Andrew Moshfeghi, MD, MBA

Researchers at six of the nation’s top ophthalmology institutions, including the University of Southern California (USC) Eye Institute, have discovered that a drug intervention commonly used for Parkinson’s disease may also significantly delay or prevent age-related macular degeneration – the leading cause of blindness in the U.S, according to the National Eye Institute (NEI).

Research experts, including Andrew Moshfeghi, MD, MBA, clinical trials director at the USC Eye Institute, along with the Marshfield Clinic, University of Arizona, Medical College of Wisconsin, the University of Miami and Essentia Health found that patients who were administered the drug L-DOPA to treat Parkinson’s disease, Restless Leg Syndrome (RLS) and other movement disorders, were significantly less likely to develop age-related macular degeneration or developed it years later – up to eight years later – than those patients who were not taking the drug.

“The research is significant because it points to a possible association between L-DOPA and AMD risk that may also result in L-DOPA use leading to a later onset of AMD diagnosis,” said Dr. Moshfeghi. “The hope is that this discovery may mean L-DOPA may play a protective role for AMD risk—the data also gives us new insights into potential treatment targets for this complex disease.” Future clinical studies will have to validate this preliminary finding.

According to the American Academy of Ophthalmology (AAO), 2.1 million Americans over age 50 have late-stage AMD and 9.1 million have early stage AMD. In addition to discovering a potential new drug therapy for AMD, researchers also illustrated the potential and power of Precision Medicine research using electronic medical records (EMRs) of large numbers of patients to test unexpected drug interactions and find new uses for old drugs.

After basic research on mice, the researchers examined the health records of 37,000 AMD patients or those taking L-DOPA for movement disorders at the Marshfield Clinic looking for racial disparities in AMD. The provocative results showed AMD patients who were also taking L-DOPA received their eye diagnosis eight years later than those who had AMD but were not on the drug.

These results were then confirmed in a much larger data set of 87 million patients nationwide where similar results were observed.

The discovery began with basic research using albino mouse models because albinos have profound vision loss and changes in the structure of the eye, especially the retina, and specifically the macula, the area of the retina that is associated with best vision and lost in AMD.

The pigmented retina epithelium is critical support layer in the retina that fosters macula development and keeps it healthy through DOPA signaling through its receptor. DOPA is made in pigmented tissues and it has been known for a long time that lower risk for AMD is associated with darker pigmentation with African Americans having a five-fold less risk for AMD than Caucasians. The researchers postulated that signaling through the DOPA receptor may underlie racial disparities in AMD incidence.

Researchers first examined the health records of 37,000 patients at the Marshfield Clinic for individuals with AMD, or those taking L-DOPA, or those with both AMD and taking L-DOPA. As seen in national statistics, the average age at which individuals are given L-DOPA is 67; the average age of those diagnosed with AMD is 71. The expectation was that for patients with both an AMD diagnosis and an L-DOPA prescription, most should have gotten L-DOPA before their AMD diagnosis.

Instead researchers found the opposite pattern. In those few who received L-DOPA before being diagnosed with AMD, their AMD was diagnosed eight years later than those not taking L-DOPA. These provocative results were then confirmed in a much larger data set of 87 million patients, where similar results were observed and the study expanded to include prevention and delay of “wet” AMD, the most devastating form of the disease.

by Meg Aldrich