Idiopathic Optic Perineuritis Masquerading as Recurrent Optic Neuritis

Clinical Correspondence Section Editors: Robert Avery, DO Karl C. Golnik, MD Caroline Froment, MD, PhD An-Guor Wang, MD Idiopathic Optic Perineuritis Masquerading as Recurrent Optic Neuritis Andrew J. Mueller, MD, Stacy M. Scofield-Kaplan, MD, Bret M. Evers, MD, PhD, Bruce Cameron Carr, MD, Ronald Mancini, MD, Robert N. Hogan, MD, PhD A 55-year-old Hispanic woman with a history of hypertension presented to the emergency room with 2 days of left eye pain worse with eye movements, decreased vision, and dyschromatopsia. She had no history of similar episodes. On examination, best-corrected visual acuity (BCVA) was 20/25 in the right eye and 20/50 in the left eye. Her pupils were pharmacologically dilated by an outside provider. Color vision was 16/16 in the right eye and 1/16 in the left eye. Visual fields were full to confrontation in each eye, extraocular movements were full, but she noted left eye pain with supraduction and abduction. Intraocular pressures were normal in both eyes. The slit-lamp and funduscopic examination were unremarkable, and both optic nerves had sharp optic disc margins without edema. MRI of the brain and orbits with gadolinium revealed enhancement of the intracanalicular segment of the left optic nerve consistent with optic neuritis with normal brain parenchyma (Fig. 1A). Laboratory evaluation included a positive ANA 1:160 nucleolar pattern, but otherwise negative or normal testing for syphilis, HIV, Lyme, Anti-neutrophil cytoplasmic autoantibody, Rheumatoid factor, angiotensin-converting enzyme, complement (C3 and C4), neuromyelitis optica/ aquaporin-4-IgG (NMO/AQP4), myelin oligodendrocyte glycoprotein antibody, erythrocyte sedimentation rate (ESR), and vitamin B9/B12. She received 1 g of intravenous Solu-Medrol followed by 2 days of oral Decadron 80 mg twice a day as per the neurology service recommendation and the patient’s desire for outpatient treatment. She reported complete resolution of blurred vision, pain, and pain with eye movements once she started the aforementioned steroids. One month later, she re-presented with 2 days of left eye pain worse with eye movements. On examination, her BCVA was 20/20 in each eye without a relative afferent pupillary deficit. Her color vision, confrontation visual fields, and extraocular movements were full, but movement of the left eye in any direction elicited pain. Her slit-lamp and fundus Departments of Ophthalmology (AJM, SMS, BCB, RM, RNH) and Pathology (BME, RNH), UT Southwestern Medical Center, Dallas, Texas. The authors report no conflicts of interest. Address correspondence to R. Nick Hogan, MD, PhD, NeuroOphthalmology, Ocular Pathology, Department of Ophthalmology, UT Southwestern Medical Center, 5323 Harry Hines Boulevard, Dallas, TX 75390; E-mail: [e-mail] e302 examination were notable for new left grade 1 optic nerve swelling with elevation most prominent nasally. Repeat MRI brain and orbits with gadolinium showed worsened signal enhancement and enlargement of the left intraconal and intracanalicular optic nerve with increasing surrounding inflammatory changes, but a normal brain parenchyma (Fig. 1B). Laboratory evaluation included an elevated ESR of 50 with negative Bartonella antibodies. A lumbar puncture was performed to send flow cytometry in addition to the routine studies. The CSF opening pressure, protein, venereal disease research laboratory, NMO/AQP4, oligoclonal bands, ACE, IgG indices, and flow cytometry were all normal or negative. She was admitted for left optic perineuritis (OPN) and received 1 g of SoluMedrol intravenously for 3 days with complete resolution of the left eye pain and pain with eye movement by the second day. Since this was a recurrence with worsening orbital inflammation and optic nerve swelling, she was discharged on oral prednisone 60 mg daily, which is 1 mg/kg based on weight. Less than 1 week following discharge while on 60 mg prednisone, she returned with 2 days of vision loss in the left eye, mild left eye pain, and a left-sided headache. On examination, her BCVA was 20/25 in the right eye and no light perception (NLP) in the left eye with a minimally reactive left pupil and a 3+ relative afferent pupillary deficit on the left side. Extraocular movements elicited pain in all gazes on the left side. Her slit-lamp examination was notable for ptosis of the left upper eyelid, 2+ injection and inferior chemosis on the left side. Funduscopic examination revealed severe Grade IV optic disc edema of the left optic nerve. MRI brain and orbits with gadolinium revealed worsening inflammatory changes of the left retrobulbar intraorbital space with thickening and enhancement of the left optic nerve and optic nerve sheath. The soft tissue enhancement extended to the left orbital apex and adjacent periclinoid intracranial space but not into the cavernous sinus. There was also enhancement of the left lacrimal gland, preseptal soft