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Aims: Abnormalities in the oculomotor system may represent an early sign of diabetic neuropathy and are currently poorly studied. We designed an eye-tracking-based test to evaluate oculomotor function in patients with type 1 diabetes., Methods: We used the SRLab-Tobii TX300 Eye tracker®, an eye-tracking device, coupled with software that we developed to test abnormalities in the oculomotor system. The software consists of a series of eye-tracking tasks divided into 4 classes of parameters (Resistance, Wideness, Pursuit and Velocity) to evaluate both smooth and saccadic movement in different directions. We analyzed the oculomotor system in 34 healthy volunteers and in 34 patients with long-standing type 1 diabetes., Results: Among the 474 parameters analyzed with the eye-tracking-based system, 11% were significantly altered in patients with type 1 diabetes (p < 0.05), with a higher proportion of abnormalities observed in the Wideness (24%) and Resistance (10%) parameters. Patients with type 1 diabetes without diabetic neuropathy showed more frequently anomalous measurements in the Resistance class (p = 0.02). The classes of Velocity and Pursuit were less frequently altered in patients with type 1 diabetes as compared to healthy subjects, with anomalous measurements mainly observed in patients with diabetic neuropathy., Conclusions: Abnormalities in oculomotor system function can be detected in patients with type 1 diabetes using a novel eye-tracking-based test. A larger cohort study may further determine thresholds of normality and validate whether eye-tracking can be used to non-invasively characterize early signs of diabetic neuropathy., Trial: NCT04608890., (© 2022. The Author(s).)

A substantial proportion of patients who have recovered from coronavirus disease-2019 (COVID-19) experience COVID-19-related symptoms even months after hospital discharge. We extensively immunologically characterized patients who recovered from COVID-19. In these patients, T cells were exhausted, with increased PD-1+ T cells, as compared with healthy controls. Plasma levels of IL-1β, IL-1RA, and IL-8, among others, were also increased in patients who recovered from COVID-19. This altered immunophenotype was mirrored by a reduced ex vivo T cell response to both nonspecific and specific stimulation, revealing a dysfunctional status of T cells, including a poor response to SARS-CoV-2 antigens. Altered levels of plasma soluble PD-L1, as well as of PD1 promoter methylation and PD1-targeting miR-15-5p, in CD8+ T cells were also observed, suggesting abnormal function of the PD-1/PD-L1 immune checkpoint axis. Notably, ex vivo blockade of PD-1 nearly normalized the aforementioned immunophenotype and restored T cell function, reverting the observed post-COVID-19 immune abnormalities; indeed, we also noted an increased T cell-mediated response to SARS-CoV-2 peptides. Finally, in a neutralization assay, PD-1 blockade did not alter the ability of T cells to neutralize SARS-CoV-2 spike pseudotyped lentivirus infection. Immune checkpoint blockade ameliorates post-COVID-19 immune abnormalities and stimulates an anti-SARS-CoV-2 immune response.