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At least 343 records · Page 19Linked to original sources

Scleral contact lenses.

BACKGROUND: Scleral contact lenses provide unique therapeutic and vision rehabilitative properties that overcome the therapeutic gaps encountered with conventional contact lens therapies. CASE REPORTS: Four case reports are presented in which serious visual impairment was remediated with the application of scleral contact lenses: kerataconus, Terriens marginal degeneration, penetrating keratoplasty from Fuchs' dystrophy, and Stevens-Johnson syndrome. CONCLUSION: The availability of new and diverse materials--in particular, the use of highly oxygen-permeable materials for scleral contact lenses--has allowed reevaluation of the clinical role of scleral lenses in the management of irregular corneal surface disorders and ocular surface disease.

Adult↗

Inflammatory cytokines in normal human tears.

PURPOSE: To elucidate inflammatory cytokine levels in normal human tears, we investigated the concentrations of interleukin-1alpha (IL-1alpha), interleukin-1beta (IL-1beta), interleukin-6 (IL-6), and interleukin-8 (IL-8) both in basal tears and reflex tears of normal healthy eyes. METHODS: Tear samples were collected from 270 healthy, normal volunteers with no past history of ocular surface disease; the total number of eyes was 295. All tear samples were collected in graduated disposable microcapillaries from the conjunctival cul-de-sac. Reflex tear stimulation was carried out by inserting an applicator into each volunteer's nose. Cytokine levels in basal tears and reflex tears were determined by ELISA. Tears were not diluted, and pooled samples were used for the cytokine assays. RESULTS: In basal tears, the concentrations of IL-1alpha, -1beta, -6 and -8 were 10.9 +/- 1.2, 12.9 +/- 2.3, 226.2 +/- 29.6 and 731.4 +/- 116.2 pg/ml, respectively. In reflex tears, IL-1beta was not detectable, and the concentrations of IL-1alpha, -6 and -8 were 9.3 +/- 2.7, 11.6 +/- 1.6 and 276.1 +/- 47.5 pg/ml respectively. IL-1beta, -6 and -8 levels in reflex tears were significantly lower than those in basal tears, except for IL-1alpha. CONCLUSIONS: In the present study, the normal concentration range of inflammatory cytokines in human basal tears was clarified, as a baseline for further studies to examine the levels of these cytokines in tears during disease states.

Adult↗

Genetics of corneal disease for the ocular surface clinician.

Advances in the understanding of inherited corneal and external diseases may allow interventions that prevent the substantial vision impairment currently caused by these diseases. The observant clinician may first recognize inherited corneal and external diseases based on clinical examination and a careful family history. Researchers using positional cloning and candidate gene techniques have identified several disease-causing genes. Identification of the genes responsible for inherited corneal and external diseases will lead to more definitive diagnoses and represent the first step in development of effective therapies. Future endeavors are directed toward identifying additional inherited corneal and external diseases, the genes that cause them, and possible gene therapies to improve visual outcomes.

Journal Article↗

Role of the ocular surface in destructive corneal disease.

Corneal destructive disease is related to the ocular surface in at least three ways. Firstly, the maintenance of surface integrity seems to protect the corneal stroma from ulceration. Such integrity is jeopardized if the corneal epithelial cells fail to replicate themselves, or if they fail to adhere tightly to the underlying stroma. Secondly, the ocular surface plays a role in ulceration. Elaboration of collagenolytic enzymes may occur in the abnormal ocular surface epithelial cells themselves. In addition, the surface may modulate the leucocytic response in the stroma, the leucocytes themselves being responsible for the ulceration of the stroma. Finally, the ocular surface appears to play a role in superficial vascularization of the cornea. When all of the corneal epithelium is lost, as is the case in widespread chemical injury, sluggish metabolic transformation of conjunctival cells is associated with vascularization.

Adhesiveness↗

Ocular surface tissue morphogenesis in normal and disease states revealed by genetically modified mice.

