathy, uveitis, inherited diseases, age-related macular degeneration, and disorders of the optic nerve is presented. OCTA is an exciting, disruptive technology. Its use is rapidly expanding in clinical practice as well as for research into the pathophysiology of diseases of the posterior pole.

Purpose To analyze the long-term growth patterns of type 1 neovascularization (NV) in eyes with age-related macular degeneration (AMD) receiving anti–vascular endothelial growth factor (VEGF) therapy. Design Retrospective cohort study. Methods Patients were enrolled from 2 eye centers and underwent optical coherence tomography angiography (OCTA) imaging with follow-up greater than 1 year. Choroidal neovascularization (CNV) was manually segmented on OCTA images and compared between time points. CNV growth was subdivided into 3 categories based on OCTA area measurement: CNV doubling, modest growth of less than 50%, and shrinkage. These growth rates were correlated with OCTA morphologic features. Results Forty-one eyes were analyzed. Mean CNV area was 1.60 ± 1.84 mm 2 at baseline and 1.80 ± 1.84 mm 2 at 1 year. Thirty-three eyes (80%) displayed an increase in CNV area at 1 year with a mean increase of 0.20 ± 0.38 mm 2 ( P = .001). Eleven eyes (27%) underwent CNV doubling, 19 eyes (46%) illustrated modest growth, and 6 (15%) showed shrinkage. Anatomic features including a capillary fringe (odds ratio [OR] = 5.3, P = .036) and immature lesion morphology (OR = 4.2, P = .015) were significantly associated with CNV doubling. CNV growth occurred in 3 predominant patterns: "symmetric" growth, "asymmetric" growth, and "finger-like projections," which reflected the orientation of expansion of CNV. "Symmetric" and "asymmetric" growth together correlated with greater frequency of CNV doubling (OR = 15, P = .0048). Conclusion OCTA provides noninvasive measurement of the area of neovascular lesions in AMD. Sustained growth of type 1 NV can be identified in the majority of lesions (80%) that display characteristic patterns of progression despite ongoing anti-VEGF therapy.

Objective To describe optical coherence tomography angiography (OCTA) reflectance artifacts secondary to retinal pigment epithelial detachment (RPED). Design Retrospective review. Methods Four eyes from 4 subjects were included. Three presented with RPED and 1 eye was a normal control. Two eyes diagnosed with RPED and the normal eye were evaluated using en face OCTA centred at the fovea acquired using the RTVue XR Avanti (Optovue Inc). In the third eye with RPED, OCTA imaging was performed using a CIRRUS 5000 prototype modified to do OCTA imaging on a spectral domain OCT platform provided by Carl Zeiss Meditec, Inc. The segmented OCTA angiograms were overlaid to determine if the flow patterns seen at the edge of the RPEDs were due to reflectance from the inner retinal vessels, also known as “decorrelation tails.” Results OCTA projection artifacts were noted when segmentation lines intersected with the boundary of the RPED. The overlaid segmented OCTA from the 3 RPED eyes imaged using each system revealed the same vasculature pattern at the edges of the RPED as that of the inner retina, demonstrating the “decorrelation tails” artifact, which caused the RPED to appear as a bright ring on the segmented OCTA. Conclusions OCTA images are susceptible to various known artifacts. This series describes the impact of the projection artifact seen at the edges of an RPED that simulates appearance of flow but is actually due to reflectance of the inner retinal vasculature on the RPED.

Background Central vision loss in diabetic retinopathy is commonly related to diabetic macular edema (DME). The objective of this study was to describe changes between consecutive visits on optical coherence tomography angiography (OCTA) of the foveal avascular zone (FAZ) in eyes with DME. Methods 20 eyes from 14 patients with DME were imaged on 2 successive clinic visits separated by at least 1 month. The mean interval between visits was 3.2 months. The only intervention used was intravitreal anti-VEGF in 11 eyes; the others were observed over time without treatment. Two different readers measured FAZ area using a pseudo-automated tool in comparison to a manual tracing tool. Qualitative changes in the appearance of the vasculature surrounding the FAZ were also recorded. The retinal capillary plexus was segmented into deep and superficial plexuses, and FAZ measurements were done on the superficial, deep, and summated plexuses. Results Pseudo-automated and manual measurements of FAZ area decreased significantly (p

