Search Results (66)

We previously showed that selective suppression of CD44 in the corneal epithelium leads to structural abnormalities in the mouse cornea. Our comparative studies of young and aged ocular biopsies revealed that CD44 expression is downregulated in aged corneas, while leucine-rich repeats and immunoglobulin-like domain 1 (Lrig1+) stem cells remain preserved in the peripheral limbus. These findings suggest an age-related shift in the corneal stem cell compartmentalization, characterized by impaired CD44 expression in the central cornea and preservation of Lrig1+ stem cells in the limbus, which become the main stem cells in the senescent cornea. To investigate this further, we performed topical tamoxifen-inducible, diphtheria toxin-mediated ablation of Lrig1+ stem cells in mouse corneas. We then assessed both activated and non-activated beta-catenin expression in wild-type (WT) and CD44 knockout (CD44KO) mice, given that CD44 modulates the Wingless-related integration site (Wnt) pathway. Our results indicate that two distinct stem cell populations operate in the mouse cornea: Lrig1-derived stem cells and Wnt-activity/CD44-dependent stem cells. The Lrig1-derived cells act as a reservoir of quiescent stem cells that regenerate the cornea upon injury, whereas under homeostatic conditions, the Wnt-activity/CD44-dependent stem cells are primarily responsible for corneal renewal. In the aged cornea, the loss of CD44 expression leads to reduced Wnt signaling, making the tissue increasingly dependent on Lrig1+ stem cells for regeneration. In mice, Lrig1+ stem cells are capable of sustaining permanent corneal renewal, even in the absence of CD44. Full article

Purpose: Pickleball, the fastest-growing sport in the United States, has seen a rapid increase in participation across all age groups, particularly among older adults. However, the sport introduces specific risks for ocular injuries due to the unique dynamics of gameplay and the physical properties of the pickleball. This study aims to explore the mechanisms of pickleball-related eye injuries, utilizing finite element modeling (FEM) to simulate ocular trauma and better understand injury mechanisms. Methods: A multi-modal approach was employed to investigate pickleball-related ocular injuries. Finite element modeling (FEM) was used to simulate blunt trauma to the eye caused by a pickleball. The FEM incorporated detailed anatomical models of the periorbital structures, cornea, sclera, and vitreous body, using hyperelastic material properties derived from experimental data. The simulations evaluated various impact scenarios, including changes in ball velocity, angle of impact, and material stiffness, to determine the stress distribution, peak strain, and deformation in ocular structures. The FEM outputs were correlated with clinical findings to validate the injury mechanisms. Results: The FE analysis revealed that the rigid, hard-plastic construction of a pickleball results in concentrated stress and strain transfer to ocular structures upon impact. At velocities exceeding 30 mph, simulations showed significant corneal deformation, with peak stresses localized at the limbus and anterior sclera. Moreover, our results show a significant stress applied to lens zonules (as high as 0.35 MPa), leading to potential lens dislocation. Posterior segment deformation was also observed, with high strain levels in the retina and vitreous, consistent with clinical observations of retinal tears and vitreous hemorrhage. Validation against reported injuries confirmed the model’s accuracy in predicting both mild injuries (e.g., corneal abrasions) and severe outcomes (e.g., hyphema, globe rupture). Conclusions: Finite element analysis provides critical insights into the biomechanical mechanisms underlying pickleball-related ocular injuries. The findings underscore the need for preventive measures, particularly among older adults, who exhibit age-related vulnerabilities. Education on the importance of wearing protective eyewear and optimizing game rules to minimize high-risk scenarios, such as close-range volleys, is essential. Further refinement of the FEM, including parametric studies and integration of protective eyewear, can guide the development of safety standards and reduce the socio-economic burden of these injuries. Full article

