Autoimmune optic neuropathy

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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.

Contents

Patients with defined SLE that go on to develop optic neuritis should be better identified as lupus optic neuritis.

Signs and symptoms

AON was first described in 1982. [1] It presents with visual loss and signs of optic nerve dysfunction, such as loss of color vision, afferent pupil defect, and sometimes abnormalities of the optic disc. The clinical features of AON can be variable and present in several unilateral or bilateral forms:

The main features that differentiate AON from the more common typical demyelinating optic neuritis is the poor recovery of vision and the chronic or recurrent or bilateral course of AON. [2] Furthermore, the workup for multiple sclerosis including MRI, will be negative. Thus, it may be necessary to diagnose AON after a period of observation, noting the problem is not behaving as expected for demyelinative disease. [3]

Pathogenesis

Approximately 1-2% of patients with defined SLE develop an optic neuropathy during the course of their disease. [4] [5] SLE-associated optic neuritis is rarely the presenting sign of the disease. The molecular pathogenesis is hypothesized, based on clinical features and the emerging understanding of mechanisms in SLE. [6] Inflammation resulting from auto-antibodies, immune complexes, T-cells and complement, probably damages the components of the optic nerve, as well as the blood vessels (vasculitis). The resulting vasculitis causes a loss of blood supply to the nerve (ischemia). This combination of inflammation and ischemia may produce reversible changes such as demyelination alone, or more permanent damage axonal (necrosis), or a combination. The poor recovery of vision in AON despite anti-inflammatory treatment suggests that ischemia from the underlying vasculitis is an important component, but the details have not been established. It may be reasonable to consider that AON pathogenesis represents an incomplete expression of the SLE-associated optic neuropathy disease process.[ citation needed ]

Diagnosis

Treatment

AON is a rare disease and the natural history of the disease process is not well defined. [7] Unlike typical optic neuritis, there is no association with multiple sclerosis, but the visual prognosis for AON is worse than typical optic neuritis. Thus AON patients have different treatment, and often receive chronic immunosuppression. No formal recommendation can be made regarding the best therapeutic approach. However, the available evidence to date supports treatment with corticosteroids and other immunosuppressive agents.[ citation needed ]

Early diagnosis and prompt treatment with systemic corticosteroids may restore some visual function but the patient may remain steroid dependent; vision often worsens when corticosteroids are tapered. As such, long-term steroid-sparing immunosuppressive agents may be required to limit the side-effects of steroids and minimize the risk of worsening vision.[ citation needed ]

Related Research Articles

Optic neuritis describes any condition that causes inflammation of the optic nerve; it may be associated with demyelinating diseases, or infectious or inflammatory processes. It is also known as optic papillitis, neuroretinitis and retrobulbar neuritis. 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:

  1. Idiopathic
  2. Hereditary optic neuritis
  3. Parainfectious optic neuritis
  4. Infectious optic neuritis (sinus related or associated with cat scratch fever, tuberculosis, lyme disease and cryptococcal meningitis in AIDS patients
  5. Autoimmune causes
Corticosteroid Class of steroid hormones

Corticosteroids are a class of steroid hormones that are produced in the adrenal cortex of vertebrates, as well as the synthetic analogues of these hormones. Two main classes of corticosteroids, glucocorticoids and mineralocorticoids, are involved in a wide range of physiological processes, including stress response, immune response, and regulation of inflammation, carbohydrate metabolism, protein catabolism, blood electrolyte levels, and behavior.

Amaurosis fugax Medical condition

Amaurosis fugax is a painless temporary loss of vision in one or both eyes.

Cryoglobulinemia Medical condition

Cryoglobulinemia is a medical condition in which the blood contains large amounts of pathological cold sensitive antibodies called cryoglobulins – proteins that become insoluble at reduced temperatures. This should be contrasted with cold agglutinins, which cause agglutination of red blood cells.

Methylprednisolone Corticosteroid medication

Methylprednisolone is a synthetic glucocorticoid, primarily prescribed for its anti-inflammatory and immunosuppressive effects. It is either used at low doses for chronic illnesses or used concomitantly at high doses during acute flares. Methylprednisolone and its derivatives can be administered orally or parenterally.

Anterior ischemic optic neuropathy (AION) is a medical condition involving loss of vision caused by damage to the optic nerve as a result of insufficient blood supply (ischemia). This form of ischemic optic neuropathy is generally categorized as two types: arteritic AION, in which the loss of vision is the result of an inflammatory disease of arteries in the head called temporal arteritis, and non-arteritic AION, which is due to non-inflammatory disease of small blood vessels.

