Lacrimal Gland and Drainage Disorders in the Era of Immune-Mediated Disease: A Systematic Review of Pathophysiology, Multimodal Imaging, and Precision Management

Abstract

Background: Lacrimal gland and lacrimal drainage disorders encompass a broad spectrum of inflammatory conditions. Advances in immunology, imaging, and pathology have increasingly identified these disorders as predominantly immune-mediated, with IgG4-related disease emerging as a major etiologic entity. However, evidence remains dispersed across specialties, limiting integrated clinical application.
Objective: To systematically review and synthesize current evidence on the pathophysiology, multimodal imaging features, and precision-based management of immune-mediated lacrimal gland and lacrimal drainage disorders.
Methods: This systematic review was conducted in accordance with PRISMA 2020 guidelines. PubMed/MEDLINE, EMBASE, Scopus, and Web of Science were searched for studies published between January 2000 and June 2025. Eligible studies addressed immune-mediated lacrimal disease with emphasis on diagnostic approaches, imaging characteristics, histopathology, and management. Data were synthesized qualitatively across predefined domains.
Results: About 93 studies met the inclusion criteria. IgG4-related disease was the most frequently reported immune-mediated lacrimal disorder, followed by Sjögren’s syndrome and idiopathic orbital inflammatory disease. Multimodal imaging, particularly MRI and CT, was central to disease characterization, with ultrasound elastography and functional imaging increasingly contributing to diagnostic stratification. Systemic corticosteroids were the most common first-line therapy; however, high relapse rates, especially in IgG4-related disease, prompted growing use of steroid-sparing immunosuppressive agents and biologic therapies, most notably rituximab. Surgical and endoscopic interventions were selectively employed for diagnostic confirmation and refractory lacrimal drainage obstruction. Short-term responses were generally favorable, while long-term outcomes remained heterogeneous.
Conclusion: Immune-mediated mechanisms represent a dominant paradigm in lacrimal disease. Optimal diagnosis and management require an integrated, multimodal, precision-based approach, combining clinical evaluation, advanced imaging, histopathology, and individualized therapy.