PRESUMPTIVE RECURRENCE OF INTRAOCULAR LYMPHOMA DESPITE CHIMERIC ANTIGEN RECEPTOR T-CELL THERAPY.

PURPOSE: To present the first reported case of presumptive intraocular recurrence of lymphoma following Chimeric Antigen Receptor (CAR) T-cell therapy despite systemic control by CD19-CAR T cells. METHODS: Observational case report. RESULTS: A 59-year-old man with diffuse, large, B-cell lymphoma subsequently developed secondary central nervous system disease despite chemotherapy. He underwent stem cell transplantation but relapsed again and was scheduled to receive CAR T-cell therapy. He developed vitritis several weeks before treatment, with vitreous biopsy showing non-Hodgkin B-cell lymphoma. He received CAR T-cell therapy following the vitrectomy. He presented 3 months following CAR T-cell therapy with nonspecific right eye floaters and discomfort, with the optical coherence tomography revealing subretinal saw-tooth deposits in the right eye, highly suggestive of lymphoma. This is despite having good systemic control with no other disease elsewhere in the body. He received intravitreal methotrexate to good effect. CONCLUSION: To our knowledge, this is the first case of a vitreoretinal lymphoma nonresponsive to CAR T-cell therapy, despite good central nervous system and systemic control. This is suggestive of anti-CD19 CAR T cells not trafficking into the eye in sufficient numbers to eliminate CD19-expressing neoplastic B cells. We suggest regular ophthalmic follow-up after CAR-T-cell therapy for patients where there is evidence of ocular involvement.

Epidemiology and survival outcomes of patients with primary intraocular lymphoma: a population-based analysis.

BACKGROUND: Primary intraocular lymphoma (PIOL) is a rare malignancy with a poor prognosis, but its optimal therapy remains unclear. Herein, we aimed to analyze the epidemiology and survival outcomes of PIOL patients based on a population-based cancer registry in the United States. METHODS: Patients diagnosed with PIOL between 1992 and 2018 were identified from the Surveillance Epidemiology and End Results program. The patients were divided into two groups: those aged < 60 years and ≥ 60 years. We used the chi-squared test to analyze the differences between the two groups. Descriptive analyses were performed to analyze epidemiological characteristics and treatment. The likely prognostic factors were analyzed by Kaplan-Meier curves and Cox proportional hazards models. RESULTS: The overall incidence of PIOL was 0.23/1,000,000, which was steadily increasing from 1992 to 2018, with an annual percentage change of 2.35. In total, 326 patients (mean age, 66.1 years) with PIOL were included in this study, 72.1% were aged ≥ 60 years, 84.4% were White, and 60.4% were female. The most common pathological type was diffuse large B-cell lymphoma (DLBCL), but in patients aged < 60 years, extranodal marginal zone lymphoma of mucosa-associated lymphoid tissue was the most common. The disease-specific survival rates were 74.2% and 61.5% 5 and 10 years after diagnosis, respectively. Survival analysis found that surgery, radiation, and chemotherapy did not lead to better prognosis. CONCLUSIONS: PIOL is a rare disease with poor prognosis, and its incidence has been increasing for nearly 30 years. It usually affects people aged ≥ 60 years, and DLBCL is the most common pathological type of PIOL. Patients aged < 60 years and with non-DLBCL type have improved survival. Survival of PIOL has improved in recent years.

Vitreoretinal lymphoma occurring after systemic chemotherapy for primary conjunctival diffuse large B cell lymphoma: A case report.

INTRODUCTION: Ocular adnexal lymphoma and vitreoretinal lymphoma are rare forms of non-Hodgkin lymphoma. They are regarded as distinct disease entities due to the differences in molecular mechanism, management, and outcome. We present a rare case of conjunctival diffuse large B cell lymphoma (DLBCL) that developed to vitreoretinal lymphoma after systemic chemotherapy. PATIENT CONCERNS: A 60-year-old man presented with a left salmon-colored conjunctival mass. DIAGNOSIS: A biopsy was performed, and histopathologic examination showed DLBCL. Immunohistochemical staining was positive for CD20 with increased κ to λ light chain ratio. INTERVENTIONS: Bone marrow biopsy also revealed DLBCL. Gallium-67 scintigraphy showed abnormal uptake only in the left orbital lesion. Ann Arbor stage was estimated as IV. The patient underwent systemic combination chemotherapy and immunotherapy. OUTCOMES: Four months after the last course of chemotherapy, primary conjunctival DLBCL relapsed, manifesting vitreous opacity. Diagnostic vitrectomy confirmed a diagnosis of vitreoretinal lymphoma. LESSONS: Conjunctival DLBCL and vitreoretinal lymphoma are both DLBCL. After systemic chemotherapy for conjunctival DLBCL, the lymphoma may relapse in intraocular sites as secondary vitreoretinal lymphoma.

