Chapter 33 Practical Diagnostic Approach to Uveitis

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Chapter 33
Practical Diagnostic Approach to Uveitis
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Proper use of office and clinical laboratory testing in the diagnosis of uveitis is not difficult. Nevertheless, the ophthalmologist's approach and timing are important if meaningful data are to be obtained in a cost-effective manner. This chapter is intended to give the clinician a simple and direct method for the use of currently available tests that should lead to a diagnosis in 75% to 80% of patients with uveitis.1

The clinical laboratory should not be viewed as the target for a battery of tests routinely ordered for all patients with uveitis. Instead, the laboratory evaluation should be seen as but one step in an organized workup of each patient, consisting of the following steps:

  1. Naming

  2. Meshing

  3. Office testing

  4. Specific and nonspecific clinical laboratory tests

  5. Specialty consultations

  6. Therapeutic tests

  7. Diagnosis and treatment

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The history and physical examination of the patient with uveitis provides more information than any subsequent test. This information must be organized with care in order to best proceed with diagnosis, avoid confusion, and confer with other ophthalmologists using a standardized terminology. Some of the ways in which uveitis can be classified are listed in Table 1. To rely on only one major classification category would lead to loss of information as well as confusion when physicians attempted to discuss their patients. It is therefore best to include a statement from each classification category in a detailed clinical description when naming every patient with uveitis.2


TABLE 1. Classification of Uveitis











 Pars planitis (peripheral uveitis, chronic cyclitis)














 Diffuse uveitis




























Young adult





Demographic Factors







Geographic factors


Occupational factors


Eating habits




Associated illnesses


Associated events


Personality factors


Stress factors


Sexual practices


Drug use




Naming Example A. Mr. Smith is a 30-year-old white man with severe acute recurrent nongranulomatous iridocyclitis, active in the right eye and quiescent in the left, with recent arthritis of the left knee and ankle as well as episodes of urethritis that have been culture negative in the past.

Naming Example B. Mr. Yonida is a 37-year-old Japanese man with a history of chronic bilateral diffuse granulomatous uveitis, headaches, hearing loss, and vitiligo. He has no known history of ocular trauma.

Naming Example C. Laurie Jones is a 9-year-old black girl with chronic nongranulomatous bilateral iridocyclitis, posterior synechiae, band keratopathy, and arthritis of the right wrist.

Naming Example D. Mr. Williams is a 28-year-old white homosexual man with acute unilateral granulomatous iridocyclitis and retinochoroiditis, weight loss, cough, and a history of intravenous drug abuse.


Obvious clues may be obtained from straightforward demographic data. Juvenile rheumatoid arthritis, retinoblastoma, Kawasaki's syndrome, and toxocariasis, for example, are seen primarily in children. Pars planitis, multiple sclerosis, and Fuchs' heterochromic iridocyclitis usually occur in young adults. Reiter's syndrome, ankylosing spondylitis, acute multifocal posterior placoid epitheliopathy, birdshot choroiditis, Vogt-Koyanagi-Harada syndrome, and Behçet's syndrome are most likely to occur in middle age, while large cell lymphoma or choroidal melanoma is found in older patients. Toxoplasmosis and sarcoidosis may present in childhood, youth, or middle age. Tuberculous or luetic uveitis can be found at any age. Primary uveitis of any origin rarely if ever makes its first appearance in old age.

Uveitis associated with juvenile rheumatoid arthritis is found much more frequently in females, while uveitis associated with ankylosing spondylitis and Reiter's syndrome is usually seen in males. Most patients with Behçet's syndrome and uveitis are males. Sympathetic ophthalmia and fungal endophthalmitis are mostly reported in males since they are more likely to have penetrating injuries or abuse intravenous drugs.

Ankylosing spondylitis, Reiter's syndrome, and other HLA-B27-associated arthritides are most common in whites. Sarcoidosis occurs most commonly in blacks. Behçet's and Vogt-Koyanagi-Harada syndromes are most prevalent in Asians; most of these patients who are not Asian or American Indian will have this lineage buried somewhere in their family history. In the United States, most patients with Behçet's syndrome are of Mediterranean ancestry. In the Mediterranean countries, Behçet's syndrome is more common and more virulent than it is in the United States. Coccidioidomycosis is more common and more severe in Filipinos and blacks than in other races comparably exposed to this New World fungus.


Histoplasmosis is highly localized to the Mississippi-Ohio-Missouri River Valleys, as well as river valleys between 45° North and 45° South latitudes worldwide. It is not found in Australia, New Zealand, Europe, England, or Japan.3 Although a syndrome identical to presumed ocular histoplasmosis has been identified in England, a specific pathogen has not been identified. Coccidioidomycosis is found primarily in the southwest United States and Central and South America. Although tuberculosis is far less prevalent in Western countries than a generation ago, extremely high new active case rates are found in parts of East Asia, Hong Kong, Japan, Africa, and South America.

A history of the ingestion of raw or undercooked meat is important when considering a diagnosis of ocular toxoplasmosis. In some parts of Western Europe and Brazil where this practice is common, positive Toxoplasma antibodies are found in most of the population.

Contact with feline feces containing oocysts of Toxoplasma gondii may occur in children who play in sandboxes frequented by stray cats, or in adults who clean kitten litter boxes. These practices should be avoided, particularly by pregnant women. A history of contact with an unwormed puppy or kitten is significant in children with suspected ocular toxocariasis.

Patients exposed to sewers or rodent urine may be at risk for leptospirosis, while farmers and veterinarians are far more likely than the general population to develop brucellosis. Persons who ingest unpasteurized milk are at risk of tuberculosis and brucellosis.

