Challenges in the diagnosis and management of vitreoretinal lymphoma – Clinical and basic approaches

Vitreoretinal lymphoma (VRL) is a subtype of diffuse large B-cell lymphoma and is sight- and life-threatening in the vast majority of patients. Lymphoma cells infiltrate the vitreous body and/or subretinal space and exhibit clinical signs of vitreous opacities and creamy white subretinal lesions. Although the intraocular signs can serve as clues to suspect VRL, they are nonspecific and may be misdiagnosed as uveitis. Histopathological evidence of malignant cells on vitreous biopsy, for instance, is the gold standard for diagnosis of VRL; however, cytological examination of the vitreous often results in a low success rate owing to the small quantity and poor quality of tissues and cells in the sample. Recent advancements in immunological, molecular, and gene analyses using intraocular samples have made it possible to accurately diagnose VRL. As for the management of VRL, local treatments with irradiation and/or intravitreal injections of anti-tumor agents (methotrexate or rituximab) are effective in suppressing intraocular VRL lesions. However, the effect of systemic chemotherapy, with or without brain irradiation, on preventing central nervous system involvements remains controversial. In this review article, we discuss the following concepts based on previous literature and our unpublished results: current ocular imaging examinations such as optical coherence tomography and fundus autofluorescence; immunological, molecular, and gene expression characterization of intraocular biopsies with special attention to flow cytometry; immunoglobulin gene rearrangement assays that use the polymerase chain reaction test; cytokine assays; gene mutations (MYD88, CD79B); and current local and systemic treatments of VRL.     

A case of intraocular malignant lymphoma diagnosed by immunoglobulin gene rearrangement and translocation,and IL-10/IL-6 ratio in the vitreous fluid

BackgroundThe diagnosis of primary intraocular lymphoma is difficult in many cases even with conventional cytological tests using vitreous samples. Recently new diagnostic tests, such as microdissection and polymerase chain reaction (PCR) and measurement of cytokines using intraocular samples, have been applied to the diagnosis of the disease. We report here a case where we used the new diagnostic tests and the results aided us to make a diagnosis of intraocular lymphoma.CaseA 68-year-old woman with an initial diagnosis of bilateral idiopathic uveitis with steroid-resistant vitreous opacities underwent a vitreous biopsy. The cytological examinations of the vitreous samples revealed class III. The microdissection and PCR using the vitreous samples detected IgH rearrangement gene in the third framework (FR3A), the complementary determining region 3(CDR3) of the V_H region and Bcl-2-associated translocation. The interleukin (IL)-10 to IL-6 ratio in the vitreous fluid was greater than 100. Because the results of the examinations strongly suggested intraocular lymphoma, the patient was treated with radiation and chemotherapy. One month after the therapy, however, the patient developed multiple metastatic lesions in the brain. The clinical course of the patient together with the new diagnostic results of examinations led to a diagnosis of intraocular lymphoma.ConclusionA combination of tests, such as conventional cytology, microdissection, and PCR, and cytokine assay using intraocular biopsy samples, is useful to make a diagnosis of intraocular lymphoma.     

Intraocular lymphoma

There are two distinct forms of intraocular lymphoma. One originates within the central nervous system (CNS) and is called primary CNS lymphoma. The second form arises outside the CNS and metastasizes to the eye. When primary CNS lymphoma initially involves the retina, it is named primary intraocular lymphoma (PIOL). Although PIOL is a rare malignancy, the incidence has dramatically increased in the past 15 years. Typical clinical manifestations include blurred vision and floaters. Ophthalmic examination reveals vitreitis and subretinal infiltrates. Diagnosis of PIOL can be difficult and requires neuroimaging, examination of the cerebrospinal fluid and/or vitreous. Molecular analysis detecting immunoglobulin gene rearrangements and ocular cytokine levels showing elevated interleukin (IL)-10 with an IL-10 to IL-6 greater than 1.0 are helpful adjuncts for the diagnosis. Treatment includes systemic chemotherapy and radiation with current regimens favoring the use of chemotherapy first. In contrast, metastatic systemic lymphoma, like other metastatic ocular tumors, is usually confined to the uvea, in particular the choroid. Compared with PIOL, metastatic systemic lymphomas have a much lower prevalence, better prognosis, and are less likely to create a diagnostic dilemma.     

