Neoplasms

Blood and Lymph Conditions

Immune System Diseases

All Conditions

Eye Diseases

Rare Diseases

Lymphoma

Intraocular Lymphoma

Neoplasms by Histologic Type

Lymphoproliferative Disorders

Lymphatic Diseases

Immunoproliferative Disorders

Eye Neoplasms

Lymphosarcoma

Primary Central Nervous System Lymphoma

Liv Dollmann

Vinodh Kakkassery, PD Dr.med.

The goal of this observational study is to gain new insights into the changes in proteins, genes and other molecular biological substances in the aqueous humour, vitreous humour, blood serum and, in rare cases, retina/choroid samples in patients with ocular lymphoma disease. The hope is that this will expand the understanding of the mechanisms of the disease and thus contribute to improved and simplified diagnosis and treatment strategies in the future. The aim is the inclusion of at least 220 patients during the study period. The main questions it aims to answer are:

* to evaluate the diagnostic quality of extended molecular diagnostics (based on standard work-up) of vitreous samples for the specific VitreoRetinalLymphoma (a type of ocular lymphoma disease) diagnosis in comparison to standard work-up alone.
* To monitor VRL patients as part of regular tumour follow-up over a period of 24 months to determine the value of biomarkers with regard to treatment response and development of recurrence in the eye. Similarly, the vitritis patients are followed up by telephone every six months for a period of 24 months, during which questions of any interim occurrence of a VRL or other cancerous tumors are asked according to a defined catalogue of questions.

Vitreoretinal lymphoma (VRL) is a rare intraocular neoplasm that is considered a variant of primary CNS lymphoma (PCNSL) and may manifest primarily or secondarily in the vitreous and retina. The distinction between vitritis/uveitis and VRL is clinically difficult and requires cytological examination of invasively obtained vitreous material for definitive diagnosis. Due to the time-consuming material collection and the clinical masquerade as vitritis, there are often significant delays in diagnosis. In addition, only a few centres have sufficient experience in the diagnosis and therapy of this rare lymphoma entity. The sensitivity of established tests (cytology, immunophenotyping, clonality analysis) on vitrectomy specimens is at most 70% for VRL. A standardised diagnostic procedure has not yet been defined.

This study aims to implement a network for standardised molecular analysis of VRL, to evaluate the impact of standardised molecular diagnostics on diagnostic quality prospectively through clinical follow-up.The network partners will prospectively send diagnostic vitreous samples from patients with suspected VRL, process them centrally in a standardised manner and subject them to multiparametric molecular diagnostics (mutation analysis and clonality detection using next generation sequencing, miRNA analysis). Due to the rarity of the disease, a recruitment period of 4 years is planned with the inclusion of at least 220 patients with suspected VRL, including 50 in whom VRL can ultimately be confirmed. At the time of surgery, the diagnostic chain (including type and duration of symptoms, clinical course up to vitrectomy) will be evaluated using questionnaires and a qualitative interview with stakeholders (patients, ophthalmologists, pathologists, oncologists). In order to validate the quality of molecular diagnostics and to evaluate the significance for the course of the disease (treatment failure, local recurrence, CNS involvement and recurrence), a prospective clinical documentation of the course of the disease with an observation period of 2 years for VRL patients is being carried out in cooperation with the CNS Lymphoma Working Group of the German Lymphoma Alliance.

Analogous to the VRL patients, the vitritis patients are asked by telephone every six months for two years whether they have been diagnosed with VRL or PCNSL. All VRL patients will be included in a clinical registry. Remaining biomaterial from vitreous bodies will be deposited in a central biobank for future research projects and biomarker establishment, independent of diagnosis.

The aim of the project is to implement a standardised and quality-assured molecular genetic analysis of VRL in specialised centres throughout Germany and thus to achieve an improved and more time-efficient diagnosis of this rare and aggressive disease. The network for the diagnosis of VRL and the clinical registry can also serve as a basis for the development of therapy studies in the future in cooperation with the CNS Lymphoma Working Group of the German Lymphoma Alliance, which is largely lacking in this entity.

