Graves' Orbitopathy: Double Vision Worse With Less Disease

Nancy A Melville

November 03, 2014

SAN DIEGO — Double vision is the predominant symptom in more than half of patients with moderate to severe Graves' orbitopathy; however, the symptom negatively correlates with inflammation and in fact primarily occurs with less active disease, according to new research.

Restrictions in eye motility are instead key indicators of double vision, or diplopia, and should be on clinicians' checklists when managing such patients, said lead author Dr Peter Laurberg (Aalborg University Institute of Clinical Medicine, Denmark), who reported the findings at the 2014 Annual Meeting of the American Thyroid Association.

"The most important message from these findings is that quantitative recording of the field of double vision is advisable, both in patients and in controlled studies of patients with Graves' orbitopathy," he said.

Asked by Medscape Medical News to comment, Dr Rebecca S Bahn (Mayo Clinic, Rochester, Minnesota) said the somewhat-counterintuitive finding of the study is intriguing.

"One might have expected no correlation because double vision occurs both in the inflammatory disease and in noninflammatory or inactive disease," she said. "The negative correlation is an interesting finding that supports the clinical observation that double vision may be more pronounced in less active or inactive disease."

She agrees that the results underscore the importance of careful, objective, and quantitative assessment of double vision in patients with Graves' orbitopathy.

"This study has important implications for both the care of patients with Graves' orbitopathy and for the design of future studies regarding novel therapy for this condition."

"While double vision is the most common cause of sick leave for patients with Graves' orbitopathy and was found to be the main indication for therapy in about half of the patients, objective quantification of this parameter is not always undertaken in clinical studies or routine clinical care," she observed.

"Future studies of immunosuppressive therapies might focus on determining whether these agents given to patients with active disease might prevent the development of diplopia during the later inactive phase of the disease."

Diplopia Associated With Asymmetrical Graves' Orbitopathy

Dr Laurberg explained that studies of Graves' orbitopathy often focus only on inflammation, although patients may present with a variety of perplexing combinations of symptoms, such as severe inflammation and deteriorating vision but no diplopia or diplopia but little inflammation.

To better understand the disease manifestation and to objectively quantify diplopia in relation to other Graves' orbitopathy characteristics, he and his colleagues prospectively evaluated a cohort of 215 patients diagnosed with incident moderate to severe Graves' orbitopathy at a thyroid eye clinic in northern Denmark.

They found the most common symptom resulting in the diagnosis of moderate to severe Graves' orbitopathy, present in 54% of patients, was double vision in 40% or more of the visual field.

Other symptoms included restricted eye movement in 40% or more of the visual field (13% of patients), impaired vision (12.5%), and combinations of symptoms, including severe inflammation (11.1%) and proptosis of 25 mm or more (9.7%).

While no significant correlation was seen between the degree of diplopia and variables including age, sex, duration of Graves' orbitopathy, and smoking, the strongest correlations were seen between the degree of diplopia and restriction of motility in the worst eye, as well as asymmetry of Graves' orbitopathy (both P < .001).

Inflammation was meanwhile negatively correlated with diplopia as well as proptosis (both < .0010.)

"A bit to our surprise there was a rather strong negative correlation between diplopia and inflammation and proptosis," Dr Laurberg said.

While the mechanisms behind the effect are not understood, Dr Laurberg and his colleagues hypothesize that a key factor may be the asymmetrical effects that occur only in less severe disease.

"Patients with more severe orbital autoimmunity, including more inflammation, proptosis, and high serum TSH-receptor autoantibodies [sTRAb], tend to have more universal and symmetrical affection of the orbits," he explained.

"On the other hand, patients with less severe autoimmunity may have more isolated affection of one eye muscle and thus more diplopia."

But Will Yet More Inflammation Worsen Vision?

Also commenting, Dr Henry B Burch (Uniformed Services University of the Health Sciences, Walter Reed Medical Center, Washington, DC) agreed that the findings are somewhat counterintuitive.

"While there was a negative correlation between active inflammation and concurrent double vision, one might suspect that those patients with the worse inflammatory changes might also ultimately be more likely to have extraocular muscle dysfunction and double vision, as the fibrosis within eye muscles gradually progresses over time," he told Medscape Medical News.

"It will be interesting to read the study in its entirety to see whether this correlation was examined."

The authors, Dr Bahn, and Dr Burch reported they had no relevant financial relationships.

2014 Annual Meeting of the American Thyroid Association; October 30, 2014; San Diego, CA. Abstract Oral 1.

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