CD5-Positive Primary Intraocular B-Cell Lymphoma Arising during Methotrexate and Tumor Necrosis Factor Inhibitor Treatment

Purpose

To report a case of CD5+ primary intraocular B-cell lymphoma arising during methotrexate (MTX) and tumor necrosis factor (TNF) inhibitor treatment in a young patient with rheumatoid arthritis and uveitis.

Case Presentation

A 39-year-old woman treated with MTX and a TNF inhibitor for rheumatoid arthritis and uveitis had steroid-resistant vitreous opacity. A vitreous sample was obtained by using diagnostic vitrectomy and was categorized as class V based on cytologic examination. Flow cytometric analysis of the vitreous sample revealed that abnormal cells were CD5+, CD10–, CD19+, CD20+ and immunoglobulin light-chain kappa+, suggesting the diagnosis of CD5+ primary intraocular B-cell lymphoma. Polymerase chain reaction (PCR) detected immunoglobulin heavy-chain gene rearrangement. Epstein-Barr virus (EBV) DNA was detected in the vitreous sample by using PCR, and immunohistochemistry revealed EBV latent membrane protein-1 expression in the abnormal cells infiltrating the vitreous. Optic nerve invasion was observed on magnetic resonance imaging.

Conclusion

Primary intraocular lymphoma (PIOL) may develop in patients receiving MTX and TNF inhibitor treatment. EBV infection may play an important role in the pathogenesis of PIOL arising during immunosuppressive therapy.Key Words: Primary intraocular lymphoma, CD5+ B-cell lymphoma, Methotrexate, Tumor necrosis factor inhibitor, Epstein-Barr virus     

Primary intraocular lymphoma

Primary intraocular lymphoma (PIOL) is a rare extranodal Non-Hodgkin lymphoma (NHL), involving the retina, the subretinal space, vitreous body and/or optic nerve. The majority of PIOL are diffuse large cell B-cell lymphomas according to the new W.H.O. lymphoma classification with an immunophenotype suggesting an origin from germinal centre cells. PIOL occurs independently or together with primary central nervous system lymphoma (PCNSL), and often presents in the form of a steroid-resistant uveitis. PIOL is one of the most challenging intraocular tumours to diagnose. Cytological examination of vitreal aspirates remains the gold standard for exclusion of neoplastic disease in patients with idiopathic uveitis. Various techniques, particularly the polymerase chain reaction analysing clonal rearrangements of the immunoglobin heavy chain or the T-cell receptor genes, prove to be useful adjuncts. Chorioretinal biopsies increase the chances of diagnosing or excluding a PIOL involving the retina and choroid. Furthermore, they allow exact subtyping of the malignant lymphoma when present, enabling exclusion of an ocular manifestation of a systemic lymphoma. Currently, most PIOL/PCNSL are treated with systemic chemotherapy. Ocular recurrences are often treated with radiotherapy, and increasingly with intraocular methotrexate. Although the prognosis of patients with PCNS/PIOL remains poor, newer methods enabling earlier diagnosis establishment and treatment are gradually increasing overall survival.     

玻璃体视网膜淋巴瘤的诊断进展

玻璃体视网膜淋巴瘤(VRL)是罕见的恶性非霍奇金淋巴瘤,因无特异性临床表现,对其早期、正确地诊断仍面临很大的挑战。病理细胞学诊断是VRL诊断的金标准,但其诊断仍需要结合临床表现、影像学检查、免疫学及分子学检测等。随着诊断技术的进步,更加高效的细胞学检查及辅助诊断技术不断被探索。细胞因子及眼内淋巴瘤诊断的白介素评分(ISOLD)、髓样分化因子88(MYD88)基因突变及二代测序检测技术有良好的诊断效能而逐渐成为重要的辅助诊断手段及研究热点。     

