Age-related dry eye disease: Redefining a distinct subtype driven by aging.

Area of Science:

• Ophthalmology
• Gerontology
• Molecular Biology

Background:

• Dry eye disease (DED) is highly prevalent in older adults, posing a significant public health challenge.
• Aging is often considered a risk factor but increasingly recognized as a direct biological driver of DED.
• A distinct aging-driven DED phenotype emerges from progressive structural and functional decline in ocular tissues.

Purpose of the Study:

• To review how biological aging disrupts ocular surface homeostasis at multiple levels.
• To synthesize current knowledge on age-associated changes in ocular tissues and their link to aging mechanisms.
• To reframe age-related DED as a distinct subtype requiring mechanism-informed therapeutic strategies.

Main Methods:

• Literature review synthesizing current knowledge on aging and DED.
• Analysis of age-associated changes in lacrimal gland, meibomian gland, cornea, and conjunctiva.
• Integration of core aging mechanisms (senescence, oxidative stress, etc.) with ocular surface dysfunction.

Main Results:

• Aging causes secretory cell exhaustion, lipid dysregulation, barrier impairment, neural degeneration, and goblet cell loss.
• These changes are linked to cellular senescence, oxidative stress, inflammaging, and stem cell decline.
• An integrated network of aging processes creates a cycle of tear instability, inflammation, and impaired repair.

Conclusions:

• Aging is a central pathogenic driver of a distinct DED subtype in the elderly.
• Current therapies may be insufficient; novel strategies targeting aging mechanisms are needed.
• Interventions addressing oxidative stress, senescence, immune dysregulation, and neuroendocrine factors could modify age-related DED.