Steroid-Sparing Immunosuppression for Uveitis

Steroid-sparing immunosuppression means using drugs other than corticosteroids to control chronic eye inflammation.

Steroids work quickly, but their side effects limit long-term use, so patients with persistent disease need a second drug.

The choice depends on the disease, the patient, and the monitoring available.

---

When Is Steroid-Sparing Immunosuppression Needed?

• A low dose of prednisone, usually about 7.5 milligrams per day, or topical drops used more than twice a day cannot control the inflammation
• Frequent relapses occur when the steroid is tapered
• Steroid side effects, such as raised pressure, cataract, diabetes, or osteoporosis, are present or likely
• The disease is sight-threatening, such as with retinal vasculitis, or macular edema
• Specific diseases, such as JIA uveitis, Behçet disease, or VKH, have a high chance of chronic course (see juvenile idiopathic arthritis uveitis)

Exclude infectious causes first, and masquerade syndromes too (see uveitis masquerade syndromes).

Steroid-Sparing Immunosuppression: Methotrexate

• An antimetabolite, given once a week by mouth or injection, at 15 to 25 milligrams, with folic acid
• Widely used and well studied, in adults and children
• Monitor blood counts and liver tests, and avoid in pregnancy and in heavy alcohol use
• Side effects include nausea, fatigue, mouth ulcers, and liver and lung effects

It takes weeks to months to reach full effect.

Mycophenolate Mofetil

• An inhibitor of lymphocyte proliferation, given twice daily at 1 to 1.5 grams
• Often used in uveitis, with good tolerance and less liver toxicity than methotrexate
• Side effects include gastrointestinal upset and low blood counts
• Contraindicated in pregnancy

The FAST trial compared methotrexate with mycophenolate in noninfectious uveitis, and found a higher rate of treatment success with methotrexate, 67 percent versus 57 percent, though the difference was not statistically significant (see the references).

Steroid-Sparing Immunosuppression: Azathioprine

• A purine analog used at 2 to 3 milligrams per kilogram per day
• Useful in Behçet disease and in some forms of intermediate uveitis
• Monitor blood counts and liver tests, and consider testing for TPMT activity
• Side effects include nausea, infection, and bone marrow suppression

Calcineurin Inhibitors

• Cyclosporine and tacrolimus: inhibit T cell activation, and can be used alone or with another drug
• Risks include kidney damage and hypertension, so blood pressure and creatinine need regular checks
• Used in Behçet disease, VKH, and refractory cases

Steroid-Sparing Immunosuppression: Alkylating Agents and Others

• Cyclophosphamide and chlorambucil: reserved for severe disease, such as scleritis or necrotizing vasculitis, under specialist control
• Biologics: including adalimumab, which has stronger evidence in several disorders, and doctors often use it when conventional agents fail (see adalimumab for uveitis)

Monitoring and Safety

• A baseline check of blood counts, liver and kidney function, and screening for infection
• Repeat blood tests every few weeks at the start, and then every few months
• Avoid live vaccines, and discuss pregnancy plans in advance
• Work with a physician or a rheumatologist who manages immunosuppression

Guidelines by expert panels describe the recommended use of these drugs (see the references).

Steroid-Sparing Immunosuppression: How Long to Treat?

Doctors often continue treatment for at least two years after the eye is quiet, and then taper it slowly under supervision.

Some patients need long-term therapy.

Choosing the First Agent

• JIA uveitis: methotrexate is the common first choice, with a biologic added if the control is not enough
• Behçet disease: doctors use azathioprine, cyclosporine, and biologics early because of the risk of vision loss (see Behçet uveitis)
• Birdshot and other posterior diseases: mycophenolate or methotrexate, with a biologic when needed
• Sarcoid uveitis: methotrexate, mycophenolate, or biologics (see sarcoid uveitis)

The choice also depends on pregnancy plans, liver disease, kidney function, and the patient’s ability to attend for blood tests.

Combination Therapy

When one drug does not control the disease, adding a second agent, such as a calcineurin inhibitor with an antimetabolite, may help.

A physician experienced with immunosuppression does this, because the risk of infection and toxicity rises.

Local Alternatives

In unilateral or asymmetric disease, local steroid implants and injections can reduce the need for systemic drugs, with a trade-off in cataract and pressure rise (see fluocinolone acetonide implants).

Communication With the Patient

Explain that these drugs take weeks to work, that blood tests are needed, and that the aim is to reduce steroid exposure.

Provide written information on side effects and on when to seek help.

Record the starting date, the dose, the blood test results, and the steroid dose at each visit, and share the file with the physician, so that you can judge the response and toxicity noticed early.

---

References

1. Rathinam SR, Gonzales JA, Thundikandy R, et al. Effect of corticosteroid-sparing treatment with mycophenolate mofetil vs methotrexate on inflammation in patients with uveitis: the FAST randomized clinical trial. JAMA. 2019;322:936-945.
2. Jabs DA, Rosenbaum JT, Foster CS, et al. Guidelines for the use of immunosuppressive drugs in patients with ocular inflammatory disorders: recommendations of an expert panel. Am J Ophthalmol. 2000;130:492-513.
3. Foster CS, Vitale AT. Diagnosis and Treatment of Uveitis. 2nd ed. Jaypee; 2013.
4. American Academy of Ophthalmology. Basic and Clinical Science Course, Section 9: Uveitis and Ocular Inflammation. AAO; current edition.