A new systematic review published in The Ocular Surface delivers a current, evidence-based appraisal of topical pharmacologic options for dry eye disease (DED), with the aim of helping eye care professionals better navigate therapeutic decision-making in this complex, multifactorial condition [1].

The reviewed article synthesizes randomized controlled trials (RCTs) and prospective observational studies evaluating topical antibiotics, immunomodulators, neurostimulants, anti-evaporative agents, and other emerging modalities. 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. Its goal was to delineate which topical pharmacologics demonstrate consistent efficacy and tolerability, and where evidence gaps persist.

Key Findings: Where Evidence Is Strongest

1. Anti-Inflammatory / Immunomodulatory Agents

As expected, much of the available high-quality evidence pertains to immunomodulatory drops, especially cyclosporine A (CsA) formulations and lifitegrast:

  • Multiple RCTs demonstrate that various CsA formulations (e.g. 0.05% emulsion, cationic emulsions, micellar formulations) significantly improve corneal staining scores, reduce conjunctival inflammation, and increase tear production over vehicle or control

  • Lifitegrast 5% (LFA-1 antagonist) likewise shows statistically significant benefits over placebo in improving both signs (e.g., staining) and symptoms in moderate-to-severe DED

  • Importantly, none of the reviewed trials reported serious ocular adverse events attributable to these agents; most reported side effects were mild to moderate (e.g. transient burning, eye irritation), and discontinuation rates were relatively low

These findings reinforce that anti-inflammatory topical therapy remains foundational in managing moderate-to-severe DED, particularly when simple lubrication proves insufficient.

2. Emerging and Novel Agents

Though fewer in number, the review also highlights newer topical approaches targeting tear-film stabilization, mucin stimulation, and anti-evaporation:

  • Evaporative-resistance agents (e.g. semifluorinated alkanes such as perfluorohexyloctane) are emerging as adjunctive options. Although evidence is more limited, studies suggest that such agents may reduce tear evaporation and maintain improvements in corneal staining and symptom scores over longer-term use.

  • Topical omega-3 fatty acid formulations also show early promise: small human and animal studies indicate possible improvements in ocular surface staining and tear break-up time compared to control, though evidence for symptom relief and increased tear production remains inconsistent.

  • The review notes other mechanistic approaches—such as neurostimulants or secretagogues—have more limited clinical trial backing to date.

Reference

1. Tong L, Liu Z, Şahin A, Gümüş K, et al. Topical Pharmacologic Treatments for Dry Eye Disease: A Systematic Review. The Ocular Surface. 2025 Jul 30. doi:10.1016/j.jtos.2025.07.010