Early elastic and viscoelastic corneal biomechanical changes after photorefractive keratectomy and small incision lenticule extraction.

PURPOSE: To compare early changes in the corneal biomechanical parameters after photorefractive keratectomy (PRK) and small incision lenticule extraction (SMILE) and their correlations with corneal shape parameters. METHODS: One hundred twenty four eyes received myopic PRK and SMILE for similar amounts of myopia. Corneal tomography with Pentacam HR, biomechanical parameters using Corvis ST, and Ocular Response Analyzer (ORA) were evaluated before and 2 weeks after surgery. The change in each parameter was compared between groups, while the difference in central corneal thickness and cornea-compensated intraocular pressure measured before and after surgery were considered as covariates. RESULTS: A significant reduction was seen in the corneal stiffness parameter at first applanation, and an increase in deformation amplitude ratio (DAR), and integrated inverse radius (IIR) in both groups after surgery (p < 0.001) Changes in DAR, and IIR were significantly greater in the SMILE than in the PRK group (p < 0.001) Corneal hysteresis (CH) and corneal resistance factor (CRF) decreased in both SMILE and PRK groups after surgery, (p < 0.001) with no statistically significant difference between groups (p > 0.05) Among new Corvis ST parameters, DAR showed a significant correlation with changes in Ambrosio relational thickness in both groups (p < 0.05). CONCLUSIONS: Both techniques caused significant changes in corneal biomechanics in the early postoperative period, with greater elastic changes in the SMILE group compared to the PRK group, likely due to lower tension in the SMILE cap and thinner residual stromal bed in SMILE. There were no differences in viscoelastic changes between them, so the lower CH may reflect the volume of tissue removed.

Development of graphitic carbon nitride quantum dots-based oxygen self-sufficient platforms for enhanced corneal crosslinking.

Keratoconus, a disorder characterized by corneal thinning and weakening, results in vision loss. Corneal crosslinking (CXL) can halt the progression of keratoconus. The development of accelerated corneal crosslinking (A-CXL) protocols to shorten the treatment time has been hampered by the rapid depletion of stromal oxygen when higher UVA intensities are used, resulting in a reduced cross-linking effect. It is therefore imperative to develop better methods to increase the oxygen concentration within the corneal stroma during the A-CXL process. Photocatalytic oxygen-generating nanomaterials are promising candidates to solve the hypoxia problem during A-CXL. Biocompatible graphitic carbon nitride (g-C3N4) quantum dots (QDs)-based oxygen self-sufficient platforms including g-C3N4 QDs and riboflavin/g-C3N4 QDs composites (RF@g-C3N4 QDs) have been developed in this study. Both display excellent photocatalytic oxygen generation ability, high reactive oxygen species (ROS) yield, and excellent biosafety. More importantly, the A-CXL effect of the g-C3N4 QDs or RF@g-C3N4 QDs composite on male New Zealand white rabbits is better than that of the riboflavin 5'-phosphate sodium (RF) A-CXL protocol under the same conditions, indicating excellent strengthening of the cornea after A-CXL treatments. These lead us to suggest the potential application of g-C3N4 QDs in A-CXL for corneal ectasias and other corneal diseases.

Effect of Corneal Allogenic Intrastromal Ring Segment (CAIRS) Implantation Surgery in Patients With Keratoconus According to Prior Corneal Cross-linking Status.

