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Olopatadine hydrochloride suppresses the rebound phenomenon after discontinuation of treatment with a topical steroid in mice with chronic contact hypersensitivity.

BACKGROUND: Olopatadine hydrochloride (olopatadine; Allelock) is one of the second-generation antihistamines that are treated for allergic disorders such as rhinitis, urticaria and eczema dermatitis. Olopatadine has recently been shown to have inhibitory effects on the chronic contact hypersensitivity induced by repeated application of oxazolone in mice. Although topical steroids have widely been prescribed for atopic dermatitis, a relapse often occurs within several days after discontinuation of their prolonged use. OBJECTIVES: We investigated the possible efficacy of olopatadine against the relapse after discontinuation of prolonged use of topical prednisolone in the Balb/c mice with oxazolone-induced chronic contact hypersensitivity. METHODS: Mice with the chronic contact hypersensitivity induced by repeated application of oxazolone were treated with olopatadine as a sequential therapeutic agent. The effects of olopatadine were quantified by measurements of ear-swelling, and levels of cytokines and histamine in the lesioned ear. Results Topical prednisolone (0.05 mg/ear/day) significantly inhibited the increases in ear swelling and production of IL-1beta, IL-4, IL-18, granulocyte-macrophage colony-stimulating factor (GM-CSF) and histamine. However, after discontinuation of the treatment with topical prednisolone, the inflammation relapsed and the IL-4 level exceeded the control one. The sequential treatment with olopatadine (10 mg/kg/day) after discontinuation of the treatment with topical prednisolone alone, or topical prednisolone with olopatadine, significantly inhibited the increases in ear swelling and levels of IL-1beta, IL-4, IL-18, GM-CSF, nerve growth factor and histamine. CONCLUSIONS: These results indicate that olopatadine is an antihistamine agent having inhibitory activities against the rebound phenomenon following the discontinuation of topical steroid therapy. Olopatadine is thus expected to be a sequential therapeutic agent after discontinuation of the chronic treatment with a topical steroid.

Animals↗

Inhaled corticosteroid therapy: a substitute for theophylline as well as prednisolone?

Topical corticosteroid treatment can be successfully achieved by inhaled therapy and can effectively provide a safe substitute for oral steroids. More than 8 million patient years of experience gained over a decade of use of inhaled steroids has shown them to be acceptable to patients and clinicians, with side effects confined to the upper airway. At daily doses of 200 to 1600 micrograms BDP or the equivalent, minor systemic activity may occasionally be demonstrated but no adverse systemic side effects have been reported. The topical anti-inflammatory treatment provided by inhaled steroids thus compares favorably with prednisolone and with other asthma therapy with respect to morbidity and mortality, suggesting that inhaled steroids combined with an inhaled beta-agonist is a safe and comprehensive treatment for chronic asthma. This parallel attack on inflammation and bronchoconstriction can be achieved with a morbidity that is much less than that of asthma and also likely to be less than that of the frequently used combination of theophylline and inhaled beta-agonist. Twice-daily regimens of inhaled steroids over a dose range of 200 to 1600 micrograms BDP or the equivalent should enable most patients with chronic asthma to receive effective therapy without recourse to potentially more toxic oral bronchodilator or steroid therapy.

Adrenal Cortex Hormones↗

Kinetics of topically administered prednisolone acetate. Optimal concentration for treatment of inflammatory keratitis.

Two types of quantitative measurements were made in rabbit corneas. First, the level that varying concentrations of topically administered prednisolone acetate attained in the cornea and aqueous humor was determined. Then, the ability of varying concentrations of this corticosteroid to suppress corneal inflammation was ascertained. The maximum dose-response curve for anti-inflammatory effect in the cornea was achieved by the 1.0% concentration, the highest concentration commercially available. Higher concentrations permitted greater quantities of the drug to gain access to the cornea and aqueous humor but produced no measurable increment in anti-inflammatory effect. These experimental observations suggest that concentrations of prednisolone acetate higher than 1.0% have an increased potential for toxicity without offering additional therapeutic benefit.

Administration, Topical↗

Oral tetracycline in the treatment of recurrent corneal erosions.

