Insulin eye drops improve corneal wound healing in STZ-induced diabetic mice by regulating corneal inflammation and neuropeptide release.

INTRODUCTION: In recent years, insulin eye drops have attracted increasing attention from researchers and ophthalmologists. The aim of this study was to investigate the efficacy and possible mechanism of action of insulin eye drops in diabetic mice with corneal wounds. METHODS: A type 1 diabetes model was induced, and a corneal epithelial injury model of 2.5 mm was established. We used corneal fluorescein staining, hematoxylin-eosin (H-E) staining and the Cochet-Bonnet esthesiometer to examine the process of wound healing. Subsequently, the expression levels of Ki-67, IL-1ß, ß3-tubulin and neuropeptides, including substance P (SP) and calcitonin gene-related peptide (CGRP), were examined at 72 h after corneal injury. RESULTS: Fluorescein staining demonstrated an acceleration of the recovery of corneal epithelial injury in diabetic mice compared with the saline treatment, which was further evidenced by the overexpression of Ki-67. Moreover, 72 h of insulin application attenuated the expression of inflammatory cytokines and neutrophil infiltration. Remarkably, the results demonstrated that topical insulin treatment enhanced the density of corneal epithelial nerves, as well as neuropeptide SP and CGRP release, in the healing cornea via immunofluorescence staining. CONCLUSIONS: Our results indicated that insulin eye drops may accelerate corneal wound healing and decrease inflammatory responses in diabetic mice by promoting nerve regeneration and increasing levels of neuropeptides SP and CGRP.

In vivo assessment of the ocular biomechanical properties in patients with idiopathic normal pressure hydrocephalus.

PURPOSE: Idiopathic normal pressure hydrocephalus (iNPH) is associated with an increased prevalence of open-angle glaucoma, attributed to variations of the pressure gradient between intraocular and intracranial compartments at the level of the lamina cribrosa (LC). As ocular biomechanics influence the behavior of the LC, and a lower corneal hysteresis (CH) has been associated to a higher risk of glaucomatous optic nerve damage, in this study we compared ocular biomechanics of iNPH patients with healthy subjects. METHODS:  Twenty-four eyes of 24 non-shunted iNPH patients were prospectively recruited. Ocular biomechanical properties were investigated using the ocular response analyzer (Reichert Instruments) for the calculation of the CH, corneal resistance factor (CRF), Goldmann-correlated intraocular pressure (IOPg), and corneal-compensated intraocular pressure (IOPcc). Results were compared with those of 25 eyes of 25 healthy subjects. RESULTS:  In iNPH eyes, the median CH value and interquartile range (IQR) were 9.7 mmHg (7.8-10) and 10.6 mmHg (9.3-11.3) in healthy controls (p = 0.015). No significant differences were found in IOPcc [18.1 mmHg (14.72-19.92) vs. 16.4 mmHg (13.05-19.6)], IOPg [15.4 mmHg (12.82-19.7) vs. 15.3 mmHg (12.55-17.35)], and CRF [9.65 mmHg (8.07-11.65) vs. 10.3 mmHg (9.3-11.5)] between iNPH patients and controls. CONCLUSIONS:  In iNPH patients, the CH was significantly lower compared to healthy subjects. This result suggests that ocular biomechanical properties may potentially contribute to the risk of development of glaucomatous optic nerve damage in iNPH patients.

Smoking, Corneal Biomechanics, and Glaucoma: Results From Two Large Population-Based Cohorts.