PURPOSE: To compare the effects of corneal allogenic intrastromal ring segment (CAIRS) implantation on topographical measurements and visual outcomes of patients with keratoconus with and without corneal cross-linking (CXL) prior to the time of implantation. METHODS: Sixty-seven eyes with corneal allograft intrastromal ring segment implantation (KeraNatural; Lions VisionGift) due to advanced keratoconus were included in the study. Thirty-seven eyes had no CXL and 30 eyes had had CXL before being referred to the authors. The changes in spherical equivalent (SE), uncorrected distance visual acuity (UDVA), corrected distance visual acuity (CDVA), steep keratometry (K1), flat keratometry (K2), mean keratometry (Kmean), maximum keratometry (Kmax), and thinnest pachymetry were retrospectively analyzed 6 months after the implantation. RESULTS: The median age was 29 years in the CXL group and 24.0 years in the non-CXL group (P > .05), respectively. All topographical and visual parameters before implantation were similar in both groups (P > .05 for all parameters). At 6 months, CDVA, K1, and Kmean showed higher improvement in the non-CXL group than the CXL group (P = .030, .018, and .039, respectively). CONCLUSIONS: CAIRS surgery has a flattening effect on both the corneas with and without CXL. The cornea with prior CXL treatment had less flattening effect due to the stiffening effect of prior CXL. [J Refract Surg. 2024;40(6):e392-e397.].

Risk Factors for Re-treatment After Keratorefractive Lenticule Extraction (KLEx) for Myopia and Myopic Astigmatism.

PURPOSE: To identify potential risk factors that increase the likelihood of re-treatment following keratorefractive lenticule extraction (KLEx) for myopia and myopic astigmatism. METHODS: This was a retrospective study of patients with myopia and myopic astigmatism who underwent KLEx using the VisuMax 500 laser (Carl Zeiss Meditec) between April 2015 and December 2020. Patients were assigned to one of two groups: the control group and the re-treatment group (if they had additional refractive surgery within 2 years of the primary treatment). The effect of different preoperative, intraoperative, and postoperative parameters on the re-treatment rate was analyzed. RESULTS: Overall 1,822 eyes of 938 patients were analyzed. In total, 2.96% of eyes (n = 54) underwent re-treatment. The re-treated patients were more likely to be women and have high myopia, high astigmatism, steep corneas, higher ocular residual astigmatism, and residual myopic and/or astigmatic refractive error. In contrast, no significant correlation was found between re-treatment rate and age, chord µ, type of astigmatism, and corneal thickness. CONCLUSIONS: Factors associated with higher rates of retreatment after KLEx included female gender, manifest refractive high myopia (> -5.00 diopters [D]), astigmatism (> 2.00 D), spherical equivalent (> 6.00 D), ocular residual astigmatism, steeper corneas, and postoperative residual myopic and astigmatic refractive errors. This study may help to preoperatively detect patients at risk for re-treatment, improve preoperative patient counseling, and optimize patient selection to reduce future re-treatment rates. [J Refract Surg. 2024;40(6):e362-e370.].

Histology, histochemistry and ultrastructure of cornea of domestic pigs (Sus scrofa domesticus).

A comprehensive light and ultrastructural examination of the cornea in Domestic Pigs (Sus scrofa domesticus) revealed four distinct layers: the anterior epithelium, corneal stroma, Descemet's membrane and endothelium. Although Bowman's layer was not distinctly identified through histology, histochemical analysis indicated the presence of a rudimentary Bowman's layer, possibly vestigial from evolution. Scanning electron microscopy of the outer corneal surface unveiled two cell types, characterized by micro-projections, with light cells exhibiting shorter, thicker projections compared to dark cells. Examination of the inner surface via scanning electron microscopy demonstrated an endothelial layer devoid of cilia and microvilli, yet faint round to oval elevations were observed, potentially representing cell nuclei. Transmission electron microscopy unveiled that basal cells of the anterior epithelium closely adhered to the basement membrane, featuring half desmosomes along the basal surface. These basal cells extensively interconnected through interdigitations and a few desmosomes. The superficial cell layer consisted of a few rows of closely attached flat cells, forming a leak-proof layer with zona occludens. The outermost cells of this layer displayed fine projections to enhance the surface area, facilitating tear film distribution. At lower magnification, Transmission electron microscopy of the corneal stroma revealed alternating light and dark bands, with light bands representing transverse sections of collagen fibril lamellae and dark bands corresponding to longitudinal or oblique sections. Spindle-shaped keratocytes (fibroblasts) were identified as the primary stromal cells, intermingled between the lamellae, and featured long processes in close contact with neighbouring keratocytes. Overall, the histomorphology of the pig cornea resembles that of the human cornea except indistinct Bowman's membrane. This detailed understanding of the normal corneal structure in pigs hold great significance for biomedical research, providing a valuable reference for studies involving this animal model.

