Corneal Endothelial Cell Damage Research Articles

Neuropeptide alpha-Melanocyte stimulating hormone preserves corneal endothelial morphology in a murine model of Fuchs dystrophy

Fuchs endothelial corneal dystrophy is a heterogenous disease with multifactorial etiology, and genetic, epigenetic, and exogenous factors contributing to its pathogenesis. DNA damage plays a significant role, with ultraviolet-A (UV-A) emerging as a key contributing factor. We investigate the potential application of neuropeptide α-melanocyte stimulating hormone (α-MSH) in mitigating oxidative stress induced endothelial damage. First, we examined the effects of α-MSH on a cultured human corneal endothelial cell line (HCEnC-21T) exposed to hydrogen peroxide (H2O2) induced oxidative DNA damage. We performed immunofluorescence and flow cytometry to assess DNA damage and cell death in the cultured cells. Additionally, we used an established mouse model that utilizes ultraviolet light to induce corneal endothelial cell damage resulting in decreased CEnC number, increased cell size variability, and decreased percentage of hexagonal cells. This endothelial decompensation leads to an increase in corneal thickness. Following UV-A exposure, the mice were systemically treated with α-MSH, either immediately after exposure (early treatment) or beginning two weeks post-exposure (delayed treatment). To evaluate treatment efficacy, we analyzed CEnC density and morphology using in vivo confocal microscopy, and central corneal thickness using anterior segment optical coherence tomography. Our findings demonstrated that α-MSH treatment effectively protects HCEnC-21T from free-radical induced oxidative DNA damage and subsequent cell death. In vivo, α-MSH treatment, mitigated the loss of CEnC density, deterioration of cell morphology and suppression of the resultant corneal swelling. These results underline the potential application of α-MSH as a therapeutic agent for mitigating corneal endothelial damage.

A Case of Irreversible Corneal Endothelial Damage Associated with Amantadine Use

Purpose: To report a case of irreversible corneal endothelial cell damage associated with amantadine administration.Case summary: A 60-year-old female patient was referred with bilateral painless corneal edema. There was no history of ocular trauma or surgery. The was no sign of ocular surface inflammation, such as, conjunctival injection, either. At presentation, her best corrected visual acuity (BCVA) was 20/100 in the right eye and 20/50 in the left eye. Review of the past medical history revealed that she had been diagnosed with Parkinson’s disease and had been taking amantadine (100 mg, twice a day) for 3 years. At 7 weeks after cessation of amantadine, corneal edema was resolved bilaterally and BCVA improved to 20/30 in the right eye and 20/20 in the left eye. However, specular microscopy showed low endothelial cell density (ECD) with 886 ± 297/mm2 in the right eye and 926 ± 374/mm2 in the left eye. At 4 months after cessation, there was no corneal edema and BCVA was 20/25 in the right eye and 20/20 in the left eye. However, ECD was low with 852 ± 249/mm2 in the right eye and 903 ± 332/mm2 in the left eye.Conclusions: In cases with bilateral corneal edema without no obvious pathology, the history of medication, such as, amantadine, should be reviewed. Although cessation of amantadine can lead to improvement of corneal edema, irreversible damage of the corneal endothelial cells may remain. Serial evaluation of corneal endothelial cells is therefore recommended in patients with systemic amantadine administration.

Traumatic Anterior Dislocation of a Clear Crystalline Lens

We present a case study of a 41-year-old patient who was admitted to the ophthalmological emergency department complaining of ocular pain and redness following trauma of the right eye. Slit-lamp examination of the right eye revealed visual acuity limited to "counting fingers", diffuse conjunctival hyperemia, anterior dislocation of a clear crystalline lens in the anterior chamber with endothelial contact (Figure 1) , and ocular hypertonia measured at 35 mm Hg. Medical treatment was swiftly initiated, incorporating both local and systemic hypotensive agents. After the eye pressure has been normalized, the patient underwent phacoemulsification lens extraction with anterior vitrectomy. Postoperative outcome was marked by normalization of intraocular pressure and by the absence of optic nerve and corneal endothelial cell damage.