Purpose To evaluate the characteristics and racial variations amongst patients with polypoidal choroidal vasculopathy (PCV) in the United States and the United Kingdom. Methods Fundus photos and indocyanine green angiography images were evaluated in a multicenter retrospective study to establish the diagnosis of PCV. Visual acuity (VA) was recorded in ETDRS letter count. Results Eighty eyes of 71 PCV patients (average age of 69.4 ± 10.4 years) were included in the analysis. Of the total 71 subjects, 46 (65%) were women, 33 (46.5%) were Blacks, 16 (22.5%) were Whites, 19 (26.8%) were Asians and 3 (4.2%) belonged to other races. The Black subgroup had vision gain of 3.5 letters. The White and Asian subgroups had vision loss of 13.1 and 3.5 letters, respectively. There was female predominance in Blacks (67%), Whites (69%), and Asians (58%). PCV was found to be a bilateral disease in 14 patients (20%). There was significant decrease of 7 letters with every decade increase in age (p = 0.005). Final VA was worse in males when compared to females (p = 0.042), and worse in Whites when compared to Blacks (p = 0.005). For every 10 letters worse in initial VA upon diagnosis with PCV, the final VA was worse by 6 letters (p

Purpose: To develop high-speed, extended-range, ultrahigh-resolution spectraldomain optical coherence tomography (UHR SD-OCT) and demonstrate scan protocols for clinical retinal imaging. Methods: A UHR SD-OCT operating at 840-nm with 150-nm bandwidths was developed. The axial imaging range was extended by dynamically matching reference arm length to the retinal contour during acquisition. Two scan protocols were demonstrated for imaging healthy participants and patients with dry age-related macular degeneration. A high-definition raster protocol with intra–B-scan reference arm length matching (ReALM) was used for high-quality cross-sectional imaging. A cube volume scan using horizontal and vertical rasters with inter–B-scan ReALM and software motion correction was used for en face and cross-sectional imaging. Linear OCT signal display enhanced visualization of outer retinal features. Results: UHR SD-OCT was demonstrated at 128-and 250-kHz A-scan rates with 2.7 μm axial resolution and a 1.2-mm, 6-dB imaging range in the eye. Dynamic ReALM was used to maintain the retina within the 6-dB imaging range over wider fields of view. Outer retinal features, including the rod and cone interdigitation zones, retinal pigment epithelium, and Bruch’s membrane were visualized and alterations observed in agerelated macular degeneration eyes. Conclusions: Technological advances and dynamic ReALM improve the imaging performance and clinical usability of UHR SD-OCT. Translational Relevance: These advances should simplify clinical imaging workflow, reduce imaging session times, and improve yield of high quality images. Improved visualization of photoreceptors, retinal pigment epithelium, and Bruch’s membrane may facilitate diagnosis and monitoring of age-related macular degeneration and other retinal diseases., National Institutes of Health (U.S.) (Grant 5-R01-EY011289-33), United States. Air Force. Office of Scientific Research (Grant FA9550-15-1-0473)

Background To investigate whether neovascularization may arise and be detectable in drusen, as reported in histopathologic studies, by OCTA prior to developing exudation and to assess its prevalence in a cohort of patients with intermediate AMD. Methods Retrospective cross-sectional study of 128 patients with intermediate AMD recruited as part of a separate ongoing clinical trial conducted at multiple large tertiary referral retina clinics. One hundred and twenty-eight consecutive patients with exudative AMD in one eye and intermediate non-exudative AMD in the fellow eye were enrolled and analyzed between September 2015 and March 2017. Results SD-OCTA identified vascularization within drusen in 7 of 128 eyes, for a prevalence of 5.5%. A total of 12 instances of vascularized drusen were noted. Out of the 12 vascularized drusen noted, 7 were located in the parafoveal region or subfoveal region and 5 was in the extrafoveal region. 9 of 12 instances of vascularized drusen exhibited a uniform sub-RPE hyperreflectivity, whilst 3 of 12 exhibited more heterogenous reflectivity. In all 12 instances, FA images failed to identify the neovascular nature of vascularized drusen. Conclusions Our results demonstrate the utility of SD-OCTA for the diagnosis of vascularized drusen in patients with intermediate non-exudative AMD. Longitudinal studies are needed to delineate the evolution and conversion risk of these lesions over time, which can be of substantial clinical relevance.

