Graves' Orbitopathy. Группа авторов

What Value Does the “Clinical Activity Score” Have?

Mourits et al. [11] devised the CAS in 1989. It remains in widespread use, as it is an easy scoring system that allows the majority of patients to be classified as either active or inactive (Table 1). Patients seen for the first time are scored for 7 points, 2 symptoms and 5 soft-tissue signs. Clarifying the presence or absence of both symptoms and signs is best achieved in conjunction with the protocol and notes of the EUGOGO atlas (www.eugogo.eu). On subsequent assessments any significant change in severity is added to the score. Since its inception, it has become apparent that a significant deterioration in any ocular excursion amounts to 8° rather than 5°, and the atlas reflects this (see also the section “How Is Severity Best Classified?” below). The evidence for the value of the CAS lies in studies correlating pretreatment CAS and response to immunomodulation. Using a cut-off of at least 4 points, the positive predictive value of the CAS alone was 80% while the negative predictive value was 64% [33]. A further study showed a significant correlation between TSH receptor antibodies and the CAS [36].

      The disadvantages of the CAS relate to 2 aspects. Firstly, all features are given equal weighting, and it is not clear whether this is appropriate. Secondly, it is a poor tool for monitoring change as it employs a binary score, whereby improvement of any feature does not alter the score unless it completely resolves [4].

Do Patients without Signs of Activity Ever Have Active Disease?

      A small minority of patients appear to show no signs of active disease but subsequently either change spontaneously or respond to immunomodulation. Identifying such patients is of course difficult; however, they may have orbital pain or gaze-related pain suggesting active disease, and/or describe worsening of severity features usually implying active disease.

What Should I Do if I Am Not Sure whether the Disease Is Active?

      In this situation management will depend on the presenting features and their severity. Unless there is clear evidence to the contrary, all sight-threatening features should be assumed to be of recent onset, implying active disease and a need for urgent intervention. At the other end of the spectrum, patients who present with only eyelid retraction and mild exophthalmos do not require any urgent intervention and can safely be sequentially assessed until their disease phase is apparent and any necessary therapy then offered.

Are There Any Other Ways to Evaluate Activity other than Clinical Examination?

Over the past 20 years, many other methods have been tried in the hope of evaluating activity more accurately than CAS alone. These include an assay of thyrotropin receptor antibodies [37] or measurement of glycosaminoglycans in either serum or urine [38], A-mode ultrasonography [39], MRI using either short tau inversion recovery sequences [40] or T2-weighted images [41–44], and scintigraphy using octreotide [45] or gallium [46]. Some studies have also examined the value of noting disease duration when determining whether GO is active [39]. A more recent study examined a wide variety of pretreatment indices in 66 patients with moderately severe GO undergoing radiotherapy [47]. These comprised disease duration, CAS, glycosaminoglycan excretion, cytokines and other cell factors related to the immune response (IL-6, IL-6R, TNF-α RI, TNF-α RII, IL-1RA, sIL-2R, sCD30, thyrotropin receptor antibodies) plus quantified measurements on A-mode ultrasound, T2-weighted MRI and octreoscan. From this, 2 models were devised to predict either response or no response to radiation. The “optimal” model evaluating all indices was compared to the “practical” model, which evaluated only duration of GO, soft-tissue involvement, restriction of elevation and A-mode ultrasound. The discriminative ability of the “practical” approach was 0.82 versus 0.93 for the “optimal” approach. Hence the practical model was significantly more robust than the CAS alone in predicting response for an individual.

The potential diagnostic value of a novel imaging technique has recently been demonstrated. This analyses thermal data from the eye and periorbital region to determine the disease phase in thyroid eye disease [48].

Table 2. Modified NOSPECS classification after Werner [49]

Class	Grade
0	No physical signs or symptoms
I	Only signs
II	Soft-tissue involvement
	aAbsent
	bMinimal
	cModerate*
	dMarked*
III	Exophthalmos (Proptosis)*
	aAbsent
	bMinimal
	cModerate
	dMarked
IV	Extraocular muscle involvement*
	aAbsent
	bLimitation of motion in extremes of gaze
	cEvident restriction of motion
	dFixation of a globe or globes
V	Corneal involvement
	aAbsent
	bStippling of the cornea
	cUlceration
	dClouding, necrosis, perforation
VI	Sight loss (due to optic nerve compression)*
	aAbsent
	bVisual acuity 0.63 – 0.5
	cVisual acuity 0.4 – 0.1
	dVisual acuity <0.1 to no light perception
Note that grades within class II, class III, and class IV are largely undefined. Severity should be scored by the method given in the section “How Reproducible Are These Assessments?”. The severity signs marked with an asterisk are also used to assess activity, namely class IIc and IId, or a defined deterioration in class III, IV, or VI.

When Should These Other Methods for Assessing Activity Be Used in Routine Clinical Practice?

      At present we do not know the value of assessing all patients using these additional methods as no data relate to patients with all grades of severity. Of course all patients in routine clinical practice can have disease duration and soft-tissue evaluation without any additional cost or facilities. At present the place for the other methods described will depend partly on their availability and cost, and partly on the presenting features of an individual patient. There is no proven necessity for additional