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PubMed2006

[Corneal epithelial diseases related to limbal stem cell deficiency].

Treatment of corneal epithelial diseases induced by limbal stem cell deficiency is an important challenge in ocular surface reconstruction. Since the 1990s, corneal stem cells have been localized in the limbus. This new concept completely changed the way we consider ocular surface reconstruction, with new diseases now found to be isolated in the ocular surface. Limbus insufficiency syndromes are specific depending on their origin (congenital or acquired), their expression (unilateral or bilateral, partial or total), their progression (acute or chronic), and the mechanism involved (burn, infection, chronic inflammation, etc.). Some of these diseases are local diseases and others are systemic diseases. Clinically, limbus insufficiency is a switch of the normal corneal epithelial phenotype (expression of a specific keratin, avascularity, and transparency of the corneal matrix) in an opaque and fibrovascularized cornea. In terms of cellular biology, a phenotype is a terminal expression of a cell differentiation process. This process is the outcome of the interaction between the genome of a cell or a group of cells with their microenvironment. In limbus insufficiency, epithelial cells and corneal matrix are destroyed, and it is the destruction of these two components that leads to limbus insufficiency syndrome.

Cell Differentiation↗
PubMed2004

Dysfunctional neural regulation of lacrimal gland secretion and its role in the pathogenesis of dry eye syndromes.

Tears are a complex fluid consisting of three layers, each of which is secreted by a different set of tissues or glands. The aqueous portion of the tear film is produced predominantly by the lacrimal gland. Dry eye syndromes are diseases in which the amount and composition of tears are altered, which can lead to ocular surface damage. There are many causes for dry eye syndromes. One such cause is the alteration in the functions of nerves innervating the lacrimal gland and the ocular surface. The autoimmune disease Sjogren syndrome can deleteriously affect the innervation of the lacrimal gland. Damage to the sensory nerves in the ocular surface, specifically the cornea, as a result of refractive surgery and normal aging, prevents the normal reflex arc to the lacrimal gland. Both defects can result in decreased tear secretion and dry eye syndromes. This review will discuss the current information regarding neurally-stimulated protein, water, and electrolyte secretion from the lacrimal gland and delineate how nerve dysfunction resulting from a variety of causes decreases secretion from this gland.

Journal Article↗
PubMed2003

Blink-related microtrauma: when the ocular surface harms itself.

Superior limbic keratoconjunctivitis results mechanically from blinking under prolonged unphysiological conditions. The pathogenic process is known as blink-related microtrauma. This review aimed to explore the validity of a general theory that besides superior limbic keratoconjunctivitis, there may be other diseases of the ocular surface arising from mechanical microtrauma. A review of relevant clinical and microscopic lesions in a range of ocular surface disorders with possible mechanical aetiology was conducted. New terms were selected to facilitate understanding of such new aetiology. Besides superior limbic keratoconjunctivitis, other ocular surface disorders regarded as primarily derived from blink microtrauma are: other filamentary keratitides; blepharospasm and severe ptosis; canthal/palpebral froth; affections from disordered eyelid lining; and contact lens related damage. A group of secondarily microtraumatic disorders was identified, including the example of microtrauma impacting upon interpalpebral bulbar prominences. Superior limbic keratoconjunctivitis is the archetype of diseases affecting a unique combination; namely, the ocular surface conjoined with its lacrimal fluid. It is only one among many diseases actively generated within the confines of 'a self-harming surface'.

Blinking↗
PubMed2003

Ocular surface impression cytology.

Impression cytology, either using cellulose acetate strips or the Biopore membrane device, is a simple, noninvasive technique that aids in the diagnosis of several disorders of the ocular surface. These disorders include ocular surface squamous neoplasia, dry eye syndrome, limbal stem-cell deficiency, specific viral infections, vitamin A deficiency, allergic disorders, conjunctival melanosis, and malignant melanoma. Another advantage is the preservation of limbal stem cells, which occur in the basal layer of the limbal epithelium and are responsible for renewal of the corneal epithelium. The Biopore membrane device is particularly user friendly, with little expertise required and adequate specimens obtained in a very high percentage of cases. The most common applications in diagnostic ocular pathology are:(i) primary diagnosis and follow-up of ocular surface squamous neoplasia, including after therapy with topical mitomycin C. The sensitivity is high (78-87%); and (ii) dry eye syndrome where squamous metaplasia and/ or hyperkeratosis are noted. Certain limitations of the technique for diagnosis of squamous neoplasia include the fact that dysplasias are often keratinizing and may yield very few or even no dysplastic cells with impression cytology. Secondly, no definite cytologic criteria reliably distinguish invasive SCC of ocular surface from in situ disease. Other applications include the rapid specific diagnosis of ocular surface infections with herpes simplex, adeno-, and varicella zoster viruses. Impression cytology samples may also be used to obtain mRNA, cells for phenotyping by flow cytometry, and proteins for Western blotting for research studies.

