Case 01-2017-Primary vitreoretinal lymphoma(PVRL):report of a case and update of literature from 1942 to 2016

Primary vitreoretinal lymphoma (PVRL), as a subset of primary central nervous system lymphoma (PCNSL), is a rare and fatal ocular malignancy. Most PVRL masquerades as chronic posterior uveitis, which makes the clinical diagnosis challenging. Vitreous cells, subretinal lesions and imaging techniques are essential for clinical diagnosis. Importantly, cytopathology/histopathology identification of malignant cells is the gold standard for the diagnosis of PVRL. In addition, molecular detection of immunoglobulin heavy chain (IgH) or T cell receptor (TCR) gene rearrangements, immunophenotyping for cell markers, and cytokine analysis of interleukine-10 elevation are often used as adjunct procedures. Current management of PVRL involves local radiation, intravitreal chemotherapy (methotrexate and rituximab), with or without systemic chemotherapy depending on the involvement of non-ocular tissues. In cases with concomitant PCNSL, systemic high-dose methotrexate/rituximab based therapy in conjunction with local therapy, whole brain radiotherapy and/or autologous stem cell transplantation is considered. Although PVRL normally responds well to initial treatment, high rates of relapse and CNS involvement usually lead to poor prognosis and limited survival. A professional team of medical experts in ophthalmologists, ocular pathologists, neuro-oncologists and hemato-oncologists is essential for optimizing patient management.

Clinical utility of cytokine analysis in the diagnosis and efficacy monitoring of vitreoretinal lymphoma

AIM:To investigate the value of cytokine analysis in aqueous humor(AH)for discriminating vitreoretinal lymphoma(VRL)from uveitis and for evaluating the efficacy of intravitreal methotrexate(MTX)injections.METHODS:This retrospective study was done on 28 VRL patients between 2013 and 2019.AH interleukin(IL)-10,IL-6,IL-8,vascular endothelial growth factor(VEGF),and vascular cell adhesion molecules(VCAM)were measured in 28 VRL patients and 38 uveitis patients.As to the respective examinations for distinguishing VRL from uveitis,the diagnostic accuracy was evaluated by receiver operating characteristic(ROC)curve analysis.The response to treatment was monitored by observing changes in bestcorrected visual acuity(BCVA),ocular manifestation,and AH cytokine levels in 21 patients with VRL who had undergo multiple intravitreal injections of MTX.RESULTS:Compared with uveitis patients,VRL patients had higher IL-10 level(P<0.001)and IL-10/IL-6 ratio(P<0.001),whereas patients with uveitis had significantly higher IL-6 level than those with VRL(P=0.003).An ROC analysis was used to identify the diagnostic threshold values for VRL,and it was found that optimal sensitivity and specificity improved to 94.1%and 100%,respectively,for IL-10/IL-6>1.55 and 88.2%and 81.1%,respectively,for IL-10>76.7 pg/m L.In 21 patients who had undergo repeated injections,improvements in BCVA,clinical remission of VRL and continuous decrease in cytokine levels over time were observed.In those patients,the BCVA correlated with the aqueous levels of IL-10 and IL-6 during the course of disease treatment.CONCLUSION:The combination of the aqueous cytokine profiles can be instrumental for conventional diagnostic methods and for progression monitoring and treatment response.

Primary vitreoretinal lymphoma masquerading as acute posterior multifocal placoid pigment epitheliopathy

Dear Editor,Primary vitreoretinal lymphoma（PVRL）is a rare form of ocular malignancy and it is usually considered as a subset of primary central nervous system lymphoma（PCNSL）.An insidious onset associated with delays in diagnosis iscommon.

Diagnosis and management of intraocular lymphoma:a narrative review

Background and Objective:Intraocular lymphoma(IOL)is a heterogenous category of rare malignancies that are often misdiagnosed and underrecognized.The rarity of IOL impedes clinical research and contributes to difficulty in standardizing its management.In this article we review the existing scientific literature to identify the current diagnostic tools and discuss comprehensive management of various categories of IOL.Our objective is to increase disease recognition of IOL as a whole and explore updated management options for each subtype.Methods:PubMed and Embase were searched for publications using the terms‘intraocular lymphoma’,‘vitreoretinal lymphoma’,‘uveal lymphoma’,‘iris lymphoma’,‘choroidal lymphoma’and‘ciliary body lymphoma’published from 1990 to June 2021.Inclusion criteria were English language articles.Exclusion criteria were non-English language articles,case reports and animal studies.Key Content and Findings:IOL often presents in middle-aged and older patients with symptoms of floaters and vision changes,but a broad array of clinical signs and symptoms are possible depending upon subtype.IOL can be subdivided by location of involvement into vitreoretinal and uveal lymphoma.These subtypes express key differences in their pathophysiology,clinical presentation,histology,prognosis,and treatment.Primary vitreoretinal lymphomas(PVRL)generally originate from B-lymphocytes and are associated with central nervous system(CNS)lymphoma.Ophthalmic findings include retinal pigment epithelium changes with yellow subretinal deposits known as“leopard spotting.”Primary uveal lymphomas generally originate from low-grade B-lymphocytes invading the choroid and carry an improved prognosis compared to vitreoretinal lymphomas.Funduscopic findings of primary uveal lymphoma include yellow to pink-yellow choroidal swelling with infiltrative subconjunctival“salmon-patch”lesions.Diagnosis for IOL is often delayed due to insidious onset,low prevalence,and tendency to mimic diseases such as uveitis.Diagnosis may be challenging,often relying on biopsy with specialized laboratory testing for confirmation of IOL.Optimal treatment regimens are currently debated among experts.Management of IOL is best coordinated in association with neuro-oncology clinicians due to the tendency for intracranial involvement.Conclusions:IOL represents a group of multiple malignancies with distinct clinicopathologic features.Future outlook for treatment and prognosis of IOL is likely to improve with less invasive molecular diagnostic techniques and increased awareness.Clinicians should be circumspect in all patients with possible IOL and promptly refer to oncologic specialists for rapid evaluation and treatment.