Anterior Uveitis

Anterior uveitis — inflammation of the iris and ciliary body — is the most common anatomical form of uveitis.¹ Etiologies span infectious (particularly viral), autoimmune, and idiopathic causes. Diagnostic classification runs along several axes: unilateral versus bilateral disease, granulomatous versus nongranulomatous inflammation (based on keratic precipitate character), and acute versus recurrent versus chronic time course — each narrows the differential meaningfully.¹²⁶

Risk factors depend on etiology: HLA-B27 positivity is associated with recurrent acute anterior uveitis, and immunocompromised states predispose to certain infectious forms.¹ In viral anterior uveitis (HSV, VZV, CMV, rubella), direct viral infection and replication in uveal tissues trigger inflammation, causing iris atrophy and corneal endothelial involvement.⁵ In autoimmune forms, immune dysregulation drives inappropriate inflammatory responses targeting uveal tissues, with HLA-B27-associated and juvenile idiopathic arthritis-associated disease reflecting distinct underlying processes.¹ Advances in molecular diagnostics have revealed viral causes in many cases previously labeled idiopathic.³

Patients typically present with eye pain, photophobia, blurred vision, and redness. Viral anterior uveitis should be suspected when accompanied by elevated intraocular pressure, corneal involvement (endothelitis/keratitis), or iris atrophic changes — fine, diffuse, stellate keratic precipitates raise suspicion for a viral cause, though there is considerable overlap between viral and noninfectious hypertensive anterior uveitis, so this sign alone should not be treated as diagnostic.⁵³ Acute CMV anterior uveitis can resemble Posner-Schlossman syndrome (recurrent hypertensive iritis), while chronic CMV disease can mimic Fuchs uveitis syndrome.⁴

Key differentials: HLA-B27-associated conditions (ankylosing spondylitis, reactive arthritis, IBD, psoriatic arthritis), juvenile idiopathic arthritis (chronic bilateral disease in children), sarcoidosis, syphilis (must be excluded before corticosteroids), Posner-Schlossman syndrome, Fuchs uveitis syndrome, masquerade syndromes including intraocular malignancy, and idiopathic disease as a diagnosis of exclusion.

Slit-lamp exam reveals anterior chamber cell and flare, keratic precipitates (fine/stellate suggesting viral, larger mutton-fat suggesting granulomatous inflammation), possible iris atrophy, elevated IOP, corneal involvement, and posterior synechiae. Posterior segment examination is essential to rule out masquerade syndromes and posterior involvement.¹² For severe, bilateral, recurrent, or chronic disease, appropriate baseline workup includes chest radiography and serology for syphilis, HLA-B27, and ACE, but additional expensive or invasive testing should be guided by clinical findings rather than ordered reflexively.⁶ When viral etiology is suspected, PCR or Goldmann-Witmer coefficient analysis of aqueous humor can identify the causative virus.⁵

The central principle of management is to rule out infection — especially syphilis and viral causes — before starting corticosteroids.² Most anatomically isolated anterior uveitis resolves with topical corticosteroids, with treatment intensity adapted to etiology and severity.⁶¹ For confirmed viral disease, acyclovir remains the mainstay for HSV/VZV, while CMV anterior uveitis responds to ganciclovir (oral valganciclovir or topical), though relapse is common; early antiviral treatment reduces the risk of eventually needing glaucoma surgery, and an extended antiviral course should generally be capped around six months to limit resistance and side effects.³⁴ Systemic immunomodulatory therapy is reserved for patients who respond poorly to corticosteroids, develop steroid-limiting side effects, need high maintenance doses, or have an associated systemic inflammatory disease — biologics in particular have transformed management of HLA-B27-associated and juvenile idiopathic arthritis-associated uveitis.⁶¹ When quiescence cannot be achieved despite maximally tolerated antimetabolite therapy, referral to a uveitis specialist for escalation is appropriate.⁶

• Clinical characterization of unilateral vs. bilateral and granulomatous vs. nongranulomatous features is the main step in etiologic diagnosis^1,2
• The priority is ruling out infection before starting corticosteroid therapy²
• Early antiviral treatment in CMV anterior uveitis reduces the risk of eventually requiring glaucoma surgery⁴
• Biologics have transformed management of HLA-B27-associated and juvenile idiopathic arthritis-associated anterior uveitis¹
• Common pitfall: initiating corticosteroids before ruling out infectious etiologies, particularly syphilis and viral causes²
• Common pitfall: ordering extensive laboratory workup without clinical orientation, of limited utility and high cost⁶
• Common pitfall: failing to examine the posterior segment, missing masquerade syndromes or posterior involvement¹
• Common pitfall: inadequate duration of antiviral therapy for CMV anterior uveitis, leading to high relapse rates³