Cytodiagnosis↗
PubMed2004

Comparison of the NEI-VFQ and OSDI questionnaires in patients with Sjögren's syndrome-related dry eye.

BACKGROUND: To examine the associations between vision-targeted health-related quality of life (VT-HRQ) and ocular surface parameters in patients with Sjögren's syndrome, a systemic autoimmune disease characterized by dry eye and dry mouth. METHODS: Forty-two patients fulfilling European / American diagnostic criteria for Sjögren's syndrome underwent Schirmer testing without anesthesia, ocular surface vital dye staining; and measurement of tear film breakup time (TBUT). Subjects were administered the Ocular Surface Disease Index (OSDI) and the 25-item National Eye Institute Vision Functioning Questionnaire (NEI-VFQ). Main outcome measures included ocular surface parameters, OSDI subscales describing ocular discomfort (OSDI-symptoms), vision-related function (OSDI-function), and environmental triggers, and NEI-VFQ subscales. RESULTS: Participants (aged 31-81 y; 95% female) all had moderate to severe dry eye. Associations of OSDI subscales with the ocular parameters were modest (Spearman r (rho) < 0.22) and not statistically significant. Associations of NEI-VFQ subscales with the ocular parameters reached borderline significance for the near vision subscale with TBUT (rho = 0.32, p =.05) and for the distance vision subscale with van Bijsterveld score (rho = 0.33, p =.04). The strongest associations of the two questionnaires were for: ocular pain and mental function with OSDI-symptoms (rho = 0.60 and 0.45, respectively); and general vision, ocular pain, mental function, role function, and driving with OSDI-function (rho = 0.60, 0.50, 0.61, 0.64, 0.57, and 0.67, respectively). CONCLUSIONS: Associations between conventional objective measures of dry eye and VT-HRQ were modest. The generic NEI-VFQ was similar to the disease-specific OSDI in its ability to measure the impact of Sjögren's syndrome-related dry eye on VT-HRQ.

Adult↗
PubMed2001

[A study on effect of basic fibroblast growth factor on human limbal stem cell proliferation cultured in low calcium medium].

OBJECTIVE: To study how to obtain relatively pure stem cells and the effects of bFGF on the human limbal stem cell proliferation in order to set up the foundation of cultured limbal stem cells for treatment of ocular surface and tear diseases. METHODS: Limbal button inoculation was used in low calcium culture. Monoclonal antibody AE5 was used to identify the stem cells. To examine the effects of bFGF (1 - 100 ng/ml) on stem cell proliferation, the technique of digital camera and computer image analysis system were used. RESULTS: Cultured cells were mostly corneal stem cells. This was the first time to combine the method of obtaining basal cell layer and culture with low calcium medium, which could harvest relatively pure and undifferentiated stem cells in localization and nature. The basic FGF (1 - 100 ng/ml) promoted cultured stem cells to proliferate significantly (P < 0.001). CONCLUSIONS: Limbal stem culture provides resources of stem cells. It is very useful in treatment of ocular surface and tear diseases. The basic FGF plays an important role in proliferation of stem cells in graft. Computer image analysis system is an effective and simple way for evaluating the proliferation of a primary culture.

Calcium↗
PubMed2001

Characteristics of the human ocular surface epithelium.