OBJECTIVE: Further insight into the flow characteristics of the vascular features associated with diabetic retinopathy (DR) may improve assessment and treatment of disease progression. The variable interscan time analysis (VISTA) algorithm is an extension of optical coherence tomography angiography (OCTA) that detects relative blood flow speeds which can then be depicted on a color-coded map. This study utilized VISTA to analyze relative blood flow speeds in the microvascular changes associated with DR. DESIGN AND PARTICIPANTS: In this cross-sectional study at New England Eye Center, Boston, Massachusetts, thirteen patients of varying severities of DR were enrolled. METHODS: OCTA images centered at the fovea were obtained on a prototype swept-source OCT device and the VISTA algorithm was applied to visualize relative blood flow speeds. MAIN OUTCOME MEASURES: Descriptive flow analysis of the retinal vascular features of DR was conducted on the VISTA-generated images. RESULTS: Twenty-six eyes were included in this study. Of these, three eyes had mild non-proliferative DR (NPDR), six eyes had moderate NPDR, four eyes had severe NPDR, nine eyes had proliferative DR, and four eyes were normal controls. Microaneurysms, intraretinal microvascular abnormalities (IRMA), and neovascularization appeared to originate from areas of relatively slow blood flow speeds. Microaneurysms showed relatively slower flow, IRMA showed turbulent, intermediate to slow flow, and venous beading and looping presented with relatively high flow speeds that progressively tapered. Neovascularization from venous origin demonstrated slower flow speeds, while that of arterial origin had relatively high flow speeds. Additionally, increased disease severity was associated with globally slower flow speeds, with particularly slower flow around the foveal avascular zone. CONCLUSIONS: VISTA appears to be a useful extension of OCTA that overcomes some of the limitations of normal gray-scale OCTA. It appears to have some potential in providing relevant insight into the pathogenesis of the microvascular changes associated with DR. These findings may assist in improving our understanding of the pathogenic changes that take place in diabetic retinopathy.

ObjectiveTo compare clinical characteristics of patients suffering from neovascular age-related macular degeneration (nAMD) with mature and immature choroidal neovascularisation (CNV) as assessed by optical coherence tomography angiography (OCTA). To explore the effect of total anti-vascular endothelial growth factor exposure on the occurrence of mature CNV when correcting for potential confounders.Methods and analysisIn this retrospective case series, we included 40 eyes of 36 patients with nAMD with CNV assessed by OCTA at the Manchester Eye Hospital between June 2016 and June 2017. A retinal specialist masked to patient information graded CNV depicted on OCTA scans. For statistical comparisons, we used t-tests, Fisher’s exact tests and a mixed-effects logistic regression model.Results18 patients (20 eyes) were treatment naïve, and the mean number of intravitreal injections (IVI) in the remaining eyes was 18.4 (range 2–71). The mean duration of nAMD was 19.3 months (range 0–87.4). 25 eyes (62.5%) exhibited mature CNV. Eyes with mature CNV did not differ from those with immature CNV regarding age (+2.8 years; p=0.288) or duration of disease (+9.4 months; p=0.061). However, they had a higher number of IVIs (+3.1; p=0.035). Among eyes with best corrected visual acuity over 25 letters, there was a strong association between the number of IVIs (0 vs 1–20: OR 68.01 [95% CI 1.30 to 3546.99; p=0.036], 0 vs >20 IVI: OR 380.01 [95% CI 2.60 to 55 464.89; p=0.019]) and maturity status when correcting for potential confounders.ConclusionMaturity status of CNV as assessed by OCTA may indicate treatment exposure of CNV in nAMD.

