Corneal Endothelial Cell Loss Research Articles

The relation between the serum level of glycosylated hemoglobin and corneal endothelial cell loss in phacoemulsification

Abstract Purpose: To evaluate corneal endothelium (CE) changes and function after uneventful phacoemulsification in relation to the level of glycosylated hemoglobin (HbA1c). Patients and Methods: A prospective interventional case-control study was conducted on 76 eyes, divided into two groups: Group 1 included 38 eyes of diabetic patients, which was further divided into three subgroups according to the level of HbA1c; Group A (strict control HbA1c < 7 mg/dL), Group B (moderate control HbA1c 7–9 mg/dL), and Group C (poorly controlled HbA1c > 9 mg/dL), and Group 2 included 38 eyes of nondiabetic patients. All participants had a full ophthalmological examination, assessment of the level of HbA1c, preoperative evaluation of CE by specular microscopy, uneventful phacoemulsification, and reassessment of CE by specular microscopy 3 weeks after surgery. Results: Three weeks after surgery, statistically significant changes in CE parameters regarding endothelial cell density, ACG, and standard deviation in both groups were found, with greater changes in diabetics. The poorer the control of diabetes (higher preoperative HbA1c), the greater the impact on postoperative CE changes, but the changes were of no statistical significance. Conclusion: Diabetics are more vulnerable to CE damage during phacoemulsification, and the higher the preoperative HbA1c, the more the damage. So, strict preoperative diabetic control is advisable before phacoemulsification.

Clinical Characteristics of Posner-Schlossman Syndrome Patients in China.

To explore the clinical characteristics of Posner-Schlossman syndrome (PSS) patients in China, especially the risk factors associated with the dynamic changes of corneal endothelial cell (CEC) density and retinal nerve fiber layer (RNFL) thickness during the course of the disease. In this retrospective cohort study, patients consequently suffering from PSS were recruited. Patients data including gender, age of onset, frequency of attack, and disease duration. We performed detailed ophthalmology examinations including intraocular pressure (IOP), best-corrected visual acuity (BCVA), slit-lamp examination, optical coherence tomography (OCT), assessing RNFL thickness, and determined CEC density in the outpatient department. The unaffected eyes served as control. We recruited 121 patients (eyes, n = 125), including 69 (57.0%) males and 52 (43.0%) females with Posner-Schlossman syndrome. The age of first-onset was 33.81 ± 13.63 years old. The majority of these patients were aged 20-50 years (80.2%). The peak IOP was 47.67 ± 13.31 mmHg in the affected eyes. The frequency of PSS attack was 2.7 ± 3.7 times per year. The disease duration was 9.5 ± 10.4 years. Among all patients, there were 27 (22.31%) patients with a history of digestive disorders, 25 (20.66%) patients with a history of allergies, and 24 (19.83%) patients with a history of infectious disease. In the affected eyes, CEC density (2532.94 ± 490.83/mm2 vs. 2777.13 ± 356.87/mm2, p < 0.001), the RNFL thickness of four quadrants (superior 105.46 ± 29.86 μm vs. 121.33 ± 17.30 μm, p < 0.001; temporal 74.58 ± 22.21 μm vs. 81.94 ± 18.20 μm, p = 0.009; inferior 110.50 ± 33.42 μm vs. 128.29 ± 14.39 μm, p < 0.001; nasal 54.85 ± 14.48 μm vs. 63.49 ± 15.40 μm, p < 0.001) and central papillary (87.11 ± 21.18 μm vs. 99.18 ± 7.97 μm, p < 0.001) were significantly reduced compared to the fellow eyes. The disease duration and recurrent frequency were significantly associated with CEC density (p < 0.001 and p = 0.029) and the disease duration was significantly associated with RNFL thickness (p = 0.002). In this study, CEC loss and RNFL thinning were present in the affected eyes. Our results indicated that disease duration and recurrent frequency played an important role in the progression of PSS.

