What is the pathophysiology of chorioretinitis secondary to histoplasmosis?

Pathophysiology of Chorioretinitis Secondary to Histoplasmosis

The pathophysiology of chorioretinitis secondary to histoplasmosis involves fungal infection with Histoplasma capsulatum leading to choroidal inflammation, disruption of the retinal pigment epithelium, and potential neovascularization that can cause significant visual impairment.

Primary Infection and Dissemination

• Histoplasma capsulatum is a dimorphic fungus primarily found in endemic areas, particularly the Ohio and Mississippi River valleys in the United States 1
• Initial infection occurs through inhalation of fungal spores, often from soil contaminated with bird or bat droppings 1
• The fungus initially causes a pulmonary infection that is often asymptomatic or presents as a mild flu-like illness
• During the primary infection, the organism can disseminate hematogenously to various organs, including the eyes

Ocular Involvement Mechanism

• The exact mechanism of ocular involvement remains incompletely understood, but evidence points to both direct fungal invasion and immune-mediated processes 2
• The fungus reaches the choroid through hematogenous spread during the initial infection phase
• Once in the choroid, Histoplasma capsulatum can cause:
  • Direct tissue damage from fungal invasion
  • Inflammatory response in the choroid
  • Formation of focal granulomas in the choroid
  • Disruption of the retinal pigment epithelium (RPE) barrier

Characteristic Lesion Development

• The initial chorioretinal lesions develop as small, focal areas of inflammation in the choroid
• These lesions evolve into the characteristic "punched-out" chorioretinal scars seen in ocular histoplasmosis syndrome (OHS) 2
• The classic clinical presentation includes:
  • Multiple small, punched-out peripheral chorioretinal scars
  • Peripapillary atrophy
  • Absence of vitreous inflammation
  • Potential macular involvement 3

Immune-Mediated Component

• There is substantial evidence that recurrent reactivation of perimacular ocular histoplasmosis lesions is partly due to host sensitivity to fungal antigens 4
• The immune response to Histoplasma antigens plays a significant role in tissue damage
• Chronic or recurrent fungal infections elsewhere in the body may trigger reactivation of ocular lesions through immune cross-reactivity 4

Choroidal Neovascularization Development

• The most vision-threatening complication is choroidal neovascularization (CNV)
• CNV occurs in approximately 5% of affected eyes 5
• The pathophysiology of CNV development involves:
  1. Disruption of the RPE and Bruch's membrane by the inflammatory process
  2. Release of angiogenic factors, particularly vascular endothelial growth factor (VEGF)
  3. Growth of new, abnormal blood vessels from the choroid into the subretinal space
  4. Leakage from these fragile vessels, causing fluid accumulation and potential hemorrhage
  5. Formation of fibrovascular scar tissue, leading to permanent vision loss if untreated

Risk Factors for Disease Progression

• Reinfection with Histoplasma capsulatum can increase the risk of reactivation 4
• Chronic fungal infections elsewhere in the body may trigger reactivation through immune mechanisms 4
• Immunosuppression, particularly HIV with CD4+ counts <150 cells/μL, increases risk of disseminated disease 1
• Ocular trauma or surgery (including LASIK) may trigger choroidal neovascularization in patients with existing OHS lesions 4

Long-Term Disease Course

• The risk of chorioretinitis increases over time, from approximately 10% in early infancy to 30% by 12 years of age in congenital cases 6
• In acquired cases, the disease can remain dormant for years before reactivation
• Macular involvement occurs in a significant percentage of cases and is the primary cause of vision loss 2
• Without treatment, CNV can lead to permanent central vision loss through scarring

Diagnostic Considerations

• Diagnosis is primarily clinical, based on the characteristic fundus appearance
• Histoplasma serology is often negative in patients with ocular histoplasmosis syndrome, making diagnosis challenging 7
• Multifocal choroiditis can mimic ocular histoplasmosis syndrome, requiring careful differential diagnosis 7
• Modern imaging technologies such as spectral-domain optical coherence tomography have improved diagnostic capabilities 2

Understanding this pathophysiology is crucial for proper management, as treatments target different aspects of the disease process, including antifungal therapy for active infection and anti-VEGF therapy for choroidal neovascularization.