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January 10, 2023; 100 (2) Research Article

Discriminating Between Papilledema and Optic Disc Drusen Using 3D Structural Analysis of the Optic Nerve Head

View ORCID ProfileMichaël J.A. Girard, View ORCID ProfileSatish Panda, Tin Aung Tun, Elisabeth A. Wibroe, View ORCID ProfileRaymond P. Najjar, Tin Aung, Alexandre H. Thiéry, Steffen Hamann, Clare Fraser, View ORCID ProfileDan Milea
First published September 29, 2022, DOI: https://doi.org/10.1212/WNL.0000000000201350
Michaël J.A. Girard
From the Ophthalmic Engineering & Innovation Laboratory (M.J.A.G., S.P.), Singapore Eye Research Institute (T.A.T., R.P.N., T.A., D.M.), Singapore National Eye Centre; Duke-NUS Graduate Medical School (M.J.A.G., T.A.T., R.P.N., T.A., D.M.), Singapore; Institute for Molecular and Clinical Ophthalmology (M.J.A.G.), Basel, Switzerland; Department of Ophthalmology (E.A.W., S.H.), Rigshospitalet, University of Copenhagen, Denmark; Yong Loo Lin School of Medicine (R.P.N., T.A.), and Department of Statistics and Applied Probability (A.H.T.), National University of Singapore; and Save Sight Institute (C.F.), Faculty of Health and Medicine, The University of Sydney, New South Wales, Australia.
MSc, PhD
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Satish Panda
From the Ophthalmic Engineering & Innovation Laboratory (M.J.A.G., S.P.), Singapore Eye Research Institute (T.A.T., R.P.N., T.A., D.M.), Singapore National Eye Centre; Duke-NUS Graduate Medical School (M.J.A.G., T.A.T., R.P.N., T.A., D.M.), Singapore; Institute for Molecular and Clinical Ophthalmology (M.J.A.G.), Basel, Switzerland; Department of Ophthalmology (E.A.W., S.H.), Rigshospitalet, University of Copenhagen, Denmark; Yong Loo Lin School of Medicine (R.P.N., T.A.), and Department of Statistics and Applied Probability (A.H.T.), National University of Singapore; and Save Sight Institute (C.F.), Faculty of Health and Medicine, The University of Sydney, New South Wales, Australia.
PhD
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Tin Aung Tun
From the Ophthalmic Engineering & Innovation Laboratory (M.J.A.G., S.P.), Singapore Eye Research Institute (T.A.T., R.P.N., T.A., D.M.), Singapore National Eye Centre; Duke-NUS Graduate Medical School (M.J.A.G., T.A.T., R.P.N., T.A., D.M.), Singapore; Institute for Molecular and Clinical Ophthalmology (M.J.A.G.), Basel, Switzerland; Department of Ophthalmology (E.A.W., S.H.), Rigshospitalet, University of Copenhagen, Denmark; