By Fred Gebhart
SAN FRANCISCO -- October 27, 2009 -- Glaucoma management continues to evolve and may include lifestyle changes and targeting changes in mitochondrial activity, according to a report presented here at the 2009 Joint Meeting of the American Academy of Ophthalmology and Pan-American Association of Ophthalmology (AAO-PAAO).
A disease that was recently defined by uncontrolled intraocular pressure is now defined by neuropathy and loss of visual function. Soon, glaucoma is likely to considered and treated as a combination of clinical, biological, epidemiological, and genetic factors.
"We propose that glaucoma can be diagnosed when a progressive structural or functional change occurs with the disk, retinal nerve fibre layer, or visual field," said Robert Weinreb, MD, Hamilton Glaucoma Center, University of California, San Diego, San Diego, California, on October 25. "It all depends on our improving understanding of the biology of glaucoma."
The clinical definition of glaucoma will come to include specific progressive optic neuropathy with characteristic structural damage and specific visual field loss, according to Dr. Weinreb. The biological definition will include specific pathophysiological changes in retinal ganglion cell axons, and epidemiological disease will be defined by established and visually significant organ damage.
Genetics will play a growing role as more genes associated with glaucoma are identified. A specific genetic anomaly has been linked to an increased risk for primary open-angle glaucoma in the Black population of Barbados, Dr. Weinreb noted. Other genetic links are being explored.
The mechanisms responsible for the cellular damage collectively known as glaucoma remain unclear. Multiple mechanisms exist, including oxidative damage to retinal ganglion cells, changes to microcirculation, changes in cytokine expression and activity, and nitric oxide levels. More effective imaging techniques will help elucidate and counteract these mechanisms. Clinicians will routinely image and count individual retinal ganglial cells to determine the type and extent of damage.
A broader concept of glaucoma that includes the entire visual pathway is expected to emerge. Many clinicians still regard glaucoma as a disease of the eye.
"Glaucoma is a neurodegenerative disorder," said Dr. Weinreb. "The primary effect may be in the brain stem or in the visual cortex of the brain. We need better imaging techniques, tests to measure visual cortex functioning, and methods to predict retinal ganglial cell death."
For now, Dr. Weinreb noted, clinicians focus on intraocular pressure largely because it is the only known risk factor for glaucoma that can be modified. As the disease is better understood, new risk factors are being identified and new treatments developed. Skin cells can now be transformed into retinal ganglial cells, offering the potential to transplant portions of the optic nerve. Small-molecule agents under development may enable clinicians to regrow optic nerve cells in place, eliminating the need for transplants.
In the shorter term, treatments that incorporate lifestyle changes such as exercise, diet, smoking cessation, and weight loss are likely to arise. Changes in mitochondrial activity are another attractive target.
"We have compelling evidence of changes in the mitochondria associated with glaucoma," Dr. Weinreb said. "This could be a causal factor in the development or progression of glaucoma and offer a new target for regulation."
[Presentation title: Miniconference: The Future of Glaucoma Management. Abstract SYM 55]
E-Mail this DGDispatch to a colleague