Factors associated with severe corneal endothelial damage following acute primary angle closure in Chinese subjects

PurposeTo investigate the corneal endothelial damage caused by acute primary angle closure (APAC) and related risk factors for severe corneal endothelial cell damage in Chinese subjects.MethodsIn this multicentre retrospective study, 160 Chinese patients (171 eyes) diagnosed with APAC were recruited. Endothelial cell density (ECD) and morphological changes short after APAC were studied. Univariate regression and multivariate regression were used to identify risk factors associated with the extent of ECD reduction, including age, gender, education level, patients’ location, systemic diseases, APAC duration (hours), highest recorded intraocular pressure (IOP), and presenting IOP. Factors associated with the probability of severe corneal damage (ECD lower than 1000/mm2) were analysed based on a linear function.ResultsAfter one APAC episode, 12.28% eyes had ECD lower than 1000/mm2, 30.41% had ECD between 1000 and 2000/mm2, and 57.31% had ECD more than 2000/mm2. Attack duration was the only factor associated with severe endothelial damage (p < 0.0001). If the attack were to be subsided within 15.0 h, possibility of ECD lower than 1000/mm2 could be controlled under 1%.ConclusionShortly after the abortion of APAC, 12.28% patients experienced severe endothelial cell damage with ECD less than 1000/mm2. The only factor associated with severe ECD decrease was attack duration. Immediate and effective treatment is pivotal for preserving corneal endothelial function in APAC patients.

Corneal endothelial cells and acoustic cavitation in phacoemulsification.

Postoperative complications of phacoemulsification, such as corneal edema caused by human corneal endothelial cell (CEC) injury, are still a matter of concern. Although several factors are known to cause CEC damage, the influence of ultrasound on the formation of free radicals during surgery should be considered. Ultrasound in aqueous humor induces cavitation and promotes the formation of hydroxyl radicals or reactive oxygen species (ROS). ROS-induced apoptosis and autophagy in phacoemulsification have been suggested to significantly promote CEC injury. CEC cannot regenerate after injury, and measures must be taken to prevent the loss of CEC after phacoemulsification or other CEC injuries. Antioxidants can reduce the oxidative stress injury of CEC during phacoemulsification. Evidence from rabbit eye studies shows that ascorbic acid infusion during operation or local application of ascorbic acid during phacoemulsification has a protective effect by scavenging free radicals or reducing oxidative stress. Both in experiments and clinical practice, hydrogen dissolved in the irrigating solution can also prevent CEC damage during phacoemulsification surgery. Astaxanthin (AST) can inhibit oxidative damage, thereby protecting different cells from most pathological conditions, such as myocardial cells, luteinized granulosa cells of the ovary, umbilical vascular endothelial cells, and human retina pigment epithelium cell line (ARPE-19). However, existing research has not focused on the application of AST to prevent oxidative stress during phacoemulsification, and the related mechanisms need to be studied. The Rho related helical coil kinase inhibitor Y-27632 can inhibit CEC apoptosis after phacoemulsification. Rigorous experiments are required to confirm whether its effect is realized through improving the ROS clearance ability of CEC.

Luxation antérieure d’un cristallin clair post-traumatique

We here report the case of a 52-year-old patient admitted to the ophthalmic emergency department with ocular pain and redness following right ocular trauma. Ophthalmologic examination of the right eye revealed impaired near visual acuity of counting fingers, diffuse conjunctival hyperaemia, dislocation of the clear crystalline lens into the anterior chamber in front of the iris with contact with endothelial cells and ocular hypertonia 40 mmHg. Ocular ultrasound was normal. The patient received emergency medical treatment based on both local and general hypotonizing drug. Then phacoemulsification including direct surgical removal of the entire lens associated with anterior vitrectomy were performed. Postoperative outcome was marked by normalization of intraocular pressure and by the absence of optic nerve and corneal endothelial cell damage.

Corneal Endothelial Morphology and Central Corneal Thickness Changes in Type 2 Diabetes Mellitus using Specular Microscopy and Ultrasonic Pachymetry: A Cross-sectional Comparative Study

