Clinical trial NCT04976816: Local Betamethasone Versus Triamcinolone Injection in Management of Thyroid Eye Disease
Official title: Local Betamethasone Versus Triamcinolone Injection in Management of Thyroid-Related Upper Lid Retraction With and Without Proptosis
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
PHASE3
Conditions: Thyroid Eye Disease
Lead sponsor: Assiut University
Sponsor class: OTHER
First posted: 2021-07-26
Enrollment: 92
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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: 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.

Eligibility criteria: 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.

Primary outcomes:
measure: to measure the change in MRD1 in mm using slit lamp biomicroscope in all groups after peri-levator injection of different types of steroid
timeFrame: 2 minutes
measure: to measure the change in proptosis in mm using Hertel's exophthalmometer in group B after retrobulbar injection of different types of steroid
timeFrame: 4 minutes
Secondary outcomes:
measure: to document any change in size of superior rectus levator complex and other extra-ocular muscles
timeFrame: 4 minutes
Other outcomes:
Locations:
city: Assiut
country: Egypt
facility: Assiut university
Study officials:
affiliation: Assiut University
name: Ahmed Abdelal, MD
role: STUDY_CHAIR
affiliation: Assiut University
name: Mohamed Shehata, MD
role: STUDY_DIRECTOR
affiliation: Assiut University
name: Salma Kedwany, MD
role: STUDY_DIRECTOR
References:
citation: De Leo S, Lee SY, Braverman LE. Hyperthyroidism. Lancet. 2016 Aug 27;388(10047):906-918. doi: 10.1016/S0140-6736(16)00278-6. Epub 2016 Mar 30.
citation: Taylor PN, Albrecht D, Scholz A, Gutierrez-Buey G, Lazarus JH, Dayan CM, Okosieme OE. Global epidemiology of hyperthyroidism and hypothyroidism. Nat Rev Endocrinol. 2018 May;14(5):301-316. doi: 10.1038/nrendo.2018.18. Epub 2018 Mar 23.
citation: Bartalena L, Baldeschi L, Boboridis K, Eckstein A, Kahaly GJ, Marcocci C, Perros P, Salvi M, Wiersinga WM; European Group on Graves' Orbitopathy (EUGOGO). The 2016 European Thyroid Association/European Group on Graves' Orbitopathy Guidelines for the Management of Graves' Orbitopathy. Eur Thyroid J. 2016 Mar;5(1):9-26. doi: 10.1159/000443828. Epub 2016 Mar 2.
citation: Kazim M, Gold KG. A review of surgical techniques to correct upper eyelid retraction associated with thyroid eye disease. Curr Opin Ophthalmol. 2011 Sep;22(5):391-3. doi: 10.1097/ICU.0b013e3283499433.
citation: Xu D, Liu Y, Xu H, Li H. Repeated triamcinolone acetonide injection in the treatment of upper-lid retraction in patients with thyroid-associated ophthalmopathy. Can J Ophthalmol. 2012 Feb;47(1):34-41. doi: 10.1016/j.jcjo.2011.12.005.
citation: Hamed-Azzam S, Mukari A, Feldman I, Saliba W, Jabaly-Habib H, Briscoe D. Fornix triamcinolone injection for thyroid orbitopathy. Graefes Arch Clin Exp Ophthalmol. 2015 May;253(5):811-6. doi: 10.1007/s00417-015-2957-7. Epub 2015 Feb 12.
citation: Joos ZP, Sullivan TJ. Peri-levator palpebrae superioris triamcinolone injection for the treatment of thyroid eye disease-associated upper eyelid retraction. Clin Exp Ophthalmol. 2017 Aug;45(6):651-652. doi: 10.1111/ceo.12939. Epub 2017 Mar 28. No abstract available.
citation: Poonyathalang A, Preechawat P, Charoenkul W, Tangtrakul P. Retrobulbar injection of triamcinolone in thyroid associated orbitopathy. J Med Assoc Thai. 2005 Mar;88(3):345-9.
citation: Bagheri A, Abbaszadeh M, Yazdani S. Intraorbital Steroid Injection for Active Thyroid Ophthalmopathy. J Ophthalmic Vis Res. 2020 Feb 2;15(1):69-77. doi: 10.18502/jovr.v15i1.5948. eCollection 2020 Jan-Mar.
citation: Wang Y, Du B, Yang M, Zhu Y, He W. Peribulbar injection of glucocorticoids for thyroid-associated ophthalmopathy and factors affecting therapeutic effectiveness: A retrospective cohort study of 386 cases. Exp Ther Med. 2020 Sep;20(3):2031-2038. doi: 10.3892/etm.2020.8896. Epub 2020 Jun 17.
citation: Smith TJ, Hegedus L. Graves' Disease. N Engl J Med. 2016 Oct 20;375(16):1552-1565. doi: 10.1056/NEJMra1510030. No abstract available.