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PubMed2003

Allergic chronic inflammation of the ocular surface in vernal keratoconjunctivitis.

PURPOSE OF REVIEW: The purpose of this review is to describe the new immunopathologic features of vernal keratoconjunctivitis: the involvement of cytokines, growth factors, cells, mediators and neurotransmitters, as well as the mechanism leading to tissue remodelling. RECENT FINDINGS: Vernal keratoconjunctivitis is an allergic eye disease affecting young boys living in a warm climate. It is characterized by conjunctival giant papillae, hyperemia and frequent involvement of the cornea. Approximately 50% of the patients with vernal keratoconjunctivitis do not have a family or medical history of atopic diseases, and do not show IgE sensitization, suggesting that this disease is not solely IgE mediated. Vernal keratoconjunctivitis is a Th2 lymphocyte driven disease with a Th2 cytokine derived pattern, increased levels of mRNA for IL-3, IL-4, IL-5 and IL-13. Th2 lymphocytes induce IgE hyperproduction, activation of mast cells, eosinophils, neutrophils and their toxic products. An overexpression of adhesion molecules, RANTES, eotaxin and metalloproteinases contribute to chronic inflammation. A role for substance P and nerve growth factor has been postulated, as well as for other growth factors (epidermal growth factor, fibroblast growth factor and transforming growth factor beta 1) that induce fibroblast growth and new collagen production. Recent studies have also pointed out the role of resident conjunctival cells, such as epithelial cells and fibroblasts, in the inflammatory and remodelling process of vernal keratoconjunctivitis. The pathogenesis of the condition is probably multifactorial, with the interaction of the immune, nervous and endocrine systems. SUMMARY: Vernal keratoconjunctivitis is a chronic inflammatory and potentially blinding disease. Understanding of the complex interactions and cross talk between cells, cytokines and other mediators is relevant for new therapeutic approaches.

Adolescent↗
PubMed2001

Resolution of microsporidial keratoconjunctivitis in an AIDS patient treated with highly active antiretroviral therapy.

PURPOSE: To report the outcome of microsporidial keratoconjunctivitis in a patient with acquired immunodeficiency syndrome (AIDS) after highly active antiretroviral therapy without any specific treatment for microsporidiosis. METHODS: Case report. A 42-year-old woman diagnosed with AIDS and severe immunodepression (CD4+ of 9 cells/mm(3) and viral load of 460,000/mm(3)), antiretroviral naive, presented with cerebral toxoplasmosis and microsporidial keratoconjunctivitis in the right eye documented by conjunctival scraping and electron microscopy. RESULTS: The patient was treated with a combination of indinavir, stavudine, and lamivudine, besides sulfadiazine and pyrimethamine. No specific treatment for the microsporidial keratoconjunctivitis was attempted. One month later, the keratoconjunctivitis had disappeared. CONCLUSION: This case suggests that microsporidial keratoconjunctivitis in the setting of AIDS and severe immunodepression can be effectively managed with highly active antiretroviral therapy alone.

AIDS-Related Opportunistic Infections↗
PubMed2004

Bilateral keratoconjunctivitis associated with lichen planus.

PURPOSE: To describe a case of bilateral keratoconjunctivitis in a patient with lichen planus. METHODS: Case report and review of the English literature. RESULTS: To our knowledge, this is the fourth reported case of keratoconjunctivitis associated with lichen planus. A 33-year-old Navajo man with lichen planus had recurrent and progressive keratoconjunctivitis that failed to improve on multiple topical medications. Tapered oral prednisone, 2% topical cyclosporin, and amniotic membrane transplantation pacified the acute exacerbation. CONCLUSIONS: Our patient with lichen planus developed an ocular surface disease with cicatricial conjunctivitis, keratouveitis, keratoconjunctivitis sicca, punctate epithelial erosions, and persistent epithelial defects leading to noninfectious or infectious corneal ulceration. Amniotic membrane transplantation may play an adjunctive role in refractory cases of lichen planus-related keratoconjunctivitis. Topical cyclosporin may stabilize the ocular surface when combined with systemic immunosuppression in severe cases.