TCF4 trinucleotide repeat expansion in Finnish patients with Fuchs' endothelial corneal dystrophy

AbstractPurpose: To study the presence and role of transcription factor 4 (TCF4) triplet repeat expansion in Finnish patients with Fuchs' endothelial corneal dystrophy (FECD) which causes a progressive loss of corneal endothelial cells, resulting in loss of corneal clarity, and is the leading cause of corneal transplantations in Western countries. FECD has a heterogeneous genetic background, but the best‐known risk variant is a CTG‐repeat expansion in the TCF4 gene. An expansion of more than 40 repeats is associated with an increased risk for the disease.Methods: One hundred and twelve Finnish patients with a clinical diagnosis of FECD treated in the Helsinki University Hospital, and 202 control individuals from the Finnish Red Cross Biobank were enrolled. The patients were examined by slit‐lamp, anterior segment photography, corneal tomography, OCT, and endothelial specular microscopy. To assess the repeat number in TCF4, short tandem repeat analysis and triplet repeat primed PCR were used.Results: Of the 112 patients with FECD, 79 were female and 33 male. A CTG‐expansion of &gt;40 was observed in 84% (95% confidence interval [CI], 76–90) of the patients of whom two had the expansion in both alleles. In contrast, only 3% (95% CI, 1–6) of the 202 control individuals had such an expansion, each of them in a heterozygous state. Of the patients with &lt;40 vs. &gt;4 0 CTG‐repeats 89% vs. 97% had transplantation surgery performed in at least one eye.Conclusions: These results indicate that the CTG‐repeat expansion in TCF4 is a notable risk factor for FECD also in the Finnish population with &gt;80% of the patients carrying the expansion. Further analysis will be performed to clarify the association of the expansion with the clinical and pathological features in these patients.

Genetics of Fuchs corneal endothelial dystrophy – An update

AbstractFuchs endothelial corneal dystrophy (FECD) is the most common primary corneal endothelial dystrophy. It is a progressive, bilateral eye disease that may lead to blindness. There is no primary prevention for FECD. Corneal transplantation remains the only definitive treatment. FECD is a complex and heterogeneous genetic disease with interaction between genetic and environmental factors, including gender, smoking and exposure to ultraviolet light. The most recent IC3D classification categorizes FECD into 2 forms: an extremely rare early‐onset and a late‐onset form.The early onset FECD is associated with autosomal dominant mutations in the gene encoding the alpha 2 subunit of collagen 8, an important structural component of the Descemet membrane (DM). Most of the cases present in the third decade with an equal distribution between men and women. When observed by light and electron microscopy, three forms are described: pure corneal guttae; DM of unusual thickness but without guttae; and guttae buried by subsequent layers of more posterior extracellular matrix.Patients with late‐onset FECD typically manifest changes by the fifth decade of life. The first defining clinical sign is the presence of guttae. As individuals age, the cornea develops more and more guttae and increases in thickness, causing glare, halos, and reduced visual acuity. With more advanced disease, stromal edema ensues along with subepithelial fibrosis. When assessed with specular microscopy, the prevalence of guttae is higher in white (11.2%) than East Asian (5.5%) populations, and higher in females (5.5%–11%) than males (1.5%–7%).Although the median age of onset for the late‐onset FECD is at least four decades later than that of the early onset form, both display a similar linear rate of disease progression. It is not clear which comes first, abnormal corneal endothelial cells (CECs) with a defective synthetic/secretory capacity producing guttae and thickening the DM, or remodelling of the DM through synthesis, degradation, reassembly and chemical modification, resulting in CEC apoptosis.The genetics of the late‐onset FECD is complex and multifactorial with variable expressivity and incomplete penetrance. The late‐onset FECD is sporadic with no family history or autosomal dominant.An overview of our current understanding of the genetics of the late‐onset FECD will be provided, with a description of the different genetic variants that segregate with the disease, including variants in TCF8, AGBL1, LOXHD1 and SLC4A11 gene. The mutations in these genes collectively account for only a small proportion of total FECD. Thus, the presentation will focus on variations in the transcription factor 4 (TCF4) gene on chromosome 18q21.1, which are the most significant genetic risk factors associated with FECD. Further, the potential molecular effects of the intronic CTG trinucleotide repeat (CTG18.1) expansion in TCF4 will be described. Finally, talk will debate the hypothesis that specific genetic subtypes of FECD harbour a unique mechanism of dysregulation in addition to sharing converging common downstream features, given that all FECD cases with or without gene mutations experience the same phenotypic endpoint: presence of guttae and loss of CECs.