Many transgenic and knockout mice exhibit pathogenic processes resembling human ocular surface diseases. Thus, the clinical manifestations of mouse lines can provide clues for identifying heritable human diseases of unknown etiology. However, mouse lines using conventional techniques of transgenesis and gene targeting often exhibit embryonic lethality and congenital defects, which preclude the use of such mouse models to study acquired ocular surface tissue diseases. These difficulties can be in part overcome by preparing mouse lines of inducible transgene expression, tissue-specific gene ablation, and inducible tissue-specific gene ablation. Conditional transgenic mouse lines live normally until administration of doxycycline and hormones that induce expression of the transgene and ablation of gene of interest. Toward this goal, we prepared 2 groups of genetically modified mouse lines: (1) transgenesis using keratocan promoter was used to create Kera-rtTA mice (doxycycline-inducible mice) and Cre-LoxP system (ie, Kera-Cre mice; conditional gene ablation in neural crest cell lineage and adult stromal keratocyte) and Kera-CrePR mice (RU-486 inducible); and (2) knock-in strategies were used to create Krt12-rtTA mice (doxycycline inducible), Krt12-Cre mice (conditional ablation in corneal epithelium), and Krt12rtTA-tet-O-Cre mice (doxycycline-inducible corneal epithelium-specific gene ablation). Using these mouse lines, we showed that transforming growth factor (TGF)-beta2 is essential for eye morphogenesis, TGF-alpha is a morphogen for eyelid formation, and lumican is a matrikine that has multiple regulatory functions on cell activities (eg, migration proliferation and gene expression) besides serving as a regulatory molecule of collagen fibrillogenesis. These mouse lines can also be used as models for development of therapeutic treatment regimens of ocular surface diseases using gene therapy and stem cell strategies.

Animals↗

Management of conjunctival cicatrizing diseases and severe ocular surface dysfunction.

Physical or chemical injuries, infections, immunologic oculocutaneous disorders, drugs, and various systemic disorders may cause scarring of the conjunctiva and disturbances of the ocular surface. Trichiasis, lid margin malposition, and dry eye may result in persistent ocular irritation. The cornea may be primarily or secondarily involved. If severe, disturbances of the ocular surface may lead to significant visual impairment. Thorough evaluation of patients and of the underlying disease process is required for optimal management. Treatment may be challenging and should be comprehensive, combining medical measures and surgical correction of structural changes. Suppression of exogenous irritants, treatment of dry eye, antiinflammatory therapy, and immunosuppressants are paramount to control the underlying disease and allow optimal surgical results. Surgical correction of trichiasis and lid margin malposition, conjunctival grafting, mucous membrane transplantation, limbal stem cell transplantation, amniotic membrane transplantation, and penetrating keratoplasty help reestablish a physiologic ocular surface. Severe cases may require keratoprosthetics for visual rehabilitation. Corneal ulceration or perforation requires prompt attention to maintain ocular integrity. Special measures should be considered for patients who require cataract or glaucoma surgery.

Cicatrix↗

[Advances in the diagnosis and therapy for diseases of the ocular surface: dry eye and ocular allergies].

The 77th meeting of the Association for Research in Vision and Ophthalmology (ARVO) presented the latest developments in clinical research and practice across a range of ophthalmic disciplines. Of particular interest was the current status of research in dry eye and ocular allergy. With these conditions being very common to ophthalmologists, and the fact that they are difficult to differentiate due to the number of overlapping symptoms, there remains a need for more rapid and accurate methods for their diagnosis. Therefore, a number of new tools were presented that have the potential for use in clinical trials and practice to improve the diagnosis and assessment of dry eye and ocular allergy. Some of these tools have been developed based on a greater understanding of the pathophysiology of dry eye and ocular allergy, and the various molecular pathways involved. Indeed, a greater understanding of the molecular mechanisms involved in the pathogenesis of dry eye and ocular allergy has identified potential targets for the treatment of these conditions. Continuing research into new agents can provide ophthalmologists with a number of options that will ultimately benefit the patient.