Administration, Oral↗
PubMed1992

Keratoconjunctivitis sicca and diabetes mellitus in a dog.

Diabetes mellitus and keratoconjunctivitis sicca were diagnosed in a female Poodle. The dog was treated for diabetes and keratoconjunctivitis sicca until blood glucose concentrations were within normal limits. Treatment for keratoconjunctivitis sicca was suspended then, and signs of this disorder did not appear again. Most of the factors known to predispose to keratoconjunctivitis sicca were not applicable to this dog. On the basis of observations made in this dog, we suggest that diabetes mellitus and keratoconjunctivitis sicca may be linked. Clinical signs of the disorders developed simultaneously and resolved when diabetes mellitus was controlled with insulin.

Animals↗
PubMed1989

Conjunctival deposition of eosinophil granule major basic protein in vernal keratoconjunctivitis and contact lens-associated giant papillary conjunctivitis.

To investigate the role of the eosinophil in vernal keratoconjunctivitis and contact lens-associated giant papillary conjunctivitis, we assessed the presence of eosinophil granule major basic protein in conjunctival tissues by immunofluorescence. Biopsy specimens of conjunctiva were taken from nine patients with vernal keratoconjunctivitis, seven patients with giant papillary conjunctivitis, and five control subjects. We performed a masked semiquantitative assessment of immunofluorescence on sections from each specimen. The vernal keratoconjunctivitis and giant papillary conjunctivitis groups had significantly (P less than .05) more major basic protein deposition than controls. No significant correlation between severity of disease and degree of major basic protein deposition was found. We found extracellular eosinophil granules in one of three vernal keratoconjunctivitis specimens examined by transmission electron microscopy. Thus, eosinophil degranulation commonly occurs in vernal keratoconjunctivitis and giant papillary conjunctivitis with release of eosinophil granule major basic protein and presumably other toxic granule proteins onto affected tissues. These cationic proteins are potent cytotoxins and are able to stimulate mast cell degranulation.

Blood Proteins↗
PubMed1984

An in vivo study of corneal surface morphologic features in patients with keratoconjunctivitis sicca.

We used wide-field color specular microscopy to study the corneal epithelium of 13 normal subjects and 13 patients with keratoconjunctivitis sicca. The frequencies of small, medium, and large cells were different in the two groups, with a shift to small cells in patients with keratoconjunctivitis sicca. Increased uptake of rose bengal dye, filaments, coarse mucus plaques, and pre-exfoliative sheets were also found in the patients with keratoconjunctivitis sicca. These findings suggest accelerated epithelial cell loss from the surface of the eye in keratoconjunctivitis sicca.

Cornea↗
PubMed1997

Microsporidial keratoconjunctivitis in a patient without human immunodeficiency virus infection.

PURPOSE: To describe a case of microsporidial keratoconjunctivitis in a patient without human immunodeficiency virus (HIV) infection. METHODS: Case report. An epithelial corneal scraping from a woman with chronic bilateral keratoconjunctivitis was evaluated by Giemsa stain. RESULTS: Giemsa stain of an epithelial corneal scraping disclosed intracellular and extracellular spores characteristic of microsporidia. An HIV enzyme-linked immunosorbent assay (ELISA) test was negative. The signs and symptoms of the bilateral keratoconjunctivitis resolved after treatment with albendazole. CONCLUSION: Microsporidia may cause a chronic epithelial keratoconjunctivitis in the absence of HIV infection.

Adult↗
PubMed1998

Echovirus keratoconjunctivitis.

PURPOSE: To investigate an outbreak of echovirus-related keratoconjunctivitis. METHODS: We undertook a retrospective study of recent cases of echovirus infection with recall and further evaluation of conjunctivitis patients. All patients from whom an echovirus was isolated in Liverpool during 1995 were included. The natural course of ocular echovirus disease was studied, including the likelihood of echovirus keratoconjunctivitis being linked with meningitis and the risk of long-term carriage of the virus in the conjunctiva. RESULTS: Of 10 unrelated patients with echovirus conjunctivitis, six also had a mild keratitis. None of these patients developed meningitis, and no cases of long-term carriage in the conjunctiva were encountered. There was no link between cases of echovirus meningitis and conjunctivitis. There was no corresponding increase in other ocular viral isolates. CONCLUSIONS: Echovirus is a relatively unrecognized cause of keratoconjunctivitis. Echoviral keratoconjunctivitis appears to be an independent ocular event unassociated with systemic sequelae. Long-term carriage in the conjunctiva does not appear to occur.

