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年龄相关性白内障的药物治疗策略

Pharmacological treatment strategies in age-related cataracts.

作者信息

Harding J J

机构信息

Nuffield Laboratory of Ophthalmology, University of Oxford, England.

出版信息

Drugs Aging. 1992 Jul-Aug;2(4):287-300. doi: 10.2165/00002512-199202040-00003.

Abstract

Cataract is the major cause of blindness worldwide and at present the only approved treatment in many countries including the UK and USA is surgical removal of the lens. In other countries various anti-cataract drugs are available without proof of their efficacy. Research is continuing into the possible benefits of several groups of drugs and some vitamins. The first to be studied were sorbitol-lowering agents (aldose reductase inhibitors) based on the sorbitol hypothesis for diabetic cataract. Sorbitol-lowering agents have distinct effects in vitro and many of them delay the development of cataract in galactose-fed rats. A few delay cataract in diabetic rats but none have been proved effective in clinical trials, although these continue. Aspirin, paracetamol (acetaminophen) and ibuprofen delay diabetic cataract in rats, and have been shown to delay other experimental cataracts. Case-control studies from 3 continents indicate that these drugs, or at least aspirin, protect against cataract. Results of studies on all 3 drugs indicate a benefit even at low doses. Population-based studies did not identify any protection against early lens opacities but tiny opacities that do not impair vision are not a problem. Bendazac protects lens proteins in vitro and delays cataractogenesis in x-irradiated rats. In humans, it reached the clinical trial stage but most trials have been small and with subjective criteria of opacification. One objectively monitored trial suffered from a high drop-out rate. Other preparations studied less extensively include vitamins, aminoguanidine to prevent protein cross-linking in diabetes and agents designed to boost glutathione levels. It is probable that some agents which may delay or prevent cataract will be proved effective soon, and in the end there may be different drugs to delay cataract in different high risk groups. This is what might be expected of a multifactorial disease, although compounds that intervene in the final common pathways to cataract could have a broad efficacy.

摘要

白内障是全球失明的主要原因,目前在包括英国和美国在内的许多国家,唯一被批准的治疗方法是手术摘除晶状体。在其他国家,有各种抗白内障药物,但没有其疗效的证据。针对几类药物和一些维生素的潜在益处的研究仍在继续。最早被研究的是基于糖尿病性白内障的山梨醇假说的降山梨醇剂(醛糖还原酶抑制剂)。降山梨醇剂在体外有明显作用,其中许多能延缓用半乳糖喂养的大鼠白内障的发展。有几种能延缓糖尿病大鼠白内障的发展,但在临床试验中没有一种被证明有效,尽管这些试验仍在继续。阿司匹林、对乙酰氨基酚和布洛芬能延缓大鼠糖尿病性白内障的发展,并且已被证明能延缓其他实验性白内障的发展。来自三大洲的病例对照研究表明,这些药物,或者至少阿司匹林,能预防白内障。对这三种药物的研究结果表明,即使低剂量也有益处。基于人群的研究没有发现对早期晶状体混浊有任何保护作用,但不损害视力的微小混浊并不是问题。苄达酸在体外能保护晶状体蛋白,并延缓受X射线照射的大鼠白内障的形成。在人类中,它已进入临床试验阶段,但大多数试验规模较小,且采用主观的混浊标准。一项客观监测的试验有很高的退出率。其他研究较少的制剂包括维生素、用于预防糖尿病中蛋白质交联的氨基胍以及旨在提高谷胱甘肽水平的药物。很可能一些可能延缓或预防白内障的药物很快就会被证明有效,最终可能会有不同的药物用于延缓不同高危人群的白内障。对于一种多因素疾病来说,这是可以预料的,尽管干预白内障最终共同途径的化合物可能具有广泛的疗效。

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