Lacrimal Gland Insufficiency in Aqueous Deficiency Dry Eye Disease: Recent Advances in Pathogenesis, Diagnosis, and Treatment

Background Aqueous deficiency dry eye disease is a chronic and potentially sight-threatening condition, that occurs due to the dysfunction of the lacrimal glands. The aim of this review was to describe the various recent developments in the understanding, diagnosis and treatment of lacrimal gland insufficiency in aqueous deficiency dry eye disease.Methods A MEDLINE database search using PubMed was performed using the keywords: "dry eye disease/syndrome", "aqueous deficient/deficiency dry eye disease", "lacrimal gland" and "Sjogren's syndrome". After scanning through 750 relevant abstracts, 73 eligible articles published in the English language from 2016 to 2021 were included in the review.Results Histopathological and ultrastructural studies have revealed new insights into the pathogenesis of cicatrising conjunctivitis-induced aqueous deficiency, where the lacrimal gland acini remain uninvolved and retain their secretory property, while significant ultrastructural changes in the gland have been observed. Recent advances in diagnosis include the techniques of direct clinical assessment of the lacrimal gland morphology and secretion, tear film osmolarity, tear film lysozyme and lactoferrin levels, tear film interferometry and lacrimal gland confocal microscopy. Developments in the treatment of aqueous deficiency dry eye disease, apart from the nanoparticle-based tear substitutes, include secretagogues like diquafosol tetrasodium and rebamipide, anti-inflammatory topical agents like nanomicellar form of cyclosporine and lifitegrast, scleral contact lenses, neurostimulation, and acupuncture for increasing the amount of tear production, minor salivary gland transplantation, faecal microbial transplantation, lacrimal gland regeneration and mesenchymal stem cell therapy.Conclusions Significant advances in the understanding, diagnosis and management of lacrimal gland insufficiency and its role in aqueous deficiency dry eye disease have taken place within the second half of the last decade. Of which, translational breakthroughs in terms of newer drug formulations and regenerative medicine are most promising.