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Update on Dry Age-Related Macular Degeneration

Joshua Dunaief, MD, PhD

Scheie Eye Institute, University of Pennsylvania

  • Expert Advice
Published on:
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New treatments for the advanced form of dry age-related macular degeneration (AMD) are on the horizon. Learn about these new experimental drugs; novel mechanisms that are actively being studied regarding the development of macular degeneration; and helpful suggestions that might decrease your risk of progression to the late stage of this eye disease.

Patients often ask, "Do I have wet AMD?" In other words, are new blood vessels growing into the retina, causing harmful leakage of blood? If the answer is "yes," then this form of macular degeneration can now be treated by injection of medicines such as Lucentis, Eylea, or Avastin into the eye. But, if the answer is "no," and the patient has the dry form of AMD, what treatment options are then available? It all depends on whether the dry AMD is in the early or late stages.

Video: Dry Macular Degeneration

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Early-Stage Dry AMD

Early dry AMD means the patient has drusen, little pebble-like deposits under the retina, and, in most cases, still has good vision. Late dry AMD, also called geographic atrophy, means that the photoreceptors (vision cells) have died in a specific region of the retina, and more are likely to die over the coming years, causing an expanding blind spot near the center of the visual field.

Fortunately, many patients with early AMD do not progress to late AMD. The risk of progression is determined by genetic factors, as well as diet, exercise, and smoking.

Decreasing Your Risk

It is very important to avoid or stop smokingeat fatty fish like salmon, tuna, mackerel, or sardines twice a week, and eat lots of vegetables and some fruit. My brother David Dunaief, MD and I have studied the effects of a vegetable-rich diet including a daily smoothie, and published articles showing that it decreases levels of a blood test that measures inflammation, called C-reactive protein (CRP). This may decrease risk of AMD, as AMD is associated with high CRP, and systemic inflammation. More information about retrospective research results with this diet can be found at: https://www.medicalcompassmd.com/research.

Wearing sunglasses when outside may also be protective.

In addition, for patients with large or numerous drusen, vitamins designed according to the AREDS II trial decrease the risk of progression by 25%. If your ophthalmologist recommends taking them, be sure to look for “AREDS II formula” on the bottle in the drug store, as there are many different vitamins marketed for eye protection. One pill should be taken in the morning and one in the evening.

Further Resources on Reducing Risk of Macular Degeneration

Late-Stage Dry AMD

For patients with late dry AMD (geographic atrophy), there is no proven treatment to prevent or slow progression, but several new drugs are in advanced clinical trials.

Targeting the Immune System

Both genetic and biochemical evidence indicate that the complement system (part of the immune system) is involved in AMD. While two phase III trials by Genentech targeting the complement protein called factor D in geographic atrophy patients recently failed, a phase II trial by Apellis targeting a different complement protein called C3 showed promising results.

Some other drugs in clinical trials for geographic atrophy include the complement inhibitor Zimura, which inhibits a different complement protein called complement factor 5. Like Lampalizumab, this treatment is injected into the eye.

Targeting Inflammation

There is also an oral drug called Oracea, the antibiotic doxycycline. It has anti-inflammatory activities that may be beneficial for patients with geographic atrophy.

Another orally administered pill just entering clinical trials is the antioxidant lipoic acid, and this study is funded in part by BrightFocus Foundation. This drug was able to protect mice against retinal degeneration in my lab, and is retina-protective in several other preclinical models.

Other Promising Avenues

Research on AMD continues to increase understanding of the disease and identify promising new drugs for testing in clinical trials. Several other mechanisms are actively being studied regarding the development of macular degeneration:

  • The inflammasome is a protein complex that can promote harmful inflammation and even retinal cell death.
  • Oxidative stress can be caused by bright light, antioxidant deficiency in a poor diet, and too much iron in the retina. Oxidative damage occurs when our bodies produce very reactive molecules that can adversely interact with other molecules inside of our cells. The resulting “inflammation” can contribute to a number of age-related diseases, including age-related macular degeneration.
  • A recent preliminary study showed that a statin drug, which inhibits cholesterol synthesis, could decrease the number of drusen in some patients.
  • In an approach to limit the toxic byproducts of vision cells, an oral drug called ALK-001 is being tested in phase III clinical trials for GA. This drug is a modified (deuterated) version of vitamin A that inhibits formation of the toxic byproduct A2E.

Summary

Given the number of new important discoveries about the mechanisms of AMD, and the results of some promising early-stage clinical trials, it is likely that within the next few years we will have new treatments for AMD that reduce the risk of vision loss.

About the author

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Joshua Dunaief, MD, PhD

Scheie Eye Institute, University of Pennsylvania

Joshua Dunaief, MD, received his BA magna cum laude in Biology from Harvard (1987), MD/PhD from Columbia College of Physicians and Surgeons (1996), completed ophthalmology residency at the Wilmer Eye Institute, Johns Hopkins in 2000, and medical retina fellowship at Scheie Eye Institute, University of Pennsylvania in 2004.

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