Adolescent↗
PubMed2001

Microsporidial keratoconjunctivitis in a healthy contact lens wearer without human immunodeficiency virus infection.

PURPOSE: To present a rare case of microsporidial keratoconjunctivitis in an otherwise healthy contact lens wearer without human immunodeficiency virus infection who responded to treatment with systemic albendazole and topical fumagillin. DESIGN: Interventional case report. METHOD: A cornea epithelial scraping from a man with unilateral keratoconjunctivitis previously treated with topical steroids was evaluated by modified trichome staining. MAIN OUTCOME MEASURES: The patient was evaluated for his symptoms, visual acuity, clinical observations, and pathologic examination of corneal scrapes. RESULTS: Modified trichome staining of an epithelial corneal scraping revealed pinkish to red organisms characteristic of microsporidia. Results of a human immunodeficiency virus (HIV) enzyme-linked immunosorbent assay test were negative. The symptoms of ocular discomfort and clinical signs of keratoconjunctivitis resolved after 2 months of treatment with albendazole and topical fumagillin. CONCLUSIONS: Ocular infection with microsporidia, although classically occurring in patients with HIV infection, may occur rarely in healthy individuals, especially if previously treated with systemic immune suppression or topical steroids. Microsporidial keratoconjunctivitis should be considered in the differential diagnosis of a contact lens wearer with atypical multifocal diffuse epithelial keratitis.

Adult↗
PubMed1984

Contact lens induced keratopathy: a severe complication extending the spectrum of keratoconjunctivitis in contact lens wearers.

A 21-year-old woman developed bilateral keratoconjunctivitis from contact lens wear, which progressed to diffuse corneal scarring and vascularization after the patient refused to discontinue wearing contact lenses. The visual disturbance became so severe that a penetrating keratoplasty had to be performed in one eye for visual rehabilitation. Examination of the penetrating keratoplasty specimen disclosed destruction of Bowman's membrane throughout the superior half of the cornea, which was replaced by a fibrous scar that was only midly chronically inflamed. Deep vascularization occurred within the stroma. This case represents an extreme expression of a recently characterized syndrome consisting of conjunctival and corneal changes in patients who may be allergic to contact lenses or the solutions used in conjunction with their care. In the milder end of the spectrum, there is superior epibulbar conjunctival injection with associated tarsal injection, and a mild superficial punctate keratopathy without filaments. Some earlier workers have termed this syndrome a variant of superior limbic keratoconjunctivitis in association with contact lens wear, but this leads to confusion with Theodore's classical superior limbic keratoconjunctivitis, to which the present entity bears no etiologic relationship; it also fails to show many of the findings of Theodore's disease. In mild cases, we would recommend the term contact lens-induced keratoconjunctivitis, and in the more severe cases, such as demonstrated by our patient, we would suggest the term contact lens-induced keratopathy.

Adult↗
PubMed1995

Superior limbic keratoconjunctivitis. A prognostic sign for severe Graves ophthalmopathy.

PURPOSE: To study superior limbic keratoconjunctivitis in a relatively large group of patients and to determine whether a relation exists with thyroid dysfunction. METHODS: The medical records of 57 patients with superior limbic keratoconjunctivitis who were examined between 1980 and 1993 were reviewed. RESULTS: Thirty-seven patients (64.9%; 95% confidence interval, 51.1-77.1) had objective evidence of thyroid dysfunction. Of patients with superior limbic keratoconjunctivitis and thyroid disease, 33 (89.2%) had ophthalmopathy, which in 16 patients (48.5%) was sufficiently severe to require orbital decompression. CONCLUSION: Superior limbic keratoconjunctivitis is associated with thyroid dysfunction and appears to be a prognostic marker for severe Graves ophthalmopathy.

