Retinal Sensitivity and Retinal Perfusion in Diabetic Retinopathy.

Importance: Retinal capillary nonperfusion seems crucial in the pathogenesis of sight-threatening diabetic retinopathy (DR); currently, no treatment prevents or reverts it. Objective: To further the understanding of the association between retinal capillary nonperfusion and sensitivity in DR. Design, Setting, and Participants: This prospective, longitudinal cohort study was conducted from April 18, 2018, to September 9, 2024, at a single center in the UK. Participants were followed up for up to 2 years; outcome assessors were masked. Adults (aged ≥18 years) with moderate or severe to very severe nonproliferative or proliferative DR with less than high-risk characteristics; at least 1 eye naive to treatment; no other retinal disorders; who were able to provide informed consent; and who were willing undergo retinal imaging were eligible for inclusion. Data analysis was performed from September 2024 to April 2025. Main Outcomes and Measures: The primary outcome was the association between retinal sensitivity (110° projection perimetry) and retinal perfusion (ultra-widefield angiography) at baseline and changes at 1 and 2 years in the study eye. Results: Of 66 people approached, 50 were eligible and recruited, and 44 individuals with at least 1 perimetric examination were included. Mean (SD) participant age was 52.1 (12.2) years, and 13 participants (29%) were female. Median hemoglobin A1c was 75.5 mmol/mol (9.1% of total hemoglobin [to convert from percentage of total hemoglobin to proportion of total hemoglobin, multiply by 0.01]); mean (SD) best-corrected visual acuity letter score was 85.7 (4.7) (Snellen equivalent, 20/20). Mean retinal sensitivity deficit at baseline was associated with perfusion status, with larger deficits in nonperfused areas (n = 354; 11.8 dBs; 95% CI, 10.8-12.8) compared to perfused areas (n = 2092; 6.6 dB; 95% CI, 5.1-8.2; P < .001). Only age correlated positively with sensitivity deficit (estimate, 0.2; 95% CI, 0.1-0.3; P = .006). A deficit of 5 dB or greater occurred in 711 of 2092 (34%) perfused areas; 105 of 354 (30%) nonperfused areas had normal sensitivity. Rates of sensitivity deficit change in perfused and nonperfused areas from baseline to 1 year were -0.20 dB/mo (95% CI, -0.24 to -0.16) and -0.28 dB/mo (95% CI, -0.41 to -0.15) (perfused vs nonperfused, P = .22), respectively (1464 areas); from baseline to 2 years, rates were -0.16 dB/mo (95% CI, -0.20 to -0.12) and -0.34 dB/mo (95% CI, -0.47 to -0.21) (perfused vs nonperfused, P = .007), respectively (542 areas). Conclusions and Relevance: In this longitudinal cohort study, although retinal capillary perfusion status was associated with function, sensitivity loss occurred in some perfused areas and normal function in some nonperfused areas; sensitivity deficit decreased over time (approximately 45% in the first year) despite poor glycemic control and high DR grades. These findings should be considered for the management of people with DR and the design of clinical trials.