A Rare Presentation of Myelin Oligodendrocyte Glycoprotein-Associated Optic Neuritis with Venous Stasis Retinopathy and Premacular Hemorrhage: A Case Report

Myelin oligodendrocyte glycoprotein (MOG) is an essential glycoprotein for the myelination of nerves within the central nervous system [1], with its synthesis controlled by the MOG gene [2]. Autoantibodies targeting MOG can lead to autoimmune inflammatory disorders that affect various central nervous system structures, including the optic nerve, spinal cord, and brain [3]. The clinical manifestations of MOG-related disorders depend on the specific organs involved. Optic neuritis is the most common presentation, accounting for 50–70% of cases during the disease course, particularly in adults. In contrast, acute encephalomyelitis tends to be more common in younger individuals younger than 18 years old [4]. Bilateral optic nerve involvement occurs in up to 40% of cases and is frequently accompanied by typical optic nerve head swelling [5, 6]. Treatment with systemic corticosteroids is effective, with most patients responding favorably and having a good prognosis. This diverse spectrum of clinical presentations highlights the varied characteristics of MOG-related autoimmune disorders and emphasizes the importance of tailored therapeutic approaches based on the specific manifestations observed.

Several ocular presentations and complications have been documented associated with MOG-associated optic neuritis. These complications include a variety of manifestations such as retinal vasculitis [7], peripheral retinal hemorrhage [8], prepapillary vitreous hemorrhage [9], dense premacular hemorrhage [10], branch retinal artery occlusion with anterior ischemic optic neuropathy [11], Roth spot [12], and venous stasis retinopathy [13], which are uncommon and occur infrequently. The ongoing documentation and analysis of these ocular comorbidities contribute significantly to our understanding of this inflammatory demyelinating disorder, enhancing our knowledge of its diverse clinical presentations and potential complications. In this report, we present an atypical case involving the simultaneous occurrence of bilateral venous stasis retinopathy alongside bilateral optic neuritis associated with MOG.

A 27-year-old female patient presented with a persistent throbbing headache for 2 weeks, which worsened over time without medical treatment and evaluation. She had a medical history of well-controlled allergic rhinitis. Two days before experiencing visual impairment, she visited an otolaryngology unit for evaluation. The examination included a normal examination of the nasopharynx and paranasal sinus film. She received symptomatic treatment and was scheduled for a follow-up appointment in 1 week. The onset of painful visual loss occurred 3 h before she visited the ambulatory unit, primarily affecting her central visual field. The patient denied any recent ocular trauma or surgical interventions. Upon ocular examination, her right eye exhibited a best-corrected visual acuity (BCVA) of 20/800, while her left eye maintained a vision of 20/20. Intraocular pressure measurements were recorded at 24 mm Hg in the right eye and 20 mm Hg in the left eye. Fundus examination of the right eye revealed a preretinal hemorrhage measuring approximately 10-disk diameters at the posterior pole involving the macular area with vitreous hemorrhage, optic disk swelling with hyperemia, scatter intraretinal hemorrhage, Roth spots, and tortuous, dilated veins without sheathing vessels. Fundoscopic examination of the left eye was unremarkable. The patient received a preliminary diagnosis of presumed central retinal vein occlusion in the right eye and was scheduled for a comprehensive laboratory workup in 2 days to investigate potential hypercoagulable states and other inflammatory etiologies.

During a scheduled appointment, the patient experienced acute visual deterioration in her left eye 4 h before admission. Her BCVA decreased to hand movements in the right eye and finger counting at a distance of at least three feet in the left eye. She noticed a significant discrepancy in visual field impairment, with the inferior half notably worse than the superior half in her left eye. Funduscopic examination revealed several findings: in her right eye, extensive preretinal hemorrhages with associated vitreous hemorrhage, markedly disk swelling with tortuous and dilated veins, scatter dot-blot hemorrhages, and Roth spots; together with the left eye, showed disk swelling with hyperemia, scatter Roth spots, dot and blot hemorrhages, and mildly tortuous and dilated veins (shown in Fig. 1). The optical coherence tomography macula and optical coherence tomography angiography were normal in the left eye. The automated perimetry revealed generalized depression in the left eye (shown in Fig. 2). The provisional diagnosis was bilateral central retinal vein occlusion or venous stasis retinopathy with dense premacular hemorrhage in the right eye. Consequently, the patient was admitted for an extensive workup to explore possibilities of hyperviscosity-related conditions and other potential masquerade diseases, such as lymphoproliferative disorders.

