Expanding Role of Optometrists in the Management of Thyroid Eye Disease

Proptosis, also known as exophthalmos, is a protrusion of the orbit and a common sign of thyroid eye disease (TED). While variants of this orbitopathy present rarely in euthyroid or hypothyroid states, globally TED affects approximately 25% to 40% of individuals with hyperthyroidism due to Graves disease.¹
 
Several antigens implicated in the autoimmune pathology of Graves disease may play a role in TED-associated proptosis.² Examples of such antigens include the insulin-like growth factor-1 receptor (IGF-1R) and the thyrotropin receptor.³ The activity of these antigens promotes extraorbital inflammation, differentiation of pluripotent orbital connective tissue cells resulting in proliferation of adipocytes, and excessive deposition of glycosaminoglycans. The resulting edema and congestion of the orbit, along with proliferation of orbital adipose and connective tissue, ultimately causes proptotic forward displacement of the eye.
 
Risk factors for TED-associated proptosis include smoking, older age, female sex, and genetic predisposition.⁴ Progression of TED-associated proptosis may result in worsening vision secondary to optic nerve compression and/or corneal deterioration.
 
Until recently, medical treatment targeting the ocular pathology of TED-associated proptosis was lacking. Prior to 2020, antithyroid drugs and radioiodine therapies were mainstays of therapy. More rarely, some patients with proptosis have been treated by thyroidectomy following normalization of thyroid activity. Direct reduction of proptosis has typically required interventions such as orbital fat resection procedures.⁵ Other procedures, such surgical correction of thyroid-associated strabismus by reducing tethering from tight or hypertrophic extraocular muscles, may worsen proptosis.⁶ In 2020, teprotumumab, a human monoclonal antibody that binds to IGF-1R in extraocular issues,¹ was the first systemic therapy approved by the US Food and Drug Administration (FDA) for the treatment of TED.
 
David P. Sendrowski, OD, FAAO, a professor at the Marshall B. Ketchum University’s Southern California College of Optometry, Fullerton, and chief of the Ophthalmology Consultation and Special Testing Service at the University Eye Center at Ketchum Health, Anaheim, California, discusses the evolving role of optometrists in management of TED. Dr Sendrowski is an author and coauthor of textbooks, book chapters, and scholarly papers about TED and other ocular diseases.

What is the current role of optometrists in multidisciplinary management of TED-related proptosis, and is it changing?

Many people with TED may not realize that they can receive effective care from an optometrist as well as an ophthalmologist. Much of the symptomatology of TED is very familiar to optometrists, so we can certainly handle the ocular clinical workload that may be required in the care of patients with thyroiditis.
 
Consider the 3 major components of the eye: First there is the cornea. In proptosis, the cornea loses moisture provided by the eyelids, resulting in exposure keratopathy. Optometrists need to perform a corneal stain to test for exposure keratopathy, and that is very easily done. Second, optometrists must make sure that the patient’s eye movements are not restricted in any field of gaze. Of course, this task is well within optometrists’ clinical comfort zone because we have been measuring the magnitude of strabismus for many years. Third, congestion in the back of the orbit may cause pathology of the optic nerve head, including swelling, visual field effects, and potentially permanent visual loss. Here, too, optometrists have been treating glaucoma from orbital congestion for a long time, and so we have experience with using optical coherence tomography to examine and test the optic nerve head.
 
Other tests we perform that are pertinent in TED include monocular color vision testing and fine threshold testing of the central portion of the visual field. In short, the field of optometry is well positioned to manage patients with TED.
 
As part of the intake process or initial patient assessment, optometrists should ask patients about systemic diseases, especially autoimmune diseases. Patients may be surprised to learn that conditions such as systemic lupus erythematosus and thyroid diseases can affect their eyes. They may complain of dry eyes but not realize that their lids are not closing. Perhaps they have experienced double vision in certain areas of their visual fields but simply attribute it to their prescription eyeglasses. In such cases, the optometrist should screen for other ocular signs consistent with TED, and go beyond the general eye wellness examination that most people come in for.

How has FDA approval of teprotumumab for the treatment of TED changed the way that optometrists manage the condition?