Exposure to infectious agents may tip-off the diagnosis of tuberculous, luetic, cytomegalic, or Reiter's uveitis. Thus, a thorough history of sexual activity and preferences, previous venereal diseases, genitourinary symptoms, and family members with contagious diseases may obviate an expensive diagnostic workup. Similarly, a history of drug abuse should be tactfully obtained when necessary. Associated illnesses, including viral syndromes, rashes, or arthritis, may also provide invaluable hints in best naming a patient's uveitis and eventually formulating a differential diagnosis.

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Once naming has been accomplished, based entirely on history and physical examination, it is time for the meshing step. All of the recognized uveitic entities have a known set of clinical characteristics. Since the number of known uveitic syndromes is finite, and the syndromes for the most part are distinct from one another, a profile of clinical characteristics for each may be assembled. This information has been condensed for 17 likely uveitic entities in Table 2. The importance of accurate and precise detail in the naming step should now be clear.


TABLE 2. Recognized Uveitic Entities

EntityAnatomyChronologyGranulomatous/NongranulomatousMale/FemaleUnilateral/BilateralLaboratory Test*

Viral/nonspecific/ traumatic


Ankylosing spondylitis

IridocyclitisAcute, recurrentNGMBESR, HLA-B27, SI jt roentgenogram, rh consult

Reiter's syndrome

IridocyclitisAcute, recurrentNGMBESR, HLA-B27, SI jt roentgenogram, med consult, (chlamydial micro FA or culture) (foot roentgenogram)

Immunologic (altered permeability, focus of infection, immunogenic focus)

IridocyclitisAcute, recurrent; chronicNG USystemic focus ESR, med consult

Still's disease (juvenile rheumatoid arthritis)/uveitis in young girls

IridocyclitisChronicNGFBESR, ANA, ped consult, (HLA-B27) (HLA-DR5), (RF), knee roentgenogram

Heterochromic iridocyclitis (Fuch's syndrome)

IridocyclitisChronicNG U 

Chronic cyclitis/peripheral uveitis/pars planitis

CyclitisChronicNG B(ESR)


Cyclitis/maculopat hy endophthalmitisChronicG/ng† UELISA, vitreous aspiration, ESR, Head CT scan, (CBC, EOS), (ocular roentgenogram), (ultrasound)


Retinitis, retinochoroiditisAcute, recurrentG  Toxoplasma dye, FA, ELISA

Cytomegalic inclusion disease

Retinitis, retinochoroiditisAcute, recurrentG BVirus studies of urine, serum, (tears), ped consult, HIV ELISA, med consult

Behçet's syndrome

Iridocyclitis, cyclitis, retinal vasculitis, retinitisAcute, recurrent chronicNG/GMBMed consult (fluorescein) (skin puncture test), (Behçet skin test), HLA-B5

Vogt-Koyanagi-Harada syndrome

Iridocyclitis, chorioretinitis, choroiditisAcute, recurrent; chronicNG/G BLP during attacks, fluorescein, (HLA-B54), (HLA-DW-Wa), (HLA-DR4)

Sympathetic ophthalmia

Iridocyclitis, choroiditisChronicNG/GMB 


Iridocyclitis, cyclitis, choroiditis, retinal vasculitisChronic; acute, recurrentG BTuberculin skin test, chest roentgenogram, ESR, med consult, (serum lysozyme)


ChoroiditisAcute, recurrentG B(Histoplasma skin test) chest roentgenogram, HLA-B7, (HLA-DR2)


AnythingChronic; acute; recurrent (less important)G/ng BChest roentgenogram, skin tests(tuberculin, Candida, mumps), conjunctival or other biopsy, Schirmer, ESR, ACE, limited gallium scan, med consult, (serum lysozyme), (serum proteins), (serum Ca, PO4), (roentgenograms hand & feet).


AnythingAcute, recurrent; ChronicG/ng BVDRL with titers, FTA-ABS, LP

* Laboratory tests in parentheses are of lesser importance.
† Lower case ng indicates lesser importance.
ACE, angiotensin-converting enzyme; ANA, antinuclear antibodies; CBC, complete blood cell count; ELISA, enzyme-linked immunosorbent assay; EOS, eosinophil count; ESR, erythrocyte sedimentation rate; FA, fluorescent antibody test; FTA-ABS, fluorescent treponemal antibody absorption test; LP, lumbar puncture; med consult, medical consultation; ped consult, pediatric consultation; rh consult, rheumatologic consultation; SI jt, sacroiliac joint; RF, rheumatoid factor; HIV, human immunodeficiency virus.


A comparison of patient characteristics to the clinical characteristics of each uveitic entity will reveal profiles similar enough to be included in a preliminary differential diagnosis. This comparison should be seen as a superimposing of clinical profiles. This is what is meant by meshing. The degree of fit or mesh is assessed, and the proposed diagnoses ranked in order of likelihood. Thus, the preliminary differential diagnosis following meshing in each of the four previous examples would be:

Example A:

  1. Reiter's syndrome

  2. Ankylosing spondylitis

  3. Immunogenic uveitis

Example B:

  1. Vogt-Koyanagi-Harada syndrome

  2. Behçet's syndrome

  3. Sympathetic ophthalmia

Example C:

  1. Juvenile rheumatoid arthritis

  2. Sarcoidosis

Example D:

  1. Cytomegalovirus inclusion disease

  2. Toxoplasmosis

  3. Tuberculous or luetic uveitis

  4. Fungal endophthalmitis

  5. Acute retinal necrosis syndrome
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