Bruno Barbosa Ribeiro,1 João Heitor Marques,1,2 Pedro Manuel Baptista,1,2 Paulo JM Sousa,1 Saúl Pires,1 Pedro Menéres,1,2 Irene Barbosa1,2 1Department of Ophthalmology, Unidade Local de Saúde Santo António, Porto, Portugal; 2School of Medicine and Biomedical Sciences (ICBAS), University of Porto, Porto, PortugalCorrespondence: Bruno Barbosa Ribeiro, Unidade Local de Saúde Santo António – Department of Ophthalmology, Largo Do Prof. Abel Salazar, Oporto, 4099-001, Portugal, Tel +351 222 077 500, Email brunot.barbosaribeiro@gmail.comPurpose: To study corneal epithelial thickness in patients with Dry Eye Disease (DED), according to symptomatology.Patients and Methods: Cross-sectional study in the outpatient clinic of the Ophthalmology Department of a tertiary hospital in Oporto, Portugal. Adult patients with a clinical diagnosis of dry eye disease were eligible for participation. Each patient underwent corneal epithelial thickness mapping with swept-source optical coherence tomography (SS-OCT, Heidelberg Anterion®) and automated ocular surface analysis (IDRA® Ocular Surface Analyzer SBM Sistemi, Italy). Schirmer’s test, tear film osmolarity (by TearLab® Osmolarity System) and Dry-Eye Related Questionnaire (OSDI-12) were also evaluated. Patients were classified accordingly the severity of symptoms in the OSDI-12 in group 1 (mild disease) and group 2 (moderate to severe disease).Results: We enrolled 200 eyes (of 100 subjects): 65 in group 1 and 135 in group 2. Median OSDI and Schirmer’s test in group 1 was 7 vs 46 points, p< 0.001 and 15 vs 11 mm, p=0.007 in group 2. Eyes from group 2 showed higher mean epithelial thickness (48.4 vs 47.1 μm, p=0.027) and lower mean stromal thickness (522.0 vs 546.6 μm, p< 0.001) in comparison with group 1. OSDI score was positively correlated with the mean epithelial thickness (r=0.188, p=0.008) and epithelial variability index (r=0.277, p=0.004) and negatively correlated with the mean stromal thickness (r=− 0.313, p< 0.001). Patients in group 2 showed higher epithelial variability index (4.5 vs 3.2, p< 0.001).Conclusion: Our study suggests that patients with more severe DED symptoms have thicker corneal epithelia and thinner stroma, which may act as a compensatory response. Epithelial variability index is positively correlated with the OSDI score and may reflect DED severity. This is the first study to report stromal thinning in patients with DED, thereby proving novel information regarding the matter. More studies are needed to confirm these results.Plain Language Summary: We have conducted original research regarding the effects of Dry Eye Disease on corneal epithelial and stromal thickness, as evaluated by Swept-Source Optical Coherence Tomography (Heidelberg Anterion®). Our study is pioneer in showing that patients with more severe symptoms have thicker epithelia with an apparent compensatory stromal thinning. Besides, corneal epithelium seems to have higher variability index in these patients, which appears to correlate with Dry Eye symptom severity. Our results may be helpful to reveal the role of dry eye disease in corneal structural changes.Keywords: dry eye, cornea, epithelium, thickness, anterion