Pharmacogenetics of complement factor H (Y402H) and treatment of exudative age-related macular degeneration with ranibizumab.
OBJECTIVE
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.
Lee
A Y
AY
Department of Ophthalmology and Visual Sciences, Washington University School of Medicine, St Louis, MO 63110, USA.
Raya
A K
AK
Kymes
S M
SM
Shiels
A
A
Brantley
M A
MA
D000368:Aged; D000369:Aged, 80 and over; D020533:Angiogenesis Inhibitors / Q000627:therapeutic use*; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D061067:Antibodies, Monoclonal, Humanized; D017242:Complement Factor H / Q000235:genetics; D005260:Female; D005838:Genotype; D006801:Humans; D008268:Macular Degeneration / Q000188:drug therapy / Q000235:genetics* / Q000503:physiopathology; D008297:Male; D000069579:Ranibizumab; D012189:Retrospective Studies; D016896:Treatment Outcome; D014792:Visual Acuity / Q000187:drug effects
D020533:Angiogenesis Inhibitors; D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; C493495:CFH protein, human; D017242:Complement Factor H; D000069579:Ranibizumab