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

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 neovascular...

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Autores principales: Parmeggiani, Francesco, Costagliola, Ciro, Semeraro, Francesco, Romano, Mario R, Rinaldi, Michele, Gallenga, Carla Enrica, Serino, Maria Luisa, Incorvaia, Carlo, D’Angelo, Sergio, De Nadai, Katia, Dell’Omo, Roberto, Russo, Andrea, Gemmati, Donato, Perri, Paolo
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4581326/
https://www.ncbi.nlm.nih.gov/pubmed/26307969
http://dx.doi.org/10.3390/ijms160819796
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author Parmeggiani, Francesco
Costagliola, Ciro
Semeraro, Francesco
Romano, Mario R
Rinaldi, Michele
Gallenga, Carla Enrica
Serino, Maria Luisa
Incorvaia, Carlo
D’Angelo, Sergio
De Nadai, Katia
Dell’Omo, Roberto
Russo, Andrea
Gemmati, Donato
Perri, Paolo
author_facet Parmeggiani, Francesco
Costagliola, Ciro
Semeraro, Francesco
Romano, Mario R
Rinaldi, Michele
Gallenga, Carla Enrica
Serino, Maria Luisa
Incorvaia, Carlo
D’Angelo, Sergio
De Nadai, Katia
Dell’Omo, Roberto
Russo, Andrea
Gemmati, Donato
Perri, Paolo
author_sort Parmeggiani, Francesco
collection PubMed
description 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.
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spelling pubmed-45813262015-09-28 Effect of Factor XIII-A G185T Polymorphism on Visual Prognosis after Photodynamic Therapy for Neovascular Macular Degeneration Parmeggiani, Francesco Costagliola, Ciro Semeraro, Francesco Romano, Mario R Rinaldi, Michele Gallenga, Carla Enrica Serino, Maria Luisa Incorvaia, Carlo D’Angelo, Sergio De Nadai, Katia Dell’Omo, Roberto Russo, Andrea Gemmati, Donato Perri, Paolo Int J Mol Sci Article 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. MDPI 2015-08-20 /pmc/articles/PMC4581326/ /pubmed/26307969 http://dx.doi.org/10.3390/ijms160819796 Text en © 2015 by the authors; licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Parmeggiani, Francesco
Costagliola, Ciro
Semeraro, Francesco
Romano, Mario R
Rinaldi, Michele
Gallenga, Carla Enrica
Serino, Maria Luisa
Incorvaia, Carlo
D’Angelo, Sergio
De Nadai, Katia
Dell’Omo, Roberto
Russo, Andrea
Gemmati, Donato
Perri, Paolo
Effect of Factor XIII-A G185T Polymorphism on Visual Prognosis after Photodynamic Therapy for Neovascular Macular Degeneration
title Effect of Factor XIII-A G185T Polymorphism on Visual Prognosis after Photodynamic Therapy for Neovascular Macular Degeneration
title_full Effect of Factor XIII-A G185T Polymorphism on Visual Prognosis after Photodynamic Therapy for Neovascular Macular Degeneration
title_fullStr Effect of Factor XIII-A G185T Polymorphism on Visual Prognosis after Photodynamic Therapy for Neovascular Macular Degeneration
title_full_unstemmed Effect of Factor XIII-A G185T Polymorphism on Visual Prognosis after Photodynamic Therapy for Neovascular Macular Degeneration
title_short Effect of Factor XIII-A G185T Polymorphism on Visual Prognosis after Photodynamic Therapy for Neovascular Macular Degeneration
title_sort effect of factor xiii-a g185t polymorphism on visual prognosis after photodynamic therapy for neovascular macular degeneration
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4581326/
https://www.ncbi.nlm.nih.gov/pubmed/26307969
http://dx.doi.org/10.3390/ijms160819796
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