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Introduction: To evaluate the anterior chamber (AC) inflammation in the early postoperative period after cataract surgery and before Descemet membrane endothelial keratoplasty (DMEK) by quantifying oxidative stress and inflammatory mediators in aqueous humor of patients with Fuchs' endothelial corneal dystrophy (FECD). Methods: In this prospective single-center study, 15 patients with FECD underwent cataract surgery and DMEK in a two-stage procedure. Aqueous humor was collected from the AC at the beginning of cataract surgery and 3 months later at the beginning of DMEK. In the control group, which consisted of 15 age-matched phakic patients without FECD, aqueous humor was only collected at the beginning of cataract surgery. Mediators of postoperative inflammation including TNF-α, VEGF, IL-2, IL-1 β, IL-4, IL-5, IL-6, IL-8, IL-10, IL-12, GM-CSF, IFN-γ, CXCL5/ENA-78, FGF-basic, G-CSF, IL-1-α, IL-1-ra, IL-17, CCL2/MCP-1, CCL3/MIP-1a, CCL4/MIP-1b, TPO, TGF-β-1, TGF-β-2, and TGF-β-3 concentrations were measured using a Multiplex-Array-System. Results: The concentration of TNF-α (p = 0.021), IL-6 (p = 0.005), IL-8 (p = 0.001), CXCL5/ENA78 (p = 0.002), CCL2/MCP-1 (p = 0.001) and CCL4/MIP-1b (p = 0.037) were significantly higher 3 months after cataract surgery at the beginning of DMEK compared to control group at beginning of cataract surgery. The levels of IL-2, IL-5, IL-8, IL-10, and IL-1-α were significantly higher in phakic eyes in the control group (p < 0.05) before cataract surgery. Conclusions: The present study indicates significantly increased proinflammatory cytokines 3 months after cataract surgery in eyes with FECD. Our findings suggest postoperative inflammation in the AC up to 3 months after cataract surgery. Therefore, it may be reasonable to combine cataract surgery with DMEK in cataract patients with FECD. [ABSTRACT FROM AUTHOR]

Abstract Fuchs’ endothelial corneal dystrophy (FECD) is a common sight-threatening condition characterised by pathological changes in the posterior cornea. Here we report observations by light, transmission and volume scanning electron microscopy on changes in the endothelium and matrix associated with the characteristic deformations of Descemet’s membrane, termed guttae. Specimens were archived full-thickness human corneal tissue, removed during graft surgery, that had been fixed, stained and embedded by conventional processing methods for examination by transmission electron microscopy more than 40-years previously. Intact archived samples can be extremely valuable where, as with FECD, new cell-based methods of therapy now avoid excision of the full cornea thickness and any tissue excised is inferior for study. Volume electron microscopy, in particular serial block face scanning electron microscopy (SBF SEM), employing backscatter electron detection from resin-embedded specimens, has become an invaluable technique for 3D imaging of biological samples. However, archived specimens are normally considered unsuitable for imaging as conventional processing methods generate low backscatter electron yield. To overcome this for SBF SEM, we subjected epoxy resin-embedded specimens to de-plastination, then applied additional contrasting agents, uranyl acetate and lead acetate, prior to re-embedding. Selected regions of interest in the new resin blocks were examined in a scanning electron microscope equipped for SBF SEM and serial image datasets acquired. Enhanced contrast enabled 3D reconstruction of endothelium and guttae in Descemet’s membrane over large tissue volumes.

Fuchs' endothelial corneal dystrophy (FECD) is a common sight-threatening condition characterised by pathological changes in the posterior cornea. Here we report observations by light, transmission and volume scanning electron microscopy on changes in the endothelium and matrix associated with the characteristic deformations of Descemet's membrane, termed guttae. Specimens were archived full-thickness human corneal tissue, removed during graft surgery, that had been fixed, stained and embedded by conventional processing methods for examination by transmission electron microscopy more than 40-years previously. Intact archived samples can be extremely valuable where, as with FECD, new cell-based methods of therapy now avoid excision of the full cornea thickness and any tissue excised is inferior for study. Volume electron microscopy, in particular serial block face scanning electron microscopy (SBF SEM), employing backscatter electron detection from resin-embedded specimens, has become an invaluable technique for 3D imaging of biological samples. However, archived specimens are normally considered unsuitable for imaging as conventional processing methods generate low backscatter electron yield. To overcome this for SBF SEM, we subjected epoxy resin-embedded specimens to de-plastination, then applied additional contrasting agents, uranyl acetate and lead acetate, prior to re-embedding. Selected regions of interest in the new resin blocks were examined in a scanning electron microscope equipped for SBF SEM and serial image datasets acquired. Enhanced contrast enabled 3D reconstruction of endothelium and guttae in Descemet's membrane over large tissue volumes. [ABSTRACT FROM AUTHOR]

Abstract This study aims to evaluate the applicability of the high-resolution WaveFront Phase Imaging Sensor (WFPI) in eyes with Fuchs’ Endothelial Corneal Dystrophy (FECD) through qualitative and quantitative analysis using a custom-designed Automatic Guttae Detection Method (AGDM). The ocular phase was measured using the t $$\cdot$$ · eyede aberrometer and then was processed to obtain its High-Pass Filter Map (HPFM). The subjects were pathological and healthy patients from the Fundación Jiménez-Díaz Hospital (Madrid, Spain). The AGDM was developed and applied in pupils with 3 and 5 mm of diameter. A set of metrics were extracted and evaluated like the Root-Mean-Square error (RMS), Number of guttae, Guttae Area, and Area of Delaunay Triangulation (DT). Finally, a Support Vector Machine (SVM) model was trained to classify between pathological and healthy eyes. Quantitatively, the HPFM reveals a dark spots pattern according to the ophthalmologist’s description of the slit-lamp examination of guttae distribution. There were significant statistical differences in all the metrics when FECD and Healthy groups were compared using the same pupil size; but comparing both pupil sizes for the same group there were significant differences in most of the variables. This sensor is a value tool to objectively diagnose and monitor this pathology through wavefront phase changes.

To report a case of keratoconus with early-onset Fuchs’ endothelial corneal dystrophy (FECD) changes in identical twins. A case report. A 22-year-old female had ocular findings of corneal protrusion, Fleischer’s ring, and corneal endothelium pigment dusting in both eyes. Corneal tomography showed increased corneal power and reduced thickness, and specular microscopy revealed loss of endothelial cells, the presence of a few non-confluent guttata, pleomorphism, and polymegathism in both eyes. Based on these findings, she was diagnosed as keratoconus with early grade FECD changes. Her family history revealed that she has an identical twin sister. Examination of her twin sister showed similar findings suggesting keratoconus with early grade FECD. This case report provides further evidence for the role of genetics in the development of keratoconus. Furthermore, it shows the diagnostic, monitoring, and treatment challenges due to the combination of two different diseases.

PurposeWe sought to define the role of Wwtr1 in murine ocular structure and function and determine the role of mechanotransduction in Fuchs' endothelial corneal dystrophy (FECD), with emphasis on interactions between corneal endothelial cells (CEnCs) and Descemet's membrane (DM).MethodsA Wwtr1 deficient mouse colony was established, and advanced ocular imaging, atomic force microscope (AFM), and histology/immunofluorescence were performed. Corneal endothelial wound healing was assessed using cryoinjury and phototherapeutic keratectomy in Wwtr1 deficient mice. Expression of WWTR1/TAZ was determined in the corneal endothelium from normal and FECD-affected patients; WWTR1 was screened for coding sequence variants in this FECD cohort.ResultsMice deficient in Wwtr1 had reduced CEnC density, abnormal CEnC morphology, softer DM, and thinner corneas versus wildtype controls by 2 months of age. Additionally, CEnCs had altered expression and localization of Na/K-ATPase and ZO-1. Further, Wwtr1 deficient mice had impaired CEnC wound healing. The WWTR1 transcript was highly expressed in healthy human CEnCs comparable to other genes implicated in FECD pathogenesis. Although WWTR1 mRNA expression was comparable between healthy and FECD-affected patients, WWTR1/TAZ protein concentrations were higher and localized to the nucleus surrounding guttae. No genetic associations were found in WWTR1 and FECD in a patient cohort compared to controls.ConclusionsThere are common phenotypic abnormalities seen between Wwtr1 deficient and FECD-affected patients, suggesting that Wwtr1 deficient mice could function as a murine model of late-onset FECD. Despite the lack of a genetic association between FECD and WWTR1, aberrant WWTR1/TAZ protein subcellular localization and degradation may play critical roles in the pathogenesis of FECD.