Purpose To evaluate the accuracy and reliability in differentiating retinal arteries from veins using widefield optical coherence tomography angiography (OCTA). Methods Ten healthy eyes and 12 eyes from diabetic patients were included. Foveal-centered swept-source OCTA images (12 × 12 mm) were obtained using the PLEX Elite 9000. Vessels were graded as arteries or veins by two independent, masked readers. Arteriovenous crossings were also evaluated in healthy eyes. The vessel identification gold standard was defined using color fundus photographs (CFP) for normal eyes and both CFP and fluorescein angiography for diabetic eyes. Grading accuracy was compared to the gold standard and reliability between readers assessed. Results The study evaluated 538 vessels (119 first order, 110 second, 309 third) in healthy eyes and 645 vessels (184 first order, 159 second, 302 third). In healthy eyes, the average accuracies identifying all, first-, second-, and third-order vessels were 98.61%, 99.16%, 100%, and 98.06%, respectively. Cohen's κ between graders in all vessels was 0.948. In diabetic eyes, the average accuracies identifying vessels were 96.90%, 99.46%, 97.77%, and 94.85%, respectively. Cohen's κ between graders for all vessels was 0.888. For crossing identification, the average accuracy and Cohen's κ were low (60.71% and 0.659, respectively). Conclusions En face OCTA allows for accurate and reliable artery and vein identification; for small branches and crossings, identification by en face OCTA alone may be less accurate and reliable. Translational relevance Arteries and veins can be differentiated on OCTA, assisting in clinically identifying pathology as arterial or venous side.

To characterize the features of choroidal neovascularization (CNV) in neovascular age-related macular degeneration with spectral domain optical coherence tomography angiography (OCTA) and to determine whether OCTA can be used to determine clinical activity of CNV.Observational, retrospective, consecutive case series.Optical coherence tomography angiography revealed CNV in 28 eyes (62.2%) while 17 eyes (37.8%) did not demonstrate CNV vessels. Choroidal neovascularization was classified as well circumscribed in 12 eyes (42.8%) and poorly circumscribed in 16 eyes (57.2%). Twenty-two eyes with a CNV on OCTA were clinically active, whereas six eyes with visible CNV on OCTA were clinically inactive. Of the 17 eyes that did not have evidence of CNV on OCTA imaging, 14 were clinically inactive and 3 were clinically active. Presence of CNV on OCTA correlated with clinical activity and absence of CNV correlated with inactivity (P0.0001).Optical coherence tomography angiography is a noninvasive imaging technique that can be used to visualize blood flow comprising CNV. Optical coherence tomography angiography detects CNV vessels in some albeit not all eyes with neovascular age-related macular degeneration. Although the presence or absence of CNV vessels on OCTA highly correlated with clinical activity of CNV, the morphologic appearance of CNV on OCTA did not have significant correlation with clinical activity.

To describe qualitative and quantitative optical coherence tomography (OCT) angiography (OCTA) parameters for choroidal neovascularization (CNV) secondary to age-related macular degeneration (AMD) and their applicability as potential clinical trial endpoints.A review of current literature related to the topic of OCTA and AMD.There are a number of promising OCTA parameters that can be used to diagnose the presence of CNV and to monitor the activity and progression of the lesion, pre- and post-treatment morphological characteristics, CNV dimensions, and automated quantitative parameters such as vessel density.The OCTA parameters described in this review have promise for the future development of clinical trial endpoints, but require further validation before they can be widely used.