Purpose: Smoking may influence measured IOP through an effect on corneal biomechanics, but it is unclear whether this factor translates into an increased risk for glaucoma. This study aimed to examine the association of cigarette smoking with corneal biomechanical properties and glaucoma-related traits, and to probe potential causal effects using Mendelian randomization (MR). Methods: Cross-sectional analyses within the UK Biobank (UKB) and Canadian Longitudinal Study on Aging (CLSA) cohorts. Multivariable linear and logistic regression models were used to assess associations of smoking (status, intensity, and duration) with corneal hysteresis (CH), corneal resistance factor, IOP, inner retinal thicknesses, and glaucoma. Two-sample MR analyses were performed. Results: Overall, 68,738 UKB (mean age, 56.7 years; 54.7% women) and 22 845 CLSA (mean age, 62.7 years; 49.1% women) participants were included. Compared with nonsmokers, smokers had a higher CH (UKB, +0.48 mm Hg; CLSA, +0.57 mm Hg; P < 0.001) and corneal resistance factor (UKB, +0.47 mm Hg; CLSA, +0.60 mm Hg; P < 0.001) with evidence of a dose-response effect in both studies. Differential associations with Goldmann-correlated IOP (UKB, +0.25 mm Hg; CLSA, +0.36 mm Hg; P < 0.001) and corneal-compensated IOP (UKB, -0.28 mm Hg; CLSA, -0.32 mm Hg; P ≤ 0.001) were observed. Smoking was not associated with inner retinal thicknesses or glaucoma status in either study. MR provided evidence for a causal effect of smoking on corneal biomechanics, especially higher CH. Conclusions: Cigarette smoking seems to increase corneal biomechanical resistance to deformation, but there was little evidence to support a relationship with glaucoma. This outcome may result in an artefactual association with measured IOP and could account for discordant results with glaucoma in previous epidemiological studies.

Squishy matters - Corneal mechanobiology in health and disease.

The cornea, as a dynamic and responsive tissue, constantly interacts with mechanical forces in order to maintain its structural integrity, barrier function, transparency and refractive power. Cells within the cornea sense and respond to various mechanical forces that fundamentally regulate their morphology and fate in development, homeostasis and pathophysiology. Corneal cells also dynamically regulate their extracellular matrix (ECM) with ensuing cell-ECM crosstalk as the matrix serves as a dynamic signaling reservoir providing biophysical and biochemical cues to corneal cells. Here we provide an overview of mechanotransduction signaling pathways then delve into the recent advances in corneal mechanobiology, focusing on the interplay between mechanical forces and responses of the corneal epithelial, stromal, and endothelial cells. We also identify species-specific differences in corneal biomechanics and mechanotransduction to facilitate identification of optimal animal models to study corneal wound healing, disease, and novel therapeutic interventions. Finally, we identify key knowledge gaps and therapeutic opportunities in corneal mechanobiology that are pressing for the research community to address especially pertinent within the domains of limbal stem cell deficiency, keratoconus and Fuchs' endothelial corneal dystrophy. By furthering our understanding corneal mechanobiology, we can contextualize discoveries regarding corneal diseases as well as innovative treatments for them.

A new R,R-RvD6 isomer with protective actions following corneal nerve injury.

The transparent cornea is the most densely innervated tissue in the body, primarily by sensory nerves originating from the trigeminal ganglia (TG). Damage to corneal nerves reduces sensitivity and tear secretion and results in dry eye. Consequently, ocular pain, for which no satisfactory therapies exist, arises in many cases. Treatment of injured corneas with pigment epithelium-derived factor (PEDF) combined with docosahexaenoic acid (DHA) stimulates nerve regeneration in models of refractive surgery, which damages nerves. The mechanism involves the synthesis of a stereoisomer of resolvin D6 (R,R-RvD6) formed after incorporating DHA into membrane lipids. Activation of a PEDF receptor (PEDF-R) with phospholipase activity releases DHA to synthesize the new resolvin isomer, which is secreted via tears. Topical treatment of mice corneas with R,R-RvD6 shows higher bioactivity in regenerating nerves and increasing sensitivity compared to PEDF+DHA. It also stimulates a transcriptome in the TG that modulates genes involved in ocular pain. Our studies suggest an important therapeutic role for R,R-RvD6 in regenerating corneal nerves and decreasing pain resulting from dry eye.

Reliability of Measurements Using Ocular Response Analyzer as a Screening Tonometer and Corneal Hysteresis Values in the Presence or Absence of Glaucomatous Changes in Fundus.

