Veterans Affairs

Histone deacetylase inhibitor for improved glaucoma surgery outcomes

An alternative to drugs that have adverse side effects

Medical & Biotechnology

The Department of Veterans Affairs has funded the research and development of a novel technology that has the potential to profoundly improve ocular surgery outcomes. The patent-pending technology is available for product development.

A major deterrent to the success of glaucoma filtration surgery is caused by aberrant post-operative wound healing resulting in excessive ECM synthesis leading to fibrosis over filtering bleb. Image: National Eye Institute, National Institutes of Health

Glaucoma is a leading cause of irreversible blindness worldwide. It affects more than 2.7 million individuals age 40 or older in the United States — almost 2% of this population.

The disease is caused by abnormally high intraocular pressure, which can be treated with medications including topical pharmaceutical solutions.

However, a significant portion of the patient populations does not respond to pharmaceutical treatment of glaucoma and glaucoma filtration surgery is performed.

A complication of glaucoma filtration surgery is excessive wound healing, which leads to fibrosis and collagen deposit at the surgical site, which can stop the pressure reducing benefit.

To deal with this, drugs such as mitomycin C (MMC) and 5-fluoroacil (5-FU) are used to reduce scar tissue formation and while effective, they are associated with negative side effects including widespread cell death, increased intraocular pressure, inflammation of the interior of the eye (endophthalmitis), and other complications.

In order to address the above, VA researcher Rajiv Mohan has investigated the use of suberoylanilide hydroxamic acid (SAHA) as a safer alternative.

This compound is a histone deacetylase inhibitor (HDACi) known to modulate gene expression and have antifibrotic effects in animal models. One such HDACi, Merck’s Zolinza, is FDA approved to treat non-Hodgkin Lymphoma.

But unlike other anti-fibrotic agents, SAHA is relatively nontoxic and does not affect the viability or proliferation of corneal fibroblasts.

Preliminary data indicate that SAHA greatly reduces postoperative scarring. SAHA-treatment after glaucoma filtration surgery shows no signs of edema, corneal opacity, endophthalmitis, or cataract formation. Morphometric analysis of SAHA-treated eyes shows higher bleb (the tissue over the drain sight) length, bleb area, lower intraocular pressure, and decreased vascularity compared to control.

This technology may also prevent or reduce corneal haze formation after photorefractive keratectomy surgery.

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