Longitudinal Analysis of Functional and Structural Outcome Measures in PRPH2-Associated Retinal Dystrophy.

Purpose: To establish disease progression rates in total lesion size (TLS), decreased autofluorescence (DAF) area, total macular volume (TMV), and mean macular sensitivity (MMS) in PRPH2-associated retinal dystrophy.

Design: Single-center, retrospective chart review.

Participants: Patients with heterozygous pathogenic or likely pathogenic PRPH2 variants.

SIBLING CONCORDANCE IN SYMPTOM ONSET AND ATROPHY GROWTH RATES IN STARGARDT DISEASE USING ULTRA-WIDEFIELD FUNDUS AUTOFLUORESCENCE.

Purpose: To investigate concordance in symptom onset, area of dark autofluorescence (DAF), and growth rate (GR) between Stargardt disease siblings at an age-matched time point.

Methods: In this retrospective longitudinal study of sibling pairs with identical biallelic ABCA4 variants, age at symptom onset, best-corrected visual acuity, atrophy area, and effective radius of DAF on ultra-widefield fundus autofluorescence were recorded. Absolute intersibling differences for both eyes were compared with absolute interocular differences using the Mann-Whitney test.

Genotype-Specific Lesion Growth Rates in Stargardt Disease.

Reported growth rates (GR) of atrophic lesions in Stargardt disease (STGD1) vary widely. In the present study, we report the longitudinal natural history of patients with confirmed biallelic mutations from five genotype groups: c.6079C>T, c.

CLASSIFYING ABCA4 MUTATION SEVERITY USING AGE-DEPENDENT ULTRA-WIDEFIELD FUNDUS AUTOFLUORESCENCE-DERIVED TOTAL LESION SIZE.

Purpose: To establish a mutation-specific age-dependent ultra-widefield fundus autofluorescence (UWF-FAF) trajectory in a large Stargardt disease (STGD1) cohort using total lesion size (TLS) and to develop a clinical method for variant classification.

Methods: A retrospective study of patients with biallelic ABCA4 mutations that were evaluated with UWF-FAF. Boundaries of TLS, defined by stippled hyper/hypoautofluorescence, were outlined manually.

Leveraging natural history biorepositories as a global, decentralized, pathogen surveillance network.

The Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) pandemic reveals a major gap in global biosecurity infrastructure: a lack of publicly available biological samples representative across space, time, and taxonomic diversity. The shortfall, in this case for vertebrates, prevents accurate and rapid identification and monitoring of emerging pathogens and their reservoir host(s) and precludes extended investigation of ecological, evolutionary, and environmental associations that lead to human infection or spillover. Natural history museum biorepositories form the backbone of a critically needed, decentralized, global network for zoonotic pathogen surveillance, yet this infrastructure remains marginally developed, underutilized, underfunded, and disconnected from public health initiatives.

Atrophy Expansion Rates in Stargardt Disease Using Ultra-Widefield Fundus Autofluorescence.

Purpose: To investigate atrophy expansion rate (ER) using ultra-widefield (UWF) fundus autofluorescence (FAF) in Stargardt disease (STGD1).

Design: Retrospective, longitudinal study.

Participants: Patients with biallelic mutations who were evaluated with UWF FAF and Heidelberg 30° × 30° and 55° × 55° FAF imaging.

A novel phenotype in a family with autosomal dominant retinal dystrophy due to c.1430A > G in retinoid isomerohydrolase (RPE65) and c.37C > T in bestrophin 1 (BEST1).

Purpose: The c.1430A > G (Asp477Gly) variant in RPE65 has been reported in Irish and Scottish families with either an autosomal dominant retinal dystrophy (adRD) that resembles choroideremia, a vitelliform macular dystrophy or an isolated macular atrophy. We report novel features on multimodal imaging and the natural history of a family harbouring this variant in combination with the BEST1 c.

Progressive sector retinitis pigmentosa due to c.440G>T mutation in in an Australian family.

Background: Heterozygous c.440 G > T mutation in the S-antigen visual arrestin gene has been described as a cause of autosomal dominant retinitis pigmentosa (adRP) in a series of patients of Hispanic origin. This study presents the early and late clinical features and disease progression rates in an Australian family with adRP.

Edge of Scotoma Sensitivity as a Microperimetry Clinical Trial End Point in Retinopathy.

Purpose: Microperimetry is commonly used to assess retinal function. We perform cross-sectional and longitudinal analysis on microperimetry parameters in retinopathy and explore end points suitable for future clinical trials.

Methods: Microperimetry was performed using two grids, Grid 1 (18° diameter) and Grid 2 (6° diameter).

Retinal pigment epithelium and age-related macular degeneration: A review of major disease mechanisms.

Age-related macular degeneration (AMD) is a progressive degenerative disease that is the leading cause of vision loss in the elderly population. Degeneration/dysregulation of the retinal pigment epithelium (RPE), a supportive monolayer of cells underlying the photoreceptors, is commonly seen in patients with AMD. While treatment exists for the neovascular/wet form of AMD, there is currently no cure for the non-exudative/dry form of AMD, making it imperative to understand the pathogenesis of this disease.

Phenotype-genotype correlations in a pseudodominant Stargardt disease pedigree due to a novel ABCA4 deletion-insertion variant causing a splicing defect.

Background: Deletion-insertion (delins) variants in the retina-specific ATP-binding cassette transporter gene, subfamily A, member 4 (ABCA4) accounts for <1% in Stargardt disease. The consequences of these delins variants on splicing cannot be predicted with certainty without supporting in vitro data.

