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PubMed1993

Diagnostic methods and treatment modalities of dry eye conditions.

One may view dry eye conditions as a group of diseases in which the ocular surface is adversely affected. Tear film instability invariably leads to some degree of cellular surface damage over the cornea and conjunctiva. In turn, ocular epitheliopathy may adversely affect tear film stability. The clinical presentation of the disease may not yield a clue as to its etiology. In recent years considerable progress was made both in the diagnosis and the treatment of the disease and promising studies are planned or are underway. The diagnostic techniques can be divided into four groups. The first is concerned with the clinical presentation. The second is concerned with the bulk properties of the aqueous tears including dynamic characteristics, composition, and colligative properties. The third is tear-film related and includes the film break-up time, evaporation rate, and lipid abnormality. The fourth is concerned with the ocular surface and includes vital staining, impression cytology, and surface microscopy. The most promising attempts are being made in the second group by attempting to elucidate the role of enzyme and enzyme activator activity and inhibitor contents as well as the tear protein profiles and correlating them with the specific disease states. The treatment modalities belong to three major groups aside from surgical intervention; the supplementation, preservation, and the stimulation of tears. The modern version of tear supplementation is expected to include the topical use of efficacious aqueous formulations that typically contain film stabilizing polymers, nutrients, and/or--in the future--biochemically active ingredients such as enzyme activators and inhibitors.

Dry Eye Syndromes↗

PubMed2005

Ocular surface findings in Hallopeau-Siemens subtype of dystrophic epidermolysis bullosa: report of a case and literature review.

PURPOSE: This article describes the clinical features and long-term changes in corneal sensitivity, tear function, and impression cytology findings in a patient with recessive dystrophic epidermolysis bullosa (DEB). METHODS: The patient underwent best-corrected Landolt visual acuity measurements, slit-lamp examinations, anterior segment photography, Schirmer test with anesthesia, tear film break-up time, corneal fluorescein and Rose-Bengal staining, assessment of corneal sensitivity, and conjunctival impression cytology at the initial and final visits. RESULTS: The patient had a recurrent corneal erosion in the right eye and a painful corneal blister with extensive superficial punctuate keratopathy in the left eye, which remained refractory to treatment with patching, lubricants, and antibiotic ointments for 10 weeks. The corneal disease in both eyes responded swiftly to topical fibronectin, topical nonpreserved tears, vitamin A ointment, and therapeutic soft contact lenses. Maintenance treatment was continued with preservative-free topical tear drops and vitamin A ointment. Corneal disease did not recur in the patient during the follow-up of 29 months. The mean corneal sensitivity and tear film break-up time were decreased initially in both eyes and attained normal values with treatment. Impression cytology revealed squamous metaplasia, loss of cellular cohesion, and total absence of goblet cells before treatment, all of which were observed to be normalized at the final follow-up. CONCLUSIONS: The ocular surface disease in DEB was characterized by low corneal sensitivity, disorder of tear quality, decreased cellular cohesion, squamous metaplasia of the conjunctiva, and goblet cell loss. Close follow-up for ocular complications in DEB is essential and a pathophysiology-oriented approach to the epithelial disease may not only provide rapid healing but might prevent recurrences as well.

Administration, Topical↗

PubMed1997

Important concepts for treating ocular surface and tear disorders.

PURPOSE: To outline important concepts for treating ocular surface and tear disorders. METHOD: A review was conducted of recently published findings. RESULTS: Five concepts were delineated: ocular surface health is ensured by a close relationship between ocular surface epithelia and the preocular tear film; a stable tear film is inherently maintained by external adnexae; the intact protective mechanism is controlled by effective neuroanatomic integration; corneal epithelial stem cells are located at the corneoscleral limbus; and ocular surface epithelial cell function is supported by stromal fibroblasts and matrix. CONCLUSIONS: These concepts stress that ocular surface epithelia and the preocular tear film function as a unit and, furthermore, that several corneal and external diseases can be categorized as ocular surface and tear disorders. These concepts also help one formulate unified diagnostic and therapeutic strategies for management of these diseases.

Animals↗

PubMed2001

Tear function and ocular surface changes in noninsulin-dependent diabetes mellitus.

