The pathogenic role and genomic characteristics of Epstein-Barr virus in vitreoretinal lymphoma

Epstein-Barr virus (EBV) infection is well-known for its association with lymphoproliferative disorders and various lymphomas, causing significant global morbidity and mortality. EBV-positive vitreoretinal lymphoma (VRL) is exceedingly rare. As a result, the pathogenic role and genomic characteristics of EBV in VRL remain poorly understood. In this study, we employed droplet digital PCR (ddPCR) combined with EBV-specific immunofluorescence assay to detect EBV in the vitreous fluid of fifty-three VRL patients. We found that approximately 28% (15/53) of the patients were EBV positive. Analysis of clinical data showed that EBV-positive VRL patients had shorter progression-free survival (PFS) compared to EBV-negative patients (P = 0.004). Additionally, through integration of EBV-targeted sequencing and PCR-based deep sequencing, we found that all five VRL-derived EBV genomes formed a distinct cluster within one phylogenetic branch. Meanwhile, several non-synonymous mutations were exclusively detected in the VRL group, including S229T in latent membrane protein 1 (LMP1) and G2248R in the Epstein-Barr virus BamHI-PraL fragment 1 (BPLF1). In conclusion, our findings suggest that EBV as a risk factor associated with poor prognosis in VRL, and we provide a genome-wide view of EBV sequence variations from VRL patients. This may offer insights into the pathogenic role of EBV in VRL and could potentially assist in the diagnosis and treatment of this disease.