Tyni T, Kivelä T, Lappi M, Summanen P, Nikoskelainen E, Pihko H
Department of Child Neurology, Children's Hospital, University of Helsinki, Finland.
Ophthalmology. 1998 May;105(5):810-24. doi: 10.1016/S0161-6420(98)95019-9.
The purpose of the study was to determine the nature and course of ophthalmic abnormalities in long-chain 3-hydroxyacyl-CoA dehydrogenase (LCHAD) deficiency, a recently discovered disorder of mitochondrial fatty acid beta-oxidation.
The study design was a cohort (case series).
A retrospective review of the records of 15 children who had died during their first 2 years was performed. Also performed were a longitudinal reanalysis and cross-sectional clinical examination of four long-term survivors aged 5 to 31 years.
Visual acuity, refraction, visual fields, ophthalmoscopy, fluorescein angiography, biometry, corneal topography, electroretinography (ERG), visual-evoked potentials (VEPs), color vision, and dark adaptation were measured.
In seven children, ophthalmoscopic findings were within normal limits at 3 days to 13 months of age (median, 4.8 months). In 11 children, a granular retinal pigment epithelium (RPE), with or without pigment clumping in the macula, was seen at 4 months to 5 years of age (median, 9 months). Two long-term survivors, 16 and 31 years of age, eventually had circumscribed atrophy of the choroid, RPE, and retina, which coincided with a posterior staphyloma type 1. They had progressive axial myopia starting at 6 and 12 years of age and later paracentral scotomas leading to poor central vision. They suffered from early difficulty with mesopic vision, glare, and a severe generalized color vision deficiency that started as a tritanomaly. A third survivor was mildly myopic at 5 years of age. All four surviving patients had visually insignificant, flake-like supranuclear opacities in the lens. The ERG initially was normal but deteriorated during the first decade and later was unrecordable. The VEP responses remained fairly normal. Initially, angiography showed no blockade of the choroidal fluorescence because of the thin RPE. Filling of choroidal vessels was delayed, and the choriocapillaris and, later, larger choroidal vessels in the posterior pole became nonperfused.
In LCHAD deficiency, the fundus is normal at birth (stage 1). Soon, however, pigment dispersion occurs in the RPE (stage 2), followed by circumscribed chorioretinal atrophy, occlusion of choroidal vessels, and deterioration of central vision, often with relative sparing of the peripheral fundus (stage 3). Finally, posterior staphylomas and central scotomas may develop (stage 4). Developmental cataract, progressive myopia, and deterioration of visual fields and color vision are new findings in LCHAD deficiency. The chorioretinopathy and abnormal ERG precede the development of myopia and posterior staphyloma, which, in turn, coincide with the loss of macular vision. The authors postulate that the RPE or choriocapillaris is primarily affected. Awareness of the characteristic ocular features is important because of an opportunity for dietary treatment, genetic counseling, and prenatal diagnosis.
本研究旨在确定长链3-羟基酰基辅酶A脱氢酶（LCHAD）缺乏症（一种最近发现的线粒体脂肪酸β氧化障碍疾病）眼部异常的性质和病程。
本研究设计为队列研究（病例系列）。
对15名在出生后2年内死亡的儿童的记录进行了回顾性分析。同时，对4名年龄在5至31岁的长期存活者进行了纵向再分析和横断面临床检查。
测量视力、屈光、视野、检眼镜检查、荧光素血管造影、生物测量、角膜地形图、视网膜电图（ERG）、视觉诱发电位（VEP）、色觉和暗适应。
7名儿童在3天至13个月龄（中位数为4.8个月）时，检眼镜检查结果正常。11名儿童在4个月至5岁龄（中位数为9个月）时，可见颗粒状视网膜色素上皮（RPE），黄斑区有或无色素沉着。两名长期存活者，年龄分别为16岁和31岁，最终出现脉络膜、RPE和视网膜的局限性萎缩，与1型后巩膜葡萄肿相符。他们在6岁和12岁时开始出现进行性轴性近视，随后出现旁中心暗点，导致中心视力下降。他们在早期就出现了中视困难、眩光和严重的全身性色觉缺陷，最初表现为蓝色色盲。第三名存活者在5岁时为轻度近视。所有4名存活患者的晶状体均有视觉上无明显影响的片状核上混浊。ERG最初正常，但在第一个十年内恶化，后来无法记录。VEP反应仍相当正常。最初，血管造影显示由于RPE较薄，脉络膜荧光无阻断。脉络膜血管充盈延迟，后极部的脉络膜毛细血管以及后来较大的脉络膜血管变得无灌注。
在LCHAD缺乏症中，出生时眼底正常（1期）。然而，很快RPE就会出现色素分散（2期），随后出现局限性脉络膜视网膜萎缩、脉络膜血管阻塞和中心视力下降，周边眼底通常相对 spared（3期）。最后，可能会出现后巩膜葡萄肿和中心暗点（4期）。发育性白内障、进行性近视以及视野和色觉恶化是LCHAD缺乏症的新发现。脉络膜视网膜病变和异常的ERG先于近视和后巩膜葡萄肿的发展，而近视和后巩膜葡萄肿又与黄斑视力丧失同时出现。作者推测主要受影响的是RPE或脉络膜毛细血管。由于有饮食治疗、遗传咨询和产前诊断的机会，了解这些特征性眼部表现很重要。
