What are the causes of chronic posterior uveitis?

Causes of Chronic Posterior Uveitis

The most common causes of chronic posterior uveitis include infectious etiologies (syphilis, toxoplasmosis, tuberculosis, and viral infections), inflammatory bowel disease, white dot syndromes, Vogt-Koyanagi-Harada disease, and masquerade syndromes such as lymphoma and leukemia. 1, 2, 3

Infectious Causes

Viral Infections

• Herpes viruses (herpes simplex virus, herpes zoster virus, cytomegalovirus) are significant causes of posterior uveitis that can lead to sight-threatening complications if not treated promptly 2, 4
• These infections may occur as isolated ocular disease or as part of systemic viral illness, with risk of reactivation depending on host immunity and comorbidities 4

Bacterial Infections

• Syphilis is a major cause of posterior uveitis that can present with various ocular manifestations 2
• Tuberculosis can cause chronic granulomatous posterior uveitis and should be considered in endemic areas or in immunocompromised patients 2

Parasitic Infections

• Toxoplasmosis is one of the most common infectious causes of posterior uveitis worldwide, typically presenting as focal necrotizing retinitis 2
• Characteristic presentation includes focal retinal lesions with overlying vitritis ("headlight in fog" appearance) 2

Autoimmune/Inflammatory Causes

Inflammatory Bowel Disease-Associated Uveitis

• Posterior uveitis occurs in less than 1% of patients with inflammatory bowel disease but can be sight-threatening if left untreated 5
• Unlike episcleritis, which tends to reflect bowel disease activity, uveitis can be independent of bowel symptoms and may precede the onset of intestinal manifestations 5

Vogt-Koyanagi-Harada Disease

• Characterized by bilateral, diffuse choroiditis with serous retinal detachments 5
• Typically affects young adults and is associated with neurologic, auditory, and integumentary manifestations 5
• Presents with rapid onset, bilateral involvement in 95% of cases, with cystoid outer retinal fluid on OCT and numerous central leakage points on fluorescein angiography 5

White Dot Syndromes

• Group of inflammatory disorders characterized by multiple white-yellow lesions at the level of the retinal pigment epithelium, choroid, or both 5
• Includes acute posterior multifocal placoid pigment epitheliopathy (APMPPE), which presents with rapid onset, progressive marked vision loss, and often slow recovery 5
• More common in females and relatively young patients 5

Masquerade Syndromes

Malignancies

• Primary intraocular lymphoma and leukemia can present as posterior uveitis and should be considered in patients with atypical presentations or poor response to anti-inflammatory therapy 3
• Immune checkpoint inhibitor therapy can induce Vogt-Koyanagi-Harada-like uveitis as a side effect 3

Other Masqueraders

• Central serous chorioretinopathy can sometimes masquerade as inflammatory exudative retinal detachment 3
• Inherited conditions like retinitis pigmentosa or autosomal dominant neovascular inflammatory vitreoretinopathy may mimic inflammatory posterior uveitis 3

Diagnostic Approach

• Careful history should include assessment of systemic symptoms, medication use (including biologics like anti-TNF agents), and recent vaccinations 3
• Multimodal imaging including fluorescein angiography, indocyanine green angiography, and optical coherence tomography is essential for differentiating between various causes 3
• Laboratory testing should be guided by clinical suspicion and may include syphilis serology, tuberculosis testing, toxoplasmosis titers, and viral PCR when appropriate 2

Treatment Considerations

• Treatment depends on the underlying etiology - infectious causes require appropriate antimicrobial therapy 1
• For non-infectious posterior uveitis, systemic immunomodulatory therapy is often required, with agents such as azathioprine, cyclosporine-A, or TNF inhibitors like adalimumab 6
• Systemic corticosteroids should be used only in combination with immunosuppressive agents, not as monotherapy, to minimize adverse effects 6
• For sight-threatening posterior uveitis, prompt and aggressive treatment is essential to prevent permanent vision loss 6

Important Pitfalls

• Failure to identify infectious causes before initiating immunosuppressive therapy can lead to worsening of infection and poor outcomes 6
• Screening for latent or active infections, particularly tuberculosis, is essential before starting systemic immunomodulatory therapy 6
• Some cases of posterior uveitis may be drug-induced, including paradoxical inflammatory effects of anti-TNF-α therapy or post-vaccination uveitis 3
• Regular monitoring by an ophthalmologist is essential during treatment and for at least 3 years after remission to detect recurrence early 6