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A new computer assisted objective method for quantifying vascular changes of the bulbar conjunctivae.

A novel computer software method was used to quantify the conjunctival plexus on the scleral background for measurement of the vascular surface area from photographs. A previously described method was used (Palmer, J. R., Owen, C. G., Ford, A. M., Jacobson, R. E. and Woodward, E. G. (1996). Optimal photographic imaging of the bulbar conjunctival vasculature. Ophthal. Physiol. Opt. 16, 144-149) to optimise photographic imaging of the bulbar conjuctival vasculature by increasing the information content in the image. Repeatability of this technique was evaluated. Twenty subjects (20 eyes) free from ophthalmological and systemic abnormality were examined on two separate occasions. The maximum 95% confidence limits for repeatability are +8.58/-3.95%. For 10 consecutive estimates of vascularity the maximum 95% confidence interval lie between +/- 6.54%. To evaluate the technique the lateral-bulbar conjunctivaein 10 soft (SCL) and 10 rigid gas permeable contact lens (RGPCL) wearers during the first 10 months of contact lens wear, were assessed and compared with subjective grading of hyperaemia. The new method showed sufficient sensitivity in detecting increased hyperaemia in the RGPCL wearing group and demonstrated statistically significant change. Subjective graded assessment of vascularity (using established classifications) detected increased hyperaemia, however, this was not statistically significant. Conjunctival vasculature is a dynamic structure and a source of valuable quantitative information where the ocular environment is varied, or where the ocular surface is affected by disease. Hence it is worthy of further investigation. A simple inexpensive method of computer assisted determination of vascularity is described.

Adult↗

[Treating severe dry eye syndromes with autologous serum].

BACKGROUND: Dry eye syndrome with tear deficiency can be improved with artificial tears, which can be associated with topical anti-inflammatory agents. Autologous serum can provide the ocular surface with beneficial growth factors and vitamins. PATIENTS AND METHODS: Twenty-one patients suffering from severe dry eye due to Sjögren's syndrome were treated with 20% autologous serum for 2 Months. The Schirmer I test, break-up time, and fluorescein and lissamine green stainings were performed before and after treatment. Subjective complaints such as burning, foreign body sensation, dryness and photophobia were assessed by a questionnaire as well as a face score reflecting the current condition of patients' eyes. RESULTS: Lissamine green and fluorescein scores improved significantly as well as subjective symptoms of burning, foreign body sensation and dryness (p<0.05). The face score was significantly improved. Bacterial culture of serum delivered to the patients all remained negative. DISCUSSION: Autologous serum provides growth factors and vitamins that are useful for an altered ocular surface due to Sjögren's disease. However, some problems still remain: risk of contamination, arbitrary dilution of autologous serum, and a current lack of regulations for use of autologous serum. A close collaboration between ophthalmologists and the Etablissement Français du Sang (French Blood Bank) is mandatory because autologous serum should be considered as a useful tool to treat severe ocular surface disorders. CONCLUSION: The use of autologous serum improved symptoms and objective signs caused by severe Sjögren's syndrome. Currently, a lack of clear regulations prevents its widespread use in severe ocular surface disorders.

Blood Transfusion, Autologous↗

[Amniotic membrane transplantation for reconstruction of the ocular surface].

Amniotic membrane transplantation has been recently gained wide-spread attention as a new method for reconstruction of the ocular surface. However long term prognosis of the surgical intervention as well as action mechanism are poorly defined. Therefore, we review the current literature concerning the application of amniotic membrane in ophthalmology and the outcome of the surgery. Amniotic membrane is used as graft or patch to promote epithelial healing of persistent epithelial defects, corneal ulcers and following penetrating keratoplasty. It is also used to seal corneal perforations and to treat bullous keratopathy. Amniotic membrane patches facilitate epithelial healing and reduce the number of complications after chemical burns. For partial limbal deficiency, amniotic membrane alone can be sufficient, while total limbal deficiency requires combination with stem-cell transplantation. Furthermore amniotic membrane grafts restore conjunctival surfaces following removal of lesions such as pterygium, tumor, scar, symblepharon, and conjunctivochalasis. The prognosis of amniotic membrane transplantation depends on the underlying disease and the quality of the ocular surface and is inversely related to the degree of inflammation. Recent investigations of the action mechanisms describe intrinsic antiinflammatory properties of the amniotic membrane.

Amnion↗

The diagnosis and management of dry eye: a twenty-five-year review.

