High-dose methotrexate and zanubrutinib combination therapy for primary central nervous system lymphoma

In this editorial I comment on the article,published in the current issue of the World Journal of Clinical Oncology.Primary central nervous system lymphoma(PCNSL)is a disease of elderly and immunocompromised patients.The authors reported clinical results of 19 patients with PCNSL treated with zanubrutinib/high dose methotrexate(HD-MTX)until disease progression.They demonstrated that the combination of zanubrutinib with HD-MTX led to a marked clinical response and tolerability among these patients.They also observed that cerebrospinal fluid liquid biopsy to detect circulating tumor DNA may be a good option for evaluating treatment response and tumor burden in patients with PCNSL.PCNSL is a challenging disease for treatment as these patients present with different neurological states and comorbidities.Treatment has evolved over the years from whole brain radiotherapy to HD-MTX followed by autologous stem cell transplant.Gradually,treatment of patients with PCNSL is going to become individualized.

Bruton’s tyrosine kinase inhibitors in primary central nervous system lymphoma:New hopes on the horizon

In this editorial,we comment on the article by Wang et al.This manuscript explores the potential synergistic effects of combining zanubrutinib,a novel oral inhibitor of Bruton’s tyrosine kinase,with high-dose methotrexate(HD-MTX)as a therapeutic intervention for primary central nervous system lymphoma(PCNSL).The study involves a retrospective analysis of 19 PCNSL patients,highlighting clinicopathological characteristics,treatment outcomes,and genomic biomarkers.The results indicate the combination’s good tolerance and strong antitumor activity,with an 84.2%overall response rate.The authors emphasize the potential of zanubrutinib to modulate key genomic features of PCNSL,particularly mutations in myeloid differentiation primary response 88 and cluster of differentiation 79B.Furthermore,the study investigates the role of circulating tumor DNA in cerebrospinal fluid for disease surveillance and treatment response monitoring.In essence,the study provides valuable insights into the potential of combining zanubrutinib with HD-MTX as a frontline therapeutic regimen for PCNSL.The findings underscore the importance of exploring alternative treatment modalities and monitoring genomic and liquid biopsy markers to optimize patient outcomes.While the findings suggest promise,the study’s limitations should be considered,and further research is needed to establish the clinical relevance of this therapeutic approach for PCNSL.

Fotemustine-based therapy in combination with rituximab as a first-line induction chemotherapy followed by WBRT for newly diagnosed primary central nervous system lymphoma: a prospective phase II trial

Objective:This study aimed to evaluate the safety,efficacy,and feasibility of the rituximab,fotemustine,pemetrexed,and dexamethasone(R-FPD)regimen followed by whole-brain radiotherapy(WBRT)for patients with primary central nervous system lymphoma(PCNSL).Methods:A prospective,single-center phase II clinical trial was conducted.Patients with PCNSL newly diagnosed at the First Affiliated Hospital of Zhengzhou University between July 2018 and July 2020 were studied.The R-FPD regimen consisted of rituximab(375 mg/m2 i.v.on D0),fotemustine(100 mg/m2 i.v.on D1),pemetrexed(600 mg/m2 i.v.on D1),and dexamethasone(40 mg i.v.on D1-5).Patients 60 years or younger who showed a complete response(CR)were treated with 23.4 Gy of WBRT after the end of chemotherapy;those older than 60 years with CR were treated with a wait-and-see approach;and those who did not show CR after the 4th cycle of chemotherapy were given salvage WBRT 30 Gy+local tumor field irradiation up to 45 Gy,regardless of age.Results:A total of 30 patients were included.After 2 cycles,the objective response rate(ORR)was 96.5%(28/29,1 CR,27 PR,0 SD,and 1 PD).After 4 cycles,the ORR was 73.1%(19/26,11 CR,8 PR,4 SD,and 3 PD).After WBRT,the ORR was 90.9%(10/11,7 CR,3 PR,and 1 SD).The grade III and IV toxicity responses were mainly leukopenia(20.0%),thrombocytopenia(23.3%),and anemia(10.0%).Conclusions:Fotemustine-based therapy in combination with rituximab chemotherapy followed by WBRT can improve outcomes,providing ORR benefits and favorable tolerability in patients newly diagnosed with PCNSL.

