Corneal Wound Healing

All forms of keratorefractive surgery are exquisitely dependent on corneal wound healing to achieve the desired results. Satisfactory results require either modifying or reducing wound healing or exploiting normal wound healing for the benefit of the patient. For example, astigmatic keratotomy requires initial weakening of the cornea followed by permanent corneal healing, with replacement of the epithelial plugs with collagen and remodeling of the collagen to ensure stability and avoid long-term hyperopic drift. PRK requires the epithelium to heal quickly, and with minimal stimulation of the underlying keratocytes, to avoid corneal scarring and haze. Lamellar keratoplasty requires intact epithelium and healthy endothelium early in the postoperative period to seal the flap. Later, the cornea must heal in the periphery to secure the flap in place and avoid late-term displacement while minimizing irregular astigmatism; also, the cornea must remain devoid of significant healing centrally to maintain a clear visual axis. In addition to stromal healing, regeneration of the corneal nerves is crucial to a normal ocular surface and good visual function. Delay or difficulty in re-innervation can lead to problems with corneal sensation and tear-film stability and to dry eye symptoms.

The understanding of corneal wound healing has advanced tremendously with recognition of the multiple factors involved in the cascade of events initiated by corneal wounding. The cascade is somewhat dependent on the nature of the injury. Injury to the epithelium can lead to loss of underlying keratocytes from apoptosis. The remaining keratocytes respond by generating new glycosaminoglycans and collagen, to a degree dependent on the duration of the epithelial defect and the depth of the stromal injury. Corneal haze is localized in the subepithelial anterior stroma and may persist for several years after surface ablation. Clinically significant haze, however, is present in only a small percentage of eyes. The tendency toward haze formation is greater with deeper ablations, increased surface irregularity, and prolonged absence of the epithelium. Despite loss of the Bowman layer, normal or even enhanced numbers of hemidesmosomes and anchoring fibrils form to secure the epithelium to the stroma.

Controversy persists over the value of different drugs for modulating wound healing in surface ablation. Typically, clinicians in the United States use corticosteroids in a tapering manner following surgery to reduce inflammation. Mitomycin C has been applied to the stromal bed after excimer surface ablation to attempt to decrease haze formation (see Chapters 5 and 6). Vitamin C has been postulated to play a role in protecting the cornea from ultraviolet light damage by the excimer laser, but no randomized, prospective clinical trial has yet been performed. Various growth factors that have been found to promote wound healing after PRK, including transforming growth factor β, may be useful in the future.

Haze formation does not seem to occur in the central flap interface after LASIK, which may be related either to lack of significant epithelial injury and consequent subcellular signaling or to maintenance of some intact surface neurons. LASIK shows very little long-term evidence of healing between the disrupted lamellae and only typical stromal healing at the peripheral wound. The lamellae are initially held in position by negative stromal pressure generated by the endothelial cells aided by an intact epithelial surface. Even years after treatment, the lamellar interface can be broken and the flap lifted, indicating that only a minimal amount of healing occurs. LASIK flaps can also be dislodged secondary to trauma many years postoperatively.

• Dupps WJ Jr, Wilson SE. Biomechanics and wound healing in the cornea. Exp Eye Res. 2006; 83(4):709–720.

• Majmudar PA, Schallhorn SC, Cason JB, et al. Mitomycin-C in corneal surface excimer laser ablation techniques: a report by the American Academy of Ophthalmology. Ophthalmology. 2015;122(6):1085–1095.

• Netto MV, Mohan RR, Sinha S, Sharma A, Dupps W, Wilson SE. Stromal haze, myofibroblasts, and surface irregularity after PRK. Exp Eye Res. 2006;82(5):788–797. Epub 2005 Nov 21.

• Schmack I, Dawson DG, McCarey BE, Waring GO III, Grossniklaus HE, Edelhauser HF. Cohesive tensile strength of human LASIK wounds with histologic, ultrastructural, and clinical correlations. J Refract Surg. 2005;21(5):433–445.

Excerpted from BCSC 2020-2021 series: Section 13 - Refractive Surgery. For more information and to purchase the entire series, please visit https://www.aao.org/bcsc.