Acute Macular Neuroretinopathy in Association with Orbital Inflammation and Optic Perineuritis

ABSTRACT

A 17-year-old girl experienced acute onset of decreased vision with pain on movement in her left eye. Her best-corrected visual acuity was 20/20 in the right eye and 20/100 in the left eye. Pupillary examination revealed a positive relative afferent pupillary defect. Fundus examination showed optic disc hyperemia and retinal folds. A central scotoma was detected on a perimetry test. Fluorescein angiography indicated mild disc leakage in the late phase. Orbital magnetic resonance imaging disclosed enhancement in the soft tissue of the left retrobulbar area and at the sheath of the left optic nerve. Optical coherence tomography (OCT) revealed subretinal fluid at the fovea, disruption of the ellipsoid zone (EZ), a hyper-reflective band at the outer plexiform layer (OPL), and hyper-reflective foci (HRF) in the inner retinal layer. Pulse therapy was administered, followed by oral steroid tapering. One week later, OCT showed almost complete resolution of subretinal fluid, no HRF, partial improvement in the thickening of the OPL, but persistent EZ disruption. One month later, her vision in the left eye improved to 0.6. Here we present a rare case of AMN associated with orbital inflammation and optic perineuritis, mimicking acute optic neuritis. Although the status of myelin oligodendrocyte glycoprotein (MOG) antibodies in our patient remains uncertain, her ophthalmologic manifestations strongly suggest myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD). This study highlights the importance of OCT examination, especially macular scanning, for establishing a proper diagnosis.

Text

Acute macular neuroretinopathy (AMN) is a rare disorder affecting the outer retina. AMN can occur following vaccinations (such as influenza and COVID-19)^1,2 or infections (including dengue fever, syphilis, influenza, and COVID-19).^3–6 Despite these various triggers, compromised microcirculation in the deep retina is believed to be the primary underlying pathophysiology.¹ The aim of this study is to describe a new association between AMN and orbital inflammation and optic perineuritis.

A 17-year-old healthy girl presented with a three-day history of acute-onset blurry vision in her left eye, accompanied by pain during eye movement. She denied any recent flu-like illness or vaccination. Her best-corrected visual acuity was 20/20 in the right eye and 20/100 in the left eye. A relative afferent pupillary defect was noted in her left eye. Her affected eye showed congestion at the temporal site of conjunctiva, but there was no evidence of iritis or vitritis. Fundus examination revealed mild optic disc hyperemia and retinal folds in the left eye (Figure 1a). Infrared (IR) photography also demonstrated the retinal folds (Figure 1b). No abnormalities were detected on fundus autofluorescence (Figure 1c). The peripapillary retinal nerve fiber layer thickness (pRNFL) slightly increased in the left eye was demonstrated by Optical coherence tomography (OCT) scanning (the average pRNFL was 109 μm in the right eye and 116 μm in the left eye) (Figure 2). A visual field test revealed a central scotoma in her left eye (Figure 3), and a visual evoked potential test demonstrated a slightly delayed p100 wave. Fluorescein angiography showed mild disc leakage in the late phase. Initially, optic neuritis was considered the most likely diagnosis. However, orbital magnetic resonance imaging (MRI) with post-contrast T1 disclosed enhancement in the soft tissue of the left retrobulbar area, lateral to the optic nerve, and at the sheath of the left optic nerve (Figure 4). OCT showed subretinal fluid at the fovea, disruption of the ellipsoid zone (EZ), thickening of the outer plexiform layer (OPL), and hyper-reflective foci (HRF) along the inner retinal surface (Figure 5a). She had a slightly elevated erythrocyte sedimentation rate (26 mm/hour) and C-reactive protein level (5.4 mg/L), but her white blood cell count and infectious, procoagulant, and immunological workup were unremarkable. She refused to take the test for aquaporin-4 and myelin oligodendrocyte glycoprotein (MOG) antibodies because the fee was at her own expense. Intravenous methylprednisolone (1,000 mg/day) was administered for three days, followed by an oral steroid taper starting at 60 mg per day. One week after presentation, her OCT showed almost complete resolution of subretinal fluid, no HRF, and improvement in the thickening of the OPL, but persistent EZ disruption (Figure 5b). One month later, her vision in the left eye improved to 0.6, but she did not continue with follow-up thereafter.

Figure 1.

(a). Fundus ophthalmoscopy showing mild optic disc edema and retinal folds in the left eye. (b). Infrared (IR) scanning demonstrating the retinal folds in the left eye. (c). No abnormalities were detected on fundus autofluorescence photography (FAF).

Figure 2.

Optical coherence tomography (OCT) Optic Head Analysis showed peripapillary retinal nerve fiber layer slightly increased in the left eye.

Figure 3.

Humphrey visual field test (24–2) revealed a central scotoma in the left eye.

Figure 4.

(a) and (b). Orbital magnetic resonance imaging post-contrast showing enhancement in the soft tissue of the left retrobulbar area lateral to the Optic Nerve (ON) as well as the sheath of the ON.

Figure 5.

(a). Optical coherence tomography (OCT) revealing subretinal fluid at the fovea, irregularity in the ellipsoid zone (EZ), a hyper-reflective band at the outer plexiform layer (OPL), and hyper-reflective foci (HRF) in the inner retinal layer. (b). After pulse therapy, subretinal fluid and HRF almost resolved with improvement in the thickening of the OPL, but the irregularity in EZ persisted.

