3 OPHTHALMOLOGIC LABORATORY AND DIAGNOSTIC TESTS

Selected Laboratory Tests in Ocular Disease

Laurance Freier

     SELECTED LABORATORY TESTS IN OCULAR DISEASE

This section lists suggested laboratory and diagnostic tests for ocular disorders and systemic diseases that may have ophthalmic manifestations. These lists are not meant to be exhaustive, nor should every test listed be done in every case. In general, diagnostic tests are ordered only when their results will have a direct bearing on the management of the patient.

For the abbreviations of tests used in the lists, see Chapter 2, “Common Laboratory Tests and Procedures.” Asterisks (*) indicate a nonspecific, initial group of tests. If the patient’s history, signs, or symptoms suggest a particular etiology, additional tests should be done as indicated. See tests listed under individual etiologies. For systemic diseases associated with anterior uveitis, see Table 3-1.

TABLE 3-1 Systemic Diseases Associated with Anterior Uveitis

Acanthamoeba

• Gram stain
  
• Giemsa stain (to help distinguish from herpes simplex)
  
• Calcofluor white stain
  
• Culture: Nonnutrient agar with Escherichia coli overlay
  
• Confocal microscopy
  
• Corneal biopsy (if stains and cultures are all negative and condition does not improve) (Figs. 3-1 and 3-2)

Figure 3-1. Acanthamoeba cornea.

Figure 3-2. Acanthamoeba keratitis.

Acute Retinal Necrosis

• Complete blood count (CBC) with differential
  
• Erythrocyte sedimentation rate (ESR)
  
• Rapid plasma reagin (RPR) and fluorescent treponemal antibody-absorption (FTA-ABS)
  
• Chest x-ray
  
• Purified protein derivative (PPD) with anergy panel
  
• Computed tomography (CT) scan of the orbit or B-scan ultrasound (to check for an enlarged optic nerve)
  
• Consider a fluorescein angiogram
  
• Consider urine studies for cytomegalovirus (especially if patient is immunocompromised)
  
• Consider toxoplasmosis enzyme-linked immunosorbent assay (ELISA) and serum titers for herpes simplex and varicella zoster
  
• Human immunodeficiency virus (HIV) test if patient is from a high-risk group for acquired immunodeficiency syndrome (AIDS) (Fig. 3-3)

Figure 3-3. Acute retinal necrosis.

Amaurosis Fugax

• Skin biopsy (if pseudoxanthoma elasticum is suspected)
  
• Cardiovascular exam to rule out aortic aneurysm
  
• Skull x-ray to rule out Paget’s disease
  
• Serum alkaline phosphatase and urine calcium level if Paget’s disease is suspected
  
• Sickle cell prep and hemoglobin electrophoresis (to rule out homozygous sickle cell disease) if patient is black or has Mediterranean background
  
• PO₄ levels (to rule out hyperphosphatemia)
  
• Fluorescein angiogram to check for neovascular membrane (Fig. 3-4A,B)

Aniridia

• Consider renal ultrasound (if Wilms tumor is suspected)
  
• Consider intravenous pyelography (if ultrasound suggests possibility of Wilms tumor)
  
• Consider chromosomal karyotype (deletion of the short arm of chromosome II suggests an increased chance of a Wilms tumor)

• Greater in light or dark (nonbenign)
  
• Light (abnormal large pupil-parasympathetic lesion)
  

  1. Weak pilocarpine test (1/16% to 0.0625%): Adies tonic pupil

  
  

  2. Strong pilocarpine test (1%): Pharmacologic versus neurologic pupil

  
  
• Dark (abnormal small pupil-sympathetic lesion)
  

  1. Aproclonidine 1%: Differentiate second versus third neuron lesion (Fig. 3-5)

Figure 3-5. Aniscoria.

Ankylosing Spondylitis

• Men: x-ray of sacroiliac joints; CT scan
  
• Women: x-ray of shoulders
  
• ESR
  
• HLA-B27

Anterior Uveitis; Iritis/Iridocyclitis*

• Antinuclear antibody (ANA)
  
• CBC
  
• ESR
  
• RPR or Venereal Disease Research Laboratory (VDRL) and FTA-ABS
  
• Chest x-ray (to rule out sarcoidosis and tuberculosis)
  
• PPD and anergy panel
  
• In endemic areas, lab tests for Lyme’s disease

Arcus Senilis (in a Patient <50 Years Old)

• Serum cholesterol
  
• Lipoprotein electrophoresis
  
• Serum triglycerides (to rule out type II or V hyperlipoproteinemia)
  
• FBS (to rule out adult onset diabetes mellitus) (Fig. 3-6)

Figure 3-6. Arcus senilis.

