Mari Tanaka

Atopic ocular surface disease : Implications on tear function and ocular surface mucins

Purpose: To describe tear function, mucin alterations, and ocular surface disorder in patients with atopic diseases. Methods: Subjects underwent corneal sensitivity measurements, Schirmer test, tear film break-up time (BUT) assay, and fluorescein and rose Bengal staining of the ocular surface. Conjunctival impression cytology and brush cytology were also conducted. Impression cytology samples underwent PAS and immunohistochemical staining for MUC5AC. Brush cytology specimens underwent evaluation for inflammatory cell expression and RT-PCR for MUC5AC mRNA expression. Differences related to tear function and ocular surface examination parameters among patients with and without corneal ulceration and healthy control subjects were studied. Results: Mean corneal sensitivity and BUT values were significantly lower in atopic patients with corneal ulcers compared with patients without ulcers and controls (P < 0.001). Brush cytology specimens from patients with corneal ulcers revealed significantly higher expression of inflammatory cells compared with patients without ulcers and controls (P < 0.001). Impression cytology samples from eyes with corneal ulcers showed significant squamous metaplasia and reduction of goblet cell density compared with eyes without ulcers and control subjects. Specimens from eyes with corneal ulcers showed PAS (+) mucin pick up and did not stain positive for MUC5AC. MUC5AC mRNA expression was significantly lower in eyes with corneal ulcers compared with in eyes without ulcers and control subjects. Conclusions: Ocular surface inflammation, tear film instability, and decreased conjunctival MUC5AC mRNA expression are important in the pathogenesis of noninfectious corneal shield ulcers in atopic ocular surface disease.

Corneal and conjunctival fibroblasts are major sources of eosinophil-recruiting chemokines

BACKGROUND Differential expression of chemokine genes were investigated in various types of ocular surface cells. METHODS Primary cultures of human corneal epithelial cells (n = 3), corneal fibroblasts (n = 2), conjunctival epithelial cells (n = 2) and conjunctival fibroblasts (n = 2) were established and incubated with or without interleukin (IL)-4 (30ng/ml) and tumor necrosis factor (TNF)-alpha(30ng/ml) for 24 hours. Gene transcription levels of 33 chemokines and production of 4 chemokines were analyzed. RESULTS After stimulation, chemokine expression increased for 18 of 33 coded chemokine gene transcripts. In stimulated conjunctival and corneal cells, CC chemokine genes increased in fibroblasts (expression of 6 out of 8 genes), while CXC chemokine genes increased in both epithelial cells (expression of 4 out of 9 genes in conjunctival epithelial cells and 7 out of 9 genes in corneal epithelial cells) and in fibroblasts (expression of 8 out of 9 genes in conjunctival and corneal fibroblasts). Except for MCP-1, gene transcription levels for most CC chemokines were inducible and, except for IP-10 and I-TAC, most CXC chemokines were constitutively expressed. Corneal epithelial cell and fibroblast production patterns for eotaxin-1, MCP-1 and IP-10 were comparable to the mRNA expression pattern. CONCLUSIONS Corneal and conjunctival fibroblasts exhibited marked increases in the expression of chemokines upon stimulation with TNF-alpha and IL-4, suggesting that fibroblasts may be one of the primary sources of chemokines in allergic conjunctival diseases. Therefore, regulation of chemokine production from these cells may be an effective strategy for treating such diseases.

Comparison of Efficacy of Bromfenac Sodium 0.1% Ophthalmic Solution and Fluorometholone 0.02% Ophthalmic Suspension for the Treatment of Allergic Conjunctivitis

AIMS Bromfenac sodium (BF) 0.1% was compared with fluorometholone (FML) 0.02% for the treatment of seasonal allergic conjunctivitis when concomitantly used with disodium cromoglycate (DSCG) 2.0%. METHODS Eighty-six patients with seasonal allergic conjunctivitis were treated with DSCG four times a day, and BF was concomitantly administered twice a day in one eye and FML was administered four times a day in the contralateral eye for 1 week. Ocular signs were scored on a four-graded severity. Patients recorded symptoms using visual analog scale. Patients were asked which concomitant treatment was more suitable for them and scored global evaluation. RESULTS All subjective symptom scores were decreased in both concomitant treatment groups compared with baseline (P < 0.05). Objective signs were significantly improved with the concomitant use of BF or FML with DSCG (P < 0.05). Neither symptoms nor signs differed significantly between the concomitant use of BF and FML. Fifteen patients selected BF and 29 patients selected FML as the more preferred concomitant eye drops, 42 patients judged no difference in efficacy between the groups. No significant difference was observed in patients global evaluation between the groups. CONCLUSIONS Bromfenac sodium for allergic conjunctivitis was effective, with efficacy equivalent to that of FML when used with DSCG.

Kaposi varicelliform eruption associated with 0.1% tacrolimus ointment treatment in atopic blepharitis

Objective To report the association of Kaposi varicelliform eruption (KVE) with 0.1% tacrolimus ointment treatment of atopic blepharitis in a patient with atopic dermatitis (AD). Method We encountered KVE in a 20-year-old male patient with atopic blepharitis and AD who developed generalized herpetic lesions on his face 28 days after commencement of treatment. Result The lesions resolved quickly with intravenous acyclovir treatment. Conclusion Ophthalmologists should be well aware of KVE as a complication of immunosuppressive treatment in patients with atopic blepharitis.

