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: Investigate the correlation and agreement between the results of semiautomated and fully automated quantitative analysis of the corneal sub-basal nerve plexus (SNP) in patients with dry eye disease (DED) with ocular pain using in vivo confocal microscopy (IVCM).
METHODS: A total of 50 voluntary participants were enrolled in this study, i.e., 25 DED patients with ocular pain and 25 healthy controls. Each patient underwent an evaluation of ocular symptoms that utilized: the Ocular Surface Disease Index (OSDI), the Ocular Pain Assessment Survey (OPAS), the tear film breakup time (TBUT) test, the Schirmer test, corneal staining, and IVCM. Five SNP images of the cornea of each eye were selected and analyzed using a semiautomated analysis software (NeuronJ) and a fully automated method (ACCMetrics) to quantify corneal nerve fiber density (CNFD), corneal nerve branch density (CNBD), and corneal nerve fiber length (CNFL).
RESULTS: The intraclass correlation coefficient (ICC) of the CNFD (0.460 [0.382-0.532], p < 0.001), CNBD (0.608 [0.545-0.665], p < 0.001), and CNFL (0.851 [0.822-0.875], p < 0.001) represents the repeatability and consistency of measurements by the NeuronJ and ACCMetrics software. The CNFL values (r = 0.881, p < 0.001) obtained using the two methods have extremely high correlation, and similarly, the CNFD values (r = 0.669, p < 0.001) and CNBD values (r = 0.703, p < 0.001) are highly correlated. The CNFL had the biggest area under the curve (AUC; 0.747 [0.700-0.793], p < 0.001) when using ACCMetrics. In DED patients with ocular pain, the mean CNFD values for semiautomated and fully automated quantization were 23.5 ± 8.1 and 23.8 ± 8.6 n/mm2; the mean CNBD values were 46.0 ± 21.3, 35.7 ± 23.3 n/mm2; and the mean CNFL values were 19.3 ± 4.3 and 15.2 ± 3.8 mm/mm2, which were significantly lower than healthy subjects (p < 0.001).
CONCLUSIONS: There is a significant correlation between the measurements obtained via ACCMetrics and NeuronJ, especially for CNFL, which can be considered as the primary indicator in the diagnosis of DED with ocular pain. The SNP of the disease was significantly lower than that of healthy subjects.

BACKGROUND: To assess in vivo confocal microscopy features of corneal sub-basal nerve plexus in patients with congenital or aponeurogenic blepharoptosis using a fully automated software (ACCMetrics).
METHODS: This prospective study included 33 patients with blepharoptosis and 17 normal controls. The corneal sub-basal nerve plexus was assessed using in vivo confocal microscopy, and the ocular surface status was evaluated by tear break-up times.
RESULTS: The mean age of 33 patients with blepharoptosis and 17 normal controls were 38.77 ± 22.81 years and 48.35 ± 17.15 years, respectively. The mean duration of blepharoptosis was 16.42 ± 15.60 years. In 13 patients with unilateral blepharoptosis, there was no significant difference between affected eyes and contralateral eyes (all ps > .05), except for wider corneal nerve fibre width (CNFW) in affected eyes (0.024 ± 0.001 versus 0.023 ± 0.001 mm/mm2, p = .021). In 20 patients with bilateral blepharoptosis, there was no significant difference between the eyes. No significant difference was detected between 19 cases with congenital blepharoptosis and 14 cases with aponeurogenic blepharoptosis. When compared with normal controls, eyes with both unilateral and bilateral blepharoptosis had significantly wider CNFW. But from the point of aetiology, only eyes with congenital blepharoptosis presented with wider CNFW (p = .001), rather than the eyes with aponeurogenic blepharoptosis (p = .093). Besides, four young patients with congenital blepharoptosis revealed very sparse sub-basal nerve plexus.
CONCLUSIONS: These data suggested that corneal confocal microscopy demonstrated no significant changes in patients with blepharoptosis as compared with normal controls, except for relatively wider CNFW in congenital affected eyes. However, in some children and young adults with congenital blepharoptosis, the density of corneal sub-basal nerve plexus was evidently decreased, which needs to be cautioned when ones with congenital blepharoptosis want to take corneal surgeries or wear contact lens.Key messagesWhen compared with normal controls, no significant effect was found in the influence of blepharoptosis on the most of corneal nerve parameters, except for corneal nerve fibre width (CNFW) in the group of congenital blepharoptosis.The age of onset of blepharoptosis may influence corneal nerve fibres, so timely surgical treatment of congenital blepharoptosis is not only conducive to the development of normal vision, but also beneficial to the reduction of corneal nerve lesions to some extent.We noted that some young blepharoptosis patients revealed sparse corneal nerve, which should be taken precaution when ones with congenital blepharoptosis who want to take corneal surgeries or wear contact lens.

