Systemic adalimumab induces peripheral corneal infiltrates: a case report.

BACKGROUND: Tumor necrosis factor-alpha inhibitors are widely used agents in the treatment of immune disorders such as rheumatoid arthritis and inflammatory bowel disease. Despite their anti-inflammatory action, paradoxical drug-induced inflammatory events have been occasionally associated with the use of infliximab, etanercept, and in a lesser extent adalimumab. However, eye involvement is uncommon and anterior uveitis is the only reported ocular adverse manifestation. It can be induced by etanercept, but has also been described during adalimumab therapy. We present here the first report of recurrent peripheral corneal infiltrates following subcutaneous injections of adalimumab. CASE PRESENTATION: A 34 year-old Caucasian woman with Crohn's disease presented to the emergency department with bilateral red eyes and discomfort 36 hours after she received her bimonthly dose of subcutaneous adalimumab. Examination revealed bilateral peripheral corneal infiltrates with characteristic features of immune infiltrates. Symptoms and infiltrates regressed after topical corticosteroid therapy, but recurred after each adalimumab injection over the following weeks. CONCLUSION: Paradoxical immune reactions associated with tumor necrosis factor-alpha inhibitors may result either from hypersensitivity mechanisms, or from immune-complex deposition via anti-adalimumab antibodies. Both mechanisms could explain this newly described manifestation. Care should be taken to search for corneal infiltrates in the event of red eye symptoms during adalimumab therapy since they respond to topical corticosteroids and do not necessarily prompt the discontinuation of the immunosuppressive therapy.

Novel strategies for managing infantile hemangiomas: a review.

Complicated infantile hemangiomas require early intervention. With the advent of an improved understanding of the pathophysiology of the condition, and the serendipitous discovery of the effects of propranolol, available treatment options have expanded from the traditional use of steroids. This article reviews the current literature on the treatment of complicated hemangiomas with steroids, interferon, vincristine, bleomycin, and propranolol. The likely mechanism of action, indications, recommended treatment regimes, and complications are discussed.

Archipelago keratitis: a clinical variant of recurrent herpetic keratitis?

OBJECTIVE: To describe archipelago keratitis, a presumed clinical variant of herpetic epithelial keratitis. DESIGN: Case series. PARTICIPANTS: A series of 6 patients with an unusual form of superficial keratitis. METHODS: History, including age, gender, clinical evolution, and treatment; slit-lamp biomicroscopy findings; in vivo confocal microscopy findings; and corneal epithelial scrapings were analyzed. MAIN OUTCOME MEASURES: Clinical ocular examination, a diagnostic workup including corneal scraping for herpesvirus polymerase chain reaction, in vivo confocal microscopy, and therapeutic outcome. RESULTS: The authors describe a series of 6 patients with keratitis consisting of foci of epithelial erosions associated with subepithelial nummular inflammatory infiltrates and disposed in a radial, centripetal, archipelagolike pattern originating from the limbus. All the patients had a past history of herpetic epithelial keratitis, herpetic vesicles on the ipsilateral lid, or both. Polymerase chain reaction-based screening for herpes simplex virus 1 and 2 in corneal scrapings demonstrated positive results in 2 patients. In vivo corneal confocal microscopy revealed focal areas of hyperreflective epithelial cells and hyperreflective subepithelial dendritic structures overlying activated keratocytes. All the patients improved with oral valacyclovir treatment followed by topical steroid therapy. CONCLUSIONS: Archipelago keratitis may be a new clinical variant of herpetic keratitis, reflecting herpetic dissemination from the limbus to the center of the cornea.

[Efficacy of prednisolone and rimexolone in HLA-B27 positive patients with acute anterior uveitis]. / Comparación de la eficacia de la prednisolona y la rimexolona en el tratamiento de iridociclitis aguda en pacientes HLA-B27 positivos.

