The Effect of Intravenous Glucocorticoids on the Tearfilm in Eyes With Thyroid-associated Ophthalmopathy

Study Overview
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Brief Summary
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Thyroid-associated ophthalmopathy (TAO), also called Graves' ophthalmopathy or thyroid eye disease, is a common orbital disease in adults. Patients with TAO, especially in its active phase, often complain about symptoms of ocular surface discomfort, including excess tearing, gritty sensation, increased sensitivity to light and foreign-body sensation, which are similar to inflammatory ocular surface disorders such as dry-eye syndrome (DES). Incomplete blink, increased proptosis and greater palpebral fissure width in TAO accelerates tear evaporation, which increases the tear fluid's osmolarity, and results in ocular surface damage. The administration of intravenous glucocorticoids can be an effective treatment for TAO. The rationale of the present study is to assess the effect of intravenously administered glucocorticoids on the signs of DES in patients with TAO with new methods such as measurement of tear film thickness, tear film osmolarity and scattering of the tear film and well established methods for assessment of the severity of DES. Additionally, impression cytology and determination of tear cytokines/chemokines will be performed to obtain information about inflammatory processes on the ocular surface.

Official Title
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The Effect of Intravenous Glucocorticoids on the Tearfilm in Eyes With Thyroid-associated Ophthalmopathy

Conditions
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Thyroid-associated Ophthalmopathy, Dry Eye Syndrome

Intervention / Treatment
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* Drug: Methylprednisolone
* Drug: Esomeprazole


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Men and women aged over 18 years Active thyroid associated ophthalmopathy with clinical activity score (CAS) of each eye more than 3 or recently experienced worsening of proptosis, lid retraction, or ocular motility disturbance. Normal ophthalmic findings except symptoms associated with TAO Scheduled for treatment with systemic glucocorticoids according to the kahaly-scheme Exclusion Criteria: Chronic inactive TAO Previous treatment with oral or intravenous glucocorticoids 3 months preceding the study Participation in a clinical trial in the 3 weeks before the screening visit Symptoms of a clinically relevant illness in the 3 weeks before the first study day Presence or history of a severe medical condition that will interfere with the study aim as judged by the clinical investigator Wearing of contact lenses Intake of dietary supplements in the 3 months preceding the study Topical treatment with any ophthalmic drug in the 4 weeks preceding the study except topical lubricants Ocular infection Ocular surgery in the 3 months preceding the study Sjögren's syndrome Stevens-Johnson syndrome Pregnancy, planned pregnancy or lactating

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: Patients<br>Patients with moderate to severe thyroid-associated ophthalmopathy | Drug: Methylprednisolone<br>* 500mg i.v. infusion once a week for 6 weeks followed by 250mg i.v. infusion once a week for 6 weeks<br>Drug: Esomeprazole<br>* 40mg i.v. infusion once a week for 12 weeks<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Tear film thickness as measured with OCT | Measurements of tear film thickness with OCT will be performed 7 or less days before start of treatment, 6 weeks after start of treatment and 12 weeks after start of treatment | 13 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Break up time (BUT) |  | 13 weeks | 
| Visual acuity |  | 13 weeks | 
| Tear film osmolarity |  | 13 weeks | 
| Degree of exophthalmia | Hertel exophthalmometry | 13 weeks | 
| Palpebral fissure width |  | 13 weeks | 
| OSI (Objective Scattering Index) |  | 13 weeks | 
| Tear cytokines/chemokines |  | 13 weeks | 
| Impression cytology |  | 13 weeks | 
| Staining of the cornea with fluorescein |  | 13 weeks | 
| Schirmer I test |  | 13 weeks | 
| Subjective symptoms of dry eye syndrome |  | 13 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Methylprednisolone, Dry Eye Syndrome, Tear Film, Thyroid-associated ophthalmopathy