Purpose: To quantify outer retina structural changes and define novel biomarkers of inherited retinal degeneration associated with biallelic mutations in RPE65 (RPE65-IRD) in patients before and after subretinal gene augmentation therapy with voretigene neparvovec (Luxturna).
Methods: Application of advanced deep learning for automated retinal layer segmentation, specifically tailored for RPE65-IRD. Quantification of five novel biomarkers for the ellipsoid zone (EZ): thickness, granularity, reflectivity, and intensity.
Purpose: The relative ellipsoid zone reflectivity (rEZR) is an innovative biomarker for photoreceptor alterations and showed association with disease staging in macular telangiectasia type 2 (MacTel). However, its prognostic relevance for the ellipsoid zone (EZ) loss is unclear.
Methods: Longitudinal spectral-domain optical coherence tomography (SD-OCT) imaging of patients with MacTel from an observational natural history study was used for en face determination of manifest EZ loss.
Advances in imaging and artificial intelligence (AI) have revolutionized the detection, quantification and monitoring for the clinical assessment of intermediate age-related macular degeneration (iAMD). The iAMD incorporates a broad spectrum of manifestations, which range from individual small drusen, hyperpigmentation, hypopigmentation up to early stages of geographical atrophy. Current high-resolution imaging technologies enable an accurate detection and description of anatomical features, such as drusen volumes, hyperreflexive foci and photoreceptor degeneration, which are risk factors that are decisive for prediction of the course of the disease; however, the manual annotation of these features in complex optical coherence tomography (OCT) scans is impractical for the routine clinical practice and research.
View Article and Find Full Text PDFPurpose: The relative ellipsoid zone reflectivity (rEZR) has been proposed as an innovative biomarker for photoreceptor integrity. This study evaluates the rEZR in macular telangiectasia type 2 (MacTel) eyes of different disease stages.
Methods: The mean rEZR (ratio ellipsoid zone [EZ]/external limiting membrane [ELM] reflectivity [arbitrary units {AUs}], grey level range = 0-1) was analyzed for an entire spectral domain optical coherence tomography volume scan (global) and for each subfield of the Early Treatment Diabetic Retinopathy Study (ETDRS) grid (topographic) in patients with MacTel and controls.
Purpose: To determine the interreader agreement for reticular pseudodrusen (RPD) assessment on combined infrared reflectance (IR) and OCT imaging in the early stages of age-related macular degeneration across a range of different criteria to define their presence.
Design: Interreader agreement study.
Participants: Twelve readers from 6 reading centers.
Purpose: To report the prevalence and topographic distribution of structural characteristics in study participants with age-related macular degeneration (AMD) and controls in the cross-sectional study part of the MACUSTAR study (ClinicalTrials.gov Identifier: NCT03349801).
Design: European, multicenter cohort study.
Drusen are hallmarks of early and intermediate age-related macular degeneration (AMD) but their quantification remains a challenge. We compared automated drusen volume measurements between different OCT devices. We included 380 eyes from 200 individuals with bilateral intermediate (iAMD, n = 126), early (eAMD, n = 25) or no AMD (n = 49) from the MACUSTAR study.
View Article and Find Full Text PDFQuantification of the relative ellipsoid zone reflectivity (rEZR) might be a structural surrogate parameter for an early disease progression in the context of age-related macular degeneration (AMD). Within the European multicenter, cross-sectional MACUSTAR study, we have devised an automatic approach to determine the mean rEZR [arbitrary units, AU] at two independent visits in SD-OCT volume scans in study participants. Linear mixed-effects models were applied to analyze the association of AMD stage and AMD associated high-risk features including presence of pigmentary abnormalities, reticular pseudodrusen (RPD), volume of the retinal-pigment-epithelial-drusenoid-complex (RPEDC) with the rEZR.
View Article and Find Full Text PDFPurpose: Relative ellipsoid zone reflectivity (rEZR) has been reported to be reduced in intermediate age-related macular degeneration (iAMD). However, longitudinal changes in rEZR remain unknown. This study investigated the natural history of rEZR in iAMD and its association with risk factors for disease progression, including the presence or extent of drusen volume, reticular pseudodrusen (RPD), and pigmentary abnormalities (PAs).
View Article and Find Full Text PDFPurpose: To analyze the intersession repeatability of structural biomarkers in eyes with early and intermediate age-related macular degeneration (iAMD) within the cross-sectional part of the observational multicenter MACUSTAR study.
Methods: Certified site personnel obtained multimodal imaging data at two visits (38 ± 20 [mean ± standard deviation] days apart), including spectral-domain optical coherence tomography (SD-OCT). One junior reader performed systematic and blinded grading at the central reading center, followed by senior reader review.
