5 February 2020
Treatment of Uveitis
With appropriate treatment the majority of episodes of anterior Uveitis disappear within a few days or weeks, but patients often suffer recurrences. Inflammation associated with posterior Uveitis can last from months to years and can cause permanent vision damage, even when treated.
Different treatments are available depending on the type and location of the Uveitis:
Anterior uveitis. This does not tend to have any severe effects in terms of vision loss and is treated with anti-inflammatory eye drops and pupil dilators (mydriatics) for a limited amount of time.
Non-infectious posterior uveitis. Usually treated with anti-inflammatories, typically corticosteroids because of their effectiveness. They can be administered orally, locally (by means of infiltrations around the eye) or as intraocular injections (via implants).
Chronic cases of uveitis or those associated with immune diseases. These may require immunosuppressants or biologic medicines.
Treatment for non-infectious 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 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).
Biologic medicines for non-infectious uveitis
There are five anti-TNF-α monoclonal antibodies currently available on the market: infliximab, adalimumab, etanercept, golimumab and certolizumab pegol.
- Infliximab (Remicade, MSD) was the first to be used to treat non-infectious uveitis and subsequently it has the most information available about its use. It is a chimeric antibody administered intravenously at an outpatient clinic. Current scientific evidence strongly supports the efficacy of infliximab in the treatment of severe, sight-threatening non-infectious uveitis, especially in cases of Behçet-related uveitis, for which it has been indicated in Japan since 2007 but has not yet been approved in the European Union or United States. It is very fast-acting and it is therefore considered a valid therapeutic option in acute cases of severe, sight-threatening intraocular inflammation.
- Adalimumab (Humira, Abbvie) is a humanised anti-TNF-α monoclonal antibody administered subcutaneously every 15 days in the outpatient clinic. Its effectiveness at treating ocular inflammatory diseases refractory to conventional treatment has been widely demonstrated in the scientific literature (Llorenç et al., 2012; Diaz-Llopis et al., 2012). Thanks to its ease of administration and the reduced risk of anaphylactic reactions as it does not include the murine portion, it is well-tolerated by patients and constitutes the anti-TNF antibody of choice in uveitis associated with JIA, VKH, sympathetic ophthalmia or birdshot retinochoroidopathy. Adalimumab is also considered a valid, more patient-friendly option for use as an outpatient maintenance treatment after starting therapy with infliximib for quick, initial treatment (to induce remission) in severe cases of uveitis.
- Golimumab (Simponi, MSD) is a novel human anti-TNF-α antibody administered subcutaneously once per month. Injections are less frequent and easier to perform with a pen-type syringe which is also less painful. There is less experience regarding the use of golimumab in ophthalmology, but there is evidence that it could constitute a valid option as an anti-TNF rescue therapy when infliximab or adalimumab fail (Cordero-Coma et al., 2014). Furthermore, golimumab is particularly useful in cases of uveitis associated with JIA and macular oedema that have become refractory to other anti-TNF treatments.
- Certolizumab pegol (Cimzia, UCB) is administered subcutaneously every 15 days and features the advantages of degrading more slowly (which means it has a longer half-life) and it does not cross the placental barrier. Although the only scientific evidence regarding its use in uveitis comes down to a single article published by our own research group (Llorenç et al., 2014), certolizumab pegol may represent a valid option for patients with uveitis who require anti-TNF treatment and who are of a child-bearing age.
Side effects of eye drops, corticosteroids or 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).