Residency · Residency · Ophthalmology
Uveitis Classification and Systematic Diagnostic Approach
Introduction
Uveitis refers to inflammation of the uveal tract (iris, ciliary body, choroid) and is a significant cause of visual morbidity, responsible for 10-15% of legal blindness in developed countries. A systematic approach to classification and workup is essential for identifying treatable underlying causes and guiding therapy.
Classification (SUN Working Group)
Anatomic Classification
Anterior uveitis -- inflammation primarily involving the anterior chamber; iritis, iridocyclitis. Intermediate uveitis -- vitreous as primary site of inflammation; vitritis, pars planitis, posterior cyclitis. Posterior uveitis -- retina or choroid as primary site; chorioretinitis, retinal vasculitis, neuroretinitis. Panuveitis -- inflammation involving anterior chamber, vitreous, and retina/choroid.
Onset and Duration
Onset: sudden vs. insidious. Duration: limited (<3 months) vs. persistent (>3 months) Course: acute (sudden onset, limited duration), recurrent (repeated episodes with inactive periods), chronic (persistent with relapse within 3 months of discontinuing therapy)
Laterality
Unilateral, bilateral, alternating.
Grading of Inflammation (SUN Criteria)
Anterior chamber cells: 0 to 4+ (based on cells per high-power field in 1x1 mm slit beam) Anterior chamber flare: 0 to 4+ (based on visibility of iris/lens detail) Vitreous haze: 0 to 4+ (based on fundus detail visibility through undilated pupil) Vitreous cells: 0 to 4+.
Clinical Approach to Diagnosis
Step 1: Characterize the Uveitis
Determine anatomic location, onset, duration, course, laterality. Identify key clinical features: granulomatous vs. non-granulomatous, keratic precipitates (KP) type, presence of hypopyon, iris nodules, synechiae, vitritis pattern, retinal/choroidal lesions.
Granulomatous vs. Non-Granulomatous
| Feature | Granulomatous | Non-Granulomatous |
|---|---|---|
| KP type | Mutton-fat (large, greasy) | Fine, stellate |
| Iris nodules | Koeppe (pupillary margin), Busacca (iris stroma) | Absent |
| Course | Chronic, insidious | Acute |
| Associations | Sarcoidosis, TB, syphilis, VKH | HLA-B27, idiopathic |
Step 2: Focused History
Systemic symptoms: joint pain, back stiffness, skin rashes, oral/genital ulcers, respiratory symptoms, neurologic symptoms. Travel history, exposures (TB endemic areas, cats, ticks) Sexual history (syphilis, HIV) Medications (rifabutin, cidofovir, bisphosphonates can cause uveitis) Prior episodes, family history of autoimmune disease.
Step 3: Tailored Laboratory Workup
Do not order a shotgun panel of tests for every patient. Select investigations based on clinical phenotype and differential diagnosis. Common baseline tests for idiopathic or recurrent uveitis: CBC, ESR/CRP. Syphilis serology (RPR/VDRL + FTA-ABS) -- the great masquerader; test in all uveitis. Chest X-ray or CT chest -- sarcoidosis, TB.
HLA-B27 -- anterior uveitis, especially young males with back pain. ACE and lysozyme -- sarcoidosis (limited sensitivity) QuantiFERON-TB Gold or PPD -- tuberculosis. Urinalysis -- tubulointerstitial nephritis and uveitis (TINU) syndrome.
Step 4: Ancillary Ophthalmic Testing
Fluorescein angiography (FA) -- retinal vasculitis, cystoid macular edema, disc leakage. Indocyanine green angiography (ICGA) -- choroidal inflammation (VKH, birdshot, multifocal choroiditis) OCT -- macular edema, subretinal fluid, epiretinal membrane. B-scan ultrasound -- posterior scleritis, vitreous opacities, choroidal thickening. Anterior chamber paracentesis -- PCR for infectious agents (HSV, VZV, CMV, toxoplasmosis), cytology for masquerade syndromes.
Common Uveitis Syndromes by Anatomic Location
Anterior Uveitis
HLA-B27-associated -- acute, recurrent, unilateral, fibrinous, may have hypopyon. Fuchs heterochromic iridocyclitis -- chronic, unilateral, diffuse small KP, heterochromia, no synechiae, cataract, glaucoma. Herpetic (HSV/VZV) -- elevated IOP, sector iris atrophy, unilateral. Posner-Schlossman syndrome (glaucomatocyclitic crisis) -- recurrent mild uveitis with markedly elevated IOP.
Intermediate Uveitis
Pars planitis -- idiopathic; snowballs and snowbanking; young adults; CME is main cause of vision loss. Associated conditions: sarcoidosis, MS, Lyme disease.
Posterior Uveitis
Toxoplasmosis -- most common cause of infectious posterior uveitis; "headlight in the fog" appearance. CMV retinitis -- immunocompromised; "pizza pie" retinitis. Birdshot chorioretinopathy -- HLA-A29; cream-colored choroidal lesions. VKH disease -- bilateral panuveitis with exudative retinal detachments; associated with vitiligo, poliosis, hearing loss.
Panuveitis
Behcet disease, sarcoidosis, VKH, syphilis, TB, endophthalmitis.
Key Clinical Pearls
Test every uveitis patient for syphilis -- it can mimic any form of uveitis. Tailor the workup to the clinical phenotype; avoid shotgun laboratory panels. SUN classification provides a standardized framework for describing and grading uveitis. Granulomatous uveitis with mutton-fat KP should prompt evaluation for sarcoidosis, TB, and syphilis. Bilateral anterior uveitis in a child should raise concern for juvenile idiopathic arthritis (JIA)
References
- Jabs DA, et al. Standardization of uveitis nomenclature (SUN) for reporting clinical data. Am J Ophthalmol. 2005;140(3):509-516.
- Rosenbaum JT. Uveitis: etiology, clinical manifestations, and diagnosis. UpToDate. 2024.
- Goto H, et al. Epidemiological survey of intraocular inflammation in Japan. Jpn J Ophthalmol. 2007;51(1):41-44.
- American Academy of Ophthalmology. Intraocular Inflammation and Uveitis. BCSC Section 9. 2023-2024.