Demyelinating and Autoimmune Optic Neuritis: Approach and Management
Background: A healthy optic nerve is a crucial conduit for impulses generated within the layers of the retina to leave the eye.
To date, the mechanism of action of optic neuritis is not entirely clear, as are the therapeutic approaches, especially in the pediatric
population. To date it is estimated that the annual incidence of optic neuritis is estimated between 0.56 and 5.1 cases per 100,000
Methodology: A systematic review was carried out through various databases from January 2015 to September 2022; The search and selection of articles were carried out in indexed journals in English.
Results: The first clinical manifestation that we can find in a patient with optic neuritis is a pain when moving the eyes, with subsequent worsening of vision. Only 0.4% of patients develop symptoms in both eyes simultaneously. Intravenous methylprednisolone at 1000 mg/day has been found to lead to more rapid recovery of vision. IV immunoglobulin and plasma exchange are used in patients refractory to initial treatment. Erythropoietin has demonstrated neuroprotective properties.
Conclusion: This review offers updated and detailed information that helps the health professional in clinical practice, to identify the main clinical symptoms and thus prevent and treat said pathology promptly.
Neuritis; Optic; Demyelinating; Autoimmune; Cross reaction
IVIg: IV Immunoglobulin; AQP4: Aquaporin 4; NMO: Neuromyelitis Optica; MOG: Myelin Oligodendrocyte Glycoprotein; IVMP: Intravenous Methylprednisolone; IVE: Intravenous Erythropoietin
A healthy optic nerve is a crucial conduit for impulses generated within the layers of the retina to leave the eye. Electrical signals are initiated by photoreceptors in response to incident light, modified by retinal bipolar cells, and transmitted via optic nerves to the lateral geniculate bodies . These signals can be compromised when there is damage or some type of alteration in the nerve fiber layers or the optic nerve. Optic neuritis is considered a variety of conditions that can affect the proper functioning of the optic nerve. Many causes can compromise it, causing neuropathies, among these, we find infections, traumas, vascular insufficiency, metastasis, toxins, or nutritional deficiency .
To date the mechanism of action is not entirely clear, but different hypotheses have been raised, such as the autoimmune reaction damaging the myelin sheath that encompasses the neurons within the optic nerve. It has been documented that patients diagnosed with autoimmune diseases are more likely to develop optic neuritis, with a causal relationship between HLA DRB1, HLA-B27 and optic neuritis . One of the causes that is having great importance is cross-reaction, through molecular mimicry either between different microorganisms or natural proteins and proteins or autoantigens belonging to optic neuritis. Neuromyelitis Optica (NMO) is associated with antibodies against aquaporin 4 (AQP4). It is hypothesized that AQP4 antibodies may be triggered by exposure to environmental proteins. Human AQP4 with plant and bacterial proteins were found to have significantly similar structures and sequences. High similarity to a known epitope for NMO-IgG, AQP4, was observed for maize ZmTIP4-1. Demonstrating cross-reactivity to plant tissue [4,5].
To date it is estimated that the annual incidence of optic neuritis is estimated between 0.56 and 5.1 cases per 100,000 people. The main risk factors that have been reported are Caucasian race, female sex, and age plays an important factor, predominantly between 20 and 40 years of age. Although optic neuritis is very infrequently identified in children, its appearance is not suggestive of developing multiple sclerosis in adulthood. Regarding the climate, it is believed that in temperate climates its incidence can increase. Optic neuritis is thought to be the initial inflammatory event in 15-20% of multiple sclerosis patients, and half of the multiple sclerosis patients will ultimately have had at least one attack of optic neuritis in the previous 15 years. Oligoclonal bands within the cerebrospinal fluid are pathognomonic for multiple sclerosis .
Optic neuritis-related vision loss in patients with neuromyelitis optica spectrum disorders and myelin oligodendrocyte glycoprotein IgG is usually more severe and results in larger scotomas. Since both disorders affect the optic nerve, chiasm, and optic pathways, bilateral vision loss is common. The damage often extends longitudinally into the spinal cord in both conditions . Given that this pathology is of great importance due to its still wide incidence and with effects that compromise the quality of life of the patient, it is necessary to carry out this study, in order to provide updated and detailed information that helps in practice. clinic to health professionals.
MATERIALS AND METHODS
In this study we carried out a systematic review, the databases used were PubMed, Scielo and ScienceDirect. Articles in English were collected from the years 2015 to 2022. The terms were used as keywords: Neuritis; Optics; Demyelinating; autoimmune; Cross reaction. In this review, 156 original and review publications related to the subject studied were identified. Only 24 articles met the inclusion requirements, articles that were in a range of no less than the year 2015, that were full-text articles and that reported on optic neuritis, its therapeutic approach, as well as its possible mechanism of action.
