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Lee DH, Li-Wang J, Chevez-Barrios P, Schefler AC. A glaucoma drainage implant functioning as a sanctuary site for vitreoretinal lymphoma. Am J Ophthalmol Case Rep 2025; 38:102299. [PMID: 40129888 PMCID: PMC11931297 DOI: 10.1016/j.ajoc.2025.102299] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/10/2024] [Revised: 02/21/2025] [Accepted: 03/03/2025] [Indexed: 03/26/2025] Open
Abstract
Purpose To report an unusual case of vitreoretinal lymphoma (VRL) in which a glaucoma drainage implant (GDI) likely functioned as a sanctuary site for relapsing disease. Observations A 54-year-old female with recently diagnosed CNS diffuse large B-cell lymphoma (DLBCL) was referred for evaluation of VRL. Ocular history at an outside center included a 4-year reported history of uveitis complicated by glaucoma and a GDI in the left eye (OS). Initial examination revealed keratic precipitates (KP), vitreous haze with clumps of white cells OS, and vitreous biopsy revealed DLBCL OS. Intravitreal methotrexate injections were initiated for primary VRL alongside systemic chemotherapy for CNS involvement with resolution of disease. One year later, the patient returned with 2+ anterior chamber (AC) and vitreous cells OS, and vitreous biopsy again revealed DLBCL OS. External radiation treatment was administered for recurrent VRL in the left eye, followed also by the right eye due to the high risk of fellow eye involvement. Autologous stem cell transplantation was then performed. Five months later, the patient returned with worsening KPs and new vitreous cells OS, and vitreous biopsy again revealed DLBCL OS. Enucleation was performed, and histopathology revealed DLBCL cells lining the GDI fibrous capsule, consistent with the GDI likely having served as a sanctuary site and source for continued local relapse. Conclusions and Importance We report a case in which a GDI functioned as a probable sanctuary site for VRL. Sanctuary sites of malignancy should be considered in patients with pre-existing ocular hardware, particularly when recurrent relapses occur despite complete treatment.
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Affiliation(s)
- Debora H. Lee
- Ruiz Department of Ophthalmology and Visual Science, University of Texas Health Science Center, Houston, TX, USA
| | | | - Patricia Chevez-Barrios
- Department of Pathology and Genomic Medicine, Weill Cornell Medicine, Houston Methodist Hospital, USA
| | - Amy C. Schefler
- Ruiz Department of Ophthalmology and Visual Science, University of Texas Health Science Center, Houston, TX, USA
- Retina Consultants of Texas, Houston, TX, USA
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Wang SY, Zhou SW, Gao J, Wang L. Primary vitreoretinal lymphoma: diagnosis, treatment, and prognosis-a review of current knowledge and future directions. BLOOD SCIENCE 2025; 7:e00233. [PMID: 40322320 PMCID: PMC12047895 DOI: 10.1097/bs9.0000000000000233] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/09/2025] [Accepted: 03/25/2025] [Indexed: 05/08/2025] Open
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.
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Affiliation(s)
- Si-Yu Wang
- Capital Medical University, Beijing, China
| | - Suo-Wang Zhou
- Aier Eye Hospital, Jinan University, Guangzhou 510071, China
| | - Jing Gao
- Department of Hematology, Beijing Tongren Hospital, Capital Medical University, Beijing, China
| | - Liang Wang
- Department of Hematology, Beijing Tongren Hospital, Capital Medical University, Beijing, China
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Biju Mark J, Smit DP, E R, Sr R. Intermediate Uveitis: An Updated Review of the Differential Diagnosis and Relevant Special Investigations. Ocul Immunol Inflamm 2025; 33:522-534. [PMID: 39810409 DOI: 10.1080/09273948.2025.2450473] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/25/2024] [Revised: 12/23/2024] [Accepted: 01/02/2025] [Indexed: 01/16/2025]
Abstract
The aim of this review is to provide an update on both the differential diagnosis of intermediate uveitis (IU) and the special investigations that may be required to determine the underlying etiology of this condition. The authors describe how they identified the relevant publications included in this review and then proceed to outline the possible causes of IU by classifying them into the following categories: Idiopathic, infectious, systemic, genetic/hereditary, drug-induced and masquerades. Thereafter, the special investigations relevant to each cause are discussed individually.
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Affiliation(s)
- Jacob Biju Mark
- Division of Ophthalmology, Faculty of Medicine and Health Sciences, Stellenbosch University, Cape Town, South Africa
| | - Derrick P Smit
- Division of Ophthalmology, Faculty of Medicine and Health Sciences, Stellenbosch University, Cape Town, South Africa
| | - Rajashree E
- Uveitis Clinic, Aravind Eye Hospital & PG Institute of Ophthalmology, Madurai, India
| | - Rathinam Sr
- Uveitis Clinic, Aravind Eye Hospital & PG Institute of Ophthalmology, Madurai, India
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Deguchi H, Nagata K, Inaba T, Aoki T, Kitano H, Sotozono C. Novel diagnostic method for B cell vitreoretinal lymphoma by identification of regulatory T cells and PD-1 + cytotoxic T lymphocytes in the vitreous via flow cytometry. Br J Ophthalmol 2025; 109:510-515. [PMID: 39401866 DOI: 10.1136/bjo-2024-326240] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/29/2024] [Accepted: 09/23/2024] [Indexed: 03/22/2025]
Abstract
AIMS To investigate the significance of regulatory T cells (Tregs) and programmed cell death 1 (PD-1)+ cytotoxic T lymphocytes (CTLs) in the vitreous of patients with vitreoretinal lymphoma (VRL) and uveitis. METHODS This study involved 51 patients with VRL and uveitis, 15 males and 36 females (mean age: 72 years, range: 51-86 years), who underwent vitrectomy at the Department of Ophthalmology, Kyoto Prefectural University of Medicine, Kyoto, Japan, from December 2019 to February 2024. All patients underwent lymphocyte surface antigen analysis via flow cytometry, and the proportion of Tregs in CD4+ T lymphocytes and PD-1+ CTLs in CD8+ T lymphocytes was measured. RESULTS This study involved B cell VRL (B-VRL, n=16), sarcoidosis (n=8), human herpesvirus (HHV)-associated uveitis (n=7), human T cell lymphotropic virus type 1 associated uveitis (HAU, n=3) and unclassifiable uveitis (n=17) cases. The median proportions of Tregs were significantly lower in B-VRL (2.2%) compared with sarcoidosis (8.5%), HHV-associated uveitis (16.4%) and unclassifiable uveitis (10.1%) (p<0.05). Conversely, a significantly higher proportion of PD-1+ CTLs was found in B-VRL (95.6%) compared with sarcoidosis (61.1%), HHV-associated uveitis (67.1%) and unclassifiable (64.8%) (p<0.05). Receiver operating characteristic analysis of Tregs and PD-1+ CTLs proportions in B-VRL revealed high area under the curve values of 0.913 and 0.940, respectively. CONCLUSIONS Our findings indicate that analysis of the ratio of Tregs and PD-1+ CTLs via flow cytometry is helpful in diagnosing B-VRL.
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Affiliation(s)
- Hideto Deguchi
- Department of Ophthalmology, Kyoto Prefectural University of Medicine, Kyoto, Japan
- Buck Institute for Research on Aging, Novato, California, USA
| | - Kenji Nagata
- Department of Ophthalmology, Kyoto Prefectural University of Medicine, Kyoto, Japan
| | - Tohru Inaba
- Department of Infection Control & Laboratory Medicine, Kyoto Prefectural University of Medicine, Kyoto, Japan
| | - Takanori Aoki
- Department of Ophthalmology, Kyoto Prefectural University of Medicine, Kyoto, Japan
| | - Hikaru Kitano
- Department of Ophthalmology, Kyoto Prefectural University of Medicine, Kyoto, Japan
- Department of Ophthalmology, Osaka Saiseikai Nakatsu Hospital, Osaka, Japan
| | - Chie Sotozono
- Department of Ophthalmology, Kyoto Prefectural University of Medicine, Kyoto, Japan
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Sugawara R, Usui Y, Saito A, Nezu N, Komatsu H, Tsubota K, Asakage M, Yamakawa N, Wakabayashi Y, Sugimoto M, Kuroda M, Goto H. An Approach to Predict Intraocular Diseases by Machine Learning Based on Vitreous Humor Immune Mediator Profile. Invest Ophthalmol Vis Sci 2025; 66:38. [PMID: 40105820 PMCID: PMC11932427 DOI: 10.1167/iovs.66.3.38] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/11/2024] [Accepted: 02/17/2025] [Indexed: 03/20/2025] Open
Abstract
Purpose This study aimed to elucidate whether machine learning algorithms applied to vitreous levels of immune mediators predict the diagnosis of 12 representative intraocular diseases, and identify immune mediators driving the predictive power of machine learning model. Methods Vitreous samples in 522 eyes diagnosed with 12 intraocular diseases were collected, and 28 immune mediators were measured using a cytometric bead array. The significance of each immune mediator was determined by employing five machine learning algorithms. Stratified k-fold cross-validation was performed to divide the dataset into training and test sets. The algorithms were assessed by analyzing precision, recall, accuracy, F-score, area under the receiver operating characteristics curve, area under the precision-recall curve, and feature importance. Results Of the five machine learning models, random forest attained the maximum accuracy in the classification of 12 intraocular diseases in a multi-class setting. The random forest prediction models for vitreoretinal lymphoma, endophthalmitis, uveal melanoma, rhegmatogenous retinal detachment, and acute retinal necrosis demonstrated superior classification accuracy, precision, and recall. The top three important immune mediators for predicting vitreoretinal lymphoma were IL-10, granzyme A, and IL-6; those for endophthalmitis were IL-6, G-CSF, and IL-8; and those for uveal melanoma were RANTES, IL-8 and bFGF. Conclusions The random forest algorithm effectively classified 28 immune mediators in the vitreous to accurately predict the diagnosis of vitreoretinal lymphoma, endophthalmitis, and uveal melanoma among 12 representative intraocular diseases. In summary, the results of this study enhance our understanding of potential new biomarkers that may contribute to elucidating the pathophysiology of intraocular diseases in the future.
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Affiliation(s)
- Risa Sugawara
- Department of Ophthalmology, Tokyo Medical University Hospital, Tokyo, Japan
| | - Yoshihiko Usui
- Department of Ophthalmology, Tokyo Medical University Hospital, Tokyo, Japan
| | - Akira Saito
- Department of AI Applied Quantitative Clinical Science, Tokyo Medical University, Tokyo, Japan
| | - Naoya Nezu
- Department of Ophthalmology, Tokyo Medical University Hospital, Tokyo, Japan
| | - Hiroyuki Komatsu
- Department of Ophthalmology, Tokyo Medical University Hospital, Tokyo, Japan
| | - Kinya Tsubota
- Department of Ophthalmology, Tokyo Medical University Hospital, Tokyo, Japan
| | - Masaki Asakage
- Department of Ophthalmology, Tokyo Medical University Hospital, Tokyo, Japan
| | - Naoyuki Yamakawa
- Department of Ophthalmology, Tokyo Medical University Hospital, Tokyo, Japan
| | | | - Masahiro Sugimoto
- Research and Development Center for Minimally Invasive Therapies, Institute of Medical Science, Tokyo Medical University, Tokyo, Japan
| | - Masahiko Kuroda
- Department of Molecular Pathology, Tokyo Medical University, Tokyo, Japan
| | - Hiroshi Goto
- Department of Ophthalmology, Tokyo Medical University Hospital, Tokyo, Japan
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Giralt L, Parrado-Carrillo A, Vidal-Robau N, Casablanca-Piñera A, Nogués-Castell J, Miguel-Escuder L, Moll-Udina A, Balagué O, Sainz-de-la-Maza M, Llorenç V, Aldecoa I, Adán A. Endoretinal biopsy outcomes in suspected vitreoretinal lymphoma after inconclusive vitreous cytology. J Fr Ophtalmol 2025; 48:104390. [PMID: 39700889 DOI: 10.1016/j.jfo.2024.104390] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/01/2024] [Revised: 09/30/2024] [Accepted: 10/16/2024] [Indexed: 12/21/2024]
Abstract
OBJECTIVE To review the clinical utility of endoretinal biopsies in diagnostically undefined cases of vitreoretinal lymphoma (VRL) with negative vitreous cytology. METHODS Retrospective case series including all consecutive patients who underwent endoretinal biopsies in a tertiary care center, Hospital Clinic of Barcelona (Spain), between 2014 and 2020. RESULTS A total of 5 patients were included in this study. Four were male and one was female, with a mean age at diagnosis of 49years. Two patients had a past medical history of extraocular involvement, both having experienced complete remission of diffuse large B-cell lymphomas (DLBCL). All patients presented retinitis-like lesions characterized by substantial retinal thickening and infiltrative deposits below the retinal pigment epithelium (RPE). Retinal biopsies clarifying the diagnosis of VRL were established in four out of the five patients. Immunohistochemical results confirmed DLBCL, enabling the diagnosis of intraocular secondary DLBCL in two patients and primary ocular DLBCL in the other two. No postoperative complications were reported. CONCLUSIONS Endoretinal biopsies clarified the diagnosis of vitreoretinal lymphoma (VRL) in 4 of 5 patients. This is a high rate of diagnosis, which is clinically meaningful, since it influences management. Our case series underscores the efficacy of employing retinal biopsy in cases where vitreous biopsy results prove inconclusive within the challenging context of suspicion of VRL.
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Affiliation(s)
- L Giralt
- Department of Ophthalmology, Hospital Clínic of Barcelona, University of Barcelona, Sabino Arana, 1, 08028 Barcelona, Spain.
| | | | - N Vidal-Robau
- Department of Pathology, CDB, Hospital Clinic of Barcelona, University of Barcelona, Barcelona, Spain
| | - A Casablanca-Piñera
- Department of Ophthalmology, Hospital Clínic of Barcelona, University of Barcelona, Sabino Arana, 1, 08028 Barcelona, Spain
| | - J Nogués-Castell
- Department of Ophthalmology, Hospital Clínic of Barcelona, University of Barcelona, Sabino Arana, 1, 08028 Barcelona, Spain
| | - L Miguel-Escuder
- Department of Ophthalmology, Hospital Clínic of Barcelona, University of Barcelona, Sabino Arana, 1, 08028 Barcelona, Spain
| | - A Moll-Udina
- Department of Ophthalmology, Hospital Clínic of Barcelona, University of Barcelona, Sabino Arana, 1, 08028 Barcelona, Spain
| | - O Balagué
- Department of Pathology, CDB, Hospital Clinic of Barcelona, University of Barcelona, Barcelona, Spain
| | - M Sainz-de-la-Maza
- Department of Ophthalmology, Hospital Clínic of Barcelona, University of Barcelona, Sabino Arana, 1, 08028 Barcelona, Spain
| | - V Llorenç
- Department of Ophthalmology, Hospital Clínic of Barcelona, University of Barcelona, Sabino Arana, 1, 08028 Barcelona, Spain
| | - I Aldecoa
- Department of Pathology, CDB, Hospital Clinic of Barcelona, University of Barcelona, Barcelona, Spain; Neurological Tissue Bank of the Biobank, FCRB/IDIBAPS, Hospital Clinic of Barcelona, Barcelona, Spain
| | - A Adán
- Department of Ophthalmology, Hospital Clínic of Barcelona, University of Barcelona, Sabino Arana, 1, 08028 Barcelona, Spain
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Hayashi I, Keino H, Nakayama M, Ando Y, Watanabe T, Okada AA. Demographic Features, Diagnoses and Real-World Clinical Management of Uveitis in Japan. Ocul Immunol Inflamm 2025:1-9. [PMID: 39792467 DOI: 10.1080/09273948.2024.2449179] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/20/2024] [Revised: 12/23/2024] [Accepted: 12/27/2024] [Indexed: 01/12/2025]
Abstract
PURPOSE This study aimed to investigate demographic features, diagnoses of uveitis (intraocular inflammation), and real-world clinical practice in the use of local and systemic therapies for patients with uveitis in Tokyo, Japan. METHODS Clinical records of 1,174 consecutive new patients (480 males, 694 females) referred to the Kyorin Eye Center, Kyorin University Hospital between January 2011 and December 2018 were retrospectively reviewed. RESULTS Mean age at presentation was 52.6 years (range 4-94 years). By anatomic location, 439 patients (37.4%) had anterior uveitis, 18 (1.5%) had intermediate uveitis, 214 (18.2%) had posterior uveitis and 503 (42.8%) had panuveitis. The 3 most common diagnoses were sarcoidosis (9.1%), Vogt-Koyanagi-Harada (VKH) disease (8.3%), and acute anterior uveitis (5.7%). Compared to our previous study, rates of herpetic anterior uveitis and cytomegalovirus (CMV) retinitis increased while tuberculosis-related uveitis decreased. Unclassified uveitis remained the most common diagnosis (44.9%). Systemic corticosteroids and/or immunomodulatory agents were used in only 18.3% of patients. Immunomodulatory drugs including biologic agents were utilized in 4.9% of patients. CONCLUSIONS The most common uveitis anatomic type was panuveitis due mainly to high rates of sarcoidosis and VKH disease. Diagnoses of herpetic anterior uveitis and CMV retinitis increased, while tuberculosis-related uveitis decreased. Less than one-fifth of uveitis patients required systemic treatment.
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Affiliation(s)
- Isami Hayashi
- Department of Ophthalmology, Kyorin University School of Medicine, Tokyo, Japan
- Department of Ophthalmology, Keio University School of Medicine, Tokyo, Japan
| | - Hiroshi Keino
- Department of Ophthalmology, Kyorin University School of Medicine, Tokyo, Japan
| | - Makiko Nakayama
- Department of Ophthalmology, Kyorin University School of Medicine, Tokyo, Japan
| | - Yoshimasa Ando
- Department of Ophthalmology, Kyorin University School of Medicine, Tokyo, Japan
| | - Takayo Watanabe
- Department of Ophthalmology, Kyorin University School of Medicine, Tokyo, Japan
| | - Annabelle A Okada
- Department of Ophthalmology, Kyorin University School of Medicine, Tokyo, Japan
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Maleki A. A NOVEL FINDING IN THE DIAGNOSIS OF PRIMARY VITREORETINAL LYMPHOMA: A CASE REPORT. Retin Cases Brief Rep 2025; 19:28-33. [PMID: 37824759 DOI: 10.1097/icb.0000000000001489] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/14/2023]
Abstract
PURPOSE Introduce a unique case of primary vitreoretinal lymphoma with a new optical coherence tomography finding. METHODS A case report. A 67-year-old healthy man with complaints of blurry vision in his right eye. RESULTS The patient's visual acuity was 20/60 and 20/20 in the right and left eyes, respectively. Anterior segment examination of the right eye demonstrated mild inflammation. Dilated fundoscopy revealed 2+ vitreous haze and 4+ disk edema. Optical coherence tomography of the macula in the right eye revealed optic nerve head swelling and thickening of the retina. Fluorescein angiography demonstrated mild leakage and staining of vessels along the inferotemporal arcade in the right eye. Labs were within normal limits except positive Herpes simplex virus 1 IgG. Initially, the patient was treated for herpetic panuveitis for 3 weeks with a favorable response. However, the clinical condition deteriorated as a new abnormality was identified in the macular region of the right eye through optical coherence tomography. Considering intraocular lymphoma as a potential diagnosis, the patient underwent a diagnostic vitrectomy. The vitreous sample analysis confirmed primary vitreoretinal lymphoma through immunohistochemistry and flow cytometry. The patient exhibited a rapid response after the initiation of intravenous and intravitreal methotrexate treatment. CONCLUSION The presence of subretinal fluid accompanied by suspended hyperreflective lesions originating from the roof of the subretinal fluid pocket on the optical coherence tomography of macula "stalactite sign" may serve as a characteristic sign indicative of primary vitreoretinal lymphoma; however, further investigation using robust studies is necessary to examine this hypothesis.
