Diabetic Retinopathy Phenotypes of Progression to Macular Edema: Pooled Analysis From Independent Longitudinal Studies of up to 2 Years' Duration.

Purpose To test the risk of progression to macular edema (ME) of different phenotypes of mild nonproliferative diabetic retinopathy (NPDR). Methods Data from 882 patients with mild NPDR, Early Treatment Diabetic Retinopathy Study grades 20 and 35, with no prior laser treatment, enrolled in four separate longitudinal studies during 2007-2015 using the same reading center and with the same inclusion criteria and were pooled for analysis. One eye per patient was followed for up to 2 years until development of ME. Ophthalmological examinations included best corrected visual acuity, color fundus photography (CFP), and optical coherence tomography (OCT). They were performed at baseline and 6 months, with the last visit at 12 or 24 months, depending on the study. The eyes/patients were classified as belonging to phenotypes A, B, and C on the basis of OCT central subfield thickness and microaneurysm activity. Results A total of 882 eyes/patients performed the 12- or 24-month visit or developed ME. Of these 882 eyes/patients that completed the studies, 103 developed ME, 14 from phenotype A (14 of 466: 3.0%), 48 from phenotype B (48 of 164: 18.6%), and 41 from phenotype C (41 of 252: 16.3%). Eyes/patients from phenotypes B and C showed much higher risks for ME development compared with phenotype A: odds ratio (OR) 95% confidence interval (CI): 13.30 (7.09-24.97) P < 0.001; OR (CI): 6.32 (3.36-11.90) P < 0.001, respectively. Conclusions NPDR phenotypes based on microaneurysm turnover and central macular thickness OCT at the 6-month visit using CFP and OCT, both noninvasive examinations, identified the eyes at increased risk of developing ME.