The ROCK‐inhibitor ripasudil suppresses the expression of extracellular matrix proteins in Fuchs endothelial corneal dystrophy

AbstractPurpose: Fuchs endothelial corneal dystrophy (FECD) is characterized by a progressive loss of human corneal endothelial cells (HCEC) and excess deposition of extracellular matrix (ECM). As FECD pathophysiology involves Rho‐associated kinase (ROCK) signalling activation, we investigated the effect of various ROCK inhibitors on the expression of ECM proteins and proteolytic enzymes using ex vivo and in vitro models.Methods: Endothelial cell‐Descemet membrane lamellae (DM) from donor corneas (n = 20) and FECD patients (n = 100) undergoing Descemet membrane endothelial keratoplasty were used as ex vivo model. A human corneal endothelial cell line (HCEC‐12) served as in vitro model. Rho‐ROCK signalling pathway components and the effects of the ROCK inhibitors ripasudil (10/30 μM), Y‐27632 (10/30 μM), and netarsudil (1 μM) on the expression of ECM proteins and proteolytic enzymes were analysed, with or without addition of transforming growth factor β1 (TGFβ1, 5 ng/ml), using quantitative real‐time PCR and Western Blot analysis.Results: Constitutive expression of components of the Rho‐ROCK signalling pathway was higher in DM specimens from FECD patients compared to DM from normal donors. Stimulation with all three ROCK inhibitors significantly downregulated the expression of ECM genes, such as collagen 3 alpha 1 (COL3A1) and fibronectin 1 (FN1), in both FECD and normal DM as well as in HCEC‐12, compared to untreated controls, with ripasudil showing the most significant effect. Downregulation of COL1A1 and FN1 by ripasudil was verified on protein level as well. Ripasudil also suppressed the TGFβ‐induced expression and phosphorylation of downstream molecules of the TGFβ pathway (SMAD2) as well as of the Rho‐ROCK pathway (MLC2). Ripasudil further upregulated gene expression of proteolytic enzymes, e.g. matrix metalloproteinase 1 (MMP1) and MMP3.Conclusions: These findings suggest that inhibition of ROCK signalling in FECD patients may have a beneficial effect by suppressing expression and stimulating turnover of abnormal ECM components.

Novel ROCK Inhibitors, Sovesudil and PHP-0961, Enhance Proliferation, Adhesion and Migration of Corneal Endothelial Cells

The loss or dysfunction of human corneal endothelial cells (hCEnCs) is a leading cause of blindness due to corneal failure. Corneal transplantation with a healthy donor cornea has been the only available treatment for corneal endothelial disease. However, the need for way to regenerate the CEnCs has been increased due to the global shortage of donor corneas. The aim of the study is to investigate whether novel Rho-kinase (ROCK) inhibitors can induce the cultivation and regeneration of hCEnCs. Cultured hCEnCs were treated with Y-27632, sovesudil, or PHP-0961 for 24 h. Cellular responses, including cell viability, cytotoxicity, proliferation, and Ki67 expression with ROCK inhibitors were evaluated. We also evaluated wound healing and cell adhesion assays. Porcine corneas were used ex vivo to evaluate the effects of Y-27632, sovesudil, and PHP-0961 on wound healing and regeneration. We performed live/dead cell assays and immunofluorescence staining for SRY (sex determining region Y)-box 2 (SOX2), β-catenin, and ZO-1 on porcine corneas after ROCK inhibitor treatments. Cell viability, cell proliferation rate, and the number of Ki67-positive cells were higher in Y-27632, sovesudil and PHP-0961 treated cells compared to the control. There was no difference in LDH cytotoxicity test between any groups. Cells treated with Y-27632, sovesudil and PHP-0961 showed faster migration, wound healing, and cell adhesion. In the porcine ex vivo experiments, wound healing, the number of live cells, and SOX2-positive cells were higher in Y-27632, sovesudil and PHP-0961 treated corneas. In all experiments, sovesudil and PHP-0961, the novel ROCK inhibitors, were equal or superior to the results of the ROCK inhibitor positive control, Y-27632. In conclusion, sovesudil and PHP-0961, novel ROCK inhibitors have the capacity to regenerate hCEnCs by enhancing cell proliferation and adhesion between cells.

