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Tear and mucus eotaxin-1 and eotaxin-2 in allergic keratoconjunctivitis.

OBJECTIVE: Eotaxin-1 and eotaxin-2 are potent eosinophil chemotactic and activating peptides that may be implicated in the pathogenesis of the chronic allergic eye diseases vernal keratoconjunctivitis (VKC) and atopic keratoconjunctivitis (AKC). The purpose of this study was to measure these chemokines in tear and mucus samples of active-disease patients and in vitro cultured conjunctival epithelial cells and fibroblasts. DESIGN: Comparative, observational case series and in vitro study. PARTICIPANTS: Sixteen patients with clinically active and untreated VKC or AKC, six age-matched control patients, and five nonactive seasonal allergic conjunctivitis patients. METHODS: Tears were collected from the active VKC and AKC patients, and from the normal patients. Mucus was collected from six of these VKC patients. Tears were also collected from an additional five allergic patients after obtaining a positive reaction to conjunctival allergen challenge. Conjunctival epithelial cell and conjunctival fibroblast cultures were exposed to interleukin (IL)-4, IL-13, and tumor necrosis factor-alpha (TNF-alpha), or to combinations of these cytokines. MAIN OUTCOME MEASURES: Levels of eotaxin-1 and eotaxin-2 in tears, mucus, and culture medium. RESULTS: High levels of eotaxin-1 and eotaxin-2 were found in mucus of VKC patients, whereas only eotaxin-2 was found to have increased significantly in tears of VKC and AKC patients compared with those of normal patients. Mucus contained higher levels of chemokines than did tears. Both tear eotaxin-1 and eotaxin-2 were correlated significantly with the percent of eosinophils in tear fluid. Eotaxin-1 also was correlated significantly with the sum clinical score and corneal involvement in VKC patients. Conjunctival epithelial cells in culture did not produce eotaxin-1 or eotaxin-2, either at baseline or after cytokine exposure. Conjunctival fibroblasts produced eotaxin-1 only after exposure to IL-4, TNF-alpha, and the combination of IL-4 plus TNF-alpha or IL-13 plus TNF-alpha. CONCLUSIONS: Eotaxin-1 and eotaxin-2 are implicated in eosinophil recruitment and in the pathogenesis of VKC and AKC. Cytokine-stimulated conjunctival fibroblasts may be one source of eotaxin-1 in severely allergic tissues.

Adolescent↗

Corneal ectasia in vernal keratoconjunctivitis.

The type of corneal ectasia, the presence of breaks in Descemet's membrane, and the success with contact lens wear or penetrating keratoplasty were studied in 61 patients with corneal ectasia and vernal keratoconjunctivitis. There were 53 patients with keratoconus, 5 with pellucid marginal corneal degeneration, 2 with keratoglobus, and 1 with superior corneal thinning. The high rate of hydrops and the corneal ectasia itself may be related to excessive eye rubbing. Success with contact lens wear or penetrating keratoplasty in vernal keratoconjunctivitis patients with keratoconus is less than in patients with keratoconus alone.

Adolescent↗

IgE, IgE receptors, and other immunocytochemical markers in atopic and nonatopic patients with vernal keratoconjunctivitis.

BACKGROUND: Vernal keratoconjunctivitis (VKC) often is associated with atopy but a considerable part of the patients lack evidence of specific hypersensitivity. An immunocytochemical study was undertaken with the aim of detecting possible differences in the tissue inflammatory response between atopic and nonatopic subjects with VKC. METHODS: Conjunctival biopsy specimens from six atopic and three nonatopic subjects with VKC (age range, 7-17 years) and eight healthy control subjects (age range, 3-15 years) were analyzed with a panel of monoclonal and polyclonal antibodies. RESULTS: No distinct differences in cell counts between atopic and nonatopic subjects with VKC were observed. Vernal keratoconjunctivitis specimens as a whole showed higher counts than control specimens for CD3+, CD4+, HLA-DR+, CD38+, EG2+, CD68+, IgE+, FC epsilon RI+, IgA+, IgG+, and IgM+ cells in the substantia propria; and for CD1a+, IgE+, and EG2+ cells in the epithelium. CONCLUSIONS: Because the number of cells expressing CD4, EG2, IgE, and the high-affinity receptor for IgE, all of which are considered relevant in infiltrates of allergic conditions, were similar in atopic and nonatopic subjects, the authors conclude that the role of allergen-specific IgE sensitization in the pathogenesis of VKC remains unclear.

