Purpose: To describe structural and systemic barriers to ophthalmic care experienced by underserved patients, particularly those facing language obstacles, immigration-related constraints, limited insurance coverage, financial hardship, and navigation challenges in an urban setting, and to examine these barriers through a complexity-informed lens. Methods: We conducted a narrative literature review focused on healthcare disparities, patient navigation, complexity in care delivery, and time-sensitive prioritization frameworks in ophthalmology. Findings were integrated with case vignettes drawn from Eyes on Wheels (EOW), a mobile eye care initiative that provides no-cost examinations at Federally Qualified Health Centers (FQHCs) and free clinics. Cases were identified through routine clinical documentation and used to illustrate how structural barriers described in the literature manifest in real-world care pathways. Results: Three recurring system-level issues were identified across EOW encounters: (A) misclassification of medically necessary, time-sensitive ophthalmic care as “non-urgent”; (B) patient disengagement driven by cumulative structural and logistical barriers; and (C) failures that arise when the healthcare system, functioning as a complex adaptive system (CAS), is unable to adapt to patients’ and systems’ changing circumstances. A review of the literature confirmed that these patterns reflect widely documented challenges faced by underserved urban populations. Three EOW case vignettes, selected from seven patients identified in 2024, are presented as illustrative examples of these systemic patterns. Conclusions: Addressing inequities in eye care requires an approach that recognizes how many parts of the healthcare system interact and affect a patient’s ability to receive timely treatment. Vision loss is often the preventable result of systems that are rigid, fragmented, or unable to adapt to a patient’s circumstances. Improving outcomes will require flexible care models, such as mobile clinics, paired with strong institutional support, patient-centered navigation, and consistent assessment of social needs and barriers to care. Sustained progress will depend on collaboration across organizations, adaptable leadership, and policies that respond to the real-world situations in which patients live.

Extracellular vesicles (EV) represent a conserved and highly efficient mechanism for cell-to-cell communication. Matrix-bound nanovesicles (MBV) are a recently identified type of EV embedded within the extracellular matrix with potent local and systemic immunomodulatory effects on myeloid cells. These effects are durable and last beyond the predicted life span of differentiated myeloid cells such as macrophages. The present study investigated MBV-directed epigenetic modification in myeloid precursors as a potential explanation for their prolonged immunomodulatory effects. Flow cytometry and ATAC sequencing studies show that MBV are internalized by myeloid cell progenitors in the bone marrow and in macrophages after terminal differentiation. This internalization is coincident with epigenetic changes that are associated with modulation of macrophage responses to inflammatory stimuli. Furthermore, MBV treatment differentially alters chromatin accessibility as a function of cell differentiation state (i.e., myeloid progenitor versus macrophage). The present study shows the epigenetic effects of MBV on myeloid cells, representing a potential avenue to exploit the therapeutic potential of biologic scaffold materials.