Long-term Topical Cyclosporine for Atopic Keratoconjunctivitis

Study Overview
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Brief Summary
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Atopic keratoconjunctivitis (AKC) is a rare type of ocular allergy that is often associated with eczema. Over time, the complications from this disease process lead to loss of vision due to continual scarring of the corneal surface. The pathophysiology of AKC has not been fully elucidated, and the triggers are still unknown. Corticosteroids are very effective in controlling the acute symptoms of AKC. However, two thirds of patients managed with a combination of oral antihistamine, topical mast cell stabilizer, and intermittent topical steroid regimen eventually developed significant keratopathy and vision loss. Additionally, there are many side effects of corticosteroids, including local immunosuppression, cataract formation, and increased risk of glaucoma. Cyclosporin A is an immunomodulator that specifically inhibits T lymphocytes by blocking the expression of the interleukin-2 receptor. It also blocks the release of inflammatory mediators from mast cells and eosinophils. Cyclosporin has no known side effects except for burning upon instillation, and safe to use over long-term . The investigators have demonstrated that a 0.05% ophthalmic emulsion of cyclosporine has been shown to be effective at improving the ocular signs and symptoms of AKC over short-term. However, the long-term efficacy of cyclosporine A in slowing the natural history of AKC and possible steroid sparing effects have not been assessed. The investigators hypothesize that cyclosporine A can be used as a mainstay treatment of AKC to control signs and symptoms over a long period of time and also prevent the progression of this disease.

Detailed Description
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Atopic keratoconjunctivitis (AKC) is a rare type of ocular allergy that is often associated with eczema. Over time, the complications from this disease process lead to loss of vision due to continual scarring of the corneal surface. The pathophysiology of AKC has not been fully elucidated, and the triggers are still unknown. Corticosteroids are very effective in controlling the acute symptoms of AKC. However, two thirds of patients managed with a combination of oral antihistamine, topical mast cell stabilizer, and intermittent topical steroid regimen eventually developed significant keratopathy and vision loss. Additionally, there are many side effects of corticosteroids, including local immunosuppression, cataract formation, and increased risk of glaucoma. Cyclosporin A is an immunomodulator that specifically inhibits T lymphocytes by blocking the expression of the interleukin-2 receptor. It also blocks the release of inflammatory mediators from mast cells and eosinophils. Cyclosporin has no known side effects except for burning upon instillation, and safe to use over long-term . The investigators have demonstrated that a 0.05% ophthalmic emulsion of cyclosporine has been shown to be effective at improving the ocular signs and symptoms of AKC over short-term. However, the long-term efficacy of cyclosporine A in slowing the natural history of AKC and possible steroid sparing effects have not been assessed. The investigators hypothesize that cyclosporine A can be used as a mainstay treatment of AKC to control signs and symptoms over a long period of time and also prevent the progression of this disease.

Official Title
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Long-term Results of Topical Cyclosporine 0.05% in the Treatment of Atopic Keratoconjunctivitis

Conditions
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Atopic Keratoconjunctivitis

Intervention / Treatment
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* Drug: Cyclosporin 0.05% ophthalmic


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patient has known diagnosis of atopic keratoconjunctivitis Patient has been on cyclosporine 0.05% eye drops for control of atopic keratoconjunctivitis Patient has been followed up for at least for 1 year Patient is able to give informed consent Patient is able to tolerate a full ophthalmic exam Exclusion Criteria: Patient has any other diagnosis (i.c. vernal keratoconjunctivitis, giant papillary conjunctivitis) that may alter the clinical appearance or behavior of their ocular surface)

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Cyclosporine 0.05% ophthalmic<br>cyclosporine 0.05% ophthalmic eye drops will be used starting with 1 drop in both eyes 6 times daily for first month, followed by 1 drop in both eyes 4 times daily for the following month, then will be adjusted by clinician as needed for appropriate disease control | Drug: Cyclosporin 0.05% ophthalmic<br>* Cyclosporine 0.05% ophthalmic solution, 1 drop 6 times in both eyes daily for first month, then 1 drop 4 times in both eyes daily for next month, then dosage was adjusted based on clinical disease by investigator.<br>* Other names: Restasis;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Ocular Symptoms and Signs Total Composite Score | Symptoms (itching, tearing, discomfort, discharge, photophobia) and signs (Bulbar conjunctival hyperemia, upper tarsal conjunctival papillae, punctate keratitis, corneal neovascularization, cicatrizing conjunctivitis, and blepharitis) evaluated on a 4 point scale of 0-3, with a minimum symptom score of 0- maximum 15, and sign score minimum 0- maximum 18. These scores are combined to yeild a total composite score of signs and symptoms of minimum 0-maximum 33. The highest score would indicate the most severe case of Atopic Keratoconjunctivitis (AKC). The composite score is reported. | Baseline and 8 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Corticosteroid Usage | Number of flare-ups requiring topical steroid-use across all participants over the entire 12 month follow-up period | Entire follow-up period (Approximately 12 months) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Atopic, Keratoconjunctivitis, Restasis, Cyclosporine