Sabucedo Villamarín, BelénGarcía Queiruga, JacoboPena Verdeal, HugoGinzo Villamayor, María JoséGarcía Resúa, CarlosGiráldez Fernández, María JesúsYebra-Pimentel Vilar, Eva2025-11-212025-11-212025-11-20Sabucedo-Villamarin, B.; Garcia-Queiruga, J.; Pena-Verdeal, H.; Ginzo-Villamayor, M.J.; Garcia-Resua, C.; Giraldez, M.J.; Yebra-Pimentel, E. Long-Term Study of the Changes in Symptoms and Signs of Dry Eye Disease in Participants Non-Adherent to Treatment. Life 2025, 15, 1783. https://doi.org/10.3390/life151117832075-1729https://hdl.handle.net/10347/43959Background: The purpose of this study was to assess differences in clinical symptoms and signs of DED in non-adherent to treatment patients to describe long-term disease progression. Methods: 120 patients previously diagnosed with Dry Eye Disease (DED) were contacted to undergo a second eye examination. The final included participants were classified into three groups based on when the second examination was scheduled: 4 years (Group 1; n = 33), 6 years (Group 2; n = 18) or 8 years (Group 3; n = 37) since the diagnostic visit. All included participants were classified as ‘non-adherent to DED treatment’, defined as patients who reported not following their prescribed DED therapy. In both examinations, Ocular Surface Disease Index (OSDI) questionnaire, tear film osmolarity, inter-eye osmolarity (osmolarity|OD-OS|), Fluorescein Break-Up Time (FBUT), Maximum Blink Interval (MBI) and corneal staining were evaluated. Results: OSDI score improved after 4 years of DED diagnosis (Group 1, mean difference close to 12 points, p < 0.001) and after 8 years (Group 3, mean difference of 9 points, p < 0.001), but remained stable after 6 years (Group 2, p = 0.328). Osmolarity worsened only after 6 years of DED diagnosis (Group 2, mean difference of 13.2 mOsm/L, p = 0.011), while osmolarity|OD–OS| showed no change (all p ≥ 0.231). FBUT values were stable across all groups (all p ≥ 0.265). MBI increased after 4 and 8 years of DED diagnosis (Groups 1 and 3, p ≤ 0.003), but not after 6 years (Group 2, p = 0.391). Corneal staining worsened after 8 years of DED diagnosis (Group 3, 0.55 points, p = 0.011), with no changes at 4 or 6 years (Groups 1 and 2, both p ≥ 0.318). Conclusions: In non-adherent DED patients, osmolarity|OD-OS| and tear film stability remain stable during the natural course of the disease, while ocular surface damage increases. However, the subjective symptomatology and the nociceptive blink reflex due to ocular discomfort decreased since the diagnostic visit.eng© 2025 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) licenseAttribution 4.0 Internationalhttp://creativecommons.org/licenses/by/4.0/DED natural courseOSDI questionnaireTear film osmolarityTear film stabilityCorneal stainingLongitudinal studyMaximum blink interval220915 Optometría