PRCIS: Use of the Ocular Response Analyzer (ORA) as a screening tonometer in clinical practice yielded reliable measurements in over 80% of eyes screened. Including corneal hysteresis (CH) data in screening may improve the accuracy of glaucoma detection. PURPOSE: To examine measurement reliability when the ORA is used as a screening tonometer, and to compare CH measurements in eyes with and those without glaucomatous changes in the fundus. PATIENTS AND METHODS: 1488 eyes of 747 patients (mean age: 53.5 ± 20.4 y, range: 6-94 y) underwent intraocular pressure (IOP) measurement using ORA as screening. The percentage of eyes with a waveform score ≥6, the recommended threshold indicating reliability, was calculated. Eyes that had waveform score ≥6 and had undergone fundus photography and optical coherence tomography were assessed for the presence or absence of glaucomatous changes in fundus from optical coherence tomography and fundus images, and CH was compared between the 2 groups. RESULTS: Mean ± SD (range) of ORA measurements were: Goldmann-correlated IOP 14.9 ± 4.8 (1.0-63.2) mm Hg, corneal-compensated IOP 16.2 ± 4.7 (3.2-73.6) mm Hg, CH 9.7 ± 1.5 (0.0-20.6) mm Hg, and waveform score 7.3 ± 1.5 (0.1-9.7). Eighty-four percent of eyes had a waveform score ≥6. Among 192 eyes (127 patients, aged 53.5 ± 18.0 y) with waveform score ≥6 and evaluable for glaucomatous changes in the fundus, 53 eyes were determined as positive and 139 eyes as negative. CH was 9.6 ± 1.4 (6.8-13.3) mm Hg in the positive group and 10.2 ± 1.2 (6.9-13.3) mm Hg in the negative group, and was significantly lower in the positive group ( P =0.003). CONCLUSION: When using ORA as a screening tonometer, reliable results were obtained in ~80% of the eyes. CH was lower in the glaucomatous change-positive group compared with the glaucomatous change-negative group, but the ranges overlapped between the 2 groups.

Trigeminal Sensitization in a Closed Head Model for Mild Traumatic Brain Injury.

Mild traumatic brain injury (mTBI) is often accompanied by neurological and ocular symptoms that involve trigeminal nerve pathways. Laser-induced shock wave (LISW) was applied to the skull of male rats as a model for mTBI, while behavioral and neural recording methods were used to assess trigeminal function. The LISW caused greater eye wiping behavior to ocular instillation of hypertonic saline (Sham = 4.83 ± 0.65 wipes/5 min, LISW = 12.71 ± 1.89 wipes/5 min, p < 0.01) and a marked reduction in the time spent in bright light consistent with enhanced periocular and intraocular hypersensitivity, respectively (Sham = 16.3 ± 5.6 s, LISW = 115.5 ± 27.3 s, p < 0.01). To address the early neural mechanisms of mTBI, single trigeminal brainstem neurons, identified by activation to corneal or dural mechanical stimulation, were recorded in trigeminal subnucleus interpolaris/caudalis (Vi/Vc) and trigeminal subnucleus caudalis/upper cervical cord (Vc/C1) regions. The LISW caused marked sensitization to hypertonic saline and to exposure to bright light in neurons of both regions (p < 0.05). Laser speckle imaging revealed an increase in meningeal arterial blood flow to bright light after LISW (Sham = 4.7 ± 2.0 s, LISW = 469.0 ± 37.9 s, p < 0.001). Local inhibition of synaptic activity at Vi/Vc, but not at Vc/C1, by microinjection of CoCl2, prevented light-evoked increases in meningeal blood flow in LISW-treated rats. By contrast, topical meningeal application of phenylephrine significantly reduced light-evoked responses of Vi/Vc and Vc/C1 neurons. These data suggested that neurons in both regions became sensitized after LISW and were responsive to changes in meningeal blood flow. Neurons at the Vi/Vc transition and at Vc/C1, however, likely serve different roles in mediating the neurovascular and sensory aspects of mTBI.

Development of a Corneal and Eye Protection Strategy in Domestic Swine.