An appreciation of the biological characteristics of the human ocular surface epithelium affords us a great insight into the physiology of the human ocular surface in health and disease. Here, we review five important aspects of the human ocular surface epithelium. First, we recognize the discovery of corneal epithelial stem cells, and note how the palisades of Vogt have been suggested as a clinical marker of their presence. Second, we introduce the concept of the gene expression profile of the ocular surface epithelium as arrived at using a new strategy for the systematic analysis of active genes. We also provide a summary of several genes abundantly or uniquely expressed in the human corneal epithelium, namely clusterin, keratin 3, keratin 12, aldehyde dehydrogenase 3 (ALDH3), troponin-I fast-twitch isoform, ssig-h3, cathepsin L2 (cathepsin V), uroplakin Ib, and Ca(2+)-activated chloride channel. Genes related to limbal and conjunctival epithelia are also described. Third, we touch upon the genetic abnormalities thought to be involved with epithelial dysfunction in Meesmann's dystrophy, gelatinous drop-like corneal dystrophy, and the ssig-h3-mutated corneal dystrophies. Fourth, we provide an update regarding the current state of knowledge of the role of cytokines, growth factors and apoptosis in relation to ocular surface homeostasis and tissue reconstruction; the main factors being epidermal growth factor (EGF), keratinocyte growth factor (KGF), hepatocyte growth factor (HGF), transforming growth factor-ss (TGF-ss), and some inflammatory cytokines. Fifth, corneal epithelial barrier function and dysfunction as measured by fluorophotometry is remarked upon, with an explanation of the FL-500 fluorophotometer and its ability to detect corneal epithelial dysfunction at a subclinical level. The research described in this review has undoubtedly generated a complete understanding of corneal epithelial pathophysiology-an understanding that, directly or indirectly, has helped advance the development of new therapeutic modalities for ocular surface reconstruction.

Apoptosis↗
PubMed2003

Amniotic membrane transplantation for ocular surface pathology: long-term results.

Amniotic membrane transplantation has been used for >90 years for cutaneous and mucous lesions for regeneration of tissues. In recent years its effectiveness has been demonstrated in the treatment of diseases of the ocular surface. We present our experience with 53 amniotic membrane transplantations for different ocular pathologies with two different forms of implantation. The 53 cases were divided into three groups according to pathology and type of implant. Group 1 included 24 eyes with amniotic membrane grafts after resection of extensive conjunctival lesions. Group 2 included 19 eyes with amniotic membrane grafts for corneal pathology, and group 3 consisted of 10 eyes with amniotic membrane patches for corneal epithelial defects without ulceration. No intra- or postoperative complications were observed during an average follow-up period of 32 months (24-48 months). Group 1 demonstrated rapid healing of the lesions with minimal scarring in all cases. In group 2 a favorable response was observed in 16 of 19 cases. In group 3 complete healing was achieved in only 3 of 10 cases, and the time for which the graft remained was related to the success of the treatment. The primary intention was to achieve prolonged fixation of the implant. Finally, amniotic membrane transplantation is a safe and effective technique for the treatment of different pathologies of the ocular surface. After the resection of extensive conjunctival lesions it is currently the preferred treatment. In corneal pathology, it represents an additional therapeutic alternative when conservative medical treatments fail.

Amnion↗
PubMed2006

Alterations of the ocular surface epithelial mucins 1, 2, 4 and the tear functions in patients with atopic keratoconjunctivitis.

BACKGROUND: An increased understanding of the ocular surface alterations at the cellular level in the conjunctiva and the cornea, may help explain the pathogenesis and the subsequent clinical appearance of atopic ocular allergies, which may be potentially blinding. PURPOSE: To investigate MUC 1, 2 and 4 alterations, tear function and the ocular surface disorder in patients with atopic keratoconjunctivitis. METHODS: Twenty-eight eyes of 14 atopic keratoconjunctivitis patients as well as 22 eyes of 11 age-and sex-matched normal subjects were studied. The subjects underwent corneal sensitivity measurements, Schirmer's test, tear film break-up time (BUT), fluorescein and Rose Bengal staining of the ocular surface, conjunctival impression cytology and brush cytology. Impression cytology samples underwent periodic acid-Schiff and immunohistochemical staining with MUC 1, 2 and 4 antibodies. Brush cytology specimens underwent evaluation for inflammatory cell numbers and quantitative real-time-PCR for MUC 1, 2 and 4 mRNA expression. Patient eyes with fluorescein and Rose Bengal scores greater than four points were regarded to have significant epithelial disease in this study. RESULTS: The mean corneal sensitivity and BUT values were significantly lower in atopic patients with significant epithelial disease, compared with patients with insignificant epithelial disease and controls (P < 0.01). Brush cytology specimens from patients with significant epithelial disease revealed significantly higher numbers of inflammatory cells (P < 0.01). Specimens from patient eyes showed positive staining for MUC 1, 2 and 4. MUC 1, 2 and 4 mRNA expressions were significantly higher in eyes with significant epithelial disease compared with eyes with insignificant epithelial disease and eyes of control subjects. CONCLUSION: Ocular surface inflammation, decline in corneal sensitivity, tear film instability, changes in conjunctival epithelial MUC 1, 2 and 4 mRNA expressions were thought to be important in the pathogenesis of atopic ocular surface disease.

