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

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.

Study Overview

• Status: Completed
• Conditions: Dry Eye Syndrome; Thyroid-associated Ophthalmopathy
• Intervention / Treatment: Drug: Methylprednisolone; Drug: Esomeprazole

• Study Type: Interventional
• Enrollment (Actual): 18
• Phase: Phase 3

Contacts and Locations

Study Locations

• Austria
  • Vienna, Austria, 1090
    • Department of Clinical Pharmacology, Medical University of Vienna

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:

• 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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Patients; Patients with moderate to severe thyroid-associated ophthalmopathy	Drug: Methylprednisolone; 500mg i.v. infusion once a week for 6 weeks followed by 250mg i.v. infusion once a week for 6 weeks; Drug: Esomeprazole; 40mg i.v. infusion once a week for 12 weeks

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Medical University of Vienna

Study record dates

Study Major Dates

• Study Start (Actual): June 27, 2013
• Primary Completion (Actual): May 18, 2017
• Study Completion (Actual): May 18, 2017

Study Registration Dates

• First Submitted: April 13, 2012
• First Submitted That Met QC Criteria: April 16, 2012
• First Posted (Estimate): April 18, 2012

Study Record Updates

• Last Update Posted (Actual): February 20, 2020
• Last Update Submitted That Met QC Criteria: February 19, 2020
• Last Verified: February 1, 2020

More Information

Terms related to this study

• Keywords: Methylprednisolone; Dry Eye Syndrome; Tear Film; Thyroid-associated ophthalmopathy
• Additional Relevant MeSH Terms: Immune System Diseases; Autoimmune Diseases; Endocrine System Diseases; Genetic Diseases, Inborn; Eye Diseases, Hereditary; Graves Disease; Exophthalmos; Orbital Diseases; Goiter; Hyperthyroidism; Lacrimal Apparatus Diseases; Keratoconjunctivitis; Conjunctivitis; Conjunctival Diseases; Keratitis; Corneal Diseases; Eye Diseases; Graves Ophthalmopathy; Thyroid Diseases; Dry Eye Syndromes; Keratoconjunctivitis Sicca; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Autonomic Agents; Peripheral Nervous System Agents; Enzyme Inhibitors; Anti-Inflammatory Agents; Antineoplastic Agents; Antiemetics; Gastrointestinal Agents; Glucocorticoids; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Antineoplastic Agents, Hormonal; Neuroprotective Agents; Protective Agents; Anti-Ulcer Agents; Proton Pump Inhibitors; Prednisolone; Methylprednisolone Acetate; Methylprednisolone; Methylprednisolone Hemisuccinate; Prednisolone acetate; Prednisolone hemisuccinate; Prednisolone phosphate; Esomeprazole
• Other Study ID Numbers: OPHT-120312

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No