Adolescent↗

Efficacy of mipragoside ophthalmic gel in vernal keratoconjunctivitis.

To evaluate the efficacy of Mipragoside, a ganglioside derivative, in vernal keratoconjunctivitis we performed a controlled randomised clinical trial involving 24 patients (mean age 10 +/- 3.4 years, range 5-20 years). Patients received either Mipragoside 0.5% aqueous ophthalmic gel or placebo four times a day for 2 weeks after a week of treatment with placebo. Ocular signs and symptoms were evaluated and considered for statistical analysis. Results show that Mipragoside significantly reduces all symptoms, being most effective on itching (p = 0.01; p = 0.0001) and hyperaemia (p = 0.01; p = 0.0006) after 1 and 2 weeks respectively when compared with placebo. Physician judgement of drug efficacy at the end of treatment was significantly in favour of Mipragoside (p = 0.0001) compared with placebo. We conclude that Mipragoside topical treatment improves symptoms of patients with vernal keratoconjunctivitis and we postulate a possible anti-inflammatory activity of this compound.

Administration, Topical↗

Topical cyclosporin A in the management of vernal keratoconjunctivitis.

PURPOSE: To study the efficacy of topical cyclosporin A in children with vernal keratoconjunctivitis in a prospective randomised double-masked trial. METHODS: Twenty-four children between 5 and 16 years of age were randomly treated with cyclosporin A (CsA) and placebo (vehicle) and followed up for 4 months. RESULTS: Of the 12 patients given CsA, 11 showed symptomatic improvement by 7 days of starting treatment whereas only 3 patients in the placebo group showed mild symptomatic improvement. CONCLUSIONS: Topical cyclosporin is a safe and effective treatment in vernal keratoconjunctivitis.

Adolescent↗

Corneal stromal sequestration and keratoconjunctivitis sicca in a horse.

A 19-year-old Shetland pony presented with unilateral ocular discomfort and abnormal ocular appearance. Keratoconjunctivitis sicca, ulcerative keratitis and brown discoloration of the corneal stroma were identified on ophthalmic examination. The etiology of keratoconjunctivitis sicca was not determined in this case. For practical and financial reasons, the owners requested enucleation of the affected eye. Histopathologic examination revealed extensive loss of corneal epithelium overlying a zone of hypereosinophilic, degenerate, and necrotic corneal stroma. This well-circumscribed region of corneal stromal sequestration was surrounded by stromal vascularization, and an intense inflammatory, predominantly polymorphonuclear, cellular infiltrate. The clinical and histopathologic features of this case were considered remarkably similar to those observed in feline corneal stromal sequestration.

Journal Article↗

Neutrophil and eosinophil participation in atopic and vernal keratoconjunctivitis.

PURPOSE: A retrospective study was conducted at three centers to examine the participation of neutrophils and eosinophils in the inflammatory processes associated with atopic keratoconjunctivitis (AKC) and vernal keratoconjunctivitis (VKC). METHODS: Conjunctival specimens were obtained from four patients with AKC, six with VKC, and five normal subjects. Indirect immunofluorescent staining was used to localize neutrophil elastase (NE) and eosinophil granule major basic protein (MBP) in serial sections of all specimens. RESULTS: Specimens from both AKC and VKC patients revealed extracellular deposition of NE and MBP. Control specimens showed no or minimal extracellular NE, and no MBP. Statistical analysis demonstrated significantly greater extracellular MBP deposition in AKC specimens compared to controls (p = 0.009), and VKC specimens showed significantly greater staining for both extracellular MBP (p = 0.005) and NE (p = 0.006). CONCLUSIONS: These results suggest that neutrophils, in addition to eosinophils, play an active role in the pathogenesis of AKC and VKC as evidenced by the extracellular deposition of their specific granule proteins.

Adult↗

Observations on the efficacy of mass treatment by subconjunctival penicillin injection for the control of an outbreak of infectious bovine keratoconjunctivitis.