This study aims to evaluate the applicability of the high-resolution WaveFront Phase Imaging Sensor (WFPI) in eyes with Fuchs' Endothelial Corneal Dystrophy (FECD) through qualitative and quantitative analysis using a custom-designed Automatic Guttae Detection Method (AGDM). The ocular phase was measured using the t · eyede aberrometer and then was processed to obtain its High-Pass Filter Map (HPFM). The subjects were pathological and healthy patients from the Fundación Jiménez-Díaz Hospital (Madrid, Spain). The AGDM was developed and applied in pupils with 3 and 5 mm of diameter. A set of metrics were extracted and evaluated like the Root-Mean-Square error (RMS), Number of guttae, Guttae Area, and Area of Delaunay Triangulation (DT). Finally, a Support Vector Machine (SVM) model was trained to classify between pathological and healthy eyes. Quantitatively, the HPFM reveals a dark spots pattern according to the ophthalmologist's description of the slit-lamp examination of guttae distribution. There were significant statistical differences in all the metrics when FECD and Healthy groups were compared using the same pupil size; but comparing both pupil sizes for the same group there were significant differences in most of the variables. This sensor is a value tool to objectively diagnose and monitor this pathology through wavefront phase changes. [ABSTRACT FROM AUTHOR]

Purpose: Report a case where the patient desired spectacle independence after phacoemulsification and Descemet membrane endothelial keratoplasty (DMEK) due to Fuchs’ endothelial dystrophy. Observations: A 52-year-old female presented with corrected distance visual acuity (CDVA) of 20/40 in both eyes with low ametropia. Slit lamp examination revealed corneal edema 1+/4+, guttae, and nuclear cataract 2+/4+ in both eyes. First, given the diagnostic suspicion of Fuchs’ endothelial corneal dystrophy and cataracts, phacoemulsification with monofocal toric intraocular lens (IOL) implantation combined with DMEK was performed in both eyes. Postoperatively, the patient was not satisfied with her near vision. Therefore, a supplementary trifocal sulcus IOL was implanted into the right eye. At 30 days postoperatively, the uncorrected distance visual acuity (UDVA) was 20/20 and the uncorrected near visual acuity (UCNVA) was J1, with clear cornea, centered IOL. Conclusions and importance: This is the first report of supplementary trifocal IOL implantation in a pseudophakic patient with a history of DMEK. This afforded spectacle-independence at all distances with high patient satisfaction. This procedure is safe, predictable, and reversible.

(1) Background: Patients with Fuchs' endothelial corneal dystrophy (FECD) may have coexisting cataracts and, therefore, may require a cataract surgery, which poses challenges due to potential endothelial cell damage. FECD is a degenerative eye disease of unclear etiology, with inflammatory cytokines maybe playing an important role in its development and progression. The present study aimed to investigate the cytokine profile in the aqueous humor of FECD eyes with cataract. (2) Methods: Fifty-two patients were included in the study, 26 with FECD + cataract and 26 with cataract as a control group. Samples of the aqueous humor were analyzed for pro- and anti-inflammatory cytokines using a Bio-Plex 200 system. (3) Results: Interleukin 1 receptor antagonist (IL-1Ra) and interleukin IL-8 levels were significantly higher in the aqueous humor of FECD + cataract patients compared to the control/cataract group. Moreover, the levels of anti-inflammatory IL-10 showed a strong trend to be higher in the FECD + cataract group compared to the control group. In contrast, there were no statistically significant differences in IL-1β, IL-6, IL-4, IL-10, IL-13, IL-17A, and tumor necrosis factor TNF-α between the groups. (4) Conclusions: Presented research contributes to a better understanding of FECD pathogenesis. Elevated levels of IL-1Ra and IL-8 may serve as a defense mechanism in people with FECD and coexisting cataract. [ABSTRACT FROM AUTHOR]

Stefan Futterknecht,1,2 Eleftherios Chatzimichail,1 Konstantin Gugleta,1,3 Georgios D Panos,4,5,&ast; Zisis Gatzioufas1,3,&ast; 1Department of Ophthalmology, University Hospital of Basel, Basel, Switzerland; 2Institute of Molecular and Clinical Ophthalmology Basel, Basel, Switzerland; 3Department of Ophthalmology, School of Medicine, University of Basel, Basel, Switzerland; 4Department of Ophthalmology, Queen’s Medical Centre, Nottingham University Hospitals, Nottingham, UK; 5Division of Ophthalmology and Visual Sciences, School of Medicine, University of Nottingham, Nottingham, UK&ast;These authors contributed equally to this workCorrespondence: Georgios D Panos, Department of Ophthalmology, Queen’s Medical Centre, Nottingham University Hospitals, Derby Road, Lenton, Nottingham, NG7 2UH, UK, Tel +44 115 924 9924, Email gdpanos@gmail.comAbstract: The cornea, as the outermost layer of the eye, plays a crucial role in vision by focusing light onto the retina. Various diseases and injuries can compromise its clarity, leading to impaired vision. This review aims to provide a thorough overview of the pharmacological properties, therapeutic potential and associated risks of Rho-associated protein kinase (ROCK) inhibitors in the management of corneal diseases. The article focuses on four key ROCK inhibitors: Y-27632, fasudil, ripasudil, and netarsudil, providing a comparative examination. Studies supporting the use of ROCK inhibitors highlight their efficacy across diverse corneal conditions. In Fuchs’ endothelial corneal dystrophy, studies on the application of Y-27632, ripasudil, and netarsudil demonstrated noteworthy enhancements in corneal clarity, endothelial cell density, and visual acuity. In pseudophakic bullous keratopathy, the injection of Y-27632 together with cultured corneal endothelial cells into the anterior chamber lead to enhanced corneal endothelial cell density and improved visual acuity. Animal models simulating chemical injury to the cornea showed a reduction of neovascularization and epithelial defects after application of fasudil and in a case of iridocorneal endothelial syndrome netarsudil improved corneal edema. Addressing safety considerations, netarsudil and ripasudil, both clinically approved, exhibit adverse events such as conjunctival hyperemia, conjunctival hemorrhage, cornea verticillata, conjunctivitis, and blepharitis. Monitoring patients during treatment becomes crucial to balancing the potential therapeutic benefits with these associated risks. In conclusion, ROCK inhibitors, particularly netarsudil and ripasudil, offer promise in managing corneal diseases. The comparative analysis of their pharmacological properties and studies supporting their efficacy underscore their potential therapeutic significance. However, ongoing research is paramount to comprehensively understand their safety profiles and long-term outcomes in diverse corneal conditions, guiding their optimal application in clinical practice.Keywords: rho kinase inhibitors, cornea, corneal diseases, corneal dystrophies, Fuchs’ endothelial corneal dystrophy, corneal transplantation

Introduction: Fuchs endothelial corneal dystrophy (FECD) is the leading cause of corneal blindness in developed countries. Corneal endothelial cells in FECD are susceptive to oxidative stress, leading to mitochondrial dysfunction and cell death. Oxidative stress causes many forms of cell death including parthanatos, which is characterized by translocation of apoptosis-inducing factor (AIF) to the nucleus with upregulation of poly (ADP-ribose) polymerase 1 (PARP-1) and poly (ADP-ribose) (PAR). Although cell death is an important aspect of FECD, previous reports have often analyzed immortalized cell lines, making the evaluation of cell death difficult. Therefore, we established a new in vitro FECD model to evaluate the pathophysiology of FECD. Methods: Corneal endothelial cells were derived from disease-specific induced pluripotent stem cells (iPSCs). Hydrogen peroxide (H2O2) was used as a source for oxidative stress to mimic the pathophysiology of FECD. We investigated the responses to oxidative stress and the involvement of parthanatos in FECD-corneal endothelial cells. Results: Cell death ratio and oxidative stress level were upregulated in FECD with H2O2 treatment compared with non-FECD control, indicating the vulnerability of oxidative stress in FECD. We also found that intracellular PAR, as well as PARP-1 and AIF in the nucleus were upregulated in FECD. Furthermore, PARP inhibition, but not pan-caspase inhibition, rescued cell death, DNA double-strand breaks, mitochondrial membrane potential depolarization and energy depletion, suggesting that cell death was mainly due to parthanatos. Conclusions: We report that parthanatos may be involved in the pathophysiology of FECD and targeting this cell death pathway may be a potential therapeutic approach for FECD.

