Bilateral multifocal chorioretinitis as the only presentation of acute West Nile virus infection: a case report.

BACKGROUND: To describe a case of bilateral multifocal chorioretinitis as the only presentation of acute West Nile virus (WNV) infection in the absence of neurological involvement. CASE PRESENTATION: A 78-year-old Italian woman was admitted to our emergency department because she noticed blurry vision in both eyes. She did not report fever, fatigue, or neurological symptoms in the last few days. Multimodal imaging showed the presence of bilateral hyperfluorescent lesions with a linear distribution, that corresponded to hypocyanescent spots on indocyanine green angiography. Antibody serology showed the presence of IgM antibodies, IgG antibodies, and ribonucleic acid (RNA) for WNV. Magnetic resonance imaging (MRI) of the brain ruled out central nervous system involvement. Three months later, the patient reported spontaneous resolution of her symptoms and remission of the chorioretinal infiltrates. CONCLUSIONS: In endemic areas, it is important to think of acute WNV infection as an explanatory etiology in cases of multifocal chorioretinitis, even without neurological involvement.

Therapy for Vitreous Seeding Caused by Retinoblastoma. A Review.

Retinoblastoma is the most common primary malignant intraocular tumor in children. Seeding, specifically the dispersion of the tumor into the adjacent compartments, represents a major parameter determining the degree of retinoblastoma according to the International Classification of Retinoblastoma. In this article we focused on vitreous seeding, one of the main limiting factors in the successful "eye preservation treatment" of retinoblastoma. This article presents an overview of the history of vitreous seeding of retinoblastoma, established treatment procedures and new-research modalities. The introduction of systemic chemotherapy in the treatment of retinoblastoma at the end of the 1990s represented a significant breakthrough, which enabled the progressive abandonment of radiotherapy with its attendant side effects. However, the attained concentrations of chemotherapeutics in the vitreous space during systemic chemotherapy are not sufficient for the treatment of vitreous seeding, and the toxic effects of systemic chemotherapy are not negligible. A significant change came with the advent of chemotherapy in situ, with the targeted administration of chemotherapeutic drugs, namely intra-arterial and intravitreal injections, contributing to the definitive eradication of external radiotherapy and a reduction of systemic chemotherapy. Although vitreous seeding remains the most common reason for the failure of intra-arterial chemotherapy, this technique has significantly influenced the original treatment regimen of children with retinoblastoma. However, intravitreal chemotherapy has made the greatest contribution to increasing the probability of preservation of the eyeball and visual functions in patients with advanced findings. Novel local drug delivery modalities, gene therapy, oncolytic viruses and immunotherapy from several ongoing preclinical and clinical trials may represent promising approaches in the treatment of vitreous retinoblastoma seeding, though no clinical trials have yet been completed for routine use.

INTRAVITREAL MELPHALAN INJECTION AS A SECOND-LINE LOCAL THERAPY IN VITREORETINAL LYMPHOMA: Case Series.

PURPOSE: To evaluate the effectiveness and safety of intravitreal melphalan (IVM) injection therapy in vitreoretinal lymphoma. METHODS: Eight eyes of five biopsy-proven vitreoretinal lymphoma patients who were treated with IVM injection as a second-line therapy after intravitreal methotrexate and rituximab injections were retrospectively evaluated between January 2011 and March 2023. RESULTS: The medical records of five vitreoretinal lymphoma patients (mean age of 62 years at the diagnosis) including 4 (80%) female patients and 1 (20%) male patient were retrospectively analyzed. Three patients (60%) either had a history of central nervous lymphoma or developed it during the follow-up. Patients were previously treated with a mean of five cycles of monthly intravitreal methotrexate and rituximab injections. All eyes showed complete response by the disappearance of vitreal and/or subretinal neoplastic cells within 6 weeks after IVM injections (range, 1-4 injections per eye). Of 12 IVM injections, 3 (25%) injections were associated with macular edema diagnosed on optical coherence tomography at 1-month follow-up and resolved spontaneously within 5 months. The IVM administration induced new retinal pigment epithelium changes in three eyes (37%). CONCLUSION: Intravitreal melphalan injection may be effective in the management of vitreoretinal lymphoma as a second-line local therapy. Randomized clinical trials with larger numbers of patients are needed to establish the efficacy, treatment protocol, and safety of IVM injection.