Argyll Robertson Pupil

• RPR or VDRL
  
• FTA-ABS or microhemagglutination assay for triponema pallidium (MHA-TP)
  
• Consider a lumbar puncture (if diagnosis of syphilis is established)

Band Keratopathy

• Behçet’s skin puncture test
  
• HLA-B27 or HLA-B5
  
• Medicine or rheumatology consult (Fig. 3-7)

Figure 3-7. Behçet’s disease.

Blind Infant

• Electro-retinagram (ERG)
  
• Visual-evoked potential (VEP)
  
• Consider a CT scan and/or MRI of the brain

Blow-Out Fracture of the Orbit

• CT scan (axial and coronal views) of the orbits and brain if surgery is planned or if the diagnosis is uncertain

Branch Retinal Artery Occlusion

• Carotid artery evaluation (Doppler and ultrasound)
  
• FBS (3-hour GTT if findings are negative)
  
• Immediate ESR, Westergren method (to rule out GCA if patient is ≥55 years old)
  
• Greater superficial temporal artery biopsy if GCA is suspected because of symptoms or ESR findings
  
• Echocardiogram
  
• Holter monitor
  
• Blood tests: ANA, CBC with differential and platelets, FTA-ABS, lipid profile, prothrombin time (PT) or partial thromboplastin time (PTT), and RF
  
• Hct and hemoglobin electrophoresis
  
• Serum protein electrophoresis (Fig. 3-8)

Figure 3-8. Branch retinal artery occlusion.

Branch Retinal Vein Occlusion (BRVO)

• FBS
  
• CBC with differential and platelets
  
• ANA
  
• ESR
  
• PT or PTT
  
• RF
  
• Fluorescein angiogram
  
• Chest x-ray
  
• Internal medicine consult (to check for cardiovascular disease) (Fig. 3-9)

Figure 3-9. Branch retinal vein occlusion.

Canaliculitis

• Cultures of material expressed from the punctum
  
• Blood agar
  
• Chocolate agar
  
• Sabouraud’s medium
  
• Thioglycolate broth
  
• Gram stain
  
• Giemsa stain

• BUN
  
• CBC
  
• Creatinine
  
• Liver function tests (see list under “Postoperative Endophthalmitis”)
  
• Blood and urine cultures for Candida
  
• Vitreous cultures (when there is a significant amount of vitreous involvement) can be used to confirm a diagnosis and to test sensitivity to antifungal agents
  
• Consider HIV tests

Cavernous Sinus Syndrome: Multiple Ocular Motor Palsies

• CT scan (axial and coronal views) or MRI of the brain, orbit, and sinuses
  
• If the CT scan and MRI are normal, consider the following:
  

  1. ANA, CBC with differential, ESR, and RF (to rule out infection, malignancy, or a systemic vasculitis)

  
  

  2. A blind nasopharyngeal biopsy (to rule out a nasopharyngeal carcinoma)

  
  

  3. Chest x-ray

  
  

  4. Lumbar puncture (three times; to rule out carcinomatous meningitis)

  
  

  5. Lymph node biopsy (if a lymphadenopathy is present)

  
  

  6. A repeat CT scan or MRI if the cavernous sinus was not well visualized

  
  

  7. A cerebral arteriogram to rule out an aneurysm or arteriovenous fistula (but these are usually seen on the CT scan)

  
  
• Blood cultures (three times) plus a culture of the presumed primary source of infection if a cavernous thrombosis is suspected

Central Retinal Artery Occlusion

• Immediate ESR, Westergren method (to rule out GCA if patient is ≥55 years old)
  
• Greater superficial temporal artery biopsy if GCA is suspected because of symptoms or ESR findings
  
• Carotid artery evaluation (Doppler and ultrasound)
  
• FBS (3-hour GTT if findings are negative)
  
• Echocardiogram
  
• Holter monitor
  
• Blood tests: ANA, CBC with differential and platelets, lipid profile, FTA-ABS, PT or PTT, and RF
  
• Hct and hemoglobin electrophoresis
  
• Serum protein electrophoresis
  
• Consider ERG or fluorescein angiogram to help confirm diagnosis

Central Retinal Vein Occlusion (CRVO)

• CBC with differential and platelets
  
• FBS
  
• Lipid profile
  
• VDRL and FTA-ABS
  
• Serum protein electrophoresis
  
• ANA
  
• Cryoglobulins
  
• ESR
  
• Hemoglobin electrophoresis
  
• PT or PTT
  
• Fluorescein angiogram (to rule out diabetic retinopathy)
  
• Ophthalmodynamometry or oculopneumoplethysmography (to help distinguish a CRVO from carotid artery disease; ophthalmic artery pressure is usually normal or elevated in a CRVO but is usually low in carotid disease)
  
• Chest x-ray (to rule out an underlying medical problem)

• Giemsa stain of conjunctival scraping (will show inclusion bodies within epithelial cells, lymphocytes, and polymorphonuclear leukocytes)
  
• Chlamydial immunofluorescence test
  
• Detection of Chlamydia antigen (enzyme immunoassay [EIA], direct fluorescent antibody [DFA]) or DNA (Fig. 3-10)

Figure 3-10. Chlamydial inclusion conjunctivitis.

