Clinical and Imaging Characteristics of PRPH2 Retinopathies in a Longitudinal Cohort and Diagnostic Implications.

Purpose: The purpose of this study was to define genotypic-phenotypic correlations related to PRPH2-associated retinopathies in an observational longitudinal cohort and to improve diagnostic accuracy.

Methods: Individuals with PRPH2 variants were identified by genetic sequencing of 263 individuals (including 59 families). Ocular examinations with multimodal imaging were evaluated.

The role of nutritional factors in transitioning between early, mid, and late stages of age-related macular degeneration: prospective longitudinal analysis.

Background: Transitions between different stages of age-related macular degeneration (AMD) are not completely captured by traditional survival models with an end point of advanced AMD.

Objectives: This study aimed to explore the transitions from early and intermediate AMD to higher non-advanced and advanced stages and determine the contributions of nutritional factors to these outcomes.

Methods: Eyes with early or intermediate AMD at baseline, classified according to the Age-Related Eye Disease Study severity scale, were included in this prospective longitudinal analysis.

Risk and protection of different rare protein-coding variants of complement component C4A in age-related macular degeneration.

Age-related macular degeneration (AMD) is the leading cause of central vision loss in the elderly. One-third of the genetic contribution to this disease remains unexplained. We analyzed targeted sequencing data from two independent cohorts (4,245 cases, 1,668 controls) which included genomic regions of known AMD loci in 49 genes.

Evaluation of Risk Prediction with Hierarchical Data: Dependency Adjusted Confidence Intervals for the AUC.

The area under the true ROC curve (AUC) is routinely used to determine how strongly a given model discriminates between the levels of a binary outcome. Standard inference with the AUC requires that outcomes be independent of each other. To overcome this limitation, a method was developed for the estimation of the variance of the AUC in the setting of two-level hierarchical data using probit-transformed prediction scores generated from generalized estimating equation models, thereby allowing for the application of inferential methods.

Family History of Age-Related Macular Degeneration and Genetics Predict Progression to Advanced Age-Related Macular Degeneration Adjusting for Macular Status, Demographic, and Lifestyle Factors.

Purpose: To determine if a family history of age-related macular degeneration (AMD) and genetic variants identify eyes at higher risk for progression to advanced AMD (AAMD), after controlling for baseline demographics, behavioral factors, and macular status.

Design: Prospective, longitudinal cohort study.

Methods: Eyes were classified using the Age-Related Eye Disease Study severity scale.

Rare Dysfunctional Genetic Variants and Progression to Advanced Age-Related Macular Degeneration.

Purpose: To evaluate associations between rare dysfunctional () genetic variant status and progression to advanced age-related macular degeneration (AAMD), geographic atrophy (GA), and neovascular disease (NV).

Design: Prospective, longitudinal study.

Participants: Patients aged 55 to 80 years at baseline identifying as White with non-AAMD in 1 or both eyes at baseline were included.

Blue Light Exposure: Ocular Hazards and Prevention-A Narrative Review.

Introduction: Exposure to blue light has seriously increased in our environment since the arrival of light emitting diodes (LEDs) and, in recent years, the proliferation of digital devices rich in blue light. This raises some questions about its potential deleterious effects on eye health. The aim of this narrative review is to provide an update on the ocular effects of blue light and to discuss the efficiency of methods of protection and prevention against potential blue light-induced ocular injury.

Deep ensemble learning for automated non-advanced AMD classification using optimized retinal layer segmentation and SD-OCT scans.

Background: Accurate retinal layer segmentation in optical coherence tomography (OCT) images is crucial for quantitatively analyzing age-related macular degeneration (AMD) and monitoring its progression. However, previous retinal segmentation models depend on experienced experts and manually annotating retinal layers is time-consuming. On the other hand, accuracy of AMD diagnosis is directly related to the segmentation model's performance.

Identifying Novel Genes and Variants in Immune and Coagulation Pathways Associated with Macular Degeneration.

Purpose: To select individuals and families with a low genetic burden for age-related macular degeneration (AMD), to inform the clinical diagnosis of macular disorders, and to find novel genetic variants associated with maculopathies.

