Emerging Age-Specific Therapeutic Approaches for Dry Eye Disease

Abstract

Dry eye disease (DED) is a common, multifactorial disorder of the ocular surface. Although DED can affect individuals at any age, its prevalence, clinical manifestations, underlying mechanisms, and optimal management strategies differ considerably across the lifespan. In children, symptoms are frequently associated with atopy and allergic disorders and environmental factors, whereas in young adults, digital device usage and contact lens wear are the predominant contributors. In older adults, systemic diseases and polypharmacy significantly elevate the risk of DED. Across all age groups, tear film instability, decreased tear production, and chronic inflammation are central pathogenic features. Key tear biomarkers, such as pro-inflammatory cytokines, have been widely linked to disease development. Cathepsin S and tumor necrosis factor-alpha have recently been implicated in age-related DED. A nuanced understanding of these age-related differences is crucial for improving diagnostic accuracy and tailoring interventions to specific patient populations. This review synthesizes current evidence on DED across age groups, focusing on prevalence, risk factors, pathophysiology, molecular mechanisms, coexisting conditions, biomarkers, and treatment options. Finally, it highlights critical unmet clinical needs in the management of age-related DED.

Keywords: age targeted; biomarkers; children; dry eye disease; elderly; ocular surface; tears; treatment; young adults.

Figure 1

Flowchart of the study selection process.

Figure 2

Age-based classification of dry eye disease (DED) and associated risk factors. (A) Classification of DED according to age group: pediatric DED (PeDED), <18 years; young adult DED (y-aDED), 18–40 years; adult DED (aDED), 40–60 years; elderly DED (eDED), >60 years. (B) Major risk factors currently associated with each age group. (C) Risk factors common across all age groups.

Figure 3

Representative images of DED across different age groups. (A) Young male with DED associated with atopy. (B) Young adult with DED related to excessive digital screen use. (C) Elderly male (92 years old) with DED secondary to ectropion. (D) Elderly male using a CPAP mask for sleep apnea; white arrows indicate mechanical traction on the lower eyelids caused by the mask. Images (A,B,D) were generated using artificial intelligence.

Figure 4

Molecular mechanisms and biomarkers involved in DED across age groups. Schematic representation of the principal molecular pathways implicated in the pathogenesis of DED in different age categories. Inflammation is a core mechanism across all age groups, often accompanied by hyperosmolarity and oxidative stress. Blue text indicates key biological processes, with specific molecules listed in brackets. Red arrows indicate proteins with increased expression; blue arrows denote decreased expression in DED. In PeDED, commonly linked to atopic and allergic conditions, the overexpression of inflammatory cytokines, neuromediators, proteases, and allergy-related molecules has been reported. In y-aDED, DED is marked by elevated levels of inflammatory cytokines and S100A family proteins, along with reduced expression of antimicrobial peptides and proteins involved in cell adhesion and growth. In eDED, activation of the senescence-associated secretory phenotype (SASP) leads to upregulation of molecules associated with chronic inflammation (inflammaging), oxidative stress, apoptosis, and specific bioactive lipids. Molecules consistently involved in all three age groups are highlighted in bold, suggesting early pathogenic mechanisms may persist and worsen with age if untreated.

Figure 5

Unmet needs in the management of DED disease. (A) Proposed care model for DED: starting with prevention and education for patients and primary care providers, followed by standardized, biomarker-driven diagnosis; targeted treatment based on age, severity, and DED subtype; and comprehensive follow-up considering comorbidities and QoL. (B) Summary of key unmet clinical needs identified in each age-based DED category.