Search Results (20)

Corneal diseases are among the leading causes of blindness worldwide and the standard treatment is the transplantation of corneal donor tissue. Treatment for cornea-related visual impairment and blindness is, however, often constrained by the global shortage of suitable donor grafts. To alleviate the shortage of corneal donor tissue, new treatment options have been explored in the last decade. The discovery of induced pluripotent stem cells (iPSCs), which has revolutionized regenerative medicine, offers immense potential for corneal repair and regeneration. Using iPSCs can provide a renewable source for generating various corneal cell types, including corneal epithelial cells, stromal keratocytes, and corneal endothelial cells. To document the recent progress towards the clinical application of iPSC-derived corneal cells, this review summarizes the latest advancements in iPSC-derived corneal cell therapies, ranging from differentiation protocols and preclinical studies to the first clinical trials, and discusses the challenges for successful translation to the clinic. Full article

Background: Schnyder corneal dystrophy (SCD) is a rare autosomal dominant disorder characterized by bilateral corneal opacification due to abnormal cholesterol and phospholipid deposition. Mutations in the UBIAD1 gene, identified as causative in 2007, underline the condition, although its exact pathogenesis remains unclear. Case Presentation: A 55-year-old female presented with persistent photophobia, blepharospasm, and corneal discomfort. She also reported joint pain related to rheumatoid arthritis (RA), managed with Ro-Actemra (tocilizumab). The ophthalmological evaluation revealed bilateral corneal stromal deposits resembling snowflakes, with visual acuities of 0.8 (right eye) and 0.7 (left eye). Multimodal imaging confirmed stromal hyperreflective deposits. Based on the clinical findings, SCD was diagnosed, although no genetic testing was performed. Symptomatic management with artificial tears was initiated. Discussion: This case illustrates the diagnostic challenges of SCD, particularly in the absence of corneal crystals, a hallmark feature that is not universally present. Advanced imaging techniques aided diagnosis, and the coexistence of SCD and RA highlights the need for multidisciplinary care. Treatment options remain limited, although emerging therapies targeting oxidative stress and lipid metabolism show promise. Conclusions: This case highlights the importance of integrating ophthalmological and systemic care in SCD management and underscores the need for further research to expand diagnostic and therapeutic strategies for this rare disorder. Full article

Background/Objectives: In this study, we aim to evaluate in vivo confocal microscopy (IVCM) findings of corneal stromal dystrophies (CSDs) including granular, macular and lattice corneal dystrophy that can be used for differential diagnosis and monitoring recurrences after surgical interventions. Methods: Patients diagnosed with CSD who were followed-up in the cornea and ocular surface unit were included in this study. IVCM was performed using the Heidelberg Retina Tomograph 3, Rostock Cornea Module (Heidelberg Engineering, Germany) and anterior segment optical coherence tomography (AS-OCT) imaging was performed using the Spectralis OCT (Heidelberg Engineering, Germany). The morphological structure, size and location of deposits, epithelial involvement and presence of inflammatory and dentritic cells were compared among the three stromal dystrophies. Results: A total of 72 eyes from 36 participants were included in this study. Twelve patients (33.33%) had granular corneal dystrophy (GCD), ten (27.77%) had macular corneal dystrophy (MCD) and fourteen (38.88%) had lattice corneal dystrophy (LCD). In GCD, highly reflective deposits varying in size (20 µm–300 µm) were observed. In MCD, diffuse hyperreflective stroma with dark striae, dentritic cells around deposits and abnormal keratocytes were observed. In LCD, there were branching, lattice-like and granular deposits with epithelial cell disruption in some of the eyes. In MCD, the central corneal thickness was thinner (449.44 ± 65.45 µm) compared to GCD and LCD (565.16 ± 49.62 µm and 569.91 ± 39.32 µm p < 0.001). Recurrence was observed in five patients following penetrating keratoplasty. Conclusions: IVCM is a valuable tool for distinguishing CSD subtypes and monitoring recurrence following surgical interventions. Full article