PURPOSE: To review the advances in the diagnosis, pathogenesis, and management of dry eye disease in the past 25 years. METHODS: Literature review. RESULTS: The preocular tear film is a hydrated mucus gel that contains soluble antimicrobial proteins and growth factors that protect and support the ocular surface. The final common pathway in dry eye is a perturbation of the integrated ocular surface/lacrimal gland reflex unit. Diagnostic tests evaluating tear composition and clearance appear to show stronger correlation with the severity of ocular irritation symptoms and keratoconjunctivitis sicca (KCS) than the conventional Schirmer tests. KCS is a condition of abnormal differentiation and mucus production by the ocular surface epithelium that results in a poorly lubricated, abnormally permeable ocular surface that has increased susceptibility to environmental insults. Chronic subclinical ocular surface inflammation appears to play a key role in the pathogenesis of KCS. New therapeutic strategies are aimed at reducing the ocular surface inflammation of dry eye disease. CONCLUSIONS: There has been a tremendous increase in knowledge regarding dry eye disease in the past 25 years that has resulted in improved diagnostic classification and new targeted therapies.

Animals↗

The defences of the ocular surface.

Bacterial infection may be responsible for mild self-limiting disease, chronic disease or acute and devasting ocular destruction. This paper and those that follow deal with some of the clinical forms of disease which are encountered, the bacteria responsible, the mechanism of invasion and the natural defences and clinical management, including selection and delivery of antibiotics.

Anti-Bacterial Agents↗

A review of bacterial keratitis and bacterial conjunctivitis.

Bacterial keratitis is an opportunistic infection of the avascular corneal stroma, initiated by a breakdown of the epithelial barrier. Corneal abrasion with infected material, extended-wear contact lenses, eyelid disease, and disorders of the ocular surface are predominant contributing factors. Acute bacterial conjunctivitis occurs when sufficient bacteria are introduced into the fornices to overwhelm normal bacteriostatic and flushing mechanisms. Chronic conjunctivitis is associated with a constant adnexal source of bacteria and resolves when the source is successfully treated. Rapid diagnosis and treatment of bacterial keratitis are essential to limit stromal scarring and minimize visual loss.

Acute Disease↗

The role of the conjunctival epithelium in ocular allergy.

PURPOSE OF REVIEW: The epithelium of target organs is playing an increasing role in allergy. Several studies have shown that epithelial cells participate actively in inflammatory processes. This review will focus on recent advances in the role of conjunctival epithelium in allergy as a potential target for therapeutic interventions. RECENT FINDINGS: Several studies have already shown the involvement of ocular surface epithelial cells in allergic inflammatory diseases, because they are able to produce and secrete cytokines and chemokines upon stimulation. They also express adhesion molecules as well as receptors for several substances implicated in inflammation. Some studies have also shown that conjunctival epithelial cells express co-stimulatory molecules when they interact with activated T cells, adding more evidence to the important role that epithelial cells play in the pathogenesis of ocular inflammatory diseases. Recent reports have also demonstrated that during inflammatory conditions, conjunctival epithelial cells show an altered expression of their neuroreceptors, suggesting that a modulation of neural regulation may be of therapeutic value. SUMMARY: The ocular surface epithelium is not just a simple physical barrier to the entrance of foreign bodies. It participates in the allergic inflammatory process by being influenced by inflammatory molecules, and by secreting inflammatory cytokines and chemokines. Moreover, the epithelium not only actively participates in the inflammation process but can also initiate it. This relevant spectrum of actions makes epithelium an attractive target for therapeutic interventions.

Conjunctiva↗

Advances in ocular allergy: basic mechanisms, clinical patterns and new therapies.

Ocular allergy presents unsolved mysteries in molecular and cellular mechanisms, and at the same time continues to challenge ophthalmologists daily in a wide array of disease forms. The recent understanding of the key role of the T helper type 2 cytokines, adhesion molecules and chemokines may provide future avenues for pharmacological targeting of releasable inflammatory mediators. More potent topical mast cell stabilizers and H1 receptor antagonists have become commercially available for the management of the prevalent and benign forms of allergic conjunctivitis. Immunostimulatory DNA sequences present an innovative and promising route for the treatment of ocular allergy, but clinical studies are needed to demonstrate their efficacy in humans. Surgical methods are suggested to reconstruct the ocular surface in the sight-threatening diseases vernal keratoconjunctivitis and atopic keratoconjunctivitis. This review presents an update of the major advances in both the basic mechanisms and clinical and therapeutic aspects of ocular allergic diseases that were reported during the past year.

Anti-Allergic Agents↗

Ocular surface disorders in the critically ill.

