Treatment algorithm
Please note that formulations/routes and doses may differ between drug names and brands, drug formularies, or locations. Treatment recommendations are specific to patient groups: see disclaimer
noninfectious: initial presentation
topical ophthalmic corticosteroid + management of any underlying disease
All patients should be referred early to an ophthalmologist for management.
Corticosteroid therapy is first-line for acute noninfectious uveitis; topical ophthalmic formulations are indicated for anterior chamber inflammation.[3]Burkholder BM, Jabs DA. Uveitis for the non-ophthalmologist. BMJ. 2021 Feb 3;372:m4979. http://www.ncbi.nlm.nih.gov/pubmed/33536186?tool=bestpractice.com [60]Foster CS, Kothari S, Anesi SD, et al. The Ocular Immunology and Uveitis Foundation preferred practice patterns of uveitis management. Surv Ophthalmol. 2016 Jan-Feb;61(1):1-17. http://www.ncbi.nlm.nih.gov/pubmed/26164736?tool=bestpractice.com Management of any underlying disease should occur concurrently.
Effective use of corticosteroid eye drops requires frequent dosing, especially at the beginning of treatment; the most common reason for treatment failure is insufficient dosing. Corticosteroid eye drops may be instilled up to hourly when initiating treatment of acute anterior uveitis, with a subsequent taper depending on the severity of the initial presentation.[60]Foster CS, Kothari S, Anesi SD, et al. The Ocular Immunology and Uveitis Foundation preferred practice patterns of uveitis management. Surv Ophthalmol. 2016 Jan-Feb;61(1):1-17. http://www.ncbi.nlm.nih.gov/pubmed/26164736?tool=bestpractice.com Dose and duration is tailored to the patient.
Adverse effects of topical corticosteroids (including elevation of intraocular pressure, posterior subcapsular cataract, and subconjunctival hemorrhage) limit their long-term use.[3]Burkholder BM, Jabs DA. Uveitis for the non-ophthalmologist. BMJ. 2021 Feb 3;372:m4979. http://www.ncbi.nlm.nih.gov/pubmed/33536186?tool=bestpractice.com [61]Mercieca K, Sanghvi C, Jones NP. Spontaneous sub-conjunctival haemorrhage in patients using long-term topical corticosteroids. Eye (Lond). 2010 Dec;24(12):1770-1. https://www.nature.com/articles/eye2010118 http://www.ncbi.nlm.nih.gov/pubmed/20930855?tool=bestpractice.com
Pregnant women should be referred early to an ophthalmologist for management; topical ophthalmic corticosteroids such as prednisolone are generally considered safe.[91]Chiam NP, Lim LL. Uveitis and gender: the course of uveitis in pregnancy. J Ophthalmol. 2014;2014:401915. https://pmc.ncbi.nlm.nih.gov/articles/PMC3941965 http://www.ncbi.nlm.nih.gov/pubmed/24683491?tool=bestpractice.com [92]Bandoli G, Palmsten K, Forbess Smith CJ, et al. A review of systemic corticosteroid use in pregnancy and the risk of select pregnancy and birth outcomes. Rheum Dis Clin North Am. 2017 Aug;43(3):489-502. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5604866 http://www.ncbi.nlm.nih.gov/pubmed/28711148?tool=bestpractice.com [93]Chambers CD, Johnson DL, Xu R, et al. Birth outcomes in women who have taken adalimumab in pregnancy: a prospective cohort study. PLoS One. 2019;14(10):e0223603. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6799916 http://www.ncbi.nlm.nih.gov/pubmed/31626646?tool=bestpractice.com
Primary options
prednisolone acetate ophthalmic: (1% solution) 1-2 drops into the affected eye(s) twice to four times daily
OR
dexamethasone ophthalmic: (0.1%) 1-2 drops into the affected eye(s) four to six times daily
OR
fluorometholone ophthalmic: (0.1%) 1-2 drops into the affected eye(s) twice to four times daily
OR
difluprednate ophthalmic: (0.05%) 1 drop into the affected eye(s) four times daily
cycloplegic
Treatment recommended for SOME patients in selected patient group
Topical cycloplegics (e.g., atropine) are used as adjunct to corticosteroid therapy to reduce pain and minimize spasm to the ciliary body.
Cycloplegics can be used if the inflammation is causing synechiae or the uveitis is fibrinous, as can happen with human leukocyte antigen (HLA)-B27-related uveitis or various granulomatous uveitic conditions.[60]Foster CS, Kothari S, Anesi SD, et al. The Ocular Immunology and Uveitis Foundation preferred practice patterns of uveitis management. Surv Ophthalmol. 2016 Jan-Feb;61(1):1-17. http://www.ncbi.nlm.nih.gov/pubmed/26164736?tool=bestpractice.com
Primary options
atropine ophthalmic: (1%) apply ointment into the affected eye(s) once or twice daily
periocular or intraocular corticosteroid
Infectious causes should be ruled out before moving to periocular or intraocular corticosteroid injections.