Background: This study evaluates the effect of limiting eyelid opening on wound closure time and surgical outcomes during cataract surgery. Methods: This retrospective study included 129 patients who had undergone cataract surgery between December 2023 and March 2024. The patients were divided into two groups based on the degree of eyelid opening: full eyelid opening group (n = 78) and 1 mm eyelid opening group (n = 51). Wound closure time, total operation time, postoperative intraocular pressure (IOP), uncorrected and best-corrected visual acuity (UCVA and BCVA, respectively), anterior chamber protein levels, and corneal endothelial cell loss were compared between the two groups. Results: The 1 mm eyelid opening group had a significantly shorter wound closure time (32.9 ± 11.2 s) compared with the full eyelid opening group (57.0 ± 21.3 s, p < 0.001), as well as reduced total operation time (547.5 ± 83.1 s vs. 606.9 ± 144 s, p = 0.02). No significant differences were observed in the postoperative IOP, BCVA, UCVA, anterior chamber protein levels, or corneal endothelial cell loss between the groups. Conclusions: Limiting the eyelid opening to 1 mm from the corneal limbus during cataract surgery can reduce wound closure time and total operation time without compromising visual outcomes or corneal endothelial health. This simple adjustment may contribute to improved surgical efficiency. Full article

Simple limbal epithelial transplantation (SLET) has emerged as an effective treatment option for limbal stem cell deficiency (LSCD). However, the precise molecular mechanisms underlying its success remain incompletely understood. This review delves into the proposed mechanisms involving the donor limbus, host microenvironment, and the amniotic membrane as a scaffold in SLET. The donor limbus contributes to SLET efficacy through various factors secreted by limbal epithelial stem cells, including hepatocyte growth factor (HGF), soluble Fms-like tyrosine kinase-1 (sFLT-1), and pigment epithelium-derived factor (PEDF), which support corneal healing and transparency. Additionally, the presence of melanocytes, immune cells, limbal fibroblasts, and adhesion molecules within the donor tissue helps preserve the integrity of the limbal niche. The host environment plays a critical role in supporting the transplanted stem cells, with mesenchymal stem cell-secreted factors promoting proliferation and differentiation. Although the amniotic membrane has traditionally been used as a scaffold, emerging evidence suggests that it may not always be necessary. Further studies are needed to validate this scaffold-free approach and to evaluate the vitality and functional contributions of individual components used in SLET. Understanding these complex interactions and molecular mechanisms sheds light on the importance of the donor tissue, host microenvironment, and scaffold in SLET, paving the way for the optimization of this technique for the effective treatment of LSCD. Full article

We have compared the biomechanical properties of human and porcine corneas using vibrational optical coherence tomography (VOCT). The elastic modulus of the cornea has been previously reported in the literature to vary from about several kPa to more than several GPa based on the results of different techniques. In addition, the formation of corneal cones near the central cornea in keratoconus has been observed in the clinic. Measurements of the resonant frequency and morphology of human and porcine corneas were used to evaluate the role of the limbus in corneal stabilization, the effect of Bowman’s layer, and the effect of collagen content on the low-strain corneal biomechanics. The results of these studies indicate that limbus stability plays an important anatomic role in preventing folding, corneal slippage, and cone formation. Machine learning studies of both human and porcine corneas indicate that Bowman’s membrane, like that of the collagen fibrils found in the anterior corneal stroma, contributes to the 110–120 Hz resonant frequency peak. Finite element and SOLIDWORKS models of normal and keratoconus corneas suggest that the deformation of the cornea is the highest at the central zone and is higher in keratoconus corneas compared to normal controls. VOCT results suggest that although collagen fibril slippage occurs first at the limbus, cone formation in keratoconus occurs centrally/paracentrally, where stress concentration and deformation due to intraocular forces are the highest. Cone formation occurs at the points of maximum curvature. Results of these studies indicate the elastic modulus of cornea fibrillar collagen dictates the corneal elastic modulus at low strains. These results suggest that tension in the cornea at the limbus results in deformation into the low modulus region of the J-shaped stress–strain curve, resulting in an in vivo strain of less than about 10%. We propose that tension in the cornea provides a baseline force that regulates corneal epithelial regeneration as well as corneal lamellae composition and matrix turnover. Full article

