Comparison of common pharmacological strategies for post-photorefractive keratectomy pain management: a systematic review and network meta-analysis

OBJECTIVE: To systematically evaluate the comparative efficacy and safety of common pharmacological strategies for managing post-photorefractive keratectomy (PRK) eye pain through a network meta-analysis, providing evidence-based guidance for clinical medication. METHODS: Randomized controlled trials (RCTs) were systematically retrieved from Cochrane Library, Web of Science, PubMed, and EMbase (from inception to November 15, 2025). Using R Studio, we conducted a network meta-analysis to assess differences in Visual Analogue Scale (VAS) scores and adverse events across pharmacological interventions. SUCRA (Surface Under the Cumulative Ranking) values were calculated to determine the relative ranking of interventions, while accounting for heterogeneities in administration timing and dosage. RESULTS: A total of 28 studies were included, involving 2,797 patients. In route-stratified analyses, Ofloxacin (SUCRA = 0.84) and Proparacaine (0.76) were the top-ranked topical agents for analgesia, while Codeine combined with Acetaminophen (0.71) ranked highest among systemic agents. The exploratory combined network yielded identical top-three rankings, though these cross-route comparisons are susceptible to transitivity violations. Notably, effect sizes for most interventions relative to placebo spanned the line of no effect. Regarding safety, Diclofenac (SUCRA = 0.81), Ketorolac (0.70), and Nepafenac (0.53) demonstrated the optimal profiles. The highest numbers of adverse events occurred with Pregabalin (39 cases), Fentanyl (20 cases), and Codeine combined with Acetaminophen (13 cases); however, safety conclusions remain limited as only seven studies reported highly heterogeneous adverse event data. CONCLUSION: Ofloxacin demonstrates superior relative efficacy for pain control following PRK, while Diclofenac offers the most favorable safety profile. Clinicians should synthesize these comparative findings with individual patient profiles to optimize drug selection, ensuring a balanced approach between effective pain relief and minimized adverse risks. SYSTEMATIC REVIEW REGISTRATION: https://www.crd.york.ac.uk/PROSPERO/view/CRD420251238092, CRD420251238092.