Leber’s hereditary optic neuropathy (LHON) is a mitochondrial disorder that causes visual impairment due to the degeneration of retinal ganglion cells. Oxidative stress (OS) and inflammatory cytokines have been implicated in its pathophysiology. We investigated, for the first time, the presence of OS biomarkers and inflammatory cytokines in the aqueous humor and peripheral blood of LHON patients compared to controls, aiming to identify potential clinical biomarkers for diagnosis and disease monitoring. A total of 38 participants were enrolled in a single-center, retrospective observational study, including 17 genetically confirmed LHON patients from different Spanish regions and 21 controls. OS biomarkers and inflammatory cytokines were quantified using spectrophotometry and fluorimetry techniques. Statistical analyses were performed to compare groups and to assess the discriminatory performance of biomarkers in identifying affected individuals. Compared to controls, LHON patients exhibited significantly higher levels of AOPP, LOOH, nitrotyrosine, GPX, GRD, and OX/AntiOX ratio in both aqueous humor and serum. Among these, serum LOOH levels and the OX/AntiOX ratio were the most reliable for identifying patients affected, with high sensitivity and specificity. However, additional data on serum IL-1ra are required to confirm its potential as an effective classifier. These findings highlight novel candidate biomarkers for the diagnosis and monitoring of LHON progression.

Background: Severe COVID-19 reflects a multi-layered host response with systemic inflammation, thrombo-inflammation, tissue damage, oxidative stress and altered antiviral interferon biology. We performed an integrated exploratory analysis of first-wave hospitalized patients to identify biomarker patterns associated with adverse clinical evolution during established admission. Methods: We analyzed 60 hospitalized COVID-19 patients and 18 healthy controls for soluble IFNAR2 (sIFNAR2) comparison. Biomarker samples were obtained during hospitalization, approximately seven days after symptom onset. Outcomes were final clinical status, severe respiratory involvement, post-sampling clinical worsening and death. Analyses included non-parametric testing, false-discovery-rate adjustment, effect-size estimation, exploratory ROC curves, parsimonious regression, penalized internal validation, composite scores and molecular-structure analyses. Results: Final status was favorable outcome in 31 patients, severe non-fatal disease in 22 and death in 7. sIFNAR2 was higher in patients than in healthy controls and highest among non-survivors, but did not distinguish favorably from severe non-fatal disease. The most consistent severity-associated signals were IL-6, D-dimer, total thiols, IL-10, LDH, ferritin, leukocytes and IL-1RA. D-dimer, IL-6 and ferritin yielded the largest exploratory univariable AUCs for severe respiratory involvement, whereas ferritin, IL-10, IL-1RA and sIFNAR2 predominated in event-limited mortality analyses, which were based on only seven deaths. Composite multi-axis scores and PLS-DA were tools requiring external validation. Conclusions: Biomarker patterns during admission were associated with adverse evolution. Conventional markers remained the most practical signals, while cytokines, redox markers and sIFNAR2 provided complementary biological information. sIFNAR2 should be interpreted as an exploratory complementary marker of the interferon receptor axis, mainly linked to mortality, not as a stand-alone clinical test or functional measure of IFNAR signaling.