All patients on their first visit were asked if their ocular complaints were worsening, stable, or improving in the past few weeks. Fifty percent of the severe group had reported worsening in their symptoms on their first visit compared with 12% of the mild group, which was highly statistically significant different (p < 0.0001).

Systemic thyroid symptoms of weight change and palpitations were not statistically different between the severe and mild groups.

Most patients (85.7% of the severe group and 87.2% of the mild group) presented with a history of hyperthyroidism. There was no significant difference between the type of primary thyroid disease nor the type of systemic thyroid treatment received between the two groups.

Tempo of Disease Onset

On their initial visit, all patients were asked to categorize the tempo of onset of their orbital and systemic thyroid symptoms as either acute (onset from 0 to 4 weeks) or chronic (onset greater than 4 weeks). There was a significant difference (p ¼ 0.0001) between the severe and mild groups with respect to orbitopathy onset rate, with the severe group having 54.8% acute and 45.2% chronic onset and the mild group having 12.8% acute and 87.2% chronic onset.

There was no significant difference (p > 0.05) between the mild and severe groups with respect to thyroid disease onset rate. The severe group had 30.9% acute onset and 66.7% chronic while the mild group had 19.1% acute onset and 68.1% chronic onset.

Clinical Features

Five parameters were recorded from the charts at both the initial and the subsequent follow-up visits: soft-tissue inflammatory features, proptosis, corneal exposure, motility, and optic neuropathy (Table 4).

Eyelid edema and chemosis scores were significantly higher in the severe group.

Table 4 Comparison of Clinical Measurements Between Disease Severity Groups at First Visit and Change Documented Between Visits (Mann–Whitney U-test)

The mean globe proptosis was 1.2 mm higher in the severe group, not statistically significant. The incidence of corneal punctate stain or ulcers was not significantly different between the groups.

The incidence of diplopia in upand horizontal gazes, and restricted ocular ductions in upgaze and abduction from the worst eye was more common in the severe group. We found no statistical difference between the groups in downgaze measurements.

Optic neuropathy was documented in none of the mild group and 10% of the severe group.

Progress and Duration of Inflammatory Features

Differences in average clinical measurements between the initial and subsequent visits were recorded and compared between the two groups.

Soft-tissue inflammatory signs of chemosis and lid edema worsened between the two visits in the severe group but improved in the mild group. This difference was statistically significant (p < 0.04).

Proptosis measurements worsened on average in the severe group and improved slightly in the mild group, a statistically significant difference (p < 0.003).

Degrees of duction in the most restricted direction of the most affected eye worsened on average 3–5 in the severe group and improved very slightly in the mild group, again statistically significant (p < 0.003).

There was no significant change in optic neuropathy status nor corneal exposure signs between the two visits in either group.

The duration of clinic management (from the first to final visit at the orbitopathy clinic when no further medical or surgical intervention was required) was significantly longer in the severe group (26.62 months) compared to the mild group (9.57 months), p < 0.00001.

DISCUSSION

Sixty-five percent of patients referred to our thyroid orbitopathy clinic in the 3-year study period were treated conservatively during their inflammatory phase, while 35% received more aggressive intervention, including systemic antiinflammatories or radiotherapy. This figure is much higher than those reported elsewhere (6), possibly because of the referral center bias; patients with mild thyroid orbitopathy are often not recognized or not referred.

Demographic characteristics of our two groups correspond well with those of other studies. In our mild group, the racial distribution reflected our referral city’s racial make-up, with 65% white, 20% Chinese, 10% Indian, and 5% other. The severe group had a much higher proportion of whites (92% compared with other races 8%), a finding noted in other studies (7).

Thyroid orbitopathy occurs most typically in the third to fifth decade (1). We found that patients with severe disease were on average 13 years older than those with mild disease, agreeing with previous observations.

While females outnumber males almost 4:1 in TO, it has been observed that males are more likely to present

with severe disease (8); in our study, the severe group contained 78% females and 22% males while the mild group contained 84% females and 16% males, an insignificant difference.

The association between smoking and thyroid orbitopathy and other immune-mediated diseases has been well documented (9,10). The prevalence of smokers in the Canadian general population is 33% in 1992. A higher percentage of patients with severe orbitopathy were smokers in our study (54%) compared with those with milder disease (44%); although suggestive, this difference did not meet statistical significance.

The clinical symptoms and signs of soft-tissue inflammation and impaired ocular motility were significantly worse in the severe, treated group compared with the mild, nontreated group. This is an expected finding since at our clinic, medical intervention is only offered for significant soft-tissue inflammatory signs, progressive ocular motility restriction, or optic neuropathy.

Proptosis is not a criterion for medical intervention, but was on average 1.2 mm worse in the severe group (not statistically significant). Interestingly, more patients with mild disease complained of proptosis than those in the severe group, presumably because lid swelling, orbital pain, and diplopia were a bigger priority for the latter group, while lid retraction may have increased the perceived prominence in the mild group.

The course of disease documented by both patient and clinician is in our opinion another indication for anti-inflam- matory intervention, although not often recognized as a deciding factor. In other words, the clinician should consider anti-inflammatory medications or radiotherapy for those patients who have progressive orbitopathy symptoms or signs. This study confirms that patients who were ultimately treated had shown significant worsening in soft-tissue inflammation and ocular motility compared to the mild, untreated group.

This study also identified that patients with severe disease requiring treatment are more likely to have an acute

onset (over several weeks) of their symptoms and signs compared with patients having a mild course whose onset may occur over several months, even based on historical observations at their first clinical visit. Patients with severe disease were four times more likely to have an acute onset compared with those with mild disease. Therefore, patients with a rapid development of symptoms (less than 4 weeks) should be considered early for medical intervention rather than waiting for further worsening. Also, patients with an indolent course and mild symptoms on their first visit may be reassured that they are less likely to develop serious disease. We have not seen this observation recorded elsewhere, but feel that it is a useful predictive variable of orbitopathy severity.

As well, patients with mild disease stabilize rapidly with regard to management, while those with serious disease on average have a more protracted course. Patients with severe disease require on average 2 years of management before reaching a stable state where no further follow-up or intervention is required.

These differences between the mild and severe orbitopathy groups may help guide the clinician to advise and manage patients with TO, even on the first visit. Younger female patients with an indolent course and mild inflammatory features can be reassured that they are less likely to develop severe orbital sequelae. Older patients, those who report recent progression, and those with an acute onset of orbital symptoms and signs (including eyelid and conjunctival edema, progressive ocular restriction, and proptosis) should be followed closely and advised to watch for progression. These patients have a statistically higher risk of developing severe clinical findings, and treatment might be discussed and offered as early as the first office visit. Patients with mild disease can be told that on average all management will be completed within 9 months, while those with more severe features can plan for medical and surgical treatments lasting up to 2 years. All patients should be encouraged to stop smoking.

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