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Abstract Introduction To describe subclinical angioid streaks (AS) as a frequent, peculiar age-related macular degeneration (AMD) phenotype, comparing features of eyes with subclinical AS with those of eyes with AMD without AS. Methods This was a retrospective, observational study. Among a patient cohort with AMD, we selected patients without known causes for AS whose eyes showed signs of angioid streaks (AS) on structural optical coherence tomography (OCT) but not on fundus examination. Selected OCT features of AS were Bruch’s membrane (BM) breaks and large BM dehiscences. Results Among 543 eyes of 274 patients with AMD (mean ± standard deviation: 82 ± 7 years), 73 eyes of 46 patients (81 ± 7 years; p = 0.432) showed AS features on OCT (OCT AS) that were not visible on fundus examination. Estimated prevalence of subclinical age-related AS was 13.4% (95% confidence interval 10.3–16.3%) in this AMD population. Fifty-three eyes (73%) with AS features were affected by peripapillary atrophy, often with a “petaloid-like” pattern, similar to typical features of AS disease. Almost all cases (97%) presented reticular pseudodrusen (RPD), with (41%) or without (59%) drusen showing a significant difference in RPD prevalence in OCT AS eyes in comparison to AMD eyes without subclinical AS using generalized estimating equations (P

IntroductionX-linked retinoschisis (XLRS) is a potential target for gene supplementation approaches. To establish potential structural and functional endpoints for clinical trials, a comprehensive understanding of the inter-eye symmetry, relationship between structural and functional parameters, and disease progression is vital.MethodsIn this retrospective multicentre study, 118 eyes of 59 XLRS patients with RS1 mutations were assessed. Information from center databases included: RS1 variant; age at presentation; best-corrected visual acuity (BCVA), central retinal thickness (CRT), macular volume (MV) at presentation and at the last follow up; full-field electroretinogram (ERG) findings; presence of peripheral retinoschisis and complications (vitreous hemorrhage, retinal detachment); treatment with systemic or topical carbonic anhydrase inhibitors (CAI).ResultsInter-eye symmetry revealed strong correlation in CRT (r = 0.77; p < 0.0001) and moderate correlations in MV (r = 0.51, p < 0.0001) and BCVA (r = 0.49; p < 0.0001). Weak or no correlations were observed between BCVA and structural parameters (CRT, MV). Peripheral retinoschisis was observed in 40 (68%), retinal detachment in 9 (15%), and vitreous hemorrhage in 5 (8%) patients, respectively. Longitudinal examinations (mean, 4.3 years) showed no BCVA changes; however, a reduction of the CRT (p = 0.02), and MV (p = 0.01) was observed. Oral and/or topical CAI treatment did not significantly alter the CRT (p = 0.34).DiscussionThe XLRS phenotype demonstrates a strong CRT symmetry between the eyes within individual patients and stable BCVA over several years. BCVA exhibits a weak correlation with the morphological parameters of retinal thickness (CRT MV). In our cohort, longitudinal functional changes were not significant, likely attributed to the short average follow-up period. Furthermore, CAI treatment didn’t influence both morphological and functional outcomes.

Abstract Objective To investigate the impact of pseudoxanthoma elasticum (PXE), a rare hereditary disease of concurrent vision impairment (VI) and cardiovascular complications (CVCs), on vision-related (VRQoL) and health-related quality of life (HRQoL). Methods VRQoL and HRQoL were assessed using the Impact of Vision Impairment (IVI) questionnaire and the Short Form Health Survey (SF-36) in 107 PXE patients. Patients were stratified into four groups: A = no VI or CVC; B = CVCs only; C = VI only; and D = both VI and CVCs. Results Following Rasch analysis, the IVI was found to function as a vision-specific functioning and emotional well-being subscale, and the SF-36 as a health-related physical functioning and mental health subscale. The presence of VI and CVC were significant predictors of vision-specific functioning and emotional well-being (p < 0.001), with a clinically meaningful decrement in vision-specific functioning in patients with VI. No associations were found for the SF-36 Physical Functioning and Mental Health scores between any groups. Conclusions Vision impaired patients with PXE report significantly poorer vision-specific functioning than PXE patients without VI. In contrast, the relative impact of PXE on reported general HRQoL was much less. Our results suggest that vision impairment has the larger impact on QoL in this sample.

