Central Retinal Artery Occlusion Associated with Myelin Oligodendrocyte Glycoprotein Antibody Disease: A Case Report

Abstract

Introduction

Myelin oligodendrocyte glycoprotein antibody disease (MOGAD) is a more recently characterized neuroinflammatory condition which has been implicated with optic neuritis (ON). While the potential causes of central retinal artery occlusion (CRAO) are several, neuroinflammatory causes should not be excluded from the differential diagnosis. Our unusual case presents a patient with prior history of MOGAD-ON and venous stasis retinopathy (VSR) in their right eye, who, in their current presentation, developed a CRAO in their left eye.

Case Presentation

A 43-year-old female with a history of concurrent VSR and MOGAD-ON (diagnosed 6 years prior and managed with long-term immunosuppression and oral steroids) in her right eye presented with a five-hour history of pain and blurry vision in her left eye. Examination of the left eye revealed a visual acuity (VA) of 20/80, a cherry red spot (without a visualized embolus), and a new generalized visual field defect. Optical coherence tomography (OCT) revealed diffuse retinal edema in her left eye with multiple layers of retinal thinning. She was referred to stroke neurology and continued oral steroid therapy. At 6-month follow-up, her VA had markedly improved to 20/30 in her left eye, and she had stable OCT parameters.

Conclusion

This unique case demonstrates sequential VSR and CRAO in opposite eyes, which were notable for their association with recurrent MOGAD-ON. Further research is needed to better elucidate the role of MOGAD in vascular occlusive events and whether this relationship may be arteritic in etiology.

Introduction

Myelin oligodendrocyte glycoprotein (MOG)-IgG is a marker that, in the setting of negative anti-aquaporin-4 IgG, correlates to patients with MOG antibody disease (MOGAD) that experience recurrent optic neuritis (ON) [1]. While the MOGAD-ON generally follows a monophasic or relapsing-remitting course, patients typically experience favorable visual outcomes [1]. To date, scarce reported cases implicate a history of MOGAD-ON with a propensity for retinal vascular events. In the literature, 1 patient had experienced poor visual outcome despite aggressive treatment from unilateral venous stasis retinopathy (VSR) secondary to MOGAD-ON [1]. However, other retinal events in the context of MOGAD-ON have not been reported. Herein, we describe the unique and extended clinical course of this patient with prior VSR secondary to MOGAD-ON [1], who, several years later, developed a central retinal artery occlusion (CRAO) in the contralateral eye. 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/10.1159/000547495).

Case Report

A 43-year-old South Asian female had first presented 6 years prior with progressive right unilateral vision loss and painful eye movements for 2 weeks [1]. Her medical history was significant for controlled hypertension treated with candesartan and a negative hypercoagulable workup [1]. In her right eye (OD), she had light perception visual acuity (VA), a relative afferent pupillary defect, severe optic disc edema with hemorrhage, tortuous retinal venules, and small dot 360° hemorrhages throughout the retina [1]. Her left eye (OS) examination was normal. Given MRI evidence of longitudinally extensive optic nerve inflammation and medium MOG-IgG seropositivity, she was diagnosed with VSR secondary to MOGAD-ON [1]. On aggressive treatment with steroids, seven plasmapheresis sessions, and initiation of long-term azathioprine, her VA OD improved to 20/20, albeit retaining a significant generalized visual field (VF) defect (mean deviation −17.71) at 6 months [1]. One year later, she had an additional inflammatory flare, presenting with 20/80 vision OD and new painful extraocular movements. She had two further recurrences within her third year of follow-up, which, in 1 case, presented with a VA of 20/100 OD. During follow-up year three, she also suffered hepatotoxicity to her azathioprine, after which she initiated her current regimen of mycophenolate mofetil and daily oral steroid therapy (with dorzolamide and timolol drops for intraocular pressure reduction). Thereafter, in follow-up year four, she had another symptomatic flare. All inflammatory flares over this period were managed with oral steroids.