Most patients who develop optic neuritis typically present primarily with impaired visual acuity, either acute or severe, with no clear diagnostic findings on ocular examination. It is very common to find it in young, otherwise healthy individuals . This pathology is considered an autoimmune disease, due to the presence of an autoimmune reaction directed against the optic nerve. This may be associated with other autoimmune diseases, especially multiple sclerosis . It is increasingly being used in clinical trials as a model for multiple sclerosis relapses, because visual function is relatively easy to measure and, in particular, because changes in the retinal nerve fiber layer can be visualized in detail with tomography. optical coherence . The incidence of optic neuritis in central Europe is 5 cases per 100,000 people per year. The mean age of onset is 36 years. It is rare in people younger than 18 or older than 50. Approximately more than 70% of patients are women. According to a current study, optic neuritis accounts for 43% of cases of clinically isolated neurological syndromes that are considered potential precursors of multiple sclerosis .
OPTIC NEURITIS CLINIC
The first clinical manifestation that we can find in a patient with optic neuritis is a pain when moving the eyes, with subsequent worsening of vision. Only 0.4% of patients develop symptoms in both eyes simultaneously . Most patients can accurately identify the day of the occurrence of symptoms. Unlike patients who present loss of vision or alteration of visual acuity associated with optic nerve tumors. In Figure 1 we can show an illustration of what a person who develops optic neuritis would look like. Patients report seeing things that are dark, unclear, and with low contrast, colors appear dirty, and pale. If the disease is not treated promptly, visual acuity could deteriorate, reaching its maximum point of deterioration in approximately one or two weeks with subsequent improvement in acuity . The pain and worsening vision are so bothersome that almost no one wants to see if it improves spontaneously; patients tend to find their way to an ophthalmologist very early in the course of the disease. Pain when moving the eyes is absent in 8% of patients whose inflammatory focus is located in the intracranial portion of the optic nerve and, therefore, proximal to its mobile portion .
VISUAL ACUITY TEST
In unilateral optic neuritis, the reaction to direct pupillary light and the accompanying consensus reaction from the opposite pupil are weaker with illumination from the affected eye than with illumination from the unaffected eye . This finding, known as a relative afferent pupillary defect, is best seen with the aid of the swinging-lantern test. Pain on eye movement should be elicited with appropriate movements if the patient does not spontaneously report that she has it. Any unusual sensation is diagnostically relevant because eye movements are normally not felt at all. In Figure 2, we can see an example of this test, this figure was taken from the study carried out by . Since it clearly shows the reactivity of the pupils in a healthy person and a person with optic neuritis. The pupils react faster, and to a greater extent, with illumination from the healthy right eye, compared to the affected left eye. The presence of central scotomas and cecal centers is frequently found in patients suffering from this disease. At the level of the optic disc, we can find mild edema, although it tends to be confused with a normal optic disc. In Figure 3, we can see the symptoms and signs that together could be considered pathognomonic of optic neuritis [17,18].
MANAGEMENT OF OPTIC NEURITIS
Intravenous methylprednisolone 1000 mg/day has been shown to lead to more rapid recovery of vision, but the result regarding visual acuity, fields, contrast and color perception was no better than with prednisone. oral alone or, indeed, with a placebo . Neurological and ophthalmological guidelines establish that optic neuritis should be treated with methylprednisolone at a dose of 500- 1000 mg/day for 3-5 days, followed by 11 days of oral prednisolone at 1 mg/kg for faster recovery, but without improvement of the final result concerning visual acuity. During steroid treatment, a proton pump inhibitor is also given to prevent peptic ulcers. Osteoporosis prophylaxis, by contrast, is not necessary because steroids are only given for a short time. Complete blood count, serum glucose, and electrolyte levels are checked before the first intravenous dose of methylprednisolone and on the third and (sometimes) fifth day of treatment.
IV immunoglobulin (IVIg) and plasma exchange have been evaluated in patients with optic neuritis refractory to high-dose corticosteroid therapy. IVIG (2 g/kg) did not improve contrast sensitivity or visual function in patients with acute optic neuritis . But plasma exchange has resulted in better visual outcomes in patients with corticosteroid-refractory optic neuritis. Although the frequency of responders varied, the majority of patients with optic neuritis treated with plasmapheresis improved their visual function.