AMN was first reported by Bos and Deutman in 1975.⁷ With the advancement of optical coherence tomography (OCT) and infrared (IR) scanning, it has been increasingly recognized in recent years. Most AMN patients are young females. Symptoms of AMN include paracentral scotoma, minor or no vision reduction, and photopsia.⁸ The scotomas may partially improve or persist. The main lesions of AMN are located in the outer retinal layers, often appearing as wedge-shaped with their apices pointing toward the fovea, forming a petalloid or tear-drop pattern observable on fundus or near-IR imaging.⁹ In the acute phase, the affected outer nuclear layer (ONL) and outer plexiform layer (OPL) show hyper-reflectivity on OCT, as well as disruption of the ellipsoid zone (EZ). Thinning of the ONL can be identified months later on OCT.¹⁰

AMN is considered to represent a group of disorders involving acute disruption of the outer segment of the photoreceptor/retinal pigment epithelium junction.¹¹ Based on imaging, AMN is divided into type 1, or paracentral acute middle maculopathy (PAMM), and type 2, or classic AMN.¹² Additionally, AMN can be categorized as “plus” with “photoreceptoritis” or “plus” with “photoreceptoritis” and “retinal pigment epithelitis”.⁵ Although the pathogenesis remains unclear, impairment of the deep retinal capillary plexus or dysregulation of blood flow in the choroid is suspected to be the leading cause.^8,9

Associations between AMN and vaccination, infection, or autoimmune disorders (such as lupus) have been described.^8,13 Half of previous cases experienced a flu-like illness preceding the visual symptoms.⁶ Environmental triggers include the use of oral contraceptives or sympathomimetic drugs, trauma, dehydration, and hypovolemia.^9,11 Additionally, Dr. Shah reported a case of AMN associated with optic disc swelling and an enlarged blind spot, though without inflammatory signs. Although a definitive diagnosis was not reached, immune disturbance was speculated as the underlying cause.¹⁴ In a retrospective study of 114 patients with acute optic neuritis (ON), six patients had AMN, including three with MOG-related ON, two with multiple sclerosis, and one with clinically isolated syndrome.⁹ More recently, Li reported a case of MOG-related optic neuritis (ON) presenting with acute macular neuroretinopathy (AMN) following a COVID-19 infection.¹⁵ Additionally, two cases of concurrent MOG-related ON and paracentral acute middle maculopathy (PAMM) have been identified.^16,17

Myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD) is an inflammatory demyelinating disease of the central nervous system associated with autoantibodies targeting MOG. Optic neuritis is the most common manifestation of MOGAD in adults and the second most common manifestation in children. Although MOG is not expressed in the retina, several cases of MOGAD with retinal involvement have been reported, including serous retinal detachment, preretinal hemorrhage, neuroretinitis, venous stasis retinopathy, and AMN.^8,18 These findings suggest a possible link between optic nerve inflammation and retinal vascular complications.

Apart from the typical findings of AMN on OCT, such as a hyper-reflective band at the OPL and irregularity in the EZ, our case also revealed macular edema and hyper-reflective foci (HRF). In the case of AMN associated with idiopathic intracranial hypertension described by Mairot et al., OCT also demonstrated peripapillary intra-retinal fluid.¹¹ HRF can be detected in various conditions, including diabetic retinopathy, age-related macular degeneration, retinal vein occlusion, retinal degenerative diseases, and intraocular inflammation. They are believed to represent extravasation of blood constituents, migrating retinal pigment epithelial cells, or microglia.¹⁹ Our case showed orbital inflammation affecting the orbital soft tissue and sheath of the optic nerve. Unfortunately, she declined to undergo testing for the MOG antibody. However, MOGAD remains highly suspected based on her clinical presentation. MOGAD encompasses a broad spectrum of clinical manifestations, including orbital inflammation syndrome.²⁰ Inflammatory edema compressing retinal circulation, immune complex deposition, and hyperviscosity from leukocytosis may contribute to ischemia and the subsequent formation of AMN.⁶

AMN needs to be distinguished from other disorders, including acute posterior multifocal placoid pigment epitheliopathy (APMPPE), PAMM, traumatic maculopathy, and solar retinopathy. The absence of retinal pigment epithelium (RPE) involvement excludes the possibility of APMPPE. In PAMM, the hyper-reflective lesions seen on OCT appear as bands or plaques at the level of the inner nuclear layer. Additionally, the lack of a history of trauma or sun exposure makes the last two disorders unlikely.

Recently, more AMN-related abnormalities have been reported. We present the first case of AMN associated with orbital inflammation and optic perineuritis. Her clinical symptoms mimicked acute optic neuritis. OCT examination, particularly macular scanning, enabled the diagnosis of AMN. Although our case did not undergo serum testing for MOG, brain MRI findings showing enhancement of intraorbital tissue and the peri-optic nerve sheath strongly suggest MOGAD. This case presentation further supports the association between AMN and optic nerve inflammation.

Funding Statement

The author(s) reported there is no funding associated with the work featured in this article.

Disclosure statement

No potential conflict of interest was reported by the author(s).

Ethics declarations

This study is in accordance with the principles in the declaration of Helsinki.