Three Different Phenotypes of Mild Nonproliferative Diabetic Retinopathy With Different Risks for Development of Clinically Significant Macular Edema

PURPOSE. To identify different phenotypes of nonproliferative diabetic retinopathy (NPDR) and their progression to clinically significant macular edema (CSME). METHODS. A prospective observational study was designed to follow eyes/patients with diabetes type 2 and NPDR with no prior laser treatment for 2 years or until development of CSME. A total of 410 patients, one eye per patient, fulfilled the inclusion/exclusion criteria and were included in the study. Ophthalmological examinations, including BCVA, fundus photography with Retmarker analysis, and optical coherence tomography (OCT), were performed at baseline, month 6 and month 24, or before laser treatment. Hierarchical cluster analysis was used to identify homogeneous subgroups and clinically significant thresholds of the data collected. RESULTS. A total of 376 eyes/patients performed the 6-month visit and were considered for cluster analysis. This mathematical method identified three different phenotypes based on statistically significant differences for the microaneurysm (MA) turnover and for the central retinal thickness (RT): phenotype A (low MA turnover and normal RT, 48.1%); phenotype B (low MA turnover and increased central RT, 23.2%); and phenotype C (high MA turnover, 28.7%). From the 348 eyes/patients that reached the study end point or completed the 24-month visit, 26 developed CSME: 3 from phenotype A (1.8%), 7 from phenotype B (8.5%), and 16 from phenotype C (16.2%). Eyes/patients from phenotype C showed a higher risk for CSME development (OR 3.536; P < 0.001). CONCLUSIONS. Hierarchical cluster analysis identifies three different phenotypes of NPDR based on MA turnover and central macular thickness. Eyes/patients from phenotype C show a higher risk for the development of CSME. (ClinicalTrials.gov number, NCT00763802.)