Neuroimaging in neuro-ophthalmologic emergencies with acute visual loss

Abstract

Neuro-ophthalmologic emergencies presenting with acute visual loss pose significant diagnostic and therapeutic challenges, with potential for irreversible vision loss if not promptly recognized. A comprehensive approach that integrates clinical evaluation with advanced imaging modalities is essential for timely diagnosis, prognostic stratification, and management. Magnetic resonance imaging remains the gold standard for demyelinating optic neuritis, enabling differentiation among multiple sclerosis, neuromyelitis optica spectrum disorder, and myelin oligodendrocyte glycoprotein antibody-associated disease through lesion morphology and distribution, and is definitive for diagnosing pituitary apoplexy through the detection of sellar hemorrhage or infarction. Computed tomography is indispensable in the emergent triage of orbital trauma and in the rapid exclusion of intracranial hemorrhage in acute stroke. Optical coherence tomography (OCT) provides high-resolution quantification of neuroaxonal injury, with macular ganglion cell-inner plexiform layer thinning serving as a sensitive early marker of permanent damage compared to peripapillary retinal nerve fiber layer changes. OCT angiography further enhances vascular assessment in ischemic optic neuropathies and giant cell arteritis (GCA), offering a noninvasive alternative to fluorescein angiography. Ultrasonography contributes to the evaluation of GCA through the detection of the “halo sign” and provides bedside utility for measuring optic nerve sheath diameter in suspected intracranial hypertension. This narrative review highlights the complementary roles of these imaging techniques, underscoring their strategic application in optimizing outcomes for vision-threatening neuro-ophthalmologic emergencies.

Introduction

Neuro-ophthalmologic emergencies can lead to severe visual impairment or even blindness. These emergencies often present with acute visual loss, which can be monocular or binocular, and may be associated with other symptoms such as eye pain, diplopia, or abnormalities in pupillary reactions. Imaging modalities such as magnetic resonance imaging (MRI), computed tomography (CT) scans, as well as B scan ultrasonography are essential tools in evaluating these acute situations, providing critical insights into the underlying causes of visual loss. In addition, optical coherence tomography (OCT) is an invaluable modality for detailed structural assessment of the optic nerve and retina, providing important information about the peripapillary retinal nerve fiber layer (pRNFL) and retinal ganglion cells. The integration of clinical evaluation with imaging techniques allows for a comprehensive approach to the diagnosis and management of diseases. In this narrative review, we discuss the specific roles and diagnostic value of imaging modalities in various neuro-ophthalmologic emergencies with acute visual loss.

Demyelinating Optic Neuritis: Multiple Sclerosis, Neuromyelitis Optica, Myelin Oligodendrocyte Glycoprotein Antibody-associated Disease

Optic neuritis involves inflammation of the optic nerve, causing sudden and often severe vision loss. Typical demyelinating optic neuritis may occur as a clinically isolated syndrome or in the context of either multiple sclerosis (MS), neuromyelitis optica, or myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD).

The earliest use of OCT in neuro-ophthalmology was in 1999 when Parisi et al. reported pRNFL thinning on OCT in MS patients with previous optic neuritis.[1] In the acute phase of ON, optic nerve head (ONH) swelling may be observed on OCT, and the elevated pRNFL measurements can be used to objectively quantify the swelling. Typically, 4–6 weeks after the acute episode of optic neuritis, pRNFL atrophy develops, which again can be quantified using OCT measurements demonstrating pRNFL thinning.[2] Although only one-third of patients with typical demyelinating optic neuritis have visible optic disc edema on fundus examination,[3] more subtle edema of the pRNFL on OCT is more common. However, mean pRNFL values do not generally reduce below 30 µm regardless of the extent of optic nerve injury, thus making it difficult to detect further change in severe optic atrophy or recurrent optic neuritis.[4] Macular ganglion cell layer or macular ganglion cell-inner plexiform layer (mGCIPL) volume and thickness analysis have been shown to be a more sensitive and reliable measure of retrobulbar neuroaxonal injury. mGCIPL thinning occurs earlier in the time course of acute optic neuritis (often after 2 weeks), even when the retinal nerve fiber layer (RNFL) remains edematous, thus serving as an early indication of possible permanent visual dysfunction [Figure 1].[4]

Figure 1.

