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

Our group reported that three diabetic retinopathy (DR) phenotypes: A, characterized by low microaneurysm turnover (MAT < 6) and normal central retinal thickness (CRT); B, low MAT (<6) and increased CRT, and C, high MAT (≥6), present different risks for development of macular edema (DME) and proliferative retinopathy (PDR). To test these findings, 212 persons with type 2 diabetes (T2D) and mild nonproliferative retinopathy (NPDR), one eye per person, were followed for five years with annual visits. Of these, 172 completed the follow-up or developed an outcome: PDR or DME (considering both clinically significant macular edema (CSME) and center-involved macular edema (CIME)). Twenty-seven eyes (16%) developed either CSME (14), CIME (10), or PDR (4), with one eye developing both CSME and PDR. Phenotype A showed no association with development of vision-threatening complications. Seven eyes with phenotype B and three with phenotype C developed CIME. Phenotype C showed higher risk for CSME development, with 17.41 odds ratio (p = 0.010), compared with phenotypes A + B. All eyes that developed PDR were classified as phenotype C. Levels of HbA_1c and triglycerides were increased in phenotype C (p < 0.001 and p = 0.018, respectively). In conclusion, phenotype C identifies eyes at higher risk for development of CSME and PDR, whereas phenotype A identifies eyes at very low risk for vision-threatening complications.