Brock Scientific Consulting, 19909 Hamil Circle, Montgomery Village, MD 20886, USA.
Int J Toxicol. 2013 May-Jun;32(3):171-88. doi: 10.1177/1091581813484500. Epub 2013 Apr 24.
The eye is a unique sensory structure, which must be evaluated for toxicity to determine the safety of drugs, industrial chemicals, and consumer products. Changes in the structure and/or function of ocular tissues following systemic administration of a potential new drug in preclinical animal models can result in significant delays in the development of a new therapeutic and in some cases lead to termination of the development. The ability to detect and characterize ocular toxicity in preclinical models and to predict risk in patients is critically dependent on the preclinical testing strategy, the availability and use of state-of-the-art ocular safety assessment tools, and the knowledge of drug mechanism of action and the current regulatory environment. This review describes the design and execution of toxicity studies with the incorporation of current methods for in vivo assessment of ocular toxicity, including methods for detecting early changes in the eye. In addition, anatomical differences among laboratory animals, preparation of globes for examination, and iatrogenic and spontaneous ocular findings are described that can affect interpretation of toxicological findings. Finally, the correlation between nonclinical outcomes and clinical evaluations is discussed in terms of expected therapeutic uses, indications, and regulatory consequences of ocular effects.
眼睛是一种独特的感觉结构，必须对其进行毒性评估，以确定药物、工业化学品和消费品的安全性。在临床前动物模型中全身给予潜在新药后，眼组织的结构和/或功能的变化可能导致新疗法的开发出现重大延迟，在某些情况下甚至导致开发终止。在临床前模型中检测和表征眼毒性并预测患者风险的能力，严重依赖于临床前测试策略、最先进的眼安全评估工具的可用性和使用情况，以及对药物作用机制和当前监管环境的了解。本综述描述了毒性研究的设计和执行，同时纳入了目前用于体内评估眼毒性的方法，包括检测眼部早期变化的方法。此外，还描述了实验动物之间的解剖差异、眼球检查的准备以及医源性和自发性眼部发现，这些差异可能会影响对毒理学发现的解释。最后，根据预期的治疗用途、适应症和眼部效应的监管后果，讨论了非临床结果与临床评估之间的相关性。
