Search Results (23)

Background and Objectives: Fuchs’ endothelial corneal dystrophy (FECD) is a progressive disorder characterized by endothelial cell loss, corneal edema, and reduced transparency. Scheimpflug tomography enables objective evaluation of the corneal structure, including densitometry as a marker of optical quality. This study aimed to assess topographic and microstructural corneal parameters in FECD patients using Pentacam tomography and to evaluate their diagnostic utility. Materials and Methods: A total of 89 subjects (178 eyes) were included: 47 patients with FECD (94 eyes) and 42 healthy controls (84 eyes). Participants were stratified by age and sex. All underwent comprehensive ophthalmic examination and corneal imaging with Pentacam HR. Corneal densitometry was analyzed in four concentric zones (0–2, 2–6, 6–10, and 10–12 mm) and three layers (anterior, central, posterior). Statistical analysis was performed using SPSS v.19, with p < 0.05 considered significant. Results: Densitometry values increased with age in both groups, with significantly higher values in FECD patients, particularly in peripheral zones (6–12 mm). The highest backscatter was consistently observed in the anterior corneal layer. Significant differences between FECD and controls were found in specific age subgroups and corneal regions. A progressive increase in backscatter from Descemet’s membrane was observed, corresponding to a transition in densitogram patterns from a “high-backed chair” to a “hammock” configuration. Disease progression appeared more pronounced in male patients. Conclusions: Corneal densitometry obtained by Scheimpflug tomography provides reliable quantitative and qualitative indicators of FECD progression. Its combined use with topographic parameters enhances early diagnosis and disease monitoring. Full article

The corneal endothelium is essential for maintaining corneal transparency through active fluid transport and barrier function. Corneal cell loss from disease, ageing or surgical trauma underlies a significant proportion of corneal blindness worldwide, with Fuchs’ endothelial corneal dystrophy (FECD) and pseudophakic bullous keratopathy (PBK) representing the dominant clinical indications for corneal transplantation. While Descemet’s membrane endothelial keratoplasty (DMEK) has substantially improved surgical outcomes, the procedure remains constrained by global donor tissue shortage. Regenerative medicine offers a compelling alternative by exploiting the latent proliferative and reparative potential of corneal endothelial progenitor populations. This review synthesises current knowledge on the foundational biology of corneal endothelial progenitor populations and the optimisation of expansion platforms to emerging preclinical and clinical evidence for both cell-based and pharmacological regenerative strategies. We also consider the outstanding translational challenges of potency standardisation, GMP-compliant manufacturing and regulatory navigation, as well as the longer-term potential of biomaterial-cell platforms and personalised iPSC-based medicine. The cumulative evidence positions progenitor-based approaches as viable and increasingly well-characterised alternatives to conventional donor transplantation, although their routine clinical use awaits the optimisation of manufacturing and regulatory platforms. Full article

Background/Objectives: The aim of this study was to compare the level of total proteins and antioxidant capacity in the corneal endothelium of patients with endothelial decompensation, due or not due to a Fuchs’ endothelial dystrophy (FECD), and analyze the influence of cataract formation. Methods: Endothelial cells from 27 patients with endothelial dystrophy and 6 from healthy human donors were used, distributed into four groups according to the presence of Fuchs’ Dystrophy and cataract. Results: Protein levels differed significantly among the five study groups (Kruskal–Wallis H = 12.19, p = 0.016). Patients with FECD, particularly those with concomitant cataract, showed the highest median protein concentrations, whereas lower values were observed in non-FECD groups. Post hoc Dunn’s test revealed a significant difference only between the non-FECD with cataract group and the controls (p < 0.05). The antioxidant capacity/protein ratio showed a marked variability across groups, with higher median values in non-FECD patients and greater dispersion in cataract groups; however, no statistically significant differences were detected (H = 5.58, p = 0.134). These findings highlight the differences in protein content and antioxidant defenses related to FECD and cataract status. Conclusions: Fuchs’ endothelial dystrophy is associated with higher protein levels and a moderately elevated but heterogeneous antioxidant capacity in the corneal endothelium, reflecting adaptive responses to chronic oxidative stress. In contrast, no FECD eyes, particularly those with cataract, showed lower or more variable antioxidant capacity, indicating reduced or inconsistent protective mechanisms. Full article