Periocular (regional) corticosteroid injections may be preferred in a patient who is noncompliant with, or poorly responsive to, topical corticosteroid therapy (that was otherwise safe and well tolerated).[60]Foster CS, Kothari S, Anesi SD, et al. The Ocular Immunology and Uveitis Foundation preferred practice patterns of uveitis management. Surv Ophthalmol. 2016 Jan-Feb;61(1):1-17. http://www.ncbi.nlm.nih.gov/pubmed/26164736?tool=bestpractice.com In patients responsive to initial topical corticosteroid, periocular corticosteroid can sustain local anti-inflammatory effects. Periocular administration is considered in patients with intermediate or posterior uveitis because it allows the corticosteroid to be delivered close to the site of inflammation.[60]Foster CS, Kothari S, Anesi SD, et al. The Ocular Immunology and Uveitis Foundation preferred practice patterns of uveitis management. Surv Ophthalmol. 2016 Jan-Feb;61(1):1-17. http://www.ncbi.nlm.nih.gov/pubmed/26164736?tool=bestpractice.com
Adverse effects of periocular corticosteroid injections include: intraocular pressure elevation (glaucoma; posterior subcapsular cataract); hyperglycemia in patients with diabetes (may occur approximately 6 hours after dexamethasone injection); injection-site scarring (can complicate repeat injections); subconjunctival hemorrhage (avoid injections at the cardinal clock hours [12, 3, 6, 9] to prevent trauma to the anterior ciliary arteries); pain (corticosteroid injections can be mixed with a local anesthetic such as lidocaine); inadvertent penetrating globe trauma.[62]Sen HN, Vitale S, Gangaputra SS, et al. Periocular corticosteroid injections in uveitis: effects and complications. Ophthalmology. 2014 Nov;121(11):2275-86. https://pmc.ncbi.nlm.nih.gov/articles/PMC4254355 http://www.ncbi.nlm.nih.gov/pubmed/25017415?tool=bestpractice.com [63]Feldman-Billard S, Du Pasquier-Fediaevsky L, Héron E. Hyperglycemia after repeated periocular dexamethasone injections in patients with diabetes. Ophthalmology. 2006 Oct;113(10):1720-3. http://www.ncbi.nlm.nih.gov/pubmed/17011953?tool=bestpractice.com [64]Polski A, Liu KC, Gupta D, et al. Incident glaucoma and ocular hypertension after periocular and intravitreal steroid injections: a claims-based analysis. BMJ Open Ophthalmol. 2023 Dec 22;8(1):e001508. https://bmjophth.bmj.com/content/8/1/e001508 http://www.ncbi.nlm.nih.gov/pubmed/38135349?tool=bestpractice.com
Intraocular corticosteroid injections are used for severe posterior uveitis and acute inflammation unresponsive to periocular corticosteroid injections; discussion of risks should be documented in medical notes.[60]Foster CS, Kothari S, Anesi SD, et al. The Ocular Immunology and Uveitis Foundation preferred practice patterns of uveitis management. Surv Ophthalmol. 2016 Jan-Feb;61(1):1-17. http://www.ncbi.nlm.nih.gov/pubmed/26164736?tool=bestpractice.com Intraocular corticosteroids may also serve as a bridge to corticosteroid-sparing therapies.
Adverse effects of intraocular corticosteroid injection include those documented for periocular corticosteroid injection. Endophthalmitis, a form of infectious panuveitis, and pseudoendophthalmitis have also been reported.[65]José-Vieira R, Ferreira A, Menéres P, et al. Efficacy and safety of intravitreal and periocular injection of corticosteroids in noninfectious uveitis: a systematic review. Surv Ophthalmol. 2022 Jul-Aug;67(4):991-1013. http://www.ncbi.nlm.nih.gov/pubmed/34896190?tool=bestpractice.com [66]Reichle ML. Complications of intravitreal steroid injections. Optometry. 2005 Aug;76(8):450-60. http://www.ncbi.nlm.nih.gov/pubmed/16150412?tool=bestpractice.com [67]Jaffe GJ, Martin D, Callanan D, et al. Fluocinolone acetonide implant (Retisert) for noninfectious posterior uveitis: thirty-four-week results of a multicenter randomized clinical study. Ophthalmology. 2006 Jun;113(6):1020-7. http://www.ncbi.nlm.nih.gov/pubmed/16690128?tool=bestpractice.com The latter presents as a dense vitritis with hypopyon 1-3 days following intravitreal injection. The anterior chamber will show a dense cellular reaction with almost no flare (as opposed to the fibrinoid reaction characteristic of infectious endophthalmitis). It clears without therapy over 1-8 weeks.
Sustained-release corticosteroid implants (e.g., dexamethasone or fluocinolone intravitreal implant) may be indicated in patients who fail to respond to, or are intolerant of, intraocular corticosteroid injections.[3]Burkholder BM, Jabs DA. Uveitis for the non-ophthalmologist. BMJ. 2021 Feb 3;372:m4979. http://www.ncbi.nlm.nih.gov/pubmed/33536186?tool=bestpractice.com [60]Foster CS, Kothari S, Anesi SD, et al. The Ocular Immunology and Uveitis Foundation preferred practice patterns of uveitis management. Surv Ophthalmol. 2016 Jan-Feb;61(1):1-17. http://www.ncbi.nlm.nih.gov/pubmed/26164736?tool=bestpractice.com Implants can be given by intravitreal injection or by surgical fixation to the sclera. Corticosteroid implants are not considered to be first-line therapeutic options.[60]Foster CS, Kothari S, Anesi SD, et al. The Ocular Immunology and Uveitis Foundation preferred practice patterns of uveitis management. Surv Ophthalmol. 2016 Jan-Feb;61(1):1-17. http://www.ncbi.nlm.nih.gov/pubmed/26164736?tool=bestpractice.com
Pregnant women should be referred early to an ophthalmologist for management; intravitreal corticosteroids may be considered by a specialist if benefits outweigh risks.[91]Chiam NP, Lim LL. Uveitis and gender: the course of uveitis in pregnancy. J Ophthalmol. 2014;2014:401915. https://pmc.ncbi.nlm.nih.gov/articles/PMC3941965 http://www.ncbi.nlm.nih.gov/pubmed/24683491?tool=bestpractice.com [92]Bandoli G, Palmsten K, Forbess Smith CJ, et al. A review of systemic corticosteroid use in pregnancy and the risk of select pregnancy and birth outcomes. Rheum Dis Clin North Am. 2017 Aug;43(3):489-502. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5604866 http://www.ncbi.nlm.nih.gov/pubmed/28711148?tool=bestpractice.com [93]Chambers CD, Johnson DL, Xu R, et al. Birth outcomes in women who have taken adalimumab in pregnancy: a prospective cohort study. PLoS One. 2019;14(10):e0223603. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6799916 http://www.ncbi.nlm.nih.gov/pubmed/31626646?tool=bestpractice.com
Primary options
triamcinolone intravitreal: consult specialist for guidance on periocular or intraocular dose
OR
dexamethasone intraocular: consult specialist for guidance on periocular or intraocular dose
Secondary options
dexamethasone intravitreal: (implant) consult specialist for guidance on dose
OR
fluocinolone intravitreal: (implant) consult specialist for guidance on dose
cycloplegic
Treatment recommended for SOME patients in selected patient group
Topical cycloplegics (e.g., atropine) are used as adjunct to corticosteroid therapy to reduce pain and minimize spasm to the ciliary body.