Abnormalities of the cornea and conjunctiva occur in association with neurological diseases, nocturnal lagophthalmos, coma, infection, and mechanical ventilation. We investigated the incidence and causes of ocular surface disorders in critically ill patients. In a retrospective study, the presence of conjunctivitis and corneal erosion was determined by reviewing the medical charts of 143 mechanically ventilated patients (intensive care unit [ICU] stay > or =7 days). In the subsequent prospective study, 15 patients who had sedatives or muscle relaxants administered continuously for more than 48 h in the ICU were investigated. Corneal erosion was examined using a slit lamp once a day. Ocular surface disorder was found in 28 of the 143 patients (20%) whose ICU stay exceeded 7 days. The incidence increased with continuous sedation (35% vs 15%). The incidence also increased with continuous neuromuscular blockade (39% vs 11%). In the prospective study, nine patients (60%) developed corneal erosion. A patient's inability to fully close his or her eyes increased the incidence (P < 0.01) of corneal erosion. Protective eyelid taping was effective in preventing and treating the corneal erosion. In conclusion, the critically ill often develop ocular surface disorders, especially when sedated and immobilized. A close relationship was observed between these conditions and the inability to close one's eyes.

Adolescent↗

The pathology of dry eye.

Homeostasis of the tear film involves delicate hormonal and neuronal regulatory mechanisms. The eye appears to be a target organ for sex hormones, particularly the androgens, as they modulate the immune system and trophic functions of the lacrimal glands and the functioning of the meibomian glands. The cornea, lacrimal glands, mucous cells, and meibomian glands are all richly innervated, indicating the importance of nervous regulation in their function. Parasympathetic, sympathetic, and sensory innervation play complex stimulatory or inhibitory roles, and neuronal pathways interact via complex surface results cascades. Abnormalities at any point in these pathways can cause overall dysregulation of lacrimal function. Whatever the initial causes of dry eye, chronic dryness of the ocular surface results in inflammatory reactions and gradual destruction of the lacrimal glands and conjunctival epithelium. Once dry eye disease has developed, inflammation is the key mechanism of ocular surface injury, as both the cause and consequence of cell damage. In practice, dry eye can be associated with Sjögren's syndrome, allergies, infection, blepharitis, and preservative-containing eye drops.

Dry Eye Syndromes↗

Ocular pharmacokinetics and safety of ciclosporin, a novel topical treatment for dry eye.

Ciclosporin is a potent immunomodulator that acts selectively and locally when administered at the ocular surface. 0.05% ciclosporin ophthalmic emulsion has recently been approved by the US FDA for treatment of keratoconjunctivitis sicca (KCS) [dry-eye disease]. After topical application, ciclosporin accumulates at the ocular surface and cornea, achieving concentrations (>/=0.236 microg/g) that are sufficient for immunomodulation. Very little drug penetrates through the ocular surface to intraocular tissues. Ciclosporin is not metabolised in rabbit or dog eyes and may not be prone to metabolism in human eyes. Cultured human corneal endothelial and stromal cells exposed to ciclosporin in vitro exhibited no adverse effects and only minor effects on DNA synthesis. No ocular or systemic toxicity was seen with long-term ocular administration of ciclosporin at concentrations up to 0.4%, given as many as six times daily for 6 months in rabbits and 1 year in dogs. Systemic blood ciclosporin concentration after ocular administration was extremely low or undetectable in rabbits, dogs and humans, obviating concerns about systemic toxicity. In 12-week and 1-year clinical safety studies in dry-eye patients, the most common adverse event associated with the ophthalmic use of ciclosporin emulsion was ocular burning. No serious drug-related adverse events occurred. These data from in vitro, nonclinical and clinical studies indicate effective topical delivery of ciclosporin to desired target tissues along with a favourable safety profile, making 0.05% ciclosporin ophthalmic emulsion a promising treatment for KCS.

Animals↗

The evolving treatment of dry eye.

Palliative treatments that historically have been the mainstay of therapy for dry eye continue to improve and are still appropriate therapy while we await new advances to control the underlying cause of dry eye disease. The approach of tear supplementation and tear preservation continues to be useful. The goal of tear stimulation or enhancement is elusive, but it may be nearer with the advent of P2Y2 agonists. The recognized importance of inflammation in producing dry eye through lacrimal gland and ocular surface damage is leading us to novel strategies to immunomodulate the disease and to restore hormonal balance to the ocular surface-lacrimal gland homeostatic cycle. It has taken 20 years of investigation to reach this threshold. The next 3 years should see promising treatments approved for dry eye disease.

Dry Eye Syndromes↗

Herpes zoster ophthalmicus in patients with human immunodeficiency virus infection.