Infectious bovine keratoconjunctivitis was diagnosed on a Manawatu beef cattle farm, with inflammation of 85% of eyes in a group of 150 6-month-old-calves. Comeal inflammation was recorded in 23% of eyes. All active lesions healed over a 3-week period following whole group subconjunctival penicillin injection. Morarellu bovis was cultured from two of seven conjunctival swabs at the time oftreatment and from four of six conjunctival swabs 9 days after treatment. Concurrently, pink-eye was noted in older cattle, with inflammation in 50% of eyes. For practical handling reasons, these older cattle were not treated. Despite nontreatment, their clinical signs regressed over a 3-week period. The rationale of whole group treatment for the control of infectious bovine keratoconjunctivitis is discussed.

Journal Article↗

Detection of Mycoplasma conjunctivae in sheep affected with conjunctivitis and infectious keratoconjunctivitis.

AIM: To determine the aetiology of a recurring and severe form of infectious keratoconjunctivitis (IKC) in sheep. METHODS: Five sheep flocks that had experienced a severe form of IKC were examined. Clinical history, conjunctival swabs and blood samples were collected from affected animals. Culture for bacteria, and also specifically for Mycoplasma and Chlamydophila spp, and detection of Mycoplasma conjunctivae DNA by polymerase chain reaction (PCR) were attempted. Serum samples were tested for antibodies to M. agalactiae, M. capricolum, M. conjunctivae and Chlamydophila spp. RESULTS: Mycoplasma conjunctivae DNA was detected using PCR in 3/5 flocks, and in all flocks antibodies to M. conjunctivae were detected in sera. A pure growth of Branhamella ovis was cultured from conjunctival swabs from a small proportion of sheep in two flocks. No other pathogens were detected. CONCLUSIONS: This investigation demonstrated that M. conjunctivae was a primary pathogen causing severe IKC in sheep, and is the first report of detection of this organism in sheep in New Zealand. Introduction of clinically normal carrier sheep appeared to have caused the outbreaks. KEYWORDS: Infectious keratoconjunctivitis, Mycoplasma conjunctivae, Chlamydophila pecorum, Branhamella ovis, polymerase chain reaction, ELISA, complement fixation test.

Journal Article↗

A comparative evaluation of the efficacy of intraoperative mitomycin C use after the excision of cobblestone-like papillae in severe atopic and vernal keratoconjunctivitis.

OBJECTIVE: To evaluate the effect of intraoperative 0.02% mitomycin-C (MMC) use after excision of cobblestone-like papillae on preventing corneal recurrences compared with simple papillary resection. METHODS: Thirteen cases of atopic keratoconjunctivitis (AKC) and 6 cases of vernal keratoconjunctivitis (VKC) with a mean age of 12.0 +/- 3.4 years participated in this study. All patients had cobblestone-like papillae on the upper tarsal conjunctiva and corneal ulcers or erosions that were refractory to conventional treatment. Seventeen eyes received simple papillary excision. Papillary excision with intraoperative application of MMC was performed in 7 eyes: 0.02% MMC was applied for 2 minutes to the upper palpebral conjunctiva immediately after papillary excision. Recurrence of corneal lesions and regrowth of papillae were evaluated and compared retrospectively between the 2 groups. Postoperative follow-up ranged from 12 to 18 months. RESULTS: Papillary regrowth was observed in 14 out of 17 eyes (82.4%) in the simple resection group, whereas regrowth was noted in 4 out of 7 eyes (57.1%) in the MMC group (P > 0.05). The recurrence of corneal lesions was observed in 8 out of 17 eyes (47.1%) in the simple resection group (mean onset 1.5 +/- 1.7 months) compared with 1 eye with corneal recurrence 6 months after surgery in the MMC group (14.3%). The difference was statistically significant (P < 0.05). No complications related to MMC use were observed during the follow-up period. CONCLUSION: MMC-aided papillary resection may be rewarding in well-selected severe AKC and VKC cases in preventing recurrence of corneal complications, but the potential complications of MMC use would suggest caution in its consideration.

Adolescent↗

Surgical management of corneal plaques in vernal keratoconjunctivitis: a clinicopathologic study.