Methods: Candidate ABCA4 variants were revealed by genetic and segregation analysis of a family with pseudodominant Stargardt disease using a commercial panel and Sanger sequencing.

Three-Year Follow-Up of Phase 1 and 2a rAAV.sFLT-1 Subretinal Gene Therapy Trials for Exudative Age-Related Macular Degeneration.

Purpose: To assess the safety and the 3-year results of combined phase 1 and 2a randomized controlled trials of rAAV.sFLT-1 gene therapy (GT) for wet age-related macular degeneration.

Design: Phase 1/2a clinical trial.

Effect of Ciliary Neurotrophic Factor on Retinal Neurodegeneration in Patients with Macular Telangiectasia Type 2: A Randomized Clinical Trial.

Purpose: To test the effects of an encapsulated cell-based delivery of a neuroprotective agent, ciliary neurotrophic factor (CNTF), on progression of macular telangiectasia type 2, a neurodegenerative disease with no proven effective therapy.

Design: Randomized sham-controlled clinical trial.

Participants: Ninety-nine study eyes of 67 eligible participants were enrolled.

ACUTE RETINAL NECROSIS ASSOCIATED WITH HERPES ZOSTER VACCINATION.

Purpose: To report a case of Zostavax-associated acute retinal necrosis in a patient with chronic lymphocytic leukemia.

Methods: Case report.

Patients: A 76-year-old white man.

Surgical Removal of Internal Limiting Membrane and Layering of AAV Vector on the Retina Under Air Enhances Gene Transfection in a Nonhuman Primate.

Purpose: To determine if the surgical removal of the internal limiting membrane (ILM) in nonhuman primates (NHPs) will result in safe and effective transfection of adeno-associated viral (AAV2) vectors using green fluorescent protein (GFP) as a reporter.

Methods: Six Macaca fascicularis NHP eyes underwent vitrectomy, ILM peel with layering of 1.7 × 1013 genome copies per milliliter of AAV2-GFP under air.

Intrasession Repeatability and Interocular Symmetry of Foveal Avascular Zone and Retinal Vessel Density in OCT Angiography.

Purpose: To measure intrasession repeatability and interocular symmetry of the foveal avascular zone area (FAZA) and superficial retinal vessel density (SRVD) using AngioVue Analytics optical coherence tomography angiography (OCTA).

Methods: Fifty healthy individuals were prospectively enrolled. OCTA scans (3 × 3 and 6 × 6 mm) were acquired twice in right and once in left eyes.

Intersession Test-Retest Variability of Microperimetry in Type 2 Macular Telangiectasia.

Purpose: Microperimetry is used as an endpoint in type 2 macular telangiectasia (mactel) trials. The change required for defining disease progression depends on measurement error. We determined the threshold of test-retest variability (TRV) of microperimetry in mactel.

Gene Therapy in Neovascular Age-related Macular Degeneration: Three-Year Follow-up of a Phase 1 Randomized Dose Escalation Trial.

Purpose: To assess the safety of rAAV.sFlt-1 subretinal injection in neovascular age-related macular degeneration (wet AMD) over 36 months.

Design: Phase 1 dose escalation trial.

Phase 2a Randomized Clinical Trial: Safety and Post Hoc Analysis of Subretinal rAAV.sFLT-1 for Wet Age-related Macular Degeneration.

Background: We present the results of a Phase 2a randomized controlled trial investigating the safety, and secondary endpoints of subretinal rAAV.sFLT-1 gene therapy in patients with active wet age-related macular degeneration (wAMD).

Methods: All patients (n=32), (ClinicalTrials.

Gene Therapy for Age-Related Macular Degeneration.

The purpose of this article was to evaluate safety and signals of efficacy of gene therapy with subretinal rAAV.sFlt-1 for wet age-related macular degeneration (wet AMD). A phase 1 dose-escalating single-center controlled unmasked human clinical trial was followed up by extension of the protocol to a phase 2A single-center trial.

Assessment of polygenic effects links primary open-angle glaucoma and age-related macular degeneration.

Primary open-angle glaucoma (POAG) and age-related macular degeneration (AMD) are leading causes of irreversible blindness. Several loci have been mapped using genome-wide association studies. Until very recently, there was no recognized overlap in the genetic contribution to AMD and POAG.

Gene therapy with recombinant adeno-associated vectors for neovascular age-related macular degeneration: 1 year follow-up of a phase 1 randomised clinical trial.

Background: Neovascular, or wet, age-related macular degeneration causes central vision loss and represents a major health problem in elderly people, and is currently treated with frequent intraocular injections of anti-VEGF protein. Gene therapy might enable long-term anti-VEGF therapy from a single treatment. We tested the safety of rAAV.

Retinal video recordings at different compression levels: a novel video-based imaging technology for diabetic retinopathy screening.

Background: To evaluate the optimal compression level of retinal color digital video recordings, a novel video-based imaging technology, in screening for diabetic retinopathy (DR).

Design: Evaluation of a diagnostic technique.

Methods: A total of 36 retinal videos, captured using EyeScan (Ophthalmic Imaging System), were compressed from original uncompressed file size of 1 GB (gigabyte) to four different compression levels-100 MB (megabyte) (Group 1); 30 MB (Group 2); 20 MB (Group 3); and 5 MB (Group 4).