The immune system plays a vital role in keeping the body in balance, fighting infection and even reducing our risk of cancer.  An overactive immune system, however, can wreak havoc, causing significant morbidity and even mortality.  Autoimmune disease occurs when the normal tolerance of the body to its own cells disappears and healthy cells are attacked. Graves Disease, Sjogren’s syndrome, diabetes mellitus, rheumatoid arthritis, lupus and multiple sclerosis are well known examples of systemic autoimmune diseases. Here we revue our latest understanding of and treatments for autoimmune disorders affecting the retina, macula and vitreous.

Pathogenesis

Autoimmune disorders in the retina, as elsewhere in the body, occur when the white blood cells (lymphocytes) of the immune system no longer recognize certain “self” proteins and now see them as foreign (“antigens”).  Examples of such proteins in the retina include arrestin (S-antigen), interphotoreceptor binding protein, and tyrosinase-related proteins.  When the body attacks the foreign looking proteins a response similar to wound healing occurs, causing inflammation and possible neovascularization, fibrosis and contraction.  The inflammatory response includes both cell-mediated immunity involving macrophages, T-cells and Natural killer cells as well as humoral immunity involving antibody release from B-cells.

Disorders

Differences in the antigen attacked by the body and the specific immune markers on the various lymphocytes involved determine the disorder that results.  For example, the lymphocyte marker HLA-DR4 is associated with Voght-Koyanagi-Harada syndrome (choroiditis in association with uveitis, aseptic meningitis, dysacusis, tinnitus, poliosis, and alopecia), HLA-B29 with birdshot retinochoroidopathy (choroidits with creamy white infiltrates), HLA-B51 with Behcet’s disease, and HLA-DR15 with pars planitis.  Inconsistent associations are found with rheumatoid sclerouvieits, sympathetic ophthalmia, multifocal choroiditis with panuveitis, sarcoidosis, juvenile idiopathic arthritis and serpigenous choroidopathy.

Testing and Treatments

Panuvieits with choroiditis are the most common features of autoimmune retinal disorders.  Initial signs usually include cells in the anterior chamber and vitreous.  Since infection may also cause this presentation, a preliminary work-up should include syphilis serologies, a chest x-ray and PPD skin test for tuberculosis.  More specific testing may be mandated by a review of systems check.  The mainstay of treatment for retinal autoimmune disease is corticosteroids.  High doses are used to begin with and then a steroid sparing immunosuppressive agent such as methotrexate, cyclosporine, immuran, or mycophenolate mofetil (CellCept), is added for more prolonged disease.  Steroids have potential systemic side with prolonged use including glucose intolerance, hypertension, increased susceptibility to infections, bone re-absorption, bruising, mood swings/insomnia, avascular necrosis of bone, abdominal striae, cataracts, glaucoma and acne. More recently, investigators have utilized combination therapy with oral steroids and immunosuppressive agents, periocular and intravitreal steroid injections as well as well as sustained-release intravitreal steroid implants. A new preservative-free formulation of triamcinolone acetate is now available for intravitreal injections.  Preliminary results at RMI have shown efficacy against uveitis using anti-VEGF therapies including intravitreal Avastin which does not have the risk of steroid-induced glaucoma or cataract.

Autoimmune retinal disorders were a significant cause of blindness.  Prompt diagnosis and long term management strategies including initial steroid and the steroid-sparing immunosuppressive drugs as well as anti-VEGF agents like Avastin have improved our short and long term results for these patients.  When retinal changes are noted checking the anterior chamber and vitreous for cells and inflammation will keep you from missing these potentially devastating conditions.

Ron P. Gallemore, M.D, Ph.D.

Founder and Director

Retina Macula Institute and the

Retina Macula Research Center

South Bay 310-944-9393   Los Angeles 323-466-9393