Effect of Head Trauma-Related Deaths on Corneal Endothelial Cell Loss in Eye Bank Donors.

The purpose of this study was to examine the effect of head trauma-related deaths on corneal endothelial cell density (ECD) in eye bank donors. This is a retrospective study of 287 corneas from donors with causes of death secondary to motor vehicle accident with sustained head trauma (n = 50), gunshot wound to the head (n = 138), fall with sustained head trauma (n = 2), and non-head-related traumatic causes of death (n = 97). Donors older than age 50 years were excluded due to concern for undiagnosed Fuchs endothelial dystrophy as a potential confounder for the cause of endothelial cell loss. Donor characteristics, ECD, and focal endothelial cell loss on specular microscopy were compared between the groups. Donors in the head trauma and nonhead trauma groups were matched by age; there were 42 age-matched donors in both groups. Age and ECD were negatively correlated (Pearson correlation coefficient = -0.57). Death-to-preservation time was not significantly different between the 2 groups ( P value = 0.59). The mean ECD in the head trauma group was 2859 ± 370 cells/mm 2 and 3041 ± 464 cells/mm 2 in the nonhead trauma group. The head trauma group had a lower ECD (178 ± 70 cells/mm 2 , P value = 0.013). After matching for age, the difference in ECD between the 2 groups was -94 ± 82 cells/mm 2 ( P value = 0.26). The adjusted odds of having focal endothelial cell loss was not statistically significant ( P value = 0.50) between the groups. After statistical adjustments, there were no differences between the head trauma and nonhead trauma groups.

Minimally Invasive Glaucoma Surgery: Safety of Individual Devices.

Primary open-angle glaucoma progression in those already on maximal medical therapy has traditionally been treated with trabeculectomy, a surgical procedure that carries a high degree of morbidity. In the last few decades, significant advances have been made in the field of minimally invasive glaucoma surgery (MIGS) devices, which aim to defer or prevent trabeculectomy via less arduous surgical techniques in certain types of glaucoma. Although reviews have been published examining the efficacy of various MIGS techniques, no article synthesises the comparative safety of all available devices. We performed a literature review examining the safety of MIGS devices. Fifteen devices were included, variously attempting to increase aqueous outflow through the trabecular meshwork or the suprachoroidal space, shunting into the subconjunctival space, or reducing aqueous production through ciliary body ablation. Notably, the earliest product attempting to increase outflow to the suprachoroidal space, Alcon's CyPass Micro-Stent, was withdrawn from the market due to concerns regarding increased corneal endothelial cell loss at five years post-implantation. All other devices were described as well-tolerated, with the most common adverse effects including hyphaema, intraocular pressure spikes, and device migration or obstruction. MIGS devices are purported to be uniformly safe, and many studies report no statistically significant increased complications beyond those associated with cataract surgery alone. It is important to note, however, the generally poor quality of current studies, with a dearth of randomised, or even prospective, data, and a large proportion of studies funded by device producers.

Comparative evaluation of the results of phacoemulsification using domestic and foreign viscoelastics

