OBJECTIVE: The corneal cap thickness is a vital parameter designed in small incision lenticule extraction (SMILE). The purpose was to investigate the changes in corneal subbasal nerve plexus (SNP) and stromal cells with different cap thicknesses and evaluate the optimized design for the surgery.
METHODS: In this prospective, comparative, non-randomized study, a total of 108 eyes of 54 patients who underwent SMILE were allocated into three groups with different corneal cap thicknesses (110 μm, 120 μm or 130 μm group). The SNP and stromal cell morphological changes obtained from in vivo corneal confocal microscopy (IVCCM) along with their refractive outcomes were collected at 1 week, 1 month, 3 months and 6 months postoperatively. One-way analysis of variance (ANOVA) was used to compare the parameters among the three groups.
RESULTS: The SNPs in the three groups all decreased after surgery and revealed a gradual increasing trend during the 6-month follow-up. The values of the quantitative nerve metrics were significantly lower in the 110 μm group than in the 120 μm and 130 μm groups, especially at 1 week postoperatively. No difference was detected between the 120 μm and 130 μm groups at any time point. Both Langerhans cells and keratocytes were activated after surgery, and the activation was alleviated during the follow-up.
CONCLUSIONS: The SMILE surgeries with 110 μm, 120 μm or 130 μm cap thickness design achieved good efficacy, safety, accuracy and stability for moderate to high myopic correction while the thicker corneal cap was more beneficial for corneal nerve regeneration.

OBJECTIVE: To compare the reliability of the whorl-like region with that of the central cornea for accurate assessment of corneal subbasal nerve plexus (SNP) by analyzing the parameter variability of these two anatomical regions in repeated measurements.
METHODS: Participants were scanned in the central cornea and whorl-like region with in vivo confocal microscopy on three occasions by two examiners within a time span of one week. Coefficients of repeatability (CoR), intra-class correlation coefficient (ICC), and Bland-Altman scatter plots with 95% limits of agreement (LOA) in the central cornea and whorl-like region were calculated, respectively, based on the nerve fiber length, then the inter-observer and intra-observer agreement were compared between these two anatomical regions.
RESULTS: The inter-observer ICC was 0.945, the inter-observer CoR was 0.052, the intra-observer ICC was 0.936, and the inter-observer CoR was 0.046, with narrow 95% LOA within 1 standard deviation in the whorl-like region, whereas the inter-observer ICC was 0.600, the inter-observer CoR was 0.207, the intra-observer ICC was 0.206, and the intra-observer CoR was 0.253, with 95% LOA nearly threefold wider than the standard deviation in the central cornea.
CONCLUSIONS: Nerve parameter in the whorl-like region showed higher inter-observer and intra-observer agreement than that of the central cornea. The whorl-like region is a more reliable site for accurate assessment of SNP.

OBJECTIVE: The purpose of this study was to determine the effect of aging on the corneal subbasal nerve plexus (SNP) by employing a wide-field mapping technique of composite images, scanned at the location of a distinctive spiraled subbasal nerve pattern located 1-2 mm inferior to the corneal apex (the inferior whorl) for SNP structural quantification.
METHODS: Central corneal tactile sensitivity (CCTS) and inferior whorl length (IWL) were compared among individuals in 3 age-groups (20-39 years, 40-59 years, and 60-79 years). Statistical analyses constituted the Kruskal-Wallis test, one-way analysis of variance (with the post hoc least significant difference test), Spearman correlation coefficient, and linear regression analysis.
RESULTS: CCTS remained stable until the age of 50 years, when it began to decrease; the mean CCTS was 58.15 ± 2.46 mm in the group aged 20-39 years, 55.74 ± 3.85 mm in the group aged 40-59 years, and 50.23 ± 3.27 mm in the group aged 60-79 years. IWL decreased with increasing age, with a corresponding linear decline of 0.2088 mm/mm2 per year, and the mean IWL was 25.43 ± 4.50 mm/mm2 in the group aged 20-39 years, 22.71 ± 6.19 mm/mm2 in the group aged 40-59 years, and 18.60 ± 4.21 mm/mm2 in the group aged 60-79 years.
CONCLUSIONS: Our work provided a more accurate and repeatable method for corneal nerve analysis using laser scanning confocal microscopy. By using this technique, we confirmed that aging is associated with progressive reduction in subbasal nerve length.

