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The Sahlgrenska Center for Pediatric Ophthalmology Research

Research group
Active research
Project owner
Institute of Neuroscience and Physiology

Short description

The Sahlgrenska Center for Pediatric Ophthalmology Research at the Institute of Neuroscience and Physiology at the University of Gothenburg is a strategic research center focused on vascular and neural development research. Our center is based on partnerships between industry, clinical and experimental sciences as well as applied mathematics.

The center

The center is focused on defining the underlying mechanisms of vascular and neural damage occurring after preterm birth and to develop strategies to better diagnose and possibly prevent these life-threatening complications.

Our studies suggest a number of ways to intervene medically in these disease processes. Studies on the disease mechanisms and the development of strategies to allow normal retinal and brain development may ultimately lead to significant reduction in the short and long-term morbidity of preterm infants.

Methods

Laboratory facilities at the Sahlgrenska Center of Pediatric Ophthalmologic Research include well-equipped analytical labs, (immunohistochemistry, western blots) and accredited clinical research lab for Pediatric studies (RIA, ELISA), molecular lab (RT-PCR, in-situ hybridisation) and image analysis (bright and fluorescence microscopy, stereology), biomarker discovery (Luminex multiplex system), and bioinformatics. Excellent animal facilities with full surgical equipment are available at the Department of Physiology at Experimental Biomedicine. The laboratories has strong national and international network within Europe and USA.

Ongoing studies

Clinical studies

  • A clinical trial – Less is more (LIM) reducing the amount of blood taken for tests from extremely preterm infants
  • A clinical trial (Mega Donna Mega) to investigate the impact of AA/DHA on retinopathy, visual and neural development
  • A clinical trial (Donna Mega) to investigate the impact of DHA/EPA on retinophaty, visual and neural development EUDRA-CT no 2008-000046-31
  • A clinical trial (phase II study) with IGF-I/IGFBP-3 administration www.clinicaltrials.gov NCT 01096784
  • Further validation of WINROP® (national & international)
  • Ophthalmologic follow-up studies of infants with perinatal adverse history
  • Investigating the impact of postnatal serum IGF-I levels on preterm morbidity and postnatal growth
  • Effect of blood components importance for neuro- and angiogenesis in premature infants
  • Metabolic and Pharmakoninetic analysis of intravenous insulin administration to very preterm infants
  • Development of a digital e-health solution for ROP screening and diagnosis

Experimental studies

  • Investigating the impact of chronic inflammation on ROP development in an experimental neonatal animal model
  • A proteomic and luminex approach for identification of biomarkers in amnion, cord blood and serum that may predict an increased risk for ROP
två personer i vita rockar undersöker ögon på ett spädbarn
Photo: Johan Wingborg

Principal Investigator

Ann Hellström
MD, PhD, Professor

Group members

Chatarina Löfqvist, PhD, Associate Professor

Anna-Lena Hård, MD, PhD

Gunnel Hellgren, PhD, Associate Professor

Eva M. Andersson, PhD

Pia Lundgren, MD, PhD

Carola Pfeiffer Mosesson, RN, Monitor

Aldina Pivodic, PhD student

Anders Nilsson, PhD

Anna Thorell, MD

Karin Sävman, MD, PhD

Lena Jacobson, MD, PhD, Associate Professor

Svetlana Najm, MD

Ulrika Sjöbom, PhD student

William Hellström, PhD student

Prediction/WINROP

WINROP® history

We have done extensive laboratory work showing that insulin like growth factor 1 (IGF-1) which mediates growth is a major factor in the development of ROP (Hellström A et al Proceedings of the National Academy of Sciences, 2001).

Based on that finding we developed and published an algorithm WINROP® based on serial neonatal measurements of body weight, which predicts ROP development. The original article including IGF measurements prompted an editorial in Archives of Ophthalmology “Screening for Retinopathy of Prematurity- The Promise of New Approaches”.

The algorithm has now been further developed (web based, free of charge) and validated retrospectively on 50 children screened for ROP 2005-2007 at various Swedish neonathal wards in, Sweden. We found that WINROP® predicted early (mean 9 weeks before ROP needing treatment was detected by present screening routines) all infants who later developed proliferative ROP requiring treatment (sensitivity 100% and specificity 54%) (Löfqvist C et al Archives Ophthalmol 2009).

In order to make WINROP® rapid and robust as well as more equipment-free we have revised the algorithm using only serial weight measurements. With this approach WINROP® predicted early all infants who later developed proliferative ROP requiring treatment and correctly identified 75% of those who did not develop proliferative ROP (Hellström A et al Pediatrics 2009), and thus would not need any ophthalmologic screening. In addition, we have validated WINROP® in a preterm population in Boston (n=375) indicating a 100% sensitivity and a 76% specificity (Wu C et al Archives Ophthalmol 2009).

