Predictive role of C677T MTHFR polymorphism in variable efficacy of photodynamic therapy for neovascular age-related macular degeneration.
Age-related macular degeneration (AMD) complicated by subfoveal choroidal neovascularization (CNV) is the leading cause of severe central blindness in developed countries. AMD-related CNVs are distinguishable in classic and occult subtypes, characterized by variable natural history and different responsiveness to therapeutic procedures. Combined and repeated use of photodynamic therapy with verteporfin (PDT-V) and antiangiogenic drugs represents the most promising strategy against neovascular AMD, but it is unavoidably associated with mounting health-resource utilization. Predictive correlations between peculiar coagulation-balance gene variants and different levels of post-PDT-V benefit have recently been documented in Caucasians with AMD-related CNVs. In particular, methylenetetrahydrofolate reductase C677T substitution, a common thrombophilic folate pathway genotypic polymorphism, influences a better CNV responsiveness to PDT-V in classic- but not in occult-CNV cases. These pharmacogenetic findings indicate the opportunities to optimize the eligibility criteria of PDT-V and/or to perform this intriguing therapy in a customized manner, for finally minimizing the socio-economic burden of neovascular AMD.
Parmeggiani
Francesco
F
Sezione di Clinica Oculistica, Dipartimento di Discipline Medico-Chirurgiche della Comunicazione e del Comportamento, Università degli Studi di Ferrara, Corso Giovecca 203, 44100 Ferrara, Italy. francesco.parmeggiani@unife.it
Gemmati
Donato
D
Costagliola
Ciro
C
Sebastiani
Adolfo
A
Incorvaia
Carlo
C
D000375:Aging / Q000473:pathology*; D020256:Choroidal Neovascularization / Q000235:genetics / Q000473:pathology / Q000517:prevention & control*; D006801:Humans; D008268:Macular Degeneration / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D042965:Methylenetetrahydrofolate Reductase (NADPH2) / Q000235:genetics*; D010778:Photochemotherapy / Q000379:methods*; D017319:Photosensitizing Agents / Q000008:administration & dosage / Q000627:therapeutic use; D020641:Polymorphism, Single Nucleotide; D011166:Porphyrins / Q000008:administration & dosage / Q000627:therapeutic use; D011237:Predictive Value of Tests; D016896:Treatment Outcome; D000077362:Verteporfin
D017319:Photosensitizing Agents; D011166:Porphyrins; D000077362:Verteporfin; D042965:Methylenetetrahydrofolate Reductase (NADPH2)