RARE DISEASE
Primary intraocular lymphoma
Primary intraocular lymphoma
Primary intraocular lymphoma
Synonyms: PIOL, Primary intraocular non-Hodgkin lymphoma
Synonyms: PIOL, Primary intraocular non-Hodgkin lymphoma
Synonyms: PIOL, Primary intraocular non-Hodgkin lymphoma
Drug discovery
1
drug
With orphan designation
Overview
Primary intraocular lymphoma (PIOL), a rare subtype of primary central nervous system lymphoma (PCNSL), is an aggressive diffuse large B-cell lymphoma affecting the retina, vitreous, and/or optic nerve. It often mimics chronic uveitis, delaying diagnosis. Definitive diagnosis requires invasive techniques, including cytokine analysis (IL-10:IL-6 >1) and vitreous biopsy. Treatment combines intravitreal methotrexate/rituximab with systemic high-dose methotrexate-based chemotherapy. Despite initial remission, CNS relapse occurs in up to 90% of patients, resulting in poor prognosis (median survival <3 years) [1][4][7][12].
Therapies
Local control: Intravitreal methotrexate (400 µg) or rituximab (1 mg) injections (induction, consolidation, maintenance phases) [3][12][16].
Systemic therapy: High-dose methotrexate (≥8 g/m²) ± rituximab for CNS prophylaxis [2][3][7].
Radiation: Low-dose ocular radiotherapy (20–40 Gy) for refractory cases; combined neuro-ophthalmic management is critical [3][12][16].
Categories: rare hematological diseases, rare neoplastic diseases, rare ophthalmic disorders, rare transplant-related disorders
Research Papers
335 drug discovery papers about Primary intraocular lymphoma, with 1 first-in-class and 2 next-in-class emerging drug candidates forecasted to outperform the average preclinical success rate. Recent publications:
335 drug discovery papers about Primary intraocular lymphoma, with 1 first-in-class and 2 next-in-class emerging drug candidates forecasted to outperform the average preclinical success rate. Recent publications:
categories:
Small molecules
cell therapies
2026-07-16 | Expanding the Horizon of CAR-T Cell Therapy: Present Obstacles and New Strategies for Future CARs in Solid Tumors.
Chimeric antigen receptor (CAR)-T cells are synthetic receptors used for the recognition of specific antigens expressed by reprogrammed T cells for targeting tumors. CAR-T cell therapy has gained remarkable clinical success for the treatment of hematological malignancies such as chronic lymphocytic leukemia (CLL), mantle cell lymphoma (MCL), diffuse large B-cell lymphoma (DLBCL), lymphoplasmacytic lymphoma (LPL), and primary intraocular lymphoma (PIL). The increasing number of preclinical investigations and clinical trials is focusing on extending CAR-T cell therapy to solid tumors due to its remarkable success in leukemia and lymphoma cancers. However, some limitations of CAR-T therapy still exist, including a lack of targetable antigen diversity, heterogeneous antigen expression, insufficient T-cell trafficking efficiency, and an immunosuppressive tumor microenvironment. This review explores the role of CAR-T cell therapy, current challenges, and emerging solutions for solid tumor malignancies. To overcome the existing limitations of CAR-T cell therapy, innovative strategies, including the optimization of novel CAR vectors with checkpoint inhibitors, have been designed to enhance the antitumor activity of CAR-T cells against solid tumors. It also explores the design of novel CAR-T cells and strategies for improving antitumor activity against solid tumors. Among the emerging strategies, universal CARs and combination approaches with checkpoint inhibitors are especially promising for extending CAR-T therapy to solid tumors.
2026-04-16 | Early diagnosis and management of primary vitreoretinal lymphoma with non-radiologic leptomeningeal involvement using MYD88 Leu265Pro variant analysis.
This case report describes a woman in her 60s diagnosed with primary vitreoretinal lymphoma (PVRL) with leptomeningeal involvement. She presented with a 3-month history of bilateral blurred vision. Funduscopy identified autofluorescent leopard spots, and optical coherence tomography demonstrated typical features of PVRL. Diagnosis was confirmed with the detection of MYD88 Leu265Pro variant in ocular fluid and cerebrospinal fluid (CSF). Abnormal lymphoid cells were seen in vitreous biopsy and CSF. There was no evidence of systemic involvement of lymphoma. Treatment consisted of systemic chemotherapy using the MATRix protocol, ASCT along with close clinical follow-up. Due to the rarity of the condition, evidence for the optimal diagnostic approach and management is limited. Therefore, this case provides an insight into our approach, using the recently published European Haematology Association-European Society for Medical Oncology clinical practice guideline for primary central nervous system lymphoma, along with our recommendations on strategies to facilitate earlier diagnosis and treatment.
2025-12-23 | Immunopathology and molecular biology of primary intraocular lymphoma
Immunopathology of primary intraocular lymphoma reveals a B-cell lymphoma with monoclonal immunoglobulin light chain on the surface. Molecular pathology of primary intraocular lymphoma demonstrates mono-clonality with rearrangements of the immunoglobulin heavy chain gene and translocation of bcl-2. HHV-8 and EBV gene may associate with primary intraocular lymphoma and play a role in oncogenesis. Elevation of inter-leukin-10 level with an IL-10 to IL-6 greater than 1 is found in the vitreous of primary intraocular lymphoma.
2023-08-31 | PRESUMPTIVE RECURRENCE OF INTRAOCULAR LYMPHOMA DESPITE CHIMERIC ANTIGEN RECEPTOR T-CELL THERAPY.
To present the first reported case of presumptive intraocular recurrence of lymphoma following Chimeric Antigen Receptor (CAR) T-cell therapy despite systemic control by CD19-CAR T cells. Observational case report. A 59-year-old man with diffuse, large, B-cell lymphoma subsequently developed secondary central nervous system disease despite chemotherapy. He underwent stem cell transplantation but relapsed again and was scheduled to receive CAR T-cell therapy. He developed vitritis several weeks before treatment, with vitreous biopsy showing non-Hodgkin B-cell lymphoma. He received CAR T-cell therapy following the vitrectomy. He presented 3 months following CAR T-cell therapy with nonspecific right eye floaters and discomfort, with the optical coherence tomography revealing subretinal saw-tooth deposits in the right eye, highly suggestive of lymphoma. This is despite having good systemic control with no other disease elsewhere in the body. He received intravitreal methotrexate to good effect. To our knowledge, this is the first case of a vitreoretinal lymphoma nonresponsive to CAR T-cell therapy, despite good central nervous system and systemic control. This is suggestive of anti-CD19 CAR T cells not trafficking into the eye in sufficient numbers to eliminate CD19-expressing neoplastic B cells. We suggest regular ophthalmic follow-up after CAR-T-cell therapy for patients where there is evidence of ocular involvement.