OBJECTIVE: To examine and compare fully-automated and manually measured corneal nerve fiber parameters in type 2 diabetes mellitus (T2DM) patients with and without diabetic peripheral neuropathy (DPN).
METHODS: A total of 128 T2DM subjects and 24 healthy controls underwent neuropathy assessment and bilateral corneal confocal microscopy (CCM). Five representative nerve fiber images were selected for each participant and analyzed manually and with fully-automated software. Corneal nerve fiber length (CNFL), branch density (CNBD), and fiber density (CNFD) were examined.
RESULTS: Manual and full-automated methods for the whole cohort were significantly positive correlated for CNFL, CNBD and CNFD (r = 0.818, 0.845, 0.457, all P < 0.001). Analysis of agreement between the two measurements using Bland-Altman method showed a bias of 2.05 mm/mm2 (95% limits of agreement: -2.03 mm/mm2, 6.13 mm/mm2), 1.62 no./mm2 (95% limits of agreement: -17.92 no./mm2, 21.17 no./mm2), and 16.0 no./mm2 (95% limits of agreement: -0.14 no./mm2, 32.14 no./mm2) for CNFL, CNBD and CNFD respectively. A progressive decrease in manual and full-automated CNFL, CNBD and CNFD accompanied with the occurrence of DPN, The fully-automated method slightly underestimated corneal nerve fiber parameters.
CONCLUSIONS: This study demonstrated strong correlations between manual and fully-automated CNFL and CNBD, but not CNFD. Fully-automated corneal nerve fiber parameter quantification may be a fast, objective way to detect DPN.

OBJECTIVE: To evaluate in vivo confocal microscopy (IVCM) features of corneal subbasal nerve plexus (SNP) in the setting of dry eye disease (DED) using fully automated software \"ACCMetrics,\" and to further investigate its diagnostic performance in discriminating DED patients.
METHODS: IVCM exams of SNP in DED patients and matched control subjects were performed using Heidelberg Retina Tomograph with the Rostock Cornea Module. The following parameters were obtained with ACCMetrics: corneal nerve fiber density (CNFD), corneal nerve branch density (CNBD), corneal nerve fiber length (CNFL), corneal nerve total branch density (CTBD), corneal nerve fiber area (CNFA), corneal nerve fiber width (CNFW), and corneal nerve fractal dimension (CNFrD). The Mann-Whitney U test was used to compare variables. Receiver operating characteristic curves with calculations of the area under the curve (AUC) were used to describe the accuracy of IVCM parameters for discriminating DED patients from controls.
RESULTS: Thirty-nine DED patients and 30 control subjects were included. Significantly, lower values of CNFD, CNBD, and CNFL and higher value of CNFW were found in DED patients compared to controls (respectively, 20.5 ± 8.7 vs 25.4 ± 6.7 n/mm2; 25.6 ± 20.1 vs 37.6 ± 21.5 n/mm2; 12.6 ± 4.4 vs 14.5 ± 2.9 mm/mm2; 0.021 ± 0.001 vs 0.019 ± 0.001 mm/mm2; always p < 0.024). CNFW value had the highest diagnostic power in discriminating DED patients (AUC = 0.828). When the diagnosis of DED was made based on either CNFW or CNBD, the sensitivity was 97.4% and the specificity 46.7%.
CONCLUSIONS: The software ACCMetrics was able to rapidly detect SNP alterations occurring in the setting of DED and showed good diagnostic performance in discriminating DED patients.