Beneficial effects on vision in patients undergoing retinal gene therapy for choroideremia.

Retinal gene therapy is increasingly recognized as a novel molecular intervention that has huge potential in treating common causes of blindness, the majority of which have a genetic aetiology. Choroideremia is a chronic X-linked retinal degeneration that was first described in 1872. It leads to progressive blindness due to deficiency of Rab-escort protein 1 (REP1).

Macular spatial distribution of preserved autofluorescence in patients with choroideremia.

Background/aims: To better understand the pattern of degeneration progression in cases with choroideremia.

Methods: A cohort of genotypically confirmed choroideremia cases who underwent optical coherence tomography (OCT) and fundus autofluorescence (FAF) imaging was studied. Using HEYEX review software, the foveal centre was marked on FAF images under guidance of corresponding OCT images, followed by application of an ETDRS grid.

Optimisation of dark adaptation time required for mesopic microperimetry.

Background: Macular Integrity Assessment (MAIA) microperimetry is increasingly used in clinical and research settings to assess point retinal sensitivity and fixation stability. Testing occurs under mesopic conditions, commonly after a period of dark adaptation. Our aim was to identify the minimum length of adaptation required to optimise microperimetry performance.

First-in-human study of the safety and viability of intraocular robotic surgery.

Microsurgery of the retina would be dramatically improved by instruments that offer supra-human precision. Here, we report the results of a first-in-human study of remotely controlled robot-assisted retinal surgery performed through a telemanipulation device. Specifically, 12 patients requiring dissection of the epiretinal or inner limiting membrane over the macula were randomly assigned to either undergo robot-assisted-surgery or manual surgery, under general anaesthesia.

Choroideremia Gene Therapy Phase 2 Clinical Trial: 24-Month Results.

Purpose: To report the final results of a phase 2 high-dose gene therapy clinical trial in choroideremia.

Methods: Design: Phase 2 clinical trial.

Participants: Six men (aged 32-72 years) with genetically-confirmed advanced choroideremia.

Re-evaluating the Utility of Stress Ulcer Prophylaxis in the Critically Ill Patient: A Clinical Scenario-Based Meta-Analysis.

Study Objective: Because recent studies have challenged the efficacy of stress ulcer prophylaxis (SUP) in the critically ill patient, our objective was to evaluate the efficacy of SUP with proton pump inhibitors (PPIs) or histamine -receptor antagonists (H RAs) against placebo, control, no therapy, or enteral nutrition alone in critically ill adults.

Design: Meta-analysis with trial sequential analysis (TSA) of 34 randomized controlled trials.

Patients: A total of 3220 critically ill adults who received PPIs or H RAs versus placebo, control, no therapy, or enteral nutrition.

Gene therapy for the treatment of X-linked retinitis pigmentosa.

Introduction: X-linked retinitis pigmentosa caused by mutations in the () gene is the most common form of recessive RP. The phenotype is characterised by its severity and rapid disease progression. Gene therapy using adeno-associated viral vectors is currently the most promising therapeutic approach.

Two-Year Results After AAV2-Mediated Gene Therapy for Choroideremia: The Alberta Experience.

Purpose: To assess the safety of a recombinant adeno-associated viral vector expressing REP1 (rAAV2.REP1) in choroideremia subjects.

Methods: Design: Phase I clinical trial.

Choroideremia: molecular mechanisms and development of AAV gene therapy.

Introduction: Choroideremia is an X-linked inherited retinal degeneration that causes blindness in afflicted males by middle age. The causative gene, CHM, plays a key role in intracellular trafficking pathways, and its disruption impairs cell homeostasis.

Areas Covered: The mechanism by which mutations in CHM cause choroideremia is still under debate.

CE: Original Research: The Efficacy and Safety of an RN-Driven Ketamine Protocol for Adjunctive Analgesia During Burn Wound Care.

Unlabelled: : Objective: Traditional analgesic regimens often fail to control the severe pain patients experience during burn wound care, and the drugs are frequently administered at doses that can cause oversedation and respiratory depression. Ketamine may be an ideal agent for adjunctive analgesia in such patients because of its unique mechanism of action and lack of association with respiratory depression. This study evaluated the efficacy and safety of a critical care RN-driven protocol for IV ketamine administration during burn wound care.

Olfactory Dysfunction in Patients With CNGB1-Associated Retinitis Pigmentosa.

Importance: Co-occurrence of retinitis pigmentosa (RP) and olfactory dysfunction may have a common genetic cause.

Objective: To report olfactory function and the retinal phenotype in patients with biallelic mutations in CNGB1, a gene coding for a signal transduction channel subunit expressed in rod photoreceptors and olfactory sensory neurons.

Design, Setting, And Participants: This case series was conducted from August 2015 through July 2017.

Slowly progressive retinitis pigmentosa caused by two novel mutations in the MAK gene.