Feasibility study of treatment of mixed astigmatism with small-incision lenticule extraction (SMILE) by using research software.

PURPOSE: To report the preliminary experience and initial clinical results following SMILE for the treatment of mixed astigmatism. METHODS: Thirteen eyes of nine patients with a mean age of 27 ± 4.36 years were included in the series. In 8/13 eyes, myopic SMILE license and in 4/13 eyes, hyperopic SMILE license (available as part of an open/research software) was used for the treatment. The mean follow-up was 9.5 ± 8.7 (0.5-24) months, and the median follow-up was 6 months. SETTING: Nethradhama Superspeciality Eye Hospital, Bangalore, India. DESIGN: Exploratory study. RESULTS: The mean preoperative sphere, cylinder, and spherical equivalent (SE) were 1.44 ± 1.63, -2.70 ± 2.30, and -0.24 ± 1.14 D, which changed to -0.03 ± 0.30, -0.28 ± 0.48, and -0.18 ± 0.49 D, respectively, 6 months postoperatively. Furthermore, 85% (11/13) eyes were within ± 0.50 D, 92% (12/13) eyes were within ± 1.00 D, while all eyes were within ± 1.50 D of SE correction. All eyes were within ± 1.00 D of cylinder correction. In addition, 92% (12/13) eyes had UDVA better than 20/32, with 54% (7/13) eyes having UDVA 20/20 or better. Safety and efficacy indices were 1.08 and 0.92, respectively. No eyes lost more than 1 line of CDVA. The mean corneal higher order aberrations (HOA) increased from 0.111 ± 0.048 to 0.209 ± 0.056 (P < 0.001). The mean objective scatter index (OSI) did not show a significant change (pre = 0.71 ± 0.69, 6 months = 0.89 ± 0.20; P = 0.35). CONCLUSION: Early experience showed that SMILE was feasible for the management of eyes with mixed astigmatism, without any intraoperative complications, unique to the procedure.

Impact of keratocyte differentiation on corneal opacity resolution and visual function recovery in male rats.

Intrastromal cell therapy utilizing quiescent corneal stromal keratocytes (qCSKs) from human donor corneas emerges as a promising treatment for corneal opacities, aiming to overcome limitations of traditional surgeries by reducing procedural complexity and donor dependency. This investigation demonstrates the therapeutic efficacy of qCSKs in a male rat model of corneal stromal opacity, underscoring the significance of cell-delivery quality and keratocyte differentiation in mediating corneal opacity resolution and visual function recovery. Quiescent CSKs-treated rats display improvements in escape latency and efficiency compared to wounded, non-treated rats in a Morris water maze, demonstrating improved visual acuity, while stromal fibroblasts-treated rats do not. Advanced imaging, including multiphoton microscopy, small-angle X-ray scattering, and transmission electron microscopy, revealed that qCSK therapy replicates the native cornea's collagen fibril morphometry, matrix order, and ultrastructural architecture. These findings, supported by the expression of keratan sulfate proteoglycans, validate qCSKs as a potential therapeutic solution for corneal opacities.

