Purpose: To provide a systematic review of the literature on the etiopathogenesis of primary acquired nasolacrimal duct obstruction (PANDO).

Methods: The authors performed a PubMed search of all articles published in English with specific reference to etiopathogenesis of PANDO or associations of PANDO. Data captured include demographics, study techniques, hypothesis, presumed or confirmed interpretations with regards to pathogenesis, mechanisms, or pathways. Specific emphasis was laid on addressing the lacunae and potential directions for future research.

Results: Numerous factors are believed to contribute to the etiopathogenesis of PANDO. The basic pathogenesis involves inflammation, vascular congestion, mucosal edema, fibrosis, obstruction, and stasis. Bony nasolacrimal duct diameter does not appear to play a significant role. There is no convincing data to substantiate nose as the site of disease origin and nasal factors appear to be comorbidities. Hormonal mechanisms are more evidence-based but can only partly explain the pathogenesis. Vascular theories are based on the behavior of perilacrimal cavernous bodies, their autonomic control, and additional structural changes in the helical patterns of connective tissue fiber arrangements. Repeated vascular malfunction leading to structural epithelial and subepithelial changes currently appears to be the most evidence-based and accepted theory. Tear proteomics holds a promise in decoding the etiopathogenesis of PANDO, at least in part.

Conclusions: The etiopathogenesis of PANDO appears to be multifactorial. Hormonal microenvironments, vascular factors, and tear proteomics are promising candidates for further work. There is a need for focused work by Clinician-Scientists and the answers can have far reaching clinical implications.