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PubMed2004

[Roles of cytokines in the development of severe allergic conjunctival diseases: analyses using animal models].

Conjunctival papillary formation and corneal damage, which are seen in severe types of allergic conjunctival diseases, are mediated by eosinophils. Eosinophils themselves are not able to recognize a specific antigen (Ag) and thus, Ag-specific T cells are thought to be important for eosinophilic infiltration into the conjunctiva. Cytokines, which are produced by Ag-specific T cells followed by Ag recognition, are considered to be involved in eosinophilic infiltration. Therefore, we investigated the involvement of cytokines, which are produced by immunocompetent cells and conjunctival cells, in the infiltration of inflammatory cells into the conjunctiva, using an animal model for allergic conjunctival diseases (experimental immune-mediated blepharoconjunctivitis, EC). The peak of expression of Th 2 cytokines such as interleukin (IL)-4 in the rat conjunctiva was 6 and 12 hours after Ag challenge. In contrast, expression of Th1 cytokines such as interferon (IFN)-gamma persisted up to 48 hours after Ag challenge. The kinetic change of IL-4 was concordant with eosinophilic infiltration into the conjunctiva and that of IFN-gamma was in accord with infiltration of macrophages. To investigate the roles of these cytokines, we induced conjunctivitis in cytokine knockout mice. The infiltration of inflammatory cells was attenuated in IL-4 knockout mice, whereas it was augmented in IFN-gamma knockout mice. To further elucidate the roles of these cytokines, we induced and analyzed EC in Brown Norway rats. Eosinophilic infiltration was increased in EC induced by the transfer of T cells, which were stimulated by IL-4. In addition, systemic treatment with IFN-gamma inhibited eosinophilic infiltration in EC induced by active immunization, but did not affect infiltration of inflammatory cells in EC induced by passive immunization. These results demonstrate that IL-4 and IFN-gamma are involved in the infiltration of eosinophils and macrophages, respectively. In addition, IFN-gamma exerts its suppressive effects on the development of EC only during the induction phase of EC. Further detailed studies investigating the roles of cytokines in the conjunctiva will elucidate the developing mechanism of allergic conjunctival diseases. These studies will provide important clues for a therapeutic approach in targeting cytokines.

Animals↗
PubMed2003

Tarsal-conjunctival disease associated with Wegener's granulomatosis.

OBJECTIVE: To describe the clinical characteristics of tarsal-conjunctival disease in a cohort of patients with Wegener's granulomatosis (WG). DESIGN: Retrospective, case-controlled study. PARTICIPANTS: The medical records of 82 consecutive WG patients who underwent an eye examination between January 1996 and June 2002 at the National Institutes of Health were reviewed. METHODS: Details of the ophthalmic examination, results of medical therapy, and histopathologic analysis results were recorded. Tarsal-conjunctival disease was defined by (1). conjunctival hyperemia and granuloma formation, areas of necrosis, or active fibrovascular changes in the tarsus or conjunctiva, or (2). evidence of inactive fibrovascular scar. The association of tarsal-conjunctival disease with major organ system involvement was assessed using Bayesian methods. MAIN OUTCOME MEASURES: The occurrence and clinical characteristics of tarsal-conjunctival disease in a cohort of patients with WG and associations with major organ system involvement. RESULTS: Tarsal-conjunctival disease occurred in 13 of 82 patients (16%) with WG examined over a 6.5-year period. The palpebral surface of the upper lid was involved most commonly, showing conjunctival hyperemia in seven patients, granulomatous lesions in three patients, tarsal-conjunctival necrosis in four patients, active fibrovascular proliferation in six patients, and inactive fibrous scar tissue in seven patients. Histopathologic analysis of eyelid biopsy specimens showed granulomatous inflammation, focal necrosis, and areas of occlusive vasculitis in the tarsus and conjunctiva. In reviewing the patterns of organ involvement in patients with and without tarsal-conjunctival disease, the association of subglottic stenosis and nasolacrimal duct obstruction with tarsal-conjunctival disease showed a high probability of clinical significance. CONCLUSIONS: Tarsal-conjunctival disease, a previously uncommon finding in patients with WG, was characterized by inflammation of the palpebral conjunctiva and tarsus followed by a fibrovascular proliferation and scar formation. Because of the important association of tarsal-conjunctival disease with subglottic stenosis, which can progress and lead to laryngeal obstruction and respiratory failure, patients with tarsal-conjunctival disease should be referred to an otolaryngologist for evaluation.

Adult↗
PubMedDate not supplied

Predominance of infiltrating IL-4-producing T cells in conjunctiva of patients with allergic conjunctival disease.