Background: The utilities of anterior segment optical coherence tomography (AS-OCT) for characterization, differential diagnosis, postoperative monitoring, and evaluation/comparison of surgical techniques in pterygium are described. Through AS-OCT, it is also possible to study the corneal astigmatic effect of pterygium. Our purpose is to study the associations between the anatomical characteristics of pterygium and the corneal topography through AS-OCT. Methods: Fifty eyes with primary pterygium in a tertiary hospital were evaluated before surgery by measuring 10 anatomical variables of pterygium and 13 topographic variables using AS-OCT (Casia 2; Tomey Corp., Nagoya, Japan). Statistical analysis was used to study the association between them. Results: Pterygium classified as flat pattern exhibited lower preoperative values of flat keratometry (K1), real flat keratometry (K1r), average keratometry (AvgK), and real average keratometry (AvgKr) compared to nodular ones. The flat pattern showed greater cylinder (CYL) and real cylinder (CLYr) values. The horizontal corneal invasion proportionally increased CYL and CYLr. Overall, larger anatomical pterygium measurements (limbus thickness (LimbusT), central pterygium thickness (CentreT), head pterygium thickness (HeadT), epithelial thickness at 1 mm (EpitT1mm), stromal thickness at 1 mm (stromT1mm), total thickness at 1 mm (TotalT1mm), total thickness at 2 mm (TotalT2mm), and total thickness at 3 mm (TotalT3mm)) resulted in lower anterior K1, K1r, AvgK, and AvgKr, and posterior K1 and AvgK values. CentreT was greater in astigmatisms against the rule than in oblique ones. Conclusions: This study demonstrates associations between preoperative topography and the NF (nodular or flat) classification of pterygium and its anatomical measurements assessed by AS-OCT. Full article

Background/Objectives: Postoperative intraocular lens (IOL) tilt is a risk associated with IOL scleral fixation. However, the cause of IOL tilt during IOL suturing remains unclear. Therefore, this study aimed to evaluate the surgical outcomes of a modified IOL suturing technique and investigate the factors contributing to postoperative IOL tilt and decentration. Methods: We included 25 eyes of 22 patients who underwent IOL suturing between April 2018 and February 2020. A modified IOL suturing technique that decreased the need for intraocular suture manipulation was used. Factors contributing to IOL tilt and decentration were investigated using an intraoperative optical coherence tomography (iOCT) system. Results: The mean postoperative best-corrected visual acuity improved from 0.15 ± 0.45 to −0.02 ± 0.19 (p = 0.02). The mean IOL tilt angle at the last visit after surgery was 1.84 ± 1.28 degrees. The present study reveals that the distance of the scleral puncture site from the corneal limbus had a stronger effect on IOL tilt; meanwhile, the suture position of the haptics had a greater effect on IOL decentration. Conclusions: The modified IOL suturing technique, which avoids intraocular suture handling, had favorable surgical outcomes with improved postoperative visual acuity and controlled IOL tilt and decentration. Accurate surgical techniques and careful measurement of distances during surgery are crucial for preventing postoperative IOL tilt and decentration. Full article

Corneal transparency and avascularity are essential for vision. The avascular cornea transitions into the vascularized conjunctiva at the limbus. Here, we explore a limbal stromal cell sub-population that expresses ABCB5 and has mesenchymal stem cell characteristics. Human primary corneal stromal cells were enriched for ABCB5 by using FACS sorting. ABCB5+ cells expressed the MSC markers CD90, CD73, and CD105. ABCB5+ but not ABCB5− cells from the same donor displayed evidence of pluripotency with a significantly higher colony-forming efficiency and the ability of trilineage differentiation (osteogenic, adipogenic, and chondrogenic). The ABCB5+ cell secretome demonstrated lower levels of the pro-inflammatory protein MIF (macrophage migration inhibitory factor) as well as of the pro-(lymph)angiogenic growth factors VEGFA and VEGFC, which correlated with reduced proliferation of Jurkat cells co-cultured with ABCB5+ cells and decreased proliferation of blood and lymphatic endothelial cells cultured in ABCB5+ cell-conditioned media. These data support the hypothesis that ABCB5+ limbal stromal cells are a putative MSC population with potential anti-inflammatory and anti-(lymph)angiogenic effects. The therapeutic modulation of ABCB5+ limbal stromal cells may prevent cornea neovascularization and inflammation and, if transplanted to other sites in the body, provide similar protective properties to other tissues. Full article