Introduction: Diabetes Mellitus (DM) is a metabolic condition characterised by chronic hyperglycaemia, causing raised blood glucose levels which result in microvascular and macrovascular disorders and may introduce ocular manifestations including changes in corneal Endothelial Cell Density (ECD), corneal thickness, and intraocular pressure. It is clinically important to analyse the corneal endothelial status in patients with type II DM as preoperative corneal endothelial cell dysfunction may cause more corneal endothelial cell damage postoperatively leading to corneal decompensation. With the advent of precise and better measurement tool Central Corneal Thickness (CCT) and corneal endothelial morphology measurement has become more accurate. Aim: To compare corneal endothelium cell density, polymorphism, polymegathism and CCT in type 2 DM with age-matched, non diabetic control subjects using CEM-530 Specular microscope and ultrasonic pachymeter Tomey SP-100. Materials and Methods: This cross-sectional, comparative study was conducted at Eye Department at ESI Post Graduate Institute of Medical Sciences and Research, Basaidarapur, Delhi, India, from October 2018 to November 2019. Patients with ages between 40 to 70 years of either gender who were diagnosed to have DM were recruited in the study through non probability convenience sampling. A total of 150 subjects that met the inclusion criteria and exclusion criteria were included in the study. Seventy five known type 2 DM patients were enrolled in diabetic group (case group) and 75 non diabetic, age-matched subjects were enrolled as control group. Cases were classified under three major groups, namely on the basis of duration of DM and severity of Diabetic Retinopathy (DR) and glycaemic control {glycosylated haemoglobin (HbA1c) level}. All the findings were endorsed on a predesigned performa. Statistical Package for Social Sciences (SPSS) version 17.0 was used for analysis of data. Age and corneal parameters compared using unpaired t-test in diabetic and control group. Also, for comparison in between subgroup of diabetic patients on HbA1c level done by using Analysis of Variance (ANOVA) test. Chi-square test applied for categorical variables. Results: Among the 150 patients evaluated, type 2 DM patient’s corneas (540.51±32.578 µ) were thicker as compared to control group 517.51±22.155 µ (p-value&lt;0.001). The mean ECD of control and diabetic group patients was 2723.75±287.253 cells/mm2 and 2716.11±296.081 cells/mm2 , respectively, found insignificant (p-value=0.821). The mean Coefficient of Variation (CV) of cell area of control and diabetic patients was 28.87±3.950 and 29.85±4.027, respectively, and was significant (p-value=0.034). The mean percentage of endothelial Hexagonal cells (HEX%) of control and diabetic patients were 67.39±6.419 and 67.41±5.493, respectively and was non significant (p-value=0.985). Thus, statistically significant difference was found with CCT (p-value&lt;0.001) and CV (p-value=0.034) but not with ECD and hexagonality, between control and diabetic eyes. There was a correlation between CCT, CV, HEX% and ECD with duration of DM2 but it was statistically insignificant. There were higher CCT, CV and HEX% and lower ECD in &gt;10 years of duration of diabetes mellitus than in patients with duration of diabetes mellitus ≤10 years. There was a correlation of CCT, CV, ECD and HEX with HbA1c level. There were significant higher CCT and CV values in &gt;7% HbA1c level group than in group with ≤7% HbA1c level. There was also increased ECD in &gt;7% group, but it was found to be insignificant. Percentage of hexagonality in &gt;7% HbA1c level group was lower than in group with ≤7% HbA1c level, but found insignificant. There were higher values of CCT and CV in Non Proliferative Diabetic Retinopathy (NPDR) subgroup compared to Proliferative Diabetic Retinopathy (PDR) and no Diabetic Retinopathy group. CCT values were significant (p-value=0.007), so as CV values (p-value=0.001). There was increase in HEX% (p-value=0.005) which was significant, along with lower ECD in NPDR (p-value=0.143), group which was insignificant. Conclusion: The present study documented that DM has considerable effects on all the layers of the cornea especially endothelial layer, causes reduction of ECD and increased CV. Diabetic cornea has increased CCT and lower percentage of hexagonal cells than normal subjects. In addition, there is a correlation between the changes in corneal parameters like ECD, CV, HEX%, CCT with the duration of DM and severity of DR and glycaemic control {glycosylated haemoglobin (HbA1c) level}.

Corneal Endothelial Morphology and Central Corneal Thickness Changes in Type 2 Diabetes Mellitus using Specular Microscopy and Ultrasonic Pachymetry: A Cross-sectional Comparative Study

Introduction: Diabetes Mellitus (DM) is a metabolic condition characterised by chronic hyperglycaemia, causing raised blood glucose levels which result in microvascular and macrovascular disorders and may introduce ocular manifestations including changes in corneal Endothelial Cell Density (ECD), corneal thickness, and intraocular pressure. It is clinically important to analyse the corneal endothelial status in patients with type II DM as preoperative corneal endothelial cell dysfunction may cause more corneal endothelial cell damage postoperatively leading to corneal decompensation. With the advent of precise and better measurement tool Central Corneal Thickness (CCT) and corneal endothelial morphology measurement has become more accurate. Aim: To compare corneal endothelium cell density, polymorphism, polymegathism and CCT in type 2 DM with age-matched, non diabetic control subjects using CEM-530 Specular microscope and ultrasonic pachymeter Tomey SP-100. Materials and Methods: This cross-sectional, comparative study was conducted at Eye Department at ESI Post Graduate Institute of Medical Sciences and Research, Basaidarapur, Delhi, India, from October 2018 to November 2019. Patients with ages between 40 to 70 years of either gender who were diagnosed to have DM were recruited in the study through non probability convenience sampling. A total of 150 subjects that met the inclusion criteria and exclusion criteria were included in the study. Seventy five known type 2 DM patients were enrolled in diabetic group (case group) and 75 non diabetic, age-matched subjects were enrolled as control group. Cases were classified under three major groups, namely on the basis of duration of DM and severity of Diabetic Retinopathy (DR) and glycaemic control {glycosylated haemoglobin (HbA1c) level}. All the findings were endorsed on a predesigned performa. Statistical Package for Social Sciences (SPSS) version 17.0 was used for analysis of data. Age and corneal parameters compared using unpaired t-test in diabetic and control group. Also, for comparison in between subgroup of diabetic patients on HbA1c level done by using Analysis of Variance (ANOVA) test. Chi-square test applied for categorical variables. Results: Among the 150 patients evaluated, type 2 DM patient’s corneas (540.51±32.578 µ) were thicker as compared to control group 517.51±22.155 µ (p-value&lt;0.001). The mean ECD of control and diabetic group patients was 2723.75±287.253 cells/mm2 and 2716.11±296.081 cells/mm2 , respectively, found insignificant (p-value=0.821). The mean Coefficient of Variation (CV) of cell area of control and diabetic patients was 28.87±3.950 and 29.85±4.027, respectively, and was significant (p-value=0.034). The mean percentage of endothelial Hexagonal cells (HEX%) of control and diabetic patients were 67.39±6.419 and 67.41±5.493, respectively and was non significant (p-value=0.985). Thus, statistically significant difference was found with CCT (p-value&lt;0.001) and CV (p-value=0.034) but not with ECD and hexagonality, between control and diabetic eyes. There was a correlation between CCT, CV, HEX% and ECD with duration of DM2 but it was statistically insignificant. There were higher CCT, CV and HEX% and lower ECD in &gt;10 years of duration of diabetes mellitus than in patients with duration of diabetes mellitus ≤10 years. There was a correlation of CCT, CV, ECD and HEX with HbA1c level. There were significant higher CCT and CV values in &gt;7% HbA1c level group than in group with ≤7% HbA1c level. There was also increased ECD in &gt;7% group, but it was found to be insignificant. Percentage of hexagonality in &gt;7% HbA1c level group was lower than in group with ≤7% HbA1c level, but found insignificant. There were higher values of CCT and CV in Non Proliferative Diabetic Retinopathy (NPDR) subgroup compared to Proliferative Diabetic Retinopathy (PDR) and no Diabetic Retinopathy group. CCT values were significant (p-value=0.007), so as CV values (p-value=0.001). There was increase in HEX% (p-value=0.005) which was significant, along with lower ECD in NPDR (p-value=0.143), group which was insignificant. Conclusion: The present study documented that DM has considerable effects on all the layers of the cornea especially endothelial layer, causes reduction of ECD and increased CV. Diabetic cornea has increased CCT and lower percentage of hexagonal cells than normal subjects. In addition, there is a correlation between the changes in corneal parameters like ECD, CV, HEX%, CCT with the duration of DM and severity of DR and glycaemic control {glycosylated haemoglobin (HbA1c) level}.

Type 2 Diabetes Mellitus Makes Corneal Endothelial Cells Vulnerable to Ultraviolet A-Induced Oxidative Damage Via Decreased DJ-1/Nrf2/NQO1 Pathway.

