PURPOSE: To investigate whether different coagulation-balance genetic backgrounds might explain the variable clinical outcomes detected, after a single photodynamic therapy with verteporfin (PDT-V), in Caucasian patients with subfoveal choroidal neovascularization (CNV) secondary to pathologic myopia (PM). DESIGN: Retrospective, consecutive, nonrandomized, interventional cases series. PARTICIPANTS: Two hundred thirty-four patients exclusively treated with standardized PDT-V for the presence of PM-related classic CNV. METHODS: The enrolled patients were subdivided in responder and non-responder basing on CNV responsiveness to the first PDT-V over a 3-month period. Three common gene polymorphisms, i.e., factor XIII-A G185T, methylenetetrahydrofolate reductase C677T, and methionine synthase reductase A66G, were PCR-genotyped in each patient. MAIN OUTCOME MEASURES: The measures of CNV responsiveness to PDT-V were the changes, respect to baseline, of fluorescein angiography CNV-leakage, greatest linear dimension and area of the lesion. Logistic regression analyses were performed to explore the predictive role of phenotypic (patient’s age, baseline visual acuity and baseline CNV area) and genotypic (all the mentioned mutations) variables regarding PDT-V efficacy. RESULTS: Responders to PDT-V were over-represented within carriers of methylenetetrahydrofolate reductase 677 T-allele (odds ratio – OR = 3.1, 95% confidence interval – CI: 1.8-5.4; P = 0.001) and, to minor extent, among patients with better visual acuity at baseline (OR = 11.8, 95% CI: 1.6-88.0; P = 0.02). On the other hand, predictors of PDT-V lack of efficacy were patient’s age (OR = 0.73, 95% CI: 0.62-0.86; P = 0.01) and, especially, factor XIII-A 185 GT/TT genotypes (OR = 0.19, 95% CI: 0.11-0.35; P = 0.0001). All the other considered predictive factors did not significantly influence the CNV responsiveness to PDT-V. CONCLUSIONS: These findings document the presence of pharmacogenetic correlations between common coagulation-balance gene polymorphisms and different CNV responsiveness to PDT-V in Caucasian patients with neovascular PM.
Impact of coagulation-balance gene predictors on efficacy of photodynamic therapy for choroidal neovascularization in pathologic myopia
PARMEGGIANI, Francesco;GEMMATI, Donato;D'ANGELO, Sergio;PERRI, Paolo;SEBASTIANI, Adolfo;INCORVAIA, Carlo
2010
Abstract
PURPOSE: To investigate whether different coagulation-balance genetic backgrounds might explain the variable clinical outcomes detected, after a single photodynamic therapy with verteporfin (PDT-V), in Caucasian patients with subfoveal choroidal neovascularization (CNV) secondary to pathologic myopia (PM). DESIGN: Retrospective, consecutive, nonrandomized, interventional cases series. PARTICIPANTS: Two hundred thirty-four patients exclusively treated with standardized PDT-V for the presence of PM-related classic CNV. METHODS: The enrolled patients were subdivided in responder and non-responder basing on CNV responsiveness to the first PDT-V over a 3-month period. Three common gene polymorphisms, i.e., factor XIII-A G185T, methylenetetrahydrofolate reductase C677T, and methionine synthase reductase A66G, were PCR-genotyped in each patient. MAIN OUTCOME MEASURES: The measures of CNV responsiveness to PDT-V were the changes, respect to baseline, of fluorescein angiography CNV-leakage, greatest linear dimension and area of the lesion. Logistic regression analyses were performed to explore the predictive role of phenotypic (patient’s age, baseline visual acuity and baseline CNV area) and genotypic (all the mentioned mutations) variables regarding PDT-V efficacy. RESULTS: Responders to PDT-V were over-represented within carriers of methylenetetrahydrofolate reductase 677 T-allele (odds ratio – OR = 3.1, 95% confidence interval – CI: 1.8-5.4; P = 0.001) and, to minor extent, among patients with better visual acuity at baseline (OR = 11.8, 95% CI: 1.6-88.0; P = 0.02). On the other hand, predictors of PDT-V lack of efficacy were patient’s age (OR = 0.73, 95% CI: 0.62-0.86; P = 0.01) and, especially, factor XIII-A 185 GT/TT genotypes (OR = 0.19, 95% CI: 0.11-0.35; P = 0.0001). All the other considered predictive factors did not significantly influence the CNV responsiveness to PDT-V. CONCLUSIONS: These findings document the presence of pharmacogenetic correlations between common coagulation-balance gene polymorphisms and different CNV responsiveness to PDT-V in Caucasian patients with neovascular PM.I documenti in SFERA sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
