May 2010




Revving up research on thyroid eye disease

by Maxine Lipner Senior EyeWorld Contributing Editor


Investigators delve into the latest on the condition

A 62-year-old man with a long history of thyroid eye disease exhibiting eyelid retraction, exophthalmos, and restrictive extraocular myopathy with loss of vision from compressive optic neuropathy in his right eye Source: Shameema Sikder, M.D.

While thyroid eye disease is an all too common phenomenon, it is a poorly understood condition, according to Robert S. Weinberg, M.D., chairman, Department of Ophthalmology, Wilmer Eye Institute, Johns Hopkins, Baltimore. “This is a disease that is frustrating to patients, ophthalmologists, and also endocrinologists because there’s no good explanation yet for why it occurs,” Dr. Weinberg said. “There’s also no specific way to manage these patients to prevent the ophthalmologic complications from this problem.”

In the November 2009 issue of Ophthalmologica, Dr. Weinberg, together with Shameema Sikder, M.D., ophthalmology resident, Wilmer Eye Institute, offered up a review of current theories of the condition and related management.

Slim literature pickings

The investigation was an outgrowth of frustration with just how little understanding there is of this condition. “Dr. Weinberg told me how he has several patients with thyroid eye disease and how frustrating it is both for him and for the patients simply because there isn’t a clear methodology for treating them,” Dr. Sikder said. “That spawned the discussion about what is in the literature and how we can use that information to formulate a better approach to treating these patients.”

There was very little in the literature. “We weren’t able to find any summary articles looking at the body of what has been done to simulate a multicenter study, looking into ways to prevent this condition from occurring or to treat it more effectively once it occurs,” Dr. Weinberg said. Thyroid eye disease can be very difficult to grasp and can often occur in those who have no inkling that they have a thyroid condition. “Thyroid eye disease can present before the lab values reflect abnormalities with the thyroid hormone,” Dr. Sikder said. “It’s not uncommon for us to see patients, clinically diagnose what we believe is thyroid eye disease, and send them back to their primary care physician only to have their labs come back normal, even when we are convinced it is thyroid eye disease.” Sometimes it is later during repeat examination that the thyroid labs actually do come back abnormal.

Dr. Weinberg finds that the most sensitive test for thyroid eye disease is an A-scan ultrasound, which can show thickening of extra-ocular muscles. “In our experience, that can occur 6 months to 2 years before a patient has abnormal laboratory studies that would confirm the underlying diagnosis,” he said.

Thyroid eye theories

While there are several theories, no one has definitively shown why thyroid eye disease occurs. Dr. Weinberg finds that these theories run the gamut. “Problems in the orbit seem to occur when there is increased orbital fat, and the question is, where does that [increased fat] come from?” he said. “The theory in the literature is that fibroblasts in the orbit enlarge and somehow become fat cells and this is mediated by auto-antibodies that transform the fibroblasts into cells that produce fat or adipogenesis.” However, the question of why this happens remains.

Some other theories that have been proposed look at the cellular level. “There’s a theory that cytokines or cyclooxygenase enzymes may have something to do with this,” Dr. Weinberg said. “The theory is that monocytes in the orbit can be hyperactive and there’s information in the orbit that causes the thyroid eye disease.” While theories abound, no one knows for sure what the origins of thyroid eye disease are. “Many researchers have proposed different theories to explain why this occurs,” Dr. Weinberg said. “The bottom line is that nobody knows and this is an area that needs to be investigated.”

Experimental treatments are also very diverse. “One that seems most attractive comes out of an article from Sweden that looked at non-steroidal anti-inflammatory agents, particularly diclofenac, which decreases the number of fat cells in the orbit,” Dr. Weinberg said. “The idea is that this may prevent transformation of the fibroblasts into fat cells.

“Another therapy being investigated is the use of rituximab, which can affect D-cells,” Dr. Weinberg said. This therapy offers treatment on the cellular level. “Unfortunate-ly, there are no multicenter, controlled studies looking at this, and it seems to warrant that.”

Overall, Dr. Sikder sees the different potential mechanisms that may contribute to thyroid eye disease as one of the main outcomes of the investigation. “I think one of the main findings of the study is the recognition that it’s not just inflammation that’s an etiology for thyroid eye disease and that the pathogenesis is actually more complex,” she said. “The key is that if we can focus on addressing some of the other reasons for thyroid eye disease, for example the adipogenesis, then there’s more chance that we can effectively treat this,” she said.

Going forward, Dr. Weinberg believes that there is still a lot of ground to cover. “There’s a lot of work that needs to be done for a relatively common disease that affects a lot of people,” he said. “We’re just trying to add to the body of concern about this.”

Editors’ note: Drs. Weinberg and Sikder have no financial interests related to their comments.

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