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.