Topical pharmacologic treatments for dry eye disease: A systematic review

Topical pharmacologic treatments for dry eye disease (DED) address different aspects of tear film deficiency by decreasing ocular surface inflammation, stimulating mucin secretion, increasing tear production, or reducing excessive evaporation. This systematic review evaluated randomized controlled trials (RCTs) and prospective observational studies of topical ophthalmic medications for DED.

PubMed and Embase were searched from 1980 to February 2024. For studies meeting inclusion criteria, efficacy outcomes (signs and symptoms of DED) and adverse event data were extracted.

A total of 107 publications covering topical prescription medications (anti-inflammatory agents cyclosporine and lifitegrast; mucin secretagogues diquafosol and rebamipide; tear evaporation inhibitor perfluorohexyloctane; tear production stimulator nasal spray varenicline), other commercially available products, and novel agents in development were identified. In RCTs, significant improvements relative to a control group were demonstrated more often for sign endpoints (e.g., corneal staining, Schirmer score) than for symptom endpoints (e.g., eye dryness, ocular discomfort). The evaluated treatments were well tolerated; instillation site reactions were the most commonly reported adverse events. Year-long safety extension studies demonstrated maintenance of efficacy, with no new safety signals identified. Studies differed in design, methodology, control group, and outcomes assessment, making it difficult to compare across products, and head-to-head studies were rare. Several new products are in late-stage development, which will likely lead to additional treatment options.

Current topical pharmacologic eye products improved signs, and sometimes symptoms, of DED and were well tolerated. Treatment selection should use a shared decision-making approach that takes DED etiology and patient preferences into account.