Teprotumumab was a game changer, and optometrists, especially those in multidisciplinary practice, should educate themselves about both how this medication has advanced the treatment of TED and key considerations for its use.
 
A patient receiving teprotumumab needs to be monitored. Again, recall the basic 3 components of the eye. For example, a patient with exposure keratopathy may benefit from the use of artificial tears during initiation of therapy with teprotumumab. This patient may need to apply a topical gel at night or elevate their head at night to reduce ocular swelling. Later, if patients report that their eyes no longer feel dry in the morning, they were able to reduce their use of artificial tears, or their diplopia is less severe, the optometrist can confirm the therapeutic effect of teprotumumab.
 
To monitor changes in proptosis for a patient taking teprotumumab, proper instrumentation is necessary. Optometrists who manage patients with TED should have a Hertel exophthalmometer to determine the axial position of their eyes. This instrument allows optometrists to measure from a consistent base whether the patient’s proptosis has increased or decreased and report the findings to the physician who is administering the teprotumumab. If a Hertel exophthalmometer is unavailable, the Luedde exophthalmometer is also effective and less expensive.
 
The exophthalmometer is a plastic device comprising a transparent ruler attached to an ophthalmic penlight. It is placed on the lateral orbital wall and used to evaluate patients for proptosis by measuring protrusion of the eye through the ruler. The disadvantage is that there is not a consistent base to start from, so it may be difficult to ensure that the same spot is being used every single time. For optometrists who are really working “in the trenches,” a clear plastic ruler can be used instead of an exophthalmometer. A consistent base is not necessary when proptosis is measured this way. In a modern private practice or a multidisciplinary practice, a high-quality exophthalmometer should be readily available to the optometrist.
 
Use of teprotumumab is associated with several systemic side effects, including tinnitus, dry skin, and tachycardia. Optometrists should review the list of side effects with the patient, first to ascertain whether the patient is experiencing any adverse treatment effects and second to report the side effects, if any, to the administering physician. I think it’s important for the optometrist to act as a monitor and even as a supporter or “cheerleader” during the treatment process. Some patients with TED give up on their teprotumumab treatment, either because of treatment side effects or because of the infusion frequency, which requires a caregiver to transport the patient for repeated visits.

What is an optometrist’s role in obtaining imaging studies for the evaluation of patients with suspected TED and diagnosed TED-associated proptosis?

A key sign that optometrists should look for in patients with TED is thickening of the muscle bellies of the 6 extraocular muscles. One of the differential diagnoses is orbital pseudotumor; in this condition, both the muscle bellies and the tendons are swollen. If a pseudotumor is suspected, a computed tomography (CT) scan should be ordered to visualize those muscles and to determine the cause of the proptosis. Magnetic resonance imaging (MRI) can be very helpful and may be needed to visualize the orbital apex and/or the status of the optic nerve head if the patient has a visual field defect. In many states, there has been legislative advancement allowing optometrists to order those studies directly. Here in California, this was approved just in the past 2 years. Previously, if TED were suspected, an optometrist would have to contact the patient’s primary care physician to request that an MRI scan be performed. This change helps avoid delaying therapy because the patient gets referred to their primary care physician or ophthalmologist with diagnostic confirmation.

Do optometrists face particular obstacles or challenges to delivering effective care for patients with TED and proptosis?

Sociobehavioral patient factors can pose challenges. In communicating with patients in this setting, optometrists have to be “guidance counselors” in a sense, to identify lifestyle changes that could improve outcomes. Ask patients about smoking, which is a huge factor for TED; the more cigarettes that the patient smokes, the greater the likelihood of a more pronounced proptosis and the greater the chance of optic nerve involvement — so talking to the patient about smoking is important. High salt intake is another challenge to good outcomes because it results in a significant influx of water into the orbit. The patient’s physician may never have educated the patient about this so the task may fall to the optometrist.
 
Patient access to appropriate imaging can be an issue. In certain geographic areas of the United States, for example, optometrists do not have easy access to imaging facilities. In some cases, the patient’s physician may prefer not to accept the optometrist’s recommendation on imaging, but will refer to the patient to an ophthalmologist for a clinical opinion first.
 
