title: Effect of Factor XIII-A G185T Polymorphism on Visual Prognosis after Photodynamic Therapy for Neovascular Macular Degeneration.
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: Eye Clinic, Department of Biomedical and Specialty Surgical Sciences, University of Ferrara, Via Aldo Moro 8, 44124 Cona-Ferrara, Italy. prmfnc@unife.it.
authors: Francesco
authors: F
authors: Parmeggiani
authors: Eye Clinic, Department of Health Sciences, University of Molise, Via Francesco de Sanctis 1, 86100 Campobasso, Italy. ciro.costagliola@unimol.it.
authors: Ciro
authors: C
authors: Costagliola
authors: Eye Clinic, Department of Neurological and Vision Sciences, University of Brescia, Piazzale Spedali Civili 1, 25123 Brescia, Italy. francesco.semeraro@unibs.it.
authors: Francesco
authors: F
authors: Semeraro
authors: 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.
authors: Mario R
authors: MR
authors: Romano
authors: Department of Ophthalmology, Second University of Naples, Via Pansini 5, 80131 Napoli, Italy. michele.rinaldi@unina2.it.
authors: Michele
authors: M
authors: Rinaldi
authors: Eye Clinic, Department of Biomedical and Specialty Surgical Sciences, University of Ferrara, Via Aldo Moro 8, 44124 Cona-Ferrara, Italy. gllcln@unife.it.
authors: Carla Enrica
authors: CE
authors: Gallenga
authors: Center of Hemostasis and Thrombosis, Department of Medical Sciences, University of Ferrara, Corso Giovecca 203, 44121 Ferrara, Italy. srnmls@unife.it.
authors: Maria Luisa
authors: ML
authors: Serino
authors: Eye Clinic, Department of Biomedical and Specialty Surgical Sciences, University of Ferrara, Via Aldo Moro 8, 44124 Cona-Ferrara, Italy. ncrcrl@unife.it.
authors: Carlo
authors: C
authors: Incorvaia
authors: Eye Clinic, Department of Biomedical and Specialty Surgical Sciences, University of Ferrara, Via Aldo Moro 8, 44124 Cona-Ferrara, Italy.
authors: Sergio
authors: S
authors: D'Angelo
authors: Eye Clinic, Department of Biomedical and Specialty Surgical Sciences, University of Ferrara, Via Aldo Moro 8, 44124 Cona-Ferrara, Italy. katia.denadai@libero.it.
authors: Katia
authors: K
authors: De Nadai
authors: Eye Clinic, Department of Health Sciences, University of Molise, Via Francesco de Sanctis 1, 86100 Campobasso, Italy. robdellomo@libero.it.
authors: Roberto
authors: R
authors: Dell'Omo
authors: Eye Clinic, Department of Neurological and Vision Sciences, University of Brescia, Piazzale Spedali Civili 1, 25123 Brescia, Italy. dott.andrea.russo@gmail.com.
authors: Andrea
authors: A
authors: Russo
authors: Center of Hemostasis and Thrombosis, Department of Medical Sciences, University of Ferrara, Corso Giovecca 203, 44121 Ferrara, Italy. cet@unife.it.
authors: Donato
authors: D
authors: Gemmati
authors: Eye Clinic, Department of Biomedical and Specialty Surgical Sciences, University of Ferrara, Via Aldo Moro 8, 44124 Cona-Ferrara, Italy. prrpla@unife.it.
authors: Paolo
authors: P
authors: Perri
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D020256:Choroidal Neovascularization / Q000188:drug therapy* / Q000209:etiology* / Q000235:genetics / Q000473:pathology; D005169:Factor VIII / Q000235:genetics*; D005260:Female; D006801:Humans; D008268:Macular Degeneration / Q000150:complications; D008297:Male; D008875:Middle Aged; D047728:Myopia, Degenerative / Q000150:complications; D010778:Photochemotherapy / Q000379:methods; D017319:Photosensitizing Agents / Q000008:administration & dosage* / Q000494:pharmacology; D020641:Polymorphism, Single Nucleotide; D011166:Porphyrins / Q000008:administration & dosage* / Q000494:pharmacology; D012189:Retrospective Studies; D016896:Treatment Outcome; D000077362:Verteporfin; D014792:Visual Acuity / Q000187:drug effects; D044465:White People / Q000235:genetics
chemical_list: D017319:Photosensitizing Agents; D011166:Porphyrins; D000077362:Verteporfin; C078147:F8 protein, human; D005169:Factor VIII
keywords: anti-thrombophilia; choroidal neovascularization; factor XIII-A G185T gene polymorphism; fibrin-clot stability; macular degenerations; pharmacogenetics; photodynamic therapy with verteporfin