PURPOSE: To compare the efficacy and safety of prednisolone acetate 1% vs. rimexolone 1% ophthalmic suspension in the treatment of acute anterior uveitis (AAU) in HLA-B27+ patients. METHODS: Sixty-eight AAU HLA-B27+ patients were randomly selected for treatment with prednisolone acetate 1% or Rimexolone 1%. All patients showed mild to moderate anterior chamber inflammation. This was a prospective, randomized, double blind, clinical trial. RESULTS: There was no statistically significant difference between both groups when anterior chamber cells were measured. In the rimexolonae group, flare diminished since the first week. In both groups the intraocular pressure (IOP) raised since the first week, the increase was highly significant in the rimexolone group. Final intraocular pressure was higher in the prednisolone group. CONCLUSION: Rimexolone 1% is as effective as prednisolone acetate 1% in the treatment of mild to moderate AAU HLA-B27+. IOP increased in both groups, but this variation was not clinically significant.

Comparación de la eficacia de la prednisolona y la rimexolona en el tratamiento de iridociclitis aguda en pacientes HLA-B27 positivos / Efficacy of prednisolone and rimexolone in HLA-B27 positive patients with acute anterior uveitis

Objetivo: Comparar la eficacia y seguridad de las suspensiones oftálmicas de acetato de prednisolona al 1% y de rimexolona al 1%, en el tratamiento de la uveítis anterior aguda (UAA) en pacientes HLA B27+. Material y métodos: Se seleccionaron al azar 68 pacientes con UAA HLA -B27+ para tratamiento con acetato de prednisolona al 1% o rimexolona al 1%. En todos los pacientes la inflamación en cámara anterior era leve a moderada. La presión intraocular (PIO) y el grado de inflamación fueron evaluados semanalmentre durante seis semanas. Fue un estudio clínico prospectivo, aleatorio y doble ciego. Resultados: Al cuantificar las células en cámara anterior no se encontraron diferencias estadísticamente significativas entre uno y otro grupos. En el grupo de rimexolona el flare disminuyó desde la primera semana. En los grupos la presión intraocular se elevó con respecto a la basal desde la primera semana, la variación fue más significativa en el grupo de rimexolona. La PIO final fue menor en el grupo de rimexolona, siendo esta diferencia estadísticamente significativa . Conclusión: Para el tratamiento de la UAA HLA -B27+, leve a moderada, la rimexolona al 1% y la prednisolona al 1% tiene una eficiencia similar. En este estudio las variaciones de presión intraocular en los dos grupos no fueron clínicamente significativas.

Purpose: To compare the efficacy and safety of prednisolone acetate 1 % vs. rimexolone 1 % ophthalmic suspension in the treatment of acute anterior uveitis (AAU) in HLA-B27+ patients. Methods: Sixty-eight AAU HLA-B27+ patients were randomly selected for treatment with prednisolone acetate 1% or Rimexolone 1%. All patients showed mild to moderate anterior chamber inflammation. This was a prospective, randomized, double blind, clinical trial. Results: There was no statistically significant difference between both groups when anterior chamber cells were measured. In the rimexolone group, flare diminished since the first week. In both groups the intraocular pressure (IOP) raised since the first week; the increase washighly significant in the rimexolone group. Final intraocular pressure was higher in the prednisolone group. Conclusion: Rimexolone 1 % is as effective as prednisolone acetate 1% in the treatment of mild to moderate AAU HLA B27+. IOP increased in both groups, but this variation was not clinically significant.

Secretoneurin in the human aqueous humor and the absence of an effect of frequently used eye drops on the levels.

Secretoneurin (SN) was detected in the aqueous humor (AH) of patients treated topically with tobramycine eye drops alone or tobramycine and cyclosporine A, tobramycine and diclofenac or tobramycine and rimexolone. The levels of the peptide were found to be higher in the uninflamed human than in the rabbit aqueous humor which may be the result of species differences and/or age-related circumstances. Furthermore, they are approximately one hundred times higher than those of classical neuropeptides indicating release from nerve fibers and/or secretion from non-pigmented ciliary epithelium cells. Despite a slight tendency by rimexolone to decrease the levels, there was no significant effect seen for either of the drops. It must be considered that aminoglycosides are known to have toxic side effects and that they can influence the levels of SN which may be not diminished by low topical doses of corticosteroids or nonsteroidal antiinflammatory drugs. The high levels of the peptide are of relevance and may indicate a significant role of secretoneurin in the anterior segment of the eye. This should encourage performing functional studies.

