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Copenhagen Ophthalmology Center

Site and position in health care system

The Glostrup Hospital is the designated center for clinical and experimental ophthalmology in the Greater Copenhagen Region, with a population of 1.6 million the largest health care unit in Denmark. Regional ophthalmology institutions include two comprehensive tertiary eye clinics at the Glostrup Hospital and the Rigshospitalet, which will merge in 2008/2009, and two secondary level eye clinics at the Frederiksberg and Hillerød Hospitals that will be managed from Glostrup. Also located in Glostrup is the Kennedy Center, the national center for genetic ophthalmology in Denmark (pop. 5.5 million).

Site and position in research and education

The Glostrup Hospital and the affiliated clinics are pregraduate and postgraduate ophthalmology training centers. Academic staff members have joint appointments at the hospitals and at the University of Copenhagen and hold national and international research grants. Research and teaching is administered by the Institute of Clinical Neuroscience, the current chairman of which is the chairman of ophthalmology at Glostrup. The Glostrup Hospital has basic science facilities at Glostrup and its academic staff conducts basic and preclinical research at the medical science campus of the University of Copenhagen.

Principal research mission

The research mission of the clinical ophthalmic institutions in Copenhagen is to conduct scientific investigations that support the prevention and treatment of sight-threatening disease and promote the rehabilitation of the visually impaired.

Recruitment platform

The joint institutions under the Glostrup Hospital will cover all subspecialities in ophthalmology. The Greater Copenhagen Region provides universal public health care in this predominantly urban geographic entity, through public hospitals and private contractors in primary health care. The Glostrup Hospital has access to electronic regional and national government databases incorporating all registered diagnoses, procedures, prescription medications, demographic data, etc. Under institutional review board approval patients with specific diseases can be identified by social security number and invited to volunteer for clinical studies.

The Glostrup Hospital has a track record in population studies and recently genotyped 7000 volunteers for four AMD-related gene polymorphisms. Services under direct administration by the Glostrup Hospital include secondary and tertiary ophthalmic care in all fields of ophthalmology plus primary care in selected fields (emergencies, diabetic retinopathy screening, hospitalized and institutionalized patients, disabled persons). This broad range of activities provides an exceptional base for recruitment of patients for clinical trials, as exemplified by an excellent track record from a large number of completed and ongoing trials.

Infrastructure

Both the Glostrup Hospital and the Rigshospitalet departments are fully equipped tertiary level eye clinics with inpatient wards, multiple operation rooms, and research facilities.

Production

The Greater Copenhagen Region eye clinics perform 15,000 surgical operations per year, mainly on an out-patient basis, including 5000 operations for cataract and 1700 operations for vitreoretinal disease, the remainder including ocular trauma, glaucoma, strabismus, ptosis, adnexal disease, and oncology. Additionally activities include approximately 3000 intravitreal injections, 3000 fundus angiograms, and 4000 fundus photocoagulation treatment sessions. Key annual production figures for each institution are available upon request.

Sections Section chair
Diabetic retinopathy Henrik Lund-Andersen, MD, DMSc, professor and chairman
Medical Retina Michael Larsen, MD, DMSc, professor, Per Haamann, MD
Surgical Retina Morten la Cour, MD, DMSc, Assoc Prof., Jørgen Villumsen, MD, DMSc, Assoc. Prof.
Glaucoma John Thygesen, MD, Associate Professor, Johan L Poulsen, MD
Cataract & Refractive Surgery Vibeke Henning, MD, Line Kessel, MD, PhD
Ocular Surface & Inflammation Josephine Fuchs, MD
Neuroophthalmology Dan Milea, MD, PhD, professor
Ophthalmic Oncology Peter Toft, MD, DMSc, Assoc. Prof., Peter K Jensen, MD, DMSc, Assoc. Prof
Noninvasive Optical Diag-nostics and Optometry Birgit Sander, MSc, PhD
Cornea Hanne Olsen, MD, PhD, Assoc. Prof., Henrik B Olesen, MD
Strabismus Troels Vinding, MD, DMSc, Jon Peiter Saunte, MD
Pediatric Ophthalmology Hanne Jensen, MD, DMSc, Assoc. Prof., Regitze Bangsgaard, MD
Public health in ophthalmol Jens Christian Nørregaard, MD, PhD, DMSc, Assoc. Prof.
Basic science Maria Thereza Perez, MSc, PhD

Fields of scientific interest

Current scientific activities emphasize diseases of the posterior segment of the eye, the optic nerve, and higher visual and oculomotor functions and include vascular, endocrine, neuronal, genetic, and neoplastic disease. Major efforts involve noninvasive optical and electrophysiological tests and molecular genetics. Preclinical studies in small rodents and in pigs cover retinal metabolism, blood flow, neuronal degeneration, and neuronal regeneration.

