Golnaz Javey¹, Stephen G. Schwartz², Harry W. Flynn Jr², Lloyd Paul Aiello³ and Matthew J. Sheetz⁴

¹Department of Ophthalmology, Baylor College of Medicine, 7200-B Cambridge Street, Houston, TX 77030. ²Department of Ophthalmology, Bascom Palmer Eye Institute, University of Miami Miller School of Medicine, 900 Northwest 17th Street, Miami, FL 33136. ³Beetham Eye Institute, Joslin Diabetes Center, and Department of Ophthalmology, Harvard Medical School, One Joslin Place, Boston, MA 02215. ⁴Lilly Research Laboratories, Eli Lilly Corporate Center, Indianapolis, IN 46285.

Abstract

Ruboxistaurin (Eli Lilly, Indianapolis, IN), an orally active inhibitor of the β isoform of protein kinase C (PKC), has been studied as a systemic treatment for diabetic retinopathy. PKC-β appears to be overactivated in response to hyperglycemia. This overactivation associates with various pathological effects within the retinal vascular system, including ischemia, vascular leakage, and angiogenesis. Several randomized clinical trials of ruboxistaurin have been performed. In most trials, the primary outcomes were not achieved. Analysis of secondary outcomes data from these trials has demonstrated some evidence of safety and efficacy in the treatment of diabetic retinopathy. At this time, ruboxistaurin has not received approval from the US Food and Drug Administration.