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Ophthalmologica. Journal International... 2014Keratoconus (KCN) is an ectatic disorder with progressive corneal thinning and a clinical picture of corneal protrusion, progressive irregular astigmatism, corneal... (Review)
Review
Keratoconus (KCN) is an ectatic disorder with progressive corneal thinning and a clinical picture of corneal protrusion, progressive irregular astigmatism, corneal fibrosis and visual deterioration. Other ectatic corneal disorders include: post-LASIK ectasia (PLE) and pellucid marginal degeneration (PMD). Corneal crosslinking (CXL) is a procedure whereby riboflavin sensitization with ultraviolet A radiation induces stromal crosslinks. This alters corneal biomechanics, causing an increase in corneal stiffness. In recent years, CXL has been an established treatment for the arrest of KCN, PLE and PMD progression. CXL has also been shown to be effective in the treatment of corneal infections, chemical burns, bullous keratopathy and other forms of corneal edema. This is a current review of CXL - its biomechanical principles, the evolution of CXL protocols in the past, present and future, indications for treatment, treatment efficacy and safety.
Topics: Collagen; Cornea; Corneal Stroma; Cross-Linking Reagents; Elasticity; Humans; Keratoconus; Photosensitizing Agents; Riboflavin; Ultraviolet Rays
PubMed: 24751584
DOI: 10.1159/000357979 -
Eye (London, England) Sep 2019Ocular chemical injuries vary in severity, with the more severe end of the spectrum having profound visual consequences and medicolegal implications. Grading of ocular... (Review)
Review
Ocular chemical injuries vary in severity, with the more severe end of the spectrum having profound visual consequences and medicolegal implications. Grading of ocular injuries is critical for determining acute treatment and visual prognosis. Poor immediate management results in more challenging treatment of acute disease. Similarly, poorly controlled acute disease results in more treatment-resistant chronic ocular disease. Despite several decades of research and public health initiatives, simple and effective interventions such as wearing protective eyewear and immediate irrigation of eyes remain as key challenges. Education and prevention are therefore important public health messages. Hurdles in the acute management of disease include poor evidence-base for commonly used treatments (e.g. based on experimental animal studies), reduced treatment adherence rates and high clinic non-attendance rates. The evolution of treatment strategies, particularly limbal stem cell transplantation, has revolutionised the visual and cosmetic outcomes in chronic phases of disease. It is therefore increasingly important to consider tertiary referral for patients with limbal stem cell failure or vision-limiting corneal scarring.
Topics: Acids; Alkalies; Animals; Burns, Chemical; Eye Burns; Humans
PubMed: 31086244
DOI: 10.1038/s41433-019-0456-5 -
Annals of Medicine Dec 2022Neurotrophic keratopathy (NK), or neurotrophic keratitis, is a degenerative condition that results from decreased innervation to the cornea. The cornea is innervated by... (Review)
Review
Neurotrophic keratopathy (NK), or neurotrophic keratitis, is a degenerative condition that results from decreased innervation to the cornea. The cornea is innervated by the ophthalmic branch of the trigeminal nerve. Neurotrophic keratopathy is most commonly caused by herpes keratitis however, any condition that disrupts the normal corneal innervation can cause NK. Neurotrophic keratopathy is a clinical diagnosis and is classified into three stages based on the disease severity. Stage 1 has mild epithelial defects, such as punctate keratopathy, stage 2 disease has persistent epithelial defects, and stage 3 is defined by the presence of ulcers. Current treatment modalities consist of medical and surgical options. Stage 1 is treated with lubrication through artificial tears, eyelid taping, and punctal plug/cautery. Stage 2 treatment can involve therapeutic contact lenses, topical autologous or allogenic serum, tarsorrhaphy, botulinum toxin injections, and possibly anti-inflammatory medications. Stage 3 disease may require human nerve growth factor, amniotic membrane transplantation, conjunctival flap, or corneal neurotization. New therapies, such as matrix regenerating therapy, plasma rich in growth factors, Thymosin β4, Substance P/Insulin like growth factor-1, and nicergoline represent exciting future options.KEY MESSAGESNeurotrophic keratopathy is a rare degenerative disease defined by decreased innervation to the cornea that is associated with significant morbidity.Treatment options range from lubrication alone to various medical and surgical treatments.Matrix regenerating therapy, plasma rich in growth factors, Thymosin β4, Substance P/Insulin like growth factor-1, and nicergoline are exciting novel therapies that will influence how neurotrophic keratopathy is treated in the future.