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Affiliation(s)
- Arash Maleki
- Department of Ophthalmology, University of Florida, Gainesville, Florida; and
- The Ocular Immunology and Uveitis Foundation, Waltham, Massachusetts
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Gu J, Huang X, Zhang Y, Bao C, Zhou Z, Tong H, Jin J. Cerebrospinal fluid IL-6 and IL-10 as promising diagnostic and therapeutic prognostic biomarkers for secondary central nervous system lymphoma. BMC Cancer 2024; 24:1443. [PMID: 39578739 PMCID: PMC11583561 DOI: 10.1186/s12885-024-13195-5] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/30/2024] [Accepted: 11/13/2024] [Indexed: 11/24/2024] Open
Abstract
BACKGROUND Accurate diagnosis and therapeutic response to secondary central nervous system lymphoma (SCNSL) are challenges that need to be addressed. We assessed the value of cerebrospinal fluid (CSF) cytokine levels for diagnosis and post-therapeutic prognosis in patients with SCNSL. METHODS This retrospective study included 234 patients with non-Hodgkin lymphoma (NHL), including the SCNSL group (n = 57) and the non-SCNSL group (n = 177). The Mann-Whitney U test was used to compare the cytokine profiles between SCNSL and non-SCNSL group. Receiver operating characteristic curve was used to determine the diagnostic ability of CSF cytokine levels for SCNSL. The predictive value of CSF cytokine concentrations for progression free survival of patients with SCNSL was evaluated using a log-rank test. RESULTS CSF IL-6 and IL-10 levels in SCNSL group were significantly elevated compared with those in the other two groups. ROC curve showed that the cutoff values of IL-6 and IL-10 in CSF were 10.13 pg/ml and 7.82pg/ml, which yielded the diagnostic sensitivity were 62.34% and 76.23%, specificity were 87.57% and 88.31%, respectively. Furthermore, combining CSF IL-6 and IL-10 levels significantly improved the diagnostic efficacy. CSF IL-6 and IL-10 levels in SCNSL patients in complete remission under chemotherapy were significantly reduced. In addition, poor progression free survival (PFS) in patients with SCNSL was related to increased CSF IL-10 levels at diagnosis, but not with increased CSF IL-6 levels. CONCLUSION CSF IL-6 and IL-10 levels are promising biomarkers for diagnosis and predictors of response for SCNSL.
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Affiliation(s)
- Jiayan Gu
- Institute of Hematology, Department of Hematology, The First Affiliated Hospital, College of Medicine, Zhejiang University, No. 79 qingchun road, Hangzhou, 310003, China
- Key Laboratory of Hematologic Malignancies, Diagnosis and Treatment, Hangzhou, Zhejiang Province, 310003, China
| | - Xin Huang
- Institute of Hematology, Department of Hematology, The First Affiliated Hospital, College of Medicine, Zhejiang University, No. 79 qingchun road, Hangzhou, 310003, China
- Key Laboratory of Hematologic Malignancies, Diagnosis and Treatment, Hangzhou, Zhejiang Province, 310003, China
| | - Yi Zhang
- Institute of Hematology, Department of Hematology, The First Affiliated Hospital, College of Medicine, Zhejiang University, No. 79 qingchun road, Hangzhou, 310003, China
- Key Laboratory of Hematologic Malignancies, Diagnosis and Treatment, Hangzhou, Zhejiang Province, 310003, China
| | - Chenhui Bao
- Institute of Hematology, Department of Hematology, The First Affiliated Hospital, College of Medicine, Zhejiang University, No. 79 qingchun road, Hangzhou, 310003, China
- Key Laboratory of Hematologic Malignancies, Diagnosis and Treatment, Hangzhou, Zhejiang Province, 310003, China
| | - Ziyang Zhou
- Institute of Hematology, Department of Hematology, The First Affiliated Hospital, College of Medicine, Zhejiang University, No. 79 qingchun road, Hangzhou, 310003, China
- Key Laboratory of Hematologic Malignancies, Diagnosis and Treatment, Hangzhou, Zhejiang Province, 310003, China
| | - Hongyan Tong
- Institute of Hematology, Department of Hematology, The First Affiliated Hospital, College of Medicine, Zhejiang University, No. 79 qingchun road, Hangzhou, 310003, China.
- Key Laboratory of Hematologic Malignancies, Diagnosis and Treatment, Hangzhou, Zhejiang Province, 310003, China.
| | - Jie Jin
- Institute of Hematology, Department of Hematology, The First Affiliated Hospital, College of Medicine, Zhejiang University, No. 79 qingchun road, Hangzhou, 310003, China.
- Key Laboratory of Hematologic Malignancies, Diagnosis and Treatment, Hangzhou, Zhejiang Province, 310003, China.
- Jinan Microecological Biomedicine Shandong Laboratory, Jinan, People's Republic of China.
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Kuji T, Komoto S, Maruyama K, Fujimoto S, Fujino T, Kitaguchi Y, Shimojo H, Morimoto T, Nishida K. A rare case of infiltrative optic neuropathy caused by vitreoretinal lymphoma with hyperreflective deposits in the intraretinal and subretinal pigment epithelial layers prior to the disease onset. BMC Ophthalmol 2024; 24:504. [PMID: 39558254 PMCID: PMC11575151 DOI: 10.1186/s12886-024-03755-5] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/17/2024] [Accepted: 11/04/2024] [Indexed: 11/20/2024] Open
Abstract
BACKGROUND To describe a rare case of infiltrative optic neuropathy (ION) caused by vitreoretinal lymphoma (VRL) with hyperreflective deposits in the intraretinal and subretinal pigment epithelial (RPE) layers before the disease onset. CASE PRESENTATION An 87-year-old Japanese female, previously treated for unexplained uveitis in the right eye, was referred for further evaluation. Despite the absence of intraocular inflammation or vitreous opacification (VO), yellowish-white deposits were noted in the macula, and OCT revealed hyperreflective deposits in the intraretinal and sub-RPE layers. One month later, she returned with acute visual deterioration. Optic disc swelling and disc hemorrhage were observed without VO or intraocular inflammation. Magnetic resonance imaging (MRI) showed no abnormalities. One week later, VO developed and we performed a 25-gauge vitrectomy. Cytology, flow cytometry, and gene rearrangement confirmed malignant B-cell lymphoma. The diagnosis of ION secondary to VRL was made, and intravitreal methotrexate injections were administered a total of 6 times. Six months postoperatively, VO and optic disc swelling resolved, and visual acuity improved to 20/50, with no recurrence on MRI. CONCLUSIONS Although there were reports on VRL advanced from hyperreflective deposits in the intraretinal or sub-RPE layers, there have been no studies that these OCT findings has progressed to ION with VRL. When differentiating optic neuropathy, OCT may assist in the diagnosis by evaluating intraretinal and sub-RPE findings.
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Affiliation(s)
- Takako Kuji
- Department of Ophthalmology, Osaka University Graduate School of Medicine, Room E7, Yamadaoka 2-2, Suita, Osaka, 565-0871, Japan
| | - Shimpei Komoto
- Department of Ophthalmology, Osaka University Graduate School of Medicine, Room E7, Yamadaoka 2-2, Suita, Osaka, 565-0871, Japan
| | - Kazuichi Maruyama
- Department of Ophthalmology, Osaka University Graduate School of Medicine, Room E7, Yamadaoka 2-2, Suita, Osaka, 565-0871, Japan.
| | - Satoko Fujimoto
- Department of Ophthalmology, Osaka University Graduate School of Medicine, Room E7, Yamadaoka 2-2, Suita, Osaka, 565-0871, Japan
| | - Takahiro Fujino
- Department of Ophthalmology, Osaka University Graduate School of Medicine, Room E7, Yamadaoka 2-2, Suita, Osaka, 565-0871, Japan
| | - Yoshiyuki Kitaguchi
- Department of Ophthalmology, Osaka University Graduate School of Medicine, Room E7, Yamadaoka 2-2, Suita, Osaka, 565-0871, Japan
| | - Hiroshi Shimojo
- Department of Ophthalmology, Osaka University Graduate School of Medicine, Room E7, Yamadaoka 2-2, Suita, Osaka, 565-0871, Japan
| | - Takeshi Morimoto
- Department of Ophthalmology, Osaka University Graduate School of Medicine, Room E7, Yamadaoka 2-2, Suita, Osaka, 565-0871, Japan
| | - Kohji Nishida
- Department of Ophthalmology, Osaka University Graduate School of Medicine, Room E7, Yamadaoka 2-2, Suita, Osaka, 565-0871, Japan
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Goto H, Umazume K, Usui Y, Nishikawa N. Clinical features and multimodal imaging of primary choroidal lymphoma. Jpn J Ophthalmol 2024; 68:722-730. [PMID: 39340726 DOI: 10.1007/s10384-024-01102-1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/29/2024] [Accepted: 06/26/2024] [Indexed: 09/30/2024]
Abstract
PURPOSE To clarify the clinical features including multimodal imaging of primary choroidal lymphoma. STUDY DESIGN Retrospective, observational case series METHODS: Six consecutive patients with primary choroidal lymphoma diagnosed at Tokyo Medical University Hospital were studied. Demographic profile, clinical features and multimodal imaging were reviewed retrospectively. RESULTS The patients comprised 3 men and 3 women with average age of 68.2 ± 12.4 years. Clinical diagnosis before referring to our hospital included Vogt-Koyanagi-Harada disease, posterior scleritis, and choroidal hemangioma, and no patients had been diagnosed with choroidal lymphoma. Average duration from onset of ocular symptoms to establishing a diagnosis was 14.2 months. Ocular fundus examination revealed yellowish orange nummular infiltration in all six cases, and granular pigment deposits at the posterior pole in four cases. Optical coherence tomography showed increased choroidal thickness and waving of the retinal pigment epithelium in all cases. Ultrasonography depicted choroidal thickening and extraocular nodular lesions adjacent to the posterior sclera in all cases. None of the cases showed elevated interleukin-10 in the aqueous humor. Ocular fundus manifestations and visual acuity improved after external beam radiation therapy, except one case with bullous retinal detachment from the initial visit. CONCLUSIONS Characteristic ocular fundus manifestation together with multimodal imaging findings are useful for the clinical diagnosis of primary choroidal lymphoma.
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Affiliation(s)
- Hiroshi Goto
- Department of Ophthalmology, Tokyo Medical University, 6-7-1 Nishi-shinjuku, Shinjuku-ku, Tokyo, 160-0023, Japan.
| | - Kazuhiko Umazume
- Department of Ophthalmology, Tokyo Medical University, 6-7-1 Nishi-shinjuku, Shinjuku-ku, Tokyo, 160-0023, Japan
| | - Yoshihiko Usui
- Department of Ophthalmology, Tokyo Medical University, 6-7-1 Nishi-shinjuku, Shinjuku-ku, Tokyo, 160-0023, Japan
| | - Noriko Nishikawa
- Department of Ophthalmology, Asahikawa Medical University, Hokkaido, Japan
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Rissotto F, Cicinelli MV, Servillo A, Berni A, Menean M, Bianco L, Antropoli A, Bandello F, Miserocchi E, Marchese A. Multimodal Imaging of Vitreo-Retinal Lymphoma: A Comprehensive Review. Ocul Immunol Inflamm 2024; 32:1983-1989. [PMID: 38436928 DOI: 10.1080/09273948.2024.2311754] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/24/2023] [Revised: 01/23/2024] [Accepted: 01/24/2024] [Indexed: 03/05/2024]
Abstract
PURPOSE Vitreoretinal lymphoma (VRL) is a rare lymphoma affecting the vitreous and the retina. Clinical diagnosis is challenging and often delayed and may lead to aggravated prognosis. This study aims to review multimodal imaging findings in VRL. METHODS We performed a comprehensive narrative review of the multimodal imaging findings that might be useful in the detection of VRL lesions. RESULTS The most frequent ocular manifestations of VRL are vitritis, and retinal and sub-retinal Pigmented Epithelium (RPE) infiltrations. Color Fundus Photography (CFP) detects vitreous haze, optic nerve, retinal and sub-RPE infiltration. Ultra-wide field imaging allows visualization of different patterns of vitreous haze and monitoring of VRL evolution through the detection of chorio-retinal atrophy (CRA). Fundus Autofluorescence shows granular hypo- and hyper-autofluorescent pattern. Optical Coherence Tomography (OCT) reveals vitreous cells, vertical hyper-reflective lesions and sub-RPE infiltrates. Fluorescein Angiography (FA) shows hypo or hyperfluorescent round lesions at the late stages of the examination, while Indocyanine Green Angiography (ICGA) detects round areas of focal hypo-fluorescence in the early phases that gradually enlarge in the late phases. B-scan ultrasonography detects vitreous opacities and homogeneous hyperreflective corpuscular material in the vitreous, and is a strongly recommended tool in suspecting VRL and is particularly useful when vitreous haze is impeding retinal examination. CONCLUSION Diagnostic vitrectomy with cytopathological analysis remains the gold standard for VRL diagnosis, however multimodal imaging allows the identification of suggestive retinal and vitreal lesions for early suspicion, diagnosis, and treatment and monitoring disease progression and response to treatment.
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Affiliation(s)
- Federico Rissotto
- Department of Ophthalmology, Scientific Institute San Raffaele, University Vita-Salute San Raffaele, Milan, Italy
| | - Maria Vittoria Cicinelli
- Department of Ophthalmology, Scientific Institute San Raffaele, University Vita-Salute San Raffaele, Milan, Italy
| | - Andrea Servillo
- Department of Ophthalmology, Scientific Institute San Raffaele, University Vita-Salute San Raffaele, Milan, Italy
| | - Alessandro Berni
- Department of Ophthalmology, Scientific Institute San Raffaele, University Vita-Salute San Raffaele, Milan, Italy
| | - Matteo Menean
- Department of Ophthalmology, Scientific Institute San Raffaele, University Vita-Salute San Raffaele, Milan, Italy
| | - Lorenzo Bianco
- Department of Ophthalmology, Scientific Institute San Raffaele, University Vita-Salute San Raffaele, Milan, Italy
| | - Alessio Antropoli
- Department of Ophthalmology, Scientific Institute San Raffaele, University Vita-Salute San Raffaele, Milan, Italy
| | - Francesco Bandello
- Department of Ophthalmology, Scientific Institute San Raffaele, University Vita-Salute San Raffaele, Milan, Italy
| | - Elisabetta Miserocchi
- Department of Ophthalmology, Scientific Institute San Raffaele, University Vita-Salute San Raffaele, Milan, Italy
| | - Alessandro Marchese
- Department of Ophthalmology, Scientific Institute San Raffaele, University Vita-Salute San Raffaele, Milan, Italy
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Metayer C, Kodjikian L, Nguyen AM, Loria O, Chaperon M, Ghesquieres H, Mathis T. INTEREST OF REGULAR ASSAYS OF AQUEOUS HUMOR INTERLEUKIN-10 LEVELS IN MONITORING OF VITREORETINAL LYMPHOMA. Retina 2024; 44:1807-1813. [PMID: 39287544 DOI: 10.1097/iae.0000000000004165] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 09/19/2024]
Abstract
PURPOSE To investigate the variation of interleukin-10 (IL-10) levels in the aqueous humor (AH) of patients with vitreoretinal lymphoma (VRL) throughout therapy and follow-up and analyze the relation of these variations with VRL clinical course and relapse. METHODS This study retrospectively included consecutive patients diagnosed with VRL in a single center. AH IL-10 samples and patient clinical course were evaluated. The response to treatment was evaluated according to the criteria set by the International Primary Central Nervous System Lymphoma Collaborative Group. RESULTS A total of 59 eyes of 34 patients were included. Interleukin-10 levels decreased significantly at first AH sample after therapy induction (median [IQR] 3.0 [2.8-3.6] months) among patients in complete clinical remission (P < 0.001). Among patients in complete clinical remission with residual detectable IL-10 in AH after therapy induction (85.3% systemic chemotherapy, 11.8% intravitreal methotrexate, 2.9% palliative care), 87.5% experienced ocular relapse within 5 years. The detection of IL-10 in AH at the first visit after induction for complete clinical remission obtained a sensitivity of 77.8% (95% CI 0.45-0.96) and a specificity of 96.4% (95% CI 0.82-0.99) to predict ocular relapse. For relapsing eyes (N = 26), IL-10 significantly increased between the last IL-10 measurement and the time of the first ocular relapse (P < 0.001). In 76.0% of cases, an increase in IL-10 was detected earlier than clinical relapse with a mean (SD) of 4.0 (2.4) months. CONCLUSION The present study suggested the usefulness of IL-10 in the prognosis of VRL. This study showed a relation between IL-10 in AH and tumoral activity, and for the first time with disease relapse.
