黄斑变性是发达国家中心性失明或低视力的主要原因。这些严重的视力障碍大多数是由于年龄相关性黄斑变性(AMD)和病理性近视(PM)。两者都经常因中央凹下脉络膜新生血管(CNV)而复杂化。在选定的病例或联合方案中,仍采用维替泊芬(PDT-V)的光动力疗法进行CNV治疗。在高加索患者中,因子XIII-A基因(FXIII-A-G185T;rs5985)的常见多态性G185T已被描述为血管造影CNV对PDT-V反应性差的预测因子。然而,该药物遗传学决定因素对PDT-V方案治疗后长期视力结局的预后影响尚未得到评估.我们回顾性选择了接受初治CNV并接受标准化PDT-V方案两年的白种人患者。研究人群包括继发于AMD或PM的中心凹下CNV患者。我们评估了FXIII-A-G185T的多态性等位基因T与以下各项之间的相关性:(1)光动力治疗的总数;(2)从基线到随访期结束的视力变化。考虑到总共412名新生血管性AMD或PM患者的研究人群,与没有接受光动力治疗的患者(GG野生型基因型)相比,FXIII-A的185个T等位基因(GT或TT基因型)的携带者接受了更多的光动力治疗(p<0.01;PDT-V的平均数量:5.51vs.分别为3.76)。此外,与具有GG-185野生基因型的患者相比,具有FXIII-A的185个T等位基因的患者在24个月时的视力恶化更明显(p<0.01;logMAR视力的平均差异:0.22vs.0.08分别)。本研究结果表明,FXIII-A基因的G185T多态性与使用标准化PDT-V方案治疗的患者的长期治疗结果的显着差异有关。对FXIII-AG185T变体引起的抗血栓形成作用和PDT-V对CNV的光血栓形成作用的综合评估为这种有趣的药物遗传相关性的基本原理提供了一些线索。有必要进行进一步的研究,以概述在新生血管性黄斑变性的联合治疗方案过程中指导PDT-V使用的适当范例。
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.