324-OR: Characterization of Aqueous Retinol Binding Protein 3 Concentrations and Diabetic Retinopathy Progression in Type 1 and Type 2 Diabetes

Joslin Medalist Study identified Retinol Binding Protein 3 (RBP3) as a potential protective factor against advanced diabetic retinopathy (DR) in the vitreous and retina of people with type 1 diabetes for 50 years or longer. There is emerging interest in DR biomarker identification in aqueous due to its easier access compared to vitreous. Quantitive aqueous RBP3 concentration, in a pilot study, correlated inversely with DR severity, but positively with vitreous RBP3, suggesting it may be a clinically useful DR biomarker. This study measured RBP3 concentration in 153 aqueous samples from patients undergoing cataract surgery at the Joslin Beetham Eye Institute to characterize RBP3 concentrations in relation to DR progression. DR progression was defined as ≥2-step worsening on the Early Treatment Diabetic Retinopathy Study severity scale. At baseline, DR severity distribution was 36% no DR, 38% mild and 26% moderate DR. The average follow-up was 5.6±3.6yrs. Aqueous RBP3 concentration was highest in patients with no visible signs of DR (median 2.1nM) compared to mild and moderate DR (1.5nM, P=0.04). There was no significant difference between aqueous RBP3 concentration in those with type 1 or type 2 diabetes (P=0.55). DR progression was present in 28.1% (N=45). Elevated aqueous RBP3 concentration was associated with less frequent diabetic macular edema (Odd Ratio (OR) 0.20, 95% Confidence Interval (CI) 0.07;0.56, P=0.002). In unadjusted analyses, less DR progression was associated with older age (OR 0.87, CI 0.79;0.96, P=0.006), lower HbA1c (OR 1.88, 95% CI 1.01;3.49, P=0.05), and elevated RBP3 concentration (OR 0.51, 95% CI 0.28;0.93, P=0.029). The performance of an Area Under the Curve model including RBP3 was 0.69 for predicting DR progression. These findings indicate that elevated aqueous RBP3 concentration is associated with less DR progression, supporting its potential as a protective factor and retinal-specific DR biomarker. Disclosure T. Chokshi: None. W. Fickweiler: None. S. Jangolla: None. I. Wu: None. J.K. Sun: Research Support; Optovue, Boehringer-Ingelheim, Novo Nordisk, Roche Pharmaceuticals. Other Relationship; Roche Pharmaceuticals. Research Support; Physical Sciences, Inc, Boston Micromachines. L.P. Aiello: Advisory Panel; Novo Nordisk. Stock/Shareholder; Kalvista. Other Relationship; Optos. Consultant; Ceramedix. G.L. King: None. Funding American Diabetes Association (7-21-PDF-022); National Eye Institute (R01EYE26080-01), the National Institute of Diabetes and Digestive and Kidney Diseases and National Institutes of Health (DP3- DK-094333-01); JDRF (17-2013-310); the Dianne Nunnally Hoppes Fund; the Beatson Pledge Fund