Arash Mirzaei

Uveitis is the most common extraarticular manifestation of juvenile idiopathic arthritis (JIA).1 JIA-associated uveitis (JIAU) typically presents as chronic anterior uveitis. However, a minority of...

Purpose: To report a child with severe treatment resistant juvenile idiopathic arthritis associated uveitis (JIAU), a condition that typically presents as chronic anterior uveitis, although severe panuveitis with retinal vasculitis may rarely occur.Methods: We describe the clinical course, treatment response, and challenge, dechallenge, and rechallenge sequence in a child with severe refractory JIAU treated with combined infliximab and tofacitinib therapy.Results: The patient showed marked improvement in ocular inflammation, macular edema, and visual acuity following addition of tofacitinib to ongoing infliximab therapy. Inflammation recurred after holding infliximab despite continuation of tofacitinib and improved again following reintroduction of infliximab.Conclusion: This challenge, dechallenge, and rechallenge sequence suggests that neither infliximab nor tofacitinib alone provided adequate disease control, whereas their combination was associated with sustained suppression of ocular inflammation. Combined tumor necrosis factor alpha and Janus kinase inhibition may represent a rescue therapeutic option for carefully selected patients with severe refractory JIAU, although its long term safety and efficacy require further evaluation.

Purpose To identify predictors of retinal detachment (RD) and final visual outcome in acute retinal necrosis (ARN). Method This retrospective cohort study included ARN patients who were treated at a tertiary center between 2009 and 2022. The incidence and risk factors of RD and predictors of final vision loss (< 20/200) were analyzed. Result 156 ARN patients (58.3% male, mean age: 47.74 ± 15.49 years) were included in our study. RD occurred in 51 eyes (32.7%), at a median of 8.0 weeks from ARN onset. Extensive retinitis (four vs. one quadrant involvement) independently predicted RD (adjusted OR 3.45, p = 0.042). Poor final visual outcome (< 20/200) occurred in 79% of eyes. Worse baseline visual acuity was the strongest predictor of poor final vision (adjusted OR 5.58, p = 0.003). In contrast, presence of retinal hemorrhages at presentation (adjusted OR 0.185, p = 0.011) were associated with better final visual outcomes. Conclusion In ARN, severe initial disease, characterized by panretinal necrosis and poor presenting acuity, predisposes to RD and profound vision loss. Most detachments occur within two months of onset, highlighting the need for vigilant early monitoring. Baseline visual acuity is a powerful prognostic indicator, whereas adjunctive treatments (prophylactic laser, intravitreal antivirals) did not independently improve outcomes. To our knowledge, this is the largest cohort of ARN patients reported from the Middle East and one of the few studies globally to incorporate time-to-event analysis and ROC-based visual prognostication. These findings provide region-specific data that refine global risk models for ARN. These findings can guide risk stratification and management decisions in ARN.

Purpose The management of persistent subretinal fluid (SRF) in neovascular age-related macular degeneration (nAMD) varies, with no comprehensive review of outcomes from different treatment approaches. This systematic review evaluates the efficacy of interventions for managing persistent SRF in nAMD patients. Methods Using a structured search strategy, a systematic review examined anti-vascular endothelial growth factor (VEGF) treatments for nAMD with persistent SRF. After removing duplicates, 861 articles were screened, 255 underwent full-text review, and 19 met the eligibility criteria. Results The included studies demonstrated variable outcomes regarding the management of persistent SRF in nAMD. Several studies supported tolerating SRF, showing no significant difference in visual acuity between patients with and without persistent SRF. Conversely, some studies advocated for more aggressive treatment, demonstrating a significant reduction in SRF and potential visual benefits. Patients with SRF generally have better visual outcomes compared to those with intraretinal fluid or cysts. High-frequency anti-VEGF regimens, especially with aflibercept, reduce SRF and maintain visual acuity. However, less aggressive protocols achieve stable outcomes with fewer injections. Conclusion Persistent SRF in nAMD does not necessarily lead to worse visual outcomes. Standardized protocols and further research are needed to improve management strategies.