A pterygium is a common conjunctival degeneration and inflammatory condition. It grows onto the corneal surface or limbus, causing blurred vision and cosmetic issues. Ultraviolet is a well-known risk factor for the development of a pterygium, although its pathogenesis remains unclear, with only limited understanding of its hereditary basis. In this study, we collected RNA-seq from both pterygial tissues and conjunctival tissues (as controls) from six patients (a total of twelve biological samples) and retrieved publicly available data, including eight pterygium samples and eight controls. We investigated the intrinsic gene regulatory mechanisms closely linked to the inflammatory reactions of pterygiums and compared Asian (Korea) and the European (Germany) pterygiums using multiple analysis approaches from different perspectives. The increased expression of antioxidant genes in response to oxidative stress and DNA damage implies an association between these factors and pterygium development. Also, our comparative analysis revealed both similarities and differences between Asian and European pterygiums. The decrease in gene expressions involved in the three primary inflammatory signaling pathways—JAK/STAT, MAPK, and NF-kappa B signaling—suggests a connection between pathway dysfunction and pterygium development. We also observed relatively higher activity of autophagy and antioxidants in the Asian group, while the European group exhibited more pronounced stress responses against oxidative stress. These differences could potentially be necessitated by energy-associated pathways, specifically oxidative phosphorylation. Full article

Stem cells (SCs) undergo asymmetric division, producing transit-amplifying cells (TACs) with increased proliferative potential that move into tissues and ultimately differentiate into a specialized cell type. Thus, TACs represent an intermediary state between stem cells and differentiated cells. In the cornea, a population of stem cells resides in the limbal region, named the limbal epithelial stem cells (LESCs). As LESCs proliferate, they generate TACs that move centripetally into the cornea and differentiate into corneal epithelial cells. Upon limbal injury, research suggests a population of progenitor-like cells that exists within the cornea can move centrifugally into the limbus, where they dedifferentiate into LESCs. Herein, we summarize recent advances made in understanding the mechanism that governs the differentiation of LESCs into TACs, and thereafter, into corneal epithelial cells. We also outline the evidence in support of the existence of progenitor-like cells in the cornea and whether TACs could represent a population of cells with progenitor-like capabilities within the cornea. Furthermore, to gain further insights into the dynamics of TACs in the cornea, we outline the most recent findings in other organ systems that support the hypothesis that TACs can dedifferentiate into SCs. Full article

The corneal epithelium (CE) is spread between two domains, the outer vascularized limbus and the avascular cornea proper. Epithelial cells undergo constant migration from the limbus to the vision-critical central cornea. Coordinated with this migration, the cells undergo differentiation changes where a pool of unique stem/precursor cells at the limbus yields the mature cells that reach the corneal center. Differentiation is heralded by the expression of the corneal-specific Krt12. Processing data acquired by scRNA-Seq showed that the increase in Krt12 expression occurs in four distinct steps within the limbus, plus a single continuous increase in the cornea. Differential gene analysis demonstrated that these domains reflect discreet stages of CE differentiation and yielded extensive information of the genes undergoing down- or upregulation in the sequential transition from less to more differentiate conditions. The approach allowed the identification of multiple gene cohorts, including (a) the genes which have maximal expression in the most primitive, Krt12-negative cell cohort, which is likely to include the stem/precursor cells; (b) the sets of genes that undergo continuous increase or decrease along the whole differentiation path; and (c) the genes showing maximal positive or negative correlation with the changes in Krt12. Full article