Typical demyelinating optic neuritis in a patient with neuromyelitis optica and positive aquaporin-4 antibodies in the right eye. In the acute phase, there is optic disc swelling in the right eye (a). Swelling of the peripapillary retinal nerve fiber layer (pRNFL) (b) with a normal macular ganglion cell-inner plexiform layer (mGCIPL) (c) was detected on optical coherence tomography. T1-weighted magnetic resonance imaging reveals longitudinally extensive contrast enhancement of the right optic nerve, involving more than 50% of its length (d). After 1 month, the pRNFL swelling improved (e), but marked mGCIPL thinning became evident (f)

MRI is the preferred modality for assessing optic neuritis, providing detailed images of the optic nerve and surrounding structures. It is particularly effective in identifying T2 hyperintense lesions and contrast enhancement on postcontrast T1-weighted sequences, which are indicative of inflammation [Figure 1]. MRI findings can also help differentiate MS, neuromyelitis optica spectrum disorder (NMOSD), and MOGAD, as these conditions exhibit distinct imaging characteristics of optic nerve involved. MS optic neuritis typically presents unilateral, anterior, short optic nerve lesions that do not involve the optic nerve sheath on MRI. According to the 2024 revision of the McDonald criteria for the diagnosis of MS, MRI evidence of disease dissemination in space is established by the presence of one or more characteristic T2-hyperintense lesions in at least two of the following five central nervous system regions: periventricular, cortical/juxtacortical, infratentorial, spinal cord, and – newly included – the optic nerve.[5]

While NMOSD optic neuritis can be bilateral or unilateral at onset, the optic nerve lesions on MRI often locate posteriorly, and are frequently longitudinally extensive, involving more than 50% of the length of the optic nerve. Chiasmal and optic tract involvement might be present. The most distinctive MRI finding associated with NMOSD is longitudinally extensive transverse myelitis, a spinal cord lesion that spans over three (or more) contiguous vertebral segments. In addition, certain MRI lesions are characteristic of NMOSD, including diencephalic lesions surrounding the third ventricles and cerebral aqueduct, dorsal brainstem lesions adjacent to the fourth ventricle (which may manifest as intractable hiccups or vomiting), and periependymal lesions surrounding the lateral ventricles.[6,7,8]

MOGAD optic neuritis is frequently bilateral, and MRI also demonstrates a longitudinally extensive optic nerve lesion, involving the optic nerve sheath [Figure 2].[9] Optic disc edema is present in 86% of patients, which is a common feature of myelin-oligodendrocyte glycoprotein-immunoglobulin-positive optic neuritis that can help distinguish these patients from patients with other demyelinating optic neuropathies.[10] Brain MRI is typically normal at the time of first attack in MOGAD patients with optic neuritis or transverse myelitis. However, involvement of the brain or brainstem in MOGAD patients can manifest as features of acute demyelinating encephalomyelitis, cerebral cortical encephalitis, brainstem symptoms, or cerebellar symptoms. Brain lesions in MOGAD patients tend to be bilateral, ill-defined, and large, often with deep grey matter involvement, and the pons is frequently involved. Large lesions in the middle cerebellar peduncle are suggestive of MOGAD, since such lesions are rare in MS or NMOSD.[11]

Figure 2.

A patient with myelin oligodendrocyte glycoprotein antibody-associated disease. (a) Fundus photography shows bilateral optic disc edema. (b) Optical coherence tomography demonstrates increased peripapillary retinal nerve fiber layer thickness. (c) Visual field testing reveals bilateral defects. (d) T1-weighted Magnetic resonance imaging shows bilateral, longitudinally extensive optic nerve lesions with enhancement of the optic nerve sheath (arrows). (Image courtesy of Dr. Tzu-Lun Huang)

Nonarteritic Anterior Ischemic Optic Neuropathy

OCT plays a similar role in the assessment of ischemic optic neuropathies as it does in the assessment of optic neuritis. In the acute phase, optic disc swelling can be diagnosed and quantified using pRNFL thickness measurements. Within 2 months, 80% of patients subsequently show pRNFL thinning, with progressive thinning and thus optic disc atrophy occurring between months 2 and 4, with stability typically reached at month 6 [Figure 3].[12,13] The value of the pRNFL in assessing axonal loss in the acute stages of NAION is limited by ONH edema, and therefore, in the early stages, mGCIPL thinning is a better indicator of axonal loss. mGCIPL thinning precedes reliable pRNFL changes and can be detected as early as 2.2 days after symptom onset and is present in 62.5% of eyes at initial evaluation.[14] Longitudinal assessment of the mGCIPL layer offers a reliable and objective tool in monitoring and follow-up.

