13th February 2025

Uveitis

Overview of uveitis

The term uveitis encompasses inflammation of one or all parts of the uvea (the layer between the retina and sclera). All types of uveitis should be referred to ophthalmology as they carry a risk of blindness.

Anatomical classification is useful both for understanding clinical features and because different aetiologies cause different patterns of inflammation:

• Anterior uveitis (iritis): iris and ciliary body
• Posterior uveitis: posterior vitreous, retina, choroid, retinal vasculature, optic nerve
• Panuveitis: all segments of uveal tract

Uveitis is most commonly idiopathic, but in many cases it is associated with systemic disease. Management is specific to the underlying cause, and systemic signs and symptoms should be sought to make a unifying diagnosis.

Clinical features of uveitis

Ocular signs and symptoms depend on the anatomical distribution of inflammation:

Table 5 Presentation of uveitis

Acute anterior uveitis can be recurrent and is most commonly unilateral. Patients may present with rapid onset of eye pain, redness and photophobia. Visual acuity is usually only mildly impaired but this may be variable, dependent on severity. Conjunctival hyperaemia is usually present, and miosis may be seen as a result of pupillary sphincter spasm. Cells may be present in the anterior chamber and hypopyon describes a cream-coloured exudate made up of inflammatory cells which may settle in the inferior part of the anterior chamber.

The rest of this section will explore key causes of uveitis.

Bacterial causes of uveitis

Tuberculosis

Infection with Mycobacterium tuberculosis predominantly affects the respiratory system but can also have extrapulmonary manifestations. Tuberculosis can cause a range of ocular pathology such as anterior uveitis, vitritis choroiditis and cystoid macular oedema. Posterior uveitis with choroiditis is the most common finding, though anterior uveitis with granulomatous findings can often be seen. Ocular symptoms may be present in the absence of systemic upset and may, therefore, prompt further investigations for suspected tuberculosis. Treatment of the systemic infection is necessary and should be referred to a respiratory specialist.

Syphilis

Anterior uveitis may be found in a small proportion of people infected with the spirochaete Treponema pallidum and may cause unilateral or bilateral disease. It is predominantly associated with secondary syphilis, and therefore, the patient may have a history of a painless genital or anal ulcer or a maculopapular rash. If suspected, the patient should be referred to a sexual health specialist for systemic assessment (HIV status should also be established) in addition to an ophthalmologist for management of uveitis.

Bacterial endophthalmitis

Bacterial endophthalmitis is a sight-threatening bacterial infection of the vitreous or aqueous humour of the eye and is an ophthalmic emergency. It is most commonly caused by exogenous contamination from surgery (most commonly Staphylococcus epidermidis when acute) or trauma to the eye. Spread from endogenous sources is less common and the risk factors are largely the same as fungal sources.

Symptoms may include pain, blurry vision and redness of the eye. Slit lamp examination may reveal a hazy cornea, chemosis, hypopyon and it may be difficult to visualise the fundus due to vitritis. Roth spots are retinal haemorrhages with white centres, and if present may indicate infective endocarditis as a potential source. Vitreous sampling for identification of the pathogen is helpful, and immediate intravitreal antibiotics are required in addition to treatment of systemic infection where present.

Viral causes of uveitis

Herpes simplex virus anterior uveitis

Herpes simplex-associated uveitis can occur in the presence of keratitis or in isolation, but there will often be a history of cold sores, keratitis or genital lesions. Patchy iris atrophy may be seen on slit lamp examination, and the affected pupil may be slightly larger. Keratic precipitates (cellular inflammatory deposits on the corneal endothelium) may be present, and IOP may be raised. It is usually treated with a combination of topical steroids, topical cycloplegic (paralyses the ciliary muscles, preventing accommodation) and an oral antiviral.

