Intraocular T-cell Lymphoma due to Mycosis Fungoides and Response to Intravitreal Methotrexate

Purpose: To report a case of mycosis fungoides with subsequent intraocular involvement and good response to intravitreal methotrexate.

Design: Case report.

Methods: Retrospective chart review.

Results: This is a rare case of intraocular T-cell lymphoma due to mycosis fungoides, which responded to intravitreal methotrexate therapy in a previous vitrectomized eye.

Conclusions: Intraocular T-cell lymphoma is a rare manifestation of mycosis fungoides and should be considered in the differential diagnosis of chronic uveitis in patients with this history. Intravitreal methotrexate may be an effective adjunctive treatment for this condition.     

A Case of Primary Intraocular Lymphoma Treated by Intravitreal Methotrexate

A 40-year-old female visited our clinic for visual disturbance of the right eye, in which a few creamy-yellow retinal lesions and visual field constrictions were noted. She had been treated for primary CNS lymphoma and was in complete remission. After failure to follow-up for three months, she lost vision in the right eye, at which time active panuveitis was seen. Decreased vision and field constriction was observed in the left eye. Her left eye showed a granular pattern and dye leakage from the vessels and disc on fluorescein angiography and small RPE humps were seen in optical coherence tomography (OCT). Diffuse large malignant B-cells with strong immunoreactivities with CD20 immunostaining were seen in the epiretinal membrane biopsy specimen. Intravitreal injections of methotrexate (MTX) (800 µg/0.1 ml in the right eye, 400 µg/0.05 ml in the left eye) were performed twice weekly for one month, once weekly for the following month, once every two weeks for the next month, followed by nine monthly injections. Both eyes were free from malignant cells on vitreous biopsy six months later. There was no leakage seen by angiography, but the granular pattern persisted. Visual field constriction was slightly improved, and the small RPE humpsdetachments seen in OCT disappeared. EOG Arden ratio was decreased in both eyes, and b wave amplitude of scotopic ERG was decreased in the left eye. She was free from recurrence until six months later. No ocular complications except minimal opacity of the crystalline lenses were noted in both eyes.     

Intravitreal Methotrexate as Adjunctive,Palliative Therapy in Intraocular T-cell Lymphoma

Purpose: To report on the rapid and sustained effect following injection of intravitreal methotrexate (IVTMTX) in intraocular T-cell lymphoma.

Design: Report of 2 cases.

Methods: A young male with natural killer/T-cell lymphoma presented with infiltrative nodular iridocyclitis and received a single IVTMTX. An elderly female with peripheral T-cell lymphoma presented with a hypopyon, infiltrative iridocyclitis, and choroidal effusions and received 3 IVTMTX over 4 months.

Results: Both patients responded well after the first injection, with resolution of signs within 1 week and improvement in vision.

Conclusions: IVTMTX may be effective as a palliative, vision-restoring measure in patients with systemic T-cell lymphoma.     

Intravitreal Methotrexate Resistance in a Patient with Primary Intraocular Lymphoma

Purpose: To describe the clinical course of a patient with multiple recurrences of primary intraocular lymphoma (PIOL). Design: Interventional case report, Methods: Retrospective chart review. Results: A 57-year-old female treated with multiple intravitreal methotrexate injections became refractory to intravitreal methotrexate after a year. Lymphoma cells evaluated using immunocytochemistry and confocal microscopy showed aberrant multidrug resistance-related protein (MRP) and decreased reduced folate carrier (RFC) and folate binding protein (FBP) expression compared to PIOL cells from another patient clinically responsive to methotrexate. Conclusions: This case suggests that alterations in the transport of methotrexate across the cell membrane might contribute to resistance following repeated intravitreal injections.     

Primary Intraocular Lymphoma: A Review

Primary intraocular lymphoma (PIOL) is a type of primary central nervous system lymphoma (PCNSL). It is the most common neoplastic masquerade syndrome involving the eye. Its protean ocular manifestations, plus in many cases the initial positive response to corticosteroid therapy for presumed uveitis, delay accurate diagnosis. A high index of suspicion is essential, followed by tissue biopsy with cytology and ancillary studies. Current treatment is based on chemotherapy featuring high-dose methotrexate and radiation therapy. Prognosis is poor due to CNS involvement, but newer therapies have had some success in prolonging survival.     

