Characterization and relevance of different diabetic retinopathy phenotypes

The natural history of initial lesions occurring in the diabetic retina has particular relevance for our understanding and management of diabetic retinal disease, one of the major causes of vision loss in the Western world. Diabetic retinal lesions are still reversible at the initial stage of mild nonproliferative diabetic retinopathy, opening real opportunities for effective intervention. Four main alterations characterize the early stages of diabetic retinopathy: microaneurysms/hemorrhages, alteration in the blood-retinal barrier, capillary closure, and alterations in the neuronal and glial cells of the retina. These alterations may be monitored by red dot counting on eye fundus images, by fluorescein methodologies and retinal thickness measurements. A combination of these methods through multimodal macula mapping has contributed to the identification of three different phenotypes, showing different patterns of evolution: pattern A, including eyes with reversible and relatively little abnormal fluorescein leakage, a slow rate of microaneurysm formation and normal foveal avascular zones (FAZ); pattern B, including eyes with persistently high leakage values, high rates of microaneurysm formation and normal FAZ; pattern C, including eyes with variable leakage, high rates of microaneurysm formation and abnormal FAZ. The identification of different phenotypes opens the door for genotype characterization, development of targeted treatments and personalized approaches in management strategy.