Topics: Cornea; Corneal Dystrophies, Hereditary; Humans; Keratitis; Nerve Transfer; Trigeminal Nerve Diseases
PubMed: 35243932
DOI: 10.1080/07853890.2022.2045035 -
American Family Physician Jan 2010Red eye is the cardinal sign of ocular inflammation. The condition is usually benign and can be managed by primary care physicians. Conjunctivitis is the most common... (Review)
Review
Red eye is the cardinal sign of ocular inflammation. The condition is usually benign and can be managed by primary care physicians. Conjunctivitis is the most common cause of red eye. Other common causes include blepharitis, corneal abrasion, foreign body, subconjunctival hemorrhage, keratitis, iritis, glaucoma, chemical burn, and scleritis. Signs and symptoms of red eye include eye discharge, redness, pain, photophobia, itching, and visual changes. Generally, viral and bacterial conjunctivitis are self-limiting conditions, and serious complications are rare. Because there is no specific diagnostic test to differentiate viral from bacterial conjunctivitis, most cases are treated using broad-spectrum antibiotics. Allergies or irritants also may cause conjunctivitis. The cause of red eye can be diagnosed through a detailed patient history and careful eye examination, and treatment is based on the underlying etiology. Recognizing the need for emergent referral to an ophthalmologist is key in the primary care management of red eye. Referral is necessary when severe pain is not relieved with topical anesthetics; topical steroids are needed; or the patient has vision loss, copious purulent discharge, corneal involvement, traumatic eye injury, recent ocular surgery, distorted pupil, herpes infection, or recurrent infections.
Topics: Algorithms; Anti-Bacterial Agents; Blepharitis; Burns, Chemical; Corneal Diseases; Corneal Ulcer; Diagnosis, Differential; Dry Eye Syndromes; Endophthalmitis; Eye Burns; Eye Diseases; Eye Foreign Bodies; Eye Infections; Eye Injuries; Family Practice; Glaucoma; Glucocorticoids; Humans; Keratoconjunctivitis; Primary Health Care
PubMed: 20082509
DOI: No ID Found -
Translational Vision Science &... Jul 2022To evaluate the efficacy of losartan and prednisolone acetate in inhibiting corneal scarring fibrosis after alkali burn injury in rabbits.
PURPOSE
To evaluate the efficacy of losartan and prednisolone acetate in inhibiting corneal scarring fibrosis after alkali burn injury in rabbits.
METHODS
Sixteen New Zealand White rabbits were included. Alkali injuries were produced using 1N sodium hydroxide on a 5-mm diameter Whatman #1 filter paper for 1 minute. Four corneas in each group were treated six times per day for 1 month with 50 µL of (1) 0.8 mg/mL losartan in balanced salt solution (BSS), (2) 1% prednisolone acetate, (3) combined 0.8 mg/mL losartan and 1% prednisolone acetate, or (4) BSS. Area of opacity and total opacity were analyzed in standardized slit-lamp photos with ImageJ. Corneas in both groups were cryofixed in Optimal cutting temperature (OCT) compound at 1 month after surgery, and immunohistochemistry was performed for alpha-smooth muscle actin (α-SMA) and keratocan or transforming growth factor β1 and collagen type IV with ImageJ quantitation.
RESULTS
Combined topical losartan and prednisolone acetate significantly decreased slit-lamp opacity area and intensity, as well as decreased stromal myofibroblast α-SMA area and intensity of staining per section and confined myofibroblasts to only the posterior stroma with repopulation of the anterior and mid-stroma with keratocan-positive keratocytes after 1 month of treatment. Corneal fibroblasts produced collagen type IV not associated with basement membranes, and this production was decreased by topical losartan.
CONCLUSIONS
Combined topical losartan and prednisolone acetate decreased myofibroblast-associated fibrosis after corneal alkali burns that produced full-thickness injury, including corneal endothelial damage. Increased dosages and duration of treatment may further decrease scarring fibrosis.
TRANSLATIONAL RELEVANCE
Topical losartan and prednisolone acetate decrease myofibroblast-mediated scarring fibrosis after corneal injury.
