Corneal Response Research Articles

Intraocular Pressure-dependent Corneal Elasticity Measurement Using High-frequency Ultrasound.

Measurement of corneal biomechanical properties can aid in predicting corneal responses to diseases and surgeries. For delineation of spatially resolved distribution of corneal elasticity, high-resolution elastography system is required. In this study, we demonstrate a high-resolution elastography system using high-frequency ultrasound for ex-vivo measurement of intraocular pressure (IOP)-dependent corneal wave speed. Tone bursts of 500 Hz vibrations were generated on the corneal surface using an electromagnetic shaker. A 35-MHz single-element transducer was used to track the resulting anti-symmetrical Lamb wave in the cornea. We acquired spatially resolved wave speed images of the cornea at IOPs of 7, 11, 15, 18, 22, and 29 mmHg. The IOP dependence of corneal wave speed is apparent from these images. Statistical analysis of measured wave speed as a function of IOP revealed a linear relation between wave speed and IOP cs = 0.37 + 0.22 × IOP, with the coefficient of determination R2 = 0.86. We also observed depth-dependent variations of wave speed in the cornea, decreasing from anterior toward posterior. This depth dependence is more pronounced at higher IOP values. This study demonstrates the potential of high-frequency ultrasound elastography in the characterization of spatially resolved corneal biomechanical properties.

Two-year changes in corneal stiffness parameters after accelerated corneal cross-linking

The objective of this non-randomized trial was comparison of two-year changes in dynamic corneal response (DCR) between 18 mW/cm2 (5- min) and 9 mW/cm2 (10-min) cross-linking (CXL) protocols, using novel stiffness parameters and correlating them to clinical indices. The two groups were evaluated before and 2 years after the procedure using Corvis ST (Oculus Optikgeräte GmbH, Germany) and DCR parameters such as deformation amplitude ratio at 1 mm and 2 mm (DA ratio-1 mm and DA ratio-2 mm) and integrated radius and stiffness parameters at A1 (SP-A1). Two-year follow-up was completed for 16 of the 30 eyes in the 5-min group and 21 of the 25 eyes in the 10-min group; data from those who were lost to follow-up was not included in the analyses. Mean age at baseline was 21.7 ± 4.9 and 21.5 ± 5.2 years in the 5- and 10-min groups, respectively (P = 0.895). At 2 years after CXL, in the 5-min group, the reduction in integrated radius (−1.12 ± 1.27 mm, P = 0.003) was significant, and the increase in SP-A1 (7.11 ± 14.86 mmHg/mm, P = 0.075) was borderline, while in the 10-min group, the decrease in DA ratio-2 mm (−0.43 ± 0.58, P = 0.003) and integrated radius (−1.89 ± 1.72 mm, P < 0.001), and increase in SP-A1 (7.67 ± 10.92 mmHg/mm, P = 0.004) were significant. In both groups, the strongest and significant correlation was observed between DCR parameters and changes in radius of curvature. In conclusion, results indicated corneal strengthening with both protocols especially with the 9 mW/cm2. Corvis ST indices can provide “in vivo” biomechanical evidence on the efficacy of CXL that may occur prior to clinical indices.

Determination of Corneal Biomechanical Behavior in-vivo for Healthy Eyes Using CorVis ST Tonometry: Stress-Strain Index.

Purpose: This study aims to introduce and clinically validate a new algorithm that can determine the biomechanical properties of the human cornea in vivo.Methods: A parametric study was conducted involving representative finite element models of human ocular globes with wide ranges of geometries and material biomechanical behavior. The models were subjected to different levels of intraocular pressure (IOP) and the action of external air puff produced by a non-contact tonometer. Predictions of dynamic corneal response under air pressure were analyzed to develop an algorithm that can predict the cornea's material behavior. The algorithm was assessed using clinical data obtained from 480 healthy participants where its predictions of material behavior were tested against variations in central corneal thickness (CCT), IOP and age, and compared against those obtained in earlier studies on ex-vivo human ocular tissue.Results: The algorithm produced a material stiffness parameter (Stress-Strain Index or SSI) that showed no significant correlation with both CCT (p > 0.05) and IOP (p > 0.05), but was significantly correlated with age (p < 0.01). The stiffness estimates and their variation with age were also significantly correlated (p < 0.01) with stiffness estimates obtained earlier in studies on ex-vivo human tissue.Conclusions: The study introduced and validated a new method for estimating the in vivo biomechanical behavior of healthy corneal tissue. The method can aid optimization of procedures that interfere mechanically with the cornea such as refractive surgeries and introduction of corneal implants.