2022-12-31 | A Case of Relapsed Primary Central Nervous System Lymphoma Treated with CD19-directed Chimeric Antigen Receptor T Cell Therapy
Although high-dose methotrexate (HD-MTX) is the standard therapy for primary central nervous system lymphoma (PCNSL), the prognosis remains poor. Because 90% of PCNSL is diffuse large B-cell lymphoma (DLBCL), chimeric antigen receptor (CAR)-T cell therapy is expected to be beneficial. However, there are limited reports on CAR-T cell therapy for PCNSL because of the concern of neurotoxicity. Here, we report a case of relapsed PCNSL treated with anti-CD19 CAR-T cell therapy. A 40-year-old woman presenting with visual disturbance in her left eye was initially diagnosed with bilateral uveitis. Her histological diagnosis was DLBCL, and she was positive for CD19. Although she received chemotherapy including HD-MTX, the tumor relapsed in her right occipital lobe. She underwent remission induction therapy and then anti-CD19 CAR-T cell therapy. Cytokine release syndrome (CRS) grade 2 occurred, but there were no complications of CAR-T cell-related encephalopathy syndrome (CRES). She has achieved complete response for more than 1 year. Anti-CD19 CAR-T cell therapy is a revolutionary immunotherapy for treating relapsed or refractory (R/R) B lineage malignancies. Although there are concerns regarding CRS and CRES in central nervous system lymphoma, the use of anti-CD19 CAR-T cells to treat R/R PCNSL is safe and feasible.
small molecules
2026-08-10 | Diagnostic and therapeutic challenges in primary vitreoretinal lymphoma: a practical clinical approach.
Primary vitreoretinal lymphoma (PVRL) is a rare but aggressive subtype of extranodal diffuse large B-cell lymphoma and is closely related to primary central nervous system lymphoma (PCNSL). Its ability to masquerade as chronic posterior uveitis frequently leads to delayed diagnosis and inappropriate treatment, with significant prognostic implications. A narrative review was performed following a comprehensive search of the PubMed/MEDLINE and Cochrane Library databases, encompassing publications from 2000 through 2025 and including randomized controlled trials, observational studies, prospective and retrospective studies, and systematic reviews. The search strategy incorporated the following keywords: "primary vitreoretinal lymphoma", "intraocular lymphoma", "diagnostic vitrectomy", "MYD88 mutation", "IL-10/IL-6 ratio", "intravitreal methotrexate", "rituximab", "CNS involvement", "optical coherence tomography". Two authors independently conducted study selection and eligibility assessment. Heightened clinical awareness remains pivotal for diagnosing PVRL, particularly when vitritis is partially responsive to steroids, when involvement is bilateral or asymmetric, and when subretinal pigment epithelial infiltrates are present. Multimodal imaging - including optical coherence tomography (OCT), fundus autofluorescence (FAF), and fluorescein angiography (FA) - facilitates early recognition and supports clinical suspicion. Diagnostic vitrectomy with cytology, immunohistochemistry, cytokine analysis (IL-10/IL-6 ratio), and molecular testing (IgH rearrangement, MYD88 L265P mutation) significantly increases diagnostic accuracy. Due to the strong association with central nervous system (CNS) involvement, neuroimaging is mandatory at diagnosis and during follow-up. Treatment options include intravitreal methotrexate and/or rituximab, systemic high-dose methotrexate-based chemotherapy, and radiotherapy. Emerging therapies in PVRL focus on targeted agents, including intravitreal biologics, BTK inhibitors, and personalized molecular-based treatments. The optimal strategy remains controversial and should be individualized based on CNS status and patient characteristics. Primary vitreoretinal lymphoma remains a diagnostic challenge due to its ability to mimic chronic inflammatory eye disorders and the frequent delay in establishing a definitive diagnosis. The integration of multimodal imaging, vitreous cytology, immunohistochemistry, cytokine profiling, and molecular testing has significantly improved diagnostic accuracy. However, management remains complex because of the close association with CNS involvement and the absence of universally accepted treatment protocols. Current therapeutic approaches, including intravitreal chemotherapy, systemic methotrexate-based regimens, and targeted therapies, require individualized selection based on disease extension and patient characteristics. Future advances in molecular diagnostics and personalized treatment strategies may contribute to earlier detection, improved disease control, and better long-term outcomes. Prompt diagnosis, combined with a structured diagnostic approach, is essential to improving outcomes in PVRL. Close collaboration among ophthalmologists, hematologists, neurologists, and pathologists is mandatory for optimal patient management.
2026-06-26 | Case Report: Longitudinal analysis of local immunoregulatory mediators in a DLBCL vitreoretinal lymphoma receiving local chemotherapy.
Vitreoretinal lymphoma (VRL) is a rare, high-grade B-cell lymphoma that affects immune-privileged sites and is classified as a variant of primary central nervous system lymphoma (PCNSL). The pathogenesis of VRL, including the origin of malignant B-cells, remains poorly understood. Cytokines, chemokines, and growth factors are thought to play critical roles in both the homing and autocrine proliferation of lymphomatous B-cells. In this study, we present the first longitudinal analysis of the dynamic interplay of vitreous immune mediators during intravitreal (IVT) methotrexate and dexamethasone therapy in a patient with VRL. A patient in their 70s with unilateral VRL underwent nine serial vitreous samplings over 12 weeks of IVT therapy with methotrexate (460 μg/injection) and dexamethasone (0.4 mg/injection). Each 0.2 mL vitreous sample was analyzed using a multiplex panel assessing 58 cytokines, chemokines, and growth factors. Vitreous levels were monitored longitudinally and correlated with clinical responses and optical coherence tomography. During therapy, key cytokines, including IL-10, IL-6, IL-16, IL-1RA, and sIL-2R, decreased progressively, with IL-10 becoming undetectable by day 22. Chemokines CXCL12 and CXCL13, involved in malignant B-cell homing, declined more slowly than IL-10, suggesting persistent microenvironmental support for tumor cells. MCP-1 remained elevated, whereas hepatocyte growth factor (HGF) was consistently high, indicating potentially aggressive behavior. Other immune mediators, including MIP-1α, MIP-1β, Mig (CXCL9), and IP-10 (CXCL10), showed variable kinetics, reflecting a dynamic interplay between the tumor and host immune response. Notably, certain cytokines previously reported in VRL cohorts, such as FGF2, IFN-γ, TNF-α, and IL-17, were not elevated, highlighting patient-specific variability in the immunological profile. This case represents the first longitudinal characterization of vitreous immune mediators during IVT MTX/dexamethasone therapy for VRL. Dynamic changes in soluble mediators mirrored clinical tumor regression and suggested potential biomarkers for disease activity, therapeutic response, and prognosis. Persistent chemokines, such as CXCL12 and CXCL13, may indicate the optimal treatment duration, whereas high HGF levels may identify patients with aggressive disease. These findings propose a novel framework for integrating intraocular immunomonitoring into personalized therapeutic strategies and deepen our understanding of the complex tumor-immune microenvironment in vitreoretinal lymphoma. As derived from a single case, these observations are hypothesis-generating and require confirmation in larger cohorts.