The laboratory investigations revealed a normal complete blood count, with white blood cell count at 7,200/µL, polymorphonuclear leukocytes at 67.5%, lymphocytes at 24.1%, and platelets at 347,000/µL. C-reactive protein levels were elevated at 6.59 mg/L, and the erythrocyte sedimentation rate was slightly elevated at 20 mm/h, within the upper limit of the standard range. Serological tests for HIV and syphilis were negative. A chest X-ray showed no abnormalities. Analysis of cerebrospinal fluid (CSF) from a lumbar puncture revealed a normal opening pressure of 16 cm H₂O, with pleocytosis characterized by 4 red blood cells/mm² and 8 white blood cells/mm², with 100% mononuclear cells; cytology results were negative. Polymerase chain reaction testing of CSF for herpes virus type 7 was negative. Hypercoagulability testing, including LA-DRVVT ratio (0.92), LA-APTT (0.97), regular prothrombin time, activated partial thromboplastin time ratio, thrombin time ratio, and international normalized ratio, was all within normal ranges. Serum analysis revealed a positive result for MOG antibodies but a negative result for aquaporin-4 (AQP-4) antibodies, while both AQP-4 and MOG antibodies were negative in CSF.

Magnetic resonance imaging of the brain and orbits demonstrated bilateral longitudinally extensive optic nerve enlargement accompanied by T2/FLAIR hypertensive signal and enhancement, particularly notable on the right side, exhibiting perineural fat strand enhancement. However, there were no fluffy lesions in either white or gray matter, and no significant findings were observed in the periventricular white matter, area postrema, infratentorial, or juxtacortical area (shown in Fig. 3, 4).

The patient received intravenous methylprednisolone at a dosage of 1 g once daily for consecutive 5 days. Subsequently, her vision in the left eye improved dramatically. Her BCVA in the left eye had improved to 20/100 by the second day of treatment, 20/50 by the third day, and 20/20 by the fifth day of corticosteroid therapy, exhibiting incredibly full recovery. Despite the recommendation for fundus fluorescein angiography (FFA), the patient declined this procedure and preferred to observe the vitreous hemorrhage, anticipating its spontaneous resolution.

Two months after the initial treatment, the patient’s visual acuity improved significantly, with the right eye able to perceive objects at least 2 feet distant. Her current medication regimen included prednisolone low dose (slowly tapering from a dose of 1 mg per kilogram per day after methylprednisolone) and azathioprine at 50 mg daily. Fundoscopic examination revealed a grade 3 vitreous hemorrhage in her right eye, while the left eye exhibited only fainted scatter dot-blot hemorrhage (shown in Fig. 5). Following extensive consultation with retinal specialists, a consensus was made to employ a conservative approach, monitoring the patient’s progress as the vitreous hemorrhage gradually subsided.

The clinical presentations of our patient align with the classic presentation of MOG-associated optic neuritis, characterized by abrupt and profound visual impairment accompanied by bilateral optic disk edema [4, 14]. Radiological imaging demonstrating bilateral optic nerve and perineural enhancement without signs of other inflammatory or demyelinating disorders further supports the inflammatory nature of the condition, consistent with typical findings seen in clinical optic neuritis [4, 14]. The rapid and favorable response observed following corticosteroid therapy provides additional evidence indicating inflammation is the primary etiology underlying this manifestation. However, venous stasis retinopathy in both eyes was an infrequent manifestation of MOG.

The patient’s persistent headache was evaluated in stages. She denied any viral prodrome or fever before a nasopharyngeal consultation, which revealed normal findings after a nasopharyngeal examination and paranasal sinus imaging. Symptomatic treatment was provided. Since there were no signs of eye problems or visual symptoms at that time, an ophthalmologist was not consulted. Investigations were limited due to the absence of specific prior infections or prodromal symptoms.

Venous stasis retinopathy, initially described by Hayreh as an incomplete occlusion of the central retinal vein, represents an early form of ocular ischemia characterized by clinical features such as tortuous and engorged retinal veins, frequently accompanied by spot or flame-shaped retinal hemorrhages, as well as hyperemic and subtly swollen optic disks [15]. The risk factors associated with central retinal vein occlusion, including hypertension, diabetes, dyslipidemia, and glaucoma, are also pertinent to venous stasis retinopathy [16]. Furthermore, this condition has been linked to various etiologies such as hypercoagulable states, infections, vasculitis, and certain medications [16]. Typically, venous stasis retinopathy manifests in older individuals; however, our case highlights an atypical presentation in a younger patient presenting with severe ocular pain. Given this unusual presentation, extensive investigations beyond the standard workup were warranted to elucidate the underlying factors contributing to the condition, particularly genetic workups like factor V Leiden mutation and prothrombin G20210A.