Varicella zoster virus anterior uveitis

Anterior uveitis can occur in around half of patients affected by herpes zoster ophthalmicus and usually occurs 1-3 weeks after the rash. In immunocompromised patients, infection with primary varicella zoster infection (chickenpox) may also lead to uveitis. Management is with topical steroids, mydriatics and systemic antivirals such as aciclovir.

Cytomegalovirus

Infection with cytomegalovirus (CMV) is more likely to be clinically significant in immunocompromised patients. Uveitis associated with CMV is usually unilateral. The mainstay of treatment is with antivirals such as ganciclovir and valganciclovir.

Fungal causes of uveitis

Rarely, fungal infections can cause endophthalmitis, which involves inflammation of the vitreous or aqueous humour. These may be exogenous, introduced by spread from fungal keratitis or surgeries, or endogenous, for example as a result of intravenous drug use or systemic infection, or immunocompromise. Aspergillus spp. are most commonly implicated in exogenous cases, followed by Candida albicans. The reverse is true for endogenous cases, with Candida spp more prominently associated.

Culture of intraocular fluid is the gold standard for diagnosis. Slit lamp examination may reveal ‘cotton wool’ or ‘fluffy’ chorioretinal infiltrates. The mainstay of treatment is systemic and, if required, intravitreal anti-fungals. Aspergillus spp. endophthalmitis tends to progress more rapidly than candidal infection and is therefore treated more aggressively.

Parasitic causes of uveitis

Toxoplasmosis

The causative organism is Toxoplasma gondii. Cats are the definitive host so contamination from cat litter into food is the most common route of infection. Infection may be congenital after maternal exposure, or acquired. Toxoplasmosis causes a posterior uveitis. Serology for Toxoplasma may be carried out to aid diagnosis.

Toxocariasis

Toxocariasis is an infestation by a common roundworm found in dogs, so may be transmitted by contaminated soil or food. Usually, it is unilateral. Variable findings include chronic endophthalmitis and a posterior pole or peripheral granuloma seen during fundoscopy. Red reflex may be reduced in the affected eye.

Onchocerciasis (river blindness)

Caused by the helminth Onchocerca volvulus. Systemic features are mostly an intensely itchy maculopapular rash and ‘leopard skin’, which describes hypo-and hyperpigmentation mostly affecting the shins. Anterior uveitis may be an early feature, and it may be possible to visualise live microfilariae in the anterior chamber if the patient is face down prior to examination. Treatment is most commonly with ivermectin, which targets larvae.

Uveitis and rheumatic disorders

Ankylosing spondylitis

Ankylosing spondylitis is an HLA-B27-associated spondyloarthropathy characterised by joint inflammation, calcification and ultimately ossification, with a predilection for the axial skeleton. It commonly affects the sacroiliac joint and also may lead to spinal fusion in later stages. Onset is usually between 20-30 years and is significantly more common in males.

Patients typically present with chronic lower back pain or stiffness (for over 3 months) which is worse in the mornings and does not improve with rest but improves with exercise and a trial of NSAIDs. A family history of ankylosing spondylitis may also be present. Enthesitis and arthritis are common and usually occur asymmetrically and in the lower limbs. Extra-articular manifestations are varied in patients with ankylosing spondylitis; importantly, the lifetime prevalence of anterior uveitis is 30-40%, which means patients may present with symptoms of a unilateral red, painful eye. It is also associated with psoriasis and inflammatory bowel disease.

Cases of suspected ankylosing spondylitis should be referred to rheumatology for further assessment. ESR, CRP and HLA-B27 testing may be appropriate in addition to imaging of the sacroiliac joints and spine. NSAIDs, exercise and physiotherapy are the mainstay of treatment, but biological treatments may be considered in refractory cases. All patients with uveitis should be referred urgently to an ophthalmologist.

Reactive arthritis

This is the triad of urethritis, eye sequelae such as conjunctivitis and uveitis, and arthritis. The prevalence of  HLA-B27 positivity in reactive arthritis varies but is estimated to be between 30-50%. Reactive arthritis is more common in males. It may present in the days or weeks following either a bacterial genitourinary or gastrointestinal infection.