The purpose of this study was to investigate whether type 2 diabetes mellitus (T2DM) makes corneal endothelial cells (CECs) suffer from more severe ultraviolet A (UVA)-induced oxidative damage and explore its mechanisms via measuring the oxidant level and the antioxidant level in vitro. Corneas of spontaneous T2DM db/db mice and non-diabetes littermate control mice were irradiated with UVA, leading to oxidative damage of CECs. Anterior segment-optical coherence tomography, corneal image, and CECs immunohistochemistry staining were taken thereafter to measure central corneal thickness, corneal edema degree, and damage extent of CECs. In vitro, human corneal endothelial cells line B4G12 (HCECs) treated with high glucose (HG) and low glucose (LG) were exposed to UVA light separately. Subsequently, cellular proliferation, apoptosis, pro-oxidant factors, such as reactive oxygen species (ROS), antioxidant factors including Parkinson's disease protein 7 (DJ-1), nuclear factor-erythroid 2 related factor 2 (Nrf2), phosphorylated-Nrf2, and NAD(P)H: quinone oxidoreductase 1 (NQO1) were measured. T2DM mice presented greater oxidant damage of CECs and more distinct corneal edema compared with control mice when they were irradiated with the 150J/cm2 UVA light. In vitro, HCECs in HG condition showed a significant decrease of proliferation, higher apoptosis extent, more ROS generation, lower expressions of DJ-1/Nrf2/NQO1, and distinct reduction of Nrf2 nuclear translocation compared to those in LG condition after exposing to 5J/cm2 UVA light. Increase of ROS, downregulation of DJ-1/Nrf2/NQO1 expressions, and decrease of Nrf2 nuclear translocation could result in that T2DM makes CECs more vulnerable to oxidative damage.

Expression of Superoxide Dismutase-1 (SOD-1) and changes of corneal endothelial morphology after phacoemulsification with hypothermic perfusion

Background: Hypothermic perfusion can be used as adjunctive therapy to reduce corneal endothelial cell damage during phacoemulsification procedures. This study aims to evaluate the effect of hypothermic perfusion on the expression of Superoxide Dismutase-1 (SOD1) and morphological changes in the corneal endothelium after ultrasound energy of phacoemulsification exposure. Methods: Sixteen New Zealand white rabbits (n=16 eyes) were randomly divided into two groups and exposed to ultrasound energy of phacoemulsification. The control group was administered room temperature (RT) (24°C) Balanced Salt Solution (BSS) intraocular perfusion, and the treatment group was administered hypothermic (4°C) BSS intraocular perfusion. Coefficient of Variation (CV) and hexagonality were measured before and one day after surgery with specular microscopy. The expression of SOD1 was examined by immunohistochemistry staining. Data were analyzed using SPSS version 26 for Windows. Results: The result showed that the SOD1 expression was significantly lower in the hypothermic perfusion group compared with the control group (p=0.024, p&lt;0.05). There were no significant differences between the two groups in CV changes (p=0.494, p&gt;0.05) and hexagonality changes (p=0.916, p&gt;0.05). There was no correlation between the expression of SOD1 and change in CV (p=0.188, p&gt;0.05) or the expression of SOD1 and change in hexagonality (p=0.763, p&gt;0.05). Conclusion: Hypothermic perfusion suppresses all metabolic processes, including the expression of SOD1 and ROS production. The coefficient of variation and hexagonality as a representative of corneal endothelial morphology changes also decrease with hypothermic perfusion after ultrasound exposure but are not statistically significant. There is no correlation between the expression of SOD1 and changes in CV and hexagonality.

Expression of Na+/K+ATPase and changes of corneal endothelium cell density after phacoemulsification with hypothermic perfusion

Background: Intraocular hypothermic perfusion can be used as an alternative to reduce corneal endothelial cell damage in phacoemulsification procedures. This study aimed to analyze the effect of hypothermic intraocular perfusion on cell density and expression of the Na+/K+-ATPase on corneal endothelial cells after exposure to ultrasonic phacoemulsification energy. Methods: Sixteen New Zealand white rabbits (n=16 eyes) were randomly divided into two groups and exposed to phacoemulsification ultrasonic energy. The control group received room-temperature Intraocular Balanced Salt Solution (BSS) hyperthermic perfusion (24oC) and the treatment group received low-temperature intraocular BSS hypothermic perfusion (4oC). Corneal endothelial cell density (ECD) was measured before and 1 day after surgery using a specular microscope. On the first postoperative day, the expression of Na+/K+ATPase was examined using immunohistochemical antibody staining. Data were analyzed using SPSS version 26 for Windows. Results: There was no statistically significant difference in the expression of corneal endothelial Na+/K+-ATPase between the control and treatment groups (p=0.053). There was no significant difference in corneal endothelial cell density changes between the control and treatment groups (p=0.115). There was no correlation between changes in cell density and corneal endothelial Na+/K+ATPase expression in the control and treatment groups (p=0.216). Conclusion: The effect of intraocular hypothermic perfusion on phacoemulsification procedures remains controversial. Endothelial cell density decreased in hypothermic perfusion after phacoemulsification and Na+/K+ATPase expression was not significantly affected by hypothermic perfusion.

