Atopic Keratoconjunctivitis
Conditions
Keywords
Atopic, Keratoconjunctivitis, Restasis, Cyclosporine
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.
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.
Interventions
DRUGCyclosporin 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.
Sponsors
Johns Hopkins University
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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 |
Countries
United States
Participant flow
Recruitment details
Patients were recruited from the PI's medical clinic.
Pre-assignment details
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.
Participants by arm
| Arm | Count |
|---|---|
| Cyclosporine 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 | 12 |
| Total | 12 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Lost to Follow-up | 2 |
Baseline characteristics
| Characteristic | Cyclosporine |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 0 Participants |
| Age, Categorical Between 18 and 65 years | 12 Participants |
| Age, Continuous | 41 years STANDARD_DEVIATION 12.6 |
| Region of Enrollment United States | 12 participants |
| Sex: Female, Male Female | 6 Participants |
| Sex: Female, Male Male | 6 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 12 |
| other Total, other adverse events | 0 / 12 |
| serious Total, serious adverse events | 0 / 12 |
Outcome results
Primary
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.
Time frame: Baseline and 8 weeks
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| Patients With Steroid Resistant/ Dependant AKC. | Ocular Symptoms and Signs Total Composite Score | Baseline | 29.1 units on a scale |
| Patients With Steroid Resistant/ Dependant AKC. | Ocular Symptoms and Signs Total Composite Score | 8 weeks | 4.7 units on a scale |
p-value: 0.002Wilcoxon (Mann-Whitney)
Secondary
Corticosteroid Usage
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)
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Patients With Steroid Resistant/ Dependant AKC. | Corticosteroid Usage | 3 Total number of flare-up episodes |