Predicting Response of Vitreous Hemorrhage after Intravitreous Injection of Highly Purified Ovine Hyaluronidase (Vitrase) in Patients with Diabetes

Abstract

To develop a predictive model for patients with diabetes who are most likely to have vitreous hemorrhage clearing by 3 months after a single, intravitreous injection of highly purified, preservative-free, ovine hyaluronidase (Vitrase; ISTA Pharmaceuticals, Inc., Irvine, CA). Post hoc data analysis was performed on two randomized, double-masked, placebo-controlled, phase 3 clinical trials of a single intravitreous injection of Vitrase for severe vitreous hemorrhage. Vitreous hemorrhage density was scored using a 0 to 4 vitreous hemorrhage grading scale in 12 radial segments of the fundus ("clock hours"). Reduction in total hemorrhage point score (DeltaTHPS) between baseline and 1 month after injection was analyzed as a predictor of vitreous hemorrhage outcome at 3 months. A strong predictive model was demonstrated by receiver operating characteristic (ROC) curve analysis; area under the curve (AUC) = 0.845 (P < 0.0001). The DeltaTHPS was higher in hyaluronidase-treated subjects than in saline-treated control subjects. Median DeltaTHPS was 8.0 and 6.0 in subjects treated with 55 IU (68 USP) and 75 IU (93 USP) of hyaluronidase respectively, versus 2.0 in saline control subjects (P < 0.0001). discussion. The DeltaTHPS at 1 month provides quantitative guidance for predicting the outcome of a single intravitreous ovine hyaluronidase injection in patients with diabetes and severe vitreous hemorrhage (ClinicalTrials.gov numbers, NCT00198510 and NCT00198497).