THERAPEUTIC VITRECTOMY AS AN ADJUNCT TREATMENT TO SYSTEMIC CHEMOTHERAPY FOR INTRAOCULAR LYMPHOMA.

PURPOSE: To report the outcome of a previously vitrectomized eye having less lymphoma disease burden compared with the contralateral nonvitrectomized eye over the course of 3.5 years while on systemic chemotherapy. METHODS: Case report. RESULTS: A 51-year-old man with vitreoretinal lymphoma with central nervous system involvement underwent vitrectomy in his left eye. Over the following 3.5 years on systemic chemotherapy, the left eye had less lymphoma disease burden compared with the contralateral nonvitrectomized right eye. CONCLUSION: Therapeutic vitrectomy may be a useful adjunct to systemic chemotherapy in vitreoretinal lymphoma, particularly in cases of vitreous predominant disease manifestation.

Are there primary intraocular lymphomas that do not develop into central nervous system lymphomas?

Primary intraocular lymphomas frequently develop into central nervous system lymphomas and vice versa. This study reviewed 22 consecutive patients with primary intraocular lymphoma diagnosed by immunostaining of vitrectomy cell blocks, and examined whether they developed central nervous system lymphoma. Seventeen patients developed central nervous system lymphoma: 3 patients developed intraocular and central nervous system lymphoma simultaneously, 9 patients developed central nervous system lymphoma 1 month to 5 years (median, 3 months) after intraocular lymphoma, and 5 patients developed central nervous system lymphoma preceding the diagnosis of intraocular lymphoma by 3 months to 9 years and 8 months (median, 1.5 years). In contrast, 5 patients did not develop central nervous system lymphoma: 2 patients did not develop local recurrence or central nervous system lymphoma in the follow-up period of 5 years and 11 years, respectively, after vitrectomy alone without additional local or systemic treatment. The remaining 3 patients with intraocular lymphoma had insufficient follow-up periods to determine the prognosis. The results of CD5 immunostaining of vitrectomy specimens were found in pathology reports of 8 patients: 3 patients with CD5-positive large cells and 4 patients with CD5-negative large cells developed central nervous system lymphoma. In summary, only a small number of patients did not develop central nervous system lymphoma based on long-term follow-up after vitrectomy alone. CD5 was not a marker of central nervous system involvement in this study population.

Tumor Control and Visual Acuity Outcomes in Vitreoretinal Lymphoma with and without Sub-Retinal Pigment Epithelium Infiltration: Analysis of 125 Eyes of 70 Patients at a Single Ocular Oncology Center.