BACKGROUND AND OBJECTIVE: To present novel software algorithms applied to spectral-domain optical coherence tomography (SD-OCT) for automated detection of diabetic retinopathy (DR). PATIENTS AND METHODS: Thirty-one diabetic patients (44 eyes) and 18 healthy, nondiabetic controls (20 eyes) who underwent volumetric SD-OCT imaging and fundus photography were retrospectively identified. A retina specialist independently graded DR stage. Trained automated software generated a retinal thickness score signifying macular edema and a cluster score signifying microaneurysms and/or hard exudates for each volumetric SD-OCT. RESULTS: Of 44 diabetic eyes, 38 had DR and six eyes did not have DR. Leave-one-out cross-validation using a linear discriminant at missed detection/false alarm ratio of 3.00 computed software sensitivity and specificity of 92% and 69%, respectively, for DR detection when compared to clinical assessment. CONCLUSION: Novel software algorithms applied to commercially available SD-OCT can successfully detect DR and may have potential as a viable screening tool for DR in future. [ Ophthalmic Surg Lasers Imaging Retina . 2016;47:410–417.]

The body of knowledge of in vivo investigation of the choroid has been markedly enhanced by recent technological advances in optical coherence tomography (OCT). New insights elucidating the morphological features of the choriocapillaris and choroidal vasculature, in both physiological and pathological conditions, indicate that the choroid plays a pivotal role in many posterior segment diseases. In this article, a review of the histological characteristics of the choroid, which must be considered for the proper interpretation of in vivo imaging, is followed by a comprehensive discussion of fundamental principles of the current state-of-the-art in OCT, including cross-sectional OCT, en face OCT, and OCT angiography using both spectral domain OCT and swept source OCT technologies. A detailed review of the tomographic features of the choroid in the normal eye is followed by relevant findings in prevalent chorioretinal diseases, focusing on major causes of vision loss such as typical early and advanced age-related macular degeneration, polypoidal choroidal vasculopathy, central serous chorioretinopathy, pachychoroid spectrum disorders, diabetic choroidopathy, and myopia.

Purpose To compare visualization of choroidal neovascularization (CNV) secondary to age-related macular degeneration (AMD) using an ultrahigh-speed swept-source (SS) optical coherence tomography angiography (OCTA) prototype vs a spectral-domain (SD) OCTA device. Design Comparative analysis of diagnostic instruments. Methods Patients were prospectively recruited to be imaged on SD OCT and SS OCT devices on the same day. The SD OCT device employed is the RTVue Avanti (Optovue, Inc, Fremont, California, USA), which operates at ∼840 nm wavelength and 70 000 A-scans/second. The SS OCT device used is an ultrahigh-speed long-wavelength prototype that operates at ∼1050 nm wavelength and 400 000 A-scans/second. Two observers independently measured the CNV area on OCTA en face images from the 2 devices. The nonparametric Wilcoxon signed rank test was used to compare area measurements and P values of, National Institutes of Health (U.S.) (R01-EY011289-28), National Institutes of Health (U.S.) (R44-EY022864-03), National Institutes of Health (U.S.) (R01-CA075289-17), United States. Air Force Office of Scientific Research (FA9550-10-1-0551), United States. Air Force Office of Scientific Research (FA9550-12-1-0499)

BACKGROUND AND OBJECTIVE: To describe the retinal vasculature and choriocapillaris, as well as the transition zone between the diseased and healthy tissue, in eyes with inherited retinal degenerations using optical coherence tomography angiography (OCTA). PATIENTS AND METHODS: Patients with inherited retinal degenerations were recruited for OCTA imaging. Retinal vasculature was assessed for increased intercapillary space and foveal avascular zone abnormalities. Choriocapillaris, retinal pigment epithelium (RPE), and photoreceptor disruption were noted, and the borders were evaluated to speculate which layers become affected first. RESULTS: Fourteen eyes of seven subjects with inherited retinal degenerations were included. All eyes (100%) demonstrated retinal thinning and increased intercapillary spaces overlying focal outer retinal changes. In all eyes, the region of choriocapillaris changes was smaller than the region of overlying RPE and photoreceptor alteration, suggesting the vascular loss was secondary. CONCLUSION: OCTA is able to provide highly detailed vascular information in eyes with inherited retinal degenerations and may be useful to better understand the pathogenesis of these diseases. [ Ophthalmic Surg Imaging Lasers Retina . 2016;47:120–127.]