The corneal epithelium, comprising three layers of cells, represents the outermost portion of the eye and functions as a vital protective barrier while concurrently serving as a critical refractive structure. Maintaining its homeostasis involves a complex regenerative process facilitated by the functions of the lacrimal gland, tear film, and corneal nerves. Crucially, limbal epithelial stem cells located in the limbus (transitional zone between the cornea and the conjunctiva) are instrumental for the corneal epithelium integrity by replenishing and renewing cells. Re-epithelialization failure results in persistent defects, often associated with various ocular conditions including diabetic keratopathy. The insulin-like growth factor (IGF) system is a sophisticated network of insulin and other proteins essential for numerous physiological processes. This review examines its role in maintaining the corneal epithelium homeostasis, with a special focus on the interplay with corneal limbal stem cells and the potential therapeutic applications of the system components. Full article

Implementing in silico corneal biomechanical models for surgery applications can be boosted by developing patient-specific finite element models adapted to clinical requirements and optimized to reduce computational times. This research proposes a novel corneal multizone-based finite element model with octants and circumferential zones of clinical interest for material definition. The proposed model was applied to four patient-specific physiological geometries of keratoconus-affected corneas. Free-stress geometries were calculated by two iterative methods, the displacements and prestress methods, and the influence of two boundary conditions: embedded and pivoting. The results showed that the displacements, stress and strain fields differed for the stress-free geometry but were similar and strongly depended on the boundary conditions for the estimated physiological geometry when considering both iterative methods. The comparison between the embedded and pivoting boundary conditions showed bigger differences in the posterior limbus zone, which remained closer in the central zone. The computational calculation times for the stress-free geometries were evaluated. The results revealed that the computational time was prolonged with disease severity, and the displacements method was faster in all the analyzed cases. Computational times can be reduced with multicore parallel calculation, which offers the possibility of applying patient-specific finite element models in clinical applications. Full article

Continuous replenishment of the corneal epithelium is pivotal for maintaining optical transparency and achieving optimal visual perception. This dynamic process is driven by limbal epithelial stem cells (LESCs) located at the junction between the cornea and conjunctiva, which is otherwise known as the limbus. In patients afflicted with diabetes, hyperglycemia-induced impairments in corneal epithelial regeneration results in persistent epithelial and other defects on the ocular surface, termed diabetic keratopathy (DK), which progressively diminish vision and quality of life. Reports of delayed corneal wound healing and the reduced expression of putative stem cell markers in diabetic relative to healthy eyes suggest that the pathogenesis of DK may be associated with the abnormal activity of LESCs. However, the precise role of these cells in diabetic corneal disease is poorly understood and yet to be comprehensively explored. Herein, we review existing literature highlighting aberrant LESC activity in diabetes, focusing on factors that influence their form and function, and emerging therapies to correct these defects. The consequences of malfunctioning or depleted LESC stocks in DK and limbal stem cell deficiency (LSCD) are also discussed. These insights could be exploited to identify novel targets for improving the management of ocular surface complications that manifest in patients with diabetes. Full article

Background and Objectives: To report a case of microbial keratitis complicated by severe corneal melting and whole corneal descemetocele. Methods: A 72-year-old male farmer presented with a right corneal ulcer involving nearly the entire cornea, which was almost completely melted down with the remaining Descemet’s membrane (DM). The pupil area was filled with melted necrotic material, with the intraocular lens partially protruding from the pupil and indenting the DM. Corneal optical coherence tomography (OCT) examination revealed a corneal thickness of 37 µm that was attached to its back surface, with the iris and a part of the intraocular lens (IOL) protruding through the pupil. The patient was hospitalized and treated with local and systemic antibiotics until control of the inflammation was achieved. Corneoscleral transplantation plus excision/transplantation of the corneal limbus were performed, and the entire corneal limbus was lamellarly incised. After completely suturing all around the transplanted corneoscleral graft, the anterior chamber was formed. Postoperative treatment included local antibiotics, anti-inflammatory drugs, and cycloplegic drops. Results: There was no recurrence of infection, and the corneal epithelium gradually regenerated and covered the whole graft. Visual acuity was light perception at 6 months after the surgery. The patient was satisfied that the globe was preserved and did not wish to undergo any further treatment. Conclusions: Corneoscleral transplantation is preferred for the treatment of large-sized descemetoceles with active microbial keratitis and extensive infiltrates, especially in cases where the whole cornea has transformed into a large cyst. Full article