Quantitative analysis of cornea endothelial cell damage from enucleation, corneal buttoning, and storage in donor corneas using trypan blue dye staining.

We aimed to quantitatively analyze the corneal endothelial cell damage by measuring the area stained with trypan blue dye, and to confirm the degree of corneal endothelial cell damage resulting from enucleation, corneal buttoning, and storage in donor corneas intended for use in human corneal transplantation. This study was a retrospective analysis of medical records and videos recorded during keratoplasty. Twenty-one corneal buttons of 21 donors that underwent endothelial cell staining using trypan blue for the donor preparation during DALK or DMEK were included in the study. The percentage of stained area in entire corneal endothelia and the percentage of the stained area in the 8-mm diameter circle were quantitatively analyzed using Adobe Photoshop. The mean percentage of the stained area in the entire corneal endothelia in 13 corneas was 8.1 ± 13.3% (range, 0.0-56.1%), and the mean percentage of the stained area in a circle with a diameter of 8 mm in 21 corneas was 3.4 ± 5.2% (range, 0.0-18.9%). The correlations between the death-to-preservation time, the training duration of the residents who performed donor corneal buttoning, and the percentage of the stained area in the 8-mm diameter circle were not significant(P = .441, P = .495, respectively). Cornea thickness and endothelial cell density did not differ between 10 eyes in the group with the percentage of the stained area in a circle with a diameter of 8 mm <5% and 5 eyes in the group with the percentage more than 5% damage (P = .854, P = .358). The corneal endothelial cell damage could be quantitatively analyzed using trypan blue staining before keratoplasty in donor cornea. The amount of corneal endothelial cell damage in the central 8-mm circle was mostly acceptable, but some cases showed significantly severe endothelial cell damage. The corneal thickness and endothelial cell density did not differ between 10 eyes in the group with the percentage of the stained area in a circle with a diameter of 8 mm <5% and 5 eyes in the group with the percentage more than 5% damage. Therefore, pachymetry and specular microscopy are not sufficient for evaluating donor corneas before keratoplasty.

Phenotypic and Transcriptomics Analyses Reveal Underlying Mechanisms in a Mouse Model of Corneal Bee Sting.

Corneal bee sting (CBS) is one of the most common ocular traumas and can lead to blindness. The ophthalmic manifestations are caused by direct mechanical effects of bee stings, toxic effects, and host immune responses to bee venom (BV); however, the underlying pathogenesis remains unclear. Clinically, topical steroids and antibiotics are routinely used to treat CBS patients but the specific drug targets are unknown; therefore, it is imperative to study the pathological characteristics, injury mechanisms, and therapeutic targets involved in CBS. In the present study, a CBS injury model was successfully established by injecting BV into the corneal stroma of healthy C57BL/6 mice. F-actin staining revealed corneal endothelial cell damage, decreased density, skeletal disorder, and thickened corneal stromal. The terminal-deoxynucleotidyl transferase mediated nick end labeling (TUNEL) assay showed apoptosis of both epithelial and endothelial cells. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis showed that cytokine–cytokine interactions were the most relevant pathway for pathogenesis. Protein–protein interaction (PPI) network analysis showed that IL-1, TNF, and IL-6 were the most relevant nodes. RNA-seq after the application of Tobradex® (0.3% tobramycin and 0.1% dexamethasone) eye ointment showed that Tobradex® not only downregulated relevant inflammatory factors but also reduced corneal pain as well as promoted nerve regeneration by repairing axons. Here, a stable and reliable model of CBS injury was successfully established for the first time, and the pathogenesis of CBS and the therapeutic targets of Tobradex® are discussed. These hub genes are expected to be biomarkers and therapeutic targets for the diagnosis and treatment of CBS.

Corneal Oedema: Aetiology, Diagnostic Testing, and Treatment.

Corneal oedema results from an underlying pathology, which can be diverse in origin, and may be mechanical, dystrophic, or inflammatory, and affect any layer of the cornea. Diagnostic tools such as Scheimpflug imaging and anterior segment optical coherence tomography have standardised quantification of corneal oedema and have become important aids in clinical practice. Timely diagnosis and treatment are key to preventing irreversible damage to the corneal ultrastructure, such as anterior corneal fibrosis or endothelial cell damage. The oedema usually resolves quickly when the underlying cause has been addressed. Symptomatic treatment using hyperosmolar agents has failed to show any benefits in oedema resolution or improvement in visual acuity compared to placebo. In contrast, rho-associated protein kinase (ROCK) inhibitors offer a promising option for medical treatment in cases of endothelial dysfunction, but their safety and efficacy must be further validated in large scale clinical trials. Until then, endothelial or penetrating keratoplasties remain the mainstay treatment where structural changes to the cornea have occurred.