Presentation, Diagnostic Testing and Initial Treatment of Vitreoretinal Lymphoma.

PURPOSE: Vitreoretinal lymphoma is a malignancy with high mortality. Incidence is rare, and there is a lack of medical evidence to direct management. This work describes presentation, diagnostic testing, and first treatment approaches in a recently diagnosed and treated patient cohort. DESIGN: Clinical registry-based observational study. SUBJECTS: Forty-eight women and 32 men (age range, 32-91 years; median age, 64 years) diagnosed with vitreoretinal lymphoma. METHODS: An international network of ophthalmologists reported clinical features and management of patients presenting with vitreoretinal lymphoma between January 1, 2020 and December 31, 2022 via an electronic platform. MAIN OUTCOME MEASURES: Visual acuity at presentation (logarithm of the minimum angle of resolution [logMAR]); basis for diagnosis; first treatment. RESULTS: Vitreoretinal lymphoma was bilateral at presentation in 65% of patients (n = 52) and an initial site of lymphoma in 78% (n = 62). Of 127 eyes with lymphoma at presentation, vitreous was involved in 89% (n = 113) and was the only involved eye tissue in 40% (n = 51), and retina was involved in 46% (n = 59) and was the only involved eye tissue in 9% (n = 11). Median logMAR visual acuity of the worse-seeing eye was 0.50. The lymphoma was diagnosed from ocular specimens in 80% of patients (64/80), usually vitreous (57/64 patients [89%]), and on other clinical information in 20% of patients (16/80). Cellular studies were performed on ocular specimens from 59 of 64 patients (92%), most often cytology. Tumor gene analysis was used in 21 of 64 patients (33%), and cytokine assays were used in 13 of 64 patients (20%). For 76 patients (95%), treatment was initiated within 6 months of diagnosis and included ocular (38/76 [48%]), extraocular (17/76 [21%]), and ocular plus extraocular (21/76 [26%]) approaches. Intravitreal methotrexate was the most common ocular treatment (83/87 eyes [95%]). CONCLUSIONS: Using data collected from 80 patients diagnosed with vitreoretinal lymphoma since 2020, we show that visual impairment is common, and that management often involves diagnosis by cellular tests and treatment with intravitreal chemotherapy. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

Clinical factors for central nervous system progression and survival in primary vitreoretinal lymphoma.

Primary vitreoretinal lymphoma (PVRL) is a rare subtype of malignant lymphoma with a poor prognosis because of high frequency of central nervous system (CNS) progression. Identification of factors associated with CNS progression is essential to improve the prognosis of patients with PVRL. We conducted a retrospective study of 54 patients diagnosed with PVRL and treated at our hospital to identify factors associated with CNS progression and prognosis. All patients were treated with intravitreal methotrexate (MTX) injections in the affected eyes until lesion resolution. Twenty-four patients were treated with systemic administration of high-dose MTX (systemic HD-MTX) every other week for a total of five cycles following intravitreal MTX injection. Of 24 patients, 20 completed five cycles of systemic HD-MTX. The 5-year cumulative incidence of CNS progression and overall survival (OS) rate were 78.0% and 69.0% respectively. By univariate and multivariate analyses, bilateral disease and the detection of B-cell clonality confirmed by flow cytometric analysis were risk factors associated with CNS progression. Moreover, systemic HD-MTX completion reduced the risk of CNS progression and was identified as a factor affecting OS. In this study, factors for CNS progression identified may potentially contribute to the optimized therapeutic stratification to improve the survival of patients with PVRL.

Four-Year Follow-Up of a Pigmented Vitreous Cyst.

This case report discusses a diagnosis of pigmented vitreous cyst in a man aged 18 years who presented with a 2-week history of seeing a floater in his right eye.

Iris Neovascularization After Vitreous Metastasis of a Cutaneous Melanoma.

This case report describes iris neovascularization secondary to vitreous metastasis of a cutaneous melanoma in a man aged 75 years who presented with elevated intraocular pressure.

Next-Generation Sequencing of Vitreoretinal Lymphoma by Vitreous Liquid Biopsy: Diagnostic Potential and Genotype/Phenotype Correlation.

