The treatment of wet age-related macular degeneration (AMD) has – by all accounts – been revolutionized by the successful use of the injectable drugs Eylea, Lucentis, and Avastin. Successful treatments for dry AMD remain more elusive, although stem cell clinical trials in progress show promise. Despite these impressive treatment gains, however, methods for the prevention of AMD remain elusive.
At the 2015 Annual Meeting of the Association for Research in Vision and Ophthalmology (ARVO), a group of American researchers presented data suggesting that L-DOPA (levodopa), a drug used to treat Parkinson’s disease, may be useful in both preventing and delaying AMD. ARVO is an international organization that encourages and assists research, training, publication, and dissemination of knowledge in vision and ophthalmology, including low vision.
About the Research
This poster presentation at the ARVO annual meeting, entitled Inverse [i.e., the opposite or reverse] association between L-DOPA and age-related macular degeneration, was authored by Kamyar Vaziri, Stephen G. Schwartz, Thomas B. Connor, Andrew A. Moshfeghi, Darius M. Moshfeghi, Krishna S. Kishor, Harry W. Flynn, Joseph Carroll, Murray Brilliant, and Brian S. McKay, who represent the following institutions: Bascom Palmer Eye Institute, University of Miami Miller School of Medicine; Medical College of Wisconsin; Retina Associates of Kentucky; Stanford Byers Eye Institute, Palo Alto, CA; University of Wisconsin, Marshfield; and the University of Arizona.
About Dry Macular Degeneration
The dry (also called atrophic) type of AMD affects approximately 80-90% of individuals with AMD. Its cause is unknown, it tends to progress more slowly than the wet type, and there is not – as of yet – an approved treatment or cure. “Atrophy” refers to the degeneration of cells in a portion of the body; in this case, the cell degeneration occurs in the retina.
In dry age-related macular degeneration, small white or yellowish deposits, called drusen, form on the retina, in the macula – the small sensitive area in the center of the retina that provides clear central vision – causing it to deteriorate or degenerate over time.
A retina with drusen
Drusen are the hallmark of dry AMD. These small yellow deposits beneath the retina are a buildup of waste materials, composed of cholesterol, protein, and fats. Typically, when drusen first form, they do not cause vision loss. However, they are a risk factor for progressing to vision loss.
Geographic atrophy is the most severe and advanced form of dry AMD, involving patches of cells in the retina that have degenerated or died off. “Atrophy,” in this case, refers to the degeneration of the deepest cells of the retina, called the retinal pigment epithelium (RPE). “Geographic” refers to any condition whose shape resembles the irregular outline of a land mass, such as the atrophied portion of the retina.
Current treatments for dry AMD include a number of non-drug-related measures, including (a) nutritional supplements recommended by the Age-Related Eye Disease Study 2 (AREDS2), and (b) controlling a range of lifestyle factors, including diet, weight, blood pressure, smoking, and ultraviolet light exposure.
About Wet Age-Related Macular Degeneration (AMD)
In wet, or exudative, macular degeneration (AMD), the choroid (a part of the eye containing blood vessels that nourish the retina) begins to sprout abnormal new blood vessels that develop into a cluster under the macula, called choroidal neovascularization or CNV (neo = new; vascular = blood vessels).
The macula is the part of the retina that provides the clearest central vision. Because these new blood vessels are abnormal, they tend to break, bleed, and leak fluid under the macula, causing it to lift up and pull away from its base. This damages the fragile photoreceptor cells, which sense and receive light, resulting in a rapid and severe loss of central vision.
The focus of current drug treatments for wet AMD is to reduce the level of a particular protein (vascular endothelial growth factor, or VEGF) that stimulates abnormal blood vessel growth in the retina and macula; thus, these drugs are classified as anti-VEGF treatments and include Lucentis, Eylea, and Avastin. They are administered by injection directly into the eye after the surface has been numbed.
Drugs to Treat Parkinson’s Disease
The following definitions of substances and drugs related to Parkinson’s disease are relevant to this research:
- Amino acids: The building blocks of protein. They carry out many important bodily functions, such as giving structure to cells and transporting and storing nutrients.
- Dopa: An amino acid that is formed in the liver and converted to dopamine in the brain
- Dopamine: A form of dopa that acts as a neurotransmitter in the brain, carrying a signal from one nerve cell to the next
- Levodopa, or L-DOPA: A medication used to treat Parkinson’s disease, which is associated with low levels of dopamine. Levodopa is converted to dopamine in the brain. The resulting increase in dopamine improves nerve signal conduction and lessens the movement disorders associated with Parkinson’s, including stiffness, tremors, spasms, and poor muscle control.
About the Research
From Parkinson’s disease drug delays onset of age-related macular degeneration, via Medical News:
L-DOPA, a routine drug taken by patients with Parkinson’s disease, has been found to delay the onset of age-related macular degeneration. The research [was] presented at the 2015 Annual Meeting of the Association for Research in Vision and Ophthalmology (ARVO) Denver, Colorado.
In a study investigating over 15 million people, individuals taking L-DOPA were significantly less likely to develop AMD, and when they did, the age of onset was significantly later. These results suggest L-DOPA may be useful in both preventing and delaying the disease.
More from The ARVO Conference Presentation
From the presentation abstract:
Methods: Using the International Classification of Diseases, Ninth Revision codes (ICD-9), we retrospectively compared the age of first diagnosis of AMD between patients taking or not taking L-DOPA, utilizing cohorts of patients from two Marshfield Clinic Research databases (including 20,000 and 17,000 patients) and the insurance claim-based Truven MarketScan databases from the years 2007-2011 (approximately 87 million outpatient individuals).
In addition, a retrospective cohort of 2,006 AMD patients was reviewed, and a prospective cohort of 47 Parkinson’s disease patients treated with L-DOPA were given comprehensive eye examinations; both cohorts were at Medical College of Wisconsin.
(Note: A retrospective study has limitations because it collects data from past records and does not follow up with patients in the present. A prospective study, on the other hand, studies and measures a group of individuals over time and follows up with study patients in the future.)
Results: In the two Marshfield Clinic samples, the mean ages of first AMD diagnosis in patients not treated with L-DOPA were 71.2 years and 71.1 years, and the mean ages of first AMD diagnosis in patients treated with L-DOPA were 79.3 years and 79.3 years respectively.
From the MarketScan databases, the mean age at first AMD diagnosis in patients not treated with L-DOPA was 71.4 years, and the mean age of first AMD diagnosis in patients treated with L-DOPA was 79.3 years.
Using the subpopulation of patients with ophthalmic ICD-9 codes, it was found that after controlling for age and gender, patients with a prescription history of L-DOPA were significantly less likely to have a diagnosis of AMD. In the retrospective cohort of 2,006 AMD patients, only 19 were using L-DOPA, and all 19 were diagnosed with AMD prior to initiating L-DOPA. In the prospective cohort of 47 Parkinson’s disease patients, 7 patients with early AMD were diagnosed, which is fewer than expected for this age group.
Conclusion: Collectively, these results suggest an inverse [i.e., the opposite or reverse] relationship between L-DOPA treatment and incidence of AMD. If these results can be confirmed, L-DOPA and its intermediaries may provide future drug targets in the prevention or treatment of AMD.
VisionAware will provide updates on this important research as they become available.