PURPOSE: To compare long-term corneal nerve status following small incision lenticule extraction (SMILE) versus laser in situ keratomileusis (LASIK). METHODS: Twenty-four patients were randomized to receive SMILE in one eye and LASIK in the other eye. In vivo confocal microscopy examination and dry eye assessments were performed at a mean of 4.1 years postoperatively. The patients were further divided into two groups based on the mean assessment time: 2.7 years postoperatively (2.7 years group) and 5.5 years postoperatively (5.5 years group). Another 6 age-matched normal patients were recruited. RESULTS: At 4.1 years, LASIK eyes had significantly less corneal nerve fiber density (CNFD), corneal nerve branch density (CNBD), corneal nerve fiber length (CNFL), and corneal total branch density and significantly more nerves with beading than SMILE eyes. The CNFD, CNBD, CNFL, and number of nerves with sprouting were significantly higher in the 5.5 years group than in the 2.7 years group, in both types of surgery, suggesting persistent nerve regeneration. The CNBD and CNFD in the 5.5 years group, regardless of surgical types, were significantly lower than those in the control group, indicating the nerve status had not recovered to normal ranges even at 5.5 years. High myopic treatment resulted in significantly reduced CNFD with LASIK but not with SMILE. There were no significant differences in the dry eye parameters between the two procedures at 4.1 years postoperatively. CONCLUSIONS: The impact on corneal nerves following refractive surgery is long-lasting. SMILE had better nerve preservation and regeneration than LASIK, but neither procedure had recovered nerve status to normal levels even at 5.5 years. [ J Refract Surg . 2020;36(10):653–660.]

Following refractive surgery, the cornea is denervated and re-innervated, hence a reproducible tool to objectively quantify this change is warranted. This study aimed to determine the repeatability and reproducibility of corneal nerve quantification between automated (ACCMetrics) and manual software (CCMetrics) following refractive surgery. A total of 1007 in vivo confocal microscopy images from 20 post-small incision lenticule extraction (SMILE) or post-laser-assisted in situ keratomileusis (LASIK) patients were evaluated by two independent observers using CCMetrics for corneal nerve fibre density (CNFD), corneal nerve branch density (CNBD), and corneal nerve fibre length (CNFL). Intra-observer and inter-observer reproducibility and repeatability, as well as agreement and correlation between the measurements obtained by ACCMetrics and CCMetrics, were assessed. We found that CNFL demonstrated the best intra- and inter-observer agreement followed by CNFD (intra-class correlation coefficient (ICC) = 0.799 and 0.740, respectively for CNFL; 0.757 and 0.728 for CNFD). CNBD demonstrated poorest intra- and inter-observer ICC. There was an underestimation in ACCMetrics measurements compared to CCMetrics measurements, although the differences were not significant. Our data suggested that both automated and manual methods can be used as reliable tools for the evaluation of corneal nerve status following refractive surgery. However, the measurements obtained with different methods are not interchangeable.

Purpose: To compare 1-year clinical outcomes, phacoemulsification energy, aqueous profiles, and patient-reported outcomes of low-energy femtosecond laser-assisted cataract surgery (FLACS) vs. conventional phacoemulsification.Methods: The study is a randomized controlled trial (RCT) with paired-eye design. Eighty-five patients were randomized to receive FLACS (Ziemer LDV Z8) in one eye and conventional phacoemulsification in the fellow eye. Clinical data including phacoemulsification energy parameters (cumulative dissipated energy, phacoemulsification power, and phacoemulsification time), uncorrected and corrected distance visual acuities (UCDVA and BCDVA), manifest refraction spherical equivalent (MRSE), central corneal thickness (CCT), endothelial cell count (ECC), anterior chamber flare, and post-operative complications were obtained for 1 year. Aqueous humor was collected for the analysis of prostaglandin (PGE)2, cytokines and chemokines concentrations. Patients' reported-outcomes on surgical experiences were evaluated using an in-house questionnaire.Results: Compared to conventional phacoemulsification, the low-energy assisted FLACS group had significantly less ECC reduction at 3 months (1.5 ± 0.3% vs. 7.0 ± 2.4%; P < 0.01) and 1 year (8.2 ± 2.8% vs. 11.2 ± 3.6%; P = 0.03). There were no significant differences in the phacoemulsification energy parameters, UCDVA, BCDVA, MRSE, CCT, occurrence of post-operative complications between the 2 groups throughout post-operative 1 year. Patients' subjective surgical experiences, including the surgical duration and perceived inconvenience, were comparable between the 2 groups. FLACS resulted in significantly higher aqueous PGE2 (P < 0.01), interleukin (IL)-6 (P = 0.03), IL-8 (P = 0.03), and interferon (IFN)-γ (P = 0.04) concentrations and greater anterior chamber flare at 1 day (P = 0.02).Conclusions: Our RCT presented 1-year longitudinal clinical and laboratory data. The long-term ECC result was more favorable in low-energy FLACS. The rest of the intraoperative and post-operative outcomes, as well as patient-reported outcomes, were comparable between these two procedures.

PURPOSE: To investigate the changes in tear neuromediators and corneal subbasal nerve plexus following small incision lenticule extraction (SMILE) and to study its association with different refractive power of corrections. METHODS: Thirty patients were included for tear neuromediator analysis (40 eyes) and corneal nerve analysis using in vivo confocal microscopy scans (20 eyes). Tear samples were collected preoperatively and 1 week and 1, 3, 6, and 12 months postoperatively and analyzed for the substance P, calcitonin gene-related peptide (CGRP), and nerve growth factor (NGF) concentrations using the enzyme-linked immunosor-bent assay (ELISA). RESULTS: Corneal nerve fiber density (CNFD), corneal nerve fiber length (CNFL), and corneal nerve branch density (CNBD) decreased significantly postoperatively, then gradually increased from 3 months onward, but did not recover to the baseline levels at 12 months. Tear substance P and CGRP levels remained stable over 12 months. Tear NGF levels demonstrated a small peak at 1 week before decreasing significantly compared to preoperative levels at 6 months ( P = .03) and 12 months ( P = .007). The 1-month reduction in CNFL, tear substance P, and CGRP concentrations were significantly correlated with the corrected spherical equivalent (SE) ( r = 0.71 for CNFL; r = −0.33 to −0.52 at different time points for substance P and CGRP, respectively, all P < .05). Compared to the low to moderate myopia group, the high myopia group (corrected SE greater than −6.00 diopters) had a significantly greater decrease in CNFD, significantly higher tear substance P concentrations at 1 week, 1 month, and 6 months, and significantly higher tear CGRP concentrations at 1 and 6 months. CONCLUSIONS: These results provide new insight into the neurobiological responses and their potential implications in corneal nerve damage and recovery after SMILE. High myopia treatment was associated with greater corneal denervation and neuroinflammation. [ J Refract Surg . 2021;37(8):516–523.]