Efficacy and safety of rimexolone 1% versus prednisolone acetate 1% in the control of postoperative inflammation following phacoemulsification cataract surgery.

PURPOSE: The aim of this study was to evaluate the efficacy and safety of rimexolone 1% ophthalmic suspension compared to that of 1% prednisolone acetate in the control of inflammation in eyes undergoing cataract extraction with phacoemulsification followed by posterior chamber intraocular lens implantation. METHODS: Forty-eight patients who underwent uncomplicated cataract extraction with phacoemulsification followed by posterior chamber IOL implantation constituted the study group of this prospective, randomized, double-masked investigation. Patients were randomly assigned to two treatment groups; rimexolone 1% ophthalmic suspension (27 subjects) or prednisolone acetate 1% (21 subjects). Postoperatively, patients used topical rimexolone or prednisolone drops four times a day for 15 days. Patients were examined at the first postoperative day (day 1), and days 3, 7 and 15. The major efficacy parameters assessed clinically on each visit were anterior chamber cells, anterior chamber flare and conjunctival hyperemia. Safety of the rimexolone was evaluated by IOP values and the presence of adverse effects. RESULTS: Regarding all three efficacy parameters, rimexolone was found to be clinically and statistically equivalent to prednisolone acetate. Intraocular pressure values during the postoperative period were also similar in both groups. CONCLUSION: Rimexolone 1% ophthalmic suspension is both an effective and safe topical steroid in controlling postoperative inflammation after cataract extraction with phacoemulsification.

Best evidence topic report. Intra-articular corticosteroid injections in acute rheumatoid monoarthritides.

A short cut review was carried out to establish whether intra-articular corticosteroid injections were effective at reducing pain in patients with acute rheumatoid monoarthritis. Altogether 215 papers were found using the reported search, of which one presented the best evidence to answer the clinical question. The author, date and country of publication, patient group studied, study type, relevant outcomes, results, and study weaknesses of this best paper are tabulated. A clinical bottom line is stated.

Efficacy and safety of 1% rimexolone versus 1% prednisolone acetate in the treatment of anterior uveitis--a randomized triple masked study.

PURPOSE: To evaluate the efficacy and safety of 1% rimexolone versus 1% prednisolone acetate ophthalmic suspension in the treatment of anterior uveitis. METHODS: A randomised triple masked, parallel comparison of rimexolone and prednisolone acetate ophthalmic suspensions was carried out on 78 patients with acute, chronic and recurrent anterior uveitis. Treatment regimen included instillation of one or two drops of drug one hourly through the waking hours during the first week, two hourly in the second week, four times a day in the third week, two times a day for the first 4 days and once a day for the 3 days in the last week. The patient was clinically evaluated on the 3-4th, 7-10th, 14th, 21st and 28th days. The patient was also reviewed on the 30th day. Anterior chamber cells and flare reactions were compared for evaluating the efficacy of the drugs. RESULT: Rimexolone is as effective as prednisolone acetate ophthalmic suspension in the treatment of anterior uveitis. The largest difference found was 0.1 in the flare reaction (statistically insignificant; p = 0.3) and 0.2 score units (statistically significant; p = 0.01) in the cells. Overall, comparison of the drugs shows no clinical significance in the treatment of anterior uveitis by either drug. Difference in intraocular pressure (IOP) was also statistically insignificant (p > 0.05). However, three patients in the prednisolone acetate group and 1 patient from the rimexolone group showed a rise in IOP. CONCLUSION: Rimexolone 1% ophthalmic suspension is as effective as and safer than prednisolone acetate 1% ophthalmic suspension in the treatment of anterior uveitis.

Topical corticosteroids of limited potency promote adenovirus replication in the Ad5/NZW rabbit ocular model.

