Eye movements and reading in glaucoma: observations on patients with advanced visual field loss

Purpose To investigate the relationship between reading speed and eye movements in patients with advanced glaucomatous visual field (VF) defects and age-similar visually healthy people. Methods Eighteen patients with advanced bilateral VF defects (mean age: 71, standard deviation [SD]: 7 years) and 39 controls (mean age: 67, SD: 8 years) had reading speed measured using short passages of text on a computer set-up incorporating eye tracking. Scanpaths were plotted and analysed from these experiments to derive measures of ‘perceptual span’ (total number of letters read per number of saccades) and ‘text saturation’ (the distance between the first and last fixation on lines of text). Another eye movement measure, termed ‘saccadic frequency’ (total number of saccades made to read a single word), was derived from a separate lexical decision task, where words were presented in isolation. Results Significant linear association was demonstrated between perceptual span and reading speed in patients (R2=0.42) and controls (R2=0.56). Linear association between saccadic frequency during the LDT and reading speed was also found in patients (R2=0.42), but not in controls (R2=0.02). Patients also exhibited greater average text saturation than controls (P=0.004). Conclusion Some, but not all, patients with advanced VF defects read slower than controls using short text passages. Differences in eye movement behaviour may partly account for this variability in patients. These patients were shown to saturate lines of text more during reading, which may explain previously-reported difficulties with sustained reading

Eye movements during visual search in patients with glaucoma

Background: Glaucoma has been shown to lead to disability in many daily tasks including visual search. This study aims to determine whether the saccadic eye movements of people with glaucoma differ from those of people with normal vision, and to investigate the association between eye movements and impaired visual search. Methods: Forty patients (mean age: 67 [SD: 9] years) with a range of glaucomatous visual field (VF) defects in both eyes (mean best eye mean deviation [MD]: –5.9 (SD: 5.4) dB) and 40 age-related people with normal vision (mean age: 66 [SD: 10] years) were timed as they searched for a series of target objects in computer displayed photographs of real world scenes. Eye movements were simultaneously recorded using an eye tracker. Average number of saccades per second, average saccade amplitude and average search duration across trials were recorded. These response variables were compared with measurements of VF and contrast sensitivity. Results: The average rate of saccades made by the patient group was significantly smaller than the number made by controls during the visual search task (P = 0.02; mean reduction of 5.6% (95% CI: 0.1 to 10.4%). There was no difference in average saccade amplitude between the patients and the controls (P = 0.09). Average number of saccades was weakly correlated with aspects of visual function, with patients with worse contrast sensitivity (PR logCS; Spearman’s rho: 0.42; P = 0.006) and more severe VF defects (best eye MD; Spearman’s rho: 0.34; P = 0.037) tending to make less eye movements during the task. Average detection time in the search task was associated with the average rate of saccades in the patient group (Spearman’s rho = −0.65; P < 0.001) but this was not apparent in the controls. Conclusions: The average rate of saccades made during visual search by this group of patients was fewer than those made by people with normal vision of a similar average age. There was wide variability in saccade rate in the patients but there was an association between an increase in this measure and better performance in the search task. Assessment of eye movements in individuals with glaucoma might provide insight into the functional deficits of the disease

Targeting medication non-adherence behavior in selected autoimmune diseases: a systematic approach to digital health program development

