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Author Spotlight: Advancing Corneal Innervation Research Through Innovative Models
Published on: December 8, 2023
Neuroprotective and anti-inflammatory strategies for corneal nerve regeneration and ocular surface stability after
Anas Alamoudi1, Abdulaziz Khalid Aldahlawi, Ahmed Alnabihi
1From the Department of Ophthalmology, Jeddah Eye Hospital, Jeddah, Saudi Arabia (Alamoudi, Aldahlawi); Department of Ophthalmology, King Khaled Eye Specialist Hospital and Research Center, Riyadh, Saudi Arabia (Alnabihi); Department of Ophthalmology, East Jeddah Hospital, Jeddah, Saudi Arabia (AlGhamdi); College of Medicine, King Saud bin Abdulaziz University for Health Sciences, Jeddah, Saudi Arabia (Aljabri); Department of Ophthalmology, King Fahad Medical City, Riyadh, Saudi Arabia (Almufarriji, Albreiki); Department of Ophthalmology, King Abdulaziz Medical City, National Guard Health Affairs, Riyadh, Saudi Arabia (Sharif); King Abdullah International Medical Research Center, Riyadh, Saudi Arabia (Sharif); Department of Ophthalmology, King Abdullah bin Abdulaziz University Hospital, Riyadh, Saudi Arabia (AlQahtani); College of Medicine, Princess Nourah bint Abdulrahman University, Riyadh, Saudi Arabia (AlQahtani).
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.