Imaging of hemorrhagic primary central nervous system lymphoma: A case report

BACKGROUND A primary central nervous system lymphoma(PCNSL)presenting with massive hemorrhage is a rare occurrence that is difficult to distinguish from a high-grade glioblastoma.Comprehensive descriptions of the imaging characteristics of such tumors have not yet been reported.Herein,we reported a case of a PCNSL with massive hemorrhage by presenting the imaging features of computed tomography(CT)imaging and structural and perfusion magnetic resonance imaging(MRI).CASE SUMMARY A 48-year-old man presented with headache lasting for 10 d.CT of the brain showed a round,heterogeneous,high-density lesion with surrounding edema in the right temporal lobe.For further diagnosis,a series of MRI examinations of the brain were subsequently performed,and a hemorrhagic lesion with ring-like enhancement was determined.The whole lesion was relatively hypoperfused on arterial spin labeling images.Surgical resection of the lesion and histopathological examination confirmed that the lesion was a diffuse large B-cell lymphoma with massive hemorrhage.CONCLUSION PCNSLs with hemorrhage occur very rarely,and structural and perfusion MRI examinations are requested exceedingly rarely.This case provided insight into some characteristics of a hemorrhagic lymphoma on CT and MRI examinations.Perfusion MRI examination may be useful for the differential diagnosis of PCNSLs and other brain tumors.

Temozolomide plus rituximab in the treatment of recurrent central nervous system lymphoma:Case report and literature review

Objective： The aim of our study was to investigate the treatment of recurrent central nervous system lymphoma. Methods： A case of recurrent central nervous system lymphoma in a 46-year-old male was treated with temozolomide 150 mg/m2 per day for 5 days; rituximab 750 mg/m2 on dl and d8, injected from Ommaya capsule to lateral ventricle, cycles were repeated every 28 days. Results： The patient achieved complete remission and the side effects was light after the treatment. Conclusion： Using this therapy method had certain curative effect on recurrent central nervous system lymphoma. Further studies should be needed on its indication.

Clinical outcomes of newly diagnosed primary central nervous system lymphoma treated with zanubrutinib-based combination therapy

BACKGROUND High-dose methotrexate(HD-MTX)combined with other chemotherapeutic agents is an effective treatment for patients with newly diagnosed primary central nervous system lymphoma(PCNSL);however,some patients have adverse reactions.AIM To retrospectively evaluate disease outcomes and mutational profiles in newly diagnosed PCNSL patients treated with a zanubrutinib/HD-MTX combination regimen.METHODS Nineteen newly diagnosed PCNSL patients were treated with zanubrutinib/HDMTX until disease progression,intolerable toxicities,or physician/patientdirected withdrawal.Safety and efficacy were assessed per the CTCAE v5.0 and RECIST v1.1 criteria,respectively.The primary endpoint was the objective response rate(ORR),and the secondary endpoints were progression-free survival,overall survival(OS),and safety.RESULTS The median follow-up duration was 14.7 mo(range,3.9–30 mo).The ORR for all patients was 84.2%,and 2-year progression-free-and OS rates were 75.6%and 94.1%,respectively.All patients completed the induction phase,and nine patients underwent autologous stem cell transplantation as consolidation therapy,resulting in an ORR of 88.9%.Ten patients received zanubrutinib as maintenance therapy and achieved an ORR of 80%.All patients showed an acceptable safety profile.The sequencing results for cerebrospinal fluid(CSF)and tumor tissue showed that PIM1 mutations were the most frequent genetic alterations.Circulating tumor DNA was correlated with disease relapse and response.CONCLUSION Our empirical observations demonstrated that the combination of zanubrutinib with HD-MTX yielded a marked clinical response and tolerability among newly diagnosed PCNSL patients.Non-invasive CSF liquid biopsy profiling may be feasible for evaluating treatment response and tumor burden.