Background 29 autoimmune diseases, including Rheumatoid Arthritis, gout, Crohn’s Disease, and Systematic Lupus Erythematosus affect 7.6-9.4% of the population. While effective therapy is available, many patients do not follow treatment or use medications as directed. Digital health and Web 2.0 interventions have demonstrated much promise in increasing medication and treatment adherence, but to date many Internet tools have proven disappointing. In fact, most digital interventions continue to suffer from high attrition in patient populations, are burdensome for healthcare professionals, and have relatively short life spans. Objective Digital health tools have traditionally centered on the transformation of existing interventions (such as diaries, trackers, stage-based or cognitive behavioral therapy programs, coupons, or symptom checklists) to electronic format. Advanced digital interventions have also incorporated attributes of Web 2.0 such as social networking, text messaging, and the use of video. Despite these efforts, there has not been little measurable impact in non-adherence for illnesses that require medical interventions, and research must look to other strategies or development methodologies. As a first step in investigating the feasibility of developing such a tool, the objective of the current study is to systematically rate factors of non-adherence that have been reported in past research studies. Methods Grounded Theory, recognized as a rigorous method that facilitates the emergence of new themes through systematic analysis, data collection and coding, was used to analyze quantitative, qualitative and mixed method studies addressing the following autoimmune diseases: Rheumatoid Arthritis, gout, Crohn’s Disease, Systematic Lupus Erythematosus, and inflammatory bowel disease. Studies were only included if they contained primary data addressing the relationship with non-adherence. Results Out of the 27 studies, four non-modifiable and 11 modifiable risk factors were discovered. Over one third of articles identified the following risk factors as common contributors to medication non-adherence (percent of studies reporting): patients not understanding treatment (44%), side effects (41%), age (37%), dose regimen (33%), and perceived medication ineffectiveness (33%). An unanticipated finding that emerged was the need for risk stratification tools (81%) with patient-centric approaches (67%). Conclusions This study systematically identifies and categorizes medication non-adherence risk factors in select autoimmune diseases. Findings indicate that patients understanding of their disease and the role of medication are paramount. An unexpected finding was that the majority of research articles called for the creation of tailored, patient-centric interventions that dispel personal misconceptions about disease, pharmacotherapy, and how the body responds to treatment. To our knowledge, these interventions do not yet exist in digital format. Rather than adopting a systems level approach, digital health programs should focus on cohorts with heterogeneous needs, and develop tailored interventions based on individual non-adherence patterns

Post-transcriptional control of tumor cell autonomous metastatic potential by the CCR4-NOT deadenylase CNOT7

Accumulating evidence supports the role of an aberrant transcriptome as a driver of metastatic potential. Deadenylation is a general regulatory node for post-transcriptional control by microRNAs and other determinants of RNA stability. Previously, we demonstrated that the CCR4-NOT scaffold component Cnot2 is an inherited metastasis susceptibility gene. In this study, using orthotopic metastasis assays and genetically engineered mouse models, we show that one of the enzymatic subunits of the CCR4-NOT complex, Cnot7, is also a metastasis modifying gene. We demonstrate that higher expression of Cnot7 drives tumor cell autonomous metastatic potential, which requires its deadenylase activity. Furthermore, metastasis promotion by CNOT7 is dependent on interaction with CNOT1 and TOB1. CNOT7 ribonucleoprotein-immunoprecipitation (RIP) and integrated transcriptome wide analyses reveal that CNOT7-regulated transcripts are enriched for a tripartite 3’UTR motif bound by RNA-binding proteins known to complex with CNOT7, TOB1, and CNOT1. Collectively, our data support a model of CNOT7, TOB1, CNOT1, and RNA-binding proteins collectively exerting post-transcriptional control on a metastasis suppressive transcriptional program to drive tumor cell metastasis

Advanced small cell carcinoma of the uterine cervix treated by neoadjuvant chemotherapy with irinotecan and cisplatin followed by radical surgery

Small cell carcinoma of the uterine cervix is a rare form of cervical cancer characterized by extreme aggressiveness and poor prognosis because of its rapid growth, frequent distant metastases, and resistance to conventional treatment modalities. We report here a case of advanced-stage small cell carcinoma of the uterine cervix treated by neoadjuvant chemotherapy, followed by radical surgery, resulting in locoregional disease control. A 39-year-old Japanese woman was diagnosed as having stage IIIb small cell carcinoma of the uterine cervix. She was treated by neoadjuvant chemotherapy with irinotecan/cisplatin, followed by extended radical hysterectomy with pelvic and paraaortic lymphadenectomy. The patient was further treated by adjuvant chemotherapy with irinotecan/cisplatin. Intrapelvic recurrence has not been detected throughout the postoperative course. However, the patient died with distant metastases of the disease, 27 months following the initial treatment. It has been suggested that neoadjuvant chemotherapy therapy followed by radical surgery is a treatment option for advanced-stage small cell carcinoma of the uterine cervix for the locoregional disease control. Further studies are necessary to obtain information regarding multimodal treatment including sequence, duration, frequency, and type of effective chemotherapy agents to be used in the treatment of small cell carcinoma of the uterine cervix

