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ASSOCIATION BETWEEN HIGH-RISK DISEASE LOCI AND RESPONSE TO ANTI–VASCULAR ENDOTHELIAL GROWTH FACTOR TREATMENT FOR WET AGE-RELATED MACULAR DEGENERATION

Orlin, Anton MD*; Hadley, Dexter MD, PhD*†; Chang, Woohyok MD; Ho, Allen C MD§¶; Brown, Gary MD§¶; Kaiser, Richard S MD§¶; Regillo, Carl D MD§¶; Godshalk, Ashlee N BA; Lier, Audun BA; Kaderli, Brian BA; Stambolian, Dwight MD, PhD*†

doi: 10.1097/IAE.0b013e31822a2c7c
Original Study
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Purpose: To investigate whether there is an association between known age-related macular degeneration genetic risk variants in the CFH, ARMS2, and HTRA1 genes and response to anti–vascular endothelial growth factor (VEGF) (ranibizumab or bevacizumab) treatment for wet age-related macular degeneration.

Methods: A retrospective review of 150 patients with documented wet age-related macular degeneration based on clinical examination and fluorescein angiogram was performed. Patients received anti-VEGF therapy with ranibizumab and/or bevacizumab. Patients were genotyped for the single-nucleotide polymorphism rs1061170, rs10490924, rs3750848, rs3793917, rs11200638, and rs932275 and for the indel del443ins54 spanning the CFH, ARMS2, and HTRA1 genes.

Results: There were 57 patients who were characterized as negative responders to anti-VEGF therapy, and 93 patients who were characterized as positive responders. There was no significant difference in mean baseline visual acuity between the groups. Negative responders were followed for a mean duration of 24.0 months, while positive responders were followed for a mean duration of 22.0 months. Although the frequency of the at-risk alleles was higher in the positive responders when compared with the negative responder, this did not reach statistical significance. Additionally, there was no significant association between genotype and the number of injections or absolute change in visual acuity in both groups of responders.

Conclusion: In our patient cohort, there was no statistically significant association between response to anti-VEGF therapy and the genotype in both positive-responder and negative-responder groups. Larger studies with more power are necessary to further determine whether a pharmacogenetic association exists between wet age-related macular degeneration and anti-VEGF therapy.

In our study cohort, there was no statistically significant association between response to anti–vascular endothelial growth factor therapy for the treatment of wet age-related macular degeneration and genotype.

From the *Scheie Eye Institute, Department of Ophthalmology, and †F.M. Kirby Center for Molecular Ophthalmology, University of Pennsylvania, Philadelphia, Pennsylvania; ‡Department of Ophthalmology, Yeungnam University College of Medicine, Daegu, South Korea; §Mid Atlantic Retina, Cherry Hill, New Jersey; and ¶Wills Eye Institute, Department of Ophthalmology, Thomas Jefferson University, Philadelphia, Pennsylvania.

Dr. Chang was supported by a Yeungnam University research grant in 2008. A. Orlin, D. Hadley, and W. Chang have contributed equally to the work and writing of this manuscript.

The authors report no proprietary interest to disclose.

Reprint requests: Anton Orlin, MD, 1305 York Avenue 11th Floor, New York, NY 10021; e-mail: aorlin@gmail.com

© The Ophthalmic Communications Society, Inc.