Treatment of Uveitis

• First-line treatment: corticosteroids

Corticosteroids are the first line of treatment in light of acute episodes of intraocular inflammation. Anterior uveitis is commonly treated with corticosteroid eye drops (topical) and pupil dilators (mydriatics). In acute cases with posterior segment involvement (retina and optic nerve) or if there is a risk of vision loss, then high doses of corticosteroids are administered systemically.

Corticosteroids can also be given via periocular or intravitreal injections (including triamcinolone or dexamethasone and fluocinolone intravitreal implants). However, the intraocular use of corticosteroids can be associated with the appearance of complications such as an increase in intraocular pressure or cataracts.

Furthermore, local corticosteroid administration does nothing to treat the systemic immunological alteration underlying the pathogenesis of non-infectious uveitis.

While it may be useful in the acute phase of active ocular inflammation, continuous corticosteroid treatment is known to be associated with the onset of side effects. Consequently, when using corticosteroids as a uveitis maintenance therapy they must be adjusted to the minimum possible dose (5–10 mg/day) and, if possible, attempts should be made to gradually withdraw the steroidal treatment.

• Immunosuppressants for chronic or recurrent uveitis

The use of systemic immunosuppressants, e.g., corticosteroid-sparing agents, is recommended in cases of chronic or recurrent uveitis (which have the capacity to cause structural damage and vision loss), in order to avoid reactivating the uveitis and to reduce the corticosteroid load to a minimum.

The most used classical immunosuppressants in the maintenance treatment of non-infectious uveitis are cyclosporine A (the only immunosuppressant in Spain with an approved indication for this use), azathioprine, methotrexate and mycophenolate mofetil/sodium.

In clinical practice, there is little evidence that one immunosuppressant is better than another. Nevertheless, cyclosporine is often the preferred choice. Children, women and the elderly are usually given methotrexate as it is better tolerated. Azathioprine and mycophenolate mofetil or mycophenolic acid 1 can be effective in patients who present, or will potentially present, unacceptable toxicity to cyclosporine. Alkylating agents have practically disappeared from the ophthalmologist’s arsenal of treatments because of their undesirable side effects.

Traditional immunosuppressants (alone or in combination) are effective against acute episodes of inflammation in a large percentage of patients with non-infectious uveitis. However, they have a relatively slow onset of action and do not always manage to control uveitis outbreaks because approximately 30% of patients are either resistant (refractory) to conventional treatment or cannot tolerate it as they present adverse effects such as nephrotoxicity, high blood pressure or hirsutism associated with cyclosporine A use, or digestive intolerance and liver dysfunction in the case of methotrexate.

In fact traditional immunosuppressants can lead to the development of severe adverse effects and therefore it should be administered under close supervision by the uveitis multidisciplinary medical team, with regular laboratory tests and check-ups with the rheumatologist/internist during follow-up.

• Biologic medicines

Biologic medicines were originally developed to treat systemic inflammatory diseases such as rheumatoid arthritis, psoriasis, psoriatic arthritis or inflammatory bowel disease, and also to prevent organ transplant rejection.

They modify the immune system by producing a “selective” immunosuppressive effect and so they are less toxic than conventional immunosuppressants.

Biologic medicines are used to treat uveitis because approximately 30% of uveitis patients do not respond to conventional treatments (corticosteroids and immunosuppressants).

Uveitis treatments incorporating eye drops, corticosteroids or immunosuppressants produce side effects that can affect patient quality of life and treatment adherence.

The use of eye drops may impact on daily life as they cause pupil dilation. In the first few weeks, the drops usually have to be instilled frequently and this also alters the patient’s daily rhythm.

Corticosteroids, for their part, can also produce several undesirable effects: gastrointestinal (peptic ulcer, gastrointestinal bleeding, pancreatitis); endocrine/metabolic (Cushing’s syndrome, menstrual disorders, impotence, high blood sugar levels, hypothalamic-pituitary-adrenal axis suppression, growth retardation); musculoskeletal (osteoporosis, aseptic osteonecrosis \[bone cell death due to a lack of blood supply], muscle compromise); dermatological (acne, hirsutism, capillary fragility, purple striae, delayed wound healing); ocular (cataracts, increased ocular pressure \[glaucoma]); cardiovascular (high blood pressure, heart failure); neuropsychiatric (mood swings and changes in personality, benign intracranial hypertension); defence system (altered defence mechanisms with susceptibility to infections).