Optic neuritis: Difference between revisions
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{{CMG}} {{AE}} {{MMJ}} | {{CMG}} {{AE}}, {{MMJ}}, {{M.B}} | ||
==Historical Perspective== | ==Historical Perspective== | ||
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==Differentiating Optic Neuritis from other Diseases== | ==Differentiating Optic Neuritis from other Diseases== | ||
Optic neuritis must be differentiated from other diseases that cause sudden [[eye pain]] and [[vision loss]] such as:<ref name="pmid3414716">{{cite journal |vauthors=Kliethermes MA |title=Working parents in two-pharmacist marriages |journal=Am J Hosp Pharm |volume=45 |issue=7 |pages=1500 |date=July 1988 |pmid=3414716 |doi= |url=}}</ref> | Optic neuritis must be differentiated from other diseases that cause sudden [[eye pain]] and [[vision loss]] such as:<ref name="pmid3414716">{{cite journal |vauthors=Kliethermes MA |title=Working parents in two-pharmacist marriages |journal=Am J Hosp Pharm |volume=45 |issue=7 |pages=1500 |date=July 1988 |pmid=3414716 |doi= |url=}}</ref> | ||
# Leber’s Hereditary Optic Neuropathy (LHON)<ref name="pmid3414716" /> | # Leber’s Hereditary Optic Neuropathy (LHON)<ref name="pmid3414716" /> which results from point [[mutations]] in [[mitochondrial DNA]] and subsequent mitochondrial dysfunction, causing bilateral central vision loss.<ref name="pmid4492634">{{cite journal |vauthors=Fujimori H |title=[Pulmonary tuberculosis--keypoints in nursing of pregnant and puerperal patients] |language=Japanese |journal=Josanpu Zasshi |volume=27 |issue=12 |pages=40–3 |date=December 1973 |pmid=4492634 |doi= |url=}}</ref> | ||
# [[Anterior ischemic optic neuropathy|Nonarteritic Anterior Ischemic Optic Neuropathy]] (AION)<ref name="pmid3414716">{{cite journal |vauthors=Kliethermes MA |title=Working parents in two-pharmacist marriages |journal=Am J Hosp Pharm |volume=45 |issue=7 |pages=1500 |date=July 1988 |pmid=3414716 |doi= |url=}}</ref> | |||
#* It is the most common form of ischemic [[optic neuropathy]] and the second most common optic neuropathy. | #* It is the most common form of ischemic [[optic neuropathy]] and the second most common optic neuropathy. | ||
#* It is more common in patients over the age of 50 years with [[Vasculopathies|vasculopathic]] risk factors such as: | #* It is more common in patients over the age of 50 years with [[Vasculopathies|vasculopathic]] risk factors such as: | ||
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==Epidemiology and Demographics== | ==Epidemiology and Demographics== | ||
===Age=== | === Incidence === | ||
===Gender=== | * The [[incidence]] of optic neuritis is approximately 5 to 6.4 per 100 000 individuals in US.<ref name="pmid3178158">{{cite journal |vauthors=Marechal F, Berthiot G, Deltour G |title=Serum levels of CA-50, CA-19.9, CA-125, CA-15.3, enolase and carcino-embryonic antigen in non neoplastic diseases of the lung |journal=Anticancer Res. |volume=8 |issue=4 |pages=677–80 |date=1988 |pmid=3178158 |doi= |url=}}</ref><ref name="pmid7854520">{{cite journal |vauthors=Rodriguez M, Siva A, Cross SA, O'Brien PC, Kurland LT |title=Optic neuritis: a population-based study in Olmsted County, Minnesota |journal=Neurology |volume=45 |issue=2 |pages=244–50 |date=February 1995 |pmid=7854520 |doi= |url=}}</ref><ref name="pmid5057861">{{cite journal |vauthors=Percy AK, Nobrega FT, Kurland LT |title=Optic neuritis and multiple sclerosis. An epidemiologic study |journal=Arch. Ophthalmol. |volume=87 |issue=2 |pages=135–9 |date=February 1972 |pmid=5057861 |doi= |url=}}</ref> | ||
=== | |||
=== Age === | |||
* Optic neuritis commonly affects patients between the ages of 15 and 49.<ref name="pmid3105615">{{cite journal |vauthors=Self SG, Grossman EA |title=Linear rank tests for interval-censored data with application to PCB levels in adipose tissue of transformer repair workers |journal=Biometrics |volume=42 |issue=3 |pages=521–30 |date=September 1986 |pmid=3105615 |doi= |url=}}</ref> | |||
=== Race === | |||
* Optic neuritis usually affects individuals of the Caucasians race eight times more frequently than Blacks and Asians.<ref name="pmid3178158">{{cite journal |vauthors=Marechal F, Berthiot G, Deltour G |title=Serum levels of CA-50, CA-19.9, CA-125, CA-15.3, enolase and carcino-embryonic antigen in non neoplastic diseases of the lung |journal=Anticancer Res. |volume=8 |issue=4 |pages=677–80 |date=1988 |pmid=3178158 |doi= |url=}}</ref><ref name="pmid17967837" /><ref name="pmid2124032" /><ref name="pmid9482360" /> | |||
* Black populations individuals are less likely to develop optic neuritis.<ref name="pmid3178158">{{cite journal |vauthors=Marechal F, Berthiot G, Deltour G |title=Serum levels of CA-50, CA-19.9, CA-125, CA-15.3, enolase and carcino-embryonic antigen in non neoplastic diseases of the lung |journal=Anticancer Res. |volume=8 |issue=4 |pages=677–80 |date=1988 |pmid=3178158 |doi= |url=}}</ref><ref name="pmid17967837">{{cite journal |vauthors=Bhigjee AI, Moodley K, Ramkissoon K |title=Multiple sclerosis in KwaZulu Natal, South Africa: an epidemiological and clinical study |journal=Mult. Scler. |volume=13 |issue=9 |pages=1095–9 |date=November 2007 |pmid=17967837 |doi=10.1177/1352458507079274 |url=}}</ref><ref name="pmid2124032">{{cite journal |vauthors=Mbonda E, Larnaout A, Maertens A, Appel B, Lowenthal A, Mbede J, Evrard P |title=Multiple sclerosis in a black Cameroonian woman |journal=Acta Neurol Belg |volume=90 |issue=4 |pages=218–22 |date=1990 |pmid=2124032 |doi= |url=}}</ref><ref name="pmid9482360">{{cite journal |vauthors=Phillips PH, Newman NJ, Lynn MJ |title=Optic neuritis in African Americans |journal=Arch. Neurol. |volume=55 |issue=2 |pages=186–92 |date=February 1998 |pmid=9482360 |doi= |url=}}</ref> | |||
