Corneal Sensitivity and Patient-Reported Dry Eye Symptoms in a Prospective Randomized Contralateral-Eye Trial Comparing Laser In Situ Keratomileusis and Small Incision Lenticule Extraction

PURPOSE

To prospectively compare corneal sensation and patient-reported symptoms of dry eye in individuals undergoing laser in situ keratomileusis (LASIK) and small incision lenticule extraction (SMILE).

DESIGN

Prospective randomized contralateral-eye clinical trial.

METHODS

80 eyes of 40 patients with myopia at Byers Eye Institute at Stanford University were randomized to receive wavefront-guided femtosecond LASIK in one eye and SMILE in the fellow eye. Cochet-Bonnet esthesiometry was performed to assess corneal sensitivity preoperatively and at the 1-, 3-, 6-, and 12-month postoperative visits. Participants also completed questionnaires at each visit to determine the Ocular Surface Disease Index (OSDI).

RESULTS

Eyes that underwent LASIK compared to SMILE demonstrated more corneal denervation at the postoperative 1-month (mean 2.1 vs 3.6 cm, P < .001), 3-month (3.5 vs 5.4 cm, P < .001), and 6-month (4.7 vs 5.7 cm, P < .001) visits. At the 12-month visit, both groups had returned to baseline corneal sensitivity (5.9 vs 5.9 cm, P = .908). There was no difference in OSDI between the 2 groups at any visit. Mean OSDI improved from the preoperative to the postoperative 12-month visit in both LASIK (15.3 to 8.6, P = .020) and SMILE (15.1 to 9.5, P = .029) groups.

CONCLUSIONS

LASIK resulted in greater corneal denervation compared to SMILE in the early postoperative period, though this difference was no longer apparent after 12 months. Despite this, there was no difference in self-reported dry eye symptoms between the 2 groups. Patient-reported dry eye symptoms improved after both LASIK and SMILE procedures.

L aser in situ keratomileusis (LASIK) is the most popular keratorefractive surgery in the United States, largely because of high rates of patient satisfaction. Dry eye is the most common adverse effect of LASIK, where the loss of homeostasis of the tear film can lead to ocular discomfort and visual disturbance. Symptoms have been reported to peak between 1 week and 3 months, though up to 40% of patients continue to report symptoms 6 months after LASIK. ^, Although incompletely understood, post-LASIK dry eye is thought to be mainly due to the disruption of afferent sensory nerve fibers from the creation of the corneal flap. Small-incision lenticule extraction (SMILE), a more recent procedure, allows for a more minimally invasive approach with a smaller incision compared with LASIK, which can theoretically lead to lower rates of postoperative dry eye disease.

Although studies have been conducted comparing dry eye symptomatology after LASIK and SMILE, there remains uncertainty as to real-world differences in postoperative dry eye disease between these two procedures. This randomized, contralateral-eye, prospective study aims to compare corneal denervation and patient-reported dry eye symptoms in participants undergoing wavefront-guided femtosecond LASIK in one eye and SMILE in the fellow eye over 12 months of follow-up.

METHODS

This was a prospective, randomized, contralateral-eye study performed at the Byers Eye Institute at Stanford University. The study adhered to the tenets of the Declaration of Helsinki, was complaint with the US Health Insurance Portability and Accountability Act, registered at ClinicalTrials.gov (identifier NCT03067077), and approved by the Institutional Review Board at the Stanford University School of Medicine. Written informed consent was obtained from all patients before their inclusion in the study.

Inclusion criteria were –0.75 to –8.00 diopters (D) of spherical myopia with less than 3.00 D of astigmatism, age ≥21 years, correctable vision to 20/20 or better, willingness to participate and return for scheduled follow-up appointments for 12 months after surgery, and ability to give informed consent. Exclusion criteria were greater than 1.5 D of spherical anisometropia or 0.50 D of cylindrical anisometropia, preoperative cornea thickness less than 500 μm, topographic evidence of keratoconus, unstable refraction as documented by change of greater than 0.50 D change in sphere or cylinder in the previous 12 months, history of previous ocular surgery, history of autoimmune diseases, or pregnancy.