Specular Microscopic Corneal Endothelial Cell Changes following Uneventful Phacoemulsification in Patients with Gout.

Purpose To assess the effects of phacoemulsification on the corneal endothelium in patients with gout and age-related cataracts. Methods Eighty-eight patients who underwent uneventful phacoemulsification for age-related cataracts were included in this retrospective comparative study. The patients were divided into two groups: group A included 31 patients with gout and tight control of uric acid levels and group B included 57 patients without gout or any other systemic disease. All patients completed follow-up assessments over 6 months, and the two groups were compared in terms of changes to their specular microscopic values. Results Both groups showed marked improvement in uncorrected and best-corrected visual acuity at the end of the follow-up period. Corneal endothelial cell loss was more severe in group A than in group B, with a mean difference of 221.35 ± 43.87 in group A and 169.88 ± 52.67 in group B at the sixth month (p < 0.001). The difference between the two groups in terms of other specular microscopic values did not reach statistical significance. Conclusion Patients with gout are more prone to corneal endothelial cell damage after phacoemulsification than those without gout. To confirm these results, future studies with a prospective design and longer durations of follow-up are needed.

Antiviral cytotoxic T lymphocyte responses for long term prognosis of corneal infection by cytomegalovirus in immunocompetent subjects

Ocular cytomegalovirus (CMV) infections in immunocompetent individuals are rare, but its activation can cause chronic and relapsing inflammation in anterior segment of the eye resulting in loss of corneal clarity and glaucoma. Fifty five patients with anterior segment CMV infection were assessed for their clinical characteristics, and CMV corneal endotheliitis was found to cause significant loss of corneal endothelial cells. The disease duration with recurrences was significantly correlated with the maximum intraocular level of CMV DNA. To examine why CMV is activated in healthy immunocompetent individuals and causing corneal endothelial cell damage, assays of cytotoxic T cells (CTLs) which directly target infected corneal endothelial cells were performed for 9 HLA-matched CMV corneal endotheliitis patients (HLA-A*2402). When the cell loss was analyzed for associations with CTL responses, CMV-induced endothelial cell damage was mitigated by pp65-specific CTL induction. The recurrence-free time was also prolonged by pp65-specific CTL induction (hazard ratio (HR): 0.93, P = 0.01). In contrast, IE1-specific CTL was associated with endothelial cell damage and reduced the time for corneal transplantation (HR: 1.6, P = 0.003) and glaucoma surgery (HR: 1.5, P = 0.001). Collectively, induction of pp65-specific CTL was associated with improved visual prognosis. However, IE1-specific CTL without proper induction of pp65-specific CTL can cause pathological damage leading to the need of surgical interventions.

Effect of longitudinal and torsional ultrasound on corneal endothelial cells: experimental study in rabbit eyes.

To compare corneal endothelial damage from longitudinal and torsional ultrasound during phacoemulsification. John A. Moran Eye Center, University of Utah, Salt Lake City, Utah, USA. Experimental study. 9 New Zealand white rabbits underwent bilateral surgery. After incision, the Intrepid Balanced Tip of the Centurion Ozil handpiece was inserted into the anterior chamber, and the following settings were used: 50 mL/min flow, 70 mm Hg intraocular pressure, 600 mm Hg vacuum, and 60% longitudinal (1 eye) or torsional (contralateral eye) ultrasound for 30 seconds. Cumulative dissipated energy (CDE) was noted. After euthanasia and enucleation, the corneas were removed, stained with trypan blue/alizarin red, and photographed (400× photographs from 5 specific areas and 1 overview photograph from each corneal button). The ImageJ program was used to evaluate cell damage and loss in the photographs obtained from each cornea. Cavitation bubbles around the phacoemulsification tip were generally observed in the longitudinal group. CDE was 17.4 ± 0.58 and 6.93 ± 0.15 in the longitudinal and torsional groups, respectively (P = .003). The percentage of intact cells was statistically higher in the torsional group (94.22% ± 5.99% vs 56.85% ± 22.29%), and the percentage of lost cells was statistically higher in the longitudinal group (42.10% ± 22.02% vs 4.97% ± 6.23%) (P = .003). This was observed in the analysis of the 400× photographs and the overview photographs. This study suggests that torsional ultrasound was associated with significantly less corneal endothelial cell damage than classical longitudinal tip motion, providing further insight on mechanisms of corneal endothelial damage during phacoemulsification.