Purpose: This study was performed to determine the demographic profile and clinical characteristics in patients with Fuchs' endothelial corneal dystrophy (FECD) reporting to a tertiary eye care center in India. It is a retrospective, single-center, observational study. Methods: The study included 280 patients (559 eyes) diagnosed with FECD presenting between January 2013 and December 2020. The data was collected from the electronic medical record system of the institute. Patient data included demographic features, clinical characteristics, investigations, and surgical interventions. Results: The mean age of the patients was 62 years. Late-onset FECD (95.7%) was more common than early-onset FECD (4.3%). Male: female ratio for late-onset FECD and early-onset FECD was 1:1.65 and 3:1, respectively. More than one-third of the patients had associated systemic history. Preexisting ocular diseases were seen in 5.9% of eyes. Blurring of vision was seen in 383 eyes (68.5%), 13 eyes (2.1%) had glare, and 163 eyes (29.2%) were asymptomatic. A total of 113 surgical interventions were done in 108 eyes (including repeat transplants). Only cataract surgery was done in 40 (7.2%) eyes, whereas penetrating keratoplasty, Descemet stripping endothelial keratoplasty, and Descemet membrane endothelial keratoplasty without or with cataract surgery (sequential or triple procedure) were done in 12 (2.1%), 47 (8.4%), and 14 (2.5%) eyes, respectively. Conclusion: Patients with FECD present mostly during the sixth decade. Posterior lamellar keratoplasty is the most common transplant procedure being performed on FECD patients.

Purpose: To report late central graft detachment after repeat Descemet membrane endothelial keratoplasty (DMEK) without visual reduction. Observations: A 71-year-old patient with Fuchs’ endothelial corneal dystrophy received a DMEK in his left eye. At 11 month post-operatively, a subtotal graft detachment was noted. Due to increasing corneal edema with vision loss, the first DMEK was removed and a repeat-DMEK was performed. At four months post repeat-DMEK, the graft was fully adherent to the posterior stroma. There was no significant corneal edema, and the best corrected visual acuity was 20/25. At 16-months after repeat-DMEK, a central graft detachment was noted, but there was no concurrent corneal edema or any loss of visual acuity. The mean density of the central endothelial cells was measured at 842 cells/mm2. Given the lack of corneal edema, visual reduction or subjective visual complaint, the graft detachment was followed-up for up to 20-months post repeat-DMEK with no further intervention, where the central cornea remained clear. Conclusions and Importance: To our knowledge, this is the first report of a central repeat-DMEK graft detachment that occurred 16 months after surgery despite initial attachment. Interestingly, there was no concurrent corneal edema or vision reduction. We describe a potential mechanism for clear central cornea in the presence of a central graft detachment after repeat-DMEK.

Highlights: What is known? The 3D visualization system allows the surgeon to operate in a more comfortable position than a conventional microscope. Looking at the surgical field on a large, high-definition 3D screen has advantages for surgical assistance and instructional purposes. What is new? The 3D visualization system can be successfully used for DSO procedures. Learning curve is short, as there is no training time required for successful use of 3D visualization system. (1) Purpose: The aim was to analyze the outcomes of Descemet's membrane endothelial keratoplasty (DMEK) and Descemet stripping only (DSO) surgeries using a glasses-assisted NGENUITY® 3D visualization system (Alcon Laboratories, Fort Worth, TX, USA). (2) Methods: Five consecutive cases of DMEK surgery and four consecutive cases of DSO were performed using the NGENUITY® system in this prospective study carried out at the Arruzafa Hospital, Córdoba, Spain. Only one eye from each patient received surgery. Best corrected distance visual acuity (CDVA) using EDTRS charts, central corneal thickness using the Casia II optical coherence tomograph (Tomey Co., Nagoya, Japan), and endothelial cell count using the Tomey EM-4000 (Tomey Co., Nagoya, Japan) for DMEK cases or the Nidek CEM-530 (Nidek Co., Ltd., Gamagori, Japan) specular microscopes for DSO cases were recorded preoperatively and at 1 and 3 months postsurgery. (3) Results: DMEK cases included one male and four female subjects, with a mean age of 73.6 ± 9.5 years. Average improvement in CDVA 3 months after surgery was 0.46 ± 0.16 decimal. Average change in cell count between 1 and 3 months postsurgery was 360.75 ± 289.38 cells/mm2. DSO cases included four female subjects, with a mean age of 64.2 ± 9.7 years. The average improvement in CDVA 3 months after surgery was 0.09 ± 0.17 decimal. All cases also had phacoemulsification carried out. He average change in cell count between 1 and 3 months after surgery was 460 ± 515.69 cells/mm2. There were no associated complications during surgery or the follow-up period in any of the cases. (4) Conclusions: In addition to the known benefits of the use of a 3D visualization system during surgery, the present study shows that the system can be successfully used in both DMEK and DSO procedures with a very short learning curve for the surgeon. [ABSTRACT FROM AUTHOR]

Fuchs' endothelial corneal dystrophy (FECD) is the occurrence of corneal edema due to endothelial cell dystrophy. Descemet membrane endothelial keratoplasty (DMEK) is considered to be the gold standard of treatment. The aim of this study was to investigate the changes in the corneal epithelial thickness of FECD patients before and after DMEK and to compare these results with a healthy control cohort. In this retrospective analysis, 38 eyes of patients with FECD that were treated with DMEK and 35 healthy control eyes received anterior segment optical coherence tomography (OCT; Optovue, XR-Avanti, Fremont, CA, USA). The corneal epithelial thicknesses in different locations were analyzed and compared between the preoperative, postoperative, and control cohorts. The median follow-up time was 9 months. There was a significant degression of the mean epithelial thickness after DMEK in the central, paracentral, and mid-peripheral zones (p < 0.01) of the cornea. The total corneal thickness and stromal thickness decreased significantly as well. No significant differences were observed between the postoperative and control cohorts. In conclusion, the FECD patients had an increased epithelial thickness compared to the healthy controls, which decreased significantly after DMEK and reached thickness levels comparable to those of healthy control eyes. This study emphasized the importance of distinguishing between the corneal layers in anterior segment pathologies and surgical procedures. Moreover, it accentuated the fact that the structural alterations in FECD extend beyond the corneal stroma. [ABSTRACT FROM AUTHOR]

• The incidence of Fuchs' endothelial corneal dystrophy (FECD) increased with age and was highest in White and lowest in Asian postmenopausal women. • The risk of FECD was lower in current versus never users of menopausal hormone therapy. • The risk of FECD was not associated with the duration of hormone therapy use, lifetime exposure to endogenous estrogen, or serum estradiol concentrations. End-stage Fuchs' endothelial corneal dystrophy is a leading cause of corneal blindness, with a higher prevalence in females than in males. Few modifiable risk factors have been identified. We examined associations between menopausal hormone therapy use (never/past/current), duration of hormone therapy use, estimated lifetime exposure to endogenous estrogen, and serum estradiol with incident Fuchs' endothelial corneal dystrophy in a cohort of postmenopausal women. This was a prospective analysis in the Women's Health Initiative Observational Study. Incident cases of Fuchs' endothelial corneal dystrophy were identified from the Women's Health Initiative Observational Study baseline (1993–1998) through 2019 using Medicare claims data. In 22,980 women, 1382 incident cases of Fuchs' endothelial corneal dystrophy (annualized incidence rate and 95 % confidence interval = 5.0 [4.8–5.3] cases per 1000 person-years) were identified. The adjusted hazard ratios and 95 % confidence intervals for Fuchs' endothelial corneal dystrophy were 1.02 (0.88–1.18) and 0.89 (0.79–0.997) for past and current hormone therapy use (vs. never use) at baseline, respectively. Adjusted hazard ratios (95 % confidence interval) were 0.90 (0.79–1.03) and 0.95 (0.84–1.08), p-trend = 0.36, for ≤10 and > 10 years, respectively, of hormone therapy use compared with no use; and the adjusted hazard ratio (95 % confidence interval) was 1.01 (0.88–1.15), p-trend = 0.87, for 46.7–59.0 versus 13.8–41.0 years of estimated lifetime exposure to endogenous estrogen. No statistically significant associations were observed with serum estradiol concentrations in a subset of participants. In this cohort of postmenopausal women, current hormone therapy use (vs. never use) showed evidence of protection against the development of Fuchs' endothelial corneal dystrophy; however, duration of hormone therapy use, estimated lifetime exposure to endogenous estrogen, or serum estradiol concentrations were not significantly associated with a decreased risk of Fuchs' endothelial corneal dystrophy. [ABSTRACT FROM AUTHOR]