PURPOSE: Previous reports have suggested that type 2 cytokine responses at the site of inflammation are important in the pathogenesis of allergic disease. In this study, we investigated the frequency of IFN-gamma- or IL-4-producing T cells from conjunctiva or peripheral blood mononuclear cells (PBMC) from patients with allergic conjunctival diseases. METHODS: We obtained conjunctival samples using Cytobrush and peripheral blood samples from the patients with allergic conjunctival disease. Conjunctival samples and PBMC were stimulated with phorbol myristate acetate and calcium ionophore. Frequencies of cytokine-producing T cells were analyzed by flow cytometry based on the intracellular cytokine staining. RESULTS: The frequency of IL-4-producing conjunctival T cells in patients with vernal keratoconjunctivitis (VKC) and atopic keratoconjunctivitis (AKC) were significantly higher than that in patients with allergic conjunctivitis (AC). The frequencies of IL-4-producing conjunctival CD4+ T cells of the patients with AC, AKC, or VKC were significantly higher than those of peripheral blood CD4+ T cells of the same disease. Further, increased frequency of P-selectin ligand expressing IL-4-producing T cells was observed in conjunctiva compared to that in PBMC of the patients with allergic conjunctival diseases. The frequencies of IL-4-producing peripheral blood T cells in the patients with ACD were significantly higher than that in normal controls. CONCLUSION: These results suggest that IL-4-producing T cells that have infiltrated into the conjunctiva play an important role in the immunopathogenesis of allergic conjunctival diseases, and P-selectin ligand is involved in the entry of T cells into allergic inflammatory site.

Adult↗
PubMed1992

Impression Cytology with Transfer in xerophthalmia and conjunctival diseases.

During a countrywide survey, we assessed the prevalence of clinical signs of xerophthalmia and of major conjunctival diseases in a randomized sample of 2,445 subjects representative of the population of the Republic of Djibouti. On a part of this sample, conjunctival Impression Cytology with Transfer (ICT) test and a plasma retinol determination were performed. Xerophthalmia as a public health problem was displayed by clinical signs (Bitot's spots, corneal scars among preschool children), low plasma retinol levels and ICT test results: 9.3% with deficient cytology in the rural area and 12.3% in the urban one (age-standardized rates). Results of ICT were related to age (p < 0.00001). Vitamin A deficiency was prevalent not only in preschool children but also up to 15 years. Moreover, ICT results are influenced by conjunctival diseases: compared to age-matched controls, there were more abnormal cytologies among patients with trachomatous inflammation (p = 0.025), conjunctivitis (p = 0.024) or Limbal Vernal Keratoconjunctivitis (p = 0.015). Thus ICT shouldn't be performed among children with conjunctival diseases. In the region under study conjunctival diseases had high rates of prevalence: 16.4% of trachomatous scarrings in the urban area (standardized rate), 8% of conjunctivitis among rural preschool children, and 5% of Limbal Vernal Keratoconjunctivitis among children between 5 and 14 years in both areas.

Adolescent↗
PubMed1995

Penetrating keratoplasty in cicatrizing conjunctival diseases.

PURPOSE: The outcome of successful penetrating keratoplasty (PK) typically is poor in eyes with end-stage chronic cicatrizing conjunctival diseases such as ocular cicatricial pemphigoid (OCP), Stevens-Johnson syndrome, and toxic epidermal necrolysis due to immunologically driven conjunctival inflammation associated with conjunctival cicatrization and lid abnormalities, severe dry eye, and extensive corneal neovascularization. The authors report the results of their experience with PK in 13 patients with OCP, Stevens-Johnson syndrome, and toxic epidermal necrolysis. METHODS: The authors reviewed the records of patients with OCP, Stevens-Johnson syndrome, or toxic epidermal necrolysis seen between 1976 and 1992. Patients who underwent PK were examined for the purpose of this study. Initial and final visual acuity, indications for PK, surgical procedure, postoperative therapy, complications, total number of repeat PKs, length of follow-up, and the final outcome were recorded. RESULTS: Thirty-two PKs were performed in 16 eyes of 13 patients with advanced OCP (6 patients), OCP as a sequela of Stevens-Johnson syndrome (2 patients), Stevens-Johnson syndrome (3 patients), and toxic epidermal necrolysis (2 patients). The indications for the first PK were corneal perforation in six eyes (37.5%) and extensive corneal scarring in ten eyes (62.5%). Preoperative visual acuity was counting fingers in five eyes, hand motions in eight, and light perception in three. Preoperative therapy included systemic chemotherapy (8 patients), mucous membrane grafting (9 eyes), lamellar keratoplasty (2 eyes), superficial keratectomy (1 eye), and corneal dye laser photocoagulation (6 eyes). The mean follow-up period was 4.6 years (3 months-13 years). Eight eyes (50%) had clear grafts, and three eyes (18.7%) had 20/200 or better visual acuity at last visit. The major causes of graft failure were epithelial defect formation/persistence, stromal ulceration, perforation, and graft rejection. CONCLUSIONS: These results indicate that PK may be performed for tectonic reasons, but prospects for restoration of sight in patients with advanced cicatrizing conjunctival diseases, even after extensive preoperative medical and surgical therapy, are limited.

