From tarsal anatomy to tear-film homeostasis: A history-informed review of the meibomian gland in ocular surface biology.

The meibomian gland was anatomically described in 1666, but its central role in ocular surface disease emerged only after tear-film physiology, in vivo imaging, lipid biochemistry, and consensus nosology converged. This review reconstructs the transition from early anatomical recognition to the modern concept of meibomian gland dysfunction (MGD) as a major contributor to evaporative dry eye. We use "epistemic activation" as an analytic term for the historical process by which a long-recognized anatomical structure becomes causally linked to disease, rendered quantitatively measurable, and codified within a shared diagnostic framework. In the case of the meibomian gland, this process involved four linked shifts: anatomical visibility, causal attribution, quantitative measurability, and definitional codification. We organize this history into five stages: pre-physiological description, early functional suspicion, instrumental and biochemical quantification, consensus-based disease stabilization, and post-consensus molecular, cellular, and computational expansion. We argue that the rise of the meibomian gland did not follow from anatomy alone, but from the coupling of tear-film theory, imaging, lipidomics, and TFOS frameworks. Contemporary research is now moving beyond gross gland dropout toward cell-state, lipid-phase, immune, and computational phenotypes, with increasing interest in treatment-response stratification, as illustrated by single-cell and spatial transcriptomics, organoid models, artificial intelligence-based image analysis, and stem-cell/regenerative studies. A historically grounded account of these shifts clarifies why the meibomian gland now occupies a pivotal place in ocular surface biology and suggests how future MGD classification may evolve from morphology-based staging toward mechanism-informed endotyping.