Response to Comment on Gange et al. Incidence of Proliferative Diabetic Retinopathy and Other Neovascular Sequelae at 5 Years Following Diagnosis of Type 2 Diabetes. Diabetes Care 2021;44:2518–2526

We appreciate the comments made by Rigalleau et al. (1) and their interest in our article (2), which quantified the incidence of proliferative diabetic retinopathy (PDR) and other neovascular complications within the first 5 years following an index diagnosis of type 2 diabetes. Further, we identified risk factors for developing PDR within 5 years of being diagnosed with type 2 diabetes, including hemoglobin A_1c (HbA_1c), renal disease, peripheral circulatory disorders, neurological disease, and older age. As has been previously reported, the diagnosis of type 2 diabetes may be delayed relative to its onset.

Rigalleau et al. (1) have reported on the use of skin autofluorescence to assess long-term metabolic memory, which may reflect glycemic levels over the preceding years. Skin autofluorescence (SAF) takes advantage of the fluorescent properties that some advanced glycation end products have and allows for a noninvasive marker of glycemic memory in type 2 diabetes. Their group currently reports a correlation between SAF and vision-threatening retinopathies, and this confirms findings by other groups that SAF correlates with diabetic retinopathy severity (3,4). Of note, SAF may be difficult to interpret in certain patients; for instance, high SAF may not correlate with retinopathy in those with renal insufficiency (5). We agree SAF warrants further study to assess its effectiveness in potentially triaging patients at high risk for macro- and microvascular complications from diabetes.

Interestingly, Rigalleau et al. (1) found no association between sex, age, BMI, arterial hypertension, lipid levels, or HbA_1c levels and sight-threatening retinopathies. This may warrant further investigation and confirmation, as these have been reported in multiple population-based studies to be relevant microvascular risk factors for diabetic retinopathy (6).

Rigalleau et al. (1) included an analysis of diabetic macular edema (DME) in their series of sight-threatening retinopathies. We agree that DME is a significant cause of vision loss among patients with diabetes. Because of this, we have planned future work specifically looking at the incidence of DME in the first 5 years after diagnosis with diabetes and risk factors associated with the development of DME.

Taken together, our studies highlight the importance of screening for diabetic retinopathy at the time of diagnosis of type 2 diabetes, given that patients may have asymptomatic hyperglycemia for years before their diagnosis of diabetes. Further, given a subset of patients with type 2 diabetes will develop PDR and other neovascular complications within 5 years of diagnosis, the study underscores the importance of at least yearly fundus exams following the initial baseline exam.