Background: Subthreshold nanosecond laser (SNL) treatment has been studied as a potential intervention in intermediate age-related macular degeneration (iAMD). This study investigated the effect of 100 SNL treatment spots on retinal structure and function.
Methods: A prospective single-arm interventional pilot study.
Introduction: This retrospective analysis assessed geographic atrophy (GA) progression in fellow eyes from the Proxima B trial intermediate age-related macular degeneration (iAMD) subcohort using high-resolution multimodal imaging anchored on optical coherence tomography (OCT).
Methods: Thirty-two patients from the Proxima B iAMD subcohort were assessed; all had GA with no macular neovascularization (MNV) in the contralateral eye. Imaging data, including color fundus photography, fluorescein angiography, near-infrared reflectance, fundus autofluorescence (FAF), and spectral-domain OCT, were obtained.
Background: Brolucizumab has recently been approved in Europe as a novel treatment for patients with neovascular age-related macular degeneration (nAMD). We report on early experiences with real-world outcomes of switch to brolucizumab therapy in previously anti-vascular endothelial growth factor (anti-VEGF)-treated patients.
Methods: Patients with recalcitrant nAMD were switched to brolucizumab therapy.
Purpose: To determine the interreader agreement for incomplete retinal pigment epithelium (RPE) and outer retinal atrophy (iRORA) and complete RPE and outer retinal atrophy (cRORA) and their related features in age-related macular degeneration (AMD).
Design: Interreader agreement study.
Participants: Twelve readers from 6 reading centers.
Purpose: Relative ellipsoid zone reflectivity (rEZR) represents a potential biomarker of photoreceptor health on spectral-domain optical coherence tomography (SD-OCT). Because manual quantification of rEZR is laborious and lacks of spatial resolution, automated quantification of the rEZR would be beneficial. The purpose of this study was to evaluate the reliability and reproducibility of an automated rEZR quantification method.
View Article and Find Full Text PDFPurpose: To 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.
Methods: This retrospective study included only eyes with non-neovascular AMD and associated SRF. Eyes with evidence of MNV were excluded.
Purpose: To examine longitudinal changes of retinal thickness and retinal sensitivity in patients with intermediate age-related macular degeneration (iAMD) and predominantly reticular pseudodrusen (RPD).
Methods: At baseline 30 eyes of 25 iAMD patients underwent optical coherence tomography imaging, mesopic and scotopic fundus-controlled perimetry (FCP) with follow-up examinations at month 12 (20 eyes), 24 (12 eyes), and 36 (11 eyes). Thicknesses of different retinal layers and results of FCP testing (n = 56 stimuli) were spatially and longitudinally analyzed using linear mixed-effects models.
Purpose: To assess the longitudinal association between outer retinal microstructure and mesopic as well as scotopic retinal sensitivity in patients with drusen secondary to intermediate age-related macular degeneration (iAMD).
Design: Prospective, longitudinal natural history study.
Participants: Fifty-nine eyes of 54 patients with large drusen (> 125 μm) associated with iAMD and 27 age-matched healthy control eyes.
Here, we investigate the extent to which re-implementing a previously published algorithm for OCT-based drusen quantification permits replicating the reported accuracy on an independent dataset. We refined that algorithm so that its accuracy is increased. Following a systematic literature search, an algorithm was selected based on its reported excellent results.
View Article and Find Full Text PDFPurpose: To investigate the association between retinal microstructure and cone and rod function in geographic atrophy (GA) secondary to age-related macular degeneration (AMD) by using artificial intelligence (AI) algorithms.
Design: Prospective, observational case series.
Methods: A total of 41 eyes of 41 patients (75.
Background: To characterise early stages of geographic atrophy (GA) development in age-related macular degeneration (AMD) and to determine the prognostic value of structural precursor lesions in eyes with intermediate (i) AMD on the subsequent GA progression.
Methods: Structural precursor lesions for atrophic areas (lesion size at least 0.5 mm² in fundus autofluorescence images) were retrospectively identified based on multimodal imaging and evaluated for association with the subsequent GA enlargement rates (square-root transformed, sqrt).
Purpose: To investigate the association between the presence of type 1 choroidal neovascularization (CNV) and the localized progression of atrophy in age-related macular degeneration (AMD).
Design: Analysis of patients' data collected in the context of 2 noninterventional, prospective studies conducted at the Department of Ophthalmology, University of Bonn, Germany.
Participants: A total of 98 eyes diagnosed with AMD of 59 patients (40 female, 19 male) with a mean (±standard deviation) age at baseline of 76.