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.

The relationship between atherosclerotic disease and relapse during ATD treatment

“…Clinically, Graves' disease (GD) represents the most common form of hyperthyroidism, accounting for 50–80% of all cases ( 1 , 2 ), and the incidence of GD has been increasing over the past few years ( 1 , 3 ). Over 30% of patients with GD suffered from Graves' orbitopathy (GO) ( 4 – 6 ), which caused vision loss ( 7 ). Additionally, it has been reported that GD was associated with the incidence of major adverse cardiac events (MACE) ( 8 , 9 ).…”

Commentary: Dysthyroid optic neuropathy: A lurking danger in thyroid eye disease

“…Fortunately, the occurrence of DON is noted only in 5%–7% of TED cases. [ 2 ] The diagnosis of established DON is majorly clinical, but the diagnosis of subclinical DON may need detailed ophthalmic examination and imaging. Patients with subclinical DON may not experience a sudden diminution of vision, abnormal pupillary reflexes, and features of orbital inflammation—classical of severe TED.…”

“…Patients with subclinical DON may not experience a sudden diminution of vision, abnormal pupillary reflexes, and features of orbital inflammation—classical of severe TED. [ 2 ]…”

“…The risk factors for clinical and subclinical DON include older age, male gender, smoking, diabetes (controlled or uncontrolled), radioisotope therapy, hyperthyroidism or Grave’s ophthalmopathy, and high level of thyroid autoantibodies. [ 1 2 ] The pathogenesis of DON involves mechanical, inflammatory, and vascular factors causing damage to the nerve cells and axons of the optic nerve. [ 2 ] TED patients can be classified as type I (predominantly fat enlargement) or type II disease (predominantly extraocular muscle enlargement).…”

“…[ 1 2 ] The pathogenesis of DON involves mechanical, inflammatory, and vascular factors causing damage to the nerve cells and axons of the optic nerve. [ 2 ] TED patients can be classified as type I (predominantly fat enlargement) or type II disease (predominantly extraocular muscle enlargement). In type II TED, the mechanical compression of optic nerve blood supply and axonal flow at the crowded orbital apex occurs due to enlarged extraocular muscles.…”