Table 1.

Clinical and radiological features of the main types of seronegative non-MS-related ON. HCVA: High-Contrast Visual Acuity. NLP: no light perception. Gd: gadolinium. IPL: inner plexiform layer. GCL: ganglion cell layer. pRNFL: peripapillary retinal nerve fiber layer.

Clinical Features	GFAP-IgG	CRMP5-IgG	CRION	Sarcoidosis	Optic Perineuritis
Sex distribution	F:M 1:1 [15]	F:M 1:1 [28]	F:M 2:1 [66]	F:M 1:1 [78]	2.5:1 [63]
Age at onset (median/mean)	44–50 years	69 years	35.7 years	42–48 years	41 years
Retro-orbital pain	Rare	Rare	Prominent	Frequent	Prominent
Visual loss severity	(1) No HCVA loss (bilateral optic disc edema) or (2) severe bilateral vision loss	Variable, median around 20/40	Severe: 20/200 in two-thirds of cases	Severe; often NLP	Mild, often central vision sparing
Optic disc edema	Very frequent; may be asymptomatic	Very frequent	Variable	Variable	Frequent
Visual loss course	Subacute	Subacute	Subacute	Subacute to slowly progressive	Subacute to slowly progressive
MRI findings	Symmetrical FLAIR hyperintensities involving basal ganglia, thalami, internal, and external capsules; Linea radial (or leptomeningeal) contrast enhancement	Optic nerve may be normal; rarely T2 hyperintensities with no Gd enhancement; brain MRI can show basal ganglia, medial temporal lobe, extensive white matter, hippocampus, cerebellum, insula, thalamus, and frontal lobe T2 hyperintensities	Normal in 40% of patients; possibly isolated T2 hyperintense lesions in periventricular or juxtacortical white matter	Leptomeningeal or pachymeningeal enhancement, including cranial nerve enhancement, MS-like white matter lesions, optic nerve T2 hyperintensities, focal parenchymal areas of contrast enhancement	Ill-defined, circumferential optic nerve sheath enhancement (“tramtrack” or “doughnut” sign) to be differentiated from optic nerve sheath meningioma, orbital pseudotumor, or sarcoidosis; possible enhancement of orbital fat surrounding optic nerve sheath or extraocular muscle
OCT findings	In cases of optic disc edema: normal outer retina with elevated retinal nerve fiber layer thickness [20]	Increased RNFL consistent with optic disc edema (acute phase); atrophy of the outer retinal layers was noted, with deepening of the foveal depression; hyperreflective dots (atrophic stage) [79,80]	Severe thinning in RNFL and thinning in intra-retinal segments of IPL, GCL, RNFL, and TMV compared with NMOSD and MS-related ON [81]	Subretinal fluid, macular edema, and loss of retinal architecture; no alterations in patients without clinical optic involvement [82]	Significant thinning of average peripapillary RNFL [83]
Steroid dependency	Limited	None	Severe	Severe	Severe