European Glaucoma Society - A guide on surgical innovation for glaucoma.

PROLOGUE: Glaucoma surgery has been, for many decades now, dominated by the universal gold standard which is trabeculectomy augmented with antimetabolites. Tubes also came into the scene to complement what we use to call conventional or traditional glaucoma surgery. More recently we experienced a changing glaucoma surgery environment with the "advent" of what we have become used to calling Minimally Invasive Glaucoma Surgery (MIGS). What is the unmet need, what is the gap that these newcomers aim to fill? Hippocrates taught us "bring benefit, not harm" and new glaucoma techniques and devices aim to provide safer surgery compared to conventional surgery. For the patient, but also for the clinician, safety is important. Is more safety achieved with new glaucoma surgery and, if so, is it associated with better, equivalent, or worse efficacy? Is new glaucoma surgery intended to replace conventional surgery or to complement it as an 'add-on' to what clinicians already have in their hands to manage glaucoma? Which surgery should be chosen for which patient? What are the options? Are they equivalent? These are too many questions for the clinician! What are the answers to the questions? What is the evidence to support answers? Do we need more evidence and how can we produce high-quality evidence? This EGS Guide explores the changing and challenging glaucoma surgery environment aiming to provide answers to these questions. The EGS uses four words to highlight a continuum: Innovation, Education, Communication, and Implementation. Translating innovation to successful implementation is crucially important and requires high-quality evidence to ensure steps forward to a positive impact on health care when it comes to implementation. The vision of EGS is to provide the best possible well-being and minimal glaucomainduced visual disability in individuals with glaucoma within an affordable healthcare system. In this regard, assessing the changes in glaucoma surgery is a pivotal contribution to better care. As mentioned, this Guide aims to provide answers to the crucial questions above. However, every clinician is aware that answers may differ for every person: an individualised approach is needed. Therefore, there will be no uniform answer for all situations and all patients. Clinicians would need, through the clinical method and possibly some algorithm, to reach answers and decisions at the individual level. In this regard, evidence is needed to support clinicians to make decisions. Of key importance in this Guide is to provide an overview of existing evidence on glaucoma surgery and specifically on recent innovations and novel devices, but also to set standards in surgical design and reporting for future studies on glaucoma surgical innovation. Designing studies in surgery is particularly challenging because of many subtle variations inherent to surgery and hence multiple factors involved in the outcome, but even more because one needs to define carefully outcomes relevant to the research question but also to the future translation into clinical practice. In addition this Guide aims to provide clinical recommendations on novel procedures already in use when insufficient evidence exists. EGS has a long tradition to provide guidance to the ophthalmic community in Europe and worldwide through the EGS Guidelines (now in their 5th Edition). The EGS leadership recognized that the changing environment in glaucoma surgery currently represents a major challenge for the clinician, needing specific guidance. Therefore, the decision was made to issue this Guide on Glaucoma Surgery in order to help clinicians to make appropriate decisions for their patients and also to provide the framework and guidance for researchers to improve the quality of evidence in future studies. Ultimately this Guide will support better Glaucoma Care in accordance with EGS's Vision and Mission. Fotis Topouzis EGS President

New findings in ATP supply in rod outer segments: insights for retinopathies.

BACKGROUND INFORMATION: The rod outer segment (OS) is the specialised organelle where phototransduction takes place. Our previous proteomic and biochemical analyses on purified rod disks showed the functional expression of the respiratory chain complexes I-IV and F1 Fo -ATP synthase in OS disks, as well as active soluble tricarboxylic acid cycle enzymes. Here, we focussed our study on the whole OS that contains the cytosol and plasma membrane and disks as native flattened saccules, unlike spherical osmotically intact disks. RESULTS: OS were purified from bovine retinas and characterised for purity. Oximetry, ATP synthesis and cytochrome c oxidase (COX) assays were performed. The presence of COX and F1F0-ATP synthase (ATP synthase) was assessed by semi-quantitative Western blotting, immunofluorescence or confocal laser scanning microscopy on whole bovine retinas and bovine retinal sections and by immunogold transmission electron microscopy (TEM) of purified OS or bovine retinal sections. Both ATP synthase and COX are catalytically active in OS. These are able to consume oxygen (O2) in the presence of pyruvate and malate. CLSM analyses showed that rhodopsin autofluorescence and MitoTracker Deep Red 633 fluorescence co-localise on rod OS. Data are confirmed by co-localisation studies of ATP synthase with Rh in rod OS by immunofluorescence and TEM in bovine retinal sections. CONCLUSIONS: Our data confirm the expression and activity of COX and ATP synthase in OS, suggestive of the presence of an extra-mitochondrial oxidative phosphorylation in rod OS, meant to supply ATP for the visual transduction. In this respect, the membrane rich OS environment would be meant to absorb both light and O2. The ability of OS to manipulate O2 may shed light on the pathogenesis of many retinal degenerative diseases ascribed to oxidative stress, as well as on the efficacy of the treatment with dietary supplements, presently utilised as supporting therapies.