Epithelial and stromal thickness profile and lens decentration in myopic orthokeratology / Perfil de espesor epitelial y estromal y descentrado del cristalino en ortoqueratología miope

Purpose: To study topographic epithelial and total corneal thickness changes in myopic subjects undergoing successful orthokeratology treatment in connection with the objective assessment of contact lens decentration. Methods: A prospective-observational and non-randomized study in 32 Caucasian myopic eyes undergoing Ortho-k for 3 months. Total, epithelial, and stromal thicknesses were studied before and after Ortho-k treatment, using optical coherence tomography with anterior segment application software. Central, paracentral, and mid-peripheral values are taken along 8 semi-meridians. Results: The central average total corneal thickness was 4.72 ± 1.04 μm thinner after Ortho-K. The paracentral corneal thickness showed no significant changes (p = 0.137), while the mid-peripheral corneal thickness was increased by 3.25 ± 1.6 μm associating this increase exclusively to the epithelial plot (p<0.001). When lens centration was assessed, a lens fitting decentration less than 1.0 mm was found for the whole sample, predominantly horizontal-temporal (87.5%) and vertical-inferior (50%) decentring. Corneal topographical analysis revealed a horizontal and vertical epithelial thickness asymmetric change profile with paracentral temporal thinnest values, and mid-peripheral nasal thickest values. Conclusions: The present study found a central corneal thinning induced by Ortho-k lenses in subjects with moderate myopia, only associated with a change in epithelial thickness, as well as mid-peripheral thickening, that seems to be mainly epithelial in origin. The authors also found a tendency of contact lens decentration toward temporal and inferior areas conditioning an asymmetric epithelial redistribution pattern.(AU)

Combined topography-guided photorefractive keratectomy and corneal collagen crosslinking.

PURPOSE: This study aimed to report the long-term results of combined topography-guided photorefractive keratectomy (PRK) and accelerated corneal collagen cross-linking (CXL) for keratoconus using the Zeiss refractive coordinated system. METHODS: A prospective interventional study was conducted in a tertiary eye care hospital in South India. Patients with mild-to-moderate progressive keratoconus and corneal pachymetry greater than 450 µm were included. They underwent customized topography-guided PRK followed by CXL. Uncorrected distance visual acuity (UDVA), corrected distance visual acuity (CDVA), and keratometry readings and complications were evaluated at 1, 3, 6, 12, and 24 months postoperatively. RESULTS: Thirty patients (30 eyes) were included in the study. All study parameters showed a statistically significant improvement postoperatively over baseline values. At 24 months, the mean UDVA improved from 0.8 ± 0.180 logarithm of the minimum angle of resolution (logMAR) to 0.38 ± 0.118 logMAR ( P -value <0.001) and CDVA improved from 0.467 ± 0.142 logMAR to 0.227 ± 0.078 logMAR ( P -value <0.001). The mean flat, steep, and maximum keratometry values were significantly reduced by 2.133, 3, and 4.54 diopters, respectively, at the last follow-up examination ( P -value <0.001). CONCLUSION: The combined topography-guided PRK and accelerated CXL procedure seem to be a promising treatment alternative for early keratoconus. This is the first such study on the Zeiss refractive coordinated system. However, further studies with a larger study population and longer follow-up periods are required to draw final conclusions about the benefits of this procedure in keratoconus.

Adjunctive bevacizumab therapy in an equine corneal stromal invasive squamous cell carcinoma with a 53-months follow-up.

A 17-year-old Appaloosa mare was referred for evaluation of presumed refractory keratitis of the left eye. Gross examination revealed ocular discomfort and corneal neovascularization with a nasal focal opacification affecting approximately 40% of the corneal surface. On ophthalmic examination, extensive subepithelial to mid-stromal vascular branching accompanied by a homogeneous white, dense opacification, which affected up to 80% of the total corneal thickness, were apparent. Signs of concurrent uveitis were absent. Deep-stromal lamellar keratectomy with a conjunctival pedicle graft was performed under general anesthesia. Histopathology confirmed a poorly differentiated corneal stromal invasive squamous cell carcinoma (SI-SCC) with neoplastic cell extension to the surgical margins. Postoperatively, 4 topical mitomycin C 0.04% chemotherapy cycles combined with oral firocoxib therapy were initiated. Seven months after surgery, regrowth of the SI-SCC was clinically suspected. A total volume of 1 ml bevacizumab 2.5% was administered in the standing sedated horse via 3 mid-stromal corneal injections. Four weeks later, intrastromal bevacizumab injections (ISBIs) were repeated, however, this time the solution was injected directly into the main corneal vessel branches.Seven weeks after the second ISBIs, the left eye was comfortable and significant remission of corneal vascularization and opacity was recognized. No recurrence has been noted for a follow-up period of more than 53 months.Equine SI-SCC usually has a very poor prognosis for globe maintenance. To the authors' knowledge this is the first report of well-tolerated intrastromal antivascular endothelial growth factor adjunctive therapy with bevazicumab 2.5% and SI-SCC resolution after a multimodal treatment approach.