Objective: This was a longitudinal study of TCF4 CTG18.1 trinucleotide repeat lengths in 17 patients (27 eyes) diagnosed with Fuchs’ endothelial corneal dystrophy (FECD), and it aimed to correlate the repeat expansion status with disease severity and progression. Design: This was a prospective cohort study looking at FECD clinical progression and TCF4 CTG18.1 repeat length expansion status over time. Methods: A total of 27 eyes from 17 patients diagnosed with FECD were recruited. Only eyes with FECD disease severity of at least Grade 4 on the modified Krachmer clinical grading scale were included; eyes that had previously undergone any form of ocular surgery prior to the first genotyping or during the duration of follow-up were excluded. CTG trinucleotide repeat genotyping was performed on peripheral blood leukocytes at two time points over an average follow-up of 10 years. Over the follow-up period, the FECD progression of each subject was examined using pachymetry, Scheimpflug imaging (Pentacam), and endothelial cell density (ECD) readings, during the baseline visit, yearly thereafter, at the time of repeat CTG18.1 genotyping, and at their latest visit. Main Outcome Measures: The clinical progression of FECD patients was assessed using central corneal thickness (CCT), ECD, and any keratoplasty performed. CTG repeat length was assessed twice over the entire follow-up period. Results: The non-expanded alleles were shown to be stable over the period of follow-up and did not develop any expanded repeats. Repeat expansion did not influence the risk of attaining Threshold Disease, although more patients in the L ≥ 40 group (CTG18.1 repeat sequence of more than or equal to 40 repeats) underwent keratoplasty. Conclusions: Through this study, we found that the CTG18.1 allele lengths of <40 repeats in peripheral blood leukocytes showed minimal change over a 10-year period, and none became an expanded repeat. Hence, a single CTG expansion assessment, performed at any point in a patient’s lifetime, is likely a good representation of genetic risk. Clinicians may use this information to better advise patients on the risk of clinical progression and the best therapeutic strategy. Full article

Late-onset Fuchs endothelial corneal dystrophy (FECD) is a hereditary, progressive, bilateral and irreversible disorder that is characterized by thickening of Descemet’s membrane, microscopic collagenous protuberances known as guttae, and accelerated loss of corneal endothelial cells. Patients initially complain of blurred vision, and as the disease progresses, painful epithelial edema develops. Untreated cases of FECD often result in blindness, and then, the only treatment is corneal transplantation. DNA polymorphisms in many genes have been implicated, among them TCF4 on chromosome 18q, encoding a transcription factor protein E2-2, which is involved in regulating cellular growth and differentiation in the cornea. In our previous published study, we confirmed the association of an intronic TCF4 SNP (rs613872) with the disease in our population. The purpose of this present study is to further investigate another intronic point of interest in the same gene, the CTG18.1 trinucleotide repeat expansion. DNA was isolated from EDTA blood from a well-ascertained group of 36 Greek patients with FECD (Krachmer scale ≥ 2) and 58 healthy individuals, age- and sex-matched after obtaining their informed consent. STR-PCR and triplet-repeat primed PCR (TP-PCR) were performed, followed by gel electrophoresis and fragment analysis on an ABI SeqStudio genetic analyzer. Our real-time qPCR genotyping method was used for the SNP in the LightCycler (Roche). Statistical analysis of both genetic results was performed with SPSS and SNPStats. Full article

