Diabetic Retinopathy Genomics Study (DRGen) - Genetic Biomarkers of Diabetic Retinopathy

Using a well-defined, clinically supported phenotypic strategy, we seek to better understand the role of common and rare genetic variants in the progression of diabetic retinopathy (DR). Whole exome/whole genome sequencing (WES/WGS) was used to systematically search the human genome to detect DR susceptibility genes or genes that protect people from developing advanced DR. Clinical data and bio specimens were obtained from clinically defined DR phenotypes such as, (i) No/Mild NPDR (non-proliferative DR) with a subset of extreme phenotype, ii) Diabetic macular edema (DME) alone and iii) Proliferative diabetic retinopathy (PDR) alone. In this ongoing comprehensive genomic study, we wish to i) Identify potential common and rare variants that may influence the phenotypic differentiation of DR into DME or PDR, ii) Define genetic variants stratified based on the "extreme phenotype," and iii) Characterize genetic factors that determine the differential response to anti-VEGF drugs in DME patients. Definition of Diabetic Retinopathy and classification of groups Study 1. Proliferative diabetic retinopathy (PDR). Anybody showing evidence of retinal neovascularization on the disc (NVD) or elsewhere (NVE) with or without pre-retinal and vitreous hemorrhage will be considered PDR. We will include only those "active" PDR patients. The total number of consented subjects in this study is 182. Study 2. Isolated Phenotype: Varied response with anti-VEGF treatment is a significant limiting factor for better clinical outcomes. We quantify the response to anti-VEGF treatment based on visual acuity changes and anatomic features of DME assessed by optical coherence tomography (OCT). Depending on the response at one month following three monthly intravitreal anti-VEGF injections, we have observed two phenotypes: 1) Good responders: Participants were considered "good responders" if the anatomical outcome to anti-VEGF treatment resulted in a significant reduction of baseline central retinal thickness (CRT) > 25% after three anti-VEGF injections. 2) Poor Responders: Participants were classified as "poor responders" if the outcome of anti-VEGF treatment resulted in a reduction of CRT < 20% or in any increase in CRT after three monthly injections. The total number of consented subjects in this study is 17. ]]>
Inclusion CriteriaDiabetes mellitus (Type 1 or 2 DM)Exclusion Criteria Participants were excluded if any of the following were present: Study 1. Proliferative diabetic retinopathy (PDR) History of unstable blood glucose over a longer time period (HbA1c >12%). Prevalence of epiretinal membrane (ERM).Branch retinal vein occlusion (BRVO)/central retinal vein occlusion (CRVO) or advanced age-related macular edema (ARMD) in the study eye History of focal laser for DME High myopia, advanced glaucoma, ocular ischemic syndrome Major eye surgery/cataract surgery within three months Study 2. Isolated Phenotype History of unstable blood glucose (HbA1c >12%) Macular edema due to epiretinal membrane (ERM) Presence of BRVO, CRVO, advanced age-related macular degeneration (ARMD), high myopia, or advanced glaucomaParticipants was included in the study if they had a diagnosis of center-involving DME. ]]>