Primary vitreoretinal lymphoma: diagnosis, treatment, and prognosis-a review of current knowledge and future directions

Abstract

Primary vitreoretinal lymphoma (PVRL), a rare subtype of primary central nervous system lymphoma (PCNSL), can lead to permanent vision loss and central nervous system (CNS) involvement, resulting in a poor prognosis. PVRL often masquerades as uveitis, and its partial response to topical corticosteroids further complicates the diagnosis. The gold standard for diagnosis is cytological analysis; however, owing to its low sensitivity, cytokine profiling and genetic testing may serve as supplementary diagnostic tools. There is no universally accepted consensus regarding PVRL treatment protocols. Combined systemic high-dose intravenous methotrexate (MTX) and intravitreal therapy may help manage bilateral ocular lesions, although this combination's ability to delay CNS relapse remains controversial. For relapsed or refractory (R/R) PVRL patients aged <60 years, intensive consolidation chemotherapy followed by autologous stem cell transplantation may be considered. Novel targeted therapies such as ibrutinib and lenalidomide have demonstrated efficacy in R/R cases. Large-scale multicenter prospective studies are urgently needed to determine optimal treatment strategies.

Keywords: Autologous stem cell transplantation; Bruton’s tyrosine kinase inhibitors; Methotrexate; Primary central nervous system lymphoma; Primary vitreoretinal lymphoma.

Figure 1.

Multimodal images of a 75-y-old female diagnosed as vitreoretinal lymphoma. Left top: Ocular B-scan ultrasonography reveals diffuse posterior vitreous haze. Left bottom: OCT shows confluent RPE detachment temporal to the macula with homogeneous hyperreflective mass beneath it. Right: Ocular fundus photograph displays an annular yellowish-white elevated lesion temporal to the macula accompanied by small pigment clumps on the surface. OCT = optical coherence tomography, RPE = retinal pigment epithelium.

Figure 2.

The current tools for diagnosing primary vitreoretinal lymphoma. MYD88 = myeloid differentiation primary response 88, NGS = next-generation sequencing, PCR = polymerase chain reaction, PVRL = primary vitreoretinal lymphoma, S-FNAB = silicone fine-needle aspiration biopsy, sIL-2Rα = soluble IL-2 receptor α, sVEGFR = soluble vascular endothelial growth factor receptor. This image was created using BioRender.

Figure 3.

Overview of treatments for primary vitreoretinal lymphoma. Therapies that target certain pathways in primary central nervous system lymphoma highlighted in red are also promising in PVRL. AKT = protein kinase B, ASCT = autologous stem cell transplantation, BCR = B-cell receptor, BTK = Bruton’s tyrosine kinase, CAR = chimeric antigen receptor, HD = high-dose, ITAM = immunoreceptor tyrosine-based activation motif, mTOR = mechanistic target of rapamycin, MYD88 = myeloid differentiation primary response 88, NF-κB = nuclear factor kappa-light-chain-enhancer of activated B cells, PI3K = phosphoinositide 3-kinase, SYK = spleen tyrosine kinase, TLR = toll-like receptor. This image was created using BioRender.