Staff Glostrup Hospital only
Physicians  1 chairman/professor, 2 consultant/professors, 5 consult- 
ant/associate professors, 3 consultants, 7 non-consultant special- 
ists, 10 residents
Academic research 1 physiology laboratory manager, 1 basic laboratory manager, 6
junior physicians in PhD programmers
Optometry  3 optometrists
Technical staff 1 clinical photographer
Registered nurses 1 nursing chair, 3 deputy nursing chairs, 35 nurses
Non-registered nurses 6 nursing assistants
Administration 1 research administrator, 1 secretarial administrator, 22 secretaries

Selected fields of study

Mechanisms of retinal disease in man

Using a spectrum of methods for noninvasive assessment of retinal function and morphology, a series of projects investigate the interaction between performance, metabolism, and perfusion in systemic and local conditions. Diabetes is of pivotal interest, not only when diabetic retinopathy is present but also before this stage, when fundamental metabolic and functional abnormalities of the retina of the hyperglycemic patient can be studied in the absence of unspecific microvascular disease. Studies include patients with uniquely informative conditions such as the ocular ischemic syndrome and patients with common diseases in transient stages of disease, such as newly diagnosed diabetes mellitus. Most recently, projects have been developed based on the vast pool of patients from the Kennedy Institute with rare metabolic disorders that may interact with diabetes and help identify the pathogenesis of diabetic retinopathy.

Clinical interventions

Interventional trials include not only studies initiated and conducted internally but also international multicenter trials where the Glostrup Hospital is a participant or a leading investigational site. Ongoing and completed trials include studies of diabetic retinopathy (MBBK/ruboxistaurin/Eli Lilly, RESOLVE/ranibizumab/Novartis, EOP1013/pegaptanib/ Pfizer, DIRECT/candesartan/EURODIAB Group, Sandostatin LAR/octreotide/Novartis, Astemizole Retinopathy Trial/astemizole vs placebo/Hershey-Copenhagen) and age-related macular degeneration (EOP1003/pegaptanib/Eyetech, POOL/verteporfin/Novartis, AART/anecortave acetate/Alcon, Pharmacological Therapy for Macular Degeneration Study/interferon alfa-2a/Roche, Mont Blanc/ranibizumab±verteporfin/Novartis), Dozolamide in AMD/trusopt vs placebo/MSD). Ongoing surgical trials include the Copenhagen Macular Hole Study and a trial in planning on the treatment of idiopathic epiretinal membranes.

Preclinical studies

Cell cultures and animal studies include investigations of retinal perfusion and function in pigs and small rodents. A full-scale experimental facility at the central health science campus of the University of Copenhagen is currently used to study neurotrophic agents and transplanted cells in normal and transgenic green fluorescent protein pigs. A small animal facility at the Glostrup Hospital Campus is performing studies of retinal metabolism in diabetes and degenerative retinal and optic nerve disease.

Optical methods of ocular investigation and therapy

Noninvasive methods, primarily optical coherence tomography, are being developed as tools for assessment of retinal structure by refining raw data analysis and image construction and by performing normative studies to enable correlation of function with structure. A separate study section investigates new photochemical methods of noninvasive laser manipulation of intraocular tissue.

Strategic plans

The retina and optic nerve are uniquely amenable to the study of neurodegenerative disorders and share essential features with other parts of the central nervous system. Advances in eye and brain research have produced a large number of new targets and new molecules with potential applicability in the treatment of retinal and optic nerve disorders. In the same manner that compounds developed in cancer pipelines have lead to breakthroughs in the treatment of neovascular eye disease, it is expected that compounds targeted for cerebral disorders will find potent applications in eye disease.

To contribute to therapeutic advances in degenerative posterior segment disorders, the longterm collaborative efforts are initiated with families with hereditary diseases, the first aim being to refine phenotyping, to implement genotyping in research and in routine clinical practice, and to promote early diagnosis of disease. New standards of early diagnosis are particularly important when a limited window of opportunity for the application of effective treatment may be present, limited perhaps to the first decade of life. This effort will create a broad foundation for interventional trials in diseases such as retinitis pigmentosa.

To achieve critical mass and competence, the ophthalmic institutions in Copenhagen will promote full clinical subspecialization among physicians, nurses, and technical staff. A multidisciplinary approach will be expanded to achieve high competence in specialized fields, including optometrists, strabismologists, and photographers.

