Man presents with gray spot in upper field of vision
Click Here to Manage Email Alerts
A 53-year-old man presented to the comprehensive ophthalmology service at New England Eye Center for a second opinion of a new dark gray spot in his upper right visual field.
He had experienced the spot for 1.5 weeks along with occasional flashing lights in the right eye. He also reported pain with extraocular movements in the right eye.
Source: Varsha Pramil, MD, and Yosbelkys Martin-Paez, MD
The patient’s medical history was significant for hypertension, possible obstructive sleep apnea and major depressive disorder. He was a former smoker with a 12 pack-year history. He had no significant family history. His ocular history was significant for nonarteritic anterior ischemic optic neuropathy (NAION) in the left eye 12 years prior. He was treated with intravenous steroids at the time with some vision recovery.
Examination
The patient’s visual acuity was 20/20 in the right eye and 20/50 in the left eye. IOPs were normal in both eyes. There was no relative afferent pupillary defect. Motility was full. Visual fields by confrontation showed a superotemporal field defect in the right eye and an inferotemporal field defect in the left eye. Anterior exam was unremarkable. Dilated fundus exam showed optic nerve swelling with disc hemorrhages in the right eye and optic nerve pallor in the left eye. Both discs were crowded. The retina and retinal vasculature were normal. OCT showed diffuse swelling of the optic nerve in the right eye and superior and inferior thinning of the retinal nerve fiber layer in the left eye. There was also diffuse ganglion cell thinning in both eyes. Humphrey visual field 24-2 showed a superior altitudinal defect in the right eye and an inferior altitudinal and superior arcuate defect in the left eye.
At a prior ophthalmology visit at an outside hospital, the patient underwent MRI of the brain and orbits with and without gadolinium, which was reportedly normal. Inflammatory markers including C-reactive protein were normal. Given the patient’s altitudinal defect in the right eye with a history of NAION in the left eye in the setting of a normal MRI and negative inflammatory markers, he was diagnosed with sequential NAION in the right eye and recommended to follow up with neuro-ophthalmology.
On 4-day follow-up with neuro-ophthalmology, the patient was found to have progressive vision loss in the right eye. The visual acuity in the right eye had decreased to count fingers at 1 foot. The visual acuity in the left eye was stable. A relative afferent pupillary defect in the right eye was seen. There was almost total visual field depression in the right eye on Humphrey visual field 30-2. At this time, his ocular history was further reviewed. MRI of the brain and orbits from the time of NAION diagnosis in the left eye 12 years ago was personally reviewed and confirmed to have no evidence of optic neuritis. The patient had also had an extensive workup at that time including lumbar puncture with unremarkable cerebrospinal fluid (CSF) analysis. No infectious or inflammatory etiology had been found, with the workup leading to diagnosis of NAION in the left eye.
Therefore, bilateral sequential NAION, now affecting the right eye, was deemed to be the most likely diagnosis. The patient’s vascular risk factors such as hypertension and possible obstructive sleep apnea in addition to the exam finding of crowded disc also supported this conclusion. However, because of the atypical presentation including pain with extraocular movements, progressive vision loss, possible prior improvement in vision improvement in the left eye after steroid treatment and the inability of a negative MRI to 100% rule out optic neuritis, the patient was started on a prednisone taper, blood work to test for neuromyelitis optica (NMO) and myelin oligodendrocyte glycoprotein (MOG) antibody-associated disease was sent, and MRI of the brain and orbits from the outside hospital was requested for personal review.
The patient tested positive for MOG antibody with a 1:20 titer. Additionally, on personal review, the MRI with and without contrast showed enhancement of the right optic nerve (Figure 1).
What is your diagnosis?
See answer below.
MOG antibody-associated optic neuritis
In a patient older than 50 years with unilateral optic nerve swelling and vision loss, the most likely diagnosis is NAION. However, it is important to have a broad differential at presentation to avoid missing a treatable, progressive disease process such as optic neuritis. In this case, further testing and imaging revealed that the patient had enhancement of the right optic nerve and positive MOG antibodies consistent with MOG antibody-associated optic neuritis.
Clinical course
The patient was diagnosed with MOG antibody-associated optic neuritis and referred to the neurology service for further workup and treatment with immunosuppressive therapy. With the prednisone taper, the patient’s visual acuity in the right eye improved to 20/400. He was started on intravenous immunoglobulin, and visual acuity improved to 20/200 in the right eye. Over the last year, his vision has continued to be stable, and there is a discussion to start the patient on immunosuppressive therapy.