Clinical Trials as Topic↗

Diseases associated with ocular surface abnormalities: the importance of reflex tearing.

AIM: To investigate the correlation between tear function tests and ocular surface integrity in patients with dry eye. METHODS: 297 dry eye patients (55 Sjögren's syndrome, two male and 53 female, average age 52.4 (SD 15.0) years, and 242 non-Sjögren's syndrome, 41 male and 201 female, average age 53.5 (14.1) years) were examined. The following tear function tests were performed: (1) cotton thread test, (2) Schirmer test with topical anaesthesia, (3) Schirmer test without anaesthesia, (4) Schirmer test with nasal stimulation, (5) tear clearance test, and (6) tear break up time (BUT). The ocular surface was evaluated by rose bengal and fluorescein staining. Correlation analysis was performed between each tear function index and vital staining scores. RESULTS: Among the six tear function tests, the Schirmer test with nasal stimulation correlated most with both of the vital stains (rho = 0.530 for rose bengal and 0.393 for fluorescein). The Schirmer test with or without anaesthesia correlated slightly with rose bengal staining, whereas tear clearance test and tear break up time slightly correlated with fluorescein staining. CONCLUSION: Vital staining of the ocular surface correlates most with reflex tearing measured by the Schirmer test with nasal stimulation.

Dry Eye Syndromes↗

The cytomorphology of ocular surface squamous neoplasia by using impression cytology.

BACKGROUND: The term ocular surface squamous neoplasia (OSSN) encompasses conjunctival and corneal intraepithelial neoplasia through to invasive squamous cell carcinoma of the ocular surface. The disease is related to prolonged exposure to solar ultraviolet light and has been proposed as an acquired immune deficiency syndrome-associated tumor. To the authors' knowledge, very few reports describing the cytology of these lesions have been published. METHODS: Impression cytology (IC) samples collected from the eyes of patients with a range of ocular surface diseases were available for study. From these, 267 sets of impressions had subsequent histopathology that had been collected within 6 months of the IC, and which indicated the presence of OSSN. The IC from these cases was used to describe the cytomorphology of intraepithelial and invasive OSSN. RESULTS: Within the intraepithelial group, keratinized dysplastic cells that often were accompanied by hyperkeratosis, syncytial-like groupings, and nonkeratinized dysplastic cells were described. Within the invasive group, cases with significant keratinization and an additional group of cases with little keratinization and sometimes also prominent macronucleoli were described. Keratinized cases were the most numerous in both the intraepithelial and invasive groups. A description also was given of a low number of cases with cytology and also subsequent histopathology indicating the presence of intraepithelial OSSN, in the absence of a clinically detectable lesion. CONCLUSIONS: This detailed description of the cytomorphology of a high number of cases of OSSN with confirmation by histopathology should assist others with little experience of the cytology of these lesions to examine them with increased confidence. Cancer (Cancer Cytopathol)

Carcinoma in Situ↗

[Dry eye disease as a complex dysregulation of the functional anatomy of the ocular surface. New concepts for understanding dry eye disease].

INTRODUCTION: Dry eye disease is a disorder of the tear film that results in epithelial damage and in a disruption of the normal homeostasis at the ocular surface. It is widespread and causes symptoms ranging from discomfort to blindness. METHODS: A review of the existing literature was used to compare different past and recent concepts for the understanding of dry eye disease with a focus on aspects of the integrating functional anatomy of the ocular surface. RESULTS: The understanding of the pathogenesis of dry eye disease has proceeded from the mere recognition of a lack of tears to a consideration of their quality and to the concept of wetting of the ocular surface. However, several other aspects as epithelial differentiation, innervation, hormonal status or immune protection contribute to the intact functional anatomy of the ocular surface. Recently it has been recognized that immunologically regulated mechanisms of inflammation represent a primary or secondary pathogenetic factor for dry eye disease. This is conceivably regulated by the cells of the physiological mucosal immune defence system, the eye-associated lymphoid tissue (EALT). Androgens represent an important trophic factor for the ocular surface and their deficiency predisposes to inflammation. CONCLUSION: Dry eye disease represents a complex dysregulation of the functional anatomy of the ocular surface that can start from different alterations (e.g. insufficient secretion, defects in wetting or innervation). Immune-based inflammation is able to interconnect and negatively reinforce these different pathomechanisms, resulting in a vicious circle.