Adolescent↗
PubMedDate not supplied

[Allergens and risk factors in pediatric patients with allergic seasonal conjunctivitis].

BACKGROUND: The seasonal allergic conjunctivitis is an inflammatory disease of the ocular surface that affects mainly children, with predominance of male sex. It is an immunological disease with a typical reaction of hypersensitivity type 1 (IgE), resulted from several biological reactions (antigen-antibody) and it's associated to several risk factors. OBJECTIVE: To determine the more frequently identified allergens and the associated risk factors to the seasonal allergic conjunctivitis in children living in Mexico City. MATERIAL AND METHODS: Ophthalmologic clinical study done to 50 patients with diagnosis of seasonal allergic conjunctivitis, during the months of March to October, 2001, at the Ophthalmology Department of the National Pediatric Institute. A control group was integrated by 50 patients of the consultation of ophthalmology with non-allergic ocular pathology, and percutaneous skin tests were made. A direct interrogation was applied to both groups to investigate associated risk factors of atopy. RESULTS: The associated risk factors to the development of allergic conjunctivitis are: family atopic background, negative antecedent of breast feeding, asthma o rhinitis (statistically significant). The most frequently identified allergens were Dermatophagoides pteronissinus, Dermatophagoides farinae, Lolium perenne and Atriplex bacteosa, of the group of dust mites and pollen, respectively. CONCLUSION: It is important to see our patients in an integral way. In the case of patients with seasonal allergic conjunctivitis, it should not be forgotten to make an interrogation of the factors associated to atopy and, if it is possible, to inform to the patient and their relatives about these, in order to prevent them.

Allergens↗
PubMed1998

Real-time telemedicine in the clinical assessment of the ocular surface.

PURPOSE: To report the feasibility of real-time video and audio transmission of slit-lamp images of the eye using conventional telephone systems. METHOD: We analyzed the feasibility and benefits of telemedicine in the diagnosis and follow-up of ocular surface disorders in referral patients using a real-time audio-video system that functions through integrated services digital network lines at a transmission speed of 384 kilobytes per second. RESULTS: Real-time slit-lamp images obtained through integrated services digital network lines offered satisfactory visual resolution of the ocular surface for the diagnosis and follow-up of ocular surface and corneal disease, while simultaneous audio transmission allowed for direct communication with the patient and attending physician when necessary. CONCLUSION: Telemedicine using conventional telecommunication infrastructures offers sufficient information for the diagnosis and follow-up of ocular surface disorders in referral patients.

Computer Communication Networks↗
PubMed2000

Vernal keratoconjunctivitis revisited: a case series of 195 patients with long-term followup.

OBJECTIVE: This study aimed at revisiting vernal keratoconjunctivitis (VKC) on the basis of anamnestic, clinical, immunologic, histopathologic, and followup data of 195 patients. DESIGN: Retrospective noncomparative case series. PARTICIPANTS: One hundred and ninety-five patients with VKC. METHODS: Clinical evaluation and outcome in 151 of 195 patients with a median followup of 47 months. Evaluation was by telephone survey in 69 patients. MAIN OUTCOME MEASURES: (1) Demographic, clinical, and immunologic features of VKC and their influence on the course of the disease; (2) conjunctival and corneal complications and efficacy of treatment observed during the followup period. RESULTS: VKC is a chronic disease. More than 60% of patients had repeated recurrences all year round. Males had an earlier presentation of symptoms than females and the male/female ratio decreased with age. Major (greater than 80%) and minor (up to 80%) diagnostic criteria were defined for clinical signs and symptoms of the disease. Negative skin test or radioallergosorbent test was present in approximately 50% of patients, whereas eosinophil infiltration was a constant histopathologic finding. A marked conjunctival sensitivity to nonspecific stimuli was noted in more than one third of patients. In 6% of cases, a reduction of visual acuity resulted from corneal scarring, and in 2% of patients, steroid-induced glaucoma was observed. The large size of giant papillae indicates poor prognosis for the persistence of the disease and its evolution into a chronic, perennial condition. CONCLUSIONS: VKC is a chronic eosinophilic disease of the ocular surface involving IgE, non IgE-mediated mechanisms, and age-sex-related influences. Although the disease has a good prognosis, severe visual impairments may result from long-standing inflammation.