After determining ocular dominance, a computer program was used to randomize the dominant eye of participants to receive either wavefront-guided femtosecond LASIK or SMILE in a 1:1 ratio. All procedures were performed by a single surgeon (E.E.M.). For eyes undergoing LASIK, a 9.0-mm-diameter flap with a superior hinge and 100 μm depth was created using the Intralase iFS femtosecond laser (Johnson & Johnson Vision). Wavefront-guided ablation, using the scans from the iDesign Advanced WaveScan Studio System aberrometer (Johnson & Johnson Vision), was performed with the VISX Star Custom Vue S4 IR excimer laser (Johnson & Johnson Vision). For eyes undergoing SMILE, a 120 μm depth, 6.0 mm (compound myopic astigmatism) or 6.5 mm (simple myopia) diameter lenticule, with a 4-mm superior tunnel incision was created using the Visumax femtosecond laser (Carl Zeiss Meditec). The refractive lenticule was then dissected and gently extracted using SMILE forceps. After surgery, patients were prescribed topical prednisolone acetate 1% ophthalmic suspension (Pred Forte; Allergan) and moxifloxacin hydrochloride 0.5% ophthalmic solution (Vigamox; Alcon) 4 times daily for 7 days.

Participants completed the PROWL questionnaire at the preoperative and the postoperative 1-, 3-, 6-, and 12-month visits. The Ocular Surface Disease Index (OSDI) score, intended to measure the severity of dry eye, was calculated for each eye from these responses. Central corneal sensitivity was measured by a single surgeon (E.E.M.) at the preoperative and the postoperative 1-, 3-, 6-, and 12-month visits using a Cochet-Bonnet esthesiometer (Luneau Technology). A sample size calculation determined that 28 participants were sufficient to detect a mean difference of 0.5 cm between preoperative and postoperative Cochet-Bonnet corneal sensitivity scores with a power of 80% at a 5% significance level.

Statistical analysis was performed using Prism (GraphPad Software). Analysis was performed using a mixed effects model. The Holm-Šídák method was used to correct for multiple comparisons. An adjusted P value of less than .05 was considered statistically significant.

RESULTS

Eighty-eight eyes of 44 patients were enrolled in the study from March 2017 to March 2021. Of these patients, 3 withdrew prior to undergoing surgery, and 1 undergoing SMILE had surgery aborted because of difficulty removing the refractive lenticule. Eighty eyes of 40 patients were treated with wavefront-guided femtosecond LASIK in one eye and SMILE in the contralateral eye. The average age of participants was 34 ± 8 years (range, 24-54 years). There were 22 men and 18 women. Thirty-nine of 40 (98%), 33 of 40 (83%), 32 of 40 (80%), and 37 of 40 (93%) participants returned for their 1-, 3-, 6-, and 12-month postoperative visits respectively. The mean ablation depth was 61 ± 23 μm (range, 21-108) for LASIK, and the mean lenticule thickness was 79 ± 26 μm (range, 31-140) for SMILE. Other preoperative characteristics are displayed in Table 1 .

TABLE 1

Preoperative Characteristics

	LASIK	SMILE	P Value
Sphere, D	−4.02 ± 1.82(–1.00 to –9.50)	−4.16 ± 1.78(–1.00 to –8.75)	.73
Cylinder, D	0.46 ± 0.36(0.00-1.75)	0.46 ± 0.38(0.00-1.75)	>.99
Spherical equivalent, D	−3.79 ± 1.75(–0.75 to –8.88)	−3.93 ± 1.70(–0.75 to –8.00)	.72
Central corneal thickness, µm	561 ± 29(508-634)	560 ± 28(509-628)	.93
Planned ablation depth, μm	61 ± 23(21-108)
Planned lenticule thickness, μm		79 ± 26(31-140)

D = diopter, LASIK = laser in situ keratomileusis, SMILE = small incision lenticule extraction.

Values are mean ± SD (range).