Endothelial Corneal Dystrophy Research Articles

Influence of surgeon learning on outcomes in new ophthalmic procedures: quantified nationwide evidence in endothelial corneal transplantation

AimsTo investigate the impact of surgeon learning on endothelial keratoplasty (EK) procedure outcomes.MethodsA prospective nationwide registry study of EK grafts in patients aged at least 21 years with Fuchs endothelial...

Impact of postoperative intraocular pressure elevation on graft endothelial cells in non-preexisting glaucoma eyes undergoing descemet membrane endothelial keratoplasty: a cohort study

BackgroundDescemet membrane endothelial keratoplasty (DMEK) has become the dominant keratoplasty procedure. However, the impact of high intraocular pressure (IOP) on the DMEK prognosis in patients without preexisting glaucoma remains unknown.MethodsNon-glaucoma patients who underwent DMEK in Peking University Third Hospital between July 2017 and March 2023 with a follow-up duration longer than six months were included in this cohort study. Eyes were divided into three groups: Group A) normal IOP; Group B) early IOP elevation (IOP ≥ 30 mmHg or increase of more than 10 mmHg from baseline within 3 days); Group C) intermediate-term IOP elevation (IOP > 21 mmHg or increase of more than 10 mmHg from baseline after 14 days postoperatively). The postoperative IOP, endothelial cell density (ECD), central corneal thickness (CCT), best-corrected visual acuity (BCVA) and rate of graft failure were analysed.ResultsForty-seven eyes from forty-seven patients were included. Thirty-seven eyes were bullous keratopathy, and ten were Fuchs endothelial corneal dystrophy. Twenty-five eyes were classified as Group A, six as Group B and sixteen as Group C. The mean peak IOP was 49.00 ± 4.99 mmHg in Group B eyes and 31.89 ± 11.75 mmHg in Group C eyes. The postoperative BCVA significantly differed from that before surgery (P < 0.001). The ECD at 3 months after surgery in eyes with intermediate-term IOP elevation was lower (P = 0.032). Four eyes with intermediate-term IOP elevation developed graft failure (P = 0.001).ConclusionsIntermediate-term IOP elevation after DMEK may reduce the graft ECD and lead to graft failure within six months after surgery. However, early IOP elevation had no effect on the prognosis. Careful IOP monitoring and intermediate-term IOP management should be conducted for graft protection.

Validation of a French Version of the Visual Function and Corneal Health Status Instrument and Correlation With Vision and Glare Measurements in Fuchs Endothelial Corneal Dystrophy.

To validate a French version of the Visual Function and Corneal Health Status (V-FUCHS) instrument in Fuchs endothelial corneal dystrophy (FECD) and to correlate questionnaire scores with objective measurements of best-corrected visual acuity (BCVA) and intraocular straylight. The original V-FUCHS 15-item instrument was designed to assess VA and glare in patients with FECD. It was translated from English to French and back translated to English by independent translators. The questionnaire was administered on 2 occasions (4 weeks apart), and BCVA, modified Krachmer grade, and straylight were measured. Construct validity, internal consistency, test-retest reliability, and predictive validity were assessed. A total of 159 subjects, aged 41 to 86 years, were prospectively recruited from July 2019 to October 2020 and classified into 6 groups: mild, moderate, or advanced FECD; unilateral or bilateral Descemet membrane endothelial keratoplasty for FECD; and healthy controls (n = 35). Construct validity was confirmed by item response theory model. Cronbach alpha demonstrated excellent internal consistency (VA: 0.91, glare: 0.88), and intraclass correlations showed good test-retest reliability (VA: 0.75 and glare: 0.82). Significant correlations were observed between both VA and glare factors and the modified Krachmer grade, BCVA, and straylight. The proposed French version of the V-FUCHS instrument provides a valid and reliable tool for the assessment of visual disability in patients with FECD. This questionnaire bridges the gap between self-reported FECD symptoms and objective clinical measurements, which may prove useful to optimize the timing of surgery and to assess postoperative improvement in symptoms.

Associations between the incidence of Fuchs' endothelial corneal dystrophy and menopausal hormone therapy use and exposure to endogenous estrogen

ObjectivesEnd-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. Study designThis was a prospective analysis in the Women's Health Initiative Observational Study. Main outcome measuresIncident cases of Fuchs' endothelial corneal dystrophy were identified from the Women's Health Initiative Observational Study baseline (1993–1998) to 2019 using Medicare claims data. ResultsIn 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 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 ratios (95 % confidence interval) were 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. ConclusionsIn 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.