基因重排检测技术联合玻璃体液中IL-10和IL-6检测对PIOL的诊断价值

目的：研究基因重排检测技术联合玻璃体液中白介素-10(IL-10)、白介素-6(IL-6)细胞因子检测对原发性眼内淋巴瘤(PIOL)的诊断价值。

方法：研究对象为本院2015-01/2019-12收治的拟诊断为PIOL患者27例的临床资料,经诊断性玻璃体切割术病理检查确诊PIOL 患者21例,葡萄膜炎6例; 回顾性分析其基因重排检测结果及玻璃体液中IL-10、IL-6水平,绘制受试者工作特征(ROC)曲线分析基因重排检测技术、玻璃体液中IL-10、IL-6水平及两者联合对PIOL的诊断价值。

结果：纳入的21例PIOL患者中,15例IhH FR2单克隆性重排序列,阳性率为71%(15/21); 4例检出TCRG克隆性基因重排序列; 经ROC曲线分析显示基因重排检测技术诊断PIOL的曲线下面积值(AUC)为0.857,敏感性、特异性分别为71.43%、100.00%; PIOL患者玻璃体液中IL-10及IL-10/IL-6水平均显著高于葡萄膜炎患者,但两种病变患者IL-6水平无差异(P>0.05); 经ROC曲线分析显示IL-10诊断PIOL的AUC值最高,以170.90pg/mL为IL-10的cut-off,其诊断PIOL的敏感性、特异性分别为66.67%、100.00%; 而以1.95为IL-10/IL-6比值的cut-off,其诊断PIOL的敏感性为52.40%、特异性为100.00%; 基因重排检测技术联合玻璃体液中IL-10、IL-10/IL-6水平检测诊断PIOL的AUC为0.893,敏感性、特异性分别为95.24%、83.33%。

结论：单一基因重排检测技术诊断PIOL敏感性欠佳,联合玻璃体液中IL-10、IL-6水平检测可获得更佳的诊断敏感性,且特异性良好。     

A case of intraocular malignant lymphoma diagnosed by immunoglobulin gene rearrangement and translocation,and IL-10/IL-6 ratio in the vitreous fluid

BACKGROUND: The diagnosis of primary intraocular lymphoma is difficult in many cases even with conventional cytological tests using vitreous samples. Recently new diagnostic tests, such as microdissection and polymerase chain reaction (PCR) and measurement of cytokines using intraocular samples, have been applied to the diagnosis of the disease. We report here a case where we used the new diagnostic tests and the results aided us to make a diagnosis of intraocular lymphoma. CASE: A 68-year-old woman with an initial diagnosis of bilateral idiopathic uveitis with steroid-resistant vitreous opacities underwent a vitreous biopsy. The cytological examinations of the vitreous samples revealed class III. The microdissection and PCR using the vitreous samples detected IgH rearrangement gene in the third framework (FR3A), the complementary determining region 3 (CDR3) of the VH region and Bcl-2-associated translocation. The interleukin (IL)-10 to IL-6 ratio in the vitreous fluid was greater than 100. Because the results of the examinations strongly suggested intraocular lymphoma, the patient was treated with radiation and chemotherapy. One month after the therapy, however, the patient developed multiple metastatic lesions in the brain. The clinical course of the patient together with the new diagnostic results of examinations led to a diagnosis of intraocular lymphoma. CONCLUSION: A combination of tests, such as conventional cytology, microdissection, and PCR, and cytokine assay using intraocular biopsy samples, is useful to make a diagnosis of intraocular lymphoma.     

