The eyes are the window to the world and the key to communication, but they are vulnerable to multitudes of ailments. More serious than is thought, corneal infection by herpes simplex viruses (HSVs) is a prevalent yet silent cause of blindness in both the paediatric and adult population, especially if immunodeficient. Globally, there are 1.5 million new cases and forty thousand visual impairment cases reported yearly. The Herpetic Eye Disease Study recommends topical antiviral as the front-line therapy for HSV keratitis. Ironically, topical eye solutions undergo rapid nasolacrimal clearance, which necessitates oral drugs but there is a catch of systemic toxicity. The hurdle of antiviral penetration to reach an effective concentration is further complicated by drugs' poor permeability and complex layers of ocular barriers. In this current review, novel delivery approaches for ocular herpetic infection, including nanocarriers, prodrugs, and peptides are widely investigated, with special focus on advantages, challenges, and recent updates on in situ gelling systems of ocular HSV infections. In general congruence, the novel drug delivery systems play a vital role in prolonging the ocular drug residence time to achieve controlled release of therapeutic agents at the application site, thus allowing superior ocular bioavailability yet fewer systemic side effects. Moreover, in situ gel functions synergistically with nanocarriers, prodrugs, and peptides. The findings support that novel drug delivery systems have potential in ophthalmic drug delivery of antiviral agents, and improve patient convenience when prolonged and chronic topical ocular deliveries are intended.
Keywords: herpes simplex virus keratitis; in situ ophthalmic gel; mucoadhesive; novel approaches; ocular drug delivery; safety.