Objectives - Age-related macular degeneration (AMD) represents the leading cause of blindness in Western populations. The majority of severe vision loss occurs in the exudative form of AMD, characterized by the development of choroidal neovascularization (CNV) beneath the fovea. Photodynamic therapy with verteporfin (PDT-V) represents one of the most largely employed modality that maybe achieves the subfoveal CNV inactivation in AMD patients. Although several ocular factors have been hitherto investigated as predictors, these researches have weakly contributed to PDT-V optimization. Since PDT-V benefit is determined by CNV photothrombosis, we have retrospectively studied several coagulation-balance gene polymorphisms as predictors of PDT-V efficacy. Methods - Ninety Caucasian patients with neovascular AMD were subdivided in responder and non-responder, basing on CNV responsiveness to PDT-V application. 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 the entire cohort. Results - Logistic regression models showed that PDT-V responders were more prevalent within patients with prothrombin G20210A mutation [OR = 5.6, 95% CI (1.2, 27.2), P = 0.03], and within methylenetetrahydrofolate reductase 677T carriers [OR = 6.9, 95% CI (2.7, 18.1), P < 0.001]. Conversely, PDT-V non-responders were over-represented in carriers for factor XIII-A 185T [OR = 0.13, 95% CI (0.05, 0.36), P < 0.001]. Conclusions - These results provide evidences for the presence of pharmacogenetic relationship between peculiar coagulation-balance gene polymorphisms and different levels of PDT-V effectiveness in patients with AMD-related CNV.

Predictive role of coagulation-balance gene polymorphisms in the efficacy of photodynamic therapy with verteporfin for classic choroidal neovascularization secondary to age-related macular degeneration

PARMEGGIANI, Francesco;GEMMATI, Donato;D'ANGELO, Sergio;PERRI, Paolo;SCAPOLI, Gian Luigi;CATOZZI, Linda;FEDERICI, Federica;SEBASTIANI, Adolfo;INCORVAIA, Carlo
2007

Abstract

Objectives - Age-related macular degeneration (AMD) represents the leading cause of blindness in Western populations. The majority of severe vision loss occurs in the exudative form of AMD, characterized by the development of choroidal neovascularization (CNV) beneath the fovea. Photodynamic therapy with verteporfin (PDT-V) represents one of the most largely employed modality that maybe achieves the subfoveal CNV inactivation in AMD patients. Although several ocular factors have been hitherto investigated as predictors, these researches have weakly contributed to PDT-V optimization. Since PDT-V benefit is determined by CNV photothrombosis, we have retrospectively studied several coagulation-balance gene polymorphisms as predictors of PDT-V efficacy. Methods - Ninety Caucasian patients with neovascular AMD were subdivided in responder and non-responder, basing on CNV responsiveness to PDT-V application. 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 the entire cohort. Results - Logistic regression models showed that PDT-V responders were more prevalent within patients with prothrombin G20210A mutation [OR = 5.6, 95% CI (1.2, 27.2), P = 0.03], and within methylenetetrahydrofolate reductase 677T carriers [OR = 6.9, 95% CI (2.7, 18.1), P < 0.001]. Conversely, PDT-V non-responders were over-represented in carriers for factor XIII-A 185T [OR = 0.13, 95% CI (0.05, 0.36), P < 0.001]. Conclusions - These results provide evidences for the presence of pharmacogenetic relationship between peculiar coagulation-balance gene polymorphisms and different levels of PDT-V effectiveness in patients with AMD-related CNV.
2007
Parmeggiani, Francesco; Costagliola, C.; Gemmati, Donato; D'Angelo, Sergio; Perri, Paolo; Scapoli, Gian Luigi; Catozzi, Linda; Federici, Federica; Seb...espandi
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11392/519578
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