Ocul Surf. 2026 Jun 10:S1542-0124(26)00069-8. doi: 10.1016/j.jtos.2026.06.003. Online ahead of print.
ABSTRACT
Dry eye disease (DED) is increasingly recognized as a metabolic disorder characterized by the disruption of lipid homeostasis rather than solely an inflammatory condition. This review synthesizes current evidence regarding the dysregulation of lipid metabolism in the pathogenesis of DED. Furthermore, this review systematically summarizes lipid metabolic alterations involving the meibomian glands, lacrimal glands, cornea, conjunctiva, and the tear film. The ocular surface functions as an integrated Ocular Lipid Unit (OLU) where metabolic crosstalk occurs among these tissues. Key pathological mechanisms include the impairment of mitochondrial fatty acid oxidation and the dysregulated synthesis of very-long-chain fatty acids (VLCFAs) which compromise meibum fluidity and stability. Furthermore, an imbalance between pro-inflammatory n-6 and pro-resolving n-3 polyunsaturated fatty acids (PUFAs) causes chronic ocular surface inflammation. These metabolic shifts promote lipid peroxidation and ferroptosis while systemic factors such as aging and diabetes mellitus further exacerbate ocular lipotoxicity. Advances in lipidomics reveal that physical properties like viscoelasticity and molecular ordering are more clinically relevant than absolute lipid quantity. Emerging therapeutic strategies encompass physical therapies, novel pharmacological agents targeting ferroptosis or specific metabolic enzymes, and dietary interventions. Future management should prioritize restoring metabolic homeostasis of the entire OLU and targeting specific lipid defects to achieve precision medicine in DED.
PMID:42270038 | DOI:10.1016/j.jtos.2026.06.003