PURPOSE: To describe the ocular surface disorder in patients with diabetes. DESIGN: A prospective, case-controlled study. PARTICIPANTS: Eighty-eight eyes of 50 noninsulin-dependent diabetes mellitus patients seen at the Department of Ophthalmology, Kobe University School of Medicine, from September 1998 through February 1999, and 40 eyes of 20 healthy control individuals were studied. INTERVENTION: All subjects underwent routine ophthalmic examinations, corneal sensitivity measurements, Schirmer test, tear film break-up time (BUT) analysis, and conjunctival impression cytologic analysis. MAIN OUTCOME MEASURES: Patients and control subjects were compared for corneal sensitivity, tear function parameters, goblet cell density, and squamous metaplasia grade. The relation of diabetic peripheral neuropathy, metabolic control, duration of disease, and status of retinopathy to the ocular surface disorder was also noted. RESULTS: The mean corneal sensitivity was significantly lower in diabetic patients, diabetic patients with peripheral neuropathy, and poorly controlled diabetes compared with control subjects (P < 0.001). The BUT and Schirmer test values were also significantly lower in the diabetic group, in patients with peripheral neuropathy and poor metabolic control. Impression cytologic analysis showed goblet cell loss and conjunctival squamous metaplasia, both of which again related to peripheral neuropathy, poor diabetic control, and decreased corneal sensitivity. The examined parameters did not relate to duration of disease or status of diabetic retinopathy. CONCLUSIONS: The ocular surface disease in diabetes is characterized by a disorder of tear quantity and quality, squamous metaplasia, and goblet cell loss, all of which seem to evolve in close proximity to the status of metabolic control and peripheral neuropathy.

Adult↗

PubMed1998

Ocular cicatricial pemphigoid.

CP is a systemic disease of presumed autoimmune etiology that may involve the skin, conjunctiva, or any mucosal surface. As many patients present with ocular symptoms, ophthalmologists must inquire about signs of potential life-threatening esophageal and laryngeal involvement. Ocular involvement is a bilateral chronic cicatricial conjunctivitis that may result in fornix foreshortening, symblepharon formation, trichiasis, and entropion and keratinization of the eyelids and conjunctiva. These mechanical factors are responsible for progressive scarring and vascularization of the ocular surface. Successful systemic treatment of the autoimmune disease is now available; however, the condition often is not diagnosed until significant structural damage to the ocular adnexa has occurred. Our ability to rehabilitate visually patients with advanced disease by penetrating keratoplasty and associated techniques remains extremely limited. Hence, the focus of treatment in OCP should be on early detection of the disease, including conjunctival biopsy, prompt systemic treatment to prevent disease progression, and early aggressive treatment of secondary eyelid and conjunctival abnormalities to avoid the blinding keratopathy so prevalent in this disease.

Conjunctival Diseases↗

PubMedDate not supplied

[Amniotic membrane utilization in ophthalmological surgical procedures].

The amniotic membrane, which is the innermost layer of the fetal membranes, is composed of a single layer of epithelial cells that lie on a basement membrane, and of a non-vascular collagenous stroma. These three components give the amniotic membrane its beneficial properties. The first therapeutic application of the amniotic membrane was in 1910, when it was used in skin transplantation. Thereafter, it was used in surgical procedures related to the abdomen, genitourinary tract and to the head and neck. In ophthalmology, De Roth, in 1940, was the first to use the amniotic membrane for conjunctival reconstruction. However, it was only in 1995 that publications on the subject started appearing again, when Tseng and many others began using the amniotic membrane again in the treatment of ocular surface (cornea and conjunctiva) diseases. In cases of total stem cell deficiency, amniotic membrane transplantation has been shown to be very useful when used in conjunction with limbal autografts or allografts. At this stage, however, further studies are needed to elucidate the real potential of the amniotic membrane in the treatment of different ocular surface (and other) disorders, and its exact mechanism(s) of action. This will help establish the applications of such treatment in medicine, in general, and in ophthalmology, in particular.

Amnion↗

PubMed1998

Eosinophil surface antigen expression and cytokine production vary in different ocular allergic diseases.

