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Genetic medicine and AMD treatment; genetic screening and glaucoma

CHICAGO Genetic medicine is the focus of two presentations at today's Scientific Program of the 2010 American Academy of Ophthalmology (AAO) Middle East-Africa Council of Ophthalmology (MEACO) Joint Meeting. The AAO-MEACO meeting is in session October 16 through 19 at McCormick Place, Chicago. It is the largest, most comprehensive ophthalmic education conference in the world.

Seeking Genetics-Specific Treatments for Age-Related Macular Degeneration

In the past decade ophthalmologists gained a powerful tool to control vision-damaging "wet" age-related macular degeneration (wet AMD): anti-vascular endothelial growth factor (anti-VEGF) medications. Anti-VEGF drugs halt or even reverse damage in many wet AMD patients, but some do not respond as well to treatment and so suffer severe vision loss. The new field of pharmacogenetics seeks to enable doctors to individualize treatment based on the patient's genetic profile for a disease. In a collaborative effort, the Hussman Institute for Human Genomics and Bascom Palmer Eye Institute at the University of Miami Miller School of Medicine studied whether specific genetic AMD risk factors and/or smoking influenced patients' responses to anti-VEGF treatment.

The researchers reviewed medical records of 36 people with wet AMD who participated in the Unifying Genetic Epidemiology of Macular Degeneration Study. In terms of anti-VEGF treatment, there were 12 responders whose vision improved, 18 maintainers, and 6 poor responders whose vision declined. All patients had been treated with bevacizumab (Avastin) and/or ranibizumab (Lucentis) for at least one year. None of the patients had vision loss due to cataract, geographic atrophy (advanced "dry" AMD), laser scar or retinal pigment epithelial tear. DNA analysis was done for two AMD-genetic risk factors: complement factor H (CFH) and age-related maculopathy susceptibility-2 (ARMS2) genes. Twenty-four patients had been smokers and three were current smokers. The average age was 80 years.

"Neither high risk genetic factors nor smoking history was significantly associated with patients' response to anti-VEGF therapy in our study," said Jaclyn L Kovach, MD. "However, more responders than poor responders carried at least one risk allele for ARMS2, CFH, or for both genes. Repeating this study in a larger population could bring us closer to a gene-guided therapy for wet AMD."

AMD is categorized as either "dry" or "wet." In the advanced "wet" form, abnormal new blood vessels develop under the retina that bleed or leak fluid and form scars. Advanced AMD destroys the detailed, central vision we need to recognize faces, read, drive, and enjoy daily life.

Genetic Screening Could Improve Glaucoma Care

Symptoms of glaucoma, a disease that destroys the optic nerve, can be so subtle that people often don't know they have the condition. About 4.3 million Americans have glaucoma, and doctors estimate that about half of them are unaware of it. Costs associated with treating the most common type of glaucoma now exceed $3 billion. Genetic screening could help catch glaucoma early on, so patients could be tracked and treated in time to save their sight. Janey L Wiggs, MD, PhD, of the Massachusetts Eye and Ear Infirmary, said genetic testing is currently able to indicate the presence of or risk for several types of glaucoma. Heredity plays a significant role in the disease.

"Blood or cheek cell samples would be collected from patients and appropriate family members, and then selected genes would be sequenced," said Dr. Wiggs. "We can identify markers for congenital glaucoma, early onset (before age 35) primary open angle glaucoma, and normal tension glaucoma, as well as several other conditions that increase glaucoma risk," she added.

Many more genetic markers may soon be available for use in screening for open angle glaucoma and other disease variants. Dr. Wiggs said the challenge will be to identify combinations of genes and/or environmental factors that will produce the most sensitive, specific screening tests.


Contact: Mary Wade
American Academy of Ophthalmology

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