The International Vitreoretinal B-Cell Lymphoma Registry: a protocol paper.

INTRODUCTION: Vitreoretinal lymphoma is a rare ocular cancer with high morbidity and mortality despite treatment. Diagnosis by cytopathology is often delayed, and various molecular and image-based investigations have been developed. Diverse treatments are used, but there is a limited medical evidence to differentiate their effectiveness. We designed an international registry that would collect diagnostic, treatment and outcomes data, to establish new evidence for the management of this cancer. METHODS AND ANALYSIS: The International Vitreoretinal B-Cell Lymphoma Registry will accrue data retrospectively for individuals aged 18 years or older, diagnosed with new or recurrent vitreoretinal B-cell lymphoma on or after 1 January 2020. A steering committee of subspecialised ophthalmologists identified 20 key clinical data items that describe patient demographics, tissue involvements, diagnostic testing, ocular and systemic treatments and treatment complications, and visual acuity and survival outcomes. Customised software was designed to permit collection of these data across a single baseline and multiple follow-up forms. The platform collects data without identifiers and at 3 month reporting intervals. Outcomes of the project will include: (1) descriptions of clinical presentations, and diagnostic and therapeutic preferences; (2) associations between clinical presentations, and diagnostics and treatments, and between diagnostics and treatments (assessed by ORs with 95% CIs); and (3) estimations of rates of vision loss, and progression-free and overall survival (assessed by Kaplan-Meier estimates). ETHICS AND DISSEMINATION: The registry has received Australia-wide approval by a national human research ethics committee. Sites located outside Australia are required to seek local human research ethics review. Results generated through the registry will be disseminated primarily by peer-reviewed publications that are expected to inform clinical practice, as well as educational materials.

Central Nervous System Progression in Primary Vitreoretinal Lymphoma with Bilateral and Unilateral Involvement: A Systematic Review and Meta-Analysis.

BACKGROUND: Primary vitreoretinal lymphoma (PVRL) is either unilateral or bilateral at initial presentation. Progression to a central nervous system (CNS) lymphoma is regularly observed and these patients seem to have an inferior survival. Knowledge of the predictive value of laterality for CNS progression may facilitate risk stratification and the development of more effective treatment strategies, and eventually, improve outcomes. The objective of this analysis is to estimate the risk of CNS progression for patients with bilateral versus unilateral involvement of PVRL. METHODS: Systematic literature search for studies on CNS progression in PVRL with bilateral and unilateral involvement according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. We assessed the risk of bias and the methodological quality of studies using the Quality in Prognosis Studies (QUIPS) tool. Risk ratios of CNS progression in PVRL with bilateral and unilateral involvement were calculated and combined via a meta-analysis. RESULTS: Twenty-five small-sized (total n = 371 cases) studies were included. The majority of the studies were at medium to high risk of bias. Results suggest no significant difference in CNS progression between bilateral and unilateral PVRL, with a pooled relative risk ratio of 1.12 (95% confidence interval 0.89-1.41). CONCLUSIONS: CNS progression is common in PVRL. From the limited available evidence, there is no significant difference in CNS progression between bilateral and unilateral PVRL.

Risk of Rhegmatogenous Retinal Detachment in Acute Retinal Necrosis With and Without Prophylactic Intervention.

PURPOSE: To study whether preventive laser or preventive vitrectomy is able to lower the risk of rhegmatogenous retinal detachment (RRD) in patients with acute retinal necrosis (ARN). DESIGN: A retrospective, interventional case series. METHODS: We performed a retrospective study of 59 patients (63 eyes) with ARN treated in a single tertiary referral center. We analyzed different groups with either no prophylaxis, prophylactic laser, or prophylactic vitrectomy. Main outcome measure was incidence of RRD. RESULTS: Overall incidence of RRD was 44.4%, including 13% at presentation. In a crude analysis, the risk of RRD was highest in 33 patients with prophylactic laser (45.5%), lower in 15 patients with no prophylaxis (26.7%), and lowest in 7 patients with prophylactic vitrectomy (14.3%). Baseline best-corrected visual acuity differed between these groups, but zone and percentage of involved retina did not. In a multivariable model including prophylactic laser and ARN severity, only zone was predictive of RRD. CONCLUSION: When correcting for severity of disease, we did not observe a reduction in the risk of RRD by prophylactic laser in eyes with ARN. Therefore, prophylactic laser may be abandoned. The role of prophylactic vitrectomy is still unclear, but deserves further investigation.