=== Gender === | |||
* Women are more commonly affected by optic neuritis than men.<ref name="pmid3414716">{{cite journal |vauthors=Kliethermes MA |title=Working parents in two-pharmacist marriages |journal=Am J Hosp Pharm |volume=45 |issue=7 |pages=1500 |date=July 1988 |pmid=3414716 |doi= |url=}}</ref> | |||
=== Region === | |||
* The [[incidence]] of optic neuritis is highest in populations located at higher latitudes such as:<ref name="pmid3178158">{{cite journal |vauthors=Marechal F, Berthiot G, Deltour G |title=Serum levels of CA-50, CA-19.9, CA-125, CA-15.3, enolase and carcino-embryonic antigen in non neoplastic diseases of the lung |journal=Anticancer Res. |volume=8 |issue=4 |pages=677–80 |date=1988 |pmid=3178158 |doi= |url=}}</ref><ref name="pmid19878630">{{cite journal |vauthors=Shams PN, Plant GT |title=Optic neuritis: a review |journal=Int MS J |volume=16 |issue=3 |pages=82–9 |date=September 2009 |pmid=19878630 |doi= |url=}}</ref><ref name="pmid4015470">{{cite journal |vauthors=Kurtzke JF |title=Optic neuritis or multiple sclerosis |journal=Arch. Neurol. |volume=42 |issue=7 |pages=704–10 |date=July 1985 |pmid=4015470 |doi= |url=}}</ref> | |||
** Northern United States | |||
** Northern and Western Europe | |||
** New Zealand and Southern Australia | |||
==Risk Factors== | ==Risk Factors== | ||
===Common Risk Factors=== | |||
* Common risk factors in the development of optic neuritis include: | |||
*# Age | |||
*#* Optic neuritis most often affects adults between the ages of 15 and 49.<ref name="pmid3105615" /> | |||
*# Sex | |||
*#* Women are much more likely to develop optic neuritis than men are.<ref name="pmid3414716" /> | |||
*# Race | |||
*#* Optic neuritis usually affects individuals of the Caucasians race eight times more frequently than Blacks and Asians.<ref name="pmid3178158" /><ref name="pmid17967837" /><ref name="pmid2124032" /><ref name="pmid9482360" /> | |||
*#* Black populations individuals are less likely to develop optic neuritis.<ref name="pmid3178158" /><ref name="pmid17967837" /><ref name="pmid2124032" /><ref name="pmid9482360" /> | |||
*# [[Genetic mutation]]<ref name="pmid20301353">{{cite journal |vauthors=Adam MP, Ardinger HH, Pagon RA, Wallace SE, Bean LJH, Stephens K, Amemiya A, Yu-Wai-Man P, Chinnery PF |title= |journal= |volume= |issue= |pages= |date= |pmid=20301353 |doi= |url=}}</ref> | |||
*# [[Multiple sclerosis]]<ref name="pmid12789593">{{cite journal |vauthors=Chan JW |title=Optic neuritis in multiple sclerosis |journal=Ocul. Immunol. Inflamm. |volume=10 |issue=3 |pages=161–86 |date=September 2002 |pmid=12789593 |doi= |url=}}</ref> | |||
*# [[Trauma]]<ref name="pmid4457437">{{cite journal |vauthors=Haslbeck M |title=[Insulin secretion after glucose loading. Studies on insulin secretion in healthy and diabetic subjects after administration of glucose] |language=German |journal=Fortschr. Med. |volume=92 |issue=32 |pages=1317–8 |date=November 1974 |pmid=4457437 |doi= |url=}}</ref> | |||
*# [[Nutritional deficiencies]]<ref name="pmid25345287">{{cite journal |vauthors=Sawicka-Pierko A, Obuchowska I, Mariak Z |title=Nutritional optic neuropathy |journal=Klin Oczna |volume=116 |issue=2 |pages=104–10 |date=2014 |pmid=25345287 |doi= |url=}}</ref> | |||
*# Compression of the [[optic nerve]]<ref name="pmid5546777">{{cite journal |vauthors=Primicerio B |title=[Competitions for the position of sanitary personnel in hospitals] |language=Italian |journal=Policlinico Prat |volume=78 |issue=2 |pages=72–7 |date=January 1971 |pmid=5546777 |doi= |url=}}</ref> | |||
*# Arteritic [[optic neuropathy]]<ref name="pmid2701125">{{cite journal |vauthors=Dyras M, Stós B, Zemowski W |title=[Possibilities of combined maxillary-orthopaedic and prosthetic treatment of malocclusion in adult patients] |language=Polish |journal=Protet Stomatol |volume=39 |issue=3 |pages=134–9 |date=1989 |pmid=2701125 |doi= |url=}}</ref> | |||
*# [[Diabetes]]<ref name="pmid6354403">{{cite journal |vauthors=Warren SA, Warren KG |title=Optic neuritis, diabetes mellitus and multiple sclerosis: a three-way association |journal=Can. J. Ophthalmol. |volume=18 |issue=5 |pages=228–32 |date=August 1983 |pmid=6354403 |doi= |url=}}</ref> | |||
*# [[Glaucoma]]<ref name="pmid3939751">{{cite journal |vauthors=Holmberg D, Lundkvist I, Forni L, Ivars F, Coutinho A |title=Absence of immunoglobulin heavy chain expression results in altered kappa/lambda light chain ratios |journal=J. Mol. Cell. Immunol. |volume=2 |issue=1 |pages=51–6 |date=1985 |pmid=3939751 |doi= |url=}}</ref> | |||
* Common risk factors in the recurrence of optic neuritis include:<ref name="pmid4177903">{{cite journal |vauthors=Dabholkar AS, Tewari HB |title=The functional significance of the presence of acid phosphatase at the nucleic-acid synthesizing sites in the nuclei of the neurons of the cephalothoracic ganglionic masses of palaemnius |journal=Acta Neurol. Scand. |volume=44 |issue=5 |pages=533–41 |date=1968 |pmid=4177903 |doi= |url=}}</ref><ref name="pmid12789593">{{cite journal |vauthors=Chan JW |title=Optic neuritis in multiple sclerosis |journal=Ocul. Immunol. Inflamm. |volume=10 |issue=3 |pages=161–86 |date=September 2002 |pmid=12789593 |doi= |url=}}</ref> | |||
*# Underlying diseases such as: | |||
*#* [[Neuromyelitis optica]] | |||
*#* [[Multiple sclerosis]] | |||
*# Unilateral optic neuritis | |||
*# Early initiation of [[glucocorticoid]] | |||
==Natural History, Complications and Prognosis== | ==Natural History, Complications and Prognosis== | ||
=== Natural History === | |||