We evaluated the clinical applications of artificial intelligence models in diagnosing corneal diseases, highlighting their performance metrics and clinical potential. A systematic search was conducted for several disease categories: keratoconus (KC), Fuch’s endothelial corneal dystrophy (FECD), infectious keratitis (IK), corneal neuropathy, dry eye disease (DED), and conjunctival diseases. Metrics such as sensitivity, specificity, accuracy, and area under the curve (AUC) were extracted. Across the diseases, convolutional neural networks and other deep learning models frequently achieved or exceeded established diagnostic benchmarks (AUC > 0.90; sensitivity/specificity > 0.85–0.90), with a particularly strong performance for KC and FECD when trained on consistent imaging modalities such as anterior segment optical coherence tomography (AS-OCT). Models for IK and conjunctival diseases showed promise but faced challenges in heterogeneous image quality and limited objective training criteria. DED and tear film models benefited from multimodal data yet lacked direct comparisons with expert clinicians. Despite high diagnostic precision, challenges from heterogeneous data, a lack of standardization in disease definitions, imaging acquisition, and model training remain. The broad implementation of artificial intelligence must address these limitations to improve eye care equity. Full article

There is growing interest in the application of Rho-associated protein kinase (ROCK) inhibitors (ROCKI) to the treatment of corneal diseases. ROCK is a key regulator of several cellular processes in the cornea, including cytoskeletal organization, cell proliferation, migration, inflammation, and wound healing. ROCKI, such as ripasudil and netarsudil, enhances endothelial cell migration, and promotes repair in conditions characterized by endothelial dysfunction. These agents also exert anti-inflammatory, anti-angiogenic, and anti-fibrotic effects for wound healing. As such, ROCKI demonstrate promise as therapeutic options for conditions such as Fuchs’ endothelial corneal dystrophy, pseudophakic bullous keratopathy, and iridocorneal endothelial syndrome. Emerging data further supports ROCKI’s potential in managing corneal neovascularization and supporting recovery following cataract surgery and keratoplasty, reducing the need for donor tissue. This narrative review provides a comprehensive evaluation of ROCKI’s mechanism of action, pharmacological properties, safety profile, applications in corneal disease management, emerging clinical trials, and novel approaches. We emphasize both preclinical and clinical findings, highlight existing evidence gaps, and outline future research priorities. Full article

Fuchs’ endothelial corneal dystrophy (FECD) is a genetically complex eye disease associated with multiple genes. A recent systematic review has raised concerns about the causal role of variants in the LOXHD1 and AGBL1 genes in the development of FECD. Conflicting data have been reported on the expression of the LOXHD1 and AGBL1 genes in the corneal endothelium. Furthermore, only partial segregation of the variants was observed in familial cases. An analysis of published datasets was conducted to examine the expression of LOXHD1 and AGBL1 genes in normal and FECD-affected corneal endothelia and progenitor cells. Neither LOXHD1 nor AGBL1 genes were expressed in normal or FECD corneal endothelia or progenitor cells. In-house cohorts were screened for carriers of previously reported LOXHD1 and AGBL1 variants. Carriers and their first-degree relatives were invited for an ophthalmological examination to reassess the causal relationship of these variants with FECD phenotype. Three carriers of LOXHD1 variants (one carrier of rs200242497 and two carriers of rs192376005) and two carriers of AGBL1 variants (rs181958589 and rs185919705) were recruited. None of the carriers or first-degree relatives over 50 years exhibited phenotypic signs of FECD via ophthalmic examination. The causal role of the AGBL1 and LOXHD1 variants found in the carriers was not confirmed. Taken together, our findings do not support a causal role for AGBL1 and LOXHD1 in the development of FECD. Full article