Pathogenesis of Fuchs endothelial corneal dystrophy, the fibrillar layer and individualized treatment

Fuchs endothelial corneal dystrophy (FECD) is agenetic and age-associated corneal disease characterized by an accelerated loss of corneal endothelial cells and an increased subendothelial deposition of extracellular matrix (ECM). Clinically, advanced disease leads to corneal edema with subsequent reduction in visual acuity. In the majority of patients with advanced FECD, afibrillar layer (FL) appears on the posterior corneal surface. This FL is mostly localized in the inferotemporal corneal quadrant, marks areas with significantly reduced endothelial cell density and increased corneal thickness in the sense of edema and can be visualized and measured using Scheimpflug backscatter analysis due to increased backscatter. FECD is currently the most common indication for corneal transplantation worldwide, usually in the form of Descemet membrane endothelial keratoplasty (DMEK). New treatment approaches include variations of DMEK surgery such as hemi- or quarter DMEK with individualized and smaller grafts or Descemet membrane stripping only (DSO). In the future, clinical imaging of the FL as aparticularly affected endothelial area could be important for FECD progression assessment and planning of surgical interventions. This article provides an overview of the current state of research on the clinical aspects, pathogenesis, fibrillar layer and individualized treatment of FECD.

Descemet Endothelial Thickness Comparison Trial II (DETECT II): multicentre, outcome assessor-masked, placebo-controlled trial comparing Descemet membrane endothelial keratoplasty (DMEK) to Descemet stripping only (DSO) with adjunctive ripasudil for Fuchs dystrophy

IntroductionIt remains uncertain whether Descemet membrane endothelial keratoplasty (DMEK) or Descemet stripping only (DSO) yields better outcomes in patients with symptomatic Fuchs endothelial corneal dystrophy (FECD). This paper presents the...

Diurnal changes of corneal epithelial and stromal thickness maps and visual quality in mild form of Fuchs' endothelial corneal dystrophy.

To investigate the functional and structural daily variations in eyes with a mild form of Fuchs' endothelial corneal dystrophy (FECD). This prospective study included 30 eyes with the mild form of FECD. Subjects underwent functional and structural testing at 8 AM, 2 PM, and 8 PM. Testing included measurement of uncorrected distance visual acuity (UDVA), best corrected twilight vision (TV), and contrast sensitivity function (CSF) testing (Vista Vision Far-Pola, DMD MedTech charts). Corneal epithelial and stromal parameters were evaluated with anterior segment optical coherence tomography (AngioVue, AvantiRTVue-XR; Optovue, CA, USA). UDVA, TV, and CSF for spatial frequencies B, C, and F showed significant changes during the day, with the lowest values in the morning (P < 0.0001 for UDVA, P = 0.0109 for TV, and P < 0.0001, P = 0.0126, and P = 0.0471 for the three spatial frequencies, respectively). There was no significant change in epithelial parameters between visits. Central corneal thickness showed significant decrease during the day (P < 0.0001), as did the central stromal thickness on the 5- and 7-mm maps (P = 0.0002 and P < 0.0001, respectively), stromal thickness in the superior section of the 5-mm map (P = 0.0107), stromal thickness in the inferior section of the 7-mm map (P = 0.0002), and minimal stromal thickness on both maps (P < 0.0001). A significant negative correlation was found between central stromal thickness and TV, implying that simultaneous evaluation of corneal layers and visual quality may be useful in assessing FECD.

TCF4 trinucleotide repeat expansions and UV irradiation increase susceptibility to ferroptosis in Fuchs endothelial corneal dystrophy

