Optic neuritis (ON) refers to a variety of inflammatory lesions involving the optic nerve and is the most common blinding optic nerve disease in young and middle-aged adults. Previously, there were four types of optic neuritis according to the site of involvement: retrobulbar optic neuritis – involving only the intraorbital, intracanalicular and intracranial segments of the optic nerve, with normal optic papillae; optic papillitis – involving the optic papillae with optic papillary edema; peripapillary optic neuritis – involving mainly the optic nerve sheath; and optic neuritis – involving mainly the optic sheath. -optic nerve sheath; optic retinitis – involves both the optic papilla and its surrounding retina.
The more common international staging method is based on etiology. The diagnosis and treatment of optic neuritis in China are relatively confusing, and standardized diagnosis and treatment are urgently needed. This consensus refers to the current evidence-based evidence on optic neuritis at home and abroad, and recommends clinical diagnosis of ON based on etiologic typing, and then selects the corresponding targeted treatment measures.
1, the etiology of optic neuritis typing
Idiopathic optic neuritis.
Idiopathic demyelinating optic neuritis (IDON), also known as classic multiple sclerosis related optic neuritis (MS-ON); optic neuritis associated with optic neuritis (NMO-ON); and other CNS demyelinating diseases related optic neuritis.
Infectious and infection-associated optic neuritis.
Autoimmune optic neuropathy.
Other unclassifiable optic neuritis.
2. Clinical manifestations
2.1 Idiopathic optic neuritis IDON: is the most common type of optic neuritis reported in European and American studies, common in 20-50 years old, with a male to female prevalence ratio of about 1:3. Most acute or subacute onset, the disease can be preceded by a variety of prodromal factors. The typical presentation is a loss of visual acuity in one eye, with varying degrees of visual impairment; patients with relatively mild visual impairment may have color vision impairment and reduced contrast sensitivity as the main manifestations. Some patients have ocular pain or ocular rotation pain.
There are various types of visual field damage, including various forms of neurofibrillary tract-type visual field defects, and prolonged latency and/or reduced wave amplitude on VEP examination. Relative afferent papillarydefect (RAPD) is seen in patients with unilateral or two or more episodes of optic neuritis with an asymmetric degree of bilateral lesions.
About 1/3 of the patients have a variable degree of optic papillarydema, and the remaining 2/3 have retrobulbar optic neuritis. The chance of transformation to MS can be as high as 70% or more. Therefore, IDON is also known as MS-ON.
The lack of systematic data from large samples in China, small sample studies suggest that although some patients with ON have better recovery of visual function, most of them are similar to those reported in other Asian countries, with heavy damage to visual function and poor recovery of ON, while MS-related IDON is relatively rare.
NMO-ON: Neuromyelitis optica (NMO) is an inflammatory demyelinating disease of the central nervous system that is different from MS in that it mainly selectively involves the optic nerve and spinal cord. Classically also known as Devic’s disease, the concept of recurrent NMO was subsequently introduced in the last decade due to the discovery of an antibody to optic neuromyelitis optica (NMO-IgG) (which has since been identified as an antibody to aquaporin 4, AQP4-Ab).
NMO, as well as NMO-associated optic neuritis (NMO-ON), is more prevalent in Asian countries than in Europe and the U.S. The clinical features of NMO-ON differ from those of IDON. Classical NMO-associated optic neuritis is characterized by rapid and severe vision loss in both eyes simultaneously or sequentially (hours, days, or even weeks apart), with eye pain relatively rare; some patients develop optic papillary edema, retinal vein tortuosity, dilatation, and peripapillary exudates; recovery of visual function is poor, and most patients are left with severe visual impairment in both eyes or at least one eye (final visual acuity below 0.1).
Acute spinal cord damage in NMO can occur before, after, or even simultaneously with vision loss, and can occur days, weeks, months, or even years apart, manifesting as paraplegia, sensory and sphincter dysfunction, and in severe cases, respiratory muscle paralysis.
Optic neuritis associated with other CNS demyelinating diseases: There are few studies reported on optic neuritis associated with other CNS demyelinating diseases at home and abroad. Acute disseminated encephalomyelitis is most commonly seen in children within 1-3 months after vaccination, and optic neuritis can occur as a result of demyelinating lesions involving the optic nerve. This optic neuritis usually occurs in both eyes at the same time with more pronounced optic papillary edema and varying degrees of visual impairment, but visual function recovers better with glucocorticoid treatment. Optic neuritis associated with concentric cirrhosis and Scherderman’s disease has been reported rarely.