Variations in the Presentation of Primary Intraocular Lymphoma: Case Reports and a Review

Primary intraocular lymphoma is a distinct subset of primary non-Hodgkin's lymphoma of the central nervous system (CNS). Diagnosis can be difficult and is often delayed, as the clinical presentation can mimic a number of other ocular conditions. This report describes four different presentations of intraocular lymphoma and focuses on its modes of clinical presentation. Primary intraocular lymphoma can present with a wide variety of manifestations frequently mimicking diffuse uveitis that is refractory to corticosteroids. Subretinal pigment epithelium tumors may be seen. However, other presentations may include multiple deep white dots in the retina secondary to tumor infiltration; retinal infiltration, causing a necrotizing retinitis; or infiltration of the retinal vasculature, causing arterial or venous obstruction. Finally, optic nerve invasion may be seen. CNS lymphoma develops in the majority of patients before, in conjunction with, or after the development of eye disease. Intraocular lymphoma often has a fatal outcome, but recognition of its modes of presentation facilitates early diagnosis and treatment that may improve prognosis.     

Intraocular lymphoma: a clinical perspective

Primary vitreoretinal lymphoma (PVRL) is a rare malignancy that is speculated to arise extraocularly, and preferentially invade and flourish in the ocular and CNS microenvironments. The eye is involved in about 20% of primary central nervous system lymphomas, but the brain is eventually involved in about 80% of PVRL. Most are B-cell lymphomas with small numbers of T-cell lymphomas metastatic to the vitreous and retina. Metastatic systemic B-cell lymphoma usually involves choroid. Primary choroidal lymphoma is rare. Intraocular lymphoma can usually be distinguished from uveitis clinically, although there are overlaps, which may be pronounced in eyes with a large component of reactive inflammation related to tumor surveillance and control. There are controversies in diagnosis and treatment. Diagnosis through examination of ocular fluid is technically difficult and can utilize cytology, immunohistochemistry, flow cytometry, molecular detection of gene rearrangements, and cytokine profiling. Treatment of intraocular lymphoma without detectable CNS disease could consist of a full course of systemic chemotherapy with ocular adjunctive treatment, or ocular treatment alone depending on the preference of the clinical center. In ocular only cases where the vitreous has been debulked to improve vision and there is no sight-threatening involvement of the RPE, orbital irradiation or intravitreal chemotherapy stabilizes the intraocular process but does not seem to modify the CNS component, which can present symptomatically in an advanced state. This is a highly malignant disease with a poor prognosis. Close collaboration with a pathologist and oncologist, and good communication with patients is essential.     

Development of Vitreoretinal Lymphoma in a Patient with Sarcoid Uveitis

ABSTRACT

Purpose

The purpose of this article is to report the first case of primary vitreoretinal lymphoma in a patient with sarcoid uveitis.     

Treatment of primary intraocular lymphoma with intravitreal methotrexate

PURPOSE: To report the efficacy of intravitreal chemotherapy for primary intraocular lymphoma (PIOL). METHODS: Retrospective, noncomparative interventional case reports are presented for six patients (ten eyes; mean age, 58.8 years) with pathologically confirmed PIOL who participated in this study and were treated at our hospital with intravitreal injections of methotrexate (MTX) between January 2004 and February 2007. Intravitreal injections of MTX (400 mug MTX/50 mul Opeguard-MA) were administered once or twice weekly for 1 month followed by ten monthly injections. Interleukin-10 (IL-10) and IL-6 were measured in the vitreous before and after injections to determine tumor activity. RESULTS: All eyes were clinically cleared of malignant cells. One eye lost vision. After intravitreal chemotherapy, the vitreous IL-10 concentration reached barely detectable levels. CONCLUSIONS: Intravitreal chemotherapy achieves clinical remission and preserves vision in patients with PIOL.     

