Autoimmune retinopathy overview
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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-In-Chief: M. Hassan, M.B.B.S
Overview
Autoimmune retinopathy is an autoimmune retinal degenerative disease cause cross reactivity of serum autoantibodies against the retinal, and retinal like antigens. It may be paraneoplastic or non-paraneoplastic.
Historical Perspective
First cases of cancer associated retinopathy (CAR) were observed in 1976. In 1987, retinal antigen, recoverin, which is targeted by antibodies in the serum of CAR patients was identified. In 1997, the first case of autoimmune retinopathy (AIR) was reported in the absence of malignancy with clinical features similar to CAR. Since then, hundreds of cases of paraneoplastic AIR, and non-paraneoplastic AIR have been reported.
Classification
Autoimmune retinopathy (AIR) can be broadly classified into two main categories: non-paraneoplastic AIR (npAIR) and paraneoplastic AIR. Paraneoplastic AIR is most frequently associated with small-cell lung cancer, followed by breast and gynecologic (uterine, ovarian and cervical) carcinoma. Other cancer associations include hematological, prostate, colon and lymphomas. Non-paraneoplastic AIR, which is the most prevalent form of AIR, is seen in the absence of neoplasms. AIR can also be a secondary complication of other conditions such as retinitis pigmentosa, ocular trauma, birdshot retinopathy, acute zonal occult outer retinopathy (AZOOR), or multiple evanescent white dot syndrome (MEWDS).
Pathophysiology
Autoimmune retinopathy (AIR) is an autoimmune retinal degenerative disease caused by serum autoantibodies cross reacting against the retinal, and retinal like antigens.
There are a significant number of anti-retinal antibodies that are associated with AIR, these include antibodies to anti-recoverin, anti-alpha-enolase, anti-transducin, anti-CAII, anti-arrestin, anti-rhodopsin, anti-Muller glial cells, anti-mitofilin, anti-tintin, anti-COX. However, seronegative disease is also common. AIR has been observed in patients with a history of autoimmune diseases and neoplastic diseases i.e melanoma.
Causes
As with all autoimmune diseases, autoimmune retinopathy is caused by antibodies cross reacting against the retinal, and retinal like antigens.
Main antibodies against retinal proteins associated with AIR include, anti-recoverin, anti-alpha-enolase, anti-transducin, anti-CAII, anti-arrestin, anti-rhodopsin, anti-Muller glial cells, anti-mitofilin, anti-tintin, anti-COX. However, seronegative disease is also common.
Differentiating Autoimmune Retinopathy from other Diseases
Autoimmune retinopathy should be differentiated from retinal vascular diseases such as Behçet and systemic lupus erythematosus, white-dot syndrome spectrum disorders (particularly acute zonal occult outer retinopathy (AZOOR)), retinal degenerative disorders (such as retinitis pigmentosa (RP) and cone-rod dystrophy), and non-infectious and infectious uveitis syndromes.
Risk Factors
Several malignancies are associated with the development of carcinoma associated retinopathy (CAR) such as, small-cell lung cancer, breast and gynecologic (uterine, ovarian and cervical) carcinoma, hematological, prostate, colon carcinomas and lymphomas.
Natural History, Complications and Prognosis
Diagnosis
History and Symptoms
Symptoms of autoimmune retinopathy depends on the type of retinal cell dysfunction. Cones dysfunction results in, photosensitivity, hemeralopia (inability to see as clearly in bright light), colour vision deficit, decreased visual acuity and central vision loss. Rods dysfunction results in, nyctalopia (night blindness), prolonged dark adaptation, and loss of peripheral vision. Photopsia is associated with dysfunction of both Rods and cones.
Non-neoplastic and neoplastic retinopathy has cones, rods or both cellular dysfunction. Cancer associated retinopathy is associated with both cones and rods dysfunction. Melanoma associated retinopathy is associated with rods dysfunction, and antibodies against bipolar cells.
Physical Examination
Autoimmune retinopathy is bilateral and may be asymmetric. Funduscopic changes include, retinal vasculature attenuation, diffuse retinal atrophy, mottling of the retinal pigment epithelium and optic disc pallor. There may also be constriction of the visual field with central or paracentral scotomas.
Laboratory Findings
Electrocardiogram
There are no ECG findings associated with autoimmune retinopathy.
Chest X Ray
Autoimmune retinopathy may be associated with small cell lung cancer, in which case hilar/perihilar mass with mediastinal widening due to lymph node enlargement may been seen on the chest X-ray.
CT
There are no CT findings associated with autoimmune retinopathy.
MRI
MRI is not indicated in the diagnosis of autoimmune retinopathy.
Echocardiography or Ultrasound
There are no echocardiography and ultrasound findings associated with autoimmune retinopathy.
Other Imaging Findings
Full field electroretinography (ERG) shows specific finding depending on whether rods, cones or other neural elements are affected. Delayed b-wave, reduced amplitudes of both a- and b-waves, reduced b-wave, and an electronegative ERG is seen with cancer associated retinopathy. Electroretinograms may also show abnormalities in scotopic and photopic responses.
Other Diagnostic Studies
Other diagnostic studies that may play an important role in the diagnosis of autoimmune retinopathy include, fluorescein angiography (FA), optical coherence tomography (OCT), and fundus autofluorescence (FAF).
Fluorescein angiography shows leakage of retinal vasculature. Optical coherence tomography shows cystoid macular edema. On fundus autofluorescence, parafoveal hyperautofluorescent ring was seen, which showed a disruption of the inner-outer segment junction and thin outer nuclear and photoreceptor layers on spectral domain. Immunohistochemistry may also be used to localize the binding of anti-retinal antibodies to the cellular structures in the retinal tissue. However, this is the least sensitive technique, and is unable to determine the type of autoimmune retinopathy. ELISA is more sensitive than immunohistochemistry, but it requires identification of the antigen of interest before testing.
Treatment
Medical Therapy
Currently no standard treatment protocol exists for autoimmune retinopathy (AIR). However, various treatment options have been described in the literature, and they include,
- Systemic and/or topical (intravitreal/sub-tenon/depot) corticosteroids
- Immunomodulators like cyclosporine (calcineurin inhibitor which prevents IL-2 transcription), infliximab (anti-TNFα antibody), mycophenolate mofetil (IMP dehydrogenase inhibitor, preventing purine synthesis), azathioprine (purine antimetabolite)
- Biological agents such as monoclonal antibodies like rituximab (anti-CD20 antibody), alemtuzumab (anti-CD52 antibody), ipilimumab (antagonist antibody against cytotoxic T-lymphocyte antigen-4), tocilizumab (anti-IL-6 receptor antibody), sarilumab (anti-IL-6 receptor antibody)
- Intravenous immunoglobulin (IVIG), and plasmapheresis
- Antioxidants vitamins like lutein, Vitamin C, Vitamin E, and beta carotene (in non-smokers) also play a role in stabilizing retinal degeneration and disease course.
Surgery
Surgical intervention is not recommended for the management of autoimmune retinopathy.
Primary Prevention
Currently there is no established method for primary prevention of autoimmune retinopathy.
Secondary Prevention
Currently there is no established method for secondary prevention of autoimmune retinopathy.