title: Involvement of genetic factors in the response to a variable-dosing ranibizumab treatment regimen for age-related macular degeneration.
abstract: OBJECTIVE
  To determine whether gene polymorphisms of the major genetic risk factor for age-related macular susceptibility 2 (ARMS2 A69S) and the complement factor H Y402H influence the response to a variable-dosing treatment regimen with ranibizumab for age-related macular degeneration.
  
  
  METHODS
  This prospective cohort study included 90 patients (90 eyes) with exudative age related macular degeneration (AMD) treated with ranibizumab. Patients underwent a 1-year treatment as in the Study of Ranibizumab in Patients with Subfoveal Choroidal Neovascularization Secondary to Age-Related Macular Degeneration (Mitchell et al.). Injections were administered monthly when a patient lost five letters on the Early Treatment Diabetic Retinopathy Study chart or gained 100 μm in central subfield retinal thickness (CSRT). Genotypes (rs10490924 and rs1061170) were analyzed using gene sequence analysis. Best-corrected visual acuity (BCVA) and CSRT values were compared between ARMS2 and complement factor H genotypes. Multiple regression analysis was used to assess the statistical significance.
  
  
  RESULTS
  Mean increase in visual acuity was 4.44±8.12 letters with a 103.63±94.7 µm decrease in CSRT. BCVA improvement was statistically significant in all genotype groups except in homozygous 69S in the AMRS2 gene. CSRT and BCVA changes were correlated (r=0.2521; 95% CI: 0.04746-0.4364, p=0.0165). Multiple regression analysis revealed a significant impact of 69S (p=0.015) on the change in BCVA.
  
  
  CONCLUSIONS
  Visual acuity did not improve during the study in patients homozygous for ARMS2 69S, despite a decrease in CSRT. Further investigation is needed to confirm our findings and understand the mechanisms involved.
authors.affiliation: Department of Ophthalmology, Okregowy Szpital Kolejowy, Katowice, Poland. slawomir.teper@gmail.com
authors.forename: Slawomir J
authors.initials: SJ
authors.lastname: Teper
authors.forename: Anna
authors.initials: A
authors.lastname: Nowinska
authors.forename: Jaroslaw
authors.initials: J
authors.lastname: Pilat
authors.forename: Andrzej
authors.initials: A
authors.lastname: Palucha
authors.forename: Edward
authors.initials: E
authors.lastname: Wylegala
mesh_terms: D000368:Aged; D019943:Amino Acid Substitution / Q000235:genetics; D020533:Angiogenesis Inhibitors / Q000008:administration & dosage* / Q000627:therapeutic use*; D000911:Antibodies, Monoclonal / Q000008:administration & dosage* / Q000627:therapeutic use*; D061067:Antibodies, Monoclonal, Humanized; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D005260:Female; D005838:Genotype; D006801:Humans; D008268:Macular Degeneration / Q000188:drug therapy* / Q000235:genetics* / Q000503:physiopathology; D008297:Male; D000069579:Ranibizumab; D012044:Regression Analysis; D012160:Retina / Q000473:pathology / Q000503:physiopathology; D016896:Treatment Outcome; D014792:Visual Acuity
chemical_list: D020533:Angiogenesis Inhibitors; D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D000069579:Ranibizumab