Article Text

Download PDFPDF
Inner retinal degeneration associated with optic nerve head drusen in pseudoxanthoma elasticum
  1. Kristina Hess1,
  2. Kristin Raming1,
  3. Peter Charbel Issa2,3,
  4. Philipp Herrmann1,
  5. Frank G Holz1,
  6. Maximilian Pfau1,4
  1. 1Department of Ophthalmology, University Hospital Bonn, Bonn, Germany
  2. 2Oxford Eye Hospital, Oxford University Hospitals NHS Foundation Trust, Oxford, UK
  3. 3Nuffield Laboratory of Ophthalmology, Department of Clinical Neurosciences, University of Oxford, Oxford, UK
  4. 4Ophthalmic Genetics and Visual Function Branch, National Eye Institute, National Institutes of Health (NIH), Bethesda, Maryland, USA
  1. Correspondence to Dr. Kristina Hess, Department of Ophthalmology, University Hospital Bonn, 53127 Bonn, Germany; kristina.hess{at}


Background/aims To determine the association of age, presence of optic nerve head drusen (ONHD) and number of previous intravitreal anti-vascular endothelial growth factor (anti-VEGF) injections with inner retinal layer thicknesses in patients with pseudoxanthoma elasticum (PXE).

Methods In this retrospective case–control study, longitudinal spectral-domain optical coherence tomography imaging data from patients with PXE were compared with controls. A custom deep-learning-based segmentation algorithm was trained and validated to quantify the retinal nerve fibre layer (RNFL) and ganglion cell layer (GCL). The association of age, number of anti-VEGF injections and ONHD with the RNFL and GCL thickness in the outer ETDRS subfields as dependent variables was investigated using mixed model regression.

Results Fourty-eight eyes of 30 patients with PXE were compared with 100 healthy eyes. The mean age was 52.5±12.9 years (range 21.3–68.2) for patients and 54.2±18.7 years (range 18.0–84.5) for controls. In patients, ONHD were visible in 15 eyes from 13 patients and 31 eyes had received anti-VEGF injections. In the multivariable analysis, age (−0.10 µm/year, p<0.001), the diagnosis of PXE (−2.03 µm, p=0.005) and an interaction term between age and the presence of ONHD (−0.20 µm/year, p=0.001) were significantly associated with the GCL thickness. Including the number of intravitreal injections did not improve the model fit. The RNFL thickness was not significantly associated with any of these parameters.

Conclusions This study demonstrates a significant association of ageing and ONHD with GCL thinning in patients with PXE, but not with the number of anti-VEGF injections. Given the severity of inner retinal degeneration in PXE, a clinical trial investigating neuroprotective therapy warrants consideration.

  • retina
  • dystrophy
  • genetics
  • optic nerve

Data availability statement

Data are available upon reasonable request.

Statistics from

Data availability statement

Data are available upon reasonable request.

View Full Text


  • Contributors Study concept—KH and MP. Collected data—KH and KR. Provided and cared for study patients—KH, PH and FGH. Data analysis—KH and MP. Manuscript preparation—KH and MP. Critical review of the manuscript—PCI, MG, PH and FGH. Supervision—MP and FGH.

    Responsible for the overall content: KH

  • Funding This work was supported by the German Research Foundation (DFG, grant HE 8960/1-1 to KH, grant PF950/1-1 to MP), the BONFOR Gerok grant (grant 2019-1 A-13) by the University of Bonn to KH and the National Institute for Health Research (NIHR), Oxford Biomedical Research Centre (BRC) to PCI.

  • Disclaimer The views expressed are those of the authors and not necessarily those of the NHS, the NIHR or the Department of Health. The funding organisation had no role in study design, data collection, analysis, or interpretation, or the writing of the report.

  • Competing interests The Department of Ophthalmology, University of Bonn, received technical support from Heidelberg Engineering, Heidelberg, Germany and Carl Zeiss Meditec, Jena, Germany (KH, KR, PH, FGH, MP).

  • Provenance and peer review Not commissioned; externally peer reviewed.

  • Supplemental material This content has been supplied by the author(s). It has not been vetted by BMJ Publishing Group Limited (BMJ) and may not have been peer-reviewed. Any opinions or recommendations discussed are solely those of the author(s) and are not endorsed by BMJ. BMJ disclaims all liability and responsibility arising from any reliance placed on the content. Where the content includes any translated material, BMJ does not warrant the accuracy and reliability of the translations (including but not limited to local regulations, clinical guidelines, terminology, drug names and drug dosages), and is not responsible for any error and/or omissions arising from translation and adaptation or otherwise.

Request Permissions

If you wish to reuse any or all of this article please use the link below which will take you to the Copyright Clearance Center’s RightsLink service. You will be able to get a quick price and instant permission to reuse the content in many different ways.