Conjunctival goblet and epithelial cell changes in antidepressant-associated dry eye disease: a case–control study

Antidepressants influence tear film stability, but their effects on goblet cell density (GCD) and conjunctival epithelium remain underexplored. This study evaluated GCD and histomorphological changes in antidepressant users versus controls. In this case-control study, 72 antidepressant users (cases), and 70 matched controls (aged 20–40 years) underwent tear break-up time (TBUT), Schirmer testing, Ocular Surface Disease Index (OSDI) assessment, corneal/conjunctival staining evaluation, and conjunctival impression cytology. GCD, nuclear-cytoplasmic (NC) fraction, cell-to-cell contact, and nuclear changes were evaluated at 400× magnification. ImageJ software was used for goblet cell counting and measuring NC fraction. Commonly prescribed antidepressants such as selective serotonin reuptake inhibitors, selective norepinephrine reuptake inhibitors and tricyclic antidepressants were included in the study. Cases showed reduced GCD (183 ± 157 vs. 366 ± 164 cells/mm², P < 0.001), NC fraction (0.34 ± 0.09 vs. 0.41 ± 0.08, P < 0.001), TBUT (6.7 ± 3.1 vs. 10.8 ± 4.1 s, P < 0.001), and Schirmer wetting (5.8 ± 2.4 vs. 7.6 ± 3.6 mm/5 min, P < 0.001), with higher OSDI scores (25.6 ± 17.6 vs. 12.3 ± 7.3, P < 0.001), corneal staining (OR 13.0, 95% CI 4.7–36.1), and conjunctival staining ( P = 0.009). Morphological grades worsened in cases (all P < 0.001). GCD correlated positively with TBUT ( r = 0.41, P < 0.001) and Schirmer ( r = 0.43, P < 0.001). No differences existed across SSRI/SNRI/TCA subgroups. Antidepressant use associates with goblet cell loss, epithelial alterations, and dry eye disease (DED), warranting routine ocular monitoring.