* The symptoms of optic neuritis usually develop in the second decade of life, and start with symptoms such as pain on movement of the eyes, followed by a worsening of [[vision]].<ref name="pmid4581115">{{cite journal |vauthors=Wilson BJ |title=12,13-Epoxytrichothecenes: potential toxic contaminants of foods |journal=Nutr. Rev. |volume=31 |issue=6 |pages=169–72 |date=June 1973 |pmid=4581115 |doi= |url=}}</ref> | |||
* Common symptoms of optic neuritis include:<ref name="pmid4581115">{{cite journal |vauthors=Wilson BJ |title=12,13-Epoxytrichothecenes: potential toxic contaminants of foods |journal=Nutr. Rev. |volume=31 |issue=6 |pages=169–72 |date=June 1973 |pmid=4581115 |doi= |url=}}</ref><ref name="pmid1734247">{{cite journal |vauthors=Beck RW, Cleary PA, Anderson MM, Keltner JL, Shults WT, Kaufman DI, Buckley EG, Corbett JJ, Kupersmith MJ, Miller NR |title=A randomized, controlled trial of corticosteroids in the treatment of acute optic neuritis. The Optic Neuritis Study Group |journal=N. Engl. J. Med. |volume=326 |issue=9 |pages=581–8 |date=February 1992 |pmid=1734247 |doi=10.1056/NEJM199202273260901 |url=}}</ref> | |||
*# Pain on movement of the eyes which is sever and so disturbing | |||
*# Seeing things darkly, unclearly, and with [[Contrast|poor contrast]] | |||
*# Dirty and pale Colors | |||
*# [[Visual field loss]] | |||
*# Disturbed [[color vision]] | |||
*# Flashing lights | |||
* After a sub acute onset, the patient’s [[visual acuity]] continues to deteriorate for a few more days; in the untreated course of the disease, it generally reaches its nadir in one to two weeks and then improves again.<ref name="pmid4581115">{{cite journal |vauthors=Wilson BJ |title=12,13-Epoxytrichothecenes: potential toxic contaminants of foods |journal=Nutr. Rev. |volume=31 |issue=6 |pages=169–72 |date=June 1973 |pmid=4581115 |doi= |url=}}</ref> | |||
=== Complications === | |||
* Common complications of optic neuritis include:<ref name="pmid3178158">{{cite journal |vauthors=Marechal F, Berthiot G, Deltour G |title=Serum levels of CA-50, CA-19.9, CA-125, CA-15.3, enolase and carcino-embryonic antigen in non neoplastic diseases of the lung |journal=Anticancer Res. |volume=8 |issue=4 |pages=677–80 |date=1988 |pmid=3178158 |doi= |url=}}</ref><ref name="pmid80680">{{cite journal |vauthors= |title=Henry Edmund Seiler |journal=Lancet |volume=2 |issue=8092 Pt 1 |pages=747 |date=September 1978 |pmid=80680 |doi= |url=}}</ref> | |||
**Side effects of [[corticosteroids]] use | |||
**Permanent [[optic nerve]] damage | |||
**Decreased [[visual acuity]] | |||
***In some cases of optic neuritis, partial loss of color discrimination might persist. | |||
=== Prognosis === | |||
* The long-term visual prognosis of idiopathic optic neuritis is generally good.<ref name="pmid3116540">{{cite journal |vauthors=Sagalovich VIa, Solov'eva IP, Kunichan AD, Nemsadze MN |title=[Effectiveness of single and fractional administration of isoniazid in the treatment of dogs infected with isoniazid-resistant strains of Mycobacterium tuberculosis] |language=Russian |journal=Probl Tuberk |volume= |issue=7 |pages=49–53 |date=1987 |pmid=3116540 |doi= |url=}}</ref> | |||
* More than 90% of the patients recover a visual acuity of 20/40 or better by 6 months.<ref name="pmid3116540">{{cite journal |vauthors=Sagalovich VIa, Solov'eva IP, Kunichan AD, Nemsadze MN |title=[Effectiveness of single and fractional administration of isoniazid in the treatment of dogs infected with isoniazid-resistant strains of Mycobacterium tuberculosis] |language=Russian |journal=Probl Tuberk |volume= |issue=7 |pages=49–53 |date=1987 |pmid=3116540 |doi= |url=}}</ref> | |||
* Findings associated with poor visual outcome at 6 months include:<ref name="pmid15477504">{{cite journal |vauthors=Achiron A, Kishner I, Sarova-Pinhas I, Raz H, Faibel M, Stern Y, Lavie M, Gurevich M, Dolev M, Magalashvili D, Barak Y |title=Intravenous immunoglobulin treatment following the first demyelinating event suggestive of multiple sclerosis: a randomized, double-blind, placebo-controlled trial |journal=Arch. Neurol. |volume=61 |issue=10 |pages=1515–20 |date=October 2004 |pmid=15477504 |doi=10.1001/archneur.61.10.1515 |url=}}</ref><ref name="pmid3116540">{{cite journal |vauthors=Sagalovich VIa, Solov'eva IP, Kunichan AD, Nemsadze MN |title=[Effectiveness of single and fractional administration of isoniazid in the treatment of dogs infected with isoniazid-resistant strains of Mycobacterium tuberculosis] |language=Russian |journal=Probl Tuberk |volume= |issue=7 |pages=49–53 |date=1987 |pmid=3116540 |doi= |url=}}</ref> | |||
** A cut-off level of vision ≤ 20/50 | |||
** Contrast sensitivity of <1.0 log units | |||
** A [[visual field]] mean deviation of ≤ – 15 dB after 1 month in the Optic Neuritis Treatment Trial. | |||
* Despite the relatively good visual outcome, most patients show a degree of long-lasting damage to the [[optic nerve]], such as:<ref name="pmid3116540">{{cite journal |vauthors=Sagalovich VIa, Solov'eva IP, Kunichan AD, Nemsadze MN |title=[Effectiveness of single and fractional administration of isoniazid in the treatment of dogs infected with isoniazid-resistant strains of Mycobacterium tuberculosis] |language=Russian |journal=Probl Tuberk |volume= |issue=7 |pages=49–53 |date=1987 |pmid=3116540 |doi= |url=}}</ref> | |||
** A pale [[optic disc]] | |||
** Loss of retinal nerve fibers | |||
** Prolonged latency in the [[Visual evoked potential|visual evoked response]] | |||
** Thinning of the [[optic nerve]] on MR | |||
==Diagnosis== | ==Diagnosis== | ||
=== | |||
=== Diagnosis studies === | |||
