Nikhil Bommakanti, MD
Wills Eye Hospital, Philadelphia, PA
Ward Fickweiler, MD, PhD was awarded one of two Fellowship Research Awards at the Retina Society Annual Meeting on Thursday, September 12, 2024 for his project entitled: Aqueous Retinol Binding Protein 3 Concentrations as a Biomarker for Predicting Diabetic Retinopathy Progression in Type 1 and Type 2 Diabetes.
Dr. Fickweiler is a Postdoctoral Fellow at Joslin Diabetes Center at Harvard Medical School. He completed his medical school, ophthalmology residency, and Ph.D. training at the University of Groningen in the Netherlands.
Dr. Fickweiler started by explaining the need for protective biomarkers and treatments for early diabetic retinopathy (DR), which is a growing public health burden. He introduced the Joslin Medalist Study, which enrolls individuals who have lived with type 1 diabetes for 50 years or more and tracks their clinical outcomes. Approximately 40% of the participants had no DR or mild NPDR, and those who did not develop PDR after the first 20 years generally did not experience DR worsening. These findings suggest there may be a protective factor at play for certain type I diabetics.
He reviewed how he and others previously determined that photoreceptor-secreted Retinol Binding Protein 3 (RBP3) is a possible protective factor, as its concentration in the retina, vitreous, and aqueous is negatively correlated with DR severity and positively correlated with retinal thickness. RBP3 is involved in transporting retinoids between the RPE and the photoreceptors, and is therefore critical to the visual cycle. In fact, mutations in the RBP3 gene cause photoreceptor loss in mice and can result in RP in humans.
The purpose of his study was to evaluate the predictive potential of aqueous RBP3 to identify eyes with early DR that are at increased risk for DR progression. He prospectively measured aqueous RBP3 concentration in 153 patients (31 with type 1 diabetes and 122 with type 2 diabetes) undergoing cataract surgery, collected clinical characteristics, and determined DR progression, which he defined as a 2 step or more worsening on the ETDRS severity scale. He found that RBP3 was highest in patients with no visible signs of DR compared to mild and moderate DR, that higher aqueous RBP concentration was associated with less DME and a lower risk of DR worsening, and that the predictive ability of certain models for DR worsening was improved when adding RBP3 to the model.
Dr. Fickweiler concluded by stating that RBP3 is the first identified protective factor for DR that could potentially be used as a biomarker for DR severity and progression. Furthermore, it may be a promising VEGF-independent target for DR.