Corneal deformation amplitude analysis for keratoconus detection through compensation for intraocular pressure and integration with horizontal thickness profile

BackgroundThe Corvis ST provides measurements of intraocular pressure (IOP) and a biomechanically-corrected IOP (bIOP). IOP influences corneal deflection amplitude (DA), which may affect the diagnosis of keratoconus. Compensating for IOP in DA values may improve the detection of keratoconus. Methods195 healthy eyes and 136 eyes with keratoconus were included for developing different approaches to distinguish normal and keratoconic corneas using attribute selection and discriminant function. The IOP compensation is proposed by dividing the DA by the IOP values. The first approaches include DA compensated for either IOP or bIOP and other parameters from the deformation corneal response (DCR). Another approach integrated the horizontal corneal thickness profile (HCTP). The best classifiers developed were applied in a validation database of 156 healthy eyes and 87 eyes with keratoconus. Results were compared with the current Corvis Biomechanical Index (CBI). ResultsThe best biomechanical approach used the DA values compensated by IOP (Approach 2) using a linear discriminant function and reached AUC 0.954, with a sensitivity of 88.2% and a specificity of 97.4%. When thickness horizontal profile data was integrated (Approach 4), the best function was the diagquadratic, resulting in an AUC of 0.960, with a sensitivity of 89.7% and a specificity of 96.4%. There was no significant difference in the results between approaches 2 and 4 with the CBI in the training and validation databases. ConclusionsBy compensating for the IOP, and with the horizontal thickness profile included or excluded, it was possible to generate a classifier based only on biomechanical information with a similar result to the CBI.

Rapamycin liposome gutta inhibiting fungal keratitis of rats.

To study the therapeutic effect of rapamycin liposome eyedrops on fungal keratitis (FK) and its effect on the expression of monocyte chemotactic protein-1 (MCP-1). This study adopted the thin film dispersion method to prepare rapamycin liposomes eyedrops, as well as used the orthogonal design to analyze and study main influencing factors that affected the quality of liposomes. Totally 96 healthy Wistar rats were randomly divided into four groups: normal control group (A), FK blank control group (B), FK blank liposomes control group (C), and 30 FK rapamycin liposome treatment group (D). Groups B, C, and D were first prepared as FK animal models. The corneal response was recorded in details on day 1, 3, 5, 7, and 14 after modeling. Six rats were obtained and immunohistochemistry and semi-quantitative reverse transcription polymerase chain reaction (RT-PCR) were used to detect the expression of MCP-1 protein and mRNA, respectively. The severity of corneal lesions in the rapamycin treatment group was reduced, and the clinical score of the slit lamp examination was lower than that of Groups B and C (P<0.01). The expression of MCP-1 in rapamycin treatment group was significantly inhibited, comparing to that of groups B and C (P<0.01). Liposome is a good drug carrier for rapamycin. Rapamycin has a good therapeutic effect on FK. It can reduce FK fungal burden and significantly inhibit the expression of MCP-1 protein and mRNA.

Corneal biomechanics and biomechanically corrected intraocular pressure in primary open-angle glaucoma, ocular hypertension and controls

AimsTo compare the biomechanically corrected intraocular pressure (IOP) estimate (bIOP) provided by the Corvis-ST with Goldmann applanation tonometry (GAT-IOP) in patients with high-tension and normal-tension primary open-angle glaucoma (POAG; HTG...

