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to 1 or several muscles. About 1 in 10 patients presents with unilateral exophthalmos of 2 mm or more [29]. Smoking is associated with more severe GO.

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      Upper eyelid retraction is multifactorial [4, 9, 26] and due to a combination of increased sympathetic stimulation of Müller’s muscle, contraction of the levator muscle due to its direct involvement, and scarring between the lacrimal gland fascia and levator, which specifically gives rise to lateral flare [8]. In addition, tight restriction of the inferior rectus leads to upper eyelid retraction, regardless of upper eyelid pathology [9].

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      In contrast, lower eyelid retraction correlates with exophthalmos and may be better described as lower eyelid displacement, as there is no evidence that the lower lid retractors are involved in the disease process.

      All corneal signs of GO are secondary phenomena of GO. A wide palpebral aperture leads to increased tear evaporation, which, combined with poor blinking, causes superficial punctate erosions and the symptoms of surface irritation [10]. The mechanism for corneal ulceration is described above in “What Are the Other Signs and Symptoms of Graves’ Orbitopathy?” and arises from lagophthalmos and corneal exposure, due to exophthalmos, lower lid retraction, and/or poor levator function, usually accompanied by a tight inferior rectus [4].

      Determining the phase of GO at each clinical assessment is fundamental to formulating an appropriate management plan. This is because immunomodulatory therapies can only be effective while there is active inflammation. On the other hand, certain surgical treatments, for example strabismus surgery, should only be undertaken when GO is inactive and there is no further chance of spontaneous change. Furthermore, sight-threatening disease occurs insidiously during active GO; therefore symptoms and signs of corneal ulceration and DON should be specifically sought during this phase [4].

      The active phase of GO is the period when the patient is most likely to be symptomatic, commonly presenting with grittiness, photophobia, watering, and/or orbital aching – either gaze evoked or spontaneous. Patients will often have noticed a change in the severity of other features over the previous 3 months, for example worsening double vision. As we cannot directly identify the degree of orbital inflammation, i.e., activity, the classical signs of inflammation are used as its surrogate markers. In addition, if there has been a change in severity of any feature, worsening or improvement, then this also suggests that the disease is active.

      In

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