Salim I. Butrus

Human conjunctival mast cells: Distribution of MCT and MCTC in vernal conjunctivitis and giant papillary conjunctivitis

The distribution and concentration of human tryptase-positive, chymase-negative mast cells (MCTS) and tryptase-positive, chymase-positive mast cells (MCTCS) were examined in conjunctival biopsy specimens from subjects with active vernal conjunctivitis (VC; n = 7), giant papillary conjunctivitis (GPC; n = 6), and allergic conjunctivitis (AC; n = 5), and from asymptomatic soft-contact lens wearers (SCL; n = 6) and normal control individuals (n = 19). Carnoys fixed tissue sections were stained by a double immunohistochemical method using a biotinylated mouse monoclonal antichymase antibody with immunoperoxidase, followed by an alkaline phosphatase-conjugated mouse monoclonal antitryptase antibody. Epithelial mast cells (MCs) were found in all VC specimens (96% MCTCs) and in three GPC specimens (100% MCTCS) but in none of the other groups. In the substantia propria, MCTCS were the predominant type of MC observed in all specimens, accounting for 95% of the total MCs in the normal control group and 100% of the total MCs in the subjects with GPC, AC, and SCL. No significant differences were found in the total MC concentration of the substantia propria among the normal control subjects (11,054 +/- 6327 MCs per cubic millimeter), subjects in the SCL group (13,168 +/- 4685 MCs per cubic millimeter), subjects with GPC (17,313 +/- 8500 MCs per cubic millimeter), and subjects with AC (15,380 +/- 5660 MCs per cubic millimeter). In subjects with VC, the percentage of MCTs (18% +/- 13%) and the total MC concentration (24,689 +/- 18,978 MCs per cubic millimeter) in the substantia propria were significantly increased as compared to the normal control group.(ABSTRACT TRUNCATED AT 250 WORDS)

The Level of Tryptase in Human Tears: An Indicator of Activation of Conjunctival Mast Cells

Tryptase, a neutral endoprotease, is secreted by activated mast cells in human tissues. Tryptase levels in various body fluids have been used as an indicator of mast cell activation. The authors determined tryptase levels in unstimulated tears collected from the following groups of patients: (1) normal control, (2) nonallergic ocular inflammation, (3) asymptomatic seasonal allergic conjunctivitis, (4) symptomatic seasonal allergic conjunctivitis, (5) vernal conjunctivitis, and (6) contact lens-associated giant papillary conjunctivitis. They also assessed the release of tryptase into the tear fluid after provoking the conjunctiva with (7) allergens, (8) compound 48/80, and (9) rubbing. Tryptase levels were elevated in tears of patients with active ocular allergy and also increased after provoking the conjunctiva with allergens in atopic subjects and with compound 48/80 and rubbing in nonatopic subjects. Tryptase levels in tear fluid may prove useful as a clinical indicator of mast cell involvement in ocular allergic disorders. In provocation experiments, tryptase levels may be used to evaluate and compare different mast cell stabilizing agents.

Aspirin Therapy in Vernal Conjunctivitis

Prostaglandin D2 is a secondary mast cell mediator that causes redness, chemosis, mucous discharge, and eosinophil chemotaxis in the eye. It may play an important role in allergic ocular disease. Although histamine is a key mediator of allergic inflammation, antihistamine therapy provides only symptomatic relief. We added aspirin therapy to the treatment regimen of three patients with vernal conjunctivitis. Aspirin acetylates the enzyme cyclooxygenase, thereby preventing the formation of prostaglandin D2. Within two weeks after initiation of aspirin therapy, we noted dramatic improvement in conjunctival and episcleral redness and resolution of keratitis and limbal infiltration. We recommend a trial of oral aspirin as adjunctive therapy for intractable cases of vernal conjunctivitis.

Contact Lens surface deposits increase the adhesion of pseudomonas aeruginosa

Soft contact lenses are bathed with tear components during wear and surface deposits accumulate. This report shows that Pseudomonas aeruginosa adheres to the surface of worn extended wear contact lenses in direct proportion to the amount of lens surface deposits as determined by the Rudko method (P less than .05). More hydrophobic bacteria adhered 10 times greater than bacteria which were relatively hydrophilic (P less than .005). The effect upon bacterial adhesion of enzyme and surfactant cleaning of worn extended wear contact lenses was investigated by two independent methods: one involving a high inoculum and the other a low inoculum of Pseudomonas. Treatment of worn lenses with commercially available enzymes such as papain and pork pancreatin as well as treatment with neuraminidase, mannosidase, glucosidase and alkylcarboxylic acid for as long as 48 hours failed to reduce subsequent bacterial adhesion in both the high and low inoculum experiments. We conclude that soft contact lens surface deposits are a major determinant in the adhesion of Pseudomonas aeruginosa to the worn lens surface and that enzyme cleaning of worn lenses does not significantly reduce bacterial adhesion.