Large animal models are essential to research in facial paralysis, face transplant, craniofacial surgery, and ophthalmology. Pigs are a well-studied species with high similarity to human anatomy and physiology for these research areas. However, in contrast to cats and dogs protecting the cornea and eye is difficult in swine due to the inability to use an Elizabethan collar (E-collar) and the complexity of placing and maintaining a temporary tarsorrhaphy for corneal protection due to the strength of the pig levator muscle. This study presents an effective method to provide corneal and eye protection in the domestic swine for at least 50 d. Furthermore, protection of the eye and face is achieved through the innovative use of a modified ophthalmologic face shield. The findings from this study will advance large animal research in these fields, enabling innovation in surgery and tissue engineering in areas of both craniofacial and ophthalmologic research.

Depth-dependent mechanical properties of the human cornea by uniaxial extension.

The purpose of this study was to investigate the depth-dependent biomechanical properties of the human corneal stroma under uniaxial tensile loading. Human stroma samples were obtained after the removal of Descemet's membrane in the course of Descemet's membrane endothelial keratoplasty (DMEK) transplantation. Uniaxial tensile tests were performed at three different depths: anterior, central, and posterior on 2 × 6 × 0.15 mm strips taken from the central DMEK graft. The measured force-displacement data were used to calculate stress-strain curves and to derive the tangent modulus. The study showed that mechanical strength decreased significantly with depth. The anterior cornea appeared to be the stiffest, with a stiffness approximately 18% higher than that of the central cornea and approximately 38% higher than that of the posterior layer. Larger variations in mechanical response were observed in the posterior group, probably due to the higher degree of alignment of the collagen fibers in the posterior sections of the cornea. This study contributes to a better understanding of the biomechanical tensile properties of the cornea, which has important implications for the development of new treatment strategies for corneal diseases. Accurate quantification of tensile strength as a function of depth is critical information that is lacking in human corneal biomechanics to develop numerical models and new treatment methods.

Functional Changes of the Ocular Surface Sensory Nerves Due to Contact Lens Use in Young Symptomatic and Asymptomatic Users.

Purpose: The purpose of this study was to analyze the differences in corneal sensory nerve functionality in young asymptomatic (CL-A) and symptomatic (CL-S) contact lens (CL) users. Methods: CL wearers (23.8 ± 1.0 years, n = 31) were classified as CL-S with an Ocular Surface Disease Index (OSDI) ≥ 13 (n = 14) or CL-A. Users of eye glasses (EG; 24.5 ± 0.8 years, n = 29) with OSDI < 13 participated as controls. The sensations evoked by mechanical, chemical (gas esthesiometer), and cold (4°C saline drops) stimuli were measured using the Visual Analogue Scales (VASs). Moreover, tear volume, tear break up time (TBUT), blinking frequency (BF), and ocular surface temperature (OST; IR thermography) were also measured. Results: Mechanical and chemical stimuli produced similar scores in the CL-A and EG participants, although the CL-A subjects referred to stronger irritation (p < 0.05). Likewise, the VAS intensity in response to cold stimuli did not differ between CL-A and EG subjects, while the ability to detect cold was significantly worse in CL-S users (p < 0.05). CL-A users had a similar tear volume, a higher BF (p < 0.01) and shorter TBUT (p < 0.001) to EG wearers, and blinking and TBUT were also altered significantly in CL-S users (p < 0.01). Interestingly, the OST was significantly lower in CL-A users (p < 0.05) than in EG wearers, but not in CL-S users. Conclusions: Using CLs modifies corneal sensitivity, blinking and tearing in young volunteers. Even if they have yet to develop clinical signs of inflammation, they display changes in corneal sensitivity consistent with the sensitization of corneal nociceptors and the inhibition cold thermoreceptors, phenomena that occur under inflammatory conditions. The differences in corneal sensitivity and OST between CL-A and CL-S users could reflect the extent of nerve damage and inflammation at the ocular surface.

Prospective assessment of corneal biomechanical properties and intraocular pressure after scleral lens wear: A 12-month follow-up study.