Abstract Retinal disease accounts significantly for visual impairment and blindness. An important role in the pathophysiology of retinal disease and aging is attributed to lipofuscin, a complex of fluorescent metabolites. Fundus autofluorescence (AF) imaging allows non-invasive mapping of lipofuscin and is a key technology to diagnose and monitor retinal disease. However, currently used short-wavelength (SW) excitation light has several limitations, including glare and discomfort during image acquisition, reduced image quality in case of lens opacities, limited visualization of the central retina, and potential retinal light toxicity. Here, we establish a novel imaging modality which uses red excitation light (R-AF) and overcomes these drawbacks. R-AF images are high-quality, high-contrast fundus images and image interpretation may build on clinical experience due to similar appearance of pathology as on SW-AF images. Additionally, R-AF images may uncover disease features that previously remained undetected. The R-AF signal increases with higher abundance of lipofuscin and does not depend on photopigment bleaching or on the amount of macular pigment. Improved patient comfort, limited effect of cataract on image quality, and lack of safety concerns qualify R-AF for routine clinical monitoring, e.g. for patients with age-related macular degeneration, Stargardt disease, or for quantitative analysis of AF signal intensity.

PurposeTo investigate the progression characteristics of ellipsoid zone (EZ) loss in eyes with macular telangiectasia type 2 (MacTel) as reflected by area and linear measurements, and their relevance for visual acuity.MethodsParticipants were selected from the MacTel Study cohort. Linear and area measurements of EZ loss were performed in Spectral-Domain Optical Coherence Tomograph (SD-OCT) volume scans. Progression characteristics and correlations between linear and area measurements were analysed using linear mixed effects models.ResultsA total of 134 eyes of 70 patients were included (85 eyes with follow-up, mean 4.7 years, range: 1.4-8 years). Ellipsoid zone (EZ) loss significantly progressed at a mean annual increment of 0.057 mm2 (p = 0.005). The progression rate was non-linear and interacted significantly with initial EZ lesion size indicating an exponential growth before reaching a plateau. There was a strong heterogeneity in area sizes between fellow eyes. EZ break length had a significant linear effect on EZ break area (b = 1.06, p

Retinopathy is a well-recognized toxic effect of hydroxychloroquine treatment. As hydroxychloroquine retinopathy is potentially a vision-threatening condition, early detection is imperative to minimize vision loss due to drug toxicity. However, early detection of hydroxychloroquine retinopathy is still challenging even with modern retinal imaging techniques. No treatment has been established for this condition, except for drug cessation to minimize further damage. In this perspective article, we aimed to summarize the knowledge gaps and unmet needs in current clinical practice and research in hydroxychloroquine retinopathy. The information presented in this article may help guide the future directions of screening practices and research in hydroxychloroquine retinopathy.

Purpose: To develop a severity classification for macular telangiectasia type 2 (MacTel) disease using multimodal imaging. Design: An algorithm was used on data from a prospective natural history study of MacTel for classification development. Subjects: A total of 1733 participants enrolled in an international natural history study of MacTel. Methods: The Classification and Regression Trees (CART), a predictive nonparametric algorithm used in machine learning, analyzed the features of the multimodal imaging important for the development of a classification, including reading center gradings of the following digital images: stereoscopic color and red-free fundus photographs, fluorescein angiographic images, fundus autofluorescence images, and spectral-domain (SD)-OCT images. Regression models that used least square method created a decision tree using features of the ocular images into different categories of disease severity. Main Outcome Measures: The primary target of interest for the algorithm development by CART was the change in best-corrected visual acuity (BCVA) at baseline for the right and left eyes. These analyses using the algorithm were repeated for the BCVA obtained at the last study visit of the natural history study for the right and left eyes. Results: The CART analyses demonstrated 3 important features from the multimodal imaging for the classification: OCT hyper-reflectivity, pigment, and ellipsoid zone loss. By combining these 3 features (as absent, present, noncentral involvement, and central involvement of the macula), a 7-step scale was created, ranging from excellent to poor visual acuity. At grade 0, 3 features are not present. At the most severe grade, pigment and exudative neovascularization are present. To further validate the classification, using the Generalized Estimating Equation regression models, analyses for the annual relative risk of progression over a period of 5 years for vision loss and for progression along the scale were performed. Conclusions: This analysis using the data from current imaging modalities in participants followed in the MacTel natural history study informed a classification for MacTel disease severity featuring variables from SD-OCT. This classification is designed to provide better communications to other clinicians, researchers, and patients. Financial Disclosure(s): Proprietary or commercial disclosure may be found after the references.