Contact Lens Wear Enhances Adherence of Pseudomonas aeruginosa and Binding of Lectins to the Cornea

Extended wear soft contact lenses are associated with an increased incidence of Pseudomonas aeruginosa keratitis. Because the first step in the pathogenesis of this disease is adherence of the microorganism to the corneal surface, we studied the effect of soft contact lens wear on the adherence of P. aeruginosa to the cornea. Rabbits were fitted for extended wear soft contact lenses in the left eye, and the right eye served as a control. Both eyes were then closed with a partial tarsorrhaphy. After 1-5 days of wear, the lenses were removed and the corneas of the left and right eye were removed. Differences in the number of adherent Pseudomonas and in lectin binding to lens-wearing corneas and non-lens-wearing corneas were determined. After 1, 3, and 5 days of soft contact lens wear, there was a significant increase in the number of P. aeruginosa adherent to the lens-wearing cornea. Three to eight times as many bacteria adhered to the lens-wearing eye as compared with the control eye (p less than 0.05). In addition, a soft contact lens placed in the eye followed by the immediate application of P. aeruginosa resulted in an eightfold increase in adherence of bacteria to the lens-wearing cornea (p less than 0.05). Lens wear also led to an increase in binding of concanavalin A (Con A), wheat germ agglutinin (WGA), and Maclura pomifera agglutinin (MPA) to surface epithelium covered by the lens. These corneal epithelial changes induced by extended wear soft contact lenses may provide some insight as to why soft contact lens wearers are predisposed to Pseudomonas keratitis.

The contribution of bacterial surface hydrophobicity to the process of adherence of Pseudomonas aeruginosa to hydrophilic contact lenses

Ten isolates of Pseudomonas aeruginosa obtained from the corneas of patients with Pseudomonas keratitis adhered to soft contact lenses in significantly greater numbers than did six isolates from other body sites (P less than .05). However, there was no predominant serotype among the 10 corneal isolates tested. Isolates grown statically in broth at 37 degrees C formed a pellicle and adhered two times as much to contact lenses as did isolates grown in broth while shaking which did not form a pellicle (P less than .01). The more adherent isolates (grown at 37 degrees C) were shown to be more hydrophobic than the less adherent bacteria (grown at 26 degrees C) by their propensity to accumulate at the interface between hexadecane and saline and their movement into polyethylene glycol from dextran. These corneal isolates agglutinated erythrocytes, a process that was inhibited by dilute solutions (as low as 0.01%) of three commonly used surfactants. These same surfactants inhibited the adherence of Pseudomonas aeruginosa to soft contact lens surfaces by as much as 52%. It is concluded that hydrophobic interactions may significantly contribute to the ability of Pseudomonas aeruginosa to adhere to contact lenses.

Wegener??s Granulomatosis Presenting as Dacryoadenitis

Wegeners granulomatosis is a life-threatening condition characterized by the triad of necrotizing granulomatous inflammation of the respiratory tract, vasculitis, and glomerulonephritis. During early stages of the disease, some patients may present with only one or two components of the triad. Other patients may be affected by the limited form of Wegeners which lacks the renal involvement. We report an 18-year-old female who initially presented with bilateral dacryoadenitis. A lacrimal gland biopsy was consistent with Wegeners granulomatosis. A few months later she developed glomerulonephritis and responded well to cyclophosphamide treatment. Wegeners granulomatosis remains a diagnostic challenge and is frequently underdiagnosed. Early diagnosis is crucial in saving many lives because the disease is potentially curable with cytotoxic therapy. Dacryoadenitis may be one of the initial presentations of Wegeners granulomatosis.

Vernal Conjunctivitis in the Hyperimmunoglobulinemia E Syndrome

Hyper-IgE syndrome (HIE) appears to be related to an immunoregulatory imbalance characterized by severe deficiency of suppressor T cells, elevated levels of IgE antibodies, and repeated infection of various organ systems. We report the association of HIE syndrome in two definite cases and one probable case of vernal conjunctivitis. This association suggests that T cell-mediated imbalance may be one factor in the pathogenesis of vernal conjunctivitis.

Advances in pharmacotherapy for allergic conjunctivitis.

Introduction: Allergy is the fifth leading group of chronic diseases, affecting as much as 40% of the first-world population. Its pathophysiology has a genetic component, and is driven by the immune system’s sensitized response to antigens and environmental factors. As research continues to uncover the mediators responsible for ocular allergy, the development of novel drugs should progress. Areas covered: A literature review of allergic conjunctivitis, ocular allergy and their treatment was performed using PubMed and Medline. Additional information is also included from clinicaltrials.gov and associated web sites for drugs currently in clinical trials. Expert opinion: The initial step of therapy remains identification and avoidance of allergic triggers. The mainstay of treatment is the new generation of dual-acting antihistamines. Drugs that improve the magnitude and duration of relief, with greater subject responder rates, are gradually making their way into the clinic. Allergic conjunctivitis is a relatively easy disease to study because of the availability of models such as the conjunctival allergen challenge. New classes of drugs that target inflammatory pathways or mediators involved in the early and late-phase allergic response are being screened in these models and we are making progress in identifying the next generation of anti-allergic therapy.

Hepatitis C-associated peripheral corneal ulceration: rapid response to intravenous steroids.

Purpose. We present a case of peripheral corneal ulceration in a patient with hepatitis C, which rapidly and dramatically responded to intravenous steroid treatment. Methods. Clinical examination and photographs were obtained to document initial presentation and therapeutic response of Moorens-type ulcers to steroids. Results. Bilateral peripheral corneal ulceration with documented progression responded to intravenous administration of steroids within 5 days. Conclusion. Previous reports of Moorens-type ulcers in patients with chronic hepatitis C have shown a response to interferon alfa-2b, but not to oral corticosteroid therapy. Given the medical contraindications to interferon use in selected patients and the cost, we suggest a trial of high-dose systemic steroids as a possible therapy.