Conjunctiva↗

A comparative approach to topical cyclosporine therapy.

Topical cyclosporine has been used by veterinary ophthalmologists since 1989 for the treatment of ocular surface inflammatory disease and keratoconjunctivitis sicca (KCS). As well as ameliorating clinical signs of ocular surface lymphocyte-driven inflammation in the dog, cat and horse, topical cyclosporine significantly raises tear production in both normal and KCS-affected animals. A licensed ointment preparation of 0.2% cyclosporine, Optimmune (Schering-Plough), is now available for administration to dogs. In this paper we examine the mechanisms by which cyclosporine exerts both its immunomodulatory and its lacrimogenic actions. The pharmacokinetics of topical cyclosporine are examined to determine whether these effects are truly local or are influenced by generalised immunosuppression caused by systemic absorption of topically applied drug. The paper reviews the few side effects of cyclosporine preparations in the experience of veterinary ophthalmologists and the experimental evidence which appears to implicate the vehicle rather than the active agent cyclosporine as causing many of these effects. Given that topical cyclosporine has been so widely accepted as a valuable ophthalmic preparation in the veterinary world and licensed as such, it is surprising that human ophthalmologists have not employed the drug to the same extent for conditions from vernal keratoconjunctivitis to Sjögren's syndrome.

Administration, Topical↗

[Evaluation of free radical production by conjunctival impression cytology of patients treated with long-term antiglaucoma drugs or of contact lens wearers].

PURPOSE: To investigate free radical production in impression cytology specimens using microplate cold light cytofluorimetry. METHODS: 60 impression cytology specimens (IC) were harvested in 30 patients aged from 20 to 90 years. IC were taken in 10 healthy subjects, 10 glaucoma patients receiving longterm treatment for glaucoma and 10 contact lens wearers for more than five years. A complete ophthalmologic examination (BUT, corneal staining) was performed. Evaluation of free radical production was done using a dichlorofluoresceine diacetate (DCFHDA) test for H(2)O(2) evaluation and a hydroethidine test for O(2)(.)- measurement. RESULTS: The BUT values in the two pathological groups were significantly lower than those of controls (p<0.001). A free radical production was found in both contact lens wearers (p<0.001 compared to control values) and glaucoma patients (p<0.001 compared to control values). Both hydrogen peroxyde and superoxide anion productions were significantly correlated to the decrease of BUT values and the increase of superficial punctuate keratitis. CONCLUSION: The results of this preliminary study confirm that conjunctival epithelial cells may abnormally produce oxygen free radicals in chronic ocular surface disorders. This may participate to the cellular alterations observed in inflammatory diseases of ocular surface.

Adult↗

Flow cytometric analysis of HLA-DR antigen in conjunctival epithelial cells of patients with cystic fibrosis.