The diagnosis of typical optic neuritis is usually made clinically.<ref name="pmid3414716">{{cite journal |vauthors=Kliethermes MA |title=Working parents in two-pharmacist marriages |journal=Am J Hosp Pharm |volume=45 |issue=7 |pages=1500 |date=July 1988 |pmid=3414716 |doi= |url=}}</ref> | |||
The classic triad for diagnosis of optic neuritis consist of:<ref name="pmid3414716">{{cite journal |vauthors=Kliethermes MA |title=Working parents in two-pharmacist marriages |journal=Am J Hosp Pharm |volume=45 |issue=7 |pages=1500 |date=July 1988 |pmid=3414716 |doi= |url=}}</ref><ref name="pmid19878630">{{cite journal |vauthors=Shams PN, Plant GT |title=Optic neuritis: a review |journal=Int MS J |volume=16 |issue=3 |pages=82–9 |date=September 2009 |pmid=19878630 |doi= |url=}}</ref><ref name="pmid3379920">{{cite journal |vauthors=Wells H |title=A discussion of the KDI Quik Test Drug Screen |journal=J Anal Toxicol |volume=12 |issue=2 |pages=111 |date=1988 |pmid=3379920 |doi= |url=}}</ref> | |||
#[[Visual loss]] | |||
#Periocular pain | |||
#[[Dyschromatopsia]] | |||
[[MRI]] is the diagnosis study of choice for visualising the [[optic nerve]]. | |||
The following result of MRI is confirmatory of optic neuritis: | |||
* Swollen retrobulbar intra-orbital segment of the optic nerve with a high T2 signal. High T2 signal persists and may be permanent; | |||
* Atrophied nerve in chronic cases | |||
Other diagnosis studies which may help to diagnosis of optic neuritis include:<ref name="pmid4347010">{{cite journal |vauthors=Ishikawa Y |title=[Electronmicroscopic observations on cultured rabbit lens cells infected with herpes virus] |language=Japanese |journal=Nippon Ganka Gakkai Zasshi |volume=76 |issue=10 |pages=1213–24 |date=October 1972 |pmid=4347010 |doi= |url=}}</ref><ref name="pmid28531809">{{cite journal |vauthors=Pihl-Jensen G, Schmidt MF, Frederiksen JL |title=Multifocal visual evoked potentials in optic neuritis and multiple sclerosis: A review |journal=Clin Neurophysiol |volume=128 |issue=7 |pages=1234–1245 |date=July 2017 |pmid=28531809 |doi=10.1016/j.clinph.2017.03.047 |url=}}</ref><ref name="pmid3005938">{{cite journal |vauthors=Rao NA, Calandra AJ, Sevanian A, Bowe B, Delmage JM, Marak GE |title=Modulation of lens-induced uveitis by superoxide dismutase |journal=Ophthalmic Res. |volume=18 |issue=1 |pages=41–6 |date=1986 |pmid=3005938 |doi=10.1159/000265413 |url=}}</ref> | |||
* [[Functional MRI]] | |||
* [[Multifocal visual evoked potential]] | |||
* [[Optical coherence tomography]] (OCT) | |||
===Symptoms=== | ===Symptoms=== | ||
* The symptoms of optic neuritis usually develop in the second decade of life, and start with symptoms such as pain on movement of the eyes, followed by a worsening of [[vision]].<ref name="pmid4581115">{{cite journal |vauthors=Wilson BJ |title=12,13-Epoxytrichothecenes: potential toxic contaminants of foods |journal=Nutr. Rev. |volume=31 |issue=6 |pages=169–72 |date=June 1973 |pmid=4581115 |doi= |url=}}</ref> | |||
* Common symptoms of optic neuritis include:<ref name="pmid4581115">{{cite journal |vauthors=Wilson BJ |title=12,13-Epoxytrichothecenes: potential toxic contaminants of foods |journal=Nutr. Rev. |volume=31 |issue=6 |pages=169–72 |date=June 1973 |pmid=4581115 |doi= |url=}}</ref><ref name="pmid1734247">{{cite journal |vauthors=Beck RW, Cleary PA, Anderson MM, Keltner JL, Shults WT, Kaufman DI, Buckley EG, Corbett JJ, Kupersmith MJ, Miller NR |title=A randomized, controlled trial of corticosteroids in the treatment of acute optic neuritis. The Optic Neuritis Study Group |journal=N. Engl. J. Med. |volume=326 |issue=9 |pages=581–8 |date=February 1992 |pmid=1734247 |doi=10.1056/NEJM199202273260901 |url=}}</ref><ref name="pmid26396053">{{cite journal |vauthors=Wilhelm H, Schabet M |title=The Diagnosis and Treatment of Optic Neuritis |journal=Dtsch Arztebl Int |volume=112 |issue=37 |pages=616–25; quiz 626 |date=September 2015 |pmid=26396053 |pmc=4581115 |doi=10.3238/arztebl.2015.0616 |url=}}</ref> | |||
*# Pain on movement of the eyes which is sever and so disturbing | |||
*# Seeing things darkly, unclearly, and with [[Contrast|poor contrast]] | |||
*# Dirty and pale Colors | |||
*# [[Visual field loss]] | |||
*# Disturbed [[color vision]] | |||
*# Flashing lights | |||
* After a sub acute onset, the patient’s [[visual acuity]] continues to deteriorate for a few more days; in the untreated course of the disease, it generally reaches its nadir in one to two weeks and then improves again.<ref name="pmid4581115">{{cite journal |vauthors=Wilson BJ |title=12,13-Epoxytrichothecenes: potential toxic contaminants of foods |journal=Nutr. Rev. |volume=31 |issue=6 |pages=169–72 |date=June 1973 |pmid=4581115 |doi= |url=}}</ref> | |||
===Physical Examination=== | ===Physical Examination=== | ||
Physical examination of patients with optic neuritis is usually remarkable for:<ref name="pmid3414716">{{cite journal |vauthors=Kliethermes MA |title=Working parents in two-pharmacist marriages |journal=Am J Hosp Pharm |volume=45 |issue=7 |pages=1500 |date=July 1988 |pmid=3414716 |doi= |url=}}</ref><ref name="pmid19878630">{{cite journal |vauthors=Shams PN, Plant GT |title=Optic neuritis: a review |journal=Int MS J |volume=16 |issue=3 |pages=82–9 |date=September 2009 |pmid=19878630 |doi= |url=}}</ref><ref name="pmid16554529">{{cite journal |vauthors=Balcer LJ |title=Clinical practice. Optic neuritis |journal=N. Engl. J. Med. |volume=354 |issue=12 |pages=1273–80 |date=March 2006 |pmid=16554529 |doi=10.1056/NEJMcp053247 |url=}}</ref> | |||
* Ophthalmic examination findings: | |||
** [[Papillitis]] with swollen [[optic disc]] | |||
** Normal [[optic disc]] appearance (2/3 of cases) in retrobulbar neuritis type of optic neuritis | |||
** Perineuritis, which involves the [[optic nerve]] sheath while the optic disc may or may not be swollen | |||
** Neuroretinitis with [[Optic disc|optic disc oedema]] and macular star exudates | |||
* Unilateral loss of [[visual acuity]] | |||
