Trabecular Meshwork Gene Expression after Selective Laser Trabeculoplasty

BACKGROUND: Trabecular meshwork and Schlemm's canal are the tissues appointed to modulate the aqueous humour outflow from the anterior chamber. The impairment of their functions drives to an intraocular pressure increase. The selective laser trabeculoplasty is a laser therapy of the trabecular meshwork able to decrease intraocular pressure. The exact response mechanism to this treatment has not been clearly delineated yet. The herein presented study is aimed at studying the gene expression changes induced in trabecular meshwork cells by selective laser trabeculoplasty (SLT) in order to better understand the mechanisms subtending its efficacy. METHODOLOGY/PRINCIPAL FINDINGS: Primary human trabecular meshwork cells cultured in fibroblast medium underwent selective laser trabeculoplasty treatment. RNA was extracted from a pool of cells 30 minutes after treatment while the remaining cells were further cultured and RNA was extracted respectively 2 and 6 hours after treatment. Control cells stored in incubator in absence of SLT treatment were used as reference samples. Gene expression was evaluated by hybridization on miRNA-microarray and laser scanner analysis. Scanning electron microscopic examination was performed on 2 Trabecular meshwork samples after SLT at 4(th) and 6(th) hour from treatment. On the whole, selective laser trabeculoplasty modulates in trabecular meshwork the expression of genes involved in cell motility, intercellular connections, extracellular matrix production, protein repair, DNA repair, membrane repair, reactive oxygen species production, glutamate toxicity, antioxidant activities, and inflammation. CONCLUSIONS/SIGNIFICANCE: SLT did not induce any phenotypic alteration in TM samples. TM is a complex tissue possessing a great variety of function pivotal for the active regulation of aqueous humour outflow from the anterior chamber. SLT is able to modulate these functions at the postgenomic molecular level without inducing damage either at molecular or phenotypic levels

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

A Scoping Review of Quality of Life Questionnaires in Glaucoma Patients

PRECIS: Multiple questionnaires exist to measure glaucoma's impact on quality of life (QoL). Selecting the right questionnaire for the research question is essential, as is patients' acceptability of the questionnaire to enable collection of relevant patient-reported outcomes. PURPOSE: QoL relating to a disease and its treatment is an important dimension to capture. This scoping review sought to identify the questionnaires most appropriate for capturing the impact of glaucoma on QoL. METHODS: A literature search of QoL questionnaires used in glaucoma, including patient-reported outcomes measures, was conducted and the identified questionnaires were analyzed using a developed quality criteria assessment. RESULTS: Forty-one QoL questionnaires were found which were analyzed with the detailed quality criteria assessment leading to a summary score. This identified the top 10 scoring QoL questionnaires rated by a synthesis of the quality criteria grid, considering aspects such as reliability and reproducibility, and the authors' expert clinical opinion. The results were ratified in consultation with an international panel of ophthalmologists (N=49) from the Educational Club of Ocular Surface and Glaucoma representing 23 countries. CONCLUSIONS: Wide variability among questionnaires used to determine vision related QoL in glaucoma and in the responses elicited was identified. In conclusion, no single existing QoL questionnaire design is suitable for all purposes in glaucoma research, rather we have identified the top 10 from which the questionnaire most appropriate to the study objective may be selected. Development of a new questionnaire that could better distinguish between treatments in terms of vision and treatment-related QoL would be useful that includes the patient perspective of treatment effects as well as meeting requirements of regulatory and health authorities. Future work could involve development of a formal weighting system with which to comprehensively assess the quality of QoL questionnaires used in glaucoma

Selective laser trabeculoplasty: past, present, and future

Over the past two decades, selective laser trabeculoplasty (SLT) has increasingly become an established laser treatment used to lower intraocular pressure in open-angle glaucoma and ocular hypertensive patients. In this review we trace the origins of SLT from previous argon laser trabeculoplasty and review the current role it has in clinical practice. We outline future directions of SLT research and introduce emerging technologies that are further developing this intervention in the treatment paradigm of glaucoma.Eye advance online publication, 5 January 2018; doi:10.1038/eye.2017.273

Conjunctival epithelium expression of HLA-DR in glaucoma patients and its influence on the outcome of filtration surgery

AIMS—To analyse the expression of HLA-DR on conjunctival epithelial cells in patients with glaucoma taking topical antiglaucoma therapy.
METHODS—10 patients taking no topical medication and 30 patients with uncontrolled glaucoma taking medical therapy participated in the study. The specimens were obtained by impression cytology preoperatively, 3 months, and 6 months after filtration surgery. The expression of HLA-DR on T lymphocytes and epithelial cells was analysed by flow cytometry.
RESULTS—A significant increase in HLA-DR on epithelial cells was found preoperatively in patients with glaucoma. A significant increased expression of HLA-DR on epithelial cells was detected 3 months and 6 months after surgery.
CONCLUSIONS—The increased expression of HLA-DR on conjunctival epithelial cells still present 6 months after surgery indicates the increased ability of epithelial cells to induce immune inflammation with subsequent fibrosis.


Self-monitoring of intraocular pressure using Icare HOME tonometry in clinical practice

Barbara Cvenkel,1,2 Makedonka Atanasovska Velkovska11Department of Ophthalmology, University Medical Centre Ljubljana, Ljubljana, Slovenia; 2Medical Faculty, University of Ljubljana, Ljubljana, SloveniaPurpose: To determine the value of self-monitoring of diurnal intraocular pressure (IOP) by Icare Home rebound tonometer in patients with glaucoma and ocular hypertension.Methods: Patients with open-angle glaucoma or ocular hypertension, controlled IOP at office visits, and at least 3 years of follow-up in the glaucoma clinic were included. Progression of glaucoma was based on medical records and defined by documented structural and/or visual field change. Patients were trained to correctly perform self-tonometry and instructed to measure diurnal IOP in a home setting for 3 days. IOP characteristics (mean, peak IOP, fluctuation of IOP as range, and SD of IOP) were documented and compared between the progressive and stable eyes.Results: Ninety-four patients (50 females) with a mean (SD) age of 57.1 (14.7) years were included. Among the 94 eyes from 94 subjects, 72 (76.6%) eyes had primary open-angle glaucoma, ten (10.6%) had pigmentary glaucoma, four (4.3%) had exfoliative glaucoma, and eight (8.5%) eyes had ocular hypertension. Thirty-six eyes showed progression and 58 eyes were stable. Patients with progression were older than those with stable disease (mean (SD) 65.8 (8.4) years vs 51.7 (15.3) years, P<0.001). The progression group had higher average IOP (mean (SD) 15.8 (4.0) mmHg vs 13.3 (3.7) mmHg, P=0.002), peak IOP (mean (SD) 21.8 (5.8) mmHg vs 18.6 (4.8) mmHg, P=0.01), and greater IOP fluctuation range (mean (SD) 11.6 (4.8) vs 9.1 (3.5) mmHg, P=0.011) compared to non-progression group.Conclusion: Self-monitoring of IOP using Icare Home tonometry provides more complete data on variability of IOP to assist in the management of glaucoma.Keywords: glaucoma, intraocular pressure, progression, self-tonometr