Adolescent↗
PubMed2006

Update on ocular graft versus host disease.

PURPOSE OF REVIEW: To summarize recent findings regarding the clinical spectrum, pathophysiology, and treatment of ocular graft versus host disease. RECENT FINDINGS: Ocular graft versus host disease is a common sequela of allogeneic hematopoietic transplantation affecting up to 80% of chronic graft versus host disease patients. Clinical features of ocular graft versus host disease encompass all parts of the eye, from the lid to the choroids, although ocular graft versus host disease is most commonly viewed as a disease of the ocular surface, with the conjunctiva and lacrimal gland most commonly affected. Clinical features of ocular graft versus host disease (keratoconjunctivitis sicca, cicatricial conjunctivitis, scleritis, and others) mirror other inflammatory ocular conditions associated with autoimmune/collagen vascular diseases. Immunohistochemistry studies of lacrimal gland dysfunction and conjunctival inflammation in chronic ocular graft versus host disease are summarized. Current diagnosis and treatment of chronic graft versus host disease are outlined in the recent publications from the National Institute of Health Chronic graft versus host disease Consensus Workshops, and the information relevant to ocular graft versus host disease is delineated. SUMMARY: Ocular graft versus host disease evaluation, diagnosis, and management should be approached in a multidisciplinary fashion in the context of the patient's overall graft versus host disease status.

Diagnosis, Differential↗
PubMed1984

Color specular microscopy of disorders involving the corneal epithelium.

Color specular microscopy, a noninvasive, in vivo microscopic technique, was utilized to study the corneal epithelium in 17 patients including eight with keratoconus, seven with bullous keratopathy, and two with Fuchs' corneal dystrophy. Color specular microscopy was also performed on rabbit corneas with experimental surgical trauma. Changes observed by specular microscopy in these diseased states correlated with alterations noted by light microscopy and scanning and transmission electron microscopy. Specular microscopy can provide detailed in vivo cellular morphology of the ocular surface, obviating the need for tissue biopsy. Thus, specular microscopy is a valuable diagnostic technique available for the clinician to monitor changes of the diseased ocular surface.

Animals↗
PubMed2000

Use of nonpreserved human amniotic membrane for the reconstruction of the ocular surface.

PURPOSE: To describe the use of nonpreserved human amniotic membrane (NP-AMT) as an alternative to preserved human amniotic membrane (AMT) for the reconstruction of the ocular surface in several diseases. METHODS: NP-AMT was used in the treatment of five patients with the following diseases: noninvasive conjunctival squamous cell carcinoma, corneal persistent epithelial defect, severe alkali burn, near total limbal deficiency secondary to multiple surgeries, and ocular cicatricial pemphigoid. In some cases, a limbal autograft or allograft was employed simultaneously, sutured on top of the NP-AMT. All sutures were made with 10-0 Nylon and were removed at two weeks. RESULTS: Ocular surface was satisfactorily reconstructed, eyes were quiet, and patients were comfortable despite prolonged deepithelialization in some cases. There was a case of a limbal autograft ischemia--in the burned patient--that caused partial corneal conjunctivalization. Initially, the NP-AMT looks thickened but thins around the fifth day and looks similar to AMT. CONCLUSION: Results using NP-AMT are similar to those of AMT. It is a good alternative and it is easily obtained in places were AMT is not available or is too expensive to procure.

Adult↗
PubMed2005

Evaluation of ocular surface inflammation in the presence of dry eye and allergic conjunctival disease.

The ocular inflammatory diseases dry eye and allergic conjunctivitis are mediated by CD4+ T cells. Th1 cells secrete interferon (IFN)-gamma and are implicated in mediating the disease process in dry eye. Allergic conjunctivitis has been classically defined as a Th2 disease because of the predominance of Th2 cytokines interleukin (IL)-4 and IL-13. A multi-hit antigen challenge mouse model of allergic conjunctivitis provides evidence that IFN-gamma, a Th1 cytokine, acts as an endothelium gatekeeper by regulating endothelial expression of vascular adhesion molecule-1 required for inflammatory conjunctival cell infiltration. Current research encourages an in-depth evaluation of the exact role Th1 and Th2 cells play in ocular inflammation.

Journal Article↗