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

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

原发性眼内淋巴瘤

原发性眼内淋巴瘤是一种少见的眼部恶性肿瘤，其淋巴瘤病理分类为结节外型弥漫型大细胞B细胞淋巴瘤，属于原发性中枢系统淋巴瘤（PCNSL）的一种。近年来发病率逐渐上升，在过去的20a里，美国PCNSL的发病率增长了3倍。该病临床表现无特异性，往往表现为假性葡萄膜炎，玻璃体或病变组织细胞病理学检查是诊断的金标准；但由于玻璃体活检手术，标本保存和病理诊断方法要求较高，所以诊断困难。治疗上主要应用大剂量甲氨蝶呤治疗。由于往往有神经系统受累，预后不佳，随着治疗方法的改进PIOL的平均存活率已经从1～1．5a提高到3a以上。     

原发性眼内淋巴瘤

原发性眼内淋巴瘤是一种少见的眼部恶性肿瘤,其淋巴瘤病理分类为结节外型弥漫型大细胞B细胞淋巴瘤,属于原发性中枢系统淋巴瘤(PCNSL)的一种。近年来发病率逐渐上升,在过去的20a里,美国PCNSL的发病率增长了3倍。该病临床表现无特异性,往往表现为假性葡萄膜炎,玻璃体或病变组织细胞病理学检查是诊断的金标准;但由于玻璃体活检手术,标本保存和病理诊断方法要求较高,所以诊断困难。治疗上主要应用大剂量甲氨蝶呤治疗。由于往往有神经系统受累,预后不佳,随着治疗方法的改进PIOL的平均存活率已经从1~1.5a提高到3a以上。     

Intraocular lymphoma

Intraocular lymphoma (IOL) is a rare lymphocytic malignancy which contains two main distinct forms. Primary intraocular lymphoma (PIOL) is mainly a sub-type of primary central nervous system lymphoma (PCNSL). Alternatively, IOL can originate from outside the central nervous system (CNS) by metastasizing to the eye. These tumors are known as secondary intraocular lymphoma (SIOL). The IOL can arise in the retina, uvea, vitreous, Bruch’s membrane and optic nerve. There are predominantly of B-cell origin; however there are also rare T-cell variants. Diagnosis remains challenging for ophthalmologists and pathologists, due to its ability to masquerade as noninfectious or infectious uveitis, white dot syndromes, or occasionally as other metastatic cancers. Laboratory tests include flow cytometry, immunocytochemistry, interleukin detection (IL-10: IL-6, ratio >1), and polymerase chain reaction (PCR) amplification. Methotrexate-based systemic chemotherapy with external beam radiotherapy and intravitreal chemotherapy with methotrexate are useful for controlling the disease, but the prognosis remains poor. Therefore, it is important to make an early diagnose and treatment. This review is focused on the clinical manifestations, diagnosis, treatment and prognosis of the IOL.     

Successful Treatment of Necrotizing Retinitis with Epstein–Barr Virus-Positive Ocular Fluid by Intravitreal Methotrexate Injection

ABSTRACT

Purpose

To present a case of necrotizing retinitis with Epstein–Barr virus (EBV)-positive ocular fluid in a patient with sudden unilateral vision loss, which was successfully treated with intravitreal methotrexate (MTX) injections.     

Triamcinolone Intravitreal Injection and Intraocular Pressure in Macular Edema Associated with Retinal Vein Occlusion

 Purpose: To study the risk factors of increased intraocular pressure (IOP) response to triamcinolone acetonide intravitreal (IVTA) injection in eyes with macular edema associated with retinal vein occlusion. Methods: Eighty-nine eyes with macular edema associated with retinal vein occlusion first received periocular injection of 40 mg triamcinolone acetonide (TA) and were followed for one month. According to the diversity of IOP after periocular TA (PTA) injection, they were divided into the elevation IOP group (group A, 26 eyes) and the normal IOP group (group B, 63 eyes). They then received 4 mg TA intravitreal injection. IOP measurements were recorded after PTA and IVTA injections, and were followed for six months. Results: Both PTA and IVTA injections caused a rise in IOP, but it was higher in the IVTA injection (40.45%) than in the PTA injection (29.21%). The mean rise in IOP was more significant in eyes with IVTA injection (28.08 ± 8.24 mmHg) than in eyes with PTA injection (20.87 ± 4.07 mmHg). Patients with an elevation IOP above 6 mmHg after PTA injection had a 73.08% chance of developing a pressure of 24 mmHg or higher, whereas only 12.70% of those with an elevation IOP below 6 mmHg after PTA injection experienced pressure elevation. Conclusion: IOP response to PTA injection is a good way to judge IOP response to IVTA. If the patient is highly sensitive to corticosteroid, treatments other than IVTA injection are used to avoid the increased risks associated with intravitreal corticosteroid injection.     