Figure 3.

Acute nonarteritic anterior ischemic optic neuropathy. Edema of the right optic nerve head is more prominent in the superior segment (a), resulting in an inferior visual field defect (b), and corresponding superior swelling of the peripapillary retinal nerve fiber layer (pRNFL) on optical coherence tomography (OCT) (c). After 1 and 3 months, OCT showed progressive thinning of the pRNFL (d and e, respectively)

OCT angiography (OCT-A) has also emerged as a valuable tool in nonarteritic anterior ischemic optic neuropathy (NA-AION). Recent studies show a structure–function relationship, with changes in vascular flow density of superficial capillaries surrounding the ONH, positively correlating with visual improvement.[15,16,17] OCT-A can also identify the boundary of the ischemic area at the level of the ONH and is comparable to optic disc filling defects detected by fluorescein angiography (FA).[18] However, it is important to note that a decrease in peripapillary capillary perfusion density on OCT-A is a common finding in many conditions with chronic optic neuropathy with atrophy and thus may not be a useful tool in differentiating different etiologies.[19]

While brain imaging is unnecessary for typical cases, MRI is mandatory in the presence of atypical features for NA-AION, to exclude other pathologies. Orbit and brain MRI in NA-AION show a normal intraorbital and intracranial optic nerve. Optic nerve enhancement is typically absent on MRI in NA-AION, whereas it is commonly observed in cases of optic neuritis.

Arteritic Anterior Ischemic Optic Neuropathy

Arteritic anterior ischemic optic neuropathy (AAION) is most commonly caused by giant cell arteritis (GCA). In patients with AAION, FA may show peripapillary delayed choroidal filling, disc leakage, and disc filling defects.[20] However, FA is invasive and may cause significant side effects such as allergy. OCT-A is found to be comparable with FA in the detection of microvascular perfusion defects of the ONH and peripapillary choroidal defects in AAION.[18] Moreover, OCT-A in AAION patients shows both lower peripapillary vessel density and tortuosity as compared to NA-AION cases.[19,21]

Noninvasive ultrasonography has become an increasingly utilized modality in the diagnostic assessment of patients with GCA, as inflammation-induced vessel wall edema appears as a hypoechoic circumferential area surrounding the vessel lumen, referred to as the “halo sign” of the temporal artery.[22] Previous studies have shown a sensitivity of 69% and specificity of 82% for the so-called halo sign compared to temporal artery biopsy.[23]

While MRI can reveal inflammation in postcontrast enhancement imaging, optic nerve sheath and orbital fat enhancement are highly indicative of vasculitis related to GCA.[24] One study evaluated the diagnostic use of fat-suppressed three-dimensional T1-weighted black-blood MRI for detecting posterior ciliary artery (PCA) involvement in patients with GCA and AAION. Thirteen out of eighteen GCA patients showed positive findings for AAION with MRI, with MRI black-blood findings displaying contrast enhancement around the optic nerve and adjacent orbital fat along the course of PCAs.[25]

Traumatic Optic Neuropathy

The optic nerve is fixed in its intracanalicular segment, where it exits the orbit through the optic foramen. In this location, it is particularly vulnerable to indirect injury from the effects of percussive forces transmitted from frontal or maxillary bone trauma. External evidence of injury may be scarce, except that an RAPD is usually present when there is unilateral vision loss. CT imaging is especially useful in assessing cases of traumatic optic neuropathy by capturing evidence of optic canal fracture, hematoma, or foreign body/fracture fragments causing impingement on the optic nerve itself.[26] In suspected cases of traumatic optic nerve injury, diffusion tensor imaging may demonstrate change in diffusivity within the affected optic nerve, which may serve as a useful biomarker.[26,27] OCT has shown that pRNFL and mGCIPL thinning manifest as early as 2 weeks after a traumatic optic nerve injury, and these OCT measures of neuroaxonal injury become stable by 20 weeks and thereafter [Figure 4].[28]

Figure 4.

