Iritis and Uveitis

Uveitis means inflammation of the uveal tract. The uveal tract consists of the iris, the ciliary body and the choroid.

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 our dedicated record - Sympathetic Ophthalmia.

The condition can be classified in various ways:

Anatomical

A common classification is by anatomical location of the pathology. Anterior uveitis affects the anterior chamber, posterior uveitis the posterior chamber. Intermediate uveitis affects the middle part of the globe and panuveitis indicates a severe infection involving many parts of the uveal tract. Spillover uveitis refers to posterior disease which is extensive enough to spread to the anterior chamber.¹

Duration

This is defined as acute when less than three months or chronic when greater than three months.

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
• Injurious - due to trauma
• Iatrogenic - caused by surgery, inadvertent trauma, or medication
• 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

Presenting clinical features^2,3

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

Although the classification of uveitis is now based primarily on anatomical distribution,⁴ a knowledge of the pathophysiology of the condition helps both to focus on the range of investigation required and the possible aetiology (see below). Uveitis is characterised by the presence of inflammatory cells. Frequently (but not invariably) this results in the development of clumps of white blood cells called keratic precipitates (KPs) on the corneal endothelium. If the KPs appear greasy, granular and large, the condition is called granulomatous uveitis. If the KPs are small to medium sized, the condition is called non-granular uveitis. Granulomatous uveitis suggests a more severe inflammatory process than the non-granulomatous type.
Other pathophysiological changes which may aid diagnosis include:

• Retinal lesions - these may develop which may be single, multifocal, disseminated (spread over a wide area) or diffuse (poorly localised). The type or distribution may be a pointer to the aetiology.
• Anterior chamber flare - the presence of white cells in acute inflammation and changes to blood vessels in more chronic forms gives a smokey appearance on examination (see below).
• 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.
• Fibrin - this is seen in severe inflammation when the inflammatory process causes massive leakage of protein from blood vessels.

• Uveitis is a relatively common condition. The existence of self-resolving forms means that the true incidence is unknown. A uveitis register kept at Leicester Royal Infirmary recorded 712 patients over a ten year period.⁵
• A study of 1417 uveitis patients presenting at an ophthalmic clinic in Rome showed that 17.43% of cases were associated with infection, of which Toxoplasma gondii was the commonest agent (6.63%).⁶
• An American study found that the incidence of uveitis in the elderly was substantially higher than previously thought. Anterior uveitis, the commonest form in this age group, had a mean incidence of 243.6 cases per 100,000 persons per year.⁷
• The epidemiology of uveitis varies with both age and geographical location. One study of uveitis cases over 35 years in tropical countries, the most commonly identified entities in the cohort included leptospiral uveitis (9.7%), tuberculous uveitis (5.6%) and herpetic uveitis (4.9%). The most common uveitis in children below 16 years is paediatric parasitic anterior uveitis, whereas herpetic anterior uveitis was the commonest cause above in patients above 60.⁸

Symptoms

• Acute anterior uveitis presents as a unilateral, painful red eye, with blurring, photophobia and excess tear production.
• Chronic anterior uveitis presents as recurrent episodes, with minimal acute symptoms.
• Posterior uveitis causes gradual visual loss, usually bilateral. There is occasional photophobia, but little or no discomfort or redness. Floaters are usually a predominant feature.

Signs

Anterior uveitis:

• Visual acuity in the affected eye may be reduced.
• Direct photophobia (shining a light directly into the affected eye) and consensual photophobia (shining a light into the unaffected eye) may be demonstrated. This helps to exclude uveitis from conjunctivitis, in which consensual photophobia is absent.⁹
• Injection around the iris is characteristic. This is fairly localised, with most of the conjunctiva being unaffected.
• The predominant signs are seen in the anterior chamber (the space bounded by the cornea and iris and filled with aqueous humor). These are best demonstrated with a slit-lamp microscope. A slit-lamp is used to shine a beam at an angle of 30 to 40 degrees on the cornea and the area is inspected with the microscope. The beam should be narrowed to about 1mm and put on its brightest setting.
• The aqueous humour is normally clear, but in anterior uveitis is cloudy, giving the appearance of a 'flare' (see Pathophysiology, above). It has been described as being similar to the appearance of a moving projector beam in a dusty room.
• The other predominant sign is the presence of cells in the aqueous humour. This can be seen by narrowing the slit lamp beam to about 1mm and put on its brightest setting. The appearance is of a shaft of sunlight shining through a floor board, with bits of dust floating through it.
• The corneal endothelium may show granulomatous or non-granulomatous KPs.

• Cells may be seen in the vitreous humor (the clear gel which fills the posterior chamber of the eye). 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, signified amongst other things, by fluffy white perivascular deposits.¹²
• Oedema of the optic nerve may be another feature.