Purpose To report a posterior segment phenotypic manifestation of Coxsackie virus infection that has not been previously appreciated. Methods The clinical course and multimodal imaging findings, including spectral domain optical coherence tomography, fluorescein angiography, near infrared reflectance, and fundus autofluorescence of two patients with Coxsackie virus infections were documented. Results A neurosensory macular detachment was present in both patients on baseline examination. Fluorescein angiography demonstrated pooling within this lesion and spectral domain optical coherence tomography identified thickening of the retinal pigment epithelial band with variable degrees of attenuation of the ellipsoid zone and interdigitation zone. Fundus autofluorescence and near infrared reflectance imaging revealed multiple satellite lesions adjacent to the neurosensory detachment. These lesions were not seen on fluorescein angiography or color photography. Satellite lesions were hyporeflective on near infrared reflectance imaging and hyperautofluorescent on fundus autofluorescence imaging. The satellite lesions correlated with sites of ellipsoid disruption on spectral domain optical coherence tomography. Both patients were observed and their condition improved over the course of time. There was total resolution of satellite lesions, reconstitution of the ellipsoid zone and interdigitation zone, and return of retinal pigment epithelial thickness to the normal range. A bull's eye pattern of macular retinal pigment epithelial disturbance persisted on color and near infrared reflectance images, despite good visual acuity. Conclusion Posterior segment Coxsackie virus infection may concurrently express the clinical characteristics of acute idiopathic maculopathy and multifocal retinitis. The visual prognosis in this variant is usually favorable. The multimodal imaging features that characterize this entity should be recognized to avoid confusion with other diseases that have a similar presentation.

Optical coherence tomography angiography (OCTA) is a noninvasive, rapid imaging technique that generates angiographic images without intravenous dye injections. Cross-sectional studies have described the presence of asymptomatic choroidal neovascularization (CNV) in patients with intermediate age-related macular degeneration (AMD). This case report describes the OCT features on longitudinal follow-up of a patient who started with unilateral asymptomatic CNV and eventually developed symptomatic exudative AMD. [ Ophthalmic Surg Lasers Imaging Retina . 2017;48:596–598. ]

In this paper we present a fully automated graph-based segmentation algorithm that jointly uses optical coherence tomography (OCT) and OCT angiography (OCTA) data to segment Bruch’s membrane (BM). This is especially valuable in cases where the spatial correlation between BM, which is usually not visible on OCT scans, and the retinal pigment epithelium (RPE), which is often used as a surrogate for segmenting BM, is distorted by pathology. We validated the performance of our proposed algorithm against manual segmentation in a total of 18 eyes from healthy controls and patients with diabetic retinopathy (DR), non-exudative age-related macular degeneration (AMD) (early/intermediate AMD, nascent geographic atrophy (nGA) and drusen-associated geographic atrophy (DAGA) and geographic atrophy (GA)), and choroidal neovascularization (CNV) with a mean absolute error of ∼0.91 pixel (∼4.1 μm). This paper suggests that OCT-OCTA segmentation may be a useful framework to complement the growing usage of OCTA in ophthalmic research and clinical communities.

Geographic atrophy (GA), the advanced stage of age-related macular degeneration, is a leading cause of blindness. GA lesions are characterized by anisotropic growth and the ability to predict growth patterns would be valuable in assessing potential therapeutics. In this study, we propose an OCT-based marker of local GA growth rate based on an axial projection of the OCT volume in the Henle fiber layer (HFL) and outer nuclear layer (ONL). We analyze the association between our proposed metric and local GA growth rates in a small longitudinal cohort of patients with AMD. These methods can potentially be used to identify risk markers, stratify patients, or assess response in future therapeutic studies.

