Kälviäinen R, Nousiainen I
University Hospital of Kuopio and University of Kuopio, Finland.
CNS Drugs. 2001;15(3):217-30. doi: 10.2165/00023210-200115030-00005.
Vigabatrin is an antiepileptic drug (AED) that acts as a selective irreversible inhibitor of gamma-aminobutyric acid (GABA) transaminase. In 1997, 3 cases of severe symptomatic and persistent visual field constriction associated with vigabatrin treatment were described. During 1997 to 1998, similar concentric visual field constrictions were described in patients with drug-resistant epilepsy who were receiving vigabatrin concurrently with other AEDs. However, a study of patients treated with vigabatrin monotherapy alone showed that there was a causal relationship between vigabatrin treatment and the specific bilateral concentric visual field constriction. The Marketing Authorisation Holders survey (involving 335 vigabatrin recipients aged >14 years) indicated that 31% of patients [95% confidence interval (CI) 26 to 36%] had a visual field defect attributable to vigabatrin, compared with a 0% incidence of visual field defects (upper 95% CI 3%) in an unexposed control group. Other studies in adults have given similar overall prevalences, with a total of 169 of 528 patients diagnosed with vigabatrin-associated field defects (32%, 95% CI 28 to 36%). Male gender seems to be associated with an increase in the relative risk of visual field loss of approximately 2-fold. The pattern of defect is typically a bilateral, absolute concentric constriction of the visual field, the severity of which varies from mild to severe. Data gathered so far suggest that the cumulative incidence increases rapidly during the first 2 years of treatment and within the first 2 kg of vigabatrin intake, stabilising at 3 years and after a total vigabatrin dose of 3 kg. The prevalence of vigabatrin-associated field defects seems to be lower in children, but there are also methodological problems and greater variability in the assessment of visual fields in children. There is particular concern that the increased risk of the visual field defects will outweigh the benefit of the drug in patients who could be controlled with other AEDs. Vigabatrin should currently be used only in combination with other AEDs for patients with resistant partial epilepsy when all other appropriate drug combinations have proved inadequate or have not been tolerated. Regular visual field testing should be performed before the start of treatment and at regular intervals during treatment. Patients with pre-existent visual field defects due to other causes should not be treated with vigabatrin. Currently, the benefits of treating infantile spasms with vigabatrin monotherapy seem to outweigh the risks, but further prospective studies and follow-up of children receiving treatment are needed to evaluate the place of vigabatrin in this indication.
氨己烯酸是一种抗癫痫药物（AED），它作为γ-氨基丁酸（GABA）转氨酶的选择性不可逆抑制剂发挥作用。1997年，有3例与氨己烯酸治疗相关的严重症状性持续性视野缩窄的病例被描述。在1997年至1998年期间，在接受氨己烯酸与其他抗癫痫药物联合治疗的耐药性癫痫患者中也描述了类似的同心性视野缩窄。然而，一项仅对接受氨己烯酸单一疗法治疗的患者的研究表明，氨己烯酸治疗与特定的双侧同心性视野缩窄之间存在因果关系。上市许可持有人调查（涉及335名年龄大于14岁的氨己烯酸接受者）表明，31%的患者[95%置信区间（CI）26%至36%]存在归因于氨己烯酸的视野缺损，而未暴露对照组的视野缺损发生率为0%（95%CI上限为3%）。其他针对成年人的研究给出了类似的总体患病率，528名患者中有169名被诊断为与氨己烯酸相关的视野缺损（32%，95%CI 28%至36%）。男性似乎与视野丧失相对风险增加约2倍有关。缺损模式通常是双侧绝对同心性视野缩窄，其严重程度从轻度到重度不等。目前收集的数据表明，累积发病率在治疗的前2年以及摄入氨己烯酸的前2千克期间迅速增加，在3年及氨己烯酸总剂量达到3千克后趋于稳定。氨己烯酸相关视野缺损的患病率在儿童中似乎较低，但在儿童视野评估中也存在方法学问题和更大的变异性。特别令人担忧的是，对于可用其他抗癫痫药物控制的患者，视野缺损风险增加将超过该药物的益处。目前，氨己烯酸仅应与其他抗癫痫药物联合用于耐药性部分性癫痫患者，前提是所有其他合适的药物组合已被证明无效或患者无法耐受。应在治疗开始前及治疗期间定期进行视野测试。因其他原因已有视野缺损的患者不应使用氨己烯酸治疗。目前，氨己烯酸单一疗法治疗婴儿痉挛症的益处似乎超过风险，但需要进一步的前瞻性研究以及对接受治疗儿童的随访，以评估氨己烯酸在该适应症中的地位。