A young female with traumatic optic neuropathy in the left eye presents 2 weeks after a motor vehicle accident. Initial fundus photography appears unremarkable (a). Optical coherence tomography shows mild thinning of the peripapillary retinal nerve fiber layer (pRNFL) in the superotemporal sector (b) and early thinning of the macular ganglion cell-inner plexiform layer (mGCIPL) (c). A visual field defect is present in the left eye (d). At 3-month follow-up, significant thinning of both the pRNFL and mGCIPL is evident (e and f, respectively)

Leber’s Hereditary Optic Neuropathy

Patients with Leber’s hereditary optic neuropathy (LHON) typically present with subacute, painless, and sequential bilateral visual loss. In the acute phase, OCT often reveals pseudo-edema characterized by increased pRNFL thickness, particularly in the temporal and inferior quadrants, which can be distinguished from inflammatory conditions by the absence of leakage on FA.[29] As with other optic neuropathies, mGCIPL thinning often precedes pRNFL atrophy, serving as a sensitive early marker of permanent neuroaxonal injury and potential visual outcome.[30,31] While brain and orbit MRI are usually normal in LHON, they remain essential for excluding compressive or inflammatory etiologies, though occasionally high T2-signal intensity may be observed within the affected optic nerves.[32]

Papilledema due to Increased Intracranial Pressure

Papilledema results from elevated intracranial pressure transmitted through the cerebrospinal fluid (CSF) within the optic nerve sheath, causing optic disc swelling. Optic nerve swelling is typically bilateral but can be asymmetric. Ophthalmoscopic findings may include ONH and peripapillary cotton-wool spots, exudates, and hemorrhage. In late stages, the disc swelling can reduce and become pale due to atrophy. Neuroimaging to exclude an intracranial mass lesion or cerebral venous thrombosis should be pursued emergently. MRI of the brain and orbits with contrast medium is ideal for evaluating papilledema, demonstrating characteristic signs of intracranial hypertension, including empty sella, posterior globe flattening, distension of the perioptic subarachnoid space, and optic nerve tortuosity,[33,34] while magnetic resonance venography can identify underlying cerebral venous sinus stenosis or thrombosis [Figure 5].[35] Normal brain imaging results should prompt a lumbar puncture for evaluation of CSF opening pressure and composition.

Figure 5.

A patient with papilledema secondary to cerebral venous thrombosis. Fundus photography and optical coherence tomography (OCT) demonstrate severe bilateral disc swelling (a and b). The patient presents with nasal step visual field defects and enlarged blind spots in both eyes (c), despite a preserved best-corrected visual acuity of 1.0 (20/20) bilaterally. Brain magnetic resonance venography reveals flow defects in the superior sagittal, bilateral transverse, and sigmoid sinuses (arrowheads), consistent with dural venous sinus thrombosis (d). Three months following endovascular treatment, the bilateral optic disc edema has resolved (e). Follow-up OCT shows a normalized peripapillary retinal nerve fiber layer, but reveals mild thinning of the macular ganglion cell-inner plexiform layer (f and g)

Ultrasonographic measurement of optic nerve sheath diameter (ONSD) has been investigated as a valuable tool for detecting elevated intracranial pressure in emergency and critical care settings.[36] Studies demonstrate good diagnostic accuracy with cutoff values ranging from 4.3 to 6.8 mm, though performance varies across populations and clinical contexts.[37,38]

OCT provides quantitative assessment through peripapillary RNFL thickening and Bruch’s membrane opening displacement (optic disc head edema), with serial measurements essential for monitoring disease progression and treatment response. In chronic cases, RNFL thinning may indicate either therapeutic resolution of disc edema or progressive optic atrophy. Combined pRNFL and mGCIPL analysis provides critical differentiation: successful treatment normalizes pRNFL while preserving mGCIPL thickness, whereas progressive neuropathy demonstrates concurrent thinning of both parameters.[39]