Vitreous aspirates, Anterior chamber water samples, whole blood.

Multicentre Implementation and Validation of a Molecular Diagnostic for VitreoRetinal Lymphoma

DECODE VRL - Multicentric Implementation and Clinical Validation of Standardized, Innovative Molecular Diagnostics for VitreoRetinal Lymphoma

The diagnostic work-up would be from patients with suspected VRL including NGS-based mutation and B-cell clonality analysis and quantification of miRNAs 19b, 21 and 92 for the participating ophthalmology centres.

The evaluation of the diagnostic sensitivity and specificity of extended molecular diagnostics (based on standard work-up) of vitreous samples for VRL diagnosis in comparison to standard work-up alone.

Follow-up of VRL patients during regular tumour follow-up over a period of 24 months to determine the predictive significance of the biomarkers with regard to therapy response, development of recurrence in the eye, second eye involvement as well as CNS involvement and recurrence. Similarly, the vitritis patients are followed up by telephone every six months for a period of 24 months, during which any interim occurrence of a VRL or a PCNSL as well as further questions are asked according to a defined catalogue of questions.

A central VRL clinical registry should be established to facilitate the exchange of information. The registry will be established with the support of the German Lymphoma Alliance and Retina.net.

Establishment of a residual material biobank (especially DNA and RNA) of VRL and the control group vitritis.

University Hospital Tuebingen

University Hospital Schleswig-Holstein

Vinodh Kakkassery, MD

PD Dr. med, principal investigator

Uveitis

Uveal Diseases

Presenting clinical features suggestive for VRL with positive finding in laboratory exam

Even if characterized as clinical features of presumed VRL, no positive laboratory investigations for lymphoma and well response to IMT

detect the tumor-related mutation in introcular fluid

mutation test

Dan D Liang, PhD

Vitreoretinal lymphoma (VRL) is a rare but aggressive masquerade syndrome, which would be easily confused with uveitis. The diagnostic gold standard remains the pathologic examination of ocular specimen with invasiveness and low sensitivity. To improve the safety and accuracy of VRL diagnosis, alternative techniques using intraocular fluid (IOF) samples are emerging. In this study, we aimed to test the diagnostic value of mutation analysis for VRL

chest CT, urinalysis, kidney, and liver function were routinely checked.

IL-10/IL-6 ratio, genetic mutation analysis and samples were IGH gene rearrangements were reviewed and analyzed retrospectively.

The diagnoses were identified after careful evaluation of treatment effects in follow-up. The diagnostic value including sensitivity, specificity, positive and negative predictive values, and test efficiency of genetic mutation analysis in diagnosing VRL were analyzed.

Furthermore, a validation group of patients including VRL and uveitis was selected to validate the diagnostic value of mutation analysis in the diagnosis of VRL. All the patients signed an informed consent and institutional review board approval was obtained. The study was performed in accordance with the tenets of the Declaration of Helsinki.

Combined ocular manifestations with the results of pathology, IL-10/IL-6 ratio, IGH gene rearrangements and patients' response to treatments, patients abtained clear diagnosis

Mutation Detection for VRL

The Diagnostic Value of Mutation Detection for VRL

any mutation detect in intraocular fluild recorded as ctDNA+

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Multicentre Implementation and Validation of a Molecular Diagnostic for VitreoRetinal Lymphoma	NCT05841914	Vitreoretinal L...		18 Years -	University of Luebeck
Mutation Detection for VRL	NCT05102994	Vitreoretinal L... Uveitis	mutation test	18 Years - 70 Years	Sun Yat-sen University
Multicentre Implementation and Validation of a Molecular Diagnostic for VitreoRetinal Lymphoma	NCT05841914	Vitreoretinal L...		18 Years -	University of Luebeck

Spots Global Cancer Trial Database for vitreoretinal lymphoma