Systemic gene therapy rescues retinal dysfunction and hearing loss in a model of Norrie disease

Deafness affects 5% of the world's population, yet there is a lack of treatments to prevent hearing loss due to genetic causes. Norrie disease is a recessive X‐linked disorder, caused by NDP gene mutation. It manifests as blindness at birth and progressive sensorineural hearing loss, leading to debilitating dual sensory deprivation. To develop a gene therapy, we used a Norrie disease mouse model (Ndp$^{tm1Wbrg}$), which recapitulates abnormal retinal vascularisation and progressive hearing loss. We delivered human NDP cDNA by intravenous injection of adeno‐associated viral vector (AAV)9 at neonatal, juvenile and young adult pathological stages and investigated its therapeutic effects on the retina and cochlea. Neonatal treatment prevented the death of the sensory cochlear hair cells and rescued cochlear disease biomarkers as demonstrated by RNAseq and physiological measurements of auditory function. Retinal vascularisation and electroretinograms were restored to normal by neonatal treatment. Delivery of NDP gene therapy after the onset of the degenerative inner ear disease also ameliorated the cochlear pathology, supporting the feasibility of a clinical treatment for progressive hearing loss in people with Norrie disease

Systemic gene therapy rescues retinal dysfunction and hearing loss in a model of Norrie disease

Deafness affects 5% of the world's population, yet there is a lack of treatments to prevent hearing loss due to genetic causes. Norrie disease is a recessive X-linked disorder, caused by NDP gene mutation. It manifests as blindness at birth and progressive sensorineural hearing loss, leading to debilitating dual sensory deprivation. To develop a gene therapy, we used a Norrie disease mouse model (Ndptm1Wbrg ), which recapitulates abnormal retinal vascularisation and progressive hearing loss. We delivered human NDP cDNA by intravenous injection of adeno-associated viral vector (AAV)9 at neonatal, juvenile and young adult pathological stages and investigated its therapeutic effects on the retina and cochlea. Neonatal treatment prevented the death of the sensory cochlear hair cells and rescued cochlear disease biomarkers as demonstrated by RNAseq and physiological measurements of auditory function. Retinal vascularisation and electroretinograms were restored to normal by neonatal treatment. Delivery of NDP gene therapy after the onset of the degenerative inner ear disease also ameliorated the cochlear pathology, supporting the feasibility of a clinical treatment for progressive hearing loss in people with Norrie disease

Tracking camera control in endoscopic dacryocystorhinostomy surgery

Objectives: Poor camera control during endoscopic dacryocystorhinostomy (EnDCR) surgery can cause inadequate visualisation of the anatomy and suboptimal surgical outcomes. This study investigates the feasibility of using computer vision tracking in EnDCR surgery as a potential formative feedback tool for the quality of endoscope control

Tracking camera control in endoscopic dacryocystorhinostomy surgery

Objectives: Poor camera control during endoscopic dacryocystorhinostomy (EnDCR) surgery can cause inadequate visualisation of the anatomy and suboptimal surgical outcomes. This study investigates the feasibility of using computer vision tracking in EnDCR surgery as a potential formative feedback tool for the quality of endoscope control

Gastric Heterotopic Pancreas Presenting as Abdominal Pain with Acute and Chronic Pancreatitis in the Resected Specimen

Heterotopic pancreas, also known as ectopic pancreas, is pancreatic tissue located outside the pancreatic parenchyma without vascular or ductal communication with the gland. Ectopic pancreas is rarely symptomatic, typically detected incidentally at surgery or autopsy. Eighty-five to 90% are in the upper GI tract, especially the gastric antrum. We report a 54-year-old man with symptomatic gastric heterotopic pancreas presenting as recurrent, initially undiagnosed, abdominal pain. Surgery revealed heterotopic pancreas including excretory ducts, acini, and islet cells. Evidence of acute pancreatitis was present, marked by inflammation and abscess formation. Chronic pancreatitis was diagnosed by fibrosis and dilated ducts containing proteinaceous material. Submucosal location with normal overlying mucosa on endoscopy increases risks of delayed or missed diagnosis. Complications include GI bleeding, acute or chronic pancreatitis, pancreatic necrosis, pseudocyst, gastric outlet obstruction, perforation, and, rarely, pancreatic carcinoma. This rare disorder mimics more common diseases. Low suspicion, nondiagnostic imaging or endoscopy contribute to frequent diagnostic delay

