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

ACUTE

non-infectious: initial presentation

1st line – topical ophthalmic corticosteroid + management of any underlying disease

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ACUTE
|
non-infectious: initial presentation
1st line – 

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 non-infectious uveitis; topical ophthalmic formulations are indicated for anterior chamber inflammation.[3][59] 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.[59]​ Dose and duration is tailored to the patient.

Adverse effects of topical corticosteroids (including elevation of intra-ocular pressure, posterior subcapsular cataract, and subconjunctival haemorrhage) limit their long-term use.[3][60]

Pregnant women should be referred early to an ophthalmologist for management; topical ophthalmic corticosteroids such as prednisolone are generally considered safe.[90][91][92]

Primary options

prednisolone 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

Consider – cycloplegic

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ACUTE
|
non-infectious: initial presentation
Consider – 

cycloplegic

Additional 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 minimise 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.[59]

Primary options

atropine ophthalmic: (1%) apply ointment into the affected eye(s) once or twice daily

2nd line – peri-ocular or intra-ocular corticosteroid

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ACUTE
|
non-infectious: initial presentation
2nd line – 

peri-ocular or intra-ocular corticosteroid

Infectious causes should be ruled out before moving to peri-ocular or intra-ocular corticosteroid injections.

Peri-ocular (regional) corticosteroid injections may be preferred in a patient who is non-compliant with, or poorly responsive to, topical corticosteroid therapy (that was otherwise safe and well tolerated).[59]​ In patients responsive to initial topical corticosteroid, peri-ocular corticosteroid can sustain local anti-inflammatory effects. Peri-ocular administration is considered in patients with intermediate or posterior uveitis because it allows the corticosteroid to be delivered close to the site of inflammation.[59]

Adverse effects of peri-ocular corticosteroid injections include: intra-ocular pressure elevation (glaucoma; posterior subcapsular cataract); hyperglycaemia in patients with diabetes (may occur approximately 6 hours after dexamethasone injection); injection-site scarring (can complicate repeat injections); subconjunctival haemorrhage (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 anaesthetic such as lidocaine); inadvertent penetrating globe trauma.[61][62][63]​​

Intra-ocular corticosteroid injections are used for severe posterior uveitis and acute inflammation unresponsive to peri-ocular corticosteroid injections; discussion of risks should be documented in medical notes.[59]​ Intra-ocular corticosteroids may also serve as a bridge to corticosteroid-sparing therapies.

Adverse effects of intra-ocular corticosteroid injection include those documented for peri-ocular corticosteroid injection. Endophthalmitis, a form of infectious panuveitis, and pseudoendophthalmitis have also been reported.[64][65]​​[66]​ 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, intra-ocular corticosteroid injections.[3][59] 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.[59]

Pregnant women should be referred early to an ophthalmologist for management; intravitreal corticosteroids may be considered by a specialist if benefits outweigh risks.[90][91][92]

Primary options

triamcinolone intravitreal: consult specialist for guidance on peri-ocular dose

OR

dexamethasone intraocular: consult specialist for guidance on peri-ocular or intra-ocular dose

Secondary options

dexamethasone intravitreal implant: consult specialist for guidance on dose

OR

fluocinolone intravitreal implant: consult specialist for guidance on dose

Consider – cycloplegic

Back
ACUTE
|
non-infectious: initial presentation
Consider – 

cycloplegic

Additional 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 minimise 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.[59]

Primary options

atropine ophthalmic: (1%) apply ointment into the affected eye(s) once or twice daily

3rd line – oral or intravenous corticosteroid

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ACUTE
|
non-infectious: initial presentation
3rd line – 

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.[59]​ An oral corticosteroid facilitates immediate control, and may be followed by peri-ocular injection (when tolerated in a patient with confirmed immune-mediated uveitis) to minimise systemic adverse effects. High-dose oral corticosteroid therapy is prescribed initially, and the dose tapered to clinical effect.[59][67]

Potential adverse effects associated with prolonged use of oral corticosteroids include hypertension, bone fracture, metabolic issues, and gastrointestinal disturbances.[68]​ 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 non-steroidal anti-inflammatory drug (NSAID).[59][67]

Post-menopausal 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.[59] 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.[59] Note that bisphosphonates are not typically recommended in individuals aged <18 years and in pregnancy; they should be used with caution in women of childbearing age.[69]

Intravenous corticosteroids (e.g., high-dose methylprednisolone) are rarely considered, but may be indicated in specific clinical scenarios: severe, non-infectious posterior uveitis or panuveitis; intra-operatively, 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).[59][67]​ A short course of intravenous corticosteroids may be administered in these circumstances, followed by a gradual taper of an oral corticosteroid.[59]

Pregnant women should be referred early to an ophthalmologist for management; systemic corticosteroids may be considered by a specialist if benefits outweigh risks.[90][91][92]

