Editing Optic neuritis (section)

== Classification and causes ==
[[File:OpticNeuritisExample.jpg|right|thumb|Example of how optic neuritis affected one eye of a person with multiple sclerosis]]

=== Definition ===
The [[optic nerve]] comprises [[axon]]s that emerge from the [[retina]] of the [[Human eye|eye]] and carry visual information to the primary visual nuclei, most of which is relayed to the [[Occipital lobe|occipital cortex]] of the [[Human brain|brain]] to be processed into vision. The phrase optic neuritis is derived from the pathophysiologic changes observed in this disorder whereby the optic nerve (''optic'') becomes inflamed (''neuritis''). As such, optic neuritis is typically a manifestation of an underlying, causative etiology. Because of the breadth of underlying causes of optic neuritis, this disorder is typically classified into the subtypes of "typical" ON and "atypical" ON. Typical ON refers to a demyelinating etiology which most commonly stems from multiple sclerosis or standalone idiopathic disease.<ref name=":12">{{Cite journal |last1=Abel |first1=Anne |last2=McClelland |first2=Collin |last3=Lee |first3=Michael S. |date=2019-11-01 |title=Critical review: Typical and atypical optic neuritis |url=https://linkinghub.elsevier.com/retrieve/pii/S0039625719300414 |journal=Survey of Ophthalmology |volume=64 |issue=6 |pages=770–779 |doi=10.1016/j.survophthal.2019.06.001 |issn=0039-6257 |pmid=31229520}}</ref> Atypical ON essentially refers to optic neuritis from any other cause.<ref name=":12"/>

=== Typical Optic Neuritis ===
ON is classified as typical optic neuritis when demyelination is the causative pathophysiologic aberrancy.<ref name=":12"/> This classification attributes the manifestation of ON primarily to multiple sclerosis or standalone idiopathic disease, of which multiple sclerosis is the most common underlying etiology of all subtypes of optic neuritis.<ref name=":12" />

==== Multiple Sclerosis ====
[[Multiple sclerosis]], in brief, is an autoimmune disease that results in demyelination of the nerves in the [[central nervous system]] (CNS). Demyelination in MS can be diffusely affect the CNS leading to a multitude of physical manifestations. Optic neuritis is acquired this way when MS spreads to the optic nerve. Optic neuritis is often among the first, if not the foremost, manifestation of MS.<ref name=":02"/> One review found that inflammatory demyelinating optic neuritic (IDON) is the initial presentation of MS in approximately 20% of studied patients, while another review found that up to 50% of MS patients will develop optic neuritis during their disease course.<ref>{{Cite journal |last1=Abou Zeid |first1=Nuhad |last2=Bhatti |first2=M. Tariq |date=July 2008 |title=Acute inflammatory demyelinating optic neuritis: evidence-based visual and neurological considerations |url=https://pubmed.ncbi.nlm.nih.gov/18617847 |journal=The Neurologist |volume=14 |issue=4 |pages=207–223 |doi=10.1097/NRL.0b013e31816f27fe |issn=1074-7931 |pmid=18617847}}</ref><ref>{{Cite journal |last=Balcer |first=Laura J. |date=2006-03-23 |title=Clinical practice. Optic neuritis |url=https://pubmed.ncbi.nlm.nih.gov/16554529 |journal=The New England Journal of Medicine |volume=354 |issue=12 |pages=1273–1280 |doi=10.1056/NEJMcp053247 |issn=1533-4406 |pmid=16554529}}</ref>