• Conjunctivitis
• Corneal abrasion
• Corneal ulceration and ulcerative keratitis
• Acute angle closure glaucoma
• Scleritis
• Ultraviolet keratitis
• Retinal detachment
• Posterior segment tumour (e.g. retinoblastoma, leukemia, malignant melanoma)
• Intraocular foreign body
• Sclerouveitis (anterior uveitis with scleral involvement)

A first episode of unilateral nongranulomatous acute uveitis can be diagnosed by history and clinical examination alone and does not need laboratory investigation.

If history and examination are normal but the uveitis is granulomatous, recurrent or bilateral, the following screening investigations should be carried out:

• Full blood count and ESR
• HLA-B27
• Antinuclear antibody
• Screening tests for syphilis and tuberculosis
• Chest x-ray
• Lyme titre

Recent advances

• Polymerase chain reaction is useful in suspected infective uveitis in immunocompromised patients.¹³
• Newer imaging techniques such as spectral domain optical coherence tomography (a method of producing extremely high-quality, micrometre-resolution, three-dimensional images) and fundus autofluorescence (a method that allows topographic mapping of lipofuscin distribution in the retinal pigment epithelium cells and other fluorophilic tissues) are increasingly being used.¹⁴

Secondary causes should be excluded as suggested by history, lifestyle, age and examination findings.

Uveitis is thought to be caused by an immune reaction.
Anterior non-granulomatous acute uveitis is associated with a variety of HLA-B27 related conditions, including:

• Sacroiliitis
• Ankylosing spondylitis
• Reiter's syndrome
• Psoriasis
• Ulcerative colitis
• Crohn's disease

Some infections are associated with 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 is associated with:

• Behcet's syndrome
• Sacroiliitis (usually bilateral)
• TB
• Syphilis
• Toxoplasmosis
• In AIDS
  • Cytomegalovirus
  • Human syncytial virus
  • Cryptococcus
  • Toxoplasma
  • Candida

Posterior uveitis may also be associated with autoimmune retinal vasculitis.

General measures

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.

Non-specific treatment is directed towards relieving discomfort and preventing visual loss and other complications.¹

Drops to dilate the pupil (cyclopegics) such as cyclopentolate 1% or atropine 1%⁹ should be prescribed, but this is best done by a specialist as this treatment is contraindicated in narrow angle glaucoma. Cyclopentolate is usually preferred as it is much shorter acting than atropine. When using cyclopegics, the patient should be warned that the pupil will appear large and they will have a temporary problem with vision in the eye in which the drops have been administered.

Steroids

Steroid eye drops such as prednisolone 1% are the first line treatment for the management of the inflammation. In more severe cases, steroid injection or even systemic therapy may be required. The BNF warn that they should normally be prescribed by a specialist, as they can cause corneal ulceration when the diagnosis is herpes simplex infection, steroid glaucoma and on prolonged use, steroid cataract.

Non-steroidal anti-inflammatory drops seem to be a useful alternative to steroids. Unfortunately, the only NSAID drops available in the UK, diclofenac, are not licensed for this use.

Adjunctive therapy

• Secondary causes should be treated as appropriate.
• Ongoing research is looking at the use of immune modulators such as tumor necrosis factor alpha blockers (e.g., etanercept, infliximab) and the interleukin-2 receptor blockers.¹² Limitations of use include cost and methods of delivery. A number of studies on less invasive sustained ocular drug delivery systems, including episcleral implants, nanospheres, and cyclodextrin particles are being conducted.¹⁵
• Interferon-alpha may also have potential in treating refractory sight-threatening uveitis from a variety of causes.¹⁶
• Azathioprine has been found to be useful in steroid-resistant autoimmune uveitis.¹⁷

Surgery

Removal of the vitreous may be necessary when persistent floaters severely impede visual acuity.¹² This procedure may also be useful as a combined therapeutic and diagnostic test as, once removed, the vitreous can be analysed to exclude infection or malignancy.¹⁸

These can include:

• Posterior synechiae - these commonest complication of anterior uveitis, if numerous can cause blockage of aqueous flow leading to a rise in intra-ocular pressure and can complicate cataract operations
• Cataract
• Glaucoma
• Retinal detachment
• Neovascularisation of the retina, optic nerve, or iris
• Cystoid macular oedema (swelling of the macula)
• Macular ischaemia, vascular occlusions and optic neuropathy - can be complications of posterior uveitis

Anterior uveitis is sometimes a self-limiting condition, although the factors which cause spontaneous resolution in some patients and complications in others are unclear.¹⁹ The mere fact that the condition has resolved should not obviate the need to investigate the cause and minimise the risk of further episodes. One study of acute uveitis comparing 119 HLA-B27 positive patients and 35 HLA-B27 negative patients found no significant difference in complications between the two groups.²⁰The 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.²¹