PURPOSE: To determine the effect of topical therapy with several corticosteroids with limited potency on viral clearance in the adenovirus type 5 (Ad5) rabbit ocular model. METHODS: Sixty rabbits were inoculated in both eyes with Ad5. On the first day, the rabbits were equally divided into four topical treatment groups: 0.12% prednisolone acetate (PA), 0.1% fluorometholone (FM), 1% rimexolone (RMX), and control. Treatment was administered four times daily, in both eyes, for 3 days. All eyes were cultured for virus on days 0, 1, 3, 4, 5, 7, 9, 11, 14, 16, 18, and 21. RESULTS: Compared with the control group, treatment with PA, FM, and RMX significantly increased the number of Ad5 positive eye cultures from days 7-21. Fluorometholone and RMX prolonged the duration of Ad5 shedding, and FM increased the mean combined Ad5 titer from days 1-5 and 7-21. CONCLUSIONS: Treatment of an experimental ocular adenovirus infection with PA, FM, and RMX for 3 days significantly enhanced adenovirus replication compared with the control group. Short-term treatment of EKC with several commercially available topical corticosteroids with limited potency may offer symptomatic relief, but may also delay viral clearance and promote office and community epidemics.

A pharmacoeconomic analysis of rimexolone for the treatment of ophthalmic inflammatory conditions.

Topical steroids are the standard first-line therapy for treating ophthalmic inflammatory conditions. However, potent ophthalmic steroids can lead to an elevation of intraocular pressure (IOP), which can result in greater medical resource utilization and increased costs. We have developed a decision analysis model from a societal perspective to evaluate the costs and consequences of the treatment of ophthalmic inflammatory conditions with two potent topical steroids: prednisolone and rimexolone. Data for the model are based on information from clinical trials, national data-bases, published literature, and responses by ophthalmologists to a questionnaire on treatment patterns for elevated IOP. Three steroid-responsive conditions are examined separately with the model: uveitis; postoperative inflammation following cataract surgery; and other ophthalmic inflammatory conditions (blepharitis, episcleritis, postoperative refractive surgery, and corneal transplant). The model evaluates patients with acute conditions versus those with chronic conditions and those with mild to moderate elevation of IOP versus those with severe elevation of IOP. Although the unit cost of rimexolone is higher than that of prednisolone, use of rimexolone leads to cost savings because the incidence of elevated IOP is decreased. If rimexolone is used instead of prednisolone for the treatment of ophthalmic inflammatory conditions, the estimated cost saved (at 1995 AWP prices) is approximately $10 million across the entire US population. The savings across the health maintenance organization population on an annualized basis is approximately $3.9 million. Even if rimexolone were priced higher than current market charges (at 130% to 150% of the AWP of prednisolone), cost savings ranging from the $2.9 million to $720,000 would accrue with use of rimexolone compared with prednisolone. However if, rimexolone were priced at 160% of the AWP of prednisolone, its use would incur an additional cost of $300,000. The primary medical resource utilized in treating elevated IOP in ophthalmic inflammatory conditions is physician visits. Medications are responsible for only one-fifth to one-third of the total cost of treating elevated IOP. This analysis indicates that rimexolone is associated with decreased medical resource utilization and cost savings to the entire healthcare system.

The effects of Rimexolone 1% in postoperative inflammation after cataract extraction. A double-masked placebo-controlled study.

AIM: A multicentre, randomized, placebo-controlled double-masked study was conducted to assess the efficacy and safety of Rimexolone 1% eye drops in reducing inflammation after cataract surgery and intra-ocular lens implantation. METHODS: Rimexolone 1% (124 patients) or placebo (58 patients) was given, four times a day for 14 days starting 22-34 hours after surgery. All patients also received tobramycin 0.3% four times a day for 7 days. The clinical signs of ocular inflammation were recorded on days 1, 3, 8, 15 and 17 or 18. RESULTS: Rimexolone 1% markedly decreased the mean inflammation severity scores, and the sum of clinical assessments of cells and flare in the anterior chamber compared with placebo at each assessment. In addition, the percentage of patients with no anterior chamber inflammation was significantly higher with Rimexolone 1% than with the placebo at each assessment. All these results were statistically significant. Intra-ocular pressure did not rise after treatment with Rimexolone 1%. CONCLUSIONS: The results suggest that Rimexolone 1% ophthalmic solution is an effective and safe steroidal anti-inflammatory agent for topical use following cataract surgery and intra-ocular lens implantation.