To maintain and develop a faculty that combines clinical productivity with high academic standards, the institutions will promote internationalization at all levels, including an international fellowship program to attracts highly qualified personnel. Recruitment policy will emphasize a productive mix of operational experts and leading clinician-scientists with international- level speaker and key opinion leader potential.

Policies

The efforts of the joint institutions is supported by government policy supporting increasing internationalization at all levels of public and private enterprise (http://www.globalisering.dk) and by a regional policy of actively promoting collaboration with industry and academic institutions (http://www.regionhovedstaden.dk).

Academic collaboration under the University of Copenhagen

Major collaborative studies with other University of Copenhagen institutions involve the Eye Pathology section of the Department of Neuroscience and Pharmacology (Assoc. Prof. Steffen Heegaard) and the Ocular Immunology Laboratory of the Department of International Health, Immunology and Microbiology (Assoc. Prof. Mogens Holst Nissen).

Bilateral international academic collaboration

Major collaborative efforts include the study of doxycyclin therapy in diabetic retinopathy with the Penn State University Diabetic Retinopathy Group (Prof. Thomas W. Gardner), a study of mitochondrial function in dominant optic neuropathy with the University of Angers (Prof. Patricia Amati-Bonneau), and a study of nanodevice delivery of brain-derived neurotrophic factor with Yale University (Assoc. Prof. Michael Young).

International network collaborations

The Glostrup Hospital is a member of the EU-sponsored European Vision Institute and the European Vision Institute Clinical Trials Sites of Excellence (EVI.CT.SE) network.

International industry collaboration

The Glostrup Hospital participates in multiple collaborative studies with industry partners (see above). The Glostrup Hospital has been a top recruiting participant in several studies. Board memberships, societies, areas of international influence, honorary positions Members of staff at the joint institutions serve on numerous boards, including, but not limited to the following: Acta Ophthalmologica (associate editors), European Board of Ophthalmology (board member), Association for Research in Vision and Ophthalmology (committee member), European Glaucoma Society (committee member), pharmaceutical and instrument industry advisory boards (members), Danish Ophthalmological Society (board members), Club Jules Gonin (members), Fluorescein Angiography Club (members).

Staff contact information

Updated contact information and curricula vitae of staff members can be supplied upon request.

Summary of advantages and competences

The ophthalmology division of the public health care system in the Greater Copenhagen Region has characteristics rarely found in other centers: 1) Primary to tertiary level integration of health insurance, health administration, health statistics, and clinical practice. 2) Integration of basic, preclinical, and clinical science across ophthalmic science, neuroscience, and genetics. 3) An attractive track record in recruitment of study participants from a population of 1.6 million. 4) Key opinion leaders within medical and surgical retina, glaucoma, pediatric ophthalmology, neuroophthalmology, and cataract surgery. 5) Direct access to regional and/or national databases and gene banks in diabetes, genetic eye diseases, visual impairment, pediatric eye disease, socioeconomics and genealogy. 6) Broad implementation of modern diagnostic methods in clinical practice, such as diabetic retinopathy screening using optical coherence tomography. 7) Integrated management of health care and research, providing a single access-point for partners in industry.

Appendix 1. Selected ongoing projects

Experimental subretinal retinal wound repair

Subretinal formation of new vessels is a prominent direct cause of visual loss in several debilitating eye diseases. Development and testing of new types of treatment relies upon experimental production of subretinal retinal wounds, the repair of which involves new vessel formation. A model has been implemented and used to test a method of repairing of Bruch’s membrane using histopathology and multifocal ERG as endpoints. PI and senior participants: (Morten la Cour, with Schepens Eye Institute (Michael Young), UC Irvine (Henry Klassen), and Yale Medical School (Erin Larvik).

Experimental optic nerve head and retinal ischemia and effect of carboanhydrase inhibition

Oxygen tension in front of the retina and the optic nerve in pigs has been studied using oxygen electrodes. Models of human disease include branch retinal vein occlusion and global retinal ischemia. Experimental interventions are carboanhydrase inhibition and treatment using glial neurotrophic development (?) factor (GNDF), the latter having demonstrated a marked neuroprotective effect. PI and senior participants: Morten la Cour, Jens Folke Kiilgaard, Daniella Bach Pedersen, Peter Koch Jensen, with the University of Reykjavik (Einar Stefanson), Harvard Medical School (Michael Young), UC Irvine (Henry Klassen), and Yale Medical School (Erin Larvik)

Retinal stem cell transplantation

The clinical aim of the project is to examine the possibility of replacing lost or damaged retinal neurons through transplantation of retinal stem cells. This experimental preclinical collaborative study is shared with major partners in the USA who provide retinal stem cells from green fluorescent protein pigs. In the first series of experiments, fluorescent stem cells have been implanted in the subretinal space of transgenic pigs with retinitis pigmentosa. PI and senior participants: Morten la Cour, Jens Folke Kiilgaard, with the Eye Pathology Section of the University of Copenhagen (Jan Ulrik Prause), Harvard Medical School (Michael Young), UC Irvine (Henry Klassen), Yale Medical School (Erin Larvik), University of Louisville (Tongalp Tezel, Henry Kaplan), North Carolina State University (Bob Petters), and the University of Lund (Frederik Ghosh).