We describe retrospectively the indications and outcomes of nine patients who present with varying degrees of deep posterior stromal scarring or endothelial failure following deep anterior lamellar keratoplasty (DALK). These patients underwent a surgical strategy coined Intraoperative Optical Coherence Tomography Guided Femtosecond Laser-Assisted Descemet Membrane Endothelial Keratoplasty (iFAD). This strategy can be used to address suboptimal visual outcomes following primary DALK. Patients undergoing iFAD first had femtosecond laser-assisted trephination of the underlying posterior lamella using the liquid keratoplasty system on the Femto LDV Z8 platform (Zeimer Ophthalmic Systems AG, Port, Switzerland). A Descemet Membrane Endothelial Keratoplasty (DMEK) graft was subsequently transplanted in place of the removed lamella. Out of nine cases, major indications for seven included post-infective, blepharokeratoconjunctivitis (BKC) and deep stromal scarring related to stromal dystrophy. The remaining two had endothelial failure following primary DALK. The main benefits of this surgical approach are (1) Utilization of integrated real-time iOCT on the femtosecond laser platform allows for precise calibration of a wide range of vertical posterior trephination depths (96–329 microns) from the endothelial surface. (2) Femtosecond laser trephination utilizing a non-applanation liquid interface preserves trephination geometries and maximises precision-based surgical outcomes. (3) iFAD is a viable and straightforward technique for surgeons addressing patients who might otherwise require complex surgery to address residual deep stromal scars post-DALK. 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

Fuchs endothelial corneal dystrophy (FECD) is a complex genetic disorder characterized by the slow and progressive degeneration of corneal endothelial cells. Thus, it may result in corneal endothelial decompensation and irreversible corneal edema. Moreover, FECD is associated with alterations in all corneal layers, such as thickening of the Descemet membrane, stromal scarring, subepithelial fibrosis, and the formation of epithelial bullae. Hence, anterior segment imaging devices that enable precise measurement of functional and anatomical changes in the cornea are essential for the management of FECD. In this review, the authors will introduce studies on the application of various imaging modalities, such as anterior segment optical coherence tomography, Scheimpflug corneal tomography, specular microscopy, in vitro confocal microscopy, and retroillumination photography, in the diagnosis and monitoring of FECD and discuss the results of these studies. The application of novel technologies, including image processing technology and artificial intelligence, that are expected to further enhance the accuracy, precision, and speed of the imaging technologies will also be discussed. Full article

The Klotho loss-of-function mutation is known to cause accelerated senescence in many organs, but its effects on the cornea have not been published. The present study aims to investigate the effects of the Klotho null mutation on cornea degeneration and to characterize the pathological features. Mouse corneas of Klotho homozygous, heterozygous, and wild-type mice at 8 weeks of age for both genders were subject to pathological and immunohistological examinations. The results show an irregular topography on the corneal surface with a Klotho null mutation. Histological examinations revealed a reduced corneal epithelial cell density, endothelial cell-shedding, and decreased cornea stromal layer thickness in the absence of the Klotho function. Furthermore, guttae formation and the desquamation of wing cells were significantly increased, which was comparable to the characteristics of Fuchs endothelial corneal dystrophy and bullous keratopathy. The mechanism analysis showed multi-fold abnormalities, including oxidative stress-induced cornea epithelium apoptosis and inflammation, extracellular matrix remodeling in the stroma, and a disruption of epithelial repair, presumably through the epithelial–mesenchymal transition. In conclusion, cornea degeneration was observed in the Klotho loss-of-function mutant mice. These pathological features support the use of Klotho mutant mice for investigating age-related cornea anomalies, including Fuchs endothelial corneal dystrophy, bullous keratopathy, and dry eye diseases. Full article