Assessment of the Association Between In Vivo Corneal Biomechanical Changes After Corneal Cross-linking and Depth of Demarcation Line.

To test for an association between stiffening following corneal cross-linking (CXL) and demarcation line depth. Sixty-six eyes of 66 patients treated with CXL for progressive keratoconus were included. Dynamic corneal response parameters (DCRs) were measured with the Corvis ST (Oculus Optikgeräte GmbH; Wetzlar, Germany) on the day of CXL and after 1 month. Demarcation line was measured 4 weeks after CXL. A multivariate general linear model was used to test for an association between the change in DCRs and the ratio between demarcation line depth and the postoperative pachymetry. The authors found no significant associations between the change in inverse concave integrated radius (1/R) and the demarcation line ratio (P = .46), age (P = .33), sex (P = .11), preoperative maximum keratometry (P = .10), and laterality (P = .82). Similarly, there was no significant correlation between the change in 1/R and the demarcation line ratio (R2 = .002 and P = .75). However, there was a significant association between the preoperative values of 1/R and the respective change in 1/R (P < .0001). The change in 1/R was inversely proportional to the patient's preoperative 1/R; stiffer corneas (lower values of 1/R) were less affected than less stiff corneas (R2 = .23, P < .0001). CXL is associated with changes in DCRs, suggesting a change in corneal biomechanics following CXL. These changes do not appear to be associated with the demarcation line depth. [J Refract Surg. 2019;35(3):202-206.].

ROLE OF VITAMIN D IN ENDOTHELIAL CELL OF RETINA

Vitamin D deficiency is a common health problem worldwide. Many parts of the human eye, including the epithelium of the cornea, lens, ciliary body, and retinal pigment epithelium, as well as the corneal endothelium, ganglion cell layer, and retinal photoreceptors, contain vitamin D receptor. Physiological effects of vitamin D From an ocular point of view, the role in macular and retinal health had been advanced, as well as the involvement in corneal inflammatory response, wound healing, and dry eye disease. The most important effect of vitamin D is on, phosphorus, calcium metabolism and on bone mineralization. Recently, it was observed that vitamin D deficiency and insufficiency are related with common cancers, cardiovascular diseases, metabolic syndromes, infectious, and many chronic diseases including autoimmune disease. Benefits of vitamin D may be amplified through synergistic interaction with topical corticosteroids which accelerates improvement in corneal shape and optics, substantially benefiting the control of ocular surface disease and dry eye symptoms. Aqueous humour is the primary source responsible for the feeding of corneal endothelial layer hence endothelial abnormalities can be expected due to accumulated inflammatory cytokines and multiple toxic products in the aqueous humour of the patients with vitamin D deficiency.&#x0D; MATERIAL AND METHODS: Subjects were selected with vitamin D deficiency in the age group of 20–55 years. 50 patients having serum vitamin D levels &lt;15 ng/ml were included in the study. Serum vitamin D levels of &lt;15 ng/ml were included in the control group. Vitamin D levels in tear fluid were measured by direct competitive chemiluminescent enzyme linked immunoassay. A complete ophthalmic evaluation was performed in all participants which includes assessment of visual acuity, anterior segment evaluation and posterior segment evaluation. Specular microscopy was performed on the eyes of the patients with vitamin D deficiency and healthy control group individuals. Corneal endothelial cell density (CD) and central corneal thickness (CCT) values were calculated automatically using the software of the specular microscope. &#x0D; RESULTS: The study group included 23 male and 27 female subjects while study group included 24 male and 26 female. Mean age of male in study group was 46.4 ± 12.56 and female was 45.6 ± 11.77. In control group mean male age was 48.5 ± 9.25 and female age was 49.56 ± 12.55. In study group Mean Corneal endothelial cell density (CD) was observed as 2632.89 ± 189.25 cells/mm 2 and Mean central corneal thickness (CCT) was 587.2 ± 25.89 μ. In control group Mean Corneal endothelial cell density (CD) was observed as 2954.97 ± 116.89 cells/mm 2 and Mean central corneal thickness (CCT) was 546.0 ± 36.22 μ. Vitamin D levels of Tears in study group was 8.4 ± 1.7 ng/ml and in control group it was 16.2 ± 2.3 ng/ml.&#x0D; CONCLUSION: It has been observed that there is statistically significant difference in the corneal endothelial cell density (CD) and central corneal thickness (CCT) in patients with vitamin D deficiency. It was observed that Vitamin D is present in tear fluid and there is significant difference in the levels of vitamin D in study and control group.