PURPOSE: To investigate outcomes in vitreoretinal lymphoma (VRL) presenting with or without sub-retinal pigment epithelial (sub-RPE) infiltration. DESIGN: Retrospective, comparative analysis. SUBJECTS: Patients with VRL at a single center from January 1, 1984, through July 30, 2018. METHODS: Record review was conducted for clinical features, treatments, and outcomes of tumor control, visual acuity (VA), and death. MAIN OUTCOME MEASURES: Ocular tumor control and VA outcome. RESULTS: The study involved 168 eyes of 95 patients with VRL, of which 45 (27%) eyes of 32 patients had sub-RPE infiltration. Comparison (of patients with vs. without sub-RPE infiltration) showed similar presenting features of mean patient age (65 vs. 68 years, P = 0.30), percentage of males (53% vs. 56%, P = 0.83), white race (84% vs. 87%, P = 0.77), bilateral ocular involvement (78% vs. 75%, P = 0.80), and VA of 20/40 or better (40% vs. 50%, P = 0.30), 20/50 to 20/200 (42% vs. 31%, P = 0.20), or worse than 20/200 (18% vs. 19%, P = 0.99). Lymphoma subtype was diffuse large B cell (59% vs. 52%) or unspecified (41% vs. 44%, P = 0.85). Follow-up data were available for 125 eyes of 70 patients. Overall treatment included systemic chemotherapy (53% vs. 64%, P = 0.29), intravitreal chemotherapy (59% vs. 28%, P = 0.005), and external beam radiotherapy (59% vs. 94%, P < 0.001). Initial ocular tumor control occurred (91% vs. 94%, P = 0.68) with subsequent recurrence (35% vs. 17%, P = 0.07). Outcomes at final follow-up (mean 24 vs. 25 months, P = 0.82) revealed ocular tumor complete regression (68% vs. 86%, P = 0.03), partial regression (3% vs. 7%, P = 0.44), or active persistent or recurrent disease (29% vs. 7%, P = 0.002). Final VA was 20/40 or better (39% vs. 53%, P = 0.18), 20/50 to 20/200 (26% vs. 34%, P = 0.53), or worse than 20/200 (34% vs. 13%, P = 0.007). Vitreoretinal lymphoma was associated with central nervous system lymphoma (41% vs. 59%, P = 0.13) or systemic lymphoma (16% vs. 21%, P = 0.60). Death occurred (63% vs. 54%, P = 0.51) at mean age (69 vs. 69 years, P = 0.94). CONCLUSION: Sub-RPE infiltration in VRL is associated with more persistent or recurrent ocular tumor and poorer VA outcome, but no difference in frequency of central nervous system/systemic lymphoma or death. Further studies are required to determine whether earlier, more aggressive, or prolonged ocular therapy for patients with VRL presenting with sub-RPE infiltration could improve these factors.

Bilateral radiation therapy followed by methotrexate-based chemotherapy for primary vitreoretinal lymphoma.

Primary vitreoretinal lymphoma (PVRL) is a subset of primary CNS lymphoma that presents as isolated ocular disease without brain involvement. Although ocular radiotherapy (RT) is an effective treatment for PVRL, the optimal treatment is uncertain. PVRL may later involve the brain in 56%-85% of patients. We report on 12 PVRL patients treated with a combination of bilateral RT and a systemic chemotherapy (CT) regimen containing high-dose methotrexate (M). Ten received RT (30-40 Gy) followed by CT, one received RT, and one was treated with intravitreal M; all achieved a complete response (CR). Three patients had tumor recurrence in the brain and received CT and one patient relapsed in the eye with a second recurrence in the brain. Three patients achieved CR-2 remain alive and one died of dementia. One died from recurrent CNS disease. With a median follow of 68 months (range, 17-154 months), median progression-free and overall survival have not been reached. Bilateral RT followed by M-based CT is an effective treatment for reducing CNS progression and prolonging survival.

Primary vitreoretinal natural killer/T-cell lymphoma with breast involvement: A case report and review of the literature.

A 50-year-old woman developed recurrent vitreous opacities in her left eye. The first diagnostic vitrectomy revealed no significant abnormality. Optical coherence tomography showed multiple high-density reflective nodules. The ratio of interleukin-6 to interleukin-10 was over 1 in her aqueous humor, and Epstein-Barr virus was present. A conventional immunohistochemistry examination of vitrectomy specimens was diffusely positive for CD2, CD3, and Ki-67. Highly metabolic nodules were found in her right breast on positron emission tomography-computed tomography scan. Immunohistochemistry of the breast biopsy was suggestive of natural killer/T-cell lymphoma. Considering the homology between the two lesions, combined with ancillary cytokine, cytology, and flow cytometry findings, the final diagnosis was primary vitreoretinal natural killer/T-cell lymphoma with involvement of the breast. The lymphoma resolved with chemotherapy, intravitreal injection of methotrexate, and ocular radiotherapy. This case shows that primary vitreoretinal natural killer/T-cell lymphoma can present with concomitant systemic involvement. We reviewed relevant published literature and summarized some new approaches that make the diagnosis easier and faster; however, the cytopathologic analysis of intraocular fluid is irreplaceable. An effective treatment strategy is still a matter of speculation.

An unusual case report of primary vitreoretinal lymphoma.