BACKGROUND: The pathophysiology of chronic ocular allergic disease is not well understood. An eosinophil infiltrate is characteristic of such disease and eosinophil activity can be related to disease severity and to keratopathy, the most serious complication. Recently, eosinophils have been shown capable of cytokine production, particularly in allergic disease, although the disease-specific cytokine spectrum of tissue eosinophils is unknown. OBJECTIVES: We sought to determine eosinophil numbers (absolute numbers and percentage of total leukocytes), cell surface antigen expression, and cytokine production in conjunctiva in chronic allergic eye disease and their relationship to corneal involvement. METHODS: Ultrathin sections of conjunctiva were examined by tissue staining and by 1- and 2-color immunohistochemistry. RESULTS: Eosinophil numbers were greater in giant papillary conjunctivitis (GPC) and vernal keratoconjunctivitis (VKC) and not related to corneal involvement. The eosinophil expression of the cell surface antigens intercellular adhesion molecule-1, CD4, IL-2R, and HLA-DR was greater in atopic keratoconjunctivitis (AKC) and VKC, the disorders with corneal disease, than in GPC, in which the cornea is not involved. For most cytokines, localization to eosinophils was greater for VKC and AKC than for GPC. RANTES, TGF-beta, and TNF-alpha localized to eosinophils in all disorders. Variations in the pattern of eosinophil-cytokine localization were found. In VKC IL-3, IL-5, IL-6, and GM-CSF were prominent; in GPC IL-5 was prominent; and in AKC IL-4, IL-8, and GM-CSF were prominent. CONCLUSIONS: Chronic ocular allergic disorders affecting the cornea are distinguished from disorders that do not do so by greater expression of eosinophil surface antigens (which may imply greater cell activation) and differences in cytokine localization to eosinophils. These differences may be secondary to the variations in T-cell subsets or a primary phenomenon. Changes in eosinophil function, rather than cell numbers, may be important in clinical variations, such as keratopathy, and may allow future therapeutic exploitation.

Adult↗

PubMed2001

Diagnosis of dry eye.

Dry eve disease is characterized by symptoms, ocular surface damage, reduced tear film stability, and tear hyperosmolarity. There are also inflammatory components. These features can be identified by various kinds of diagnostic tests (symptom questionnaires, ocular surface staining, tear break-up time, and osmometry), although there may not be a direct correlation between the number or severity of symptoms and the degree of ocular surface damage or tear deficiency. Once the diagnosis of dry eye disease has been established, further tests can be used to classify the condition into tear-deficient or evaporative dry eve. The two forms of dry eye are not mutually exclusive and often co-exist. The optimal diagnosis of dry eye disease, therefore, depends on the results of several tests, and this article suggests an appropriate order for performing these tests at a single clinic visit.

Diagnostic Techniques, Ophthalmological↗

PubMedDate not supplied

Cross-linking of human amniotic membrane by glutaraldehyde.

PURPOSE: The transplantation of cryopreserved human amniotic membrane has been introduced recently for the reconstruction of the ocular surface. However, in some diseases the transplant usually dissolves rather quickly and early detachment may occur. Therefore, we tried to stabilize the amniotic transplant by applying glutaraldehyde for collagen cross-linking of the membrane. METHODS: 18 human amnions were prepared. 4 x 4 cm pieces of amnion were treated with 0.1% glutaraldehyde solution for 30 min. Biomechanical force-elongation measurements were performed and resistance to enzymatic digestion by 0.1% collagenase solution was tested and compared to cryopreserved and untreated fresh amnion. 8 patients with various ocular surface defects were treated with cross-linked amnion and compared to 5 patients with cryopreserved amnion. RESULTS: The force of the amnion cross-linked with glutaraldehyde at 2.5 mm elongation was increased statistically significant by 175% versus fresh amnion and 76.8% versus the cryopreserved amnion. Glutaraldehyde-treated membranes were virtually completely resistant to enzymatic digestion, while fresh and cryopreserved amnions were dissolved completely by day 7. In patients, the cross-linked membrane was preserved for up to 90 days without any signs of dissolution of the membrane and good transparency. CONCLUSIONS: Collagen cross-linking using glutaraldehyde leads to a significant increase in the biomechanical strength and enzymatic resistance of amnion, better transparency and less wrinkling. The cross-linked membrane does not dissolve for months and is well suited for the surface reconstruction of the cornea.