Cycloplegics can be used if the inflammation is causing synechiae or the uveitis is fibrinous, as can happen with HLA-B27-related uveitis or various granulomatous uveitic conditions.[60]Foster CS, Kothari S, Anesi SD, et al. The Ocular Immunology and Uveitis Foundation preferred practice patterns of uveitis management. Surv Ophthalmol. 2016 Jan-Feb;61(1):1-17. http://www.ncbi.nlm.nih.gov/pubmed/26164736?tool=bestpractice.com
Primary options
atropine ophthalmic: (1%) apply ointment into the affected eye(s) once or twice daily
oral or intravenous corticosteroid
Infectious causes should be ruled out before moving to systemic corticosteroids.
Oral corticosteroids may be used in severe bilateral or recalcitrant uveitis, or if patients cannot tolerate corticosteroid injections.[60]Foster CS, Kothari S, Anesi SD, et al. The Ocular Immunology and Uveitis Foundation preferred practice patterns of uveitis management. Surv Ophthalmol. 2016 Jan-Feb;61(1):1-17. http://www.ncbi.nlm.nih.gov/pubmed/26164736?tool=bestpractice.com An oral corticosteroid facilitates immediate control, and may be followed by periocular injection (when tolerated in a patient with confirmed immune-mediated uveitis) to minimize systemic adverse effects. High-dose oral corticosteroid therapy is prescribed initially, and the dose tapered to clinical effect.[60]Foster CS, Kothari S, Anesi SD, et al. The Ocular Immunology and Uveitis Foundation preferred practice patterns of uveitis management. Surv Ophthalmol. 2016 Jan-Feb;61(1):1-17. http://www.ncbi.nlm.nih.gov/pubmed/26164736?tool=bestpractice.com [68]American Academy of Ophthalmology. EyeWiki: treatment of uveitis. Dec 2023 [internet publication]. https://eyewiki.org/Treatment_of_Uveitis
Potential adverse effects associated with prolonged use of oral corticosteroids include hypertension, bone fracture, metabolic issues, and gastrointestinal disturbances.[69]Rice JB, White AG, Scarpati LM, et al. Long-term systemic corticosteroid exposure: a systematic literature review. Clin Ther. 2017 Nov;39(11):2216-29. https://www.clinicaltherapeutics.com/article/S0149-2918(17)30985-2/fulltext http://www.ncbi.nlm.nih.gov/pubmed/29055500?tool=bestpractice.com H2 antagonists or proton-pump inhibitors (PPIs) are recommended to reduce the risk for gastric ulcer among patients receiving high-dose oral corticosteroids, particularly when taking a concomitant systemic nonsteroidal anti-inflammatory drug (NSAID).[60]Foster CS, Kothari S, Anesi SD, et al. The Ocular Immunology and Uveitis Foundation preferred practice patterns of uveitis management. Surv Ophthalmol. 2016 Jan-Feb;61(1):1-17. http://www.ncbi.nlm.nih.gov/pubmed/26164736?tool=bestpractice.com [68]American Academy of Ophthalmology. EyeWiki: treatment of uveitis. Dec 2023 [internet publication]. https://eyewiki.org/Treatment_of_Uveitis
Postmenopausal or older women maintained on corticosteroid therapy for >3 months should be encouraged to supplement their diet with calcium and vitamin D (to reduce osteoporosis risk), and to perform regular weight-bearing exercise.[60]Foster CS, Kothari S, Anesi SD, et al. The Ocular Immunology and Uveitis Foundation preferred practice patterns of uveitis management. Surv Ophthalmol. 2016 Jan-Feb;61(1):1-17. http://www.ncbi.nlm.nih.gov/pubmed/26164736?tool=bestpractice.com Bone mineral density screening is recommended for patients taking corticosteroids >3 months, or for those taking high doses. Bone preservation therapy (e.g., a bisphosphonate) should be considered.[60]Foster CS, Kothari S, Anesi SD, et al. The Ocular Immunology and Uveitis Foundation preferred practice patterns of uveitis management. Surv Ophthalmol. 2016 Jan-Feb;61(1):1-17. http://www.ncbi.nlm.nih.gov/pubmed/26164736?tool=bestpractice.com Note that bisphosphonates are not typically recommended in individuals age <18 years and in pregnancy; they should be used with caution in women of childbearing age.[70]Losada I, Sartori L, Di Gianantonio E, et al. Bisphosphonates in patients with autoimmune rheumatic diseases: Can they be used in women of childbearing age? Autoimmun Rev. 2010 Jun;9(8):547-52. http://www.ncbi.nlm.nih.gov/pubmed/20307690?tool=bestpractice.com
Intravenous corticosteroids (e.g., high-dose methylprednisolone) are rarely considered, but may be indicated in specific clinical scenarios: severe, noninfectious posterior uveitis or panuveitis; intraoperatively, in patients at substantial risk of postoperative inflammation; in patients at imminent danger of visual loss, and/or with extreme pain (usually due to scleritis).[60]Foster CS, Kothari S, Anesi SD, et al. The Ocular Immunology and Uveitis Foundation preferred practice patterns of uveitis management. Surv Ophthalmol. 2016 Jan-Feb;61(1):1-17. http://www.ncbi.nlm.nih.gov/pubmed/26164736?tool=bestpractice.com [68]American Academy of Ophthalmology. EyeWiki: treatment of uveitis. Dec 2023 [internet publication]. https://eyewiki.org/Treatment_of_Uveitis A short course of intravenous corticosteroids may be administered in these circumstances, followed by a gradual taper of an oral corticosteroid.[60]Foster CS, Kothari S, Anesi SD, et al. The Ocular Immunology and Uveitis Foundation preferred practice patterns of uveitis management. Surv Ophthalmol. 2016 Jan-Feb;61(1):1-17. http://www.ncbi.nlm.nih.gov/pubmed/26164736?tool=bestpractice.com
