Optic neuritis

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Optic neuritis
Optic Neuritis.png
Optic Neuritis following a febrile infection in a young woman
Specialty Ophthalmology, optometry, neurology
Symptoms loss of vision, loss of colour vision, pain worsening on eye movements
Complications multiple sclerosis, MOG-disease, NMO
Usual onsetsubacute
Duration1-3 months
TypesMS-ON, MOG-ON, AQP4-ON, CRMP5-ON, SION, RION, CRION, post-infectious ON, post-vaccination ON, ON as complication of systemic diseases or meidication
Causesautoimmune, infection, vaccination, medication
Risk factors genetic
Diagnostic method Diagnostic criteria
Prognosis Prognosis depends on the subtype of ON
Frequencycan be relapsing

Optic neuritis describes any condition that causes inflammation of the optic nerve; it may be associated with demyelinating diseases, or infectious or inflammatory processes. [1]

Contents

It is also known as optic papillitis (when the head of the optic nerve is involved), neuroretinitis (when there is a combined involvement of the optic disc and surrounding retina in the macular area) and retrobulbar neuritis (when the posterior part of the nerve is involved). Prelaminar optic neuritis describes involvement of the non-myelinated axons in the retina. [1] It is most often associated with multiple sclerosis, and it may lead to complete or partial loss of vision in one or both eyes. Other causes include: [2]

  1. Leber's hereditary optic neuropathy
  2. Parainfectious optic neuritis (associated with viral infections such as measles, mumps, chickenpox, whooping cough and glandular fever)
  3. Infectious optic neuritis (sinus related or associated with cat-scratch fever, tuberculosis, Lyme disease and cryptococcal meningitis in AIDS patients
  4. Autoimmune causes (sarcoidosis, systemic lupus erythematosus, polyarteritis nodosa, MOG antibody disease, granulomatosis with polyangiitis)
  5. Diabetes mellitus
  6. Low phosphorus levels
  7. Hyperkalaemia

Partial, transient vision loss (lasting less than one hour) can be an indication of early onset multiple sclerosis. [3]

Signs and symptoms

Example of how optic neuritis affected one eye of a person with multiple sclerosis OpticNeuritisExample.jpg
Example of how optic neuritis affected one eye of a person with multiple sclerosis

Major symptoms are sudden loss of vision (partial or complete), sudden blurred or "foggy" vision, and pain on movement of the affected eye. [4] Early symptoms that require investigation include symptoms from multiple sclerosis (twitching, lack of coordination, slurred speech, frequent episodes of partial vision loss or blurred vision), episodes of "disturbed/blackened" rather than blurry indicate moderate stage and require immediate medical attention to prevent further loss of vision. Other early symptoms are reduced night vision, photophobia and red eyes. Many patients with optic neuritis may lose some of their color vision in the affected eye (especially red), with colors appearing subtly washed out compared to the other eye. Patients may also experience difficulties judging movement in depth, which can be particular troublesome during driving or sport (Pulfrich effect). Likewise, transient worsening of vision with increase of body temperature (Uhthoff's phenomenon) and glare disability are a frequent complaint. However, several case studies in children have demonstrated the absence of pain in more than half of cases (approximately 60%) in their pediatric study population, with the most common symptom reported simply as "blurriness". [5] [6] Other remarkable differences between the presentation of adult optic neuritis as compared to pediatric cases include more often unilateral optic neuritis in adults, while children much predominantly present with bilateral involvement.

On medical examination the head of the optic nerve can easily be visualized by a slit lamp with a high positive lens or by using direct ophthalmoscopy; however, frequently there is no abnormal appearance of the nerve head in optic neuritis (in cases of retrobulbar optic neuritis), though it may be swollen in some patients (anterior papillitis or more extensive optic neuritis). In many cases, only one eye is affected, and patients may not be aware of the loss of color vision until they are asked to close or cover the healthy eye.

Imaging of the optic nerve with MRI shows increased signal on the affected side. There is contrast enhancment of the symptomatic optic nerve and sheaths acutely or intrinsic signal increase (looking brighter) within ≥ 3 months [1] .

Magnetic Resonnance Imaging (MRI) during an episode of optic neuritis. Case-3-mri.png
Magnetic Resonnance Imaging (MRI) during an episode of optic neuritis.

