Pharmacogenetics of complement factor H (Y402H) and treatment of exudative age-related macular degeneration with ranibizumab

Abstract

Aims To determine whether complement factor H (CFH) genotypes have a pharmacogenetic effect on the treatment of exudative age-related macular degeneration (AMD) with ranibizumab. Methods A retrospective study of 156 patients with exudative AMD treated with intravitreal ranibizumab monotherapy was conducted. AMD phenotypes were characterized by clinical examination, visual acuity, fundus photography, fluorescein angiography, and injection timing. Patients received intravitreal ranibizumab injections as part of routine ophthalmologic care and were followed for a minimum of nine months. Each patient was genotyped for the single nucleotide polymorphism rs1061170 (Y402H) in the CFH gene. Results Baseline lesion size and angiographic type, as well as mean visual acuities at baseline, 6 months, and 9 months were similar among the three CFH genotypes. Over 9 months, patients with both risk alleles received approximately one more injection (p = 0.09). In a recurrent event analysis, patients homozygous for the CFH Y402H risk allele had a 37% significantly higher risk of requiring additional ranibizumab injections (p = 0.04) Conclusions In our cohort, response to treatment of AMD with ranibizumab differed according to CFH genotype, suggesting that determining patients' CFH genotype may be helpful in the future in tailoring treatment for exudative AMD with intravitreal ranibizumab.

Importance of genetic polymorphisms in the response to age-related macular degeneration treatment

“…(62,67) Recently, two studies have demonstrated the association between gene polymorphisms and the response to intravitreal injections of the antivascular endothelial growth factor (anti-VEGF) agents bevacizumab and ranibizumab. (69,70) Brantley et al conducted a study in which eighty-six patients with exudative AMD undergoing treatment with 1.25 mg intravitreal bevacizumab in one eye were enrolled. Intravitreal injections were performed at 6-week intervals until there was no longer evidence of active neovascularization.…”

“…Nevertheless, over 9 months, patients with both risk alleles received approximately 1 more intravitreal injection. (70) There is only one study with a large number of patients that addresses the preventive treatment of dry AMD related to the genetic polymorphisms. As we can observe, the majority of published articles about the therapeutic response of exudative AMD are related the photodynamic therapy and many of them are controversial.…”

The non-Responsiveness to Anti-Vascular Endothelial Growth Factor Agents in the Treatment of Neovascularage-Related Macular Degeneration

“…In the light of the recent reports, it can be considered that the potential risk factors for non-responsiveness to anti-VEGF agent in the treatment of n-AMD are an initial lesion with subfoveal fibrosis or atrophy in retina pigment epithelium and photoreceptors, lesion in large size, type 1 choroidal neovascularization, serous pigment epithelium detachment (PED), haemorrhagic PED, fibrovascular PED, polypoidal choroidal vasculopathy, foveal scarring and vitreomacular traction, outer retinal tubulation, cystoid degeneration in outer retina, genetic disposition or an anti-VEGF resistance [Table 1, 13-22]. Table 1: The possible risk factors for non-responsiveness to anti-VEGF agents in the patients with nAMD [6][7][8][9][10][11][12][13][14][15][16][17][18][19][20][21][22].…”

Exudative AMD subtypes and eligibility for treatment with ranibizumab

“…[2][3][4][5] Pivotal and post-licensing studies of PDT and antiangiogenic agents have suggested that lesion position and type influences the response to treatment. 3,6,7 Healthcare providers who are faced with expensive new therapies may seek to limit treatment to specific clinical groups who were shown to experience maximum benefit or to patients who fulfil the eligibility criteria that were set in the key licensing trials. Examples of this include the guidance that has been issued by the National Institute for Clinical Excellence (NICE) in the United Kingdom, limiting PDT treatment to specific angiographic subtypes and more recently by issuing guidance on eligibility for treatment with antiangiogenic agents.…”