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: not pregnant

1st line – corticosteroid eye drops + management of any underlying disease

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ACUTE
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non-infectious, initial presentation: not pregnant
1st line – 

corticosteroid eye drops + management of any underlying disease

All patients should be referred early to an ophthalmologist for management.

Corticosteroids achieve immediate control of inflammation most rapidly and effectively. They decrease the production and migration of most immune cells via the inhibition of phospholipase A2, decreasing both prostaglandin and leukotriene production, and are the first-choice drug for patients who present with ocular inflammation that is not believed to be infectious.

The key to successful use of corticosteroid eye drops is very frequent administration initially. The most common reason for failure to control inflammation with these drugs is insufficient dosing. Generally they are started hourly for acute anterior uveitis, with a subsequent taper depending on the severity of the initial presentation.

Topical corticosteroids have numerous side effects that ultimately limit their usefulness for long-term control, including intra-ocular pressure elevation, posterior subcapsular cataracts, and subconjunctival haemorrhages.

Any related underlying condition should also be managed as appropriate.

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

Consider – peri-ocular or intra-ocular corticosteroids

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ACUTE
|
non-infectious, initial presentation: not pregnant
Consider – 

peri-ocular or intra-ocular corticosteroids

Additional treatment recommended for SOME patients in selected patient group

Once topical corticosteroids have been found to be effective and safe, a peri-ocular injection can be considered. This modality of administration is useful for a more sustained local anti-inflammatory effect.

Patients should be made aware that this use of corticosteroids is off-label and carries risks. This discussion should be documented in the medical records.

Side effects include intra-ocular pressure elevation, posterior subcapsular cataracts, hyperglycaemia (in diabetes), injection site scarring, subconjunctival haemorrhage, pain (with dexamethasone and betamethasone injections), and inadvertent penetrating globe trauma. The 'cardinal clock hours' (12, 3, 6, 9) should be avoided in peri-ocular injections, as trauma to branches of the anterior ciliary arteries can cause marked haemorrhage. If systemic absorption should be minimised (e.g., in diabetes), subconjunctival injections are superior to peribulbar injections. Dexamethasone and betamethasone should be mixed with lidocaine to reduce pain.

Intra-ocular corticosteroid injections are used for severe posterior uveitis. Side effects include intra-ocular pressure elevation, posterior subcapsular cataracts, endophthalmitis (a form of infectious panuveitis), pseudoendophthalmitis, pain, subconjunctival haemorrhage, and acute damage to the intra-ocular structures. The injection site should be rotated around different clock hours for repeat injections, to reduce the potential for pain.

Infectious causes should be ruled out before moving to systemic, peri-ocular, or intravitreal corticosteroids.

Primary options

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

OR

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

OR

betamethasone sodium phosphate: consult specialist for guidance on peri-ocular or intra-ocular dose

Consider – oral corticosteroid

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ACUTE
|
non-infectious, initial presentation: not pregnant
Consider – 

oral corticosteroid

Additional treatment recommended for SOME patients in selected patient group

Oral corticosteroids may be used in severe bilateral or recalcitrant uveitis, or if patients cannot tolerate corticosteroid injections.

Oral corticosteroids cause adrenal suppression after 1 week of therapy, so after 7 days the dose should be lowered gradually to avoid this. The speed of the taper depends on the clinical circumstances. A rapid taper would involve decreasing the dose by 10 mg/day (e.g., 50 mg one day, 40 mg the next, and so on) until discontinuation. A slower taper would be to decrease the daily prednisolone dose by 10 mg every week, while monitoring to see how much the dose can be lowered before the inflammation recurs.

If it is anticipated that oral corticosteroid therapy will be continued at any dose for longer than 1 month, concomitant bisphosphonate therapy is often added. Note that bisphosphonates are contra-indicated in girls and in women of child-bearing age.

Primary options

prednisolone: 1 mg/kg/day orally initially, maximum 80 mg/day, followed by rapid or slow taper

Consider – cycloplegic

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ACUTE
|
non-infectious, initial presentation: not pregnant
Consider – 

cycloplegic

Additional treatment recommended for SOME patients in selected patient group

Cycloplegics can be used if the inflammation is causing synechiae or the uveitis is fibrinous in nature, as can happen with human leukocyte antigen-B27-related uveitis or various granulomatous uveitic conditions.

Primary options

atropine ophthalmic: (1% solution) 1 drop into the affected eye(s) twice daily

OR

homatropine ophthalmic: (5% solution) 1 drop into the affected eye(s) twice daily

OR

cyclopentolate ophthalmic: (1% solution) 1 drop into the affected eye(s) two or three times daily

non-infectious, initial presentation: pregnant

1st line – prednisolone eye drops + management of any underlying disease

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

prednisolone eye drops + management of any underlying disease

Ocular inflammation in pregnancy is rare, and many women with a long history of chronic uveitis observe that their disease becomes inactive during pregnancy and returns afterwards.[41] All patients should be referred early to an ophthalmologist for management.