Primary central nervous system lymphoma presenting as a single choroidal lesion mimicking metastasis:A case report

BACKGROUND Primary choroidal lymphoma is usually an indolent B-cell lymphoma and rarely progresses to extraocular sites.Herein,we report a case of primary choroidal lymphoma diagnosed as diffuse large B-cell lymphoma(DLBL),which progressed to the brain parenchyma after 4 mo.CASE SUMMARY A 78-year-old man presented with diminution of vision in his right eye.A choroidal lesion suspected of metastatic lesion was observed in the right eye by ophthalmologic examination.To discover the primary tumor,imaging investigations were performed but no malignant lesion was detected.After 4 mo,the patient returned to the clinic presenting with neurological symptoms.Brain magnetic resonance imaging revealed an abnormal contrast-enhancing mass in the left cerebellum.A stereotactic biopsy was performed,and DLBL was confirmed.The patient received the high dose methotrexate-based chemotherapy and he achieved complete remission.CONCLUSION Primary choroidal lymphoma is usually known to have a benign clinical course without systemic involvement.We present a rare case of primary choroidal lymphoma diagnosed as DLBL that progressed to the brain parenchyma within months.

Distinctive magnetic resonance imaging features in primary central nervous system lymphoma:A case report

BACKGROUND Primary central nervous system lymphoma(PCNSL)is a rare malignant tumor originating from the lymphatic hematopoietic system.It exhibits unique imaging manifestations due to its biological characteristics.CASE SUMMARY Magnetic resonance imaging(MRI)with diffusion-weighted imaging(DWI),perfusion-weighted imaging(PWI),and magnetic resonance spectroscopy was performed.The imaging findings showed multiple space-occupying lesions with low signal on T1-weighted imaging,uniform high signal on T2-weighted imaging,and obvious enhancement on contrast-enhanced scans.DWI revealed diffusion restriction,PWI demonstrated hypoperfusion,and spectroscopy showed elevated choline peak and decreased N-acetylaspartic acid.The patient's condition significantly improved after hormone shock therapy.CONCLUSION This case highlights the distinctive imaging features of PCNSL and their importance in accurate diagnosis and management.

Differential Diagnostic Value of Texture Feature Analysis of Magnetic Resonance T2 Weighted Imaging between Glioblastoma and Primary Central Neural System Lymphoma

Objective To investigate the difference in tumor conventional imaging findings and texture features on T2 weighted images between glioblastoma and primary central neural system(CNS) lymphoma. Methods The pre-operative MRI data of 81 patients with glioblastoma and 28 patients with primary CNS lymphoma admitted to the Chinese PLA General Hospital and Hainan Hospital of Chinese PLA General Hospital were retrospectively collected. All patients underwent plain MR imaging and enhanced T1 weighted imaging to visualize imaging features of lesions. Texture analysis of T2 weighted imaging(T2 WI) was performed by use of GLCM texture plugin of ImageJ software, and the texture parameters including Angular Second Moment(ASM), Contrast, Correlation, Inverse Difference Moment(IDM), and Entropy were measured. Independent sample t-test and Mann-Whitney U test were performed for the between-group comparisons, regression model was established by Binary Logistic regression analysis, and receiver operating characteristic(ROC) curve was plotted to compare the diagnostic efficacy. Results The conventional imaging features including cystic and necrosis changes(P = 0.000), ‘Rosette' changes(P = 0.000) and ‘incision sign'(P = 0.000), except ‘flame-like edema'(P = 0.635), presented significantly statistical difference between glioblastoma and primary CNS lymphoma. The texture features, ASM, Contrast, Correlation, IDM and Entropy, showed significant differences between glioblastoma and primary CNS lympoma(P = 0.006,0.000, 0.002, 0.000, and 0.015 respectively). The area under the ROC curve was 0.671, 0.752, 0.695, 0.720 and 0.646 respectively, and the area under the ROC curve was 0.917 for the combined texture variables(Contrast, cystic and necrosis, ‘Rosette' changes, and ‘incision sign') in the model of Logistic regression. Binary Logistic regression analysis demonstrated that cystic and necrosis changes, ‘Rosette' changes and ‘incision sign' and texture Contrast could be considered as the specific texture variables for the differential diagnosis of glioblastoma and primary CNS lymphoma. Conclusion The texture features of T2 WI and conventional imaging findings may be used to distinguish glioblastoma from primary CNS lymphoma.