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Affiliation(s)
- Charline Metayer
- Service d'Ophtalmologie, Hôpital Universitaire de la Croix-Rousse, Hospices Civils de Lyon, Lyon, France
| | - Laurent Kodjikian
- Service d'Ophtalmologie, Hôpital Universitaire de la Croix-Rousse, Hospices Civils de Lyon, Lyon, France
- Laboratoire UMR-CNRS 5510 MATEIS, INSA, Université Lyon 1, Villeurbanne, France
| | - Anh-Minh Nguyen
- Service d'Ophtalmologie, Hôpital Universitaire de la Croix-Rousse, Hospices Civils de Lyon, Lyon, France
- Centre Ophtalmologique Pôle Vision, Clinique du Val d'Ouest, Ecully, France; and
| | - Olivier Loria
- Service d'Ophtalmologie, Hôpital Universitaire de la Croix-Rousse, Hospices Civils de Lyon, Lyon, France
| | - Mayeul Chaperon
- Service d'Ophtalmologie, Hôpital Universitaire de la Croix-Rousse, Hospices Civils de Lyon, Lyon, France
| | - Hervé Ghesquieres
- Service d'Hématologie, Hôpital Universitaire de Lyon Sud, Hospices Civils de Lyon, Pierre-Bénite, France
| | - Thibaud Mathis
- Service d'Ophtalmologie, Hôpital Universitaire de la Croix-Rousse, Hospices Civils de Lyon, Lyon, France
- Laboratoire UMR-CNRS 5510 MATEIS, INSA, Université Lyon 1, Villeurbanne, France
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Kurisu N, Hiyama T, Harada Y, Fukushima N, Katsuya N, Ureshino H, Ichinohe T, Kiuchi Y. Vitreoretinal Lymphoma in a Patient with Rheumatoid Arthritis with a History of Methotrexate-associated Lymphoproliferative Disorders. Ocul Immunol Inflamm 2024; 32:1070-1075. [PMID: 36395469 DOI: 10.1080/09273948.2022.2144384] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/30/2022] [Revised: 10/10/2022] [Accepted: 10/31/2022] [Indexed: 11/18/2022]
Abstract
Methotrexate (MTX) may induce immunosuppression and facilitate the onset of lymphoproliferative disorders (LPD). Most cases of MTX-LPD occur in patients with rheumatoid arthritis; the incidence is high in Japan. Vitreoretinal lymphoma (VRL) is a rare non-Hodgkin's lymphoma that can masquerade as steroid-resistant chronic uveitis, leading to fatal diagnostic delay. A 68-year-old woman exhibited optic disc swelling and retinal vasculitis causing floaters in the right eye. She was undergoing long-term MTX treatment for rheumatoid arthritis; she previously had been diagnosed with MTX-LPD, which regressed upon discontinuation of MTX. Steroid therapy was ineffective for optic disc swelling and retinal vasculitis; her best-corrected visual acuity decreased to 20/400. Vitreous biopsy revealed VRL, which was successfully treated with high-dose MTX-based systemic chemotherapy and intravitreal injections of MTX. To our knowledge, this is the first case report of VRL in a patient with an autoimmune disease who have a history of MTX-LPD.
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Affiliation(s)
- Naho Kurisu
- Department of Ophthalmology and Visual Science, Graduate School of Biomedical Sciences, Hiroshima University, Hiroshima, Japan
- Department of Ophthalmology, Miyoshi Central Hospital, Hiroshima, Japan
| | - Tomona Hiyama
- Department of Ophthalmology and Visual Science, Graduate School of Biomedical Sciences, Hiroshima University, Hiroshima, Japan
| | - Yosuke Harada
- Department of Ophthalmology and Visual Science, Graduate School of Biomedical Sciences, Hiroshima University, Hiroshima, Japan
| | - Noriyasu Fukushima
- Department of Haematology, Graduate School of Biomedical Sciences, Hiroshima University, Hiroshima, Japan
- Department of Internal Medicine, Karatsu Red Cross Hospital, Saga, Japan
| | - Narutaka Katsuya
- Department of Molecular Pathology, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan
| | - Hiroshi Ureshino
- Department of Haematology, Graduate School of Biomedical Sciences, Hiroshima University, Hiroshima, Japan
| | - Tatsuo Ichinohe
- Department of Haematology, Graduate School of Biomedical Sciences, Hiroshima University, Hiroshima, Japan
| | - Yoshiaki Kiuchi
- Department of Ophthalmology and Visual Science, Graduate School of Biomedical Sciences, Hiroshima University, Hiroshima, Japan
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Guan W, Zhang Y, Zhang X, Peng X. In Vivo Confocal Microscopy of Keratic Precipitates in Vitreoretinal Lymphoma. Ocul Immunol Inflamm 2024; 32:919-924. [PMID: 36508690 DOI: 10.1080/09273948.2022.2151020] [Citation(s) in RCA: 3] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/24/2022] [Revised: 11/12/2022] [Accepted: 11/18/2022] [Indexed: 12/14/2022]
Abstract
PURPOSE To investigate the morphological features of keratic precipitates (KPs) with in vivo confocal microscopy (IVCM) in vitreoretinal lymphoma (VRL). METHODS Patients with biopsy-proven VRL were reviewed, and 12 patients (16 eyes) with KPs examined by IVCM were included. RESULTS Five distinct KP morphologies on IVCM were observed: dendritic, nibbling, linear, globular, and stippled. Dendritic KPs were discovered in 9 eyes (56.3%), with a hyperreflective core and multiple thin pseudopodia. Nibbling KPs were found in 8 eyes (50.0%), featuring irregularly hyperreflective borders and a mottled reflective interior. Linear, stippled, and globular KPs were self-explanatory and affected nearly all eyes. Globular KPs seem to be formed by hyperreflective cells with large nuclei and prominent nucleoli, similar to atypical lymphocytes in vitreous cytology. CONCLUSIONS IVCM could provide more insight into the morphological traits of KPs than clinical observation, highlighting its potential for identifying VRL involving the anterior segment.
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Affiliation(s)
- Wenxue Guan
- Beijing Tongren Hospital, Capital Medical University, Beijing, China
| | - Yang Zhang
- Beijing Tongren Hospital, Capital Medical University, Beijing, China
| | - Xu Zhang
- Beijing Tongren Hospital, Capital Medical University, Beijing, China
| | - Xiaoyan Peng
- Beijing Tongren Hospital, Capital Medical University, Beijing, China
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16
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Kim JY, Kim JJ, Kim RY, Kim M, Park YG, Park YH. Factors related to central nervous system involvement of primary vitreoretinal lymphoma. Graefes Arch Clin Exp Ophthalmol 2024; 262:2421-2429. [PMID: 38446203 DOI: 10.1007/s00417-024-06434-9] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/05/2023] [Revised: 02/13/2024] [Accepted: 02/27/2024] [Indexed: 03/07/2024] Open
Abstract
PURPOSE This single center retrospective study aimed to investigate the factors associated with central nervous system (CNS) involvement of primary vitreoretinal lymphoma (PVRL). METHODS Clinical features of patients with PVRL (Group 1), those diagnosed with vitreoretinal lymphoma (VRL) after primary CNS lymphoma diagnosis (Group 2), and those concurrently diagnosed with CNS lymphoma and VRL (Group 3), were compared. The main outcomes included sex, age, types of treatment, survival, visual acuity, diagnostic methods, VRL recurrence, ocular manifestations, and interleukin levels in the aqueous humor. RESULTS Groups 1, 2, and 3 included 66 eyes in 38 patients, 29 eyes in 18 patients, and 14 eyes in 8 patients, respectively. Group 3 had shorter overall survival (OS) than Groups 1 and 2 (P = 0.042 and P = 0.009, respectively). The three groups did not differ in progression-free survival (P = 0.060). The 5-year survival rates of Groups 1, 2, and 3 were 56.5%, 44.0%, and 25.0%, respectively (P = 0.001). Patients with CNS involvement in Group 1 exhibited VRL recurrence (P < 0.001), high interleukin-10 (P = 0.024), and sub-retinal pigment epithelium (RPE) infiltration (P = 0.009). Patients experiencing VRL recurrence in Group 1 tended to show CNS involvement (P < 0.001). CONCLUSION Patients concurrently diagnosed with CNS lymphoma and VRL had a shorter OS and a lower 5-year survival rate. In patients with PVRL, the recurrence of VRL, high interleukin-10, and sub-RPE infiltration were associated with CNS involvement.
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Affiliation(s)
- Joo Young Kim
- Department of Ophthalmology and Visual Science, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, 222 Banpo-daero, Seocho-Gu, Seoul, 06591, Korea
- Catholic Institute for Visual Science, College of Medicine, The Catholic University of Korea, Seoul, Korea
| | - Jae Jung Kim
- Department of Ophthalmology and Visual Science, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, 222 Banpo-daero, Seocho-Gu, Seoul, 06591, Korea
| | - Rae Young Kim
- Department of Ophthalmology and Visual Science, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, 222 Banpo-daero, Seocho-Gu, Seoul, 06591, Korea
- Catholic Institute for Visual Science, College of Medicine, The Catholic University of Korea, Seoul, Korea
| | - Mirinae Kim
- Department of Ophthalmology and Visual Science, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, 222 Banpo-daero, Seocho-Gu, Seoul, 06591, Korea
- Catholic Institute for Visual Science, College of Medicine, The Catholic University of Korea, Seoul, Korea
| | - Young Gun Park
- Department of Ophthalmology and Visual Science, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, 222 Banpo-daero, Seocho-Gu, Seoul, 06591, Korea
- Catholic Institute for Visual Science, College of Medicine, The Catholic University of Korea, Seoul, Korea
| | - Young-Hoon Park
- Department of Ophthalmology and Visual Science, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, 222 Banpo-daero, Seocho-Gu, Seoul, 06591, Korea.
- Catholic Institute for Visual Science, College of Medicine, The Catholic University of Korea, Seoul, Korea.
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17
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Marchese A, Di Biase C, Cicinelli MV, Menean M, Ferrari G, Bandello F, Modorati G, Goldstein DA, Miserocchi E. Anterior segment involvement in vitreoretinal lymphoma: clinical manifestations, molecular findings and in vivo confocal microscopy. Br J Ophthalmol 2024; 108:1168-1171. [PMID: 37963712 DOI: 10.1136/bjo-2023-324303] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/23/2023] [Accepted: 10/13/2023] [Indexed: 11/16/2023]
Abstract
BACKGROUND Intermediate and posterior manifestations of vitreoretinal lymphoma (VRL) are well characterised. However, there is limited information on anterior segment involvement in VRL. This study aimed to describe the anterior manifestations of VRL, and their association with molecular testing. METHODS Retrospective analysis of patients with biopsy-proven VRL. Study variables included anterior segment manifestations, findings from slit-lamp photos and in vivo confocal microscopy (IVCM) when available. MYD88 L265P mutation and cytology in the aqueous humour, retinal and systemic findings were also analysed. RESULTS The analysis included 108 eyes of 55 VRL patients. Anterior segment involvement was present in at least one visit in 55 eyes (51%) of 33 patients (60%); it included keratic precipitates (dendritiform with branching and irregular margins in 33 eyes, dust-like in 16 eyes and large granulomatous in 12 eyes), cells in the anterior chamber (51 eyes) and posterior synechiae (2 eyes). IVCM was available for 41 eyes and showed different morphologies of keratic precipitates, including floral, spikes and mulberry patterns (66%, 56% and 20%, respectively). MYD88 L265P mutation in the aqueous humour was detected in 10/21 (48%) eyes with no anterior segment involvement and 24/37 (65%) eyes with anterior segment involvement. CONCLUSIONS Anterior segment manifestations are often present in VRL and include dendritiform and dust-like keratic precipitates. IVCM in VRL can identify different patterns associated with keratic precipitates. MYD88 L265P mutation in the aqueous humour of VRL patients can also be found in eyes without significant anterior segment involvement.
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Affiliation(s)
- Alessandro Marchese
- Department of Ophthalmology, San Raffaele Scientific Institute, Milan, Italy
- School of Medicine, Vita-Salute San Raffaele University, Milan, Italy
- Department of Ophthalmology, Northwestern University Feinberg School of Medicine, Chicago, Illinois, USA
| | - Carlo Di Biase
- Department of Ophthalmology, San Raffaele Scientific Institute, Milan, Italy
- School of Medicine, Vita-Salute San Raffaele University, Milan, Italy
- Department of Ophthalmology, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy
| | - Maria Vittoria Cicinelli
- Department of Ophthalmology, San Raffaele Scientific Institute, Milan, Italy
- School of Medicine, Vita-Salute San Raffaele University, Milan, Italy
| | - Matteo Menean
- Department of Ophthalmology, San Raffaele Scientific Institute, Milan, Italy
- School of Medicine, Vita-Salute San Raffaele University, Milan, Italy
| | - Giulio Ferrari
- IRCCS San Raffaele Scientific Institute, Division of Neuroscience, Cornea and Ocular Surface Disease Unit, Eye Repair Laboratory, Milan, Italy
- Department Of Ophthalmology, Vita-Salute San Raffaele University, Milan, Italy
| | - Francesco Bandello
- Department of Ophthalmology, San Raffaele Scientific Institute, Milan, Italy
- School of Medicine, Vita-Salute San Raffaele University, Milan, Italy
| | - Giulio Modorati
- Department of Ophthalmology, San Raffaele Scientific Institute, Milan, Italy
- School of Medicine, Vita-Salute San Raffaele University, Milan, Italy
| | - Debra Anne Goldstein
- Department of Ophthalmology, Northwestern University Feinberg School of Medicine, Chicago, Illinois, USA
| | - Elisabetta Miserocchi
- Department of Ophthalmology, San Raffaele Scientific Institute, Milan, Italy
- School of Medicine, Vita-Salute San Raffaele University, Milan, Italy
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Gu J, Chen Q, Zhang P, Zhang T, Zhou X, Zhang K, Jiang T, Liu S, Chen W, Zhou M, Jiang R, Huang X, Xu G, Chang Q. Characteristics of Vitreoretinal Lymphoma in B-Scan Ultrasonography: A Case-Control Study. Ophthalmol Retina 2024; 8:264-269. [PMID: 37820767 DOI: 10.1016/j.oret.2023.10.002] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/20/2023] [Revised: 09/10/2023] [Accepted: 10/03/2023] [Indexed: 10/13/2023]
Abstract
PURPOSE To explore the characteristics of vitreoretinal lymphoma (VRL) in B-scan ultrasonography. DESIGN Single-center case-control study. PARTICIPANTS A total of 106 eyes of 56 patients with biopsy-proven VRL and 86 eyes of 59 patients with uveitis were included. METHODS B-scan ultrasonography of the included eyes was performed. Evaluated were the ultrasonographic signs as well as a special pattern termed centrifugal condensation, which refers to the peripherally hyperreflective appearance of the vitreous haze in ultrasonography. MAIN OUTCOME MEASURES Posterior vitreous detachment, vitreoretinal adhesion, location of vitreous haze, thickening or occupying lesions of the retina, retinal detachment, and centrifugal condensation pattern of vitreous haze were evaluated through B-scan ultrasonography. The incidences of these signs were compared between the 2 groups; odds ratios (ORs) were calculated. RESULTS The incidence of vitreoretinal adhesion in patients with VRL (6/106) was lower than in patients with uveitis (20/86; P = 0.001; OR: 0.195; 95% confidence interval [CI]: 0.073-0.522). The incidence of retinal thickening or occupying lesions in patients with VRL (21/106) was higher than that in patients with uveitis (1/86; P = 0.005; OR: 19.068; 95% CI: 2.455-148.265). The incidences of posterior vitreous detachment and retinal detachment were not significantly different between the 2 groups (P = 0.453 and P = 0.310, respectively). The centrifugal condensation pattern was more likely to be observed in patients with VRL (49/106) than in patients with uveitis (13/86; P < 0.001; OR: 4.831; 95% CI: 2.416-9.660). CONCLUSIONS B-scan ultrasonography might help to provide clues for the suspicion of VRL. Thickening or occupying lesions of the retina and centrifugal condensation pattern of vitreous haze might be suggestive of VRL. FINANCIAL DISCLOSURE(S) Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.
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Affiliation(s)
- Junxiang Gu
- Department of Ophthalmology, Fudan University Eye and ENT Hospital, Fudan University, Shanghai, China; Shanghai Key Laboratory of Visual Impairment and Restoration, Fudan University Eye and ENT Hospital, Fudan University, Shanghai, China; NHC Key Laboratory of Myopia (Fudan University), Key Laboratory of Myopia, Chinese Academy of Medical Sciences, Shanghai, China
| | - Qian Chen
- Department of Ophthalmology, Fudan University Eye and ENT Hospital, Fudan University, Shanghai, China; Shanghai Key Laboratory of Visual Impairment and Restoration, Fudan University Eye and ENT Hospital, Fudan University, Shanghai, China; NHC Key Laboratory of Myopia (Fudan University), Key Laboratory of Myopia, Chinese Academy of Medical Sciences, Shanghai, China
| | - Peijun Zhang
- Department of Ophthalmology, Fudan University Eye and ENT Hospital, Fudan University, Shanghai, China; Shanghai Key Laboratory of Visual Impairment and Restoration, Fudan University Eye and ENT Hospital, Fudan University, Shanghai, China; NHC Key Laboratory of Myopia (Fudan University), Key Laboratory of Myopia, Chinese Academy of Medical Sciences, Shanghai, China
| | - Ting Zhang
- Department of Ophthalmology, Fudan University Eye and ENT Hospital, Fudan University, Shanghai, China; Shanghai Key Laboratory of Visual Impairment and Restoration, Fudan University Eye and ENT Hospital, Fudan University, Shanghai, China; NHC Key Laboratory of Myopia (Fudan University), Key Laboratory of Myopia, Chinese Academy of Medical Sciences, Shanghai, China
| | - Xinyi Zhou
- Shanghai Medical College, Fudan University, Shanghai, China
| | - Kaiyu Zhang
- Shanghai Medical College, Fudan University, Shanghai, China
| | - Tingting Jiang
- Department of Ophthalmology, Fudan University Eye and ENT Hospital, Fudan University, Shanghai, China; Shanghai Key Laboratory of Visual Impairment and Restoration, Fudan University Eye and ENT Hospital, Fudan University, Shanghai, China; NHC Key Laboratory of Myopia (Fudan University), Key Laboratory of Myopia, Chinese Academy of Medical Sciences, Shanghai, China
| | - Shixue Liu
- Department of Ophthalmology, Fudan University Eye and ENT Hospital, Fudan University, Shanghai, China; Shanghai Key Laboratory of Visual Impairment and Restoration, Fudan University Eye and ENT Hospital, Fudan University, Shanghai, China; NHC Key Laboratory of Myopia (Fudan University), Key Laboratory of Myopia, Chinese Academy of Medical Sciences, Shanghai, China
| | - Wenwen Chen
- Department of Ophthalmology, Fudan University Eye and ENT Hospital, Fudan University, Shanghai, China; Shanghai Key Laboratory of Visual Impairment and Restoration, Fudan University Eye and ENT Hospital, Fudan University, Shanghai, China; NHC Key Laboratory of Myopia (Fudan University), Key Laboratory of Myopia, Chinese Academy of Medical Sciences, Shanghai, China
| | - Min Zhou
- Department of Ophthalmology, Fudan University Eye and ENT Hospital, Fudan University, Shanghai, China; Shanghai Key Laboratory of Visual Impairment and Restoration, Fudan University Eye and ENT Hospital, Fudan University, Shanghai, China; NHC Key Laboratory of Myopia (Fudan University), Key Laboratory of Myopia, Chinese Academy of Medical Sciences, Shanghai, China
| | - Rui Jiang
- Department of Ophthalmology, Fudan University Eye and ENT Hospital, Fudan University, Shanghai, China; Shanghai Key Laboratory of Visual Impairment and Restoration, Fudan University Eye and ENT Hospital, Fudan University, Shanghai, China; NHC Key Laboratory of Myopia (Fudan University), Key Laboratory of Myopia, Chinese Academy of Medical Sciences, Shanghai, China
| | - Xin Huang
- Department of Ophthalmology, Fudan University Eye and ENT Hospital, Fudan University, Shanghai, China; Shanghai Key Laboratory of Visual Impairment and Restoration, Fudan University Eye and ENT Hospital, Fudan University, Shanghai, China; NHC Key Laboratory of Myopia (Fudan University), Key Laboratory of Myopia, Chinese Academy of Medical Sciences, Shanghai, China
| | - Gezhi Xu
- Department of Ophthalmology, Fudan University Eye and ENT Hospital, Fudan University, Shanghai, China; Shanghai Key Laboratory of Visual Impairment and Restoration, Fudan University Eye and ENT Hospital, Fudan University, Shanghai, China; NHC Key Laboratory of Myopia (Fudan University), Key Laboratory of Myopia, Chinese Academy of Medical Sciences, Shanghai, China
| | - Qing Chang
- Department of Ophthalmology, Fudan University Eye and ENT Hospital, Fudan University, Shanghai, China; Shanghai Key Laboratory of Visual Impairment and Restoration, Fudan University Eye and ENT Hospital, Fudan University, Shanghai, China; NHC Key Laboratory of Myopia (Fudan University), Key Laboratory of Myopia, Chinese Academy of Medical Sciences, Shanghai, China.
