Parmeggiani Francesco, Gemmati Donato, Costagliola Ciro, Sebastiani Adolfo, Incorvaia Carlo
Sezione di Clinica Oculistica, Dipartimento di Discipline Medico-Chirurgiche della Comunicazione e del Comportamento, Università degli Studi di Ferrara, Corso Giovecca 203, 44100 Ferrara, Italy.
Pharmacogenomics. 2009 Jan;10(1):81-95. doi: 10.2217/14622416.10.1.81.
Age-related macular degeneration (AMD) complicated by subfoveal choroidal neovascularization (CNV) is the leading cause of severe central blindness in developed countries. AMD-related CNVs are distinguishable in classic and occult subtypes, characterized by variable natural history and different responsiveness to therapeutic procedures. Combined and repeated use of photodynamic therapy with verteporfin (PDT-V) and antiangiogenic drugs represents the most promising strategy against neovascular AMD, but it is unavoidably associated with mounting health-resource utilization. Predictive correlations between peculiar coagulation-balance gene variants and different levels of post-PDT-V benefit have recently been documented in Caucasians with AMD-related CNVs. In particular, methylenetetrahydrofolate reductase C677T substitution, a common thrombophilic folate pathway genotypic polymorphism, influences a better CNV responsiveness to PDT-V in classic- but not in occult-CNV cases. These pharmacogenetic findings indicate the opportunities to optimize the eligibility criteria of PDT-V and/or to perform this intriguing therapy in a customized manner, for finally minimizing the socio-economic burden of neovascular AMD.
年龄相关性黄斑变性（AMD）合并黄斑中心凹下脉络膜新生血管（CNV）是发达国家严重中心性失明的主要原因。与AMD相关的CNV可分为典型和隐匿亚型，其特点是自然病程不同，对治疗方法的反应也不同。光动力疗法联合维替泊芬（PDT-V）和抗血管生成药物的联合及重复使用是治疗新生血管性AMD最有前景的策略，但不可避免地会导致医疗资源利用的增加。最近在患有AMD相关CNV的白种人中发现，特殊的凝血平衡基因变异与PDT-V后不同程度的获益之间存在预测相关性。特别是，亚甲基四氢叶酸还原酶C677T替代，一种常见的血栓形成性叶酸途径基因多态性，在典型CNV病例中影响CNV对PDT-V的更好反应，但在隐匿性CNV病例中则不然。这些药物遗传学研究结果表明，有可能优化PDT-V的入选标准和/或以定制方式进行这种有趣的治疗，最终将新生血管性AMD的社会经济负担降至最低。