Potential Diagnosis of Vitreoretinal Lymphoma by Detection of MYD88 Mutation in Aqueous Humor With Ultrasensitive Droplet Digital Polymerase Chain Reaction.

Importance: The diagnostic workup of patients suspected of having vitreoretinal lymphoma (VRL) is primarily based on vitreous fluid analysis, including the recently emerging myeloid differentiation primary response gene 88 (MYD88) mutation analysis. Aqueous humor paracentesis is a relatively less invasive and safer procedure than taking vitreous fluid specimens, and aqueous humor-based MYD88 mutation analysis would provide an additional liquid biopsy tool to diagnose and monitor patients with VRL. Objective: To investigate whether the detection of MYD88 L265P by highly sensitive droplet digital polymerase chain reaction (ddPCR) is feasible in the vitreous fluid and aqueous humor of patients with VRL. Design, Setting, and Participants: This cohort study includes aqueous humor and vitreous fluid samples from patients with VRL who were treated at the University Medical Center Utrecht, in Utrecht, the Netherlands, from August 2005 to August 2017. Ocular fluids were randomized and masked before MYD88 L265P analysis, which was performed using an in-house validated ddPCR platform. Patients with uveitis were included as a comparison group. Main Outcomes and Measures: The presence of MYD88 L265P mutation detected by ddPCR in AH and VF. Results: The study included 96 samples from 63 individuals, including 23 patients with VRL (of whom 10 were female and 13 male, with a mean [SD] age of 72 [7.3] years) and 40 individuals with uveitis (of whom 23 were female and 17 male, with a mean [SD] age of 58 [20.9] years). In 17 of 23 patients with VRL (74%), MYD88 L265P was detected; it was not detected in any of the patients with uveitis. It was detectable in both vitreous fluid and aqueous humor samples. In the paired samples, the mutation was detected in 8 of 9 aqueous humor samples (89%) of the MYD88 L265P-positive vitreous fluid samples. In vitreous fluid, the MYD88 ddPCR test showed a sensitivity of 75% (95% CI, 50%-92%) and a positive predictive value of 100%; in aqueous humor, sensitivity was 67% (95% CI, 42%-92%), and positive predictive value was 100%. Specificity was 100% in both fluids. After treatment, the mutation was no longer detectable in any ocular fluids. Conclusions and Relevance: The high concordance between aqueous humor and vitreous fluid samples suggests that use of the easily accessible aqueous humor is nearly as informative as vitreous fluid in the identification of key somatic mutations in patients with VRL. This approach may provide an additional minimally invasive tool for accurate diagnosis, detection of recurrence, and monitoring of treatment.

Potential Predictors of Poor Visual Outcome in Human Leukocyte Antigen-B27-Associated Uveitis.

PURPOSE: To identify potential predictors of permanent vision loss in patients with human leukocyte antigen (HLA)-B27-associated uveitis in a tertiary referral center. DESIGN: Retrospective case-control study. METHODS: The charts of 212 patients (338 eyes) with HLA-B27-associated uveitis that visited the University Medical Center Utrecht with a follow-up of at least 6 months were retrospectively studied. Clinical features at presentation and during follow-up were compared to final visual outcome in quiescent state. Eyes with (sub-) normal vision (>20/50) were compared with visually impaired (≤20/50) and blind (≤5/50, or a visual field of <10 degrees) eyes, using survival analysis. A multivariate Cox proportional hazards analysis was performed to analyze potential predictors for permanent vision loss. RESULTS: Median follow-up was 10.4 years (range, 0.5-44.7 years). During follow-up 226 eyes (66%) experienced vision loss up to 20/50, but most recovered. Twenty patients (9%) became permanently visually impaired or blind in at least 1 eye because of uveitis, after a median of 9.7 years (range, 0-20.9 years). The main cause was secondary glaucoma or related to glaucoma surgery (12/22 eyes, 55%). Survival analysis showed, after adjustment for age and sex, an ocular pressure of >21 mm Hg, hypotony, and panuveitis to be potential predictors at presentation, and the development of secondary glaucoma or hypotony to be predictors of blindness or visual impairment during follow-up. CONCLUSIONS: The long-term visual prognosis of HLA-B27-associated uveitis is relatively good, but the true incidence of permanent vision loss is probably still underestimated. Our findings highlight the importance of proper control of intraocular pressure.