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Komatsu H, Usui Y, Tsubota K, Fujii R, Yamaguchi T, Maruyama K, Wakita R, Asakage M, Hamada K, Yamakawa N, Nezu N, Ueda K, Goto H. Vitreous Humor Proteomic Profile in Patients With Vitreoretinal Lymphoma. Invest Ophthalmol Vis Sci 2023; 64:2. [PMID: 38038618 PMCID: PMC10697174 DOI: 10.1167/iovs.64.15.2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/29/2023] [Accepted: 11/10/2023] [Indexed: 12/02/2023] Open
Abstract
Purpose Vitreoretinal lymphoma is a high-grade malignant non-Hodgkin lymphoma with poor prognosis. The objective of this study was to elucidate the proteome profile of the vitreous in patients with vitreoretinal lymphoma (VRL), aiming to advance understanding of the pathophysiology of VRL. Methods Comprehensive proteomic analyses of vitreous humor using liquid chromatography with tandem mass spectrometry were performed for 10 patients with VRL, 10 control patients with idiopathic epiretinal membrane or macular hole, and 10 patients with ocular sarcoidosis. Differentially expressed proteins (DEPs) were identified by comparing VRL with controls and sarcoidosis, and functional pathway analysis was performed. Finally, vitreous concentrations of representative DEPs that were significantly upregulated in proteomics study were measured by ELISA using a separate cohort. Results In total, 1594 proteins were identified in the vitreous humor of VRL, control, and sarcoidosis samples. Also, 282 DEPs were detected in VRL, 249 upregulated and 33 downregulated, compared with controls. Enrichment pathway analysis showed alterations in proteasome-related pathways. Compared to controls and sarcoidosis, 14 DEPs in VRL showed significant upregulation. In the validation study, ELISA confirmed significantly higher vitreous concentrations of PSAT1, YWHAG, and 20S/26S proteasome complex in VRL compared with controls and sarcoidosis. Among the upregulated DEPs, vitreous PITHD1 and NCSTN concentrations correlated positively with vitreous IL-10 concentrations. Conclusions This study highlights aberrations in protein expression pattern in the vitreous of patients with VRL. The DEPs identified in this study may play pivotal roles in VRL pathogenesis, providing insights to enhance understanding of VRL pathophysiology and contribute to the development of VRL biomarkers.
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Affiliation(s)
- Hiroyuki Komatsu
- Department of Ophthalmology, Tokyo Medical University, Tokyo, Japan
| | - Yoshihiko Usui
- Department of Ophthalmology, Tokyo Medical University, Tokyo, Japan
| | - Kinya Tsubota
- Department of Ophthalmology, Tokyo Medical University, Tokyo, Japan
| | - Risa Fujii
- Cancer Proteomics Group, Cancer Precision Medicine Center, Japanese Foundation for Cancer Research, Tokyo, Japan
| | - Takefumi Yamaguchi
- Department of Ophthalmology, Tokyo Dental College Ichikawa General Hospital, Chiba, Japan
| | - Kazuichi Maruyama
- Department of Ophthalmology, Osaka University Graduate School of Medicine, Osaka, Japan
| | - Ryo Wakita
- Department of Ophthalmology, Tokyo Medical University, Tokyo, Japan
| | - Masaki Asakage
- Department of Ophthalmology, Tokyo Medical University, Tokyo, Japan
| | - Kazuki Hamada
- Department of Ophthalmology, Tokyo Medical University, Tokyo, Japan
| | - Naoyuki Yamakawa
- Department of Ophthalmology, Tokyo Medical University, Tokyo, Japan
| | - Naoya Nezu
- Department of Ophthalmology, Tokyo Medical University, Tokyo, Japan
| | - Koji Ueda
- Cancer Proteomics Group, Cancer Precision Medicine Center, Japanese Foundation for Cancer Research, Tokyo, Japan
| | - Hiroshi Goto
- Department of Ophthalmology, Tokyo Medical University, Tokyo, Japan
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20
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Kwak JJ, Lee KS, Lee J, Kim YJ, Choi EY, Byeon SH, Chang WS, Kim YR, Kim JS, Shin S, Lee ST, Kim SS, Lee CS. Next-Generation Sequencing of Vitreoretinal Lymphoma by Vitreous Liquid Biopsy: Diagnostic Potential and Genotype/Phenotype Correlation. Invest Ophthalmol Vis Sci 2023; 64:27. [PMID: 37975847 PMCID: PMC10664732 DOI: 10.1167/iovs.64.14.27] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/17/2023] [Accepted: 08/31/2023] [Indexed: 11/19/2023] Open
Abstract
Purpose To determine the diagnostic potential of next-generation sequencing (NGS) in vitreous samples, analyze genotype-phenotype characteristics, and compare NGS of matched vitreous and brain samples in patients with associated central nervous system lymphoma (CNSL). Methods A total of 32 patients suspected of vitreoretinal lymphoma (VRL) who underwent diagnostic vitrectomy and NGS were included in this retrospective observational case-series. Fresh vitreous specimens from diagnostic vitrectomy of VRL-suspected patients underwent NGS using a custom panel targeting 747 candidate genes for lymphoma. They also underwent malignancy cytology, interleukin (IL)-10/IL-6, immunoglobulin heavy chain (IGH)/immunoglobulin kappa light chain (IGK) monoclonality testing. MYD88 L265P mutation was examined from anterior chamber tap samples. The diagnosis of VRL was made based on typical clinical characteristics for VRL, as well as malignant cytology, IGH/IGK clonality, or IL-10/IL-6 > 1. Sensitivity and specificity of NGS were compared with conventional diagnostic tests. Brain tissues suspected of lymphoma were collected by stereotactic biopsy and underwent NGS. Genetic variations detected in NGS of vitreous and brain tissue specimens were compared. Results The sensitivity values for cytology, IL-10/IL-6 > 1, clonality assays for IGH and IGK, MYD88 L265P detection in anterior chamber tap samples, and vitreous NGS were 0.23, 0.83, 0.68, 0.79, 0.67, and 0.85, with specificity values of 1.00, 0.83, 0.50, 0.25, 0.83, and 0.83, respectively. The sensitivity (0.85) of vitreous NGS was the highest compared to other conventional diagnostic tests for VRL. The most common mutations were MYD88 (91%), CDKN2A (36%), PIM1 (32%), IGLL5 (27%), and ETV6 (23%). Although several gene alterations demonstrated heterogeneity between the brain and eyes, some common mutational profiles were observed in matched vitreous and brain samples. Conclusions Overall, NGS of the vitreous demonstrated high sensitivity among conventional diagnostic tests. VRL and CNSL appeared to have both shared and distinct genetic variations, which may suggest site-specific variations from a common origin.
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Affiliation(s)
- Jay Jiyong Kwak
- Department of Ophthalmology, The Institute of Vision Research, Yonsei University College of Medicine, Seoul, Korea
| | - Kwang Seob Lee
- Department of Laboratory Medicine, Yonsei University College of Medicine, Seoul, Korea
| | - Junwon Lee
- Department of Ophthalmology, The Institute of Vision Research, Yonsei University College of Medicine, Seoul, Korea
| | - Yong Joon Kim
- Department of Ophthalmology, The Institute of Vision Research, Yonsei University College of Medicine, Seoul, Korea
| | - Eun Young Choi
- Department of Ophthalmology, The Institute of Vision Research, Yonsei University College of Medicine, Seoul, Korea
| | - Suk Ho Byeon
- Department of Ophthalmology, The Institute of Vision Research, Yonsei University College of Medicine, Seoul, Korea
| | - Won Seok Chang
- Department of Neurosurgery, Yonsei University College of Medicine, Seoul, Korea
| | - Yu Ri Kim
- Division of Hematology, Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Korea
| | - Jin Seok Kim
- Division of Hematology, Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Korea
| | - Saeam Shin
- Department of Laboratory Medicine, Yonsei University College of Medicine, Seoul, Korea
| | - Seung-Tae Lee
- Department of Laboratory Medicine, Yonsei University College of Medicine, Seoul, Korea
| | - Sung Soo Kim
- Department of Ophthalmology, The Institute of Vision Research, Yonsei University College of Medicine, Seoul, Korea
| | - Christopher Seungkyu Lee
- Department of Ophthalmology, The Institute of Vision Research, Yonsei University College of Medicine, Seoul, Korea
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21
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Makita J, Yoshikawa Y, Kanno J, Igawa Y, Kumagai T, Takano S, Katsumoto T, Shoji T, Shibuya M, Shinoda K. Electroretinographic and Optical Coherence Tomographic Evaluations of Eyes with Vitreoretinal Lymphoma. J Clin Med 2023; 12:3957. [PMID: 37373651 DOI: 10.3390/jcm12123957] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/16/2023] [Revised: 05/19/2023] [Accepted: 06/02/2023] [Indexed: 06/29/2023] Open
Abstract
Vitreoretinal lymphomas (VRLs) present with different clinical characteristics. However, only a few case reports have been published that evaluated the retinal function and the retinal morphology. The relationship between retinal morphology and function of eyes with a vitreoretinal lymphoma (VRL) was investigated via optical coherence tomography (OCT) and electroretinography (ERG). The ERG and OCT findings in 11 eyes of 11 patients (69.4 ± 11.5 years old) who were diagnosed with VRL at the Saitama Medical University Hospital between December 2016 to May 2022 were studied. The decimal best-corrected visual acuity ranged from hand movements to 1.2 (median 0.2). Histopathological studies of the vitreous specimens showed class II VRL in one eye, class III VRL in seven eyes, class IV VRL in two eyes, and class V VRL in one eye. The IgH gene rearrangement was positive in three of the six eyes tested. The OCT images showed morphological abnormalities in 10 of the 11 (90.9%) eyes. Severe attenuation was found for the amplitudes of the b-wave of the DA 0.01 ERG in 6 of 11 eyes (54.5%), the DA 3.0 a-wave in 5 of 11 eyes (45.5%), the DA 3.0 b-wave in 36.4%, the LA 3.0 a-wave in 36.4%, the LA 3.0 b-wave in 18.2%, and flicker responses in 36.4% of the eyes. None of the DA 3.0 ERGs had a negative shape (b/a < 1.0). In the five eyes in which the a-wave was severely attenuated, hyperreflective dots were observed subretinally. The ERG analysis in eyes with a VRL indicates a relatively severe dysfunction of the outer retinal layer and was helpful in determining the site of the morphological changes in eyes with VRL.
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Affiliation(s)
- Jun Makita
- Department of Ophthalmology, Saitama Medical University, Saitama 350-0495, Japan
| | - Yuji Yoshikawa
- Department of Ophthalmology, Saitama Medical University, Saitama 350-0495, Japan
| | - Junji Kanno
- Department of Ophthalmology, Saitama Medical University, Saitama 350-0495, Japan
| | - Yuro Igawa
- Department of Ophthalmology, Saitama Medical University, Saitama 350-0495, Japan
| | - Tomoyuki Kumagai
- Department of Ophthalmology, Saitama Medical University, Saitama 350-0495, Japan
| | - Shunichiro Takano
- Department of Ophthalmology, Saitama Medical University, Saitama 350-0495, Japan
| | - Takeshi Katsumoto
- Department of Ophthalmology, Saitama Medical University, Saitama 350-0495, Japan
| | - Takuhei Shoji
- Department of Ophthalmology, Saitama Medical University, Saitama 350-0495, Japan
- Koedo Eye Institute, Saitama 350-1123, Japan
| | - Masayuki Shibuya
- Department of Ophthalmology, Saitama Medical University, Saitama 350-0495, Japan
| | - Kei Shinoda
- Department of Ophthalmology, Saitama Medical University, Saitama 350-0495, Japan
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22
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Kaburaki T, Taoka K. Diagnosis and management of vitreoretinal lymphoma: present and future treatment perspectives. Jpn J Ophthalmol 2023:10.1007/s10384-023-00997-6. [PMID: 37209195 DOI: 10.1007/s10384-023-00997-6] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/17/2023] [Accepted: 03/29/2023] [Indexed: 05/22/2023]
Abstract
Intraocular lymphoma (IOL) is a rare malignant intraocular lymphocytic tumor that mimics uveitis. IOL is anatomically classified into vitreoretinal lymphoma (VRL) and uveal lymphoma; most IOLs are VRLs, while uveal lymphoma is rare. VRL is highly malignant, with 60%-85% of patients developing central nervous system (CNS) lymphoma; primary VRL (PVRL) is an ocular disease with poor prognosis. We aimed to review the management and both current and future treatments for VRL. VRL diagnosis is based on the results of cytopathological examination using vitreous biopsy. However, the positive ratio of vitreous cytology remains 29%-70%. A combination of adjunctive tests may improve diagnostic accuracy, but as yet no gold-standard regimen has been established. Methotrexate intravitreal injections are effective in controlling ocular lesions; however, this treatment allows CNS dissemination. The efficacy of systemic chemotherapy in suppressing CNS dissemination has been recently debated. A multicenter prospective study with a unified treatment protocol is required to clarify this issue. In addition, establishing a treatment protocol for elderly patients and those with poor general health is necessary. Moreover, relapsed/refractory VRL and secondary VRL are more difficult to treat than PVRL because they are prone to recurrence. Ibrutinib, lenalidomide with or without rituximab, and temozolomide are promising treatments for relapsed/refractory VRL. In Japan, Bruton's tyrosine kinase (BTK) inhibitors have been approved for treating refractory CNS lymphoma. Furthermore, a randomized prospective study of tirabrutinib, a highly selective BTK inhibitor, is ongoing for evaluating the suppressing of CNS progression in patients with PVRL.
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Affiliation(s)
- Toshikatsu Kaburaki
- Department of Ophthalmology, Jichi Medical University Saitama Medical Center, 1-847 Amanuma, Ohmiya-ku, Saitama, Saitama, 330-8503, Japan.
- Department of Ophthalmology, The University of Tokyo Graduate School of Medicine, Hongo, Bunkyo-ku, Tokyo, Japan.
| | - Kazuki Taoka
- Department of Ophthalmology, The University of Tokyo Graduate School of Medicine, Hongo, Bunkyo-ku, Tokyo, Japan
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23
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Tom JP, Gupta P, Radotra BD, Gupta N, Takkar A, Singh S, Gupta V. Role of vitreous cytology in the diagnosis of primary central nervous system lymphoma: A report of an unusual presentation. Diagn Cytopathol 2023. [PMID: 37148480 DOI: 10.1002/dc.25152] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/09/2022] [Revised: 04/28/2023] [Accepted: 04/28/2023] [Indexed: 05/08/2023]
Abstract
Primary central nervous system lymphoma (PCNSL) is a rare subtype of non-Hodgkin lymphoma confined to the brain, spinal cord, meninges, intraocular compartment, and cranial nerves. Intraocular lymphoma (IOL) is a rare subtype of PCNSL. Intravitreal involvement by a PCNSL is an infrequent but potentially fatal event. The role of vitreous cytology in diagnosing IOLs is vital but has been sporadically described in the literature due to its variable sensitivity. Herein, we present a case of PCNSL, who primarily presented with ocular symptoms and could be accurately diagnosed based on vitreous cytology and subsequently confirmed on stereotactic brain biopsy.
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Affiliation(s)
- Jesty Pullattu Tom
- Department of Cytology and Gynecologic Pathology, Postgraduate Institute of Medical Education and Research, Chandigarh, India
| | - Parikshaa Gupta
- Department of Cytology and Gynecologic Pathology, Postgraduate Institute of Medical Education and Research, Chandigarh, India
| | - Bishan Das Radotra
- Department of Histopathology, Postgraduate Institute of Medical Education and Research, Chandigarh, India
| | - Nalini Gupta
- Department of Cytology and Gynecologic Pathology, Postgraduate Institute of Medical Education and Research, Chandigarh, India
| | - Aastha Takkar
- Department of Neurology, Postgraduate Institute of Medical Education and Research, Chandigarh, India
| | - Sofia Singh
- Department of Neurology, Postgraduate Institute of Medical Education and Research, Chandigarh, India
| | - Vishali Gupta
- Department of Ophthalmology, Postgraduate Institute of Medical Education and Research, Chandigarh, India
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24
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Bennassi A, Girinsky T. Orbital follicular lymphoma with large cell component treated with low-dose radiotherapy: A case report and review of literature. Cancer Radiother 2023:S1278-3218(23)00051-3. [PMID: 37095054 DOI: 10.1016/j.canrad.2022.11.001] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/10/2022] [Revised: 11/08/2022] [Accepted: 11/10/2022] [Indexed: 04/26/2023]
Abstract
A 77-year-old woman was referred for a one-eyed palpebral edema associated with diplopia. An orbit magnetic resonance imaging showed an orbital mass in the superior medial portion of the internal right orbit without any intraorbital involvement. Biopsies demonstrated a nodular lymphoma with mixed follicular grade 1-2 (60%) and large cell components. The tumor mass was treated with a low-dose radiation therapy (4Gy in 2 fractions) with a complete disappearance of diplopia within one week. At 2-year follow-up, patient was in complete remission. To the best of our knowledge, this is the first case of mixed component follicular and large components orbital lymphoma managed by first-intent low-dose radiation therapy.
