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Purpose: We sought to develop and validate a deep learning model for segmentation of 13 features associated with neovascular and atrophic age-related macular degeneration (AMD)., Design: Development and validation of a deep-learning model for feature segmentation., Methods: Data for model development were obtained from 307 optical coherence tomography volumes. Eight experienced graders manually delineated all abnormalities in 2712 B-scans. A deep neural network was trained with these data to perform voxel-level segmentation of the 13 most common abnormalities (features). For evaluation, 112 B-scans from 112 patients with a diagnosis of neovascular AMD were annotated by 4 independent observers. The main outcome measures were Dice score, intraclass correlation coefficient, and free-response receiver operating characteristic curve., Results: On 11 of 13 features, the model obtained a mean Dice score of 0.63 ± 0.15, compared with 0.61 ± 0.17 for the observers. The mean intraclass correlation coefficient for the model was 0.66 ± 0.22, compared with 0.62 ± 0.21 for the observers. Two features were not evaluated quantitatively because of a lack of data. Free-response receiver operating characteristic analysis demonstrated that the model scored similar or higher sensitivity per false positives compared with the observers., Conclusions: The quality of the automatic segmentation matches that of experienced graders for most features, exceeding human performance for some features. The quantified parameters provided by the model can be used in the current clinical routine and open possibilities for further research into treatment response outside clinical trials., (Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.)

Purpose: To investigate lipofuscin-related quantitative autofluorescence measures and their association with demographic characteristics, retinal structure, retinal function and genotype in ABCA4-related retinopathy (Stargardt disease 1)., Design: Cross-sectional study with age-matched healthy control subjects., Methods: A total of 77 patients with ABCA4-related retinopathy and 110 control subjects underwent quantitative fundus autofluorescence (qAF) imaging using a confocal scanning laser ophthalmoscope equipped with an internal fluorescent reference to measure qAF as surrogate for lipofuscin accumulation. Measures of qAF were correlated with demographic characteristics, structural alterations on optical coherence tomography and fundus autofluorescence imaging, retinal function assessed by full-field electroretinography (ERG) and fundus-controlled perimetry, and genotype., Results: Most patients (76.6%) had qAF levels >95% prediction interval of the age-related control group, with best discrimination between cases and control subjects in younger patients. Reduced discrimination based on qAF measures was associated with mild disease, more advanced disease with dark flecks, or older age because of the physiological age-related increase in qAF and a ceiling effect in patients. Nullizygous patients presented with high qAF levels earlier in life compared with those with at least 1 milder ABCA4 variant. Within the sectors of qAF measurements, at approximately 7-9° eccentricity, increased qAF without flecks or with only bright flecks was associated with topographically related preserved retinal thickness and fundus-controlled perimetry results, and with normal full-field ERG recordings. All 3 parameters were increasingly abnormal with the development of dark flecks and decreasing qAF., Conclusions: The accumulation of lipofuscin depends on the severity of ABCA4 variants, precedes other structural changes, and may remain without clinically relevant effect on retinal function., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Purpose: To investigate the development and progression of retinal pigment epithelial and outer retinal atrophy (RORA) secondary to maternally inherited diabetes and deafness (MIDD)., Design: Retrospective observational case series., Methods: Thirty-six eyes of 18 patients (age range, 22.4-71.6 years) with genetically proven MIDD and serial optical coherence tomography (OCT) images were included. As proposed reference standard to diagnose and stage atrophy, OCT images were longitudinally evaluated and analyzed for presence and precursors of RORA. RORA was defined as an area of (1) hypertransmission, (2) disruption of the retinal pigment epithelium, (3) photoreceptor degeneration, and (4) absence of other signs of a retinal pigment epithelial tear., Results: The majority of patients revealed areas of RORA in a circular area around the fovea of between 5° and 15° eccentricity. Over the observation time (range, 0.5-8.5 years), evidence for a consistent sequence of OCT features from earlier disease stages to the end stage of RORA could be found, starting with loss of ellipsoid zone and subretinal deposits, followed by loss of external limiting membrane and loss of retinal pigment epithelium with hypertransmission of OCT signal into the choroid, and leading to loss of the outer nuclear layer bordered by hyporeflective wedges. Outer retinal tabulations seemed to develop in regions of coalescent areas of RORA., Conclusions: The development and progression of RORA could be tracked in MIDD patients using OCT images, allowing potential definition of novel surrogate markers. Similarities to OCT features in age-related macular degeneration, where mitochondrial dysfunction has been implicated in the pathogenesis, support wide-ranging benefits from proof-of-concept studies in MIDD., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Purpose: To investigate the prognostic value of demographic, functional, and imaging parameters on retinal pigment epithelium (RPE) atrophy progression secondary to maternally inherited diabetes and deafness (MIDD) and to evaluate the application of these factors in clinical trial design., Design: Retrospective observational case series., Methods: Thirty-five eyes of 20 patients (age range, 24.9-75.9 years) with genetically proven MIDD and demarcated RPE atrophy on serial fundus autofluorescence (AF) images were included. Lesion size and shape-descriptive parameters were longitudinally determined by 2 independent readers. A linear mixed-effect model was used to predict the lesion enlargement rate based on baseline variables. Sample size calculations were performed to model the power in a simulated