Article

Prescribing Supplements for AMD

A look at the research and patient considerations

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.

SUPPLEMENTATION AND DARK ADAPTATION

RECENTLY, IMPAIRED DARK ADAPTATION has been proposed as an early biomarker of AMD. There is evidence that these patients may benefit from the early use of supplementation. Currently, the NEI is recruiting subjects for a clinical trial to investigate; the role of vitamin A supplementation in AMD patients and delayed dark adaptation.

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

OCULAR NUTRITIONAL SUPPLEMENTS FOR AMD

WHAT FOLLOWS IS A LIST OF NUTRITIONAL SUPPLEMENTS designed to benefit patients who have AMD. The listing is a sampling of those available, based on an Optometric Management editorial questionnaire completed by supplement companies. Each of the company’s responses appear below in alphabetical order. See the online version of this list, available at optometricmanagement.com, for the most updated version of this list.

Bausch+Lomb

Product name or brand family(s) name for multiple products: PreserVision AREDS 2 formula eye vitamins; Ocuvite eye vitamin and mineral supplement

Website: preservision.com
ocuvite.com

Is your manufacturing third-party GMP certified? Yes

Clinical research, published in peer-reviewed journals, that may inform readers about the company's supplement(s) specifically:

→ Age-Related Eye Disease Study Research Group. The Age-Related Eye Disease Study (AREDS): Design Implications AREDS Report No. 1. Control Clin Trials. 1999 Dec; 20(6): 573-600.

→ AREDS2 Research Group. The Age-Related Eye Disease Study 2 (AREDS2): Study Design and Baseline Characteristics (AREDS2 Report Number 1). Ophthalmology. 2012 Nov; 119(11): 2282-2289.

Active ingredients: See label.

How is the supplement sold? Amazon/OTC outlets

Contact information: preservision.com
ocuvite.com

EyePromise

Product name or brand family(s) name for multiple products: EyePromise Restore Line (Restore, AREDS 2 Plus Multi-Vitamin, and AREDS 2 Plus Zinc-Free)

Website: eyepromise.com

Is your manufacturing third-party GMP certified? Yes

Clinical research, published in peer-reviewed journals, that may inform readers about the company's supplement(s) specifically:

→ Herman JP, Goudey JK, Davis RL. Case report of dietary supplements improving macular pigment and visual function. Advances in Ophthalmology & Visual System. Jan. 2017. Accessed March 31. https://medcraveonline.com/AOVS/AOVS-06-00166.pdf

Active ingredients: Zeaxanthin, lutein, CoQ10, folic acid, vitamin B6, vitamin B12, omega-3s, alpha lipoic acid, zinc, vitamin C, vitamin D, vitamin E, mixed tocopherols

How is the supplement sold? In office, company website, through a personalized practice ecommerce page and Amazon

Contact information: bit.ly/2JtIqSo

Focus Vision Supplements

Product name or brand family(s) name for multiple products: Focus Select AREDS2 based

Website: focusvitamins.com

Is your manufacturing third-party GMP certified? Yes

Active ingredients: Vitamins C, E, lutein, zeaxanthin

How is the supplement sold? Company website

Contact information: info@focusvitamins.com or 855-663-6287

Fortifeye Vitamins

Product name or brand family(s) name for multiple products: Fortifeye Vitamins and Fortifeye Performance Nutrition

Website: fortifeye.com

Is your manufacturing third-party GMP certified? Yes

Active ingredients: Lutein, zeaxanthin, astaxanthin

How is the supplement sold? In office, company website, personal website and Amazon/OTC outlets

Contact information: Contact jpurdy@fortifeye.com or (352) 318-0990.

Guardion Health Sciences

Product name or brand family(s) name for multiple products: Lumega-Z

Website: guardionhealth.com

Is your manufacturing third-party GMP certified? Yes

Active ingredients: Micronized, lipid-based liquid formula of: lutein, zeaxanthin, meso-zeaxanthin, lycopene, astaxanthin, NAC, taurine, alpha-lipoic acid, billberry, acetyl-l-carnitine, CoQ10, quercetin plus complete multi-vitamin.

