Search Results (127)

Background/Objectives: The management of ocular tumors often necessitates surgery, either alone or in combination with radiotherapy, chemotherapy, or other modalities. While crucial for tumor control, these treatments can significantly impact the ocular surface, leading to both acute and chronic complications. This review examines iatrogenic ocular surface diseases resulting from oncologic interventions, emphasizing their pathophysiology, diagnostic challenges, and management strategies. Methods: A literature review was conducted to identify studies on iatrogenic ocular surface complications associated with ocular tumor treatments. Results: Ocular surface complications include direct damage from surgical manipulation, leading to corneal opacities and persistent epithelial defects, as well as dry eye disease secondary to postoperative chemosis. These disruptions may progress to more severe conditions such as keratopathy, corneal ulcers, limbal stem cell deficiency, and stromal scarring, further impairing visual function. Structural alterations contribute to eyelid malpositions—including ectropion, entropion, round eye, and lagophthalmos—which exacerbate exposure-related damage and ocular surface instability. In cases of uveal melanomas, the exposure of episcleral brachytherapy plaques can induce chronic conjunctival irritation, promoting adhesion formation and symblepharon. Surgical interventions disrupt ocular surface homeostasis, while radiotherapy and chemotherapy exacerbate these effects through cytotoxic and inflammatory mechanisms. Conclusions: Preventing and managing iatrogenic ocular surface complications require a multidisciplinary approach involving early diagnosis, personalized treatment strategies, and targeted postoperative care. Comprehensive pre- and postoperative planning is essential to optimize both visual function and long-term ocular surface integrity, ultimately ensuring a balance between oncologic control with functional and aesthetic preservation. Full article

MicroRNA-204-5p (miR-204-5p) is a critical regulator of differentiation, structural maintenance, and inflammation in limbal epithelial cells (LECs). This study examined the role of miR-204-5p in modulating the gene expression related to transcription factors, cell structure, extracellular matrix remodeling, and retinoic acid signaling under normal and lipopolysaccharide (LPS)-induced inflammatory conditions. Using qPCR, we analyzed the mRNA levels of FOSL2, FOXC1, Meis2, PPARγ, ABCG2, PTGES2, IL-1β, IL-6, KRT3, KRT12, MMP2, MMP9, RARA, RARB, RXRA, RXRB, CRABP2, RBP1, RDH10, ADH7, ADH1A1, FABP5, CYP1B1, and CYP26A1, while changes in protein levels were assessed via Western blot or ELISA. Our data revealed that the overexpression of miR-204-5p reduced the mRNA levels of FOXC1, KRT12, and RDH10 under normal and inflammatory conditions (p ≤ 0.039). Additionally, it decreased FOSL2 and RXRA mRNA under normal conditions (p = 0.006, p = 0.011) and KRT3 and FABP5 mRNA under inflammatory conditions (p = 0.010, p = 0.001). The IL-6 mRNA expression was significantly increased following the LPS treatment in cells overexpressing miR-204-5p (p = 0.029). A protein analysis revealed significant reductions in FOXC1 and KRT3 in the miR-204-5p-transfected cells during LPS-induced inflammation (p = 0.020, p = 0.030). These findings suggest that miR-204-5p modulates genes critical to the differentiation, migration, and inflammatory response of LECs. The modulation of FOXC1 and KRT3 by miR-204-5p highlights these proteins as novel targets under inflammatory conditions. Full article

Persistent corneal epithelial defects (PCEDs) are a challenging ocular condition characterized by the failure of complete corneal epithelial healing after an insult or injury, even after 14 days of standard care. There is a lack of therapeutics that target this condition and encourage re-epithelialization of the corneal surface in a timely and efficient manner. This review aims to provide an overview of current standards of management for PCEDs, highlighting novel, emerging treatments in this field. While many of the current non-surgical treatments aim to provide lubrication and mechanical support, novel non-surgical approaches are undergoing development to harness the proliferative and healing properties of human mesenchymal stem cells, platelets, lufepirsen, hyaluronic acid, thymosin ß4, p-derived peptide, and insulin-like growth factor for the treatment of PCEDs. Novel surgical treatments focus on corneal neurotization and limbal cell reconstruction using novel scaffold materials and cell-sources. This review provides insights into future PCED treatments that build upon current management guidelines. Full article

