Coagulation-balance genetic predictors for efficacy of photodynamic therapy in occult choroidal neovascularization secondary to age-related macular degeneration
Francesco Parmeggiani 1*,
Ciro Costagliola 2,
Donato Gemmati 3,
Sergio D'Angelo 4,
Paolo Perri 4,
Claudio Campa 4,
Linda Catozzi 3,
Federica Federici 3,
Adolfo Sebastiani 4,
and
Carlo Incorvaia 4
1 Ophthalmology, University of Ferrara, Corso Giovecca, 203, Ferrara, 44100, Italy
2 Health Sciences, University of Molise, Campobasso, Campobasso, Italy
3 Hematology, University of Ferrara, Ferrara, Ferrara, Italy
4 Ophthalmology, University of Ferrara, Ferrara, Ferrara, Italy
* To whom correspondence should be addressed. E-mail: francesco.parmeggiani{at}unife.it.
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Abstract |
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PURPOSE. To determine whether different coagulation-balance genetic polymorphisms might explain the variable clinical outcomes of photodynamic therapy with verteporfin (PDT-V) in Caucasian patients with occult subfoveal choroidal neovascularization (CNV) due to age-related macular degeneration (AMD).
METHODS. The clinical records of consecutive patients with AMD-related occult CNV, treated with PDT-V for evidences of disease progression, were retrospectively examined. Eighty-four eligible subjects were subdivided in responder and non-responder basing on CNV responsiveness to the first PDT-V over a 3-month period. 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. Logistic regression analyses were performed to explore the predictive role of phenotypic and genotypic variables for PDT-V effectiveness.
RESULTS. Regression models documented that PDT-V non-responders were more frequent in patients with the hyper-fibrinolytic G185T mutation of factor XIII-A (OR = 0.28; 95% confidence interval [95% CI], 0.11-0.73; P < 0.01). Univariate logistic regression was indicative for an over-representation of PDT-V responder among the combined carriers for thrombophilic factor V 1691A and prothrombin 20210A alleles (OR = 3.8; 95% confidence interval [95% CI], 0.94-15.6; P = 0.07). All the other considered predictors did not significantly influence the short-term CNV responsiveness to PDT-V.
CONCLUSIONS. These data provide evidences for the presence of pharmacogenetic relationship between peculiar coagulation-balance genetic backgrounds and different levels of PDT-V effectiveness in AMD patients affected by occult CNV.
Key Words:
age-related macular degeneration, neovascularization, photodynamic therapy, thrombo-coagulative factors, single nucleotide polymorphisms, pharmacogenetics