Objectives: To provide an overview of the preoperative indications for endothelial graft in patients with Fuchs endothelial corneal dystrophy (FECD). Methods: A comprehensive database search without date restrictions was performed in PubMed. Keywords included Descemet membrane endothelial keratoplasty (DMEK), Descemet stripping automated endothelial keratoplasty (DSAEK), corneal keratoplasty, preoperative visual acuity, preoperative central corneal thickness, and densitometry. Articles aiming to describe or evaluate preoperative indications for endothelial keratoplasty were considered eligible and were included in this review. Results: The indications for surgery in FECD are disparate between the different studies. The tendency is to operate on patients earlier to obtain a better postoperative visual acuity at 1 year. The surgical decision is based on a number of arguments (visual acuity, CCT, densitometry). A preoperative visual acuity worse than 20/40 is generally considered a surgical indication for DMEK, based on current literature. Conclusions: Surgical decisions for Fuchs’ dystrophy should be individualized, guided by preoperative visual acuity, corneal OCT, and advanced imaging, with future risk scores potentially refining the timing of intervention to optimize outcomes. Full article

Fuchs’ endothelial corneal dystrophy (FECD) is a progressive eye disease characterized by accelerated loss of endothelial cells and the development of focal excrescence (guttae) on Descemet’s membrane, resulting in cornea opacity and vision deterioration. The development of FECD is assumed to be due to the interplay between genetic and environmental factor risks, causing abnormal extracellular-matrix organization, increased oxidative stress, apoptosis and unfolded protein response. However, the molecular knowledge of FECD is limited. The development of genome-wide platforms and bioinformatics approaches has enabled us to identify numerous genetic loci that are associated with FECD. In this review, we gathered genome-wide studies (n = 31) and sorted them according to genomics (n = 9), epigenomics (n = 3), transcriptomics (n = 15), proteomics (n = 3) and metabolomics (n = 1) levels to characterize progress in understanding FECD. We also extracted validated differentially expressed/spliced genes and proteins identified through comparisons of FECD case and control groups. In addition, highlighted loci from each omics layer were combined according to a comparison with similar study groups from original studies for downstream gene-set enrichment analysis, which provided the most significant biological pathways related to extracellular-matrix organization. In the future, multiomics study approaches are needed to increase the sample size and statistical power to identify strong candidate genes for functional studies on animal models and cell lines for better understanding FECD. Full article

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. Full article

Background: Age and sex are the most significant risk of factors for advanced Fuchs dystrophy. Nevertheless, few data are available on the hormone’s receptor pattern expressed in adult and advanced fuchs endothelial corneal dystrophy (FECD). We investigated the impact of gender, growth factors and extracellular matrix (ECM) regulatory proteins expressed by the dystrophic endothelia. Methods: Ten dystrophic endothelial tissues and 10 normal endothelial sheets (corneoscleral specimens; Eye Bank) were used for this characterization study. Hormones’ receptors (ERα, AR, PR, SHBG), few growth factors (VEGFA, βNGF, TGFβ1), some ECM regulators (MMP1, MMP7) and few inflammatory cytokines (IFNγ, IL10) were analyzed by real-time RT-PCR. Results: ERα transcripts were significantly increased, AR and SHBG transcripts were decreased in Fuchs endothelia from female patients, and no changes were detected for PR transcripts. VEGFA, βNGF and TGFβ1 transcripts were upregulated in Fuchs’ endothelia, but not significantly linked to gender. High MMP1 and low MMP7 transcripts’ expression were detected in Fuchs’ specimens, mainly in males than females. An increased IFNγ (Th1) transcript expression was observed in females than males, and a trend to increase for IL10 (Th2) transcripts was detected in males than females. Conclusions: Our findings clearly indicate that hormone receptors, growth factors and matrix mediators as well as a Th1 pathway are predominant in Fuchs’ dystrophy, displaying a pattern of expression specific for the female phenotype. The differential expression of hormones’ receptors and the Th1/Th2 ratio might prompt to new theories to be tested in vitro and in vivo models, such as the use of hormonal substitute for counteracting this endothelial cell lost. Full article