Mechanical properties of double-layer and graded composite coatings of YSZ obtained by atmospheric plasma spraying

Double-layer and graded composite coatings of yttria-stabilized zirconia were sprayed on metallic substrates by atmospheric plasma spray. The coating architecture was built up by combining two different feedstocks: one micro- and one nanostructured. Microstructural features and mechanical properties (hardness and elastic modulus) of the coatings were determined by FE-SEM microscopy and nanoindentation technique, respectively. Additional adherence and scratch tests were carried out in order to assess the failure mechanisms occurring between the layers comprising the composites. Microstructural inspection of the coatings confirms the two-zone microstructure. This bimodal microstructure which is exclusive of the layer obtained from the nanostructured feedstock negatively affects the mechanical properties of the whole composite. Nanoindentation tests suitably reproduce the evolution of mechanical properties through coatings thickness on the basis of the position and/or amount of nanostructured feedstock used in the depositing layer. Adhesion and scratch tests show the negative effect on the coating adhesion of layer obtained from the nanostructured feedstock when this layer is deposited on the bond coat. Thus, the poor integrity of this layer results in lower normal stresses required to delaminate the coating in the adhesion test as well as minor critical load registered by using the scratch test.This work has been supported by the Spanish Ministry of Science and Innovation (Project MAT2012-38364-C03) and co-funded by ERDF (European Regional Development Funds).Carpio-Cobo, P.; Rayón Encinas, E.; Salvador Moya, MD.; Lusvarghi, L.; Sanchez, E. (2016). Mechanical properties of double-layer and graded composite coatings of YSZ obtained by atmospheric plasma spraying. Journal of Thermal Spray Technology. 25(4):778-787. https://doi.org/10.1007/s11666-016-0390-zS778787254Y.S. Tian, C.Z. Chen, D.Y. Wang, and J.I. Quianmao, Recent Developments in Zirconia Thermal Barrier Coatings, Surf. Rev. Lett., 2005, 12, p 369-378S. Sampath, U. Schulz, M.O. Jarligo, and S. Kuroda, Processing Science of Advanced Thermal-Barrier Systems, MRS Bull., 2012, 37(10), p 903-910D.R. Clarke, M. Oeschsner, and N.P. Padture, Thermal-Barrier Coatings for More Efficient Gas-Turbine Engines, MRS Bull., 2012, 37(10), p 891-898A. Feuersein, J. Knapp, T. Taylor, A. Ashary, A. Bolcavage, and N. Hitchman, Technical and Economical Aspects of Current Thermal Barrier Coating Systems for Gas Turbine Engines by Thermal Spray and EBPVD: A Review, J. Therm. Spray Technol., 2008, 17(2), p 199-213R.S. Lima and B.R. Marple, Thermal Spray Coatings Engineered from Nanostructured Ceramic Agglomerated Powders for Structural, Thermal Barrier and Biomedical Applications: A Review, J. Therm. Spray Technol., 2007, 16(1), p 40-63P. Fauchais, G. Montavon, R.S. Lima, and B.R. Marple, Engineering a New Class of Thermal Spray Nano-based Microstructures from Agglomerated Nanostructured Particles, Suspensions and Solutions: An Invited Review, J. Phys. D Appl. Phys., 2011, 44(9), p 093001P. Carpio, Q. Blochet, B. Pateyron, L. Pawlowski, M.D. Salvador, A. Borrell, and E. Sánchez, Correlation of Thermal Conductivity of Suspension Plasma Sprayed Yttira Stabilized Zirconia Coatings with some Microstructural Effects, Mater. Lett., 2013, 107, p 370-373R. Vassen, A. Stuke, and D. Stöver, Recent Developments in the Field of Thermal Barrier