Different Phenotypes of Mild Nonproliferative Diabetic Retinopathy with Different Risks for Development of Macular Edema (C-TRACER Study)

Abstract

Purpose: To evaluate diabetic retinopathy (DR) progression in patients with diabetes mellitus type 2 in 2 populations of different ethnicity. Methods: A prospective observational study was designed to follow eyes/patients with mild nonproliferative DR, for 2 years or until the development of central-involved macular edema (CIME), in 2 centers from different regions of the world. A total of 205 eyes/patients fulfilled the inclusion/exclusion criteria and were included in this study. Ophthalmological examinations, fundus photography with RetmarkerDR analysis, and optical coherence tomography were performed at baseline and at 6, 12 and 24 months. Results: Of the 158 eyes/patients that completed this study, 24 eyes developed CIME and 134 eyes were present at the last study visit. Eighty-eight eyes (56.4%) were classified as phenotype A, 49 (31.4%) as phenotype B, and 19 (12.2%) as phenotype C. Phenotype A is associated with a very low risk for development of CIME in comparison with phenotypes B and C. The OR for development of CIME was 19.0 for phenotype B and 25.1 for phenotype C. Conclusion: Eyes in the initial stages of DR show different phenotypes with different risks of progression to ME. The phenotypes associated with increased risks of progression show different distributions in patients of different ethnicities.

Retinopathy Phenotypes in Type 2 Diabetes with Different Risks for Macular Edema and Proliferative Retinopathy

“…A prospective longitudinal observational cohort study (ClinicalTrials.gov identifier: NCT03010397) was designed to follow people with T2D with mild NPDR (one eye per person), graded 20 or 35 on Early Treatment Diabetic Retinopathy Study (ETDRS classification) grading scale [10]. This study is an extension of three previous studies (NCT0114599 [9], NCT01607190 [7], and EudraCT2012-001200-38 [11]). The patients in the study here reported were included according to specified inclusion and exclusion criteria and they were followed for a period of five years or until the time of development of PDR or DME, considering clinically significant macular edema (CSME) and center involved macular edema (CIME).…”

“…Laboratory analyses included HbA 1C concentration, glucose, creatinine, and red blood cell count, white blood cell count, platelet amount, and packed cell volume. Plasma concentrations of lipid fractionation identifying total cholesterol, high-density lipoprotein (HDL), low-density lipoprotein (LDL), and triglycerides, were measured to assess metabolic control The calculation of the sample size was based on previous studies [6][7][8][9], where the existence of three distinct phenotypes of DR progression in T2D was proposed. Their incidence on the DR population was 50% for phenotype A, 30% for phenotype B, and 20% for phenotype C. Individuals with phenotypes B and C were shown to be at higher risk of developing CSME needing treatment, with 11% of phenotype B and 30% of phenotype C developing CSME in a two-year interval.…”

“…Our group has reported on two-year and three-year follow up studies of people with type 2 diabetes (T2D) and mild nonproliferative DR (NPDR) and found marked individual variations in the progression of DR and development of complications [5][6][7][8][9]. Namely, using noninvasive methods, we have identified three different phenotypes of NPDR, based on microaneurysm turnover (MAT) and central retinal thickness (CRT), that appear to be related with different risks for the development of clinically significant macular edema.…”

Subclinical Macular Edema as a Predictor of Progression to Central-Involved Macular Edema in Type 2 Diabetes

“…The baseline results for the 205 eyes/patients included in the study have been published previously [4]. From these, only 158 eyes/patients reached either the study endpoint, CIME (24 eyes/patients), or performed the last study visit (at 24 months) without developing CIME (134 eyes/patients).…”

“…Details of this study have been previously reported [4]. In brief, 205 subjects with diabetes type 2, aged over 35 years, with mild NPDR (levels 20–35, according the Early Treatment Diabetic Retinopathy Study (ETDRS) diabetic retinopathy severity scale) and best-corrected visual acuity (BCVA) > 20/25 on the ETDRS chart, HbA 1C ≤11%, with no previous treatment with laser or anti-VEGF or steroid intravitreal injections, no other retinal vascular disease or glaucoma, or inadequate ocular media and/or pupil dilatation that did not permit good-quality fundus photography, were included in a prospective observational study for 2 years or until the development of CIME, at 2 clinical sites (AIBILI, Coimbra, Portugal, and LV-Prasad Eye Institute, Hyderabad, India).…”