Idiopathic multifocal choroiditis (IMFC) is a spontaneously occurring inflammatory disease that presents with multiple lesions in the retina and choroid. It involves recurrent episodes of inflammation and can occur bilaterally, either simultaneously or sequentially.
In 1984, Deutsch and Tessler reported 28 cases as “pseudo-POHS.” In 1986, Morgan and Shatz described 11 cases as “recurrent multifocal choroiditis,” noting vitreous inflammation as a feature not seen in POHS patients. IMFC is a distinct disease differentiated from PIC (punctate inner choroidopathy), multifocal choroiditis with panuveitis (MFCwP), and progressive subretinal fibrosis and uveitis syndrome.
Both MFC and PIC are subtypes of white dot syndromes (WDS), a group of inflammatory diseases primarily affecting the outer retina, choriocapillaris, and choroid 1). It has been suggested that MFC and PIC may represent a spectrum of the same disease 1).
The main difference is the presence or absence of vitritis. POHS does not involve vitritis, whereas IMFC typically shows vitritis in one or both eyes. Additionally, mild anterior chamber inflammation may be present in IMFC.
Lesions are classified into four types: active inflammatory lesions, inactive inflammatory lesions, secondary active choroidal neovascularization, and secondary inactive choroidal neovascularization.
Active Lesions
Color: Yellow to gray lesions with indistinct borders and associated retinal edema.
Size: Range 45–350 μm. Scattered or clustered in the posterior pole and periphery.
Associated findings: Subretinal fluid, optic disc swelling/hyperemia, cystoid macular edema, and choroidal neovascularization may occur.
Inactive Lesions
Color: Gray with well-defined borders. Scarring fibrosis and pigmentation are seen.
Morphology: Seen as atrophic punched-out discolored retinal pigment epithelium lesions.
Prognosis: Visual recovery may be difficult once the lesions become scarred.
Other complications (cystoid macular edema occurs in 14–41%):
The etiology of IMFC is unknown. There is a hypothesis that a preceding infection stimulates an immune response, but no specific pathogen has been identified.
Epidemiological features:
Genetic predisposition: Idiopathic multifocal choroiditis is associated with haplotypes of IL-10 and tumor necrosis factor (TNF).
Pathophysiological hypothesis: Inflammatory lesions begin at the level of the retinal pigment epithelium and choriocapillaris. Antigen sensitization may occur in the photoreceptors and retinal pigment epithelium due to exogenous antigens, potentially compromising the integrity of Bruch’s membrane. This creates space for the development of choroidal neovascular membranes, which can occur in up to 60% of patients.
Idiopathic multifocal choroiditis is a clinical diagnosis and a diagnosis of exclusion. It is essential to rule out infectious, malignant, and systemic diseases.
| Examination | Active Lesion Findings | Inactive Lesion Findings |
|---|---|---|
| Fluorescein Angiography (FA) | Early hyperfluorescence → late staining | Hyperfluorescence due to window defect |
| Indocyanine Green Angiography (ICG) | Early to mid-phase hypofluorescence | Hypofluorescent spots in all phases |
| Fundus autofluorescence | Hyperautofluorescent lesions (peripapillary, posterior pole) | Hypoautofluorescent atrophic lesions |
Optical coherence tomography (OCT) findings:
Fluorescein angiography findings: Acute inflammatory lesions show late staining; if choroidal neovascularization is suspected, leakage patterns are evaluated in combination with OCT findings1).
Infectious: POHS, syphilis, tuberculosis, toxoplasmosis, West Nile virus, Pneumocystis choroiditis
Non-infectious: sarcoidosis, PIC (punctate inner choroidopathy), birdshot retinochoroidopathy, acute posterior multifocal placoid pigment epitheliopathy
Malignant: lymphoma, metastasis
Basic clinical tests: complete blood count, comprehensive metabolic panel, angiotensin-converting enzyme, chest X-ray, syphilis testing, QuantiFERON-TB Gold
In tuberculosis-endemic regions (e.g., India), up to 40% of multifocal choroiditis may be associated with ocular tuberculosis2), and may be observed as inflammatory lesions beneath the retinal pigment epithelium on optical coherence tomography2).
Multimodal imaging is useful for differentiation. In tuberculous multifocal choroiditis, optical coherence tomography may show disruption of the external limiting membrane and focal loss of the ellipsoid zone overlying inflammatory lesions of the retinal pigment epithelium 2). Evaluation combines QuantiFERON-TB Gold testing and imaging.
Treatment is selected based on the degree of inflammation, active lesions, complications, and visual impairment. Indications for treatment include cystoid macular edema, dense vitritis, or choroidal neovascular membrane.
Oral steroids: First-line treatment. Start at high to moderate doses and taper according to inflammation resolution.
Local steroids:
In severe or refractory cases, consider immunomodulatory agents such as antimetabolites, biologics, or T-cell inhibitors.
An international study group survey reported that immunomodulatory agents such as methotrexate and adalimumab are frequently used for multifocal choroiditis-PIC spectrum disease 3).
Intravitreal anti-VEGF therapy is used for active choroidal neovascularization and macular edema.
Inflammatory lesions begin at the level of the retinal pigment epithelium and choriocapillaris, and it is hypothesized that antigen sensitization occurs in the retinal pigment epithelium in response to foreign antigens.
Idiopathic multifocal choroiditis and punctate inner choroidopathy both involve the outer retina, choriocapillaris, and choroid, and may represent a spectrum of the same disease 1). Multifocal choroiditis is a chronic, bilateral, recurrent inflammatory disease characterized by posterior lesions with anterior uveitis and vitritis, whereas punctate inner choroidopathy differs in that it does not involve vitritis or anterior segment inflammation 1).
OCT angiography findings show distinct areas of decreased blood flow at the level of the choriocapillaris corresponding to active inflammatory lesions, supporting the possibility that outer retinal changes are secondary to primary choroidal involvement 1).
Inflammation disrupts the integrity of Bruch’s membrane, which serves as a foothold for the development of choroidal neovascular membranes. In idiopathic multifocal choroiditis, choroidal neovascularization can occur in up to 60% of patients.
Genetic factors such as associations with haplotypes of IL-10 and tumor necrosis factor have been reported, but the exact mechanism remains unclear.
OCT angiography shows distinct areas of decreased blood flow in the choriocapillaris of punctate inner choroidopathy and multifocal choroiditis lesions, corresponding to active inflammatory lesions 1). It is also applied to monitor choroidal vascular changes after treatment.
OCT angiography has been shown to delineate areas of decreased choriocapillaris blood flow corresponding to retinal pigment epithelial elevations on optical coherence tomography and hypofluorescent spots on indocyanine green angiography, deepening pathophysiological understanding 1).
Multimodal imaging has led to the concept that multifocal choroiditis with panuveitis and punctate inner choroidopathy are part of the same disease spectrum. More precise classification and development of personalized treatments are progressing. 1)