The precise pathophysiological mechanisms underlying venous stasis retinopathy remain unclear, necessitating further investigation. According to hypothesized mechanisms, severe inflammation may cause swelling and congestion within the optic nerve head, potentially leading to secondary obstruction of blood outflow [15] and damage to the venous vasculature [17, 18], ultimately resulting in a manifestation of venous stasis retinopathy [17, 18]. The prompt and positive response observed following high-dose corticosteroid therapy provides clinical support for this proposed hypothesis, highlighting the potential role of inflammation in the pathogenesis of this condition.

To date, only one documented case of venous stasis retinopathy associated with MOG-associated optic neuritis has been reported in the literature [13]. Lukewich et al. [13] reported on a 38-year-old female patient who presented with unilateral optic neuritis accompanied by secondary venous stasis retinopathy. Unlike our case, there was no preretinal hemorrhage or vitreous hemorrhage. Her initial assessment revealed that the visual acuity was limited to light perception. The patient received a 5-day course of high-dose corticosteroids at 1 g daily for 5 days, followed by seven sessions of plasmapheresis. Oral corticosteroids were gradually decreased over 4 months. By the 6-month follow-up, the patient demonstrated a remarkable improvement in visual acuity, achieving 20/20 vision, albeit with residual generalized visual field defects persisting.

Several cases suggesting a milder form of venous stasis retinopathy have also been documented in the literature [9, 10, 12]. These cases were described in terms of their clinical course, treatment, and visual outcomes.

Aboab et al. [12] reported on a 49-year-old female patient presenting with painful visual loss in her left eye, with visual acuity reduced to at least counting fingers at 2 feet. Fundoscopic examination revealed severe optic disk edema accompanied by multiple peripapillary and peripheral retinal hemorrhages and Roth spots. Following a prompt 6-day course of high-dose corticosteroids, the patient’s vision improved and the fundus background was completely normal. Eventually, she achieved a vision of 20/20 with residual optic disk pallor.

In another report by Mudri et al. [9], a 6-year-old boy diagnosed with bilateral MOG-associated optic neuritis subsequently developed unilateral peripapillary vitreous hemorrhage without abnormal retinal vessels. Extensive investigations suggested MOG as the likely cause of the vitreous hemorrhage in this case. Following inflammatory treatment with corticosteroids, the vitreous hemorrhage resolved, resulting in complete vision recovery.

Furthermore, Budoff et al. [10] reported a 17-year-old male patient with acute unilateral visual loss lasting 2 days, with hand motion as the BCVA. Fundus examination revealed optic disk edema and dense premacular hemorrhage, while magnetic resonance imaging demonstrated enhancement of the affected optic nerve alongside positive serum MOG antibody findings.

To the best of our knowledge, our case is the first case reported with an atypical case of bilateral severe visual loss with venous stasis retinopathy in both eyes, premacular hemorrhage, and vitreous hemorrhage in one eye resulting from MOG-associated optic neuritis. Promptly corticosteroid therapy resulted in an excellent response to treatment with rapidly achieved good visual acuity. One limitation of our study is the absence of FFA due to the patient’s refusal to undergo this investigation. FFA is a useful diagnostic tool for evaluating retinal vasculature conditions such as retinal circulation abnormalities and retinal vessel inflammation, which is helpful for a better understanding of the mechanism in our case. Consequently, there is a lack of evidence regarding decreased blood flow to the retinal circulation and other inflammatory signs including retinal vasculitis. 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/10.1159/000540776).

Venous stasis retinopathy represents a rare ocular complication associated with MOG-associated optic neuritis. Clinicians should maintain a high index of suspicion for atypical presentations, particularly venous stasis retinopathy in younger patients without any previous medical illness, to ensure timely diagnosis and appropriate management. While this association is noteworthy, thorough investigations are required to rule out alternative treatable etiologies. The specific pathogenesis of venous stasis retinopathy in the context of MOG-related optic neuritis remains elusive, highlighting the necessity for further research and additional evidence to determine the precise mechanisms.

We are grateful to Dr. Thitiporn Ratanapojnard for her invaluable guidance. Her expertise and insights shaped our study. We also thank the ophthalmology division of Phramongkutklao Hospital for their generous resources and support.

The Institutional Review Board Royal Thai Army reviewed and approved this study protocol, Approval No. S038h/67_Exp. Written informed consent was obtained from the patient for publication of the details of their medical case and any accompanying images.

The authors have no conflicts of interest to declare.

This study was not supported by any sponsor or funder.

Worapot Srimanan: study concept and design, manuscript drafting, and study supervision. Yaninsiri Ngathaweesuk: interpretation of imaging data and critical revision. All authors approved the final version of the manuscript.

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