Association of complement factor H and LOC387715 genotypes with response of exudative age-related macular degeneration to intravitreal bevacizumab.
OBJECTIVE
To investigate whether there is an association between complement factor H (CFH) or LOC387715 genotypes with response to treatment with intravitreal bevacizumab for exudative age-related macular degeneration (AMD).


METHODS
Retrospective cohort study.


METHODS
The study cohort consisted of 86 patients being treated for neovascular AMD with bevacizumab alone.


METHODS
Genotype determination for the CFH Y402H and LOC387715 A69S polymorphisms was performed by allele-specific digestion of polymerase chain reaction products. All patients were treated with 1.25 mg intravitreal bevacizumab at 6-week intervals until choroidal neovascularization was no longer active.


METHODS
CFH Y402H and LOC387715 A69S polymorphisms. Choroidal neovascular lesion characteristics were ascertained by fluorescein angiography. Snellen visual acuity (VA) was measured before and after treatment.


RESULTS
For the CFH Y402H polymorphism, patients with the CFH TT genotype had the largest choroidal neovascular lesions (P = 0.02). With treatment, VA improved from 20/248 to 20/166 for the CFH TT genotype and from 20/206 to 20/170 for the TC genotype, but fell from 20/206 to 20/341 for the CFH CC genotype (P = 0.016). Only 10.5% of patients with the CFH CC genotype demonstrated improved VA with treatment, compared with 53.7% of CFH TT and TC genotypes (P = 0.004). For the LOC387715 A69S variant, patients with the TT genotype had the largest choroidal neovascular lesions (P = 0.012). There was no significant difference in response to bevacizumab treatment according to LOC387715 genotype.


CONCLUSIONS
The AMD-associated CFH Y402H and LOC387715 A69S variants were associated with differences in choroidal neovascular lesion size in this study. Patients with the CFH CC genotype fared significantly worse with intravitreal bevacizumab than did those with the CFH TC and TT genotypes, suggesting a potential pharmacogenetic relationship. Prospective studies to confirm or refute this observation should be considered.
Department of Ophthalmology and Visual Sciences, Washington University School of Medicine, St. Louis, Missouri 63110, USA. Brantley@vision.wustl.edu
Milam A
MA
Brantley
Amy M
AM
Fang
Jennifer M
JM
King
Asheesh
A
Tewari
Steven M
SM
Kymes
Alan
A
Shiels
D000368:Aged; D000369:Aged, 80 and over; D020533:Angiogenesis Inhibitors / Q000627:therapeutic use*; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D061067:Antibodies, Monoclonal, Humanized; D000068258:Bevacizumab; D020256:Choroidal Neovascularization / Q000188:drug therapy / Q000235:genetics; D017242:Complement Factor H / Q000235:genetics; D005122:Exudates and Transudates; D005260:Female; D005451:Fluorescein Angiography; D005838:Genotype; D006801:Humans; D007267:Injections; D008268:Macular Degeneration / Q000188:drug therapy* / Q000235:genetics*; D008297:Male; D010597:Pharmacogenetics; D016133:Polymerase Chain Reaction; D020641:Polymorphism, Single Nucleotide; D011506:Proteins / Q000235:genetics*; D012189:Retrospective Studies; D042461:Vascular Endothelial Growth Factor A / Q000037:antagonists & inhibitors; D014792:Visual Acuity; D014822:Vitreous Body
C514392:ARMS2 protein, human; D020533:Angiogenesis Inhibitors; D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; C493495:CFH protein, human; D011506:Proteins; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; D000068258:Bevacizumab; D017242:Complement Factor H