PURPOSE: Cystic fibrosis (CF) is an autosomal-recessive genetic disorder. The disease affects all secretory epithelia including the eye and belongs to the group of ocular surface epithelial diseases, termed keratoconjunctivitis sicca that develop in dry eye. In the pathogenesis of dry eye, inflammation plays a crucial role. The aim of this study was to investigate the expression of HLA-DR on conjunctival epithelial cells from patients with CF. MATERIALS AND METHODS: Twenty-five patients with CF and 25 normal subjects underwent ocular examination. Tear film break-up time (TBUT), Schirmer test, lissamine green staining, and conjunctival impression cytology were carried out. Cells were processed for flow cytometry, by using monoclonal antibodies to HLA-DR. RESULTS: The Schirmer test and TBUT scores were significantly lower in CF patients compared with controls. A significant increase of HLA-DR expression on epithelial cells was found in patients with CF compared with normal eyes. The Schirmer and TBUT test were positively correlated with HLA-DR expression for the percentage of cells. CONCLUSION: These results suggest that conjunctival epithelial cells play an important proinflammatory role in ocular changes in CF patients. Our findings confirm the presence of an inflammatory background and the immune nature of this disease. HLA-DR measurement might be a useful method for monitoring of inflammatory processes in the conjunctiva and could be helpful in the use of anti-inflammatory drugs in the treatment of ocular findings in CF patients.

Adolescent↗

Aging and Corneal Nerve Health: Mechanisms of Degeneration and Emerging Therapies for the Cornea.

Corneal nerves play a crucial role in maintaining ocular surface homeostasis by supporting the functional integrity of corneal epithelial, stromal, and endothelial cells; modulating tear secretion; and facilitating sensory responses essential for overall ocular health. With advancing age, these highly specialized peripheral sensory fibers undergo progressive attrition and morphologic distortion driven by the canonical hallmarks of aging including genomic instability, impaired proteostasis, mitochondrial dysfunction, and chronic low-grade inflammation. The resulting neuro-immune dysregulation reduces trophic support, delays wound healing, and predisposes older adults to dry-eye disease, neurotrophic keratopathy, and postsurgical hypoesthesia. Age-exacerbating cofactors including diabetes, dyslipidemia, neurodegenerative disorders, topical preservatives, chronic contact-lens wear, herpes zoster ophthalmicus, and ocular-surface hypoxia further accelerate sub-basal nerve rarefaction and functional decline. This review provides an overview of age-related physiological alterations in ocular surface nerves, with a particular emphasis on corneal innervation. It also discusses risk factors that speed up these changes. Given the inherently limited regenerative capacity of corneal nerves and their inability to fully restore to baseline conditions following injury or degeneration, it is critical to identify and develop effective strategies aimed at mitigating or delaying physiological nerve degeneration and promoting nerve regeneration. This review also brings up emerging therapeutic strategies, including regenerative medicine, neuroprotective agents, and lifestyle interventions aimed at mitigating age-related corneal nerve degeneration.

Humans↗

Current concepts and challenges in ocular surface reconstruction using cultivated mucosal epithelial transplantation.

Ocular surface disorders wherein corneal stem cells are deficient result in total conjunctivalization leading to severe visual dysfunction and blindness. Treatment of these diseases requires reconstruction of the ocular surface using epithelial transplantation to provide a smooth refractive corneal surface and biologic and physical barriers against a variety of destructive factors. Recently, regenerative medicine focusing on tissue-engineered techniques has been developed and established as a new clinical field. In particular, cultivated mucosal epithelial transplantation using well-differentiated, stratified epithelial sheets on amniotic membrane allows a rapid re-epithelial cover over the entire corneal surface, resulting in early reduction of inflammation and cicatrization. This surgical approach dramatically improves the prognosis of severe ocular surface diseases, especially severely inflamed corneal stem cell deficiency. This new approach not only provides early epithelialization but also allows reconstruction of the corneal surface using autologous cultivated epithelium including the cornea and oral mucosa from a small number of cell sources after amplification. Tissue-engineered strategies using autologous corneal or oral mucosal epithelial sheet transplantation avoid the risk of rejection and complications associated with immunosuppressive treatments. In addition to new cellular transplantation, combined automated lamellar therapeutic keratoplasty provides better refractive stromal interference and contributes to performance and safety of cataract surgery in severe corneal opacity cases. Although long-term prognosis and cell biologic behavior of tissue-engineered epithelium after transplantation should be carefully monitored, these recent surgical treatments have opened a new field for ocular surface reconstruction.

Corneal Transplantation↗