Treatment of Active Moderate-to-Severe Graves' Orbitopathy with Exophthalmos and Diplopia
When Graves' orbitopathy (GO) is both moderate-to-severe in severity and immunologically active, it meets the threshold where intensive systemic treatment is warranted. This clinical scenario is defined by a combination of objective orbital findings and an active inflammatory state.
Defining Clinical Features
- Clinical activity score (CAS) ≥ 3/7 — disease classified as active
- Lid retraction ≥ 2 mm
- Moderate or severe soft-tissue involvement
- Exophthalmos ≥ 3 mm above normal for race and gender
- Inconstant or constant diplopia
Treatment Approach — Partial Overview
For most patients in this category, first-line management involves a combination of intravenous immunosuppressive therapy with a concurrent oral immunomodulatory agent. For patients at the more severe end of the spectrum — including significant diplopia or markedly elevated exophthalmos — an alternative intravenous monotherapy regimen at a higher intensity may be preferred instead. Coexisting hyperthyroid state is controlled medically throughout the course of orbital treatment.
Treatment Goals
- ≥ 2 mm reduction in lid aperture
- ≥ 1 point reduction in the five-item CAS
- ≥ 2 mm reduction in exophthalmos
- ≥ 8° increase in eye muscle duction
- Improvement in ≥ 2 features in one eye without deterioration in the other
- Response assessed 3 months after the last intervention (changes at 6 months also considered)
References
DOI: 10.1530/EJE-21-0479
- GO is defined as active if CAS is ≥ 3/7 (Table 2).
- Lid retraction ≥ 2 mm; moderate or severe soft-tissue involvement; exophthalmos ≥ 3 mm above normal for race and gender; inconstant or constant diplopia.
- Patients without sight-threatening GO whose eye disease has sufficient impact on daily life to justify the risks of immunosuppression (if active) or surgical intervention (if inactive).
- Intravenous methylprednisolone in combination with oral mycophenolate sodium (or mofetil) represents the first-line treatment for moderate-to-severe and active GO.
- In the more severe forms of moderate-to-severe and active GO, including constant/inconstant diplopia, severe inflammatory signs and exophthalmos > 25 mm, i.v. methylprednisolone at the highest cumulative dose (7.5 g per cycle) as monotherapy represents an additional valid first-line treatment.
- Moderate-to-severe and active GO: hyperthyroidism should be treated with ATDs until treatment of GO is completed.
- It is composed of entirely objective measures: ≥2-mm reduction of lid aperture, ≥1 point reduction in five-item CAS (excluding subjective, patient-reported spontaneous or gaze-evoked pain), ≥2 mm reduction in exophthalmos, ≥8° increase of eye muscle duction.
- Improvement in ≥2 features in one eye without deterioration in the other eye might be considered a positive response to treatment.
- Optimally, the outcome of treatment should be assessed 3 months after the last therapeutic intervention, but, in addition, changes after 6 months can also be considered.