The goal of uveitis treatment is to control inflammation and prevent vision loss while minimizing side effects from treatment. The treatment strategy varies depending on the cause, severity, and course of inflammation.
If the underlying disease is infectious, appropriate treatment against the pathogen is prioritized. For non-infectious or autoimmune cases, a stepwise approach using anti-inflammatory therapy and immunomodulatory therapy (stepladder approach) is necessary. When systemic autoimmune disease is present, collaboration with other departments such as rheumatology is common 1).
In an international survey of 221 uveitis specialists from 53 countries, 68.8% co-managed with other specialists (93.4% with rheumatology) when using systemic immunomodulatory drugs 1).
In infectious uveitis, antimicrobial drugs targeting the causative pathogen are the highest priority. Steroid monotherapy may worsen the infection. In non-infectious uveitis, steroids are used as the basis for anti-inflammatory treatment, and immunomodulatory drugs are added stepwise as needed.
Subjective symptoms of uveitis vary depending on the location and severity of inflammation.
Findings correspond to the location and severity of inflammation.
The causes of uveitis are broadly classified into infectious and non-infectious.
In Japan, sarcoidosis is the most common cause of uveitis.
Before starting treatment for uveitis, it is essential to differentiate between infectious and non-infectious causes.
Blood tests, imaging studies, and referral to other specialties are important for identifying the underlying cause.
Before initiating immunomodulatory therapy, pretreatment screening is performed in all cases1). International surveys report blood chemistry tests (98.2%), blood tests (93.7%), and QuantiFERON tests (88.7%)1).
Mydriatics relieve spasm of the ciliary muscle and pupillary sphincter, reducing pain and photophobia. They are also used to prevent or break posterior synechiae. If posterior synechiae are present, frequent instillation of mydriatics is attempted to break the adhesions.
The duration of action of main mydriatics is shown below.
| Drug | Duration |
|---|---|
| Tropicamide 0.5–1% | 6 hours |
| Cyclopentolate 0.5–1% | 24 hours |
| Homatropine 2% | Up to 2 days |
| Atropine 1% | Up to 2 weeks |
In Japan, tropicamide (Mydrin M) is often prescribed as 1–3 drops per day.
Corticosteroids are the mainstay of uveitis treatment. Routes of administration are broadly divided into eye drops, local injection, and systemic administration.
These are the first choice for anterior uveitis. Depending on the degree of inflammation, drops are administered 1–8 times per day, and the dose is tapered as inflammation subsides.
In Japan, betamethasone sodium phosphate (Rinderon 0.1%) is often used 4–6 times daily. 0.05% difluprednate 4 times daily is as effective as 1% prednisolone acetate 8 times daily.
After inflammation subsides, switching to NSAID eye drops or fluorometholone is important to prevent steroid-induced glaucoma.
Considered for severe unilateral uveitis, cystoid macular edema (CME), or when systemic therapy is contraindicated. Routes include subconjunctival, sub-Tenon, and intravitreal.
Indicated when local treatment is insufficient, or in bilateral or systemic disease.
In Behçet’s disease, severe inflammatory attacks may occur after tapering or discontinuing systemic steroid therapy. Short-term use for about one week is limited to cases with marked exudative changes in the macula.
In Vogt-Koyanagi-Harada disease, high-dose steroid therapy (pulse therapy) is common. Tapering should be done slowly, and even without recurrence, discontinuation should take at least 6 months.
Side Effects of Steroids
Ocular side effects: Cataracts, increased intraocular pressure, glaucoma. Long-term use of 3 months or more increases the risk of elevated intraocular pressure 2).
Systemic side effects: Diabetes, hypertension, peptic ulcer, insomnia, osteoporosis, moon face, withdrawal syndrome.
Measures for long-term use: Calcium and vitamin D supplementation, regular intraocular pressure monitoring are necessary.
Principles of Steroid Tapering
Rapid tapering: For 60–30 mg/day, reduce by 10 mg every 2 days.
Standard tapering: For 60–30 mg/day, reduce by 10 mg weekly. Below 15 mg, reduce cautiously by 2.5 mg.
At recurrence: Increase the dose temporarily, then taper more slowly than before.
To avoid long-term steroid use, immunomodulatory therapy is essential for managing non-infectious uveitis.