Absence of enhancement in a lesion does not preclude primary central nervous system T-cell lymphoma:A case report

BACKGROUND Primary central nervous system lymphoma(PCNSL)is a non-Hodgkin lymphoma that originates in the central nervous system(CNS)and is exclusively limited to the CNS.Although most PCNSLs are diffuse large B-cell lymphomas,primary CNS T-cell lymphomas(PCNSTLs)are rare.PCNSTLs typically demonstrate some degree of enhancement on contrast-enhanced magnetic resonance imaging(MRI).To the best of our knowledge,non-enhancing PCNSTL has not been reported previously.CASE SUMMARY A 69-year-old male presented to the neurology department with complaints of mild cognitive impairment and gradual onset of left lower leg weakness over a span of two weeks.Initial MRI showed asymmetric T2-hyperintense lesions within the brain.No enhancement was observed on the contrast-enhanced T1 image.The initial diagnosis was neuro-Behçet’s disease.Despite high-dose steroid therapy,no alterations in the lesions were identified on initial MRI.The patient’s symptoms deteriorated further.An MRI performed one month after the initial scan revealed an increased lesion extent.Subsequently,brain biopsy confirmed the diagnosis of PCNSTL.The patient underwent definitive combined chemoradiotherapy.However,the patient developed bacteremia and died of septic shock approximately three months after diagnosis.CONCLUSION The absence of enhancement in the lesion did not rule out PCNSTL.A biopsy approach is advisable for pathological confirmation.

Prognostic value of clinical characteristics and immunophenotypic biomarkers in 115 patients with primary central nervous system lymphoma

Background Clinical outcome in patients with primary central nervous lymphoma （PCNSL） is variable and poorly predictable. This study investigated the association of clinical features and immune markers with prognosis of patients with PCNSL. Methods One hundred and fifteen newly diagnosed PCNSL patients at the study institution were considered eligible for this study. Clinical characteristics and biochemical assay data were collected. Immunohistochemical staining of Cyclin D3, Cyclin E, Foxpl, and LMO2 were performed. All cases were followed-up regularly. Results The common sites of involvement were frontal lobe （54.8%） and thalamus （16.5%）. Diffuse large B-cell lymphoma composed of 96.5% of the cases. The median overall survival was 22 （4-41） months, and the 5-year survival rate was 22.8%. Age 〉65 years, serum globulin 〉40 g/L, large size of tumor, lymphocyte count ≥1×10^9/L, and expression of Cyclin D3 and Cyclin E were associated with poor prognosis of PCNSL. Expressions of Foxpl, LMO2, and CD44 were not related to the survival. Expression of Cyclin E, large tumor size, and high serum globulin were independent prognostic factors for PCNSL. Conclusions PCNSL prognosis is relatively poor. Age, high tumor burden, higher lymphocyte count, expression of Cyclin D3, and Cyclin E are inferior prognostic factors for PCNSL.

Primary central nervous system lymphoma:status and advances in diagnosis,molecular pathogenesis,and treatment

Primary central nervous system lymphoma(PCNSL)is a rare group of extra-nodal non-Hodgkin lymphoma which is confined to the central nervous system or eyes.This article aims to present a brief profile of PCNSL diagnosis and treatment in immunocompetent patients.The authors retrieved information from the PubMed database up to September 2019.The annual incidence of PCNSL increased over the last four decades.The prognosis of PCNSL has improved mainly due to the introduction and wide-spread use of high-dose methotrexate,which is now the backbone of all first-line treatment polychemotherapy regimens.Gene expression profiling and next-generation sequencing analyses have revealed mutations that induce activation of nuclear factor-kB,B cell antigen receptor,and Janus kinases/signal transducer and activator of transcription proteins signal pathways.Some novel agents are investigated in the treatment of relapsed PCNSL including immunotherapy and targeted therapy.In particular,lenalidomide and ibrutinib have demonstrated durable efficiency.Treatment of PCNSL has evolved in the last 40 years and survival outcomes have improved in most patient groups,but there is still room to improve outcome by optimizing current chemotherapy and novel agents.