We report the results of a prospective, randomised controlled, 24 week trial to assess the efficacy of oral tetracycline and oral tetracycline with topical prednisolone in the treatment of recalcitrant recurrent corneal erosions, i.e. those which fail to respond to standard therapy. A total of 30 patients were randomly allocated to either standard treatment (group A), standard treatment and oral tetracycline (group B) or standard treatment, oral tetracycline and topical prednisolone (group C). Treatment groups B and C were instructed to perform daily lid hygiene. There was a significant reduction in the number of recurrent corneal erosions during the 24 week study period in group B (p = 0.04) and in group C (p = 0.0003) but not in group A (p = 0.66). There was a significant difference in the accelerated healing time of recurrent corneal microerosions between groups A and B (p = 0.001) and between groups A and C (p = 0.001). There was a significant improvement in the symptom scores during the study in treatment groups B and C (p = 0.005) but not in group A (p = 0.15). We conclude that lid hygiene and oral oxytetracycline 250 mg twice daily for 12 weeks with or without topical prednisolone for the first 7 days is beneficial in the management of recalcitrant recurrent corneal erosions.

Administration, Oral↗

Penetration of topically administered prednisolone acetate into the human aqueous humor.

A single standardized drop of 1.0% prednisolone acetate labeled with tritiated thymidine was administered topically to one eye of 58 patients shortly before elective cataract extraction. An aqueous humor sample was aspirated at varying intervals and its corticosteroid content was determined. Peak drug concentration in aqueous humor was 1.13 mug/ml, which occurred 30 to 45 minutes after instillation of the medication. Substantial quantitites of corticosteroid were found in the aqueous humor five minutes after drug administration. The area under the drug concentration in aqueous humor-vs-time curve (a measure of the drug's bioavailability in aqueous humor) was 88 mug min/ml, and its half-life in human aqueous humor was 28 minutes. None of these values were significantly different from the comparable values in rabbit eyes.

Adult↗

Treatment of androgenetic alopecia in females in reproductive age with topical estradiolbenzoate, prednisolon and salicylic acid.

INTRODUCTION: Women generally regard their hair loss as socially unacceptable; it is a stressful condition that considerably undermines their self-image and can even be the basis for psychologic disorders. AIM: The aim of the present study was to evaluate the efficacy and safety of topical treatment of androgenetic alopecia (AGA) with estradiolbenzoate, prednisolon and salicylic acid solution (EPS) in females. MATERIAL AND METHODS: An open trial with topical solution containing estradiolbenzoate, prednisolon and salicylic acid was performed in females suffering from AGA. Forty five female patients aged 18 to 42 years were enrolled in a 32-week trial. Forty two of the patients completed the trial. The mean nonvellus hair count taken within 1 cm2 in one and the same area was used to assess the treatment effect. RESULTS: At the end of the trial 59.52% +/- 7.57% of the patients had no hair regrowth, 33.33% +/- %7.27% presented with minimal and 7.14% +/- 3.97% moderate hair growth. The mean count of nonvellus hair increased with 15.79 +/- 1.35. The treated patients showed no significant adverse effects. CONCLUSION: Topical solution of estradiolbenzoate, prednisolon and salicylic acid is an efficacious and safety treatment of androgenetic alopecia in females.

Administration, Topical↗

Penetration of topically applied prednisolone sodium phosphate into human aqueous humour.

Gas Chromatography with Mass Spectrometry (GCMS) was utilised to determine the penetration of prednisolone sodium phosphate into the aqueous humour of human volunteers undergoing routine cataract extraction. Detectable levels of prednisolone were measured in the aqueous humour within 15 minutes. Peak concentrations occurred between 90 and 240 minutes, and the steroid could not be detected in samples taken 10 hours or more after topical administration.

Administration, Topical↗

Design and organization of the herpetic eye disease study (HEDS).

The Herpetic Eye Disease Study (HEDS) includes three double-masked, placebo-controlled clinical trials for potentially blinding herpes simplex virus (HSV) eye infections. One study compares a tapering dosage of topical prednisolone or placebo eye drops for HSV stromal keratitis (HEDS-SKN). Two other trials compare oral acyclovir to placebo capsules for HSV stromal keratitis (HEDS-SKS) or iridocyclitis (HEDS-IRT) in patients on a tapering dosage of topical prednisolone drops. All medications are administered for 10 weeks. Outcome is judged by time to recurrent disease or treatment failure. This paper presents the design, estimated sample size and recruitment as of July 25, 1990.

