Abstract
Purpose: :
Choroidal neovascularization (CNV) beneath the fovea represents the leading cause of severe central low-vision in developed countries. The most common form of subfoveal CNV is that secondary to age-related macular degeneration (AMD). Photodynamic therapy with verteporfin (PDT-V) is one of the first-line treatments for AMD-related CNV. Because PDT-V benefit is determined by CNV photothrombosis, we have studied several common coagulation-balance gene polymorphisms as predictors of PDT-V efficacy in Caucasians affected by neovascular AMD.
Methods: :
The clinical records of consecutive AMD patients with classic or predominantly classic CNV, treated with PDT-V according to the Treatment of Age-Related Macular Degeneration with Photodynamic Therapy study criteria, were retrospectively examined. Ninety-two eligible patients were subdivided in responder and non-responder basing on the modifications of best-corrected visual acuity between baseline and 12-month checks. Three widespread gene polymorphisms, i.e. factor XIII-A G185T, methylenetetrahydrofolate reductase C677T, and methionine synthase reductase A66G, were genotyped in each patient. Binary logistic regression models were used to explore the predictive role of genotypic variables for PDT-V effectiveness.
Results: :
PDT-V responders were more prevalent among the combined carriers for methylenetetrahydrofolate reductase 677 T-allele (OR = 4.1 with a 95% CI of 1.6-10.1; P < 0.01), and methionine synthase reductase 66 G-allele (OR = 2.9 with a 95% CI of 1.2-6.9; P < 0.05). Conversely, PDT-V non-responders were over-represented in patients with factor XIII-A 185 T-allele (OR = 0.19 with a 95% CI of 0.09-0.41; P < 0.01).
Conclusions: :
In Caucasian patients treated with standardized PDT-V protocol for AMD-related classic CNV, several pharmacogenetic correlations between common coagulation-balance gene variants and different levels of 12-month visual prognosis are present.
Keywords: age-related macular degeneration • gene/expression • photodynamic therapy