Local Betamethasone Versus Triamcinolone Injection in Management of Thyroid Eye Disease

Study Overview
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Brief Summary
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To compare the efficacy of local injections of two different types of steroid (betamethasone suspension versus triamcinolone acetate) in management of patients with thyroid-related upper lid retraction either isolated or associated with proptosis.

Detailed Description
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Thyroid Eye Disease (TED) is a complex autoimmune disorder that causes substantial morbidity. It can result in enlargement and scarring of orbital fat and muscles with orbital disfigurement, diplopia, and even vision loss. Although the disease is self-limited following an inflammatory phase of 12 - 18 months, its long-term changes to periocular tissues may have a significant effect on the quality of life, mental health, and socioeconomic status of patients. Most patients with TED (>90%) have Graves' disease, which is an inflammatory autoimmune condition that is caused by thyrotropin (TSH) receptor autoantibodies. Graves' disease is common around the world and it mainly affects middle-aged women with an overall prevalence of 0.5%. Several validated assessment scores are used to assess different components of the disease. The two main current TED classifications are from the European Group on Graves Orbitopathy (EUGOGO); and Vision, Inflammation, Strabismus, Appearance (VISA). EUGOGO has introduced one score for clinical activity (CAS) and one for severity Clinical Severity Score (CSS). The baseline CAS asses 7 subjective symptoms and inflammatory signs with 3 additional points in follow-up for increased proptosis, decreased ocular motility, or decreased visual acuity (the CAS 10- point scale). In comparison, CSS evaluates the magnitude of the exophthalmometer or proptosis values, lid retraction, diplopia grades, and corneal involvement. Periorbital inflammation can cause swelling, fatty infiltration, and scarring of the eyelid muscles, resulting in eyelid retraction and upper scleral exposure, which are the most common clinical features of TED. Several treatment options have been described for correction of eyelid retraction (ELR), including local steroid, Botox and filler injection, and surgeries in the fibrotic stage. Although surgical treatment remains an effective option, the outcomes may be unpredictable. In addition, there are some situations where surgery is inappropriate or contraindicated, where temporary or definitive measures are required during the active phase of the disease, or where patients may prefer less invasive options. Systemic steroid therapy is a well-established form of immunosuppressive treatment for TED. There have been reports showing promising results with local steroid injection for the treatment of upper eyelid retraction (UER), There are also some reports about the retrobulbar and periocular injection of steroids for management of proptosis in TED.

Official Title
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Local Betamethasone Versus Triamcinolone Injection in Management of Thyroid-Related Upper Lid Retraction With and Without Proptosis

Conditions
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Thyroid Eye Disease

Intervention / Treatment
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* Procedure: peri-levator betamethasone injection
* Procedure: peri-levator triamcinolone injection
* Procedure: peri-levator and retrobulbar betamethasone injection
* Procedure: peri-levator and retrobulbar triamcinolone injection


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Clinical diagnosis of Thyroid Eye Disease. Thyroid function within normal range. Exclusion Criteria: Patients on systemic steroid and or immunosuppressive therapy. Patients underwent thyroidectomy. Sight threatening (severe) TED which requires immediate surgery. Patients with fibrotic ocular muscles who need surgery. Contraindications to steroid therapy as in pregnant women.

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
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: A1 peri-levator betamethasone injection<br>patients with isolated thyroid-related upper lid retraction who will be given the Peri-levator injection of betamethasone suspension | Procedure: peri-levator betamethasone injection<br>* The injection dose was 1 ml of betamethasone suspension (1 ml contains 5 mg betamethasone dipropionate &2 mg betamethasone sodium phosphate). The needle was introduced percutaneously superior to the globe and advanced towards the orbital roof to a depth of approximately 15 mm where the injection was delivered. The injection was repeated every 4 weeks according to the clinical response up to 5 injections.<br>|
| Experimental: A2 Peri-levator triamcinolone acetate injection<br>patients with isolated thyroid-related upper lid retraction who will be given Peri-levator injection of triamcinolone acetate | Procedure: peri-levator triamcinolone injection<br>* The needle was introduced percutaneously superior to the globe and advanced towards the orbital roof to a depth of approximately 15 mm where 1ml (40mg/ml) triamcinolone acetate was injected. The injection was repeated every 4 weeks according to the clinical response up to 5 injections.<br>|
| Experimental: B1 Peri-levator and retrobulbar betamethasone injection<br>patients with thyroid-related upper lid retraction and proptosis who will be given Peri-levator and retrobulbar injection of betamethasone suspension | Procedure: peri-levator and retrobulbar betamethasone injection<br>* In addition to peri-levator betamethasone injection for UER, a retrobulbar injection for proptosis was given with the needle introduced through the skin of the lateral one-third of the lower eyelid and passed posteriorly, medially, and upward to reach the retrobulbar space.<br>|
| Experimental: B2 Peri-levator and retrobulbar triamcinolone acetate injection<br>patients with thyroid-related upper lid retraction and proptosis who will be given Peri-levator and retrobulbar injection of triamcinolone acetate | Procedure: peri-levator and retrobulbar triamcinolone injection<br>* In addition to peri-levator triamcinolone injection for UER, a retrobulbar injection for proptosis was given with the needle introduced through the skin of the lateral one-third of the lower eyelid and passed posteriorly, medially, and upward to reach the retrobulbar space.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| to measure the change in MRD1 in mm using slit lamp biomicroscope in all groups after peri-levator injection of different types of steroid | The technique was considered; 1) Effective if the MRD1 reached the normal value< or= 4.5mm, 2) Partially effective if the MRD1 was improved but did not reach the normal values, 3) Ineffective if no improvement occured in MRD1 | 2 minutes | 
| to measure the change in proptosis in mm using Hertel's exophthalmometer in group B after retrobulbar injection of different types of steroid | The technique will be considered; 1) Effective if the reading of Hertel's exophthalmometer reached the normal value (16±2mm), 2) Partially effective if the proptosis was improved but did not reach the normal values, 3) Ineffective of no improvement occured in proptosis | 4 minutes | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| to document any change in size of superior rectus levator complex and other extra-ocular muscles | measuring size of superior rectus levator complex and other extra-ocular muscles before and after injections by orbital imaging techniques (CT or MRI). | 4 minutes |