Background We aimed to evaluate the retinal vascular changes in the superficial and deep retinal vascular networks in the fellow eye of patients with central retinal artery occlusion (CRAO) and compare them with controls using optical coherence tomography angiography (OCT-A). Methods In a cross-sectional study, 27 patients with CRAO and 189 normal controls were included. Ophthalmic examination and OCT-A images were performed on all participants. Results The total vascular density of the superficial capillary network in the 6-mm scan was significantly lower in the fellow eye of patients with CRAO than in the control group (p = 0.02). No significant difference was observed in the FAZ area of the affected eyes and their fellow eyes compared with the controls. Total vascular density at 300 microns around the fovea was lower in the fellow eye compared with the control group (p = 0.034). Conclusions The retinal vascular network changes in the fellow eyes of patients with CRAO suggest that persistent microvascular changes may be present before the onset of CRAO. This finding indicates that such changes could serve as an early diagnostic window for systemic vascular changes before catastrophic vascular events occur.

Extracellular vesicles (EVs), a diverse group of cell-derived exocytosed particles, are pivotal in mediating intercellular communication due to their ability to selectively transfer biomolecules to specific cell types. EVs, composed of proteins, nucleic acids, and lipids, are taken up by cells to affect a variety of signaling cascades. Research in the field has primarily focused on stem cell-derived EVs, with a particular focus on mesenchymal stem cells, for their potential therapeutic benefits. Recently, tissue-specific EVs or cell type-specific extracellular vesicles (CTS-EVs), have garnered attention for their unique biogenesis and molecular composition because they enable highly targeted cell-specific communication. Various studies have outlined the roles that CTS-EVs play in the signaling for physiological function and the maintenance of homeostasis, including immune modulation, tissue regeneration, and organ development. These properties are also exploited for disease propagation, such as in cancer, neurological disorders, infectious diseases, autoimmune conditions, and more. The insights gained from analyzing CTS-EVs in different biological roles not only enhance our understanding of intercellular signaling and disease pathogenesis but also open new avenues for innovative diagnostic biomarkers and therapeutic targets for a wide spectrum of medical conditions. This review comprehensively outlines the current understanding of CTS-EV origins, function within normal physiology, and implications in diseased states.

Extracellular vesicles (EVs), a diverse group of cell-derived exocytosed particles, are pivotal in mediating intercellular communication due to their ability to selectively transfer biomolecules to specific cell types. EVs, composed of proteins, nucleic acids, and lipids, are taken up by cells to affect a variety of signaling cascades. Research in the field has primarily focused on stem-cell derived EVs, with a particular focus on mesenchymal stem cells, for their potential therapeutic benefits. Recently, tissue specific EVs or cell type specific extracellular vesicles (CTS-EVs), have garnered attention for their unique biogenesis and molecular composition because they enable highly targeted cell-specific communication. Various studies have outlined the roles that CTS-EVs play in signaling for physiological function and maintenance of homeostasis, including immune modulation, tissue regeneration, and organ development. These properties are also exploited for disease propagation, such as in cancer, neurological disorders, infectious diseases, autoimmune conditions, and more. The insights gained from analyzing CTS-EVs in different biological roles not only enhance our understanding of intercellular signaling and disease pathogenesis, but also open new avenues for innovative diagnostic biomarkers and therapeutic targets for a wide spectrum of medical conditions. This review comprehensively outlines current understanding of CTS-EV origins, function within normal physiology, and implications in diseased states.

Mesenchymal stem/stromal cells (MSCs) are considered a valuable option to treat ocular surface disorders such as mustard keratopathy (MK). MK often leads to vision impairment due to corneal opacification and neovascularization and cellular senescence seems to have a role in its pathophysiology. Herein, we utilized intrastromal MSC injections to treat MK. Thirty-two mice were divided into four groups based on the exposure to 20 mM or 40 mM concentrations of mustard and receiving the treatment or not. Mice were clinically and histopathologically examined. Histopathological evaluations were completed after the euthanasia of mice after four months and included hematoxylin and eosin (H&E), CK12, and beta-galactosidase (β-gal) staining. The treatment group demonstrated reduced opacity compared to the control group. While corneal neovascularization did not display significant variations between the groups, the control group did register higher numerical values. Histopathologically, reduced CK12 staining was detected in the control group. Additionally, β-gal staining areas were notably lower in the treatment group. Although the treated groups showed lower severity of fibrosis compared to the control groups, statistical difference was not significant. In conclusion, it seems that delivery of MSCs in MK has exhibited promising therapeutic results, notably in reducing corneal opacity. Furthermore, the significant reduction in the β-galactosidase staining area may point towards the promising anti-senescence potential of MSCs.