Clinical Review: Treatment of Vitreoretinal Lymphoma

Vitreoretinal lymphoma is the most common type of intraocular lymphoma. It is mostly a high-grade B-cell malignancy with a poor prognosis, and is often associated with primary central nervous system lymphoma. Since intraocular lymphoma was first recognized almost 60 years ago, its treatment has gradually evolved. In the early years enucleation was often performed. Since that time, radiation therapy alone, systemic chemotherapy alone, or a combination of the two have been used extensively Because of the limited intraocular penetration of drugs administered systemically, the systemic and local toxicity of chemotherapy and radiation therapy and the high rate of recurrence, intravitreous chemotherapy, mainly using methotrexate, has become popular in the last decade, with encouraging results. More recently, biological treatment with intravitreal injections of rituximab has been investigated, with good results and minimal side effects. This review summarizes the present knowledge on vitreoretinal lymphoma therapy, with an eye to future molecular approaches.     

Clinical Characteristics of Primary Vitreoretinal Lymphoma in an Indian Population

Purpose: Primary vitreoretinal lymphomas (PVRL) pose a major diagnostic challenge, especially in the countries with a high prevalence of infectious variety of uveitis. The present study aims to report the clinical characteristics and diagnostic difficulties in patients with PVRL in an Indian Population.Methods: Retrospective chart reviews of 12 patients with a diagnosis of PVRL.Results: The study included 6 men and 6 women, with a mean age of 55.66 ± 8.76 years. All had bilateral disease. The clinical signs included anterior uveitis (12 eyes; 50.0%); vitritis (18 eyes; 75%); vitreous clumps (16 eyes; 66.6%); subretinal deposits (11 eyes; 45.8%); retinal vasculitis (6 eyes; 25%); and optic disc swelling (2 eyes; 8.3%). The most commonly mistaken diagnosis was intraocular tuberculosis. The intraocular lesions responded to multiple intravitreal methotrexate injections.Conclusions: PVRL in India was likely to be mistaken for an infectious variety of uveitis. A high index of suspicion and thorough clinical examination is necessary to make the diagnosis.     

B-scan ultrasound and cytology of the vitreous in primary central nervous system lymphoma with vitreoretinal involvement

AIM: To evaluate the diagnostic value of B-scan ultrasound and explore the cytological characteristics of patients with vitreoretinal lymphoma (VRL) and primary central nervous system lymphoma (PCNSL). METHODS: The clinical data and pathologic specimens from patients with VRL diagnosed at the North Huashan Hospital from 2016 to 2017 were retrospectively reviewed. The patients were diagnosed by slit lamp ophthalmoscopy, B-scan ultrasound, cytology of the vitreous, which was obtained by vitrectomy, and cytokine measurements of interleukin (IL)-10 and IL-6. RESULTS: Twenty-six eyes (19.4%) out of 134 eyes of 67 patients (47 men and 20 women) with PCNSL were diagnosed with VRL by B-scan ultrasound, and 14 eyes (10.4%) were diagnosed by slit lamp ophthalmoscopy. Twenty-four eyes (17.9%) of 17 patients were confirmed as having VRL with cytology. No difference in the association between intracranial lesion location and ocular involvement was found. VRL patients had higher levels of vitreous IL-10 and IL-10/IL-6 when compared with macular hole cases, but the difference was not statistically significant. CONCLUSION: A total of 25.4% of the PCNSL patients had VRL, B-scan ultrasound examination had characteristic features and is recommended over slit lamp ophthalmoscopy for the screening diagnosis of PCNSL with intraocular involvement. Moreover, the cytological and immunohistochemical analyses performed after 25-gauge diagnostic vitrectomy were accurate diagnostic techniques.