It is very important to support patients in following through with and completing their infusion regimen. One approach is to ask the patient to keep an “eye diary.” Whenever a patient sees me for a scheduled visit, we can discuss whether the symptoms recorded in the diary are worse or better, and through this conversation I learn what I need to do to alleviate those symptoms and improve that patient’s quality of life. 
 
I do think that optometrists are getting better at integrating themselves into the medical care of TED. The profession has “climbed half the mountain,” so to speak, toward that point where optometrists feel confident in saying, “I’m going to order over-the-counter selenium for early stages of the orbital disease,” or “I’m going to send you to a physician for a prescription of teprotumumab,” or “I’m going to move you forward therapeutically.” Until fairly recently, an optometrist might have simply said, “Well, I don’t know what’s wrong with your eyes so I’m going send you to the ophthalmologist to take a look.” I believe that in the future, more optometrists will want to take charge and initiate therapy for TED, because it is always better to start treatment in the early stages when the patient has that gritty eye feeling, early proptosis, or lid retraction (Dalrymple’s sign).

Yu and colleagues noted that early studies of teprotumumab have included mostly patients who are White, indicating that future work will need to include more diverse patient populations.¹ What other gaps exist in research on therapies for proptosis? How might trial results differ among different patient populations?

As I mentioned, teprotumumab was absolutely a game changer. It is the first pharmaceutical I’ve heard of being FDA-approved in the last 20 years for TED since approval of short-term use of steroids. Of course, steroids given at high doses can cause secondary problems, especially when administered intravenously. So again, it’s not a surprise that teprotumumab is the hot drug right now.
 
In terms of improved treatment for TED, we have just scratched the surface with teprotumumab infusion. For example, is there a better way to stop the systemic side effects? Would it be better to administer a slow-dissolving pellet into the orbit that would be just as clinically effective as an infusion? A delivery system like that could be easier for patients than the multiple office visits currently required for patients to receive teprotumumab infusions.
 
Also, we do not know whether teprotumumab works similarly for all patients. This issue of variable treatment effects arises, for example, with macular toxicity from hydroxychloroquine: We know that in patients who are White, treatment with hydroxychloroquine can cause central visual field loss, but in the Asian population, the loss of sensitivity seems to be more significant pericentrally⁷; this means that we have to test different patients differently.
 
In the case of teprotumumab, are there analogous differences in side effects for different ethnic or racial groups? We don’t know at this stage. Another question is whether it might be less effective in some groups due to differences in tissue receptors. I predict that we will learn more about what doses should be used, what delivery systems are most appropriate, and which specific receptor targets are going to yield the fastest and greatest improvement with teprotumumab in diverse patient populations.
 
Finally, there is the question of whether teprotumumab can still be effective for patients who have severe TED with compressive optic neuropathy. If they require surgical decompression, will they still be able to benefit from teprotumumab afterward?

What should optometrists tell their patients who have, or are at risk of, TED-associated proptosis to ensure that they seek care promptly and minimize risks to their eye health and vision?

Patients with TED need to understand that they have an autoimmune disease and therefore should be evaluated for other autoimmune diseases. This is particularly true for women because TED affects women 5 to 10 times more often than men.⁸ Women may be at greater risk for thyroid cancer as well.⁹ Men seem to develop TED later in life and tend to have more complications of the disease. When I see patients with presumptive TED, I ask them when they last saw their physician, considering that they should have a complete blood workup to rule out other disorders.
 
The optometrist also needs to inform the patient that certain standard systemic treatments for TED (that were in use prior to approval of teprotumumab) can cause hypothyroidism.⁴ Patients with hypothyroidism are at risk for adverse effects such as cardiovascular disease because hypothyroidism has a tendency to increase cholesterol levels and promote arterial changes in the heart. Because patients may mistakenly attribute many signs and symptoms of hypothyroidism to the effects of normal aging, patient education is essential.
 
In fact, I would say that patient education is optometrists’ highest priority because it helps us detect disease earlier. Spend time with patients; find out what they do for a living and for their avocations. Based on how the patient has been functioning (well or poorly), help them relate that to the disease. Then you can tell the patient, “If you develop X symptom, I need to see you.” This kind of patient education allows you to deliver much better care.
 
