Insights into Current Management Strategies for Dysthyroid Optic Neuropathy: A Review

Abstract

Dysthyroid optic neuropathy (DON) is a potentially sight-threatening eye disease associated with Graves' orbitopathy (GO). DON is not common in GO patients, reportedly occurring in only about 5% of patients. The pathogenesis of severe DON is considered to involve both muscular nerve strangulation and impaired blood flow. There is some objective grading of physical examination findings and the severity of GO, including a clinical activity score (CAS) and EUropean Group On Graves' Orbitopathy (EUGOGO), but no specialized protocol completely characterizes DON. Most clinicians have decided that the combination of clinical activity findings, including visual acuity, color vision, and central critical fusion frequency, and radiological findings, including magnetic resonance imaging (MRI), can be used to diagnose DON. MRI has the most useful findings, with T2-weighted and fat-suppressed images using short-tau inversion recovery (STIR) sequences enabling detection of extraocular changes including muscle and/orbital fat tissue swelling and inflammation and, therefore, disease activity. The first-choice treatment for DON is intravenous administration of steroids, with or without radiotherapy. Unfortunately, refractoriness to this medical treatment may indicate the need for immediate orbital decompression within 2 weeks. Especially in the acute phase of DON, thyroid function is often unstable, and the surgeon must always assume the risk of general anesthesia and intra- and post-operative management. In addition, there are currently many possible therapeutic options, including molecular-targeted drugs. The early introduction and combination of these immunomodulators, including Janus kinase inhibitors and insulin-like growth factor-1 receptor antibody (teprotumumab), may be effective for GO with DON. However, this is still under investigation, and the number of case reports is small. It is possible that these options could reduce systemic adverse events due to unfocused glucocorticoid administration. The pathophysiology of DON is not yet fully understood, and further studies of its treatment and long-term visual function prognosis are needed.

Keywords: Graves’ orbitopathy; Janus kinase inhibitors; MRI; dysthyroid optic neuropathy; magnetic resonance imaging; orbital decompression; teprotumumab; visual outcome.

Figure 1

MRI findings of GO with DON (T2-weighted and fat-suppressed images using short-tau inversion recovery (STIR) sequences). Right: extraocular muscle swelling in both orbital cavity/. Left: extraocular muscle swelling compressing the optic nerve around the common tendinous ring.

Figure 2

Algorithm for the management of sight-threatening Graves’ orbitopathy including DON. The first-line treatment for optic neuropathy is high-dose IV methylprednisolone or steroid pulse therapy (single doses of 500 to 1000 mg) for three consecutive days, or preferably and for safety reasons, every second day (alternate days) during the first week, which can be repeated for a second week. When the response is absent or poor, with deterioration in visual acuity or CFF, urgent orbital decompression surgery will be needed. Data from Bartalena L, Kahaly GJ, Baldeschi L, et al. The 2021 European Group on Graves’ orbitopathy (EUGOGO) clinical practice guidelines for the medical management of Graves’ orbitopathy. Eur J Endocrinol. 2021;185(4):G43–G67.

Figure 3

Schema of this review: Summary.