Conversion from dry AMD to wet AMD is not necessarily inevitable, in that several modifiable risk factors can impact the risk of disease progression. These include smoking status, cardiovascular disease, diet and systemic antioxidant levels. Studies also have suggested that healthy macular pigment optical density (MPOD) can play a role. As a brief refresher, the macular pigment is comprised of three carotenoids: (1) lutein, (2) zeaxanthin and (3) meso-zeaxanthin. Together, they protect the macula from oxidative stress and blue light. (On the heels of this finding, office-based devices have been created to measure MPOD to aid optometrists in their management decisions).

This article discusses the research and patient considerations associated with the treatment used to increase MPOD and the vitamins shown to reduce the risk of AMD progression: ocular nutritional supplementation. Optometrists can use this information to make prescribing decisions.

Note: Because it would not be possible in this space to present a detailed discussion of all research related to nutritional supplements, I recommend optometrists conduct their own research via Pubmed, talking to colleagues and reaching out to various manufacturers. There is a breadth and variety of information out there: Our duty is to educate ourselves and stay abreast of the latest in literature and critical opinions to best serve our individual patients’ needs. (See "Ocular Nutritional Supplements for AMD," pps. 25 and 26.)

THE RESEARCH

The foundational evidence for the role of ocular nutrition in age-related eye disease was provided by AREDS (Age-Related Eye Disease Study) and AREDS2.

AREDS shows that a supplement formulation comprised of vitamin C, vitamin E, beta-carotene, zinc and copper led to a 25% risk reduction of progressing to late AMD over five years in patients who had intermediate or advanced AMD. Additionally, for those who had advanced AMD in one eye, this risk reduction applied to the fellow eye. Finally, no significant benefit was seen in patients without AMD or early AMD.

AREDS2 studied the addition of lutein, zeaxanthin and omega-3 and the elimination of beta-carotene and a reduced level of zinc to the AREDS ocular nutritional supplement. Results show that the combination of lutein and zeaxanthin had a small beneficial effect in patients who had intermediate or advanced disease, especially in those patients who had the lowest levels of dietary intake of the carotenoids, and that omega-3 had no beneficial effect. Additionally, as beta-carotene increases the risk of lung cancer in current and former smokers, AREDS2 researchers concluded that substituting lutein and zeaxanthin for beta-carotene in an ocular nutritional supplement was advised.

Both foundational studies received criticism for the following:

• Study subjects. The patients enrolled in the AREDS studies differ from the average American socioeconomically, in that these patients tended to have higher levels of education and better baseline nutrition.
• Other supplementation use. Some of the patients were taking antioxidant vitamin supplementation prior to the initiation of the trial.
• A missing carotenoid. The AREDS2 ocular nutritional supplement did not contain meso-zeaxanthin. Some research shows that an ocular nutritional supplement that contains all three carotenoids benefits AMD patients.
• Not enough omega-3. It has been questioned whether the formulation of omega-3 used in AREDS2 was optimal, as other research shows dietary oily fish and seafood consumption was substantially lower in AMD patients, and serum red blood cell EPA and EPA and DHA were linked with a substantially reduced risk of wet AMD. (See “Supplementation and Dark Adaptation,” below.)
• No benefit for early AMD. Observational studies demonstrate an association between increased macular pigment levels and de-creased prevalence of macular disease. Additional studies demonstrate the ability of nutritional supplementation to increase the macular pigment level of an individual patient. Therefore, one may draw the conclusion that supplementation has the potential to decrease risk for AMD in individuals who have low levels of macular pigment, especially in those who have a positive family history of AMD.

PATIENT CONSIDERATIONS

O.D.s should assess the following information prior to prescribing an ocular nutritional supplement:

• Smoking. In patients who smoke, research shows that supplementation with high-dose beta-carotene can increase the risk of lung cancer. As a result, O.D.s should turn to formulations that do not contain beta-carotene.
• Genetics. A subgroup analysis of the AREDS data suggests that different genotypes respond differently to supplementation. Specifically, patients who have one or two CFH (complement factor H) risk alleles but no ARMS2 (age-related maculopathy sensitivity 2) risk alleles were at an increased risk for progression to advanced AMD with zinc supplementation. As a result, some clinicians and researchers advocate for the routine use of genetic testing before beginning supplementation.
  An independent study published in the British Journal of Ophthalmology corroborated these results, but NEI researchers did not reach the same conclusion. In the absence of a prospective clinical trial to assess the value of genotyping, controversy remains regarding the role of routine genotyping in supplement choice.
• Anticoagulants. Patients using anticoagulants, such as warfarin sodium (Coumadin, Bristol-Meyers Squibb), may experience complications from supplementation. Specifically, high doses of vitamin E may inhibit platelet aggregation, interacting with this medication. In addition, omega-3s may increase the risk of bleeding in those using anticoagulant therapy. Due to these findings, O.D.s should communicate with patients’ other medical providers before prescribing supplements that contain vitamin E or omega-3.
  For those patients who cannot use supplementation, O.D.s should tell them to avoid smoking and second-hand smoke and eat a diet rich in omega-3 long-chain polyunsaturated fatty acids (such as fish), and low in saturated fats and cholesterol, among other risk-decreasing information.

AT THE READY

Our patients intuitively understand that diet is one of the most important modifiable risk factors for various diseases, including AMD. Some of them are even reminded of their mothers telling them, “You are what you eat.” This tees us up nicely to discuss the role of ocular nutritional supplements in AMD. But, to be able to provide a prescription for a specific supplement and answer related patient questions, we must be knowledgeable of the available research and patient considerations. Patients depend on us. The pharmacy's supplement section has a dizzying array of options. OM

DR. MCNULTY is in private practice in Louisville, KY. He has wide interests across ocular disease and contact lenses. You can e-mail him at mcnulty.aaron@gmail.com.