BACKGROUND: Phacoemulsification, being the safest technique, is the golden standard of cataract surgery worldwide. However, as any surgery, it is accompanied by inevitable damage to intraocular structures. The most prevalent among them is the loss of corneal endothelial cells. In order to prevent these complications, various viscoelastics with particular features and characteristics are widely used.&#x0D; AIM: To compare the anatomical and functional state of ocular structures after standard phacoemulsification with monofocal posterior chamber intraocular lens (IOL) implantation using domestic (Kogevisc and Adgevisc) and foreign (Viscoat and Amvisc Plus) viscoelastics.&#x0D; MATERIALS AND METHODS: 60 cataract patients (60 eyes) were included in the clinical study, which were divided into two equal groups. In the first group (30 patients, 30 eyes), Adgevisc and Kogevisc (Solofarm, Russia) were used during the procedure. The mean age of the patients was 66 11 years. In the second group (30 patients, 30 eyes), Viscoat (Alcon) and Amvisc Plus (BauschLomb) were used. The mean age of the patients was 69.03 10.44 years. All patients underwent phacoemulsification with the implantation of the AcrySof IOL (model SA60AT, Alcon) according to the standard technique. Visual acuity, IOP level, CCT, corneal endothelial cell density were assessed. All studies were performed before surgery, the next day, 7 days and 1 month after surgery.&#x0D; RESULTS: In patients of the second group, on the 1st (p 0.05) and 7th day (p 0.01) after surgery, a statistically significant increase in IOP was revealed compared to the first group. The central cornea thickness in the early postoperative period was higher in patients of the second group, however, it was not statistically significant. The loss of corneal endothelial cells 1 month after surgery was 8.5 7.0% (p 0.01) in the first group and 6.6 6.4% in the second group (p 0.01). The mean value of endothelial cell loss in patients of the first group was higher, however, it was not statistically significant. The best corrected visual acuity in both groups at all stages of follow-up after surgery (days 1, 7 and 30) was comparable, there was no significant difference between the groups.&#x0D; CONCLUSIONS: The clinical efficacy of domestic adhesive and cohesive viscoelastics Adgevisc and Kogevisc (Solofarm, Russia) in phacoemulsification using the soft-shell technique is comparable to the foreign analogues Viscoat (Alcon) and Amvisc Plus (Bausch Lomb), which is confirmed by the absence of statistically significant differences in the studied parameters of the postoperative state of ocular structures and explained by their similar composition, molecular weight and viscosity.

Corneal endothelium, retinal nerve fiber layer, ganglion cell complex, and perimetry measurements in normal eyes and those with primary open-angle glaucoma.

Corneal endothelial cell (CEC) loss in glaucoma can be attributed to the direct compressive effect of elevated intraocular pressure. Herein, we aimed to evaluate specular microscopic changes in CEC count and morphology in correlation to retinal nerve fiber layer (RNFL) changes detected by spectral-domain optical coherence tomography (SD-OCT) in early and advanced primary open-angle glaucoma (POAG). This descriptive-analytical study involved patients with medically controlled POAG versus non-glaucomatous patients of the same age group. Specular microscopy, visual field testing, and SD-OCT of the RNFL and macular ganglion cell complex (GCC) were performed. Eyes with POAG were further subcategorized into early and advanced stages. The study included 130 eyes of 130 participants; 70 were eyes with POAG (40 eyes with early-stage POAG, 30 eyes with advanced-stage POAG), and 60 were healthy eyes. The groups were comparable regarding mean age and sex. No significant difference was found in corneal parameters between healthy eyes, eyes with early POAG, and eyes with advanced POAG (all P > 0.05). In eyes with early-stage POAG, a significant negative correlation was found between the coefficient of variation (CV) and superior RNFL thickness (r = - 0.5; P = 0.018), and between the percentage of hexagonal cells (hexagonality) and vertical cup-to-disc ratio (r = - 0.43; P = 0.035). A significant positive correlation was found between hexagonality and superior as well as inferior RNFL thickness (r = + 0.53; P = 0.008 and r = + 0.50; P = 0.015, respectively). However, in the advanced glaucomatous eyes, no significant correlation was found between RNFL thickness and CEC parameters. CEC parameters were not affected in eyes with early or advanced POAG compared with healthy eyes, despite a significant thinning of RNFL and macular GCC. In eyes with early-stage POAG, a significant correlation was found between morphological characteristics of CECs, such as CV and hexagonality, with superior and inferior RNFL thickness in the optic nerve head on SD-OCT images. Future longitudinal studies with larger sample sizes are needed to verify our results.

Single Administration of Intracameral Bimatoprost Implant 10µg in Patients with Open-Angle Glaucoma or Ocular Hypertension.