Coatings, J. Therm. Spray Technol., 2009, 18(2), p 181-186H. Dai, X. Zhong, J. Li, Y. Zhang, J. Meng, and X. Cao, Thermal Stability of Double-Ceramic-Layer Thermal Barrier Coatings with Various Coating Thickness, Mater. Sci. Eng. A—Struct., 2006, 433(1), p 1–7V. Viswanathan, G. Dwivedi, and S. Sampath, Multimaterial Thermal Barrier Coating Systems: Design, Synthesis, and Performance Assessment, J. Am. Ceram. Soc., 2015, 98(6), p 1769-1777M. Saremi and Z. Valefi, Thermal and Mechanical Properties of Nano-YSZ-Alumina Functionally Graded Coatings Deposited by Nano-agglomerated Powder Plasma Spraying, Ceram. Int., 2014, 40(8), p 13453-13459A. Portinham, V. Teixeira, J. Carneiro, J. Martins, M.F. Costa, R. Vassen, and D. Stoever, Characterization of Thermal Barrier Coatings with a Gradient Porosity, Surf. Coat. Technol., 2005, 195(2), p 245-251P. Carpio, E. Bannier, M.D. Salvador, R. Benavente, and E. Sánchez, Multilayer and Particle Size-Graded YSZ Coatings Obtained by Plasma Spraying of Micro- and Nanostructured Feedstocks, J. Therm. Spray Technol., 2014, 23(8), p 1362-1372S. Nath, I. Manna, and J.D. Majumdar, Nanomechanical Behavior of Yttria Stabilized Zirconia (YSZ) Based Thermal Barrier Coating, Ceram. Int., 2015, 41(4), p 5247-5256P. Carpio, E. Rayón, L. Pawlowski, A. Cattini, R. Benavente, E. Bannier, M.D. Salvador, and E. Sánchez, Microstructure and Indentation Mechanical Properties of YSZ Nanostructured Coatings Obtained by Suspension Plasma Spraying, Surf. Coat. Technol., 2013, 220, p 237-243H.B. Guo, H. Murakami, and S. Kuroda, Effect of Hollow Spherical Powder Size Distribution on Porosity and Segmentation Cracks in Thermal Barrier Coatings, J. Am. Ceram. Soc., 2006, 89(12), p 3797-3804R.S. Lima, A. Kucuk, and C.C. Berndt, Integrity of Nanostructured Partially Stabilized Zirconia After Plasma Spray Processing, Mater. Sci. Eng. A, 2001, 313(1), p 75-82E. Rayón, V. Bonache, M.D. Salvador, and E. Sánchez, Hardness and Young’s Modulus Distributions in Atmospheric Plasma Sprayed WC-Co Coatings Using Nanoindentation, Surf. Coat. Technol., 2011, 205(17), p 4192-4197J.A. Wollmershauser, B.N. Feigelson, E.P. Gorzkowski, C.T. Ellis, R. Goswami, S.B. Qadri, J.G. Tischler, F.J. Kub, and R.K. Everett, An Extend Hardness Limit in Bulk Nanoceramics, Acta Mater., 2014, 69, p 9-16L. Wang, Y. Wang, X.G. Sun, J.Q. He, Z.Y. Pan, and C.H. Wang, Microstructure and Indentation Mechanical Properties of Plasma Sprayed Nano-Bimodal and Conventional ZrO2-8 wt% Y2O3 Thermal Barrier Coatings, Vacuum, 2012, 86(8), p 1174-1185G.S. Barroso, W. Krenkel, and G. Motz, Low Thermal Conductivity Coating System for Application up to 1000 °C by Simple PDC Processing with Active and Passive Fillers, J. Eur. Ceram. Soc., 2015, 35(12), p 3339-3348R. Ghasemi, R. Shoja-Razavi, R. Mozafarinia, H. Jamali, M. Hajizadh-Oghaz, and R. Ahmadi-Pidani, The Influence of Laser Treatment on Hot Corrosion Behavior of Plasma-Sprayed Nanostructured Yttria Stabilized Zirconia Thermal Barrier Coatings, J. Eur. Ceram. Soc., 2014, 34(8), p 2013-2021E. Rayón, V. Bonache, M.D. Salvador, E. Bannier, E. Sánchez, A. Denoirjean, and H. Ageorges, Nanoindentation Study of the Mechanical and Damage Behaviour of Suspension Plasma Sprayed TiO2 Coatings, Surf. Coat. Technol., 2012, 206(10), p 2655-2660J.J. Roa, E. Jiménez-Piqué, R. Martínez, G. Ramírez, J.M. Tarragó, R. Rodríguez, and L. Llanes, Contact Damage and Fracture Micromechanisms of Multilayered TiN/CrN Coatings at Micro- and Nano-length Scales, Thin Solid Films, 2014, 571(2), p 308-31

