Idiopathic Optic Perineuritis in a Pediatric Patient

Abstract

Optic perineuritis is an inflammatory disorder of the optic nerve sheath, presenting with visual deficits, dyschromatopsia, and pain with extraocular movement, often confused with optic neuritis. Most cases are believed to be idiopathic but can be associated with autoimmune, infectious, and neoplastic etiologies. Treatment involves corticosteroids, and when administered promptly has been associated with rapid recovery. Delays in treatment have been linked to poor visual outcomes. Few pediatric cases have been described. We report a teenager who presented with 2 months of unilateral visual loss and paracentral scotoma, found to have optic perineuritis. She was treated aggressively with high-dose corticosteroids, therapeutic plasma exchange, and intravenous immunoglobulin, but had limited symptomatic recovery attributable to delays in seeking treatment. Optic perineuritis is rare in children but should be included in the differential for visual deficits, especially as delayed treatment is associated with irreversible visual loss. Further studies are needed for children to better identify underlying causes and establish consistent treatment paradigms.

Optic perineuritis is a disorder of orbital inflammation targeting the optic nerve sheath, classically associated with blurring of vision, visual field deficits, pain with extraocular movement, and dyschromatopsia. ¹ Optic perineuritis is exceedingly rare in children, with less than a dozen reported pediatric cases.^2–5 Although frequently idiopathic, optic perineuritis can be secondary to autoimmune, infectious, or neoplastic etiologies as well. ⁶ We present the case of a 13-year-old who presented with 2 months of right monocular paracentral scotoma with associated optic perineuritis, who was treated with high-dose intravenous methylprednisolone, therapeutic plasma exchange, and intravenous immunoglobulin, but with persistent visual deficits.

Case Report

A 13-year-old girl presented with 2 months of progressive right monocular vision loss with associated dyschromatopsia. She denied any pain with extraocular movement, and there was no erythema, proptosis, or diplopia. Her medical history was notable for elevated antinuclear antibody (ANA) with titer of 1:640, elevated anti-thyroid peroxidase (TPO) antibodies (94 IU/mL), and migratory arthralgias that had been treated with prednisone approximately six months prior by pediatric rheumatology. She had no other recent medical history or immunizations, and no significant family history for autoimmune conditions.

Ophthalmologic examination was notable for visual acuity of 20/200 on the right with associated relative afferent pupillary defect, dyschromatopsia (Ishihara 0/14), and paracentral scotoma. Anterior segment examination was normal, while dilated fundoscopic examination demonstrated mild peripapillary edema and inferotemporal blurring of the right optic disc margin. Visual acuity and ophthalmologic examination on the left was normal. MRI brain and orbits with and without contrast (Figure 1) demonstrated T2 hyperintensity of the right optic nerve sheath and intraconal fat with associated enhancement, but without abnormalities of the optic nerve itself, consistent with optic perineuritis.

Figure 1.

MR (magnetic resonance) images in axial T2 with fat suppression (A), coronal T2 with fat suppression (B) and postgadolinium (C) demonstrating T2 hyperintensity and subtle contrast enhancement of the right optic nerve sheath and intraconal fat, with tram-track sign (arrow, A) and doughnut sign (arrow, B).

Broad infectious, autoimmune, and neoplastic workup (Table 1) was performed. Antinuclear antibody was positive with 1:160 titer and a smooth/speckled pattern. Anti-TPO antibodies were again elevated (99 IU/mL) as were anti-thyroglobulin (TG) antibodies (28.1 IU/mL). Although suggestive of underlying autoimmune process, workup did not elucidate any definitive cause of her optic perineuritis. She was then treated empirically with high-dose intravenous methylprednisolone for 5 days with prolonged oral prednisone taper, concurrently with therapeutic plasma exchange and then intravenous immunoglobulin at 2 g/kg, without significant symptomatic improvement during hospitalization. Repeat ophthalmologic examination 5 months later demonstrated persistent right paracentral scotoma with visual acuity of 20/100, with persistent relative afferent pupillary defect and dyschromatopsia (Ishihara 0/14). Repeat testing for anti-myelin oligodendrocyte glycoprotein (MOG) immunoglobulin G and anti-aquaporin-4 (AQP4) immunoglobulin G was completed around this time and was negative.

Table 1.

Laboratory Workup.

