PURPOSE: To determine whether different coagulation-balance genetic polymorphisms explain the variable clinical outcomes of photodynamic therapy with verteporfin (PDT-V) in Caucasian patients with classic or predominantly classic choroidal neovascularization (CNV) due to age-related macular degeneration (AMD). METHODS: The clinical records of consecutive AMD patients with classic or predominantly classic CNV, treated with PDTV according to the Treatment of Age-Related Macular Degeneration with Photodynamic Therapy study criteria, were retrospectively examined. Eighty-six eligible patients were subdivided in responder and non-responder basing on the modifications of best-corrected visual acuity between baseline and 12-month checks. Six gene polymorphisms, i.e. factor V G1691A, prothrombin G20210A, factor XIII-A G185T, methylenetetrahydrofolate reductase C677T, methionine synthase A2756G, and methionine synthase reductase A66G, were genotyped in each patient. Binary logistic regression models were used to explore the predictive role of phenotypic and genotypic variables for PDT-V effectiveness. RESULTS: PDT-V responders were more prevalent among the combined carriers for factor V 1691A and prothrombin 20210A alleles (OR = 5.1 with a 95% CI of 1.0-24.4; P = 0.05), methylenetetrahydrofolate reductase 677 T-allele (OR = 4.3 with a 95% CI of 1.8-10.8; P = 0.002), and methionine synthase reductase 66 G-allele (OR = 2.8 with a 95% CI of 1.1-6.8; P = 0.04). Conversely, PDT-V non-responders were over-represented in patients with factor XIII-A 185 T-allele (OR = 0.22 with a 95% CI of 0.09-0.56; P = 0.001). The other considered predictors did not significantly modify PDT-V effectiveness. CONCLUSIONS: Our study provides evidences for the presence of pharmacogenetic relationship between peculiar coagulation-balance gene polymorphisms and different levels of visual prognosis at 12 months in AMD patients treated with standardized PDT-V protocol for classic subfoveal CNV.

Coagulation-balance gene predictors influencing visual prognosis in patients treated with photodynamic therapy for classic choroidal neovascularization secondary to age-related macular degeneration.

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2010

Abstract

PURPOSE: To determine whether different coagulation-balance genetic polymorphisms explain the variable clinical outcomes of photodynamic therapy with verteporfin (PDT-V) in Caucasian patients with classic or predominantly classic choroidal neovascularization (CNV) due to age-related macular degeneration (AMD). METHODS: The clinical records of consecutive AMD patients with classic or predominantly classic CNV, treated with PDTV according to the Treatment of Age-Related Macular Degeneration with Photodynamic Therapy study criteria, were retrospectively examined. Eighty-six eligible patients were subdivided in responder and non-responder basing on the modifications of best-corrected visual acuity between baseline and 12-month checks. Six gene polymorphisms, i.e. factor V G1691A, prothrombin G20210A, factor XIII-A G185T, methylenetetrahydrofolate reductase C677T, methionine synthase A2756G, and methionine synthase reductase A66G, were genotyped in each patient. Binary logistic regression models were used to explore the predictive role of phenotypic and genotypic variables for PDT-V effectiveness. RESULTS: PDT-V responders were more prevalent among the combined carriers for factor V 1691A and prothrombin 20210A alleles (OR = 5.1 with a 95% CI of 1.0-24.4; P = 0.05), methylenetetrahydrofolate reductase 677 T-allele (OR = 4.3 with a 95% CI of 1.8-10.8; P = 0.002), and methionine synthase reductase 66 G-allele (OR = 2.8 with a 95% CI of 1.1-6.8; P = 0.04). Conversely, PDT-V non-responders were over-represented in patients with factor XIII-A 185 T-allele (OR = 0.22 with a 95% CI of 0.09-0.56; P = 0.001). The other considered predictors did not significantly modify PDT-V effectiveness. CONCLUSIONS: Our study provides evidences for the presence of pharmacogenetic relationship between peculiar coagulation-balance gene polymorphisms and different levels of visual prognosis at 12 months in AMD patients treated with standardized PDT-V protocol for classic subfoveal CNV.
Romano, Mario
SEBASTIANI, Adolfo
BOREA, Pier Andrea
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11392/2389331
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