Experimental treatment of proliferative vitreoretinopathy

Proliferative vitreoretinopathy involves proliferating retinal pigment epithelial cells, control of which has been attempted using antineoplastic agents. The effect has been limited by poor penetration through the blood-retina barrier and rapid elimination from the vitreous. The project seeks to circumvent these limitations by developing a drug delivery system for the antimetabolite 5-fluorouracil for use in complicated recurrent retinal detachment. PI and senior participants: Morten la Cour, with Bente Steffansen, university of Copenhagen.
Epidemiology of age-related macular degeneration and precursor conditions
A study of incidence and prevalence of AMD in central Copenhagen (Østerbro undersøgelsen) has been published in part. PI and participants: Helena Buch Hesgaard, Niels Vesti Nielsen, Troels Vinding, Morten la Cour. A study of macular degeneration in Greenland has been begun in 2000. PI and senior participants: Nis Andersen, Morten la Cour.

Retinopathy of prematurity

The number of new cases per year of retinopathy of prematurity in Denmark has increased, although no change in apparent risk factors has occurred. The study is based on a national register of premature children, a retrospective case-control assessment of risk factors, and a clinical study of functional outcomes in children treated for retinopathy of prematurity, comparing measures of ocular and cerebral damage. PI and senior participants: Morten la Cour, Hans Fledelius, Regitze Bangsgaard, with the Neonatal Care Department of the Rigshospitalet (Gorm Greisen).

Long-term quality assessment of ocular surgery based on public registers

Surgical procedures and diagnoses in Denmark are registered in the LandsPatientRegisteret (LPR). Data can be cross-referenced with other public data bases (demographic, mortality, socioeconomics, etc.). This provides an exceptional chance of correlating procedural detail (surgical options) with long-term outcome (rate of complications). Studies in progress include rates of intraocular infection and recurrent detachment after cataract or vitreoretinal surgery. PI and senior participants: Morten la Cour, Gøril Boberg-Ans, Jørgen Villumsen, Andreas Helgesen, Henrik Bom Olesen.

Macular hole surgery randomized controlled clinical trial

Surgical treatment offers an attractive outcome, when successful, for patients with macular holes and the procedure is increasing in frequency. Validation is complicated because cataract, a confounding factor, follows almost invariably after vitrectomy. The project is a randomized masked controlled clinical trial of two different surgical procedures. The study has recruited 80 patients in 18 months and is to be completed in 2008. PIs: Morten la Cour and Michael Larsen.

Epiretinal membrane surgery controlled clinical trial

A randomized controlled clinical trial of epiretinal membrane surgery will allocate patients with good visual acuity to surgery or deferral until a specified degree of visual loss has occurred. Participants will be stratified for metamorphopsia and binocular visual function. PI and senior participants: Morten la Cour, Michael Larsen, Jørgen Villumsen, and Vibeke Henning.

Molecular composition of epiretinal membranes

The stimulus for epiretinal membrane formation is unknown. The project examines the composition of epiretinale membranes removed during vitrectomy using explorative proteomics and mass spectrometry assays and confirmatory Western blotting, comparing material from idiopathic epiretinal membranes, ILM from eyes with macular holes, and uveitic membranes. PI and senior participants: Morten la Cour and Jørgen Villumsen, with the Eye Pathology Section of the University of Copenhagen and Henrik Vorum, University of Århus.

Vitreous biopsy in uveitis

The etiology of uveitis is variable and the differential diagnosis difficult, meaning that cases labeled idiopathic may harbor undiagnosed infectious agents. The range of assays available for analysis of vitreous biopsies is largely limited to a herpes viruses whereas many other agents of potential relevance are unaivailable. The ongoing project collects vitreous biopsies and performs experimental analyses for tuberculosis, leptospira, and toxoplasmosis infection. PI and senior participants: Morten la Cour and Jørgen Villumsen, with Statens Serum Institut.

Information about Copenhagen Ophthalmology Center

created October 2, 2007 by Rikke Fléron - Edited February 1, 2008 by Michael Larsen