Background: The growing number of clinical trials currently underway for inherited retinal diseases has highlighted the importance of achieving a molecular diagnosis for all new cases presenting to hospital eye services. The male germ cell-associated kinase (MAK) gene encodes a cilium-associated protein selectively expressed in the retina and testis, and has recently been implicated in autosomal recessive retinitis pigmentosa (RP). Whole exome sequencing has previously identified a homozygous Alu insertion in probands with recessive RP and nonsense and missense mutations have also been reported.

Half-Dose Photodynamic Therapy versus High-Density Subthreshold Micropulse Laser Treatment in Patients with Chronic Central Serous Chorioretinopathy: The PLACE Trial.

Purpose: To compare the anatomic and functional efficacy and safety of half-dose photodynamic therapy (PDT) versus high-density subthreshold micropulse laser (HSML) treatment in patients with chronic central serous chorioretinopathy (cCSC).

Design: Open-label, multicenter, randomized controlled clinical trial.

Participants: Patients with cCSC whose disease had to be confirmed by both clinical characteristics and findings on multimodal imaging.

Environmental concentrations of metformin exposure affect aggressive behavior in the Siamese fighting fish, Betta splendens.

Metformin, the medicine most commonly prescribed for treatment of Type II diabetes, is among the most abundant pharmaceuticals being introduced into the environment. Pharmaceuticals are increasingly found in wastewater and surface waters around the world, often due to incomplete metabolism in humans and subsequent excretion in human waste. Risk analyses and exposure studies have raised concerns about potential negative impacts of pharmaceuticals at current environmental levels.

Divergent humoral responses to 23-valent pneumococcal polysaccharide vaccine in critically-ill burn and neurosurgical patients.

Introduction: Critically ill hospitalized patients are at increased risk of infection so we assessed the immunogenicity of 23-valent pneumococcal polysaccharide vaccine (PPSV23) administered within six days of injury.

Methods: This prospective observational study compared the immunogenicity of PPSV23 among critically ill burn and neurosurgical patients at a tertiary, academic medical center. Patients received PPSV23 vaccination within six days of ICU admission per standard of care.

The Biological Activity of AAV Vectors for Choroideremia Gene Therapy Can Be Measured by Prenylation of RAB6A.

Choroideremia (CHM) is a rare, X-linked recessive retinal dystrophy caused by mutations in the gene. is ubiquitously expressed in human cells and encodes Rab escort protein 1 (REP1). REP1 plays a key role in intracellular trafficking through the prenylation of Rab GTPases, a reaction that can be reproduced .

Differential roles for cryptochromes in the mammalian retinal clock.

Cryptochromes 1 and 2 (CRY1/2) are key components of the negative limb of the mammalian circadian clock. Like many peripheral tissues, Cry1 and -2 are expressed in the retina, where they are thought to play a role in regulating rhythmic physiology. However, studies differ in consensus as to their localization and function, and CRY1 immunostaining has not been convincingly demonstrated in the retina.

VASCULAR ALTERATIONS REVEALED WITH OPTICAL COHERENCE TOMOGRAPHY ANGIOGRAPHY IN PATIENTS WITH CHOROIDEREMIA.

Purpose: Choroideremia is a rare degenerative retinal disease that causes incurable blindness. It occurs as a result of the deficiency of the X-linked CHM gene, which encodes the Rab escort protein 1 (REP1). Gene therapy has been developed to treat CHM using adeno-associated viral vectors and is currently undergoing clinical trials.

Implantation, removal and replacement of subretinal electronic implants for restoration of vision in patients with retinitis pigmentosa.

Purpose Of Review: The purpose of this review is to provide an update on the efforts to restore vision through subretinal implants in patients with degenerative retinal diseases. In addition to the current technique and its latest improvements, it will focus on the surgical technique of implantation as well as explantation and reimplantation.

Recent Findings: The durability of the current subretinal implant RETINA IMPLANT Alpha AMS has increased substantially compared with the predecessor model RETINA IMPLANT Alpha IMS.

Emerging In Vitro 3D Tumour Models in Nanoparticle-Based Gene and Drug Therapy.

3D models are emerging as valuable tools for personalised nanoparticle-based cancer treatments. 3D models represent in vivo cancers more realistically than 2D patterns that are grown in Petri dishes. However, creating a 3D cancer model that mimics the complexity and heterogeneity of cancers in vivo remains difficult.

Real-world refractive outcomes of toric intraocular lens implantation in a United Kingdom National Health Service setting.

Background: With increasing availability of toric intraocular lenses (IOL) for cataract surgery, real-world refractive outcome data is needed to aid the counselling of patients regarding lens choice. We aim to assess the outcomes of toric intraocular lens use in the non-specialist environment of a typical United Kingdom NHS cataract service.

Methods: A retrospective cohort study conducted at the Oxford Eye Hospital, Oxford University Hospitals NHS Foundation Trust, UK.

Misdiagnosis of X-linked retinitis pigmentosa in a choroideremia patient with heavily pigmented fundi.

Inherited retinal diseases are thought to be the leading cause of sight loss in the working age population. Mutations found in the RPGR and CHM genes cause retinitis pigmentosa (RP) and choroideremia, respectively. In the first instance, an X-linked family history of visual field loss commonly raises the suspicion of one of these two genes.