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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.