Adult↗
PubMed1999

Topical nonpreserved methylprednisolone therapy for keratoconjunctivitis sicca in Sjögren syndrome.

OBJECTIVE: To review the efficacy and side effects of topical nonpreserved corticosteroid therapy for treatment of severe keratoconjunctivitis associated with Sjögren syndrome. DESIGN: Retrospective, noncomparative case series. PARTICIPANTS: Twenty-one patients with Sjögren syndrome-associated keratoconjunctivitis sicca and annoying ocular irritation. INTERVENTION: Treatment with topical nonpreserved methylprednisolone sodium succinate. MAIN OUTCOME MEASURES: Symptom severity, frequency of instillation of artificial tears, corneal fluorescein staining scores, resolution of filamentary keratitis, steroid-related side effects. RESULTS: Before starting methylprednisolone therapy, all patients were experiencing moderate-to-severe eye irritation despite prior punctal occlusion in most cases and frequent use of nonpreserved artificial tears by all. After 2 weeks of topical application, three to four times per day, moderate (43%) or complete (57%) relief of irritation symptoms was experienced by all patients and no complications were observed. An average decrease in corneal fluorescein scores of 2.6 +/- 0.5 points (on a 12-point scale) was observed, and filamentary keratitis resolved in all ten eyes with this condition. Therapy was stopped after 2 weeks in eight patients, and six of these patients reported that their symptoms remained at a tolerable level for weeks to months. Lower dose steroid therapy was continued in the remaining patients, whose symptoms worsened after attempted weaning. Complications of corticosteroid therapy in patients receiving prolonged therapy included increased intraocular pressure in one patient at 3 months, worsening of pre-existing posterior subcapsular cataracts in one patient at 6 months, and formation of posterior subcapsular cataracts in another patient at 6 months. CONCLUSIONS: These findings indicate that topical nonpreserved methylprednisolone is an effective treatment option for patients suffering from severe keratoconjunctivitis sicca who continue to experience bothersome eye irritation despite maximum aqueous enhancement therapies. They also suggest that inflammation is a key pathogenic factor in this condition. Careful monitoring is essential in dry eye patients treated with corticosteroids for more than 2 weeks because steroid-related complications (increased intraocular pressure and cataract formation) were observed after several months of therapy in this series. Because of the chronic nature of this disease and the likelihood of patients developing steroid-related complications with their long-term use, topical nonpreserved methylprednisolone therapy appears to be most appropriate for short-term "pulse" treatment of exacerbations of keratoconjunctivitis sicca.

Administration, Topical↗
PubMed1999

Altered cytokine balance in the tear fluid and conjunctiva of patients with Sjögren's syndrome keratoconjunctivitis sicca.