* Reduced contrast sensitivity | |||
* Ipsilateral relative afferent pupillary defect | |||
* [[Visual field]] defect | |||
* [[Color blindness|Dyschromatopsia]] | |||
===Laboratory Findings=== | ===Laboratory Findings=== | ||
* There are no specific diagnostic laboratory findings associated with optic neuritis. | |||
* If [[multiple sclerosis]] is suspected, extensive laboratory testing is recommended in the neurologic guidelines.<ref name="pmid4581115">{{cite journal |vauthors=Wilson BJ |title=12,13-Epoxytrichothecenes: potential toxic contaminants of foods |journal=Nutr. Rev. |volume=31 |issue=6 |pages=169–72 |date=June 1973 |pmid=4581115 |doi= |url=}}</ref><ref name="pmid5398757">{{cite journal |vauthors=Mialaret J |title=[Apropos of M. Lagrot's article entitled "Dispute" in vagotomy on selection, chemical tests and associated antrectomy] |language=French |journal=Mem Acad Chir (Paris) |volume=95 |issue=6 |pages=194–6 |date=1969 |pmid=5398757 |doi= |url=}}</ref> | |||
* Other recommended laboratory tests for all patients with optic neuritis include:<ref name="pmid4581115">{{cite journal |vauthors=Wilson BJ |title=12,13-Epoxytrichothecenes: potential toxic contaminants of foods |journal=Nutr. Rev. |volume=31 |issue=6 |pages=169–72 |date=June 1973 |pmid=4581115 |doi= |url=}}</ref><ref name="pmid1857074">{{cite journal |vauthors=Kanareĭkin KF |title=[Soviet neuropathology in the Great Patriotic War 1941-1945] |language=Russian |journal=Klin Med (Mosk) |volume=69 |issue=5 |pages=4–6 |date=May 1991 |pmid=1857074 |doi= |url=}}</ref> | |||
** [[C-reactive protein]] | |||
** [[Complete blood count]] | |||
** Serum chemistry | |||
** [[Blood sugar]] | |||
** [[Vitamin B12|Vitamin B<sub>12</sub>]] | |||
** [[Rheumatoid factor]] | |||
** [[Antinuclear antibodies]] | |||
** [[Antiphospholipid antibodies|Anti-phospholipid antibodies]] | |||
** [[Anti-dsDNA antibody|Anti-ds-DNA antibodies]] | |||
** [[Lupus anticoagulant]] | |||
** Serum [[angiotensin-converting enzyme]] test | |||
** ''[[Borrelia burgdorferi|Borrelia]]'' serology | |||
** [[Urinalysis]] | |||
===Imaging Findings=== | ===Imaging Findings=== | ||
Among all imaging studies, [[MRI]] is the diagnosis study of choice for visualising the [[optic nerve]]. | |||
The following result of [[Magnetic resonance imaging|MRI]] is confirmatory of optic neuritis: | |||
* Swollen retrobulbar intra-orbital segment of the optic nerve with a high T2 signal. High T2 signal persists and may be permanent; | |||
* Atrophied nerve in chronic cases | |||
Other diagnosis studies which may help to diagnosis of optic neuritis include:<ref name="pmid4347010" /><ref name="pmid28531809" /><ref name="pmid3005938" /> | |||
* [[Functional MRI]] | |||
* [[Multifocal visual evoked potential]] | |||
* [[Optical coherence tomography]] (OCT) | |||
===Other Diagnostic Studies=== | ===Other Diagnostic Studies=== | ||
There are no widely used other diagnosis studies for diagnosis of optic neuritis. | |||
==Treatment== | ==Treatment== | ||
===Medical Therapy=== | ===Medical Therapy=== | ||
Optic neuritis requires prompt treatment. | |||
The mainstay of treatment for optic neuritis is [[corticosteroid]] therapy and is recommended among all patients who develop optic neuritis.<ref name="pmid4581115">{{cite journal |vauthors=Wilson BJ |title=12,13-Epoxytrichothecenes: potential toxic contaminants of foods |journal=Nutr. Rev. |volume=31 |issue=6 |pages=169–72 |date=June 1973 |pmid=4581115 |doi= |url=}}</ref> | |||
Some [[pharmacologic]] medical therapies for optic neuritis include:<ref name="pmid4581115">{{cite journal |vauthors=Wilson BJ |title=12,13-Epoxytrichothecenes: potential toxic contaminants of foods |journal=Nutr. Rev. |volume=31 |issue=6 |pages=169–72 |date=June 1973 |pmid=4581115 |doi= |url=}}</ref> | |||
# [[Prednisone|Oral prednisone]] treatment at a dose of 1 mg/kg body weight /day for 14 days | |||
# intravenous [[methylprednisolon]]<nowiki/>e treatment at 500–1000 mg/day for 3_5 days followed by oral prednisolone (1 mg/kg BW) for 11 days | |||
===Surgery=== | ===Surgery=== | ||
*In the case of [[optic canal]] compression in patients with severe optic neuritis, [[surgery]] is used to decompress the orbital compartment by exposure of the intracanalicular part of the [[optic nerve]].<ref name="pmid3721018">{{cite journal |vauthors=Cieciura L, Krakowski G |title=Ultrastructural studies on the mitochondria of the pinealocyte under conditions of persistent lighting--L24 |journal=Folia Histochem. Cytobiol. |volume=24 |issue=1 |pages=33–7 |date=1986 |pmid=3721018 |doi= |url=}}</ref> | |||
*Modern craniomaxillofacial surgery requires detailed consideration of the diagnosis and treatment of traumatic visual pathway damage with the ultimate goal of preserving [[visual acuity]].<ref name="pmid3721018">{{cite journal |vauthors=Cieciura L, Krakowski G |title=Ultrastructural studies on the mitochondria of the pinealocyte under conditions of persistent lighting--L24 |journal=Folia Histochem. Cytobiol. |volume=24 |issue=1 |pages=33–7 |date=1986 |pmid=3721018 |doi= |url=}}</ref> | |||
===Prevention=== | ===Prevention=== | ||
There are no established measures for the primary prevention of optic neuritis. | |||
==References== | ==References== |
Latest revision as of 07:38, 15 March 2021
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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1] Associate Editor(s)-in-Chief: , Mohamadmostafa Jahansouz M.D.[2], Mohsen Basiri M.D.