==== Idiopathic Disease ====
Idiopathic optic neuritis (ION) generally refers to optic neuritis that does not present with serologic markers attributable to a known underlying cause (eg, NMOSD, MOGAD, etc.).<ref name=":35">{{Cite journal |last=Bennett |first=Jeffrey L. |date=October 2019 |title=Optic Neuritis |journal=Continuum (Minneapolis, Minn.) |volume=25 |issue=5 |pages=1236–1264 |doi=10.1212/CON.0000000000000768 |issn=1538-6899 |pmc=7395663 |pmid=31584536}}</ref> Opinions among specialists seem to differ as to whether idiopathic optic neuritis should be classified as MS-associated ON or if it should not be exclusively associated with MS.<ref name=":4">{{Cite journal |last1=Wei |first1=Siqian |last2=Du |first2=Yi |last3=Luo |first3=Wenjing |date=2023 |title=Idiopathic Optic Neuritis Should Neither Be Defined as a Subtype nor an Early Sign of Multiple Sclerosis |journal=Neuro-Ophthalmology (Aeolus Press) |volume=47 |issue=4 |pages=230–231 |doi=10.1080/01658107.2023.2205931 |issn=0165-8107 |pmc=10332215 |pmid=37434669}}</ref> A group of reviewers from China propose that ION should not be associated with MS and hence defined with the literal meaning of "idiopathic" as ON with an unknown cause.<ref name=":4" /> On the other hand, multiple groups of Western reviewers propose that ION should be considered a preceding manifestation, among a collection of manifestations, that precedes the development of MS in the absence of other serologic findings.<ref name=":22">{{Cite journal |last1=Beck |first1=Roy W. |last2=Cleary |first2=Patricia A. |last3=Anderson |first3=Malcolm M. |last4=Keltner |first4=John L. |last5=Shults |first5=William T. |last6=Kaufman |first6=David I. |last7=Buckley |first7=Edward G. |last8=Corbett |first8=James J. |last9=Kupersmith |first9=Mark J. |last10=Miller |first10=Neil R. |last11=Savino |first11=Peter J. |last12=Guy |first12=John R. |last13=Trobe |first13=Jonathan D. |last14=McCrary |first14=John A. |last15=Smith |first15=Craig H. |date=1992-02-27 |title=A Randomized, Controlled Trial of Corticosteroids in the Treatment of Acute Optic Neuritis |url=https://www.nejm.org/doi/full/10.1056/NEJM199202273260901 |journal=New England Journal of Medicine |volume=326 |issue=9 |pages=581–588 |doi=10.1056/NEJM199202273260901 |pmid=1734247 |issn=0028-4793}}</ref><ref name=":35"/>

=== Atypical Optic Neuritis ===
ON is classified as atypical optic neuritis when the underlying cause is an etiology other than multiple sclerosis or standalone idiopathic disease. Atypical ON is most frequently seen as an early manifestation of [[neuromyelitis optica spectrum disorder]] (NMOSD), formerly known as neuromyelitis optica (NMO).<ref name=":52">{{Cite journal |last1=Sarkar |first1=Prathama |last2=Mehtani |first2=Amit |last3=Gandhi |first3=H. C. |last4=Dubey |first4=Vinita |last5=Tembhurde |first5=Parag Maroti |last6=Gupta |first6=Mohit Kumar |date=January 2021 |title=Atypical optic neuritis: An overview |journal=Indian Journal of Ophthalmology |volume=69 |issue=1 |pages=27–35 |doi=10.4103/ijo.IJO_451_20 |doi-access=free |issn=1998-3689 |pmc=7926095 |pmid=33323567}}</ref> Other causes of atypical ON include myelin oligodendrocyte glycoprotein-antibody-associated disease (MOGAD), other autoimmune disorders (eg, [[Sarcoidosis]], [[Sjögren's disease|Sjogren syndrome]], [[rheumatoid arthritis]], [[Lupus|systemic lupus erythematosus]]), and infections (Bacterial [<nowiki/>[[Tuberculosis]], [[Syphilis|syphillis]], [[meningitis]], [[Lyme disease|Lyme’s disease]], [[Bartonella]]] or Viral [<nowiki/>[[measles]], [[mumps]], [[rubella]], [[Chickenpox|chicken pox]], [[Herpes simplex virus|herpes]]]).<ref name=":52"/>

==== NMOSD (Formerly NMO) ====
Neuromyelitis optica spectrum disorder (NMOSD) is a disorder consisting of six syndromes that cause inflammation and demyelination of the CNS.<ref name=":6">{{Citation |last1=Shumway |first1=Caleb L. |title=Neuromyelitis Optica Spectrum Disorder (NMOSD) |date=2025 |work=StatPearls |url=https://www.ncbi.nlm.nih.gov/books/NBK572108/ |access-date=2025-03-19 |place=Treasure Island (FL) |publisher=StatPearls Publishing |pmid=34283474 |last2=Patel |first2=Bhupendra C. |last3=Tripathy |first3=Koushik |last4=De Jesus |first4=Orlando}}</ref> The hallmark diagnostic criteria of NMOSD is the presence of the aquaporin-4 immunoglobulin G antibodies (AQP4-IgG) found on serology, which is the underlying aberrancy of this autoimmune condition that engenders its distinction from multiple sclerosis.<ref name=":6" /> Clinical manifestations of NMOSD, such as optic neuritis, occur due to antibody-mediated damage against the aquaporin-4 transmembrane water channels which are found in the foot processes of [[astrocyte]]s at high concentrations within the optic nerve, brainstem, and spinal cord.<ref name=":6" />