IntroductionThis study evaluated the intraocular pressure (IOP)-lowering efficacy and safety of a single intracameral administration of bimatoprost implant 10 µg in adults with open-angle glaucoma or ocular hypertension.MethodsTwo identically designed, randomized, 20-month, parallel-group, phase 3 clinical trials (one study eye/patient) compared three administrations of 10- or 15-µg bimatoprost implant (day 1, weeks 16 and 32) with twice-daily topical timolol maleate 0.5%. An open-label, 24-month, phase 1/2 clinical trial compared one or two implants administered in the study eye with once-daily topical bimatoprost 0.03% in the fellow eye. Separate analyses of the pooled phase 3 and phase 1/2 study datasets evaluated outcomes in the 10-µg bimatoprost implant and comparator treatment arms after a single implant administration, up to the time of implant re-administration or rescue with IOP-lowering medication.ResultsIn the phase 3 studies, 10-µg bimatoprost implant single administration demonstrated IOP reductions (hour 0) of 4.9–7.0 mmHg through week 15 from a mean (standard deviation, SD) baseline IOP of 24.5 (2.6) mmHg (n = 374); IOP in the topical timolol BID group was reduced by 6.0–6.3 mmHg from a mean (SD) baseline IOP of 24.5 (2.6) mmHg (n = 373). In the phase 1/2 study (n = 21), median time to use of additional IOP-lowering treatment (Kaplan–Meier analysis) was 273 days (approximately 9 months), and 5 of 21 enrolled patients (23.8%) required no additional IOP-lowering treatment up to 24 months after single administration. In each study, after a single implant administration there were no reports of corneal edema, corneal endothelial cell loss, or corneal touch, and no patients had 20% or greater loss in corneal endothelial cell density.ConclusionsBimatoprost implant single administration lowers IOP and has a favorable safety profile. Additional studies are needed to further evaluate the duration of effect and factors predicting long-term IOP lowering after a single implant administration.Trial registration numbersClinicalTrials.gov NCT02247804, NCT02250651, and NCT01157364.Supplementary InformationThe online version contains supplementary material available at 10.1007/s40123-022-00527-6.

Comparison of pre-chop technique using a reverse chopper and classic stop-and-chop technique in the treatment of high myopia associated with nuclear cataract

BackgroundTo evaluate the safety and efficacy of the pre-chop technique using a novel reverse chopper vs. the classic stop-and-chop technique in phacoemulsification for patients with high myopia and associated grade III–IV nuclear cataracts.MethodsIn this prospective cohort study, a total of 44 consecutive patients (44 eyes) with grade III–IV nuclear cataracts who were admitted to our hospital for cataract surgery between March 2018 and September 2018 were enrolled. All patients had ocular axial length > 27 mm and myopic refraction more than -10 diopters. Patients were randomly divided into a pre-chop group and stop-and-chop group using a randomization table. Nucleus splitting was performed surgically in both groups using either the pre-chop technique with reverse chopper or the classic stop-and-chop technique.ResultsPostoperative visual acuity was significantly improved in both groups compared with preoperative values. Significantly better visual acuity, lower degree of corneal edema and lower rates of corneal endothelial cell loss were observed in the pre-chop group compared to those in the classic stop-and-chop group. No complications were reported in either group.ConclusionsIn treating patients with high myopia associated with grade III–IV cataracts, the pre-chop technique using a reverse chopper reduces damage to corneal endothelial cells and improves visual acuity better than the classic stop-and-chop technique.

Corneal Endothelial Cell Loss in Patients After Minimally Invasive Glaucoma Surgery: Current Perspectives.

Minimally invasive glaucoma surgery (MIGS) is a rapidly expanding category of surgical glaucoma treatment options that offer a superior safety profile compared with traditional approaches for reducing intraocular pressure. However, MIGS may cause corneal endothelial cell loss; therefore, it has been receiving increasing attention. This systematic review aimed to evaluate and compare the rate and degree of corneal endothelial loss after MIGS. First, this paper presents an overview of the theoretical effectiveness of MIGS, the fundamental aspects regarding the roles of endothelial cells, and the effect of cataract surgery on the quality and count of endothelial cells. Further, we detail the various surgical techniques involved in MIGS, the development of these techniques over the time, and clinical aspects to consider with respect to the endothelial cell count. We discuss in detail the COMPASS-XT study, which was based on data collected over 5 years, reported that withdrawal of the CyPass Micro-Stent (Alcon Laboratories) yielded increased corneal endothelial cell loss. Generally, MIGS procedures are considered safe, with the incidence of complications ranging from 1% to 20% depending on the surgery type; however, there is still need for studies with longer follow-up. Thus, an adequate count of endothelial cells in the central cornea portion is recommended as necessary for candidate patients for MIGS.

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.

Comparison of effective phacoemulsification time and corneal endothelial cell loss using three different ultrasound frequencies: A randomized controlled trial.