Topics: Adrenal Cortex Hormones; Alkalies; Animals; Burns, Chemical; Cicatrix; Collagen Type IV; Corneal Diseases; Corneal Injuries; Fibrosis; Losartan; Myofibroblasts; Rabbits
PubMed: 35819289
DOI: 10.1167/tvst.11.7.9 -
Experimental Eye Research Dec 2022Corneal neovascularization can cause devastating consequences including vision impairment and even blindness. Corneal inflammation is a crucial factor for the induction...
Corneal neovascularization can cause devastating consequences including vision impairment and even blindness. Corneal inflammation is a crucial factor for the induction of corneal neovascularization. Current anti-inflammatory approaches are of limited value with poor therapeutic effects. Therefore, there is an urgent need to develop new therapies that specifically modulate inflammatory pathways and inhibit neovascularization in the cornea. The interaction of chemokines and their receptors plays a key role in regulating leukocyte migration during inflammatory response. CXCR3 is essential for mediating the recruitment of activated T cells and microglia/macrophages, but the role of CXCR3 in the initiation and promotion of corneal neovascularization remains unclear. Here, we showed that the expression of CXCL10 and CXCR3 was significantly increased in the cornea after alkali burn. Compared with WT mice, CXCR3 mice exhibited significantly increased corneal hemangiogenesis and lymphangiogenesis after alkali burn. In addition, exaggerated leukocyte infiltration and leukostasis, and elevated expression of inflammatory cytokines and angiogenic factor were also found in the corneas of CXCR3 mice subjected to alkali burn. With bone marrow (BM) transplantation, we further demonstrated that the deletion of CXCR3 in BM-derived leukocytes plays a key role in the acceleration of alkali burn-induced corneal neovascularization. Taken together, our results suggest that upregulation of CXCR3 does not exhibit its conventional action as a proinflammatory cytokine but instead serves as a self-protective mechanism for the modulation of inflammation and maintenance of corneal avascularity after corneal alkali burn.
Topics: Mice; Animals; Corneal Neovascularization; Burns, Chemical; Alkalies; Eye Burns; Corneal Injuries; Cornea; Inflammation; Cytokines; Disease Models, Animal
PubMed: 36206861
DOI: 10.1016/j.exer.2022.109265 -
International Journal of Molecular... May 2021Corneal transparency relies on the precise arrangement and orientation of collagen fibrils, made of mostly Type I and V collagen fibrils and proteoglycans (PGs). PGs are...
Corneal transparency relies on the precise arrangement and orientation of collagen fibrils, made of mostly Type I and V collagen fibrils and proteoglycans (PGs). PGs are essential for correct collagen fibrillogenesis and maintaining corneal homeostasis. We investigated the spatial and temporal distribution of glycosaminoglycans (GAGs) and PGs after a chemical injury. The chemical composition of chondroitin sulfate (CS)/dermatan sulfate (DS) and heparan sulfate (HS) were characterized in mouse corneas 5 and 14 days after alkali burn (AB), and compared to uninjured corneas. The expression profile and corneal distribution of CS/DSPGs and keratan sulfate (KS) PGs were also analyzed. We found a significant overall increase in CS after AB, with an increase in sulfated forms of CS and a decrease in lesser sulfated forms of CS. Expression of the CSPGs biglycan and versican was increased after AB, while decorin expression was decreased. We also found an increase in KS expression 14 days after AB, with an increase in lumican and mimecan expression, and a decrease in keratocan expression. No significant changes in HS composition were noted after AB. Taken together, our study reveals significant changes in the composition of the extracellular matrix following a corneal chemical injury.
Topics: Alkalies; Animals; Biomarkers; Burns, Chemical; Corneal Diseases; Dermatan Sulfate; Disease Models, Animal; Extracellular Matrix; Eye Burns; Fluorescent Antibody Technique; Gene Expression; Glycosaminoglycans; Heparitin Sulfate; Keratan Sulfate; Mice; Proteoglycans
PubMed: 34071909
DOI: 10.3390/ijms22115708 -
Aging Sep 2023This study aimed to investigate the senescent phenotypes of human corneal and conjunctival epithelial cells.
PURPOSE
This study aimed to investigate the senescent phenotypes of human corneal and conjunctival epithelial cells.
METHODS
We examined cell morphology, senescence-associated β-galactosidase (SA-β-gal) activity, cell proliferation, and expression of senescence markers (p16 and p21). RNA sequencing analysis was conducted to compare gene expression profiles between senescent and non-senescent cells. Finally, the potential involvement of senescent cells in the pathogenesis of ocular surface diseases was investigated.