2026-02-15 | Real world outcomes of intravitreal and systemic therapy in primary and secondary vitreoretinal lymphoma.
Vitreoretinal large B-cell lymphoma (VR-LBCL) is a rare hematologic malignancy. It is classified as primary (PVR-LBCL) or secondary (SVR-LBCL) based on the initial site of manifestation. Owing to limited prospective data and absent standardized guidelines, treatment remains challenging. This dual-center retrospective study aimed to evaluate outcomes of methotrexate (MTX) intravitreal (itv.), Rituximab itv., or combinatorial itv. therapy (R-MTX) and assess the impact of additional systemic immunochemotherapy. Among 65 patients (median age 72 years) included, 55.4% (n = 36) had PVR-LBCL. The median time to diagnosis was 31 days (1–2805). Over a median follow-up of 23.2 months, 35 patients relapsed. MTX itv. showed a trend toward better ocular relapse-free-survival than Rituximab itv. (P = 0.07). Intriguingly, patients receiving R-MTX itv. experienced no relapses throughout follow-up. In general, addition of systemic therapy was associated with significantly longer relapse-free-survival compared to itv. monotherapy (P = 0.05). Keratopathy and elevated intraocular pressure were common side effects with MTX itv. and Rituximab itv., respectively. Despite compelling findings and being one of the largest cohorts published to date, the heterogeneity of the patient population and small subgroups limit direct clinical translation. Nonetheless, this study provides a strong foundation for the design of future clinical trials. The online version contains supplementary material available at 10.1038/s41598-026-37804-4.
2026-01-15 | Intravitreal Management of Ocular Lymphoma Should Use Adjusted Drug Concentrations Not Fixed Dosages.
Most vitreo-retinal lymphoma are rare high-grade B cell lymphoma of immune privileged sites. As there is considerable heterogeneity, the clinical management hampers the optimisation of treatment protocols. While most patients respond to a fixed intravitreal dose of 400 µg, corneal toxicity is seen in 20 to 50% of patients when administered at short intervals under 1 month. Local recurrence of disease is also seen in about 20% of patients. While systemic chemotherapy is weight or surface dependent, most intraocular treatment protocols follow a fixed dose regimen. By analysing existing published data, we show that both experimentally and clinically, the elimination of intraocular methotrexate follows a first order kinetic model. Starting with an initial concentration of 100 µg/ml of vitreous volume, in most instances, a therapeutic level is present for 3 to 5 days. Systemic therapy alone does not achieve these sustained ocular levels. Furthermore, with vitreous volumes which can vary between 3 and 10 ml, using a fixed Mtx dose can either lead to increased risk of toxicity or under treatment. Future treatment protocols should make use of fixed initial concentrations rather than a fixed dose, thus allowing a better comparison of outcomes. Formulas to adjust the concentration of Mtx to be delivered in a fixed volume are provided.
2025-12-30 | Intravitreal methotrexate injection for intraocular lymphoma
Objectives: To review the clinical outcomes of five patients with intraocular lymphoma (IOL) who were treated with intravitreal methotrexate (MTX) injections at the Hong Kong Eye Hospital after 2022.Methods: We retrospectively reviewed medical records of five patients with definite or presumed IOL without systemic or central nervous system (CNS) involvement at the time of diagnosis, who were treated with intravitreal MTX injections.Results: In total, eight eyes in one man and four women of Chinese ethnicity aged 54 to 90 (mean, 68.4) years underwent intravitreal MTX injections for IOL.Three patients had primary IOL; one patient had a relapse of diffuse large B-cell lymphoma with secondary IOL; and one patient had a relapse of primary CNS lymphoma with ocular involvement.All five patients underwent diagnostic pars plana vitrectomy.Definitive cytology of malignant large B-cell lymphoma was achieved in only one eye, whereas four eyes were diagnosed cytologically with a lymphoproliferative lesion.All patients received local intravitreal MTX injections with a mean of 20.9 injections given to each eye.All patients achieved ocular disease regression; however, two patients with primary IOL eventually had CNS involvement. Conclusion:Primary IOL carries a high risk of CNS disease progression.Local ocular treatments such as intravitreal MTX injections can effectively control the disease locally but do not prevent or treat CNS or systemic involvement.Monitoring by a multidisciplinary team using magnetic resonance imaging, positron emission tomography-computed tomography, and/or lumbar punctures can detect CNS or systemic disease early.
antibodies
2026-07-16 | Long-term observation of treatment strategies for primary vitreoretinal lymphoma in a multicenter Chinese cohort.
To compare outcomes of different treatment regimens for primary vitreoretinal lymphoma (PVRL) without central nervous system (CNS) involvement, specifically assessing their association with subsequent onset of central nervous system lymphoma (CNSL). This retrospective study collected data from 64 PVRL patients (118 eyes) from January 2015 to June 2023 at 4 ophthalmologic centers in China. Clinical, laboratory, and imaging data of these patients has been reviewed, focusing on the incidence of CNS manifestations during follow-up. Among the 64 patients with PVRL, 26 patients received only intravitreal injection of methotrexate (group A), and 38 patients received combined intraocular and systemic treatment (group B). The median follow-up time was 36.1 months, the median CNS progression-free survival (PFS) was 23.5 months, and the median overall survival (OS) was not-reached. CNSL developed in 44 of the 64 patients (68.8%) during the follow-up, including 19 of the 26 patients (73.1%) in group A, and 25 of the 38 (65.8%) in group B. Increased cerebrospinal fluid IL-10 levels (range: 2.2-472 pg/ml, mean 63.715 pg/ml) were significantly correlated with the progression of CNSL (P < 0.001). In this observational cohort, combined therapeutic approach of systemic and intraocular therapy was associated with higher OS (P = 0.002). No significant differences in CNS-PFS was observed between the two treatment groups (P = 0.095). In this cohort of patients with PVRL, combined intraocular and systemic therapy may be associated with longer OS, while no significant difference in CNS-PFS was observed.
2026-05-27 | Successful use of intravitreal rituximab as salvage therapy for relapsed vitreoretinal lymphoma.
To describe the outcomes, response patterns, and complications of intravitreal rituximab (IVR) in eyes with relapsed vitreoretinal lymphoma (VRL) despite previous treatment with ocular radiotherapy (EBRT). Retrospective observational single-center study. This study included all patients diagnosed with relapsed VRL who received IVR between 2011 and 2024 at our National Ocular Oncology Service in the United Kingdom. Demographic data, systemic and ocular lymphoma history, treatment details, visual acuity, and ocular adverse events were collected from medical records. Ten eyes of six patients with relapsed VRL were treated with IVR. All eyes had been previously treated with ocular EBRT and with whole brain radiotherapy (WBRT) (83.3%) and systemic chemotherapy (66.7%) for CNS lymphoma. Eyes with relapsed VRL were treated with a mean of four IVR injections (1 mg/0.1 mL) per treatment course using weekly to monthly intervals. Complete ocular remission was achieved in all eyes after a single course of IVR. One eye experienced a further relapse 14 months later, successfully treated with a second course of IVR. Ocular adverse events potentially attributable to IVR included transient intraocular hypertension and mild uveitis; other complications, such as cataract, radiation retinopathy, and retinal atrophy were likely related to EBRT rather than IVR. In our cohort of relapsed VRL despite previous ocular EBRT, IVR used as a sole focal therapy was associated with high rates of ocular remission and acceptable local toxicity. These findings support the use of IVR as a standard salvage treatment in cases of relapsed VRL.