In her current presentation, she had presented with a 5-h history of pain and blurry vision OS. Ophthalmic examination revealed a VA of 20/25+1 OD and 20/80 OS, a relative afferent pupillary defect, and her intraocular pressures were 18 mm Hg OU. Her extraocular movements were full. Anterior segment examination was unremarkable. Dilated fundus examination revealed optic disc pallor OD, diffuse retinal edema with a cherry red spot OS, and no visualized emboli. An OCT 5-line raster demonstrated increased thickness, distortion, and hyperreflectivity of the inner retinal layers, with linear back-shadowing which attenuated signal from the outer retinal layers (shown in Fig. 1). These findings were suggestive of an event consistent with ischemic and cytotoxic inner retinal edema. Bilateral OCT of the optic nerve head also showed nerve fiber layer thinning OD secondary to prior ON, whereas no nerve fiber thinning was noted OS (shown in Fig. 2). Humphrey 24-2 SITA-Fast VFs at this presentation showed a generalized VF defect OU (shown in Fig. 3) that was more extensive OS (mean deviation: −8.06 dB OD and −17.99 dB OS). Altogether, this patient’s clinical and OCT features were consistent with a diagnosis of CRAO in her left eye. She was referred to stroke neurology but was outside the time window for acute management. Her same-day admission to hospital for systemic workup precluded fluorescein angiography or color fundus photography, which were not readily available in the neuro-ophthalmology clinic. An MRI orbits and brain with contrast (Fig. 2b) showed enhancement of the anterior part of the intraorbital optic nerve near its insertion into the left globe. She also underwent a CTA head and neck, echocardiogram, and Holter monitoring which were normal. As her prior VSR improved rapidly with steroids and her MRI was suggestive of MOGAD-ON recurrence, she was treated acutely with intravenous steroids (methylprednisolone 1 g daily) for 5 days, followed by prednisone 1 mg/kg with a slow taper. She was also initiated on rituximab infusions. She felt subjective improvement on the steroid treatment, and at 6-month follow-up, her VA had improved to 20/30-2 OD and 20/30 OS. OCT parameters remained stable, albeit there was trace progression of optic disc pallor OS, though markedly less than that compared to her right eye. At last follow-up, her treatment regimen consisted of prednisone 10 mg daily, mycophenolate mofetil 500 mg twice daily, intravenous immunoglobulin every 2 weeks, and rituximab infusions every 6 months. She reported good adherence to this regimen and tolerated her medications without side effects.

Fig. 1.

Optical coherence tomography 5-line raster of the left eye. There is elevated thickness, reflectivity, and distortion of the retinal inner layers, whereas there is signal attenuation of the outer retinal layers. Altogether, these findings are suggestive of retinal edema in the setting of central retinal artery occlusion.

Fig. 2.

Optical coherence tomography optic nerve head and retinal nerve fiber layer (RNFL). There is RNFL thinning in the right eye secondary to the patient’s history of recurrent optic neuritis. In their acute presentation for CRAO, there is no RNFL thinning observed in the left eye.

Fig. 3.

a Humphrey 24-2 SITA-Fast visual fields (VF). The right eye exhibits a sustained generalized VF loss secondary to their history of recurrent optic neuritis. In the left eye, there is a new diffuse VF defect, more severe than in their right eye, which coincided with the patient’s diagnosis of central retinal artery occlusion. b Magnetic resonance imaging of the orbits with contrast demonstrating a new enhancement within anterior portion of the intraorbital left optic nerve near its insertion into the left ocular globe.

Discussion

This case highlights the rare occurrence of CRAO in a patient with recurrent MOGAD-ON. To our knowledge, no prior report has documented CRAO in the context of MOGAD. The development of CRAO in this patient suggests a possible pathophysiological link between MOGAD and vascular events, such as CRAO. Given the patient’s history of neuroinflammatory disease without a known uncontrolled non-arteritic risk factor, it remains reasonable to consider whether the etiology of this link is arteritic. As an embolus was not visualized in this case, the pathophysiology may involve MOGAD-mediated vasculitis of the central retinal artery or compression of the central retinal artery from optic nerve inflammation. Further research is needed to better elucidate the role of MOGAD in vascular occlusive events.