Amnion↗

PubMed2003

[Histopathology of the ocular surface].

Explore the source record for details and available documents.

Conjunctival Diseases↗

PubMed1998

N-linked glycoside and glucuronide conjugates of the retinoid, acitretin, are biologically active in cornea and conjunctiva.

The purpose of this study was to test two water-soluble, synthetic retinoids, glucoseamido acitretin and glucuronamido acitretin, for biological activity in cells of the cornea and conjunctiva. Vitamin A-deficient, xerophthalmic rats were treated topically with these retinoids, and corneas were examined histologically for effects on epithelial keratinization. The effect of these retinoids on the proliferation of rabbit conjunctival fibroblasts in culture was also investigated. Glucoseamido acitretin treatment restored a normal cornea after eight to nine days of treatment, while no improvement was observed in the vehicle-treated corneas. Likewise, glucuronamido acitretin application restored a normal corneal surface and reversed keratinization after eight to ten days of treatment. These retinoids caused no irritation of the eye or ocular adnexa. In culture, exposure of conjunctival fibroblasts to glucoseamide acitretin inhibited cell proliferation. Cultures exposed to glucoseamido acitretin at 10(-8) M or 10(-6) M had cell densities 77.3% and 51.9% of control, respectively, after seven days. Glucuronamido acitretin also inhibited cell proliferation. Cultures exposed to glucuronamido acitretin at 10(-8) M had a cell density of 69.2% of control at day seven, while at 10(-6) M this retinoid completely inhibited cell proliferation. These results show that glucoseamide acitretin and glucuronamido acitretin are biologically active in the cornea and conjunctiva, and may be considered for ophthalmic use in diseases involving abnormalities of ocular surface cell differentiation or hyperproliferation of fibroblasts.

Acitretin↗

PubMed1991

Ocular surface and lacrimal disturbances in chronic graft-versus-host disease: the role of conjunctival biopsy.

Forty-four patients (21 male, 23 female) were studied following bone marrow transplantation (BMT): 40 after allogeneic, one after syngeneic and three after autologous transplantation. Diffuse punctate conjunctival and corneal epitheliopathy was seen in 27 (61%), reduced or disordered tear film in 26 (59%), acquired lacrimal outflow obstruction in three (7%) and posterior subcapsular lens opacities in five (12%) patients. Conjunctival histology showed abnormal features, including those of graft-versus-host disease (GVHD) in 41 patients. Of these, 28 (64%) had clinical and laboratory features of GVHD and six patients with no systemic evidence of GVHD had conjunctival histology specific for GVHD. We conclude that after BMT, subclinical changes of GVHD are very common in the periocular tissues and may be universal in long-term survivors following allogeneic BMT. Some minor conjunctival changes are more likely to be due to the primary disease or the transplant conditioning regimen. Conjunctival biopsy is useful in demonstrating low-grade GVHD or GVHD confined to the ocular structures and may be diagnostic in some cases.

Adolescent↗

PubMed2005

[Ocular allergies].

Recent developments indicate that ocular allergy is more than an IgE-mediated allergic conjunctivitis. Ocular allergy is a disease affecting the entire ocular surface including conjunctiva, lids, cornea, lacrimal gland and tear film. Besides an IgE-mediated reaction, a complex chronic inflammation is involved in the pathogenesis of many ocular allergies. According to their pathogenesis and clinical picture, ocular allergies are classified into mild forms, such as seasonal and perennial allergic conjunctivitis as well as giant papillary conjunctivitis, and chronic, potentially blinding forms such as atopic keratoconjunctivitis and vernal keratoconjunctivitis. New therapeutics act on the entire inflammatory process or try to modulate the allergic reaction early and specifically. The association with non-ocular allergic symptoms requires an interdisciplinary approach.

Adrenal Cortex Hormones↗

PubMed1994

Risk factors in the development of ocular surface epithelial dysplasia.