Pregnant women should be referred early to an ophthalmologist for management; systemic corticosteroids may be considered by a specialist if benefits outweigh risks.[91]Chiam NP, Lim LL. Uveitis and gender: the course of uveitis in pregnancy. J Ophthalmol. 2014;2014:401915. https://pmc.ncbi.nlm.nih.gov/articles/PMC3941965 http://www.ncbi.nlm.nih.gov/pubmed/24683491?tool=bestpractice.com [92]Bandoli G, Palmsten K, Forbess Smith CJ, et al. A review of systemic corticosteroid use in pregnancy and the risk of select pregnancy and birth outcomes. Rheum Dis Clin North Am. 2017 Aug;43(3):489-502. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5604866 http://www.ncbi.nlm.nih.gov/pubmed/28711148?tool=bestpractice.com [93]Chambers CD, Johnson DL, Xu R, et al. Birth outcomes in women who have taken adalimumab in pregnancy: a prospective cohort study. PLoS One. 2019;14(10):e0223603. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6799916 http://www.ncbi.nlm.nih.gov/pubmed/31626646?tool=bestpractice.com
Primary options
prednisone: 1 mg/kg/day orally initially, followed by rapid or slow taper according to response, maximum 80 mg/day
Secondary options
methylprednisolone sodium succinate: consult specialist for guidance on dose
and
prednisone: 1 mg/kg/day orally initially (start after methylprednisolone course), followed by rapid or slow taper according to response, maximum 80 mg/day
cycloplegic
Treatment recommended for SOME patients in selected patient group
Topical cycloplegics (e.g., atropine) are used as adjunct to corticosteroid therapy to reduce pain and minimize spasm to the ciliary body.
Cycloplegics can be used if the inflammation is causing synechiae or the uveitis is fibrinous, as can happen with HLA-B27-related uveitis or various granulomatous uveitic conditions.[60]Foster CS, Kothari S, Anesi SD, et al. The Ocular Immunology and Uveitis Foundation preferred practice patterns of uveitis management. Surv Ophthalmol. 2016 Jan-Feb;61(1):1-17. http://www.ncbi.nlm.nih.gov/pubmed/26164736?tool=bestpractice.com
Primary options
atropine ophthalmic: (1%) apply ointment into the affected eye(s) once or twice daily
infectious
referral to specialist
Uveitis secondary to an infection is often aggressive and may lead to permanent blindness. Seek specialist advice.
Treatment of the infection may be regional and/or systemic. Antiviral, antimicrobial, antifungal, and antiparasitic treatment is considered depending on etiology.[3]Burkholder BM, Jabs DA. Uveitis for the non-ophthalmologist. BMJ. 2021 Feb 3;372:m4979. http://www.ncbi.nlm.nih.gov/pubmed/33536186?tool=bestpractice.com [49]Gueudry J, Muraine M. Anterior uveitis. J Fr Ophtalmol. 2018 Jan;41(1):e11-21. http://www.ncbi.nlm.nih.gov/pubmed/29290458?tool=bestpractice.com [60]Foster CS, Kothari S, Anesi SD, et al. The Ocular Immunology and Uveitis Foundation preferred practice patterns of uveitis management. Surv Ophthalmol. 2016 Jan-Feb;61(1):1-17. http://www.ncbi.nlm.nih.gov/pubmed/26164736?tool=bestpractice.com
Numerous infectious agents can result in uveitis. These may include: HIV-associated opportunistic infections (e.g., cytomegalovirus [CMV], Pneumocystis carinii, tuberculosis [TB], toxoplasmosis, candida); sexually transmitted infections (e.g., syphilis, gonorrhea, herpes simplex virus [HSV], chlamydia); congenital infections (TORCH: Toxoplasmosis, Other agents, Rubella, CMV, HSV); infections related to occupation/leisure (e.g., leptospirosis, brucellosis, toxoplasmosis, Bartonella henselae [cat-scratch disease]); geography-specific infections (e.g., histoplasmosis, coccidioidomycosis, Borrelia burgdorferi [Lyme disease], TB, malaria, leprosy); environment-specific infection (e.g., TB) exposure.[3]Burkholder BM, Jabs DA. Uveitis for the non-ophthalmologist. BMJ. 2021 Feb 3;372:m4979. http://www.ncbi.nlm.nih.gov/pubmed/33536186?tool=bestpractice.com [49]Gueudry J, Muraine M. Anterior uveitis. J Fr Ophtalmol. 2018 Jan;41(1):e11-21. http://www.ncbi.nlm.nih.gov/pubmed/29290458?tool=bestpractice.com [94]Ngathaweesuk Y, Hendrikse J, Groot-Mijnes JDF, et al. Causes of infectious pediatric uveitis: a review. Surv Ophthalmol. 2024 May-Jun;69(3):483-94. https://www.surveyophthalmol.com/article/S0039-6257(23)00172-8/fulltext http://www.ncbi.nlm.nih.gov/pubmed/38182040?tool=bestpractice.com
noninfectious: after immediate control of inflammation
immunomodulatory therapy + continued management of any underlying disease
Long-term treatment aims to control ocular and systemic disease while minimizing corticosteroid exposure.[3]Burkholder BM, Jabs DA. Uveitis for the non-ophthalmologist. BMJ. 2021 Feb 3;372:m4979. http://www.ncbi.nlm.nih.gov/pubmed/33536186?tool=bestpractice.com [60]Foster CS, Kothari S, Anesi SD, et al. The Ocular Immunology and Uveitis Foundation preferred practice patterns of uveitis management. Surv Ophthalmol. 2016 Jan-Feb;61(1):1-17. http://www.ncbi.nlm.nih.gov/pubmed/26164736?tool=bestpractice.com
Systemic immunomodulatory therapy is indicated in the presence of ocular factors (e.g., sight-threatening disease, chronic severe inflammation) and/or therapeutic factors (e.g., failure of regional or systemic corticosteroid therapy, high doses of systemic corticosteroid therapy).[68]American Academy of Ophthalmology. EyeWiki: treatment of uveitis. Dec 2023 [internet publication]. https://eyewiki.org/Treatment_of_Uveitis [71]Dick AD, Rosenbaum JT, Al-Dhibi HA, et al. Guidance on noncorticosteroid systemic immunomodulatory therapy in noninfectious uveitis: Fundamentals Of Care for UveitiS (FOCUS) Initiative. Ophthalmology. 2018 May;125(5):757-73. https://www.aaojournal.org/article/S0161-6420(17)32446-6/fulltext http://www.ncbi.nlm.nih.gov/pubmed/29310963?tool=bestpractice.com If prolonged oral corticosteroid therapy is anticipated (>3 months), systemic immunomodulatory therapy should be considered.[60]Foster CS, Kothari S, Anesi SD, et al. The Ocular Immunology and Uveitis Foundation preferred practice patterns of uveitis management. Surv Ophthalmol. 2016 Jan-Feb;61(1):1-17. http://www.ncbi.nlm.nih.gov/pubmed/26164736?tool=bestpractice.com Severe sight-threatening uveitis requires long-term immunomodulatory therapy.