2024-11-05 | Primary Vitreoretinal Lymphoma: A Comprehensive Retrospective Analysis of 65 Cases at Two European Centers
Introduction. Primary vitreoretinal lymphoma (PVRL) is a distinct subset of primary central nervous system lymphoma (PCNSL), characterized by its emergence within the intraocular environment without initial brain involvement. The pathogenesis of PVRL remains unclear, though it is hypothesized to originate outside the CNS, subsequently migrating to ocular regions where an immune-permissive microenvironment facilitates its manifestation. Diagnostically, PVRL presents significant challenges due to its clinical mimicry of uveitis and the fragility of lymphoma cells in the vitreous. The treatment of PVRL is demanding as well, with diverse and heterogeneous strategies, encompassing localized intravitreal therapy, radiotherapy, systemic chemotherapy, and targeted therapy. However, as a rare disease, data on PVRL are limited, and prospective trials are largely absent. Through collaboration between two European centers, we conducted a comprehensive retrospective analysis of PVRL cases to evaluate treatment outcomes and relapse behavior, aiming to enhance understanding of this challenging condition. Methods. A retrospective analysis of PVRL cases was performed at the University Hospital Tübingen and the Medical University Graz. Electronic health records were analyzed for demographic data, clinical presentation, diagnostic procedure, treatments and outcome, relapse manifestations and adverse events. Descriptive statistics are provided for the entire cohort and center-specific cohorts. Statistical comparisons using SPSS were performed where possible. Results. A total of 65 cases with intraocular lymphoma involvement were identified (Tübingen n=34, Graz n=31), comprising 40 cases of primary vitreoretinal lymphoma (PVRL), 9 cases of primary central nervous system lymphoma (PCNSL) with later ocular involvement, 5 cases of PCNSL with simultaneous eye infiltration, and 11 cases of systemic diffuse large B-cell lymphoma (DLBCL) at initial diagnosis. The mean age at diagnosis was 72.7 years (range 49-96), 55.4% were female, and the median follow-up time was 18 months. The median time to diagnosis from the onset of the first symptoms was 31 days (range 1-2805). There was considerable heterogeneity in treatment modalities and clinical management. Intravitreal (itv.) treatment primarily involved Rituximab (n=34), Methotrexate (n=19), or combinations thereof (n=5). Intravitreal Methotrexate resulted in clinically significant keratopathy in 11 of 12 cases (91.7%), while Rituximab caused increased intraocular pressure in 9 of 34 cases (26.4%). Intravitreal treatment (n=58) resulted in 55.2% complete responses, and 34.6% partial responses, without a significant difference between modalities. A total of 69.2% (n=45) of patients received systemic chemotherapy at some point, including 11 patients who received systemic immunochemotherapy despite having exclusive eye manifestations. Despite intensive therapy, 70% of cases developed a single documented relapse of any kind, while 52.4% developed a second relapse, considering high rates of patients lost to follow-up (n=25). Conclusions. This retrospective analysis of a large cohort highlights the significant heterogeneity in treatment approaches for PVRL. The study found no significant differences in overall outcomes between intravitreal rituximab and intravitreal methotrexate. However, each treatment had distinct adverse effects, with methotrexate causing keratopathy and rituximab associated with increased intraocular pressure. Despite diverse treatment strategies, the high rate of relapses underscores the need for standardized treatment protocols. Future prospective trials are essential to optimize therapeutic strategies and improve long-term outcomes for PVRL patients, addressing both intraocular disease control and CNS relapse prevention.
2024-08-27 | Hypopyon Uveitis as a Manifestation of Primary Choroidal Lymphoma.
A 78-year-old female was referred to our hospital due to a decrease of visual acuity in her left eye. On examination, presence of left choroidal folds and subretinal fluid was disclosed. After being misdiagnosed as neovascular age-related macular degeneration treatment with intravitreal injections of Aflibercept was started. Despite improvement of fluid, persistence of choroidal folds encouraged a magnetic resonance imaging revealing a left retrobulbar nodular lesion. Furthermore, development of hypopyon during follow-up allowed a flow cytometry analysis of an aqueous humour sample that confirmed infiltration by a non-Hodgkin mature B-cell lymphoproliferative process. Finally, treatment with Rituximab and intravenous corticosteroids achieved complete resolution. Primary choroidal lymphoma may occur with an atypical presentation, including hypopyon uveitis. Thus, familiarity with its clinical features is fundamental for an early recognition and correct management.
2024-06-12 | A case of ocular diffuse large B-cell lymphoma unveiled through Pars Plana Vitrectomy: surgical insight and multidisciplinary management.
We present a rare case of ocular diffuse large B-cell lymphoma (DLBCL) unveiled through Pars Plana Vitrectomy in a 74-year-old immunocompromised male, highlighting the surgical insight and multidisciplinary management required for similar cases. The patient's progressive vision impairment led to a Pars Plana Vitrectomy, which confirmed DLBCL through cytogenetic analysis. Initial intraocular rituximab treatment showed promise; however, the lymphoma's systemic progression necessitated a shift to more aggressive chemotherapy, underscored by pleural and pericardial effusions and central nervous system involvement. This case emphasizes the critical role of surgical techniques in diagnosing ocular lymphomas and the importance of a multidisciplinary approach in managing the disease's ocular and systemic manifestations. The complexities introduced by the patient's immunosuppression highlight the necessity for individualized treatment strategies. This case calls for further research into ocular lymphomagenesis and exploring therapies with enhanced efficacy and reduced toxicity, and emphasizes the importance of early diagnosis in ocular DLBCL cases.
oligonucleotides
2026-02-25 | Exosome-Based Approaches in Regenerative Medicine and Targeted Therapy for Eye Malignancies: A Comprehensive Review.
