Effect of factor XIII-a G185T polymorphism on visual prognosis after photodynamic therapy for neovascular macular degeneration

Francesco Parmeggiani, Ciro Costagliola, Francesco Semeraro, Mario R. Romano, Michele Rinaldi, Carla Enrica Gallenga, Maria Luisa Serino, Carlo Incorvaia, Sergio D’Angelo, Katia De Nadai, Roberto Dell’Omo, Andrea Russo, Donato Gemmati, Paolo Perri

Research output: Contribution to journalArticle

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.

Original languageEnglish
Pages (from-to)19796-19811
Number of pages16
JournalInternational Journal of Molecular Sciences
Volume16
Issue number8
DOIs
Publication statusPublished - Aug 20 2015

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Factor XIII
Photodynamic therapy
degeneration
prognosis
polymorphism
angiogenesis
Photochemotherapy
Macular Degeneration
Choroidal Neovascularization
Polymorphism
therapy
myopia
visual acuity
Myopia
Visual Acuity
Pharmacogenetics
Alleles
Genotype
genes
Therapeutics

Keywords

  • Anti-thrombophilia
  • Choroidal neovascularization
  • Factor XIII-A G185T gene polymorphism
  • Fibrin-clot stability
  • Macular degenerations
  • Pharmacogenetics
  • Photodynamic therapy with verteporfin

ASJC Scopus subject areas

  • Physical and Theoretical Chemistry
  • Organic Chemistry
  • Spectroscopy
  • Inorganic Chemistry
  • Catalysis
  • Molecular Biology
  • Computer Science Applications

Cite this

Parmeggiani, F., Costagliola, C., Semeraro, F., Romano, M. R., Rinaldi, M., Gallenga, C. E., ... 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), 19796-19811. https://doi.org/10.3390/ijms160819796

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.

In: International Journal of Molecular Sciences, Vol. 16, No. 8, 20.08.2015, p. 19796-19811.

Research output: Contribution to journalArticle

Parmeggiani, F, Costagliola, C, Semeraro, F, Romano, MR, Rinaldi, M, Gallenga, CE, Serino, ML, 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, vol. 16, no. 8, pp. 19796-19811. https://doi.org/10.3390/ijms160819796
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. In: International Journal of Molecular Sciences. 2015 ; Vol. 16, No. 8. pp. 19796-19811.
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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

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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.

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KW - Pharmacogenetics

KW - Photodynamic therapy with verteporfin

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