Background: Descemet Membrane Endothelial Keratoplasty (DMEK) has been widely adopted to treat Fuchs endothelial dystrophy (FED) and Bullous keratopathy (BK). Graft detachment (GD) is one of the common earliest post-operatory complications, and it is usually recovered by Air Rebubbling (ARB). Methods: Retrospectively, we investigated predictive factors related to GD between January 2016 and March 2020, a pre-COVID era, in 72 patients, 72 eyes, and their donors’ lamellar characteristics, focusing on donor’s cause of death. The patients were divided according to the posterior lamellar keratoplasty technique adopted. Results: GD and consequent ARB were most common but not significantly prevalent in DMEK (p = 0.11). It was more common in FED for both surgical approaches. Only in BK treated with DSAEK were host steeper mean astigmatism (p = 0.03) and donors with smaller graft pre-cut diameters (p = 0.02) less likely to be related to GD. Regarding donor’s cause of death, only cardiovascular accident could be related to GD in BK treated with DMEK (p = 0.04). Conclusions: Our study shows that the conventional match between pathology and corneal lenticule is not sufficient to prevent ARB. Donor’s cause of death can impair graft and host attachment. In particular, cardiovascular death may impair the efficiency of donors’ endothelial cells, inducing GD after DMEK in BK. Full article

The study investigated a profile of chemokines and growth factors in the aqueous humor (AH) of eyes with Fuch’s endothelial corneal dystrophy (FECD) and cataracts in comparison with cataract patients as a control group. A total of 52 AH samples (26 FECD + cataract and 26 cataract/control) were collected before cataract surgery. None of the patients had any clinically apparent inflammation at the time of AH collection. The AH levels of MCP-1 (CCL2), MIP-1α (CCL3), MIP-1β(CCL4), RANTES (CCL5), eotaxin (CCL11), IP-10 (CXCL10), FGF basic, G-CSF, GM-CSF, PDGF-bb, and VEGF were compared between the groups. The analyses were performed using the Bio-Plex 200 System from Bio-Rad. Among the studied parameters, the AH levels of RANTES, eotaxin, and IP-10 significantly increased in the FECD + cataract eyes, compared with the cataract controls (p < 0.05). Elevated levels of the RANTES, Eotaxin, and IP-10 indicate more intense inflammation in the eyes of patients in the FECD + cataract group. Moreover, these factors exhibit potential as predictive biomarkers for early detection of FECD in cataract patients. The discovery of elevated concentrations of biochemical markers in a patient, who has not yet received a clinical diagnosis, may suggest the need for heightened observation of the other eye to monitor the potential development of FECD. Full article

Purpose: To report on the surgical maneuvers recommended for a successful unfolding of very young donors in order to accomplish an uneventful Descemet Membrane Endothelial Keratoplasty (DMEK) surgery. Methods: Five patients (three females and two males, mean age 71.2 ± 6.7 years) with Fuchs endothelial cell dystrophy who underwent DMEK with very young donors (between 20 and 30 years old) were included. The following demographic data were assessed: donor’s age, donor’s endothelial cell density (ECD), preservation time, recipient’s age and sex and unfolding surgical time. Best-corrected visual acuity (BCVA; decimal system), ECD and corneal central thickness (CCT) were assessed preoperatively and at 6-month follow-up. Results: Donors’ mean age was 23.6 ± 3.6 years (range 21 to 30) and the mean ECD was 2748.6 ± 162.6 cells/mm². All of them underwent an uneventful DMEK as a single procedure performed by one experienced surgeon (MAG) with a mean unfolding time of 7.2 ± 4.9 min (range 4 to 15). The essential steps, including patient preparation as well as DMEK graft implantation, orientation, unrolling and centering are detailed. At 6 months, BCVA was 0.6 ± 0.2, ECD was 1945.0 ± 455.5 cells/mm² and CCT was 497.0 ± 19.7 microns. Conclusions: We hereby present the keys to overcome tightly scrolled grafts of very young donors, which prove perfectly suitable for DMEK surgery. The graft shape tends towards a double-roll and specific maneuvers are strongly recommended. Full article