Diagnosing and treating ocular malignancies-such as uveal melanoma, retinoblastoma, intraocular lymphoma, and conjunctival tumors-can be very difficult given their rarity, complicated pathophysiology, and a high potential for complications that threaten vision or life. Traditional treatments such as chemotherapy, radiation, and surgery result in limited clinical value because of systemic toxicity, versatile drug resistance, and insufficient local control. Exosomes (EXOs)-naturally occurring nanoscale vesicles held in biocompatible structures-represent a uniquely advantageous platform for targeting and delivering miRNAs, proteins and/or gene editing molecules across ocular barriers to create corrective, sustained, and targeted diagnostics, drug delivery, and immune modulation. Mesenchymal stem cell-derived exosomes (MSC-EXOs) also possess regenerative potential in both animal and human models of retinal and ocular injury, engaging biological pathways involved in modulating inflammation and neuroprotection such as HMGB1 and PI3K/AKT pathways. While the use of EXOs presents a promising option for ocular treatment application, several factors complicate actual clinical translation, including standardization of isolation, scalable manufacture, and regulatory issues. In general, EXO-based nanomedicine may be a promising new direction for precision therapy and regenerative ophthalmology with the increasing introduction of synthetic and bioengineered EXOs introducing precursor paving new avenues for clinically scalable and biologically customizable EXO therapeutics.
cell therapies
2026-07-16 | Expanding the Horizon of CAR-T Cell Therapy: Present Obstacles and New Strategies for Future CARs in Solid Tumors.
Chimeric antigen receptor (CAR)-T cells are synthetic receptors used for the recognition of specific antigens expressed by reprogrammed T cells for targeting tumors. CAR-T cell therapy has gained remarkable clinical success for the treatment of hematological malignancies such as chronic lymphocytic leukemia (CLL), mantle cell lymphoma (MCL), diffuse large B-cell lymphoma (DLBCL), lymphoplasmacytic lymphoma (LPL), and primary intraocular lymphoma (PIL). The increasing number of preclinical investigations and clinical trials is focusing on extending CAR-T cell therapy to solid tumors due to its remarkable success in leukemia and lymphoma cancers. However, some limitations of CAR-T therapy still exist, including a lack of targetable antigen diversity, heterogeneous antigen expression, insufficient T-cell trafficking efficiency, and an immunosuppressive tumor microenvironment. This review explores the role of CAR-T cell therapy, current challenges, and emerging solutions for solid tumor malignancies. To overcome the existing limitations of CAR-T cell therapy, innovative strategies, including the optimization of novel CAR vectors with checkpoint inhibitors, have been designed to enhance the antitumor activity of CAR-T cells against solid tumors. It also explores the design of novel CAR-T cells and strategies for improving antitumor activity against solid tumors. Among the emerging strategies, universal CARs and combination approaches with checkpoint inhibitors are especially promising for extending CAR-T therapy to solid tumors.
2026-04-16 | Early diagnosis and management of primary vitreoretinal lymphoma with non-radiologic leptomeningeal involvement using MYD88 Leu265Pro variant analysis.
This case report describes a woman in her 60s diagnosed with primary vitreoretinal lymphoma (PVRL) with leptomeningeal involvement. She presented with a 3-month history of bilateral blurred vision. Funduscopy identified autofluorescent leopard spots, and optical coherence tomography demonstrated typical features of PVRL. Diagnosis was confirmed with the detection of MYD88 Leu265Pro variant in ocular fluid and cerebrospinal fluid (CSF). Abnormal lymphoid cells were seen in vitreous biopsy and CSF. There was no evidence of systemic involvement of lymphoma. Treatment consisted of systemic chemotherapy using the MATRix protocol, ASCT along with close clinical follow-up. Due to the rarity of the condition, evidence for the optimal diagnostic approach and management is limited. Therefore, this case provides an insight into our approach, using the recently published European Haematology Association-European Society for Medical Oncology clinical practice guideline for primary central nervous system lymphoma, along with our recommendations on strategies to facilitate earlier diagnosis and treatment.
2025-12-23 | Immunopathology and molecular biology of primary intraocular lymphoma
Immunopathology of primary intraocular lymphoma reveals a B-cell lymphoma with monoclonal immunoglobulin light chain on the surface. Molecular pathology of primary intraocular lymphoma demonstrates mono-clonality with rearrangements of the immunoglobulin heavy chain gene and translocation of bcl-2. HHV-8 and EBV gene may associate with primary intraocular lymphoma and play a role in oncogenesis. Elevation of inter-leukin-10 level with an IL-10 to IL-6 greater than 1 is found in the vitreous of primary intraocular lymphoma.
2023-08-31 | PRESUMPTIVE RECURRENCE OF INTRAOCULAR LYMPHOMA DESPITE CHIMERIC ANTIGEN RECEPTOR T-CELL THERAPY.
To present the first reported case of presumptive intraocular recurrence of lymphoma following Chimeric Antigen Receptor (CAR) T-cell therapy despite systemic control by CD19-CAR T cells. Observational case report. A 59-year-old man with diffuse, large, B-cell lymphoma subsequently developed secondary central nervous system disease despite chemotherapy. He underwent stem cell transplantation but relapsed again and was scheduled to receive CAR T-cell therapy. He developed vitritis several weeks before treatment, with vitreous biopsy showing non-Hodgkin B-cell lymphoma. He received CAR T-cell therapy following the vitrectomy. He presented 3 months following CAR T-cell therapy with nonspecific right eye floaters and discomfort, with the optical coherence tomography revealing subretinal saw-tooth deposits in the right eye, highly suggestive of lymphoma. This is despite having good systemic control with no other disease elsewhere in the body. He received intravitreal methotrexate to good effect. To our knowledge, this is the first case of a vitreoretinal lymphoma nonresponsive to CAR T-cell therapy, despite good central nervous system and systemic control. This is suggestive of anti-CD19 CAR T cells not trafficking into the eye in sufficient numbers to eliminate CD19-expressing neoplastic B cells. We suggest regular ophthalmic follow-up after CAR-T-cell therapy for patients where there is evidence of ocular involvement.
2022-12-31 | A Case of Relapsed Primary Central Nervous System Lymphoma Treated with CD19-directed Chimeric Antigen Receptor T Cell Therapy
Although high-dose methotrexate (HD-MTX) is the standard therapy for primary central nervous system lymphoma (PCNSL), the prognosis remains poor. Because 90% of PCNSL is diffuse large B-cell lymphoma (DLBCL), chimeric antigen receptor (CAR)-T cell therapy is expected to be beneficial. However, there are limited reports on CAR-T cell therapy for PCNSL because of the concern of neurotoxicity. Here, we report a case of relapsed PCNSL treated with anti-CD19 CAR-T cell therapy. A 40-year-old woman presenting with visual disturbance in her left eye was initially diagnosed with bilateral uveitis. Her histological diagnosis was DLBCL, and she was positive for CD19. Although she received chemotherapy including HD-MTX, the tumor relapsed in her right occipital lobe. She underwent remission induction therapy and then anti-CD19 CAR-T cell therapy. Cytokine release syndrome (CRS) grade 2 occurred, but there were no complications of CAR-T cell-related encephalopathy syndrome (CRES). She has achieved complete response for more than 1 year. Anti-CD19 CAR-T cell therapy is a revolutionary immunotherapy for treating relapsed or refractory (R/R) B lineage malignancies. Although there are concerns regarding CRS and CRES in central nervous system lymphoma, the use of anti-CD19 CAR-T cells to treat R/R PCNSL is safe and feasible.
small molecules
2026-08-10 | Diagnostic and therapeutic challenges in primary vitreoretinal lymphoma: a practical clinical approach.