BACKGROUND: Primary vitreoretinal lymphoma (PVRL) is a rare ocular condition and its diagnosis remains a challenge. The clinical presentation is variable and it can masquerade as chronic intermediate or posterior uveitis. We report an unusual case of primary central nervous system lymphoma (PCNSL) presenting as migrating retinal lesions with unique shapes. The diagnostic challenges are described and the clinical features of intraocular lymphoma are reviewed. CASE PRESENTATION: A 53 year-old gentleman presented with unilateral visual disturbance and a wide area of retinal whitening with sharp borders temporal to the macula, corresponding to hyper-reflective subretinal changes on optical coherence tomography (OCT). The lesion resolved spontaneously after 6 weeks but was replaced by multiple punctate sub-retinal and sub-retinal pigment epithelial lesions. The second eye was involved 4 months later and there were new areas of hyper-reflective changes in both eyes, which migrated nasally within a week, with no evidence of scarring in the previous sites. The diagnosis of diffuse B-cell lymphoma was made on brain biopsy when the patient subsequently presented with acute confusion and magnetic resonance imaging brain scan showed a frontal lesion. Following systemic chemotherapy, the sub-retinal changes resolved with complete restoration of retinal architecture and improvement in visual acuity. CONCLUSION: We report an unusual case of PVRL presenting as migrating retinal lesions with unique shapes. PVRL is a great imitator and a high index of clinical suspicion is required in unexplained ocular lesions to prevent a delay in diagnosis.

Clinical Features and Treatment Outcomes of Vitreoretinal Lymphoma according to Its Association with CNS Lymphoma.

PURPOSE: To compare the clinical features and treatment outcomes of different types of vitreoretinal lymphoma (VRL) that presents primarily, secondarily, or concurrently in association with CNS lymphoma. METHODS: We retrospectively reviewed the medical records of 53 patients with VRL pathologically confirmed between 2000 and 2014 in two of the largest tertiary hospitals in Korea. RESULTS: The proportions of primary, secondary, and concurrent VRL were 26%, 34%, and 40%, respectively. The primary VRL group had retinal infiltration most frequently (68%) among all groups and presented with the worst visual acuity at diagnosis (P = 0.035). The diagnostic delay was significantly shorter in patients with secondary VRL (1.4 months; P < 0.001). Median overall survival was 31 months in the entire cohort, and it was shortest in the concurrent VRL/CNS lymphoma group (18 months; P = 0.007). CONCLUSIONS: Ocular presentation and survival times may be different in VRL patients according to the association with CNS involvement.

Intraocular Lymphoma: Descriptive Data of 26 Patients Including Clinico-pathologic Features, Vitreous Findings, and Treatment Outcomes.

PURPOSE: To describe clinical manifestations, diagnostic approaches, therapy, and outcomes of biopsy-proven intraocular lymphoma. METHODS: Review of tertiary referral center records between 2005 and 2015. RESULTS: A total of 51 eyes of 26 patients were included; mean age of onset was 60.42 years. Common ocular complaints included floaters (42%) and blurred vision (35%); 62% of patients had ocular and central nervous system involvement; 11% had systemic lymphoma; and 27% had only ocular involvement. Vitreous analysis was positive for malignant cells in 77% of patients on initial biopsy, and in 100% of patients on repeat biopsy. In total, 20/26 patients received systemic and topical treatment before IOL diagnosis was made; 25 patients received intravitreal methotrexate and/or rituximab; one patient received intracameral rituximab. All patients achieved remission by their final visit. CONCLUSIONS: Intraocular lymphoma often masquerades as intraocular inflammation, resulting in delayed or misdiagnosis with subsequent inappropriate management. Optimal therapy is a challenge for oncologists and ophthalmologists.

Combined intravitreal methotrexate and immunochemotherapy followed by reduced-dose whole-brain radiotherapy for newly diagnosed B-cell primary intraocular lymphoma.

