Neuroprotective and anti-inflammatory strategies for corneal nerve regeneration and ocular surface stability after corneal refractive surgeries: systematic review

Vollständiger Abstract

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Topic: This study aimed to systematically synthesize and critically appraise all controlled trials evaluating neuroprotective and anti-inflammatory pharmacotherapies for enhancing corneal nerve regeneration and ocular surface stability after corneal refractive surgeries. Clinical Relevance: Postrefractive surgery dry eye and hypoesthesia are common and often persistent, underscoring the need for evidence-based pharmacologic strategies to promote corneal nerve recovery and tear film stability. Methods: The authors registered a PROSPERO-guided protocol (CRD42024610462) and systematically searched Clinicaltrials.gov, CENTRAL, Google scholar, Medline from inception to March 2025 for randomized controlled trials (RCTs) evaluating neuroprotective or anti-inflammatory pharmacotherapies after laser-assisted in situ keratomileusis (LASIK), photorefractive keratectomy (PRK), laser-assisted subepithelial keratectomy, or femto-LASIK. 2 independent reviewers screened records, extracted data, and assessed risk of bias using the Cochrane Risk of Bias 2 tool. Results: 7 trials (n = 484 participants/eyes, 6 countries) met eligibility. Topical cyclosporine 0.05% (2 RCTs) consistently hastened flap sensitivity recovery (Δ + 4 cm at 3 months) and improved 6-month ocular surface metrics (ocular surface disease index −5 points; tear breakup time [TBUT] +4 seconds; Schirmer +5.5 mm; P < .001). Topical chloroquine 0.03% produced similar but smaller gains. Topical diclofenac 0.1% reduced PRK pain by ∼50% within 24 hours without delaying epithelial closure. Topical citicoline 1% accelerated sensory normalization by 2 weeks and transiently enhanced Schirmer/TBUT, whereas autologous platelet-rich plasma reduced epithelial staining but did not affect nerve density. Oral pregabalin (150 mg 2 times a day) and oral gabapentin (300 mg perioperatively) reduced first-week pain after surface ablation yet had no measurable impact on nerve metrics or dry eye indices through 6 months. Conclusions: Among tested strategies, topical cyclosporine provides the strongest evidence for enhancing corneal nerve function and long-term tear film stability after refractive surgery. However, overall evidence remains limited. Larger, double-masked trials with extended follow-up are needed to further elucidate the roles of these interventions.