Second harmonic generation microscopy of electromechanical reshaping on corneal collagen.

Refractive errors remain a global health concern, as a large proportion of the world's population is myopic. Current ablative approaches are costly, not without risks, and not all patients are candidates for these procedures. Electromechanical reshaping (EMR) has been explored as a viable cost-effective modality to directly shape tissues, including cartilage. In this study, stromal collagen structure and fibril orientation was examined before and after EMR with second-harmonic generation microscopy (SHG), a nonlinear multiphoton imaging method that has previously been used to study native corneal collagen with high spatial resolution. EMR, using a milled metal contact lens and potentiostat, was performed on the corneas of five extracted rabbit globes. SHG was performed using a confocal microscopy system and all images underwent collagen fibril orientation analysis. The collagen SHG signal in controls is uniform and is similarly seen in samples treated with pulsed potential, while continuous EMR specimens have reduced, nonhomogeneous signal. Collagen fibril orientation in native tissue demonstrates a broad distribution with suggestion of another peak evolving, while with EMR treated eyes a bimodal characteristic becomes readily evident. Pulsed EMR may be a means to correct refractive errors, as when comparing its SHG signal to negative control, preservation of collagen structures with little to no damage is observed. From collagen fiber orientation analysis, it can be inferred that simple DC application alters the structure of collagen. Future studies will involve histological assessment of these layers and multi-modal imaging analysis of dosimetry.

Comparative Study of Primary SMILE, SMILE Enhancement, and Femtosecond Laser-Assisted LASIK on Higher Order Aberrations and Corneal Densitometry.

PURPOSE: To compare differences in corneal densitometry (CD) and higher order aberrations (HOAs) in eyes that underwent small incision lenticule extraction (SMILE) and femtosecond laser-assisted laser in situ keratomileusis (FS-LASIK) for the treatment of myopia and myopic astigmatism at postoperative months 3, 6, and 12, and to evaluate their changes in a separate cohort of eyes after SMILE enhancement. METHODS: In this prospective, randomized, paired-eye clinical trial, consecutive eligible participants were randomized to undergo SMILE or FS-LASIK in either eye. Main outcome measures were CD and HOAs preoperatively and at 3, 6, and 12 months postoperatively. A separate cohort of consecutive patients who had SMILE and underwent enhancement were also included for comparison. RESULTS: For CD, no significant differences were found between SMILE and FS-LASIK up to month 12. For HOA measured by wavefront aberrometry, both SMILE and FS-LASIK had an increase in total root mean square (RMS) HOAs, spherical aberration (SA), and vertical coma up to month 12. SMILE had an additional increase in vertical quatrefoil, and FS-LASIK had an increase in horizontal coma at month 12. FS-LASIK had higher SA than SMILE, whereas SMILE had higher vertical quatrefoil than FS-LASIK at month 12. Central and posterior zone CD had significantly decreased after SMILE enhancement compared to after primary SMILE up to 2 years after enhancement. RMS HOAs, lower order aberrations, and SA were all increased after SMILE enhancement compared to after primary SMILE. CONCLUSIONS: SMILE induced lower SA but higher vertical quatrefoil than FS-LASIK at 1 year. Both SMILE and FS-LASIK had similar increases in RMS HOAs and vertical coma up to 1 year. There were no differences in CD between both groups. SMILE enhancement additionally had decreased central and posterior CD but greater RMS HOAs and SA compared to primary SMILE. [J Refract Surg. 2024;40(5):e291-e303.].