Fuchs endothelial corneal dystrophy (FECD), the leading indication for corneal transplantation in the U.S., causes loss of corneal endothelial cells (CECs) and corneal edema leading to vision loss. FECD pathogenesis is linked to impaired response to oxidative stress and environmental ultraviolet A (UVA) exposure. Although UVA is known to cause nonapoptotic oxidative cell death resulting from iron-mediated lipid peroxidation, ferroptosis has not been characterized in FECD. We investigated the roles of genetic background and UVA exposure in causing CEC degeneration in FECD. Using ungenotyped FECD patient surgical samples, we found increased levels of cytosolic ferrous iron (Fe2+) and lipid peroxidation in end-stage diseased tissues compared with healthy controls. Using primary and immortalized cell cultures modeling the TCF4 intronic trinucleotide repeat expansion genotype, we found altered gene and protein expression involved in ferroptosis compared to controls including elevated levels of Fe2+, basal lipid peroxidation, and the ferroptosis-specific marker transferrin receptor 1. Increased cytosolic Fe2+ levels were detected after physiologically relevant doses of UVA exposure, indicating a role for ferroptosis in FECD disease progression. Cultured cells were more prone to ferroptosis induced by RSL3 and UVA than controls, indicating ferroptosis susceptibility is increased by both FECD genetic background and UVA. Finally, cell death was preventable after RSL3 induced ferroptosis using solubilized ubiquinol, indicating a role for anti-ferroptosis therapies in FECD. This investigation demonstrates that genetic background and UVA exposure contribute to iron-mediated lipid peroxidation and cell death in FECD, and provides the basis for future investigations of ferroptosis-mediated disease progression in FECD.

Long-term persistent exposure to cigarette smoke induces AhR driven corneal endothelial dysfunction in mice

Epidemiological studies show cigarette smoking enhances corneal endothelial dysfunction, but mechanisms remain unclear. Our study reveals that prolonged smoke exposure activates the aryl hydrocarbon receptor (AhR), increasing CYP1B1 expression and accelerating senescence and fibrosis in corneal endothelium, potentially reflecting adaptive responses to maintain corneal resilience. Although these molecular modifications indicate early endothelial dysfunction, no pathological changes were observed. The findings indicate that while chronic cigarette smoke exposure triggers initial molecular alterations and endothelial dysfunction, the progression to Fuchs endothelial corneal dystrophy likely requires additional environmental or genetic factors beyond smoke exposure alone.

Cataract surgery with corneal endothelial pathology

Abstract: It is not uncommon for Fuch’s endothelial corneal dystrophy (FECD) patients to present with a co-existent cataract. Surgeons are often faced with a choice between simultaneous and staged corneal and cataract surgery. Descemet’s membrane endothelial keratoplasty (DMEK) has been found to have better visual outcomes as compared to Descemet’s stripping endothelial keratoplasty (DSEK) and penetrating keratoplasty and is currently the preferred surgery for FECD. Endothelial cell count and pachymetry cutoffs were earlier used for decision-making. Various other investigations such as Scheimpflug imaging and confocal microscopy are now used to prognosticate the outcome when performing cataract surgery only. Triple DMEK has the advantage of a definite treatment in a single sitting. Whereas, a staged approach with DMEK followed by cataract surgery has a better visual outcome. This is due to variable refractive changes in the cornea post-DMEK or DSEK that can lead to inaccurate intraocular lens (IOL) power calculation. Even though the graft detachment rates and rebubbling rates have been found to be comparable in triple DMEK versus a staged surgery, in view of increasing patient demands and expectations for a spectacle-independent outcome, a staged surgery is now preferable. Conventionally, surgeons favored the use of only monofocal lenses; however, the use of premium IOLs, especially extended depth of focus lenses, is now increasing. In this review, we will discuss the various advantages and disadvantages of a simultaneous and staged approach and pearls on decision-making in FECD with cataracts.

Fuchs’ Endothelial Corneal Dystrophy evaluation using a high-resolution wavefront sensor

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·\\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\usepackage{upgreek} \\setlength{\\oddsidemargin}{-69pt} \\begin{document}$$\\cdot$$\\end{document}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.

Rapid detection of guttae area using aniline blue staining in Fuchs endothelial corneal dystrophy mouse model.

Fuchs endothelial corneal dystrophy (FECD) is a leading cause of corneal endothelial degeneration resulting in impaired visual acuity. Excessive deposition of extracellular matrix (guttae) on Descemet's membrane (DM) is the hallmark of FECD. We sought to detect the guttae area rapidly using aniline blue (AB) staining in FECD mouse model. FECD mouse model was established via ultraviolet A (UVA) exposure. Masson's trichrome staining was utilized to stain the corneal sections. AB staining was utilized to stain both whole cornea tissues and stripped Descemet's membrane-endothelium complex (DMEC) flat mounts, while immunofluorescence staining of collagen I was employed to stain guttae areas. In Masson's trichrome staining, corneal collagen fibrils were stained blue with AB. The DMEC flat mounts were stained into relative dark blue areas and relative light blue areas using 2% AB staining. The areas of dark blue could almost overlap with collagen I-positive areas, and have an acellular centre and a moderately distinct boundary line with the surrounding corneal endothelial cells. In conclusion, AB staining is a rapid and effective method for the evaluation of the guttae areas in the FECD mouse model.