Purpose: Evaluating the learning curve of individual surgeons for Descemet Membrane Endothelial Keratoplasty (DMEK) and Triple-DMEK and assessing outcome with experience. Methods: The first 41 and the last 41 surgeries of each of the four surgeons were retrospectively included. Surgery duration and graft preparation time were recorded. Corrected distance visual acuity (CDVA, logMAR) and central corneal thickness (CCT, µm) were collected preoperatively after 6 and 12 months, as well as postoperative complications, e.g., re-bubbling or repeat penetrating keratoplasty. Results: Surgical duration for Triple-DMEK and DMEK decreased significantly by 21 min and 14 min between the two periods (p < 0.001; p < 0.001). Graft preparation time decreased significantly from 13.3 ± 5.2 min (95%CI 12.8–14.3) in period 1 to 10.7 ± 4.8 min (95%CI 10.2–11.4) in period 2 (p = 0.002). The postoperative changes in CDVA and CCT over both periods were not significant (p = 0.900; p = 0.263). The re-bubbling rate decreased significantly from 51.2% in period 1 to 26.2% in period 2 (p < 0.001). The repeat penetrating keratoplasty (PKP) was 7.3% in period 1 and 3.7% in period 2 (p = 0.146). Re-DMEK was necessary in 6.1% in period 1 and 4.9% in period 2 (p = 0.535). Several parameters showed significant differences between the surgeons in both periods (surgical duration: period 1: p < 0.001, period 2 p < 0.001; graft preparation: period 1: p < 0.001, period 2 p < 0.001). Conclusion: Significant decrease in surgery duration, graft preparation time, and the re-bubbling rate can be attributed to gained individual experience. [ABSTRACT FROM AUTHOR]

Purpose: This study was performed to determine the demographic profile and clinical characteristics in patients with Fuchs' endothelial corneal dystrophy (FECD) reporting to a tertiary eye care center in India. It is a retrospective, single-center, observational study. Methods: The study included 280 patients (559 eyes) diagnosed with FECD presenting between January 2013 and December 2020. The data was collected from the electronic medical record system of the institute. Patient data included demographic features, clinical characteristics, investigations, and surgical interventions. Results: The mean age of the patients was 62 years. Late-onset FECD (95.7%) was more common than early-onset FECD (4.3%). Male: female ratio for late-onset FECD and early-onset FECD was 1:1.65 and 3:1, respectively. More than one-third of the patients had associated systemic history. Preexisting ocular diseases were seen in 5.9% of eyes. Blurring of vision was seen in 383 eyes (68.5%), 13 eyes (2.1%) had glare, and 163 eyes (29.2%) were asymptomatic. A total of 113 surgical interventions were done in 108 eyes (including repeat transplants). Only cataract surgery was done in 40 (7.2%) eyes, whereas penetrating keratoplasty, Descemet stripping endothelial keratoplasty, and Descemet membrane endothelial keratoplasty without or with cataract surgery (sequential or triple procedure) were done in 12 (2.1%), 47 (8.4%), and 14 (2.5%) eyes, respectively. Conclusion: Patients with FECD present mostly during the sixth decade. Posterior lamellar keratoplasty is the most common transplant procedure being performed on FECD patients. [ABSTRACT FROM AUTHOR]

To identify factors associated with receipt of endothelial keratoplasty (EK) and penetrating keratoplasty (PK) in patients with Fuchs' endothelial corneal dystrophy (FECD). Retrospective cohort study. Medicare beneficiaries 65 years of age or older with a FECD diagnosis between 2011 and 2019. The 100% Medicare fee-for-service administrative claims database was queried for treatment-naïve FECD patients. A multivariate logistic regression model including age, race and ethnicity, sex, geography, ocular comorbidities and surgeries, Charlson comorbidity index (CCI), and socioeconomic status was used to identify factors associated with receipt of EK and PK. Kaplan-Meier survival analyses were used to determine the rate of EK after cataract or complex or other anterior segment surgery. Factors associated with receipt of an EK or PK, plus rate of EK after cataract or complex or other anterior segment surgery. Of 719 066 beneficiaries identified, 31 372 (4.4%) received an EK and 2426 (0.3%) received a PK. In a multivariate analysis, female sex decreased likelihood of both EK and PK (adjusted odds ratio 0.83 [95% confidence interval 0.81–0.85] and 0.84 [0.78–0.92], respectively), while Western residence (1.33 [1.29–1.38]; 1.25 [1.11–1.42]) compared to Southern and history of complex or other anterior segment surgery (1.62 [1.54–1.70]; 5.52 [4.97–6.12]) increased the likelihood of both. Compared to Whites, the likelihood of EK was decreased for Black (0.76 [0.72–0.80]), Asian or Pacific Islander (0.54 [0.48–0.61]), and Hispanic or Latino (0.62 [0.55–0.70]) race and ethnicity, while for the same groups likelihood of PK was increased (for Black 1.32 [1.14–1.53]; Asian/Pacific Islander 1.46 [1.13–1.89]; and Hispanic/Latino 1.62 [1.25–2.11]). Following cataract or complex/other anterior segment surgery, rates of EK were 1.3% and 3.3% at 1 year and 2.3% and 5.6% at 8 years, respectively. In a multivariate analysis, women beneficiaries are less likely to receive EK or PK for FECD compared with men, whereas non-White beneficiaries are less likely to receive EK and more likely to receive PK compared with White beneficiaries. [ABSTRACT FROM AUTHOR]

Objective: Seventy percent of Fuchs’ endothelial corneal dystrophy (FECD) cases are caused by an intronic trinucleotide repeat expansion in the transcription factor 4 gene (TCF4). The objective of this study was to characterize the corneal subbasal nerve plexus and corneal haze in patients with FECD with (RE+) and without the trinucleotide repeat expansion (RE−) and to assess the correlation of these parameters with disease severity. Design: Cross-sectional, single-center study. Participants: Fifty-two eyes of 29 subjects with a modified Krachmer grade of FECD severity from 1 to 6 were included in the study. Fifteen of the 29 subjects carried an expanded TCF4 allele length of ≥ 40 cytosine-thymine-guanine repeats (RE+). Main Outcomes Measures: In vivo confocal microscopy assessments of corneal nerve fiber length (CNFL), corneal nerve branch density, corneal nerve fiber density (CNFD), and anterior corneal stromal backscatter (haze); Scheimpflug tomography densitometry measurements of haze in anterior, central, and posterior corneal layers. Results: Using confocal microscopy, we detected a negative correlation between FECD severity and both CNFL and CNFD in the eyes of RE+ subjects (Spearman ρ = −0.45, P = 0.029 and ρ = −0.62, P = 0.0015, respectively) but not in the eyes of RE− subjects. Additionally, CNFD negatively correlated with the repeat length of the expanded allele in the RE+ subjects (Spearman ρ = −0.42, P = 0.038). We found a positive correlation between anterior stromal backscatter and severity in both the RE+ and RE− groups (ρ = 0.60, P = 0.0023 and ρ = 0.44, P = 0.024, respectively). The anterior, central, and posterior Scheimpflug densitometry measurements also positively correlated with severity in both the RE+ and RE− groups (P = 5.5 × 10−5, 2.5 × 10−4, and 2.9 × 10−4, respectively, after adjusting for the expansion status in a pooled analysis. However, for patients with severe FECD (Krachmer grades 5 and 6), the posterior densitometry measurements were higher in the RE+ group than in the RE− group (P < 0.05). Conclusions: Loss of corneal nerves in FECD supports the classification of the TCF4 trinucleotide repeat expansion disorder as a neurodegenerative disease. Haze in the anterior, central, and posterior cornea correlate with severity, irrespective of the genotype. Quantitative assessments of corneal nerves and corneal haze may be useful to gauge and monitor FECD disease severity in RE+ patients.