Association of myopia and astigmatism with postoperative ocular high order aberration after small incision lenticule extraction.

OBJECTIVE: To investigate the correlation between higher-order aberrations (HOA) after small incision lenticule extraction (SMILE) and the severity of myopia and astigmatism, along with the relevant factors. These findings will provide valuable insights for decreasing the occurrence of HOA after SMILE and enhancing visual quality. METHODS: A total of 75 patients (150 eyes) with myopia and astigmatism who underwent SMILE were categorized into four groups based on the severity of myopia and astigmatism: Myopia Group 1 (Group M1, spherical diopter ranged from -1.00 D to -4.00 D), Myopia Group 2 (Group M2, spherical diopter ranged from -4.10 D to -10.00 D), Astigmatism Group 1 (Group A1, cylindrical diopter ranged from 0 D to -1.00 D), and Astigmatism Group 2 (Group A2, cylindrical diopter ranged from -1.10 D to -3.00 D). A comprehensive assessment was performed to examine the association between HOA and various relevant factors, including a detailed analysis of the subgroups. RESULTS: Group M1 had significantly lower levels of total eye coma aberration (CA), corneal total HOA (tHOA), internal tHOA, and vertical CA ( Z 3 - 1 ) after SMILE than Group M2 (P < 0.05). Similarly, Group A1 had significantly lower levels of total eye tHOA, CA, trefoil aberration (TA), corneal tHOA, TA, and vertical TA ( Z 3 - 3 ) after SMILE than Group A2 (P < 0.05). Pearson correlation analysis indicated a statistically significant positive relationship between the severity of myopia/astigmatism and most HOA (P < 0.05). Subgroup evaluations demonstrated a notable increase in postoperative HOA associated with myopia and astigmatism in Groups M2 and A2 compared with the control group. Lenticule thickness, postoperative central corneal thickness (CCT), postoperative uncorrected distance visual acuity (UDVA), and postoperative corneal Km and Cyl were strongly correlated with most HOA. Age, eyes, and postoperative intraocular pressure (IOP) were only associated with specific HOA. CONCLUSION: HOA positively correlated with the severity of myopia and astigmatism after SMILE. However, this relationship was not linear. HOA after SMILE was influenced by various factors, and additional specialized investigations are required to establish its clinical importance.

SmartSight Correction of Compound Myopic Astigmatism Treatments With Preoperative Astigmatism > 1.00 Diopter Using the SCHWIND ATOS: A Retrospective Case Series.

PURPOSE: To evaluate moderate to high astigmatism corrections on the outcomes of SmartSight lenticule extraction for myopic astigmatism with a new femtosecond laser system. METHODS: Two hundred ninety-two eyes consecutively treated for myopic astigmatism with astigmatism magnitude greater than 1.00 diopter (D) were evaluated at the 6-month follow-up visit. The mean age of the patients was 29 ± 6 years with a mean spherical equivalent of -5.06 ± 2.20 diopters (D) and a mean magnitude of refractive astigmatism of 1.74 ± 0.61 D. RESULTS: At 6 months, astigmatism was 0.10 ± 0.20 D. Uncorrected and corrected distance visual acuities (UDVA and CDVA, respectively) were both 0.0 ± 0.1 logMAR. Differences between postoperative UDVA and preoperative CDVA and the change in CDVA were both +0.4 ± 0.7 lines better than preoperatively (P < .0003). CONCLUSIONS: Lenticule extraction treatment using Smart-Sight is safe and efficacious at 6 months. Findings suggest that moderate to high astigmatism improves after SmartSight lenticule extraction in the treatment of myopic astigmatism. [J Refract Surg. 2024;40(5):e328-e335.].