Posterior ischemic optic neuropathy (PION) is a medical condition characterized by damage to the retrobulbar portion of the optic nerve due to inadequate blood flow (ischemia) to the optic nerve. Despite the term posterior, this form of damage to the eye's optic nerve due to poor blood flow also includes cases where the cause of inadequate blood flow to the nerve is anterior, as the condition describes a particular mechanism of visual loss as much as the location of damage in the optic nerve. In contrast, anterior ischemic optic neuropathy (AION) is distinguished from PION by the fact that AION occurs spontaneously and on one side in affected individuals with predisposing anatomic or cardiovascular risk factors.

Neuritis Inflammation of a nerve or generally any part of the nervous system

Neuritis 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.

Mixed connective tissue disease, commonly abbreviated as MCTD, is an autoimmune disease characterized by the presence of elevated blood levels of a specific autoantibody, now called anti-U1 ribonucleoprotein (RNP) together with a mix of symptoms of systemic lupus erythematosus (SLE), scleroderma, and polymyositis. The idea behind the "mixed" disease is that this specific autoantibody is also present in other autoimmune diseases such as systemic lupus erythematosus, polymyositis, scleroderma, etc. MCTD was characterized as an individual disease in 1972 by Sharp et al., and the term was introduced by Leroy in 1980.

Graves ophthalmopathy Medical condition

Graves’ ophthalmopathy, also known as thyroid eye disease (TED), is an autoimmune inflammatory disorder of the orbit and periorbital tissues, characterized by upper eyelid retraction, lid lag, swelling, redness (erythema), conjunctivitis, and bulging eyes (exophthalmos). It occurs most commonly in individuals with Graves' disease, and less commonly in individuals with Hashimoto's thyroiditis, or in those who are euthyroid.

Optic neuropathy is damage to the optic nerve from any cause. Damage and death of these nerve cells, or neurons, leads to characteristic features of optic neuropathy. The main symptom is loss of vision, with colors appearing subtly washed out in the affected eye. On medical examination, the optic nerve head can be visualised by an ophthalmoscope. A pale disc is characteristic of long-standing optic neuropathy. In many cases, only one eye is affected and patients may not be aware of the loss of color vision until the doctor asks them to cover the healthy eye.

An overlap syndrome is a medical condition which shares features of at least two more widely recognised disorders. Examples of overlap syndromes can be found in many medical specialties such as overlapping connective tissue disorders in rheumatology, and overlapping genetic disorders in cardiology.

Discoid lupus erythematosus Autoimmune skin condition

Discoid lupus erythematosus is the most common type of chronic cutaneous lupus (CCLE), an autoimmune skin condition on the lupus erythematosus spectrum of illnesses. It presents with red, painful, inflamed and coin-shaped patches of skin with a scaly and crusty appearance, most often on the scalp, cheeks, and ears. Hair loss may occur if the lesions are on the scalp. The lesions can then develop severe scarring, and the centre areas may appear lighter in color with a rim darker than the normal skin. These lesions can last for years without treatment.

Cerebritis is the inflammation of the cerebrum, which performs a number of important functions, such as memory and speech. It is also defined as a purulent nonencapsulated parenchymal infection of brain which is characterized by nonspecific features on CT and cannot reliably be distinguished from neoplasms.

Lupus erythematosus Human disease

Lupus erythematosus is a collection of autoimmune diseases in which the human immune system becomes hyperactive and attacks healthy tissues. Symptoms of these diseases can affect many different body systems, including joints, skin, kidneys, blood cells, heart, and lungs. The most common and most severe form is systemic Lupus erythematosus.

Lupus Human autoimmune disease

Lupus, technically known as systemic lupus erythematosus (SLE), is an autoimmune disease in which the body's immune system mistakenly attacks healthy tissue in many parts of the body. Symptoms vary among people and may be mild to severe. Common symptoms include painful and swollen joints, fever, chest pain, hair loss, mouth ulcers, swollen lymph nodes, feeling tired, and a red rash which is most commonly on the face. Often there are periods of illness, called flares, and periods of remission during which there are few symptoms.

