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Open AccessArticle

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