Purpose: To determine the diagnostic potential of next-generation sequencing (NGS) in vitreous samples, analyze genotype-phenotype characteristics, and compare NGS of matched vitreous and brain samples in patients with associated central nervous system lymphoma (CNSL). Methods: A total of 32 patients suspected of vitreoretinal lymphoma (VRL) who underwent diagnostic vitrectomy and NGS were included in this retrospective observational case-series. Fresh vitreous specimens from diagnostic vitrectomy of VRL-suspected patients underwent NGS using a custom panel targeting 747 candidate genes for lymphoma. They also underwent malignancy cytology, interleukin (IL)-10/IL-6, immunoglobulin heavy chain (IGH)/immunoglobulin kappa light chain (IGK) monoclonality testing. MYD88 L265P mutation was examined from anterior chamber tap samples. The diagnosis of VRL was made based on typical clinical characteristics for VRL, as well as malignant cytology, IGH/IGK clonality, or IL-10/IL-6 > 1. Sensitivity and specificity of NGS were compared with conventional diagnostic tests. Brain tissues suspected of lymphoma were collected by stereotactic biopsy and underwent NGS. Genetic variations detected in NGS of vitreous and brain tissue specimens were compared. Results: The sensitivity values for cytology, IL-10/IL-6 > 1, clonality assays for IGH and IGK, MYD88 L265P detection in anterior chamber tap samples, and vitreous NGS were 0.23, 0.83, 0.68, 0.79, 0.67, and 0.85, with specificity values of 1.00, 0.83, 0.50, 0.25, 0.83, and 0.83, respectively. The sensitivity (0.85) of vitreous NGS was the highest compared to other conventional diagnostic tests for VRL. The most common mutations were MYD88 (91%), CDKN2A (36%), PIM1 (32%), IGLL5 (27%), and ETV6 (23%). Although several gene alterations demonstrated heterogeneity between the brain and eyes, some common mutational profiles were observed in matched vitreous and brain samples. Conclusions: Overall, NGS of the vitreous demonstrated high sensitivity among conventional diagnostic tests. VRL and CNSL appeared to have both shared and distinct genetic variations, which may suggest site-specific variations from a common origin.

Therapy for Vitreous Seeding Caused by Retinoblastoma. A Review.

Retinoblastoma is the most common primary malignant intraocular tumor in children. Seeding, specifically the dispersion of the tumor into the adjacent compartments, represents a  major parameter determining the degree of retinoblastoma according to the International Classification of Retinoblastoma. In this article we focused on vitreous seeding, one of the main limiting factors in the successful "eye preservation treatment" of retinoblastoma. This article presents an overview of the history of vitreous seeding of retinoblastoma, established treatment procedures and new-research modalities. The introduction of systemic chemotherapy in the treatment of retinoblastoma at the end of the 1990s represented a  significant breakthrough, which enabled the progressive abandonment of radiotherapy with its attendant side effects. However, the attained concentrations of chemotherapeutics in the vitreous space during systemic chemotherapy are not sufficient for the treatment of vitreous seeding, and the toxic effects of systemic chemotherapy are not negligible. A significant change came with the advent of chemotherapy in situ, with the targeted administration of chemotherapeutic drugs, namely intra-arterial and intravitreal injections, contributing to the definitive eradication of external radiotherapy and a reduction of systemic chemotherapy. Although vitreous seeding remains the most common reason for the failure of intra-arterial chemotherapy, this technique has significantly influenced the original treatment regimen of children with retinoblastoma. However, intravitreal chemotherapy has made the greatest contribution to increasing the probability of preservation of the eyeball and visual functions in patients with advanced findings. Novel local drug delivery modalities, gene therapy, oncolytic viruses and immunotherapy from several ongoing preclinical and clinical trials may represent promising approaches in the treatment of vitreous retinoblastoma seeding, though no clinical trials have yet been completed for routine use.

Prevalence, Concordance, and Heritability of Vitreomacular Interface Abnormalities in a Twin Study.

