Retinal Sensitivity and Retinal Perfusion in Diabetic Retinopathy

TL;DR

This study finds that retinal capillary nonperfusion is linked to reduced retinal sensitivity in people with advanced diabetic retinopathy, with sensitivity loss occurring in both perfused and nonperfused areas over time.

Contribution

The study reveals that retinal sensitivity deficits decrease over time in both perfused and nonperfused areas, despite poor glycemic control and high disease severity.

Findings

Retinal sensitivity deficits were larger in nonperfused areas compared to perfused areas at baseline.

Sensitivity deficit rates declined more rapidly in nonperfused areas over 2 years compared to perfused areas.

Normal retinal function was observed in some nonperfused areas, suggesting complex functional dynamics.

Abstract

Is there an association between retinal capillary nonperfusion and retinal sensitivity in people with higher stages of diabetic retinopathy, and how does this association change over time?

In this longitudinal cohort study including people with moderate nonproliferative through less than high-risk proliferative diabetic retinopathy (n = 44), retinal capillary nonperfusion was associated with reduced retinal sensitivity, with a reduction in functional deficits occurring in both perfused and nonperfused retinal areas during the follow-up of up to 2 years.

These findings further the understanding of diabetic retinopathy and should be considered in the design of interventional trials for capillary nonperfusion.

Retinal capillary nonperfusion seems crucial in the pathogenesis of sight-threatening diabetic retinopathy (DR); currently, no treatment prevents or reverts it.

To further the understanding of the association between retinal capillary nonperfusion and sensitivity in DR.

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.

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.

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).

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.

This longitudinal cohort study conducted in the UK explores the association between retinal capillary nonperfusion and sensitivity in diabetic retinopathy.

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