The drug and the regimen should be determined by a specialist.[60]Foster CS, Kothari S, Anesi SD, et al. The Ocular Immunology and Uveitis Foundation preferred practice patterns of uveitis management. Surv Ophthalmol. 2016 Jan-Feb;61(1):1-17. http://www.ncbi.nlm.nih.gov/pubmed/26164736?tool=bestpractice.com The timing and choice of systemic immunomodulatory therapy is informed by the cause of intraocular inflammation.[60]Foster CS, Kothari S, Anesi SD, et al. The Ocular Immunology and Uveitis Foundation preferred practice patterns of uveitis management. Surv Ophthalmol. 2016 Jan-Feb;61(1):1-17. http://www.ncbi.nlm.nih.gov/pubmed/26164736?tool=bestpractice.com [71]Dick AD, Rosenbaum JT, Al-Dhibi HA, et al. Guidance on noncorticosteroid systemic immunomodulatory therapy in noninfectious uveitis: Fundamentals Of Care for UveitiS (FOCUS) Initiative. Ophthalmology. 2018 May;125(5):757-73. https://www.aaojournal.org/article/S0161-6420(17)32446-6/fulltext http://www.ncbi.nlm.nih.gov/pubmed/29310963?tool=bestpractice.com
Antimetabolites (e.g., methotrexate, azathioprine, mycophenolate) are commonly used, are dosed orally, and have manageable adverse effects.[3]Burkholder BM, Jabs DA. Uveitis for the non-ophthalmologist. BMJ. 2021 Feb 3;372:m4979. http://www.ncbi.nlm.nih.gov/pubmed/33536186?tool=bestpractice.com [60]Foster CS, Kothari S, Anesi SD, et al. The Ocular Immunology and Uveitis Foundation preferred practice patterns of uveitis management. Surv Ophthalmol. 2016 Jan-Feb;61(1):1-17. http://www.ncbi.nlm.nih.gov/pubmed/26164736?tool=bestpractice.com [71]Dick AD, Rosenbaum JT, Al-Dhibi HA, et al. Guidance on noncorticosteroid systemic immunomodulatory therapy in noninfectious uveitis: Fundamentals Of Care for UveitiS (FOCUS) Initiative. Ophthalmology. 2018 May;125(5):757-73. https://www.aaojournal.org/article/S0161-6420(17)32446-6/fulltext http://www.ncbi.nlm.nih.gov/pubmed/29310963?tool=bestpractice.com Methotrexate and mycophenolate are first-line antimetabolites.[71]Dick AD, Rosenbaum JT, Al-Dhibi HA, et al. Guidance on noncorticosteroid systemic immunomodulatory therapy in noninfectious uveitis: Fundamentals Of Care for UveitiS (FOCUS) Initiative. Ophthalmology. 2018 May;125(5):757-73. https://www.aaojournal.org/article/S0161-6420(17)32446-6/fulltext http://www.ncbi.nlm.nih.gov/pubmed/29310963?tool=bestpractice.com Methotrexate may offer better inflammation control and corticosteroid-sparing benefit than mycophenolate.[76]Edwards Mayhew RG, Li T, McCann P, et al. Non-biologic, steroid-sparing therapies for non-infectious intermediate, posterior, and panuveitis in adults. Cochrane Database Syst Rev. 2022 Oct 31;10(10):CD014831. https://www.cochranelibrary.com/cdsr/doi/10.1002/14651858.CD014831.pub2/full http://www.ncbi.nlm.nih.gov/pubmed/36315029?tool=bestpractice.com Azathioprine is less commonly used in some territories, including the US.[3]Burkholder BM, Jabs DA. Uveitis for the non-ophthalmologist. BMJ. 2021 Feb 3;372:m4979. http://www.ncbi.nlm.nih.gov/pubmed/33536186?tool=bestpractice.com
Calcineurin inhibitors (e.g., cyclosporine, tacrolimus) are occasionally added to the regimen when there is incomplete disease control with antimetabolites.[60]Foster CS, Kothari S, Anesi SD, et al. The Ocular Immunology and Uveitis Foundation preferred practice patterns of uveitis management. Surv Ophthalmol. 2016 Jan-Feb;61(1):1-17. http://www.ncbi.nlm.nih.gov/pubmed/26164736?tool=bestpractice.com Cyclosporine is widely used; major risks include bone marrow suppression and renal toxicity.[60]Foster CS, Kothari S, Anesi SD, et al. The Ocular Immunology and Uveitis Foundation preferred practice patterns of uveitis management. Surv Ophthalmol. 2016 Jan-Feb;61(1):1-17. http://www.ncbi.nlm.nih.gov/pubmed/26164736?tool=bestpractice.com Tacrolimus may also be considered.[71]Dick AD, Rosenbaum JT, Al-Dhibi HA, et al. Guidance on noncorticosteroid systemic immunomodulatory therapy in noninfectious uveitis: Fundamentals Of Care for UveitiS (FOCUS) Initiative. Ophthalmology. 2018 May;125(5):757-73. https://www.aaojournal.org/article/S0161-6420(17)32446-6/fulltext http://www.ncbi.nlm.nih.gov/pubmed/29310963?tool=bestpractice.com In one small randomized open-label trial, tacrolimus appeared to have a more favorable safety profile than cyclosporine with comparable efficacy.[79]Murphy CC, Greiner K, Plskova J, et al. Cyclosporine vs tacrolimus therapy for posterior and intermediate uveitis. Arch Ophthalmol. 2005 May;123(5):634-41. https://jamanetwork.com/journals/jamaophthalmology/fullarticle/417021 http://www.ncbi.nlm.nih.gov/pubmed/15883282?tool=bestpractice.com However, the trial was underpowered.
