Long-term Topical Cyclosporine for Atopic Keratoconjunctivitis

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

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 Overview

• Status: Completed
• Conditions: Atopic Keratoconjunctivitis
• Intervention / Treatment: Drug: Cyclosporin 0.05% ophthalmic

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 Type: Interventional
• Enrollment (Actual): 12
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • Maryland
    • Baltimore, Maryland, United States, 21287
      • Johns Hopkins Hospital - Wilmer Eye Institute

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: NA
• Interventional Model: SINGLE_GROUP
• Masking: NONE

Number of Arms

1

Arms and Interventions

Participant Group / 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 Names: Restasis

What is the study measuring?

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)

Collaborators and Investigators

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

Publications and helpful links

General 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. doi: 10.1016/j.ophtha.2003.05.035.

Study record dates

Study Major Dates

• Study Start: August 1, 2007
• Primary Completion (ACTUAL): September 1, 2009
• Study Completion (ACTUAL): September 1, 2009

Study Registration Dates

• First Submitted: September 30, 2009
• First Submitted That Met QC Criteria: September 30, 2009
• First Posted (ESTIMATE): October 1, 2009

Study Record Updates

• Last Update Posted (ACTUAL): April 2, 2018
• Last Update Submitted That Met QC Criteria: March 6, 2018
• Last Verified: March 1, 2018

More Information

Terms related to this study

• Keywords: Cyclosporine; Keratoconjunctivitis; Restasis; Atopic
• Additional Relevant MeSH Terms: Eye Diseases; Conjunctivitis; Conjunctival Diseases; Keratitis; Corneal Diseases; Keratoconjunctivitis; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Enzyme Inhibitors; Antirheumatic Agents; Immunosuppressive Agents; Immunologic Factors; Dermatologic Agents; Antifungal Agents; Calcineurin Inhibitors; Cyclosporine; Cyclosporins
• Other Study ID Numbers: NA_00010864