Advanced imaging using optical coherence tomography (OCT) is very sensitive reveal damage to the optic nerve. The OCT shows corresponding optic disc swelling acutely or an inter-eye difference in the thickness of the neurons and their nerves connecting the eye with the brain in above 4-5% within ≥ 3 months after onset [1] .


Cause

The optic nerve comprises axons that emerge from the retina of the eye and carry visual information to the primary visual nuclei, most of which is relayed to the occipital cortex of the brain to be processed into vision. Inflammation of the optic nerve causes loss of vision, usually because of the swelling and destruction of the myelin sheath covering the optic nerve.

The most common cause is multiple sclerosis (MS) or ischemic optic neuropathy due to thrombosis or embolism of the vessel that supplies the optic nerve. [7] [8] Up to 50% of patients with MS will develop an episode of optic neuritis, and 20–30% of the time optic neuritis is the presenting sign of MS.[ citation needed ] The presence of demyelinating white matter lesions on brain MRI at the time of presentation of optic neuritis is the strongest predictor for developing clinically definite MS. Almost half of the patients with optic neuritis have white matter lesions consistent with multiple sclerosis.

Some other common causes of optic neuritis include infection (e.g. a tooth abscess in the upper jaw, syphilis, Lyme disease, herpes zoster), autoimmune disorders (e.g. lupus, neurosarcoidosis, neuromyelitis optica), methanol poisoning, vitamin B12 deficiency, beriberi, dysautonomia (i.e. autonomic nervous system dysfunction), and diabetes, or an injury to the eye. [9] In neuromyelitis optica higher AQP4 autoantibody levels are associated with the occurrence of optic neuritis. [10]

Less common causes are: papilledema, brain tumor or abscess in the occipital region, cerebral trauma or hemorrhage, meningitis, arachnoidal adhesions, sinus thrombosis, liver dysfunction, or late stage kidney disease.

Approximate Cause Data (Other TOP Ranking diseases include: Cancer, Heart Disease, Respiratory, Stroke, Diabetes, Alzheimers, Kidney Disease, Parkinsons, Suicide) [11]
Cause and Rank based on DeathsAnnual Num Cases TOTAL (US) (2011)Annual Cases leading to Optic NeuritisPercentPrognosis and Treatment
Multiple sclerosis (Rank 33)400,042146,23245%Most common cause. Almost all patients will experience some form of vision dysfunction. Partial vision loss can occur through the duration of the disease; total vision loss occurs in severe cases and late stages.
Blood clot (Rank 29) (Optic ONLY)17,00016,7775%Reversible if early and before reduced blood flow causes permanent damage.
Nerve pinch (0)NOT REPORTED-4%Usually heals itself, treatment not needed.
Injury to optic nerve (including poisoning, i.e. methanol) (0)23,82720,121<1%Depends on severity, usually treatable.
Liver dysfunction (Rank 19); if untreated can lead to Failure (Rank 8)141,21111,9827%Poor outcomes and progresses and can lead to total vision loss.
Reduced kidney function (treatable with diet change) (Rank 67 – If untreated, can progress to late stage with much greater mortality rates)509,89816,2819%Good outcomes if early, and can usually be treated with diet changes, progresses and can lead to total vision loss.
Late stage kidney failure (Rank 7)33,2121,1122%Poor outcomes – usually permanent nerve damage at this stage.
Papilledema (brain tumor or abscess) (Rank 10)45,8889,2313%Depends on severity.
Meningitis (Rank 61)2,521189<1%Depends on severity.
Other infections (not from abscess)5,561-<1%Good outcomes, treatable with antibiotics or other microbial drugs.
Diabetes (early stage treatable, late Stage has worse prognosis) (Rank 6)49,56221,11215% Type 1 carries poor prognosis, type 2 can be treated and vision returned.
Unknown--2%

Demyelinating recurrent optic neuritis and non-demyelinating (CRION)

The repetition of an idiopathic optic neuritis is considered a distinct clinical condition, and when it shows demyelination, it has been found to be associated to anti-MOG and AQP4-negative neuromyelitis optica. [12]

When an inflammatory recurrent optic neuritis is not demyelinating, it is called chronic relapsing inflammatory optic neuropathy (CRION). [13]

When it is anti-MOG related, it is demyelinating and it is considered inside the anti-MOG associated inflammatory demyelinating diseases.

