Investigations

1st investigations to order

clinical diagnosis

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Uveitis may be idiopathic, or associated with HLA-B27-related disease or systemic inflammatory disease, viral eye disease or other localised infections, or systemic infection. Onset and duration of the ocular symptoms offer clues to the aetiology. Diagnosis of underlying disease may require investigation.

In patients with a first-episode unilateral, non-granulomatous uveitis without symptoms or systemic manifestations, no further evaluation is warranted. This is also true for patients with a recent history of trauma or surgery or with clinical signs of herpes simplex virus or herpes zoster virus infection.

If the patient presents with bilateral, recurrent, or granulomatous uveitis, further evaluation is needed. CBC, ACE level (elevated in sarcoidosis), syphilis serology, and HLA-B27 help to identify a related systemic disease. Testing for rheumatoid factor and anticyclic citrullinated peptide antibodies should be done in the setting of suspected rheumatoid arthritis. Antinuclear antibodies (ANA) and anti-double-stranded DNA (anti-dsDNA) antibodies are important diagnostic markers for SLE. Other HLA antigens may point to the presence of specific disorders. Elevated levels of antineutrophil cytoplasmic antibodies point to the presence of a vasculitic condition.

Result

diagnosis is based on history, symptoms, and eye signs

Investigations to consider

FBC

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Non-specific marker for infectious disease.

Result

high WBC (in infection)

erythrocyte sedimentation rate

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Non-specific inflammatory marker.

Result

elevated (in inflammatory disease); values >80 mm/hour are always significant

CRP

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Non-specific inflammatory marker.

Result

elevated (in inflammatory disease)

fluorescent treponemal antibody (FTA-ABS), Venereal Disease Research Laboratory (VDRL), and rapid plasma reagin (RPR)

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Tests help to identify syphilis infection. Ocular manifestations of syphilis involve secondary, tertiary, and neurosyphilis, and RPR and VDRL are usually positive in these patients. A positive FTA-ABS test result does not necessarily indicate active syphilis but a history of syphilis at some point, since the test remains positive for life after syphilis infection. False-positive results may occur in Lyme disease, leprosy, and diseases with high antinuclear antibody levels. False-negative results may occur in tertiary syphilis.

Result

positive (in syphilis)

serum ACE

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ACE is elevated in patients with sarcoidosis. Important to note if the patient is on ACE inhibitors, as the medicine will lower ACE levels.

May also be elevated in hyperthyroidism, acute hepatitis, multiple myeloma, tuberculosis, and leprosy.

Result

elevated (in sarcoidosis and some other conditions associated with uveitis)

antinuclear antibodies

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A general marker of collagen vascular disease.

Seen in juvenile idiopathic arthritis, and so may be particularly useful in children.

Antinuclear antibody is positive in virtually all patients with SLE.[18]

Result

positive (in many collagen vascular diseases)

HLA-B27

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Approximately 49% of patients with anterior uveitis test positive for HLA-B27.[10]

Presence suggests seronegative spondylo-arthropathy. Often positive in recurrent iritis.

Result

positive (in many patients with uveitis)

Lyme titre

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A Lyme titre testing for Borrelia burgdorferi should be ordered in endemic areas.[19]

Result

positive (in Lyme disease)

purified protein derivative (PPD) skin test

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Should be ordered for patients with suspected tuberculosis (TB), and for those with HIV or history of alcohol abuse. Should also be ordered in endemic regions or after recent contact with an infected person.

Active TB should be ruled out if test is positive.

Special considerations should be taken when interpreting the test in patients receiving the Bacillus Calmette-Guérin vaccine (false positive) and in immunosuppressed patients (false negative).

Interferon-gamma release assays are a newer test that may help to diagnose TB.

Result

positive (in TB) if >5 mm in HIV patients, 10 mm or greater in high-risk patients, 15 mm or greater in low-risk patients

cytoplasmic antineutrophil cytoplasmic antibodies (c-ANCA)

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Most patients with granulomatosis with polyangiitis (formerly known as Wegener's granulomatosis) have a positive c-ANCA.

Proteinase 3 is the c-ANCA target antigen.

Result

positive (in granulomatosis with polyangiitis)

perinuclear antineutrophil cytoplasmic antibodies (p-ANCA)

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Levels elevated in microscopic polyangiitis, Churg-Strauss syndrome, and other vasculitides.

Myeloperoxidase is the p-ANCA target antigen.

Result

elevated (in various vasculitic conditions)

antidouble-stranded DNA antibody (anti-dsDNA)

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Positive in systemic lupus erythematosus (SLE).

Result

positive (in SLE)

rheumatoid factor

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Levels elevated in rheumatoid arthritis; levels also elevated in Sjogren's syndrome and other autoimmune diseases.

Result

elevated (in rheumatoid arthritis and some other autoimmune diseases)

anticyclic citrullinated peptide (anti-CCP) antibodies

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Elevated levels specific for rheumatoid arthritis; not used in children.

Result

elevated (in rheumatoid arthritis)

Bartonella henselae titre

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Positive serology is highly indicative of cat-scratch disease.

Result

positive (in cat-scratch fever)

toxoplasma serological titre

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If positive, highly indicative of toxoplasmosis as the causative agent.

Result

positive (in toxoplasma infection)

other HLA antigens

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Presence may indicate the presence of specific conditions (HLA-A29 in birdshot retinochoroidopathy [a bilateral inflammatory disease affecting the choroid layer]; HLA B*0501 in Behçet's disease; HLA DR*0405 in Vogt-Koyanagi-Harada syndrome, a multi-system autoimmune disorder characterised by chronic uveitis with skin, neurological, and auditory manifestations).

Result

present or absent

chemistry screen

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May identify renal and hepatic dysfunction associated with uveitis-related inflammatory diseases.

Result

may be abnormal in systemic inflammatory disorders

CXR

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Should be ordered to look for tuberculosis (TB) or sarcoidosis.

Result

sarcoidosis: enlarged lymph nodes or pulmonary infiltration; active TB: clear or infiltrate or consolidation, cavitary lesion with or without surrounding calcification, nodule with poorly defined margins, pleural effusion, hilar or mediastinal lymphadenopathy

polymerase chain reaction (PCR)

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Performed on aqueous fluid from the anterior chamber of the eye in cases of suspected viral infection.

Result

may be positive for herpes simplex virus, varicella zoster virus, or cytomegalovirus DNA

Emerging tests

vitreous biopsy

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Result
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Removal of vitreous fluid for analysis allows helpful diagnostic data for uveitis of unknown cause.[20] Cytological analysis, flow cytometry, and culture may be performed.

Result

may show positive culture or cellular abnormality

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