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Alexandra Mouallem, Rocio Blanco-Garavito, Florence Richard, Camille JUNG, Eric H SOUIED; Genetics of large pigment epithelial detachment in neovascular age related macular degeneration highlights the role of Complement alternative pathway in this particular phenotype.. Invest. Ophthalmol. Vis. Sci. 2017;58(8):1838.
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© ARVO (1962-2015); The Authors (2016-present)
To analyze the genetics of variants of patients presenting large neovascular pigment epithelium detachment (PED) resistant to ranibizumab in neovascular age related macular degeneration (nAMD) through a genetic association study.
Sixty eight patients presenting a large pigment epithelium detachment resistant to ranibizumab (the ARI2 study) are compared to 300 patients presenting unilateral nAMD (the NAT2 study), 1229 patients with exudative nAMD and 444 controls derived from two prospective clinical studies previously published that took place in Hopital Intercommunal de Creteil. nAMD groups were based on visual acuity measurement, fundus examination, treatment response, Spectral Domain Optical Coherence Tomography (SD-OCT) and angiographic data. All samples were genotyped for five single-nucleotide polymorphisms (SNPs) in genes previously associated with AMD: CFH (rs1061170), ARMS2 (rs10490924), C3(rs2230199) and APOE(rs429358 and rs7412) . Significant difference in allele frequency between participants with nAMD and control is the main outcome criteria.
The frequency of the C allele of CFH rs1061170 was significantly higher in the large vascular PED group than in the control group (0.66 vs 0.38, Chi2= 37.23 ; p = 1.01e-09) with an increased frequency in the large neovascular PED group compared to the unilateral nAMD group (0.66 vs 0.55; Chi2 = 5.21; p value = 0,02 ) and to the other nAMD group (0.66 vs 0.52; Chi2 =9.39, p value =0.002). The frequency of the G allele of C3 rs2230199 was also significantly higher compared to the control group (0.74 vs 0.18; Chi2 =177.85 ; p < 2.2e-16), to the unilateral nAMD group (0.74 vs 0.25; Chi2=111.59 p<2.2e-16 ) and to the other nAMD group (0.74 vs 0.25; Chi2= 147.65 p< 2.2e-16). The frequency of the T allele of ARMS2 rs10490924 was significantly higher in the large PED group than in the control group (0.50 vs 0.22; Chi2=49.447; p value= 2.03e-12) but no difference was found with other nAMD groups.
The C allele of CFH rs1061170 and the G allele of C3 rs2230199, known as susceptibility risk alleles of AMD, are associated to the particular phenotype of large neovascular PED resistant to ranibizumab. Other prospective genetic studies should analyze the role of other Complement alternative pathway factors.
This is an abstract that was submitted for the 2017 ARVO Annual Meeting, held in Baltimore, MD, May 7-11, 2017.
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