Some reports point to the possibility to establish a difference via optical coherence tomography. [14]

Treatment

In most MS-associated optic neuritis, visual function spontaneously improves over 2–3 months, and there is evidence that corticosteroid treatment does not affect the long term outcome. However, for optic neuritis that is not MS-associated (or atypical optic neuritis) the evidence is less clear and therefore the threshold for treatment with intravenous corticosteroids is lower. [1] Intravenous corticosteroids also reduce the risk of developing MS in the following two years in patients with MRI lesions; but this effect disappears by the third year of follow up. [15]

Paradoxically, oral administration of corticosteroids in this situation may lead to more recurrent attacks than in non-treated patients (though oral steroids are generally prescribed after the intravenous course, to wean the patient off the medication). This effect of corticosteroids seems to be limited to optic neuritis and has not been observed in other diseases treated with corticosteroids. [16]

A Cochrane systematic review studied the effect of corticosteroids for treating people with acute optic neuritis. [17] Specific corticosteroids studied included intravenous and oral methylprednisone, and oral prednisone. The authors conclude that current evidence does not show a benefit of either intravenous or oral corticosteroids for rate of recovery of vision (in terms of visual acuity, contrast sensitivity, or visual fields). [17] There are a number of reasons why this might be the case. [15] [18]

Epidemiology

Optic neuritis typically affects young adults ranging 18–45 years of age, with a mean age of 30–35 years. There is a strong female predominance. The annual incidence is approximately 5/100,000, with a prevalence estimated to be 115/100,000 (0.12%). [19]

Society and culture

In Charles Dickens' Bleak House , the main character, Esther Summerville, has a transient episode of visual loss, the symptoms of which are also seen in people who have optic neuritis. [20] Legal historian William Searle Holdsworth suggested that the events in Bleak House took place in 1827.

In an episode of Dr. Quinn, Medicine Woman ("Season of Miracles", season five), Reverend Timothy Johnson is struck blind by optic neuritis on Christmas Day 1872. He remains blind for the duration of the series.

See also

Related Research Articles

<span class="mw-page-title-main">Acute disseminated encephalomyelitis</span> Autoimmune disease

Acute disseminated encephalomyelitis (ADEM), or acute demyelinating encephalomyelitis, is a rare autoimmune disease marked by a sudden, widespread attack of inflammation in the brain and spinal cord. As well as causing the brain and spinal cord to become inflamed, ADEM also attacks the nerves of the central nervous system and damages their myelin insulation, which, as a result, destroys the white matter. The cause is often a trigger such as from viral infection or vaccinations.

<span class="mw-page-title-main">Transverse myelitis</span> Medical condition of the spinal cord

Transverse myelitis (TM) is a rare neurological condition wherein the spinal cord is inflamed. The adjective transverse implies that the spinal inflammation (myelitis) extends horizontally throughout the cross section of the spinal cord; the terms partial transverse myelitis and partial myelitis are sometimes used to specify inflammation that affects only part of the width of the spinal cord. TM is characterized by weakness and numbness of the limbs, deficits in sensation and motor skills, dysfunctional urethral and anal sphincter activities, and dysfunction of the autonomic nervous system that can lead to episodes of high blood pressure. Signs and symptoms vary according to the affected level of the spinal cord. The underlying cause of TM is unknown. The spinal cord inflammation seen in TM has been associated with various infections, immune system disorders, or damage to nerve fibers, by loss of myelin. As opposed to leukomyelitis which affects only the white matter, it affects the entire cross-section of the spinal cord. Decreased electrical conductivity in the nervous system can result.

<span class="mw-page-title-main">Demyelinating disease</span> Any neurological disease in which the myelin sheath of neurons is damaged

A demyelinating disease refers to any disease affecting the nervous system where the myelin sheath surrounding neurons is damaged. This damage disrupts the transmission of signals through the affected nerves, resulting in a decrease in their conduction ability. Consequently, this reduction in conduction can lead to deficiencies in sensation, movement, cognition, or other functions depending on the nerves affected.

Neuromyelitis optica spectrum disorders (NMOSD) are a spectrum of autoimmune diseases characterized by acute inflammation of the optic nerve and the spinal cord (myelitis). Episodes of ON and myelitis can be simultaneous or successive. A relapsing disease course is common, especially in untreated patients.