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Affiliation(s)
- A Bennassi
- Department of Radio-Oncology, Lausanne University Hospital, centre hospitalier universitaire Vaudois, rue du Bugnon 46, CH-1011 Lausanne, Switzerland.
| | - T Girinsky
- Department of Radio-Oncology, Institut Gustave-Roussy, Villejuif, France
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25
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Kim M, Suh H, Park YG, Park YH. Clinical features predictive of vision loss in patients with vitreoretinal lymphoma: a single tertiary center experience. Sci Rep 2023; 13:4478. [PMID: 36934118 PMCID: PMC10024690 DOI: 10.1038/s41598-023-31414-0] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/06/2022] [Accepted: 03/11/2023] [Indexed: 03/20/2023] Open
Abstract
To clarify the long-term visual prognosis and prognostic factors for vision loss in patients with vitreoretinal lymphoma (VRL). This retrospective longitudinal study included 64 consecutive patients with VRL. We analyzed the best-corrected visual acuity (BCVA), optical coherence tomography findings, and clinical features at every visit. Significant vision loss was defined as a final BCVA ≥ 0.5 logMAR. Predictors of significant vision loss following treatment were evaluated using univariate and multivariate linear regression analyses. We included 113 eyes of 64 patients (mean age, 64.2 ± 10.9 years), and 49 patients (76.6%) showed bilateral ocular involvement. The mean follow-up duration was 35.4 ± 25.8 months. At diagnosis, 36 (56.3%), 17 (26.6%), and 11 (17.2%) patients had primary, secondary, and concurrent VRL, respectively. All eyes received intraocular methotrexate injections (mean, 17.1 ± 5.5 injections). The mean BCVA improved from 0.44 ± 0.28 at diagnosis to 0.33 ± 0.29 1 month after treatment initiation. Vision improved significantly after treatment (final mean BCVA, 0.24 ± 0.21). Univariate and multivariate analyses showed that baseline BCVA and retinal/subretinal infiltration were significantly correlated with vision loss. In this study, a good visual outcome was maintained for > 35 months in patients with VRL. Baseline BCVA and retinal/subretinal infiltration were significant predictors of vision loss after treatment for VRL.
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Affiliation(s)
- Mirinae Kim
- Department of Ophthalmology and Visual Science, College of Medicine, The Catholic University of Korea, 222 Banpo-daero, Seocho-Gu, Seoul, 06591, South Korea
- Seoul St. Mary's Hospital, Seoul, South Korea
| | - Hyun Suh
- Department of Ophthalmology and Visual Science, College of Medicine, The Catholic University of Korea, 222 Banpo-daero, Seocho-Gu, Seoul, 06591, South Korea
- Seoul St. Mary's Hospital, Seoul, South Korea
| | - Young Gun Park
- Department of Ophthalmology and Visual Science, College of Medicine, The Catholic University of Korea, 222 Banpo-daero, Seocho-Gu, Seoul, 06591, South Korea
- Seoul St. Mary's Hospital, Seoul, South Korea
| | - Young-Hoon Park
- Department of Ophthalmology and Visual Science, College of Medicine, The Catholic University of Korea, 222 Banpo-daero, Seocho-Gu, Seoul, 06591, South Korea.
- Seoul St. Mary's Hospital, Seoul, South Korea.
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26
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Guan W, Xiao Y, Zhao H, Hu F, Chen C, Peng X. Spectral-domain optical coherence tomography biomarkers in vitreoretinal lymphoma. Clin Exp Ophthalmol 2023; 51:144-153. [PMID: 36567492 DOI: 10.1111/ceo.14197] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/31/2022] [Revised: 12/13/2022] [Accepted: 12/18/2022] [Indexed: 12/27/2022]
Abstract
BACKGROUND Although early detection is critical, diagnosing vitreoretinal lymphoma (VRL) remains difficult. We sought to assess the potential diagnostic value of spectral-domain optical coherence tomography (SD-OCT) in VRL. METHODS We reviewed the clinical records and pre-treatment SD-OCT images of biopsy-confirmed VRL and uveitis patients, with primary involvement of the sub-retinal pigment epithelium (RPE) and the outer retina, including acute syphilitic posterior placoid chorioretinitis (ASPPC), chronic stage sympathetic ophthalmitis (SO), and idiopathic multifocal choroiditis (MFC). RESULTS We included 45 eyes of 45 VRL patients and 40 eyes of 40 uveitis patients (17 ASPPC eyes, eight chronic SO eyes, and 15 MFC eyes). On SD-OCT, lymphoma cell infiltration was observed in various retinal layers, most commonly in the sub-RPE (80%) and sub-retinal space (62%). Highly sensitive features for VRL as compared to uveitis included vitreous cells (93%), focal hyper-reflective sub-retinal infiltration (51%), and diffuse RPE elevations (56%). The features strongly specific for VRL included preretinal deposits (92.5%), intra-retinal infiltration (except the incomplete vertical hyper-reflective type, 100%), banded hyper-reflective sub-retinal infiltration (90%), and confluent RPE detachments (100%). We identified an approach to VRL diagnosis based on these SD-OCT findings: (1) two highly sensitive features plus one strongly specific feature; or (2) one highly sensitive feature plus two strongly specific features, demonstrated a sensitivity of 80% and specificity of 95% for VRL. CONCLUSIONS The SD-OCT may enable the detection of detailed lymphoma infiltration characteristics and provide significant supplemental value for VRL diagnosis, particularly when combining highly sensitive and specific VRL-associated SD-OCT features.
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Affiliation(s)
- Wenxue Guan
- Department of Ophthalmology, Beijing Tongren Hospital, Capital Medical University, Beijing, China
| | - Yuanyuan Xiao
- Department of Ophthalmology, Beijing Tongren Hospital, Capital Medical University, Beijing, China
| | - Huiying Zhao
- Department of Ophthalmology, Beijing Tongren Hospital, Capital Medical University, Beijing, China.,Department of Ophthalmology, Beijing Geriatric Hospital, Beijing, China
| | - Feng Hu
- Department of Ophthalmology, Beijing Tongren Hospital, Capital Medical University, Beijing, China
| | - Chunli Chen
- Department of Ophthalmology, Beijing Tongren Hospital, Capital Medical University, Beijing, China
| | - Xiaoyan Peng
- Department of Ophthalmology, Beijing Tongren Hospital, Capital Medical University, Beijing, China
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27
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Sakai A, Tagami M, Katsuyama-Yoshikawa A, Misawa N, Haruna Y, Azumi A, Honda S. Relationship between Vitreous IL-6 Levels, Gender Differences and C-Reactive Protein (CRP) in a Blood Sample of Posterior Uveitis. J Clin Med 2023; 12:jcm12051720. [PMID: 36902507 PMCID: PMC10003048 DOI: 10.3390/jcm12051720] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/13/2023] [Revised: 02/08/2023] [Accepted: 02/19/2023] [Indexed: 02/24/2023] Open
Abstract
This study retrospectively determined the relationship between vitreous IL-6 levels and clinical and laboratory data collected from uveitis patients. We examined an unknown cause of posterior uveitis, collecting vitreous fluid to investigate vitreous IL-6 levels. The samples were analyzed in consideration of clinical and laboratory factors, such as the male/female ratio. The present study included 82 eyes from 77 patients with a mean age of 66.20 ± 15.41 years. The IL-6 concentrations of the vitreous specimens were 6255.0 ± 14,108.3 pg/mL in males and 277.6 ± 746.3 pg/mL in females, which was found to be a statistically significant difference (p = 0.048) (n = 82). There was also a statistically significant correlation between vitreous IL-6 concentrations, serum C-reactive protein (CRP) value and white blood cell counts (WBCs) (n = 82). In multivariate analysis, vitreous IL-6 levels were significantly correlated with gender and CRP in all cases (p = 0.048 and p < 0.01, respectively) and were also significantly correlated with CRP in non-infectious uveitis (p < 0.01). In infectious uveitis, there were no significant differences between IL-6 level and several variables. Vitreous IL-6 concentrations were higher in males than in females in all cases. In non-infectious uveitis, vitreous IL-6 levels were correlated with serum CRP. These results might suggest that intraocular IL-6 levels depend on gender differences in posterior uveitis, and intraocular IL-6 levels in non-infectious uveitis may reflect systemic inflammations, including increased serum CRP.
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Affiliation(s)
- Atsushi Sakai
- Department of Ophthalmology and Visual Sciences, Graduate School of Medicine, Osaka Metropolitan University, Osaka 545-8585, Japan
| | - Mizuki Tagami
- Department of Ophthalmology and Visual Sciences, Graduate School of Medicine, Osaka Metropolitan University, Osaka 545-8585, Japan
- Correspondence: ; Tel.: +81-6-6645-3867; Fax: +81-6645-3867
| | | | - Norihiko Misawa
- Department of Ophthalmology and Visual Sciences, Graduate School of Medicine, Osaka Metropolitan University, Osaka 545-8585, Japan
| | - Yusuke Haruna
- Department of Ophthalmology and Visual Sciences, Graduate School of Medicine, Osaka Metropolitan University, Osaka 545-8585, Japan
| | - Atsushi Azumi
- Department of Ophthalmology, Kobe Kaisei Hospital, Kobe 657-0068, Japan
| | - Shigeru Honda
- Department of Ophthalmology and Visual Sciences, Graduate School of Medicine, Osaka Metropolitan University, Osaka 545-8585, Japan
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28
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Iizuka-Honma H, Takizawa H, Mitsumori T, Okura H, Ishii H, Noguchi M. Refractory Primary Vitreoretinal Lymphoma Involving the Spinal Cord with a Temporary Complete Response to Tirabrutinib. Intern Med 2023; 62:459-463. [PMID: 35793963 PMCID: PMC9970806 DOI: 10.2169/internalmedicine.9591-22] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/04/2023] Open
Abstract
Many patients with primary vitreoretinal lymphoma (PVRL) exhibit central nervous system (CNS) involvement either at the diagnosis or during follow-up. The prognosis in the patients of PVRL with relapsed or refractory CNS remains extremely poor. We herein report a patient with refractory PVRL who had recurrence in the spinal cord despite receiving high-dose methotrexate-based chemotherapy and whole-brain radiotherapy. The patient surprisingly responded to tirabrutinib temporarily. We believe that this case suggests the utility of this new target therapy.
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Affiliation(s)
| | - Haruko Takizawa
- Department of Hematology, Juntendo University Urayasu Hospital, Japan
| | - Toru Mitsumori
- Department of Hematology, Juntendo University Urayasu Hospital, Japan
| | - Hidehiro Okura
- Department of Neurosurgery, Juntendo University Urayasu Hospital, Japan
| | - Hisato Ishii
- Department of Neurosurgery, Juntendo University Urayasu Hospital, Japan
| | - Masaaki Noguchi
- Department of Hematology, Juntendo University Urayasu Hospital, Japan
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29
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Yang M, Zhang T, Yan B, Huang Y. Value of Combined Diagnosis for Choroidal Lymphoma: A Case Report. Curr Oncol 2022; 29:8835-8845. [PMID: 36421348 PMCID: PMC9689627 DOI: 10.3390/curroncol29110695] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/19/2022] [Revised: 10/26/2022] [Accepted: 11/16/2022] [Indexed: 11/19/2022] Open
Abstract
Intraocular lymphoma (IOL) comprises a group of malignant tumours originating from lymphohematopoietic tissues that have a poor prognosis. These tumours predominantly occur in the vitreous and retina but are rarely found in the choroid. A few case reports and case series of choroidal lymphoma (CL) have been reported in the literature. CL is prone to misdiagnosis and incorrect treatment because it often mimics other intraocular diseases such as uveitis. This may seriously affect localisation of the primary lesion and delay treatment, which may even affect the patient's survival. Herein, we report a case of CL and propose the combination of characteristic ophthalmic imaging with systemic imaging and aqueous humour detection to establish a robust basis for the early diagnosis of CL.
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30
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Lee D, Lee J, Nahm JH, Kim M. Diagnostic Accuracy of Vitreous Cytology in Patients with Vitreoretinal Lymphoma. J Clin Med 2022; 11:jcm11216450. [PMID: 36362676 PMCID: PMC9656894 DOI: 10.3390/jcm11216450] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/16/2022] [Revised: 10/23/2022] [Accepted: 10/29/2022] [Indexed: 11/06/2022] Open
Abstract
(1) Background: To determine the diagnostic value of vitreous cytology in patients with vitreoretinal lymphoma (VRL) and evaluate its diagnostic accuracy relative to that of other diagnostic tests. (2) Methods: In total, 38 eyes from 38 patients with VRL who underwent diagnostic vitrectomy and were followed up for at least 6 months were analyzed. The clinical manifestations and VRL diagnostic rates for all diagnostic tests were determined. (3) Results: The presence of vitreous cells/opacity was the most common ophthalmic finding (97.4%), followed by sub-retinal pigment epithelial infiltration (65.8%) and retinal hemorrhage (21.1%). The VRL diagnostic rates were 89.3% for interleukin (IL)-10 levels > 50 pg/mL; 82.1% for IL-10/IL-6 ratios > 1; 60.0% and 63.3% for immunoglobulin heavy chain and kappa light chain clonality assays, respectively; and 44.4% for vitreous cytology. The VRL diagnostic rate for vitreous cytology was significantly lower in the steroid pretreatment group than in the non-steroid pretreatment group (p = 0.007). (4) Conclusions: The VRL detection rate for vitreous cytology was lower than that for the other tests, especially in patients who received steroid pretreatment. These findings suggest that even if vitreous cytology findings are negative, other tests and characteristic fundus findings should be evaluated to confirm VRL diagnosis.
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Affiliation(s)
- Donghyun Lee
- Department of Ophthalmology, Inha University Hospital, Inha University College of Medicine, Incheon 22332, Korea
- Department of Ophthalmology, Gangnam Severance Hospital, Yonsei University College of Medicine, Seoul 03722, Korea
| | - Junwon Lee
- Department of Ophthalmology, Gangnam Severance Hospital, Yonsei University College of Medicine, Seoul 03722, Korea
| | - Ji-Hae Nahm
- Department of Pathology, Gangnam Severance Hospital, Yonsei University College of Medicine, Seoul 03722, Korea
| | - Min Kim
- Department of Ophthalmology, Gangnam Severance Hospital, Yonsei University College of Medicine, Seoul 03722, Korea
- Correspondence: ; Tel.: +82-2-2019-3440
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31
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Gozzi F, Aldigeri R, Mastrofilippo V, De Simone L, Bolletta E, Marzano J, Iannetta D, Coassin M, Ilariucci F, Ferrari A, Luminari S, Merli F, Croci S, Zerbini A, Farnetti E, Nicoli D, Valli R, Tamagnini I, Cavazza A, Salvarani C, Fontana L, Cimino L. Survival and Recurrence in Vitreoretinal Lymphoma Simulating Uveitis at Presentation: The Possible Role of Combined Chemotherapy. Ocul Immunol Inflamm 2022; 30:1833-1841. [PMID: 34379571 DOI: 10.1080/09273948.2021.1962916] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/16/2022]
Abstract
PURPOSE To investigate the role of combined systemic and local chemotherapy in improving the survival of patients with vitreoretinal lymphoma (VRL). METHODS Patients with VRL consecutively seen from 2006 to 2020 were retrospectively reviewed; data on the presence and time of central nervous system (CNS) involvement and treatment regimen (systemic, local or combined chemotherapy) were collected. Overall survival (OS) and progression-free survival (PFS) were calculated for each group. RESULTS Forty-three eyes of 22 subjects with histology-proven VRL were included. Mean time of survival was 64.8 months (SE±10.8). Twelve patients (57%) presented CNS involvement, which was significantly associated with progression (r = 0.48, P = .03) and death (r = 0.56, P = .009). The isolated primary VRL group had a 5-year OS of 80%. Combined systemic and local chemotherapy reduced the risk of death by 82% (hazard ratio 0.18[0.04- 0.85]) in the entire cohort. CONCLUSION Combined systemic and local chemotherapy significantly improved OS but not PFS of patients affected by VRL.
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Affiliation(s)
- Fabrizio Gozzi
- Ocular Immunology Unit, Azienda USL-IRCCS, Reggio Emilia, Italy
| | | | | | - Luca De Simone
- Ocular Immunology Unit, Azienda USL-IRCCS, Reggio Emilia, Italy
| | - Elena Bolletta
- Ocular Immunology Unit, Azienda USL-IRCCS, Reggio Emilia, Italy
| | - Jacopo Marzano
- Department of Medical, Surgical and Experimental Sciences, University of Sassari, Sassari, Italy
| | | | - Marco Coassin
- Department of Ophthalmology, University Campus Bio-Medico of Rome, Rome, Italy
| | | | - Angela Ferrari
- Hematology Unit, Azienda USL-IRCCS, Reggio Emilia, Italy
| | - Stefano Luminari
- Hematology Unit, Azienda USL-IRCCS, Reggio Emilia, Italy.,Department of Surgery, Medicine, Dentistry and Morphological Sciences, with Interest in Transplants, Oncology and Regenerative Medicine, University of Modena and Reggio Emilia, Modena, Italy
| | | | - Stefania Croci
- Clinical Immunology, Allergy and Advanced Biotechnologies Unit, Azienda USL-IRCCS, Reggio Emilia, Italy
| | - Alessandro Zerbini
- Clinical Immunology, Allergy and Advanced Biotechnologies Unit, Azienda USL-IRCCS, Reggio Emilia, Italy
| | - Enrico Farnetti
- Molecular Biology Laboratory, Azienda USL-IRCCS, Reggio Emilia, Italy
| | - Davide Nicoli
- Molecular Biology Laboratory, Azienda USL-IRCCS, Reggio Emilia, Italy
| | | | | | | | - Carlo Salvarani
- Department of Surgery, Medicine, Dentistry and Morphological Sciences, with Interest in Transplants, Oncology and Regenerative Medicine, University of Modena and Reggio Emilia, Modena, Italy.,Rheumatology Unit, Azienda USL-IRCCS of Reggio Emilia, Reggio Emilia, Italy
| | - Luigi Fontana
- Ophthalmology Unit, Azienda USL-IRCCS, Reggio Emilia, Italy
| | - Luca Cimino
- Ocular Immunology Unit, Azienda USL-IRCCS, Reggio Emilia, Italy
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32
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Chen T, Liu Y, Wang Y, Chang Q, Wu J, Wang Z, Geng D, Yu JT, Li Y, Li XQ, Chen H, Zhuang D, Li J, Wang B, Jiang T, Lyu L, Song Y, Qiu X, Li W, Lin S, Zhang X, Lu D, Lei J, Chen Y, Mao Y. Evidence-based expert consensus on the management of primary central nervous system lymphoma in China. J Hematol Oncol 2022; 15:136. [PMID: 36176002 PMCID: PMC9524012 DOI: 10.1186/s13045-022-01356-7] [Citation(s) in RCA: 29] [Impact Index Per Article: 9.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/04/2022] [Accepted: 09/19/2022] [Indexed: 12/13/2024] Open
Abstract
Primary central nervous system lymphoma (PCNSL) is a type of central nervous system restricted non-Hodgkin lymphoma, whose histopathological diagnosis is majorly large B cell lymphoma. To provide specific, evidence-based recommendations for medical professionals and to promote more standardized, effective and safe treatment for patients with PCNSL, a panel of experts from the Chinese Neurosurgical Society of the Chinese Medical Association and the Society of Hematological Malignancies of the Chinese Anti-Cancer Association jointly developed an evidence-based consensus. After comprehensively searching literature and conducting systematic reviews, two rounds of Delphi were conducted to reach consensus on the recommendations as follows: The histopathological specimens of PCNSL patients should be obtained as safely and comprehensively as possible by multimodal tomography-guided biopsy or minimally invasive surgery. Corticosteroids should be withdrawn from, or not be administered to, patients with suspected PCNSL before biopsy if the patient's status permits. MRI (enhanced and DWI) should be performed for diagnosing and evaluating PCNSL patients where whole-body PET-CT be used at necessary time points. Mini-mental status examination can be used to assess cognitive function in the clinical management. Newly diagnosed PCNSL patients should be treated with combined high-dose methotrexate-based regimen and can be treated with a rituximab-inclusive regimen at induction therapy. Autologous stem cell transplantation can be used as a consolidation therapy. Refractory or relapsed PCNSL patients can be treated with ibrutinib with or without high-dose chemotherapy as re-induction therapy. Stereotactic radiosurgery can be used for PCNSL patients with a limited recurrent lesion who were refractory to chemotherapy and have previously received whole-brain radiotherapy. Patients with suspected primary vitreoretinal lymphoma (PVRL) should be diagnosed by vitreous biopsy. PVRL or PCNSL patients with concurrent VRL can be treated with combined systemic and local therapy.