Choroidal Detachment

• B-scan ultrasonography if melanoma is suspected

Congenital Cataract

• B-scan ultrasound if fundus view is obscured
  
• Red blood cell (RBC) galactokinase activity and RBC galactose-l-phosphate-uridyltransferase activity (to rule out galactosemia)
  
• Serum calcium (to rule out hypocalcemia or hypoparathyroidism)
  
• Serum glucose (to check for diabetes mellitus and hypoglycemia)
  
• Urine copper level (to check for Wilson’s disease)
  
• Urine amino acid content (to check for Lowe’s syndrome)
  
• Urine protein and blood quantitation (to check for Alport’s syndrome)
  
• Urine sodium nitroprusside test (to rule out homocystinuria)
  
• Rubella antibody detection test

Conjunctival Laceration

• B-scan ultrasound
  
• CT scan of the orbit (axial and coronal views) to rule out an intraorbital or intraocular foreign body or a ruptured globe

Hyperacute Conjunctivitis

• Gram stain
  
• Cultures:
  

  1. Blood agar (supports growth of most bacteria)

  
  

  2. Chocolate agar (enhances isolation of Haemophilus, Moraxella, and Neisseria)

  
  

  3. Thayer-Martin plate (isolates Neisseria)

  
  
• Antibiotic sensitivity testing (Fig. 3-11)

Figure 3-11. Hyperacute conjunctivitis.

Cornea: Central Crystalline Dystrophy

• Fasting serum cholesterol
  
• Serum triglycerides (to check for hypercholesterolemia and hyperlipidemia) (Fig. 3-12)

Figure 3-12. Crystalline dystrophy.

Corneal Thinning

Cranial Arteritis (See Headache)

Cystoid Macular Edema

• Fluorescein angiography (may show classic “flower petal” pattern)
  
• When indicated:
  

  1. FBS

  
  

  2. GTT

  
  

  3. CRVO lab tests

  
  

  4. BRVO lab tests

  
  

  5. ERG (retinitis pigmentosa [RP]); other lab tests indicated by suspected etiology

Cytomegalovirus (CMV) Retinopathy

• Urine studies for CMV
  
• ESR
  
• Consider fluorescein angiography
  
• Complement fixation test
  
• Internal medicine consult
  
• Consider HIV tests (Fig. 3-13)

Figure 3-13. Cytomegalovirus retinopathy.

Dacryoadenitis

Acute Infectious

•   Cultures of any discharge:
  

  1. Blood agar

  
  

  2. Chocolate agar

  
  

  3. Sabouraud’s medium

  
  

  4. Thioglycolate broth

  
  

  5. Gram stain

  
  
• CBC with differential (if patient is febrile)
  
• CT scan (axial and coronal views) of the orbit and brain (if a mass is suspected, if there is a motility restriction, or if there is a proptosis)

Chronic

• CBC with differential
  
• ESR
  
• ACE
  
• PPD with anergy panel
  
• Chest x-ray (to help detect sarcoidosis or TB)
  
• RPR or VDRL and FTA-ABS
  
• CT scan (axial and coronal views) of the orbit
  
• Lacrimal gland biopsy (if a malignant tumor is suspected or if the diagnosis is uncertain)
  
• If a lymphoma is suspected:
  

  1. Bone marrow biopsy

  
  

  2. CT scan of the abdomen

  
  

  3. CT scan of the brain

  
  

  4. Serum protein electrophoresis

  
  

  5. Internal medicine or oncology consult

• FBS
  
• HB A1c
  
• GTT
  
• Fluorescein angiogram if neovascularization or macular edema is suspected
  
• Consider blood tests for hyperlipidemia if much exudate is found (Fig. 3-14)

Figure 3-14. Diabetic retinopathy.

Episcleritis

• ANA
  
• ESR
  
• RF and CBC with differential (if collagen vascular disease is suspected)
  
• Serum uric acid (if gout is suspected)
  
• RPR or VDRL and FTA-ABS (if syphilis is suspected)

Eyelid Laceration

• Consider CT scan (axial and coronal views) of the orbit and brain (to rule out an intraorbital foreign body, or a ruptured globe, or in cases of significant orbital trauma)

Malignant Tumors of the Eyelid

• Incisional biopsy
  
• Excisional biopsy (preferable for malignant melanoma)
  
• Internal medicine consult for metastatic workup if sebaceous cell carcinoma is confirmed
  
• Oil red-O stain of frozen or nonfixed tissue if sebaceous cell carcinoma is suspected (Fig. 3-15)

Figure 3-15. Lid tumor.

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