Dr. Suren Sanmugasunderam (biography, no disclosures)
What I did before
There are 2 major forms of Age-Related Macular Degeneration (ARMD). The dry form is characterized by drusen, pigmentary mottling and retinal and retinal pigment epithelial atrophy. The wet form is characterized by choroidal neovascular membranes (CNVM). Diagnosis in a general practice is difficult unless one is able to carefully examine the macula. However, symptoms like metamorphopsia (distortion of images), central scotomas (blind spots) and decreased central vision would be suggestive of ARMD. Patients who already have known ARMD can be given an Amsler grid and told to check for increasing distortion or blind spots once or twice a week. When I finished my residency, the only treatment for the dry form was sun protection (hat or sunglasses), which, needless to say, was ineffective. The treatment for wet ARMD used to be laser ablation of the CNVM. Unfortunately, most CNVM were too poorly localized or located under the fovea and thus, laser treatment was relatively ineffective.
What changed my practice
A number of randomized multi-center trials have been published since I started in practice which have redefined treatment of ARMD. The first was the Age-Related Eye Disease Study (AREDS)1. It randomized people who already had dry ARMD to placebo or Vitamin A – 15 mg per day as beta-carotene, Vitamin C 500 mg per day, Vitamin E 400 IU per day or Zinc 80 mg per day, Copper 2 mg per day or Vitamins and Zinc. It found a reduction in progression of AMD in all the treatment groups compared to placebo of roughly 20%. Unfortunately, after the trial started, there were reports of increased risk of lung cancer in smokers and ex-smokers who took beta-carotene2. This along with suggestions that lutein/zeaxanthin and omega-3 fatty acids were also beneficial led to the AREDS 2 study3. The AREDS 2 study left people on the AREDS formula but added either lutein and zeaxanthin, omega-3 fatty acids or both. The study found no additive effect of these agents on the standard AREDS baseline.
The underlying cause of ARMD is also being elucidated. While the above discussion seems to suggest that ARMD is mostly due to light damage, polymorphisms in Complement Factor H have been strongly linked to the development of ARMD suggesting an immune mechanism4. This may lead to more specific treatments for AMD.
Treatments for wet ARMD have also progressed significantly. Initially, photodynamic therapy with verteporfin5 was used for lesions that couldn’t be treated by laser. The idea of this treatment was to inject a dye that remained in the abnormal vessels which was then activated by a laser to cause formation of reactive oxygen species and close the abnormal vessels. While effective, it has been superseded by drugs that target Vascular Endothelial Growth Factor A (VEGF-A). The prototype drug is Ranibizumab which is a recombinant humanized monoclonal antibody Fab which has been shown to be effective in treatment of wet ARMD6. These drugs work by blocking VEGF-A which seems to be on the final common pathway required to develop new blood vessels. They require episodic injection directly into the vitreous cavity of the eye.
What I do now
For patients who have no ARMD, I stratify them into low risk and high risk. Low risk patients have no first-degree relatives with ARMD and do not smoke. I counsel them to simply wear good sun-protection (a hat with a broad brim or sunglasses) and to ingest anti-oxidants in their diet (leafy greens) or to take a multi-vitamin a day.
The AREDS study did not look at people who had no ARMD. However, since the proposed mechanism of action is preventing light damage or light-mediated immune damage, it is reasonable to assume that starting therapy earlier will yield benefits in people who are likely to develop this disease. Thus, I counsel high-risk normals to take the AREDS formulation if they are non-smokers. If they smoke, I counsel them to omit the beta-carotene and consider using lutein or omega-3 fatty acids and to stop smoking. There are a number of patients who cannot tolerate the AREDS formulation due to GI side-effects. I suggest that they try the separate components of the AREDS formulation to see what they cannot tolerate (frequently zinc) and omit that component. I encourage these patients to add omega-3 fatty acids or lutein.
For patients who already have dry ARMD, I encourage them to use the full AREDS formulation and try to encourage them to stay on it long-term. I also screen them regularly with Amsler Grid testing and follow-up appointments to look for development of wet ARMD. Approximately 1/3 of patients with ARMD eventually develop wet ARMD.
The development of wet ARMD is typically heralded by the development of distortion in central vision, a central blind spot or simply blurry vision. Since it usually occurs in only one eye, it can be missed if patients do not check each eye individually. Current treatments for wet ARMD are most effective if started within 1-2 months of onset. Wet ARMD is primarily managed by retinal specialists as the specific drug and dosing strategies are currently in flux.
- A Randomized , Placebo-Controlled, Clinical Trial of High-Dose Supplementation with Vitamins C and E, Beta Carotene, and Zinc for Age-Related Macular Degeneration and Vision Loss. AREDS Report 8. Arch Ophthalmol. 2001;119(10):1417-1436 (Request from CPSBC or view with UBC)
- Effects of a Combination of Beta Carotene and Vitamin A on Lung Cancer and Cardiovascular Disease. Omenn G et al N Eng J Med 1996; 334:1150-1155 (Request from CPSBC or view with UBC)
- Lutein and zeaxanthin and omega-3 fatty acids for age-related macular degeneration: The Age-Related Eye Disease Study 2 (AREDS2) randomized clinical trial. JAMA 2013 May 15;309(19):2005-15 (Request from CPSBC or view with UBC)
- Complement Factor H Polymorphism in Age-Related Macular Degeneration. Klein et al. Science 15 Apr 2005 Vol. 308 no. 5720 pp. 385-9 (Request from CPSBC or view with UBC)
- Photodynamic Therapy of Subfoveal Choroidal Neovascularization in Age-related Macular Degeneration with Verteporfin. Arch Ophthalmol 1999;117(10):1329-1345 (Request from CPSBC or view with UBC)
- Ranibizumab for Neovascular Age-Related Macular Degeneration. Rosenfeld et al. N Engl J Med 2006;355:1419-1431 (Request from CPSBC or view with UBC)