Man vs Machine: Software training for surgeons -an objective evaluation of human and computer-based training tools for cataract surgical performance

Both human and machine systems are currently used to train cataract surgeons but their performance has not been directly compared. This study aimed to address two queries. Firstly, the relationship between two cataract surgical feedback tools for training, one human and one software-based; and secondly, evaluate microscope control during phacoemulsification using the software. Videos of surgeons with varying experience were enrolled, and independently scored with the validated PhacoTrack motion capture software and the Objective Structured Assessment of Cataract Surgical Skill (OSACCS) human scoring tool. Microscope centration and path length travelled were also evaluated with the PhacoTrack software. Twenty-two videos correlated PhacoTrack motion capture with OSACCS. The PhacoTrack path length, number of movements and total procedure time were found to have high levels of Spearman's rank correlation of -0.6792619(p=0.001), - 0.6652021(p=0.002) and -0.771529(p=0001) respectively with OSACCS. The Bland-Altman plot found strong agreement within the +/-1.96 standard deviation. The path length measurements may overestimate /underestimate a surgeon's OSACSS score by 15 units, whilst for the log number of movements, an overestimate/underestimate of a surgeon's OSACSS score by 68 % was found. Sixty-two videos evaluated microscope camera control. Novice surgeons had their camera off the pupil centre at a far greater mean distance (SD) of 6.9(3.3) mm, compared with experts of 3.6 (1.6) mm (p<< 0.05). The expert surgeons maintained good microscope camera control and limited total pupil path length travelled 2512 (1031) mm compared with novices of 4049 (2709) mm (p<<0. 05). Good agreement between human and machine-quantified measurements of surgical skill exists. Our results demonstrate that surrogate markers for camera control are predictors of surgical skills

Man vs Machine: Software training for surgeons -an objective evaluation of human and computer-based training tools for cataract surgical performance

Both human and machine systems are currently used to train cataract surgeons but their performance has not been directly compared. This study aimed to address two queries. Firstly, the relationship between two cataract surgical feedback tools for training, one human and one software-based; and secondly, evaluate microscope control during phacoemulsification using the software. Videos of surgeons with varying experience were enrolled, and independently scored with the validated PhacoTrack motion capture software and the Objective Structured Assessment of Cataract Surgical Skill (OSACCS) human scoring tool. Microscope centration and path length travelled were also evaluated with the PhacoTrack software. Twenty-two videos correlated PhacoTrack motion capture with OSACCS. The PhacoTrack path length, number of movements and total procedure time were found to have high levels of Spearman's rank correlation of -0.6792619(p=0.001), - 0.6652021(p=0.002) and -0.771529(p=0001) respectively with OSACCS. The Bland-Altman plot found strong agreement within the +/-1.96 standard deviation. The path length measurements may overestimate /underestimate a surgeon's OSACSS score by 15 units, whilst for the log number of movements, an overestimate/underestimate of a surgeon's OSACSS score by 68 % was found. Sixty-two videos evaluated microscope camera control. Novice surgeons had their camera off the pupil centre at a far greater mean distance (SD) of 6.9(3.3) mm, compared with experts of 3.6 (1.6) mm (p<< 0.05). The expert surgeons maintained good microscope camera control and limited total pupil path length travelled 2512 (1031) mm compared with novices of 4049 (2709) mm (p<<0. 05). Good agreement between human and machine-quantified measurements of surgical skill exists. Our results demonstrate that surrogate markers for camera control are predictors of surgical skills