Intraocular lymphoma remains one of the most challenging “masquerade syndromes” in ophthalmology. These rare malignancies, which include vitreoretinal lymphoma (VRL) and choroidal lymphoma (CL), frequently simulate benign inflammatory conditions, often leading to diagnostic delays of up to two years. However, recent advancements in multimodal imaging have provided clinicians with a suite of non-invasive biomarkers that can heighten clinical suspicion and facilitate earlier life-saving interventions.
Vitreoretinal Lymphoma (VRL): The Classic Masquerader
VRL is typically a high-grade diffuse large B-cell lymphoma and is closely associated with primary central nervous system lymphoma (PCNSL).
- Vitreous Biomarkers: While vitreous cells are nearly ubiquitous, the “aurora borealis” pattern—cells aligned along radial vitreous fibrils—is highly specific for lymphoma.
- OCT Insights: Optical coherence tomography (OCT) has become a “required” diagnostic tool. Key findings include:
- Preretinal Deposits: Hyperreflective material on the inner retinal surface, which is 92.5% specific for VRL.
- Vertical Hyperreflective Lesions (VHRL): Infiltrates extending through retinal layers, often around vessels.
- Sub-RPE Deposits: Homogeneous hyperreflective material between the RPE and Bruch’s membrane.
- Novel Imaging: En face OCT angiography (OCTA) has identified perivascular flower-bud-like lesions (PFBLs), providing a new way to visualize vascular infiltration.
- Fundus Autofluorescence (FAF): Active lesions often present with a granular or “leopard spot” pattern, characterized by alternating hyper- and hypoautofluorescent spots.
Choroidal Lymphoma (CL): Navigating the “Seasick” Choroid
In contrast to VRL, choroidal lymphoma is often a low-grade, slow-growing B-cell malignancy.
- Fundus Appearance: Characterized by ubiquitous yellow-white, discrete, or placoid choroidal infiltrates.
- The “Seasick” Topography: Using Enhanced Depth Imaging (EDI)-OCT, clinicians can identify a characteristic undulating anterior surface of the choroid, often described as a “seasick” or “rippled” configuration.
- Indocyanine Green Angiography (ICGA): ICGA is superior to fluorescein angiography for CL, typically revealing multifocal hypofluorescent lesions that may be more extensive than they appear on clinical exam.
- B-scan Ultrasonography: Classic CL presents as smooth, diffuse, hypoechoic choroidal thickening, occasionally with posterior epibulbar extension.
Differentiating Lymphoma from Uveitis
Distinguishing these malignancies from uveitis is critical. For instance, cystoid macular edema (CME) and subretinal fluid are common in inflammatory uveitis but are notably rare in untreated VRL. Conversely, the presence of sub-RPE deposits or VHRLs should immediately pivot the differential toward a neoplastic process.
The Future of Monitoring
Beyond diagnosis, multimodal imaging serves as a vital tool for tracking treatment response. Resolution of vitreous cells, flattening of RPE undulations, and disappearance of intraretinal infiltrates on OCT are reliable markers of tumor regression following therapies like intravitreal methotrexate.
By integrating these modality-specific biomarkers, clinicians can move beyond the “masquerade” to ensure accurate diagnosis and improved survival for patients affected by these rare ocular malignancies.
Reference Ibrahim A, Swaminathan VB, Smith WM, Dalvin LA. Ocular Imaging in Intraocular Lymphoma: A Review. Clinical & Experimental Ophthalmology. 2026. [Source Document]