interventional study., Results: The mean follow-up time was 4.27 years. The mean progression rate of RPE atrophy was 2.33 mm 2 /year, revealing a dependence on baseline lesion size (+0.04 [0.02-0.07] mm 2 /year/mm 2 , P < .001), which was absent after square root transformation. The fovea was preserved in the majority of patients during the observation time. In the case of foveal involvement, the loss of visual acuity lagged behind central RPE atrophy in AF images. Sex, age, and number of atrophic foci predicted future progression rates with a cross-validated mean absolute error of 0.13 mm/year and to reduce the required sample size for simulated interventional trials., Conclusions: Progressive RPE atrophy could be traced in all eyes using AF imaging. Shape-descriptive factors and patients' baseline characteristics had significant prognostic value, guiding appropriate subject selection and sample size in future interventional trial design., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Purpose: To investigate near-infrared fundus autofluorescence (NIR-AF) characteristics in patients with choroideremia and to correlate these with anatomic and functional parameters., Design: Retrospective, observational case series., Methods: In this multicenter study, 43 consecutive choroideremia patients (79 eyes) underwent multimodal retinal imaging, including near-infrared fundus autofluorescence (NIR-AF), blue autofluorescence (B-AF), optical coherence tomography (OCT), fundus photography, and functional testing including fundus-controlled microperimetry., Results: All eyes could be categorized into 3 groups based on patterns of NIR-AF over the island of surviving retinal pigment epithelium: Group 1 (preserved NIR-AF centrally), Group 2 (only disrupted NIR-AF), or Group 3 (absence of NIR-AF). Group 1 eyes showed areas of NIR-AF that matched the areas of B-AF islands (R 2  = 0.94, slope 0.84 ± 0.04) while Group 2 eyes showed significantly smaller areas of NIR-AF compared with B-AF (R 2  = 0.08; slope 0.02 ± 0.01). The 3 groups differed significantly in terms of residual B-AF island size (P < .0001), length of foveal ellipsoid zone (P = .03), foveal thickness (P = .04), and foveal sensitivity (P = .01). Visual acuity (P = .07) and central retinal thickness (P = .06) did not differ statistically. The length of the ellipsoid zone line was similar to the horizontal diameter of NIR-AF in Group 1 (R 2  = 0.97, slope 0.96 ± 0.04), while Group 2 eyes showed broader ellipsoid zone than NIR-AF (R 2  = 0.60, slope 0.19 ± 0.03)., Conclusions: Choroideremia patients can be stratified into 3 groups based on NIR-AF imaging, which showed morphologic and functional changes correlating with different stages of retinal pigment epithelium degeneration. NIR-AF could be a marker for disease staging in choroideremia, and could be used for patient selection or as an outcome parameter in interventional trials., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Purpose: To investigate the involvement of the retinal and choriocapillaris microvasculature in intermediate uveitis on optical coherence tomography angiography (OCT-A)., Design: Case-control study., Methods: Patients and age-matched controls were imaged with swept-source OCT-A. Using ImageJ, superficial and deep retinal vasculature were semi-automatically analyzed for vessel (VD) and skeleton density (SD), vessel diameter index (VDI), and fractal dimension (FD). Choriocapillaris layer was automatically graded for mean signal intensity, signal intensity standard deviation, kurtosis of signal intensity distribution, and flow signal voids., Results: Twenty-nine intermediate uveitis eyes and 30 control eyes were included. Both superficial and deep retinal layers showed significant reduction in all OCT-A parameters (eg, superficial retinal layer: 0.31 vs 0.40 VD, 5.6e -8 vs 6.4e -8 SD, 5.4e 6 vs 6.1e 6 VDI, and 1.78 vs 1.79 FD, respectively, all P < .05). At the choriocapillaris layer a greater heterogeneity of perfusion with a shift toward a higher proportion of large confluent flow signal voids was present. Also in the absence of macular edema OCT-A parameters were reduced when compared with healthy controls (all parameters except for VDI in the superficial retinal layer and the choriocapillaris kurtosis and flow signal void analyses)., Conclusions: In intermediate uveitis, reduced vascular density and complexity in superficial as well as deep retinal layers and altered choriocapillaris perfusion are present. Moreover, these findings indicate impairment of the macular microvasculature even in the absence of macular edema. The results of our study may aid in the diagnosis as well as the monitoring of intermediate uveitis., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Purpose: To investigate the impact of Bruch membrane pathology on the choroid in pseudoxanthoma elasticum (PXE)., Design: Monocenter cross-sectional prospective case series., Methods: The study included 61 eyes of 51 patients with PXE and 54 eyes of 54 normal subjects. The diagnosis of PXE was based on skin biopsy, genetic analysis or both. Eyes with PXE were subdivided into 3 groups: eyes without choroidal neovascularization (CNV) or chorioretinal atrophy (Group 1); eyes with active or fibrotic CNV (Group 2); and eyes with chorioretinal atrophy only (Group 3). Choroidal thickness was measured using enhanced-depth imaging optical coherence tomography (EDI-OCT)., Results: Compared to controls (331 μm ± 24; mean ± 95% CI), mean subfoveal choroidal thickness in eyes of patients with PXE was significantly reduced within all 3 groups (Group 1: 243 μm ± 29; Group 2: 184 μm ± 28; Group 3: 104 μm ± 28; P < 0.001). Associated structural changes included apparent loss of small choroidal vessels. The difference of PXE compared to control eyes was largest close to the optic disc and approximated the level of controls toward the periphery. Within the PXE subgroups, eyes without CNV or chorioretinal atrophy (Group 1) showed the least reduction of choroidal thickness, while it was most pronounced in Group 3., Conclusions: The results indicate that changes of Bruch membrane can be associated with choroidal alterations, which are most pronounced in the presence of advanced disease. A role of Bruch membrane in choroidal homeostasis may reflect a possible contribution of Bruch membrane alterations to CNV and geographic atrophy development in age-related macular degeneration., (Copyright © 2014 Elsevier Inc. All rights reserved.)