Analysis of the genomic landscape of primary central nervous system lymphoma using whole-genome sequencing in Chinese patients

Primary central nervous system lymphoma(PCNSL)is an uncommon non-Hodgkin’s lymphoma with poor prognosis.This study aimed to depict the genetic landscape of Chinese PCNSLs.Whole-genome sequencing was performed on 68 newly diagnosed Chinese PCNSL samples,whose genomic characteristics and clinicopathologic features were also analyzed.Structural variations were identified in all patients with a mean of 349,which did not significantly influence prognosis.Copy loss occurred in all samples,while gains were detected in 77.9%of the samples.The high level of copy number variations was significantly associated with poor progression-free survival(PFS)and overall survival(OS).A total of 263 genes mutated in coding regions were identified,including 6 newly discovered genes(ROBO2,KMT2C,CXCR4,MYOM2,BCLAF1,and NRXN3)detected in≥10%of the cases.CD79B mutation was significantly associated with lower PFS,TMSB4X mutation and high expression of TMSB4X protein was associated with lower OS.A prognostic risk scoring system was also established for PCNSL,which included Karnofsky performance status and six mutated genes(BRD4,EBF1,BTG1,CCND3,STAG2,and TMSB4X).Collectively,this study comprehensively reveals the genomic landscape of newly diagnosed Chinese PCNSLs,thereby enriching the present understanding of the genetic mechanisms of PCNSL.

A Case of Primary Central Nervous System Lymphoma with Ciliary Body Involvement

INTRODUCTION Primary central nervous system lymphoma （PCNSL） is defined as lymphoma confined to the brain, eye, spinal cord, or leptomeninges. It constitutes approximately 3% of all brain tumors, and 2-3% of all cases of non-Hodgkin lymphoma. Ocular involvement can be detected during clinical staging in about 20% of patients with PCNSL, with primary vitreous retinal lymphoma being the most common subtype. Uveal involvement of PCNSL is uncommon, and PCNSL with ciliary body involvement （CBL）, to the best of our knowledge, has not been reported.

Interstitial pneumonitis during rituximab-containing chemotherapy for primary central nervous system lymphomas: a case report and review of literature

Background: Primary central nervous system lymphoma(PCNSL) is a rare kind of non-Hodgkin lymphoma. Rituximab combined with high-dose methotrexate, cytarabine and dexamethasone (R-MAD regimen) were reported effective for PCNSL patients. Rituximab can cause several side effects, including fever, chills and rigors. Case presentation: In this case report, we demonstrate rituximab-induced interstitial pneumonitis in a PCNSL patient who has been treated with R-MAD regimen. The patient recovered after treatment and she remains complete remission after following consolidation chemotherapy. Conclusions: Here is no report of potential fatal complications of Rituximab like interstitial pneumonitis nowadays in PCNSL patients. As Rituximab is widely used, physicians should raise their awareness of this rare complication and detect RTX-ILD in early stage.

New risk factors and new tendency for central nervous system relapse in patients with diffuse large B-cell lymphoma:a retrospective study

Background: In patients with difuse large B?cell lymphoma(DLBCL), central nervous system(CNS) relapse is uncom?mon but is nearly always fatal. This study aimed to determine the risk factors for CNS relapse in DLBCL patients and to evaluate the eicacy of rituximab and intrathecal chemotherapy prophylaxis for CNS relapse reduction.Methods: A total of 511 patients with newly diagnosed DLBCL treated at the Sun Yat?sen University Cancer Center between January 2003 and December 2012 were included in the study. Among these patients, 376 received R?CHOP regimen(rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone) as primary treatment, and 135 received CHOP regimen(cyclophosphamide, doxorubicin, vincristine, and prednisone) as primary treatment. Intrathe?cal chemotherapy prophylaxis(methotrexate plus cytarabine) was administered to those who were deemed at high risk for CNS relapse. In the entire cohort and in the R?CHOP set in particular, the Kaplan–Meier method coupled with the log?rank test was used for univariate analysis, and the Cox proportional hazards model was used for multivariate analysis. Diferences were evaluated using a two?tailed test, and P < 0.05 was considered signiicant.Results: At a median follow?up of 46 months, 25(4.9%) patients experienced CNS relapse. There was a trend of reduced occurrence of CNS relapse in patients treated with rituximab; the 3?year cumulative CNS relapse rates were 7.1% in CHOP group and 2.7% in R?CHOP group(P = 0.045). Intrathecal chemotherapy prophylaxis did not confer much beneit in terms of preventing CNS relapse. Bone involvement [hazard ratio(HR) = 4.21, 95% conidence interval(CI) 1.38–12.77], renal involvement(HR = 3.85, 95% CI 1.05–14.19), alkaline phosphatase(ALP) >110 U/L(HR = 3.59, 95% CI 1.25–10.34), serum albumin(ALB) <35 g/L(HR = 3.63, 95% CI 1.25–10.51), treatment with rituxi?mab(HR = 0.34, 95% CI 0.12–0.96), and a time to complete remission ≤ 108 days(HR = 0.22, 95% CI 0.06–0.78) were independent predictive factors for CNS relapse in the entire cohort. Bone involvement(HR = 4.44, 95% CI 1.08–18.35), bone marrow involvement(HR = 11.70, 95% CI 2.24–60.99), and renal involvement(HR = 10.83, 95% CI 2.27–51.65) were independent risk factors for CNS relapse in the R?CHOP set.Conclusions: In the present study, rituximab decreased the CNS relapse rate of DLBCL, whereas intrathecal chemo?therapy prophylaxis alone was not suicient for preventing CNS relapse. Serum levels of ALB and ALP, and the time to complete remission were new independent predictive factors for CNS relapse in the patients with DLBCL. In the patients received R?CHOP regimen, a trend of increased CNS relapse was found to be associated with extranodal lesions.

