Correlation between Diabetic Retinopathy Severity and Oxygen Metabolism in Patients with Diabetic Macular Edema during Treatment with Intravitreal Aflibercept

Purpose: To attribute data on changes in diabetic retinopathy (DR) severity during treatment of diabetic macular edema (DME) with vascular endothelial growth factor inhibitors (anti-VEGF), this study aimed to (1) examine the correlation between oxygen saturations in retinal vessels and the number of DR lesions on ultra-wide field color fundus photographs prior to anti-VEGF treatment and (2) compare changes in oxygen saturations in retinal vessels with changes in the number of DR lesions after a loading dose of three monthly intravitreal injections of 2.0 mg of aflibercept. Methods: This 3-month prospective study included 37 eyes of patients with DME and varying severity of peripheral DR lesions. DR lesions were graded on wide field images and retinal oxygen saturations were evaluated by retinal oximetry. Patients were then treated with three monthly intravitreal injections of 2 mg aflibercept and wide field imaging and retinal oximetry were repeated 4 weeks after the last injection. Patients with proliferative DR or previous panretinal photocoagulation were excluded. Results: Baseline retinal arteriolar oxygen saturation increased with increasing DR severity and numbers of microaneurysms, hemorrhages, and cotton wool spots (p = 0.03, 0.01, 0.03, and <0.001), while no correlation between the severity of DR lesions and retinal venular oxygen saturation was found. After treatment with intravitreal aflibercept, the severity of DR lesions significantly reduced, while retinal arteriolar and venular oxygen saturation as well as the arteriolar-venular difference remained unchanged (95.5 vs. 95.8%, p = 0.44; 62.9 vs. 64.5%, p = 0.08; 32.5 vs. 31.4%, p = 0.33). Conclusion: This study demonstrated that structural DR lesions correlate with retinal arteriolar oxygen saturation in patients with DME prior to anti-VEGF treatment and that improvement in the severity of DR lesions can occur without corresponding changes in retinal oxygen metabolism during intravitreal therapy. Our results suggest that DR severity on color fundus photographs should be interpreted with caution once intravitreal therapy is initiated.