Primary vitreoretinal lymphoma (PVRL) is a rare but aggressive subtype of extranodal diffuse large B-cell lymphoma and is closely related to primary central nervous system lymphoma (PCNSL). Its ability to masquerade as chronic posterior uveitis frequently leads to delayed diagnosis and inappropriate treatment, with significant prognostic implications. A narrative review was performed following a comprehensive search of the PubMed/MEDLINE and Cochrane Library databases, encompassing publications from 2000 through 2025 and including randomized controlled trials, observational studies, prospective and retrospective studies, and systematic reviews. The search strategy incorporated the following keywords: "primary vitreoretinal lymphoma", "intraocular lymphoma", "diagnostic vitrectomy", "MYD88 mutation", "IL-10/IL-6 ratio", "intravitreal methotrexate", "rituximab", "CNS involvement", "optical coherence tomography". Two authors independently conducted study selection and eligibility assessment. Heightened clinical awareness remains pivotal for diagnosing PVRL, particularly when vitritis is partially responsive to steroids, when involvement is bilateral or asymmetric, and when subretinal pigment epithelial infiltrates are present. Multimodal imaging - including optical coherence tomography (OCT), fundus autofluorescence (FAF), and fluorescein angiography (FA) - facilitates early recognition and supports clinical suspicion. Diagnostic vitrectomy with cytology, immunohistochemistry, cytokine analysis (IL-10/IL-6 ratio), and molecular testing (IgH rearrangement, MYD88 L265P mutation) significantly increases diagnostic accuracy. Due to the strong association with central nervous system (CNS) involvement, neuroimaging is mandatory at diagnosis and during follow-up. Treatment options include intravitreal methotrexate and/or rituximab, systemic high-dose methotrexate-based chemotherapy, and radiotherapy. Emerging therapies in PVRL focus on targeted agents, including intravitreal biologics, BTK inhibitors, and personalized molecular-based treatments. The optimal strategy remains controversial and should be individualized based on CNS status and patient characteristics. Primary vitreoretinal lymphoma remains a diagnostic challenge due to its ability to mimic chronic inflammatory eye disorders and the frequent delay in establishing a definitive diagnosis. The integration of multimodal imaging, vitreous cytology, immunohistochemistry, cytokine profiling, and molecular testing has significantly improved diagnostic accuracy. However, management remains complex because of the close association with CNS involvement and the absence of universally accepted treatment protocols. Current therapeutic approaches, including intravitreal chemotherapy, systemic methotrexate-based regimens, and targeted therapies, require individualized selection based on disease extension and patient characteristics. Future advances in molecular diagnostics and personalized treatment strategies may contribute to earlier detection, improved disease control, and better long-term outcomes. Prompt diagnosis, combined with a structured diagnostic approach, is essential to improving outcomes in PVRL. Close collaboration among ophthalmologists, hematologists, neurologists, and pathologists is mandatory for optimal patient management.
2026-06-26 | Case Report: Longitudinal analysis of local immunoregulatory mediators in a DLBCL vitreoretinal lymphoma receiving local chemotherapy.
Vitreoretinal lymphoma (VRL) is a rare, high-grade B-cell lymphoma that affects immune-privileged sites and is classified as a variant of primary central nervous system lymphoma (PCNSL). The pathogenesis of VRL, including the origin of malignant B-cells, remains poorly understood. Cytokines, chemokines, and growth factors are thought to play critical roles in both the homing and autocrine proliferation of lymphomatous B-cells. In this study, we present the first longitudinal analysis of the dynamic interplay of vitreous immune mediators during intravitreal (IVT) methotrexate and dexamethasone therapy in a patient with VRL. A patient in their 70s with unilateral VRL underwent nine serial vitreous samplings over 12 weeks of IVT therapy with methotrexate (460 μg/injection) and dexamethasone (0.4 mg/injection). Each 0.2 mL vitreous sample was analyzed using a multiplex panel assessing 58 cytokines, chemokines, and growth factors. Vitreous levels were monitored longitudinally and correlated with clinical responses and optical coherence tomography. During therapy, key cytokines, including IL-10, IL-6, IL-16, IL-1RA, and sIL-2R, decreased progressively, with IL-10 becoming undetectable by day 22. Chemokines CXCL12 and CXCL13, involved in malignant B-cell homing, declined more slowly than IL-10, suggesting persistent microenvironmental support for tumor cells. MCP-1 remained elevated, whereas hepatocyte growth factor (HGF) was consistently high, indicating potentially aggressive behavior. Other immune mediators, including MIP-1α, MIP-1β, Mig (CXCL9), and IP-10 (CXCL10), showed variable kinetics, reflecting a dynamic interplay between the tumor and host immune response. Notably, certain cytokines previously reported in VRL cohorts, such as FGF2, IFN-γ, TNF-α, and IL-17, were not elevated, highlighting patient-specific variability in the immunological profile. This case represents the first longitudinal characterization of vitreous immune mediators during IVT MTX/dexamethasone therapy for VRL. Dynamic changes in soluble mediators mirrored clinical tumor regression and suggested potential biomarkers for disease activity, therapeutic response, and prognosis. Persistent chemokines, such as CXCL12 and CXCL13, may indicate the optimal treatment duration, whereas high HGF levels may identify patients with aggressive disease. These findings propose a novel framework for integrating intraocular immunomonitoring into personalized therapeutic strategies and deepen our understanding of the complex tumor-immune microenvironment in vitreoretinal lymphoma. As derived from a single case, these observations are hypothesis-generating and require confirmation in larger cohorts.
2026-02-15 | Real world outcomes of intravitreal and systemic therapy in primary and secondary vitreoretinal lymphoma.
Vitreoretinal large B-cell lymphoma (VR-LBCL) is a rare hematologic malignancy. It is classified as primary (PVR-LBCL) or secondary (SVR-LBCL) based on the initial site of manifestation. Owing to limited prospective data and absent standardized guidelines, treatment remains challenging. This dual-center retrospective study aimed to evaluate outcomes of methotrexate (MTX) intravitreal (itv.), Rituximab itv., or combinatorial itv. therapy (R-MTX) and assess the impact of additional systemic immunochemotherapy. Among 65 patients (median age 72 years) included, 55.4% (n = 36) had PVR-LBCL. The median time to diagnosis was 31 days (1–2805). Over a median follow-up of 23.2 months, 35 patients relapsed. MTX itv. showed a trend toward better ocular relapse-free-survival than Rituximab itv. (P = 0.07). Intriguingly, patients receiving R-MTX itv. experienced no relapses throughout follow-up. In general, addition of systemic therapy was associated with significantly longer relapse-free-survival compared to itv. monotherapy (P = 0.05). Keratopathy and elevated intraocular pressure were common side effects with MTX itv. and Rituximab itv., respectively. Despite compelling findings and being one of the largest cohorts published to date, the heterogeneity of the patient population and small subgroups limit direct clinical translation. Nonetheless, this study provides a strong foundation for the design of future clinical trials. The online version contains supplementary material available at 10.1038/s41598-026-37804-4.
