First Author: V.Chaudhary CANADA
Co Author(s): M. Brent W.C. Lam J. Teichman F. Farrokhyar R. Carter R. Devenyi 0 0 0 0 0 0 0 0 0
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Wet age related macular degeneration (AMD) patients experience variable response to standard care ranibizumab therapy with 10 to 15% of individuals continuing to lose vision following intervention. Those factors implicated in response variability remain unclear. Herein, we seek to identify the pharmacogenetic contribution mutations in the CFH, C3, ARMS2, and mtDNA genes have in vision outcomes over six months.
This was a prospective, multi-centered study with patients recruited from the St. Joseph’s Healthcare Hamilton Regional Eye Institute and the Toronto Western Hospital Eye Clinic in Canada.
Treatment naive patients with active subfoveal choroidal neovascularization secondary to AMD were included in this study if significant ocular disease and prior retinal surgery were absent. At baseline, visual acuity (VA) was assessed using 2-meter ETDRS charts, central macular thickness (CMT) was recorded from Cirrus HD OCT 4000 scans, significant confounders of vision outcomes including smoking status, presence of hypertension and lesion type were documented, and a cheek swab was taken. DNA from swabbed cells was extracted and analyzed for the genotypes in question using the Macula Risk© test. VA and CMT were recorded during monthly follow-up visits until study conclusion.
70 eyes from 70 patients were included. The study population had a mean age of 80.8±7.6 and were predominately Caucasian (97.1%) females (62.9%). Univariate analysis was used to assess the relationship between genotype and change in VA from baseline to month 6. Only CFH haplotypes were significantly associated with vision change (p<0.05). Stepwise, logistic regression was used to identify the probability of moderate vision gain (a gain of 15 or more letters) from baseline to six months, in patients with CFH risk haplotypes compared to those without after adjusting for confounders. The CFH haplotypes were a predictor of gaining ≥ 15 letters at the study conclusion with patients expressing reduced risk haplotypes being more likely to achieve a gain of ≥15 letters relative to the greatly increased risk haplotypes OR 6.58 (CI95: 1.37, 31.59). The only other factor included in the model was number of injections (p =0.05). The p value for a Hosmer-Lemeshow goodness-of-fit test was 0.877.
CFH is implicated in the treatment response of wet AMD patients to ranibizumab.