Applying these figures of reduced screening to the European preterm population the number of ophthalmological examinations could be safely reduced by 200,000 examinations/year, yet include 100% of infants requiring treatment for ROP. WINROP®  has been further validatet in multiple clinical settings international, see PUB Med for scientific publications.

In order to establish this as the new standard of care worldwide WINROP® is now validated in Sweden, North America, Great Britain, Germany, Switzerland, Mexico, China, South Korea, Netherlands, India, Scotland, Canada and Brasil. WINROP® is now up and running in 56 countries, used by 348 caregivers in 215 different sites (2018).

The use of WINROP® for screening would identify early children at risk and could lead to early interventions.  Global health personnel could focus on the right patients at the right time. Thus, WINROP® (simple to perform with minimal training) would supply a decision making tool in ROP screening -an approach that is clearly cost effective and makes better use of resources.

Some of our collaborating partners:

  • Associate Professor David Ley, Ingrid Pupp Hansen MD, PhD and coworkers Neonatology Dep. University of Lund, Lund, Sweden.
  • Professor Lois Smith and coworkers, Children’s Hospital, Harvard Medical School, Boston, USA.
  • Professor Changlian Zhu, Zhengzhou University, China.
  • Fortes Filho JB, MD, PhD and coworkers, Departments of Ophthalmology and Pediatrics, Hospital de Clínicas de Porto Alegre, Federal University of Rio Grande do Sul, Brazil.
  • Brian Fleck, MD PhD and coworkers, Princess Alexandra Eye Pavilion, Chalmers Street, Edinburgh, UK.
  • Professor Hans Ulrich Bucher, Dr. Veit Sturm, Dr Sandra Arri and coworkers, Departments of Neonatology & Ophthalmology, University Hospital of Zurich, University Hospital of Zurich, Switzerland.
  • Dr Consuelo Zepeda, Hospital Civil de Guadalajara El Carmen, Guadlajara Mexico.
  • Dr Anand Vinekar, Narayana Nethralaya Postgraduate Institute of Ophthalmology, Bangalore, India.
  • Dr Maria Marta Galan, La Plata Calleih, La Plata Argentina.
  • Dr Adam James, Paediatric Specialist Registrar, Coombe Womens and Infants University Hospital, Dublin, Irland.

Commercial partner

Winrop application

If you want to apply for WINROP®, visit www.winrop.com 

WINROP® is free of charge.

Prevention/Premiplex

We have previously demonstrated that low levels of serum IGF-1 and IGFBP-3 in children born preterm are strongly associated with ROP as well as other morbidities in preterm infants (e.g. poor growth, lung disease and poor brain development).

Based on these results we have clinically investigated the concept of restoring IGF-1/IGFBP-3 to in utero levels in premature infants. We have conducted and finalized a Phase I, pharmacokinetic study of intravenously administered rhIGF-I/rhIGFBP-3 complex (mecasermin rinfabate) to five very preterm children (GA 26-29 weeks). No side effects (b-glucose, heart rate, blood pressure) were seen and the dose and mode of delivery was established for Phase II study (Hellström A et al Ped Res 2009) (Ley D et al Ped Res 2013).

Carrying out this project is a major multi-disciplinary project with many participants, contributing with a broad range of competences, involved. For a successful implementation of the project, national and international experts in ophthalmology, neonatology, pharmacokinetics, pharmaceutics, GMP (Good Manufacturing Practice), GCP (Good Clinical Practice), GLP (Good Laboratory Practice) are needed. The Phase II study is an international multi-center trial with participation from the neonatal clinics in Lund and Stockholm.

The pharmaceutical company, Premacure AB, Uppsala, Sweden now acquired by Shire®, is coordinating all activities before, during and after the trial and is also in charge of obtaining all regulatory authorizations before the study can commence. Pharma Consulting Group AB (PCG), Uppsala, Sweden  has been contracted as independent monitor of the study. This will guarantee that the work is carried out in accordance with the regulatory provisions (GCP).

As we are focusing on factors that promote neural, vascular and metabolic development, our findings regarding ROP are likely to be applicable on several aspects of complications of premature birth and will hopefully provide benefits for the whole lifespan.

  • Associate Professor David Ley, Ingrid Pupp Hansen MD, PhD and     coworkers Neonatology Department, University of Lund, Lund, Sweden.
  • Boubou Hallberg MD, PhD, Dirk Wackernagel MD, Mireille Vanpee MD, PhD  and coworkers Neonatology Department, The Karolinska University Hospital, Stockholm, Sweden.
  • Professor Lois Smith and coworkers, Children’s Hospital, Harvard Medical School, Boston, USA.
  • PREVENTROP partners
  • Professor Manon Benders and coworkers, Wilhelmina   Children’s hospital of the University Medical Center in Utrecht, the Netherlands.

Commercial partners