Patient management is improved if the patient understands the process of TED. The first 6 to 18 months of the disease, known as the active stage, is when the degree of proptosis increases. That is also when the “gritty eye” sensation tends to arise; because it can occur even if the patient does not have actual thyroid pathology, we have to screen for those signs and symptoms. Next, patients go through a stabilization, or “quiet” stage, in which some of the signs and symptoms reverse but not to the patient’s full satisfaction. Then comes a convalescent stage, which is usually maintained for the longest period of time although the disease can recur in some patients. We want to treat patients early in that active stage so that we can reduce ocular pain and visual problems and patient can maintain their visual activities of daily living.
 
When a patient demonstrates objective improvement, that drives good outcomes. You can say, “Look how the proptosis is responding to the teprotumumab, particularly now that you’ve stopped smoking. During this stabilization stage when the proptosis is reversing, it’s reversing a little bit more, probably because you have quit smoking. We’re not seeing any signs of optic neuropathy now. You were 6 prism diopters of strabismus before but now you’re at 4. Plus you can see in the mirror how good you look. Keep up the good work.”
 
Optometrists have to be part physician, part educator, and part cheerleader. Education of our patients goes a long way toward making them physically, emotionally, and behaviorally better. While a patient’s physician may not have enough time for detailed patient education, an optometrist’s efforts here, in addition to sharing the treatment results and their implications in detail, inspires patients to follow their treatment protocols.

This Q&A was edited for clarity and length.

Disclosure

David P. Sendrowski, OD, FAAO, reported relationships with Alcon Laboratories, Inc. and Allergan, Inc.

References

1. Yu CY, Keen JA, Shriver EM. Teprotumumab: a major advance in the treatment of thyroid eye disease management. Adv Ophthalmol Optom. Published online June 27, 2022. doi:10.1016/j.yaoo.2022.03.008
 
2. Winn BJ, Kersten RC. Teprotumumab: interpreting the clinical trials in the context of thyroid eye disease pathogenesis and current therapies. Ophthalmology. 2021;128(11):P1627-P1651. doi:10.1016/j.ophtha.2021.04.024
 
3. Kahaly GJ, Douglas RS, Holt RJ, Sile S, Smith TJ. Teprotumumab for patients with active thyroid eye disease: a pooled data analysis, subgroup analyses, and off-treatment follow-up results from two randomised, double-masked, placebo-controlled, multicentre trials. Lancet Diabetes Endocrinol. 2021;9(6):P360-P372. doi:10.1016/S2213-8587(21)00056-5
 
4. Hoang TD, Stocker DJ, Chou EL, Burch HB. 2022 Update on clinical management of Graves disease and thyroid eye disease. Endocrinol Metab Clin N Am. 2022;51(2):287-304. doi:10.1016/j.ecl.2021.12.004
 
5. Liao SL, Huang SW. Correlation of retrobulbar volume change with resected orbital fat volume and proptosis reduction after fatty decompression for Graves ophthalmopathy. Am J Ophthalmol. 2011;151(3):P465-P469. doi:10.1016/j.ajo.2010.08.042
 
6. Gomi CF, Yang SW, Granet DB, et al. Change in proptosis following extraocular muscle surgery: effects of muscle recession in thyroid-associated orbitopathy. J Am Assoc Pediatr Ophthalmol Strabismus. 2007;11(4):P377-P380. doi:10.1016/j.jaapos.2007.01.115
 
7. Melles RB, Marmor MF. Pericentral retinopathy and racial differences in hydroxychloroquine toxicity. Ophthalmology. 2015;122(1):P110-P116. doi:10.1016/j.ophtha.2014.07.018
 
8. Zloto O, Sagiv O, Priel A, et al. Gender differences in clinical presentation and prognosis of thyroid eye disease. Eur J Ophthalmol. 2021;31(5):2717-2723. doi:10.1177/1120672120964112
 
9. Dong M, Cioffi G, Wang J, et al. Sex differences in cancer incidence and survival: a pan-cancer analysis. Cancer Epidemiol Biomarkers Prev. 2020;29(7):1389-1397. doi:10.1158/1055-9965.EPI-20-0036

Posted by Haymarket’s Clinical Content Hub. The editorial staff of Optometry Advisor had no role in this content’s preparation.