All forms of keratorefractive surgery are exquisitely dependent on corneal wound healing to achieve the desired results. Satisfactory outcomes require ­either modifying the pro­cess of wound healing or exploiting normal wound healing for the benefit of the patient. For example, AK requires initial weakening of the cornea followed by permanent corneal heal­ ing, with replacement of the epithelial plugs by collagen and remodeling of the collagen to ensure stability and to avoid long-­term hyperopic drift. In PRK, the epithelium is intended to heal quickly, with minimal stimulation of the under­lying keratocytes, to avoid corneal scarring and haze. LASIK depends on 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; moreover, the central cornea must remain devoid of significant healing to maintain a clear visual axis.

In addition to stromal healing, regeneration of the corneal nerves is crucial to main­ taining a normal ocular surface and good visual function. Delay or difficulty in reinner­ vation can lead to decreased or abnormal corneal sensitivity, tear film instability, and dry eye symptoms.

The understanding of corneal wound healing has advanced tremendously with rec­ ognition 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, for example, can lead to loss of under­lying keratocytes from apoptosis. The remaining keratocytes respond by generating new glycosaminoglycans and collagen, de­ pending in part on the duration of the epithelial defect and the depth of the stromal injury.

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

In some cases, the cascade following injury can result in corneal haze that is localized in the subepithelial anterior stroma and which can 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 increases with deeper ablations, greater sur­ face irregularity, and longer 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. Haze formation very rarely occurs 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.

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

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.

Controversy persists over the value of dif­fer­ent drugs in modulating wound healing ­after sur­ face ablation. In the United States, clinicians typically use a tapering regimen of corticosteroids to reduce inflammation after surgery. Mitomycin C has been applied to the stromal bed after excimer surface ablation to attempt to decrease haze formation (see Chapters 4 and 5). 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.

Intraocular light scatter, or straylight, is a phenomenon caused by reflection, refraction, and diffraction of light from the cornea, lens, or retina, as well as from light penetrating through the sclera and iris. It decreases light transmission, reduces image contrast, and degrades retinal image quality. The scatter may be forward or backward. In forward scatter (ie, toward the retina), the scattered light is deviated less than 90^° relative to the direction of incident light. It produces a veiling luminance on the retina, which reduces the contrast of the retinal image and causes glare. Scattered light that is deviated more than 90^° is referred to as backward scatter; its main result is a reduction in the amount of light reaching the retina. Because forward light scatter directly affects visual performance, measuring this type of scatter is vital.

Several devices are commercially available to quantify forward light scatter. One of the most common methods is a double-­pass technique that mea­sures forward scatter caused by localized deviations of light on an objective scatter index (OSI). The OSI shows the objective amount of scattering caused by tear film irregularities and the loss of ocular transparency. OSI values range from 0 (no scatter) to a maximum of 25 (highly scattered system). Other approaches mea­sure forward light scatter by quantifying optical straylight or by using psychophysical mea­sure­ments.

Donnelly WJ 3rd, Applegate RA. Influence of exposure time and pupil size on a Shack-­ Hartmann metric of forward scatter. J Refract Surg. 2005;21(5):S547–­S551.

The corneal epithelium can alter its thickness profile to compensate for irregularities in the stromal surface. Thus, epithelial thickening is observed in areas of tissue loss. For example, in keratoconus, the epithelium tends to thin over the cone and to thicken over adjacent areas of stromal thinning (Fig 1-23). Similarly, ­after myopic LASIK, the magni­ tude of central epithelial thickening has been correlated to the degree of myopic refractive error ablated. Remodeling of the corneal epithelium may have a significant impact on corneal topography interpretation.

Corneal epithelial mapping can be performed with spectral-­domain OCT or very high-­frequency digital ultrasound. Epithelial thickness variations can be used to screen for early stages of corneal ectasia, to detect corneal warpage patterns, and to evaluate sta­ bility ­after ­laser vision correction.

Reinstein DZ, Gobbe M, Archer TJ, Silverman RH, Coleman DJ. Epithelial, stromal, and total corneal thickness in keratoconus: three-­dimensional display with Artemis very-­high frequency digital ultrasound. J Refract Surg. 2010;26(4):259–271.

Reinstein DZ, Silverman RH, Raevsky T, et al. Arc-­scanning very high-­frequency digital ultrasound for 3D pachymetric mapping of the corneal epithelium and stroma in ­laser in situ keratomileusis [published correction appears in J Refract Surg. 2001;17(1):4]. J Refract Surg. 2000;16(4):414–430.

Rocha KM, Krueger RR. Spectral-­domain optical coherence tomography epithelial and flap thickness mapping in femtosecond laser-­assisted in situ keratomileusis. Am J Ophthalmol. 2014;158(2):293–301.e1.

Rocha KM, Perez-­Straziota CE, Stulting RD, Randleman JB. Epithelial and stromal remodeling ­after corneal collagen cross-­linking evaluated by spectral-­domain OCT. J Refract Surg. 2014;30(2):122–127.

Rocha KM, Perez-­Straziota CE, Stulting RD, Randleman JB. SD-­OCT analy­sis of regional epithelial thickness profiles in keratoconus, postoperative corneal ectasia, and normal eyes. J Refract Surg. 2013;29(3):173–179.