Measurement of Corneal Biomechanical Properties in Diabetes Mellitus Using the Ocular Response Analyzer and the Corvis ST.

Hyperglycemia in diabetes mellitus (DM) might induce changes in corneal biomechanics. Therefore, biomechanical properties of the cornea were measured using the ocular response analyzer and the Corvis ST. In the study, 35 eyes of 35 diabetic patients were included. After an ophthalmological examination, measurements with the ocular response analyzer and the Corvis ST were taken. Additionally, biometry and corneal topography were performed and HbA1c values were collected. Results were compared to an age-, pachymetry- and intraocular pressure-matched group of 35 healthy subjects. Mean age (67.6 ± 10.3; 64.1 ± 8.3 years), intraocular pressure (13.4 ± 2.9; 12.8 ± 2.8 mm Hg), and central corneal thickness (556.4 ± 31.7; 548.6 ± 32.9 μm) were not significantly different between the groups (P > 0.05). In DM, the corneal hysteresis (CH) and the corneal resistance factor (CRF) were increased (CH: 10.8 ± 2 vs. 9.4 ± 1.6, P = 0.002; CRF: 10.6 ± 2.1 vs. 9.6 ± 1.5, P = 0.022). Also, most dynamic corneal response parameters showed significant differences. Beside others, A1 and A2 deflection amplitudes were increased (P < 0.001) and highest concavity and A2 time were extended (P < 0.001 and 0.007) in DM. According to current HbA1c value, DM was classified as controlled (≤7%) and poorly controlled (>7%) and significant biomechanical differences were measured between both groups. In DM, significant changes in corneal biomechanical properties were detectable. In patients, CH and CRF were increased and most dynamic corneal response parameters were different compared to healthy subjects.

Biomechanical Impact of the Sclera on Corneal Deformation Response to an Air-Puff: A Finite-Element Study.

Aim or Purpose: To describe the effect of varying scleral stiffness on the biomechanical deformation response of the cornea under air-puff loading via a finite-element (FE) model.Methods: A two-dimensional axisymmetric stationary FE model of the whole human eye was used to examine the effects varying scleral stiffness and intraocular pressure (IOP) on the maximum apical displacement of the cornea. The model was comprised of the cornea, sclera, vitreous, and surrounding air region. The velocity and pressure profiles of an air-puff from a dynamic Scheimpflug analyzer were replicated in the FE model, and the resultant profile was applied to deform the cornea in a multiphysics study (where the air-puff was first simulated before being applied to the corneal surface). IOP was simulated as a uniform pressure on the globe interior. The simulation results were compared to data from ex vivo scleral stiffening experiments with human donor globes.Results: The FE model predicted decreased maximum apical displacement with increased IOP and increased ratio of scleral-to-corneal Young's moduli. These predictions were in good agreement (within one standard deviation) with findings from ex vivo scleral stiffening experiments using human donor eyes. These findings demonstrate the importance of scleral material properties on the biomechanical deformation response of the cornea in air-puff induced deformation.Conclusion: The results of an air-puff induced deformation are often considered to be solely due to IOP and corneal properties. The current study showed that the stiffer the sclera, the greater will be the limitation on corneal deformation, separately from IOP. This may have important clinical implications to interpreting the response of the cornea under air-puff loading in pathologic conditions.

Biomechanical changes in the cornea following cataract surgery: A prospective assessment with the Corneal Visualisation Scheimpflug Technology.