Duchenne muscular dystrophy (DMD) is a muscle disease caused by mutations in the dystrophin gene characterized by myofiber fragility and progressive muscle degeneration. The genetic defect results in a reduced number of self-renewing muscle stem cells (MuSCs) and an impairment of their activation and differentiation, which lead to the exhaustion of skeletal muscle regeneration potential and muscle replacement by fibrotic and fatty tissue. In this study, we focused on an unexplored strategy to improve MuSC function and to preserve their niche based on the regenerative properties of mesenchymal stromal cells from the amniotic membrane (hAMSCs), that are multipotent cells recognized to have a role in tissue repair in different disease models. We demonstrate that the hAMSC secretome (CM hAMSC) and extracellular vesicles (EVs) isolated thereof directly stimulate the in vitro proliferation and differentiation of human myoblasts and mouse MuSC from dystrophic muscles. Furthermore, we demonstrate that hAMSC secreted factors modulate the muscle stem cell niche in dystrophic–mdx-mice. Interestingly, local injection of EV hAMSC in mdx muscles correlated with an increase in the number of activated Pax7+/Ki67+ MuSCs and in new fiber formation. EV hAMSCs also significantly reduced muscle collagen deposition, thus counteracting fibrosis and MuSCs exhaustion, two hallmarks of DMD. Herein for the first time we demonstrate that CM hAMSC and EVs derived thereof promote muscle regeneration by supporting proliferation and differentiation of resident muscle stem cells. These results pave the way for the development of a novel treatment to counteract DMD progression by reducing fibrosis and enhancing myogenesis in dystrophic muscles. Full article

The aim of the study was to investigate oxidative stress as well as cellular protein accumulation in corneal diseases including keratoconus (KC), macular corneal dystrophy (MCD), and Fuchs endothelial corneal dystrophy (FECD) at their primary affecting sites. Corneal buttons from KC, MCD, and FECD patients, as well as healthy controls, were analyzed immunohistochemically to evaluate the presence of oxidative stress and the function of the proteostasis network. 4-Fydroxynonenal (4-HNE) was used as a marker of oxidative stress, whereas the levels of catalase and heat-shock protein 70 (HSP70) were analyzed to evaluate the response of the antioxidant defense system and molecular chaperones, respectively. Sequestosome 1 (SQSTM1) levels were determined to assess protein aggregation and the functionality of autophagic degradation. Basal epithelial cells of the KC samples showed increased levels of oxidative stress marker 4-HNE and antioxidant enzyme catalase together with elevated levels of HSP70 and accumulation of SQSTM1. Corneal stromal cells and endothelial cells from MCD and FECD samples, respectively, showed similarly increased levels of these markers. All corneal diseases showed the presence of oxidative stress and activation of the molecular chaperone response to sustain protein homeostasis. However, the accumulation of protein aggregates suggests insufficient function of the protective mechanisms to limit the oxidative damage and removal of protein aggregates via autophagy. These results suggest that oxidative stress has a role in KC, MCD, and FECD at the cellular level as a secondary outcome. Thus, antioxidant- and autophagy-targeted therapies could be included as supporting care when treating KC or corneal dystrophies. Full article

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. Full article

Progressive corneal opacification can result from multiple etiologies, including corneal dystrophies or systemic and genetic diseases. We describe a novel syndrome featuring progressive epithelial and anterior stromal opacification in a brother and sister and their mildly affected father, with all three family members having sensorineural hearing loss and two also with tracheomalacia/laryngomalacia. All carried a 1.2 Mb deletion at chromosome 13q12.11, with no other noteworthy co-segregating variants identified on clinical exome or chromosomal microarray. RNAseq analysis from an affected corneal epithelial sample from the proband’s brother revealed downregulation of XPO4, IFT88, ZDHHC20, LATS2, SAP18, and EEF1AKMT1 within the microdeletion interval, with no notable effect on the expression of nearby genes. Pathway analysis showed upregulation of collagen metabolism and extracellular matrix (ECM) formation/maintenance, with no significantly down-regulated pathways. Analysis of overlapping deletions/variants demonstrated that deleterious variants in XPO4 were found in patients with laryngomalacia and sensorineural hearing loss, with the latter phenotype also being a feature of variants in the partially overlapping DFNB1 locus, yet none of these had reported corneal phenotypes. Together, these data define a novel microdeletion-associated syndromic progressive corneal opacification and suggest that a combination of genes within the microdeletion may contribute to ECM dysregulation leading to pathogenesis. Full article

