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CFH, VEGF and HTRA1 promoter genotype may influence the response to intravitreal ranibizumab therapy for neovascular age-related macular degeneration
  1. Martin McKibbin1,2,
  2. Manir Ali2,
  3. Shveta Bansal1,2,
  4. Paul D Baxter3,
  5. Kumi West1,
  6. Grange Williams2,
  7. Frances Cassidy1,
  8. Chris F Inglehearn2
  1. 1Eye Clinic, St. James's University Hospital, Leeds, UK
  2. 2Section of Ophthalmology and Neuroscience, Leeds Institute of Molecular Medicine, University of Leeds, Leeds, UK
  3. 3Division of Biostatistics, Leeds Institute of Genetics, Health and Therapeutics, University of Leeds, Leeds, UK
  1. Correspondence to Martin McKibbin, Eye Clinic, St James's University Hospital, Leeds LS9 7TF, UK; martin.mckibbin{at}


Aims To investigate an association between genotype for three single nucleotide polymorphisms strongly associated with the development of age-related macular degeneration (AMD) and the early response to treatment with intravitreal ranibizumab for neovascular AMD.

Methods Best corrected visual acuity letter score was recorded at baseline and each subsequent visit. Age, sex, smoking history, lesion type and the number of injections were also recorded. Genotypes were obtained for rs11200638 in HTRA1, rs1061170 in CFH and rs1413711 in VEGF. Data were analysed with treatment response at month 6 as both a binary (>5 letter improvement vs ≤5 letter gain) and a linear trait.

Results This initial study cohort consisted of 104 Caucasian neovascular AMD patients treated with intravitreal ranibizumab. Trends towards a more favourable outcome were seen with the higher AMD risk genotypes in CFH and VEGF in both the linear and binary models and in HTRA1 in the linear model alone. For CFH, mean letter score change after 6 months was +1.6, +5.9 and +7.2 letters for the TT, TC and CC genotypes and a >5 letter gain was seen in 34.6%, 56.6% and 56%, respectively. For VEGF, mean letter score change after 6 months was +1.3, +5.8 and +7.4 letters for the TT, TC and CC genotypes and a >5 letter gain was seen in 40%, 55.8% and 51.9%, respectively. For HTRA1, mean letter score change was +2.2, +7.5 and +2.9 letters for the GG, GA and AA genotypes.

Conclusions This study reports preliminary evidence suggesting that the higher AMD risk genotypes in CFH, VEGF and HTRA1 may influence the short-term response to treatment with ranibizumab for neovascular AMD.

  • Ranibizumab
  • age-related macular degeneration
  • pharmacogenetics
  • retina
  • genetics
  • treatment medical

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  • A poster including some of these data has been presented at the ARVO meeting, May 2010.

  • Funding This project was supported by a grant from Yorkshire Eye Research and by an investigator-initiated research grant from Novartis Pharmaceuticals UK. The funding organisations had no role in either the design or the conduct of the research.

  • Competing interests None.

  • Ethics approval This study was conducted with the approval of the Leeds East Research Ethics Committee.

  • Provenance and peer review Not commissioned; externally peer reviewed.