2.2 Infectious and infection-related optic neuritis is associated with a wide variety of pathogens, including bacterial infections such as syphilis, tuberculosis, Lyme disease, cat-scratch disease, and brucellosis, as well as various viruses such as hepatitis virus, human immunodeficiency virus type 1, and varicella zoster virus. Local infections such as intraocular, intraorbital, sinus, mastoid, oral and intracranial infections, as well as systemic infections can be the cause of optic neuritis.
Pathogens can directly invade the optic nerve through direct spread and hematogenous dissemination (infectious optic neuritis, such as syphilitic optic neuritis and tuberculosis infectious optic neuritis) or can cause inflammation of the optic nerve by triggering immune mechanisms (infection-associated optic neuritis). It is worth noting that various pathogenic infections, especially viral infections, can act as triggers for idiopathic optic neuritis, and therefore infection-associated optic neuritis overlaps with IDON in concept and classification, pending future large-scale case studies for further clarification.
Infectious or infection-associated optic neuritis may have an acute or subacute onset in one or both eyes. It may present clinically as optic papillitis, retrobulbar optic neuritis, optic retinitis, or peri-optic neuritis. The prognosis varies widely depending on the pathogen and the degree of infection. Some infectious optic neuritis is white-healing (e.g., optic nerve papillitis, peri-optic nerve inflammation), or if the disease is not severe enough to be diagnosed early and treated with targeted antibiotics, the recovery of visual function is better; some cases (e.g., syphilitic spirochete or Mycobacterium tuberculosis-infected optic neuritis) or severe infections, if not treated promptly, have a poor recovery. The degree of visual recovery is better in most cases of infection-associated optic neuritis.
2.3 Autoimmune optic neuropathy can be part of a systemic autoimmune disease (e.g., systemic lupus erythematosus, dry syndrome, leukoaraiosis, nodular disease, etc.) or as the first manifestation of a systemic autoimmune disease. It is most commonly seen in young to middle-aged women and can involve either one or both eyes. Compared with IDON, the degree of visual impairment is more severe and recovery is poorer; most have optic papilloedema, partly accompanied by a small amount of small pieces of peri-disc hemorrhage; can be combined with multiple system and organ damage and autoimmune antibody positivity; easy to relapse, some patients have glucocorticoid dependence phenomenon.
3. Diagnosis and differential diagnosis ON and diagnostic criteria for each etiological type.
The clinical diagnosis of each type of optic neuritis is mainly based on the typical age of onset, mode, symptoms and signs, and evolution of the disease course. Those with atypical clinical manifestations are diagnosed after excluding other possible diseases by combining auxiliary examinations as appropriate. Those who meet the following simplified conditions can be considered for the corresponding diagnosis, and careful differential diagnosis is recommended in actual clinical work.
Differential diagnosis: Other types of optic nerve diseases that need to be differentiated from optic neuritis include: non-arteritic ischemic optic neuropathy, compressive and infiltrative, traumatic, toxic and nutritional metabolic, and hereditary optic neuropathies. Knowledge of the clinical features of different types of optic neuropathies, detailed history taking and proper selection of the appropriate ancillary tests are important for differential diagnosis.
Optic cross and central optic lesions mainly present as bilateral temporal hemianopia or different types of synoptic hemianopia and are generally not easily confused with optic neuritis, but may be misdiagnosed in rare cases. Other ophthalmic diseases (refractive error, glaucoma, retinopathy, orbital inflammation, etc.) and even hysterical or fraudulent blindness (non-organic vision loss) require a strict combination of history and signs and the correct use of ancillary tests to make a more accurate differential diagnosis.
4.Treatment
Treatment of optic neuritis is advocated to address the cause of the disease and to maximize visual function while preventing or reducing or delaying further neurological damage. The diagnosis of optic neuritis should be clarified first, followed by the nature and cause of the lesion as much as possible, so that the appropriate targeted treatment can be selected. It is important to note that visual dysfunction may only be a symptom of an underlying systemic disease, so if a possible related condition is identified, it should be promptly referred to a relevant specialty such as neurology, rheumatology, infection, or otorhinolaryngology for systemic systemic treatment.
4.1 Glucocorticoids are the first choice for the acute treatment of non-infectious optic neuritis. At present, the commonly used preparations in China include prednisone, methylprednisolone, dexamethasone, hydrocortisone and so on. Common uses include intravenous drip and/or oral administration. Post- or peribulbar injection of glucocorticoid therapy is not recommended. Be aware of drug side effects when applying.
NMO-ON: There is a lack of clinical trials at home and abroad that provide a high level of evidence for the treatment of NMO-ON.