Background and purpose: It has been generally thought that activation and sensitization of the trigeminovascular system may contribute to the pathogenesis of migraine. Nevertheless, there is little evidence on abnormalities in peripheral trigeminal afferent nerves from humans in vivo. Alterations of corneal nerves from the ophthalmic branch of the trigeminal nerve may support the notion that trigeminal afferent nerves are involved in migraine pathophysiology. The aim of the present study was to investigate the structural changes in corneal subbasal nerve plexus in patients with episodic migraine (EM) with in vivo confocal microscope (IVCM). Methods: In this cross-sectional observational study, 10 EM patients and 10 age- and sex-matched healthy controls were included. Analysis of IVCM images with Image J software was performed to quantify the changes in the corneal subbasal nerve plexus. Results: EM patients showed an increase in nerve fiber length (25.0±2.65 vs 22.3±2.41 mm/mm2, p=0.047) and nerve fiber density (36.3±7.29 vs 30.5±6.19 fibers/mm2, p=0.104) as compared with normal controls, but this difference was not statistically significant. Nerve branching and tortuosity were significantly increased in the EM subjects compared to the normal subjects (91.3±13.8 vs 75.0±14.2 branches/mm2, p=0.030 and 2.30±0.46 versus 1.63±0.52, p=0.011, respectively). In addition, nerve sprouts and increased number of Langerhans cells were observed in the EM patients. Conclusion: The morphologic changes of corneal subbasal nerve plexus and Langerhans cell aggregation suggest the presence of nerve regeneration and inflammation in EM. Furthermore, the alterations of corneal nerves from the ophthalmic branch of the trigeminal nerve offer support for the hypothesis that the peripheral trigeminal system may be involved in the pathogenesis of migraine.

BACKGROUND: To study basal epithelial cell (BEC), sub-basal nerve plexus (SBN) and Langerhans cell (LC) density in patients with type 2 diabetes mellitus (T2DM) with corneal punctate epitheliopathy (CPE) and to assess their association with time to healing of CPE.
METHODS: Retrospective study of in vivo confocal microscopy (IVCM) in 160 eyes from 160 patients with T2DM diagnosed with CPE due to a single cause. Key exclusion criteria included multiple-causes for CPE or treatment with autologous serum. A total of 149 eyes from 149 gender- age- and aetiolgy-matched patients with CPE without T2DM comprised the control group. Electronic records were reviewed for demographic features, history of T2DM and aetiology of CPE. Density of BEC, SBN and LC were compared between the two groups.
RESULTS: The healing time in days for CPE with different aetiologies in the T2DM and control groups were as follows: dry eye (21.56 ± 2.41; 7.00 ± 2.19; P = 0.001); meibomian gland dysfunction (26.42 ± 6.04; 9.21 ± 2.55; P = 0.001); cataract extraction (38.00 ± 19.62; 25.83 ± 11.49; P = 0.043); drug induced (53.19 ± 18.83; 41.86 ± 23.87; P = 0.018) and exposure (38.25 ± 14.13; 29.00 ± 13.67; P = 0.026). LC density was 38.70 ± 9.65 cells/mm2 in the T2DM group comparedwith 25.53 ± 3.54 cells/mm2 in the controls (P = 0.001). SBN density was 11.76 ± 1.69 mm/mm2 in the T2DM group compared with 20.92 ± 1.43 mm/mm2 in the controls (P = 0.001). BEC density in the T2DM group was 4982 ± 1178 cells/mm2 compared with 5739 ± 394 cells/mm2 in the control group (P = 0.018). Age and duration of T2DM had no relationship with healing time (multiple linear regression, P = 0.618; P = 0.787). The density of LC in the T2DM group showed a negative correlation with SBN density (r = 0.350; R2 = 0.1225; P = 0.034). The density of SBN in the T2DM group showed a positive correlation with BEC density (r = 0.427; R2 = 0.1823; P = 0.008). The density of BEC in the T2DM group showed a negative correlation with healing time (r = 0.931; R2 = 0.8668; P = 0.001).
CONCLUSIONS: Utilising IVCM, we have demonstrated increased LC and decreased SBN in patients with T2DM and CPE. Both may be related to lower BEC density and nuclei enhanced reflection. Furthermore, decreased BEC density may lead to delay in cornea epithelium healing in the T2DM group comparedwith controls. An immune-mediated response may play a role in delayed wound closure in patients with T2DM.