Swept-source optical coherence tomography angiography findings in a case of primary vitreoretinal lymphoma over a three-year follow-up.

BACKGROUND: Vitreoretinal lymphoma (VRL) still represents a diagnostic challenge for retinal specialists. Early diagnosis and treatment are critical for a better prognosis. Several diagnostic tools have proven helpful in the identification of VRL abnormalities. However, swept-source OCT angiography (SS-OCT-A) findings and their long-term follow-up are yet to be explored. CASE PRESENTATION: a 42-year-old man presented with blurred vision in his left eye for 2 weeks. He denied any systemic symptoms. A multimodal imaging examination was performed, raising the clinical suspicion of VRL and guiding the ensuing diagnostic procedures. The patient underwent treatment and at the last FU visit three years later, no disease signs were present on fundus examination, nor on oncologic evaluation. Some novel SS-OCT-A features were identified, and uncommonly reported findings were examined over a long-term follow-up. At baseline multiple hyperreflective alterations were detected on the enface outer retina slabs and choriocapillary analysis revealed low reflectance areas in the foveal and parafoveal areas. One month after the first presentation, multiple hyperreflective retinal lesions in a vertical shape were detected on OCT which appeared on midretinal slabs of enface SS-OCT-A as hyperreflective spots mainly located near second-order retinal vessels. These alterations remarkably reduced after treatment. CONCLUSION: SS-OCT-A may be a useful imaging technique in the detection of VRL, providing ophthalmologists additional findings that assist the diagnosis and follow-up of this disease. This may prove useful for a more timely and precise diagnosis, prompt therapy, and treatment response monitoring. The original aspects found in this case may provide grounds for future studies, ultimately fostering a better understanding of the disease.

MR-based radiomics signature in differentiating ocular adnexal lymphoma from idiopathic orbital inflammation.

OBJECTIVES: To assess the value of the MR-based radiomics signature in differentiating ocular adnexal lymphoma (OAL) and idiopathic orbital inflammation (IOI). METHODS: One hundred fifty-seven patients with pathology-proven OAL (84 patients) and IOI (73 patients) were divided into primary and validation cohorts. Eight hundred six radiomics features were extracted from morphological MR images. The least absolute shrinkage and selection operator (LASSO) procedure and linear combination were used to select features and build radiomics signature for discriminating OAL from IOI. Discriminating performance was assessed by the area under the receiver-operating characteristic curve (AUC). The predictive results were compared with the assessment of radiologists by chi-square test. RESULTS: Five radiomics features were included in the radiomics signature, which differentiated OAL from IOI with an AUC of 0.74 and 0.73 in the primary and validation cohorts respectively. There was a significant difference between the classification results of the radiomics signature and those of a radiology resident (p < 0.05), although there was no significant difference between the results of the radiomics signature and those of a more experienced radiologist (p > 0.05). CONCLUSIONS: Radiomics features have the potential to differentiate OAL from IOI. KEY POINTS: • Clinical and imaging findings of OAL and IOI often overlap, which makes diagnosis difficult. • Radiomics features can potentially differentiate OAL from IOI non invasively. • The radiomics signature discriminates OAL from IOI at the same level as an experienced radiologist.

An unusual case report of primary vitreoretinal lymphoma.

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

Mucosa-associated lymphoid tissue lymphoma with intraocular and orbital involvement: case presentation and review of the literature.

Primary ocular lymphomas are typically confined to either the eye or the orbit. Rarely, in immune-competent patients, lymphomas affect both the eye and the orbit simultaneously. Mucosa-associated lymphoid tissue (MALT) lymphomas are the most common ocular lymphomas. They usually present primarily in the orbit but sometimes can present primarily in intraocular tissue. MALT lymphomas that occur initially in the uvea can sometimes spread to the adjacent orbit. We report a case of progressively enlarging MALT lymphoma in a 62-year-old immune-competent patient causing a severe mass effect in the orbit and simultaneously presenting with intraocular involvement. There was radiographic evidence of lymphoma confined to the orbit with intraocular involvement. The simultaneous presentation makes it difficult to determine if the lymphoma initially presented in the orbit or intraocular tissue, although the orbital component was more impressive. The case also includes a literature review of simultaneous orbital and intraocular MALT lymphomas. The patient responded to systemic chemotherapy with regression in size of the lymphoma, relief of the mass effect seen in the orbit, and the regression of the intraocular involvement.