Aim: a review of miRNA expression connected to epithelial mesenchymal transition studies in Fuchs' endothelial corneal dystrophy (FECD). Methods: literature search strategy—PubMed central database, using "miRNA" or "microRNA" and "epithelial mesenchymal transition" or "EMT" and "Fuchs' endothelial corneal dystrophy" or "FECD" as keywords. Experimental or clinical studies on humans published in English regarding miRNA profiles of epithelial mesenchymal transition in Fuchs' endothelial corneal dystrophy published between 2009 and 2022 were included. Conclusion: The publications regarding the miRNA profiles of epithelial mesenchymal transition in Fuchs' endothelial corneal dystrophy are scarce but provide some valuable information about the potential biomarkers differentiating aging changes from early disease stages characterized by epithelial mesenchymal transition. In the corneal tissue of FECD patients, miRNA-184 seed-region mutation as well as unidirectional downregulation of total miRNA expression led by the miRNA-29 were demonstrated. For early diagnostics the miRNA of epithelial mesenchymal transition in aqueous humor should be analyzed and used as biomarkers. [ABSTRACT FROM AUTHOR]

Purpose. To highlight the comparative results of surgical treatment of patients with primary Fuchs’ endothelial corneal dystrophy (FECD) using the methods of classical ultrasonic phacoemulsification and femtolaser-assisted phacoemulsification of cataract. Material and methods. To perform the review, literature sources were searched through the PubMed and Scopus abstract databases for the period up to 2021 inclusively using the keywords «endothelial Fuchs corneal dystrophy», «femtolaser-assisted phacoemulsification», «classical ultrasonic phacoemulsification». In total, 23 articles related to the topic of the review were selected. Results. According to a number of researchers, there are significant advantages of femtosecond laser-assisted cataract surgery (FLACS) in patients with FECD. However, the analysis of the published results does not allow us to unequivocally state that femtolaser support of cataract surgery in patients with FECD provides the best result. Obviously, the variability of the results obtained is associated with many factors. Conclusion. The performed analysis of the literature allows us to assert that the data of studies published to date are contradictory. in this connection, we can conclude that this issue requires further research.

Purpose. To describe the clinical cases and surgery results in patients with concomitant of keratoconus and Fuchs’ corneal endothelial dystrophy. Material and methods. Retrospective analysis of 3 patients using different surgical techniques. All patients were female, they underwent diagnostic procedures including: keratotopography, optical coherence tomography of the anterior segment of the eye, Scheimpflug keratotomography, endothelial microscopy. First patient underwent penetrating keratoplasty (PKP), the second one – descemet stripping automated endothelial keratoplasty (DSEK), and the third one – descemet membrane endothelial keratoplasty (DMEK). Results. In all cases the combination of keratoconus and fuchs endothelial corneal dystrophy occurred in one eye, while cornea guttata was observed in both eyes. The diagnosis of keratoconus was complicated by the presence of corneal edema due to endothelial dysfunction. As a result, visual rehabilitation was achieved in 2 patients after PKP and DSEK, and in the third case (DMEK), the presence of pronounced opacities of the stroma in the central zone did not result in increase of visual acuity, despite the good function of the graft endothelium, which required the PKP. Conclusion. Surgical tactics should be based primary on the replacement of the pathologically altered endothelial monolayer (DSEK, DMEK). As for the simultaneous replacement of the corneal stroma (PKP), the decision is based on the progression of keratoconus, the degree of corneal thinning, and the presence of its surface irregularity.

Purpose: To evaluate graft detachment after Descemet membrane endothelial keratoplasty (DMEK) in pseudophakic eyes and DMEK combined with cataract surgery (triple DMEK). Design: Analysis of 3 single-center prospective cohort studies and 1 randomized controlled trial. Participants: Participants with Fuchs’ endothelial corneal dystrophy. Methods: A validated neural network for image segmentation quantified graft detachment on anterior segment OCT (AS-OCT) images 3 days after DMEK and at the 2-week postoperative visit. Area and volume of graft detachment were compared between DMEK only and triple DMEK using generalized estimating equation models and adjusting for participant age and the size of the air bubble. Main Outcome Measures: Area and volume of DMEK graft detachment. Results: Among 207 participants with 270 eyes included, 75 pseudophakic eyes had DMEK only and 195 eyes had triple DMEK. A total of 147 eyes had less than one third of detachment at day 3. In 139 of these eyes (95%), detachment was still less than one third at the 2-week scan, indicating that postoperative graft detachment at 2 weeks occurred mainly in eyes with early detachment. When superimposing all 3-dimensional maps from 2 weeks after surgery, the central graft was mainly attached and detachment was located at the graft margin. The mean area of graft detachment decreased from 28% in DMEK only and 38% in triple DMEK to 16% in DMEK only and 25% in triple DMEK at the 2-week postoperative visit. At 2 weeks, the mean area of detachment was 1.85-fold higher (95% confidence interval [CI], 1.34–2.56) and the mean volume was 2.41-fold higher (95% CI, 1.51–3.86) in triple DMEK compared with DMEK. A total of 46 eyes received rebubbling procedures, with 7 eyes (9%) in the DMEK group and 39 eyes (20%) in the triple DMEK group (adjusted risk ratio, 3.1; 95% CI, 1.3–7.1), indicating that rebubbling was more common in eyes undergoing triple DMEK. Conclusions: Automated segmentation of AS-OCT images allowed precise quantification of graft detachment over time and identified DMEK combined with cataract surgery as a risk factor. Frequency of operative follow-up might be guided by extent of detachment in the first postoperative days after DMEK.

Ellen H Koo, Vikram Paranjpe, William J Feuer, Patrice J Persad, Kendall E Donaldson Bascom Palmer Eye Institute, Department of Ophthalmology, Miller School of Medicine at the University of Miami, Miami, FL, USACorrespondence: Ellen H KooBascom Palmer Eye Institute, Department of Ophthalmology, Miller School of Medicine at the University of Miami, Miami, FL, USATel + 1 561-515-1544Email exk126@med.miami.eduPurpose: To investigate the refractive outcomes of eyes with Fuchs’ endothelial corneal dystrophy (FECD) following phacoemulsification.Methods: This is a retrospective chart review of patients with FECD who underwent phacoemulsification. Manifest refraction at the early postoperative period (1– 6 weeks) and late postoperative period (3– 12 months) was collected. The spherical equivalent (SE) and variance of SE from target in diopters (D) were analyzed.Results: A total of 219 eyes from 175 FECD patients (73 FLACS, 146 conventional phacoemulsification) were included. In the early postoperative period, when comparing variance from intended target, 62% (n=126) had a SE variance of ≤ 0.5 D, 22% (n=44) > 0.5 D and ≤ 1 D, and 17% (n=34) > 1 D. In the late postoperative period, 62% (n=85) had a SE variance of ≤ 0.5 D, 19% (n=26) > 0.5 D and ≤ 1 D, and 20% (n=27) > 1 D. There was no difference in the variance of SE comparing FLACS versus conventional phacoemulsification in either the early postoperative period (p=0.78) or the late postoperative period (p=0.29).Conclusion: Patients with mild-to-moderate FECD had favorable refractive outcomes with phacoemulsification. There was no difference in refractive outcomes in eyes with FECD between the group that underwent FLACS versus the group that underwent conventional phacoemulsification.Keywords: femtosecond laser assisted cataract surgery, Fuchs’ dystrophy, Fuchs’ endothelial corneal dystrophy, refractive error, refractive outcome

Purpose: Fuchs' endothelial corneal dystrophy (FECD) has been considered a genetically heterogeneous disease but is increasingly associated with the transcription factor 4 (TCF4) gene. This study investigates the prevalence of the cytosine‐thymine‐guanine (CTG)n repeat expansion in TCF4 among FECD patients in northern Sweden coupled to the phenotype. Methods: Blood samples were collected from 85 FECD cases at different stages. Short tandem repeat PCR and triplet repeat‐primed PCR were applied in order to determine TCF4 (CTG)n genotype. Results: A (CTG)n repeat expansion (n > 50) in TCF4 was identified in 76 of 85 FECD cases (89.4%) and in four of 102 controls (3.9%). The median (CTG)n repeat length was 81 (IQR 39.3) in mild FECD and 87 (IQR 13.0) in severe FECD (p = 0.01). A higher number of (CTG)n repeats in an expanded TCF4 allele increased the probability of severe FECD. Other ocular surgery was overrepresented in FECD cases without a (CTG)n repeat expansion (44.4%, n = 4) compared with 3.9% (n = 3) in FECD cases with an (CTG)n repeat expansion (p < 0.001). Conclusion: In northern Sweden, the FECD phenotype is associated with (CTG)n expansion in the TCF4 gene, with nearly 90% of patients being hetero‐ or homozygous for (CTG)n expansion over 50 repeats. Furthermore, the severity of FECD was associated with the repeat length in the TCF4 gene. Ocular surgery might act as an environmental factor explaining the clinical disease in FECD without a repeat expansion in TCF4. [ABSTRACT FROM AUTHOR]

