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Study: Response to anti-VEGF therapy not predictable by AMD-associated genes
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A genetic profile of patients enrolled in the Comparison of Age-related Macular Degeneration Treatments Trials found that four well-documented single-nucleotide polymorphisms within four different genes associated with age-related macular degeneration did not predict response to anti-VEGF treatment in patients with neovascular AMD.
“Physicians in the clinic and in CATT have seen a difference in response to therapy,” principal investigator Stephanie A. Hagstrom, PhD, told Ocular Surgery News. “The question then becomes, why do some patients respond better to one drug or the other, or why do they need to receive more or less of a drug? Is there a genetic background effect that might be taking place?”
The authors assessed four single nucleotide polymorphisms (SNPs) — rs1061170 (CFH), rs10490924 (ARMS2), rs11200638 (HTRA1) and rs2230199 (C3). Because of their consistently strong association with the development and progression of AMD, the authors hypothesized that the genotypes might also predict the response to therapy, Hagstrom said.
Results were published in Ophthalmology.
Genotypes
Participants comprised a subset of 834 (73%) of the 1,149 patients participating in the CATT. Each patient was genotyped for the four SNPs using TaqMan SNP genotyping assays (Applied Biosystems).
Anti-VEGF therapy consisted of either Lucentis (ranibizumab, Genentech) or Avastin (bevacizumab, Genentech).
The study compared genotype frequencies to clinical measures of response to therapy at 1 year. Measures included mean visual acuity, mean change in visual acuity, increase in visual acuity of at least 15 letters, retinal thickness, mean change in total foveal thickness, presence of fluid on optical coherence tomography, presence of leakage on fluorescein angiography, mean change in lesion size and mean number of injections administered.
Lack of association
“For all these parameters, we saw nothing significant,” Hagstrom said. “We were hopeful that we would find something meaningful in these top four SNPs. However, it is not surprising that we were unable to find an association based on the biological mechanisms behind these genes.”
Each individual SNP, plus the cumulative effect of two or more SNPs, was evaluated. Regardless of how the numbers were calculated, however, a statistically significant difference in response to anti-VEGF therapy was not found, Hagstrom said.
“Although there is evidence that these high-risk variants will predispose a person to developing AMD, at this point I do not think it is likely that a physician will change therapy based on the results from these genetic tests,” she said.
Hagstrom and colleagues are hopeful that other SNPs such as those in the VEGF and other pathways will correlate more decisively with the response to therapy. “We are going to be looking at many more SNPs in a number of pathways, as well as conducting an exome analysis, assessing all of the genes within a person that codes for proteins,” Hagstrom said. – by Bob Kronemyer