Hahnmadden0857

Aims To investigate the efficacy of a bi-modality deep convolutional neural network (DCNN) framework to categorise age-related macular degeneration (AMD) and polypoidal choroidal vasculopathy (PCV) from colour fundus images and optical coherence tomography (OCT) images. Methods A retrospective cross-sectional study was proposed of patients with AMD or PCV who came to Peking Union Medical College Hospital. Diagnoses of all patients were confirmed by two retinal experts based on diagnostic gold standard for AMD and PCV. Patients with concurrent retinal vascular diseases were excluded. Colour fundus images and spectral domain OCT images were taken from dilated eyes of patients and healthy controls, and anonymised. All images were pre-labelled into normal, dry or wet AMD or PCV. ResNet-50 models were used as the backbone and alternate machine learning models including random forest classifiers were constructed for further comparison. For human-machine comparison, the same testing data set was diagnosed by three retinal experts independently. All images from the same participant were presented only within a single partition subset. Results On a test set of 143 fundus and OCT image pairs from 80 eyes (20 eyes per-group), the bi-modal DCNN demonstrated the best performance, with accuracy 87.4%, sensitivity 88.8% and specificity 95.6%, and a perfect agreement with diagnostic gold standard (Cohen's κ 0.828), exceeds slightly over the best expert (Human1, Cohen's κ 0.810). For recognising PCV, the model outperformed the best expert as well. Conclusion A bi-modal DCNN for automated classification of AMD and PCV is accurate and promising in the realm of public health.Background/aims To better understand seasonal and weekday intraocular pressure (IOP) variations, long-term daily IOP measurements were assessed in patients with glaucoma using an intraocular telemetric sensor. Methods This prospective, open-label, multicentre observational study analysed the IOP variation patterns in 22 eyes of 22 patients with primary open-angle glaucoma (67.8±6.8 years, 36.4% female) who had undergone placement of an intraocular telemetric sensor at the time of cataract surgery. The telemetric system combines an implantable IOP sensor with a hand-held reading device. Patients were instructed to self-measure their IOP as often as desired, but at least four times daily. Analysis of variance and Tukey multiple-comparison correction were used to assess the statistical significance of average and peak IOP variations between individual weekdays and months. Results Each enrolled patient recorded daily IOP measurements for an average duration of 721 days. On average, IOPs were highest on Wednesdays and lowest on Fridays (p=0.002). There were significant variations of IOP throughout the year, and IOP showed a seasonal pattern. Between mid-winter (December-January) and mid-summer months, there was a reduction in mean IOP of 8.1% (-1.55 mm Hg, p less then 0.05). Conclusion This study confirms previously observed seasonal variations of IOP. IOP was significantly higher in winter compared with summer months. Moreover, IOP was lower on Friday than on other days. The explanation for these results is not known.Objective To test the hypothesis that antidrug antibodies (ADAs) against alemtuzumab could become relevant after repeated treatments for some individuals, possibly explaining occasional treatment resistance. Methods Recombinant alemtuzumab single-chain variable fragment antibody with a dual tandem nanoluciferase reporter linker was made and used to detect binding ADAs. Alemtuzumab immunoglobulin G Alexa Fluor 488 conjugate was used in a competitive binding cell-based assay to detect neutralizing ADAs. The assays were used to retrospectively screen, blinded, banked serum samples from people with MS (n = 32) who had received 3 or more cycles of alemtuzumab. find more Lymphocyte depletion was measured between baseline and about 1 month postinfusion. Results The number of individuals showing limited depletion of lymphocytes increased with the number of treatment cycles. Lack of depletion was also a poor prognostic feature for future disease activity. ADA responses were detected in 29/32 (90.6%) individuals. Neutralizing antibodies occurred before the development of limited depletion in 6/7 individuals (18.8% of the whole sample). Preinfusion, ADA levels predicted limited, postinfusion lymphocyte depletion. Conclusions Although ADAs to alemtuzumab have been portrayed as being of no clinical significance, alemtuzumab-specific antibodies appear to be clinically relevant for some individuals, although causation remains to be established. Monitoring of lymphocyte depletion and the antidrug response may be of practical value in patients requiring additional cycles of alemtuzumab. ADA detection may help to inform on retreatment or switching to another treatment.Objective To describe the clinical and radiologic neurologic characteristics of patients with cytotoxic T-lymphocyte antigen-4 (CTLA4) haploinsufficiency. Methods Three patients from 2 families had neurologic manifestations in the context of CTLA4 haploinsufficiency. Their clinical and MRI findings are presented. Results A 16-year-old boy with a previous diagnosis of combined immunodeficiency presented with severe recurrent episodes of headaches, motor deficit, and seizures associated with waxing and waning gadolinium-enhancing FLAIR cortical/juxtacortical hyperintensities. His sister, who also had combined immunodeficiency, had a brain MRI when she was aged 13 years due to recent headaches and transient right hemianopsia. It revealed a gadolinium-enhancing left occipital white matter hyperintensity. Another 49-year-old woman had progressive visual loss and cerebellar ataxia in the context of recurrent pulmonary infections. All 3 patients were found to have inherited CTLA4 haploinsufficiency. Patient 1's general condition and neurologic manifestations were completely controlled with abatacept (CTLA4-Ig). Conclusions These cases suggest that in addition to the variable clinical penetrance and wide spectrum of CTLA4 haploinsufficiency, its neurologic spectrum is broad, ranging from recurrent tumefactive lesions to progressive deficits including cerebellar ataxia and optic atrophy with leukoencephalopathy. These phenotypes must be recognized, and should lead to a complete immunologic workup, because potentially effective targeted immunotherapy exists.