Primary intraocular lymphoma (IOL) has a propensity for central nervous system (CNS) relapse within 2 years of initial diagnosis, affecting clinical outcome. To reduce CNS relapse, we performed the combination treatment protocols of intravitreal methotrexate injections, methotrexate-based systemic induction chemotherapy and consolidation high-dose cytarabine and reduced-dose whole brain radiation therapy (rdWBRT, 23·4 Gy) for B-cell primary IOL with or without newly diagnosed CNS involvement. All patients underwent longitudinal brain magnetic resonance imaging (MRI) and cognitive assessment for evaluation of treatment-induced leucoencephalopathy. Seventeen patients initiated and 16 completed the protocol treatment. CNS relapse occurred in 2 patients and intraocular relapse in 3. Four-year progression-free survival (PFS) was 74·9% and 4-year overall survival (OS) was 86·3%, with a median follow-up period of 48·9 months. Of 11 patients without CNS involvement, 1 had CNS relapse and 3 intraocular relapse, and 4-year PFS and OS was 72·7% and 88·9%, respectively. Although white matter abnormalities shown by MRI were significantly increased at 4 years after rdWBRT, only one patient developed mild cognitive impairment. The combination of intravitreal chemotherapy, prophylactic systemic chemotherapy and rdWBRT for primary IOL showed a potential to reduce CNS relapse rate and improved 4-year PFS and OS without increase of cognitive dysfunction.

How we diagnose and treat vitreoretinal lymphoma.

The eye is a rare site for the development of malignant lymphoma. Based on cell type and involved intraocular structures, which as a whole represent an immune-privileged site, several subtypes of primary intraocular lymphoma need to be discerned. Primary vitreoretinal lymphoma (PVRL), the most common form, is an aggressive B-cell malignancy and considered a subtype of primary central nervous system (CNS) lymphoma. Ocular symptoms are non-specific and often mimic uveitis, frequently resulting in delayed diagnosis. Bilateral ocular involvement and dissemination/relapse in the CNS are common. Diagnosis of PVRL is usually based on the analysis of vitreous biopsy material. In addition to cytological and immunocytochemical examination, measurements of cytokine levels and molecular determination of B-cell clonality and recurrent mutations increase the diagnostic yield. Both systemic chemotherapy and exclusively local treatment, including ocular radiotherapy and intravitreal chemotherapy, are successful approaches for the management of PVRL, although it is currently not predictable which patients require systemic treatment in order to avoid cerebral dissemination, a complication associated with a considerably worse prognosis.

Chemoimmunotherapy with methotrexate, cytarabine, thiotepa, and rituximab (MATRix regimen) in patients with primary CNS lymphoma: results of the first randomisation of the International Extranodal Lymphoma Study Group-32 (IELSG32) phase 2 trial.

BACKGROUND: Standard treatment for patients with primary CNS lymphoma remains to be defined. Active therapies are often associated with increased risk of haematological or neurological toxicity. In this trial, we addressed the tolerability and efficacy of adding rituximab with or without thiotepa to methotrexate-cytarabine combination therapy (the MATRix regimen), followed by a second randomisation comparing consolidation with whole-brain radiotherapy or autologous stem cell transplantation in patients with primary CNS lymphoma. We report the results of the first randomisation in this Article. METHODS: For the international randomised phase 2 International Extranodal Lymphoma Study Group-32 (IELSG32) trial, HIV-negative patients (aged 18-70 years) with newly diagnosed primary CNS lymphoma and measurable disease were enrolled from 53 cancer centres in five European countries (Denmark, Germany, Italy, Switzerland, and the UK) and randomly assigned (1:1:1) to receive four courses of methotrexate 3·5 g/m(2) on day 1 plus cytarabine 2 g/m(2) twice daily on days 2 and 3 (group A); or the same combination plus two doses of rituximab 375 mg/m(2) on days -5 and 0 (group B); or the same methotrexate-cytarabine-rituximab combination plus thiotepa 30 mg/m(2) on day 4 (group C), with the three groups repeating treatment every 3 weeks. Patients with responsive or stable disease after the first stage were then randomly allocated between whole-brain radiotherapy and autologous stem cell transplantation. A permuted blocks randomised design (block size four) was used for both randomisations, and a computer-generated randomisation list was used within each stratum to preserve allocation concealment. Randomisation was stratified by IELSG risk score (low vs intermediate vs high). No masking after assignment to intervention was used. The primary endpoint of the first randomisation was the complete remission rate, analysed by modified intention to treat. This study is registered with ClinicalTrials.gov, number NCT01011920. FINDINGS: Between Feb 19, 2010, and Aug 27, 2014, 227 eligible patients were recruited. 219 of these 227 enrolled patients were assessable. At median follow-up of 30 months (IQR 22-38), patients treated with rituximab and thiotepa had a complete remission rate of 49% (95% CI 38-60), compared with 23% (14-31) of those treated with methotrexate-cytarabine alone (hazard ratio 0·46, 95% CI 0·28-0·74) and 30% (21-42) of those treated with methotrexate-cytarabine plus rituximab (0·61, 0·40-0·94). Grade 4 haematological toxicity was more frequent in patients treated with methotrexate-cytarabine plus rituximab and thiotepa, but infective complications were similar in the three groups. The most common grade 3-4 adverse events in all three groups were neutropenia, thrombocytopenia, anaemia, and febrile neutropenia or infections. 13 (6%) patients died of toxicity. INTERPRETATION: With the limitations of a randomised phase 2 study design, the IELSG32 trial provides a high level of evidence supporting the use of MATRix combination as the new standard chemoimmunotherapy for patients aged up to 70 years with newly diagnosed primary CNS lymphoma and as the control group for future randomised trials. FUNDING: Associazione Italiana del Farmaco, Cancer Research UK, Oncosuisse, and Swiss National Foundation.

