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 progression (DR).

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 ≥2-step 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 non-proliferative diabetic retinopathy (NPDR), and 23% moderate NPDR. Aqueous RBP3 decreased from a median of 2.1nM [IQR 0.8-3.4nM] in eyes with no DR to 1.5nM [0.8-3.8nM] in eyes with mild-moderate NPDR (P=0.047). There was no significant difference between aqueous RBP3 levels in those with type 1 or type 2 diabetes. Elevated RBP3 (β -0.701, 95% CI -1.151--0.250, P=0.002) was associated with no DME history. With mean follow up of 5.5 ± 3.6 years, elevated RBP3 at baseline was associated with less subsequent DR progression (OR 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 adding RBP3 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.