Purtschers retinopathy Medical condition

Purtscher's retinopathy is a disease where part of the eye (retina) is damaged. Usually associated with severe head injuries, it may also occur with other types of trauma, such as long bone fractures, or with several non-traumatic systemic diseases. However, the exact cause of the disease is not well understood. There are no treatments specific for Purtscher's retinopathy, and the prognosis varies. The disease can threaten vision, sometimes causing temporary or permanent blindness.

Atacicept is a recombinant fusion protein designed to inhibit B cells, thereby suppressing autoimmune disease. The designer protein combines the binding site for two cytokines that regulate maturation, function, and survival of B cells - B-lymphocyte stimulator (BLyS) and A proliferation-inducing ligand (APRIL), with the constant region of immunoglobin. Atacicept blocks activation of B cells by the tumor necrosis factor receptor superfamily member 13B, a transmembrane receptor protein found predominantly on the surface of B cells. Like the monoclonal antibody belimumab, atacicept blocks the binding of BLyS, but it also blocks APRIL. Binding of these TACI ligands induces proliferation, activation, and longevity of B cells and thus their production of autoantibodies. Atacicept is thought to selectively impair mature B cells and plasma cells with less impact on progenitor cells and memory B cells.

Anti-SSA/Ro autoantibodies

Anti-SSA autoantibodies are a type of anti-nuclear autoantibodies that are associated with many autoimmune diseases, such as systemic lupus erythematosus (SLE), SS/SLE overlap syndrome, subacute cutaneous lupus erythematosus (SCLE), neonatal lupus and primary biliary cirrhosis. They are often present in Sjögren's syndrome (SS). Additionally, Anti-Ro/SSA can be found in other autoimmune diseases such as systemic sclerosis (SSc), polymyositis/dermatomyositis (PM/DM), rheumatoid arthritis (RA), and mixed connective tissue disease (MCTD), and are also associated with heart arrhythmia.

Chronic relapsing inflammatory optic neuropathy (CRION) is a form of recurrent optic neuritis that is steroid responsive. Patients typically present with pain associated with visual loss. CRION is a diagnosis of exclusion, and other demyelinating, autoimmune, and systemic causes should be ruled out. Early recognition is crucial given risks for severe visual loss and because it is treatable with immunosuppressive treatment such as steroids. Relapse that occurs after reducing or stopping steroids is a characteristic feature.

References

  1. Dutton, JJ; Burde, RM; Klingele, TG (1982). "Autoimmune retrobulbar optic neuritis". American Journal of Ophthalmology. 94 (1): 11–7. doi:10.1016/0002-9394(82)90184-2. PMID   6979934.
  2. Kupersmith, M J; Burde, R M; Warren, F A; Klingele, T G; Frohman, L P; Mitnick, H (1988). "Autoimmune optic neuropathy: Evaluation and treatment". Journal of Neurology, Neurosurgery & Psychiatry. 51 (11): 1381–1386. doi:10.1136/jnnp.51.11.1381. PMC   1032806 . PMID   3266235.
  3. Riedel, Patrick; Wall, Michael; Grey, Allen; Cannon, Thomas; Folberg, Robert; Thompson, H. Stanley (1998). "Autoimmune optic neuropathy". Archives of Ophthalmology. 116 (8): 1121–4. PMID   9715702.
  4. Estes, Dorothy; Christian, Charles L. (1971). "The Natural History of Systemic Lupus Erythematosus by Prospective Analysis". Medicine. 50 (2): 85–96. doi:10.1097/00005792-197103000-00001.
  5. Siatkowski, R. Michael; Scott, Ingrid U.; Verm, Alan M.; Warn, Ann A.; Farris, Bradley K.; Strominger, Mitchell B.; Sklar, Evelyn M.L. (2001). "Optic Neuropathy and Chiasmopathy in the Diagnosis of Systemic Lupus Erythematosus". Journal of Neuro-Ophthalmology. 21 (3): 193–8. doi:10.1097/00041327-200109000-00006. PMID   11725184.
  6. Tsokos, George C. (2011). "Systemic Lupus Erythematosus". New England Journal of Medicine. 365 (22): 2110–21. doi:10.1056/NEJMra1100359. PMID   22129255.
  7. Frohman, L; Dellatorre, K; Turbin, R; Bielory, L (2009). "Clinical characteristics, diagnostic criteria and therapeutic outcomes in autoimmune optic neuropathy". British Journal of Ophthalmology. 93 (12): 1660–6. doi:10.1136/bjo.2009.159350. PMID   19692378.