Uneven Corneal Epithelial Redistribution After Femtosecond Laser-Assisted Lenticule Intrastromal Keratoplasty in Correcting Moderate-to-High Hyperopia.

PURPOSE: To evaluate the characteristic of corrective epithelial thickness after femtosecond laser-assisted lenticule intrastromal keratoplasty (LIKE) to correct moderate-to-high hyperopia. METHODS: The prospective case series study of the LIKE procedure was performed to correct moderate-to-high hyperopia. The epithelial thickness map was generated by anterior segment optical coherence tomography (AS-OCT) in the corneal central 9-mm zone. Keratometry and corneal higher order aberrations were analyzed by Pentacam (Oculus Optikgeräte GmbH) preoperatively and postoperatively. RESULTS: In the 26 eyes of 13 participants who underwent the LIKE procedure for moderate-to-high hyperopia, the attempted spherical equivalence (SEQ) was +6.50 ± 1.09 diopters (D). Compared to the preoperative epithelial thickness maps, the postoperative epithelial thickness had become significantly thinner in the central 5-mm zone; the difference was 6 to 7 µm. The paracentral epithelium performed nonuniform remodeling; the thinnest epithelial thickness was located in the inferotemporal section, which has the greatest difference from the superonasal; the difference between these two was approximately 3 µm. Through correlation analysis, it was found that the sections with thinner epithelium were significantly related to corneal curvature and corneal vertical coma. CONCLUSIONS: The LIKE procedure can be used to correct moderate-to-high hyperopia. This study further indicated the epithelial remodeling characteristic after the LIKE procedure: the central and paracentral corneal epithelial thickness becomes thinner, and the epithelial thickness distributes non-uniformly, which may be the important factor of the postoperative curvature asymmetric distribution and induction of corneal vertical coma. [J Refract Surg. 2024;40(5):e321-e327.].

Impact of Obesity and Age on Mouse Corneal Innervation at the Epithelial-Stromal Interface.

Purpose: The corneal epithelium is the most highly innervated structure in the body. Previously, we reported a novel event whereby stromal axons fuse with basal epithelial cells, limiting nerve penetration into the epithelium. Although corneal-epithelial nerves undergo changes in sensitivity and distribution throughout life and in response to an obesogenic diet, it is unknown if neuronal-epithelial cell fusion is altered. Here, we sought to determine if neuronal-epithelial cell fusion frequency correlates with obesogenic diet consumption and age. Methods: Corneas were collected from C57BL/6 mice and evaluated for neuronal-epithelial cell fusion frequency using serial block-face scanning electron microscopy. To assess the correlation between diet-induced obesity and fusion frequency, 6-week-old mice were fed either a normal diet or an obesogenic diet for 10 weeks. To assess changes in fusion frequency between young and adult mice under normal dietary conditions, 9- and 24-week-old mice were used. Results: Mice fed a 10-week obesogenic diet showed 87% of central-cornea stromal nerves engaged in fusion compared with only 54% in age-matched controls (16 weeks old). In 9-week-old normal-diet animals, 48% of central-cornea stromal nerves contained fusing axons and increased to 81% at 24 weeks of age. Corneal sensitivity loss correlated with increased body weight and adiposity regardless of age and diet. Conclusions: Neuronal-epithelial cell fusion positively correlates with age and obesogenic diet consumption, and corneal nerve sensitivity loss correlates with increased body weight and adiposity, regardless of age and diet. As such, neuronal-epithelial cell fusion may play a role in corneal nerve density and sensitivity regulation.

Corneal Stroma Analysis and Related Ocular Manifestations in Recovered COVID-19 Patients.