RESULTS
X-irradiated corneal and conjunctival epithelial cells exhibited typical senescence phenotypes, i.e., flattened morphologies, increased SA-β-gal activity, decreased cell proliferation, and increased expression of senescence markers, p16 and p21. RNA-seq analysis revealed substantial differences in gene expression profiles between senescent corneal (SCo) and conjunctival epithelial cells (SCj). Moreover, SCj were detected in pathological conjunctival tissues associated with limbal stem cell deficiency (LSCD) due to Stevens-Johnson syndrome or chemical burns, potentially being involved in abnormal differentiation.
CONCLUSION
This study highlights the cellular and molecular characteristics of senescent ocular surface cells, particularly in SCj that show abnormal keratin expression, and their potential roles in severe ocular surface diseases and pathology.
Topics: Humans; Transcriptome; Limbus Corneae; Cornea; Epithelial Cells; Conjunctiva
PubMed: 37770232
DOI: 10.18632/aging.205113 -
Indian Journal of Ophthalmology Apr 2023Bilateral corneal blindness with severe dry eye disease (DED), total limbal stem cell deficiency with underlying corneal stromal scarring and vascularization, combined... (Review)
Review
Bilateral corneal blindness with severe dry eye disease (DED), total limbal stem cell deficiency with underlying corneal stromal scarring and vascularization, combined with adnexal complications secondary to chronic cicatrizing conjunctivitis is a highly complex situation to treat. In such eyes, procedures such as penetrating keratoplasty alone or combined with limbal stem cell transplantation are doomed to fail. In these eyes, keratoprosthesis (Kpro) or an artificial cornea is the most viable option, eliminating corneal blindness even in eyes with autoimmune disorders such as Stevens-Johnson syndrome, ocular mucous membrane pemphigoid, Sjogren's syndrome, and nonautoimmune disorders such as chemical/thermal ocular burns, all of which are complex pathologies. Performing a Kpro in these eyes also eliminates the need for systemic immunosuppression and may provide relatively early visual recovery. In such eyes, the donor cornea around the central cylinder of the Kpro needs to be covered with a second layer of protection to avoid desiccation and progressive stromal melt of the underlying cornea, which is a common complication in eyes with severe DED. In this review, we will focus on Kpro designs that have been developed to survive in eyes with the hostile environment of severe DED. Their outcomes in such eyes will be discussed.
Topics: Humans; Cornea; Prostheses and Implants; Corneal Diseases; Dry Eye Syndromes; Blindness; Retrospective Studies; Prosthesis Implantation
PubMed: 37026247
DOI: 10.4103/IJO.IJO_2817_22 -
Cells May 2023Limbal stem cell deficiency (LSCD) is a debilitating ocular surface disease that eventuates from a depleted or dysfunctional limbal epithelial stem cell (LESC) pool,... (Review)
Review
Limbal stem cell deficiency (LSCD) is a debilitating ocular surface disease that eventuates from a depleted or dysfunctional limbal epithelial stem cell (LESC) pool, resulting in corneal epithelial failure and blindness. The leading cause of LSCD is a chemical burn, with alkali substances being the most common inciting agents. Characteristic features of alkali-induced LSCD include corneal conjunctivalization, inflammation, neovascularization and fibrosis. Over the past decades, animal models of corneal alkali burn and alkali-induced LSCD have been instrumental in improving our understanding of the pathophysiological mechanisms responsible for disease development. Through these paradigms, important insights have been gained with regards to signaling pathways that drive inflammation, neovascularization and fibrosis, including NF-κB, ERK, p38 MAPK, JNK, STAT3, PI3K/AKT, mTOR and WNT/β-catenin cascades. Nonetheless, the molecular and cellular events that underpin re-epithelialization and those that govern long-term epithelial behavior are poorly understood. This review provides an overview of the current mechanistic insights into the pathophysiology of alkali-induced LSCD. Moreover, we highlight limitations regarding existing animal models and knowledge gaps which, if addressed, would facilitate development of more efficacious therapeutic strategies for patients with alkali-induced LSCD.
Topics: Animals; Limbus Corneae; Limbal Stem Cells; Phosphatidylinositol 3-Kinases; Stem Cells; Limbal Stem Cell Deficiency; Inflammation; Models, Animal
PubMed: 37174694
DOI: 10.3390/cells12091294