PURPOSE: To investigate the long-term influence of scleral lens (SL) wear on corneal biomechanical properties and intraocular pressure (IOP) in irregular and regular corneas. Secondary goal comprised evaluate the fluid reservoir (FR) thickness overtime and correlate it with the changes in corneal biomechanical parameters and IOP. METHODS: Seventy (70) eyes with irregular corneas (IC Group) and 21 eyes with regular corneas (RC Group) were fitted with 16.4 mm SL and wore the lenses for 12 months. Corrected IOP (IOPcc), Goldmann equivalent IOP (IOPg) and corneal biomechanical parameters (Corneal Hysteresis (CH) and Corneal Resistance Factor (CRF)) were measured with Ocular Response Analyzer. Slit lamp images were analyzed with ImageJ software to assess FR thickness overtime. Measurements were taken at lens dispensing visit prior lens wear (LDV1) and after 60 min of lens wear (LDV2) and at 1, 6 and 12-month follow-up visits. Measurements were done immediately after lens removal. RESULTS: There were no statistically significant differences on IOPcc, IOPg, CRF and CH over the follow-up visits in both groups. Mean IOPcc and IOPg fluctuations overtime were clinically insignificant and below 1 mmHg in both groups. IOPg, CH and CRF were significantly lower on IC Group (p < 0.001), although no statistically significant differences were found between groups for IOPcc. Regarding FR thickness, statistically significant differences were found over the follow-up on both groups, with a mean decrease of 186.29 µm on IC Group and 175.32 µm on RC Group (p < 0.001). Statistically significant moderate to high negative correlations between FR and IOPg, CRF and CH were found only in the RC Group. CONCLUSIONS: Long-term SL wear was not associated to changes in corneal biomechanical parameters neither on IOP as measured after lens removal. Besides IOP measurement without SL removal, more studies are needed to investigate the potential relationship with SL fitting characteristics (namely FR thickness).

Intereye Differences in the Clinical Assessment of Intraocular Pressure and Ocular Biomechanics.

SIGNIFICANCE: Clinicians and researchers will have evidence whether intereye differences confound clinical measurements of intraocular pressure or of ocular biomechanical parameters. PURPOSE: The purpose of this study was to determine whether intraocular pressure and biomechanical parameters, as measured by the Ocular Response Analyzer (ORA) and by Cornea Visualization with Scheimpflug Technology (CorVis ST), are different between the first and second eye measured. METHODS: Intraocular pressure and biomechanical parameters were collected from both eyes of healthy participants (N = 139). The ORA measured corneal-compensated intraocular pressure, Goldmann-correlated intraocular pressure, and corneal hysteresis. The CorVis ST measured biomechanically corrected intraocular pressure, stiffness parameter at first applanation, and stiffness parameter at highest concavity. For each measurement, a paired t test compared the value of the first eye measured against that of the second eye measured. RESULTS: For the ORA, Goldmann-correlated intraocular pressure was significantly higher ( P = .001) in the first eye (14.8 [3.45] mmHg) than in the second eye (14.3 [3.63] mmHg). For the CorVis ST, biomechanically corrected intraocular pressure was significantly higher ( P < .001) in the second eye (14.7 [2.14] mmHg) than in the first eye (14.3 [2.11] mmHg). Stiffness parameter at first applanation (intereye difference, 6.85 [9.54] mmHg/mm) was significantly ( P < .001) higher in the first eye than in the second eye. Stiffness parameter at highest concavity was significantly higher ( P = .01) in the second eye (14.3 [3.18] mmHg/mm) than in the first eye (14.0 [3.13] mmHg/mm). CONCLUSIONS: Although there were statistically significant intereye differences in intraocular pressure and in biomechanical parameters for both devices, the variations were small and thus unlikely to affect clinical outcomes.

Corneal biomechanics after small incision lenticule extraction and femtosecond laser in situ keratomileusis: A systematic review and meta-analysis.

