Explain uveitis, including its etiology, clinical presentation, diagnostic work‑up, and management, in an understandable way.

Understanding Uveitis: A Comprehensive Overview

What Is Uveitis?

Uveitis is inflammation of the uveal tract (iris, ciliary body, and choroid) and adjacent intraocular structures including the retina, vitreous, and optic nerve, representing one of the leading causes of vision loss worldwide. 1, 2

The condition affects predominantly adults aged 20 to 50 years and requires urgent evaluation to prevent permanent blindness. 2, 3

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Anatomical Classification and Clinical Presentation

Uveitis is categorized by the anatomical location of inflammation:

Anterior Uveitis (41-60% of cases)

• Involves the iris and ciliary body 2, 4
• Classic symptoms include eye pain, blurred vision, photophobia, headache, and eye redness 3
• May present with tearing and eye discomfort 3
• Treated primarily with topical corticosteroids and cycloplegic agents 5

Intermediate Uveitis (9-15% of cases)

• Affects the pars plana and peripheral retina 2
• Mild cases may be monitored without initial treatment 2
• Moderate to severe cases require systemic therapy 2

Posterior Uveitis (17-23% of cases)

• Involves the choroid and/or retina 2
• Can be asymptomatic but nonetheless proceed to visual loss 1
• Patients may report floaters 4
• Requires aggressive systemic treatment due to sight-threatening nature 2

Panuveitis (7-32% of cases)

• Involves all uveal layers 2
• Highest risk for complications and vision loss 1

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Etiology: Infectious vs. Noninfectious

Infectious Causes (11-21% in high-income countries, 50% in low-middle income countries) 2

Viral infections:

• Herpes simplex virus, varicella-zoster virus, cytomegalovirus, Epstein-Barr virus 6

Parasitic infections:

• Toxoplasmosis is a frequent specific cause in children and remains important in adults 6

Fungal infections:

• Candida species can cause endogenous endophthalmitis through hematogenous spread 6
• All patients with candidemia require dilated retinal examination within the first week 6

Bacterial infections:

• Tuberculosis requires screening before starting immunomodulatory therapy 6

Noninfectious/Autoimmune Causes (37-49% associated with systemic disease) 2

HLA-B27-associated conditions:

• Ankylosing spondylitis, psoriatic arthritis, inflammatory bowel disease 6, 4
• Anterior uveitis is a classification criterion for seronegative arthritis 4

Other systemic associations:

• Juvenile idiopathic arthritis (significant cause in children) 6
• Behçet's disease (associated with HLA-B51 and posterior uveitis) 4, 5
• Sarcoidosis 7
• Inflammatory bowel disease can cause posterior uveitis 6
• Psoriasis, especially with psoriatic arthritis 6

Idiopathic:

• 27-51% of cases have no identifiable cause 2

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Diagnostic Work-Up

When to Suspect Uveitis

Visual disturbance, photophobia, or moderate to severe pain should prompt urgent ophthalmologic referral to prevent progression to permanent vision loss. 3

Distinguishing from Mimics

Episcleritis can be distinguished from uveitis by:

• Being relatively painless 3
• Hyperemic sclera and conjunctiva 3
• Itching and burning 3
• No visual changes 3

Essential Diagnostic Steps

Laboratory screening:

• Complete blood count and inflammatory markers (ESR, CRP) 5
• Screening for latent or active tuberculosis before starting immunomodulatory therapy 6

Ophthalmologic evaluation:

• Assessment of visual acuity 1
• Anterior chamber cells and flare 1, 5
• Vitreous haze 1
• Chorioretinal lesions 1
• Retinal vascular lesions 1
• Macular or optic nerve involvement 1

Imaging when indicated:

• MRI shows increased gadolinium enhancement of the uveal tract in active uveitis 7
• Can help differentiate from masquerade syndromes (malignancy, retinal degeneration) 1, 7

Critical Pitfall: Masquerade Syndromes

Treatment nonadherence, infections, and masquerade syndromes must be considered in any patient with noninfectious uveitis before a change in therapy is considered. 1

Masquerade syndrome incidence may be as high as 2.5% in tertiary referral clinics and includes lymphoma and retinal degeneration. 1

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Management Approach

Treatment Goals

The goal is to suppress ocular inflammation, achieve inactive disease state or drug-induced remission, while minimizing corticosteroid use to reduce adverse effects. 1, 2

Anterior Uveitis Management

First-line treatment:

• Topical corticosteroids 5, 2
• Cycloplegic agents 5

When to escalate:

• Systemic therapy required if refractory to topical treatment, frequent relapses, or sight-threatening complications develop 5

Posterior Uveitis and Panuveitis Management

Patients with moderate to severe intermediate uveitis, posterior uveitis, and panuveitis are at high risk of sight-threatening complications and require systemic and/or intravitreal corticosteroids and immunosuppressive agents. 2

First-line systemic therapy:

• Disease-modifying antirheumatic drugs (DMARDs) such as methotrexate achieved remission in 52.1% (95% CI, 38.6%-67.1%) of patients 2
• Mycophenolate mofetil controlled inflammation in 70.9% (95% CI, 57.1%-83.5%) 2

Second-line biologic therapy:

• Adalimumab extended time to treatment failure to 24 weeks vs 13 weeks with placebo and reduced frequency of treatment failure from 78.5% to 54.5% (P < .001) 2
• Indicated for patients who do not improve or worsen with first-line therapy 2

Infectious Uveitis Management

Uveitis caused by systemic infection should be treated with antimicrobials, and local or systemic steroids may be used depending on the severity of uveitis and the specific microorganism. 2

When to Modify Treatment

Criteria for inadequate response (requiring therapy adjustment):

• 2-step increase in inflammation level or increase to maximum grade (worsening) 1
• Lack of 2-step decrease in inflammation level despite therapy 1
• Deterioration in visual function, anterior chamber cells/flare, vitreous haze, chorioretinal lesions, retinal vascular lesions, or macular/optic nerve involvement 1

Before changing therapy, reconsider:

• Patient nonadherence 1
• Infection 1
• Masquerade syndrome 1

Options when first-line therapy fails:

• Dose escalation to maximum tolerated therapeutic dose 1
• Transition to alternative or additional agent 1
• Individualize based on patient history, underlying cause, patient preference, cost, and convenience 1

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Complications and Prognosis

Untreated uveitis causes:

• Cataracts 1, 2
• Glaucoma and elevated intraocular pressure 1, 2
• Macular edema 1, 2
• Retinal detachment 2
• Optic nerve damage 2
• Permanent vision loss or blindness 1, 2

Systemic therapy (corticosteroid-supplemented immunomodulatory therapy and biologics) improved visual outcomes, controlled inflammation, and reduced macular edema compared with intravitreous fluocinolone acetonide implant in patients with panuveitis, intermediate uveitis, and posterior uveitis. 1

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Key Clinical Pearls

• Any suspicious ocular signs and symptoms should be investigated by an ophthalmologist, as early detection allows initiation of treatment to prevent permanent ocular damage 3
• When related to systemic inflammatory conditions like Crohn's disease, uveitis is frequently bilateral and insidious in onset 3
• Behçet's disease uveitis can be independent of other disease manifestations and may require aggressive systemic immunosuppression 5
• Shared decision-making and communication among providers are essential components of treatment recommendations 1