Purpose: The relative importance of genetic factors in common vitreomacular interface (VMI) abnormalities is unknown. The aim of this classical twin study is to determine the prevalence case wise concordance between monozygotic and dizygotic twin pairs, and heritability of common VMI abnormalities, including epiretinal membrane (ERM), posterior vitreous detachment (PVD), vitreomacular adhesion (VMA), vitreomacular traction (VMT), lamellar macular holes (LMHs), and full-thickness macular holes (FTMHs). Methods: This is a single-center, cross-sectional classical twin study of 3406 TwinsUK participants over the age of 40 years who underwent spectral domain macular optical coherence tomography (SD-OCT) scans which were graded for signs of VMI abnormalities. Case wise concordance was calculated and the heritability of each VMI abnormality was estimated using OpenMx structural equation modeling. Results: In this population (mean age = 62.0 years [SD = 10.4 years], range = 40-89 years) the overall prevalence of ERM was 15.6% (95% confidence interval [CI] = 14.4-16.9) and increased with age, posterior vitreous detachment affected 21.3% (20.0-22.7), and VMA was diagnosed in 11.8% (10.8-13.0). Monozygotic twins were more concordant for all traits than dizygotic twins, and age, spherical equivalent refraction (SER), and lens status-adjusted heritability was estimated at 38.9% (95% CI = 33.6-52.8) for ERM, 53.2% (95% CI = 41.8-63.2) for PVD, and 48.1% (95% CI = 33.6-58) for VMA. Conclusions: Common VMI abnormalities are heritable and therefore have an underlying genetic component. Given the sight-threatening potential of VMI abnormalities, further genetic studies, such as genomewide association studies, would be useful to identify genes and pathways implicated in their pathogenesis.

VITREORETINAL INVOLVEMENT BY INDOLENT T-CELL LYMPHOPROLIFERATIVE DISORDER OF THE GASTROINTESTINAL TRACT DIAGNOSED BY FLUORESCENCE IN SITU HYBRIDIZATION.

PURPOSE: The purpose of this study was to describe an exceedingly rare presentation of secondary vitreoretinal involvement by the uncommon entity "indolent T-cell lymphoproliferative disorder of the gastrointestinal tract" and illustrate the utility of fluorescence in situ hybridization for diagnosis. METHODS: This is a case report. RESULTS: A 57-year-old woman with presumed iritis on chronic topical prednisolone acetate presented with increased vitreous opacities in the right eye. She had a history of biopsy-confirmed indolent T-cell lymphoproliferative disorder of the gastrointestinal tract involving the stomach and duodenum, JAK2 -rearrangement positive, controlled on maintenance oral methotrexate. Vitreous biopsy was unremarkable with small CD3-positive and CD4-positive and CD20-negative lymphocytes, along with histiocytes and fibroblasts. Immunostains showed CD4 positivity, and fluorescence in situ hybridization revealed a JAK2 gene rearrangement, consistent with the patient's previously diagnosed indolent T-cell lymphoproliferative disorder of the gastrointestinal tract. Intravitreal methotrexate injections were started in the right eye. MRI of the brain and lumbar puncture with cytology, MYD88 , IL10, and flow cytometry performed at the time of right eye vitreoretinal lymphoma diagnosis revealed no evidence of central nervous system lymphoma, but subsequent bone marrow biopsy demonstrated 5% involvement by indolent T-cell lymphoproliferative disorder of the gastrointestinal tract, JAK2 -rearrangement positive, with a lung nodule on PET computed tomography. She returned 4 months later with fatigue, night sweats, and blurry vision in the left eye with vitreous and anterior chamber cellular infiltration and retinal vasculitis. CONCLUSION: T-cell vitreoretinal lymphoma is rare, and diagnosis can be challenging. Despite inconclusive cytology in this case, interphase fluorescence in situ hybridization detected a JAK2 gene rearrangement, which confirmed the involvement by indolent T-cell lymphoproliferative disorder of the gastrointestinal tract and prompted appropriate treatment and workup for recurrent systemic or central nervous system lymphoma.

The adhesion behavior of the retina.