BACKGROUND: Small incision lenticule extraction (SMILE) and femtosecond laser in situ keratomileusis (FS-LASIK) have been extensively studied as the main surgical methods for corneal refractive surgery. However, there is no consensus on whether SMILE is superior to FS-LASIK in corneal biomechanics. Therefore, this systematic review and meta-analysis used the results of ocular response analyzer and corvis ST to explore whether SMILE is superior to FS-LASIK in corneal biomechanics. METHODS: The literature was searched in PubMed, EMBASE, and Controlled Trials Register databases. The Cochrane Collaboration's "risk of bias" tool was used to evaluate the quality of the included randomized clinical trials, and the Newcastle-Ottawa Scale was used to evaluate the included non-randomized controlled trials. The results were analyzed using Revman 5.3. RESULTS: Sixteen studies (3 randomized clinical trials and 13 non-randomized controlled trials) were included in this meta-analysis. There was no statistical difference in corneal biomechanics between SMILE and FS-LASIK in corneal hysteresis [mean difference (MD), 0.20; 95% confidence interval (CI): -0.09, 0.49; P = .18] and corneal resistant factor (MD, 0.31; 95% CI: -0.09, 0.71; P = .13), A1 time (MD, -0.02; 95% CI: -0.11, 0.07; P = .66), A1 length (MD, 0.01; 95% CI: -0.01, 0.03; P = .42), A1 velocity (MD, 0.00; 95% CI: -0.01, 0.01; P = .85), A2 velocity (MD, -0.01; 95% CI: -0.11, 0.09; P = .86), HC time (MD, 0.12; 95% CI: -0.13, 0.38; P = .35), The stiffness parameter at first applanation (MD, -7.91; 95% CI: -17.96, 2.14; P = .12), The ratio between the deformation amplitude 2 mm away from apex and the apical deformation (MD, 0.01; 95% CI: -0.26, 0.27; P = .96). CONCLUSION: A comprehensive assessment of the parameters of ocular response analyzer and corvis ST showed that SMILE is not superior to LASIK in corneal biomechanics 3 months post-surgery.

The Changes in Ocular Biomechanical Response Parameters and Intraocular Pressure After Surgical Treatment for Thyroid Eye Disease.

Purpose: To investigate changes in ocular biomechanical response parameters and intraocular pressure (IOP) in patients with thyroid eye disease (TED) undergoing orbital decompression or anterior blepharotomy. Methods: Eighty-three eyes from 46 patients receiving orbital decompression (the orbital decompression group) and 45 eyes from 28 patients receiving anterior blepharotomy (the anterior blepharotomy group) were retrospectively enrolled from a tertiary center. Corvis ST tonometry was used to assess ocular biomechanical response and biomechanically corrected IOP (bIOP) pre- and postoperatively. Non-contact tonometry (IOP-NCT) was also performed. Results: In the anterior blepharotomy group, the margin reflex distance decreased (P < 0001). The highest concavity radius (P = 0.026) and whole eye movement (P = 0.003) increased. Neither IOP-NCT nor bIOP had a significant change. In the orbital decompression group, the extent of exophthalmos decreased (P < 0.001). The A2 length (P = 0.009) decreased. The bIOP did not show a significant change (16.4 ± 2.7 vs. 16.7 ± 4.5; P = 0.415), but the IOP-NCT decreased significantly (17.5 ± 3.3 vs. 16.0 ± 3.3; P < 0.001). Higher baseline IOP-NCT (ß = -0.40, P < 0.001) and greater reduction in stiffness parameter A1 (SP-A1; ß = 0.05, P = 0.002) were associated with more significant IOP-NCT reduction after the orbital decompression. Conclusions: Ocular biomechanical response parameters may change after TED surgery, potentially affecting IOP measurements, particularly in patients receiving orbital decompression.

Interobserver agreement between central topography and Scheimpflug tomography for premium intraocular lens selection.

PURPOSE: To assess the inter-observer agreement and reliability of central topography (CT) of IOL Master 700 with that of Pentacam HR, as a screening tool for determining the suitability for premium (toric, monofocal and presbyopia correcting) intraocular lens (IOL) implants. SETTING: Nethradhama Superspeciality Eye Hospital, Bangalore, India. METHOD: 200 eyes of eligible patients undergoing unilateral or bilateral phacoemulsification with premium IOL's were included in the study. Preoperatively, IOL Master 700 CT and Pentacam scans were performed for corneal topography evaluation. 2 experienced clinicians were randomised to interpret the axial map of either of the scans at a time and their responses were then enclosed in an envelope, and forwarded to a third observer for analysis. If there was a conflict, final decision was based on the interpretation of the Pentacam scan. RESULTS: Of the total scans interpreted by the 2 observers, 77.5% (n = 155) showed agreement whereas 22.5% (n = 45) showed disagreement. The sensitivity, specificity, positive predictive value and negative predictive value (NPV) of IOL Master 700 CT in diagnosing irregular corneas when compared with Pentacam HR, was 72.73%, 78.09%, 29.09% and 95.86% respectively. The Cohen's κ inter-observer agreement value was 0.44, signifying a moderate degree of agreement, which was statistically significant (P < .00). CONCLUSIONS: High NPV of IOL Master CT suggested that the device efficiently ruled out irregular corneas, while any suspicious scan should be confirmed with Pentacam HR or a similar device for appropriate decision-making regarding premium IOL selection. TRIAL REGISTRATION NUMBER: CTRI/2021/11/038053.

