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Genetic Testing for AMD

It is now well established the genetic factors have an important role in the development of age-related macular degeneration (AMD). Numerous genes are known to contribute to AMD, and the strongest association has been noted with the complement factor H (CFH) and the age-related maculopathy sensitivity 2 (ARMS2) genes. While the role of genetics in AMD is a fascinating issue for research purposes, the role of genetic testing in the clinical care of patients with AMD remains controversial.

The standard preventative therapy for patients with dry AMD has been AREDS vitamin supplementation. In 2001, the results of the Age-Related Eye Disease Study (AREDS), a randomized, placebo-controlled trial sponsored by the National Eye Institute (NEI), showed that oral supplementation with antioxidant vitamins and zinc reduced the risk of progression to late AMD by 25% in persons with intermediate AMD in at least one eye(1). Recently, Awh et al. have published some studies, using AREDS data, suggesting that only patients with certain genotypes benefit from AREDS supplementation, while patients with other genotypes could potentially be harmed with worsening of their AMD(2,3). These researchers have suggested the need to genotype all patients taking the AREDS supplements. This has become a controversial issue because the AREDS researchers have not found any evidence of a variation in response to vitamin supplements based on patient genotype, and they have not been able to replicate the results of Awh et al(4,5). The NEI investigators have shown evidence to support the fact that the statistical analysis performed by Awh et al. was biased and flawed(5).

If patient genotype truly does predict how patients respond to vitamin treatment, then one would expect that this might be true for other AMD treatments as well. The main treatment for neovascular AMD is intravitreal injections of agents that block vascular endothelial growth factor (VEGF). Early small retrospective studies suggested that patient response to anti-VEGF treatment might in fact be predicted by genotype. However, several large prospective studies have not been able to show any association between genotype and response to anti-VEGF therapy(6-9).

In summary, the role of genetic testing in the care of patients with AMD remains highly controversial, as strong evidence to support this is lacking. Both the NEI and the American Academic of Ophthalmology (AAO) advise against obtaining genetic testing as part of the clinical care of patients with AMD(5,10). Until stronger and more conclusive evidence is available, it would seem prudent for eye care professionals to refrain from obtaining genetic testing in patients with AMD.


  1. Age-Related Eye Disease Study Research G. 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 no. 8. Arch Ophthalmol. Oct 2001;119(10):1417-1436.
  2. Awh CC, Lane AM, Hawken S, Zanke B, Kim IK. CFH and ARMS2 genetic polymorphisms predict response to antioxidants and zinc in patients with age-related macular degeneration. Ophthalmology. Nov 2013;120(11):2317-2323.
  3. Awh CC, Hawken S, Zanke BW. Treatment response to antioxidants and zinc based on CFH and ARMS2 genetic risk allele number in the Age-Related Eye Disease Study. Ophthalmology. Jan 2015;122(1):162-169.
  4. Chew EY, Klein ML, Clemons TE, et al. No clinically significant association between CFH and ARMS2 genotypes and response to nutritional supplements: AREDS report number 38. Ophthalmology. Nov 2014;121(11):2173-2180.
  5. Chew EY, Klein ML, Clemons TE, Agron E, Abecasis GR. Genetic testing in persons with age-related macular degeneration and the use of the AREDS supplements: to test or not to test? Ophthalmology. Jan 2015;122(1):212-215.
  6. Hagstrom SA, Ying GS, Pauer GJ, et al. Pharmacogenetics for genes associated with age-related macular degeneration in the Comparison of AMD Treatments Trials (CATT). Ophthalmology. Mar 2013;120(3):593-599.
  7. Lotery AJ, Gibson J, Cree AJ, et al. Pharmacogenetic associations with vascular endothelial growth factor inhibition in participants with neovascular age-related macular degeneration in the IVAN Study. Ophthalmology. Dec 2013;120(12):2637-2643.
  8. Hagstrom SA, Ying GS, Pauer GJ, et al. Endothelial PAS domain-containing protein 1 (EPAS1) gene polymorphisms and response to anti-VEGF therapy in the comparison of AMD treatments trials (CATT). Ophthalmology. Aug 2014;121(8):1663-1664 e1661.
  9. Hagstrom SA, Ying GS, Pauer GJ, et al. VEGFA and VEGFR2 gene polymorphisms and response to anti-vascular endothelial growth factor therapy: comparison of age-related macular degeneration treatments trials (CATT). JAMA Ophthalmol. May 2014;132(5):521-527.
  10. Stone EM, Aldave AJ, Drack AV, et al. Recommendations for genetic testing of inherited eye diseases: report of the American Academy of Ophthalmology task force on genetic testing. Ophthalmology. Nov 2012;119(11):2408-2410.


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