Optical coherence tomography (OCT) is a commonly used ophthalmic imaging modality. While OCT has traditionally been viewed cross-sectionally (i.e., as a sequence of B-scans), higher A-scan rates have increased interest in en face OCT visualization and analysis. The recent clinical introduction of OCT angiography (OCTA) has further spurred this interest, with chorioretinal OCTA being predominantly displayed via en face projections. Although en face visualization and quantitation are natural for many retinal features (e.g., drusen and vasculature), it requires segmentation. Because manual segmentation of volumetric OCT data is prohibitively laborious in many settings, there has been significant research and commercial interest in developing automatic segmentation algorithms. While these algorithms have achieved impressive results, the variability of image qualities and the variety of ocular pathologies cause even the most robust automatic segmentation algorithms to err. In this study, we develop a user-assisted segmentation approach, complementary to fully-automatic methods, wherein correction propagation is used to reduce the burden of manually correcting automatic segmentations. The approach is evaluated for Bruch’s membrane segmentation in eyes with advanced age-related macular degeneration.

Purpose To combine advances in high-speed, wide-field optical coherence tomography angiography (OCTA) with image processing methods for semiautomatic quantitative analysis of capillary nonperfusion in patients with diabetic retinopathy (DR). Methods Sixty-eight diabetic patients (73 eyes), either without retinopathy or with different degrees of retinopathy, were prospectively recruited for volumetric swept-source OCTA imaging using 12 mm × 12 mm fields centered at the fovea. A custom, semiautomatic software algorithm was used to quantify areas of capillary nonperfusion. Results The mean percentage of nonperfused area was 0.1% (95% confidence interval: 0.0-0.4) in the eyes without DR; 2.1% (95% confidence interval: 1.2-3.7) in the nonproliferative DR eyes (mild, moderate, and severe), and 8.5% (95% confidence interval: 5.0-14.3) in the proliferative DR eyes. The percentage of nonperfused area increased in a statistically significant manner from eyes without DR, to eyes with nonproliferative DR, to eyes with proliferative DR. Conclusion Capillary nonperfusion area in the posterior retina increases with increasing DR severity as measured by swept-source OCTA. Quantitative analysis of retinal nonperfusion on wide-field OCTA may be useful for early detection and monitoring of disease in patients with diabetes and DR.

Background/AimsHydroxychloroquine (HCQ) retinopathy may result in severe and irreversible vision loss, emphasising the importance of screening and early detection. The purpose of this study is to report the novel finding of early optical coherence tomography (OCT) abnormalities due to HCQ toxicity that may develop in the setting of normal Humphrey visual field (HVF) testing.MethodsData from patients with chronic HCQ exposure was obtained from seven tertiary care retina centres. Ten patients with HCQ-associated OCT abnormalities and normal HVF testing were identified. Detailed analysis of the OCT findings and ancillary tests including colour fundus photography, fundus autofluorescence, multifocal electroretinography and microperimetry was performed in these patients.ResultsSeventeen eyes from 10 patients illustrated abnormalities with OCT and normal HVF testing. These OCT alterations included (1) attenuation of the parafoveal ellipsoid zone and (2) loss of a clear continuous interdigitation zone. Several eyes progressed to advanced parafoveal outer retinal disruption and/or paracentral visual field defects.ConclusionPatients with high risk HCQ exposure and normal HVF testing may develop subtle but characteristic OCT abnormalities. This novel finding indicates that, in some cases of early HCQ toxicity, structural alterations may precede functional impairment. It is therefore important to employ a screening approach that includes OCT to assess for these early findings. Ancillary testing should be considered in cases with suspicious OCT changes and normal HVFs.

