Cryptococcal choroiditis is an infectious choroiditis caused by the encapsulated yeast-like fungus Cryptococcus neoformans¹˒². It is one of the AIDS-defining illnesses and an important cause of infectious choroiditis in immunocompromised patients³.
Choroidal lesions may appear as an initial ocular manifestation of disseminated cryptococcosis or meningitis. Without treatment, the disease can become fatal within weeks, making early detection and treatment extremely important.
Pathogen and Infection Route
Pathogen: Cryptococcus neoformans (encapsulated yeast-like fungus)
Source of infection: Most commonly found in dried pigeon droppings
Route of infection: Inhalation of aerosolized spores leads to pulmonary infection → hematogenous dissemination
Epidemiology: 957,900 cases of cryptococcal meningoencephalitis annually, with over 600,000 deaths (2008 survey)
Major Risk Factors
HIV/AIDS: CD4 < 100 cells/µL is the greatest risk
Other immunodeficiencies: Organ transplantation, malignancy, immunosuppressant use, long-term corticosteroid use
Environmental exposure: Pigeon droppings, decaying wood, tree hollows, contaminated soil
Prevention: Promptly administer prophylactic antifungal drugs once CD4 < 100 cells/µL is identified
Cryptococcal chorioretinitis presents with nonspecific symptoms in the early stage.
In severely immunocompromised states, the inflammatory response itself is poor, and there is a risk of progression with minimal symptoms.
Fundus findings:
Cryptococcal chorioretinitis typically presents with the following findings.
In severe immunodeficiency, inflammatory reactions such as vitritis are often minimal. This is because the immune function required to mount an intraocular immune response is markedly reduced.
Imaging findings:
| Test | Findings |
|---|---|
| Fluorescein angiography (FA) | Early: blockage of choroidal filling (hypofluorescence). Late: lesions with reduced filling |
| Indocyanine green angiography (ICG) | Used to evaluate choroidal lesions |
| OCT | Choroidal thickening, hyperreflective choroidal lesions. Retinal pigment epithelium (RPE) destruction is not typical |
Note that these imaging findings are nonspecific.
In severe immunodeficiency, the immune function itself is significantly impaired, making it difficult to recruit inflammatory cells into the vitreous. Since CD4-positive T cells are reduced to 100 cells/µL or less, inflammatory responses to infection are less likely to occur. Therefore, vitritis and anterior chamber inflammation, which are typically seen in infectious endophthalmitis, are often mild.
C. neoformans is an encapsulated yeast-like fungus widely present in the environment. It is particularly abundant in dried pigeon droppings, and inhalation of aerosolized spores is the main route of infection.
Major risk factors:
Environmental risks:
Since cryptococcal chorioretinitis is an ocular manifestation of systemic disease, systemic evaluation is essential.
Initial Evaluation Process:
Accuracy of diagnostic tests:
| Test | Characteristics |
|---|---|
| LFA method (CrAg lateral flow assay) | Sensitivity and specificity both >98%. Recommended diagnostic method. |
| CSF fungal culture | Used for definitive diagnosis. Sensitivity decreases with early or prior antifungal therapy. |
| Mucicarmine stain | Identifies the thick capsule of C. neoformans. |
| India Ink Stain | Identifies thick capsule. Useful for rapid diagnosis |
Differential Diagnosis:
Differential diagnosis of cryptococcal chorioretinitis in advanced AIDS patients:
Fundus findings (milky-white to yellow choroidal lesions + hemorrhage with central white spots) are characteristic, but definitive diagnosis requires serum and cerebrospinal fluid CrAg testing and culture. FA, ICG, and OCT findings are all non-specific, and differentiation from other infectious chorioretinitis may be difficult based on ocular findings alone. It is important to comprehensively evaluate the systemic condition (degree of immunodeficiency, risk of other infections).
The global guidelines of the European Confederation of Medical Mycology (ECMM) and the International Society for Human and Animal Mycology (ISHAM) (Chang et al., 2024)¹, as well as the clinical practice guidelines of the Infectious Diseases Society of America (IDSA) (Perfect et al., 2010)², recommend that all disseminated cryptococcosis outside the central nervous system and lungs, including ocular lesions, be treated in the same manner as central nervous system disease.
Three-Step Treatment Regimen:
| Step | Regimen | Duration |
|---|---|---|
| Induction therapy | Liposomal amphotericin B 3–4 mg/kg/day + flucytosine 25 mg/kg 4 times daily | 2 weeks |
| Consolidation therapy | Fluconazole 400–800 mg once daily | 8 weeks |
| Maintenance therapy | Fluconazole 200 mg once daily | 12–18 months |
Alternative therapy in resource-limited settings (induction phase):
Single high-dose liposomal amphotericin B (10 mg/kg) + flucytosine 100 mg/kg/day + fluconazole 1200 mg/day for 2 weeks.
In some cases, the condition may rapidly progress to endophthalmitis, requiring the following surgical treatments:
With appropriate treatment, acute infection can be controlled, but long-term maintenance therapy (fluconazole for 12–18 months) is required. Due to high risk of recurrence, maintenance therapy must be tapered carefully. Management of underlying immunodeficiency (especially HIV) is also essential, and recovery of CD4 count significantly affects long-term prognosis. Visual prognosis depends on the extent of lesions at the time of detection and the speed of treatment initiation.
C. neoformans is a yeast-like fungus with a polysaccharide capsule. The capsule functions as an immune evasion mechanism by suppressing complement activation and avoiding phagocytosis by macrophages.
Progression of infection:
Under normal immune conditions, Th1-type cellular immunity is activated against infection, causing inflammation. However, when CD4-positive T cells are severely depleted, this inflammatory response is not triggered. Therefore, in cryptococcal choroiditis, inflammatory signs such as vitritis are scarce, and the disease progresses with mild symptoms.
The abundant blood flow and vascular structure (fenestrated capillaries) of the choroid facilitate the colonization of hematogenously disseminated C. neoformans. Proliferation of fungal colonies leads to the formation of milky-white to yellow choroidal lesions. Spread to adjacent retinal capillaries may cause intraretinal hemorrhages with central white spots (resembling Roth spots).
Cryptococcosis continues to impose a severe disease burden, especially in low- and middle-income countries¹. Visual impairment is frequent in cryptococcal meningitis, and irreversible vision loss due to optic neuropathy or elevated intracranial pressure has been reported⁴˒⁵. Recent research trends include the following:
