Uveitis

oPatientPlus articles are written by UK doctors and are based on research evidence, UK and European Guidelines. They are designed for health professionals to use, so you may find the language more technical than the condition leaflets.

The uveal tract is the highly vascular and densely pigmented layer of the eyeball, lying between the sclera (superficial to it) and the retina (deep to it).

The anterior, visible portion is the iris. This extends back into the ciliary body (at the level of the lens) and then extends round to the posterior pole, where it is known as the choroid.

Uveitis means inflammation at any point of the uveal tract, with or without inflammation of neighbouring structures (eg, the retina or vitreous).[1]

You will find more detail on posterior uveitis in the separate articles Chorioretinal Inflammation and Choroidal Disorders.

The condition can be classified in various ways:

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Anatomical

A common classification is by anatomical location of the pathology:

  • Anterior uveitis refers to an inflammation of the iris (hence, its previous name, still used by many, iritis). It may also be referred to as iridocyclitis (iris + ciliary body involvement) or anterior cyclitis (anterior portion of the ciliary body affected) depending on the exact structures involved.
  • Intermediate uveitis affects the vitreous and posterior part of the ciliary body; hence, it may be called pars planitis, posterior cyclitis or hyalitis, the latter referring to the anterior portion of the vitreous.
  • Posterior uveitis describes an inflammation of the choroid which may be referred to as choroiditis or chorioretinitis if the retina is also involved. It may also affect the retinal blood vessels, giving rise to retinal vasculitis. Posterior uveitis is further defined as being focal, multifocal or diffuse, depending on the nature of the inflammatory lesions seen on the fundus.
  • Panuveitis indicates inflammation throughout the uveal tract and is an indication of serious disease.

Onset, duration, course[2]

The onset may be sudden or insidious and the duration is defined as acute, when less than three months, or chronic, when greater than three months. The course may be recurrent (repeated episodes separated by periods of inactivity of at least three months' duration) or chronic (relapses occur less than three months after discontinuing treatment).

Aetiology

This may be classified into:

  • Inflammatory - due to autoimmune disease.
  • Infectious - caused by known ocular and systemic pathogens.
  • Infiltrative - secondary to invasive neoplastic processes (sometimes referred to as masquerade syndromes).
  • Injurious - due to trauma.
  • Iatrogenic - caused by surgery, inadvertent trauma, or medication (eg, rifabutin, cidofovir).[1]
  • Inherited - secondary to metabolic or dystrophic disease.
  • Ischaemic - caused by impaired circulation.
  • Idiopathic - a category used when thorough evaluation has failed to find an underlying cause.

There are also some ocular syndromes that may give rise to anterior uveitis (eg, Posner-Schlossman syndrome, Fuchs' heterochromic cyclitis, Schwartz' syndrome).[3]

Sympathetic ophthalmia (sometimes referred to as sympathetic ophthalmitis or sympathetic uveitis) is a rare form of bilateral panuveitis. It is a specific type of uveitis in response to trauma to one of the eyes. For further information, see separate article Sympathetic Ophthalmia.

Presenting clinical features[4][5]

A new system based on a number of presenting clinical features is being proposed by the International Uveitis Study Group. These criteria include:

  • Location of inflammation
  • Anterior chamber cells
  • Anterior chamber flare
  • Vitreous cells (present or absent)
  • Vitreous haze

In many cases, especially anterior disease, the aetiology of uveitis is idiopathic. Regardless of the aetiology and mechanism leading to the inflammation, the eye's ultimate response is the same, characterised by classic signs seen on slit-lamp examination (see 'Signs', below). These can be summarised as the presence of inflammatory cells in the anterior chamber, vitreous or posteriorly, depending on the location of the inflammatory response. Other pathological changes found in uveitis include:

  • Anterior chamber flare - severely inflamed vessels become leaky and protein gets out, so clouding the normally clear aqueous. As the slit-lamp beam of light is shone through this, it appears hazy and the beam is dispersed - hence, the term flare. This is a marker of severe inflammation.
  • Synechiae - these are adhesions of the iris to the cornea (anterior synechiae) or to the lens (posterior synechiae) which develop as a result of the inflammatory process.
  • Keratic precipitates (KPs) - these are another finding in anterior uveitis: inflammatory cells clump together on the posterior (endothelial) part of the cornea, giving rise to the appearance of little white spots known as keratic precipitates (KPs). When KPs appear large and granular or greasy, the uveitis is said to be granulomatous. This suggests sarcoidosis or tuberculosis as an underlying cause.[1]
  • Retinal lesions - these may develop and may be single, multifocal, disseminated or diffuse. The type or distribution may be a pointer to the aetiology.
  • Uveitis is a relatively common condition; it is thought to account for 10% of blindness in people of working age in the Western world.[2] The existence of self-resolving forms means that the true incidence is unknown.
  • The epidemiology of uveitis varies with both age and geographical location.
  • Although uveitis is regarded as a disease of adults of working age (aged 20-50 years), an American study found that the incidence of uveitis in the elderly was substantially higher than previously thought. Anterior uveitis, the most common form in this age group, had a mean incidence of 243.6 cases per 100,000 persons per year.[6]
  • Racial predisposition to uveitis is related to the patient's underlying systemic disease (eg, HLA-B27 positivity in Caucasians, Behçet's disease in individuals of Mediterranean origin, etc).
  • Acute anterior uveitis is the most common type of uveitis in the UK.[2]

It is important to take a detailed history and, if the history suggests systemic symptoms, a full physical examination, as there may be signs relating to one of the many associated systemic diseases.[2][3] Immunosuppression causes a particular risk of infection-related uveitis.

Clinical features of uveitis vary depending on the location of the inflammation. Symptoms may develop over hours or days (acute uveitis), or onset may be gradual (chronic uveitis).

Symptoms

  • Acute anterior uveitis:
    • Presents as a progressive (over a few hours/days) unilateral (usually but not always), painful red eye, with blurred vision and photophobia. Eye pain is often worse when trying to read.
    • There may be excess tear production and an accompanying headache is common.
    • Not all of these symptoms may be present at the start of an attack.[2]
  • Chronic anterior uveitis:
    • Presents as recurrent episodes, with less acute symptoms.
    • Patients may find that one symptom predominates (this tends to be blurred vision) and they tend to get very good at spotting this early.
  • Posterior uveitis:
    • Causes gradual visual loss, usually bilateral, often associated with floaters.
    • There is occasional photophobia, but little or no discomfort or redness.

Some types of uveitis are more insidious and may be asymptomatic (eg, that associated with juvenile idiopathic arthritis).[2]

Signs

Anterior uveitis

  • Visual acuity in the affected eye is often reduced.
  • The pupil may be abnormally shaped or of a different size to the unaffected eye.
  • Direct photophobia (shining a light directly into the affected eye) and consensual photophobia (shining a light into the unaffected eye) may be demonstrated.
  • Injection around the corneal limbus (edge of the cornea) is characteristic and referred to as circumlimbal injection. This can be fairly localised but, as the uveitis progresses, the entire conjunctiva may appear red to the naked eye.
  • The predominant signs are seen in the anterior chamber (the space bound by the cornea and iris and filled with aqueous humour). These are best demonstrated with a slit-lamp microscope:
    • A slit lamp is used to shine a beam at an angle of 30-40° on the cornea and the area is inspected with the microscope. The beam should be narrowed to about 1 mm and put on its brightest setting and highest magnification.
    • The characteristic sign is the presence of cells in the aqueous humour. As you shine the slit-lamp beam through the anterior chamber, the appearance is of a shaft of light shining through darkness with bits of dust floating through it.
    • Ophthalmologists grade the severity of the uveitis by the number of cells seen, ranging from 0 (no cells seen) to +4 (>50 cells seen).
    • The aqueous humour is normally clear but in anterior uveitis it may become cloudy, giving the appearance of a 'flare' (see 'Pathophysiology', above). This appears rather like a shaft of light shining through a darkened, smoky room. Flare is also graded from 0 (no flare) to +4 (fibrin deposition).
    • Other findings may include synechiae and keratic precipitates.

A full dilated examination is mandatory on presentation, to exclude posterior segment disease or complications.[1]

Intermediate uveitis[8] 

  • Intermediate uveitis is inflammation in the anterior vitreous, ciliary body and the peripheral retina.
  • The term intermediate uveitis should be used for that subset of uveitis where the vitreous (the clear gel which fills the bulk of the globe, just behind the posterior chamber) is the major site of the inflammation and if there is an associated infection (eg, Lyme disease) or systemic disease (eg, sarcoidosis).
  • The inflammatory cells in the vitreous are best seen with a slit lamp and following dilation of the pupil. If you do have access to a slit lamp, get the patient to look just past you and focus in through the pupil, past the iris. The cells can be seen as little specks crossing the clear orange-red background of the fundus.
  • Pars planitis refers to a subset of intermediate uveitis where there is snow bank or snowball formation occurring in the absence of an associated infection or systemic disease (ie idiopathic). Clumps of white cells form the globular yellow-white 'snowballs' in the inferior peripheral vitreous and yellow-white exudates band to form 'snowbanks'.

Posterior uveitis

  • Inflammatory lesions may be seen on the retina or choroid. They may look yellow when fresh, whilst older ones have a more distinct edge and a whitish appearance.
  • Inflammation of the retinal blood vessels (retinal vasculitis) may occur.
  • Oedema of the optic nerve may be another feature.
  • The inflammation may 'spill over' anteriorly and give rise to cells in the vitreous.

Any cause of a red eye or visual disturbance should be included in the differential diagnosis.

  • A first episode of unilateral non-granulomatous acute uveitis can be diagnosed by history and clinical examination alone and does not need laboratory investigation.
  • Imaging may be helpful where there is posterior disease in order to assess site or severity of posterior inflammation. Fundus fluorescein angiography and optical coherence tomography (OCT) are the commonly used techniques, the latter being particularly helpful because it is a non-invasive test that only takes a few minutes to perform in clinic.
  • If history and examination are normal but the uveitis is granulomatous, recurrent or bilateral, further investigations are necessary to hunt for underlying causes. The exact nature of the investigation is guided by clinical suspicion - eg, a history of weight loss and unexplained diarrhoea might prompt a search for inflammatory bowel disease.
  • The value of doing a routine un-targeted screen is not clear.[2] The role of some investigations (eg, HLA-B27 status) remains controversial.
  • Laboratory tests on a sample of aqueous (anterior chamber) or vitreous (posterior part of the globe) may be helpful where infection or malignancy is suspected.

Uveitis is thought to be caused by an immune reaction. The underlying trigger varies according to genetic and environmental factors.[2]

About 50% of cases of uveitis are idiopathic. The remainder may be associated with a number of conditions. There are specific conditions associated with subcategories of uveitis (anterior, intermediate, posterior and panuveitis).

A selection of the more common associations is presented here but full lists can be obtained in the 'Further reading & references' section, below.[1]

About 50% of patients with acute anterior uveitis are HLA-B27 positive. Nongranulomatous disease can be associated with:

The only group of patients currently screened for uveitis is children with juvenile idiopathic arthritis.

Some infections are associated with anterior uveitis and this is thought to be due to an immune reaction to the organism. They include herpes simplex and herpes zoster.

Granulomatous anterior and posterior uveitis are associated with:

Non-infectious causes of posterior disease include:

  • Behçet's disease
  • Sacroiliitis (usually bilateral)
  • Lymphoma
  • Vogt-Koyanagi-Harada disease

Posterior uveitis may also be associated with autoimmune retinal vasculitis.

If uveitis is suspected, immediate specialist referral is appropriate to confirm diagnosis and facilitate treatment. Delay in appropriate management can lead to the development of significant complications and irreversible loss of vision. Exact treatment is determined by the type of uveitis (anterior versus posterior), whether the uveitis is secondary to an infection or not and whether it is likely to threaten sight. All patients with anterior disease and most with intermediate or posterior disease require treatment. For patients with systemic disease, a collaborative approach between ophthalmologists and other specialities is important.

Refer people with suspected uveitis for an assessment by an ophthalmologist within 24 hours. Also refer people who have had uveitis before and feel the symptoms coming on before the signs are present. Do not initiate treatment for recurrent uveitis in primary care, unless asked to do so by an ophthalmologist.

  • Corticosteroids are used to reduce inflammation and prevent adhesions in the eye. They may be given topically, orally, intravenously, intramuscularly, or by peri-ocular or intra-ocular injection, depending on the severity of the uveitis. Corticosteroids are reduced slowly, as withdrawing them too quickly may lead to rebound inflammation.
  • A cycloplegic-mydriatic drug (for example, cyclopentolate 1% or atropine 1%) is also given to paralyse the ciliary body. This relieves pain and prevents adhesions between the iris and lens.
  • Infectious uveitis (bacterial, viral, fungal, or parasitic) is treated with an appropriate antimicrobial drug as well as corticosteroids and cycloplegics.
  • People with severe or chronic uveitis may also be given systemic (non-corticosteroid) immunosuppressive drugs, laser phototherapy, or cryotherapy, or have the vitreous removed surgically (vitrectomy).

Adjunctive therapy

  • Secondary causes should be treated as appropriate. Where there is an infection, this needs to be treated as a priority.[2] (See the separate article on Chorioretinal Inflammation for more details about treatment of ocular toxoplasmosis.)
  • Ongoing research is looking at the use of immune modulators such as tumour necrosis factor alpha-blockers (eg, etanercept, infliximab) and the interleukin-2 receptor blockers. A number of studies on less invasive sustained ocular drug delivery systems, including episcleral implants, nanospheres, and cyclodextrin particles are being conducted.[9] Interferon alfa may also have potential in treating refractory sight-threatening uveitis from a variety of causes.[10]
  • Azathioprine has been found to be useful in steroid-resistant autoimmune uveitis.[11] Ciclosporin and tacrolimus have also been investigated and have been shown to be associated with control of ocular inflammation and preservation or restoration of sight. However, currently immunosuppressive treatment has not been licensed for uveitis.
  • There may be a role for the family of anti-vascular endothelial growth factor drugs (eg, ranibizumab, Lucentis®, which is currently used for 'wet' age-related macular degeneration) in managing chronic, non-infective uveitis but these drugs are not yet licensed for this use.[2] Furthermore, any intravitreal injection carries a small inherent risk of complications (including sight loss) in itself.

Surgery

Surgery is only considered in a small proportion of patients with severe or intractable disease or where a diagnostic vitreous sample is required (eg, to diagnose infection or malignancy). Other reasons for surgery include removal of a secondary cataract or for preservation of vision in uveitic glaucoma.[2]

Monitoring the disease[3]

  • This is almost entirely by clinical examination but some investigations provide a useful adjunct.
  • Optical coherence tomography (OCT) is very helpful in looking for macular causes of worsening vision, particularly where slit-lamp view is not good.
  • Fluorescein angiography is helpful where retinal vascular involvement needs to be assessed. Visual fields are also helpful for monitoring optic nerve damage.

Visual loss as a result of:[2]

  • Cystoid macular oedema (swelling of the macula) - this is the leading cause of visual loss in the UK along with secondary cataract formation.
  • Secondary cataract.
  • Acute rise in intraocular pressure, with or without glaucoma:
    • This may occur either as a direct consequence of the inflammatory process or secondary to steroid treatment.
    • Some patients, especially those with a history of glaucoma, are prone to developing high intraocular pressure as a result of steroid treatment and require treatment to reduce the intraocular pressure. Treatment to reduce intraocular pressure can be stopped when the steroid treatment is stopped if the patient doesn't have pre-existing glaucoma.
  • Vitreous opacities (inflammatory debris or haemorrhage).
  • Retinal detachment.
  • Neovascularisation of the retina, optic nerve, or iris.
  • Macular ischaemia, vascular occlusions and optic neuropathy - can be complications of posterior uveitis.