PURPOSE: To compare epidermal growth factor (EGF) concentration in tear fluid and levels of inflammatory cytokines in the conjunctival epithelium of patients with Sjögren's syndrome keratoconjunctivitis sicca with those of normal controls. METHODS: Schirmer 1 tear testing, corneal fluorescein staining and conjunctival impression cytology for quantitation of goblet cell density were performed in ten patients with Sjögren's syndrome-associated keratoconjunctivitis sicca and ten asymptomatic normal controls. ELISA was used to detect the concentration of EGF in tear fluid and interleukin 6 in lysates of conjunctival cytology specimens obtained from all subjects. The levels of RNA transcripts encoding inflammatory cytokines [interleukin 1alpha_(IL-1alpha), interleukin 6 (IL-6), interleukin 8 (IL-8), tumor necrosis factor alpha_(TNF-alpha), and transforming growth factor beta1 (TGF-beta1)] as well as a housekeeping gene (G3PDH) were evaluated in conjunctival cytology specimens taken from all subjects by semiquantitative competitive reverse transcriptase polymerase chain reaction (RT-PCR). RESULTS: Decreased tear fluid EGF concentration was noted in Sjögren's syndrome patients (mean 0.68 +/- 0.59 ng/ml) compared to controls (mean 1.66 +/- 0.45 ng/ml, P = 0.004). Significantly increased levels of IL-1alpha, IL-6, IL-8, TNF-alpha and TGF-beta1 RNA transcripts were found in the conjunctival epithelium of Sjögren's syndrome patients compared to controls (P < 0.05), while the level of G3PDH was similar in both groups. The concentration of IL-6 protein was significantly higher in Sjögren's syndrome conjunctiva samples (P = 0.012). Tear EGF concentration correlated with Schirmer 1 scores (rho 0.767, P < 0.001), corneal fluorescein staining scores (rho -0.562, P = 0.01), conjunctival goblet cell density (rho 0.661, P = 0.001) and the levels of IL-1alpha_and IL-8 RNA in the conjunctival epithelium (rho -0.677 and -0.747, respectively, P = 0.001). Both IL-1alpha_and IL-8 RNA in the conjunctival epithelium increased as Schirmer 1 scores decreased (P </= 0.001). IL-8 RNA level correlated with corneal fluorescein staining (rho 0.690, P = 0.001) and conjunctival goblet cell density (rho -0.767, P < 0.001). A significant decrease in IL-8 RNA level, corresponding to improvement in irritation symptoms and ocular surface disease, was observed in six eyes after two weeks of topical corticosteroid therapy. CONCLUSIONS: The balance of cytokines in the tear fluid and conjunctival epithelium is altered in Sjögren's syndrome. The severity of keratoconjunctivitis sicca in this condition increases as tear fluid EGF concentration decreases and levels of inflammatory cytokines in the conjunctival epithelium increase. These findings provide new insight into the pathogenesis of keratoconjunctivitis and provide potential targets for therapy.

Adult↗
PubMed2003

Bilateral microsporidial keratoconjunctivitis in an immunocompetent non-contact lens wearer.

PURPOSE: To describe an immunocompetent male with bilateral microsporidial keratoconjunctivitis who responded to treatment with albendazole, propamidine, and fumagillin. METHODS: Corneal and conjunctival epithelial scrapings from a man with bilateral keratoconjunctivitis previously treated with topical corticosteroids were evaluated by Gram stain and by fluorescence microscopy. RESULTS: Gram stain and fluorescence microscopy of corneal epithelial scraping revealed organisms characteristic of microsporidia. Results of human immunodeficiency virus antibody testing were reported as nonreactive. Symptoms of ocular discomfort and clinical signs of keratoconjunctivitis resolved after five weeks of treatment that included systemic albendazole and topical propamidine isethionate 0.1% and fumagillin bicyclohexylammonium salt. A follow-up conjunctival scraping failed to detect any residual organisms 2 weeks after cessation of all treatment. CONCLUSION: Microsporidial ocular infection occurred in an immunocompetent non-contact lens wearer. Microsporidial keratoconjunctivitis should be considered in any individual with atypical multifocal diffuse epithelial keratitis, regardless of immune status or recent history of contact lens wear.

Adult↗
PubMed1980

Restriction endonucleases in identification of a genome type of adenovirus 19 associated with keratoconjunctivitis.

Adenovirus type 19 (Ad19) was first associated with disease in 1973 when several outbreaks of keratoconjunctivitis were reported from Europe and North America. We have examined Ad19 isolates by deoxyribonucleic acid restriction with BamHI, BglI, and SmaI restriction endonucleases. All keratoconjunctivitis-associated Ad19 isolates were identical but different from the Ad19 prototype. The total number of resolved restriction fragments of the Ad19 prototype genome was 31, only 17 of which migrated as the restriction fragments of keratoconjunctivitis-associated genomes. We conclude that two different genome types of Ad19 exist, one of which has been responsible for the recent outbreaks of keratoconjunctivitis.

Adenoviruses, Human↗
PubMed2005

Five new genome types of adenovirus type 37 caused epidemic keratoconjunctivitis in Sapporo, Japan, for more than 10 years.

