Long-term Topical Cyclosporine for Atopic Keratoconjunctivitis

• ClinicalTrials.gov Identifier: NCT00987467
• Recruitment Status: Completed
• First Posted: October 1, 2009
• Results First Posted: October 8, 2013
• Last Update Posted: April 2, 2018
• Sponsor: Johns Hopkins University
• Information provided by (Responsible Party): Johns Hopkins University

Study Description

Brief Summary:

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.

Condition or disease	Intervention/treatment	Phase
Atopic Keratoconjunctivitis	Drug: Cyclosporin 0.05% ophthalmic	Not Applicable

Detailed Description:

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.

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 12 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Long-term Results of Topical Cyclosporine 0.05% in the Treatment of Atopic Keratoconjunctivitis
• Study Start Date: August 2007
• Actual Primary Completion Date: September 2009
• Actual Study Completion Date: September 2009

Arms and Interventions

Arm	Intervention/treatment
Experimental: Cyclosporine 0.05% ophthalmic; 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; 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.; Other Name: Restasis

Outcome Measures

Primary Outcome Measures :

1. Ocular Symptoms and Signs Total Composite Score [ Time Frame: Baseline and 8 weeks ]
   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.

Secondary Outcome Measures :

1. Corticosteroid Usage [ Time Frame: Entire follow-up period (Approximately 12 months) ]
   Number of flare-ups requiring topical steroid-use across all participants over the entire 12 month follow-up period

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

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)

Contacts and Locations

Locations

United States, Maryland

Johns Hopkins Hospital - Wilmer Eye Institute

Baltimore, Maryland, United States, 21287

Sponsors and Collaborators

Johns Hopkins University

Investigators

• Principal Investigator: Esen K Akpek, MD; Johns Hopkins Hospital - Wilmer Eye Institute

More Information

Publications:

Akpek EK, Dart JK, Watson S, Christen W, Dursun D, Yoo S, O'Brien TP, Schein OD, Gottsch JD. A randomized trial of topical cyclosporin 0.05% in topical steroid-resistant atopic keratoconjunctivitis. Ophthalmology. 2004 Mar;111(3):476-82.

• Responsible Party: Johns Hopkins University
• ClinicalTrials.gov Identifier: NCT00987467
• Other Study ID Numbers: NA_00010864
• First Posted: October 1, 2009
• Results First Posted: October 8, 2013
• Last Update Posted: April 2, 2018
• Last Verified: March 2018

Keywords provided by Johns Hopkins University:

Atopic; Keratoconjunctivitis; Restasis; Cyclosporine

Additional relevant MeSH terms:

Keratoconjunctivitis; Conjunctivitis; Conjunctival Diseases; Eye Diseases; Keratitis; Corneal Diseases; Cyclosporine; Cyclosporins; Enzyme Inhibitors; Molecular Mechanisms of Pharmacological Action; Immunosuppressive Agents; Immunologic Factors; Physiological Effects of Drugs; Antifungal Agents; Anti-Infective Agents; Dermatologic Agents; Antirheumatic Agents; Calcineurin Inhibitors