tissues, and the sclera, but the brain parenchyma was again normal (Fig. 1C, D). Normal studies included serum protein electrophoresis, anticardiolipin Ab, antiphospholipid Ab, beta-2 glycoprotein Ab, antithrombin activity, activated protein C resistance, protein S activity, silica clotting time ratio, Dil Russell venom viper time ratio, IgG indices, ace/lysozyme, Tspot, Epstein-Barr Virus IgM, and filaria IgG. She was admitted and treated with 1 g intravenous Solu-Medrol for 5 days given the severity of the Mueller et al: J Neuro-Ophthalmol 2022; 42: e302-e305 Copyright © North American Neuro-Ophthalmology Society. Unauthorized reproduction of this article is prohibited. Clinical Correspondence FIG. 1. MRI images of the orbit from the initial presentation (A), first recurrence (B), and second recurrence (C–D). A. Is an axial post contrast image revealing enhancement of the intracanalicular segment of the left optic nerve. B. An postcontrast axial image with worsening signal, enhancement and interval enlargement of the left intraconal and intracanalicular optic nerve, with increasing surrounding inflammatory changes. An precontrast axial image (C) and an postcontrast coronal image (D) with interval worsening of inflammatory changes involving the left retrobulbar space with thickening and enhancement of the left optic nerve and the optic nerve sheath. There was also enhancement of the left lacrimal gland and preseptal soft tissues. vision loss in the left eye, there was significant worsening of her examination (new ptosis, new chemosis, significantly worse optic nerve swelling) and the significant worsening of inflammatory changes on the aforementioned MRI. On day 4 of the admission, she underwent a left anterior orbitotomy through an eyelid crease approach with optic nerve sheath fenestration and biopsy of the optic nerve sheath, retrobulbar fat, and lacrimal gland. Histopathologic analysis (Fig. 2A–C) showed prominent perivascular chronic inflammation of the optic nerve sheath, perineural orbital tissue, and lacrimal gland, without evidence of infection or malignancy. Additionally, the lacrimal gland showed areas of acinar destruction with concomitant fibrosis. Immunohistochemically, the inflammatory infiltrate was composed of both B and T cells. By postoperative Day 5, while still on the oral steroids, she reported resolution of her left eye pain and headache. She was maintained at 100 mg prednisolone by mouth for 1 week before decreasing to 80 mg daily without recurrence of pain. On follow-up visits, her vision remained NLP in the left eye with slowly improving optic disc edema, and her steroids were very slowly tapered. A repeat MRI of the orbits with gadolinium one month after the biopsy showed improvement of orbital inflammation. Two months after the biopsy, she had a cerebral angiogram negative for vasculitis (this was planned for closer to discharge but was Mueller et al: J Neuro-Ophthalmol 2022; 42: e302-e305 delayed by insurance approval). She was started on 50 mg azathioprine orally 4 months after the biopsy as a steroidsparing agent. At most recent follow-up visit 11 months after the biopsy, she was taking 5 mg prednisone and 50 mg azathioprine, both orally, with 20/20 vision in the right eye and NLP vision in the left eye. OPN is an uncommon inflammatory disorder that involves the optic nerve sheath (1). Although many cases present as inflammation of the optic nerve sheath in isolation, OPN represents a form of idiopathic orbital inflammatory disease and can present with orbital myositis, dacryoadenitis, or inflammation in other aspects of the orbit (2). Although the majority of cases are idiopathic, there have been associations with other systemic conditions, including syphilis, sarcoidosis, tuberculosis, giant cell arteritis, granulomatosis with polyangiitis, Behcet disease, Crohn disease, and IgG-4 related disease (1,3–5). Differentiating between OPN and optic neuritis can be challenging because the inflammation involves adjacent sites, and oftentimes, the initial presentation can be virtually identical, but the response to therapy can assist in determining the diagnosis (1,4,6). OPN, when compared with optic neuritis, typically involves a broader age range, progressive vision loss over weeks, a prompt and dramatic response to steroids, and one or multiple relapses. MRI often reveals perineural e303 Copyright © North American Neuro-Ophthalmology Society. Unauthorized reproduction of this article is prohibited. Clinical Correspondence FIG. 2. Pictomicrographs of hematoxylin and eosin–stained sections of lacrimal gland (A), perineural orbital tissue (B), and optic nerve sheath (C). Lacrimal gland sections (A) show multiple areas of acinar dropout and concomitant fibrosis (asterisks) as well as perivascular chronic inflammation (arrowhead). Similar amounts of perivascular and orbital fibroadipose tissue chronic inflammation (arrowheads) are also seen in sections of the perineural orbital tissue (B) and optic nerve sheath (C). Scale bars: 300 mm (A, B), 200 mm (C). enhancement and streaky fat enhancement with or without enhancement of the extraocular muscles (6). Furthermore, OPN classically presents with pain because it is the most predominant symptom, but on examination, there can be chemosis, diplopia, proptosis, extraocular muscle restriction, and optic disc swelling (6). Our case is unique in that her initial presentation was classic for optic neuritis and the MRI was consistent with inflammation of the nerve parenchyma rather than the nerve sheath. Although her dramatic response to steroids was classic for OPN, it can also be seen with optic neuritis (7). The diagnosis of OPN became more apparent in the setting of her recurrence, which was predominantly eye pain with new optic nerve swelling. Her first recurrence was treated with Solu-Medrol 1 g daily for 3 days followed by oral prednisone 60 mg daily (1 mg/kg/day) since her symptoms quickly resolved with the initiation of intravenous steroids. The second recurrence while on oral steroids was incredibly atypical given the degree of vision loss that she presented with. Furthermore, her presentation involved new injection, chemosis, ptosis, Grade IV optic disc edema, and significant MRI inflammatory changes, which for the first time involved the optic nerve sheath along with the optic nerve and orbital soft tissues. Despite 5 days of intravenous Solu-Medrol and an optic nerve sheath fenestration to relieve pressure on the optic nerve from optic nerve swelling, her vision remained NLP. The majority of cases reported that severe vision impairment is very uncommon in OPN unless the initiation of steroids is very delayed or it is secondary to an underlying condition like granulomatosis with polyangitis or Bechet disease (1–7). In the secondary OPN cases with a final visual acuity of NLP, they all presented with NLP vision and remained NLP despite treatment (1,5,8). In one other case where the final visual acuity was NLP, there was a 6-month progression before diagnosis and initiation of steroid treatment (6). Other than the time to steroid initiation, the other factor that was found to influence visual prognosis is the frequency of recurrent attacks (6). It appears that initiating treatment with higher dosages of corticosteroids (such as prednisone 80 mg/day po) for a prolonged period decreased the likelihood of recurrence and therefore improved the overall visual prognosis (6). e304 It is incredibly atypical for a patient to progress to NLP with OPN despite being on oral steroids dosed at 1 mg/kg per day orally. The histopathology of the optic nerve sheath, perineural orbital tissue, and lacrimal gland revealed perivascular chronic inflammation similar to prior reports (6,10). Previous reports have attributed vision loss in OPN to ischemia or infarction of the optic nerve from compression of the thickened optic nerve sheath or vascular occlusion (6,9,10). The rapid vision loss and progression to NLP along with the presence of grade IV optic disc edema, which could compress the optic nerve, suggests that there was infarction of the optic nerve as the underlying etiology of the vision loss. It is important to consider OPN in patients presenting with apparent optic neuritis, especially if the case becomes atypical or there are one or more recurrences. Additionally, it is important to initiate steroids quickly and consider intravenous steroids followed by higher doses of oral steroids than 1 mg/kg, especially in cases that involve optic nerve swelling as this may contribute to ischemia or infarction of the optic nerve in severe cases. STATEMENT OF AUTHORSHIP Category 1: a. Conception and design: A. J. Mueller, S. M. ScofieldKaplan, B. M. Evers, B. C. Carr, R. Mancini, and R. N. Hogan; b. Acquisition of data: A. J. Mueller, S. M. Scofield-Kaplan, B. M. Evers, and B. C. Carr; c. Analysis and interpretation of data: A. J. Mueller, S. M. Scofield-Kaplan, B. M. Evers, B. C. Carr, R. Mancini, and R. N. Hogan. Category 2: a. Drafting the manuscript: A. J. Mueller, S. M. Scofield-Kaplan, B. M. Evers, B. C. Carr, R. Mancini, and R. N. Hogan; b. Revising it for intellectual content: A. J. Mueller, S. M. ScofieldKaplan, B. M. Evers, B. C. Carr, R. Mancini, and R. N. Hogan. Category 3: a. Final approval of the completed manuscript: A. J. Mueller, S. M. Scofield-Kaplan, B. M. Evers, B. C. Carr, R. Mancini, and R. N. Hogan. REFERENCES 1. Hickman SJ. Optic perineuritis. Curr Neurol Neurosci Rep. 2016;16:16. 2. Nalcacioglu P, Acaroglu G. Unilateral optic perineuritis due to nonspecific orbital inflammation: a case report. Orbit. 2017;36:452–455. 3. McClelland C, Zaveri M, Walsh R, Fleisher J, Galetta S. Optic perineuritis as the presenting feature of Crohn disease. J Neuroophthalmol. 2012;32:345–347. Mueller et al: J Neuro-Ophthalmol 2022; 42: e302-e305 Copyright © North American Neuro-Ophthalmology Society. 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