Intravitreal enzyme replacement for inherited retinal diseases.

Purpose Of Review: This paper provides an update on intravitreal (IVT) enzyme replacement therapy (ERT) in metabolic retinal diseases; particularly neuronal ceroid lipofuscinosis type 2 (CLN2) also known as Batten disease.

Recent Findings: ERT is being explored in CLN2 related Batten disease, a fatal neurodegenerative condition associated with retinopathy and blindness that is caused by the deficiency of lysosomal enzyme TPP1. Cerliponase alfa, a recombinant human tripeptidyl-peptidase1 (rhTPP1) administered by intraventricular infusions has been demonstrated to slow the rate of neurodegenerative decline but not retinopathy.

First in man study of intravitreal tripeptidyl peptidase 1 for CLN2 retinopathy.

Background/objectives: CLN2 Batten Disease is a fatal neurodegenerative condition of childhood associated with retinal dystrophy and blindness. Intracerebroventricular infusion of rhTPP1 greatly slows the rate of neurodegenerative decline but not retinopathy. Intravitreal rhTPP1 is known to slow retinal degeneration in a canine model of CLN2.

Evolution and Applications of Artificial Intelligence to Cataract Surgery.

Topic: Despite significant recent advances in artificial intelligence (AI) technology within several ophthalmic subspecialties, AI seems to be underutilized in the diagnosis and management of cataracts. In this article, we review AI technology that may soon become central to the cataract surgical pathway, from diagnosis to completion of surgery.

Clinical Relevance: This review describes recent advances in AI in the preoperative, intraoperative, and postoperative phase of cataract surgery, demonstrating its impact on the pathway and the surgical team.

Spectrum of Mutations in Resulting in Ocular Disease; a Systematic Review.

The inner retina is supplied by three intraretinal capillary plexi whereas the outer retina is supplied by the choroidal circulation: NDP is essential for normal intraretinal vascularisation. Pathogenic variants in NDP (Xp11.3) may result in either a severe retinal phenotype associated with hearing loss (Norrie Disease) or a moderate retinal phenotype (Familial Exudative Vitreoretinopathy, FEVR).

Automated feature-based grading and progression analysis of diabetic retinopathy.

Background: In diabetic retinopathy (DR) screening programmes feature-based grading guidelines are used by human graders. However, recent deep learning approaches have focused on end to end learning, based on labelled data at the whole image level. Most predictions from such software offer a direct grading output without information about the retinal features responsible for the grade.

Acute Angle Closure in Knobloch Syndrome.

We report cases of acute angle closure in 2 young highly myopic siblings with Knobloch syndrome. To our knowledge, this is the first report of acute angle closure in Knobloch syndrome. Both patients were homozygous for a likely pathogenic variant in COL18A1.

Evidence Based Prediction and Progression Monitoring on Retinal Images from Three Nations.

Purpose: The aim of this work is to demonstrate how a retinal image analysis system, DAPHNE, supports the optimization of diabetic retinopathy (DR) screening programs for grading color fundus photography.

Method: Retinal image sets, graded by trained and certified human graders, were acquired from Saudi Arabia, China, and Kenya. Each image was subsequently analyzed by the DAPHNE automated software.

Novel non-sense mutation in RP2 (c.843_844insT/p.Arg282fs) is associated with a severe phenotype of retinitis pigmentosa without evidence of primary retinal pigment epithelium involvement.

Retinitis pigmentosa (RP) relates to a heterogeneous group of rod-cone dystrophies of varying genetic aetiology. There is currently great interest in gene replacement therapy. Phenotyping is of particular importance because some RP genes are expressed ubiquitously and it is critically important to understand which retinal layer is primarily affected.

Report on the incidence of squamous cell carcinomas affecting the eyelids in England over a 15-year period (2000-2014).

Aims: The authors report on trends in the incidence of squamous cell carcinoma (SCC) affecting the eyelids in England over a 15-year period and identify associations between demographic factors and SCC risk.

Methods: The National Cancer Registration and Analysis Service identified all cases of eyelid SCC in England between 2000 and 2014. The crude and age-standardised rates of eyelid SCCs in England were calculated.

Scaling the punctum and canaliculus in patients undergoing punctoplasty surgery: A prospective cohort study.

Optical Coherence Tomography (OCT) is a safe and non-invasive method of high-resolution cross-sectional imaging of tissue microstructures using infrared radiation. This study investigates how the appearance of the punctum and proximal canaliculus differs pre- and post-operatively in patients undergoing punctoplasty surgery. Patients with symptomatic punctal stenosis warranting punctoplasty surgery were prospectively invited to enrol from a single centre.

An Automated Detection System for Microaneurysms That Is Effective across Different Racial Groups.

Patients without diabetic retinopathy (DR) represent a large proportion of the caseload seen by the DR screening service so reliable recognition of the absence of DR in digital fundus images (DFIs) is a prime focus of automated DR screening research. We investigate the use of a novel automated DR detection algorithm to assess retinal DFIs for absence of DR. A retrospective, masked, and controlled image-based study was undertaken.

Man versus Machine: Software Training for Surgeons-An Objective Evaluation of Human and Computer-Based Training Tools for Cataract Surgical Performance.

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, evaluating 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.

Feasibility of Human Factors Immersive Simulation Training in Ophthalmology: The London Pilot.

Importance: Human factors training can enhance teamworking and reduce error. It is used regularly in certain medical disciplines, but its use has not been established for ophthalmology to our knowledge.

Objective: To explore the feasibility of providing immersive simulation human factors training for ophthalmic surgical teams.

Shunt Testing In Vivo: Observational Study of Problems with Ventricular Catheter.

Most shunt obstructions happen at the inlet of the ventricular catheter. Three hundred six infusion studies from 2007 to 2011 were classified as having a typical pattern of either proximal occlusion or patency. We describe different patterns of shunt ventricular obstruction.

Optical coherence tomography imaging of the proximal lacrimal system.

Introduction: There are currently no routinely used imaging modalities for the proximal lacrimal system. Optical Coherence Tomography (OCT) is a safe and non-invasive method of high resolution cross-sectional imaging of tissue microstructures using infra-red radiation. In this study we investigate whether OCT may be used to image the punctum and proximal canaliculus.

Deferred use of bevacizumab for recurrent glioblastoma is not associated with diminished efficacy.

Background: The optimal timing to initiate bevacizumab (BV) therapy for recurrent glioblastoma (GBM) is currently unclear. To address this issue, we examined progression-free survival (PFS) and survival time (ST) in a large retrospective cohort of GBM patients treated with BV at different recurrences.

Methods: We identified 468 primary GBM patients who underwent biopsy or surgery followed by radiation therapy and temozolomide (RT/TMZ), and then received BV.

Antagonism at NMDA receptors, but not β-adrenergic receptors, disrupts the reconsolidation of pavlovian conditioned approach and instrumental transfer for ethanol-associated conditioned stimuli.

Rationale: Reconsolidation is the process by which memories require restabilisation following destabilisation at retrieval. Since even old, well-established memories become susceptible to disruption following reactivation, treatments based upon disrupting reconsolidation could provide a novel form of therapy for neuropsychiatric disorders based upon maladaptive memories, such as drug addiction. Pavlovian cues are potent precipitators of relapse to drug-seeking behaviour and influence instrumental drug seeking through at least three psychologically and neurobiologically distinct processes: conditioned reinforcement, conditioned approach (autoshaping) and conditioned motivation (pavlovian-instrumental transfer or PIT).