Advancements in Ischemic Retinopathies, Volume II: Precision Phenotyping, Early Interception, and Neurovascular Rescue

Ischemic retinopathies have traditionally been classified according to clinical diagnosis, vascular territory, or visible complications such as edema, neovascularization, and retinal non-perfusion. These categories remain clinically useful, but they do not fully capture the biological heterogeneity, temporal evolution, or reversibility of ischemic retinal injury. Patients with apparently similar vascular lesions may differ substantially in metabolic stress, inflammatory activation, glial responses, neurovascular uncoupling, systemic vascular risk, and capacity for retinal recovery.Volume I of this Research Topic examined molecular mechanisms, biomarkers, clinical indicators, and emerging therapeutic approaches across diabetic retinopathy, retinopathy of prematurity, retinal vascular occlusion, and other ischemic retinal disorders. Building on this foundation, Volume II moves toward a more translational challenge: how can retinal ischemia be detected, classified, and treated before neurovascular damage becomes irreversible?Rather than considering ischemic retinopathies only as established disease entities, this collection will examine them as dynamic biological states that evolve from compensated vascular stress to neurovascular dysfunction, tissue injury, and irreversible degeneration. Particular attention will be given to therapeutic windows, biologically defined disease endotypes, and biomarkers capable of distinguishing active, reversible, progressive, and treatment-resistant forms of ischemic injury. A major focus will be the transition from biomarker discovery to biomarker validation and clinical use. Contributions addressing reproducibility, longitudinal performance, prognostic value, treatment-response prediction, real-world evidence, multicenter validation, and clinical implementation are especially encouraged. Equally important is the integration of multimodal retinal imaging with molecular, metabolic, functional, and systemic vascular data. OCT, OCT angiography, retinal oximetry, adaptive optics, electrophysiology, ocular-fluid biomarkers, circulating markers, multi-omics technologies, and artificial intelligence may together provide a more complete view of ischemic burden and recovery potential than any single measure alone.This volume will also explore the retina as a window into systemic vascular health. Retinal ischemic phenotypes may reveal cerebrovascular, cardiovascular, metabolic, inflammatory, or endothelial abnormalities beyond the eye. Studies linking ocular findings with systemic mechanisms, risk stratification, or clinical outcomes are therefore highly relevant. Finally, Volume II seeks to attract work on therapeutic strategies designed not merely to suppress late complications, but to preserve or restore the retinal neurovascular unit. These may include vascular normalization, neuroprotection, metabolic rescue, mitochondrial support, glial modulation, regenerative strategies, targeted ocular delivery, gene- and RNA-based therapies, extracellular-vesicle-based interventions, and rational combinations with established anti-VEGF or anti-inflammatory treatments. By linking dynamic phenotyping with mechanism-guided treatment, this second volume aims to support a transition from reactive management of established retinal ischemia toward earlier, biologically informed, and patient-specific intervention. Particular areas of interest include:Early Detection and Biomarker Validation• Dynamic staging, reversibility, disease endotypes, therapeutic windows, and predictors of recovery• Molecular, imaging-based, functional, digital, ocular-fluid, and circulating biomarkers• Real-world evidence and multicenter validation for clinical and regulatory translationMultimodal Imaging and Data Integration• OCT, OCT angiography, retinal oximetry, adaptive optics, electrophysiology, and molecular imaging• Artificial intelligence, multimodal prediction models, and multi-omics approachesDisease Mechanisms and Systemic Implications• Neurovascular coupling, glial-vascular interactions, pericyte and endothelial dysfunction• Mitochondrial injury, metabolic insufficiency, ferroptosis, senescence, and maladaptive stress responses• Retinal ischemia as a marker of systemic vascular, metabolic, inflammatory, cardiovascular, or neurological diseaseTherapeutic Interventions and Neurovascular Rescue• Vascular, metabolic, neuroprotective, regenerative, gene-, RNA-, cell-, and extracellular-vesicle-based strategies• Targeted delivery, sustained-release technologies, and mechanism-based combination therapiesClinical Translation and Precision Medicine• Precision and adaptive clinical trials, patient-centered outcomes, digital biomarkers, human-relevant models, and implementation studies Topic editors: Ravirajsinh N Jadeja, Dario Rusciano, Snježana Kaštelan Source: https://www.frontiersin.org/research-topics/84329/advancements-in-ischemic-retinopathies-volume-ii-precision-phenotyping-early-interception-and-neurovascular-rescue