BACKGROUND: Ocular surface epithelial dysplasia involves a spectrum of diseases ranging from only minor eye irritation to blindness and potentially death. METHODS: A case-control study involving 60 patients with ocular surface epithelial dysplasia treated between 1972 and 1991 and 60 age- and sex-matched individuals was conducted to compare relative ultraviolet light exposures over their lifetimes. A standardized self-administered ultraviolet exposure questionnaire was used for assessment. RESULTS: Risk factors identified include phenotypic features such as fair skin (odds ratio [OR], 5.4; 95% confidence interval [CI], 1.1, 25.6), pale iris (OR, 1.8; 95%; CI, 0.9, 3.8), and propensity to sunburn (OR, 3.8; 95% CI, 0.7, 19.7), history of previous skin cancers removed (OR, 15; 95% CI, 2.0, 113.6), and being outdoors more than 50% of time in the first 6 years of life while living 30 degrees or less from the equator (OR, 7.5; 95% CI, 1.8, 30.6). CONCLUSION: These risk factors suggest that ocular surface epithelial dysplasia is an ultraviolet light-related disease.

Adult↗

PubMed2005

Herpetic eye disease in diabetic patients.

PURPOSE: To study the incidence of herpetic eye disease (HED) of the ocular surface in diabetics. DESIGN: Observational historical cohort study. SETTING: A district of the largest health maintenance organization in Israel (the Central District of Clalit Health Services). PARTICIPANTS: We reviewed the electronic medical records of all patients older than 50 years (159634 patients) in the district, and of these, 22382 (14.0%) patients had diabetes mellitus. METHODS: All filled prescriptions for acyclovir eye ointment between January 1, 2001 and December 31, 2003 (1483 tubes) and all hemoglobin A1c laboratory tests during 2003 (41910 tests) were documented. An ocular surface HED event was defined when a patient consumed at least 1 tube of topical acyclovir per month, whereas no acyclovir use was documented 3 months before and 3 months after that event. MAIN OUTCOME MEASURES: Incidence of ocular surface HED events in diabetics compared with nondiabetics adjusted for age and gender. RESULTS: After age and gender adjustment, significantly more diabetics had ocular surface HED (5.21 per thousand) compared with nondiabetics (4.27 per thousand; P<0.0001). Stratification by age revealed a significantly higher prevalence of HED in diabetics, aged 60 to 79 years. Recurrent herpetic events occurred during the study period in 25.2% of HED-affected diabetics, and in 16.6% of HED-affected nondiabetics (P = 0.05). Diabetics with poor glycemic control (mean annual hemoglobin A1c > 9%) consumed significantly more ocular acyclovir (P = 0.01). Multivariate analysis revealed this effect to be independent of age, gender, place of birth, or place of residency. CONCLUSIONS: Ocular surface HED is significantly more common among patients with diabetes mellitus. Poor glycemic control correlates with increased consumption of ocular acyclovir in diabetic patients.

Acyclovir↗

PubMed2006

Patient-reported symptoms in dry dye disease.

Clinically, dry eye has often been reported as a "symptom-based" disease, and definitions of dry eye based on symptoms have been used to define dry eye prevalence in population-based studies. Given this, patient-reported symptoms often do not correlate with diagnostic tests unless disease is severe or testing is tightly controlled. Progress in the understanding of dry eye symptoms has been made over the last 10 years; however, the link between symptoms and disease status, such as ocular surface damage or inflammation, remains elusive. Although several surveys for dry eye have been developed for screening or diagnosis, an accepted, validated survey capable of accurately monitoring changes with time or treatment is not available. Common symptoms, available surveys, and the associations between diagnostic tests and symptoms are reviewed.

Dry Eye Syndromes↗

PubMed1999

[Amniotic membrane transplantation (AMT) for ocular surface reconstruction].

The authors present current opinions about the possibility of amniotic membrane transplantation for ocular surface treatment in patients with chemical and thermal burns, Stevens-Johnson syndrome, ocular cicatrical pemphigoid, persistent epithelial defects with ulceration and large conjunctival defects. Amniotic membrane facilitates migration of epithelial cells, promotes their differentiation, prevents epithelial apoptosis, does not provoke neovascularization and a typical host-versus-graft rejection. Amniotic membrane transplantation is an advance in techniques for managing ocular surface reconstruction revolutionizing corneal disease treatment.

Amnion↗

PubMed2005

[Ocular allergies].

Conjunctivitis, Allergic↗