Acyclovir↗

Treatment of refractory vernal ulcers with large-diameter bandage contact lenses.

PURPOSE: To report two cases of refractory vernal ulcers in which the fitting of a large-diameter (22 mm) hydrogel (Contaflex T75) bandage contact lens (BCL) ameliorated the signs and symptoms of the condition. METHODS: Two patients with refractory vernal ulcers are described. Mechanisms of the effect of a large-diameter lens across the ocular surface are discussed in this condition. RESULTS: The first patient is a 10-year-old boy who had been treated unsuccessfully for a left vernal corneal ulcer with topical prednisolone 0.5% and olopatadine. The vernal ulcer resolved 2 weeks after the fitting of a large-diameter BCL. The second patient is a 4-year-old boy who had been intolerant of all his previous topical medications partly because of his ocular discomfort in association with the right vernal ulcer. A large-diameter BCL was fitted in his right eye. The BCL was removed 2 weeks later with complete healing of the corneal vernal ulcer. Owing to his improved comfort, the patient was able to tolerate topical prednisolone 0.5% drops. CONCLUSIONS: Large-diameter BCLs may be a useful treatment option in the management of refractory vernal ulcers.

Child↗

Topical 0.1% prednisolone lowers nerve growth factor expression in keratoconjunctivitis sicca patients.

PURPOSE: To compare nerve growth factor (NGF) levels in tears and on the ocular surfaces of normal control and non-Sjögren's type keratoconjunctivitis sicca subjects, and to investigate the effect of 0.1% prednisolone eyedrops on NGF levels in keratoconjunctivitis sicca patients. DESIGN: Prospective, double-masked, randomized, comparative clinical trial. PARTICIPANTS: Forty-one keratoconjunctivitis sicca patients and 23 age- and gender-matched healthy subjects. METHODS: Baseline tear NGF levels were measured in keratoconjunctivitis sicca patients and healthy control subjects using enzyme-linked immunosorbent assays. Keratoconjunctivitis sicca patients received 0.1% prednisolone drops in one eye and 0.1% hyaluronic acid drops in the other, 3 times a day for 28 days. Also, impression cytology (IC) and immunostaining for NGF on conjunctival epithelium were performed on both groups. MAIN OUTCOME MEASURES: Tear NGF/total tear protein (TP) concentration ratio, IC and NGF immunocytologic staining, subjective symptom scale, tear breakup time, and Schirmer values. RESULTS: Keratoconjunctivitis sicca patients were found to have baseline tear NGF concentrations higher than those of age- and gender-matched healthy control subjects (65.9+/-14.5 vs. 122.1+/-45.3 pg/mug, P<0.0001). In keratoconjunctivitis sicca patients, prednisolone treatment for 28 days resulted in a decrease in tear NGF levels, symptom scores, and IC scores, whereas hyaluronic acid treatment had no such effect (68.2+/-25.0 pg/mug vs. 108.0+/-43.4 pg/mug, P<0.0001 for tear NGF/TP ratio; 2.16+/-1.01 vs. 3.39+/-1.50, P = 0.0014 for symptom scale; 1.05+/-0.67 vs. 1.61+/-0.86, P = 0.0317 for IC). Measurements taken at both 14 and 28 days indicated that neither prednisolone nor hyaluronic acid treatment affected breakup time or Schirmer values. CONCLUSION: Keratoconjunctivitis sicca patients showed elevated levels of tear NGF, which were decreased by treatment with 0.1% prednisolone. These data suggest that ocular surface NGF may play an important role in ocular surface inflammation processes associated with dry eyes.

Administration, Topical↗

The effects of topical steroids on refractive outcome and corneal haze, thickness, and curvature after photorefractive keratectomy with a 6.0-mm ablation diameter.