Intraocular pressure (IOP) is often reduced following cataract surgery. Postoperative changes in corneal stiffness are likely to be at least partly responsible for any reduction in IOP measured with applanation tonometry. To determine the effect of cataract surgery and corneal incision size on corneal biomechanics. Prospective randomized trial. One hundred prospectively enrolled patients qualifying for cataract surgery. Participants were randomized to clear corneal incisions with a 2.20 or 2.85 mm keratome. Corneal Visualisation Scheimpflug Technology (Corvis-ST) tonometry and dynamic corneal response measurements were obtained preoperatively, and 3 mo postoperatively. Multiple regression analysis was completed using R software. Corvis-ST biomechanical parameters. Ninety-three eyes of 93 patients were included in the final analysis. Mean Corvis-ST biomechanically corrected IOP decreased by 3.63 mmHg postoperatively (95% confidence interval = 2.97-4.35, P ≤ 0.01), and central pachymetry increased by 6.96 μm (4.33-9.59, P ≤ 0.01). Independent of IOP and pachymetry changes, mean (±SE) corneal first applanation stiffness parameter reduced by 9.761 ± 3.729 (P = 0.01) postoperatively. First applanation velocity increased by 0.007 ± 0.002 ms, second applanation velocity increased by 0.012 ± 0.004 ms (P ≤ 0.01), the first applanation deformation amplitude increased by 0.008 ± 0.002 mm (P ≤ 0.01) and the deflection amplitude at highest concavity increased by 0.030 ± 0.069 (P ≤ 0.01). There were no significant differences between different incision size groups. Corneal stiffness is reduced 3 mo following cataract surgery and is associated with falsely low IOP measurements. This finding may be important for glaucoma patients and in particular when assessing the effectivity of minimally invasive glaucoma surgery devices.

Development of a microwave stunning system for cattle 2: Preliminary observations on behavioural responses and EEG

DTS: Diathermic Syncope® (DTS) is a novel system for rendering animals insensible prior to slaughter, utilizing microwave energy to induce a rise in temperature in the brain to a point at which the animal is expected to lose consciousness. During development and optimisation of the system, two trials were carried out utilizing non-anaesthetized adult cattle, to gather data on behavioural outcomes and EEG changes following energy application. In trial1, ten cattle received DTS treatments (high energy >290 kJ, n = 3; low energy <200 kJ, n = 4; and intermediate 200 < 290 kJ, n = 3), and seven received captive bolt stunning, prior to exsanguination. In trial 2, following improvements to the efficiency of energy delivery, 20 cattle received DTS (200–360 kJ). Post treatment EEG was characterized by seizure-like activity and reductions in 95% spectral edge and median frequencies; with EEG suppression persisting for at least 80 s up to over 4 min post treatment application. Animals showed: Loss of posture, Loss of corneal responses; Loss of withdrawal response (pinprick); Eye staring, not following movement. The animals remained unresponsive to stimuli for up to 4 min post DTS, and behavioural expression of distress was not observed. Seventeen of the 30 animals showed indications of returning reflex responses after 100 s post treatment, suggesting that animals receiving lower energy applications may recover from the stun.

A novel role for CRIM1 in the corneal response to UV and pterygium development

Pterygium is a pathological proliferative condition of the ocular surface, characterised by formation of a highly vascularised, fibrous tissue arising from the limbus that invades the central cornea leading to visual disturbance and, if untreated, blindness. Whilst chronic ultraviolet (UV) light exposure plays a major role in its pathogenesis, higher susceptibility to pterygium is observed in some families, suggesting a genetic component.In this study, a Northern Irish family affected by pterygium but reporting little direct exposure to UV was identified carrying a missense variant in CRIM1 NM_016441.2: c.1235 A > C (H412P) through whole-exome sequencing and subsequent analysis. CRIM1 is expressed in the developing eye, adult cornea and conjunctiva, having a role in cell differentiation and migration but also in angiogenesis, all processes involved in pterygium formation. We demonstrate elevated CRIM1 expression in pterygium tissue from additional individual Northern Irish patients compared to unaffected conjunctival controls.UV irradiation of HCE-S cells resulted in an increase in ERK phosphorylation and CRIM1 expression, the latter further elevated by the addition of the MEK1/2 inhibitor, U0126. Conversely, siRNA knockdown of CRIM1 led to decreased UV-induced ERK phosphorylation and increased BCL2 expression.Transient expression of the mutant H412P CRIM1 in corneal epithelial HCE-S cells showed that, unlike wild-type CRIM1, it was unable to reduce the cell proliferation, increased ERK phosphorylation and apoptosis induced through a decrease of BCL2 expression levels.We propose here a series of intracellular events where CRIM1 regulation of the ERK pathway prevents UV-induced cell proliferation and may play an important role in the in the pathogenesis of pterygium.

