PG Series: Laboratory Investigations of Uveitis

Routine Tests:

Routine blood tests are of limited value for the diagnosis of specific causes of uveitis. However, they are important when immunosuppressants are planned for the treatment of uveitis. They also provide a base line to note therapeutic response and drug side effects.

• Total and differential counts sometimes could give clues to the etiology of the disease like
  • Total count can be increased in bacterial infections
  • Eosinophilia is seen in patients with sarcoidosis and parasitic infection
  • Lymphocytosis is seen in tuberculosis and viral infections
• Erythrocyte sedimentation rate are raised in connective tissue disorders, sarcoidosis and also in infectious conditions such as tuberculosis, syphilis, etc.

CD4/CD8 Lymphocytes ratio:

Done in patients with suspected HIV infection. This ratio is said to have a sensitivity of 85% but a lower specificity.

• Normal CD4 count above 400/cu.mm
• Normal CD8 count 200-800/cu.mm
• The CD4/CD8 ratio is usually 2.0
• AIDS patient becomes reversed with a value of 0.5-1.0.

Immunological Investigation:  

A. Rheumatoid Factor:

Rheumatoid factor is an autoantibody directed against the Fc region of IgG.

Various immunoassays are available for detection of rheumatoid factor.

• • The classic Rose-Waaler test (hemagglutination test)
  • The latex agglutination test (can identify only the IgM isotype of rheumatoid factor).
  • Enzyme - linked immunosorbent assay (ELISA) can measure IgG, IgA, and IgM rheumatoid factors.

B. Antinuclear Antibodies (ANA):

Antinuclear antibodies (ANA) are usually autoantibodies that are reactive with antigens in the nucleoplasm. Detected by indirect immunofluorescence or ELISA.

• The presence of ANA in the serum shows that there is possibility of an existing autoimmune disease
• It can be found in normal individuals also.
• It is a very sensitive screening test for systemic lupus erythematous.
• It is a very useful investigation for JIA

C. Anti-DNA Antibodies:

• Anti-DNA Antibodies is considered to be relatively specific for SLE
• American Rheumatoid Arthritis Association considers it a criterion in the diagnosis of this disease.
• Anti-DNA Antibodies are also useful in monitoring disease activity in SLE patients.

D. Anti-Neutrophil Cytoplasmic Antibodies (ANCA):

ANCA are a group of autoantibodies that occur in a large majority of patients with systemic small vessel vasculitis. Depending on the pattern of neutrophil staining when seen by indirect immunofluorescence, two patterns are recognized:

Cytoplasmic pattern (c-ANCA)

• Detects a neutrophil serine proteinase and exhibits a diffuse staining throughout the cytoplasm.
• Seen in granulomatosis polyangiitis (Wegener’s granulomatosis)
• c-ANCA has a greater specificity than p-ANCA.

Perinuclear staining pattern (p-ANCA)

• Exhibited when antibodies detect lysosomal enzymes such as myeloperoxidase.
• p-ANCA has been linked to renal vasculitis and microscopic polyarteritis.

E. Angiotensin Converting Enzyme (ACE) & Serum Lysozyme:

Both these tests measure the same parameter i.e. macrophage products produced by the sarcoid granulomas.

ACE is an enzyme of the renin-angiotensin pathway,

Normal level in serum is approximately 55 IU/L.

The level of serum ACE reflects the total body mass of active sarcoid granulomas.

However, ACE is normally secreted by pulmonary macrophages and vascular endothelium. That’s why it is not pathognomonic of sarcoidosis.

Raised levels of ACE:

• Children. 
• Diabetes mellitus
• Leprosy
• Hyperthyroidism
• Chronic renal disease,
• Cirrhosis,
• Amyloidosis
• Tuberculosis

Serum lysozyme levels may also be raised above its normal limit of 8 mg/L in patients with sarcoidosis.

G. Serum C - reactive protein (CRP):

• CRP is a non-specific indicator of inflammatory activity in the body.
• It increases earlier and declines faster than ESR at the onset and resolution respectively of inflammation.

I. HLA Typing:

• Human leukocyte antigen (HLA) is a protein present on the surface of the cells that constitutes the major histocompatibility complex (MHC).
• HLA genes are located in short arm of chromosome.
• HLA typing is an expensive test and should be ordered only for patients in whom it would make a therapeutic or prognostic difference.
• The HLAs are present on most nucleated cells of the body. Usually blood lymphocytes are tested for HLA.

J. Radiological Investigations:

• Chest X ray to rule out tuberculosis and sarcoidosis. Bilateral hilar lymphadenopathy (BHL) is the most common radiological finding in systemic sarcoidosis and often regarded as pathognomonic.
• High resolution computerised tomography (HRCT) has been found to be a useful boon in diagnosis of ocular tuberculosis. CT scan is superior to conventional X-rays due to its ability to image the mediastinum, and may be useful in cases where a systemic focus of tuberculosis is strongly suspected.
• X-ray Sacro-Iliac joint to diagnose ankylosing spondylitis
• Gallium scan in some cases of sarcoidosis.

K. Skin tests:

The basis for all skin tests is delayed hypersensitivity reaction of type IV.

L. Diagnostic Surgery:

Surgical procedures are frequently the only method of distinguishing a disease of presumed autoimmune etiology from an infectious or malignant ocular process, since the clinical appearance may not always be diagnostic.

The indications for invasive procedures are usually:

• Uncontrolled vision threatening uveitis,
• Doubtful malignancy,
• Endophthalmitis
• Viral retinitis.

There are different invasive procedures, each with its own merit and disadvantages. They include: