Thyroid Eye Disease Overview and Treatment
Jennifer Duran
UAG School of Medicine – MS4
September 2022
Thyroid Eye Disease
Thyroid eye disease, or TED, is an autoimmune disorder in which there is a progressive
inflammation of the extraocular muscles and fatty and connective tissue resulting in
the enlargement of these structures. This results in protrusion of the eyes or “exophthalmos”.
This condition has two phases. The first is the active or inflammatory phase, which can last anywhere from 6 to 36 months. Symptoms typically include dry eyes, orbital or ocular surface pain, periorbital swelling, and eyelid retraction. Some
patients experience proptosis, diplopia, and vision loss. The second phase is the inactive or
chronic phase in which TED no longer progresses, but tissue damage and symptoms persist. This
phase is characterized by fibrosis, along with permanent disfigurement and functional vision
loss.
About 90% of TED cases are associated with hyperthyroidism (overactive thyroid), and
approximately 10% of patients either have a normal-functioning thyroid (euthyroid) or an
underactive thyroid (hypothyroidism, i.e. Hashimoto’s thyroiditis). Environmental risk factors
for TED include cigarette smoking, which is the most consistently linked risk factor, or exposure
to secondhand smoke; stress; and history of radioactive iodine treatment for thyroid
dysfunction. Genetic risk factors include a family history of TED or another autoimmune disease
such as type I diabetes or rheumatoid arthritis. Additionally, the risk for TED increases if the
patient has other autoimmune diseases. TED is five times more common in women than men.
The exact prevalence is unknown, but it is estimated to be 16 per 100,000 women in the
general population, with 2.9 per 100,000 men. The average age is 43 years for all patients,
ranging from the ages of 8 to 88. People over the age of 50 have the worst prognosis overall.
The underlying mechanisms of TED are not fully understood, but it is postulated that
orbital fibroblasts are activated by Graves’ disease-related autoantibodies. In people with
Graves’ disease, the immune system produces an abnormal antibody called thyroid-stimulating
immunoglobulin, which imitates the action of thyroid-stimulating hormone. T-cells interact with
CD40 receptors that are found on orbital fibroblasts and activate pro-inflammatory cytokines,
synthesizing glycosaminoglycans (GAGs) and hyaluronic acid. The orbital fibroblasts can
differentiate into adipocytes or myofibroblasts. Patients with TED have an overexpression of a
protein called insulin-like growth factor 1 receptor (IGF-1R).
The diagnosis of TED depends on characteristic symptoms, a detailed patient history, a
thorough clinical evaluation, and a variety of specialized tests. A complete eye exam can
determine the degree of proptosis and displacement. Typical symptoms of TED include
photophobia, lacrimation, dry eyes, discomfort, gritty sensations, and forward protrusion of the
eye. In more advanced cases of TED, patients experience orbital pain, diplopia, or blurred
vision. Thyroid function tests can help determine the underlying cause of TED, and A-scan and
B-scan transocular echograms assess the orbital structures and enlarged recti muscle. Imaging
that can be performed to diagnose TED includes a CT, or computed tomography, scan and an
MRI, or magnetic resonance imaging. A CT scan has several functions: it determines whether
the optic nerve is compressed by inflamed, enlarged muscles in the eye; differentiates between
normal and abnormal structures of different tissue densities; and examines the relationship
between the optic nerve and muscles at the apex. An MRI determines enlargement of the
rectus and orbital fat expansion and evaluates water content in the muscles and other soft
tissues.
There are numerous conservative and surgical treatments for TED. Conservative
treatments include lifestyle modifications such as smoking cessation; restricting sodium to
decrease water retention and tissue edema; oral NSAIDs for periocular pain; selenium, which is
an over-the-counter supplement and a mineral typically found in soil; and elevating the head of
the bed while sleeping to reduce orbital edema. For corneal exposure, lubricants, taping, and
protective shields may be used, and if necessary, tarsorrhaphy may be performed. For diplopia,
Fresnel prisms may be used or occlusion therapy may be done. Teprotumumab (brand name
Tepezza) is the first and only FDA-approved prescription drug for TED. Its function is to inhibit
the activation and signaling of the insulin-like growth factor-1 protein and helps with proptosis
and diplopia. Corticosteroids are useful in reducing orbital inflammation. A common
corticosteroid is oral prednisone in a dose of 1 – 1.5 mg/kg given for a maximum of 2 months,
with prednisolone as an alternative. To decrease inflammation, orbital radiation can be
performed individually or together with corticosteroids.
One surgical option for TED is orbital decompression, which enlarges the existing space
of the orbit through partial removal of bony walls, allowing the eye to fall back into its natural
position within the eye socket. A second surgical option is strabismus surgery, but this
procedure should only be considered after the completion of orbital decompression and
stabilization of muscle alignment. Another surgical option is eyelid retraction repair and
tarsorrhaphy for eyelid retraction or exposure keratitis.
There are various medications that are being investigated for TED, with some in clinical
trials, but more research needs to be conducted in order to establish their long-term safety and
effectiveness. These medications include tocilizumab, rituximab, and mycophenolate mofetil. A
therapy for TED that is being researched is orbital radiation therapy, which is directed toward
the eye socket and uses x-rays or similar forms of radiation to directly destroy damaged tissue.
It can be performed individually or simultaneously with corticosteroids or decompression
surgery.
Bibliography
Dosiou C, Kossler AL. Thyroid Eye Disease: Navigating the New Treatment Landscape. J Endocr
Soc. 2021; 5(5):bvab034. doi: 10.1210/jendso/bvab034.
Jain AP, Jaru-Ampornpan P, Douglas RS. Thyroid eye disease: Redefining its management-A
review. Clin Exp Ophthalmol. 2021; 49(2):203-211. doi: 10.1111/ceo.13899.
National Organization for Rare Disorders. Thyroid Eye Disease. https://rarediseases.org/rarediseases/thyroid-eye-disease/. Accessed September 19, 2022.
Thyroid Eye Disease (TED) An Introductory Tutorial and Overview of Disease. The University of
Iowa Ophthalmology and Visual sciences website. https://webeye.ophth.uiowa.edu/
eyeforum/tutorials/thyroid-eye-disease/index.htm. Accessed September 18, 2022.
Thyroid Eye Disease. EyeWiki website. https://eyewiki.aao.org/Thyroid_Eye_Disease. Accessed
September 18, 2022.
What Are The Phases of Thyroid Eye Disease? ThyroidEyeDisease.net website. https://thyroid
eyedisease.net/phases. Accessed September 18, 2022.