Long-term Topical Cyclosporine for Atopic Keratoconjunctivitis
Study Details
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 |
|---|---|---|
|
N/A |
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
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 Names:
|
Outcome Measures
Primary Outcome Measures
- Ocular Symptoms and Signs Total Composite Score [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
- Corticosteroid Usage [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
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
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | 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
Study Documents (Full-Text)
None provided.More Information
Publications
- NA_00010864
Study Results
Participant Flow
| Recruitment Details | Patients were recruited from the PI's medical clinic. |
|---|---|
| Pre-assignment Detail | Patients started with a conjunctival biopsy prior to enrolling in the study. Following biopsy, for one week, patients were discontinued on antiinflammatories and given only topical antibiotic prior to the study treatment of topical cyclosporin. |
| Arm/Group Title | Cyclosporine |
|---|---|
| Arm/Group Description | Patients with atopic keratoconjunctivitis were started with cyclosporine 0.05% ophthalmic eye drops, 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 adjusted by clinician as needed for appropriate disease control. Cyclosporins : Cyclosporine 0.05% ophthalmic solution, 6 times in both eyes daily for first month, then 4 times in both eyes daily for next month, then dosage was adjusted based on clinical disease by investigator |
| Period Title: Overall Study | |
| STARTED | 12 |
| COMPLETED | 10 |
| NOT COMPLETED | 2 |
Baseline Characteristics
| Arm/Group Title | Cyclosporine |
|---|---|
| Arm/Group Description | Patients with atopic keratoconjunctivitis were started with cyclosporine 0.05% ophthalmic eye drops, 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 adjusted by clinician as needed for appropriate disease control. Cyclosporins : Cyclosporine 0.05% ophthalmic solution, 6 times in both eyes daily for first month, then 4 times in both eyes daily for next month, then dosage was adjusted based on clinical disease by investigator |
| Overall Participants | 12 |
| Age (Count of Participants) | |
| <=18 years |
0
0%
|
| Between 18 and 65 years |
12
100%
|
| >=65 years |
0
0%
|
| Age (years) [Mean (Standard Deviation) ] | |
| Mean (Standard Deviation) [years] |
41
(12.6)
|
| Sex: Female, Male (Count of Participants) | |
| Female |
6
50%
|
| Male |
6
50%
|
| Region of Enrollment (participants) [Number] | |
| United States |
12
100%
|
Outcome Measures
| Title | Ocular Symptoms and Signs Total Composite Score |
|---|---|
| Description | 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. |
| Time Frame | Baseline and 8 weeks |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title | Patients With Steroid Resistant/ Dependant AKC. |
|---|---|
| Arm/Group Description | Ten patients with significant AKC either steroid dependent or resistant who were having active inflammation were enrolled in this study. |
| Measure Participants | 10 |
| Baseline |
29.1
|
| 8 weeks |
4.7
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Patients With Steroid Resistant/ Dependant AKC. |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.002 |
| Comments | ||
| Method | Wilcoxon (Mann-Whitney) | |
| Comments | ||
| Title | Corticosteroid Usage |
|---|---|
| Description | Number of flare-ups requiring topical steroid-use across all participants over the entire 12 month follow-up period |
| Time Frame | Entire follow-up period (Approximately 12 months) |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title | Topical Steroid Resistant/Dependant AKC |
|---|---|
| Arm/Group Description | Patients with topical steroid resistant or dependant AKC were used for this study. |
| Measure Participants | 10 |
| Number [Total number of flare-up episodes] |
3
|
Adverse Events
| Time Frame | ||
|---|---|---|
| Adverse Event Reporting Description | ||
| Arm/Group Title | Cyclosporine | |
| Arm/Group Description | Patients with atopic keratoconjunctivitis were started with cyclosporine 0.05% ophthalmic eye drops, 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 adjusted by clinician as needed for appropriate disease control. Cyclosporins : Cyclosporine 0.05% ophthalmic solution, 6 times in both eyes daily for first month, then 4 times in both eyes daily for next month, then dosage was adjusted based on clinical disease by investigator | |
All Cause Mortality |
||
| Cyclosporine | ||
| Affected / at Risk (%) | # Events | |
| Total | 0/12 (0%) | |
Serious Adverse Events |
||
| Cyclosporine | ||
| Affected / at Risk (%) | # Events | |
| Total | 0/12 (0%) | |
Other (Not Including Serious) Adverse Events |
||
| Cyclosporine | ||
| Affected / at Risk (%) | # Events | |
| Total | 0/12 (0%) | |
Limitations/Caveats
More Information
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
Results Point of Contact
| Name/Title | Esen Akpek, MD, Associate Professor of Ophthalmology, Wilmer Eye Institute |
|---|---|
| Organization | Johns Hopkins University, Wilmer Eye Institute |
| Phone | 410-955-5214 |
| esakpek@jhmi.edu |
- NA_00010864