Uveitis is not a single disease but rather a collection of many heterogeneous infectious and immune-mediated disorders that are characterized by association with systemic disease, primary anatomic location, presence (or absence) of key clinical findings, and results of a diagnostic workup. A thorough history of present illness, review of systems, and a complete physical and ocular examination will aid in the creation of an appropriate differential diagnosis and guide an appropriate workup. There is no one “uveitis workup.” The use of a “shotgun” approach to diagnostic testing is not only not cost-effective but can lead to “red herrings,” incorrect diagnoses and treatment based on a misunderstanding of the sensitivity, specificity, and positive and negative predictive values of a given test.

• Obtain a thorough history and review of systems (see Table 12.0.1)

  TABLE 12.0.1: Review of Systems

  Musculoskeletal
  Arthritis	Behçet disease, Lyme disease, SLE, HLA-B27, relapsing polychondritis, JIA
  Heel pain	Reactive arthritis, HLA-B27
  Pulmonary
  Asthma	Sarcoidosis, TB, granulomatosis with polyangiitis
  Pneumonia	Cytomegalovirus, AIDS, aspergillosis, SLE, sarcoidosis, granulomatosis with polyangiitis
  Ear–Nose–Throat
  Auditory	VKH, Susac syndrome
  Gastrointestinal
  Diet/hygiene	Poor handwashing (toxoplasmosis and toxocariasis); raw or undercooked meat and game (toxoplasmosis and cysticercosis); unpasteurized milk (brucellosis and TB)
  Diarrhea	Whipple disease, ulcerative colitis, Crohn disease
  Oral ulcers	Behçet disease, reactive arthritis, ulcerative colitis, herpes
  Genitourinary
  Genital ulcers	Behçet disease, reactive arthritis, syphilis
  Hematuria	Polyarteritis nodosum, SLE, granulomatosis with polyangiitis, TINU
  Urethral discharge	Reactive arthritis, syphilis, chlamydia associated with reactive arthritis
  Skin
  Erythema nodosum	Behçet disease, sarcoidosis
  Maculopapular rash on palms and soles	Syphilis
  Erythema chronicum migrans	Lyme disease
  Lupus pernio (purple malar rash)	Sarcoidosis
  Psoriasis	Psoriatic arthritis
  Vitiligo and poliosis	VKH, sympathetic ophthalmia
  Shingles	Varicella zoster
  Pets
  Puppy	Toxocariasis
  Cat	Toxoplasmosis
  Social History
  Drug abuse	Candida, HIV/AIDS
  Venereal disease	Syphilis, HIV/AIDS, chlamydia associated with reactive arthritis
  Medications	Systemic: moxifloxacin and other fluoroquinolones, tetracyclines, rifabutin, cidofovir, bisphosphonates, TNF-α inhibitors, sulfonamides, immune checkpoint inhibitors, MEK inhibitors, BRAF inhibitors. Topical: Brimonidine, prostaglandin analogues, metipranolol. Intraocular: Vancomycin, anti-VEGF, triamcinolone acetonide.

  SLE, systemic lupus erythematosus; JIA, juvenile idiopathic arthritis; TB, tuberculosis; AIDS, acquired immune deficiency syndrome; VKH, Vogt-Koyanagi-Harada syndrome; TINU, tubulointerstitial nephritis and uveitis; HIV, human immunodeficiency virus; VEGF, vascular endothelial growth factor.

• Descriptors of uveitis

  • Onset

    • Sudden

    • Insidious

  • Duration

    • Limited (≤3 months)

    • Persistent (>3 months)

  • Course

    • Acute (sudden onset and limited duration, <3 months)

    • Recurrent (repeated episodes separated by periods of inactivity without treatment ≥3 months in duration)

    • Chronic (persistent inflammation with recurrence of inflammation <3 months after stopping or tapering therapy)

• Laterality

  • Unilateral

  • Bilateral alternating

  • Bilateral simultaneous

• Anatomic classification of uveitis

  • Anterior uveitis: Primary inflammation of the anterior chamber (AC) (iritis) or AC and anterior vitreous (iridocyclitis)

    • AC cells must be greater than vitreous cells.

    • A dilated examination should always be performed in the initial setting of AC cells to ensure there is no inflammation of more posterior structures.

  • Intermediate uveitis: Primary inflammation of the vitreous cavity (vitritis); may have mild AC cells

    • Vitreous cells must be greater than AC cells.

  • Posterior uveitis: Primary inflammation of the retina or choroid or both

    • Retinitis

    • Choroiditis

      • Focal

      • Multifocal

      • Diffuse

    • Retinochoroiditis: primary retinal inflammation with secondary choroidal involvement

    • Chorioretinitis: primary choroidal inflammation with secondary retinal involvement

  • Panuveitis

    • Concurrent inflammation of the AC, vitreous, and retina or choroid

  • Primary retinal vasculitis

    • Primary phlebitis

    • Primary arteritis

    • Mixed phlebitis and arteritis

NOTE Equal inflammation in the AC and vitreous (more vitritis than in iridocyclitis and more AC inflammation than in intermediate uveitis) should be referred to as anterior and intermediate uveitis, not as panuveitis.

NOTE Macular edema and secondary retinal vasculitis do not, in isolation, constitute posterior uveitis (e.g., pars planitis may have cystoid macular edema [CME], peripheral vascular sheathing, and optic disc edema but it is still considered an intermediate uveitis).

When creating a uveitis differential diagnosis list, consider grouping possible etiologies into broad categories to organize your differential diagnosis:

• Infectious

• Inflammatory

• Neoplastic

• Vascular

• Traumatic

• Genetic

• Drug induced

The principles of the uveitis workup should be as follows:

1. Distinguish infectious from noninfectious uveitis.

2. Distinguish purely ocular disease from uveitis associated with systemic conditions.

3. Consider masquerade syndromes (e.g., retained intraocular foreign body [IOFB], lymphoma, chronic retinal detachment, etc.).

4. Obtain additional testing only if the results will influence the differential diagnosis, medical or surgical management, prognosis, or referral patterns.

5. Recognize that up to 40% of uveitis is undifferentiated (this term is preferred to “idiopathic”) and not associated with any identifiable associated disease.

6. Ocular imaging, like laboratory testing, should be based on the disease presentation and not used indiscriminately. Testing may include:

   • Optical coherence tomography (OCT)

   • Intravenous fluorescein angiography (IVFA)

   • Indocyanine green angiography (ICGA)

   • Fundus autofluorescence (FAF)

   • OCT angiography (OCTA)

   • Visual field testing

   • Electrophysiology