Discussion
In this case, the patient was initially thought to have bilateral sequential NAION due to no enhancement seen on MRI of the brain and orbits and negative extensive workup including CSF analysis 12 years ago. The presence of peripapillary hemorrhage, acute disc swelling and bilateral small optic discs as well as vascular risk factors further suggested this diagnosis. However, the initial episode of NAION in the left eye at the younger age of 41 years, current pain with extraocular movements and progressive vision loss is an atypical presentation for NAION and warranted further investigation. Further testing for MOG antibodies and review of recent MRI of the orbits confirmed the alternate diagnosis of MOG antibody-associated optic neuritis.
Review of the literature has indicated multiple cases of MOG antibody-associated optic neuritis misdiagnosed as NAION. Positive serum MOG antibodies increase the likelihood of optic neuritis. Women are slightly more predisposed to develop this condition than men, and age of diagnosis can vary from 2 to 79 years old. Clinical characteristics include severe vision loss and pain with extraocular movement in addition to diffuse optic disc edema, which it shares with the diagnosis of NAION. MRI of the orbits typically shows longitudinally extensive optic nerve lesions with perineural enhancement, according to Bennett. In 2023, a new criterion was proposed for diagnosis of MOG antibody-associated disease. This classification stated that a core demyelinating event, positive MOG-IgG test and exclusion of better diagnosis must be present. If the MOG antibody titer is less than 1:100 or testing is negative but CSF analysis is positive, then additional supporting clinical or MRI features of optic neuritis, myelitis or brain/brainstem/cerebral syndrome must be identified to conclude that a patient has MOG antibody-associated disease. In this example, the patient was found to have a 1:20 titer with optic neuritis and MRI orbits showing optic nerve MOG antibody-associated optic neuritis.
The patient’s diagnosis of NAION was also questioned due to the improvement of visual acuity with steroid treatment during both episodes of acute progressive vision loss. The use and benefits of steroids in acute NAION are controversial. Hayreh and colleagues first reported that patients treated with steroids had a higher probability for improvement in visual acuity and visual field. However, there were limitations to this study. It may be that some of the patients enrolled in these studies had MOG antibody-associated disease, which may be the reason that they improved. A meta-analysis that included eight studies evaluating the benefits of steroid treatment in NAION showed there was no improvement in visual acuity in these patients with steroid treatment, according to Chen and colleagues. Additionally, a randomized double-masked clinical trial with two groups of patients in the acute phase of NAION, one of which received oral corticosteroids as treatment, found no statistically significant differences in visual acuity or visual field, according to Saxena and colleagues.
There continues to be controversy and differing opinions when it comes to utilizing steroids in NAION, but based on these more recent studies, it may be important to reconsider the use of this treatment. It should also be emphasized that steroids are not without side effects or their own risks, especially in patients with NAION who are generally older and have many vascular risk factors.
In conclusion, although NAION is the most common cause of optic neuropathy in adults older than 50 years, it is important to consider alternate diagnoses when there is an atypical presentation. In these cases, consider obtaining MRI of the brain and orbits with and without contrast and NMO/MOG testing. Finally, there is no conclusive evidence supporting steroid treatment in NAION, and it should be used with caution in these patients.
- References:
- Banwell B, et al. Lancet Neurol. 2023;doi:10.1016/S1474-4422(22)00431-8.
- Bennett JL. Continuum (Minneap Minn). 2019;doi:10.1212/CON.0000000000000768.
- Chen J, et al. Medicine (Baltimore). 2019;doi:10.1097/MD.0000000000017861.
- Hayreh SS, et al. Graefes Arch Clin Exp Ophthalmol. 2008;doi:10.1007/s00417-008-0805-8.
- Matar T, et al. SVOA Neurol. 2023;doi:10.58624/SVOANE.2023.04.0119.
- Miller NR, et al. Eye (Lond). 2015;doi:10.1038/eye.2014.144.
- Park GT, et al. Neurol Neuroimmunol Neuroinflamm. 2024;doi:10.1212/NXI.0000000000200240.
- Saxena R, et al. Ophthalmology. 2018;doi:10.1016/j.ophtha.2018.03.032.
- Schroeder A, et al. Mult Scler Relat Disord. 2020;doi:10.1016/j.msard.2020.102142.
- For more information:
- Edited by William W. Binotti, MD, and Julia Ernst, MD, PhD, of New England Eye Center, Tufts University School of Medicine. They can be reached at william.binotti@tuftsmedicine.org and julia.ernst@tuftsmedicine.org.
Collapse
Click Here to Manage Email Alerts