DAZL Relieves miRNA-Mediated Repression of Germline mRNAs by Controlling Poly(A) Tail Length in Zebrafish

BACKGROUND:During zebrafish embryogenesis, microRNA (miRNA) miR-430 contributes to restrict Nanos1 and TDRD7 to primordial germ cells (PGCs) by inducing mRNA deadenylation, mRNA degradation, and translational repression of nanos1 and tdrd7 mRNAs in somatic cells. The nanos1 and tdrd7 3'UTRs include cis-acting elements that allow activity in PGCs even in the presence of miRNA-mediated repression. METHODOLOGY/PRINCIPAL FINDINGS:Using a GFP reporter mRNA that was fused with tdrd7 3'UTR, we show that a germline-specific RNA-binding protein DAZ-like (DAZL) can relieve the miR-430-mediated repression of tdrd7 mRNA by inducing poly(A) tail elongation (polyadenylation) in zebrafish. We also show that DAZL enhances protein synthesis via the 3'UTR of dazl mRNA, another germline mRNA targeted by miR-430. CONCLUSIONS/SIGNIFICANCE:Our present study indicated that DAZL acts as an "anti-miRNA factor" during vertebrate germ cell development. Our data also suggested that miRNA-mediated regulation can be modulated on specific target mRNAs through the poly(A) tail control

Fabrication of Worm-Like Nanorods and Ultrafine Nanospheres of Silver Via Solid-State Photochemical Decomposition

Worm-like nanorods and nanospheres of silver have been synthesized by photochemical decomposition of silver oxalate in water by UV irradiation in the presence of CTAB and PVP, respectively. No external seeds have been employed for the synthesis of Ag nanorods. The synthesized Ag colloids have been characterized by UV-visible spectra, powder XRD, HRTEM, and selected area electron diffraction (SAED). Ag nanospheres of average size around 2 nm have been obtained in the presence of PVP. XRD and TEM analyses revealed that top and basal planes of nanorods are bound with {111} facets. Williamson–Hall plot has revealed the presence of defects in the Ag nanospheres and nanorods. Formation of defective Ag nanocrystals is attributed to the heating effect of UV-visible irradiation

