Long-term effects of adenoviral keratoconjunctivitis on conjunctival goblet cell density and tear film parameters: a prospective case-control study

Abstract

Background: Adenoviral keratoconjunctivitis (AKC) is a common ocular infection that causes acute inflammation of the ocular surface. However, the long-term effects of AKC on conjunctival goblet cell density and tear film stability remain poorly understood. This study aimed to evaluate the long-term impact of AKC on goblet cell morphology, density, and tear film parameters. Methods: This prospective case-control study included 95 eyes of 64 patients with a history of AKC diagnosed during epidemic outbreaks based on strict clinical criteria (mean follow-up: 18.3 ± 6.8 months after the acute episode) and 92 eyes of 55 age-matched healthy controls. All participants underwent Schirmer test with anesthesia, tear breakup time (TBUT) measurement, slit-lamp evaluation of lid margin and meibomian gland function, and conjunctival impression cytology. Goblet cell density was quantified, and epithelial changes were graded using the Nelson classification system. Adenovirus serotyping was performed by multiplex PCR in a subset of patients during the acute phase. Post-hoc power analysis and multivariable logistic regression adjusting for sex and age were performed. Results: The mean age was 45.2 ± 14.6 years in the case group and 42.8 ± 13.9 years in the control group (p = 0.312). Goblet cell density was significantly lower in the AKC group (116 [58–289] cells/mm²) compared with controls (463 [123–1063] cells/mm²; p < 0.001), representing a 75% reduction. The median Nelson score was higher in the AKC group (2.0 [1.0–2.0]) than in controls (1.0 [0.0–1.75]; p < 0.001), indicating more advanced squamous metaplasia. Schirmer test values (10.0 [8.0–13.0] vs. 14.0 [10.25–17.0] mm; p < 0.001) and TBUT (8.16 ± 2.98 vs. 11.1 ± 3.20 s; p < 0.001) were significantly reduced in the AKC group. Adenovirus serotype 8 was identified in 80% of typed samples. Sex-stratified analysis confirmed significant goblet cell reduction in both sexes. Multivariable regression confirmed AKC as an independent predictor of goblet cell loss after adjusting for sex and age (adjusted OR: 4.82; 95% CI: 2.61–8.91; p < 0.001). Conclusions: AKC leads to persistent goblet cell loss and squamous metaplasia, resulting in decreased tear film stability and dry eye symptoms at 18 months post-infection, independent of sex and age. Future studies should incorporate validated patient-reported outcome measures to fully characterise the symptomatic burden of post-AKC ocular surface disease.