Joint pain and swelling is most common in the knee or ankle and is often worse in the mornings. Enthesitis (e.g. Achilles tendonitis and plantar fasciitis) or dactylitis may also be a feature. Skin features include keratoderma blennorrhagica on the palms or soles and painless mouth ulceration. Ocular features include self-limiting conjunctivitis, acute anterior uveitis and occasionally episcleritis. Management is typically with NSAIDs, corticosteroids and disease-modifying anti-rheumatic drugs (DMARDs).

Psoriatic arthritis

Characterised by arthritis which usually develops around 10 years after the onset of preceding psoriasis. Patients can present with asymmetrical oligoarticular or monoarticular joint involvement and may also have dactylitis and sacroiliitis. Nail changes such as pitting or onycholysis may be present. Acute anterior uveitis develops in around 7% of patients with psoriatic arthritis, with conjunctivitis also being associated. Psoriatic arthritis is also associated with HLA-B27. Management of psoriatic arthritis includes NSAIDs and corticosteroids, with DMARDs and biological treatments considered for more severe cases.

Sarcoidosis

Sarcoidosis is one of the most common systemic associations of uveitis. It is a multi-systemic inflammatory disorder of unknown cause, characterised by non-caseating granuloma formation. It is more common in females and has a bimodal age of onset between 20-40 years, and again in older age. Respiratory symptoms such as a dry cough and shortness of breath are common and attributed to variable disease progression from hilar adenopathy to significant pulmonary fibrosis. Malaise and arthralgia may also be present. Skin manifestations are reasonably common and may be specific and granulomatous or non-specific, such as erythema nodosum.

Ocular involvement (usually bilateral) may be seen in 20-75% of patients, most commonly granulomatous anterior uveitis. There are several key findings in ocular sarcoid; ‘mutton fat’ keratic precipitates are large grey-white inflammatory deposits of cells on the corneal endothelium and are a key sign of ocular sarcoid. Trabecular meshwork nodules, vitreous opacities (which may have a ‘snowball’ or ‘string of pearls’ appearance) and optic disc granulomas may also be seen.

Findings in sarcoidosis include elevated serum ACE (angiotensin converting enzyme) levels, deranged liver enzymes (most commonly ALP is raised) and bilateral hilar lymphadenopathy on chest X-ray. Tuberculosis should be ruled out. Treatment of sarcoidosis is by respiratory specialists. Spontaneous remission can occur (with likelihood inversely related to the severity of the disease), and therefore, treatment is not always indicated. If treated, this is usually with corticosteroids.

Behçet’s disease

Behçet’s disease is a multi-system vasculitis characterised by aphthous ulcers of the mouth and genitals, ocular manifestations, and skin lesions such as erythema nodosum. There are a range of CNS, gastrointestinal and other vasculitic manifestations, including pulmonary artery aneurysm. Ocular manifestations are usually bilateral and affect the entire uveal tract (panuveitis), which can be recurrent and may involve a range of sight-threatening complications such as retinal vasculitis and angle-closure glaucoma.

Typically, Behçet’s affects younger patients aged 20-40 years old, with a relatively equal gender distribution. It is more commonly found in people of Turkish, Mediterranean, Israeli or East Asian descent. HLA-B51 is a frequent association.

Investigations may reveal HLA-B51 positivity, a positive pathergy skin test and raised inflammatory markers. Full autoimmune screening should be carried out, and further investigations as appropriate to the clinical findings. Treatment is often with corticosteroids and immunosuppressive therapies.

Other systemic associations of uveitis

Other systemic associations of anterior uveitis include inflammatory bowel disease (uveitis is more common in patients who are also positive for HLA-B27), IgA nephropathy and juvenile idiopathic arthritis.

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