Purpose:To evaluate ophthalmic involvement of systemic immunoglobulin-G4-related disease (IgG4-RD) and describe the changes in both ocular surface parameters and corneal subbasal nerve plexus.Materials and Methods:Twenty eyes of 10 patients with systemic IgG4-RD and 20 eyes of 10 control subjects were enrolled in this study. Demographic information, medical history, serum IgG4 levels, orbital imaging, and follow-up data of subjects were recorded. Ocular surface tests were carried out in the order of tear break-up time (BUT), lissamine green (LG) staining, Schirmer I test with anesthesia, and ocular surface disease index (OSDI) questionnaire for all participants. Corneal subbasal nerves and basal epithelial cell layer were evaluated using in vivo confocal microscopy.Results:Among the 10 patients with IgG4-RD, 11 eyes of 7 patients had orbital involvement. Among these 7 patients with IgG4-related ophthalmic disease, 4 presented with painless eyelid or periorbital swelling, 2 with diplopia and restricted ocular motility, and 1 with proptosis. Patients with IgG4-RD had higher OSDI (5.9 6.6 vs. 1.7 +/- 2.4, P < 0.001) and LG staining scores (0.7 +/- 1.0 vs. 0.0 +/- 0.0, P = 0.011) and lower BUT (5.6 +/- 1.4 vs. 10.2 +/- 1.0, P < 0.001) and Schirmer values (11.9 +/- 10.3 vs. 18.3 +/- 4.4, P = 0.021) as compared with those of control subjects. Total nerve density and nerve fiber length were found to be significantly lower in patients with IgG4-RD.Conclusions:The orbit is frequently involved during the course of IgG4-RD. These patients should be evaluated in terms of ocular surface disease and dry eye, which may be associated with lacrimal gland and/or orbital nerve involvement.