PURPOSE: To investigate the ocular complications of herpes zoster ophthalmicus in patients with human immunodeficiency virus (HIV) infection. METHODS: This was a retrospective cohort study of 48 HIV-infected patients (48 eyes) treated at San Francisco General Hospital for herpes zoster ophthalmicus from December 1985 through March 1994. RESULTS: All patients were initially treated with either intravenous or oral acyclovir. The median CD4 lymphocyte count at diagnosis was 48 per mm3 (range, 2 to 490 per mm3). Fifteen patients (31%) had mild or no ocular involvement. Seventeen patients (35%) had stromal keratitis, mostly mild, and two (4)% developed chronic infectious pseudodendritic keratitis. Twenty-four study patients (50%) had iritis, but only three (6%) had elevations in intraocular pressure. Two patients (4%) developed postherpetic neuralgia, and two others (4%) had zoster-associated central nervous system disease. Only two patients (4%) developed necrotizing retinitis, both in the form of the progressive outer retinal necrosis syndrome. CONCLUSIONS: Excluding the patients with retinitis and central nervous system disease, the rate of sight-threatening complications in our series was lower than expected. Almost one third of study patients had no ocular complications or only mild surface epithelial disease. Although the relatively low incidence of sight-threatening disease in our study population may have been a consequence of aggressive management with acyclovir, chronic infectious pseudodendritic keratitis, retinitis, and central nervous system disease, complications of ophthalmic zoster whose pathogenesis is largely a consequence of active viral replication, were particularly devastating and difficult to manage.

Acyclovir↗

[Be aware of toxicity of eye drops to ocular surface].

Ocular surface toxicity caused by the abuse of eye drops is often overlooked. The clinical signs are usually nonspecific and can be mistaken resulting from other eye surface diseases. Pathogenic mechanisms vary widely with different application of eye drops. Ophthalmologist should be aware of the ocular surface toxicity induced by eye drops and its prevention and treatment.

Conjunctival Diseases↗

[In vivo imaging of the conjunctival epithelium using confocal laser scanning microscopy].

BACKGROUND: In various ocular diseases, cytomorphological findings of the ocular surface are an essential component of clinical diagnostics. When evaluating the conjunctival epithelium, minimally invasive acquisition of biomaterial is necessary for lab and technical processing and in vitro histological examination. To examine corneal structures in vivo, confocal laser scanning microscopy is a successful standard method. Our aim was to employ in vivo confocal laser scanning microscopy also for examining the conjunctival epithelium. MATERIAL AND METHOD: Results were analyzed and compared with cytomorphological findings of impression cytology. Accordingly, the basic features of conjunctival in vivo examination using RLSM were described and defined. In vivo images were analyzed and compared with impression cytological slide preparations (n=110) of 23 healthy test persons. Examination was standardized. Finally, the confocal laser scan images were compared to the impression cytological patterns. RESULTS: Due to the distribution of reflectors (pixel brightness), diagnostic analysis of important morphological structures (cell nucleus, cytoplasm, nucleus/plasma relation) of the conjunctiva is possible. Secretory cells of the epithelium (goblet cells) can be easily recognized by their size. Highly reflective pixels depict cell walls or wide intercellular spaces with high contrast. CONCLUSIONS: The in vivo investigation of important anatomical and morphological structures of the conjunctival epithelium is possible using RLSM. The distribution pattern of goblet cell pixel brightness may correlate with various secretion contents or suggest distinct, recognizable, functional conditions (hypo- or hypersecretion).

Conjunctiva↗

Characterization of a carbohydrate epitope defined by the monoclonal antibody H185: sialic acid O-acetylation on epithelial cell-surface mucins.

Sialic acids comprise a large family of derivatives of neuraminic acid containing methyl, acetyl, sulfate, and phosphate among other groups, which confer specific physicochemical properties (e.g., hydrophobicity and resistance to hydrolases) to the molecules carrying them. Several years ago, a monoclonal antibody, designated H185, was developed, which binds to cell membranes of human corneal, conjunctival, laryngeal, and vaginal epithelia and whose distribution is altered on the ocular surface of patients with keratinizing disease. Recent findings using immunoprecipitation and immunodepletion techniques have demonstrated that, in human corneal epithelial cells, the H185 antigen is carried by the membrane-associated mucin MUC16. In this study, we show that the H185 epitope on human corneal cells and in tear fluid is an O-acetylated sialic acid epitope that can be selectively hydrolyzed in an enzyme-concentration-dependent manner by sialidase from Arthrobacter ureafaciens and to a lesser extent by sialidases from Newcastle disease virus, Clostridium perfringens, and Streptococcus pneumoniae. Binding of the H185 antibody was impaired by treatment of tear fluid with a recombinant 9-O-acetylesterase from influenza C virus. Two O-acetyl derivatives, Neu5,7Ac(2) and Neu5,9Ac(2), were identified in human tear fluid by fluorometric high-performance liquid chromatography (HPLC) and electrospray mass spectrometry (MS). Immunoprecipitation of the H185 epitope from human corneal epithelial cells revealed that Neu5,9Ac(2) was the major derivative on the mucin isolate. These results indicate that exposed wet-surfaced epithelia are decorated with O-acetyl sialic acid derivatives on membrane-associated mucins and suggest that O-acetylation on cell surfaces may protect against pathogen infection by preventing degradation of membrane-associated mucins.

Antibodies, Monoclonal↗