PURPOSE: To describe the surgical management and histopathologic and immunohistochemical findings in corneal plaques of shield ulcers in vernal keratoconjunctivitis. PATIENTS AND METHODS: Three children (ages 4, 7.5, and 9) presented with corneal plaques unresponsive to conservative systemic and topical medical treatment. Plaques were scraped under general anesthesia, and soft bandage contact lenses were placed. The excised tissue was evaluated by histopathology and immunohistochemistry. RESULTS: During surgery, plaques were found to extend beyond the ulcer margins. Histopathology revealed granular, deeply-eosinophilic, laminar material, firmly attached to the Bowman layer in all cases. Immunohistochemistry confirmed this to be eosinophil-derived major basic protein (MBP). After surgical removal, complete epithelization was evident within 1-4 weeks in all cases. CONCLUSIONS: Corneal plaque is a rare complication of vernal keratoconjunctivitis. These plaques usually do not resolve with standard conservative measures. Failure to epithelialize may be a result of the plaque material extending below the edges of adjacent epithelium. We suggest that MBP plaques precipitate on the denuded stromal bed, thereby playing a pathogenic role in nonhealing shield ulcers.

Blood Proteins↗

Bilateral infectious ulcers associated with atopic keratoconjunctivitis.

PURPOSE: A case of atopic keratoconjunctivitis complicated by bilateral infectious ulcers is described. METHODS: Both eyes underwent complete ophthalmologic examination and in vivo confocal microscopy imaging by using the Heidelberg Retina Tomograph II Rostock-cornea-module (HRT II-RCM) and were photographed. RESULTS: Topical antibiotics and corticosteroids associated with oral antibiotics and corticosteroids were given. After 4 weeks of treatment, the corneal lesions healed completely. CONCLUSION: Bilateral infectious ulcers with perforation are a rare and severe complication of atopic keratoconjunctivitis. HRT II-RCM in vivo confocal microscopy imaging is useful in monitoring the progression of ocular surface diseases.

Anti-Bacterial Agents↗

Atopic keratoconjunctivitis.

Atopic keratoconjunctivitis (AKC) represents a disease usually classified under the term of allergic conjunctivitis together with seasonal allergic conjunctivitis (SAC), perennial allergic conjunctivitis (PAC) and vernal keratoconjunctivitis (VKC). However, AKC and VKC have clinical and pathophysiological features quite different from SAC and PAC, in spite of some common markers of allergy. This article aims to review personal studies suggesting that allergic conjunctivitis (similarly to asthma, rhinitis and atopic dermatitis) is a heterogeneous disease entity with different preferential pathogenetic mechanisms and a spectrum of clinical expression which varies according to individual cases. AKC and VKC may thus represent a model of atopy quite distinct from the classical type-1 hypersensitivity mechanism.

Conjunctivitis, Allergic↗

Case series of 406 vernal keratoconjunctivitis patients: a demographic and epidemiological study.

PURPOSE: To evaluate the specific allergic sensitization and epidemiological characteristics of vernal keratoconjunctivitis (VKC). METHODS: This retrospective non-comparative case series included 406 VKC patients. Data included patient and family histories, and results of allergic tests. Annual incidence and prevalence rates were calculated for a cohort of 128 VKC patients from the greater Padua area. RESULTS: The great majority of VKC patients were male (76%), with a male : female ratio of 3.3 : 1. A skin prick test, specific serum IgE or conjunctival challenge was positive in 43%, 56% and 58% of patients, respectively. In the cohort of patients from the Padua area, the prevalence of the disease was 7.8/100,000, with a higher rate in young males (57/100,000) compared with young females (22/100,000), and lower rates in people over 16 years of age (3.8/100,000 in males, 1/100,000 in females). The incidence of VKC was 1/100,000, with a higher rate in males under 16 years of age (10/100,000) compared with females (4.2/100,000). In people over 16 years of age, the incidence of the disease was 0.06/100,000, with no difference between males and females. CONCLUSION: An IgE-mediated sensitization was found in only half of the VKC patients. Vernal keratoconjunctivitis is not a rare event in the paediatric population but is an extremely rare new disease in adults.

Adolescent↗

A Chromosomal Locus Which Controls the Ability of Shigella flexneri to Evoke Keratoconjunctivitis.

The primary step in the pathogenesis of bacillary dysentery is the penetration of intestinal epithelial cells by shigellae. Lacking this capacity, Shigella flexneri becomes avirulent. By means of intergeneric conjugation between various Escherichia coli K-12 Hfr strains and S. flexneri 2a virulent recipients and by reciprocal transduction analysis with phage P1 vir, we established a locus on the genome of S. flexneri 2a which is necessary for the ability of this strain to penetrate epithelial cells as measured by the Sereney test for keratoconjunctivitis. This locus, termed kcpA (in reference to its involvement in provoking keratoconjunctivitis), has been positioned between the lac and gal chromosomal markers and is contransducible with the purE allele.