Long-term use of hydroxychloroquine can cause retinopathy, which may result in severe and progressive visual loss. In the past decade, hydroxychloroquine use has markedly increased and modern retinal imaging techniques have enabled the detection of early, pre-symptomatic disease. As a consequence, the prevalence of retinal toxicity in long-term hydroxychloroquine users is known to be higher than was previously estimated. The pathophysiology of the retinopathy is incompletely characterised, although significant advances have been made in understanding the disease from clinical imaging studies. Hydroxychloroquine retinopathy elicits sufficient public health concern to justify the implementation of retinopathy screening programs for patients at risk. Here, we describe the historical background of hydroxychloroquine retinopathy and summarize its current understanding. We review the utility and limitations of each of the mainstream diagnostic tests used to detect hydroxychloroquine retinopathy. The key considerations towards a consensus on the definition of hydroxychloroquine retinopathy are outlined in the context of what is known of the natural history of the disease. We compare the current screening recommendations for hydroxychloroquine retinopathy, identifying where additional evidence is required, and the management of proven cases of toxicity. Finally, we highlight the areas for further investigation, which may further reduce the risk of visual loss in hydroxychloroquine users.

Hydroxychloroquine retinopathy is an increasingly recognized cause of iatrogenic, irreversible visual impairment due to the expanding use of hydroxychloroquine in combination with improvements in disease detection following advances in retinal imaging techniques. The prevalence of disease is estimated to be greater than 5% amongst individuals who have used the drug for 5 years or more. In addition to conventional imaging modalities, such as spectral-domain optical coherence tomography (OCT) and fundus autofluorescence (FAF), novel retinal imaging techniques such as en face OCT, OCT angiography, fluorescence lifetime imaging ophthalmoscopy, quantitative autofluorescence, and retromode imaging are capable of detecting structural changes in the retina. These novel retinal imaging techniques have shown promise in detecting earlier disease than is possible with current mainstream imaging modalities. Moreover, these techniques may identify disease progression as well as enabling functional correlation. In the future, these novel imaging techniques may further reduce the risk of visual loss from hydroxychloroquine retinopathy through the earlier detection of pre-clinical disease.

Accumulation of fluorescent metabolic byproducts of the visual (retinoid) cycle is associated with photoreceptor and retinal pigment epithelial cell death in both Stargardt disease and atrophic (nonneovascular) age-related macular degeneration (AMD). As a consequence of this observation, small molecular inhibitors of enzymes in the visual cycle were recently tested in clinical trials as a strategy to protect the retina and retinal pigment epithelium in patients with atrophic AMD. To address the clinical translational needs for therapies aimed at both diseases, a workshop organized by the Foundation Fighting Blindness was hosted by the Department of Pharmacology at Case Western Reserve University on February 17, 2017, at the Tinkham Veale University Center, Cleveland, OH, USA. Invited speakers highlighted recent advances in the understanding of the pathophysiology of Stargardt disease, in terms of its clinical characterization and the development of endpoints for clinical trials, and discussed the comparability of therapeutic strategies between atrophic age-related macular degeneration (AMD) and Stargardt disease. Investigators speculated that reducing the concentrations of visual cycle precursor substances and/or their byproducts may provide valid therapeutic options for the treatment of Stargardt disease. Here we review the workshops presentations in the context of published literature to help shape the aims of ongoing research endeavors and aid the development of therapies for Stargardt disease.

Retinitis pigmentosa (RP) is an inherited degenerative disease causing severe retinal dystrophy and visual impairment mainly with onset in infancy or adolescence. Targeted next-generation sequencing (NGS) has become an efficient tool to encounter the enormous genetic heterogeneity of diverse retinal dystrophies, including RP. To identify disease-causing mutations in unselected, consecutive RP patients, we conducted Sanger sequencing of genes commonly involved in the suspected genetic RP subtype, followed by targeted large-panel NGS if no mutation was identified, or NGS as primary analysis. A high (70%) detection rate of disease-causing mutations was achieved in a large cohort of 116 unrelated patients. About half (48%) of the solved RP cases were explained by mutations in four genes: RPGR, EYS, PRPF31 and USH2A. Overall, 110 different mutations distributed across 30 different genes were detected, and 46 of these mutations were novel. A molecular diagnosis was achieved in the majority (82-100%) of patients if the family history was suggestive for a particular mode of inheritance, but only in 60% in cases of sporadic RP. The diagnostic potential of extensive molecular analysis in a routine setting is also illustrated by the identification of unexpected genotype-phenotype correlations for RP patients with mutations in CRX, CEP290, RPGRIP1, MFSD8. Furthermore, we identified numerous mutations in autosomal dominant (PRPF31, PRPH2, CRX) and X-linked (RPGR) RP genes in patients with sporadic RP. Variants in RP2 and RPGR were also found in female RP patients with apparently sporadic or dominant disease. In summary, this study demonstrates that massively parallel sequencing of all known retinal dystrophy genes is a valuable diagnostic approach for RP patients.