Alkylating agents (e.g., cyclophosphamide, chlorambucil) are rarely used due to associated toxicity and the increasing use of biologics but are considered for severe, stubborn, or refractory uveitis.[3]Burkholder BM, Jabs DA. Uveitis for the non-ophthalmologist. BMJ. 2021 Feb 3;372:m4979. http://www.ncbi.nlm.nih.gov/pubmed/33536186?tool=bestpractice.com [60]Foster CS, Kothari S, Anesi SD, et al. The Ocular Immunology and Uveitis Foundation preferred practice patterns of uveitis management. Surv Ophthalmol. 2016 Jan-Feb;61(1):1-17. http://www.ncbi.nlm.nih.gov/pubmed/26164736?tool=bestpractice.com
Tumor necrosis factor (TNF)-alpha inhibitors (e.g., adalimumab, infliximab) are the most commonly used biologics used in the treatment of noninfectious uveitis.[3]Burkholder BM, Jabs DA. Uveitis for the non-ophthalmologist. BMJ. 2021 Feb 3;372:m4979. http://www.ncbi.nlm.nih.gov/pubmed/33536186?tool=bestpractice.com [71]Dick AD, Rosenbaum JT, Al-Dhibi HA, et al. Guidance on noncorticosteroid systemic immunomodulatory therapy in noninfectious uveitis: Fundamentals Of Care for UveitiS (FOCUS) Initiative. Ophthalmology. 2018 May;125(5):757-73. https://www.aaojournal.org/article/S0161-6420(17)32446-6/fulltext http://www.ncbi.nlm.nih.gov/pubmed/29310963?tool=bestpractice.com [80]Jaffe GJ, Dick AD, Brézin AP, et al. Adalimumab in patients with active noninfectious uveitis. N Engl J Med. 2016 Sep 8;375(10):932-43. https://www.nejm.org/doi/10.1056/NEJMoa1509852 http://www.ncbi.nlm.nih.gov/pubmed/27602665?tool=bestpractice.com [81]Nguyen QD, Merrill PT, Jaffe GJ, et al. Adalimumab for prevention of uveitic flare in patients with inactive non-infectious uveitis controlled by corticosteroids (VISUAL II): a multicentre, double-masked, randomised, placebo-controlled phase 3 trial. Lancet. 2016 Sep 17;388(10050):1183-92. http://www.ncbi.nlm.nih.gov/pubmed/27542302?tool=bestpractice.com [82]National Institute for Health and Care Excellence. Adalimumab and dexamethasone for treating non-infectious uveitis. Jul 2017 [internet publication]. https://www.nice.org.uk/guidance/ta460 They are typically considered in patients who are intolerant of, or who do not respond to, more traditional immunosuppressants. Meta-analysis indicates that infliximab and adalimumab have similar therapeutic efficacy and corticosteroid-sparing effect in patients with noninfectious uveitis.[83]Liu W, Bai D, Kou L. Comparison of infliximab with adalimumab for the treatment of non-infectious uveitis: a systematic review and meta-analysis. BMC Ophthalmol. 2023 May 29;23(1):240. https://pmc.ncbi.nlm.nih.gov/articles/PMC10226205 http://www.ncbi.nlm.nih.gov/pubmed/37248486?tool=bestpractice.com TNF-alpha inhibitors are used in the management of autoimmune inflammatory diseases. Adalimumab and infliximab may, therefore, be of particular value for the treatment of uveitis associated with Behçet disease and human leukocyte antigen (HLA)-B27+ ankylosing spondylitis.[84]Renton WD, Jung J, Palestine AG. Tumor necrosis factor (TNF) inhibitors for juvenile idiopathic arthritis-associated uveitis. Cochrane Database Syst Rev. 2022 Oct 14;10(10):CD013818. https://www.cochranelibrary.com/cdsr/doi/10.1002/14651858.CD013818.pub2/full http://www.ncbi.nlm.nih.gov/pubmed/36239193?tool=bestpractice.com In patients with Behçet uveitis, adalimumab may be superior to infliximab with respect to ocular inflammation remission, drug retention, and the incidence of severe infusion or injection reactions.[85]Guan X, Zhao Z, Xin M, et al. Long-term efficacy, safety, and cumulative retention rate of antitumor necrosis factor-alpha treatment for patients with Behcet's uveitis: a systematic review and meta-analysis. Int J Rheum Dis. 2024 Feb;27(2):e15096. http://www.ncbi.nlm.nih.gov/pubmed/38402428?tool=bestpractice.com
Rituximab, an anti-CD20 monoclonal antibody, may be of benefit for patients with uveitis associated with rheumatoid arthritis, granulomatosis with polyangiitis (formerly known as Wegener granulomatosis), or systemic lupus erythematosus-associated vasculitis.[60]Foster CS, Kothari S, Anesi SD, et al. The Ocular Immunology and Uveitis Foundation preferred practice patterns of uveitis management. Surv Ophthalmol. 2016 Jan-Feb;61(1):1-17. http://www.ncbi.nlm.nih.gov/pubmed/26164736?tool=bestpractice.com [87]Ng CC, Sy A, Cunningham ET Jr. Rituximab for non-infectious uveitis and scleritis. J Ophthalmic Inflamm Infect. 2021 Aug 16;11(1):23. https://pmc.ncbi.nlm.nih.gov/articles/PMC8364894 http://www.ncbi.nlm.nih.gov/pubmed/34396463?tool=bestpractice.com [88]Miserocchi E, Modorati G, Berchicci L, et al. Long-term treatment with rituximab in severe juvenile idiopathic arthritis-associated uveitis. Br J Ophthalmol. 2016 Jun;100(6):782-6. http://www.ncbi.nlm.nih.gov/pubmed/26396026?tool=bestpractice.com [89]Ahmed A, Foster CS. Cyclophosphamide or rituximab treatment of scleritis and uveitis for patients with granulomatosis with polyangiitis. Ophthalmic Res. 2019;61(1):44-50. http://www.ncbi.nlm.nih.gov/pubmed/29635229?tool=bestpractice.com [90]You C, Ma L, Lasave AF, et al. Rituximab induction and maintenance treatment in patients with scleritis and granulomatosis with polyangiitis (Wegener's). Ocul Immunol Inflamm. 2018;26(8):1166-73. http://www.ncbi.nlm.nih.gov/pubmed/28628344?tool=bestpractice.com
