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

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

1. Jabs DA, et al. Standardization of uveitis nomenclature (SUN) for reporting clinical data. Am J Ophthalmol. 2005;140(3):509-516.
2. Rosenbaum JT. Uveitis: etiology, clinical manifestations, and diagnosis. UpToDate. 2024.
3. Goto H, et al. Epidemiological survey of intraocular inflammation in Japan. Jpn J Ophthalmol. 2007;51(1):41-44.
4. American Academy of Ophthalmology. Intraocular Inflammation and Uveitis. BCSC Section 9. 2023-2024.

For the intern

When you encounter uveitis at 3am, your immediate priority is distinguishing sight-threatening emergencies from conditions that can wait until morning. Assess visual acuity, check intraocular pressure (IOP), and examine for hypopyon or severe vitritis. Acute angle-closure masquerading as anterior uveitis requires immediate intervention. True anterior uveitis with normal IOP can usually wait for ophthalmology consultation in the morning with cycloplegic drops for comfort. Any posterior or panuveitis, especially with decreased vision, warrants urgent ophthalmology involvement. Never miss endophthalmitis—recent surgery, injection, or trauma with pain and decreased vision needs immediate attention and intravitreal antibiotics.

Common pitfalls

• Ordering reflexive "uveitis panels" without clinical context wastes resources and generates false positives. Tailor your workup to the anatomic location and clinical pattern. A young man with acute unilateral anterior uveitis doesn't need the same testing as someone with bilateral granulomatous panuveitis.

• Forgetting to test for syphilis in every uveitis patient. Syphilis truly is "the great masquerader" and can present as any anatomic pattern of inflammation.

• Missing masquerade syndromes like intraocular lymphoma or leukemia that mimic chronic uveitis. Unresponsive "uveitis" in older patients warrants diagnostic vitrectomy.

• Treating empirically without proper characterization. Document anatomic location, laterality, onset pattern, and inflammatory grade using Standardization of Uveitis Nomenclature (SUN) criteria before starting steroids—this guides both workup and monitoring.

Make it stick (one 80-word vignette)

A 34-year-old male presents to the emergency department with acute onset, painful red eye and photophobia for 2 days. Visual acuity is 20/40. Slit lamp examination reveals 2+ anterior chamber cells and flare, fine keratic precipitates, and mild conjunctival injection. His intraocular pressure is 18 mmHg. He reports no systemic symptoms but had a similar episode in the other eye a year ago that resolved spontaneously. Your supervising resident immediately asks about his back pain history and orders an HLA-B27 test, highlighting how specific clinical patterns guide targeted investigations.

If you remember one thing

Always consider syphilis in every uveitis patient, regardless of presentation, as it can mimic any form of ocular inflammation. And remember to tailor your laboratory workup to the clinical picture rather than ordering a broad, untargeted panel.

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