Ocular diseases and treatment related to rhegmatogenous retinal detachment (RRD) are highly correlated with retinal adhesion behavior. Therefore, this paper proposes to study the adhesion behavior of the intact retina. This can provide theoretical guidance for the treatment and research of retinal detachment (RD) related diseases. To systematically analyze this aspect, two experiments were performed on the porcine retina. The pull-off test combined with the modified JKR theory was used to study the adhesion behavior of the vitreoretinal interface, while the peeling test was used to study the adhesion behavior of the chorioretinal interface. In addition, the adhesion phase involved in the pull-off test was simulated and analyzed by building the corresponding finite element method (FEM). The experimental results of adhesion force on the vitreoretinal interface were obtained by pull-off test with five sizes of rigid punch. The experimental value of the pull-off force FPO tends to increase gradually with increasing punch radius in the range of 0.5-4 mm. A comparison of the experimental results with the simulation results shows that they are in a well agreement. And there is no statistical difference between the experimental and theoretical values of the pull-off force FPO. In addition, the values of retinal adhesion work were also obtained by pull-off test. Interestingly, there is a significant scale effect of the retinal work of adhesion. Finally, the peeling test gave a maximum peeling strength TMax of about 13 mN/mm and a stable peeling strength TD of about 11 mN/mm between the retina and the choroid. The pull-off test well shows the process of retinal traction by the diseased vitreous at the beginning of RRD. A comparison of the experimental results with the finite element results verifies the accuracy of the simulation. The peeling test well investigated the adhesion behavior between the retina and the choroid and obtained key biomechanical data (peeling strength, etc.). The combination of the two experiments allows a more systematic study of the whole retina. This research can provide more complete material parameters for finite element modeling of retina-related diseases, and it also can provide the theoretical guidance for individualized design of retinal repair surgery.

[Age-related changes in human vitreous]. / Vozrastnye izmeneniya steklovidnogo tela.

There are two main age-related changes that can occur in the vitreous body of healthy individuals throughout life: liquefaction (synchesis) and aggregation of collagen fibrils into dense bundles (syneresis). Progressive age-related degradation leads to posterior vitreous detachment (PVD). At present many classifications of PVD exist, in which authors relied either on the morphological features, or on the differences in pathogenesis before and after widespread use of OCT. The course of PVD can be either normal or anomalous. Physiological PVD induced by age-related vitreous changes progresses in specific stages. The review emphasizes that PVD can occur initially not only in the central zone of the retina, but also on the periphery with further spread to the posterior pole. Anomalous PVD can lead to various negative effects on the retina, as well as on the vitreous as a result of traction in the area of vitreoretinal interface.

Suprachoroidal and vitreous haemorrhage as a presenting feature of metastatic melanoma.

A man in his 70s presented with right ocular pain, vision loss and temporal headache 4 days after undergoing laser peripheral iridotomy. The patient had lost 10 lbs over the preceding 6 weeks and had a medical history significant for a previously excised melanoma of the left arm. During the course of investigations, the patient was referred to oncology for workup, ultimately leading to a diagnosis of metastatic melanoma. Visceral metastases were identified in the lungs, right anterior fourth rib, left femoral distal diaphysis and medial side of the right globe. The patient decompensated and died shortly after his first radiotherapy treatment.This is the first published report of suprachoroidal haemorrhage secondary to metastasis from suspected cutaneous melanoma. The case highlights the importance of considering malignancy on the differential diagnosis for a suprachoroidal haemorrhage of unknown aetiology and involving oncology early for workup and treatment.

Spontaneous regression of secondary vitreoretinal lymphoma after diagnostic vitrectomy: case report.

PURPOSE: Our purpose is to report a patient with secondary intraocular mucosa-associated lymphoid tissue (MALT) who experienced spontaneous regression after diagnostic vitrectomy. METHODS: We retrospectively reviewed the clinical and imaging features of the case. Multimodal imaging, including fundus photograph, optical coherence tomography, fundus fluorescein angiography and ultrasound scan was presented. RESULTS: A 71-year-old female presented with a subretinal lesion temporal to macula and scattered multifocal creamy lesions deep to retina in her left eye. Optical coherence tomography of the left eye showed multifocal nodular hyper-reflective signals between the Bruch's membrane and RPE. She had a history of gastric MALT lymphoma. Diagnostic vitrectomy was performed. IL-10 level of aqueous was 187.7pg/ml. Cytology, gene rearrangement and flow cytometry of the vitreous were inconclusive. Systemic evaluation was normal. Secondary vitreoretinal MALT lymphoma was considered. Interestingly, her subretinal lesions regressed gradually without any chemotherapy. And IL-10 level of aqueous declined to 64.3pg/ml. CONCLUSIONS: Secondary vitreoretinal MALT lymphoma is extremely rare. Spontaneous regression of intraocular lymphoma does occur.