Historical Perspective
Discovery
- Optic neuritis was first discovered by von Graefe and Nettleship, in late nineteenth century when ophthalmoscopy became part of the ophthalmic examination.[1]
- The association between systemic sclerosis and optic neuritis was made by the early 1900's but there was much controversy and misunderstanding about its differential diagnosis, pathogenesis, and possible treatment.[1]
- Optic neuritis was first distinguished from infectious,hereditary, toxic, nutritional, and ischemic optic neuropathies during the twentieth century.[1]
- During late twentieth century, the development of MRI and the results from recent clinical trials, discovered the relationship between optic neuritis and multiple sclerosis.[1]
Classification
Optic neuritis may be classified into atypical or typical subtypes based on its clinical features.[2]
- Atypical optic neuritis entails clinical manifestations that deviate from classic pattern of optic neuritis features.[3]
- Atypical features to consider include:[3]
- Lack of pain
- Simultaneous or near-simultaneous onset
- Lack of response to or relapse upon tapering from corticosteroids
- Optic neuritis due nerve head or peripapillary hemorrhages
Pathophysiology
Pathogenesis
- The exact pathogenesis of optic neuritis is not completely understood.[4][5]
- But It is likely due to some inflammatory process which leads to delayed type IV hypersensitivity reaction induced by released cytokines and other inflammatory mediators from activated peripheral T-cells which can cross the blood brain barrier and cause destruction of myelin, neural cell death and axonal degeneration.[4][5]
- In addition to involvement of the myelin sheath (white matter), latest technologies such as optical coherence tomography (OCT) suggest involvement of axons (gray matter) in this process.[4][5]
- Findings suggestive of optic neuritis in microscopic histopathological analysis include:[6]
- Reduced axon counts
- Optic atrophy
- Inflammation
- Demyelination
- Axonal loss
- Intracellular neurofilaments
Causes
- The exact cause of optic neuritis is unknown.[7][8][9]
- But It is likely due invasion of the immune system to the myelin, resulting in inflammation and damage to the myelin.
The following autoimmune are associated with optic neuritis:[7][8][9]
- Multiple sclerosis:
- Multiple sclerosis is the first main cause of optic neuritis.[8]
- 50% of patients with multiple sclerosis finally develop optic neuritis.[9]
- Neuromyelitis optica
- In Neuromyelitis optica, inflammation recurs in the optic nerve and spinal cord.
- Infections:
Differentiating Optic Neuritis from other Diseases
Optic neuritis must be differentiated from other diseases that cause sudden eye pain and vision loss such as:[2]
- Leber’s Hereditary Optic Neuropathy (LHON)[2] which results from point mutations in mitochondrial DNA and subsequent mitochondrial dysfunction, causing bilateral central vision loss.[10]
- Nonarteritic Anterior Ischemic Optic Neuropathy (AION)[2]
- It is the most common form of ischemic optic neuropathy and the second most common optic neuropathy.
- It is more common in patients over the age of 50 years with vasculopathic risk factors such as:
Epidemiology and Demographics
Incidence
Age
- Optic neuritis commonly affects patients between the ages of 15 and 49.[13]
Race
- Optic neuritis usually affects individuals of the Caucasians race eight times more frequently than Blacks and Asians.[7][14][15][16]
- Black populations individuals are less likely to develop optic neuritis.[7][14][15][16]
Gender
- Women are more commonly affected by optic neuritis than men.[2]
Region
- The incidence of optic neuritis is highest in populations located at higher latitudes such as:[7][17][18]
- Northern United States
- Northern and Western Europe
- New Zealand and Southern Australia
Risk Factors
Common Risk Factors
- Common risk factors in the development of optic neuritis include:
- Age
- Optic neuritis most often affects adults between the ages of 15 and 49.[13]
- Sex
- Women are much more likely to develop optic neuritis than men are.[2]
- Race
- Genetic mutation[19]
- Multiple sclerosis[20]
- Trauma[21]
- Nutritional deficiencies[22]
- Compression of the optic nerve[23]
- Arteritic optic neuropathy[24]
- Diabetes[25]
- Glaucoma[26]
- Age
- Common risk factors in the recurrence of optic neuritis include:[27][20]
- Underlying diseases such as:
- Unilateral optic neuritis
- Early initiation of glucocorticoid
Natural History, Complications and Prognosis
Natural History
- The symptoms of optic neuritis usually develop in the second decade of life, and start with symptoms such as pain on movement of the eyes, followed by a worsening of vision.[28]
- Common symptoms of optic neuritis include:[28][29]
- Pain on movement of the eyes which is sever and so disturbing
- Seeing things darkly, unclearly, and with poor contrast
- Dirty and pale Colors
- Visual field loss
- Disturbed color vision
- Flashing lights
- After a sub acute onset, the patient’s visual acuity continues to deteriorate for a few more days; in the untreated course of the disease, it generally reaches its nadir in one to two weeks and then improves again.[28]
Complications
- Common complications of optic neuritis include:[7][30]
- Side effects of corticosteroids use
- Permanent optic nerve damage
- Decreased visual acuity
- In some cases of optic neuritis, partial loss of color discrimination might persist.
Prognosis
- The long-term visual prognosis of idiopathic optic neuritis is generally good.[31]
- More than 90% of the patients recover a visual acuity of 20/40 or better by 6 months.[31]
- Findings associated with poor visual outcome at 6 months include:[32][31]
- A cut-off level of vision ≤ 20/50
- Contrast sensitivity of <1.0 log units
- A visual field mean deviation of ≤ – 15 dB after 1 month in the Optic Neuritis Treatment Trial.
- Despite the relatively good visual outcome, most patients show a degree of long-lasting damage to the optic nerve, such as:[31]
- A pale optic disc
- Loss of retinal nerve fibers
- Prolonged latency in the visual evoked response
- Thinning of the optic nerve on MR
Diagnosis
Diagnosis studies
The diagnosis of typical optic neuritis is usually made clinically.[2]
The classic triad for diagnosis of optic neuritis consist of:[2][17][33]
- Visual loss
- Periocular pain
- Dyschromatopsia
MRI is the diagnosis study of choice for visualising the optic nerve.