Human adenovirus type 37 (HAdV-37) is a major cause of epidemic keratoconjunctivitis and has recently been the largest causative agent of keratoconjunctivitis in Japan. To investigate the genetic characteristics of HAdV-37 strains isolated in Sapporo, we analyzed the genome types and genetic relationships of 51 strains isolated there from 1990 through 2001. By using DNA restriction analysis, eight genome types (HAdV-37/D1, HAdV-37/D3, and HAdV-37/D6 to HAdV-37/D11) were identified, including five new ones. The restriction fragments of these genome types shared more than 95% identity with those of the prototype strain. By DNA sequence analysis, five and three single nucleotide substitutions, respectively, were found in partial sequences of the hexon and fiber genes. The combinations of mutations resulted in four hexon and fiber types (hx1 to hx4 and f1 to f4) and six hexon/fiber pairs (hx1/f1, hx2/f1, hx1/f2, hx1/f3, hx3/f4, and hx4/f4). The six pairs correlated well with certain genome types. In all three epidemics of keratoconjunctivitis to strike Sapporo in the past 12 years, specific genome types and fiber types were usually isolated: in the first epidemic, HAdV-37/D1 (f1) and HAdV-37/D3 (f1); in the second, HAdV-37/D6 (f2) and HAdV-37/D8 (f3); and in the third, HAdV-37/D10 (f4) and HAdV-37/D11 (f4). We conclude that mutations in the adenovirus genome occurred chronologically and that certain mutations were correlated with the epidemics of adenoviral keratoconjunctivitis.

Adenovirus Infections, Human↗
PubMed1977

Epidemic keratoconjunctivitis and chronic papillary conjunctivitis in London due to adenovirus type 19.

Since July 1973 cases of keratoconjunctivitis resembling epidemic keratoconjunctivitis were observed in the External Eye Disease Clinic at Moorfields Eye Hospital; City Road, London. Adenovirus type 19 was isolated in human embryonic kidney cells from 21 patients. The majority were males between 20 and 40 years old. A small hospital outbreak involving six patients occurred. Clinical features of the disease, consisting of moderate to severe follicular conjunctivitis, major subepithelial punctate keratitis, sometimes with pseudomembrane and scarring, were closely similar to those of epidemic keratoconjunctivitis caused by adenovirus type 8. This similarity, as well as the ability of the agent to cause hospital outbreaks, indicates that adenovirus type 19 is a cause of epidemic keratoconjunctivitis. A case of bilateral chronic papillary conjunctivitis that persisted for 16 months following an acute onset was described. Adeno 19 was isolated from the eye of the patient after 12 months of recrudescent or recurrent illness. Chronic adenovirus infection lacking the usual clinical picture of an acute follicular reaction has not hitherto been described. Such cases are probably important because of the obvious danger of continuing the carriage and shedding of infective adeno 19 from one outbreak to another, by presenting subsequently in eye clinics, and providing an unrecognised source of infection to initiate further outbreaks of hospital transmission.

Adenoviridae↗
PubMed1995

Topical fumagillin in the treatment of microsporidial keratoconjunctivitis in AIDS.

OBJECTIVE: To report microsporidial keratoconjunctivitis in a patient infected with HIV who was treated with topical fumagillin. CASE SUMMARY: A 37-year-old white man who was experiencing redness, pain, irritation, decreased vision, and a foreign body sensation occurring in both eyes was referred to the ophthalmology clinic. The patient had a medical history significant for AIDS, Pneumocystis carinii pneumonia, and Cytomegalovirus retinitis. Conjunctival smears were taken and stained positive for the presence of Microsporidia. The patient was diagnosed with bilateral microsporidial keratoconjunctivitis and fumagillin therapy was initiated. After 5 days of therapy, the patient reported significant improvements characterized by a decrease in blurred vision with only slight blurring in the left eye, decrease in headache, and decreased foreign body sensation. The patient continued topical fumagillin therapy for more than 14 months, with only slight blurring in the left eye and no apparent ocular toxicity as a result of fumagillin therapy. DISCUSSION: Although rare in occurrence, increasing numbers of documented microsporidial infections are being reported in the medical literature, particularly in individuals who are seropositive for HIV. Clinicians need to be cognizant of microsporidial keratoconjunctivitis as another opportunistic infection in this patient population. CONCLUSIONS: Although a curative agent has yet to be discovered, fumagillin represents a safe, effective, low-cost, topical agent for the treatment of microsporidial keratoconjunctivitis.

AIDS-Related Opportunistic Infections↗