PurposeBoston Terriers (BTs) have a greater prevalence of corneal endothelial dystrophy (CED), in comparison to other canine breeds. Similar to Fuchs' endothelial corneal dystrophy (FECD), this condition is characterized by endothelial cell degeneration with secondary corneal edema. This study assessed corneal morphology using in vivo confocal microscopy (IVCM) and Fourier-domain optical coherence tomography (FD-OCT) in BTs with and without CED.MethodsThe corneas of 16 BTs with CED and 15 unaffected, age-matched BTs underwent clinical evaluation and were imaged using IVCM and FD-OCT. A two-sample t-test or Mann-Whitney rank sum test were used to statistically compare parameters between groups. Data are presented as mean ± SD or median (range).ResultsMean age did not significantly differ between affected and unaffected dogs at 10.0 ± 2.0 and 10.6 ± 2.4 years, respectively (P = 0.437). Females (69%) were overrepresented among the CED-affected dogs. In CED patients, IVCM demonstrated endothelial polymegathism and pleomorphism. Corneal endothelial density was significantly less (P < 0.001) in dogs with CED (1026 ± 260 cells/mm2) versus age-matched controls (2297 ± 372 cells/mm2). Fourier-domain OCT demonstrated a significant increase (P < 0.01) in central corneal and endothelium-Descemet's complex thickness in dogs with CED versus age-matched controls at 1019 (485-1550) or 536 (464-650) μm and 32 (22-56) or 25 (15-34) μm, respectively.ConclusionsCorneal endothelial dystrophy in BTs is a bilateral, adult-onset condition that shares many similarities with FECD. Thus, CED could serve as a spontaneous disease model to study the pathogenesis of and develop novel treatments for FECD.

The management of Fuchs' endothelial corneal dystrophy (FECD) has evolved rapidly since the introduction of endothelial keratoplasty (EK). In recent years, advances in our understanding of endothelial cell biology, in particular with respect to the regenerative capacity of endothelial cells, have opened the door to novel therapeutic options that stray from the traditional paradigm of allograft transplantation. We review the development of descemetorhexis without EK (DWEK) as a primary treatment for FECD and discuss the lessons learned to date about the mechanism of wound healing, surgical technique, patient selection, and refractive outcomes. Multiple randomized clinical trials are currently underway to evaluate the potential for pharmacological supplementation with rho-associated kinase inhibitors to increase the success rate of corneal clearance following DWEK. Biologic supplementation with intracameral endothelial cell injection and acellular Descemet's membrane transplantation are other avenues of adjuvant therapy. DWEK is a promising surgical option for management of a subset of FECD patients.

Purpose: The aim of this study was to investigate the association between alterations in corneal subbasal nerve plexus and tactile corneal sensitivity in patients with Fuchs' endothelial corneal dystrophy (FECD). Methods: This retrospective, cross-sectional study included 24 (10 M/14 F) patients with FECD and 25 age- and sex-matched (10 M/15 F) healthy subjects as controls. Subjects with FECD were classified as having early (grades 1 and 2) and late (grades 3 and 4) disease. All subjects underwent central corneal tactile sensitivity measurements with the Cochet–Bonnet esthesiometer (Luneau Ophthalmologie, Chartres, France) and subbasal nerve density evaluation using in vivo confocal microscopy (IVCM). Association between corneal nerve plexus density and corneal sensitivity alterations were evaluated using the Mann–Whitney U test and the Spearman correlation test. Results: Compared to healthy subjects (mean age = 60.4 ± 7.5 years), patients with FECD (mean age = 60.6 ± 8.0 years) had worse central corneal sensitivity scores (5.9 ± 0.1 cm vs. 4.2 ± 0.8 cm; P < 0.001), reduced corneal nerve fibers (3.4 ± 1.3 nerves/frame vs. 5.0 ± 0.9 nerves/frame; P < 0.001) and lower corneal subbasal nerve plexus densities (2229.4 ± 364.3 μm/mm2 vs. 1901.6 ± 486.8 μm/mm2; P = 0.050). Patients with late stage FECD demonstrated lower subbasal nerve densities as compared to those with early disease (2204.3 ± 313.1 μm/mm2 (range = 1523–2552 μm/mm2); 1397.1 ± 227.4 μm/mm2 (range = 1120-1834 μm/mm2); P < 0.001). In the FECD group, subbasal nerve density was found to be directly correlated with corneal sensitivity scores (r = 0.457, P = 0.025). Conclusion: Progressive loss of the corneal subbasal nerve plexus appears to be a consistent feature of FECD. Reduction of the corneal nerve plexus parallels the decrease in corneal sensitivity in this patient population.

Purpose: This study aimed to evaluate the clinical outcomes up to 10 years after Descemet membrane endothelial keratoplasty (DMEK). Methods: In this retrospective, consecutive, single-center case series the medical files of eyes which have received DMEK between 2009 and 2012 for the treatment of endothelial dysfunction was evaluated regarding follow-up time and clinical outcomes. Annual examinations of best-corrected visual acuity (BCVA), endothelial cell density (ECD), central corneal thickness (CCT) of 66 eyes which fulfilled the criterion of a minimum of 8 years follow-up were analyzed. Results: BCVA improved from 0.55 ± 0.37 logMAR (n = 54) to 0.15 ± 0.11 (n = 47) in eyes without ocular comorbidities one year after DMEK (p < 0.001), and remained stable up to 10 years after DMEK. Mean ECD decreased to 744 ± 207 cells/mm2 (n = 39) after 9 years, and to 729 ± 167 cells/mm2 (n = 21) after 10 years, respectively. CCT decreased from 650 ± 67 μm before DMEK to 525 ± 40 μm (n = 56) after 1 year, increasing slowly to 563 ± 40 µm (n = 39) after 9 years, and to 570 ± 42 µm (n = 21) after 10 years, respectively. Graft failure occurred in 4 of 66 eyes after year 8. These 4 eyes required repeat DMEK after 101–127 months. Conclusion: This study shows the long-term outcomes in a small subset of DMEK grafts. Visual acuity remained stable in spite of slowly increasing corneal thickness and diminishing endothelial cell density during the 10-year period after DMEK. [ABSTRACT FROM AUTHOR]

The article discusses the effectiveness of accelerated collagen crosslinking in the treatment of patients with corneal diseases, a common basic pathogenetic link of which is endothelial corneal decompensation. This method was used to treat patients with bullous keratopathy and endothelial dystrophy of Fuchs’ cornea with a long postoperative follow-up. In connection with the controversial results of researchers, reflecting the positive dynamics of the postoperative period, the question of the expediency of accelerated collagen cross-linking in patients with this pathology as a monotherapy is discussed.The study included 25 patients (26 eyes) with mean age 69.10 ± 10.61 years (40 to 82 years). There was Fuchs corneal endothelial dystrophy in 16 patients (17 eyes), in 9 patients (10 eyes) — stage II, in 7 patients (7 eyes) — stage III. Bullous keratopathy was present in 9 patients (9 eyes). All patients underwent treatment according to the method of accelerated collagen corneal crosslinking. In patients with bullous keratopathy (9 eyes), the data on the central thickness of the cornea and the maximum corrected visual acuity did not differ from the initial data at any of the postoperative visits, and did not differ from each other (p > 0.83). On the contrary, in some patients the dystrophic process progressed in the form of the appearance of fibrotic changes in the stroma of the cornea. Corneal transplantation was recommended to all patients under observation after treatment at different periods of observation. In patients with Fuchs endothelial dystrophy, a significant difference in the maximum corrected visual acuity from the initial data was observed only 6 months after surgery.The expediency of accelerated collagen cross-linking in the treatment of patients with corneal diseases accompanied by endothelial decompensation as monotherapy is very doubtful. The study of combined surgical methods for treating this complex corneal pathology using cross-linking as an auxiliary method seems promising.

Fuchs’ endothelial corneal dystrophy (FECD) is the most prominent reason for corneal-endothelial transplantations across the globe. The disease pathophysiology manifests through a combination of various genetic and non-heritable factors. This review provides a comprehensive list of known genetic players that cause FECD, and discusses the prominent pathological features that participate in disease progression, such as channel dysfunction, abnormal extracellular matrix deposition, RNA toxicity, oxidative stress, and apoptosis. Although current practices to correct visual acuity involve surgical intervention, this review also discusses the scope of various non-surgical therapeutics to remedy FECD.