MitoQ relieves mitochondrial dysfunction in UVA and cigarette smoke-induced Fuchs endothelial corneal dystrophy

Fuchs endothelial corneal dystrophy (FECD), a degenerative corneal condition, is characterized by the droplet-like accumulation of the extracellular matrix, known as guttae and progressive loss of corneal endothelial cells ultimately leading to visual distortion and glare. FECD can be influenced by environmental stressors and genetic conditions. However, the role of mitochondrial dysfunction for advancing FECD pathogenesis is not yet fully studied. Therefore, in the present study we sought to determine whether a combination of environmental stressors (ultraviolet-A (UVA) light and cigarette smoke condensate (CSC)) can induce mitochondrial dysfunction leading to FECD. We also investigated if MitoQ, a water-soluble antioxidant, can target mitochondrial dysfunction induced by UVA and CSC in human corneal endothelial cells mitigating FECD pathogenesis. We modeled the FECD by increasing exogenous oxidative stress with CSC (0.2%), UVA (25J/cm2) and a combination of UVA + CSC and performed a temporal analysis of their cellular and mitochondrial effects on HCEnC-21T immortalized cells in vitro before and after MitoQ (0.05 μM) treatment. Interestingly, we observed that a combination of UVA + CSC exposure increased mitochondrial ROS and fragmentation leading to a lower mitochondrial membrane potential and increased levels of cytochrome c release leading to apoptosis and cell death. MitoQ intervention successfully mitigated these effects and restored cell viability. The UVA + CSC model could be used to study stress induced mitochondrial dysfunction. Additionally, MitoQ can serve as a viable antioxidant in attenuating mitochondrial dysfunction, underscoring its potential as a molecular-focused treatment approach to combat FECD pathogenesis.

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

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

Fuchs endothelial corneal dystrophy: aspects of pathogenesis

Fuchs endothelial corneal dystrophy (FECD) – multigenic bilateral disorder, characterized by dysfunction of corneal endothelium cells (CECs) that eventually results in loss of transparency. Purpose: To evaluate the pathogenesis of FECD with histological and immunohistochemical methods, immunofluorescence, scanning electron microscopy (SEM). Methods: Endothelium–Descemet membrane (EDM) complexes, corneal buttons were obtained from 76 patients (85 eyes) with FECD during keratoplasty and divided into 1A, 2A, 3A groups, 15 EDMs (donor tisuue) – 1B, 2B, 3B groups (control). Morphological (hematoxylin/eosin staining) and immunohistochemical (primary antibodies to cytokeratin AE1/AE3 and vimentin) studies (1A, 1B groups), phase-contrast microscopy and immunofluorescence analysis of tight junction protein ZO-1 (2A, 2B groups), SEM (3A, 3B groups) were performed. Results: FECD is characterized by decline of CECs, cell and nuclear enlargement. Nuclear-cytoplasmic ratio of CECs is relative to control. CECs expression ZO-1 is decreased in the area of guttae ingrowth. Coexpression of cytokeratin AE1/AE3 and vimentin is found. Morphological and immunohistochemical studies show DM’ thickening, stromal and epithelial edema and local fibrosis, vimentin (stromal cells) and cytokeratin AE1/AE3 (epithelium) expression in FECD. Conclusion: Pathogenesis of FECD include CECs’ epithelial-mesenchymal transition, followed by guttae formation – the excrescences, which destroy cytosketon and lead to progressive loss of CECs. Changes in permeability of endothelium cause edema and fibrosis of stroma and epithelial layer.