The main indications for starting systemic immunomodulatory drugs are as follows 1).
| Class | Main Drugs |
|---|---|
| Antimetabolites | Methotrexate, Mycophenolate Mofetil, Azathioprine |
| Calcineurin Inhibitors | Cyclosporine, Tacrolimus |
| Alkylating Agents | Cyclophosphamide, Chlorambucil |
In international surveys, methotrexate is the most commonly used first-line agent (57.0%)1). Methotrexate successfully controls inflammation in over 70% of uveitis patients, but the discontinuation rate in the first year is about 30% due to side effects such as liver dysfunction, nausea, and hair loss2). Concomitant folic acid supplementation is recommended2).
Mycophenolate mofetil is a useful alternative with a lower risk of side effects2). The FAST trial showed equivalent efficacy between methotrexate and mycophenolate mofetil.
Cyclosporine is an effective second-line agent, but its use is limited by side effects such as renal dysfunction and hypertension2). In Japan, it is administered at a target dose of 5 mg/kg/day for Behçet’s disease, with regular monitoring of blood concentration (trough level 50–200 ng/mL) and renal function. Caution is needed for myopathy when used with colchicine.
Cyclophosphamide has stronger immunosuppressive potency than methotrexate or mycophenolate mofetil2). Chlorambucil is used for severe cases resistant to steroids and steroid-sparing agents2).
In an international survey, 97.7% of specialists considered adalimumab as the first-line biologic agent1).
Adalimumab has demonstrated efficacy in non-infectious intermediate, posterior, and panuveitis in the VISUAL I, II, and III trials.
In Behçet’s disease, when inflammatory attacks cannot be controlled with colchicine or cyclosporine, infliximab (Remicade) 5 mg/kg is administered as an intravenous infusion every 2 months. Attack suppression can be expected in many cases, but primary and secondary non-response also occur.
In the traditional step-ladder approach, conventional agents are used first, but 60.2% of specialists reported having used biologics first-line for specific diagnoses1). Efficacy assessment is performed after a trial period of 3–6 months (81.9%)1).
If prednisone at >7.5 mg/day is continued for 3 months or longer, introduction of a steroid-sparing agent (immunomodulatory drug) is recommended to reduce side effects. International surveys show that the majority of specialists avoid long-term high-dose steroid use 1).
Surgical treatment may be necessary for complications of uveitis.
Macular edema is a major cause of vision loss in uveitis.
Yes, they differ. International surveys show that for juvenile idiopathic arthritis-associated uveitis, methotrexate (93.2%) and adalimumab (97.3%) are preferred; for birdshot retinochoroidopathy, mycophenolate mofetil (39.8%) and adalimumab (93.2%) are often selected, indicating that recommended drugs vary by disease 1).
The pathology of non-infectious uveitis is primarily driven by autoimmune and autoinflammatory mechanisms.
The essence of inflammation is the migration and activation of immune cells into the uveal tissue. Infiltration of T cells, macrophages, neutrophils, and others leads to tissue damage. Cytokines, particularly TNF-α, play a central role in amplifying and sustaining inflammation.
Normally, the blood-ocular barrier restricts the entry of immune cells and proteins into the eye. In uveitis, this barrier breaks down, leading to increased vascular permeability, flare, and cellular infiltration.
Each therapeutic agent intervenes in the inflammatory cascade through the following mechanisms:
Key clinical trials on uveitis treatment are listed below.
In an international survey of 53 countries (Branford et al., 2025), contrary to the traditional step-ladder approach, 60.2% of specialists reported having used biologics prior to conventional drugs for specific diagnoses 1). Treatment strategies are shifting toward optimal drug selection for each disease and personalized treatment.
As a new-generation drug, the phase III CLARITY trial evaluating the oral TYK2/JAK1 dual inhibitor brepocitinib (for non-infectious intermediate, posterior, and panuveitis) is ongoing. Additionally, the phase III MEERKAT/SANDCAT trials evaluating the intravitreal IL-6 pathway inhibitor vamikibart (for uveitic macular edema) are being conducted. Local inhibition of IL-6 may control ocular inflammation and macular edema while avoiding systemic side effects.
Small molecule targeted drugs such as JAK inhibitors (tofacitinib, baricitinib) are attracting attention as new treatment options. In addition, drugs targeting various cytokine pathways, such as anti-IL-17A (secukinumab) and anti-IL-12/23 (ustekinumab), are also being investigated.