Purpose:Comparison of three ultrasound (US) frequencies for phacoemulsification of hard cataracts to determine a frequency that makes phacoemulsification more efficacious and safer.Methods:A randomized controlled trial was undertaken at a medical college and hospital. In total, 207 patients with grade 5.6–6.9 (LOCS III) senile cataract were randomized into three groups. Group I underwent phacoemulsification with 28-kHz frequency, group II with 42-kHz frequency, and group III with 53-kHz frequency. The effective phacoemulsification time (EPT) and estimated fluid usage (EFU) were compared intraoperatively. The endothelial cell parameters were analyzed for 6 months.Results:The groups were matched for age (P = 0.467), gender (P = 0.497), nuclear grade (P = 0.321), and anterior chamber depth (P = 0.635). The EPT and EFU were significantly lower in group III, compared to group II and group I, with P < 0.0001 and P < 0.0001, respectively. Postoperatively, the endothelial cell density (ECD) was significantly higher in group III at 1 month (P < 0.0001), 3 months (P < 0.0001), and 6 months (P < 0.0001). The percentages of ECD loss were also significantly lower in group III; the difference was statistically significant (P < 0.0001) up to 6 months postoperativelyConclusion:Higher frequency ultrasound was associated with a lower EPT and EFU as well as better endothelial preservation than lower frequencies in hard cataracts.

Clinical characteristics of virus-related uveitic secondary glaucoma: focus on cytomegalovirus and varicella zoster virus

BackgroundWe aimed to analyze the clinical characteristics of secondary glaucoma related to cytomegalovirus (CMV)- and varicella zoster virus (VZV)-positive uveitis.MethodsIn this retrospective study, we enrolled patients with anterior uveitic secondary glaucoma. All the patients underwent aqueous and serum analyses for viral antibody through enzyme-linked immunosorbent assay. Among the 60 included patients, 22 had CMV-negative Posner-Schlossman syndrome (CMV-negative PSS), 25 had CMV-positive PSS, and 13 had VZV-positive anterior uveitis secondary glaucoma (VZV-AUSG). We evaluated the following main indicators: age, disease duration, intraocular pressure (IOP), cup-to-disc ratio, best corrected visual acuity (BCVA), corneal endothelial cell (CEC) count, ocular morphological changes, and medical treatments.ResultsWe found that 53.2% (25/47) patients with PSS were CMV-positive. Patients with CMV-positive PSS had a larger cup-to-disc ratio (p = .043), lower CEC density (p = .017), more severe CEC loss (p < .001), and more iris depigmentation (p = .006) than CMV-negative PSS patients. Compared with patients with CMV-positive PSS, those with VZV-AUSG were older (p = .003), presented a higher IOP (p = .015), and had poorer BCVA (p < .001). Patients with CMV-positive PSS and VZV-AUSG all accepted ganciclovir treatment, and those with CMV-positive PSS used fewer antiglaucoma agents simultaneously compared with CMV-negative PSS (p = .005) and VZV-AUSG (p < .001). All three groups had a comparable proportion of patients requiring antiglaucoma surgery.ConclusionsWe observed some distinctive clinical features in CMV-positive PSS compared with CMV-negative PSS. Further, we found that patients with VZV-AUSG presented with a higher IOP and worse visual acuity, and required more antiglaucoma medication than those with CMV-positive PSS.

CyPass microstent trimming with special cutting forceps : Video article

A CyPass®-microstent (Alcon, Fort Worth, TX, USA) extending too far into the anterior chamber should be trimmed as close as possible to the scleral spur to avoid progression of endothelial cell reduction. After CyPass implantation, if there is a significant loss of corneal endothelial cells due to the Cypass microstent extending too far into the anterior chamber, trimming or removal of the CyPass stent is necessary. There are no contraindications. As shown in our video, which is available online, aspecial cutter (19 Gauge Ahmed Micro Stent Cutter, MicroSurgical Technology Inc, Redmond, WA, USA) is inserted into the anterior chamber via a 1.5-mm wide corneal paracentesis made directly opposite to the CyPass stent. It is then possible to trim the anterior part of the stent. The severed fragment is removed using the head of the forceps. Finally, the previously inserted viscoelastic agent can be aspirated and the paracentesis can be hydrated. After the surgery vision testing as well as control of intraocular pressure and location of the stent are carried out. Antibiotic eye drops and ointment are postoperatively applied. There is still no standardized protocol for the procedure to trim the CyPass stent. Performing the trimming in our clinic using the procedure described here has so far not led to any complications. Long-term data about the development of the endothelial cell measurement after CyPass trimming are not yet available.