Besides alternative surgical methods for bilateral limbal deficiency, such as KLAL (keratolimbal allograft), living-related conjunctival limbal allograft (LR-CLAL), and keratoprosthesis, regenerative medicine often necessitates the use of alternative sources of limbal cells in cases where access to fellow eye source cells is limited. Mucosal cells are most commonly used to restore limbal tissue in such scenarios. Current techniques involving mucosal cells include cultivated oral mucosal transplantation (COMT), oral mucosal graft transplantation (OMGT), and simple oral mucosal transplantation (SOMT). COMT requires suspension of cells and a culturing process that is time-consuming and cost-prohibitive. In contrast, OMGT requires solely a strip of mucosal graft for transplanting into the deficient eye. The most recently developed practice, SOMT, in which chopped biopsy tissue is transplanted into the deficient area, compensates for problems associated with both COMT and OMGT, making the process of addressing bilateral limbal deficiency easy, time-saving, and affordable. Although some undesirable outcomes, such as angiogenesis, can occur post-transplantation, and the ultimate goal of differentiation into limbal epithelial stem cells may not be achieved, mucosal cell sources can be a good alternative for stabilizing the ocular surface. Some studies emphasize that co-culturing limbal niches in mucosal cell cultures can enhance differentiation capability. This concept highlights the importance of the limbal environment in the differentiation process. In this review, we demonstrate the ongoing changes in surgical technique trends and how they have made mucosal cell transplantation easier and more effective for limbal regeneration. Full article

Background/Objectives: Evaluation of stem cell, keratin, retinoic acid metabolism markers and non-coding micro-RNAs (miRNAs) in conjunctival and corneal samples of patients with epithelial basal membrane dystrophy (EBMD), Salzmann nodular degeneration (SND), pterygium and congenital aniridia (CA), to detect similarities and differences in their pathogenesis. Methods: Impression cytology (IC) samples and corneal epithelial samples (CEs) of patients with EBMD, SND, pterygium, congenital aniridia, and healthy control subjects have been analyzed. The IC samples were subjected to qPCR, and the epithelial samples were subjected to qPCR and WB. Limbal epithelial stem cell markers, keratins, retinoic acid metabolism markers, and miRNAs were analyzed. Results: In conjunctival IC samples, PAX6 mRNA expression was significantly lower in EBMD, SND, pterygium, and CA compared to healthy controls (p ≤ 0.02). KRT13 mRNA expression was significantly higher in EBMD, SND, and pterygium (p ≤ 0.018), and FABP5 was increased in pterygium samples (p = 0.007). MiRNA-138-5p was significantly higher in aniridia samples than in normal controls (p = 0.037). In corneal epithelial samples, PAX6 protein, DSG1 mRNA and protein, miRNA-138-5p, and miR-204-5p expression were significantly lower in EBMD, SND, and pterygium samples than in controls (p ≤ 0.02). ALDHA1 mRNA expression was significantly lower (p < 0.0001), and FABP5 mRNA expression was significantly higher (p = 0.014) in pterygium samples than in controls. Conclusions: PAX6, DSG1, miR-138-5p, and miR-204-5p expression is decreased in the corneal epithelium of epithelial basal membrane dystrophy, Salzmann nodular degeneration, and pterygium subjects. In addition, there is a dysregulation of markers of the retinoic acid signaling pathway, such as ADH1A1 and FABP5, in the corneal epithelium of pterygium subjects. These changes may offer therapeutic targets in the treatment of these ocular surface diseases. 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

The World Health Organization estimates that approximately 285 million people suffer from visual impairments, around 5% of which are caused by corneal pathologies. Currently, the most common clinical treatment consists of a corneal transplant (keratoplasty) from a human donor. However, worldwide demand for donor corneas amply exceeds the available supply. Lamellar keratoplasty (transplantation replacement of only one of the three layers of the cornea) is partially solving the problem of cornea undersupply. Obviously, cell therapy applied to every one of these layers will expand current therapeutic options, reducing the cost of ophthalmological interventions and increasing the effectiveness of surgery. Mesenchymal stem cells (MSCs) are adult stem cells with the capacity for self-renewal and differentiation into different cell lineages. They can be obtained from many human tissues, such as bone marrow, umbilical cord, adipose tissue, dental pulp, skin, and cornea. Their ease of collection and advantages over embryonic stem cells or induced pluripotent stem cells make them a very practical source for experimental and potential clinical applications. In this review, we focus on recent advances using MSCs from different sources to replace the damaged cells of the three corneal layers, at both the preclinical and clinical levels for specific corneal diseases. Full article