Cytopathological analysis of vitreous in intraocular lymphoma

OBJECTIVE: To describe the cytopathological method used in the analysis of vitreous samples in the diagnosis of primary intraocular lymphoma (PIOL). PARTICIPANTS: Seven patients with refractory posterior uveitis referred to a regional ocular inflammatory service were diagnosed as having PIOL between 1999 and 2006. METHODS: Clinical features of the uveitis and cytopathological preparation of the samples were described. All patients underwent vitrectomy and samples were placed in formal saline or prepared fresh. Following paraffin embedding generating a cell block, immunostaining, and polymerase chain reactions were performed. RESULTS: Five women (71.4%) and two men (28.6%) (mean age 67.7 years) were included. Five patients had diagnostic vitrectomy performed within 6 months of presentation, but in two patients diagnosis was delayed up to 2 years. Uveitis was bilateral in two patients. Cytologic and immunohistochemical staining prepared from the vitreous specimens showed PIOL in all patients, and PCR displayed single band of immunoglobulin heavy chain rearrangement in five out of six samples tested. CONCLUSIONS: Diagnosis of PIOL is difficult due to small volume of sample with low number of malignant cells and inadequate preparation of samples. Our method of analysis with fresh samples together with immunohistochemistry and PCR analysis demonstrates a high yield of diagnosis reducing diagnostic delay.     

Intraocular Cysts of Toxoplasma gondii in Patients with Necrotizing Retinitis following Periocular/Intraocular Triamcinolone Injection

Abstract

Purpose: To report the detection of Toxoplasma gondii cysts in intraocular aspirates of patients with necrotizing retinitis following periocular/intraocular corticosteroid injection.

Design: Case report.

Methods: Two patients (2 eyes) with widespread necrotizing retinitis in a steroid-exposed eye posed a diagnostic challenge and underwent pars plana vitrectomy (PPV). Intraocular samples (vitreous fluid, retinal tissue, and subretinal aspirate in case 1, and vitreous fluid in case 2) were subjected to cytological examination.

Results: The subretinal aspirate (case 1) revealed encysted bradyzoites of Toxoplasma gondii. Vitreous fluid (case 2) tested positive for anti-toxoplasma antibodies and the smear showed encysted forms of Toxoplasma gondii on cytology.

Conclusion. Toxoplasma gondii cysts were detected in eyes with necrotizing retinitis that developed secondary to injudicious use of corticosteroids.     

25-gauge transconjunctival diagnostic vitrectomy in suspected cases of intraocular lymphoma:a case series and review of the literature

AIM: To report the cytology results of 25-gauge transconjunctival (25G-TSV) diagnostic vitrectomy in cases suspicious for intraocular lymphoma (IOL), and compare the results to those reported in the literature.METHODS: Clinical and cytopathological records of 18 vitreous biopsy specimens obtained via 25G-TSV diagnostic vitrectomy in 12 patients suspicious for IOL were reviewed retrospectively. A review of the literature in regards to the diagnostic yields of vitreous specimens obtained via 25-gauge and 20-gauge diagnostic vitrectomy in suspected cases of IOL was performed.RESULTS: Eighteen eyes from 12 patients with clinical suspicion of IOL underwent diagnostic 25G-TSV. The cytopathological investigations demonstrated IOL in 15 eyes (83.3%). Vitreous analysis was non-diagnostic in 3 eyes (16.7%).CONCLUSION: Twenty-five-gauge diagnostic vitrectomy yields adequate sample for cytological evaluation of the vitreous in cases suspicious for IOL. The diagnostic results of the 25G-TSV in the current study are superior to those reported for 20-gauge vitrectomy but equivalent to those reported for 25G-TSV in the published literature.     

Primary intraocular lymphoma of T-cell type: report of a case and review of the literature

