Source: DGNews  |  Posted 2 years ago

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