2026-01-15 | Intravitreal Management of Ocular Lymphoma Should Use Adjusted Drug Concentrations Not Fixed Dosages.
Most vitreo-retinal lymphoma are rare high-grade B cell lymphoma of immune privileged sites. As there is considerable heterogeneity, the clinical management hampers the optimisation of treatment protocols. While most patients respond to a fixed intravitreal dose of 400 µg, corneal toxicity is seen in 20 to 50% of patients when administered at short intervals under 1 month. Local recurrence of disease is also seen in about 20% of patients. While systemic chemotherapy is weight or surface dependent, most intraocular treatment protocols follow a fixed dose regimen. By analysing existing published data, we show that both experimentally and clinically, the elimination of intraocular methotrexate follows a first order kinetic model. Starting with an initial concentration of 100 µg/ml of vitreous volume, in most instances, a therapeutic level is present for 3 to 5 days. Systemic therapy alone does not achieve these sustained ocular levels. Furthermore, with vitreous volumes which can vary between 3 and 10 ml, using a fixed Mtx dose can either lead to increased risk of toxicity or under treatment. Future treatment protocols should make use of fixed initial concentrations rather than a fixed dose, thus allowing a better comparison of outcomes. Formulas to adjust the concentration of Mtx to be delivered in a fixed volume are provided.
2025-12-30 | Intravitreal methotrexate injection for intraocular lymphoma
Objectives: To review the clinical outcomes of five patients with intraocular lymphoma (IOL) who were treated with intravitreal methotrexate (MTX) injections at the Hong Kong Eye Hospital after 2022.Methods: We retrospectively reviewed medical records of five patients with definite or presumed IOL without systemic or central nervous system (CNS) involvement at the time of diagnosis, who were treated with intravitreal MTX injections.Results: In total, eight eyes in one man and four women of Chinese ethnicity aged 54 to 90 (mean, 68.4) years underwent intravitreal MTX injections for IOL.Three patients had primary IOL; one patient had a relapse of diffuse large B-cell lymphoma with secondary IOL; and one patient had a relapse of primary CNS lymphoma with ocular involvement.All five patients underwent diagnostic pars plana vitrectomy.Definitive cytology of malignant large B-cell lymphoma was achieved in only one eye, whereas four eyes were diagnosed cytologically with a lymphoproliferative lesion.All patients received local intravitreal MTX injections with a mean of 20.9 injections given to each eye.All patients achieved ocular disease regression; however, two patients with primary IOL eventually had CNS involvement. Conclusion:Primary IOL carries a high risk of CNS disease progression.Local ocular treatments such as intravitreal MTX injections can effectively control the disease locally but do not prevent or treat CNS or systemic involvement.Monitoring by a multidisciplinary team using magnetic resonance imaging, positron emission tomography-computed tomography, and/or lumbar punctures can detect CNS or systemic disease early.
antibodies
2026-07-16 | Long-term observation of treatment strategies for primary vitreoretinal lymphoma in a multicenter Chinese cohort.
To compare outcomes of different treatment regimens for primary vitreoretinal lymphoma (PVRL) without central nervous system (CNS) involvement, specifically assessing their association with subsequent onset of central nervous system lymphoma (CNSL). This retrospective study collected data from 64 PVRL patients (118 eyes) from January 2015 to June 2023 at 4 ophthalmologic centers in China. Clinical, laboratory, and imaging data of these patients has been reviewed, focusing on the incidence of CNS manifestations during follow-up. Among the 64 patients with PVRL, 26 patients received only intravitreal injection of methotrexate (group A), and 38 patients received combined intraocular and systemic treatment (group B). The median follow-up time was 36.1 months, the median CNS progression-free survival (PFS) was 23.5 months, and the median overall survival (OS) was not-reached. CNSL developed in 44 of the 64 patients (68.8%) during the follow-up, including 19 of the 26 patients (73.1%) in group A, and 25 of the 38 (65.8%) in group B. Increased cerebrospinal fluid IL-10 levels (range: 2.2-472 pg/ml, mean 63.715 pg/ml) were significantly correlated with the progression of CNSL (P < 0.001). In this observational cohort, combined therapeutic approach of systemic and intraocular therapy was associated with higher OS (P = 0.002). No significant differences in CNS-PFS was observed between the two treatment groups (P = 0.095). In this cohort of patients with PVRL, combined intraocular and systemic therapy may be associated with longer OS, while no significant difference in CNS-PFS was observed.
2026-05-27 | Successful use of intravitreal rituximab as salvage therapy for relapsed vitreoretinal lymphoma.
To describe the outcomes, response patterns, and complications of intravitreal rituximab (IVR) in eyes with relapsed vitreoretinal lymphoma (VRL) despite previous treatment with ocular radiotherapy (EBRT). Retrospective observational single-center study. This study included all patients diagnosed with relapsed VRL who received IVR between 2011 and 2024 at our National Ocular Oncology Service in the United Kingdom. Demographic data, systemic and ocular lymphoma history, treatment details, visual acuity, and ocular adverse events were collected from medical records. Ten eyes of six patients with relapsed VRL were treated with IVR. All eyes had been previously treated with ocular EBRT and with whole brain radiotherapy (WBRT) (83.3%) and systemic chemotherapy (66.7%) for CNS lymphoma. Eyes with relapsed VRL were treated with a mean of four IVR injections (1 mg/0.1 mL) per treatment course using weekly to monthly intervals. Complete ocular remission was achieved in all eyes after a single course of IVR. One eye experienced a further relapse 14 months later, successfully treated with a second course of IVR. Ocular adverse events potentially attributable to IVR included transient intraocular hypertension and mild uveitis; other complications, such as cataract, radiation retinopathy, and retinal atrophy were likely related to EBRT rather than IVR. In our cohort of relapsed VRL despite previous ocular EBRT, IVR used as a sole focal therapy was associated with high rates of ocular remission and acceptable local toxicity. These findings support the use of IVR as a standard salvage treatment in cases of relapsed VRL.
