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Alan J. Franklin, Magdalena F. Shuler, Sunil Gupta, John Myers, Wright B. Lauten; Arms2 In/del Polymorphism Predicts Response To Intra Vitreal Anti-vegf Therapy For Choroidal Neovascular Age-related Macular Degeneration (amd). Invest. Ophthalmol. Vis. Sci. 2012;53(14):6507.
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To determine hereditary genetic predictors of anti-VEGF therapy for AMD. While anti-VEGF therapy may effectively restore vision to those with CNV, the response is eclectic. Hereditary disease risk genetic polymorphisms CC (rs1061170) in the complement factor H gene (CFH) may predict response (Kloeckener-Gruissem, IOVS 52:4694), Brantley Ophthal 114:2168), Nischler Acta Ophthalmol 89 3344). A relationship between treatment response and polymorphisms within the LOC387715/ARMS2 has not been identified. We report data supporting this association
We studied the purported pathophysiological insertion/deletion polymorphism in the 3’ portion of the Ch 10 ARMS2 gene (NM_001099667.1:C.* 372_815del443ins54) (Fritsche Nat Gen 40:892) in peripheral blood lymphocytes in patients with neovascular AMD undergoing anti-VEGF therapy. Patients were identified to have neovascular AMD by fundoscopy, OCT or fluorescent angiography. Patients received standard does IV ranibizumab or bevacizumab for an average of 5.4 treatments over a 12 month period. Patients were unselected for presenting VA, age or ethnicity and were derived from a single referral practice. Identification of the ARMS2 indel polymorphism was by Hybe Probe Assay (Roche Applied Science). Visual acuity was expressed as the change in log minimal angle of resolution (MAR) from presentation to 12 months after treatment initiation.
Patients (66) with at least one insertion deletion polymorphic site within the ARMS2 gene (42) had an average improvement in the log MAR of 0.12 compared to a deterioration of 0.137 in those with the ancestral genotype ( p = 0.0262 Wilcoxan Rank Sum Test), indicating a clinically and statistically significant association. Patients with with or without deletions did not differ by age (76.5 vs 76.2 year, p NS) or presenting visual acuity (0.78 vs 0.69 p = 0.84).
This data supports the use of hereditary genetics along with clinical data to predict the outcome of anti-VEGF treatment for AMD. A tool to predict response may be used to personalize treatment for AMD and increase the cost utility of expensive therapies.
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