Diffuse Large B-Cell Lymphoma of the Central Nervous System. Immunophenotype, Clinicopathological Features and Differential Diagnosis

Background: Diffuse large B-cell lymphomas of the central nervous system (DLBCL CNS) represent less than 1% of all lymphomas and between 2% and 3% of all cerebral tumors. They occur in adults of 60 years of age or more. The objective of this work is to describe the clinical-pathological characteristics, the immunophenotype and the differential diagnosis. Clinical Case: From the files of the surgical pathology unit we found four cases of primary diffuse large B cell lymphoma of the central nervous system in a 6-year period. Three corresponded to women over 47 years of age and the other to a 42-year-old man. The time of evolution was between 2 and 4 months. The symptoms were headache, blurred vision, hemiparesis, and seizures. Localization was in the pineal region, the frontal, parietal regions, and the right thalamus. Morphologically, large lymphoid cells with a diffuse growth pattern and necrosis were observed. Immunohistochemical markers, such as CD 20 and bcl2 were positive, one was positive to CD3. Expression of bcl6 and CD 10 was positive in one case, and MUM-1 was positive in three cases. All the cases were negative for Epstein-Barr virus. Conclusions: The diffuse large-B cell lymphoma of the central nervous system is rare. Its average age of presentation is at 60 years or older. The localization is in the pineal, frontal, parietal and thalamic regions. Three cases were originated by activated B lymphocyte (MUM-1 expression) and other from the Germinal Center (GC) (CD 10 expression). The clinical course was bad. The four patients died shortly after the diagnosis.

Primary Central Nervous System Lymphoma

Primary central nervous system lymphoma （PCNSL） is an aggressive non-Hodgkin Lymphoma, most frequently diffuse large B-cell lymphoma in immunocompetent patients, which is confined to the central nervous system. In the past two decades, its incidence has been steadily increasing.

Successful Treatment of Elderly Diffuse Large B-Cell Lymphoma with Central Nervous System Recurrence by Rituximab, Ranimusutine, Ifosfamide, Procarbazine, Dexamethasone, and Etoposide Therapy

The prognosis of CD20-positive (CD20+) diffuse large B-cell lymphoma (DLBCL) with central nervous system (CNS) recurrence is still poor. A standard treatment for CD20+ DLBCL with CNS recurrence in elderly patients has not been established mainly due to adverse effects. We previously reported the efficacy and safety of MIND-E (ranimustine, ifosfamide, procarbazine, dexamethasone, and etoposide) therapy for elderly CD20+ DLBCL patients with CNS recurrence. Here, we report the use of R-MIND-E therapy (rituximab, ranimustine, ifosfamide, procarbazine, dexamethasone and etoposide) in an elderly CD20+ DLBCL patient with CNS recurrence. The patient achieved a complete response according to Revised Response Criteria for Malignant Lymphoma, and treatment-related toxicity was tolerable. R-MIND-E therapy may be a feasible and useful treatment option for elderly CD20+ DLBCL patients with CNS recurrence.

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.