Corneal regeneration strategies: From stem cell therapy to tissue engineered stem cell scaffolds.

Corneal epithelial defects and excessive wound healing might lead to severe complications. As stem cells can self-renew infinitely, they are a promising solution for regenerating the corneal epithelium and treating severe corneal epithelial injury. The chemical and biophysical properties of biological scaffolds, such as the amniotic membrane, fibrin, and hydrogels, can provide the necessary signals for stem cell proliferation and differentiation. Multiple researchers have conducted investigations on these scaffolds and evaluated them as potential therapeutic interventions for corneal disorders. These studies have identified various inherent benefits and drawbacks associated with these scaffolds. In this study, we provided a comprehensive overview of the history and use of various stem cells in corneal repair. We mainly discussed biological scaffolds that are used in stem cell transplantation and innovative materials that are under investigation.

Human cornea thermo-viscoelastic behavior modelling using standard linear solid model.

BACKGROUND: Corneal biomechanics is of great interest to researchers recently. Clinical findings relate them to corneal diseases and to outcomes of refractive surgery. To have a solid understanding of corneal diseases' progression, it is important to understand corneal biomechanics. Also, they are essential for better explaining outcomes of refractive surgeries and their undesired consequences. There is a difficulty for studying corneal biomechanics in-vivo and multiple limitations arise for ex-vivo studies. Hence mathematical modelling is considered as a proper solution to overcome such obstacles. Mathematical modelling of cornea in-vivo allows studying corneal viscoelasticity with taking into consideration all boundary conditions existing in real in-vivo situation. METHODS: Three mathematical models are used to simulate corneal viscoelasticity and thermal behavior in two different loading situations: constant and transient loading. Two models of the three are used for viscoelasticity simulation which are Kelvin-Voigt and standard linear solid models. Also, temperature rise due to the ultrasound pressure push is calculated using bioheat transfer model for both the axial direction and as a 2D spatial map using the third model (standard linear solid model). RESULTS: Viscoelasticity simulation results show that standard linear solid model is efficient for describing the viscoelastic behavior of human cornea in both loading conditions. Results show also that the deformation amplitude obtained from standard linear solid model is more reasonable for corneal soft-tissue deformation with respect to corresponding clinical findings than that obtained from Kelvin-Voigt model. Thermal behavior results estimated corneal temperature rise to be roughly 0.2 °C, which conforms with FDA regulations for soft tissue safety. CONCLUSION: Standard Linear Solid (SLS) model is better describing the human corneal behavior in response to constant and transient load more efficiently. Temperature rise (TR) for the corneal tissue of about 0.2 °C is conforming with FDA regulations and even less than the FDA regulations for soft tissue safety.

The Cornea: No Difference in the Wound Healing Response to Injury Related to Whether, or Not, There's a Bowman's Layer.