Journal Article↗

Vernal keratoconjunctivitis in Nigerians: 109 consecutive cases.

Vernal keratoconjunctivitis was the most common conjunctival disease seen over a 2 year period (January 1997-December 1998) at the University of Benin Teaching Hospital, Benin City, Nigeria. One hundred and nine consecutive patients were seen with vernal keratoconjunctivitis. There was a male to female ratio of 1:1.3. The age range of the patients was 5 months to 38 years with a mean age of 15.5 +/- 8.3 years (SD). Of the patients 54.1% were children. Itching was the most common symptom, followed by redness, tearing, aching eye and photophobia. Ninety patients (82.6%) had predominantly tarsal papillae, while the others had mixed and limbal papillae. A history of atopic diseases such as asthma and rhinitis was present in only five patients (4.5%). There was no patient with corneal ulcer or scarring. Although the complications were few, health education of the patients about the dangers of self medication with steroids should be emphasized.

Adolescent↗

Supra-tarsal injection of dexamethasone in the treatment of patients with refractory vernal keratoconjunctivitis.

The response to supratarsal injection of dexamethasone in severe refractory vernal keratoconjunctivitis was studied in 20 patients (14 males and 6 females) at the ophthalmology department of Menelik II Hospital, Addis Ababa in 1997. Majority of the patients were in the age range of 11-20 years with mean age of 14.6 years. Although all patients experienced relief of symptoms in the first 2 days of dexamethasone injection, symptoms recurred in the majority 16 (80%) of the patients. Cobble stone papillae and limbal signs disappeared in 2 (11%) and 5 (38%) of the patients respectively. Resolution of limbal form of the disease is more dramatic when compared to the palpebral form. This study showed that supratarsal injection of dexamethasone in severe vernal keratoconjunctivitis is effective in few, partially effective in some and ineffective in many of our patients. Further studies, particularly a randomized controlled trial is recommended prior to utilization of this new therapeutic modality as a standard form of treatment in Ethiopian patients.

Adolescent↗

[The relationship between Staphylococcus aureus and atopic keratoconjunctivitis].

PURPOSE: To investigate the role of Staphylococcus aureus in patients with vernal keratoconjunctivitis (VKC) and atopic keratoconjunctivitis (AKC) complicated by atopic dermatitis (AD). SUBJECTS AND METHODS: Microbiological culture from the conjunctival sac of acute exacerbated patients with VKC and AKC complicated by AD was performed. The subjects were 29 patients (31 eyes) with VKC and AKC who showed acute exacerbated clinical symptoms of conjunctivitis. Antigen specific IgE antibodies to staphylococcal enterotoxin A (SEA) and staphylococcal enterotoxin B (SEB) in serum were also examined. In this study, the patients were divided into two groups: An AD group consisting of 22 patients with VKC and AKC complicated by AD, and a control group consisting of 8 patients with allergic conjunctivitis without AD. We also examined SEA/SEB specific IgE antibody in tears from the 5 patients who underwent bacteriological examinations of the conjunctival sac at the same time. RESULTS: Twenty-seven out of 31 eyes were gram-positive in the bacteriological culture from the conjunctival sac (87.1%). Staphylococcus aureus was detected in 21 out of the 27 eyes (77.8%). In the AD group, 2 of the 22 cases were gram-positive for serum SEA specific IgE antibodies, 2 cases of the 22 cases were gram-positive for SEB specific IgE antibodies, and 9 cases were gram-positive for both SEA and SEB specific IgE antibodies. Serum SEA and SEB specific IgE antibodies were all gram-negative in the control group. Either SEA or SEB specific IgE antibody in tears was detected in all of the above 5 patients who underwent bacteriological examinations of the conjunctival sac, and 4 of the 5 were gram-positive. Staphylococcus aureus was isolated in 3 out of the 5 patients, and 1 case was gram-negative. CONCLUSION: Staphylococcus is one of the exacerbating factors in VKC and AKC. It is important to evaluate both bacteriological examinations of the conjunctival sac and SEA/SEB specific IgE in tears.

Conjunctiva↗