Prevalence of Transcription Factor 4 Gene Triplet Repeat Expansion Associated with Fuchs’ Endothelial Corneal Dystrophy in the United States and Global Populations

ObjectiveAn intronic CTG triplet repeat expansion in the transcription factor 4 gene (TCF4) gene (CTG18.1) confers significant risk for the development of Fuchs’ endothelial corneal dystrophy (FECD). The objective of this study was to conduct an unbiased survey of the CTG18.1 repeat expansion allele frequencies in a multi-ethnic, population-based cohort from the United States and in global populations. DesignCross-sectional study SubjectsDallas Heart Study (DHS) cohort including 1,599 African Americans (AAs), 1,028 European Americans (EAs), and 458 Latinos; 2,500 individuals from the 1000 Genomes Project (1KGP) sampled from 26 populations across 5 continents. MethodsWe genotyped the CTG18.1 short tandem repeat in DHS using targeted polymerase chain reaction amplification followed by fragment analysis. We also inferred the CTG18.1 repeat genotype based on short-read whole-genome sequencing in 1KGP using the computational tool ExpansionHunter. Main Outcome MeasuresThe prevalence of an expanded CTG18.1 allele with ≥40 repeats was determined in U.S. and global populations. ResultsThe carrier rates of the expanded allele were 3.1%, 8.1%, and 3.3% in AAs, EAs, and Latinos, respectively, in the DHS, and 2.7%, 9.5%, 5.2%, 7.2%, and 5.2% in the African (AFR), European (EUR), East Asian (EAS), South Asian (SAS), and admixed American (AMR) continental populations, respectively, in the 1KGP. The distributions of the CTG18.1 repeat in DHS and in 1KGP are similar. The median repeat length was ∼17 with the interquartile range (IQR) between 12 and 23 in the DHS populations. The median repeat length was ∼19 in all the 1KGP populations with the IQR between 13 and 26. The highest prevalence of the expanded allele carriers ranging from 12.1% to 12.5% was observed in some EUR and AMR subpopulations. The frequency of expanded alleles carriers was absent or low (0 - 1.9%) in subpopulations of East Africa but was present at 6.2% in a Kenyan subpopulation in West Africa. ConclusionsThe TCF4 repeat expansion is most prevalent in people of European ancestry and least in African ancestry, which is consistent with FECD prevalence. The expanded TCF4 CTG18.1 allele is the most common disease-causing short tandem repeat in humans with worldwide implications for corneal disease.

Guttae Morphology After Cultured Corneal Endothelial Cell Transplant in Fuchs Endothelial Corneal Dystrophy

Whether guttae in Fuchs endothelial corneal dystrophy (FECD) can be removed by polishing without Descemet stripping and whether postoperative maintenance of reduced guttae can be achieved through cultured corneal endothelial cell (CEC) transplant therapy are critical issues to be addressed. To investigate the decrease of guttae through polishing degenerated CECs and abnormal extracellular matrix (ECM) without Descemet stripping and to observe the behavior of guttae following cultured CEC transplant. This case series prospective observational study was conducted in a hospital outpatient clinic setting. Between December 2013 and January 2019, 22 eyes with corneal endothelial failure caused by FECD received cultured CEC transplant therapy at Kyoto Prefectural University Hospital. Of these, 15 eyes were consistently monitored at the same central corneal area during the preoperative phase, as well as in the early (within 1 year) and late (after 3 years) postoperative phases. The images from these phases were categorized into 3 groups: typical guttae, atypical guttae, and no guttae. Cultured CEC transplant therapy. Proportion of guttae in the observable area was measured, comparing the early and late postoperative phases for each group. The mean age of the patients at the time of surgery was 69 years (range, 49-79 years). All 15 eyes exhibited the presence of confluent guttae preoperatively (100%). Among these, 3 of 15 eyes belonged to male patients. The early postoperative phase of guttae morphologies was classified into 3 groups: 5 eyes with typical guttae, 7 with atypical guttae, and 3 with no guttae. The decrease in the number of these guttae was achieved by surgical procedures. The median percentage of guttae in the typical guttae, atypical guttae, and no guttae groups was 41.8%, 44.4%, and 16.2%, respectively, in the early phase, and 42.2%, 38.2%, and 18.8%, respectively, in the late phase. The findings demonstrate that in some cases of FECD, guttae can be removed by scraping and polishing abnormal ECM and degenerated CECs, while preserving the Descemet membrane. Furthermore, cultured CEC transplant resulted in no increase in guttae for up to 3 years, providing insights into surgically eliminating guttae.