Despite the promising potential of cell-based therapies developed using tissue engineering techniques to treat a wide range of diseases, including limbal stem cell deficiency (LSCD), which leads to corneal blindness, their commercialization remains constrained. This is primarily attributable to the limited cell sources, the use of non-standardizable, unscalable, and unsustainable techniques, and the extended manufacturing processes required to produce transplantable tissue-like surrogates. Herein, we present the first demonstration of the potential of a novel approach combining collagen films (CF), hyaluronic acid (HA), human telomerase-immortalized limbal epithelial stem cells (T-LESCs), and macromolecular crowding (MMC) to develop innovative biomimetic substrates for limbal epithelial stem cells (LESCs). The initial step involved the fabrication and characterization of CF and CF enriched with HA (CF-HA). Subsequently, T-LESCs were seeded on CF, CF-HA, and tissue culture plastic (TCP). Thereafter, the effect of these matrices on basic cellular function and tissue-specific extracellular matrix (ECM) deposition with or without MMC was evaluated. The viability and metabolic activity of cells cultured on CF, CF-HA, and TCP were found to be similar, while CF-HA induced the highest (p < 0.05) cell proliferation. It is notable that CF and HA induced cell growth, whereas MMC increased (p < 0.05) the deposition of collagen IV, fibronectin, and laminin in the T-LESC culture. The data highlight the potential of, in particular, immortalized cells and MMC for the development of biomimetic cell culture substrates, which could be utilized in ocular surface reconstruction following further in vitro, in vivo, and clinical validation of the approach. Full article

The limited availability of corneal tissue grafts poses significant challenges in the treatment of corneal blindness. Novel treatment utilizes stem cell grafts transplanted from the healthy side of the cornea to the damaged side. However, this procedure is only possible for those who have one-sided corneal blindness. Human stem cells offer promising potential for corneal tissue engineering, providing an alternative solution. Among the different types of stem cells, mesenchymal stem cells (MSCs) stand out due to their abundance and ease of isolation. Human MSCs can be derived from bone marrow, adipose, and umbilical cord tissues. Differentiating MSC toward corneal tissue can be achieved through several methods including chemical induction and co-culture with adult corneal cells such as human limbal epithelial stem cells (LESCs) and human corneal epithelial cells (hTCEpi). Adipose-derived stem cells (ADSCs) are the most common type of MSC that has been studied for corneal differentiation. Corneal epithelial cells are the most common corneal cell type targeted by researchers for corneal differentiation. Chemical induction with small molecules, especially bone morphogenetic protein 4 (BMP4), all-trans retinoic acid (ATRA), and epidermal growth factor (EGF), has gained more popularity in corneal epithelial cell differentiation. This review highlights the current progress in utilizing MSCs for corneal differentiation studies, showcasing their potential to revolutionize treatments for corneal blindness. Full article

The cornea is a vital component of the visual system, and its integrity is crucial for optimal vision. Damage to the cornea resulting from trauma, infection, or disease can lead to blindness. Corneal regeneration using mesenchymal stem cells (MSCs) and MSC-derived extracellular vesicles (MSC-EVs) offers a promising alternative to corneal transplantation. MSCs are multipotent stromal cells that can differentiate into various cell types, including corneal cells. They can also secrete a variety of anti-inflammatory cytokines and several growth factors, promoting wound healing and tissue reconstruction. This review summarizes the current understanding of the molecular and cellular mechanisms by which MSCs and MSC-EVs contribute to corneal regeneration. It discusses the potential of MSCs and MSC-EV for treating various corneal diseases, including corneal epithelial defects, dry eye disease, and keratoconus. The review also highlights finalized human clinical trials investigating the safety and efficacy of MSC-based therapy in corneal regeneration. The therapeutic potential of MSCs and MSC-EVs for corneal regeneration is promising; however, further research is needed to optimize their clinical application. Full article

Dye-based angiography is the main imaging modality in evaluating the vasculature of the eye. Although most commonly used to assess retinal vasculature, it can also delineate normal and abnormal blood vessels in the anterior segment diseases—but is limited due to its invasive, time-consuming methods. Thus, anterior segment optical coherence tomography angiography (AS-OCTA) is a useful non-invasive modality capable of producing high-resolution images to evaluate the cornea and ocular surface vasculature. AS-OCTA has demonstrated the potential to detect and delineate blood vessels in the anterior segment with quality images comparable to dye-based angiography. AS-OCTA has a diverse range of applications for the cornea and ocular surface, such as objective assessment of corneal neovascularization and response to various treatments; diagnosis and evaluation of ocular surface squamous neoplasia; and evaluation of ocular surface disease including limbal stem cell deficiency and ischemia. Our review aims to summarize the new developments and clinical applications of AS-OCTA for the cornea and ocular surface. 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