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

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

Clinical Relevance of the High Prevalence of MYD88 L265P Mutated Vitreoretinal Lymphoma Identified by Droplet Digital Polymerase Chain Reaction.

Purpose: To investigate the frequency and clinical relevance of missense mutation at position 265 changing leucine to proline in the myeloid differentiation factor 88 gene (MYD88 L265P) in the vitreous of Chinese patients with vitreoretinal lymphoma (VRL) using droplet digital polymerase chain reaction (ddPCR).Methods: Vitreous fluid (VF) from 29 eyes of 20 VRL patients at the North Huashan Hospital were included. MYD88 L265P analysis of VF was performed using ddPCR. Associations between clinicopathologic characteristics and MYD88 mutation were analyzed using t-test or Fisher's exact test.Results: MYD88 L265P mutations were detected in 22 of 29 samples from 14 patients with diffuse large B-cell lymphomas and one patient with lymphoplasmacytoid lymphoma. However, no significant associations were found between MYD88 L265P mutation status and age, sex, lymphoma subtype or location of the primary lesion.Conclusion: The high prevalence of MYD88 L265P identified by ddPCR suggests that this method of evaluating the frequency of MYD88 L265P is a promising tool for accurate diagnosis of VRL.

Vertical Hyperreflective Lesions on Optical Coherence Tomography in Vitreoretinal Lymphoma.

Importance: Vitreoretinal lymphoma is a diagnostic challenge and the pathophysiology is still unclear. Objective: To describe an imaging finding seen on optical coherence tomography (OCT) of patients with vitreoretinal lymphoma. Design, Setting, and Participants: This case series study was a retrospective medical record review of patients who received a diagnosis of vitreoretinal lymphoma at the Department of Ophthalmology at Northwestern University between July 2014 and January 2016. Main Outcomes and Measures: Optical coherence tomography findings in vitreoretinal lymphoma. Results: We identified 7 patients (4 women [57.1%]; mean [range] age, 62.4 [45-75] years; 12 eyes) with intraocular lymphoma involving the retina (5 patients [71.4%] with primary vitreoretinal or central nervous system lymphoma with ocular involvement, 1 patient [14.3%] with testicular lymphoma with secondary central nervous system lymphoma and vitreoretinal lymphoma, and 1 patient [14.3%] with secondary vitreoretinal lymphoma). We identified vertical hyperreflective lesions that showed moderate or high reflectivity and affected all layers of the neuroretina in 5 patients (7 of 12 eyes [58.3%]). These often preceded the development of subretinal pigment epithelial deposits and were often localized around second-order and third-order retinal vessels. In most cases, they resolved with minimal or no scarring after the initiation of chemotherapy. Conclusions and Relevance: Vertical hyperreflective lesions are a common physical finding on OCT in eyes with vitreoretinal lymphoma.

Aurora borealis and string of pearls in vitreoretinal lymphoma: patterns of vitreous haze.

AIMS: Peculiar retinal signs of vitreoretinal lymphoma (VRL) have been identified. However, limited information on the vitreous features of VRL is available. This study aims to characterise the vitreous involvement in VRL with the help of multimodal imaging. METHODS: In this retrospective, observational study, we reviewed charts and imaging of all patients with biopsy-proven VRL seen from January 2016 to April 2018 at a single referral centre. These included ultrawide-field imaging, ophthalmic ultrasonography and slit-lamp photography. The main outcome measures were patterns of vitreous haze of VRL, as observed by combining clinical and multimodal imaging information. RESULTS: Twenty-six eyes of 13 patients were included. At presentation, vitreous haze was present in 24 eyes (92%) and was the only sign of VRL in 4 eyes (15%). Three patterns of vitreous haze were identified in VRL. An aurora borealis pattern was present in 12 eyes and showed linear opacities with a myriad of cells aligned along the vitreous fibrils. A string of pearls pattern was present in two eyes at baseline and developed in other four eyes after vitrectomy, showing fine fibrils connecting bunches of inflammatory material. A non-specific pattern was observed in 10 eyes. Ophthalmic ultrasound showed corpuscular material correlating with the grading of vitreous haze. CONCLUSION: VRL shows different patterns of vitreous haze. Multimodal imaging, including ultrawide-field imaging and slit-lamp photography, helps in recognising these patterns, raising suspicion for VRL.

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

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

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

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