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Affiliation(s)
- Tong Chen
- Department of Hematology, Institute of Medicine, Huashan Hospital, Fudan University, Shanghai, 200040, China.
| | - Yuanbo Liu
- Department of Hematology, Beijing Tiantan Hospital, Capital Medical University, Beijing, 100070, China
| | - Yang Wang
- Department of Radiation Oncology, Huashan Hospital, Fudan University, Shanghai, 201107, China.,National Center for Neurological Disorders, Huashan Hospital, Fudan University, Shanghai, 200040, China
| | - Qing Chang
- Department of Ophthalmology, Eye and ENT Hospital, Fudan University, Shanghai, 200031, China
| | - Jinsong Wu
- Department of Neurosurgery, National Center for Neurological Disorders, Huashan Hospital, Fudan University, Shanghai, 200040, China.,Institute of Medicine, Huashan Hospital, Fudan University, Shanghai, 200040, China
| | - Zhiliang Wang
- Department of Ophthalmology, Huashan Hospital, Fudan University, Shanghai, 200040, China
| | - Daoying Geng
- Department of Radiology, Huashan Hospital, Fudan University, Shanghai, 200040, China
| | - Jin-Tai Yu
- Department of Neurology, Huashan Hospital, Fudan University, Shanghai, 200040, China
| | - Yuan Li
- Department of Radiology, Huashan Hospital, Fudan University, Shanghai, 200040, China
| | - Xiao-Qiu Li
- Department of Pathology, Fudan University Shanghai Cancer Center, Shanghai, 200032, China
| | - Hong Chen
- Department of Pathology, Huashan Hospital, Fudan University, Shanghai, 200040, China
| | - Dongxiao Zhuang
- Department of Neurosurgery, National Center for Neurological Disorders, Huashan Hospital, Fudan University, Shanghai, 200040, China
| | - Jianyong Li
- Department of Hematology, The First Affiliated Hospital of Nanjing Medical University, Jiangsu Province Hospital, Nanjing, 210029, China
| | - Bin Wang
- Department of Pharmacy, Huashan Hospital, Fudan University, Shanghai, 200040, China
| | - Tao Jiang
- Department of Neurosurgery, Beijing Neurosurgical Institute, Beijing Tiantan Hospital, Capital Medical University, Beijing, 100070, China
| | - Lanting Lyu
- School of Public Administration and Policy, Health Technology Assessment and Policy Evaluation Group, Renmin University of China, Beijing, 100872, China
| | - Yuqin Song
- Department of Lymphoma, Peking University Cancer Hospital and Institute, Beijing, 100142, China
| | - Xiaoguang Qiu
- Department of Radiation Oncology, Beijing Tiantan Hospital, Capital Medical University, Beijing, 100070, China
| | - Wenbin Li
- Department of Neuro-Oncolgoy, Cancer Center, National Clinical Research Center for Neurological Diseases, Beijing Tiantan Hospital, Capital Medical University, Beijing, 100070, China
| | - Song Lin
- Department of Neurosurgery, Beijing Neurosurgical Institute, Beijing Tiantan Hospital, Capital Medical University, Beijing, 100070, China
| | - Xinghu Zhang
- Department of Neurology, Neuroimmunology and Neuroinfection Center, Beijing Tiantan Hospital, Capital Medical University, Beijing, 100070, China
| | - Dehong Lu
- Department of Pathology, Xuanwu Hospital, Capital Medical University, Beijing, 100053, China
| | - Junqiang Lei
- Department of Radiology, The First Hospital of Lanzhou University, Lanzhou, 730000, China
| | - Yaolong Chen
- Research Unit of Evidence-Based Evaluation and Guidelines, Chinese Academy of Medical Sciences (2021RU017), School of Basic Medical Sciences, Lanzhou University, Lanzhou, 730000, China. .,WHO Collaborating Center for Guideline Implementation and Knowledge Translation, Lanzhou University, Lanzhou, 730000, China. .,Lanzhou University GRADE Center, Lanzhou, 730000, China.
| | - Ying Mao
- Department of Neurosurgery, National Center for Neurological Disorders, Huashan Hospital, Fudan University, Shanghai, 200040, China. .,Institute of Medicine, Huashan Hospital, Fudan University, Shanghai, 200040, China.
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33
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Heiferman MJ, Yu MD, Mruthyunjaya P. Update in Molecular Testing for Intraocular Lymphoma. Cancers (Basel) 2022; 14:4546. [PMID: 36230469 PMCID: PMC9558525 DOI: 10.3390/cancers14194546] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/22/2022] [Revised: 09/11/2022] [Accepted: 09/16/2022] [Indexed: 11/21/2022] Open
Abstract
The diagnosis of primary vitreoretinal lymphoma and central nervous system lymphoma is challenging. In cases with intraocular involvement, vitreous biopsy plays a pivotal role. Several diagnostic tests are employed to confirm a diagnosis and include cytologic evaluation, immunohistochemistry, flow cytometry, and cytokine analysis. The limitations of these conventional diagnostic tests stem from the often paucicellular nature of vitreous biopsy specimens and the fragility of malignant cells ex vivo. Several emerging molecular techniques show promise in improving the diagnostic yield of intraocular biopsy, possibly enabling more accurate and timely diagnoses. This article will review existing diagnostic modalities for intraocular lymphoma, with an emphasis on currently available molecular tests.
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Affiliation(s)
- Michael J. Heiferman
- Department of Ophthalmology and Visual Sciences, Illinois Eye and Ear Infirmary, University of Illinois at Chicago, Chicago, IL 60612, USA
- Department of Ophthalmology, Byers Eye Institute, Stanford University, Palo Alto, CA 94303, USA
| | - Michael D. Yu
- Department of Ophthalmology, Byers Eye Institute, Stanford University, Palo Alto, CA 94303, USA
| | - Prithvi Mruthyunjaya
- Department of Ophthalmology, Byers Eye Institute, Stanford University, Palo Alto, CA 94303, USA
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Tian S, Chen K, Xiao J, Zhou X, Shi H, Li Y, Huang H, Ma Y, Chen B, Wang Q, Guan M. Logistic regression models of cytokines in differentiating vitreoretinal lymphoma from uveitis. J Clin Lab Anal 2022; 36:e24689. [PMID: 36098043 PMCID: PMC9550960 DOI: 10.1002/jcla.24689] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/18/2022] [Revised: 08/18/2022] [Accepted: 08/25/2022] [Indexed: 11/09/2022] Open
Abstract
Background Vitreoretinal lymphoma (VRL) can commonly masquerade as chronic idiopathic uveitis due to its nonspecific clinical presentation. Thus, its early diagnosis is difficult. In this study, new logistic regression models were used to classify VRL and uveitis. Additionally, the diagnostic performance of interleukin (IL)‐10, the IL‐10/IL‐6, and the Interleukin Score for IntraOcular Lymphoma Diagnosis (ISOLD) are evaluated. Methods Sixty‐nine aqueous humors (AH) (46 VRL, 23 uveitis) and 65 vitreous humors (VH) (49 VRL, 16 uveitis) were collected from a single‐center retrospective cohort. Logistic regression models were conducted based on IL‐6 and IL‐10. The cut‐off values, area under the receiver operating characteristic curve (ROC) curve (AUC), sensitivity and specificity of IL‐10, the IL‐10/IL‐6, the ISOLD, and the models were calculated from the ROC. Furthermore, Spearman's rank correlation analysis was performed to determine cytokine levels in VH and AH. Results We redefined the cut‐off values of IL‐10, the IL‐10/IL‐6, the ISOLD, and the logistic regression models. In AH, the AUC values of IL‐10, ISOLD, IL10/IL6, and the model were 0.91, 0.953, 0.952, and 0.967. In VH, they were 0.93, 0.95, 0.954, and 0.954, respectively. IL‐6 (r = 0.7844) and IL‐10 (r = 0.8506) in AH and VH showed a strong correlation. Conclusions IL‐6 and IL‐10 levels were introduced into new logistic regression models. The diagnostic efficacy of the models improved compared to the indicators mentioned above among Chinese patients. Additionally, the models could predict the probability of VRL more accurately. A strong correlation of cytokine levels showed the great potential of AH as prioritized auxiliary diagnostic for VRL.
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Affiliation(s)
- Sha Tian
- Department of Ophthalmology, Huashan Hospital, Fudan University, Shanghai, China.,Department of Ophthalmology, Jinshan Hospital, Fudan University, Shanghai, China
| | - Kun Chen
- Department of Laboratory Medicine, Huashan Hospital, Fudan University, Shanghai, China
| | - Jianjiang Xiao
- Department of Ophthalmology, Huashan Hospital, Fudan University, Shanghai, China
| | - Xian Zhou
- Department of Ophthalmology, Huashan Hospital, Fudan University, Shanghai, China
| | - Huimin Shi
- Department of Ophthalmology, Huashan Hospital, Fudan University, Shanghai, China
| | - Yi Li
- Department of Ophthalmology, Huashan Hospital, Fudan University, Shanghai, China
| | - Hehe Huang
- Department of Ophthalmology, Huashan Hospital, Fudan University, Shanghai, China
| | - Yanchun Ma
- Department of Laboratory Medicine, Huashan Hospital, Fudan University, Shanghai, China
| | - Bobin Chen
- Department of Hematology, Huashan Hospital, Fudan University, Shanghai, China
| | - Qingping Wang
- Department of Ophthalmology, Huashan Hospital, Fudan University, Shanghai, China
| | - Ming Guan
- Department of Laboratory Medicine, Huashan Hospital, Fudan University, Shanghai, China
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35
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Wang X, Su W, Gao Y, Feng Y, Wang X, Chen X, Hu Y, Ma Y, Ou Q, Liang D, Huang H. A pilot study of the use of dynamic analysis of cell-free DNA from aqueous humor and vitreous fluid for the diagnosis and treatment monitoring of vitreoretinal lymphomas. Haematologica 2022; 107:2154-2162. [PMID: 35142151 PMCID: PMC9425330 DOI: 10.3324/haematol.2021.279908] [Citation(s) in RCA: 10] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/07/2021] [Accepted: 02/02/2022] [Indexed: 12/02/2022] Open
Abstract
The diagnosis of vitreoretinal lymphoma (VRL), a rare subtype of primary central nervous system lymphoma, is challenging. We aimed to investigate the mutational landscape of VRL by sequencing circulating tumor DNA (ctDNA) from aqueous humor (AH) and/or vitreous fluid (VF), as well as applying ctDNA sequencing to diagnosis and treatment monitoring. Baseline AH and/or VF specimens from 15 VRL patients underwent comprehensive genomic profiling using targeted next-generation sequencing. The molecular profiles of paired baseline AH and VF specimens were highly concordant, with comparable allele frequencies. However, the genetic alterations detected in cerebrospinal fluid ctDNA only partially overlapped with those from simultaneously collected AH/VF samples, with much lower allele frequencies. Serial post-treatment AH or VF samples were available for five patients and their changes in ctDNA allele frequency displayed a similar trend as the changes in interleukin-10 levels; an indicator of response to treatment. A cohort of 23 patients with primary central nervous system lymphoma was included as a comparison group for the genetic landscape and evaluations of the efficacy of ibrutinib. More MYD88 mutations, but fewer IRF4 mutations and CDKN2A/B copy number losses were observed in the baseline samples of primary central nervous system lymphoma than VRL patients. The objective response rate to ibrutinib treatment was much higher for patients with primary central nervous system lymphoma (64.7%, 11/17) than for those with VRL (14.3%, 1/7). In summary, we provide valuable clinical evidence that AH is a good source of tumor genomic information and can substitute VF. Moreover, molecular profiling of AH has clinical utility for the diagnosis of VRL and treatment monitoring.
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Affiliation(s)
- Xiaoxiao Wang
- State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, China; Department of Medical Oncology, Sun Yat-sen University Cancer Center, Guangzhou
| | - Wenru Su
- State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangzhou
| | - Yan Gao
- State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, China; Department of Medical Oncology, Sun Yat-sen University Cancer Center, Guangzhou
| | - Yanfen Feng
- State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, China; Department of Pathology, Sun Yat-sen University Cancer Center, Guangzhou
| | - Xiaoxia Wang
- Geneseeq Research Institute, Nanjing Geneseeq Technology Inc., Nanjing, Jiangsu
| | - Xiaoqing Chen
- State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangzhou
| | - Yunwei Hu
- State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangzhou
| | - Yutong Ma
- Geneseeq Research Institute, Nanjing Geneseeq Technology Inc., Nanjing, Jiangsu
| | - Qiuxiang Ou
- Geneseeq Research Institute, Nanjing Geneseeq Technology Inc., Nanjing, Jiangsu
| | - Dan Liang
- State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangzhou.
| | - Huiqiang Huang
- State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, China; Department of Medical Oncology, Sun Yat-sen University Cancer Center, Guangzhou.
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Zhuang Z, Zhang Y, Zhang X, Zhang M, Zou D, Zhang L, Jia C, Zhang W. Circulating cell-free DNA and IL-10 from cerebrospinal fluids aid primary vitreoretinal lymphoma diagnosis. Front Oncol 2022; 12:955080. [PMID: 36059608 PMCID: PMC9434796 DOI: 10.3389/fonc.2022.955080] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/28/2022] [Accepted: 06/29/2022] [Indexed: 11/17/2022] Open
Abstract
Primary vitreoretinal lymphoma (PVRL) is a rare variant of primary central nervous system lymphoma (PCNSL) that presents diagnostic challenges. Here, we focused on circulating cell-free DNA (cfDNA) and interleukin-10 (IL-10) isolated from cerebrospinal fluid. Twenty-three VRL patients (17 PVRL, 2 PCNSL/O, and 4 relapsed VRL, from 10/2018 to 12/2021) and 8 uveitis patients were included in this study. CSF samples from 19 vitreoretinal lymphoma patients had sufficient cfDNA for next-generation sequencing. Of these patients, 73.7% (14/19) had at least one meaningful non-Hodgkin lymphoma-related mutation. The characteristic MYD88 L265P mutation was detected in the CSF of 12 VRL patients, with a sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of 63.2%, 100%, 100%, and 46.2%, respectively. No meaningful lymphoma related mutations were found in CSF samples from uveitis controls with typical intraocular lesions. Meanwhile, CSF IL-10 levels were elevated in 95.7% of the VRL patients, with a sensitivity, specificity, PPV, and NPV of 95.7%, 100%, 100% and 88.9%, respectively. Key somatic mutations like MYD88 L265P and CD79B detected from CSF cfDNA and elevated CSF IL-10 levels can be promising adjuncts for primary vitreoretinal lymphoma diagnosis.
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Affiliation(s)
- Zhe Zhuang
- Department of Hematology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China
| | - Yan Zhang
- Department of Hematology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China
| | - Xiao Zhang
- Department of Ophthalmology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China
| | - Meifen Zhang
- Department of Ophthalmology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China
| | - Dongmei Zou
- Department of Hematology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China
| | - Li Zhang
- Department of Clinical Laboratory, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China
| | - Congwei Jia
- Department of Pathology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China
| | - Wei Zhang
- Department of Hematology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China,*Correspondence: Wei Zhang,
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37
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Tanaka R, Kaburaki T, Taoka K, Karakawa A, Tsuji H, Nishikawa M, Yatomi Y, Shinozaki-Ushiku A, Ushiku T, Araki F. More Accurate Diagnosis of Vitreoretinal Lymphoma Using a Combination of Diagnostic Test Results: A Prospective Observational Study. Ocul Immunol Inflamm 2022; 30:1354-1360. [PMID: 33793360 DOI: 10.1080/09273948.2021.1873394] [Citation(s) in RCA: 12] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/14/2020] [Revised: 12/15/2020] [Accepted: 01/04/2021] [Indexed: 10/21/2022]
Abstract
PURPOSE To establish diagnostic criteria for vitreoretinal lymphoma (VRL) using cytology and laboratory tests from vitreous samples: interleukin (IL)-10/IL-6 ratio, immunoglobulin (Ig) H gene rearrangement, and clonal B-cells on flow cytometry. METHODS Fifty-six patients with and 39 without VRL were included. We assessed the sensitivity and specificity of each test and those of diagnostic criteria based on combinations of these tests. RESULTS The sensitivity values for malignant cytology, IL-10/IL-6 > 1, IgH gene rearrangement, and flow cytometry were 0.554, 0.821, 0.732, and 0.625 with specificity of 1.000, 1.000, 0.846, and 0.974, respectively. When the diagnostic criteria were set at malignant cytology or at two or more of of four tests (atypical cells, IL-10/IL-6 > 1, IgH gene rearrangement, and flow cytometry), the sensitivity and specificity values for accurate diagnosis were 0.929 and 1.00, respectively. CONCLUSION Malignant cytology or positive results for two or more of four tests may be adequate for VRL diagnosis.
