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Int. J. Mol. Sci. 2015, 16(8), 19796-19811; doi:10.3390/ijms160819796

Effect of Factor XIII-A G185T Polymorphism on Visual Prognosis after Photodynamic Therapy for Neovascular Macular Degeneration

1
Eye Clinic, Department of Biomedical and Specialty Surgical Sciences, University of Ferrara, Via Aldo Moro 8, 44124 Cona-Ferrara, Italy
2
Eye Clinic, Department of Health Sciences, University of Molise, Via Francesco de Sanctis 1, 86100 Campobasso, Italy
3
Eye Clinic, Department of Neurological and Vision Sciences, University of Brescia, Piazzale Spedali Civili 1, 25123 Brescia, Italy
4
Eye Clinic, Department of Neuroscience, Reproductive and Odonto-Stomatological Sciences, “Federico II” University of Naples, Via Pansini 5, 80131 Napoli, Italy
5
Department of Ophthalmology, Second University of Naples, Via Pansini 5, 80131 Napoli, Italy
6
Center of Hemostasis and Thrombosis, Department of Medical Sciences, University of Ferrara, Corso Giovecca 203, 44121 Ferrara, Italy
*
Author to whom correspondence should be addressed.
Academic Editor: Sabrina Angelini
Received: 12 May 2015 / Revised: 23 July 2015 / Accepted: 11 August 2015 / Published: 20 August 2015
(This article belongs to the Special Issue Pharmacogenetics and Personalized Medicine)
View Full-Text   |   Download PDF [705 KB, uploaded 20 August 2015]   |  

Abstract

Macular degenerations represent leading causes of central blindness or low vision in developed countries. Most of these severe visual disabilities are due to age-related macular degeneration (AMD) and pathologic myopia (PM), both of which are frequently complicated by subfoveal choroidal neovascularization (CNV). Photodynamic therapy with verteporfin (PDT-V) is still employed for CNV treatment in selected cases or in combined regimen. In Caucasian patients, the common polymorphism G185T of factor XIII-A gene (FXIII-A-G185T; rs5985) has been described as predictor of poor angiographic CNV responsiveness to PDT-V. Nevertheless, the prognostic implications of this pharmacogenetic determinant on long-term visual outcome after a PDT-V regimen have not been evaluated. We retrospectively selected Caucasian patients presenting with treatment-naive CNV and receiving standardized PDT-V protocol for two years. The study population included patients affected by subfoveal CNV secondary to AMD or PM. We assessed the correlations between the polymorphic allele T of FXIII-A-G185T and: (1) total number of photodynamic treatments; and (2) change in visual acuity from baseline to the end of the follow-up period. Considering a total study population of 412 patients with neovascular AMD or PM, the carriers of 185 T-allele of FXIII-A (GT or TT genotype) received a higher number of photodynamic treatments than patients without it (GG wild-type genotype) (p < 0.01; mean number of PDT-V: 5.51 vs. 3.76, respectively). Moreover, patients with 185 T-allele of FXIII-A had a more marked worsening of visual acuity at 24 months than those with the GG-185 wild genotype (p < 0.01; mean difference in logMAR visual acuity: 0.22 vs. 0.08, respectively). The present findings show that the G185T polymorphism of the FXIII-A gene is associated with significant differences in the long-term therapeutic outcomes of patients treated with standardized PDT-V protocol. The comprehensive appraisal of both anti-thrombophilic effects due to FXIII-A G185T variant and photo-thrombotic action of PDT-V toward CNV provides several clues about the rationale of this intriguing pharmacogenetic correlation. Further investigations are warranted to outline the appropriate paradigm for guiding PDT-V utilization in the course of the combined therapeutic protocol for neovascular macular degeneration. View Full-Text
Keywords: macular degenerations; choroidal neovascularization; pharmacogenetics; photodynamic therapy with verteporfin; fibrin-clot stability; factor XIII-A G185T gene polymorphism; anti-thrombophilia macular degenerations; choroidal neovascularization; pharmacogenetics; photodynamic therapy with verteporfin; fibrin-clot stability; factor XIII-A G185T gene polymorphism; anti-thrombophilia
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MDPI and ACS Style

Parmeggiani, F.; Costagliola, C.; Semeraro, F.; Romano, M.R.; Rinaldi, M.; Gallenga, C.E.; Serino, M.L.; Incorvaia, C.; D’Angelo, S.; De Nadai, K.; Dell’Omo, R.; Russo, A.; Gemmati, D.; Perri, P. Effect of Factor XIII-A G185T Polymorphism on Visual Prognosis after Photodynamic Therapy for Neovascular Macular Degeneration. Int. J. Mol. Sci. 2015, 16, 19796-19811.

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