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Research hightlights, AAO-SOE Joint Meeting, Nov. 9 sessions

ATLANTA The 2008 Joint Meeting of the American Academy of Ophthalmology (Academy) and European Society of Ophthalmology (SOE ), the largest and most comprehensive ophthalmic educational meeting in the world, is in session November 8 to 11 at the Georgia World Congress Center, Atlanta. Offerings include 277 continuing medical education courses, 179 "Breakfast with the Experts" roundtables, 95 skills transfer courses, and more than 100 hours of scientific presentations, at no charge.

Today's scientific program includes reports on a potential biomarker for age-related macular degeneration (AMD) that may also imply common biological signaling mechanisms for general aging and AMD, and on positive results in keratoconus patients treated with a promising technique, corneal collagen crosslinking.

Plasma Interleukin 6 as a Potential Biomarker of Age-related Macular Degeneration (AMD)

In its advanced stages, AMD destroys the detailed, central vision we need to read, drive, recognize faces, and enjoy daily life, and is a major cause of vision loss in the U.S. Ophthalmic researchers are making rapid progress in understanding how genetics, immune system factors, nutrition choices, and other variables interact to produce or prevent AMD. These discoveries will enable ophthalmologists (Eye M.D.s) to more precisely identify those who are likely to develop AMD, to select optimal, individualized treatments, and to monitor the disease.

Janice C. Law, MD, and her colleagues at the Vanderbilt Eye Institute, looked for plasma (blood) biochemical markers, or biomarkers, that would indicate systemic oxidative stress and an inflammatory response in 57 patients with AMD and in an age-matched control group. Oxidative stress occurs in the body when there is an imbalance between cells' production of reactive oxygen (such as superoxide and hydrogen peroxide) and cells' ability to detoxify byproducts of reactive oxygen, such as free radicals, which can damage protein, DNA and other cell components. In an inflammatory response, the body's vascular and immune systems work in concert to remove disease-causing agents, damaged cells, or other irritants, and to initiate tissue healing. If immune system regulation goes awry, an overly strong inflammatory response--such as hay fever or atherosclerosis--can result.

In Dr. Law's study an inflammation-promoting biochemical, interleukin 6 (IL-6), was found to be significantly higher in the AMD patients, and IL-6 levels also correlated with oxidative stress measurements in these patients. This suggests that IL-6 is a good candidate for further study as a potential AMD biomarker. It also indicates that common biological signaling mechanisms may be involved in both oxidative stress and inflammation and may contribute to AMD development as well as general aging.

Other recent research has established that AMD is closely associated with certain genetic variations that control aspects of the immune system, especially the inflammatory response. Numerous studies have also confirmed the role of oxidative stress in AMD development and progression. Dr. Law's study focused on plasma-based biomarkers because blood sample screening is a relatively simple yet accurate diagnostic tool.

This preliminary cohort study did not attempt to determine whether IL-6 levels varied with AMD types--"wet" AMD, characterized by rapid growth of abnormal blood vessels and heightened risk of vision loss, or the more common "dry" type--or with disease severity.

Corneal Collagen Crosslinking: Treatment Results in Keratoconus Patients

Keratoconus is an eye disorder that causes corneal tissue to become abnormally thin and the central area to protrude in a cone shape, distorting vision. The cornea is the clear tissue that covers the front of the eye and is crucial to focusing light on the back of the eye. In the US, keratoconus occurs in 50 to200 per 100,000 people; reported rates vary with the criteria used for diagnosis. Unofficial reports indicate this disorder may be more prevalent in the Indian subcontinent, Arabia, and New Zealand. Although usually a progressive disease, recent data suggests that it stabilizes after time in most patients, and that treatment with rigid contact lenses is successful for many. Ten to 20 percent of keratoconus patients in the US eventually receive corneal transplants to restore their vision.

Co-investigators Mohan Rajan, MD, and Sujatha Mohan, MD, of the Rajan Eye Care Hospital, India, studied collagen crosslinking in 48 patients (60 eyes), aged 12 to 48 years, who had progressive keratoconus. The collagen crosslinking technique, developed in recent years, is under study for the treatment of several eye disorders. When the technique is used to treat keratoconus patients, drops containing riboflavin, a B-complex vitamin, are applied to the cornea and then the cornea is exposed UVA light; this stimulates collagen fibers to connect to one another, or crosslink. Collagen is the primary protein constituent of the body's connective tissues. The procedure helps restore appropriate curvature and structure to the cornea, and makes it possible for most patients who need them to wear rigid contact lenses again. Collagen crosslinking may prove a viable alternative to cornea transplant, and three FDA-approved trials are now underway in the US.

The Rajan-Mohan study involved 60 eyes total: in 40 eyes (group A) the epithelium was abraded, meaning the thin top layer of cells was scraped, and in 20 eyes (group B) the epithelium was left intact prior to treatment. Patients received follow-up exams at one, three, six and twelve months. Vision corrected with eyeglasses or contact lenses improved in 45 percent of patients by six months, but no change was noted in any patients' vision when measured without eyeglasses or contact lenses. The corneal curve flattened appropriately in 51 of 60 eyes (85 percent), with more significant flattening in group A patients. Based on subjective reports, 46.6 percent of participants were better able to tolerate wearing contact lenses. No significant side effects were noted.

"In our study collagen crosslinking showed promising results," said Dr. Mohan. "The positive corneal changes observed in these patients, together with improved vision and contact lens tolerance, indicates that it was a safe and effective procedure for these keratoconus patients." Because it is less invasive than corneal transplant, the patient's surgery-related risks are reduced. As a less expensive, technically simpler procedure, collagen crosslinking could be particularly useful in developing countries where corneal transplant and other procedures may be difficult to access.


Contact: Mary Wade
American Academy of Ophthalmology

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