Design: Genetic association study based on targeted and whole-exome sequencing.

Participants: A total of 758 subjects (481 individuals with maculopathy and 277 controls), including 316 individuals in 72 families.

A Screening Tool for Self-Evaluation of Risk for Age-Related Macular Degeneration: Validation in a Spanish Population.

Purpose: The objectives of this study were the creation and validation of a screening tool for age-related macular degeneration (AMD) for routine assessment by primary care physicians, ophthalmologists, other healthcare professionals, and the general population.

Methods: A simple, self-administered questionnaire (Simplified Théa AMD Risk-Assessment Scale [STARS] version 4.0) which included well-established risk factors for AMD, such as family history, smoking, and dietary factors, was administered to patients during ophthalmology visits.

Functional analysis of rare genetic variants in complement factor I in advanced age-related macular degeneration.

Factor I (FI) is a serine protease inhibitor of the complement system. Heterozygous rare genetic variants in complement factor I (CFI) are associated with advanced age-related macular degeneration (AMD). The clinical impact of these variants is unknown since a majority have not been functionally characterized and are classified as 'variants of uncertain significance' (VUS).

Exploring Consensus on Preventive Measures and Identification of Patients at Risk of Age-Related Macular Degeneration Using the Delphi Process.

Background: Early identification of AMD can lead to prompt and more effective treatment, better outcomes, and better final visual acuity; several risk scores have been devised to determine the individual level of risk for developing AMD. Herein, the Delphi method was used to provide recommendations for daily practice regarding preventive measures and follow-up required for subjects at low, moderate, and high risk of AMD evaluated with the Simplified Test AMD Risk-assessment Scale (STARS) questionnaire.

Methods: A steering committee of three experts drafted and refined 25 statements on the approach to be recommended in different clinical situations [general recommendations ( = 2), use of evaluation tools ( = 4), general lifestyle advice ( = 3), and AREDS-based nutritional supplementation ( = 5)] with the help of a group of international experts, all co-authors of this paper.

Increased Risk of Skin Cancer in 1,851 Long-Term Retinoblastoma Survivors.

Patients with hereditary retinoblastoma are at risk for developing cutaneous melanoma, but little is known about the role of sun exposure or other factors, and the incidence of nonmelanoma skin cancer (NMSC) is poorly understood. We investigated the incidence of melanoma and NMSC in a cohort of 1,851 White, long-term retinoblastoma survivors (1,020 hereditary and 831 nonhereditary) diagnosed during 1914‒2006. During follow-up through 2016, 33 hereditary and 7 nonhereditary survivors developed melanoma, and 26 hereditary and 9 nonhereditary survivors developed NMSC.

Benign Tumors in Long-Term Survivors of Retinoblastoma.

Hereditary retinoblastoma survivors have substantially increased risk of subsequent malignant neoplasms (SMNs). The risk of benign neoplasms, a substantial cause of morbidity, is unclear. We calculated the cumulative incidence of developing benign tumors at 60 years following retinoblastoma diagnosis among 1128 hereditary (i.

Long-term risk of subsequent cancer incidence among hereditary and nonhereditary retinoblastoma survivors.

Background: Increased sarcoma and melanoma risks after hereditary retinoblastoma are well established, whereas less is known about epithelial subsequent malignant neoplasms (SMNs) and risks for multiple (≥2) SMNs.

Methods: Leveraging long-term follow-up and detailed histologic information, we quantified incident SMN risk among 1128 hereditary and 924 nonhereditary retinoblastoma survivors (diagnosed 1914-2006; follow-up through 2016). Standardised incidence ratios (SIRs) compared cancer risk after retinoblastoma relative to the general population.

Rare and Common Genetic Variants, Smoking, and Body Mass Index: Progression and Earlier Age of Developing Advanced Age-Related Macular Degeneration.

Purpose: To determine behavioral and genetic factors associated with incidence and age of progression to advanced age-related macular degeneration (AMD), geographic atrophy (GA), and neovascular disease (NV), and to quantify these effects.