Assessment of the influence of viscoelasticity of cornea in animal ex vivo model using air-puff optical coherence tomography and corneal hysteresis.

Application of the air‐puff swept source optical coherence tomography (SS‐OCT) instrument to determine the influence of viscoelasticity on the relation between overall the air‐puff force and corneal apex displacement of porcine corneas ex vivo is demonstrated. Simultaneous recording of time‐evolution of the tissue displacement and air pulse stimulus allows obtaining valuable information related in part to the mechanical properties of the cornea. A novel approach based on quantitative analysis of the corneal hysteresis of OCT data is presented. The corneal response to the air pulse is assessed for different well‐controlled intraocular pressure (IOP) levels and for the progression of cross‐linking‐induced stiffness of the cornea. Micrometer resolution, fast acquisition and noncontact character of the air‐puff SS‐OCT measurements have potential to improve the in vivo assessment of mechanical properties of the human corneas.

Immune Response and Mechanisms of IFN-γ in Administration for Keratomycosis

ABSTRACTPurpose: To investigate the immune response and mechanisms of interferon-γ (IFN-γ) in the fungal keratitis in mice.Methods: Mice were divided into two groups: group A, topical PBS four times daily post-infection; group B: topical IFN-γ four times daily post-infection. At1, 3, 5, and 7 days, the corneal lesions and inflammatory responses were observed by slit lamp, and immunofluorescence staining was performed to evaluate F4/80+ and CD4+ cells. Using ELISA, and RT–PCR to detect the expression levels of macrophage migration inhibitory factor (MIF), macrophage inflammatory protein-2 (MIP-2), IL-4, IL-10, IL-12, and IFN-γ.Results: The treatment with IFN-γ decreased clinical scores and expression levels of IL-4, increased expression of F4/80+ and CD4+ cells, whereas IL-12, MIF, and MIP-2 were expressed highly, and the peaks of IL-10 and IFN-γ move forward.Conclusion: This experiment showed that IFN-γ eye drops increase the accumulation of macrophages and shorten the duration of fungal keratitis.

The long-term effect of tacrolimus on alkali burn-induced corneal neovascularization and inflammation surpasses that of anti-vascular endothelial growth factor.

PurposeTo investigate the effect of tacrolimus in alkali burn-induced corneal neovascularization (NV) and inflammation and to compare with anti-vascular endothelial growth factor (anti-VEGF).MethodsAfter corneal alkali-burn, 84 Wistar rats were randomly divided into three groups and received either saline solution or 0.05% tacrolimus (0.5 mg/mL) four times daily, or subconjunctival anti-VEGF injection (0.5 mg/0.05 mL). Corneal NV, opacity and epithelial defects, the status of inflammation, and the levels of proinflammatory and angiogenic cytokines were assessed on Days 3, 7, 14 and 28 post-injury.ResultsCompared with the control, tacrolimus significantly reduced corneal NV on Days 7, 14 and 28 post-injury, and anti-VEGF significantly reduced corneal NV at each assessment. Nevertheless, the tacrolimus group had significantly less corneal NV than the anti-VEGF group on Days 14 and 28. Furthermore, both tacrolimus and anti-VEGF significantly decreased the VEGF-A expression on Days 7 and 14, with no significant difference between the two groups. Moreover, corneal inflammatory response was alleviated, and corneal opacity and epithelial defects were significantly reduced by tacrolimus. Additionally, the expression of IL-1β, IL-6, monocyte chemotactic protein-1, macrophage inflammatory protein-1α and TGF-β were significantly decreased by tacrolimus.ConclusionOur findings suggested that 0.05% tacrolimus suspension eye drops effectively reduced alkali burn-induced corneal NV and inflammation, with a better effect than subconjunctival anti-VEGF injections on Days 14 and 28.