Nanotopography by chromatic confocal microscopy of the endothelium in Fuchs endothelial corneal dystrophy, pseudophakic bullous keratopathy and healthy corneas

AimTo investigate the interest of chromatic confocal microscopy (CCM) to characterise guttae in Fuchs endothelial corneal dystrophy (FECD).MethodsDescemet’s membranes (DM) were obtained during endothelial keratoplasty in patients with FECD and...

Enhanced Migration of Fuchs Corneal Endothelial Cells by Rho Kinase Inhibition: A Novel Ex Vivo Descemet's Stripping Only Model.

Descemet's Stripping Only (DSO) is a surgical technique that utilizes the peripheral corneal endothelial cell (CEnC) migration for wound closure. Ripasudil, a Rho-associated protein kinase (ROCK) inhibitor, has shown potential in DSO treatment; however, its mechanism in promoting CEnC migration remains unclear. We observed that ripasudil-treated immortalized normal and Fuchs endothelial corneal dystrophy (FECD) cells exhibited significantly enhanced migration and wound healing, particularly effective in FECD cells. Ripasudil upregulated mRNA expression of Snail Family Transcriptional Repressor (SNAI1/2) and Vimentin (VIM) while decreasing Cadherin (CDH1), indicating endothelial-to-mesenchymal transition (EMT) activation. Ripasudil activated Rac1, driving the actin-related protein complex (ARPC2) to the leading edge, facilitating enhanced migration. Ex vivo studies on cadaveric and FECD Descemet's membrane (DM) showed increased migration and proliferation of CEnCs after ripasudil treatment. An ex vivo DSO model demonstrated enhanced migration from the DM to the stroma with ripasudil. Coating small incision lenticule extraction (SMILE) tissues with an FNC coating mix and treating the cells in conjunction with ripasudil further improved migration and resulted in a monolayer formation, as detected by the ZO-1 junctional marker, thereby leading to the reduction in EMT. In conclusion, ripasudil effectively enhanced cellular migration, particularly in a novel ex vivo DSO model, when the stromal microenvironment was modulated. This suggests ripasudil as a promising adjuvant for DSO treatment, highlighting its potential clinical significance.

Microkeratome versus manually dissected donor tissue for Descemet stripping endothelial keratoplasty: A randomized prospective study.

To compare the visual outcomes, postoperative complications, and graft asymmetry between precut and manually dissected donor tissues for Descemet stripping automated endothelial keratoplasty (DSAEK) and Descemet stripping endothelial keratoplasty (DSEK) procedures, respectively. Seventy eyes of 70 patients undergoing DSEK/DSAEK at a tertiary eyecare center in eastern India were included in this prospective randomized control study. The 70 eyes were divided equally into two groups. Group A (n = 35) and Group B (n = 35) underwent DSEK and DSAEK procedures, respectively. the operating surgeons prepared the manually dissected corneal grafts using lamellar dissectors. the eye bank technicians prepared the precut corneal grafts using a microkeratome. The patients were investigated postoperatively after 1 day, 1 week, 1 month, 3 months, and 6 months. The data were compared for visual outcomes [uncorrected visual acuity (UCVA), best-corrected visual acuity (BCVA), spherical and cylindrical refraction, and spherical equivalent], incidence of postoperative complications, and pachymetry. The mean age was 56.5 (±17.8) years, and the male-to-female ratio was 1.3:1. The most common indications were pseudophakic bullous keratopathy (45.71%, 32/70), failed graft (32.86%, 23/70), and Fuchs' endothelial corneal dystrophy (10%, 7/70). The indications for surgery (P = 0.732) and donor (P = 0.258) and host pachymetry (P = 0.986) were comparable between both groups. There was no significant difference in change of UCVA, BCVA, and postoperative refraction (mean spherical refraction, P = 0.849; mean cylindrical refraction, P = 0.516; spherical equivalent, P = 0.518) between the two groups. Postoperative complications like graft detachment (P = 0.179), graft failure (P = 0.513), graft infiltrate (P = 0.428), and endophthalmitis (P = 0.493) were higher in the DSAEK group; however, the difference between the groups was insignificant. The graft asymmetry index was higher in DSAEK than in DSEK; the difference was significant till the 1-month follow-up (P = 0.005). The outcome was similar in both groups. Therefore, manual donor dissection can be an alternative for microkeratome-assisted dissection in low-resource centers and countries to achieve good results.