2024-11-05 | Primary Vitreoretinal Lymphoma: A Comprehensive Retrospective Analysis of 65 Cases at Two European Centers
Introduction. Primary vitreoretinal lymphoma (PVRL) is a distinct subset of primary central nervous system lymphoma (PCNSL), characterized by its emergence within the intraocular environment without initial brain involvement. The pathogenesis of PVRL remains unclear, though it is hypothesized to originate outside the CNS, subsequently migrating to ocular regions where an immune-permissive microenvironment facilitates its manifestation. Diagnostically, PVRL presents significant challenges due to its clinical mimicry of uveitis and the fragility of lymphoma cells in the vitreous. The treatment of PVRL is demanding as well, with diverse and heterogeneous strategies, encompassing localized intravitreal therapy, radiotherapy, systemic chemotherapy, and targeted therapy. However, as a rare disease, data on PVRL are limited, and prospective trials are largely absent. Through collaboration between two European centers, we conducted a comprehensive retrospective analysis of PVRL cases to evaluate treatment outcomes and relapse behavior, aiming to enhance understanding of this challenging condition. Methods. A retrospective analysis of PVRL cases was performed at the University Hospital Tübingen and the Medical University Graz. Electronic health records were analyzed for demographic data, clinical presentation, diagnostic procedure, treatments and outcome, relapse manifestations and adverse events. Descriptive statistics are provided for the entire cohort and center-specific cohorts. Statistical comparisons using SPSS were performed where possible. Results. A total of 65 cases with intraocular lymphoma involvement were identified (Tübingen n=34, Graz n=31), comprising 40 cases of primary vitreoretinal lymphoma (PVRL), 9 cases of primary central nervous system lymphoma (PCNSL) with later ocular involvement, 5 cases of PCNSL with simultaneous eye infiltration, and 11 cases of systemic diffuse large B-cell lymphoma (DLBCL) at initial diagnosis. The mean age at diagnosis was 72.7 years (range 49-96), 55.4% were female, and the median follow-up time was 18 months. The median time to diagnosis from the onset of the first symptoms was 31 days (range 1-2805). There was considerable heterogeneity in treatment modalities and clinical management. Intravitreal (itv.) treatment primarily involved Rituximab (n=34), Methotrexate (n=19), or combinations thereof (n=5). Intravitreal Methotrexate resulted in clinically significant keratopathy in 11 of 12 cases (91.7%), while Rituximab caused increased intraocular pressure in 9 of 34 cases (26.4%). Intravitreal treatment (n=58) resulted in 55.2% complete responses, and 34.6% partial responses, without a significant difference between modalities. A total of 69.2% (n=45) of patients received systemic chemotherapy at some point, including 11 patients who received systemic immunochemotherapy despite having exclusive eye manifestations. Despite intensive therapy, 70% of cases developed a single documented relapse of any kind, while 52.4% developed a second relapse, considering high rates of patients lost to follow-up (n=25). Conclusions. This retrospective analysis of a large cohort highlights the significant heterogeneity in treatment approaches for PVRL. The study found no significant differences in overall outcomes between intravitreal rituximab and intravitreal methotrexate. However, each treatment had distinct adverse effects, with methotrexate causing keratopathy and rituximab associated with increased intraocular pressure. Despite diverse treatment strategies, the high rate of relapses underscores the need for standardized treatment protocols. Future prospective trials are essential to optimize therapeutic strategies and improve long-term outcomes for PVRL patients, addressing both intraocular disease control and CNS relapse prevention.
2024-08-27 | Hypopyon Uveitis as a Manifestation of Primary Choroidal Lymphoma.
A 78-year-old female was referred to our hospital due to a decrease of visual acuity in her left eye. On examination, presence of left choroidal folds and subretinal fluid was disclosed. After being misdiagnosed as neovascular age-related macular degeneration treatment with intravitreal injections of Aflibercept was started. Despite improvement of fluid, persistence of choroidal folds encouraged a magnetic resonance imaging revealing a left retrobulbar nodular lesion. Furthermore, development of hypopyon during follow-up allowed a flow cytometry analysis of an aqueous humour sample that confirmed infiltration by a non-Hodgkin mature B-cell lymphoproliferative process. Finally, treatment with Rituximab and intravenous corticosteroids achieved complete resolution. Primary choroidal lymphoma may occur with an atypical presentation, including hypopyon uveitis. Thus, familiarity with its clinical features is fundamental for an early recognition and correct management.
2024-06-12 | A case of ocular diffuse large B-cell lymphoma unveiled through Pars Plana Vitrectomy: surgical insight and multidisciplinary management.
We present a rare case of ocular diffuse large B-cell lymphoma (DLBCL) unveiled through Pars Plana Vitrectomy in a 74-year-old immunocompromised male, highlighting the surgical insight and multidisciplinary management required for similar cases. The patient's progressive vision impairment led to a Pars Plana Vitrectomy, which confirmed DLBCL through cytogenetic analysis. Initial intraocular rituximab treatment showed promise; however, the lymphoma's systemic progression necessitated a shift to more aggressive chemotherapy, underscored by pleural and pericardial effusions and central nervous system involvement. This case emphasizes the critical role of surgical techniques in diagnosing ocular lymphomas and the importance of a multidisciplinary approach in managing the disease's ocular and systemic manifestations. The complexities introduced by the patient's immunosuppression highlight the necessity for individualized treatment strategies. This case calls for further research into ocular lymphomagenesis and exploring therapies with enhanced efficacy and reduced toxicity, and emphasizes the importance of early diagnosis in ocular DLBCL cases.
oligonucleotides
2026-02-25 | Exosome-Based Approaches in Regenerative Medicine and Targeted Therapy for Eye Malignancies: A Comprehensive Review.
Diagnosing and treating ocular malignancies-such as uveal melanoma, retinoblastoma, intraocular lymphoma, and conjunctival tumors-can be very difficult given their rarity, complicated pathophysiology, and a high potential for complications that threaten vision or life. Traditional treatments such as chemotherapy, radiation, and surgery result in limited clinical value because of systemic toxicity, versatile drug resistance, and insufficient local control. Exosomes (EXOs)-naturally occurring nanoscale vesicles held in biocompatible structures-represent a uniquely advantageous platform for targeting and delivering miRNAs, proteins and/or gene editing molecules across ocular barriers to create corrective, sustained, and targeted diagnostics, drug delivery, and immune modulation. Mesenchymal stem cell-derived exosomes (MSC-EXOs) also possess regenerative potential in both animal and human models of retinal and ocular injury, engaging biological pathways involved in modulating inflammation and neuroprotection such as HMGB1 and PI3K/AKT pathways. While the use of EXOs presents a promising option for ocular treatment application, several factors complicate actual clinical translation, including standardization of isolation, scalable manufacture, and regulatory issues. In general, EXO-based nanomedicine may be a promising new direction for precision therapy and regenerative ophthalmology with the increasing introduction of synthetic and bioengineered EXOs introducing precursor paving new avenues for clinically scalable and biologically customizable EXO therapeutics.
Access all drug discovery papers and probability of success in trials forecasts:
Access all drug discovery papers and probability of success in trials forecasts:
Drug Discovery Landscape
1 orphan drug designation for Primary intraocular lymphoma.
1 orphan drug designation for Primary intraocular lymphoma.
Drug | Therapy type | Regulator | Orphan designation | Approval | Sponsor |
|---|---|---|---|---|---|
methotrexate (intravitreal) | small molecules | FDA | 2021-07-19 | — | Aldeyra Therapeutics, Inc. |
Let's accelerate rare disease drug discovery
Let's accelerate drug discovery
Get access to Explority AI’s forecasts to outperform average preclinical success rates. Whether you’re expanding your R&D pipeline, evaluating a partnership, or simply have a question — we’d love to hear from you.