Ocul Surf. 2026 Jun 11:S1542-0124(26)00077-7. doi: 10.1016/j.jtos.2026.06.011. Online ahead of print.
ABSTRACT
Dry eye disease (DED) is highly prevalent in older adults and represents a growing public health burden in aging societies. Although age is a well-recognized risk factor for DED, it is still often treated as a background variable rather than an active biological driver of disease. Emerging evidence indicates that aging itself promotes progressive structural remodeling and functional decline across multiple ocular surface tissues, giving rise to a distinct, aging-driven DED phenotype. In this review, we synthesize current knowledge on how biological aging disrupts ocular surface homeostasis at tissue, cellular, and molecular levels. We describe age-associated changes on the lacrimal gland (LG), meibomian gland (MG), cornea, and conjunctiva, including secretory cell exhaustion, lipid dysregulation, epithelial barrier impairment, neural degeneration, and goblet cell (GC) loss. These structural changes are tightly linked to core aging mechanisms such as cellular senescence, oxidative stress, mitochondrial dysfunction, inflammaging, neuroendocrine imbalance, and stem/progenitor cell decline. Importantly, these processes interact as an integrated network, creating a self-reinforcing cycle of tear film instability, chronic low-grade inflammation, and impaired tissue repair that differs mechanistically from environmentally induced or autoimmune forms of DED. By reframing aging as a central pathogenic driver and considering age-related DED as a distinct subtype, this perspective highlights the need for mechanism-informed therapeutic strategies. Beyond conventional lubrication and anti-inflammatory therapy, interventions targeting oxidative stress, cellular senescence, immune dysregulation, neurosensory decline, and hormonal alterations may offer more fundamental disease modification in elderly patients.
PMID:42276417 | DOI:10.1016/j.jtos.2026.06.011