Purpose Primary intraocular lymphoma (PIOL) is an uncommon non-Hodgkin lymphoma and is usually of B-cell type. Intraocular T-cell or T/NK-cell lymphomas are extremely rare and mostly represent a secondary manifestation of either a cutaneous or a systemic lymphoma. The aim of the current paper is to report the clinical, histopathological and molecular biological findings of a PIOL of T-cell type.Methods Conventional cytological and immunocytological examination of vitrectomy specimens. Conventional histology, immunohistochemistry and polymerase chain reaction (PCR) for the detection of immunoglobulin heavy chain (IgH) and T-cell-receptor gamma (TCR-) gene rearrangement, GeneScan analysis, and DNA sequencing were performed on the chorioretinal biopsy.Results Cytology of the right vitreous aspirate revealed a moderate cellular infiltrate consisting of medium-sized T-cells with pleomorphic nuclei. Similar atypical lymphocytes were seen in the partially necrotic chorioretinal biopsy. These lymphocytes expressed CD3, CD4, F1 and CD30, with a growth fraction of 90%. TCR--PCR, GeneScan analysis and DNA sequencing demonstrated a monoclonal amplification product within the expected range. In contrast, IgH-PCR revealed oligoclonal amplificates. The patient was treated with low-dose radiotherapy (total 45 Gy), and was in complete remission at final follow-up.Conclusion A rare PIOL of T-cell type was diagnosed on the basis of vitreous aspiration and chorioretinal biopsy. In addition to conventional cytology and immunocytology, the utilisation of gene rearrangement studies on vitreous or chorioretinal biopsies increases the chances of diagnosing or excluding a PIOL of either B-cell or T-cell type. Despite its rarity, ophthalmic pathologists should always consider the diagnosis of T-PIOL when reviewing vitreous samples.     

IL-10 measurement in aqueous humor for screening patients with suspicion of primary intraocular lymphoma

PURPOSE: To determine the value of IL-10 measurement in aqueous humor (AH) for screening in primary intraocular lymphoma (PIOL). METHODS: One hundred consecutive diagnostic or therapeutic vitrectomies were performed in patients with uveitis. During surgery, 100 microL of both AH and pure vitreous was taken. IL-10 levels were determined with a standard quantitative sandwich enzyme immunoassay technique. Patients were distributed in two groups: 51 patients with proven PIOL, 108 patients with uveitis divided into 74 with uveitis of proven etiology and 34 with idiopathic uveitis. Groups were compared by ANOVA and the Tukey-Kramer test or nonparametric Wilcoxon test. Distributions were compared by using the chi(2) test. Segmentation was derived from the ROC curves by choosing a tradeoff between sensitivity and specificity. RESULTS: In patients with PIOL, IL-10 mean values were 2205.5 pg/mL (median: 1467 pg/mL) in the vitreous and 543.4 pg/mL (median: 424 pg/mL) in AH. In patients with uveitis (idiopathic and diagnostic uveitis), mean values were 26.6 pg/mL (median: 8 pg/mL) in the vitreous, and 21.9 pg/mL (median: 8 pg/mL) in AH. IL-10 mean values were significantly different between patients with PIOL and patients with uveitis (P < 10(-3)). The areas under the curves were 0.989 and 0.962 for vitreous and AH, respectively. A cutoff of 50 pg/mL in the AH was associated with a sensitivity of 0.89 and a specificity of 0.93. In the vitreous, a cutoff value of 400 pg/mL yielded a specificity of 0.99 and a sensitivity of 0.8. CONCLUSIONS: Diagnosis of PIOL is often made months or years after the initial onset of ocular symptoms. Cytology remains the gold standard for diagnosis. However, measurement of IL-10 in the AH is a good screening test to reduce diagnostic delays.     

Primary intraocular lymphoma: a review of the clinical,histopathological and molecular biological features

Introduction Primary intraocular lymphoma (PIOL) is a rare non-Hodgkin lymphoma which arises in the retina or the vitreous. It can occur either together with or independently of primary cerebral nervous system lymphoma (PCNSL); the incidence of the latter has significantly increased over the past three decades. PIOL remains one of the most difficult diagnoses to establish, particularly due to its ability to mimic other diseases in the eye and to the limited material which is often available for examination.Methods The article reviews the clinical, histopathological, molecular biological and biochemical approaches to the diagnosis of PIOL. The differential diagnoses, including other lymphomatous manifestations in the eye, e.g. primary uveal lymphoma, as well as non-neoplastic uveal diseases are addressed. Furthermore, the treatment strategies for PIOL are summarised.Results Diagnostic progress has been made in various fields, including flow cytometry and immunocytology, cytokine analysis, and as well as molecular biological analysis of the immunoglobulin heavy and light chains using polymerase chain reaction on both fixed and non-fixed material. The optimal therapy of PIOL remains to be determined: the current trends suggest that combined radiotherapy and chemotherapy, as well as intravitreal chemotherapy, are of value. Novel therapies which may have a role in the future include oral trofosfamide.Conclusion Our understanding of the pathogenesis of PIOL/PCNSL remains far from complete. Intensified efforts must be made to determine the cell of origin of PIOL, as well as to establish molecular signatures, which could be used to decrease diagnostic delay. Further studies, possibly prospective ones, are required to establish the optimal therapy for initial and recurrent disease.     

