Abstract
Acute retinal necrosis (ARN) is a sight-threatening ophthalmic emergency that requires aggressive treatment to prevent irreversible vision loss. However, primary treatment failure (PTF), where the initial antiviral therapy is ineffective, is a common challenge in ARN management. This comprehensive review examines PTF in ARN, drawing insights from a systematic literature search spanning 1997 to 2022, which identified 35 relevant cases from 23 reports. The analysis focuses on drug resistance patterns, alternative antiviral agents, combination therapies, and emerging treatments. Potential causes of drug resistance, including host factors, viral mutations, and drug-related considerations, are elucidated. Alternative agents such as foscarnet, cidofovir, and brivudine, as well as combination approaches involving systemic and intravitreal administration, high-dose therapy, judicious use of steroids, and potential treatment-related complications, are discussed. The review also highlights emerging therapies, including vaccines, monoclonal antibodies, and natural compounds, offering insights into future directions for addressing this challenging condition.