If immediate control of inflammation is necessary, topical prednisolone is generally safe in pregnancy.

Any related underlying condition should also be managed as appropriate.

Primary options

prednisolone ophthalmic: (1% solution) 1-2 drops into the affected eye(s) twice to four times daily

Consider – cycloplegic

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ACUTE
|
non-infectious, initial presentation: pregnant
Consider – 

cycloplegic

Additional treatment recommended for SOME patients in selected patient group

Cycloplegics can be used if the inflammation is causing synechiae or the uveitis is fibrinous in nature, as can happen with human leukocyte antigen-B27-related uveitis or various granulomatous uveitic conditions.

Primary options

atropine ophthalmic: (1% solution) 1 drop into the affected eye(s) twice daily

OR

homatropine ophthalmic: (5% solution) 1 drop into the affected eye(s) twice daily

OR

cyclopentolate ophthalmic: (1% solution) 1 drop into the affected eye(s) two or three times daily

infectious

1st line – specialty consultation

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ACUTE
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infectious
1st line – 

specialty consultation

Uveitis secondary to an infection should be treated urgently as it is often more aggressive and may lead to permanent blindness long term.

Numerous infectious agents can result in uveitis, including 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), and infections related to occupational/leisure (e.g., leptospirosis, brucellosis, toxoplasmosis, Bartonella henselae [cat scratch disease]), geographic (e.g., histoplasmosis, coccidioidomycosis, Borrelia burgdorferi [Lyme disease], TB, malaria, leprosy), or environmental (e.g., TB) exposure.

The treatment of infectious uveitis depends on the causative organism and, due to the aforementioned array of potential infective aetiologies, specialist advice should be sought regarding appropriate management.

ONGOING

non-infectious, after immediate control of inflammation: not pregnant

1st line – long-term local corticosteroid therapy + continuing management of any underlying disease

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ONGOING
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non-infectious, after immediate control of inflammation: not pregnant
1st line – 

long-term local corticosteroid therapy + continuing management of any underlying disease

The primary goal of long-term treatment is to achieve control of both ocular and associated systemic disease, while minimising exposure to corticosteroids in order to avoid corticosteroid-related side effects. When considering long-term therapy, alternatives to corticosteroids are typically preferred, although local therapy with peri-ocular injections or ocular implants is sometimes used.

Peri-ocular triamcinolone injections can reduce inflammation in an eye for several months. In such cases, patients may undergo periodic injections as needed to maintain long-term control. Such patients may require treatment of cataracts and glaucoma after a few years.

Fluocinolone implants have been found to be very effective in reducing the frequency and severity of uveitis recurrences and the amount of adjunctive treatment needed. Typically the duration of action is about 2 to 3 years. More than half of recipients sustain an increase in intra-ocular pressure >10 mmHg, and cataracts can invariably be expected to worsen over time.[25]​​ Incisional glaucoma surgery is frequently required in patients who have the implant.

A dexamethasone intravitreal implant is also available. The implant is biodegradable and releases dexamethasone over a 4- to 6-month period. It is injected using a preloaded injector.

Any related underlying condition should also be managed as appropriate.

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

Consider – immunomodulatory drugs

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ONGOING
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non-infectious, after immediate control of inflammation: not pregnant
Consider – 

immunomodulatory drugs

Additional treatment recommended for SOME patients in selected patient group

Patients with chronic or potentially sight-threatening disease often benefit from corticosteroid-sparing immunomodulatory drugs.[26] These drugs can eliminate the need for a prolonged corticosteroid use, which is often fraught with an even greater side-effect profile and more immunosuppression than the immunomodulatory drugs.

The agent and the regimen should be determined by a specialist. Immunomodulatory drugs include antimetabolites (e.g., methotrexate, azathioprine, mycophenolate), calcineurin inhibitors (e.g., ciclosporin, tacrolimus), alkylating agents (e.g., cyclophosphamide, chlorambucil), and biological response modifiers (e.g., adalimumab, infliximab, rituximab).

The selection of the appropriate immunomodulatory therapy is an inexact science, and experienced practitioners often disagree about what is the 'correct' first-line agent for a given disease. Overall, however, antimetabolites are usually the drug class of choice as they have the advantage of oral dosing, manageable adverse effects, and minimal monitoring requirements. However, specific drug selection varies between practitioners as there are no large prospective clinical trials, and the use of these agents in uveitis is off-label (apart from adalimumab). Methotrexate and mycophenolate are the most common first-line antimetabolites; there is no clear difference in efficacy between these drugs for controlling inflammation in adults with non-infectious uveitis.[27] Where there is incomplete disease control with antimetabolites, calcineurin inhibitors are occasionally added to the regimen. Tumour necrosis factor (TNF)-alpha inhibitors are used as a next step in many cases either in place of or in addition to antimetabolites. In many cases, patients are treated with monotherapy, but combination therapy may be effective in recalcitrant cases.[28] The use of alkylating agents is falling out of favour now that biological agents are increasingly being used. 