International Central Nervous System and Ocular Lymphoma Workshop: Recommendations for the Future

Purpose: To bring together multidisciplinary experts to discuss primary central nervous system lymphoma (PCNSL) and primary intraocular lymphoma (PIOL). Methods: NIH campus workshop discussion focusing on future work in both clinical and basic lymphoma research. Results: The discussion lead to recommendations on elucidating disease pathobiology, improving diagnostic accuracy and sensitivity, and novel therapeutic strategies. Conclusions: Approaches which have been successfully applied to other neoplasms, such as microarray, may be applied to improve diagnostic accuracy and sensitivity of PCNSL and PIOL and should be systematically incorporated into clinical trials of both. Development of animal models of PCNSL and PIOL may be useful in understanding the unique ocular and CNS milieu. Disease detection by radiological, nuclear medicine, molecular and flow cytometric approaches should be systematically studied to improve early diagnosis, accurate staging, and response evaluation. Improved therapy remains the ultimate goal. Efforts in these arenas should be coordinated on a national and international level.     

Diagnostic cellular yield is superior with full pars plana vitrectomy compared with core vitreous biopsy

Purpose

Vitreous biopsy for the cytological assessment of suspected intraocular lymphoma and vitritis of uncertain aetiology is a standard investigation. The types of specimens generated and the diagnostic rate are variable within and between centres. There are many reasons for this but one observation that has not been considered previously is the differential distribution of cells in the vitreous gel. To test this possibility, five consecutive patients with suspected vitreous involvement by lymphoma or vitritis of uncertain aetiology underwent a core vitreous biopsy immediately before a planned full pars plana vitrectomy (PPV) and the cellularity of the two sampling techniques compared.

Methods

A prospective study of five consecutive patients requiring vitreous sampling to secure a firm diagnosis. For each of five patients, the core vitreous biopsy specimen was received in a universal tube and the PPV specimen was received in a vitreous cassette. Fluid (0.25 ml) was removed from both specimens, centrifuged and haematoxylin and eosin (H&E) stained slides prepared per sampling method. The slides were examined with a light microscope, the most cellular field selected and the number of cells per mm² counted and compared between sampling techniques.

Results

PPV specimen''s, revealed a cellularity range that was 7.4 to 78 × (average 31 ×) greater than a core vitreous biopsy. In the two cases of a final diagnosis of intraocular lymphoma, the vitreous core biopsy was non-diagnostic. Furthermore, the PPV specimen generated additional cellular material for numerous ancillary investigations to permit a secure diagnosis.

Conclusions

The results of this differential vitreous sampling study has strengthened our anecdotal slit lamp clinical observations that inflammatory cells and lymphoma cells are concentrated more in the cortical vitreous. Therefore, vitreous cells have less chance to be sampled if a single core vitreous biopsy is performed. Indeed, the two cases of confirmed lymphoma generated a non-diagnostic core vitreous biopsy. In our centre, this study has lead to PPV being performed as a gold standard on all patients with suspected intraocular lymphoma or vitritis of uncertain aetiology.     