Safety and Feasibility of Intrastromal Injection of Cultivated Human Corneal Stromal Keratocytes as Cell-Based Therapy for Corneal Opacities.

To evaluate the safety and feasibility of intrastromal injection of human corneal stromal keratocytes (CSKs) and its therapeutic effect on a rodent early corneal opacity model. Twelve research-grade donor corneas were used in primary culture to generate quiescent CSKs and activated stromal fibroblasts (SFs). Single and repeated intrastromal injections of 2 to 4 × 104 cells to rat normal corneas (n = 52) or corneas with early opacities induced by irregular phototherapeutic keratectomy (n = 16) were performed, followed by weekly examination of corneal response under slit-lamp biomicroscopy and in vivo confocal microscopy with evaluation of haze level and stromal reflectivity, and corneal thickness using anterior segment optical coherence tomography (AS-OCT). Time-lapse tracing of Molday ION-labelled cells was conducted using Spectralis OCT and label intensity was measured. Corneas were collected at time intervals for marker expression by immunofluorescence, cell viability, and apoptosis assays. Injected CSKs showed proper marker expression with negligible SF-related features and inflammation, hence maintaining corneal clarity and stability. The time-dependent loss of injected cells was recovered by repeated injection, achieving an extended expression of human proteoglycans inside rat stroma. In the early corneal opacity model, intrastromal CSK injection reduced stromal reflectivity and thickness, resulting in recovery of corneal clarity, whereas noninjected corneas were thicker and had haze progression. We demonstrated the safety, feasibility, and therapeutic efficacy of intrastromal CSK injection. The cultivated CSKs can be a reliable cell source for potential cell-based therapy for corneal opacities.

Diagnostic Ability of Corneal Shape and Biomechanical Parameters for Detecting Frank Keratoconus.

To assess the diagnostic capability of corneal shape and biomechanical parameters for distinguishing normal eyes from frank keratoconus (KCN). This is a retrospective analysis of eyes of 137 control subjects and 145 patients with KCN, with one of their eyes randomly selected as the study eye. Corneal biomechanical parameters were assessed using the Corvis ST (Oculus Optikgeräte GmbH) and Oculus Response Analyzer (Reichert Ophthalmic Instruments). Corneal tomography was performed using the Oculus Pentacam. The clinical diagnosis of KCN was based on slit-lamp findings (eg, Fleischer ring, Vogt striae) and abnormal topographic patterns on the sagittal (axial) front curvature map, disregarding tomographic and biomechanical findings. The discriminative ability for each parameter was tested using the Mann-Whitney U test. The accuracy of each parameter with statistically significant differences was determined using receiver operating characteristic curves, which were compared using the DeLong method. Statistically significant differences were observed for all corneal shape and biomechanical parameters tested (P < 0.05) except peak distance at the highest concavity (P = 0.504). The area under the curve (AUC), sensitivity, and specificity for corneal hysteresis (CH) and corneal resistance factor (CRF) were 0.894, 80.7%, and 84.7% and 0.946, 85.5%, and 89.1%, respectively. The dynamic corneal response parameters from the Corvis ST, stiffness parameter at first applanation, integrated radius (IR), and deformation amplitude ratio at 2 mm (DA-2 mm) had AUC, sensitivity, and specificity of 0.965, 86.2%, and 94.9%; 0.961, 87.6%, and 93.4%; and 0.950, 80.7%, and 98.5%. The Corvis biomechanical index had an AUC of 0.998 (95% confidence interval, 0.983-1.000), with 96.6% sensitivity and 99.3% specificity. The Belin-Ambrósio enhanced ectasia deviation index (BAD-Dv3) and the tomographical/biomechanical index (TBI) had an AUC of 1.0 (95% confidence interval, 0.987-1.000), with sensitivity and specificity of 100%. The combined indices, Corvis biomechanical index, BAD-D, and TBI, had a statistically higher AUC than that of all corneal biomechanical parameters (DeLong, P < 0.001). The Scheimpflug-derived shape and biomechanical parameters are able to accurately distinguish normal corneas from frank (clinical) keratoconic corneas. However, the combined parameters were more effective. Further studies should test milder ectasia cases.