Methods: Longitudinal analyses were conducted among 5421 eyes with nonadvanced AMD at baseline in 2976 participants in the Age-Related Eye Disease Study (mean age of 68.8 (±5.

Eye Diseases Direct Interest to Complement Pathway and Macrophages as Regulators of Inflammation in COVID-19.

Many of the risk factors for developing severe coronavirus disease 2019 (COVID-19) are also risk factors for eye diseases such as age-related macular degeneration (AMD). During the past decades, macrophages and the complement pathway (as a part of the innate immune system) have been identified as important contributors to the development of AMD, and we suggest that these mechanisms are of similar importance for the clinical course of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections. Based on the experience with AMD, we discuss how behavioral factors such as diet, smoking and higher body mass index, as well as genetic determinants such as the complement and immune pathway genes may lead to the overactive inflammatory phenotypes seen in some patients with COVID-19, and may in part explain the heterogeneity of disease manifestations and outcomes.

Genetic Susceptibility, Diet Quality, and Two-Step Progression in Drusen Size.

Purpose: To investigate the relationship of growth in drusen size with genetic susceptibility and adherence to the alternate Mediterranean diet.

Methods: Participants in this analysis had complete ocular, genetic, and dietary data with mean follow-up time of 10.2 years in the Age-Related Eye Disease database.

Choriocapillaris dropout in early age-related macular degeneration.

Loss of choriocapillaris (CC) in advanced age-related macular degeneration (AMD) is well documented but changes in early AMD have not been quantified. Postmortem eyes from donors with clinically documented early AMD were examined in choroidal whole mounts to determine the area, pattern, and severity of CC loss. Choroids from postmortem human eyes without AMD (n = 7; mean age = 86.

Association Between Perifoveal Drusen Burden Determined by OCT and Genetic Risk in Early and Intermediate Age-Related Macular Degeneration.

Purpose: The purpose of this study was to determine associations between macular drusen parameters derived from an automatic optical coherence tomography (OCT) algorithm, nonadvanced age-related macular degeneration (AMD) stage, and genetic variants.

Methods: Eyes classified as early or intermediate AMD with OCT imaging and genetic data were selected (n = 239 eyes). Drusen area and volume measurements were estimated using the Zeiss Cirrus advanced retinal pigment epithelium analysis algorithm in a perifoveal zone centered on the fovea.

Bone and Soft-Tissue Sarcoma Risk in Long-Term Survivors of Hereditary Retinoblastoma Treated With Radiation.

Purpose: Survivors of hereditary retinoblastoma have excellent survival but substantially increased risks of subsequent bone and soft-tissue sarcomas, particularly after radiotherapy. Comprehensive investigation of sarcoma risk patterns would inform clinical surveillance for survivors.

Patients And Methods: In a cohort of 952 irradiated survivors of hereditary retinoblastoma who were originally diagnosed during 1914 to 2006, we quantified sarcoma risk with standardized incidence ratios (SIRs) and cumulative incidence analyses.

Patterns of Cause-Specific Mortality Among 2053 Survivors of Retinoblastoma, 1914-2016.

Background: Previous studies of hereditary retinoblastoma survivors have reported elevated mortality, particularly for sarcomas, compared with the general population. However, cause-specific mortality patterns for long-term hereditary and nonhereditary retinoblastoma survivors are poorly understood.

Methods: Among 2053 retinoblastoma patients diagnosed during 1914-2006 at two major US treatment centers and followed to 2016, we estimated cumulative mortality, standardized mortality ratios (SMRs), and absolute excess risks (AERs) compared with the US general population.

Validated Prediction Models for Macular Degeneration Progression and Predictors of Visual Acuity Loss Identify High-Risk Individuals.

Purpose: To determine predictive factors and risk scores for conversion to overall advanced age-related macular degeneration (AMD), geographic atrophy (GA), neovascular disease (NV), and loss of vision, and to validate the model for AMD in an external cohort.

Methods: Progression to advanced AMD was evaluated using stepwise survival analysis. Risk scores including genetic, demographic, behavioral, and ocular factors were derived for 3 AMD endpoints and were validated and calibrated in a large independent cohort.