<span class="mw-page-title-main">Myelin oligodendrocyte glycoprotein</span>

Myelin oligodendrocyte glycoprotein (MOG) is a glycoprotein believed to be important in the myelination of nerves in the central nervous system (CNS). In humans this protein is encoded by the MOG gene. It is speculated to serve as a necessary "adhesion molecule" to provide structural integrity to the myelin sheath and is known to develop late on the oligodendrocyte.

<span class="mw-page-title-main">Neuritis</span> Inflammation of a nerve or generally any part of the nervous system

Neuritis, from the Greek νεῦρον), is inflammation of a nerve or the general inflammation of the peripheral nervous system. Inflammation, and frequently concomitant demyelination, cause impaired transmission of neural signals and leads to aberrant nerve function. Neuritis is often conflated with neuropathy, a broad term describing any disease process which affects the peripheral nervous system. However, neuropathies may be due to either inflammatory or non-inflammatory causes, and the term encompasses any form of damage, degeneration, or dysfunction, while neuritis refers specifically to the inflammatory process.

Uhthoff's phenomenon is the worsening of neurologic symptoms in multiple sclerosis (MS) and other demyelinating diseases when the body is overheated. This may occur due to hot weather, exercise, fever, saunas, hot tubs, hot baths, and hot food and drink. Increased temperature slows nerve conduction, but the exact mechanism remains unknown. With an increased body temperature, nerve impulses are either blocked or slowed in a damaged nerve. Once the body temperature is normalized, signs and symptoms typically reverse.

<span class="mw-page-title-main">Chronic inflammatory demyelinating polyneuropathy</span> Medical condition

Chronic inflammatory demyelinating polyneuropathy (CIDP) is an acquired autoimmune disease of the peripheral nervous system characterized by progressive weakness and impaired sensory function in the legs and arms. The disorder is sometimes called chronic relapsing polyneuropathy (CRP) or chronic inflammatory demyelinating polyradiculoneuropathy. CIDP is closely related to Guillain–Barré syndrome and it is considered the chronic counterpart of that acute disease. Its symptoms are also similar to progressive inflammatory neuropathy. It is one of several types of neuropathy.

<span class="mw-page-title-main">Lesional demyelinations of the central nervous system</span>

Multiple sclerosis and other demyelinating diseases of the central nervous system (CNS) produce lesions and glial scars or scleroses. They present different shapes and histological findings according to the underlying condition that produces them.

Optic neuropathy is damage to the optic nerve from any cause. The optic nerve is a bundle of millions of fibers in the retina that sends visual signals to the brain.

Inflammatory demyelinating diseases (IDDs), sometimes called Idiopathic (IIDDs) due to the unknown etiology of some of them, are a heterogenous group of demyelinating diseases - conditions that cause damage to myelin, the protective sheath of nerve fibers - that occur against the background of an acute or chronic inflammatory process. IDDs share characteristics with and are often grouped together under Multiple Sclerosis. They are sometimes considered different diseases from Multiple Sclerosis, but considered by others to form a spectrum differing only in terms of chronicity, severity, and clinical course.

<span class="mw-page-title-main">Marburg acute multiple sclerosis</span> Medical condition

Marburg acute multiple sclerosis, also known as Marburg multiple sclerosis or acute fulminant multiple sclerosis, is considered one of the multiple sclerosis borderline diseases, which is a collection of diseases classified by some as MS variants and by others as different diseases. Other diseases in this group are neuromyelitis optica (NMO), Balo concentric sclerosis, and Schilder's disease. The graver course is one form of malignant multiple sclerosis, with patients reaching a significant level of disability in less than five years from their first symptoms, often in a matter of months.

<span class="mw-page-title-main">Signs and symptoms of multiple sclerosis</span> Neurological signs and symptoms

Multiple sclerosis can cause a variety of symptoms: changes in sensation (hypoesthesia), muscle weakness, abnormal muscle spasms, or difficulty moving; difficulties with coordination and balance; problems in speech (dysarthria) or swallowing (dysphagia), visual problems, fatigue and acute or chronic pain syndromes, bladder and bowel difficulties, cognitive impairment, or emotional symptomatology. The main clinical measure in progression of the disability and severity of the symptoms is the Expanded Disability Status Scale or EDSS.

<span class="mw-page-title-main">Tumefactive multiple sclerosis</span> Medical condition

Tumefactive multiple sclerosis is a condition in which the central nervous system of a person has multiple demyelinating lesions with atypical characteristics for those of standard multiple sclerosis (MS). It is called tumefactive as the lesions are "tumor-like" and they mimic tumors clinically, radiologically and sometimes pathologically.