Objective To characterize features of extravascular OCT angiography (OCTA) signals corresponding to hyperreflective intraretinal fluid across various exudative maculopathies. Design Multicenter, retrospective, observational study. Participants Patients whose eyes had various forms of exudative maculopathy, including diabetic retinopathy (DR), retinal vein occlusion (RVO), and neovascular age-related macular degeneration (nvAMD). Methods Patients with extravascular OCTA signal identified on en face OCTA images were included in this study. This signal was readily distinguishable from projection artifacts. The regions with the extravascular motion signal on OCTA were named “suspended scattering particles in motion” (SSPiM). Depth-encoded, color en face OCTA images (3 mm × 3 mm) centered on the fovea and their corresponding structural OCT scans were used to quantify features of SSPiM and the corresponding hyperreflective fluid. Longitudinal data were collected when available. Main Outcome Measures Anatomic location, the association with hyperreflective material, changes in location and appearance of SSPiM over time, and replication of SSPiM OCTA signal in an in vitro phantom. Results Seventy-six eyes in 62 patients with various forms of exudative maculopathy were evaluated (60 eyes with DR, 9 eyes with RVO, and 5 eyes nvAMD, 1 eye with macroaneurysm, and 1 eye with radiation retinopathy). Intraretinal accumulations of fluid with increased OCT signal intensity corresponded to regions of SSPiM in several exudative maculopathies. An in vitro phantom model demonstrates that particulate matter in suspension can generate a similar OCTA signal. SSPiM showed an anatomic preference for vascular–avascular junctions. The hyperreflective fluid corresponding to SSPiM appeared more frequently in the Henle fiber layer (HFL) than the inner nuclear layer (INL) and was highly associated with hyperreflective material (HRM) found bordering the fluid. In 5 of 8 longitudinal cases, the resolution of SSPiM resulted in the formation of confluent HRM. Clinically, this appeared as hard exudate on funduscopic images. Conclusions Clinical data suggest that SSPiM is a novel imaging feature of retinal vascular diseases that was not appreciated before the use of OCTA. We characterized several novel features of SSPiM and demonstrated that at least in some cases it resolves with residual hard exudate.

To compare the sensitivity of detection and the measured size of choroidal neovascularization (CNV) on two commercially available spectral domain optical coherence tomography angiography (OCTA) devices, the Optovue RTVue XR Avanti with AngioVue and the Zeiss Cirrus HD-OCT with AngioPlex.Patients with CNV lesions were imaged consecutively on both OCTA devices on the same day of their visit. 3 × 3 mm and 6 × 6 mm scans centered at the fovea were obtained. Two independent masked readers evaluated the OCTA images for CNV identification and its area measurements.No significant differences were observed between the 2 OCTA devices in CNV area measurements on their 3 × 3 mm and 6 × 6 mm scans. However, there was suboptimal performance of their automated segmentation algorithms as compared to manually adjusted segmentation for visualizing CNV lesions.There was no significant difference in the size of the CNV lesion as measured on either commercially available spectral domain OCTA device. Both devices were comparable in their detection of CNV lesions on manual adjustment of segmentation lines. However, their automated segmentation algorithms need improvement to allow for accurate measurement of CNV lesions for routine clinical application.

Age-related macular degeneration (AMD) is a leading cause of central vision loss worldwide. The progression of dry AMD from early to intermediate stages is primarily characterized by increasing drusen formation and adverse impact on outer retinal cells. Late stage AMD consists of either geographic atrophy (GA), the non-exudative (dry) AMD subtype, or choroidal neovascularization, the exudative (wet) AMD subtype. GA is characterized by outer retinal and choroidal atrophy, specifically the photoreceptor layer, RPE, and choriocapillaris. Much remains to be discovered regarding the pathogenesis of AMD progression and subsequent development of GA. As the functionality of all three layers is closely linked, the temporal sequence of events that end up in atrophy is important in the understanding of the pathogenic pathway of the disease. The advent of OCTA, and particularly of swept-source technology, has allowed for depth-resolved imaging of retinal vasculature and the choriocapillaris. With the use of OCTA, recent studies demonstrate that choriocapillaris flow alterations are closely associated with the development and progression of AMD. Such changes may even possibly offer predictive value in determining progression of GA. This article reviews studies demonstrating choriocapillaris changes in dry AMD and summarizes the existing literature on the potential role of the choriocapillaris as a key factor in the pathogenesis of AMD.

We investigated automatic detection of micro aneurysms in optical coherence tomo-graphy angiography. Data of two patients was gathered at the New England Eye Center. Patients with diabetic retinopathy were imaged on an Optovue Avanti device.