Once a patient is started on an immunomodulatory drug, the initial corticosteroid dose (eye drops or oral corticosteroid started at initial presentation) is generally gradually tapered (e.g., over 1 to 2 months) and the patient’s response monitored.

There are some conditions where TNF-alpha inhibitors would be considered first line (e.g., human leukocyte antigen B27+ uveitis with ankylosing spondylitis). Adalimumab is approved in the US and Europe for the treatment of non-infectious intermediate and posterior uveitis and panuveitis.[29][30][31] In case reports, adalimumab has been associated with severe thrombocytopenia.[32]

In cases of juvenile idiopathic arthritis (JIA)-associated anterior uveitis, immunomodulatory therapy is employed to improve long-term visual prognosis and to reduce the risk of ocular complications. In children ages <11 years, chronic corticosteroid use causes heightened concern about cataract and glaucoma development.[37][38][39] While methotrexate remains part of the treatment armamentarium for JIA uveitis, TNF-alpha inhibitors - especially adalimumab - are being increasingly used with or without concurrent methotrexate to achieve disease remission.[38][39]​​ The US Food and Drug Administration has approved adalimumab for the treatment of pediatric uveitis in children aged ≥2 years.[40] 

In cases of treatment failure with these agents, other options include returning to corticosteroid treatment, using an alternative immunomodulatory drug, or switching to another biological agent either within the same class or to another class altogether. Rituximab, a monoclonal antibody against CD20, is particularly useful in associated conditions such as rheumatoid arthritis, granulomatosis with polyangiitis (formerly known as Wegener's granulomatosis), or systemic lupus erythematosus-associated vasculitis.

The pros and cons of immunomodulatory therapy versus corticosteroids must be carefully considered. These drugs all carry their own side effects, they take several weeks to show an effect, and they are less reliably effective than corticosteroids. Choice of therapy also depends on any associated conditions. Immunomodulatory therapy should be used only with the full support, understanding, and consent of the patient, after clearly discussing risks and the underlying evidence base.

Standard baseline laboratory tests for immunosuppression are a full blood count and liver and renal function tests. For cyclophosphamide, a urinalysis should also be performed. Tests to exclude latent tuberculosis and hepatitis should also be performed. For ciclosporin and tacrolimus, blood pressure should be assessed before starting treatment.

Patients should receive killed influenza vaccines, and any other vaccines they receive must also be killed. They should never receive live vaccines. Male and female patients taking these drugs should be using birth control. Patients who have even minor infections while taking immunosuppressive drugs should stop the drug until symptoms have resolved.

These therapies should be initiated only under specialist guidance; consult specialist for guidance on dose and treatment course.

Primary options

methotrexate

OR

mycophenolate mofetil

OR

adalimumab

OR

azathioprine

Secondary options

ciclosporin

OR

tacrolimus

OR

infliximab

Tertiary options

cyclophosphamide

OR

chlorambucil

OR

rituximab

non-infectious, after immediate control of inflammation: pregnant

1st line – prednisolone eye drops + continuing management of any underlying disease

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ONGOING
|
non-infectious, after immediate control of inflammation: pregnant
|
inflammation limited to anterior segment
1st line – 

prednisolone eye drops + continuing management of any underlying disease

Inflammation limited to the anterior segment can be controlled indefinitely during pregnancy with prednisolone eye drops.

Any related underlying condition should also be managed as appropriate.

Primary options

prednisolone ophthalmic: (1% solution) 1-2 drops into the affected eye(s) twice to four times daily

1st line – specialty consultation

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ONGOING
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non-infectious, after immediate control of inflammation: pregnant
|
inflammation involving posterior segment
1st line – 

specialty consultation

If inflammation involves the posterior segment, control cannot be achieved with topical medications and peri-ocular triamcinolone injections are not universally acknowledged to be safe in pregnancy.

During pregnancy, systemic immunomodulatory therapy is typically avoided. In severe cases of sight-threatening disease, certain options can be discussed with the patient’s obstetric clinicians, including oral corticosteroids, adalimumab, and locally delivered corticosteroids.[41][42][43] 

Options for locally delivered corticosteroids include intravitreal triamcinolone, dexamethasone intravitreal implant, and fluocinolone intravitreal implant.[41]

Intravitreal triamcinolone is considered safer than peri-ocular triamcinolone, since the volume of drug is much less and the drug is limited to the interior of the eye.

Corticosteroid implants should only be used if the potential benefits outweigh the risks to the fetus.

Treatment options should only be initiated under specialist guidance.

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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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