What is Thyroid Eye Disease?
Thyroid Eye Disease (TED) - otherwise known as Graves Orbitopathy (GO) - is the most common orbital disease in the UK, affecting 1 in 20 people. Thyroid Eye Disease is generally associated with thyroid immune disorders, such as Graves' Disease or Hashimoto's Thyroiditis, and affects more women than men - usually between their second and sixth decades.
Most patients with eye disease have a current or past history of abnormal systemic thyroid hormone levels, while some may go on to develop abnormal levels, and a small number of patients may be euthyroid. While 25 to 50% of patients with immune thyroid disease develop orbital involvement, commonly within 12-18 months of their hormonal disorder, 5 to 10% of these may develop more severe consequences - such as increased inflammation and congestion, impaired motility, or compressive optic neuropathy. Other contributing factors include smoking and a family history of thyroid disorders.
What causes Thyroid Eye Disease?
The cells of the thyroid gland (epithelial cells) are covered in surface receptors, which bind to the thyroid stimulating hormone (TSH, thyrotropin) - a hormone which is secreted by the pituitary gland to control the release of thyroid hormones. In both Graves' Disease and Hashimoto's Thyroiditis, thyrotropin-receptor antibodies (TSH-R Antibodies, TRAb) are also present, and these can bind to the receptors: initiating and perpetuating the disease.
These circulating antibodies are thought to be mediators in orbit disease, with their likely target being the orbital fibroblasts, which are found in the extra-ocular muscles and in the orbital fat. This is why orbital fibroblasts from patients with Thyroid Eye Disease have increased numbers of TSH receptors, which are thought to bind to circulating autoantibodies (TRAb): thereby stimulating fat cell formation and the deposition of hyaluronic acid within orbital muscle and fat - the histologic hallmark of Thyroid Eye Disease (see figure 1).
Fig 1: Enlargement of the fat & extra ocular muscles of the eye socket in GO
How do you treat Thyroid Eye Disease?
Thyroid Eye Disease symptoms are graded into activity (on a scale of 0 to 10, based on inflammatory signs) and severity (mild, moderate, severe and sight-threatening). While mild, non-inflammatory disease is generally treated with lubricant drops and oral selenium (200 mcg/day for 6 months), mild inflammatory disease may also require additional non-steroidal anti-inflammatory drugs (NSAIDS) or steroids. Double vision is managed with stick on Fresnel prisms, which can be placed on spectacle lenses to help realign the eyes. Immunosuppressive treatment with steroids, radiotherapy and surgery in the "active" phase is reserved for moderate and severe, sight-threatening eye disease with an increasing inflammatory index.
Pulsed Intravenous methylprednisolone has been found to be 85% effective, and oral prednisolone to be 60% effective in reducing inflammatory signs of Thyroid Eye Disease. Other immunosuppressive drugs like Azathioprine, Cyclosporine and Rituximab are also used in some cases. Urgent orbital decompression is a treatment option for sight-threatening dysthyroid optic neuropathy, whilst lid surgery is reserved for corneal exposure threatening the sight.
Radiotherapy has been found to be useful in active progressive disease, while rehabilitative or restorative surgery is offered once the disease is stable and quiescent in the post-inflammatory phase. This includes orbital decompression for bulging eyes, squint surgery to help correct double vision, lid-lowering surgery for staring eyes, and blepharoplasty surgery for eye bags. Rundle first described the activity pattern of the disease, and the plot of orbital disease severity against time has been called Rundle's curve (see figure 2).
Fig 2: Rundle's Curve
Publications
Stability of eyelid height after graded anterior-approach lid lowering for dysthyroid upper lid retraction.
Thyroid orbitopathy possibly predisposes to late-onset of periocular lymphoma.