Corneal endothelial cell damage after scleral fixation of intraocular lens surgery.

To analyze corneal endothelial cell damage after scleral fixation of intraocular lens (SFIOL) surgery. Retrospective study. Medical records of consecutive eyes undergoing SFIOL surgery performed by a single surgeon were reviewed between January 2011 and June 2019. The patients were classified into three groups according to surgical methods: Group I, re-fixating the existing intraocular lens (IOL) or fixating a new IOL in an aphakic eye; Group II, removing the existing IOL and fixating a new IOL; and Group III, phacoemulsification and fixating a new IOL simultaneously. Preoperative and postoperative specular microscopy (SM) status were compared. Changes in SM were compared among the three groups. Ninety-four eyes were included. Thirty-four eyes in Group I, 39 in Group II, and 21 in Group III. The endothelial cell density (ECD) loss in Group I was 1.5%, less than the ECD loss of 14.3% (p < 0.001) in Group II and 15.4% (p = 0.005), in Group III. In no eye was there an ECD decrease to < 1000/mm2 following the surgical procedure. ECD loss was related to IOL removal or phacoemulsification rather than SFIOL surgery. SFIOL using the existing IOL should be considered preferential in eyes with low ECD and dislocated IOL.

Clinical efficacy of modified phacoemulsification in the treatment of high myopia with cataract: a systematic review and meta-analysis.

To use meta-analysis to evaluate the clinical effect of modified phacoemulsification in the treatment of high myopia with cataract. The English language databases of PubMed, Web of Science, and Embase, and Chinese language databases China National Knowledge Infrastructure (CNKI) and Wanfang were searched for relevant studies published from January 2010 to May 2021. The participants were divided into 2 groups according to different treatment methods; the control group mainly used traditional phacoemulsification, while the treatment group used modified phacoemulsification. The differences in the postoperative complication rate, visual acuity recovery rate at 1 month after surgery, and corneal endothelial cell count at 1 and 3 months after surgery were analyzed. A total of 12 articles were included. The results of comparison confirmed that the treatment group was superior to the control group in the postoperative complication rate, visual acuity recovery rate at 1 month after surgery, and corneal endothelial cell count at 1 and 3 months after surgery. Both treatment methods are effective, but modified phacoemulsification has greater advantages in reducing the damage of corneal endothelial cells and postoperative complications and in improving patient prognosis. Additionally, modified phacoemulsification in the treatment of high myopia with cataract can achieve better visual acuity recovery than traditional phacoemulsification, suggesting a high value for clinical application.

Role of interferon regulatory factor 7 in corneal endothelial cells after HSV-1 infection

Viral infections of the cornea including herpes simplex virus 1 (HSV-1) cause visual morbidity, and the corneal endothelial cell damage leads to significant visual impairment. Interferon regulatory factor 7 (IRF7) has been identified as a significant regulator in corneal endothelial cells after an HSV-1 infection. To examine the role played by IRF7, the DNA binding domain (DBD) of IRF7 of human corneal endothelial cells (HCEn) was disrupted. An RNAi inhibition of IRF7 and IRF7 DBD disruption (IRF7 ∆DBD) led to an impairment of IFN-β production. Impaired IFN-β production by IRF7 ∆DBD was regained by IRF7 DNA transfection. Transcriptional network analysis indicated that IRF7 plays a role in antigen presentation function of corneal endothelial cells. When the antigen presentation activity of HCEn cells were examined for priming of memory CD8 T cells, IRF7 disruption abolished the anti-viral cytotoxic T lymphocyte (CTL) response which was dependent on the major histocompatibility complex (MHC) class I. To further examine the roles played by IRF7 in CTL induction as acquired immunity, the contribution of IRF7 to MHC class I-mediated antigen presentation was assessed. Analysis of IRF7 ∆DBD cells indicated that IRF7 played an unrecognized role in MHC class I induction, and the viral infection induced-MHC class I induction was abolished by IRF7 disruption. Collectively, the IRF7 in corneal endothelial cells not only contributed to type I IFN response, but also to the mediation of viral infection-induced MHC class I upregulation and priming of CD8 arm of acquired immunity.