Sancy Low1,2,3, Ryian Mohamed4, Alice Davidson5,6, Maria Papadopoulos7, Piergiacomo Grassi7,8, Andrew R Webster7,5,6, Graeme C Black9,10, Paul J Foster7,5,6, David F Garway-Heath7,5,6, Philip A Bloom11. 1. Moorfields Eye Hospital NHS Foundation Trust, London, UK. sancy.low@ucl.ac.uk. 2. UCL Institute of Ophthalmology, London, UK. sancy.low@ucl.ac.uk. 3. Department of Ophthalmology, Guys and St. Thomas' Hospital NHS Foundation Trust, London, UK. sancy.low@ucl.ac.uk. 4. Department of Ophthalmology, Central Middlesex Hospital, London, UK. 5. UCL Institute of Ophthalmology, London, UK. 6. NIHR BRC for Ophthalmology at Moorfields Eye Hospital and UCL Institute of Ophthalmology, London, UK. 7. Moorfields Eye Hospital NHS Foundation Trust, London, UK. 8. Department of Ophthalmology, Guys and St. Thomas' Hospital NHS Foundation Trust, London, UK. 9. Centre for Genomic Medicine, Institute of Human Development, Faculty of Medical and Human Sciences, University of Manchester, Manchester, UK. 10. Central Manchester University Hospitals NHS Foundation Trust, Manchester, UK. 11. Imperial College NHS Foundation Trust, London, UK.
Abstract
BACKGROUND: The availability and reduced cost of genotyping has improved gene susceptibility testing and our scientific understanding of disease pathophysiology. Whilst several personalised translational models exist within medical frameworks, genetic-based surgical therapy is a translational application not widely used in surgical specialties. METHOD: We present a clinical series of five patients with genetically confirmed bestrophinopathy and malignant glaucoma (MG). Patients were followed up for 12 months or more after receiving surgical intervention to manage refractory intraocular pressure (IOP) resistant to medical treatment. FINDINGS: Patients with BEST1 gene mutations are at higher risk of MG after filtration surgery. A multi-disciplinary approach after four patients experienced poor outcomes concluded that traditional first-line glaucoma surgery was not sufficient to prevent visual loss. A fifth patient presenting with the identified at-risk phenotype underwent primary pars plana vitrectomy, with pars plana Baerveldt tube insertion, successfully preventing MG and had no glaucoma progression after 5 years. INTERPRETATION: We provide proof-of-principle that genetic analysis can be used to inform the selection of surgical therapy to improve outcomes. In this case, a refinement of current surgical methods to avoid MG. Although challenges remain, personalised surgery has the potential to improve clinical outcomes beyond the scope of current surgical practice.
BACKGROUND: The availability and reduced cost of genotyping has improved gene susceptibility testing and our scientific understanding of disease pathophysiology. Whilst several personalised translational models exist within medical frameworks, genetic-based surgical therapy is a translational application not widely used in surgical specialties. METHOD: We present a clinical series of five patients with genetically confirmed bestrophinopathy and malignant glaucoma (MG). Patients were followed up for 12 months or more after receiving surgical intervention to manage refractory intraocular pressure (IOP) resistant to medical treatment. FINDINGS:Patients with BEST1 gene mutations are at higher risk of MG after filtration surgery. A multi-disciplinary approach after four patients experienced poor outcomes concluded that traditional first-line glaucoma surgery was not sufficient to prevent visual loss. A fifth patient presenting with the identified at-risk phenotype underwent primary pars plana vitrectomy, with pars plana Baerveldt tube insertion, successfully preventing MG and had no glaucoma progression after 5 years. INTERPRETATION: We provide proof-of-principle that genetic analysis can be used to inform the selection of surgical therapy to improve outcomes. In this case, a refinement of current surgical methods to avoid MG. Although challenges remain, personalised surgery has the potential to improve clinical outcomes beyond the scope of current surgical practice.
Authors: Remi Stevelink; Maurits Wcb Sanders; Maarten P Tuinman; Eva H Brilstra; Bobby Pc Koeleman; Floor E Jansen; Kees Pj Braun Journal: Epileptic Disord Date: 2018-04-01 Impact factor: 1.819
Authors: Sancy Low; Alice E Davidson; Graham E Holder; Chris R Hogg; Shomi S Bhattacharya; Graeme C Black; Paul J Foster; Andrew R Webster Journal: Mol Vis Date: 2011-08-23 Impact factor: 2.367