Uveitic glaucoma-like features in Yap conditional knockout mice.

Glaucoma is a multifactorial neurodegenerative disease characterized by the progressive and irreversible degeneration of the optic nerve and retinal ganglion cells. Despite medical advances aiming at slowing degeneration, around 40% of treated glaucomatous patients will undergo vision loss. It is thus of utmost importance to have a better understanding of the disease and to investigate more deeply its early causes. The transcriptional coactivator YAP, an important regulator of eye homeostasis, has recently drawn attention in the glaucoma research field. Here we show that Yap conditional knockout mice (Yap cKO), in which the deletion of Yap is induced in both Müller glia (i.e. the only retinal YAP-expressing cells) and the non-pigmented epithelial cells of the ciliary body, exhibit a breakdown of the aqueous-blood barrier, accompanied by a progressive collapse of the ciliary body. A similar phenotype is observed in human samples that we obtained from patients presenting with uveitis. In addition, aged Yap cKO mice harbor glaucoma-like features, including deregulation of key homeostatic Müller-derived proteins, retinal vascular defects, optic nerve degeneration and retinal ganglion cell death. Finally, transcriptomic analysis of Yap cKO retinas pointed to early-deregulated genes involved in extracellular matrix organization potentially underlying the onset and/or progression of the observed phenotype. Together, our findings reveal the essential role of YAP in preserving the integrity of the ciliary body and retinal ganglion cells, thereby preventing the onset of uveitic glaucoma-like features.

Seven-Year Follow-up of the RANZCO-Cambodian Ophthalmological Society Partnership CPD Program.

In 2013 the Royal Australian and New Zealand College of Ophthalmologists partnered with the Cambodian Ophthalmological Society (COS) to develop a continuing professional development program for COS using a college-college twinning model. The program was reviewed seven years after launch. No evidenceof a functioning CPD program was identified. Reasons may include lack of engagement by ophthalmologists and lack of COS resources. A planning checklistfor international CPD collaborations is discussed.

The International Council of Ophthalmology 360-degree assessment tool: development and validation.

BACKGROUND: The Accreditation Council for Graduate Medical Education and other organizations recommend 360-degree assessments for evaluation of interpersonal and communication skills, professional behaviours, and some aspects of patient care and system-based practice. No such tool has been developed for ophthalmology or received international content validation. OBJECTIVE: To develop a valid, internationally applicable, ophthalmology-specific 360-degree assessment tool. DESIGN: Exploratory study. METHODS: A literature review was conducted. Individual 360-degree evaluation items from several publications were catalogued and classified according to different groups of assessors. A panel of international authors reviewed the list and voted on items that were most appropriate for international use. The list was trimmed to reduce redundancy and to make it as brief as possible while still capturing the essential components for each category. A second panel of international ophthalmic educators reviewed the international applicability and appropriateness of this collated list; relevant comments and suggestions were incorporated. RESULTS: A tool for the evaluation of interpersonal and communication skills, professionalism, and system-based practice was developed. The tool has face and content validity. CONCLUSION: This assessment tool can be used internationally for giving formative feedback based on the opinions of the different groups of people who interact with residents.

Developing educators for continuing professional development.

Continuing professional development (CPD) is part of the medical education continuum, has been shown to produce improved physician practice and good patient outcomes, and is increasingly required for revalidation of medical licensure. CPD can be considered a discipline in its own right but is the least formally organized stage in medical education. CPD educators play a central role, but there has been remarkably little published work specifically describing CPD educators. This narrative review, using ophthalmology as exemplar medical specialty, describes trends affecting CPD educators and their sources, attributes, and development needs, mainly extrapolated from information regarding other medical educators in the medical education continuum spectrum. Future research needs are discussed.

Contact lenses as drug controlled release systems: a narrative review / As lentes de contacto como sistema de libertação controlada de fármacos: uma revisão narrativa

ABSTRACT Topically applied therapy is the most common way to treat ocular diseases, however given the anatomical and physiological constraints of the eye, frequent dosing is required with possible repercussions in terms of patient compliance. Beyond refractive error correction, contact lenses (CLs) have, in the last few decades emerged as a potential ophthalmic drug controlled release system (DCRS). Extensive research is underway to understand how to best modify CLs to increase residence time and bioavailability of drugs within therapeutic levels on the ocular surface.These devices may simultaneously correct ametropia and have a role in managing ophthalmic disorders that can hinder CL wear such as dry eye, glaucoma, ocular allergy and cornea infection and injury. In this narrative review the authors explain how the ocular surface structures determine drug diffusion in the eye and summarize the strategies to enhance drug residence time and bioavailability. They synthesize findings and clinical applications of drug soaked CLs as DCRS combined with delivery diffusion barriers, incorporation of functional monomers, ion related controlled release, molecular imprinting, nanoparticles and layering. The authors draw conclusions about the impact of these novel ophthalmic agents delivery systems in improving drug transport in the target tissue and patient compliance, in reducing systemic absorption and undesired side effects, and discuss future perspectives.

RESUMO A forma mais frequente de aplicação terapêutica em oftalmologia consiste na instilação de gotas oculares, mas dadas as limitações anatómicas e fisiológicas do olho, é necessária dosagem frequente com possível repercussão na adesão do paciente à terapêutica. Nas últimas décadas, as lentes de contacto (CLs) têm surgido como um potencial sistema de libertação controlada de fármacos na superfície ocular (DCRS) para correção do erro refrativo. Está em curso uma extensa investigação para entender a melhor forma de modificar as CLs, de modo a aumentar o tempo de residência e a biodisponibilidade do medicamento na superfície ocular dentro de níveis terapêuticos. Ao corrigirem a ametropia, estes dispositivos poderão simultaneamente desempenhar um papel na gestão de perturbações oftalmológicas, tais como a síndrome do olho seco, glaucoma, alergia ocular e infecção corneana, que podem comprometer o porte seguro e confortável das CLs. Nesta revisão narrativa, os autores explicam como as estruturas da superfície ocular determinam a difusão de fármacos no olho e sintetizam as estratégias para aumentar a permanência e biodisponibilidade dos mesmos. Em seguida, apresentam os resultados e as aplicações clínicas das CLs embebidas em fármacos, como DCRS, através da incorporação de barreiras de difusão, de monómeros funcionais, da liberação controlada por iões, da impressão molecular, de nanopartículas e pelo processo camada sobre camada. Os autores concluem avaliando o impacto destes novos sistemas de entrega de agentes farmacológicos ao melhorar o seu transporte no tecido alvo, reduzindo a sua absorção sistémica e os seus efeitos colaterais indesejáveis, e discutem perspectivas futuras.