Dysthyroid Optic Neuropathy Complicated by Neuromyelitis Optica Spectrum Disorder: A Case Report

Neuromyelitis optica spectrum disorder (NMOSD) is an infrequent autoimmune inflammatory demyelinating disease of the central nervous system that primarily affects the spinal cord and/or optic nerves. NMOSD usually manifests through acute instances of optic neuritis and/or myelitis [1, 2]. In those suffering from NMOSD, thyroid pathologies, such as chronic thyroiditis, Graves’ disease, and benign thyroid tumors, are frequently observed complications [3]. Thyroid eye disease (TED), also termed Graves’ orbitopathy or ophthalmopathy, is an autoimmune disorder associated with Graves’ and other autoimmune thyroid diseases [4, 5]. It is an autoimmune condition linked with Graves’ and other autoimmune thyroid disorders, characterized by inflammation and hypertrophy of orbital fat, extraocular muscles, and lacrimal glands. Dysthyroid optic neuropathy (DON), a grave consequence of TED, can lead to irreversible visual impairment, necessitating immediate medical intervention [6]. This report details a patient potentially afflicted with DON and NMOSD concurrently.

A 44-year-old Japanese female experienced diminishing visual acuity, initially in her left eye, later affecting the right. Six months later, an evaluation at Olympia Eye Hospital revealed a decimal best-corrected visual acuity (BCVA) of 0.8 (20/25 Snellen equivalent) in the right eye (OD) and 0.02 (20/1,000 Snellen equivalent) in the left (OS). In her medical history, she was diagnosed with Graves’ disease and treated with thiamazole at the age of 37. Her anthropometric measurements included a height of 158 cm, weight of 60 kg, and a body mass index of 24.0 kg/m. She reported orbital pain, and eye movements were restricted in all directions bilaterally. Kinetic Goldmann perimetry revealed a central scotoma in both eyes (OU) (Fig. 1a). Optical coherence tomography indicated slight atrophy of the left optic nerve’s temporal side of circumpapillary retinal nerve fiber layer thickness, while the right appeared normal (Fig. 1b). Magnetic resonance imaging (MRI) of the brain and orbits demonstrated bilateral enlargement of all four rectus muscles, sparing their tendinous insertions, and compressing the optic nerve in coronal (Fig. 2a, b) and axial (Fig. 2c) sections. Laboratory tests indicated elevated serum levels of the third-generation thyroid-stimulating hormone receptor antibody at 26.4% (reference value: <15%) and thyroid-stimulating antibodies at 5,008% (reference value: <120%). The patient was diagnosed with bilateral DON, based on clinical and imaging findings, and elevated serum thyroid-stimulating antibody levels. These findings, alongside the clinical symptoms and MRI results, led to a diagnosis of bilateral DON. Upon hospitalization, the patient underwent triple courses of steroid semi-pulse therapy, consisting of 500 mg daily methylprednisolone for 3 days, followed by an oral prednisolone regimen starting at 30 mg daily. This treatment improved her BCVA to 1.2 (Snellen equivalent 20/16.7) in OD and 0.1 (Snellen equivalent 20/200) in OS. Over the next 2 months, as her oral steroid dose was tapered, she underwent left orbital decompression surgery, which alleviated optic nerve compression by reducing the size of the enlarged muscles (Fig. 3). Despite this intervention, her BCVA in OS stagnated at 0.1, with persistent central scotomas in OU (Fig. 4a). Subsequent testing for anti-aquaporin-4 antibody (AQP4-Ab) returned positive results (3.1 U/mL, reference value: <3.0); thereafter, the patient was referred to The Jikei University Katsushika Medical Center. At that point, the optic nerves were already atrophic in OU (Fig. 4b). The circumpapillary retinal nerve fiber layer thickness was thinner compared to the initial examination (Fig. 1b) even in OS. The patient’s BCVA remained at 1.2 in OD and 0.1 in OS, with intraocular pressures of 18 mm Hg in OD and 15 mm Hg in OS. Relative afferent pupillary defect was positive on OS. Critical flicker fusion frequency was slowly measured, resulting in 28 Hz in OD and 23 Hz in OS. Neurological examination revealed no further symptoms, and MRI showed no lesions in the brain or spinal cord. However, STIR MRI of the orbit indicated swelling and high signal intensity in the left optic nerve, suggestive of optic neuritis (Fig. 5). Ultimately, she received a diagnosis of anti-AQP4-Ab-positive NMOSD. In addition to 10 mg of daily oral prednisolone, satralizumab, a humanized anti-interleukin-6 receptor antibody, was administered to the patient for vision maintenance. The patient was followed up regularly. Her last follow-up was 18 months after the first visit to Olympia Eye Hospital. Her BCVA was 1.5 (Snellen equivalent 20/13.3) in OD and 0.15 (Snellen equivalent 20/133) in OS at the last visit. No recurrence of optic neuritis and DON was noted. Visual function in OD, which was immediately after onset at the initial visit, recovered relatively well, but visual function in OS, which was 6 months after onset, improved only slightly.