Zeba A Syed,1 Gustavo Rosa Gameiro,1 Marco Ruggeri,1 Amr Elsawy,1,2 Ibrahim Sayed-Ahmed,1 Vatookarn Roongpoovapatr,1 Mohamed Abdel-Mottaleb,2 Mohamed Abou Shousha11Department of Ophthalmology, Bascom Palmer Eye Institute, University of Miami Miller School of Medicine, Miami, FL, USA; 2Department of Electrical and Computer Engineering, University of Miami College of Engineering, Coral Gables, FL, USAObjective: We present a novel method for screening eye bank donor corneas using high definition optical coherence tomography (HD-OCT). This technology allows for the quantification of endothelial/Descemet membrane (En/DM) complex thickness ex vivo.Design: Prospective interventional study.Participants: Fifty-two corneal grafts from 27 donors were included in this study. Twenty additional control eyes and 11 eyes with Fuchs’ endothelial corneal dystrophy were also evaluated for comparison.Methods: A custom built, high speed HD-OCT device (Envisu R2210, Bioptigen, Buffalo Grove, IL, USA) was used to obtain images, and custom-made graph-based segmentation software was used to automatically deconstruct corneal images into micro-layers. HD-OCT imaging was used to scan through the sealed sterile case of donor corneas stored in McCarey-Kaufman medium to image their En/DM complex through the center of the cornea.Results: This technology allowed for quantification of En/DM complex thickness in all donor corneas through the sealed sterile container used to transport graft tissue. Mean En/DM complex thickness of donor corneas was 17±4 μm. The difference between donor cornea En/DM thickness and that of control subjects (16±2 μm) was not statistically significant (p=0.3), suggesting that the transport container and media do not affect measurements. There was a significant difference between En/DM thickness of Fuchs’ endothelial corneal dystrophy eyes (25±5 μm) and both donor corneas (p

Purpose: The aim of this study was to investigate the association between alterations in corneal subbasal nerve plexus and tactile corneal sensitivity in patients with Fuchs' endothelial corneal dystrophy (FECD).Methods: This retrospective, cross-sectional study included 24 (10 M/14 F) patients with FECD and 25 age- and sex-matched (10 M/15 F) healthy subjects as controls. Subjects with FECD were classified as having early (grades 1 and 2) and late (grades 3 and 4) disease. All subjects underwent central corneal tactile sensitivity measurements with the Cochet-Bonnet esthesiometer (Luneau Ophthalmologie, Chartres, France) and subbasal nerve density evaluation using in vivo confocal microscopy (IVCM). Association between corneal nerve plexus density and corneal sensitivity alterations were evaluated using the Mann-Whitney U test and the Spearman correlation test.Results: Compared to healthy subjects (mean age = 60.4 ± 7.5 years), patients with FECD (mean age = 60.6 ± 8.0 years) had worse central corneal sensitivity scores (5.9 ± 0.1 cm vs. 4.2 ± 0.8 cm; P < 0.001), reduced corneal nerve fibers (3.4 ± 1.3 nerves/frame vs. 5.0 ± 0.9 nerves/frame; P < 0.001) and lower corneal subbasal nerve plexus densities (2229.4 ± 364.3 μm/mm2 vs. 1901.6 ± 486.8 μm/mm2; P = 0.050). Patients with late stage FECD demonstrated lower subbasal nerve densities as compared to those with early disease (2204.3 ± 313.1 μm/mm2 (range = 1523-2552 μm/mm2); 1397.1 ± 227.4 μm/mm2 (range = 1120-1834 μm/mm2); P < 0.001). In the FECD group, subbasal nerve density was found to be directly correlated with corneal sensitivity scores (r = 0.457, P = 0.025).Conclusion: Progressive loss of the corneal subbasal nerve plexus appears to be a consistent feature of FECD. Reduction of the corneal nerve plexus parallels the decrease in corneal sensitivity in this patient population. [ABSTRACT FROM AUTHOR]

The management of Fuchs' endothelial corneal dystrophy (FECD) has evolved rapidly since the introduction of endothelial keratoplasty (EK). In recent years, advances in our understanding of endothelial cell biology, in particular with respect to the regenerative capacity of endothelial cells, have opened the door to novel therapeutic options that stray from the traditional paradigm of allograft transplantation. We review the development of descemetorhexis without EK (DWEK) as a primary treatment for FECD and discuss the lessons learned to date about the mechanism of wound healing, surgical technique, patient selection, and refractive outcomes. Multiple randomized clinical trials are currently underway to evaluate the potential for pharmacological supplementation with rho-associated kinase inhibitors to increase the success rate of corneal clearance following DWEK. Biologic supplementation with intracameral endothelial cell injection and acellular Descemet's membrane transplantation are other avenues of adjuvant therapy. DWEK is a promising surgical option for management of a subset of FECD patients. [ABSTRACT FROM AUTHOR]

Nuclear factor, erythroid 2 like 2 (Nrf2), is an oxidative stress induced transcription factor that regulates cytoprotective gene expression. Thus, Nrf2 is essential for cellular redox homeostasis. Loss or dysregulation of Nrf2 expression has been implicated in the pathogenesis of degenerative diseases, including diseases of the cornea. One of the most common diseases of the cornea in which Nrf2 is implicated is Fuchs’ endothelial cornea dystrophy (FECD). FECD is the leading indication for corneal transplantation; and is associated with a loss of corneal endothelial cell (CEC) function. In this review, we propose that Nrf2 is an essential regulator of CEC function. Furthermore, we demonstrate that deficiency of Nrf2 function is a hallmark of FECD. In addition, we advocate that pharmacological targeting of Nrf2 as a possible therapy for FECD.

Purpose: To determine whether excimer laser ablation of guttae is a viable strategy for removal of diseased tissue in Fuchs' endothelial corneal dystrophy (FECD) on excised human Descemet membranes and whether an excimer laser‐created wound on healthy human corneas ex vivo is recolonized with corneal endothelial cells. Methods: Descemet membranes of FECD patients and corneal endothelium of normal human corneas were ablated ex vivo using an excimer laser licensed for glaucoma surgery. Specimens were kept in cell culture medium supplemented with 10 μm of rho‐kinase inhibitor ripasudil. Corneal endothelial cell regeneration was observed using light and electron scanning microscopy. Furthermore, the whole corneal samples were evaluated by haematoxylin/eosin staining and immunohistochemical analysis using antibodies against Na+/K+‐ATPase. Results: Guttae and corneal endothelium could be ablated with an excimer laser without total ultrastructural damage to the Descemet membrane or stroma. Nearly complete endothelial wound closure was accomplished after 26–38 days in treated corneas. Light and electron scanning microscopy suggested the establishment of a layer of flat endothelial cells. Additionally, Na+/K+‐ATPase expression could only be observed on the inner side of the Descemet membrane. Conclusion: Our proof of concept study demonstrated that excimer lasers can be used to ablate diseased tissue from excised FECD Descemet membranes ex vivo. Additionally, corneal endothelial cells recolonize a previously ablated endothelial area in healthy human corneas ex vivo under treatment with ripasudil. Thus, our results are the first experimental basis to further investigate the feasibility of an excimer laser ablation as a graftless FECD treatment option. [ABSTRACT FROM AUTHOR]

Purpose: To report 12-month results of small incision lenticule extraction (SMILE) in the treatment of myopia with corneal guttae (CG). Methods: We conducted a retrospective analysis of 12 eyes from six patients who had preoperative CG without clinical sign of Fuchs' endothelial corneal dystrophy (FECD) and had SMILE for correction of myopia. Preoperative and 12-month postoperative measurements included uncorrected distance visual acuity (UDVA), spherical equivalent (SE), endothelial cell density (ECD), the coefficient of variation (CV), the percentage of hexagonal cells (HEX), and central corneal thickness (CCT). The changes in ECD, CV, HEX, and CCT after SMILE were subjected to statistical analysis. Results: Twelve months postoperatively, the mean SE was − 0.10 ± 0.32 D and all eyes had a UDVA of 0 logMAR or better. No eyes developed corneal edema or other complication during the follow-up period. There were no significant changes in the ECD, CV, or HEX at 12 months (all p> 0.05). Conclusion: SMILE yielded improvement in visual acuity and no adverse effects to corneal endothelial cells were found when correcting myopia or myopic astigmatism in patients with CG. However, studies with a greater number of patients and longer follow-up periods are needed to establish the long-term outcomes and safety. [ABSTRACT FROM AUTHOR]