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Affiliation(s)
- Rie Tanaka
- Department of Ophthalmology, The University of Tokyo Hospital, Tokyo, Japan
| | - Toshikatsu Kaburaki
- Department of Ophthalmology, The University of Tokyo Hospital, Tokyo, Japan
- Department of Ophthalmology, Jichi Medical University Saitama Medical Center, Saitama, Japan
| | - Kazuki Taoka
- Department of Haematology and Oncology, The University of Tokyo Hospital, Tokyo, Japan
| | - Ayako Karakawa
- Department of Ophthalmology, The University of Tokyo Hospital, Tokyo, Japan
| | - Hideki Tsuji
- Department of Ophthalmology, The Cancer Institute Hospital of JFCR, Tokyo, Japan
| | - Masako Nishikawa
- Department of Clinical Laboratory, The University of Tokyo Hospital, Tokyo, Japan
| | - Yutaka Yatomi
- Department of Clinical Laboratory, The University of Tokyo Hospital, Tokyo, Japan
| | | | - Tetsuo Ushiku
- Department of Pathology, The University of Tokyo Hospital, Tokyo, Japan
| | - Fumiyuki Araki
- Department of Ophthalmology, The University of Tokyo Hospital, Tokyo, Japan
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38
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Zamani G, Hajipour A, Ganjeifar B, Ebrahimiadib N, Hosseini SM. Intraocular lymphoma masquerading as unilateral hypopyon anterior uveitis: a case report. J Ophthalmic Inflamm Infect 2022; 12:25. [PMID: 35900606 PMCID: PMC9334462 DOI: 10.1186/s12348-022-00302-5] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/12/2022] [Accepted: 07/17/2022] [Indexed: 11/24/2022] Open
Abstract
Purpose To report an unusual case of unilateral anterior segment large B-cell intraocular lymphoma (IOL) presenting as a recurrent hypopyon anterior uveitis. Case presentation A 55-year-old female was referred because of recurrent unilateral anterior hypopyon uveitis with partial response to topical corticosteroid. All of the laboratory tests, review of systems and ocular sampling results were unremarkable. Given a high concern for masquerades syndromes, cytological specimens were obtained 3 times and the last sample showed large B cell lymphoma. First, it appeared confined to the eye and initially responded favorably to local chemotherapy (methotrexate and rituximab) but later went on to develop systemic involvement. CNS lymphoma was detected on the third brain MRI 6 months following ocular involvement. At this time, systemic chemotherapy was started. In the last 18 months’ follow-up, visual acuity was 20/30 in the right eye without posterior segment or fellow eye involvement. Conclusion Unusual presentation of intraocular lymphoma as a unilateral isolated anterior hypopyon uveitis should be kept in mind. This report emphasizes the importance of precise work-ups and multiple ocular biopsies to confirm the diagnosis of intraocular lymphoma.
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Affiliation(s)
- Ghodsieh Zamani
- Eye Research Center, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Atefeh Hajipour
- Eye Research Center, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Babak Ganjeifar
- Department of Neurosurgery, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Nazanin Ebrahimiadib
- Ophthalmology Department, Retina Service, Farabi Eye Hospital, Tehran University of Medical Sciences, Tehran, Iran.,Ophthalmology Department, Ocular Immunology and Uveitis Foundation, Waltham, MA, USA
| | - Seyedeh Maryam Hosseini
- Eye Research Center, Mashhad University of Medical Sciences, Mashhad, Iran. .,Eye Research Center, Khatam-al-Anbia Eye Hospital, Qarani Blvd, Mashhad, 9195965919, Iran.
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Gu J, Jiang T, Liu S, Ping B, Li R, Chen W, Wang L, Huang X, Xu G, Chang Q. Cell-Free DNA Sequencing of Intraocular Fluid as Liquid Biopsy in the Diagnosis of Vitreoretinal Lymphoma. Front Oncol 2022; 12:932674. [PMID: 35928872 PMCID: PMC9343589 DOI: 10.3389/fonc.2022.932674] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/30/2022] [Accepted: 06/13/2022] [Indexed: 12/15/2022] Open
Abstract
Purpose To seek novel diagnostic approaches, we improved the workflow of cell-free DNA (cfDNA) sequencing and evaluated its feasibility in vitreoretinal lymphoma (VRL) specimens; the profile of mutations was preliminarily analyzed for potential diagnostic value. Methods The study was a diagnostic trial. 23 eyes of 23 patients with VRL and 25 eyes of 25 patients with inflammatory eye diseases were enrolled. Approximate 500μl undiluted vitreous humor and 10ml diluted vitreous fluid was obtained through diagnostic vitrectomy and sent for cytopathological examinations. 500μl of the diluted vitreous fluid was spared for cfDNA sequencing. For cfDNA sequencing, DNA fragmentation procedure was added to the workflow to improve the extraction efficiency; mutations detected were analyzed for potential diagnostic model. The sensitivity and specificity of the cytopathology and cfDNA sequencing were compared. The clinical manifestations were preliminarily analyzed for potential correlations with the genotypes. Results CfDNA sequencing was accomplished in 23 eyes with VRL and 20 eyes with inflammatory eye diseases. VRL-related mutated genes included MYD88 (18 eyes, 78%), ETV6 (11 eyes, 48%), PIM1 (11 eyes,48%), BTG2 (7 eyes, 30%), IRF4 (7 eyes, 30%), CD79B (6 eyes, 26%), LRP1B (6 eyes, 26%), etc. Logistic regression based on the mutations of MYD88 and ETV6 was of the potential for the diagnosis of VRL (P<0.001, adjusted R2 = 0.789, sensitivity 0.913, specificity 0.950); by comparison, the sensitivity and specificity of the vitreous cytopathology were 0.826 and 1.000, respectively. Further analysis of the mutation profile showed that patients carrying CD79B mutation tended to have higher intraocular interleukin-10 level (P=0.030), that CARD11 mutation was correlated with younger age at ocular onset (P=0.039), and that patients with intracranial involvement carried more multiple-site mutations in the BTG2 gene (P=0.013). Conclusions The improved workflow of CfDNA sequencing is of sound feasibility in a limited amount of vitreous humor. The logistic model based on the mutations could help to provide reliable clues for the diagnosis of VRL.
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Affiliation(s)
- Junxiang Gu
- Department of Ophthalmology, Eye and ENT Hospital of Fudan University, Fudan University, Shanghai, China
- Shanghai Key Laboratory of Visual Impairment and Restoration, Eye and ENT Hospital of Fudan University, Fudan University, Shanghai, China
- National Health Commission (NHC) Key Laboratory of Myopia (Fudan University), Key Laboratory of Myopia, Chinese Academy of Medical Science, Shanghai, China
| | - Tingting Jiang
- Department of Ophthalmology, Eye and ENT Hospital of Fudan University, Fudan University, Shanghai, China
- Shanghai Key Laboratory of Visual Impairment and Restoration, Eye and ENT Hospital of Fudan University, Fudan University, Shanghai, China
- National Health Commission (NHC) Key Laboratory of Myopia (Fudan University), Key Laboratory of Myopia, Chinese Academy of Medical Science, Shanghai, China
| | - Shixue Liu
- Department of Ophthalmology, Eye and ENT Hospital of Fudan University, Fudan University, Shanghai, China
- Shanghai Key Laboratory of Visual Impairment and Restoration, Eye and ENT Hospital of Fudan University, Fudan University, Shanghai, China
- National Health Commission (NHC) Key Laboratory of Myopia (Fudan University), Key Laboratory of Myopia, Chinese Academy of Medical Science, Shanghai, China
| | - Bo Ping
- Department of Pathology, Fudan University Shanghai Cancer Center, Fudan University, Shanghai, China
| | - Ruiwen Li
- Department of Nursing, Eye and ENT Hospital of Fudan University, Fudan University, Shanghai, China
| | - Wenwen Chen
- Department of Ophthalmology, Eye and ENT Hospital of Fudan University, Fudan University, Shanghai, China
- Shanghai Key Laboratory of Visual Impairment and Restoration, Eye and ENT Hospital of Fudan University, Fudan University, Shanghai, China
- National Health Commission (NHC) Key Laboratory of Myopia (Fudan University), Key Laboratory of Myopia, Chinese Academy of Medical Science, Shanghai, China
| | - Ling Wang
- Department of Ophthalmology, Eye and ENT Hospital of Fudan University, Fudan University, Shanghai, China
- Shanghai Key Laboratory of Visual Impairment and Restoration, Eye and ENT Hospital of Fudan University, Fudan University, Shanghai, China
- National Health Commission (NHC) Key Laboratory of Myopia (Fudan University), Key Laboratory of Myopia, Chinese Academy of Medical Science, Shanghai, China
| | - Xin Huang
- Department of Ophthalmology, Eye and ENT Hospital of Fudan University, Fudan University, Shanghai, China
- Shanghai Key Laboratory of Visual Impairment and Restoration, Eye and ENT Hospital of Fudan University, Fudan University, Shanghai, China
- National Health Commission (NHC) Key Laboratory of Myopia (Fudan University), Key Laboratory of Myopia, Chinese Academy of Medical Science, Shanghai, China
| | - Gezhi Xu
- Department of Ophthalmology, Eye and ENT Hospital of Fudan University, Fudan University, Shanghai, China
- Shanghai Key Laboratory of Visual Impairment and Restoration, Eye and ENT Hospital of Fudan University, Fudan University, Shanghai, China
- National Health Commission (NHC) Key Laboratory of Myopia (Fudan University), Key Laboratory of Myopia, Chinese Academy of Medical Science, Shanghai, China
| | - Qing Chang
- Department of Ophthalmology, Eye and ENT Hospital of Fudan University, Fudan University, Shanghai, China
- Shanghai Key Laboratory of Visual Impairment and Restoration, Eye and ENT Hospital of Fudan University, Fudan University, Shanghai, China
- National Health Commission (NHC) Key Laboratory of Myopia (Fudan University), Key Laboratory of Myopia, Chinese Academy of Medical Science, Shanghai, China
- *Correspondence: Qing Chang,
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Comprehensive Proteomic Profiling of Vitreous Humor in Ocular Sarcoidosis Compared with Other Vitreoretinal Diseases. J Clin Med 2022; 11:jcm11133606. [PMID: 35806888 PMCID: PMC9267904 DOI: 10.3390/jcm11133606] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/07/2022] [Revised: 06/04/2022] [Accepted: 06/19/2022] [Indexed: 12/10/2022] Open
Abstract
Ocular sarcoidosis is an inflammatory disease that manifests as uveitis, and is often difficult to distinguish from other forms of uveitis based on nonspecific findings alone. Comprehensive proteomic analyses of vitreous humor using LC-MS/MS were performed in each patient with ocular sarcoidosis, vitreoretinal lymphoma (VRL), and controls with epiretinal membrane or macular hole. Differential expression proteins (DEPs) were identified by comparing with VRL and controls, and functional pathway analysis was performed. The candidate biomarker proteins for ocular sarcoidosis were validated using enzyme-linked immunosorbent assay. A total of 1590 proteins were identified in all samples. Of these, 290 and 174 DEPs were detected in vitreous of ocular sarcoidosis compared with controls and VRL, respectively. Enrichment pathway analysis revealed that pathways related to the immune system were most upregulated. Validation of two candidate biomarkers for ocular sarcoidosis, neutrophil gelatinase-associated lipocalin (NGAL) and junctional adhesion molecules B (JAMB), confirmed upregulated NGAL and JAMB protein expressions in ocular sarcoidosis compared to controls and VRL. The results of this study revealed that altered vitreous protein expression levels may discriminate ocular sarcoidosis from other uveitis diseases. Vitreous NGAL and JAMB are potential biomarkers and may serve as an auxiliary tool for the diagnosis of ocular sarcoidosis.
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van Rooij JLM, Tokarska KA, ten Dam-van Loon NH, Wessels PH, Seute T, Minnema MC, Snijders TJ. Central Nervous System Progression in Primary Vitreoretinal Lymphoma with Bilateral and Unilateral Involvement: A Systematic Review and Meta-Analysis. Cancers (Basel) 2022; 14:2967. [PMID: 35740632 PMCID: PMC9221335 DOI: 10.3390/cancers14122967] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/03/2022] [Revised: 06/06/2022] [Accepted: 06/14/2022] [Indexed: 02/04/2023] Open
Abstract
BACKGROUND Primary vitreoretinal lymphoma (PVRL) is either unilateral or bilateral at initial presentation. Progression to a central nervous system (CNS) lymphoma is regularly observed and these patients seem to have an inferior survival. Knowledge of the predictive value of laterality for CNS progression may facilitate risk stratification and the development of more effective treatment strategies, and eventually, improve outcomes. The objective of this analysis is to estimate the risk of CNS progression for patients with bilateral versus unilateral involvement of PVRL. METHODS Systematic literature search for studies on CNS progression in PVRL with bilateral and unilateral involvement according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. We assessed the risk of bias and the methodological quality of studies using the Quality in Prognosis Studies (QUIPS) tool. Risk ratios of CNS progression in PVRL with bilateral and unilateral involvement were calculated and combined via a meta-analysis. RESULTS Twenty-five small-sized (total n = 371 cases) studies were included. The majority of the studies were at medium to high risk of bias. Results suggest no significant difference in CNS progression between bilateral and unilateral PVRL, with a pooled relative risk ratio of 1.12 (95% confidence interval 0.89-1.41). CONCLUSIONS CNS progression is common in PVRL. From the limited available evidence, there is no significant difference in CNS progression between bilateral and unilateral PVRL.
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Affiliation(s)
- Josephus L. M. van Rooij
- Department of Neurology and Neurosurgery, UMC Utrecht Brain Center, University Medical Center Utrecht, 3508 GA Utrecht, The Netherlands; (J.L.M.v.R.); (K.A.T.); (T.S.)
| | - Klaudia A. Tokarska
- Department of Neurology and Neurosurgery, UMC Utrecht Brain Center, University Medical Center Utrecht, 3508 GA Utrecht, The Netherlands; (J.L.M.v.R.); (K.A.T.); (T.S.)
| | | | - Peter H. Wessels
- Department of Neurology, St Antonius Hospital Utrecht/Nieuwegein, 3430 EM Nieuwegein, The Netherlands;
| | - Tatjana Seute
- Department of Neurology and Neurosurgery, UMC Utrecht Brain Center, University Medical Center Utrecht, 3508 GA Utrecht, The Netherlands; (J.L.M.v.R.); (K.A.T.); (T.S.)
| | - Monique C. Minnema
- Department of Hematology, University Medical Center Utrecht, 3508 GA Utrecht, The Netherlands;
| | - Tom J. Snijders
- Department of Neurology and Neurosurgery, UMC Utrecht Brain Center, University Medical Center Utrecht, 3508 GA Utrecht, The Netherlands; (J.L.M.v.R.); (K.A.T.); (T.S.)
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Advanced OCT Analysis of Biopsy-proven Vitreoretinal Lymphoma. Am J Ophthalmol 2022; 238:16-26. [PMID: 34843686 DOI: 10.1016/j.ajo.2021.11.023] [Citation(s) in RCA: 24] [Impact Index Per Article: 8.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/10/2021] [Revised: 11/17/2021] [Accepted: 11/18/2021] [Indexed: 11/21/2022]
Abstract
PURPOSE Although diagnosing vitreoretinal lymphoma (VRL) can be challenging, early detection is critical for visual prognosis. We analyzed the spectrum of optical coherence tomography (OCT) findings in patients with biopsy-proven VRL and correlate these features with clinical parameters. DESIGN This retrospective cross-sectional study was a multicenter chart review from 13 retina, uveitis, and ocular oncology clinics worldwide from 2008 to 2019. We included patients with a diagnosis of biopsy-proven VRL imaged with OCT at presentation. Ocular information, systemic information, and multimodal retinal imaging findings were collected and studied. The main outcome measure was the characteristics of VRL on OCT. RESULTS A total of 182 eyes of 115 patients (63 women, mean age 65 years) were included in this study. The disease was bilateral in 81 patients (70%), and mean baseline visual acuity was 0.2 ± 0.89 logMAR (Snellen equivalent, 20/32). At baseline, 38 patients (33%) presented with isolated ocular involvement, 54 (45%) with associated central nervous system involvement, and 11 (10%) with other systemic lymphomatous involvement; an additional 12 patients (10%) presented with central nervous system and other systemic involvement. On OCT, tumor infiltration was identified in various retinal layers, including lesions in the subretinal pigment epithelium compartment (91% of eyes), the subretinal compartment (43% of eyes), and the intraretinal compartment (7% of eyes). OCT analysis of eyes with VRL identified 3 main regions of retinal infiltration. Subretinal pigment epithelium location, with or without subretinal infiltration, was the most common pattern of involvement and isolated intraretinal infiltration was the least.
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Sakai A, Tagami M, Misawa N, Yamamoto M, Kohno T, Honda S. Safety and efficacy of 27-gauge transconjunctival vitrectomy for the diagnosis of posterior uveitis or pan uveitis of unknown origin. BMC Ophthalmol 2022; 22:178. [PMID: 35439966 PMCID: PMC9020057 DOI: 10.1186/s12886-022-02405-y] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/29/2021] [Accepted: 04/14/2022] [Indexed: 11/21/2022] Open
Abstract
Background Diagnostic vitrectomy is an important method for evaluating uveitis, and its diagnostic utility is high regardless of whether the uveitis is infectious or non-infectious. The course of diagnostic vitreous surgery with 27-gauge pars plana vitrectomy and perioperative complications is reported. Methods An observational retrospective study of patients who underwent 27-gauge diagnostic vitrectomy due to atypical intraocular inflammation was conducted. The final diagnosis rate, complications due to surgery, preoperative visual acuity, and postoperative visual acuity (1 month and 6 months after surgery) were examined retrospectively. Results Diagnostic vitreous surgery was performed in 32 patients and 35 eyes (14 males and 18 females, age 14–85 years, median 67 years) during the study period. The average operation time was 52 min for 19 eyes with cataract surgery and 35 min for 16 eyes without cataract surgery. Preoperative log(minimum angle of resolution [MAR]) visual acuity was 0.84 ± 0.87, 1-month postoperative logMAR visual acuity was 0.41 ± 0.55 (p = 0.004, n = 28), and 6-month postoperative average logMAR visual acuity was 0.45 ± 0.73 (p = 0.012, n = 15). The diagnosis was made by diagnostic vitrectomy in 19 cases (54%). Postoperative complications were observed in 2 of 35 postoperative patients (5%); one involved increased intraocular pressure, and the other case involved vitreous hemorrhage of the eye, necessitating reoperation. Conclusion Diagnostic 27-gauge vitrectomy could be effective for evaluating intraocular inflammation.