Background: Early therapeutic penetrating keratoplasty (TKP) for Acanthamoeba keratitis (AK) is thought to have a worse visual prognosis than the delayed optical penetrating keratoplasty (OKP) after successful conservative treatment of AK. This has led to a tendency to prolong conservative therapy and delay penetrating keratoplasty in patients with AK. This retrospective series presents the results of patients with AK that underwent early penetrating keratoplasty after reducing the corneal amoeba load through intensive conservative therapy, so-called “low load keratoplasty” (LLKP). Patients and methods: The medical records of our department were screened for patients with AK, confirmed by histological examination and/or PCR and/or in vivo confocal microscopy, which underwent ab LLKP and had a follow-up time of at least one year between 2009 and 2023. Demographic data, best corrected visual acuity (BCVA) and intraocular pressure at first and last visit, secondary glaucoma (SG), and recurrence and graft survival rates were assessed. Results: 28 eyes of 28 patients were included. The average time from initiation of therapy to penetrating keratoplasty (PKP) was 68 ± 113 days. The mean follow-up time after LLKP was 53 ± 42 months. BCVA (logMAR) improved from 1.9 ± 1 pre-operatively to 0.5 ± 0.6 at last visit (p < 0.001). A total of 14% of patients were under medical therapy for SG at the last visit, and two of them underwent glaucoma surgery. The recurrence rate was 4%. The Kaplan–Meier graft survival rate of the first graft at four years was 70%. The second graft survival rate at four years was 87.5%. Conclusion: LLKP appears to achieve a good visual prognosis with an earlier visual and psychological habilitation, as well as low recurrence and SG rates. These results should encourage us to reconsider the optimal timing of PKP in therapy-resistant AK. Full article

Limbal mesenchymal stromal cells (LMSCs) reside in the limbal niche, supporting corneal integrity and facilitating regeneration. While mesenchymal stem/stromal cells (MSCs) are used in regenerative therapies, there is limited knowledge about LMSC subpopulations and their characteristics. This study characterized human LMSC subpopulations through the flow cytometric assessment of fifteen cell surface markers, including MSC, wound healing, immune regulation, ASC, endothelial, and differentiation markers. Primary LMSCs were established from remnant human corneal transplant specimens and passaged eight times to observe changes during subculture. The results showed the consistent expression of typical MSC markers and distinct subpopulations with the passage-dependent expression of wound healing, immune regulation, and differentiation markers. High CD166 and CD248 expressions indicated a crucial role in ocular surface repair. CD29 expression suggested an immunoregulatory role. Comparable pigment-epithelial-derived factor (PEDF) expression supported anti-inflammatory and anti-angiogenic roles. Sustained CD201 expression indicated maintained differentiation capability, while VEGFR2 expression suggested potential endothelial differentiation. LMSCs showed higher VEGF expression than fibroblasts and endothelial cells, suggesting a potential contribution to ocular surface regeneration through the modulation of angiogenesis and inflammation. These findings highlight the heterogeneity and multipotent potential of LMSC subpopulations during in vitro expansion, informing the development of standardized protocols for regenerative therapies and improving treatments for ocular surface disorders. Full article

Diabetes mellitus (DM) is a chronic metabolic disorder marked by hyperglycemia due to defects in insulin secretion, action, or both, with a global prevalence that has tripled in recent decades. This condition poses significant public health challenges, affecting individuals, healthcare systems, and economies worldwide. Among its numerous complications, ocular surface disease (OSD) is a significant concern, yet understanding its pathophysiology, diagnosis, and management remains challenging. This review aims to explore the epidemiology, pathophysiology, clinical manifestations, diagnostic approaches, and management strategies of diabetes-related OSD. The ocular surface, including the cornea, conjunctiva, and associated structures, is vital for maintaining eye health, with the lacrimal functional unit (LFU) playing a crucial role in tear film regulation. In DM, changes in glycosaminoglycan metabolism, collagen synthesis, oxygen consumption, and LFU dysfunction contribute to ocular complications. Persistent hyperglycemia leads to the expression of cytokines, chemokines, and cell adhesion molecules, resulting in neuropathy, tear film abnormalities, and epithelial lesions. Recent advances in molecular research and therapeutic modalities, such as gene and stem cell therapies, show promise for managing diabetic ocular complications. Future research should focus on pathogenetically oriented therapies for diabetic neuropathy and keratopathy, transitioning from animal models to clinical trials to improve patient outcomes. Full article