Bowman's layer is an acellular layer in the anterior stroma found in the corneas of humans, most other primates, chickens, and some other species. Many other species, however, including the rabbit, dog, wolf, cat, tiger, and lion, do not have a Bowman's layer. Millions of humans who have had photorefractive keratectomy over the past thirty plus years have had Bowman's layer removed by excimer laser ablation over their central cornea without apparent sequelae. A prior study showed that Bowman's layer does not contribute significantly to mechanical stability within the cornea. Bowman's layer does not have a barrier function, as many cytokines and growth factors, as well as other molecules, such as EBM component perlecan, pass bidirectionally through Bowman's layer in normal corneal functions, and during the response to epithelial scrape injury. We hypothesized that Bowman's layer represents a visible indicator of ongoing cytokine and growth factor-mediated interactions that occur between corneal epithelial cells (and corneal endothelial cells) and stromal keratocytes that maintain the normal corneal tissue organization via negative chemotactic and apoptotic effects of modulators produced by the epithelium on stromal keratocytes. Interleukin-1 alpha, produced constitutively by corneal epithelial cells and endothelial cells, is thought to be one of these cytokines. Bowman's layer is destroyed in corneas with advanced Fuchs' dystrophy or pseudophakic bullous keratopathy when the epithelium becomes edematous and dysfunctional, and fibrovascular tissue commonly develops beneath and/or within the epithelium in these corneas. Bowman's-like layers have been noted to develop surrounding epithelial plugs within the stromal incisions years after radial keratotomy. Although there are species-related differences in corneal wound healing, and even between strains within a species, these differences are not related to the presence or absence of Bowman's layer.

Analysis of potential impact factors of corneal biomechanics in myopia.

PURPOSE: To investigate potential impact factors associated with corneal biomechanical properties in Chinese myopia and further to investigate quantifying corneal biomechanics in clinical work. METHODS: Three hundred fifty-five eyes from 181 healthy myopic subjects with a mean age of 25.1 ± 9.4 were recruited in this study. Each patient carried out a comprehensive ophthalmic examination, including corneal hysteresis(CH), corneal resistance factor(CRF), central corneal thickness(CCT), axial length(AL), intraocular pressure(IOP), spherical equivalence(SE) and corneal curvature (K). CH and CRF were measured with the ocular response analyzer(ORA). To analyze the corneal biomechanical characteristics of myopia patients and their association with other parameters. RESULT: The multiple linear regression analysis showed that CH was positively associated with CCT, and corneal curvature (all with P < 0.05) and negatively associated with SE and AL)(all with P < 0.05); CRF was positively correlated with CCT, corneal curvature and IOP(all with P < 0.05), but negatively correlated with SE and AL(all with P < 0.05). The CH and CRF values in children group were both higher than adults group (≥ 18 years old) (P < 0.05), but it attributed to that the CCT of children was thicker than adults. Excluding factor of CCT, there was no significant difference in CH and CRF between children group and adult group. Excluding factor of CCT, there was no significant difference in CH and CRF among different stage of age (age 18-48). CONCLUSION: The CCT played the most important role of affecting the CH and CRF. The SE, corneal curvature, AL and IOP had a certain influence on corneal biomechanics. Whether the CH and CRF values of individual patient are normal in clinical work, it should refer to the CH and CRF values corresponding CCT sectional range and SE.

On the Mechanical Roles of Glycosaminoglycans in the Tensile Properties of Porcine Corneal Stroma.

Purpose: The cornea is primarily composed of collagen fibrils that are embedded in a ground substance rich in proteoglycans and other glycoproteins. It is known that glycosaminoglycan (GAG) side chains of proteoglycans form anti-parallel duplexes between collagen fibrils. The present work was done in order to investigate the mechanical function of GAGs in defining the tensile properties of porcine corneal stroma. Methods: Porcine corneal stromal strips dissected from the nasal-temporal direction were divided into control, buffer-treated, and enzyme-treated groups. The samples in the control group were used immediately after dissection. However, the buffer-treated and enzyme-treated samples were, respectively, incubated for 18 hours at 37°C in a buffer solution made up of 100-mM sodium acetate at pH 6.0 or in an enzyme solution containing keratanase II. The Blyscan assay was used to quantify the total GAG content and assess GAG depletion in the samples treated with the enzyme and buffer solutions. Uniaxial tensile tests were also performed to determine the effect of GAG removal on mechanical properties of the cornea. Results: The GAG content in enzyme-treated samples was significantly lower than that of the normal and buffer-treated specimens (P < 0.05). Moreover, GAG-depleted strips showed significantly softer mechanical responses in comparison with the control and buffer samples (P < 0.05). Conclusions: Removing GAGs from the corneal extracellular matrix led to significant tensile property reduction; supporting the hypothesis that there exists a strong correlation between the GAG content and mechanical properties of the corneal stroma.