Efficacy and safety of rimexolone 1% ophthalmic suspension vs 1% prednisolone acetate in the treatment of uveitis.

PURPOSE: Two multicenter studies compared the efficacy and safety of rimexolone 1% ophthalmic suspension (Vexol 1%, Alcon) and 1% prednisolone acetate (Pred Forte, Allergan). METHODS: Patients with acute uveitis, recurrent iridocyclitis, or chronic uveitis treatable by topical corticosteroid were enrolled. Treatment regimen was one or two drops every hour during Week 1, every two hours during Week 2, four times a day during Week 3, and once a day for the last three days. Efficacy and safety were determined on Days 3, 4, 7 to 10, 14, 21, and 28. A poststudy evaluation was conducted 36 to 72 hours after treatment was stopped. RESULTS: When anterior chamber cell and flare were measured, rimexolone 1% was found to be as effective as 1% prednisolone. The largest difference observed between treatments was 0.5 score unit, not clinically significant. There were no statistically significant differences in cell scores in either study (P > .05). No statistically significant differences in flare scores were found except at Day 28 in Study One (P = .04). Also, prednisolone was found to be more likely than rimexolone to cause a clinically significant increase (10 mm Hg or more) in intraocular pressure (1.7 times more likely in Study One, eight times more likely in Study Two). CONCLUSION: Rimexolone 1% ophthalmic suspension is safe and effective for the treatment of uveitis.

Clinical effects of danazol on endometrial hyperplasia in menopausal and postmenopausal women.

Much evidence has been suggested that cystic, adenomatous, and atypical hyperplasia as well as adenocarcinoma in situ of the endometrium may ultimately progress to invasive cancer. Consequently, these lesions should be considered to be precursors of endometrial cancer. Twelve postmenopausal and three perimenopausal women with vaginal bleeding due to endometrial hyperplasia received 400 mg/d of danazol orally for 3 months. After 15 to 30 days of continuous danazol therapy, the endometrial glands ceased to grow and became smaller and rounder. The lumina of glands were narrow and contained no secretion. The nucleic mitosis of the glands disappeared. All women showed regression of hyperplastic endometrium within 2 to 3 months of initial treatment. In the 15 cases treated, endometrial hyperplasia could be controlled successfully with danazol without further recurrence and/or progression of the disease. In summary, danazol should be an effective and safe alternative therapy to progesterone for the treatment of endometrial hyperplasia.

Protective effect of rimexolone on cartilage damage in arthritic mice: a comparative study with triamcinolone hexacetonide.

We studied the effect of the local steroid preparation rimexolone on cartilage metabolism in arthritis and normal joints. Prolonged anti-inflammatory action was evident after intraarticular injection of a single dose of 450 micrograms into mice with monoarticular antigen-induced arthritis. Suppression of inflammation lasted for at least 21 days. A single dose of 25 micrograms of the anti-inflammatory steroid triamcinolone hexacetonide (THA) induced comparable suppression in the initial stage of the arthritis, but the suppressive action was of shorter duration. Both drugs significantly prevented osteophyte formation, which is a characteristic feature of this type of experimental arthritis. Although chondrocyte proteoglycan (PG) synthesis in patellar cartilage was significantly suppressed upon injection in normal joints, both steroids counteracted the severe suppression of PG synthesis in arthritic joints. These data indicate that although steroids may have significant side effects on chondrocytes, the overall effect on arthritic chondrocytes is beneficial. An advantage of rimexolone over THA is its prolonged retention, which may explain its sustained anti-inflammatory action, and the lack of systemic effects.