Retinal Blood Flow as a Predictive Biomarker of Retinopathy Progression and Systemic Co-Morbidities in Patients With Diabetes: A 15 Year Longitudinal Study

Abstract

Purpose: : To assess retinal blood flow (RBF) as a predictor of diabetic retinopathy (DR) progression, ocular outcomes, and systemic co-morbidities over the ensuing 15 years.

Methods: : RBF was measured in 137 eyes of 77 diabetic subjects using scanning laser ophthalmoscope fluorescein angiography dye dilution technique. Subsequent data including dates of DR progression, laser treatments, and systemic co-morbidities were collected retrospectively on standardized forms by observers masked to RBF outcome. Early Treatment Diabetic Retinopathy Study clinical levels of DR severity were assessed at baseline and last follow-up.

Results: : Subjects had a mean follow-up of 11.4 + 2.8 [range: 1.9, 15.5] yrs (75% ≥ 10 yrs), duration of DM 12.2 + 10.1 [1.4, 43.4] yrs, age 38.7 + 12.1 [19.4, 66.2] yrs, and hemoglobin A1c 7.6 + 1.2 [4.9, 10.6] %. The cohort was 55% male, and 78% type 1 DM. Baseline median RBF was 37.8 (Q1, Q3: 26.3, 76.5) AU. No-mild DR was present in 91.2% of eyes at baseline and in 66.4% at last visit. RBF was significantly higher in eyes with more severe DR at endpoint (49.3 vs 34.8 AU, p = 0.02). Risk of progression to more advanced DR during follow-up was also associated with higher RBF (HR=1.01, p < 0.001). Patients with higher median RBF were more likely to have any microvascular complication (DR, neuropathy, or nephropathy) (69.7 vs 41.8 AU, p = 0.02) and to undergo macular laser (65.1 vs 41.8 AU, p = 0.03). Subjects with systemic co-morbidities, including cardiovascular disease, hyperlipidemia, or hypertension had consistently higher median RBF than patients without (53.9 vs 41.8, 60.4 vs 38.5, and 51.9 vs 39.0 AU), as did eyes that underwent panretinal photocoagulation (58.0 vs 40.4 AU), although these differences were not statistically significant.

Conclusions: : These findings suggest that faster baseline RBF might be used as a surrogate biomarker for progression of DR, need for subsequent laser treatment, and the presence of microvascular complications over the ensuing decade. If these findings are confirmed in a prospective manner within a larger cohort of subjects, they could have a significant impact on the manner in which novel therapies for DR are evaluated as well as on the future counseling and management of patients with diabetes.

Keywords: diabetic retinopathy • clinical (human) or epidemiologic studies: risk factor assessment • clinical (human) or epidemiologic studies: outcomes/complications