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Effect of Factor XIII-A G185T Polymorphism on Visual Prognosis after Photodynamic Therapy for Neovascular Macular Degeneration.
Int J Mol Sci. 2015 Aug 20; 16(8):19796-811.IJ

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.

Authors+Show Affiliations

Eye Clinic, Department of Biomedical and Specialty Surgical Sciences, University of Ferrara, Via Aldo Moro 8, 44124 Cona-Ferrara, Italy. prmfnc@unife.it.Eye Clinic, Department of Health Sciences, University of Molise, Via Francesco de Sanctis 1, 86100 Campobasso, Italy. ciro.costagliola@unimol.it.Eye Clinic, Department of Neurological and Vision Sciences, University of Brescia, Piazzale Spedali Civili 1, 25123 Brescia, Italy. francesco.semeraro@unibs.it.Eye Clinic, Department of Neuroscience, Reproductive and Odonto-Stomatological Sciences, "Federico II" University of Naples, Via Pansini 5, 80131 Napoli, Italy. mario.romano4@unina.it.Department of Ophthalmology, Second University of Naples, Via Pansini 5, 80131 Napoli, Italy. michele.rinaldi@unina2.it.Eye Clinic, Department of Biomedical and Specialty Surgical Sciences, University of Ferrara, Via Aldo Moro 8, 44124 Cona-Ferrara, Italy. gllcln@unife.it.Center of Hemostasis and Thrombosis, Department of Medical Sciences, University of Ferrara, Corso Giovecca 203, 44121 Ferrara, Italy. srnmls@unife.it.Eye Clinic, Department of Biomedical and Specialty Surgical Sciences, University of Ferrara, Via Aldo Moro 8, 44124 Cona-Ferrara, Italy. ncrcrl@unife.it.Eye Clinic, Department of Biomedical and Specialty Surgical Sciences, University of Ferrara, Via Aldo Moro 8, 44124 Cona-Ferrara, Italy.Eye Clinic, Department of Biomedical and Specialty Surgical Sciences, University of Ferrara, Via Aldo Moro 8, 44124 Cona-Ferrara, Italy. katia.denadai@libero.it.Eye Clinic, Department of Health Sciences, University of Molise, Via Francesco de Sanctis 1, 86100 Campobasso, Italy. robdellomo@libero.it.Eye Clinic, Department of Neurological and Vision Sciences, University of Brescia, Piazzale Spedali Civili 1, 25123 Brescia, Italy. dott.andrea.russo@gmail.com.Center of Hemostasis and Thrombosis, Department of Medical Sciences, University of Ferrara, Corso Giovecca 203, 44121 Ferrara, Italy. cet@unife.it.Eye Clinic, Department of Biomedical and Specialty Surgical Sciences, University of Ferrara, Via Aldo Moro 8, 44124 Cona-Ferrara, Italy. prrpla@unife.it.

Pub Type(s)

Journal Article
Multicenter Study
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

26307969

Citation

Parmeggiani, Francesco, et al. "Effect of Factor XIII-A G185T Polymorphism On Visual Prognosis After Photodynamic Therapy for Neovascular Macular Degeneration." International Journal of Molecular Sciences, vol. 16, no. 8, 2015, pp. 19796-811.
Parmeggiani F, Costagliola C, Semeraro F, et al. Effect of Factor XIII-A G185T Polymorphism on Visual Prognosis after Photodynamic Therapy for Neovascular Macular Degeneration. Int J Mol Sci. 2015;16(8):19796-811.
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. (2015). Effect of Factor XIII-A G185T Polymorphism on Visual Prognosis after Photodynamic Therapy for Neovascular Macular Degeneration. International Journal of Molecular Sciences, 16(8), 19796-811. https://doi.org/10.3390/ijms160819796
Parmeggiani F, et al. Effect of Factor XIII-A G185T Polymorphism On Visual Prognosis After Photodynamic Therapy for Neovascular Macular Degeneration. Int J Mol Sci. 2015 Aug 20;16(8):19796-811. PubMed PMID: 26307969.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Effect of Factor XIII-A G185T Polymorphism on Visual Prognosis after Photodynamic Therapy for Neovascular Macular Degeneration. AU - Parmeggiani,Francesco, AU - Costagliola,Ciro, AU - Semeraro,Francesco, AU - Romano,Mario R, AU - Rinaldi,Michele, AU - Gallenga,Carla Enrica, AU - Serino,Maria Luisa, AU - Incorvaia,Carlo, AU - D'Angelo,Sergio, AU - De Nadai,Katia, AU - Dell'Omo,Roberto, AU - Russo,Andrea, AU - Gemmati,Donato, AU - Perri,Paolo, Y1 - 2015/08/20/ PY - 2015/05/12/received PY - 2015/07/23/revised PY - 2015/08/11/accepted PY - 2015/8/27/entrez PY - 2015/8/27/pubmed PY - 2016/5/18/medline KW - anti-thrombophilia KW - choroidal neovascularization KW - factor XIII-A G185T gene polymorphism KW - fibrin-clot stability KW - macular degenerations KW - pharmacogenetics KW - photodynamic therapy with verteporfin SP - 19796 EP - 811 JF - International journal of molecular sciences JO - Int J Mol Sci VL - 16 IS - 8 N2 - 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. SN - 1422-0067 UR - https://www.unboundmedicine.com/medline/citation/26307969/Effect_of_Factor_XIII_A_G185T_Polymorphism_on_Visual_Prognosis_after_Photodynamic_Therapy_for_Neovascular_Macular_Degeneration_ L2 - https://www.mdpi.com/resolver?pii=ijms160819796 DB - PRIME DP - Unbound Medicine ER -