Abstract by Pernille May Hansen

Atopic keratoconjunctivitis (AKC) is a severe ocular surface disease (OSD) that significantly affects patients' quality of life and can lead to blindness. AKC is associated with atopic dermatitis (AD), a common chronic inflammatory skin disease affecting both children and adults. This thesis investigates the prevalence, clinical features, and underlying mechanisms of OSD and AKC in AD patients, aiming to improve the understanding and management of these conditions.

Two distinct questionnaire studies were conducted to assess the association of OSD symptoms in AD patients within the general population (I) and to identify risk factors associated with OSD in AD patients (II). To further explore AKC, a cohort of AD patients with and without AKC was established. This cohort underwent clinical examinations and tear fluid analyses to characterize the clinical phenotype and cytokine profiles associated with AKC (III). Complementary in vitro studies on conjunctival goblet cells (GCs) were also conducted. These experiments explored the effects of key cytokines involved in AD (interleukin (IL)-13, IL-4, and interferon-gamma (IFNγ)) on GC proliferation and mucin production. The findings aimed to provide insights into the roles of these cytokines in GC function, which is important for maintaining ocular surface homeostasis (IV).

In a study involving 57,464 participants, OSD symptoms were found to be associated with both current AD (adjusted odds ratio (aOR): 1.16) and previous AD (aOR: 1.19), revealing a significantly higher occurrence of symptoms among individuals with AD (I). Among 7,044 AD patients, the prevalence of current conjunctivitis was 12.7% while the lifetime prevalence was 66.6% (II). Additionally, the prevalence of OSD was associated with AD severity and the occurrence of atopic comorbidities (II). Moderate-severe AKC was linked to higher levels of IL4, IL-13, and IFN-γ in the tear fluid, as well as more severe AD, and higher occurrence of atopic comorbidities (III). Studies of GC cultures revealed contrasting effects of IL-13, IL-4, and IFN-γ, with IL-13 and IL-4 promoting GC proliferation and increasing mucin messenger ribonucleic acid (mRNA) expression (IV).

The findings presented in this thesis highlight the strong association between AD and OSD, showing that the risk of OSD is increased by the cumulative burden of AD. Furthermore, the results reveal that increased AKC severity is linked to altered cytokine levels in the tear fluid, specifically elevated levels of IL-13, IL-4, and IFN-γ. Additionally, IL-13, IL-4, and IFN-γ demonstrate opposing effects on conjunctival GC function, suggesting these cytokines play essential roles in modulating ocular surface integrity in AKC. This research contributes to the growing understanding of the link between AD and OSD, identifying potential biomarkers and therapeutic targets for improved management of AKC.