This patient was initially diagnosed with and treated for DON; nonetheless, two clinical findings were incongruent with DON, prompting the suspicion of optic neuritis due to observed bilateral optic atrophy (Fig. 4b). The first discrepancy involved the visual field defect, atypical for DON, which characteristically presents with a central or paracentral scotoma and additional peripheral field anomalies [7], not solely a central scotoma as seen in this case (Fig. 1a). Second, the rapid progression to optic nerve atrophy (Fig. 4c), within 6 months of visual acuity loss, is premature for DON, which often shows papillary redness without atrophy in its early stages. In addition, the visual function recovery in the left eye was suboptimal despite aggressive interventions. This resistance, alongside the MRI findings of optic nerve swelling with increased STIR signal (Fig. 5), strengthens the possibility of optic neuritis [8], although the optic disc atrophy (Fig. 4b) could also be the result of compressive optic neuropathy as well.

Recovery of visual function in OS was poor despite steroid semi-pulse therapy administration and left orbital decompression surgery. Steroid semi-pulse therapy was administered immediately after onset on the right eye, but the central scotoma remained, and subsequent optic nerve atrophy occurred (Fig. 4b). Comparing this case with the diagnostic criteria for anti-AQP4-Ab-positive NMOSD in the 2015 international diagnostic criteria for NMOSD [9], the existence of optic neuritis, a hallmark of NMOSD, was evident. Although steroid therapy typically decreases serum anti-AQP4-Ab levels [10, 11], the modest elevation detected post-therapy suggests higher levels at the onset of optic neuritis. This case also highlights the association of anti-AQP4-Ab-positive optic neuritis with significant thyroid-associated autoantibodies and thyroidal complications. The coexistence of TED and DON with NMOSD is unprecedented in the literature. This report underscores the complex and intertwined pathogenesis of NMOSD and DON, with indistinct onset timings. Earlier detection methods, such as gadolinium-enhanced or STIR MRI at initial presentation, could have clarified the presence of optic neuritis. Accumulating similar cases may aid in understanding the relationship between these conditions. Therefore, early anti-AQP4-Ab titer testing is crucial where DON does not solely account for visual impairment. This report delineates the first instance of a patient with potentially concurrent optic neuropathies related to DON and NMOSD, associated with autoimmune diseases. The CARE Checklist has been completed by the authors for this case report, attached as online supplementary material (for all online suppl. material, see https://doi.org/10.1159/000540496).

Written informed consent was obtained from the patient for publication of the details of their medical case and any accompanying images. This report does not include any identifying patient information. All actions related to this report were performed in accordance with the World Medical Association Declaration of Helsinki. Ethical approval is not required for this case report in accordance with local or national guidelines.

The authors report no conflicts of interest regarding this report.

This report did not receive any relevant funding support.

T.T., T.H., S.O., and T.N. drafted and edited the manuscript. A.K. and T.I. performed the medical treatment, conducted the follow-up of the patient, and critically reviewed the manuscript. All authors of this report are to fulfill the ICMJE Criteria for authorship.

All data generated during this report are included in this article. Further inquiries can be directed to the corresponding author.