The following result of MRI is confirmatory of optic neuritis:
- Swollen retrobulbar intra-orbital segment of the optic nerve with a high T2 signal. High T2 signal persists and may be permanent;
- Atrophied nerve in chronic cases
Other diagnosis studies which may help to diagnosis of optic neuritis include:[34][35][36]
Symptoms
- The symptoms of optic neuritis usually develop in the second decade of life, and start with symptoms such as pain on movement of the eyes, followed by a worsening of vision.[28]
- Common symptoms of optic neuritis include:[28][29][37]
- Pain on movement of the eyes which is sever and so disturbing
- Seeing things darkly, unclearly, and with poor contrast
- Dirty and pale Colors
- Visual field loss
- Disturbed color vision
- Flashing lights
- After a sub acute onset, the patient’s visual acuity continues to deteriorate for a few more days; in the untreated course of the disease, it generally reaches its nadir in one to two weeks and then improves again.[28]
Physical Examination
Physical examination of patients with optic neuritis is usually remarkable for:[2][17][9]
- Ophthalmic examination findings:
- Papillitis with swollen optic disc
- Normal optic disc appearance (2/3 of cases) in retrobulbar neuritis type of optic neuritis
- Perineuritis, which involves the optic nerve sheath while the optic disc may or may not be swollen
- Neuroretinitis with optic disc oedema and macular star exudates
- Unilateral loss of visual acuity
- Reduced contrast sensitivity
- Ipsilateral relative afferent pupillary defect
- Visual field defect
- Dyschromatopsia
Laboratory Findings
- There are no specific diagnostic laboratory findings associated with optic neuritis.
- If multiple sclerosis is suspected, extensive laboratory testing is recommended in the neurologic guidelines.[28][38]
- Other recommended laboratory tests for all patients with optic neuritis include:[28][39]
Imaging Findings
Among all imaging studies, MRI is the diagnosis study of choice for visualising the optic nerve.
The following result of MRI is confirmatory of optic neuritis:
- Swollen retrobulbar intra-orbital segment of the optic nerve with a high T2 signal. High T2 signal persists and may be permanent;
- Atrophied nerve in chronic cases
Other diagnosis studies which may help to diagnosis of optic neuritis include:[34][35][36]
Other Diagnostic Studies
There are no widely used other diagnosis studies for diagnosis of optic neuritis.
Treatment
Medical Therapy
Optic neuritis requires prompt treatment.
The mainstay of treatment for optic neuritis is corticosteroid therapy and is recommended among all patients who develop optic neuritis.[28]
Some pharmacologic medical therapies for optic neuritis include:[28]
- Oral prednisone treatment at a dose of 1 mg/kg body weight /day for 14 days
- intravenous methylprednisolone treatment at 500–1000 mg/day for 3_5 days followed by oral prednisolone (1 mg/kg BW) for 11 days
Surgery
- In the case of optic canal compression in patients with severe optic neuritis, surgery is used to decompress the orbital compartment by exposure of the intracanalicular part of the optic nerve.[40]
- Modern craniomaxillofacial surgery requires detailed consideration of the diagnosis and treatment of traumatic visual pathway damage with the ultimate goal of preserving visual acuity.[40]
Prevention
There are no established measures for the primary prevention of optic neuritis.
References
- ↑ 1.0 1.1 1.2 1.3 Volpe NJ (December 2001). "Optic neuritis: historical aspects". J Neuroophthalmol. 21 (4): 302–9. PMID 11756864.
- ↑ 2.0 2.1 2.2 2.3 2.4 2.5 2.6 2.7 2.8 Kliethermes MA (July 1988). "Working parents in two-pharmacist marriages". Am J Hosp Pharm. 45 (7): 1500. PMID 3414716.
- ↑ 3.0 3.1 Gaier ED, Boudreault K, Rizzo JF, Falardeau J, Cestari DM (December 2015). "Atypical Optic Neuritis". Curr Neurol Neurosci Rep. 15 (12): 76. doi:10.1007/s11910-015-0598-1. PMID 26467052.
- ↑ 4.0 4.1 4.2 Hoorbakht H, Bagherkashi F (2012). "Optic neuritis, its differential diagnosis and management". Open Ophthalmol J. 6: 65–72. doi:10.2174/1874364101206010065. PMC 3414716. PMID 22888383.
- ↑ 5.0 5.1 5.2 Toosy AT, Mason DF, Miller DH (January 2014). "Optic neuritis". Lancet Neurol. 13 (1): 83–99. doi:10.1016/S1474-4422(13)70259-X. PMID 24331795.
- ↑ Taniguchi S, Kawano T, Kakunaga T, Baba T (May 1986). "Differences in expression of a variant actin between low and high metastatic B16 melanoma". J. Biol. Chem. 261 (13): 6100–6. PMID 3700386.
- ↑ 7.0 7.1 7.2 7.3 7.4 7.5 7.6 7.7 7.8 Marechal F, Berthiot G, Deltour G (1988). "Serum levels of CA-50, CA-19.9, CA-125, CA-15.3, enolase and carcino-embryonic antigen in non neoplastic diseases of the lung". Anticancer Res. 8 (4): 677–80. PMID 3178158.
- ↑ 8.0 8.1 8.2 Bourdial J (April 1969). "[Otorhinolaryngologic action in asthmatics]". Maroc Med (in French). 49 (523): 209–17. PMID 5398737.
- ↑ 9.0 9.1 9.2 9.3 Balcer LJ (March 2006). "Clinical practice. Optic neuritis". N. Engl. J. Med. 354 (12): 1273–80. doi:10.1056/NEJMcp053247. PMID 16554529.
- ↑ Fujimori H (December 1973). "[Pulmonary tuberculosis--keypoints in nursing of pregnant and puerperal patients]". Josanpu Zasshi (in Japanese). 27 (12): 40–3. PMID 4492634.
- ↑ Rodriguez M, Siva A, Cross SA, O'Brien PC, Kurland LT (February 1995). "Optic neuritis: a population-based study in Olmsted County, Minnesota". Neurology. 45 (2): 244–50. PMID 7854520.
- ↑ Percy AK, Nobrega FT, Kurland LT (February 1972). "Optic neuritis and multiple sclerosis. An epidemiologic study". Arch. Ophthalmol. 87 (2): 135–9. PMID 5057861.
- ↑ 13.0 13.1 Self SG, Grossman EA (September 1986). "Linear rank tests for interval-censored data with application to PCB levels in adipose tissue of transformer repair workers". Biometrics. 42 (3): 521–30. PMID 3105615.
- ↑ 14.0 14.1 14.2 14.3 Bhigjee AI, Moodley K, Ramkissoon K (November 2007). "Multiple sclerosis in KwaZulu Natal, South Africa: an epidemiological and clinical study". Mult. Scler. 13 (9): 1095–9. doi:10.1177/1352458507079274. PMID 17967837.
- ↑ 15.0 15.1 15.2 15.3 Mbonda E, Larnaout A, Maertens A, Appel B, Lowenthal A, Mbede J, Evrard P (1990). "Multiple sclerosis in a black Cameroonian woman". Acta Neurol Belg. 90 (4): 218–22. PMID 2124032.