Antisense oligonucleotides (ASOs) are synthetic nucleic acids that recognize complementary RNA sequences inside cells and modulate gene expression. In this study, we explore the feasibility of ASO delivery to the cornea. We used quantitative polymerase chain reaction to test the efficacy of a benchmark ASO targeting a noncoding nuclear RNA, Metastasis-Associated Lung Adenocarcinoma Transcript 1 (MALAT1), in a human corneal endothelial cell line, ex vivo human corneas, and in vivo in mice. In vivo delivery was via intravitreal or intracameral injections as well as topical administration. The anti-MALAT1 ASO significantly reduced expression of MALAT1 in a corneal endothelial cell line. We achieved a dose-dependent reduction of target gene expression in endothelial tissue from ex vivo human donor corneas. In vivo mouse experiments confirmed MALAT1 reduction in whole corneal tissue via intravitreal and intracameral routes, 82% and 71% knockdown, respectively (P < 0.001). Effects persisted up to at least 21 days, 32% (P < 0.05) and 43% (P < 0.05) knockdown, respectively. We developed protocols for the isolation and analysis of mouse corneal endothelium and observed reduction in MALAT1 expression upon both intravitreal and intracameral administrations, 64% (P < 0.05) and 63% (P < 0.05) knockdown, respectively. These data open the possibility of using ASOs to treat corneal disease. [ABSTRACT FROM AUTHOR]

Purpose: To characterize and correlate guttata severity, Descemet's membrane thickness (DMT), central cornea thickness (CCT) in corneas with guttae using specular microscopy and spectral-domain optical coherence tomography (SD-OCT) and test the Doheny Image Reading Center (DIRC) specular microscopy-based corneal guttata severity scale. Methods: Forty-nine eyes of 49 patients with guttata and 36 eyes of age-matched of 36 normal controls were enrolled in the study. Three images of the central cornea and four of the peripheral cornea (inferior, superior, nasal and temporal) of each eye were taken using the Konan NSP-9900 specular microscope. A volume scan of the central cornea cross-section was collected on each eye using the Heidelberg Spectralis SD-OCT. The density of endothelial guttata based on specular images was graded on a 0–4 scale, and the Descemet's membrane thickness (DMT) and central corneal thickness (CCT) were manually measured by two trained graders. Results: The DIRC corneal guttata severity scale showed good reproducibility of all corneal endothelial images (weighted Kappa = 0.87). Mean DMT was 16.1 ± 2.4 µm in controls and 25.5 ± 10.9 µm in corneas with guttata (P < 0.001). Mean CCT was 552 ± 26 µm in controls and 603 ± 55 µm in corneas with guttata (P < 0.001). Guttata severity was significantly correlated with both DMT (r = 0.743, P < 0.001) and CCT (r = 0.569, P < 0.001). Age was moderately correlated with DMT (r = 0.472, P = 0.003) and mildly correlated with guttata severity (r = 0.285, P = 0.031), but was not correlated with CCT (r = 0.058, P = 0.681). Guttatta grade 3 corneas displayed an increase in DMT and guttata grade 4 was associated with a significant increase in CCT. Conclusions: The DMT and CCT are increased in corneas with guttata. The higher density of guttae is correlated with increased thickness. Specular microscopy combined with SD-OCT can be used as a good approach to assess the severity of FECD. [ABSTRACT FROM AUTHOR]

Objective: To assess the efficacy of an endothelial keratoplasty procedure at defined intervals to 1 year postoperatively for the treatment of corneal endothelial dystrophy (CED) in a canine patient. Procedure: A dog diagnosed with CED with progressive corneal edema underwent an endothelial keratoplasty. The patient was examined pre‐ and postoperatively with slit lamp biomicroscopy and ultrasonic pachymetry. Results: Mean central corneal thickness (CCT) measured with pachymetry was >1400 μm preoperatively and decreased postoperatively to 725 μm. The transplanted donor tissue became transparent 2 weeks postoperatively and incorporated with the recipient cornea. The graft remained transparent throughout the duration of the postoperative period evaluated in this study (2 weeks postoperatively to 1 year). The canine patient was comfortable pre‐ and postoperatively. Conclusions: Endothelial keratoplasty is a potential therapeutic option for canine cases with progressive corneal thickening due to CED. As this is a single case study, further investigation into the use of endothelial keratoplasty to treat CED is warranted. Moreover, canine patients with CED might serve as a surgical model for human patients with Fuchs' Endothelial Corneal Dystrophy. [ABSTRACT FROM AUTHOR]

Purpose: This study evaluates the long-term results of surgical treatment of patients with Fuchs' endothelial corneal dystrophy and cataract., Material and Methods: The study included 24 patients (24 eyes) with primary Fuchs' endothelial corneal dystrophy and cataract, who underwent cataract phacoemulsification with IOL implantation and of Descemet's membrane endothelial keratoplasty with a semicircular graft (hemi-DMEK). The effect of treatment was assessed by best corrected visual acuity (BCVA), central corneal thickness (CCT) and endothelial cell density (ECD)., Results: In total, surgical treatment involved 14 donor corneas that were divided in half during the preparation and isolation of the Descemet's membrane (DM). By month 12 after the surgery an increase in visual functions and graft transparency were observed in 23 patients (23 eyes) out of 24. Repeated keratoplasty was required in one case due to fibrosis of the posterior layers of recipient's corneal stroma. At 12 months postoperatively, the study group showed an increase in BCVA from 0.16±0.1 to 0.75±20, a decrease in CCT from 650.9±4.5 μm to 519.6±43.9, and a decreased in ECD from 2850.5±84.7 cells/mm 2 up to 1285.5±277.2 cells/mm 2 . Thus, the loss of endothelial cells at one year after surgery amounted to 54.9%., Conclusions: The developed method for transplantation of a semicircular DM fragment provides a tissue-saving approach to endothelial keratoplasty, and considering the high percentage of transparent engraftment of grafts and complete visual rehabilitation, it can be recommended in the treatment of patients with cataract and Fuchs' endothelial corneal dystrophy.

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Abstract We provide the evidence for G protein-coupled receptor 35 (GPR35) presence and distribution in the human cornea. The initial data on GPR35 gene expression were retrieved from microarray repositories and were further confirmed by western blotting and immunohistochemical analysis. Immunoblotting suggested that GPR35 exists predominantly as a dimer in corneal tissue. Moreover, corneal tissues were significantly richer in GPR35 compared to the adjacent sclera. Immunoreactivity for GPR35 was detected in normal corneas, keratoconus and Fuchs' dystrophy, mainly in the corneal epithelium and endothelium. In corneas with Fuchs' dystrophy, less intensive immunoreactivity for GPR35 in endothelium was revealed. The physiological relevance of this phenomenon requires further investigation. Highlights • GPR35 is present in the eye. • GPR35 may be linked to ocular pathologhies. • Activation of corneal GPR35 may serve as potential target for new ophthalmic drugs. [ABSTRACT FROM AUTHOR]

Purpose: To report the observation of a triple corneal dystrophy association consisting of keratoconus (KC), epithelial basement membrane corneal dystrophy (EBMCD) and Fuchs' endothelial corneal dystrophy (FECD). Methods: A 55-year-old male patient was referred to our cornea service for blurred vision and recurrent foreign body sensation. He reported bilateral recurrent corneal erosions with diurnal visual fluctuations. He underwent corneal biomicroscopy, Scheimpflug tomography, in vivo HRT confocal laser scanning microscopy and genetic testing for TGFBI and ZEB1 mutations using direct DNA sequencing. Results: Biomicroscopic examination revealed the presence of subepithelial central and paracentral corneal opacities. The endothelium showed a bilateral flecked appearance, and the posterior corneal curvature suggested a possible concomitant ectatic disorder. Corneal tomography confirmed the presence of a stage II KC in both eyes. In vivo confocal laser scanning microscopy revealed a concomitant bilateral EBMCD with hyperreflective deposits in basal epithelial cells, subbasal Bowman's layer microfolds and ridges with truncated subbasal nerves as pseudodendritic elements. Stromal analysis revealed honeycomb edematous areas, and the endothelium showed a strawberry surface configuration typical of FECD. The genetic analysis resulted negative for TGFBI mutations and positive for a heterozygous mutation in exon 7 of the gene ZEB1. Conclusion: This is the first case reported in the literature in which KC, EBMCD and FECD are present in the same patient and associated with ZEB1 gene mutation. The triple association was previously established by means of morphological analysis of the cornea using corneal Scheimpflug tomography and in vivo HRT II confocal laser scanning microscopy.