Combined effects of genetic and non-genetic risk factors affect response to ranibizumab in exudative age-related macular degeneration.
OBJECTIVE
To investigate whether genetic and non-genetic risk factors influence 12-month response to ranibizumab treatment for exudative age-related macular degeneration (AMD).


METHODS
A cohort of 94 Caucasian patients with unilateral exudative AMD received intravitreal ranibizumab. After a three-injection loading phase, a PRN regimen was followed. Patients were genotyped for three single-nucleotide polymorphisms: CFH rs1061170, ARMS2 rs10490924 and C3 rs2230199. Non-genetic risk factors [choroidal neovascularization (CNV) phenotype, smoking habit, hypertension and body mass index] were considered. The selected end-point was the 12-month variation of number of ETDRS letters.


RESULTS
Complement factor H (CFH) risk alleles, smoking history and arterial hypertension each independently influenced treatment response, with worse 12-month BCVA outcomes (p = 0.036, 0.037, 0.043, respectively). A significant cumulative effect of these risk factors was also observed: patients homozygous for the CFH risk alleles and with a positive smoking history showed a mean loss of 8.0 ETDRS letters (p = 0.010). Patients with CFH risk alleles, smoking history and hypertension had a mean loss of 13.9 ETDRS letters (p = 0.013). CNV phenotypes did not influence visual outcomes, nor were they associated with other genetic/non-genetic risk factors.


CONCLUSIONS
Complement factor H risk alleles, smoking history and hypertension affect the mid-term response to ranibizumab in exudative AMD.
Neuroscience Department, University of Padova, Padova, Italy.
Stefano
S
Piermarocchi
Neuroscience Department, University of Padova, Padova, Italy.
Stefania
S
Miotto
Research and Innovation, S.r.l., Padova, Italy.
Davide
D
Colavito
Research and Innovation, S.r.l., Padova, Italy.
Alberta
A
Leon
Neuroscience Department, University of Padova, Padova, Italy.
Tatiana
T
Segato
D000368:Aged; D000369:Aged, 80 and over; D020533:Angiogenesis Inhibitors / Q000627:therapeutic use*; D003176:Complement C3 / Q000235:genetics; D017242:Complement Factor H / Q000235:genetics; D005260:Female; D060005:Genotyping Techniques; D006801:Humans; D006973:Hypertension / Q000150:complications; D058449:Intravitreal Injections; D008297:Male; D008875:Middle Aged; D010597:Pharmacogenetics; D020641:Polymorphism, Single Nucleotide; D011446:Prospective Studies; D011506:Proteins / Q000235:genetics; D000069579:Ranibizumab / Q000627:therapeutic use*; D012307:Risk Factors; D012907:Smoking / Q000009:adverse effects; D042461:Vascular Endothelial Growth Factor A / Q000037:antagonists & inhibitors; D014792:Visual Acuity / Q000502:physiology; D057135:Wet Macular Degeneration / Q000188:drug therapy* / Q000235:genetics* / Q000503:physiopathology
C514392:ARMS2 protein, human; D020533:Angiogenesis Inhibitors; C493495:CFH protein, human; D003176:Complement C3; D011506:Proteins; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; D017242:Complement Factor H; D000069579:Ranibizumab
ARMS2; C3; CFH; age-related macular degeneration; arterial hypertension; ranibizumab; smoking habit