BACKGROUND AND OBJECTIVE: To study the effect of topical prednisolone acetate after photorefractive keratectomy (PRK) using a 6.0-mm ablation diameter on the refractive and visual outcomes, corneal haze, corneal thickness, and corneal curvature in a prospective, double-masked, randomized manner. PATIENTS AND METHODS: Seventy-two eyes of 36 patients who had excimer laser PRK for correction of myopia ranging from -3.00 to -6.00 D (-4.11 +/- 0.84 D in eyes treated with steroids and -4.38 +/- 0.79 D in eyes treated with placebo; mean +/- SD) were enrolled. PRK procedures were performed using a 193-nm argon-fluoride excimer laser with 180-ml/cm2 fluence, a 10-Hz repetition rate, and a 6.0-mm ablation diameter. One eye of each patient was treated with the steroid (prednisolone acetate) and the other eye with placebo. Patients were observed for at least 12 months after PRK. RESULTS: There was no statistically significant difference between the steroid and the placebo groups with regard to refraction measurements that were taken postoperatively at 3 months (P = .39) and 12 months (P = .51). The corneas showed an increase in thickness after PRK in both groups, but the difference was not statistically significant at 12 months postoperatively (P = .45). The corneal haze score was not statistically different at any stage between groups (P = .30 at 3 months, P = .84 at 12 months). Keratometric data derived from corneal topography did not show any statistically significant difference (P = .85 at 3 months, P = .96 at 12 months). The rate of uncorrected visual acuity of 20/40 or more was 79.4% (27 eyes) in the steroid group and 70.5% (24 eyes) in the placebo group (P = .40). The rate of loss of 2 or more lines in best spectacle-corrected visual acuity was 5.85% (2 eyes) in the steroid group and 8.8% (3 eyes) in the placebo group (P = 1.0). CONCLUSION: Topical prednisolone acetate use for 3 months after PRK with a 6.0-mm ablation diameter has no effect on refractive and visual outcome, corneal haze, corneal thickness, and corneal curvature.

Administration, Topical↗

The role of fibroblast inhibitors on corneal healing following photorefractive keratectomy with 193-nanometer excimer laser in rabbits.

Corneal stromal haze has been seen following photorefractive keratectomy with the 193-nanometer excimer laser. Topical antimetabolites aimed at decreasing the haze have been investigated in the rabbit model. We used the VISX 193-nanometer excimer laser to create 6.0-millimeter, -5.00-diopter ablations in 10 Dutch rabbits. Each rabbit was randomized to treatment groups using topical prednisolone acetate, 5-fluorouracil, heparin, prednisolone and heparin, or prednisolone and 5-fluorouracil. Topical agents were instilled twice daily for 2 weeks. Corneal stromal haze developed in all of the eyes. At 2 weeks, there was a significant difference between the degree of haze in the treated eyes and in the untreated controls (P = .02). At 6 weeks, no significant difference remained (P = .07). There were no significant differences in corneal haze among the treatment groups. Thus, all treatments reduced haze at 2 weeks, but the effect was transient, with controls clearing to an equivalent haze by 6 weeks. We conclude that the agents investigated in this rabbit model provided only a transient benefit in reducing corneal haze following excimer laser photoablation.

Animals↗

The effects of topical S(+)-ibuprofen on interleukin-1 induced ocular inflammation in a rabbit model.

Topical non-steroidal anti-inflammatory drugs may serve as an alternative or adjunct to topical corticosteroid therapy for iritis. We have tested the efficacy of topically given S(+)-ibuprofen in a rabbit model of uveitis secondary to the intravitreal injection of human recombinant interleukin 1-alpha. Topically administered S(+)-ibuprofen was found to inhibit increased vascular permeability associated with this model. These results with topical S(+)-ibuprofen compare favorably to the results seen with topical prednisolone and are significantly superior to the results seen with topical flurbiprofen. Topical S(+)-ibuprofen did not significantly reduce the cellular infiltration associated with interleukin-1 induced inflammation. These findings suggest a potential role for topical S(+)-ibuprofen in the treatment of ocular inflammation and, in this animal model, it appears to be superior to an alternative non-steroidal compound, but further studies are indicated to assess its activity in alternate models of ocular inflammation.

Administration, Topical↗