Purpose: To describe a patient with high myopia who experienced slight myopic regression twice during follow-up after small incision lenticule extraction (SMILE), which can be eased by topical treatment of timolol. Methods: Case report. Results: Six months after a SMILE procedure for high myopia in both eyes, the patient's uncorrected distance visual acuity (UDVA) was 0.8 and both eyes lost one line compared to preoperative corrected distance visual acuity (CDVA) by myopic shift, which was accompanied by central corneal epithelial thickening. After 2 months of treatment with topical timolol eye drops, the UDVA improved two more lines with flattened corneal curvature and thinned epithelial thickness. After 5 months without timolol treatment, he lost two lines of UDVA again with thicker epithelial thickness. After another 2 months of treatment with timolol, the epithelial thickness could be seen to have thinned month by month, and the UDVA improved two or more lines. There was no notable myopic shift in both eyes for the next 3 months with medication withdrawal. During the whole follow-up period, the change in corneal and epithelial thickness remarkably fluctuated with the timolol treatment, but the posterior corneal curvature was stable. Conclusions: This case report describes refractive regression that can repeatedly occur in the middle and long term after a SMILE procedure for high myopia, which could be correlated with the thickening of the central corneal epithelium. Treatment with timolol eye drops can help to improve visual acuity by thinning the compensated epithelial thickness to flatten corneal curvature. [ Journal of Refractive Surgery Case Reports. 2023;3(4):e47–e52.]
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