Management for Demyelinating Optic Neuritis
Erythropoietin, best recognized as a regulator of erythropoiesis, has shown potential neuroprotective properties in animal models of brain injury, including those of ischemia, trauma, epilepsy, and optic neuropathy. A rat model using myelin oligodendrocyte glycoprotein (MOG) immunization showed functional and histopathological improvement of retinal ganglion cells and optic nerves when erythropoietin treatment was combined with highdose methylprednisolone. The use of erythropoietin in humans with optic neuropathy has been reported in multiple studies from Iran. Conditions treated included traumatic optic neuropathy, anterior ischemic optic neuropathy, multiple sclerosis, and methanol optic neuropathy .
It evaluated the addition of intravenous recombinant human erythropoietin (IVE) to intravenous methylprednisolone (IVMP) in patients with retrobulbar optic neuritis. Thirty-five patients were treated with IVMP alone and twenty-seven with the combination of IVMP and IVE (20,000 international units). Both groups were treated with intravenous agents for 3 days and then received 11 days of oral prednisolone at 1 mg/kg. The primary outcome measure was the change in best-corrected visual acuity, which was assessed up to 120 days. The use of erythropoietin appears to be safe, which is encouraging .
Optic neuritis is still a disease that requires extensive study, mainly to clarify its mechanism of action, and provide adequate care. To date, one of the mechanisms that is having great importance is that of autoimmunity caused by cross-reactivity, either between different environmental epitopes or microorganisms. One of the criteria for this to happen is that the two epitopes can share the same sequence or that they present similarity in their structure, as well as that this autoimmunity is reproducible in other sample organisms. Humanity had one of the pandemics that had a great impact on the population recently, it is one caused by COVID-19, therefore, the association that optic neuritis and SARS.COV-2 can have has been studied. The study carried out by  reports a clinical case of a patient who developed optic neuritis after SARSCOV- 2. The most common neurological symptoms of COVID-19 are headache, anosmia, and dysgeusia. In this study, they propose a possible cause for the development of optic neuritis, which is molecular mimicry causing cross-reactivity.
The pediatric population is not exempt from the development of optic neuritis, the study carried out by Silvia, in which they carry out a systematic review, reports that children are more likely to require hospitalization and to undergo magnetic resonance imaging of the orbits for correct diagnosis. In Table 1, we can identify the main preventive/chronic therapies proposed depending on the clinical condition . Although many studies are searching for better therapeutic measures for both the pediatric and adult populations, there is still no clear consensus on effective therapies to treat this disease. A strength of the current study is the methodology implemented, regarding the literature search, and steps in the selection of relevant articles, quality assessment, and data extraction. However, this study has several limitations, which should be taken into account before concluding, among these, we find little evidence from studies, analysis of clinical trials and invitro studies that demonstrate the proposed mechanisms of action for neuritis. optics, to focus on the correct handling, so more studies, are needed to answer these questions.
This pathology is considered an autoimmune disease, due to the presence of an autoimmune reaction directed against the optic nerve. This may be associated with other autoimmune diseases, especially multiple sclerosis.
The first clinical manifestation that we can find in a patient with optic neuritis is a pain when moving the eyes, with subsequent worsening of vision. Only 0.4% of patients develop symptoms in both eyes simultaneously. In Figure 1,2 we can identify the clinical aspects of a patient with optic neuritis. Intravenous methylprednisolone at 1000 mg/day has been found to lead to more rapid recovery of vision. IV immunoglobulin (IVIg) and plasma exchange have been evaluated in patients with optic neuritis refractory to highdose corticosteroid therapy. Erythropoietin, best recognized as a regulator of erythropoiesis, has shown potential neuroprotective properties in animal models of brain injury, including those of ischemia, trauma, epilepsy, and optic neuropathy.
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Received Date: December 06, 2022
Published: January 24, 2023
Address for correspondence
María Isabel Silva Sánchez, University Teaching Physician, Universidad El Bosque, Colombia; https://orcid.org/0000-0002-7608- 8817
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How to cite this article
María Isabel SS, Paula Andrea FU, Juan Pablo GM, Génesis GCR, Daniela AA, et. al. Demyelinating and Autoimmune Optic Neuritis: Approach and Management. 2023- 5(1) OAJBS.ID.000534.
Figure 1: A vision of a person who develops optic neuritis.
Figure 2: Oscillating flashlight test in a patient with left optic neuritis.
Figure 3: Pathognomonic symptoms and signs of optic neuritis.
Table 1: Preventive/chronic therapies in the pediatric population depending on their clinical condition.