Our results support the hypothesis that rituximab is beneficial and well tolerated in managing refractory myasthenia gravis and nearly doubles published cases. We propose that B-cell-directed therapies may become an attractive option and suggest pursuit of a prospective trial.

Background: The microvasculature, the smallest blood vessels in the body, has key roles in maintenance of organ health as well as tumorigenesis. The retinal fundus is a window for human in vivo non-invasive assessment of the microvasculature. Large-scale complementary machine learning-based assessment of the retinal vasculature with phenome-wide and genome-wide analyses may yield new insights into human health and disease. Methods: We utilized 97,895 retinal fundus images from 54,813 UK Biobank participants. Using convolutional neural networks to segment the retinal microvasculature, we calculated fractal dimension (FD) as a measure of vascular branching complexity, and vascular density. We associated these indices with 1,866 incident ICD-based conditions (median 10y follow-up) and 88 quantitative traits, adjusting for age, sex, smoking status, and ethnicity. Results: Low retinal vascular FD and density were significantly associated with higher risks for incident mortality, hypertension, congestive heart failure, renal failure, type 2 diabetes, sleep apnea, anemia, and multiple ocular conditions, as well as corresponding quantitative traits. Genome-wide association of vascular FD and density identified 7 and 13 novel loci respectively, which were enriched for pathways linked to angiogenesis (e.g., VEGF, PDGFR, angiopoietin, and WNT signaling pathways) and inflammation (e.g., interleukin, cytokine signaling). Conclusions: Our results indicate that the retinal vasculature may serve as a biomarker for future cardiometabolic and ocular disease and provide insights on genes and biological pathways influencing microvascular indices. Moreover, such a framework highlights how deep learning of images can quantify an interpretable phenotype for integration with electronic health records, biomarker, and genetic data to inform risk prediction and risk modification.

Myasthenia gravis (MG) is an immune-mediated disorder with a variable response to treatment. In this study, patients with refractory MG who were treated with rituximab were identified. A review of patients referred to the Yale Neuromuscular Clinic was performed. Patients with refractory MG who were treated with rituximab were reviewed for response to treatment. Patients who had muscle-specific kinase (MuSK(+)) or acetylcholine receptor (AChR(+)) antibodies were included. Six patients were identified who met the criteria described. All patients tolerated rituximab without side effects and had a reduced need for immunosuppressants and/or improvement in clinical function. Patients with refractory MG appeared to respond to rituximab in this small, retrospective study. This result suggests that a larger, prospective trial is indicated.

PURPOSE.To characterize the 24-hour pattern of intraocular pressure (IOP) in untreated ocular hypertensive (OHTN) patients.METHODS. IOP measurements were taken every 2 hours during a 24-hour period from 15 untreated OHTN patients (ages 41-77 years). Measurements were both sitting and supine (diurnal) and supine only (nocturnal). Mean diurnal and nocturnal IOPs in the OHTN group were compared to previously reported values in age-matched healthy and glaucomatous eyes. Post hoc analysis compared the 24-hour IOP pattern of the OHTN patients who converted to glaucoma and those who did not with that in the same healthy and glaucomatous eyes.RESULTS. Mean sitting and supine IOPs were significantly higher in the OHTN group than in the healthy control but not the glaucoma group. Similar to the glaucoma group, the OHTN group demonstrated significant differences from healthy controls in diurnal IOP variation and IOP changes upon awakening in habitual and supine positions. The 24-hour IOP curve acrophases and amplitudes for OHTNs were closer to those of the glaucoma than the healthy control group in the habitual position. Thirty-three percent of OHTNs developed glaucoma during a mean follow-up period of 4.3 6 3.8 years. Similar to findings in the glaucoma group, habitual IOP curve phase delay, habitual IOP variation, diurnal-to-nocturnal IOP changes, and IOP changes upon awakening of the converters were significantly different from those in healthy controls. There were no differences between nonconverters and other groups.CONCLUSIONS. Baseline 24-hour IOP pattern in OHTN patients is similar to that in glaucomatous patients. In contrast to nonconverters, OHTN patients who converted to glaucoma are significantly different from healthy controls. (Invest Ophthalmol Vis Sci. 2013;54:512-517)