Posterior synechiae are a common complication of anterior uveitis; if numerous they can cause blockage of the aqueous flow, leading to a rise in intra-ocular pressure, and can complicate cataract operations

  • Anterior uveitis is sometimes a self-limiting condition.
  • With prompt and effective treatment, there is usually a good visual outcome (a study found that 91% of these patients retain normal vision).[2]
  • The factors which cause spontaneous resolution in some patients and complications in others are unclear.[12]
  • Relapse after a first episode of acute anterior uveitis is probably more common than previously thought - a recent study suggested an incidence of about 24% per person-year, this occurring more commonly in the younger patient age group (18-35 year-olds).[13]
  • The prognosis of chronic granulomatous uveitis depends on the cause and whether the underlying condition is recognised and treated early enough.
  • Outcomes have been improved by the use of immune modulators in previously refractory cases.[14]

Further reading & references

  1. Jackson TL; Moorfields Manual of Ophthalmology, Mosby (2008)
  2. Guly CM, Forrester JV; Investigation and management of uveitis. BMJ. 2010 Oct 13;341:c4976. doi: 10.1136/bmj.c4976.
  3. Denniston AKO, Murray PI; Oxford Handbook of Ophthalmology (OUP), 2009
  4. Kempen JH, Ganesh SK, Sangwan VS, et al; Interobserver Agreement in Grading Activity and Site of Inflammation in Eyes of Patients with Uveitis. Am J Ophthalmol. 2008 Aug 5.
  5. Deschenes J, Murray PI, Rao NA, et al; International Uveitis Study Group (IUSG): clinical classification of uveitis. Ocul Immunol Inflamm. 2008 Jan-Feb;16(1):1-2.
  6. Reeves SW, Sloan FA, Lee PP, et al; Uveitis in the elderly: epidemiological data from the National Long-term Care Survey Medicare Cohort. Ophthalmology. 2006 Feb;113(2):307.e1. Epub 2006 Jan 10.
  7. Uveitis; NICE CKS, November 2009
  8. Babu BM, Rathinam SR; Intermediate uveitis. Indian J Ophthalmol. 2010 Jan-Feb;58(1):21-7. doi: 10.4103/0301-4738.58469.
  9. Jap A, Chee SP; Immunosuppressive therapy for ocular diseases. Curr Opin Ophthalmol. 2008 Nov;19(6):535-40.
  10. Plskova J, Greiner K, Forrester JV; Interferon-alpha as an effective treatment for noninfectious posterior uveitis and panuveitis. Am J Ophthalmol. 2007 Jul;144(1):55-61.
  11. Pacheco PA, Taylor SR, Cuchacovich MT, et al; Azathioprine in the management of autoimmune uveitis. Ocul Immunol Inflamm. 2008 Jul-Aug;16(4):161-5.
  12. Curi A; Acute anterior uveitis Clinical Evidence 2005; Requires registration
  13. Grunwald L, Newcomb CW, Daniel E, et al; Risk of Relapse in Primary Acute Anterior Uveitis. Ophthalmology. 2011 Jun 14.
  14. Kahn P, Weiss M, Imundo LF, et al; Favorable response to high-dose infliximab for refractory childhood uveitis.; Ophthalmology. 2006 May;113(5):864.e1-2. Epub 2006 Mar 20.

Disclaimer: This article is for information only and should not be used for the diagnosis or treatment of medical conditions. EMIS has used all reasonable care in compiling the information but make no warranty as to its accuracy. Consult a doctor or other health care professional for diagnosis and treatment of medical conditions. For details see our conditions.

Original Author:
Dr Laurence Knott
Current Version:
Peer Reviewer:
Dr Olivia Scott
Last Checked:
10/07/2013
Document ID:
1599 (v26)
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