In contrast with standard systemic drugs, the toxicity study of ophthalmic drug has unique design and packaging characteristics. The present survey aimed to characterize the nonclinical toxicological strategy of intravitreal administration (IVT) drugs by summarizing the toxicity study packages and comparing toxicity findings with clinical side effects. Safety pharmacology studies, toxicity studies, and clinical adverse reactions of the following seven IVT drugs were surveyed: pegaptanib sodium, ranibizumab, aflibercept, brolucizumab, faricimab, triamcinolone acetonide, and ranibizumab biosimilar. The toxicity study packages for IVT drugs were constructed according to ICH guidelines, although there were several differences between the modalities, application categories, and drugs. The characteristics of toxicity study packages include the fact that many safety pharmacology and acute toxicity endpoints need not be conducted as separate studies owing to the low systemic exposure. In addition, local toxicity findings (especially intraocular inflammation) require caution due to the relatively invasive administration method necessitates, and monkeys were mainly used as animal species in the IVT studies. Notably, certain drugs were found to have the severe adverse reactions of retinal vascular lesions, probably owing to immunoreaction. Importantly, these immunoreaction-related adverse reactions were not detected in these nonclinical toxicity studies. Therefore, risk assessments using toxicity studies, immunogenicity, and host impurities are important for the prediction and control of adverse reactions. This survey provides valuable information for the construction of a toxicity study design for IVT drug development.