Visual outcome, treatment results, and prognostic factors in patients with scleritis.

PURPOSE: To analyze the visual outcome, systemic associations, effectiveness of treatment, and predicting features of 104 scleritis patients. DESIGN: Retrospective case series. PARTICIPANTS: One hundred four patients treated for scleritis at the University Medical Centers of Groningen and Utrecht, The Netherlands. METHODS: The clinical records of 104 patients diagnosed with scleritis between 1992 and 2011 at the University Medical Centers of Groningen (n = 64) and of Utrecht (n = 40) were analyzed retrospectively. MAIN OUTCOME MEASURES: Loss of visual acuity, ocular complications, related systemic disease, type of treatment, time to treatment success, and predictive features. RESULTS: Mean age ± standard deviation (SD) was 51.5 ± 13.6 years, and 63 (60.6 %) patients were female. Mean follow-up ± SD was 38.2 ± 33.8 months. A loss of more than 2 lines of Snellen acuity was observed in 23 patients, 3 of whom had a final visual acuity of no light perception. In general, patients with necrotizing scleritis (n = 15) had a poorer outcome. Ocular complications were observed in 88 (84.6%) patients. Underlying systemic disease was identified in 34 (32.7%) patients. Steroid-sparing immunosuppressive medication was used in 47 patients, 36 of whom were treated with methotrexate (MTX). This treatment was successful in 17 (47.2%) patients over the course of a mean ± SD of 103.7 ± 83.7 weeks. Mycophenolate mofetil was the treatment in 10 patients, and in 5 of these patients, treatment success was achieved in a mean ± SD of 65.3 ± 37.4 weeks. Treatment with tumor necrosis factor α (TNF-α) antagonists led to treatment success in a mean ± SD of 32.6 ± 21.8 weeks in 5 of the 11 treated patients. Patients with loss of visual acuity or those treated with steroid-sparing immunosuppressive drugs more often had an underlying associated disease, bilateral scleritis, and a longer duration of symptoms at presentation. CONCLUSIONS: Scleritis is a severe ocular inflammatory disease often associated with ocular complications. In this population, roughly half of the patients were treated with systemic immunosuppressive medication. Mycophenolate mofetil and TNF-α antagonists can be used in case of MTX failure. Tumor necrosis factor α antagonists seemed to be more effective than MTX. Within this group, an underlying associated disease, bilateral scleritis, and a longer duration of symptoms at presentation were predictive features for a more severe disease course.

Identification of new pathogens in the intraocular fluid of patients with uveitis.

PURPOSE: To determine infectious causes in patients with uveitis of unknown origin by intraocular fluids analysis. DESIGN: Case-control study. METHODS: Ocular fluids from 139 patients suspected of infectious uveitis, but negative for herpes simplex virus, varicella-zoster virus, cytomegalovirus, and Toxoplasma gondii by polymerase chain reaction and/or antibody analysis in intraocular fluids, were assessed for the presence of 18 viruses and 3 bacteria by real-time polymerase chain reaction (PCR). The ocular fluids from 48 patients with uveitis of known etiology or with cataract were included as controls. RESULTS: Positive PCR results were found for Epstein-Barr virus, for rubella virus, and for human herpesvirus 6 each in 1 patient and for human parechovirus in 4 patients. Of the human parechovirus-positive patients, 1 was immunocompromised and had panuveitis. The other 3 patients were immunocompetent and had anterior uveitis, all with corneal involvement. CONCLUSIONS: Human parechovirus might be associated with infectious (kerato)uveitis.