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 Contributors All contributors have provided the appropriate COI visible in detail at www.eugs.org/pages/guidesurgical/ This manuscript reflects the work and thoughts of the list of individuals recognized above, but importantly, it reflects EGS views on the subject matter. Its strength originates from a team effort, where a cohesive group of authors and reviewers have worked towards a common goal and now stand behind the text in its entirety. The EGS nevertheless wishes to thank the following external contributors for their additional expertise, which was particularly valuable to the development of this Surgical Guide: Amanda Bicket, Jonathan Bonnar, Catey Bunce, Kuan Hu, Sheffinea Koshy, Jimmy Le, Tianjing Li, Francisco Otarola, Riaz Qureshi, Anupa Shah, Richard Stead and Marta Toth. A particular appreciation goes to Ian Saldanha for drafting the introductory overview on Core Outcomes onchapter 8. Finally, EGS would like to acknowledge Augusto Azuara Blanco, Chair of the Scientific and Guidelines Committee, for his expertise and advisory role throughout the entire process. Luis Abegao Pinto, Centro Hospitalar Universitário Lisboa Norte Editor Gordana Sunaric Mégevand, Eye Research Centre, Adolphe de Rothschild Hospital, Geneva, Switzerland and Centre Ophtalmologique de Florissant, Geneva, Switzerland Editor Ingeborg Stalmans, Ingeborg Stalmans, University Hospitals UZ Leuven, Catholic University KU Leuven Editor Luis Abegao Pinto, Centro Hospitalar Universitário Lisboa Norte Hana Abouzeid, Clinical Eye Research Centre Adolph de Rothschild, AZ Ophthalmologie Eleftherios Anastasopoulos, Aristotle University of Thessaloniki, Papageorgiou Hospital, Thessaloniki, Greece Augusto Azuara Blanco, Centre for Public Health, Queen's University Belfast Luca Bagnasco, Clinica Oculistica, DiNOGMI University of Genoa Alessandro Bagnis, Clinica Oculistica, IRCCS Ospedale Policlinico San Martino Joao Barbosa Breda, Faculty of Medicine of the University of Porto, Porto, Portugal. Centro Hospitalar e Universitário São João, Porto, Portugal. KULeuven, Belgium Keith Barton, University College London, Moorfields Eye Hospital Amanda Bicket, University of Michigan (Ann Arbor, MI, USA) Jonathan Bonnar, Belfast Health and Social Care Trust Chiara Bonzano, Clinica Oculistica, IRCCS Ospedale Policlinico San Martino Rupert Bourne, Cambridge University Hospital Alain Bron, University Hospital Dijon Catey Bunce, King's College London Carlo Cutolo, Clinica Oculistica, DiNOGMI University of Genoa, and IRCCS Ospedale Policlinico San Martino Barbara Cvenkel, University Medical Centre Ljubljana Faculty of Medicine, University of Ljubljana Antonio Fea, University of Turin Theodoros Filippopoulos, Athens Vision Eye Institute Panayiota Founti, Moorfields Eye Hospital NHS Foundation Trust Stefano Gandolfi, U.O.C. Oculistica, University of Parma Julian Garcia Feijoo, Hospital Clinico San Carlos, Universidad Complutense, Madrid Gerhard Garhoefer, Medical University of Vienna, Austria David Garway Heath, Moorfields Eye Hospital NHS Foundation Trust, London. Institute of Ophthalmology, University College London. Gus Gazzard, Moorfields Eye Hospital NHS Foundation Trust, London. Institute of Ophthalmology, University College London. Stylianos Georgoulas, Addenbrooke's, Cambridge University Hospitals Dimitrios Giannoulis, Aristotle University of Thessaloniki, AHEPA Hospital, Thessaloniki, Greece Franz Grehn, University Hospitals Wuerzburg Kuang Hu, NIHR Moorfields Biomedical Research Centre, London - Institute of Ophthalmology - University College London Michele Iester, Clinica Oculistica, DiNOGMI University of Genoa, and IRCCS Ospedale Policlinico San Martino Hari Jayaram, Moorfields Eye Hospital Gauti