We combine the clinical characteristics of domestic patients, refer to the European Academy of Neurology, Chinese guidelines for the diagnosis and treatment of optic neuromyelitis optica and authoritative reviews on NMO treatment abroad, and recommend the following treatment regimen: preferred intravenous methylprednisolone drip treatment, methylprednisolone drip 1 g/d × 3 d, followed by oral prednisone 1 mg/kg body weight per day and gradual reduction, and oral sequential treatment should be maintained for Oral sequential therapy should be maintained for not less than 4-6 months.
If the visual impairment is severe and combined with AQP4 positivity, or recurrent episodes and glucocorticoid dependence, methylprednisolone may be given 1 g/d×3-5 d, followed by halving the dose step by step as appropriate, each dose for 2-3 d, to less than 120 mg, and changing to oral prednisone tablets 1 mg/kg body weight per day and gradually decreasing the dose, maintaining the total course of treatment for not less than 6-12 months.
Autoimmune optic neuropathy: This type of optic neuritis is still controversial due to the diagnosis and classification, and the lack of evidence for treatment studies. Given that systemic leukodystrophy is often associated with NMO and certain common immunopathophysiological mechanisms exist between the two, it is recommended to refer to the NMO-ON regimen. Some patients with autoimmune optic neuropathy are glucocorticoid-dependent, and oral glucocorticoids should be maintained for a longer period of time, as appropriate, with low-dose maintenance for more than 1-2 years being considered.
Commonly used drugs include: azathioprine, cyclosporine A, cyclophosphamide, methotrexate, mescaline, rituximab, etc. There is no uniform usage, and it is recommended to choose the drug and dosage according to the patient’s condition, tolerance and economic conditions. Among them, AQP4 antibody-positive or recurrent NMO-ON can be considered as the first choice of azathioprine (25 mg/dose orally, 2 times/d; gradually increase the dosage to 50 mg/dose, 2 times/d if tolerated.
If recurrence is frequent, or if other parts of the spinal cord are involved, cyclosporine A or cyclophosphamide may be used instead; however, special attention should be paid to the side effects of severe myelosuppression and hepatic and renal impairment of azathioprine, and routine and timely blood tests and hepatic and renal functions should be performed. Patients with autoimmune optic neuropathy combined with systemic autoimmune disease should be referred to the Department of Rheumatology and Immunology for specialized immunotherapy in time.
4.3 Multiple sclerosis disease modifying agents (DMA) DMA is mainly used for the treatment of multiple sclerosis. Foreign studies [28-32] have initially demonstrated that DMA helps to reduce the risk of transformation from IDON to MS, so in recent years DMA has been used in patients with IDON. Recommended indications: typical IDON patients with demyelinating lesions visible in cranial MRI. Commonly used drugs include: β-interferon, glatiramer acetate, mitoxantrone, and natalizumab have also been reported in research applications.
4.4 Other treatment plasma replacement: can be used in the acute phase in patients with severe optic neuritis and poor recovery, including NMO-ON as well as autoimmune optic neuropathies [33-35], especially in those with positive AQP4 antibodies or frequent relapses. Reference use: plasma replacement at 40 ml/kg body weight, depending on the severity of the disease, 2-4 times a week for 1-2 weeks.
Immunoglobulins: may be considered as one of the treatment options for patients with IDON or NMO-ON in the acute phase [10, 35]. However, there is still a lack of sufficient evidence to support its exact efficacy. Reference use: 0.2-0.4 g/kg body weight daily by intravenous infusion for 3-5 d.
Antibiotics: Infectious optic neuritis with a definite pathogen should be treated with regular, full course and dose of antibiotics as early as possible. Syphilitic optic neuritis should be treated with anti-syphilitic therapy (including penicillin drip and long-acting penicillin intramuscular injection); tuberculous optic neuritis should be treated with standard anti-TB therapy (including isoniazid, ethambutol, rifampin, streptomycin, pyrazinamide, etc.); Lyme disease should be treated with a long course of ceftriaxone; fungal sinusitis optic neuritis should be treated with adequate amount of antifungal therapy based on appropriate surgical intervention. Antifungal treatment should be given based on appropriate surgical intervention.
Chinese herbal medicine: Based on the above immunotherapy, together with Chinese herbal medicine, it is helpful to reduce the recurrence of optic neuritis, reduce the side effects of hormone therapy, and promote the recovery of visual function.
Nerve-nourishing drugs: such as B vitamins (methylcobalamin), nerve growth factor, gangliosides, etc., have certain auxiliary effects on optic neuritis treatment.