Adjustment of systemic immunomodulatory therapy may be clinically indicated in certain circumstances including: deterioration of visual function, anterior chamber cells or flare, vitreous haze, chorioretinal or retinal vascular lesions, macular or optic nerve involvement.[71]Dick AD, Rosenbaum JT, Al-Dhibi HA, et al. Guidance on noncorticosteroid systemic immunomodulatory therapy in noninfectious uveitis: Fundamentals Of Care for UveitiS (FOCUS) Initiative. Ophthalmology. 2018 May;125(5):757-73. https://www.aaojournal.org/article/S0161-6420(17)32446-6/fulltext http://www.ncbi.nlm.nih.gov/pubmed/29310963?tool=bestpractice.com Before therapy is changed, exclude treatment nonadherence, infections, and masquerade syndromes as factors in a patient with inadequate response to therapy.[71]Dick AD, Rosenbaum JT, Al-Dhibi HA, et al. Guidance on noncorticosteroid systemic immunomodulatory therapy in noninfectious uveitis: Fundamentals Of Care for UveitiS (FOCUS) Initiative. Ophthalmology. 2018 May;125(5):757-73. https://www.aaojournal.org/article/S0161-6420(17)32446-6/fulltext http://www.ncbi.nlm.nih.gov/pubmed/29310963?tool=bestpractice.com Consideration may then be given to dose escalation to the maximum tolerated therapeutic dose or switching to alternative systemic immunomodulatory drugs or treatments. Consider individualized therapy based on history, cause of uveitis, and patient preference.[71]Dick AD, Rosenbaum JT, Al-Dhibi HA, et al. Guidance on noncorticosteroid systemic immunomodulatory therapy in noninfectious uveitis: Fundamentals Of Care for UveitiS (FOCUS) Initiative. Ophthalmology. 2018 May;125(5):757-73. https://www.aaojournal.org/article/S0161-6420(17)32446-6/fulltext http://www.ncbi.nlm.nih.gov/pubmed/29310963?tool=bestpractice.com If a patient is not benefiting adequately from immunomodulatory therapy, the diagnosis should be reconsidered.
Patients receiving immunomodulatory therapy require close monitoring.[71]Dick AD, Rosenbaum JT, Al-Dhibi HA, et al. Guidance on noncorticosteroid systemic immunomodulatory therapy in noninfectious uveitis: Fundamentals Of Care for UveitiS (FOCUS) Initiative. Ophthalmology. 2018 May;125(5):757-73. https://www.aaojournal.org/article/S0161-6420(17)32446-6/fulltext http://www.ncbi.nlm.nih.gov/pubmed/29310963?tool=bestpractice.com Evaluation of baseline organ function and screening for active or latent infectious diseases (e.g. tuberculosis, hepatitis) via history, laboratory, and clinically relevant nonocular imaging is recommended before initiation of therapy.[71]Dick AD, Rosenbaum JT, Al-Dhibi HA, et al. Guidance on noncorticosteroid systemic immunomodulatory therapy in noninfectious uveitis: Fundamentals Of Care for UveitiS (FOCUS) Initiative. Ophthalmology. 2018 May;125(5):757-73. https://www.aaojournal.org/article/S0161-6420(17)32446-6/fulltext http://www.ncbi.nlm.nih.gov/pubmed/29310963?tool=bestpractice.com Efficacy and toxicity of the immunomodulatory agent is monitored at 6- to 8-week intervals via blood work (e.g., complete blood count, renal function tests, liver function tests), and ancillary tests as required. Rheumatologist or hematologist input may be required.[60]Foster CS, Kothari S, Anesi SD, et al. The Ocular Immunology and Uveitis Foundation preferred practice patterns of uveitis management. Surv Ophthalmol. 2016 Jan-Feb;61(1):1-17. http://www.ncbi.nlm.nih.gov/pubmed/26164736?tool=bestpractice.com [71]Dick AD, Rosenbaum JT, Al-Dhibi HA, et al. Guidance on noncorticosteroid systemic immunomodulatory therapy in noninfectious uveitis: Fundamentals Of Care for UveitiS (FOCUS) Initiative. Ophthalmology. 2018 May;125(5):757-73. https://www.aaojournal.org/article/S0161-6420(17)32446-6/fulltext http://www.ncbi.nlm.nih.gov/pubmed/29310963?tool=bestpractice.com
Pregnant women should be referred early to an ophthalmologist for management; systemic immunomodulatory therapy is typically avoided during pregnancy, although adalimumab may be used in severe cases where the benefits outweigh the risks.[91]Chiam NP, Lim LL. Uveitis and gender: the course of uveitis in pregnancy. J Ophthalmol. 2014;2014:401915. https://pmc.ncbi.nlm.nih.gov/articles/PMC3941965 http://www.ncbi.nlm.nih.gov/pubmed/24683491?tool=bestpractice.com [92]Bandoli G, Palmsten K, Forbess Smith CJ, et al. A review of systemic corticosteroid use in pregnancy and the risk of select pregnancy and birth outcomes. Rheum Dis Clin North Am. 2017 Aug;43(3):489-502. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5604866 http://www.ncbi.nlm.nih.gov/pubmed/28711148?tool=bestpractice.com [93]Chambers CD, Johnson DL, Xu R, et al. Birth outcomes in women who have taken adalimumab in pregnancy: a prospective cohort study. PLoS One. 2019;14(10):e0223603. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6799916 http://www.ncbi.nlm.nih.gov/pubmed/31626646?tool=bestpractice.com
Any related underlying condition should also be managed as appropriate.