==== MOGAD ====
Myelin oligodendrocyte glycoprotein-antibody-associated disease (MOGAD) is an autoimmune condition against the myelin oligodendrocyte glycoprotein (MOG) located on both the myelin sheathe and oligodendrocyte cell surfaces of the CNS.<ref name=":7">{{Cite journal |last1=Sechi |first1=Elia |last2=Cacciaguerra |first2=Laura |last3=Chen |first3=John J. |last4=Mariotto |first4=Sara |last5=Fadda |first5=Giulia |last6=Dinoto |first6=Alessandro |last7=Lopez-Chiriboga |first7=A. Sebastian |last8=Pittock |first8=Sean J. |last9=Flanagan |first9=Eoin P. |date=2022 |title=Myelin Oligodendrocyte Glycoprotein Antibody-Associated Disease (MOGAD): A Review of Clinical and MRI Features, Diagnosis, and Management |journal=Frontiers in Neurology |volume=13 |pages=885218 |doi=10.3389/fneur.2022.885218 |doi-access=free |issn=1664-2295 |pmc=9247462 |pmid=35785363}}</ref> Cell-mediated and complement-mediated inflammation results hallmark findings of perivenous and confluent white matter demyelination.<ref name=":7" />

==== Infection ====
A wide range of attributable infectious etiologies have been found to cause optic neuritis and can arise from varying pathophysiologic mechanisms.<ref name=":52"/> The underlying inflammation and demyelination has been shown to manifest as anterior optic neuritis, retrobulbar optic neuritis (normal [[optic disc]]), neuroretinitis (optic disc [[edema]] with the macular star), or anterior optic neuropathy.<ref name=":52" /> It has been proposed that optic nerve involvement secondary to [[Varicella zoster virus|herpes zoster virus]] infection can arise from direct nerve inflammation or an [[Ischemia|ischemic]] mechanism leading to inflammatory [[thrombosis]].<ref name=":52" /> Optic nerve involvement secondary to [[cytomegalovirus]] (CMV) infection has been proposed to involve a similar mechanism in patients with [[Cytomegalovirus retinitis|CMV retinitis]].<ref>{{Cite journal |last=Mansour |first=A. M. |date=June 1997 |title=Cytomegalovirus optic neuritis |url=https://pubmed.ncbi.nlm.nih.gov/10168894 |journal=Current Opinion in Ophthalmology |volume=8 |issue=3 |pages=55–58 |doi=10.1097/00055735-199706000-00010 |issn=1040-8738 |pmid=10168894}}</ref> The pathogenesis of ON secondary to [[HIV]] has been proposed to arise from autoimmune, vascular, and degenerative ischemic pathways.<ref name=":52" />

==== Other Causes ====
Other etiologies associated with optic neuritis include [[congenital anomalies]], [[glaucoma]], elevated [[intracranial pressure]] (i.e. [[papilledema]]), compression, nutritional and toxic optic neuropathy, trauma, inherited optic neuropathy, or infiltration (eg, [[Neoplasm|neoplastic]] or [[granuloma]]tous).<ref>{{Cite journal |last=Riordan-Eva |first=P. |date=November 2004 |title=Clinical assessment of optic nerve disorders |url=https://www.nature.com/articles/6701575 |journal=Eye |volume=18 |issue=11 |pages=1161–1168 |doi=10.1038/sj.eye.6701575 |pmid=15534601 |issn=1476-5454}}</ref>

When an inflammatory recurrent optic neuritis is not demyelinating, it is called [[chronic relapsing inflammatory optic neuropathy]] (CRION).<ref>{{cite journal |vauthors=Kidd D, Burton B, Plant GT, Graham EM |date=February 2003 |title=Chronic relapsing inflammatory optic neuropathy (CRION) |journal=Brain |volume=126 |issue=Pt 2 |pages=276–284 |doi=10.1093/brain/awg045 |pmid=12538397 |doi-access=free}}</ref>