Primary Vitreoretinal Lymphoma: Management of Isolated Ocular Disease.

BACKGROUND: The prognosis for patients with primary vitreoretinal is dismal. The close association of primary vitreoretinal lymphoma with primary central nervous system lymphoma is responsible for high rates of mortality. Traditional treatments consist of systemic chemotherapy and whole-brain radiotherapy. The optimal approach for the treatment of isolated primary vitreoretinal lymphoma is unclear. METHODS: A review of the relevant medical and scientific literature was performed, focusing on the clinical features of primary vitreoretinal lymphoma and the progress made in the management of isolated ocular disease. RESULTS: Ocular treatment options for primary vitreoretinal lymphoma have recently expanded with the addition of intravitreal chemotherapeutic agents and localized radiation. Based on several retrospective reports, a general shift has been made toward local therapy (eg, orbital radiotherapy, intravitreal chemotherapy) for ocular disease. No prospective, randomized clinical trials yet exist to guide therapy. CONCLUSIONS: Optimal treatment regimens for isolated primary vitreoretinal lymphoma continue to evolve. Further investigations into novel therapies and protocols are needed to decrease recurrence rates, reduce or prevent central nervous system involvement, and improve rates of overall survival.

Intensive chemoimmunotherapy and bilateral globe irradiation as initial therapy for primary intraocular lymphoma.

BACKGROUND: Primary intraocular lymphoma is a rare variant of primary CNS lymphoma for which the optimum treatment strategy remains unknown. METHODS: We performed a retrospective single-center study including patients who underwent uniform management from October 2007 in which patients were offered sequential rituximab, methotrexate, procarbazine, and vincristine (R-MPV) followed by binocular radiotherapy and consolidative high-dose cytarabine. RESULTS: Eleven patients with median age 66 years (range, 48-72) were included. All patients received binocular radiotherapy to a median dose of 36 Gy (range, 30.6-39.6) in 20 fractions. Grade 3+ anemia, thrombocytopenia, and neutropenia occurred in 1 (9%), 2 (18%), and 3 (27%) patients, respectively; raised creatinine and peripheral sensory neuropathy occurred in 4 (36%) and 3 (27%) patients, respectively. Grade 3+ ocular toxicities included cataract formation and keratitis in 6 (54%) and 3 (27%) patients, respectively. Ten patients (91%) achieved complete response and 1 (9%) partial response. After median follow-up of 4.2 years (range, 1.8-7.6), the median progression-free survival was 3.8 years and the estimated 4-year overall survival was 75.8% (95% CI: 30.5%-93.7%). The initial site of disease progression was the CNS in 4 of 7 patients (57%) and within the eye in 3 of 7 (43%). Five patients achieved responses to salvage therapies. CONCLUSIONS: Combined modality treatment with R-MPV, binocular radiation, and high-dose cytarabine is effective with moderate toxicity. Both local and CNS relapses occur; however, the achievement of second and subsequent remissions is possible.

Survival Outcomes of Primary Intraocular Lymphoma: A Single-institution Experience.

