Optic Neuropathy: Characteristic Pathology for Identifying Drugs with Potential to Cause Mitochondrial Toxicity

Abstract

Deleterious effects on mitochondria are known to be frequently caused by prescription drugs, however, there is no standard and specific testing by pharmaceutical companies on these effects on mitochondria during drug development. The objective of this study is to determine if cases of optic neuropathy are related to drug-induced mitochondrial toxicity in a way that could be used to predict patient harm. To determine this, all cases of optic neuropathy within a fifty-eight-month timeframe were reviewed in the food and drug administration adverse effect reporting system. The drugs listed as the suspected causes of optic neuropathy in each case were analyzed for frequency of occurrence and frequently occurring drugs were evaluated for documented mechanisms of mitochondrial toxicity. The odds of occurrence of drugs with and without mitochondrial toxicity implemented in these cases were compared with all other adverse drug events excluding optic neuropathy. Our findings indicate that mitochondrial toxicity plays a major role in drug-induced optic neuropathy. We found that the drugs with known mitochondrial toxicity had a 1.47 (95% CI 1.30-1.67, p<0.0001) times higher risk of causing optic neuropathy compared to drugs associated with non-mitochondrial mechanisms of toxicity. Therefore, optic neuropathy is a significantly correlated adverse event of drugs with mitochondrially toxic properties. Although most of these properties are known, there were still 691 cases of optic neuropathy reported in less than a five-year period, which could have potentially been avoided using effective postmarket research and warnings. Implementing standard mitochondrial toxicity analyses during drug development will help identify drugs with the potential to cause optic neuropathy or other potential harm. Furthermore, several drugs were identified without known mitochondrially toxic mechanisms but possessed significant rates of optic neuropathy suggesting that a mechanism may exist and some of them have been proven mitochondrially toxic in other species.