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Affiliation(s)
- Atsushi Sakai
- Department of Ophthalmology and Visual Sciences, Graduate School of Medicine, Osaka City University, Osaka, Japan
| | - Mizuki Tagami
- Department of Ophthalmology and Visual Sciences, Graduate School of Medicine, Osaka City University, Osaka, Japan.
| | - Norihiko Misawa
- Department of Ophthalmology and Visual Sciences, Graduate School of Medicine, Osaka City University, Osaka, Japan
| | - Manabu Yamamoto
- Department of Ophthalmology and Visual Sciences, Graduate School of Medicine, Osaka City University, Osaka, Japan
| | - Takeya Kohno
- Department of Ophthalmology and Visual Sciences, Graduate School of Medicine, Osaka City University, Osaka, Japan
| | - Shigeru Honda
- Department of Ophthalmology and Visual Sciences, Graduate School of Medicine, Osaka City University, Osaka, Japan
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Kase S, Namba K, Iwata D, Mizuuchi K, Suzuki K, Ito T, Hase K, Kitaichi N, Ishida S. Diagnostic Accuracy of Cell Block Preparations and Clinical Features Affecting It in Vitreoretinal Lymphoma. J Clin Med 2022; 11:jcm11051391. [PMID: 35268483 PMCID: PMC8911042 DOI: 10.3390/jcm11051391] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/10/2022] [Revised: 02/24/2022] [Accepted: 03/02/2022] [Indexed: 12/10/2022] Open
Abstract
Purpose: The purpose of this study was to examine the diagnostic accuracy of the cell block (CB) method and clinical features affecting it in patients with vitreoretinal lymphoma (VRL). Methods: This study enrolled 38 eyes in 33 VRL patients, and 7 eyes in 7 patients with idiopathic uveitis who underwent diagnostic vitrectomy. Medical records including the results of CB cytology, interleukin (IL)-10/-6 concentrations, and immunoglobulin heavy chain gene (IgH) rearrangement were retrospectively searched. Results: Patients with VRL comprised 16 women and 17 men, and the age of onset ranged from 44 to 85 years (mean: 70 years). CB preparations detected large malignant cells in 35 eyes (92%), whereas the other 3 VRL eyes were negative. Two of the latter three eyes showed subretinal infiltrates, which existed in 7 of 35 CB-positive eyes. Intravitreal IL-10 and -6 concentrations were 1866 ± 4088 pg/mL and 98 ± 139 pg/mL, respectively, and the rate of IL-10/-6 >1 was 86.9%. The presence of IgH monoclonality was 63.2%. In patients with uveitis, CB specimens revealed no atypical but small inflammatory cells. IL-6 concentration was 311.1 ± 240 pg/mL, whereas IL-10 was undetectable in six eyes, and the IL-negative rate was 85.7%. Six eyes (85.7%) with uveitis showed no IgH monoclonality. Conclusions: Diagnostic accuracy of CB preparations in VRL could achieve an equivalent outcome to IL ratio calculation and IgH monoclonality detection. The appearance of subretinal infiltrates may diminish the CB positivity.
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Affiliation(s)
- Satoru Kase
- Department of Ophthalmology, Faculty of Medicine and Graduate School of Medicine, Hokkaido University, Sapporo 060-8638, Japan; (S.K.); (D.I.); (K.M.); (K.S.); (T.I.); (K.H.); (N.K.); (S.I.)
| | - Kenichi Namba
- Department of Ophthalmology, Faculty of Medicine and Graduate School of Medicine, Hokkaido University, Sapporo 060-8638, Japan; (S.K.); (D.I.); (K.M.); (K.S.); (T.I.); (K.H.); (N.K.); (S.I.)
- Correspondence: ; Tel.: +81-11-706-5944; Fax: +81-11-706-5948
| | - Daiju Iwata
- Department of Ophthalmology, Faculty of Medicine and Graduate School of Medicine, Hokkaido University, Sapporo 060-8638, Japan; (S.K.); (D.I.); (K.M.); (K.S.); (T.I.); (K.H.); (N.K.); (S.I.)
| | - Kazuomi Mizuuchi
- Department of Ophthalmology, Faculty of Medicine and Graduate School of Medicine, Hokkaido University, Sapporo 060-8638, Japan; (S.K.); (D.I.); (K.M.); (K.S.); (T.I.); (K.H.); (N.K.); (S.I.)
| | - Kayo Suzuki
- Department of Ophthalmology, Faculty of Medicine and Graduate School of Medicine, Hokkaido University, Sapporo 060-8638, Japan; (S.K.); (D.I.); (K.M.); (K.S.); (T.I.); (K.H.); (N.K.); (S.I.)
| | - Takako Ito
- Department of Ophthalmology, Faculty of Medicine and Graduate School of Medicine, Hokkaido University, Sapporo 060-8638, Japan; (S.K.); (D.I.); (K.M.); (K.S.); (T.I.); (K.H.); (N.K.); (S.I.)
| | - Keitaro Hase
- Department of Ophthalmology, Faculty of Medicine and Graduate School of Medicine, Hokkaido University, Sapporo 060-8638, Japan; (S.K.); (D.I.); (K.M.); (K.S.); (T.I.); (K.H.); (N.K.); (S.I.)
| | - Nobuyoshi Kitaichi
- Department of Ophthalmology, Faculty of Medicine and Graduate School of Medicine, Hokkaido University, Sapporo 060-8638, Japan; (S.K.); (D.I.); (K.M.); (K.S.); (T.I.); (K.H.); (N.K.); (S.I.)
- Department of Ophthalmology, Health Sciences University of Hokkaido, Sapporo 061-0293, Japan
| | - Susumu Ishida
- Department of Ophthalmology, Faculty of Medicine and Graduate School of Medicine, Hokkaido University, Sapporo 060-8638, Japan; (S.K.); (D.I.); (K.M.); (K.S.); (T.I.); (K.H.); (N.K.); (S.I.)
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Zhou X, Tian S, Zhou X, Shi H, Li Y, Xiao J, Chen K, Chen B, Xu G, Wang Q. Optical Coherence Tomography Benefits the Diagnosis and Follow-Up of Primary Central Nervous System Lymphoma with Intraocular Involvement. Cancer Manag Res 2022; 14:1007-1018. [PMID: 35283643 PMCID: PMC8906865 DOI: 10.2147/cmar.s353142] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/17/2021] [Accepted: 02/24/2022] [Indexed: 01/25/2023] Open
Abstract
Purpose To describe the characteristic manifestations of vitreoretinal lymphoma (VRL) with optical coherence tomography (OCT) and monitor their outcomes after treatmEnt. Patients and Methods Patients with primary central nervous system lymphoma (PCNSL) and intraocular involvement were assigned to the VRL group. OCT manifestations were analyzed and changes in abnormalities were recorded after intravitreal methotrexate injections. OCT manifestations of PCNSL patients without intraocular involvement were analyzed as well (non-VRL group). Results There were 48 eyes with high-quality OCT records in the VRL group, of which 19 had abnormal manifestations. The most frequent abnormality was outer retina (OR) fuzzy borders (14 of 19, 73.7%). Other abnormalities included: focal subretinal deposits (8 of 19, 42.1%), hyperreflective subretinal dots (2 of 19, 10.5%), pigment epithelium detachment (PED) (5 of 19, 26.3%), preretinal deposits (5 of 19, 26.3%), epiretinal membrane (3 of 19, 15.8%), cystoid macular edema (3 of 19, 15.8%), subretinal fluid (3 of 19, 15.8%), outer retina atrophy (2 of 19, 10.5%), unilateral optic papilledema (2 of 19, 10.5%), retinal thickening (1 of 19, 5.3%), and subretinal fibrosis (1 of 19, 5.3%). Nine eyes with retinal abnormalities were receiving regular intravitreal methotrexate. The retinal structure of seven eyes (only outer retina involved) returned to almost normal on OCT images. The remaining two eyes (with severe retinal vasculitis) showed little improvement after treatment. Conclusion OCT is helpful for the diagnosis of PCNSL with intraocular involvement and long-term follow-up of the disease. Summary Statement The characteristic manifestations of vitreoretinal lymphoma (VRL) with optical coherence tomography (OCT) were described and their outcomes after treatment were monitored. These findings suggested that OCT is helpful for the diagnosis of PCNSL with intraocular involvement and long-term follow-up of the disease.
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Affiliation(s)
- Xianjin Zhou
- Eye Institute, Eye and ENT Hospital, College of Medicine, Fudan University, Shanghai, People’s Republic of China
- Shanghai Key Laboratory of Visual Impairment and Restoration, Science and Technology Commission of Shanghai Municipality, Shanghai, People’s Republic of China
- Department of Ophthalmology, Huashan Hospital, Fudan University, Shanghai, People’s Republic of China
| | - Sha Tian
- Department of Ophthalmology, Huashan Hospital, Fudan University, Shanghai, People’s Republic of China
| | - Xian Zhou
- Department of Ophthalmology, Huashan Hospital, Fudan University, Shanghai, People’s Republic of China
| | - Huimin Shi
- Department of Ophthalmology, Huashan Hospital, Fudan University, Shanghai, People’s Republic of China
| | - Yi Li
- Department of Ophthalmology, Huashan Hospital, Fudan University, Shanghai, People’s Republic of China
| | - Jianjiang Xiao
- Department of Ophthalmology, Huashan Hospital, Fudan University, Shanghai, People’s Republic of China
| | - Kun Chen
- Department of Laboratory Medicine, Huashan Hospital, Fudan University, Shanghai, People’s Republic of China
| | - Bobin Chen
- Department of Hematology, Huashan Hospital, Fudan University, Shanghai, People’s Republic of China
| | - Gezhi Xu
- Eye Institute, Eye and ENT Hospital, College of Medicine, Fudan University, Shanghai, People’s Republic of China
- Shanghai Key Laboratory of Visual Impairment and Restoration, Science and Technology Commission of Shanghai Municipality, Shanghai, People’s Republic of China
- Gezhi Xu, Department of Ophthalmology, Eye & ENT Hospital, Fudan University, No. 83 Fenyang Road, Shanghai, 200031, People’s Republic of China, Email
| | - Qingping Wang
- Department of Ophthalmology, Huashan Hospital, Fudan University, Shanghai, People’s Republic of China
- Correspondence: Qingping Wang, Department of Ophthalmology, Huashan Hospital, Fudan University, No. 12 Middle Urumqi Road, Shanghai, 200040, People’s Republic of China, Email
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Zhao XY, Cheng TT, Meng LH, Zhang WF, Chen YX. Clinical Features, Diagnosis, Management and Prognosis of Primary Intraocular Lymphoma. Front Oncol 2022; 12:808511. [PMID: 35186744 PMCID: PMC8851327 DOI: 10.3389/fonc.2022.808511] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/04/2021] [Accepted: 01/11/2022] [Indexed: 11/13/2022] Open
Abstract
PurposeTo evaluate the clinical features, diagnostic techniques, various treatment strategies and prognosis of primary intraocular lymphoma (PIOL).MethodsThe databases PubMed, EMBASE, and Ovid were searched from inception to March 2021 to identify relevant studies. Statistical analyses were performed with R version 3.3.1.Results87 studies involving 1484 patients (aged from 14 to 90 years old) were finally included. The pooling results indicated PIOL patients were female, elderly, binocular and B cell type dominated. About 19% have central nervous system (CNS) involvement at the first visit. During follow-up, the incidence of CNS involvement, death rate, 2-year and 5-year survival rate, 1-year and 2-year progression-free survival, and recurrence rate were 58%, 33%, 82%, 70%, 88%, 70%, 44%, respectively. The most common recurrent site was CNS. The delayed diagnosis rate was 85%, the misdiagnosed rate was 64%. The diagnostic technique with the highest positive rate was IL10:IL6>1 of aqueous (98%). The most common symptoms, signs, FFA and OCT features were blurring of vision (72%), vitreous inflammatory opacity (92%), FA/FAF reversal (91%) and hyper-reflective foci in posterior vitreous (53%), respectively. The prognosis of PIOL patients without CNS involvement was obviously better than those with CNS involvement. Overall, intravitreal injection of chemotherapy drug plus systemic chemotherapy (IV+CT) could achieve satisfactory prognosis, the combination of local radiotherapy (RT) could further decrease the recurrent and death rate.ConclusionPIOL patients with CNS involvement had significantly worse prognosis. The aqueous humor examination should be regarded as first-line and routine diagnostic technique. IV+CT could achieve satisfactory prognosis, the combination of RT was also beneficial.
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Affiliation(s)
- Xin-yu Zhao
- Department of Ophthalmology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Beijing, China
- Key Laboratory of Ocular Fundus Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Tian-tian Cheng
- Department of Ophthalmology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Beijing, China
- Key Laboratory of Ocular Fundus Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Li-hui Meng
- Department of Ophthalmology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Beijing, China
- Key Laboratory of Ocular Fundus Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Wen-fei Zhang
- Department of Ophthalmology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Beijing, China
- Key Laboratory of Ocular Fundus Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - You-xin Chen
- Department of Ophthalmology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Beijing, China
- Key Laboratory of Ocular Fundus Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
- *Correspondence: You-xin Chen, ;
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Takase H, Arai A, Iwasaki Y, Imai A, Nagao T, Kawagishi M, Ishida T, Mochizuki M. Challenges in the diagnosis and management of vitreoretinal lymphoma – Clinical and basic approaches. Prog Retin Eye Res 2022; 90:101053. [DOI: 10.1016/j.preteyeres.2022.101053] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/24/2021] [Revised: 01/30/2022] [Accepted: 02/06/2022] [Indexed: 12/13/2022]
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Gong D, Aronow ME, Eliott D. Rapid, Spontaneous Resolution of Prominent Subretinal Infiltrate in Vitreoretinal Lymphoma. JOURNAL OF VITREORETINAL DISEASES 2022; 6:80-85. [PMID: 37007723 PMCID: PMC9976220 DOI: 10.1177/24741264211009804] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 11/17/2022]
Abstract
Purpose: This case report describes a patient with vitreoretinal lymphoma who subacutely developed a large, peripapillary subretinal infiltrate that rapidly and spontaneously resolved. Methods: A case report is presented. Results: A 65-year-old Asian-American woman was referred for evaluation of a dense, peripapillary subretinal infiltrate in the left eye. A diagnostic vitrectomy revealed large, atypical lymphocytes with irregularly shaped nuclei, and mutational testing was positive for myeloid differentiation primary response 88 ( MYD88). Prior to surgery, the patient’s subretinal infiltrate had begun to resolve spontaneously, a process that continued after surgery without initiation of systemic or local ocular therapy. Conclusions: Patients with vitreoretinal lymphoma may present with transient, subretinal infiltrates that can resolve without treatment.
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Affiliation(s)
- Dan Gong
- Retina Service, Massachusetts Eye and Ear, Department of Ophthalmology, Harvard Medical School, Boston, MA, USA
| | - Mary E. Aronow
- Retina Service, Massachusetts Eye and Ear, Department of Ophthalmology, Harvard Medical School, Boston, MA, USA
| | - Dean Eliott
- Retina Service, Massachusetts Eye and Ear, Department of Ophthalmology, Harvard Medical School, Boston, MA, USA
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Asakage M, Umazume K, Takoi H, Akahane D, Ishibashi Y, Yamaguchi H, Gondo M, Goto H. A case of intravascular lymphoma diagnosed with a primary vitreoretinal lymphoma-like fundus lesion. J Ophthalmic Inflamm Infect 2021; 11:47. [PMID: 34951670 PMCID: PMC8709800 DOI: 10.1186/s12348-021-00280-0] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/07/2021] [Accepted: 12/08/2021] [Indexed: 11/29/2022] Open
Abstract
Purpose We report a case of intravascular lymphoma with primary vitreoretinal lymphoma-like fundus findings. Case A 61-year-old man with a one-week history of temporal visual field defect in the left eye was referred by a local ophthalmologist to our department. A yellowish-white raised patchy lesion was found in the nasal fundus of the left eye. Vitreoretinal lymphoma was suspected, and vitrectomy was performed in the left eye for diagnostic purpose. However, vitreous interleukin-10 concentration was low and no significant result was obtained. He had fever of around 38 °C, and respiratory failure that started 2 weeks before ophthalmological examination, worsened. Intravascular lymphoma was diagnosed from the results of histopathological examinations of transbronchial lung biopsy, bone marrow biopsy and random skin biopsy. With the start of systemic chemotherapy, the subretinal lesions shrank gradually and systemic condition was stable. However, 5 months after the start of chemotherapy, spread to the central nervous system was observed, and chimeric antigen receptor T cell (CAR-T) therapy was started in another hospital. After the start of CAR-T therapy, the subretinal lesions shrank further. Conclusions Intravascular lymphoma may be accompanied by primary vitreoretinal lymphoma-like intraocular lesions. If intraocular lesions are accompanied by systemic symptoms such as fever of unknown origin, the possibility of intravascular lymphoma should be suspected and systemic work-up should be performed.
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Relationship between vitreoretinal lymphoma and the site of lymphoma development in the central nervous system. Jpn J Ophthalmol 2021; 66:142-150. [PMID: 34860298 DOI: 10.1007/s10384-021-00891-z] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/12/2021] [Accepted: 10/28/2021] [Indexed: 10/19/2022]
Abstract
PURPOSE To investigate diffuse large B-cell lymphoma lesions with central nervous system (CNS) involvement in patients with vitreoretinal lymphoma (VRL) during long-term clinical courses. STUDY DESIGN Multicenter, retrospective, and observational research. METHODS Seventy-one patients participated in this study, 45 were newly diagnosed VRL patients with CNS involvement initially or during follow-up of at least 12 months. We identified the CNS lesions in the patients that had VRL and investigated whether the onset sites of the CNS lesions were associated with the VRL lesions or optic pathways. RESULTS There were 42 patients with bilateral ocular lesions; 29 had unilateral lesions; 26 had incidental CNS lymphomas. Twenty patients developed recurrent CNS lymphoma 1-73 months after VRL diagnosis; 25 patients had no CNS lesions during the follow-up period. Most CNS lesions were in forebrain-originating tissues (95 lesions/total 124 CNS lesions total), followed by hindbrain-originating tissues, especially the cerebellum. Sixty-seven lesions were found in the non-optic pathway or non-visual cortex. CONCLUSION Over 60% of the VRL patients had CNS lesions. CNS involvement was not associated with the optic pathway or visual cortex, suggesting that clinicians should carefully examine CNS lesions occurring in both forebrain- and hindbrain-originating tissues during a patient's clinical course. Moreover, the CNS lymphomas that manifest as VRL show multifocal tumor development.
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