Thyroid eye disease tends to follow Rundle’s curve (see Figure 1), where there is an initial worsening of the signs and symptoms, followed by a stage of improvement, followed by a chronic and inactive stage.
Each stage can last variable amounts of time (months to years), but on average, individuals require approximately 1 to 3 years to reach the third, chronic and inactive stage of thyroid eye disease (TED). When they reach Stage III, progression of TED is unlikely and surgical restorative therapies can be considered.
Figure 1: Thyroid Eye Disease Staging
Clinical Activity Score
No single test or biomarker can determine the stage of TED, so clinicians use the clinical activity score (CAS) to help quantify TED activity over time.
In general, patients with TED are seen every 4 to 6 months to obtain a CAS and undergo an eye evaluation. If the CAS continues to increase, the individual is likely in Stage I. As the CAS improves, the person’s disease may be in Stage II or III. The CAS alone does not indicate the particular stage; instead, other eye measurements are assessed for stability or improvement to help make this determination.
The CAS is made up of various signs and symptoms, each given a score of 0 or 1 (see Table I). The initial visit is assessed a score out of 7 and follow up assessments are scored out of 10, with a higher score indicating more active and progressive disease. In general, a score of 4 or more is considered moderate to severe activity. Of note, one of the biggest concerns about the CAS includes high inter-observer variability between providers.
It may be challenging for a non-opthalmologist to accurately determine the CAS, since the slit lamp examination provides a great deal of information regarding the conjunctival injection, chemosis, plica, and caruncle. An individual with TED may experience eye redness from something other than TED such as ocular dryness, which may further affect assessment of the CAS.
While the internist can assess visual acuity, color vision, eyelid edema, and redness, they may not feel comfortable with the repeatability of eye movements or strabismus measurements.
Patients with significant loss of visual acuity or color vision warrant an urgent referral to an ophthalmologist for more careful evaluation.
Eye Exam
The accompanying eye examination should include an evaluation of visual acuity, color vision, pupils, extraocular motility, ocular alignment, Hertel exophthalmometry, and external and slit lamp examinations every 4 to 6 months. Visual acuity, color vision, and pupils can help determine if an optic neuropathy is present. Extraocular motility and strabismus stability can help determine the stage of TED. The external and slit lamp examinations include measures for the CAS, but they can also identify areas of corneal dryness, exposure, or ulceration.
Other Markers of Thyroid Eye Disease Activity
Some controversy exists over the use of serum thyroid stimulating immunoglobulin (TSI) and thyroid stimulating hormonereceptor antibody (TRAb) as markers of activity. There is no clear correlation between TSI/TRab and CAS.
However, a recent study found that preoperative TSI and TRab predicted recurrence of proptosis following orbital decompression. This would suggest that TSI and TRab are useful adjunct data in determining whether a patient has truly entered stage III of TED and is ready for surgical rehabilitation.
Treatment Considerations
From a systemic standpoint, the primary care physician or endocrinologist often decides on management of abnormal thyroid function, typically with anti-thyroid medications. Other interventions include radioactive iodine (RAI) ablation, which can lead to significant worsening of TED, or a thyroidectomy, which does not appear to have this same risk, and may be an option when medications are found ineffective. However, prophylactic use of corticosteroids before, during, and after treatment of RAI appears to mitigate this risk. Teprotumumab is approved for moderate to severe TED treatment yet generally requires stable and normal thyroid function before prescribing, and is typically only considered in cases with a CAS of 4 or higher.
