The pathogenesis of primary acquired nasolacrimal duct obstruction (PANDO) remains unclear, with several factors implicated, including anatomical structures, hormones, and tear components. This study explored tear proteins to better understand PANDO etiology by comparing protein expression in tears from patients with PANDO and healthy controls. Tear samples were collected from 22 patients with PANDO (mucous and membranous types) and 8 controls using Weck-Cel sponges. Protein analysis was conducted using LC-MS/MS to identify and quantify tear proteins. Female patients with PANDO had higher numbers of differentially expressed proteins (DEPs) compared with males. Certain DEPs associated with inflammatory pathways or the lacrimal duct epithelium, including SERPINB1, SERPINA3, CTSG, SLPI, and EZR, were identified in male patients. Although this is a preliminary study, our results offer insights into the pathogenesis of PANDO, with potential to distinguish between mucous and membranous subtypes. The potential biomarkers identified in this study could enhance early diagnosis and treatment, shedding light on inflammatory and immune processes in PANDO.

Primary acquired nasolacrimal duct obstruction (PANDO) is a common cause of epiphora in adults, yet the biochemical environment within the nasolacrimal duct (NLD) remains poorly understood. This study aimed to characterize the proteomic composition of NLD lavage fluid and identify subtype-specific molecular features distinguishing membranous and mucinous obstruction. Paired tear and NLD lavage fluid (NLD-LF) samples were collected from patients undergoing dacryoendoscopic recanalization, and proteomic profiling was performed using LC–MS/MS. A total of 1345 proteins were identified in NLD-LF and 767 in tear fluid, revealing a distinct NLD-specific proteome. Although the membranous and mucinous subtypes shared broadly similar protein compositions, differentially expressed proteins highlighted divergent biochemical pathways. The membranous subtype showed enrichment of keratinization-related processes involving KRT1, KRT9, and KLK13, suggesting epithelial remodeling and cornification. In contrast, the mucinous subtype exhibited upregulation of proteins involved in lipid metabolism, carboxylic acid biosynthesis, and sulfur compound metabolism, including ALOX15B, LCAT, and GSTM4, indicating metabolic conditions that promote mucin–lipid interactions, glycan sulfation, and redox-dependent mucin cross-linking. These findings provide new insights into the protein composition of NLD lavage fluid and suggest molecular differences between the membranous and mucinous obstruction subtypes.