Overview

The primary objective of this clinical trial is to assess the safety and tolerability of sub-tenon aflibercept in combination with either saline or hyaluronidase (HA) in patients with acute Thyroid Eye Disease (TED) as assessed by the incidence and severity of adverse events from baseline to day 45.

Participants will undergo clinical examinations and receive three injections of aflibercept with saline, aflibercept with hyaluronidase, or hyaluronidase.

Eligibility

Inclusion Criteria:

1. Minimum of 18 years-old
2. Active Thyroid Eye Disease
3. Clinical Activity Score (CAS) between 3 and 5, inclusive
4. Phakic and pseudophakic eyes are allowed in the study.
5. Willing and able to provide written informed consent after the nature of the study has been explained, and prior to any research-related procedures
6. Willing and able to comply with clinic visits and study-related procedures
7. Only one eye will be enrolled. The worse eye (demonstrating any of these features:

        worse HVF results, worse restricted motility, worse visual acuity, worse edema, worse
        proptosis, worse eyelid retraction) will be enrolled. If both eyes are equivalent, we will
        enroll the non-dominant eye.
        Exclusion Criteria:
          1. History of orbital, strabismus, or eyelid surgery or orbital radiation
          2. Optic neuropathy or other vision-threatening signs
          3. Patients currently on systemic or topical steroids. If they received steroids in the
             past, they would require a 6 week washout period and the cumulative dose of steroids
             must be less than 1 gram of methylprednisolone (or equivalent). During the washout
             period we will contact patients by phone weekly to monitor their safety and address
             any concerns they may have related to no longer taking steroids .
          4. Patients who have taken teprotumumab (Tepezza.)
          5. Patients who have received intraocular anti-VEGF medications within 1 year of
             screening
          6. Patients who have a history of receiving systemic anti-VEGF
          7. Presence of other retinal vascular diseases (diabetic retinopathy, vein occlusion)
             that could affect the VEGF levels within the eye
          8. History of stroke or prior myocardial infarction
          9. Known hypersensitivity to aflibercept
         10. Infectious conjunctivitis, keratitis, or endophthalmitis of either eye
         11. Presence of a glaucoma shunting or filtration device that is subconjunctival
         12. Previous participation in any studies of investigational drugs within 1 month
             preceding Day 0
         13. Any clinically significant acute or chronic medical condition that would preclude
             participation in a clinical study
         14. Pregnant or breast-feeding women
         15. Sexually active men or women of childbearing potential* who are unwilling to
             practice adequate contraception during the study (adequate contraceptive measures
             include stable use of oral contraceptives or other prescription pharmaceutical
             contraceptives for 2 or more menstrual cycles prior to screening; intrauterine device
             [IUD]; bilateral tubal ligation; vasectomy; condom plus contraceptive sponge, foam, or
             jelly, or diaphragm plus contraceptive sponge, foam, or jelly)
         16. History of hyaluronidase (HA) injection after the diagnosis of thyroid eye disease
         17. Taking part in other research studies in the past 12 months that have involved
             radiation exposure
         18. Participated in other research studies in the past 12 months that required radiologic
             imaging (particularly CT scans and not MRIs)