Future glaucoma therapies may target optic nerve, posterior segment

Posterior segment delivery devices could be the key to providing therapeutic benefit for glaucoma patients.

Issue: November 15, 2006

ByErin L. Boyle

Richard A. Lewis, MD

While there are myriad IOP-lowering agents on the market, the future of glaucoma therapeutics could be the use of neuroscience to stimulate growth of the optic nerve to restore sight, according to one expert.

Richard A. Lewis, MD, OSN Glaucoma Section Member, said there are many effective ways to lower IOP through medications, noninvasive laser procedures and surgery. The next logical step in trying to prevent glaucomatous nerve damage, he said, would be to protect the nerves themselves. Future treatments might target the nerve cells in the retina or the optic nerve directly, possibly through the implantation of sustained-release drug delivery devices, he said.

“I think the next big push in glaucoma is going to be on the posterior segment side,” Dr. Lewis told Ocular Surgery News in a telephone interview. “When we finally get a neuroprotective drug, we will need to get a means of delivering it to the retina and optic nerve. Whether that will be orally or through injection or placement posteriorly, it remains to be determined, but we still don’t have the drug yet. All of this is still on the drawing boards.”

He said regenerating nerve cells in the retina or optic nerve could possibly allow patients who have lost their vision to regain it.

“The next big move is going to be finding alternative ways of protecting the optic nerve, the neuroprotective side of it,” he said. “Part of the challenge is to find the right drug. The other part is to deliver it. In terms of IOP-reducing agents, we’ve already got a lot of good options. Not that we can’t improve on it, but I don’t think any IOP-lowering agent will be as exciting as something that can protect the nerve or regenerate the nerve.”

Restoration of the nerve cells will most likely come through pharmaceutical or genetic manipulation rather than surgical transplant, Dr. Lewis suggested. Transplantation seems to be a less promising area for development than a technology that stimulates the regrowth of the patient’s own nerves, he said.

Delivery options

There are no glaucoma implants or drug delivery devices currently in development, although one was used in the past, Dr. Lewis said. A reservoir-like device, Ocusert (CIBA Vision), was inserted once a week under the lower lid to release low-dose levels of pilocarpine. For patients who could tolerate it, it was an excellent delivery source, he said, but there is currently nothing similar on the horizon with more recently developed glaucoma drugs.

Many possibilities exist for delivering drugs into the eye, Dr. Lewis said. For instance, an IOL could be coated with antibiotics to prevent endophthalmitis or with an anti-inflammatory agent to prevent cystoid macular edema after cataract surgery. Other possibilities might be developed to deliver IOP-lowering drugs. However, the ophthalmic pharmaceutical industry has not risen to this challenge yet, he said.

“We have a lot of potential, but it’s an expensive process, and I’m not sure the industry sees much upside in it yet,” he said.

In the future, the use of injectable, long-lasting delivery sources such as gels or plates could prove effective for drug therapy, but there is still “a long distance between what we have now and what some of these ideas are,” Dr. Lewis said.

Role of surgery

Surgical approaches to regeneration of the optic nerve are not likely to be developed, Dr. Lewis said. Current surgical approaches concentrate on reducing IOP, not direct neuroprotection or nerve regeneration, he said.

He said the development of a surgical nerve transplant approach seems unlikely. He compared the nerve complex in the retina to a network of connecting cords hooked up to a computer. In a transplant operation, each of those multiple connecting cords would have to be correctly reconnected. He said the complexity of the operation seems to suggest it would not be practical.

“There are too many connections there. It makes more sense to do a chemical stimulus to regenerate the optic nerve,” he said. “Transplants work when they are straightforward tissue, but this is a network of connecting cables.”

The optimal situation would be to stimulate the nerves to regrow, whether with stem cells or some other method, allowing the nerves to become normal again, Dr. Lewis said.

“That would be a great thing,” he said. “That would solve the whole problem.”

For more information:

Richard A. Lewis, MD, can be reached at 1515 River Park Drive, Sacramento, CA 95815; 916-649-1515; fax: 916-649-1516; e-mail: rlewiseyemd@yahoo.com.

Erin L. Boyle is an OSN Staff Writer who covers all aspects of ophthalmology.