Pathogenic Role of Endoplasmic Reticulum Stress in Diabetic Corneal Endothelial Dysfunction.

PurposeProgressive corneal edema and endothelial cell loss represent the major corneal complications observed in diabetic patients after intraocular surgery. However, the underlying pathogenesis and potential treatment remain incompletely understood.MethodsWe used streptozotocin-induced type 1 diabetic mice and db/db type 2 diabetic mice as diabetic animal models. These mice were treated with the endoplasmic reticulum (ER) stress agonist thapsigargin; 60-mmHg intraocular pressure (IOP) with the ER stress antagonist 4-phenylbutyric acid (4-PBA); mitochondria-targeted antioxidant SkQ1; or reactive oxygen species scavenger N-acetyl-l-cysteine (NAC). Corneal thickness and endothelial cell density were measured before and after treatment. Human corneal endothelial cells were treated with high glucose with or without 4-PBA. The expression of corneal endothelial- and ER stress–related genes was detected by western blot and immunofluorescence staining. Mitochondrial bioenergetics were measured with an Agilent Seahorse XFp Analyzer.ResultsIn diabetic mice, the appearance of ER stress preceded morphological changes in the corneal endothelium. The persistent ER stress directly caused corneal edema and endothelial cell loss in normal mice. Pharmacological inhibition of ER stress was sufficient to mitigate corneal edema and endothelial cell loss in both diabetic mice after high IOP treatment. Mechanistically, inhibiting ER stress ameliorated the hyperglycemia-induced mitochondrial bioenergetic deficits and improved the barrier and pump functional recovery of the corneal endothelium. When compared with NAC, 4-PBA and SkQ1 exhibited better improvement of corneal edema and endothelial cell loss in diabetic mice.ConclusionsHyperglycemia-induced ER stress contributes to the dysfunction of diabetic corneal endothelium, and inhibiting ER stress may offer therapeutic potential by improving mitochondrial bioenergetics.

Identification of novel therapeutic targets for Fuchs' endothelial corneal dystrophy based on gene bioinformatics analysis.

Fuchs’ endothelial corneal dystrophy (FECD) is a disease where progressive visual impairment occurs by the thickening of the Descemet’s membrane and the gradual degeneration and loss of corneal endothelial cells. This study aimed to investigate the key changes in gene expression associated with FECD and explore potential biomarkers and new therapeutic strategies for FECD. To explore the potential therapeutic targets of FECD, we downloaded the gene expression dataset GSE171830 from the Gene Expression Omnibus (GEO) database. A total of 303 differentially expressed genes (DEGs) were identified by the limma package. The enriched Gene Ontology (GO) annotations and the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways of DEGs mostly included the extracellular matrix organization, collagen-containing extracellular matrix, and the structural constituents of the extracellular matrix. Fifteen hub genes from the most significant module were ascertained by Cytoscape. Both collagen-containing extracellular matrix and extracellular matrix hit to ANXA1, VCAN, GPC3, TNC, IGFBP7, MATN3, and SPARCL1 genes in the GO cellular components. Among these genes, the expression of SPARCL1 was down-regulated in the FECD samples, whereas the expression of GPC3, MATN3, IGFBP7, TNC, VCAN, and ANXA1 was up-regulated in the FECD samples. Gene set enrichment analysis (GSEA) plots showed that among the 20,937 genes, SPARCL1 played an important role in three pathways, cytokine-cytokine receptor interaction, the TGF-beta signaling pathway, and antigen processing and presentation. The top three pathways enriched by the GPC3, MATN3, IGFBP7, TNC, VCAN, and ANXA1 genes were those for cytokine-cytokine receptor interaction, TGF-beta signaling, and RIG-I-like receptor signaling. In conclusion, the DEGs identified here might assist clinicians in understanding the pathogenesis of FECD. Furthermore, these identified biomarkers might serve as potential therapeutic targets for the treatment of FECD.