Test	Result
C-reactive protein (CRP)	<1.0 mg/L
Erythrocyte sedimentation rate (ESR)	3 mm/hour
Thyroid-stimulating hormone (TSH)	2.675 µIU/mL
Thyroxine, free (fT4)	0.85 ng/dL
IgA	106 mg/dL
IgG	1285 mg/dL
IgE	27 IU/mL
C3	107 mg/dL
C4	22 mg/dL
Antinuclear antibody (ANA) survey	Positive
ANA titer	1:160
ANA pattern	Smooth/speckled
Anti–double-stranded DNA IgG	9 IU/mL
Anti-SSA (Ro) IgG	Negative
Anti-SSB (La) IgG	Negative
Anti-Scl-70 IgG	Negative
Anti-Smith (Sm) IgG	Negative
Anti-ribonucleoprotein (RNP) IgG	Negative
Anti-myeloperoxidase	4.89 units
Anti-protease 3	2.64 units
Anti-myelin oligodendrocyte glycoprotein (MOG) IgG	Negative
Anti-aquaporin-4 (AQP4) IgG	Negative
Angiotensin-converting enzyme (ACE)	56 U/L
Anti-thyroglobulin antibody	28.1 IU/mL
Anti-thyroid peroxidase antibody	99.0 IU/mL
Treponemal IgG	Negative
Bartonella henselae IgM/IgG	<1:16
EBV IgM/IgG	Negative
CMV IgM/IgG	Negative
Herpes simplex virus 1/2 PCR	Negative
Varicella zoster PCR	Negative
Tuberculosis quantiferon	Negative
Hepatitis B antibody panel	Negative
Hepatitis C antibody panel	Negative
CSF cell count	4 nucleated cells, 2150 red blood cells
CSF glucose	112 mg/dL
CSF protein	37 mg/dL
CSF oligoclonal bands	No CSF-specific oligoclonal bands
CSF flow cytometry	Negative
CSF bacterial culture	No growth
CSF fungal culture	No growth
Lysozyme	3.02 µg/mL
Peripheral blood smear	No malignant cells
Chest radiograph	Negative without granulomatous disease

Abbreviations: CMV, cytomegalovirus; CSF, cerebrospinal fluid; EBV, Epstein-Barr virus; Ig, immunoglobulin; PCR, polymerase chain reaction; anti-SSA, anti–Sjögren's-syndrome-related antigen A; anti-SSB, anti–Sjögren's-syndrome-related antigen B.

Discussion

Optic perineuritis is an uncommon form of orbital inflammation, distinct from optic neuritis. Compared to optic neuritis, optic perineuritis is more likely to present clinically with arcuate or paracentral scotoma with sparing of central vision, whereas dyschromatopsia and relative afferent pupillary defect are often present, both are less dramatic than in optic neuritis. ¹ Radiographically, there is typically sparing of the optic nerve but will demonstrate perineural enhancement. The tram-track sign in axial slices and doughnut appearance in coronal slices are suggestive of the diagnosis, and orbital fat or extraocular muscle enhancement may be seen as well. ⁷

Diagnosis is typically based on clinical and radiographic findings, although optic nerve biopsy can be considered for patients without response to corticosteroids and without clear underlying etiology.^1,8 Although response to steroids in optic perineuritis is typically rapid and dramatic, prompt diagnosis and treatment is paramount as vision progressively deteriorates without recovery in the absence of treatment, ⁷ exemplified by our case. Chronic inflammatory infiltration and fibrous tissue deposition, leading to compressive optic neuropathy and optic nerve ischemia, has been postulated to reduce efficacy of delayed treatment. ⁸ By definition, optic perineuritis is not self-limited and requires intervention. Without early intervention, visual impairment can be irreversible, as seen in our patient, despite the use of multiple immunomodulators in the treatment course. Other risk factors for poorer prognosis include systemic, rather than idiopathic, etiologies. ⁹

Although frequently idiopathic, optic perineuritis can also be secondary to myriad other conditions as well. Infectious etiologies including syphilis, tuberculosis, toxoplasmosis, cytomegalovirus, and bacterial and fungal meningitis ¹⁰ have all been implicated. Autoimmune and inflammatory syndromes including sarcoidosis, ¹¹ immunoglobulin G4–related disease, systemic lupus erythematosus, granulomatosis with polyangiitis, and Behçet disease ¹⁰ have all been associated with optic perineuritis in adults. Optic nerve sheath meningioma as well as leukemia or lymphoma with optic nerve sheath involvement can produce similar MRI features. ¹²

MOG-associated disease (MOGAD) is an established cause of optic neuritis. MOGAD-associated optic neuritis often presents with visible optic disc edema, or optic nerve sheath enhancement, and is exquisitely sensitive to corticosteroids, ¹³ similar to presentations of optic perineuritis. MOGAD is more likely to lead to bilateral circumferential perineural enhancement of the optic nerve sheath.^13,14 Despite association with MOGAD, there does not seem to be an association between optic perineuritis and multiple sclerosis. ¹⁵

Optic perineuritis in children is exceptionally rare, limited to case reports. The majority have been idiopathic,^3–5 with good clinical recovery after prompt treatment with corticosteroids, consistent with adult data, although one was associated with herpes zoster dermatitis with ischemic optic neuropathy as well as optic perineuritis, with poor outcome despite antiviral and corticosteroid treatment. ²

Treatment is not standardized, although treatment in adults universally involves corticosteroids, typically with robust response within hours to days, ¹ although slow taper is generally recommended to prevent risk of recurrence. Indomethacin has been trialed in adults, ⁷ and radiation therapy and immunosuppressants including azathioprine have been used for refractory cases with good outcomes.^1,8 Intravenous immunoglobulin and therapeutic plasma exchange have also been used in cases with equivocal results. ¹⁶ We present the first documented case of a child being treated with intravenous immunoglobulin and therapeutic plasma exchange, although our case reinforces the findings in adults that delays in treatment of optic perineuritis can lead to irreversible visual impairment. ⁷ Thus, further investigation and discussion regarding optic perineuritis in the pediatric population is paramount to aid in early recognition and early treatment initiation that can help avoid the irreversible vision impairment as seen in our patient.