How is the supplement sold? In office

Contact information: Visit guardionhealth.com/contact/

MacuHealth LLC

Product name or brand family(s) name for multiple products: MacuHealth

Website: macuhealth.com

Is your manufacturing third-party GMP certified? Yes

Clinical research, published in peer-reviewed journals, that may inform readers about the company's supplement(s) specifically:

→ Akuffo KO, Beatty S, Peto T, et al. The impact of supplemental antioxidants on visual function in nonadvanced age-related macular degeneration: a head-to-head randomized clinical trial. Invest Ophthalmol Vis Sci. 2017;58:5347–5360. DOI:10.1167/iovs.16-21192.

→ Akuoffo KO, Nolan JM, Howard AN, et al. Sustained supplementation and monitored response with offering carotenoid formulations in early age-related macular degeneration. Eye advance online publication, 15 May 2015; doi:10.1038/eye.2015.64.

→ Sabour-Pickett S, Nolan JM, Loughman J, Beatty S. A review of the evidence germane to the putative protective role of the macular carotenoids for age-related macular degeneration. Mol. Nutr. Food Res. 2012, 56, 270-286. DOI 10.1002/mnfr.201100219.

Active ingredients: Lutein 10 mg, meso-zeaxanthin 10 mg, zeaxanthin 2 mg

How is the supplement sold? Company website and wholesale to eye care professionals

Contact information: Call (866) 704-0845 to place your order or speak with a MacuHealth supplement specialist.

Medop Health, Inc.

Product name or brand family(s) name for multiple products MaxiVision and MaxiTears

Website: maxivision.com

Is your manufacturing third-party GMP certified? No

Clinical research, published in peer-reviewed journals, that may inform readers about the company's supplement(s) specifically:

→ Girodon F, Galan P, Monget AL, et al. Impact of Trace Elements and Vitamin Supplementation on Immunity and Infections in Institutionalized Elderly Patients. Arch Intern Med. 1999;159: 748-754.

Active ingredients: Lutein (FloraGlo) 20 mg, zeaxanthin 5 mg, vitamin E, vitamin C, zinc, copper, proprietary blend that includes N-acetyl-L-cysteine, acetyl-L-camitline, alpha lipoid acid, CoQ10, quercetin and rasveratrol

How is the supplement sold? In office

Contact information: Call (813) 343-5555

ScienceBased Health

Product name or brand family(s) name for multiple products: MacularProtect Complete

Website: SBH.com

Is your manufacturing third-party GMP certified? Yes

Clinical research, published in peer-reviewed journals, that may inform readers about the company's supplement(s) specifically:

→ Semeraro F, Gambicordi E, Cancarini A, et al. Treatment of exudative age-related macular degeneration with aflibercept combined with pranoprofen eye drops or nutraceutical support with omega-3: A randomized trial. Br J Clin Pharmacol. Epub Jan. 24, 1019.

→ Christen WG, Glynn RJ, Chew EY, et al. Folic acid, pyridoxine, and cyanocobalamin combination treatment and age-related macular degeneration in women: the Women's Antioxidant and Folic Acid Cardiovascular Study. Archives of Internal Medicine 169.4 (2009): 335-341.

→ Age-Related Eye Disease Study 2 Research Group. Lutein+ zeaxanthin and omega-3 fatty acids for age-related macular degeneration: the Age-Related Eye Disease Study 2 (AREDS2) randomized clinical trial. Journal of the American Medical Association. 309.19 (2013): 2005-2015.

Active ingredients: Vitamin B, lutein, zeaxanthin, alpha lipoic acid, quercetin, trans-resveratrol, lycopene, extracts of turmeric, ginkgo, bilberry, olive leaf, and a complete multivitamin, among others.

How is the supplement sold? In office or by referral to SBH

Contact information: Email info@sbh.com OM

Optometric Management will update this list online as needed.