Adolescent↗
PubMed2001

Histamine release test and measurement of antigen-specific IgE antibody in the diagnosis of allergic conjunctival diseases.

Although systemic allergic laboratory tests for the quantification of allergen-specific serum IgE antibody have been widely used, in these tests a high titer of serum specific IgE does not necessarily indicate evidence of allergy. We evaluated the diagnostic value of the glass microfiber-based histamine release test (HRT) using small amounts of whole blood, in 36 cases of allergic conjunctival diseases: 17 cases of allergic conjunctivitis and 19 of atopic keratoconjunctivitis. The patients were evaluated by HRT, capsulated hydrolic carrier polymer (CAP)-RAST, and conjunctival provocation test (CPT) against ten allergens. The positive rates for all allergens were higher in CAP-RAST than in HRT. The mean concordance of HRT with CAP-RAST results was 0.789. The mean concordance of HRT with CPT was 0.892 and that of CAP-RAST with CPT was 0.693. A significantly higher concordance was observed in HRT than CAP-RAST for Japanese cedar and mite antigen. The mean sensitivity, specificity, and efficiency of HRT were higher than those of CAP-RAST. These results indicate that CAP-RAST is good for the screening of allergens and that HRT has an advantage in the confirmation of clinical allergens in allergic conjunctival diseases because of its high sensitivity, specificity, efficiency, and higher concordance with CPT.

Adolescent↗
PubMed2003

[Clinical evaluation of measurement method for antigen specific IgE in tears of patients with allergic conjunctival disease].

PURPOSE: To investigate a method for determining antigen specific IgE antibodies in tears of patients with allergic keratoconjunctival disease. SUBJECTS AND METHODS: Antigen specific IgE antibodies to Japanese cedar pollen or Housedust-Mites in tears of patients with allergic conjunctival diseases were examined. Both eyes in each patient were examined. The right eye was examined in normal healthy volunteers as a control. The number of eyes examined for IgE antibodies to Japanese ceder pollen was 32 eyes with seasonal allergic conjunctivitis(SAC), 12 eyes with perennial allergic conjunctivitis(PAC), 12 eyes with atopic keratoconjunctivitis (AKC), 4 eyes with vernal keratoconjunctivitis (VKC), and 12 eyes of the controls. The number of eyes examined for IgE antibodies to Housedust-Mites was 32 eyes with SAC, 20 eyes with PAC, 30 eyes with AKC, 22 eyes with VKC, and 10 eyes with the control. Tears were sampled by the method of Schirmer Test-1. Sampled tears were eluded with 200 microliters of phosphate buffered solution(pH 7.2, 0.05 M) and analyzed by the AlaSTAT-IMMULYZE method. Recovery rate of absorbance by filter paper for IgE antibodies in tears was determined by ratio to the standard sample of serum solution containing Housedust-Mite specific IgE antibodies with known concentration. RESULTS: Recovery rate of filter paper for IgE antibodies in tears was 83.6%. IgE antibodies in tears to Japanese cedar pollen were detected in 11 of 32 eyes of SAC. In other subjects, IgE antibodies were under the limit of the detection concentration except one eye of a patient with AKC. In the positive cases of Japanese cedar pollen specific IgE antibodies, there was no significant difference in the concentration between the right and the left eyes. IgE antibodies to Housedust-Mites were significantly higher not only in incidence but also in concentration in 18 of 22 eyes with VKC than in that in other in 8 of 20 eyes with PAC and 12 of 30 eyes with AKC. CONCLUSION: The method for determining antigen specific IgE antibodies in tears is clinically useful to diagnose and to investigate pathophysiology of allergic conjunctival diseases.

Adolescent↗
PubMed1982

Immunoassay of tear lysozyme in conjunctival diseases.

The tear lysozyme content in 111 normal subjects and in 159 patients with various conjunctival diseases was determined by a single radial immunodiffusion technique. Tear lysozyme level in normal people was 1.33/mg/ml. (SI conversion: mg/ml = g/l.) The mean tear lysozyme levels in patients with chronic irritative conjunctivitis (0.97 mg/ml) and nutritional deficiency with epithelial xerosis (0.76 mg/ml) were significantly lower than in the normal controls. The mean tear lysozyme levels in tears from patients with vernal conjuctivitis (1.20 mg/ml), phlyctenular conjunctivitis (1.10 mg/ml), and acute bacterial conjunctivitis (1.48 mg/ml) were not significantly different from those in the normal controls. Superimposition of acute bacterial conjunctivitis on trachoma did not alter the low tear lysozyme level that existed before in these patients.

