0000000001144913

AUTHOR

Robert N. Weinreb

A new vicious cycle involving glutamate excitotoxicity, oxidative stress and mitochondrial dynamics

Glutamate excitotoxicity leads to fragmented mitochondria in neurodegenerative diseases, mediated by nitric oxide and S-nitrosylation of dynamin-related protein 1, a mitochondrial outer membrane fission protein. Optic atrophy gene 1 (OPA1) is an inner membrane protein important for mitochondrial fusion. Autosomal dominant optic atrophy (ADOA), caused by mutations in OPA1, is a neurodegenerative disease affecting mainly retinal ganglion cells (RGCs). Here, we showed that OPA1 deficiency in an ADOA model influences N-methyl-D-aspartate (NMDA) receptor expression, which is involved in glutamate excitotoxicity and oxidative stress. Opa1enu/+mice show a slow progressive loss of RGCs, activation …

research product

Macula structural and vascular differences in glaucoma eyes with and without high axial myopia

AbstractAimsTo assess the thickness of various retinal layers, and the superficial vessel density (sVD) in the macula of glaucomatous eyes and their associations with axial length (AL) and visual field mean deviation (VFMD) to identify parameters useful for glaucoma management in myopic eyes.Methods248 glaucoma patients (401 eyes) participating in the Diagnostic Innovations in Glaucoma Study observational cohort representing 3 axial myopia groups (non-myopia: n=146 eyes; mild myopia: n=208 eyes; high myopia (AL>26 mm): n=47 eyes) who completed macular OCT and OCT-Angiography imaging were included. The cross-sectional associations of AL and VFMD with the thickness of the ganglion cell inn…

research product

Effects of Study Population, Labeling and Training on Glaucoma Detection Using Deep Learning Algorithms

Author(s): Christopher, Mark; Nakahara, Kenichi; Bowd, Christopher; Proudfoot, James A; Belghith, Akram; Goldbaum, Michael H; Rezapour, Jasmin; Weinreb, Robert N; Fazio, Massimo A; Girkin, Christopher A; Liebmann, Jeffrey M; De Moraes, Gustavo; Murata, Hiroshi; Tokumo, Kana; Shibata, Naoto; Fujino, Yuri; Matsuura, Masato; Kiuchi, Yoshiaki; Tanito, Masaki; Asaoka, Ryo; Zangwill, Linda M | Abstract: PurposeTo compare performance of independently developed deep learning algorithms for detecting glaucoma from fundus photographs and to evaluate strategies for incorporating new data into models.MethodsTwo fundus photograph datasets from the Diagnostic Innovations in Glaucoma Study/African Descent…

research product

Intraocular Pressure Telemetry for Managing Glaucoma during the COVID-19 Pandemic

Purpose To evaluate in glaucoma patients the feasibility and use of remote monitoring of intraocular pressure (IOP) with an implanted telemetry sensor during the coronavirus disease 2019 (COVID-19) lockdown. Design Cross-sectional study. Participants Patients previously implanted with a telemetric IOP sensor (Eyemate; Implandata GmbH) were included. Methods Intraocular pressure measurements acquired by the patients during the lockdown were collected by physicians who were located remotely. A questionnaire was sent to 10 participating study centers to evaluate the clinical impact of remote monitoring of IOP via the IOP sensor system. Main Outcome Measures Number of patients who obtained home…

research product

Intereye Spatial Relationship of Abnormal Neuroretinal Rim Locations in Glaucoma Patients from the Diagnostic Innovations in Glaucoma Study

Purpose To determine the spatial relationship in neuroretinal rim parameter values between eyes in ocular hypertensives, glaucoma suspects, and glaucoma patients. Design Observational-cross-sectional study. Methods A total of 334 eyes of 167 patients were included. All patients underwent confocal scanning laser ophthalmoscopy imaging in both eyes. Intereye concordance ratio of abnormal rim sectors as classified by the Moorfield regression analysis (MRA) was calculated as the ratio of matching abnormal rim areas to the total number of abnormal rim areas. The amount of agreement was calculated for each sector separately. Results Of the right (left) eyes, 39 (39) eyes were classified “borderli…

research product

Expanding the clinical spectrum of COL1A1 mutations in different forms of glaucoma

Background Primary congenital glaucoma (PCG) and early onset glaucomas are one of the major causes of children and young adult blindness worldwide. Both autosomal recessive and dominant inheritance have been described with involvement of several genes including CYP1B1, FOXC1, PITX2, MYOC and PAX6. However, mutations in these genes explain only a small fraction of cases suggesting the presence of further candidate genes. Methods To elucidate further genetic causes of these conditions whole exome sequencing (WES) was performed in an Italian patient, diagnosed with PCG and retinal detachment, and his unaffected parents. Sanger sequencing of the complete coding region of COL1A1 was performed in…

research product

Deep Learning Estimation of 10-2 and 24-2 Visual Field Metrics Based on Thickness Maps from Macula OCT.

Purpose To develop deep learning (DL) systems estimating visual function from macula-centered spectral-domain (SD) OCT images. Design Evaluation of a diagnostic technology. Participants A total of 2408 10-2 visual field (VF) SD OCT pairs and 2999 24-2 VF SD OCT pairs collected from 645 healthy and glaucoma subjects (1222 eyes). Methods Deep learning models were trained on thickness maps from Spectralis macula SD OCT to estimate 10-2 and 24-2 VF mean deviation (MD) and pattern standard deviation (PSD). Individual and combined DL models were trained using thickness data from 6 layers (retinal nerve fiber layer [RNFL], ganglion cell layer [GCL], inner plexiform layer [IPL], ganglion cell-IPL […

research product

Agreement among 3 optical imaging methods for the assessment of optic disc topography.

Purpose To assess the agreement of disc topography measurements between the Heidelberg Retina Tomograph (HRT II), Retinal Thickness Analyzer (RTA), and Optical Coherence Tomograph (StratusOCT). Design Observational cross-sectional study. Participants Forty-two randomly chosen eyes of 42 subjects. Methods Each subject underwent HRT II, RTA, and StratusOCT examination. Two experienced examiners drew the contour lines for the HRT II and RTA. Bland and Altman plots were used to evaluate agreement for each topographic parameter among the instruments. The Spearman coefficient of rank correlation was evaluated for each topographic parameter. Main Outcome Measures Agreement in the measurement of op…

research product