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Retinotopic cortical mapping in objective functional monitoring of macular therapy
  1. Markus Ritter1,
  2. Allan Hummer2,
  3. Maximilian Pawloff1,
  4. Anna A Ledolter1,
  5. David Linhardt2,
  6. Michael Woletz2,
  7. Gabor Gyoergy Deak1,
  8. Stefan Sacu1,
  9. Robin Ristl3,
  10. Dariga Ramazanova3,
  11. Graham E Holder4,5,
  12. Christian Windischberger2,
  13. Ursula Margarethe Schmidt-Erfurth1
  1. 1 Department of Ophthalmology, Medical University of Vienna, Vienna, Austria
  2. 2 MR Center of Excellence, Center for Medical Physics and Biomedical Engineering, Medical University of Vienna, Vienna, Austria
  3. 3 Section for Medical Statistics, Center for Medical Statistics, Informatics and Intelligent Systems, Medical University of Vienna, Vienna, Austria
  4. 4 Department of Ophthalmology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore
  5. 5 UCL Institute of Ophthalmology, London, UK
  1. Correspondence to Professor Ursula Margarethe Schmidt-Erfurth, Department of Opththalmology, Medical University of Vienna, Wien, Vienna, Austria; ursula.schmidt-erfurth{at}meduniwien.ac.at

Abstract

Background/Aims To determine the suitability of functional MRI (fMRI) as an objective measure of macular function following therapeutic intervention; conventional psychophysical measures rely heavily on patient compliance.

Methods Twenty patients with neovascular age-related macular degeneration (nAMD) were studied with high-resolution fMRI, visual acuity, reading accuracy and speed, contrast sensitivity (CS) and microperimetry (MP) before and after 3 monthly intravitreal injections of ranibizumab. Population-receptive field retinotopic maps calculated from fMRI data were compared with psychophysical measures and optical coherence tomography.

Results Best-corrected visual acuity (BCVA) responders (≥5 letters) showed an increase of 29.5% in activated brain area, while non-responders showed a decrease of 0.8%. Radial histograms over eccentricity allowed quantification of the absolute number of significant voxels and thus differences before and after treatment. Responders showed increases in foveal (α<0.5°) activation, while non-responders did not. Absence of intraretinal fluid and preservation of outer retinal layers was associated with higher numbers of active V1 voxels and better BCVA. Higher voxel numbers were associated with improved reading performance and, less marked, with BCVA, CS and MP.

Conclusion The data show that retinotopic mapping using fMRI can successfully be applied objectively to evaluate the therapeutic response in nAMD patients treated with anti-vascular endothelial growth factor therapy. This demonstrates the ability of retinotopic mapping to provide an objective assessment of functional recovery at a cortical level; the technique can therefore be applied, in other degenerative macular diseases, to the assessment of potential therapeutic interventions such as gene therapy or cell replacement therapy.

  • Retina
  • Imaging
  • Visual (cerebral) Cortex

Data availability statement

All data relevant to the study are included in the article or uploaded as supplementary information.

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Data availability statement

All data relevant to the study are included in the article or uploaded as supplementary information.

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Footnotes

  • Contributors MR and AH conceptualised the study, analysed the data, drafted and revised the paper. RR, DR and DL cleaned and analysed the data, performed the statistical analysis, drafted and revised the paper. MP, AAL, MW, GGD and SS investigated the patients and healthy controls, collected and analysed the data. GEH, CW and UMS-E conceptualised and supervised the study, drafted and revised the paper. UMS-E is guarantor

  • Funding This work was supported by Novartis grant number CRFB002AAT06T.

  • Competing interests None declared.

  • 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.