Bowman’s layer is an acellular layer in the anterior stroma found in the corneas of humans, most other primates, chickens, and some other species. Many other species, however, including the rabbit, dog, wolf, cat, tiger, and lion, do not have a Bowman’s layer. Millions of humans who have had photorefractive keratectomy over the past thirty plus years have had Bowman’s layer removed by excimer laser ablation over their central cornea without apparent sequelae. A prior study showed that Bowman’s layer does not contribute significantly to mechanical stability within the cornea. Bowman’s layer does not have a barrier function, as many cytokines and growth factors, as well as other molecules, such as EBM component perlecan, pass bidirectionally through Bowman’s layer in normal corneal functions, and during the response to epithelial scrape injury. We hypothesized that Bowman’s layer represents a visible indicator of ongoing cytokine and growth factor-mediated interactions that occur between corneal epithelial cells (and corneal endothelial cells) and stromal keratocytes that maintain the normal corneal tissue organization via negative chemotactic and apoptotic effects of modulators produced by the epithelium on stromal keratocytes. Interleukin-1 alpha, produced constitutively by corneal epithelial cells and endothelial cells, is thought to be one of these cytokines. Bowman’s layer is destroyed in corneas with advanced Fuchs’ dystrophy or pseudophakic bullous keratopathy when the epithelium becomes edematous and dysfunctional, and fibrovascular tissue commonly develops beneath and/or within the epithelium in these corneas. Bowman’s-like layers have been noted to develop surrounding epithelial plugs within the stromal incisions years after radial keratotomy. Although there are species-related differences in corneal wound healing, and even between strains within a species, these differences are not related to the presence or absence of Bowman’s layer. Full article

Corneal dystrophies are a group of non-inflammatory inherited disorders of the cornea. This review considers treatment options for epithelial-stromal and stromal corneal dystrophies: namely Reis–Bücklers, Thiel–Behnke, lattice, Avellino, granular, macular and Schnyder corneal dystrophies. Where there is visual reduction, treatment options may include either phototherapeutic keratectomy (PTK) or corneal transplantation. Due to the anterior location of the deposits in Reis-Bücklers and Thiel–Behnke dystrophies, PTK is considered the treatment of choice. For lattice, Avellino, granular and macular corneal dystrophies, PTK provides temporary visual improvement; however, with recurrences, repeat PTK or a corneal transplant would be needed. For Schnyder dystrophy, should treatment be required, PTK may be the preferred option due to the potential for recurrence of the disease in corneal transplantation. This review discusses the literature and evidence base for the treatment of corneal dystrophies in terms of visual outcomes and recurrence rate. Full article

Decorin is an archetypal member of the small leucine-rich proteoglycan gene family and is involved in various biological functions and many signaling networks, interacting with extra-cellular matrix (ECM) components, growth factors, and receptor tyrosine kinases. Decorin also modulates the growth factors, cell proliferation, migration, and angiogenesis. It has been reported to be involved in many ischemic and fibrotic eye diseases, such as congenital stromal dystrophy of the cornea, anterior subcapsular fibrosis of the lens, proliferative vitreoretinopathy, et al. Furthermore, recent evidence supports its role in secondary posterior capsule opacification (PCO) after cataract surgery. The expression of decorin mRNA in lens epithelial cells in vitro was found to decrease upon transforming growth factor (TGF)-β-2 addition and increase upon fibroblast growth factor (FGF)-2 addition. Wound healing of the injured lens in mice transgenic for lens-specific human decorin was promoted by inhibiting myofibroblastic changes. Decorin may be associated with epithelial–mesenchymal transition and PCO development in the lens. Gene therapy and decorin administration have the potential to serve as excellent therapeutic approaches for modifying impaired wound healing, PCO, and other eye diseases related to fibrosis and angiogenesis. In this review, we present findings regarding the roles of decorin in the lens and ocular diseases. Full article

Inherited retinal dystrophies and retinal degenerations related to more common diseases (i.e., age-related macular dystrophy) are a major issue and one of the main causes of low vision in pediatric and elderly age groups. Advancement and understanding in molecular biology and the possibilities raised by gene-editing techniques opened a new era for clinicians and patients due to feasible possibilities of treating disabling diseases and the reduction in their complications burden. The scope of this review is to focus on the state-of-the-art in somatic cell therapy medicinal products as the basis of new insights and possibilities to use this approach to treat rare eye diseases. Full article