The Effect of a Combined Therapy with a Histamine H1 Antagonist and a Chemical Mediator Release Inhibitor on Allergic Conjunctivitis

Purpose: To evaluate the efficacy of a combined therapy with levocabastine hydrochloride ophthalmic suspension and pemirolast potassium ophthalmic solution compared to single therapy with levocabastine hydrochloride ophthalmic suspension alone. Methods: Thirty-two allergic conjunctivitis patients were randomized to combined-treatment (n = 15) or single-treatment groups (n = 17). The improvement of subjective symptoms as well as objective findings were evaluated. Results: The degree of improvement was significantly higher in the combined-treatment group for lacrimation (p = 0.008) among the subjective symptoms, for conjunctival edema (p = 0.030), eyelid edema (p = 0.032) and conjunctival papilla formation(p = 0.040) among the objective findings. Conclusions: Both objective assessments and subjective symptoms of allergic conjunctivitis showed the greatest improvements when patients were treated with combined therapy as compared to single-agent therapy. The enhanced benefits of combined therapy may result from these agents having different mechanisms of action.

Randomized, Multicenter, Double-Blind Study of the Safety and Efficacy of 1%D-3-Hydroxybutyrate eye drops for Dry Eye Disease.

In a previous study, we demonstrated that topical D-beta-hydroxybutyrate ameliorates corneal epithelial erosion and superficial punctate keratopathy in a rat model of dry eye disease. In the current investigation, we performed a prospective, randomized, multicentre, double-blind, placebo-controlled study to assess the safety and efficacy of 1% D-3-hydroxybutyrate eye drops in patients with dry eye disease. A total of 65 patients were randomly assigned to either the placebo group or the 1% D-3-hydroxybutyrate group, and the treatments were administered 6 times a day for 4 weeks. We then evaluated corneal fluorescein staining, corneal and conjunctival rose Bengal staining, tear film break-up time (BUT), Schirmer score, and subjective symptoms. At both 2 and 4 weeks, the corneal rose Bengal score was significantly better in the 1% D-3-hydroxybutyrate group than in the placebo group. Among patients with an initial Schirmer score of ≤5 mm, the corneal fluorescein staining score was significantly better in the 1% D-3-hydroxybutyrate group than in the placebo group at two weeks. Mild ocular symptoms occurred in both groups, and these spontaneously resolved. The present study suggested that 1% D-3-hydroxybutyrate eye drops are safe and effective in treating ocular surface disorders in patients with tear-deficient dry eye disease.

A case of human seminal plasma allergy sensitized with dog prostatic kallikrein, Can f 5

Human seminal plasma allergy (HSPA) is a rare phenomenon in women that was first described by Specken in 19581 andwhichwas thought to be an allergic reaction to a specific protein in seminal plasma. The clinical responses vary from local reactions (e.g., vulvar and vaginal itching and erythema) to life-threatening anaphylaxis. While the mechanism underlying HSPA is unclear, prostate-specific antigen (PSA) is thought to be a causative allergen.2,3 We describe a patient with HSPA who developed anaphylaxis after coitus. A 37-year-old woman presented with a history of anaphylactic reaction 30 min after sexual intercourse with her husband. She developed general urticaria, swelling of her lips and eyelids, cough and dyspnea. She took oral antihistamines, and the symptoms disappeared within several hours. She experienced vulvar and cutaneous itching, erythema and swelling immediately after contact with seminal fluid a few months before developing the anaphylactic reaction. The use of a condom during sexual intercourse prevented these symptoms. Her medical history included chronic thyroiditis. She was treated with levothyroxine sodium and was symptomfree. She had only experienced mild atopic dermatitis in early infancy and had no eczema when she was referred to our hospital. She experienced an extrauterine pregnancy at 21 years of age. A laboratory examination revealed a total serum IgE titer of 158 IU/ ml. Her specific IgE antibody levels for dog dander, cat dander, human seminal fluid, and latex, as determined using an ImmunoCAP system (Phadia, Uppsala, Sweden), were 13.00 UA/mL, 1.39UA/mL 1.02UA/mL, and 0.1 >UA/mL, respectively. A skin prick test was performed using seminal fluid from her husband. When the average wheal diameter induced by the allergen was >50% of the positive control response induced by histamine hydrochloride at 10 mg/ ml, the result was considered positive. The results were positive for 10and 100-fold diluted seminal fluid (wheal diameters, 6 6 and 6 5 mm, respectively; positive control [10 mg/ml histamine hydrochloride]: wheal diameter, 6 6 mm; negative control [saline]: wheal diameter, 0 0 mm). She developed cough and pruritic erythema on her thigh 15min after the prick test. Antihistamines were administered intravenously and the symptoms disappeared within 30 min. Next, seminal fluid from her husband was separated into spermatozoa and seminal plasma by a percol gradient technique, and the spermatozoa were washed three times with spermwash media. A skin prick test was performed using spermatozoa, seminal plasma, percol and