Purpose: The purpose of this study was to assess the impact of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) on corneal stroma characteristics, ocular manifestations, and post-recovery refractive surgery outcomes after varying recovery durations. Methods: Fresh corneal lenticules from patients with post-coronavirus disease 2019 (COVID-19; recovered within 135 days) and healthy controls (HCs) after small incision lenticule extraction (SMILE) surgery were obtained for experimental validation of SARS-CoV-2 susceptibility, morphological changes, and immune response of the corneal stroma. Corneal optical density (CD) was measured using the Pentacam HR. Corneal epithelium thickness (ET) and endothelium parameters were evaluated by wide-field optical coherence tomography (OCT) and non-contact specular microscopy (SP-1P), respectively. All the patients were assessed after SMILE surgery until 3 month of follow-up. Results: The cornea was susceptible to SARS-CoV-2 with the presence of SARS-CoV-2 receptors (CD147 and ACE2) and spike protein remnants (4 out of 58) in post-recovery corneal lenticules. Moreover, SARS-CoV-2 infection triggered immune responses in the corneal stroma, with elevated IL-6 levels observed between 45 and 75 days post-recovery, which were then lower at around day 105. Concurrently, corneal mid-stromal nerve length and branching were initially higher in the 60D to 75D group and returned to control levels by day 135. A similar trend was observed in CD within zones 0 to 2 and 2 to 6 and in the hexagonal cells (HEX) ratio in endothelial cells, whereas ET remained consistent. Notably, these changes did not affect the efficacy, safety, or predictability of post-recovery SMILE surgery. Conclusions: SARS-CoV-2 induces temporal alterations in corneal stromal morphology and function post-recovery. These findings provided a theoretical basis for corneal health and refractive surgery management in the post-COVID-19 milieu.

Investigation of the optimal cutting depth in small incision lenticule extraction based on a collagen fibril crimping constitutive model of the cornea.

To investigate the optimal cutting depth (Cap) in small incision lenticule extraction from the perspective of corneal biomechanics, a three-dimensional finite element model of the cornea was established using a stromal sub-regional material model to simulate small incision lenticule extraction. The displacement difference PΔ at the central point of the posterior corneal surface before and after lenticule extraction, as well as the von Mises stress at four points of different thicknesses in the center of the cornea, were analyzed using the finite element model considering the hyperelastic property and the difference in stiffness between the anterior and posterior of the cornea. The numerical curves of PΔ-Cap and von Mises Stress-Cap relations at different diopters show that the displacement difference PΔ has a smallest value at the same diopter. In this case, the von Mises stress at four points with different thicknesses in the center of the cornea was also minimal. Which means that the optimal cutting depth exsisting in the cornea. Moreover, PΔ-Cap curves for different depth of stromal stiffness boundaries show that the optimal cap thickness would change with the depth of the stromal stiffness boundary. These results are of guiding significance for accurately formulating small incision lenticule extraction surgery plans and contribute to the advancement of research on the biomechanical properties of the cornea.

Diagnostic utility of in vivo confocal microscopy in Acanthamoeba keratitis following corneal crosslinking.

Acanthamoeba keratitis (AK) is a rare but potentially sight-threatening complication of corneal collagen crosslinking (CXL) for keratoconus. In this report, we describe an early adolescent male who underwent routine CXL for progressive keratoconus in his left eye. Preprocedural left visual acuity (VA) was 6/9. At day 5 postprocedure, multifocal corneal infiltrates were identified. Corneal scrape, bandage contact lens cultures and herpetic and Acanthamoeba PCR were negative. In vivo, confocal microscopy (IVCM) identified Acanthamoeba cysts within the corneal stroma. Intensive amoebicidal therapy was initiated, but recovery was complicated by significant inflammation, resulting in widespread aggressive corneal vascularisation necessitating topical steroids and steroid-sparing agents. At 10 months, his left VA was 6/24. This report emphasises the importance of maintaining a high index of suspicion for AK in cases of post-CXL microbial keratitis and highlights the diagnostic value of IVCM, particularly in culture-negative and PCR-negative cases.