Novel strategies considered for treating, preventing RVO

November 4, 2014

The advent of anti-vascular endothelial growth factor (VEGF) therapy has been a tremendous advance for the treatment of retinal vein occlusion (RVO), but many other opportunities exist, said Joan W. Miller, MD.

Boston-The advent of anti-vascular endothelial growth factor (VEGF) therapy has been a tremendous advance for the treatment of retinal vein occlusion (RVO), but many other opportunities exist, said Joan W. Miller, MD.

Understanding of the events involved in alteration of the blood-retinal-barrier that leads to macular edema after RVO provides a basis for identifying potential therapeutic interventions. In that regard, Dr. Miller-Henry Willard Williams Professor of Ophthalmology, chief and chair of ophthalmology, Harvard Medical School, Boston, MA-discussed a role for treatments targeting cellular junction proteins and metabolic alterations.

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Pertaining to the latter, Dr. Miller noted that work being led by her colleague, Demetrios G. Vavvas, MD, PhD, is focusing on aminoimidazole carboxamide ribonucleotide (AICAR) as a possible treatment for macular edema. AICAR, currently being investigated as a cardioprotectant in phase III clinical trials, is a small-molecule AMP analogue that activates AMP kinase.

Interest in AICAR as a treatment for macular edema relates to evidence suggesting that AMP kinase has a protective role for vascular permeability. Results from studies investigating AICAR show that it suppresses endocytosis, inhibits MMP-9, and inhibits VEGF-induced vascular tube formation.

 

In addition, AICAR has been shown to promote endothelial and pericyte cell survival as well as to prevent aging changes in retinal neurons, Dr. Miller said.

Neuroprotection strategies are also of interest for treatment of RVO since photoreceptor degeneration is the ultimate cause of vision loss after RVO. Findings from studies in models of retinal disease showing that there are redundant cell death pathways indicate that preservation of photoreceptors may require combination therapy targeting both apoptosis and programmed necrosis, Dr. Miller said.

In addition, stem cell therapy may have a role for delivery of trophic factors or for integration and repopulation of retinal tissue.

Dr. Miller also proposed the possibility of using new diagnostic technologies to identify patients at risk for RVO.

“It would be a great advance if we could use new technologies to detect blood flow abnormalities or vessel wall changes before the onset of clinically evident RVO,” she said.