Purpose
To determine whether genetic risk single nucleotide polymorphisms (SNPs) for age-related macular degeneration (AMD) influence short-term response to intravitreal ranibizumab treatment.
Methods
Forty-four treatment-naive AMD patients were included in a prospective observational study. They underwent three monthly injections of intravitreal ranibizumab for neovascular AMD. After an initial clinical examination (baseline measurement), a follow-up visit was performed to determine treatment response one month after the third injection (treatment evaluation). Patients were evaluated based on ophthalmoscopy, fluorescein angiography, optical coherence tomography (OCT), and OCT angiography. Peripheral venous blood was collected for DNA analysis at baseline visit. Patients were genotyped for single-nucleotide polymorphisms within AMD-relevant genes and classified on good or poor responders based on visual acuity, central retinal thickness, intraretinal fluid, and subretinal fluid.
Results
One hundred ten AMD-associated SNPs have been analyzed. Six were found to be relevant when associated to ranibizumab treatment response. The genetic variants rs890293 (
CYP2J2),
rs11200638 (
HTRA1),
rs405509
(APOE),
rs9513070
(FLT1)
, and rs8135665 (
SLC16A8
) predisposed patients to a good response, whereas rs3093077 (CRP) was associated with a poor response.
FTL1
,
SLC16A8
, and
APOE
were the SNPs that showed significance (
P
< 0.05) but did not pass Bonferroni correction.
Conclusions
This is the first study that links novel polymorphisms in genes such as
CRP, SCL16A8
, or
CYP2J2
to treatment response to ranibizumab therapy. On the other hand,
HTRA1, FLT1
, and
APOE
are linked to a good ranibizumab response. These SNPs may be good candidates for short-term treatment response biomarkers in AMD patients. However, further studies will be necessary to confirm our findings.