Primary options
methotrexate: consult specialist for guidance on dose
OR
mycophenolate mofetil: consult specialist for guidance on dose
Secondary options
azathioprine: consult specialist for guidance on dose
OR
methotrexate: consult specialist for guidance on dose
or
mycophenolate mofetil: consult specialist for guidance on dose
or
azathioprine: consult specialist for guidance on dose
-- AND --
cyclosporine modified: consult specialist for guidance on dose
or
tacrolimus: consult specialist for guidance on dose
OR
adalimumab: consult specialist for guidance on dose
OR
infliximab: consult specialist for guidance on dose
Tertiary options
cyclophosphamide: consult specialist for guidance on dose
OR
chlorambucil: consult specialist for guidance on dose
OR
rituximab: consult specialist for guidance on dose
continued corticosteroid therapy and taper
Treatment recommended for ALL patients in selected patient group
Therapeutic response to systemic immunomodulatory therapy varies greatly. Therefore, patients require continued treatment with a corticosteroid (topical or systemic) until immunomodulatory therapy is effective, and the corticosteroid can then be tapered according to response.[71]Dick AD, Rosenbaum JT, Al-Dhibi HA, et al. Guidance on noncorticosteroid systemic immunomodulatory therapy in noninfectious uveitis: Fundamentals Of Care for UveitiS (FOCUS) Initiative. Ophthalmology. 2018 May;125(5):757-73. https://www.aaojournal.org/article/S0161-6420(17)32446-6/fulltext http://www.ncbi.nlm.nih.gov/pubmed/29310963?tool=bestpractice.com
long-term local corticosteroid therapy
Alternatives to corticosteroids are usually preferred for long-term control. However, periocular injections or ocular implants are sometimes used.
Triamcinolone periocular injections can reduce inflammation for several months. There is a risk of glaucoma and/or cataract after several years of therapy.[3]Burkholder BM, Jabs DA. Uveitis for the non-ophthalmologist. BMJ. 2021 Feb 3;372:m4979. http://www.ncbi.nlm.nih.gov/pubmed/33536186?tool=bestpractice.com [60]Foster CS, Kothari S, Anesi SD, et al. The Ocular Immunology and Uveitis Foundation preferred practice patterns of uveitis management. Surv Ophthalmol. 2016 Jan-Feb;61(1):1-17. http://www.ncbi.nlm.nih.gov/pubmed/26164736?tool=bestpractice.com
Fluocinolone intravitreal implants reduce the severity and frequency of uveitis recurrence, minimizing the use of adjunctive treatment. They are effective for 2-3 years. There is a risk of elevated intraocular pressure and cataracts; incisional glaucoma surgery is often required.[3]Burkholder BM, Jabs DA. Uveitis for the non-ophthalmologist. BMJ. 2021 Feb 3;372:m4979. http://www.ncbi.nlm.nih.gov/pubmed/33536186?tool=bestpractice.com [60]Foster CS, Kothari S, Anesi SD, et al. The Ocular Immunology and Uveitis Foundation preferred practice patterns of uveitis management. Surv Ophthalmol. 2016 Jan-Feb;61(1):1-17. http://www.ncbi.nlm.nih.gov/pubmed/26164736?tool=bestpractice.com [67]Jaffe GJ, Martin D, Callanan D, et al. Fluocinolone acetonide implant (Retisert) for noninfectious posterior uveitis: thirty-four-week results of a multicenter randomized clinical study. Ophthalmology. 2006 Jun;113(6):1020-7. http://www.ncbi.nlm.nih.gov/pubmed/16690128?tool=bestpractice.com
Dexamethasone intravitreal implants release dexamethasone over 4-6 months.[3]Burkholder BM, Jabs DA. Uveitis for the non-ophthalmologist. BMJ. 2021 Feb 3;372:m4979. http://www.ncbi.nlm.nih.gov/pubmed/33536186?tool=bestpractice.com [60]Foster CS, Kothari S, Anesi SD, et al. The Ocular Immunology and Uveitis Foundation preferred practice patterns of uveitis management. Surv Ophthalmol. 2016 Jan-Feb;61(1):1-17. http://www.ncbi.nlm.nih.gov/pubmed/26164736?tool=bestpractice.com
Primary options
triamcinolone intravitreal: consult specialist for guidance on periocular dose
OR
fluocinolone intravitreal: (implant) consult specialist for guidance on dose
OR
dexamethasone intravitreal: (implant) consult specialist for guidance on dose
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