<span class="mw-page-title-main">Behçet's disease</span> Inflammatory disorder

Behçet's disease (BD) is a type of inflammatory disorder which affects multiple parts of the body. The most common symptoms include painful sores on the mucous membranes of the mouth and other parts of the body, inflammation of parts of the eye, and arthritis. The sores can last from a few days, up to a week or more. Less commonly there may be inflammation of the brain or spinal cord, blood clots, aneurysms, or blindness. Often, the symptoms come and go.

Malignant multiple sclerosis is used to describe MS patients who reach significant level of disability in a short period of time. Malignant MS cases are not common, less than 5% of patients with MS experience this type of progression.

Autoimmune optic neuropathy (AON), sometimes called autoimmune optic neuritis, may be a forme fruste of systemic lupus erythematosus (SLE) associated optic neuropathy. AON is more than the presence of any optic neuritis in a patient with an autoimmune process, as it describes a relatively specific clinical syndrome. AON is characterized by chronically progressive or recurrent vision loss associated with serological evidence of autoimmunity. Specifically, this term has been suggested for cases of optic neuritis with serological evidence of vasculitis by positive ANA, despite the lack of meeting criteria for SLE. The clinical manifestations include progressive vision loss that tends to be steroid-responsive and steroid dependent.

Chronic relapsing inflammatory optic neuropathy (CRION) is a form of recurrent optic neuritis that is steroid responsive and dependent. Patients typically present with pain associated with visual loss. CRION is a clinical diagnosis of exclusion, and other demyelinating, autoimmune, and systemic causes should be ruled out. An accurate antibody test which became available commercially in 2017 has allowed most patients previously diagnosed with CRION to be re-identified as having MOG antibody disease, which is not a diagnosis of exclusion. Early recognition is crucial given risks for severe visual loss and because it is treatable with immunosuppressive treatment such as steroids or B-cell depleting therapy. Relapse that occurs after reducing or stopping steroids is a characteristic feature.

MOG antibody disease (MOGAD) or MOG antibody-associated encephalomyelitis (MOG-EM) is an inflammatory demyelinating disease of the central nervous system. Serum anti-myelin oligodendrocyte glycoprotein antibodies are present in up to half of patients with an acquired demyelinating syndrome and have been described in association with a range of phenotypic presentations, including acute disseminated encephalomyelitis, optic neuritis, transverse myelitis, and neuromyelitis optica.

Anti-AQP4 diseases, are a group of diseases characterized by auto-antibodies against aquaporin 4.