Johannesson, Umea University Stylianos Kandarakis, National and Kapodistrian University of Athens, G. Gennimatas Hospital, Athens, Greece. Efthymios Karmiris, Hellenic Air Force General Hospital National and Kapodistrian University of Athens, G. Gennimatas Hospital, Athens Alan Kastner, Clinica Oftalmologica Pasteur, Santiago, Chile Andreas Katsanos, University of Ioannina, Greece Christina Keskini, Aristotle University of Thessaloniki, AHEPA Hospital Anthony Khawaja, Moorfields Eye Hospital and UCL Institute of Ophthalmology Anthony King, Nottingham University Hospitals NHS Trust James Kirwan, Portsmouth hospitals university NHS trust Miriam Kolko, University of Copenhagen, Copenhagen University Hospital Rigshospitalet Sheffinea Koshy, University of Galway Antoine Labbe, Quinze-Vingts ­ National Ophthalmology Hospital Jimmy Le, Johns Hopkins Bloomberg School of Public Health, Baltimore Sanna Leinonen, Tays Eye Centre, Tampere University Hospital Sophie Lemmens, University Hospitals UZ Leuven Tianjing Li, School of Medicine, University of Colorado Anschutz Medical Campus Giorgio Marchini, Clinica Oculistica, University Hospital, AOUI, Verona, Italy José Martinez De La Casa, Hospital Clinico San Carlos. Universidad Complutense Andy McNaught, Gloucestershire Eye Unit Frances Meier Gibbons, Eye Center Rapperswil, Switzerland Karl Mercieca, University Hospitals Eye Clinic, Bonn, Germany Manuele Michelessi, IRCCS - Fondazione Bietti Stefano Miglior, University of Milan Bicocca Eleni Nikita, Moorfields Eye Hospital NHS Foundation Trust Francesco Oddone, IRCCS ­ Fondazione Bietti Francisco Otarola, Universidad de La Frontera Marta Pazos, Institute of Ophthalmology. Hospital Clínic Barcelona. Researcher at Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS) Norbert Pfeiffer, Mainz University Medical Center Verena Prokosh, University of Cologne, Center for ophthalmology. Riaz Qureshi, Johns Hopkins Medicine, Baltimore Gokulan Ratnarajan, Queen Victoria Hospital, East Grinstead, UK Herbert Reitsamer, University Clinic Salzburg / SALK Luca Rossetti, University of Milan, ASST Santi Paolo e Carlo, Milano, Italy Ian Saldanha, Johns Hopkins Bloomberg School of Public Health, Baltimore Cedric Schweitzer, CHU Bordeaux, Univ. Bordeaux, ISPED, INSERM, U1219 - Bordeaux Population Health Research Centre, France Andrew Scott, Moorfields Eye Hospital London Riccardo Scotto, Clinica Oculistica, DiNOGMI University of Genoa Anupa Shah, Queen's University Belfast George Spaeth, Wills Eye Hospital/Sidney Kimmel Medical College/Thomas Jefferson University Richard Stead, Nottingham University Hospitals NHS Trust Francesco Stringa, University Hospital Southampton NHS FT Gordana Sunaric, Centre Ophtalmologique de Florissant, Centre de Recherche Clinique en Ophtalmologie Mémorial Adolphe de Rothschild Andrew Tatham, University of Edinburgh, Princess Alexandra Eye Pavilion Mark Toeteberg, University Hospital Zurich Fotis Topouzis, Aristotle University of Thessaloniki, AHEPA Hospital Marta Toth, Moorfields Eye Hospital NHS Foundation Trust Carlo Traverso, Clinica Oculistica, DiNOGMI University of Genoa, and IRCCS Ospedale Policlinico San Martino Anja Tuulonen, Tays Eye Centre, Tampere University Hospital Clemens Vass, Medical University of Vienna Ananth Viswanathan, Moorfields Eye Hospital NHSFT and UCL Institute of Ophthalmology Richard Wormald, UCL Institute of Ophthalmology External Reviewers American Glaucoma Society Asia-Pacific Glaucoma Society Middle East Africa Glaucoma Society World Glaucoma Society www.eugs.org/pages/externalreviewers The team of Clinica Oculistica of the University of Genoa for medical editing and illustration Luca Bagnasco Alessandro Bagnis Chiara Bonzano Carlo Cutolo Michele Iester Riccardo Scotto Carlo Travers