Primary options

prednisolone: 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

prednisolone: 1 mg/kg/day orally initially (start after methylprednisolone course), followed by rapid or slow taper according to response, maximum 80 mg/day

Consider – cycloplegic

Back
ACUTE
|
non-infectious: initial presentation
Consider – 

cycloplegic

Additional 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 minimise 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.[59]

Primary options

atropine ophthalmic: (1%) apply ointment into the affected eye(s) once or twice daily

infectious

1st line – referral to specialist

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ACUTE
|
infectious
1st line – 

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 aetiology.[3]​​[49][59]

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, gonorrhoea, 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][49][93]

ONGOING

non-infectious: after immediate control of inflammation

1st line – immunomodulatory therapy + continued management of any underlying disease

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ONGOING
|
non-infectious: after immediate control of inflammation
1st line – 

immunomodulatory therapy + continued management of any underlying disease

Long-term treatment aims to control ocular and systemic disease while minimising corticosteroid exposure.[3][59]

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).​[67][70]​ If prolonged oral corticosteroid therapy is anticipated (>3 months), systemic immunomodulatory therapy should be considered.[59] Severe sight-threatening uveitis requires long-term immunomodulatory therapy. 

The drug and the regimen should be determined by a specialist.[59] The timing and choice of systemic immunomodulatory therapy is informed by the cause of intra-ocular inflammation.[59][70]

Antimetabolites (e.g., methotrexate, azathioprine, mycophenolate) are commonly used, are dosed orally, and have manageable adverse effects.[3][59][70] Methotrexate and mycophenolate are first-line antimetabolites.[70] Methotrexate may offer better inflammation control and corticosteroid-sparing benefit than mycophenolate.[75]​ Azathioprine is less commonly used in some territories, including the US.[3]

Calcineurin inhibitors (e.g., ciclosporin, tacrolimus) are occasionally added to the regimen when there is incomplete disease control with antimetabolites.[59] Ciclosporin is widely used; major risks include bone marrow suppression and renal toxicity.[59] Tacrolimus may also be considered.[70] In one small randomised open-label trial, tacrolimus appeared to have a more favourable safety profile than ciclosporin with comparable efficacy.[78]​ 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][59]

Tumour necrosis factor (TNF)-alpha inhibitors (e.g., adalimumab, infliximab) are the most commonly used biologics used in the treatment of non-infectious uveitis.[3][70][79][80][81] 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 non-infectious uveitis.[82]​ 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's disease and human leukocyte antigen (HLA)-B27+ ankylosing spondylitis.[83]​ In patients with Behçet's uveitis, adalimumab may be superior to infliximab with respect to ocular inflammation remission, drug retention, and the incidence of severe infusion or injection reactions.[84]

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's granulomatosis), or systemic lupus erythematosus-associated vasculitis.[59][86][87][88][89]

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.[70] Before therapy is changed, exclude treatment non-adherence, infections, and masquerade syndromes as factors in a patient with inadequate response to therapy.[70] Consideration may then be given to dose escalation to the maximum tolerated therapeutic dose or switching to alternative systemic immunomodulatory drugs or treatments. Consider individualised therapy based on history, cause of uveitis, and patient preference.[70] If a patient is not benefiting adequately from immunomodulatory therapy, the diagnosis should be reconsidered.

Patients receiving immunomodulatory therapy require close monitoring.[70] Evaluation of baseline organ function and screening for active or latent infectious diseases (e.g. tuberculosis, hepatitis) via history, laboratory, and clinically relevant non-ocular imaging is recommended before initiation of therapy.[70] Efficacy and toxicity of the immunomodulatory agent is monitored at 6- to 8-week intervals via blood work (e.g., full blood count, renal function tests, liver function tests), and ancillary tests as required. Rheumatologist or haematologist input may be required.[59][70]

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.[90][91][92]

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 --

ciclosporin: 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

Plus – continued corticosteroid therapy and taper

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ONGOING
|
non-infectious: after immediate control of inflammation
Plus – 

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.[70]

2nd line – long-term local corticosteroid therapy

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ONGOING
|
non-infectious: after immediate control of inflammation
2nd line – 

long-term local corticosteroid therapy

Alternatives to corticosteroids are usually preferred for long-term control. However, peri-ocular injections or ocular implants are sometimes used.

Triamcinolone peri-ocular injections can reduce inflammation for several months. There is a risk of glaucoma and/or cataract after several years of therapy.[3][59]

Fluocinolone intravitreal implants reduce the severity and frequency of uveitis recurrence, minimising the use of adjunctive treatment. They are effective for 2-3 years. There is a risk of elevated intra-ocular pressure and cataracts; incisional glaucoma surgery is often required.[3][59][66]

Dexamethasone intravitreal implants release dexamethasone over 4-6 months.[3][59]​​

Primary options

triamcinolone intravitreal: consult specialist for guidance on peri-ocular 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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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

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