Reduced Aqueous Retinol-Binding Protein 3 Concentration Is Associated With Diabetic Macular Edema and Progression of Diabetic Retinopathy

OBJECTIVE To evaluate the association of aqueous retinol-binding protein 3 (RBP3) with history of diabetic macular edema (DME) and diabetic retinopathy (DR) progression. RESEARCH DESIGN AND METHODS RBP3 concentration was measured by ELISA in aqueous from patients undergoing cataract surgery at Joslin Diabetes Center. DR progression was defined as two-step or more worsening on the Early Treatment Diabetic Retinopathy Study severity scale, and DME history was determined by clinical diagnosis. RESULTS In 153 eyes (31 with type 1 and 122 with type 2 diabetes; n = 149 patients), 37% had no signs of DR, 40% had mild nonproliferative DR (NPDR), and 23% had moderate NPDR. Aqueous RBP3 decreased from a median of 2.1 nmol/L (interquartile range 0.8–3.4) in eyes with no DR to 1.5 nmol/L (0.8–3.8) in eyes with mild-to-moderate NPDR (P = 0.047). The difference between aqueous RBP3 levels in those with type 1 or type 2 diabetes was not significant. Elevated RBP3 (β = −0.701, 95% CI −1.151 to 0.250, P = 0.002) was associated with no DME history. With a mean follow-up of 5.5 ± 3.6 years, elevated RBP3 at baseline was associated with less subsequent DR progression (odds ratio 0.51, 95% CI 0.28–0.93, P = 0.03). In multivariable analyses, RBP3 remained significantly associated with a DR progression and history of DME. A 5% improvement was seen in the area under the curve when RBP3 was added to clinical models for predicting DR progression (P < 0.05). CONCLUSIONS This study suggests that aqueous RBP3 may be an important protective factor, the first neuroretinal-specific biomarker of DME or DR progression, and a possible therapeutic target.