Detection of the bcl-2 t(14;18) translocation and proto-oncogene expression in primary intraocular lymphoma

PURPOSE: Primary intraocular lymphoma (PIOL) is a diffuse large B cell lymphoma that initially infiltrates the retina, vitreous, or optic nerve head, with or without central nervous system involvement. This study examined the expression of the bcl-2 t(14;18) translocation, the bcl-10 gene, and high expression of bcl-6 mRNA in PIOL cells. METHODS: Microdissection and PCR analysis were used to examine vitreous specimens in patients with PIOL for the presence of bcl-2 t(14;18) translocations, the bcl-10 gene, and expression of bcl-6 mRNA. A medical record review was also conducted to determine whether the bcl-2 t(14;18) translocation correlated with prognosis. RESULTS: Forty of 72 (55%) PIOL patients expressed the bcl-2 t(14;18) translocation at the major breakpoint region. Fifteen of 68 (22%) patients expressed the translocation at the minor cluster region. The bcl-10 gene was detected in 6 of 26 (23%) patients, whereas 4 of 4 (100%) PIOL patients expressed higher levels of bcl-6 mRNA compared with inflammatory lymphocytes. An analysis of clinical outcome in 23 PIOL patients revealed no significant association between bcl-2 t(14;18) translocations and survival or relapse. However, patients with the translocation were significantly younger. CONCLUSIONS: PIOL has unique molecular patterns of bcl-2, bcl-10, and bcl-6 when compared with other systemic lymphomas. This study lays the foundation for future studies aimed at exploring the genotypic classification of PIOL based on the quantitative molecular framework of gene expression profiling, with the goal of providing useful adjuncts to the pathologic diagnosis of this complex disease.     

玻璃体腔注射甲氨蝶呤治疗原发性眼内淋巴瘤的临床研究

目的观察玻璃体腔注射甲氨蝶呤(MTX)个体化治疗原发性眼内淋巴瘤(PIOL)的疗效和安全性。 方法收集2013年4月至2019年12月于首都医科大学附属北京朝阳医院眼科就诊的PIOL患者20例(30只眼)的临床资料进行研究。其中，男性6例(6只眼)，女性14例(24只眼)。患者年龄34~81岁，平均年龄(55.9±12.4)岁。所有患者肿瘤性质均为弥漫性大B细胞淋巴瘤。治疗方案为"根据淋巴瘤临床表现"的个体化治疗，所有患眼均接受单次玻璃体腔注射MTX(400 μg：0.1ml)治疗。如出现玻璃体混浊加重、眼底病灶范围扩大或IL-10/IL-6比值增高行再次注射。自治疗开始随访12~30个月。所有患眼均行最佳矫正视力(BCVA)、眼压、裂隙灯显微镜、彩色眼底照相、光学相干断层扫描(OCT)及荧光素眼底血管造影(FFA)检查并行房水或玻璃体IL-10/IL-6浓度检测。BCVA转换为LogMAR视力和眼压的检查数据先行正态性检验。眼压符合正态分布采用±s表示，治疗前后眼压的比较采用配对t检验；BCVA不符合正态分布，采用中位数和上下四分位数表示，治疗前后BCVA的比较采用Wilcoxon配对秩和检验。裂隙灯显微镜检查、彩色眼底照相、OCT、FFA及IL-10/IL-6的比值采用文字形式进行描述。 结果治疗前后LogMAR视力中位数为0.75(0.47，1.43)和0.4(0.2，0.57)，差异具有统计学意义(Z＝3.43，P<0.05)。治疗前后眼压分别为(16.56±4.31)mmHg(1 mmHg＝0.133 kPa)和(16.13±3.87)mmHg，差异无统计学意义(t＝0.40，P>0.05)。所有患者经玻璃体腔注射MTX治疗后玻璃体混浊程度较治疗前好转者有12例(19只眼)，占63%(19/30)；视网膜下黄白色奶油样浸润灶减轻或消失者有15例(20只眼)，占66%(20/30)；视网膜色素上皮下的高反射病灶减轻或消失的为13例(18只眼)，占60%(18/30)。注射次数为1~8次，平均(3.00±2.37)次。 结论"根据淋巴瘤临床表现"进行个体化玻璃体腔注射MTX治疗PIOL安全有效，可达到临床缓解。