In a prior report, this patient had presented with coinciding VSR and MOGAD-ON, where it was proposed that MOGAD-mediated intraorbital optic nerve involvement may have placed the central retinal vein at risk of partial or complete occlusion [1]. This may be related to co-local inflammation and swelling of the optic nerve head, in proximity to the retinal vasculature [1]. In the current presentation with CRAO, there were also inflammatory changes in the anterior part of the intraocular optic nerve, suggesting that MOGAD was responsible. The CRAO may have shared a similar mechanism with their prior VSR, this time potentially related to co-inflammation and/or compression of the central retinal artery due to nearby optic nerve inflammation. Unlike the patient’s episode of VSR, the patient was on long-term oral steroid therapy prior to the occurrence of CRAO [1]. This likely reduced the severity of the patient’s most recent MOGAD-ON episode, which may have nonetheless reprecipitated inflammation and/or compression of nearby retinal vasculature. This case supports the use of steroids in a patient with a CRAO that is associated with MOGAD.

While MOGAD predominantly manifests as a syndrome of central nervous system demyelination, the literature contains rare reports of MOGAD in patients with pathologically proven central nervous system vasculitis [2]. However, whether vasculitis is a primary or secondary complication of MOGAD, or possibly unrelated, remains unclear [2]. Of note, while arteritic CRAO is most commonly caused by temporal arteritis, other autoimmune disorders (e.g., polyarteritis nodosa, Susac syndrome, systemic lupus erythematosus) may manifest as vasculitis [3]. Altogether, further evidence is needed to elucidate the potential role of MOGAD in vasculitis and related retinal vascular events.

To date, the management of CRAO remains controversial with no consensus on an evidence-based treatment protocol [4]. In our case, our patient was referred to stroke neurology but was outside the time window for acute management of her CRAO. Nonetheless, at 6-month follow-up, this patient experienced a significant six-line VA recovery to 20/30 OS, which is considerable given that 80% of patients with CRAO are expected to have a final VA of 20/400 or worse in the affected eye [5].

The main strength of this case report is its exhibition of clinical symptoms and signs of CRAO, further supported by OCT imaging, in the concurrent context of MOGAD-ON recurrence. Both features thereafter improved with further steroid administration. The main limitation of this case report is its single patient sample size, which cannot infer statistical inferences on a potential connection between MOGAD, vasculitis, and CRAO.

In summary, this case highlights the rare occurrence of CRAO in a patient with history of recurrent MOGAD-ON. The development of CRAO in this patient suggests a possible pathophysiological link between MOGAD and vascular events, such as CRAO, and so clinicians should not neglect the potential role of neuroinflammatory disease in development of CRAO. Given the patient’s history of neuroinflammatory disease without a known uncontrolled non-arteritic risk factor, it remains reasonable to consider whether the etiology of this link is arteritic. As an embolus was not visualized in this case, the pathophysiology may involve MOGAD-mediated vasculitis of the central retinal artery or compression of the central retinal artery from optic nerve inflammation. Further research is needed to better elucidate the role of MOGAD in vascular occlusive events.

Statement of Ethics

The need for ethics approval was waived by the University of Toronto Research Ethics Board. Written informed consent for publication was obtained from the patient for publication of this case report and any accompanying images. The patient declined to offer their subjective perspective for publication.

Conflict of Interest Statement

The authors have no conflicts of interest to declare.

Funding Sources

This study was not supported by any sponsor or funder.

Author Contributions

B.K.T. and J.M.: conceptualization, methodology, data curation, visualization, investigation, writing (original draft), and writing (reviewing and editing).

Funding Statement

This study was not supported by any sponsor or funder.

Data Availability Statement

All data generated or analyzed during this study are included in this article and its online supplementary material. Further inquiries can be directed to the corresponding author.