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  • Pharmacogenetics of complement factor H (Y402H) and treatment of exudative age-related macular degeneration with ranibizumab

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Original Article
Pharmacogenetics of complement factor H (Y402H) and treatment of exudative age-related macular degeneration with ranibizumab
  1. A Y Lee1,
  2. A K Raya1,
  3. S M Kymes1,
  4. A Shiels1,
  5. M A Brantley, Jr1,2
  1. 1
    Department of Ophthalmology and Visual Sciences, Washington University School of Medicine, St Louis, Missouri, USA
  2. 2
    Barnes Retina Institute, 1600 S Brentwood Blvd, St Louis, Missouri, USA
  1. Dr M A Brantley, Jr, Department of Ophthalmology and Visual Sciences/Campus Box 8096, Washington University School of Medicine, 660 S Euclid Avenue, St Louis, MO 63110, USA; brantley{at}vision.wustl.edu

Abstract

Aims: To determine whether complement factor H (CFH) genotypes have a pharmacogenetic effect on the treatment of exudative age-related macular degeneration (AMD) with ranibizumab.

Methods: A retrospective study of 156 patients with exudative AMD treated with intravitreal ranibizumab monotherapy was conducted. AMD phenotypes were characterised by clinical examination, visual acuity, fundus photography, fluorescein angiography and injection timing. Patients received intravitreal ranibizumab injections as part of routine ophthalmological care and were followed for a minimum of 9 months. Each patient was genotyped for the single nucleotide polymorphism rs1061170 (Y402H) in the CFH gene.

Results: Baseline lesion size and angiographic type, as well as mean visual acuities at baseline, 6 months, and 9 months were similar among the three CFH genotypes. Over 9 months, patients with both risk alleles received approximately one more injection (p = 0.09). In a recurrent event analysis, patients homozygous for the CFH Y402H risk allele had a 37% significantly higher risk of requiring additional ranibizumab injections (p = 0.04).

Conclusions: In this study cohort, the response to treatment of AMD with ranibizumab differed according to CFH genotype, suggesting that determining patients’ CFH genotype may be helpful in the future in tailoring treatment for exudative AMD with intravitreal ranibizumab.

https://doi.org/10.1136/bjo.2008.150995

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    Footnotes

    • Competing interests: SMK receives funding from Allergan and Pfizer.

    • Funding: This work was supported by NIH grant T32RR023255 and UL1RR024992 to Washington University School of Medicine (AYL and AKR), the Jahnigen Career Development. Award from the American Geriatrics Society (MAB), the Carl M & Mildred A Reeves Foundation (MAB), NEI grant EY012284 (AS), NEI Core Grant 5 P30 EY02687, and a grant from Research to Prevent Blindness to the Department of Ophthalmology and Visual Sciences at Washington University School of Medicine.

    • Ethics approval: Ethics approval was provided by the Human Research Protection Office at Washington University in St Louis.

    • Patient consent: Obtained.