References

  1. 1 2 3 4 5 Petzold, Axel; Fraser, Clare L; Abegg, Mathias; Alroughani, Raed; Alshowaeir, Daniah; Alvarenga, Regina; Andris, Cécile; Asgari, Nasrin; Barnett, Yael; Battistella, Roberto; Behbehani, Raed; Berger, Thomas; Bikbov, Mukharram M; Biotti, Damien; Biousse, Valerie (December 2022). "Diagnosis and classification of optic neuritis". The Lancet Neurology. 21 (12): 1120–1134. doi:10.1016/S1474-4422(22)00200-9. PMID   36179757. S2CID   252564095.
  2. ↑ Khurana, A K; Khurana, Aruj K; Khurana, Bhawna P (2019). Comprehensive Ophthalmology (7th ed.). New Delhi: Jaypee Brothers Medical Publishers. ISBN   978-93-5270-686-0.
  3. ↑ Marcovitch, Harvey, ed. (2018). Black's Medical Dictionary (43rd ed.). A&C Black – via Credo Reference.
  4. ↑ "Optic neuritis". Mayo Clinic.
  5. ↑ Lucchinetti, C. F.; L. Kiers; A. O'Duffy; M. R. Gomez; S. Cross; J. A. Leavitt; P. O'Brien; M. Rodriguez (November 1997). "Risk factors for developing multiple sclerosis after childhood optic neuritis". Neurology. 49 (5): 1413–1418. doi:10.1212/WNL.49.5.1413. PMID   9371931. S2CID   33205877.
  6. ↑ Lana-Peixoto, MA; Andrade, GC (June 2001). "The clinical profile of childhood optic neuritis". Arquivos de Neuro-Psiquiatria. 59 (2–B): 311–7. doi: 10.1590/S0004-282X2001000300001 . PMID   11460171.
  7. ↑ Rizzo JF, Lessell S (1991). "Optic neuritis and ischemic optic neuropathy. Overlapping clinical profiles". Arch. Ophthalmol. 109 (12): 1668–72. doi:10.1001/archopht.1991.01080120052024. PMID   1841572.
  8. ↑ Biousse, Valérie; Campion, Edward W.; Newman, Nancy J. (2015). "Ischemic Optic Neuropathies". New England Journal of Medicine. 372 (25): 2428–2436. doi:10.1056/NEJMra1413352. ISSN   0028-4793. PMID   26083207.
  9. ↑ Riordan-Eva, P. (1 January 2004). "Clinical assessment of optic nerve disorders". Eye. 18 (11): 1161–1168. doi: 10.1038/sj.eye.6701575 . PMID   15534601.
  10. ↑ Isobe N, Yonekawa T, Matsushita T, et al. Clinical relevance of serum aquaporin-4 antibody levels in neuromyelitis optica. Neurochem Res. 2013;38(5):997-1001. doi:10.1007/s11064-013-1009-0
  11. ↑ Nicolaie, MA; van Houwelingen, HC; Putter, H (December 2015). "Vertical modelling: Analysis of competing risks data with missing causes of failure". Statistical Methods in Medical Research. 24 (6): 891–908. doi:10.1177/0962280211432067. PMID   22179822. S2CID   43277083.
  12. ↑ Chalmoukou Konstantina; et al. (2015). "Recurrent Optic Neuritis (rON) is characterised by Anti-MOG Antibodies: A follow-up study". Neurology. 84 (14): 274. doi:10.1212/WNL.84.14_supplement.P5.274.
  13. ↑ Kidd D.; Burton B.; Plant G. T.; Graham E. M. (2003). "Chronic relapsing inflammatory optic neuropathy (CRION)". Brain. 126 (2): 276–284. doi: 10.1093/brain/awg045 . PMID   12538397.
  14. ↑ Narayan et al. Unique characteristics of optical coherence tomography (OCT) results and visual acuity testing in myelin oligodendrocyte glycoprotein (MOG) antibody positive pediatric patients, November 2018, MS and related disorders, Volume 28, February 2019, Pages 86-90, doi: https://doi.org/10.1016/j.msard.2018.11.026
  15. 1 2 Beck RW, Cleary PA, Trobe JD, Kaufman DI, Kupersmith MJ, Paty DW, Brown CH (1993). "The effect of corticosteroids for acute optic neuritis on the subsequent development of multiple sclerosis. The Optic Neuritis Study Group". N. Engl. J. Med. 329 (24): 1764–9. doi: 10.1056/NEJM199312093292403 . PMID   8232485.
  16. ↑ Beck RW, Cleary PA, Anderson MM, Keltner JL, Shults WT, Kaufman DI, Buckley EG, Corbett JJ, Kupersmith MJ, Miller NR (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.
  17. 1 2 Gal RL, Vedula SS, Beck R (2015). "Corticosteroids for treating optic neuritis". Cochrane Database Syst Rev. 14 (8): CD001430. doi:10.1002/14651858.CD001430.pub4. PMC   4730547 . PMID   26273799.
  18. ↑ Petzold A, Braithwaite T, Oosten BV, Balk L, Martinez-Lapiscina EH, Wheeler R, Wiegerinck N, Waters C, Plant GT (2019). "Case for a new corticosteroid treatment trial in optic neuritis: review of updated evidence". J Neurol Neurosurg Psychiatry. 91 (1): jnnp-2019-321653. doi: 10.1136/jnnp-2019-321653 . PMC   6952848 . PMID   31740484.
  19. ↑ Rodriguez M, Siva A, Cross SA, O'Brien PC, Kurland LT (1995). "Optic neuritis: a population-based study in Olmsted County, Minnesota". Neurology. 45 (2): 244–50. doi:10.1212/WNL.45.2.244. PMID   7854520. S2CID   25800388.
  20. ↑ Petzold A (2013). "Optic Neuritis: Another Dickensian Diagnosis". Neuro-Ophthalmology. 37 (6): 247–250. doi:10.3109/01658107.2013.830313. PMC   5291069 . PMID   28167994.
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