Indications

The use of IMT in treatment of uveitis is warranted for consideration in the following settings:

• vision-threatening intraocular inflammation

• inadequate response to corticosteroid treatment

• corticosteroids contraindicated because of systemic problems or intolerable adverse effects

• long-term corticosteroid dependence

Certain ocular inflammatory entities warrant the early use of IMT, including ocular cicatricial pemphigoid, serpiginous choroiditis, Behçet disease, sympathetic ophthalmia, Vogt-Koyanagi-Harada (VKH) syndrome, and necrotizing scleritis associated with systemic vasculitis. Although these disorders may initially respond well to corticosteroids, the initial treatment of these entities with IMT has been shown to improve long-term prognosis and lessen visual morbidity. Several expert-panel recommendations have been published to establish consensus on how and when to select, initiate, modify, and withdraw nonbiologic-IMT or biologic agents.

Treatment

Before initiation of IMT, the physician should evaluate the following:

• absence of infection

• absence of recent live vaccine administration

• absence of hepatic, renal, and hematologic contraindications

• absence of pregnancy or breastfeeding

• family planning and contraception

• meticulous follow-up available from a physician who is, by virtue of training and experience, qualified to counsel, prescribe, and safely monitor such medications and personally manage their potential toxicities

• objective longitudinal evaluation of the disease process

• informed consent

There may be a delay in therapeutic response for weeks to months after initiation of nonbiologic-IMT; biologic agents typically have a more rapid onset. Most patients need to be maintained on corticosteroids until the immunomodulatory agent begins to take effect, at which time the corticosteroid dose may be gradually tapered.

Because of the potentially serious complications associated with the use of IMT, patients must be monitored closely by a practitioner experienced with IMT. Blood monitoring, including complete blood count with differential and liver and renal function tests, should be performed regularly. Serious complications of nonbiologic-IMT include renal and hepatic toxicity and bone marrow suppression. Alkylating agents may cause sterility and are associated with an increased risk of malignancies, such as leukemia or lymphoma. Certain biologic agents may promote an infusion or injection reaction; TNF inhibitors increase the risk of multiple sclerosis and lymphoma. All IMT increases the risk of opportunistic and secondary infection.

However, the SITE cohort study of 7957 patients (66,802 patient-years) with noninfectious uveitis treated with IMT showed that patients who took azathioprine, methotrexate, mycophenolate mofetil, cyclosporine, or systemic corticosteroids had overall cancer mortality rates similar to those who never took those medications; the study confirmed that TNF inhibitors were associated with increased overall (twofold) and cancer (3.8-fold) risk of mortality. While there is no direct evidence in uveitis patients, IMT may be associated with an increased risk of nonmelanoma skin cancer, warranting sunscreen counseling. Trimethoprim–sulfamethoxazole prophylaxis against Pneumocystis jirovecii infection should be considered in patients receiving alkylating agents, or in those on intermediate-term high-dose steroids and IMT. The physician should obtain thorough informed consent prior to initiating IMT.

Male and female patients require counseling regarding fertility, birth control, and family planning prior to initiation of IMT. Many IMT medications have absolute contra-indications in pregnancy. Generally, IMT should be discontinued 3 months prior to trying to conceive.

• Dick AD, Rosenbaum JT, Al-Dhibi HA, et al; Fundamentals of Care for Uveitis International Consensus Group. Guidance on noncorticosteroid systemic immunomodulatory therapy in noninfectious uveitis: Fundamentals Of Care for UveitiS (FOCUS) initiative. Ophthalmology. 2018;125(5):757–773.

• Jabs DA. Immunosuppression for the uveitides. Ophthalmology. 2018;125(2):193–202.

• 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(4):492–513.

• Kempen JH, Daniel E, Dunn JP, et al. Overall and cancer related mortality among patients with ocular inflammation treated with immunosuppressive drugs: retrospective cohort study. BMJ. 2009;339:b2480.

• Leroy C, Rigot J-M, Leroy M, et al. Immunosuppressive drugs and fertility. Orphanet J Rare Dis. 2015;10:136.

• Levy-Clarke G, Jabs DA, Read RW, Rosenbaum JT, Vitale A, Van Gelder RN. Expert panel recommendations for the use of anti-tumor necrosis factor biologic agents in patients with ocular inflammatory disorders. Ophthalmology. 2014;121(3):785–796.

• Nguyen QD, Callanan D, Dugel P, Godfrey DG, Goldstein DA, Wilensky JT. Treating chronic noninfectious posterior segment uveitis: the impact of cumulative damage. Proceedings of an expert panel roundtable discussion. Retina. 2006;26(8)1–16.

• Wakefield D, McCluskey P, Wildner G, et al. Inflammatory eye disease: pre-treatment assessment of patients prior to commencing immunosuppressive and biologic therapy: recommendations from an expert committee. Autoimmun Rev. 2017;16(3):213–222.

• Yates WB, Vajdic CM, Na R, McCluskey PJ, Wakefield D. Malignancy risk in patients with inflammatory eye disease treated with systemic immunosuppressive therapy: a tertiary referral cohort study. Ophthalmology. 2015;122(2):265–273.

Excerpted from BCSC 2020-2021 series: Section 9 - Uveitis and Ocular Inflammation. For more information and to purchase the entire series, please visit https://www.aao.org/bcsc.