- ↑ 16.0 16.1 16.2 16.3 Phillips PH, Newman NJ, Lynn MJ (February 1998). "Optic neuritis in African Americans". Arch. Neurol. 55 (2): 186–92. PMID 9482360.
- ↑ 17.0 17.1 17.2 Shams PN, Plant GT (September 2009). "Optic neuritis: a review". Int MS J. 16 (3): 82–9. PMID 19878630.
- ↑ Kurtzke JF (July 1985). "Optic neuritis or multiple sclerosis". Arch. Neurol. 42 (7): 704–10. PMID 4015470.
- ↑ Adam MP, Ardinger HH, Pagon RA, Wallace SE, Bean L, Stephens K, Amemiya A, Yu-Wai-Man P, Chinnery PF. PMID 20301353. Vancouver style error: initials (help); Missing or empty
|title=
(help) - ↑ 20.0 20.1 Chan JW (September 2002). "Optic neuritis in multiple sclerosis". Ocul. Immunol. Inflamm. 10 (3): 161–86. PMID 12789593.
- ↑ Haslbeck M (November 1974). "[Insulin secretion after glucose loading. Studies on insulin secretion in healthy and diabetic subjects after administration of glucose]". Fortschr. Med. (in German). 92 (32): 1317–8. PMID 4457437.
- ↑ Sawicka-Pierko A, Obuchowska I, Mariak Z (2014). "Nutritional optic neuropathy". Klin Oczna. 116 (2): 104–10. PMID 25345287.
- ↑ Primicerio B (January 1971). "[Competitions for the position of sanitary personnel in hospitals]". Policlinico Prat (in Italian). 78 (2): 72–7. PMID 5546777.
- ↑ Dyras M, Stós B, Zemowski W (1989). "[Possibilities of combined maxillary-orthopaedic and prosthetic treatment of malocclusion in adult patients]". Protet Stomatol (in Polish). 39 (3): 134–9. PMID 2701125.
- ↑ Warren SA, Warren KG (August 1983). "Optic neuritis, diabetes mellitus and multiple sclerosis: a three-way association". Can. J. Ophthalmol. 18 (5): 228–32. PMID 6354403.
- ↑ Holmberg D, Lundkvist I, Forni L, Ivars F, Coutinho A (1985). "Absence of immunoglobulin heavy chain expression results in altered kappa/lambda light chain ratios". J. Mol. Cell. Immunol. 2 (1): 51–6. PMID 3939751.
- ↑ Dabholkar AS, Tewari HB (1968). "The functional significance of the presence of acid phosphatase at the nucleic-acid synthesizing sites in the nuclei of the neurons of the cephalothoracic ganglionic masses of palaemnius". Acta Neurol. Scand. 44 (5): 533–41. PMID 4177903.
- ↑ 28.0 28.1 28.2 28.3 28.4 28.5 28.6 28.7 28.8 28.9 Wilson BJ (June 1973). "12,13-Epoxytrichothecenes: potential toxic contaminants of foods". Nutr. Rev. 31 (6): 169–72. PMID 4581115.
- ↑ 29.0 29.1 Beck RW, Cleary PA, Anderson MM, Keltner JL, Shults WT, Kaufman DI, Buckley EG, Corbett JJ, Kupersmith MJ, Miller NR (February 1992). "A randomized, controlled trial of corticosteroids in the treatment of acute optic neuritis. The Optic Neuritis Study Group". N. Engl. J. Med. 326 (9): 581–8. doi:10.1056/NEJM199202273260901. PMID 1734247.
- ↑ "Henry Edmund Seiler". Lancet. 2 (8092 Pt 1): 747. September 1978. PMID 80680.
- ↑ 31.0 31.1 31.2 31.3 Sagalovich V, Solov'eva IP, Kunichan AD, Nemsadze MN (1987). "[Effectiveness of single and fractional administration of isoniazid in the treatment of dogs infected with isoniazid-resistant strains of Mycobacterium tuberculosis]". Probl Tuberk (in Russian) (7): 49–53. PMID 3116540. Vancouver style error: initials (help)
- ↑ Achiron A, Kishner I, Sarova-Pinhas I, Raz H, Faibel M, Stern Y, Lavie M, Gurevich M, Dolev M, Magalashvili D, Barak Y (October 2004). "Intravenous immunoglobulin treatment following the first demyelinating event suggestive of multiple sclerosis: a randomized, double-blind, placebo-controlled trial". Arch. Neurol. 61 (10): 1515–20. doi:10.1001/archneur.61.10.1515. PMID 15477504.
- ↑ Wells H (1988). "A discussion of the KDI Quik Test Drug Screen". J Anal Toxicol. 12 (2): 111. PMID 3379920.
- ↑ 34.0 34.1 Ishikawa Y (October 1972). "[Electronmicroscopic observations on cultured rabbit lens cells infected with herpes virus]". Nippon Ganka Gakkai Zasshi (in Japanese). 76 (10): 1213–24. PMID 4347010.
- ↑ 35.0 35.1 Pihl-Jensen G, Schmidt MF, Frederiksen JL (July 2017). "Multifocal visual evoked potentials in optic neuritis and multiple sclerosis: A review". Clin Neurophysiol. 128 (7): 1234–1245. doi:10.1016/j.clinph.2017.03.047. PMID 28531809.
- ↑ 36.0 36.1 Rao NA, Calandra AJ, Sevanian A, Bowe B, Delmage JM, Marak GE (1986). "Modulation of lens-induced uveitis by superoxide dismutase". Ophthalmic Res. 18 (1): 41–6. doi:10.1159/000265413. PMID 3005938.
- ↑ Wilhelm H, Schabet M (September 2015). "The Diagnosis and Treatment of Optic Neuritis". Dtsch Arztebl Int. 112 (37): 616–25, quiz 626. doi:10.3238/arztebl.2015.0616. PMC 4581115. PMID 26396053.
- ↑ Mialaret J (1969). "[Apropos of M. Lagrot's article entitled "Dispute" in vagotomy on selection, chemical tests and associated antrectomy]". Mem Acad Chir (Paris) (in French). 95 (6): 194–6. PMID 5398757.
- ↑ Kanareĭkin KF (May 1991). "[Soviet neuropathology in the Great Patriotic War 1941-1945]". Klin Med (Mosk) (in Russian). 69 (5): 4–6. PMID 1857074.
- ↑ 40.0 40.1 Cieciura L, Krakowski G (1986). "Ultrastructural studies on the mitochondria of the pinealocyte under conditions of persistent lighting--L24". Folia Histochem. Cytobiol. 24 (1): 33–7. PMID 3721018.