Ischemic and Hemorrhagic Stroke

Ischemic and hemorrhagic stroke of the postchiasm visual pathways manifests as acute homonymous visual field loss. CT is the first-line imaging modality in acute stroke, with noncontrast CT rapidly excluding hemorrhage, typically hyperdense within minutes, and detecting early ischemic changes. MRI offers greater sensitivity for early infarcts, especially in the posterior fossa and cortical regions affecting visual pathways. Diffusion-weighted imaging detects acute ischemia within minutes, while susceptibility-weighted imaging is valuable for identifying microbleeds and structural lesions in hemorrhagic stroke.[40,41]

OCT reveals transsynaptic retrograde degeneration, characterized by thinning of the pRNFL and mGCIPL, typically emerging 4–6 weeks poststroke and stabilizing by 20 weeks, providing prognostic information.[42,43,44] Retrochiasmal pathologies, such as those caused by ischemic strokes, may present as contralateral homonymous hemianopia, accompanied by corresponding homonymous hemi-atrophy of the mGCIPL, and respecting the vertical meridian.[45]

Acute Chiasmal Lesions

While chronic progressive visual loss resulting from gradual chiasmal compression is beyond the scope of this narrative review, acute chiasmal syndromes constitute true neuro-ophthalmologic emergencies that require immediate recognition. Pituitary apoplexy, the most common cause of acute chiasmal dysfunction, results from sudden hemorrhage or infarction of a pituitary gland tumor. It typically presents with an acute, severe headache, ophthalmoplegia, and rapid visual disturbances, such as vision loss or visual field defects; pituitary hormonal imbalances are also frequent.

Although standard noncontrast CT has low sensitivity for pituitary apoplexy due to axial image spacing limitations, MRI serves as the definitive diagnostic tool. MRI effectively visualizes hemorrhage, necrosis, and edema within the pituitary gland, with signals that evolve over time: the acute phase (0–7 days) typically shows hypointensity on T2-weighted images (T2WI) and iso-to-hypointensity on T1-weighted images (T1WI) or heterointensity [Figure 6]; the subacute phase (7–21 days) reveals hyperintensity on both T1WI and T2WI; and the chronic phase (>21 days) demonstrates marked hypointensity on both sequences due to hemosiderin and ferritin deposition.[46,47]

Figure 6.

A 37-year-old male presented with sudden-onset, pupil-sparing complete cranial nerve III palsy and headache with bitemporal hemianopia. Magnetic resonance imaging showed a heterogeneous mass compressing the optic chiasm, characteristic of pituitary apoplexy

Beyond the acute diagnosis, OCT plays a predictive role in visual recovery. Distinct patterns of binasal mGCIPL thinning that respect the vertical meridian provide objective evidence of chiasmal damage and correlate with visual field defects. Furthermore, mGCIPL has been reported to correlate more closely with postoperative visual field recovery than pRNFL, assisting clinicians in predicting the degree of visual improvement following urgent surgical decompression.[48,49]

Summary

Neuro-ophthalmologic emergencies with acute visual loss require an integrated diagnostic approach that combines clinical examinations with neuroimaging studies. MRI remains the gold standard for characterizing demyelinating optic neuritis, differentiating MS, NMOSD, and MOGAD based on lesion morphology, detecting signs of increased intracranial pressure, and diagnosing acute chiasmal syndromes like pituitary apoplexy. CT plays a vital role in the emergent triage of orbital trauma and in the rapid exclusion of hemorrhage in acute stroke. Supplementing these, OCT provides high-resolution quantification of neuroaxonal injury, with mGCIPL thinning often serving as a more sensitive early marker of permanent damage than pRNFL changes in the acute phases of optic neuropathy. In addition, OCT-A offers a noninvasive method for vascular assessment. Collectively, the strategic application of these imaging modalities is crucial for timely diagnosis, prognostic stratification, and management of vision-threatening disorders.

Data availability statement

The datasets generated during and/or analyzed during the current study are available from the corresponding author on reasonable request.

Conflicts of interest

Prof. Rong-Kung Tsai, an editorial board member at Taiwan Journal of Ophthalmology, had no role in the peer review process of or decision to publish this article. All authors declared no conflicts of interest in writing this paper.

Funding Statement

Nil.