Adolescent↗
PubMed2002

[Topical Fk506 in inflammatory corneal and conjunctival diseases. A pilot study].

BACKGROUND: Topical corticosteroids are the only effective measure in serious inflammatory corneal and conjunctival diseases. Although results obtained with topical cyclosporin A are encuraging it is not effective in all patients. The mode of action of Fk506 is similar to that of cyclosporin A, i.e. it exerts an inhibitory effect on transcription of interleukin 2 in T lymphocytes. The immunosuppressive potential of Fk506, however, is much larger. Furthermore, it penetrates more easily into cornea and conjunctiva. To find out whether the theoretical advantages of topical Fk506 can be translated into clinical practice, a selected group of patients refractory to conventional therapy was treated in this pilot study. PATIENTS AND METHODS: Fk506 0.06 % was administered initially three times daily in 15 patients with atopic blepharokeratoconjunctivitis, Mooren's ulcer, ocular pemphigoid, Thygeson's superficial punctate keratitis, nummular adenoviral keratitis, graft-versus-host reaction of the conjunctiva and steroid response glaucoma after penetrating keratoplasty. RESULTS: Within a follow-up of 26 +/- 15 weeks improvement was recorded in 5/15 patients and stabilization in 5/15 patients. In two patients progression of the disease was noted (one patient with progression of ocular pemphigoid, another patient with suspected automutilation). Premature withdrawal the drug was judged to be necessary in two patients with ocular surface disorders and in one patient with non-compliance. CONCLUSIONS: Topical Fk506 seems to be a promising new immunosuppressive drug for patients with atopic blepharokeratoconjunctivitis, Thygeson's superficial punctate keratitis and nummular adenoviral keratitis. Exact efficacy in these and other corneal and conjunctival inflammatory diseases has to be determined in randomised clinical studies. Before these studies may start the risk of side-effects must be reduced via an improvement of the drops.

Adult↗
PubMed2001

[Immunology-related chronic progressive cicatricial conjunctival diseases: diagnosis, therapy and prognosis].

PURPOSE: We reviewed the records of patients with chronic cicatricial disease of the conjunctiva for differences in prognosis between clinical and histopathological subgroups of the disease and in therapeutic options. PATIENTS: In 30 patients (58 eyes) with an average age of 69 years (52-86) chronic cicatricial disease of the conjunctiva was diagnosed clinically. Only in 22/30 patients conjunctival biopsies could be performed. The correlation of histopathological and immunohistochemical diagnoses with clinical course under systemic immunosuppression was studied. RESULTS: 15/22 biopsies led to a classification into different subgroups. Under systemic immunosuppression disease ceased to progress for a mean time of 15 months in 13 of 15 patients with positive biopsies and in 9 of 15 without classification. The results after cyclosporine A therapy (4 of 5 patients stabilized after a mean of 27.5 months) and mycophenolate mofetil (8 of 11 patients stabilized at a mean of 7.8 months) were better than those after therapy with dapsone, azathioprine and cyclophosphamide. CONCLUSIONS: Histopathological and immunohistochemical examinations led to a classification in two-thirds of the patients with clinical aspects of chronic cicatricial disease of the conjunctiva. There was no correlation between different histopathological subgroups, success of therapy and prognosis of the disease. There is little hope in using new systemic immunosuppression such as cyclosporine A and mycophenolate mofetil.

Aged↗
PubMed2002

Tear osteopontin levels in patients with allergic conjunctival diseases.

BACKGROUND: Recent reports have revealed the importance of several cytokines in chronic conjunctival allergic diseases (ACD) such as vernal keratoconjunctivitis (VKC) and atopic keratoconjunctivitis (AKC). Osteopontin (OPN) is a noncollagenous adhesive matrix protein that is expressed by activated macrophages. There has been considerable interest in the potential role of OPN in monocyte infiltration at sites of inflammation. We measured OPN level in tears using ELISA, to determine whether the level of this cytokine is elevated in ACD. METHODS: The level of OPN in tears was measured by ELISA using samples from patients with VKC, AKC or allergic conjunctivitis (AC) and from normal subjects. The level of OPN in tears was compared with the clinical severity of ACD and serum level of total IgE. RESULTS: The level of OPN in tears in AKC patients was significantly higher than that in AC and normal controls. Tear level of OPN in patients with VKC was also significantly elevated compared to those with AC and to normal controls. The clinical severity of ACD correlated significantly with the level of OPN. However, no correlation was observed between tear OPN level and serum level of total IgE. CONCLUSIONS: These results indicate that OPN plays an important pathophysiological role in severe ocular allergic conditions and that an elevated level of OPN in tear fluid reflects the local clinical status of ocular allergy, which may be an example of tissue remodeling.

Adolescent↗