OBJECTIVES: We report the clinical outcomes of 22 patients with primary intraocular lymphoma (PIOL) treated over a 15-year period. MATERIALS AND METHODS: Patients with confirmed PIOL by central pathology review treated from 1994 to 2010 with isolated ocular (N=13) or central nervous system (CNS) plus ocular involvement (N=9) were included. Intraocular and CNS failure-free survival, relapse-free survival, and overall survival outcomes were analyzed. RESULTS: Median follow-up was 29.0 (range, 10.2 to 96.4) months. Sixteen patients (9 with isolated ocular, 7 with ocular and CNS disease) received combined modality therapy (CMT) consisting of systemic chemotherapy (usually high-dose methotrexate based) and orbital +/- whole-brain radiation. Two patients were treated with chemotherapy and 4 with local ocular therapy alone. Among patients with isolated ocular versus CNS involvement, CNS failure-free survival was 79% versus 57%, and intraocular failures were 62% versus 78% at 24 months. Median relapse-free survival was 34.0 versus 21.3 months (P=0.368), and overall survival 43.4 versus 30.3 months (P=0.744), respectively. Three patients treated with CMT (2 with isolated ocular and 1 with CNS involvement) with >1-year follow-up alive at the time of analysis never relapsed, and one remains disease-free >4.5 years after treatment. CONCLUSIONS: In this series of patients with PIOL+/- CNS disease, CNS and intraocular relapse were common. A trend toward better survival was seen among patients with isolated ocular presentation, and a limited number of long-term disease-free survivors seen after CMT.

[Research progress in primary intraocular lymphoma].

Primary intraocular lymphoma (PIOL) is a rare and fatal ocular malignancy. The diagnosis and treatment of PIOL is usually challenging as it often masquerades as uveitis. PIOL demonstrates characteristic features on fundus autofluorescence (FAF), fundus fluorescein angiography (FFA) and optical coherence tomography (OCT). These methods although not as a basis for diagnosis of PIOL, but can be used as the evaluation of PIOL progress and prognosis. Eye tissue biopsy is the gold standard for diagnosis of PIOL. The methods to obtain ocular fluid include anterior chamber paracentesis, fine needle aspiration biopsies of the vitreous and diagnostic pars plana vitrectomy. Cytology, immunohistochemistry, flow cytometry, cytokine analysis and molecular pathology are often used in combination to improve the diagnosis rate of PIOL. While current management of PIOL mainly involves local intraocular chemotherapy, combination therapy protocol yields effective control and prevention of PIOL relapse. This article reviewed recent research progress to improve the clinical understanding of PIOL.

Intraocular Relapse with Hypopyon and Retinal Infiltrates after Chemotherapy and Peripheral Blood Stem Cell Transplantation for Extranodal NK/T-Cell Lymphoma.

We report a case of intraocular relapse of extranodal NK/T-cell lymphoma with anterior chamber hypopyon and retinal infiltrates. A 55-year-old man developed fever, malaise, anorexia, and hepatosplenomegaly, and was diagnosed with NK/T-cell lymphoma by liver biopsy. He underwent 2 courses of SMILE (dexamethasone, methotrexate, ifosfamide, L-asparaginase, and etoposide) chemotherapy, followed by myeloablative peripheral blood stem cell transplantation, donated by his brother. Two months later, he developed high-grade fever, hepatosplenomegaly, and peritoneal lymphadenopathy, and the relapse with hemophagocytic syndrome was diagnosed by bone marrow biopsy. He underwent 2 courses of SMILE salvage chemotherapy, followed by non-myeloablative peripheral blood stem cell transplantation, donated by his son. Two months later, he noticed blurred vision in both eyes. The right eye had aqueous cells and keratic precipitates, but no retinal lesions. The left eye had hypopyon in the anterior chamber with numerous aqueous cells, and retinal white infiltrates with retinal hemorrhages. The aqueous cells, obtained by anterior chamber paracentesis, were positive for CD3, CD56, and Epstein-Barr virus-encoded RNA, but negative for CD20 by immunocytochemical staining. Head magnetic resonance imaging demonstrated white matter lesions in the anterior to parietal lobes on the right side. The patient underwent intrathecal methotrexate injection and external beam radiation at 40 Gy, covering the entire brain and both eyes. The retinal lesions and hypopyon disappeared. Two months later, the patient died of renal failure, and autopsy demonstrated multi-organ involvement of lymphoma cells. In conclusion, we report a case of NK/T-cell lymphoma relapse with intraocular lesions, after combined chemotherapy and hematopoietic stem cell transplantation.