Mixed Model Analysis of Between-Subject Variability in Overnight Corneal Swelling and Deswelling With Silicone Hydrogel Lenses.

To model between subject variability of corneal swelling (CS) and deswelling after overnight wear of silicone hydrogel (SiHy) contact lenses. A total of 29 neophyte subjects wore 12 SiHy lenses with central transmissibility range of 31 to 211 Dk/t units on separate nights, in random order, and on one eye only. The contralateral eye served as the control. Central corneal thickness was measured using digital optical pachymetry before lens insertion, immediately after lens removal on waking, then 20, 40 minutes, 1, 2, and 3 hours later. Mixed modelling was conducted for simultaneous analysis of group and between-subject effects of CS and deswelling. The best model for overnight CS versus Dk/t was linear with a random intercept showing constant between-subject differences in CS for different Dk/t values. The best fit for corneal deswelling versus time was a curvilinear random intercept and random slope model. About 90% of the total between-subject deswelling variance in either lens or control eyes was due to the intercept variability with much less (∼10%) being due to the variability of the individual deswelling rate (slope). Subject age, sex, and ametropia were not predictors of individual corneal swelling in the swelling versus Dk/t analysis. Age, however, was a significant (inverse) predictor of the rate of corneal deswelling, only in lens-wearing eyes. A large proportion of variability in corneal swelling is because of subject-specific differences in corneal response to hypoxia. This shows that "low swellers" and "high swellers" actually do exist.

Boxb mediate BALB/c mice corneal inflammation through a TLR4/MyD88-dependent signaling pathway in Aspergillus fumigatus keratitis.

To investigate whether high-mobility group box 1 (HMGB1) Boxb exacerbates BALB/c mice corneal immune responses and inflammatory through the Toll-like receptor 4 (TLR4)/myeloid differentiation primary response 88 (MyD88)-dependent signaling pathway in Aspergillus fumigatus (A. fumigatus) keratitis. The mice corneas were pretreated with phosphate buffer saline (PBS), Boxb before A. fumigatus infection. The abdominal cavity extracted macrophages were pretreated with PBS, Boxb, TLR4 inhibitor (CLI-095), Dimethyl sulfoxide (DMSO) separately before A. fumigatus hyphae stimulation. HMGB1 was detected in normal and infected mice corneas and macrophages by real-time reverse transcriptase polymerase chain reaction (RT-PCR), the TLR4, MyD88, interleukin-1β (IL-1β), tumor necrosis factor-α (TNF-α) were detected by Western blot and PCR. In BALB/c mice corneas, the expressions of TLR4, HMGB1, IL-1β, TNF-α were increased after A. fumigatus infection. While pretreatment with Boxb significantly increased the expressions of TLR4, HMGB1, MyD88, IL-1β, TNF-α compared with PBS control after infection. In BALB/c mice abdominal cavity extracted macrophages, pretreatment with Boxb increased the expressions of TLR4, HMGB1, MyD88, IL-1β, TNF-α, while pretreatment with CLI-095 and Boxb significantly decreased the expressions of TLR4, HMGB1, MyD88, IL-1β, TNF-α. In A. fumigatus keratitis, Boxb play a pro-inflammatory role in corneal anti-fungi immune response through the HMGB1-TLR4-MyD88 signal pathway.