In the JournalsPerspective

Study links genetic variants to poor outcomes after anti-VEGF treatment for AMD

Variants in genes connected to age-related macular degeneration were associated with poor visual outcomes after treatment with ranibizumab or bevacizumab, according to a study.

The prospective study included 224 patients with neovascular AMD who underwent intravitreal injections of 0.5 mg Lucentis (ranibizumab, Genentech) or 1.25 mg Avastin (bevacizumab, Genentech).

Patients underwent three monthly injections and as-needed injections for an additional 9 months; patients received an average of 6.4 injections.

Investigators examined the influence of 17 single nucleotide polymorphisms (SNPs) in known AMD risk-associated genes on mean change in ETDRS visual acuity at 12 months.

The mean change in visual acuity at 12 months was a gain of 3.2 lines.

The AA genotype at the rs11200638 SNP on the HTRA1 promoter gene and GG genotype at rs10490924 (A69S) in LOC387715/ARMS2 correlated significantly with poor visual acuity outcome at 12 months after multiple correction (P = .001 and P = .002, respectively).

Patients with the AA genotype at the rs11200638 SNP on HTRA1 lost a mean 2.9 letters. Patients with the AG or GG genotypes at the same SNP gained a mean of 5.1 letters. The difference was statistically significant (P = .001).

Disclosure: The study authors have no relevant financial disclosures.

Variants in genes connected to age-related macular degeneration were associated with poor visual outcomes after treatment with ranibizumab or bevacizumab, according to a study.

The prospective study included 224 patients with neovascular AMD who underwent intravitreal injections of 0.5 mg Lucentis (ranibizumab, Genentech) or 1.25 mg Avastin (bevacizumab, Genentech).

Patients underwent three monthly injections and as-needed injections for an additional 9 months; patients received an average of 6.4 injections.

Investigators examined the influence of 17 single nucleotide polymorphisms (SNPs) in known AMD risk-associated genes on mean change in ETDRS visual acuity at 12 months.

The mean change in visual acuity at 12 months was a gain of 3.2 lines.

The AA genotype at the rs11200638 SNP on the HTRA1 promoter gene and GG genotype at rs10490924 (A69S) in LOC387715/ARMS2 correlated significantly with poor visual acuity outcome at 12 months after multiple correction (P = .001 and P = .002, respectively).

Patients with the AA genotype at the rs11200638 SNP on HTRA1 lost a mean 2.9 letters. Patients with the AG or GG genotypes at the same SNP gained a mean of 5.1 letters. The difference was statistically significant (P = .001).

Disclosure: The study authors have no relevant financial disclosures.

    Perspective

    Abedi and colleagues show a relationship between anti-VEGF treatment outcomes in neovascular AMD and selected genetic variants. The worse visual outcomes with either ranibizumab or bevacizumab in the first year of therapy were in patients with AMD risk genotypes in HTRA1 and ARMS2 genes, and the authors provide a logical pathogenic mechanism to explain why these patients may not respond as well. These results are somewhat consistent with a few other previously published relatively small studies, but the influence of genotypes with regards to treatment response remains poorly defined and controversial, as larger, better designed studies with fixed monthly treatment regimens, such as CATT and others, have not shown such relationships to exist. What can be said at this time is that certain genotypes have been shown to be independent risk factors for development of AMD, but the evidence for playing a role in influencing neovascular AMD treatment response remains inconclusive.

    • Carl D. Regillo, MD, FACS
    • OSN Retina/Vitreous Board Member

    Disclosures: Regillo is a consultant for and receives grant support from Genentech and Regeneron.