Investigations
1st investigations to order
clinical diagnosis
Test
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 (may be elevated in sarcoidosis), syphilis serology, and HLA-B27 help to identify a related systemic disease. Testing for rheumatoid factor and anti-cyclic 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 systemic lupus erythematosus (SLE). Other HLA antigens may point to the presence of specific disorders. Elevated levels of anti-neutrophil cytoplasmic antibodies point to the presence of a vasculitic condition.
Infectious aetiologies are ruled out before considering autoimmune-mediated aetiologies.
Result
diagnosis is based on history, symptoms, and eye signs
slit-lamp biomicroscopy
Test
Upon slit-lamp examination, anterior uveitis may show conjunctival injection with exacerbation around the limbus (ciliary flush), a slight decrease in visual acuity, lymphocyte aggregates in the corneal endothelium (keratic precipitates), corneal oedema, and white blood cells or protein in the anterior chamber (flare).
Simultaneous dilated fundoscopic examination allows visualisation of the posterior segment, vitreous cell and haze, choroidal or retinal inflammation, vasculitis, optic nerve pathology, and macular oedema.[41]
Result
identifies subclassification of uveitis (anterior, intermediate, posterior, or panuveitis)
tonometry
Test
Performed at slit-lamp examination. Goldmann applanation tonometry is recommended. Determines precise intra-ocular pressure (IOP). Elevated IOP may indicate infectious uveitis (acute setting) or risk of uveitic glaucoma (chronic setting).[41][49]
Result
decrease in intra-ocular pressure (rarely increased)
gonioscopy
Test
Performed at slit-lamp examination. Gonioscopy of both eyes should be performed on all patients in whom angle closure is suspected. Gonioscopy is used to visualise the anterior chamber angle of the eye, which is essential for evaluating and managing glaucoma.[40][41][42]
Result
gonio-synechiae or neovascularisation in angles
Investigations to consider
visual field testing
optical coherence tomography (OCT)
fluorescein angiography
FBC
Test
Non-specific marker for infectious disease.
Result
high WBC (in infection)
erythrocyte sedimentation rate
Test
Non-specific inflammatory marker.
Result
elevated (in inflammatory disease); values >80 mm/hour are always significant
CRP
Test
Non-specific inflammatory marker.
Result
elevated (in inflammatory disease)
fluorescent treponemal antibody (FTA-ABS), Venereal Disease Research Laboratory (VDRL), and rapid plasma reagin (RPR)
Test
Ocular manifestations of syphilis involve secondary, tertiary, and neurosyphilis; 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, because the test remains positive for life after syphilis infection.
Result
positive (in syphilis)
serum ACE
Test
ACE levels may be elevated in patients with sarcoidosis, but the correlation with disease activity is inconsistent.[53][54]
ACE levels may be elevated in hyperthyroidism, acute hepatitis, multiple myeloma, tuberculosis, and leprosy.
ACE inhibitors lower ACE levels; confirm drug history with the patient.
Result
elevated (in sarcoidosis and some other conditions associated with uveitis)
antinuclear antibodies (ANAs)
Test
A general marker of collagen vascular disease.
Antinuclear antibody is positive in virtually all patients with systemic lupus erythematosus (SLE).[55]
Result
positive (in many collagen vascular diseases)
HLA-B27
Test
Approximately 49% of patients with anterior uveitis test positive for HLA-B27.[11]
Presence suggests seronegative spondylo-arthropathy. Often positive in recurrent iritis.
Result
positive (in many patients with uveitis)
Lyme titre
Test
A Lyme titre testing for Borrelia burgdorferi should be ordered in endemic areas.[56]
Result
positive (in Lyme disease)
purified protein derivative (PPD) skin test
Test
Should be ordered for patients with: HIV; a history of alcohol abuse; suspected tuberculosis (TB) or in an endemic region; recent contact with a person infected with TB.
Screening tests to identify latent tuberculosis infection should be interpreted with caution, taking into account the person's immune status, history of exposure to TB and the Bacillus Calmette-Guérin (BCG) vaccination, and other risk factors.
There is no reliable way to distinguish a positive PPD skin test reaction caused by BCG vaccination from a reaction caused by true TB infection.[44] Active TB should be ruled out if the PPD test is positive.
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 anti-neutrophil cytoplasmic antibodies (c-ANCA)
Test
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 anti-neutrophil cytoplasmic antibodies (p-ANCA)
Test
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)
Test
Positive in systemic lupus erythematosus (SLE).
Result
positive (in SLE)
rheumatoid factor
Test
Levels elevated in rheumatoid arthritis; levels also elevated in Sjogren syndrome and other autoimmune diseases.
Result
elevated (in rheumatoid arthritis and some other autoimmune diseases)
anti-cyclic citrullinated peptide (anti-CCP) antibodies
Test
Elevated levels specific for rheumatoid arthritis.
Result
elevated (in rheumatoid arthritis)
Bartonella henselae titre
Test
Positive serology is highly indicative of cat-scratch disease.
Result
positive (in cat-scratch fever)
toxoplasma serological titre
Test
If positive, highly indicative of toxoplasmosis as the causative agent.
Result
positive (in toxoplasma infection)
other HLA antigens
Test
Presence may suggest 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
may be present
biochemistry screen
Test
May identify renal and hepatic dysfunction associated with uveitis-related inflammatory diseases.
Result
may be abnormal in systemic inflammatory disorders
chest x-ray
Test
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
real-time polymerase chain reaction (PCR) for ocular infectious disease
Test
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
diagnostic vitrectomy biopsy
Test
Intra-ocular sampling, including diagnostic vitrectomy, may be of value in the setting of a diagnostic dilemma.[46]
Diagnostic testing may include cytology, flow cytometry, Gram stain, culture (bacterial, fungal, and nocardial infection), polymerase chain reaction (PCR) testing (bacterial endophthalmitis and infection with mycobacterium tuberculosis; viral retinitides and ocular toxoplasmosis), antibody (toxoplasmosis and toxocariasis), and cytokine evaluation, depending upon the patient presentation.[46]
Result
may show positive culture or cellular abnormality
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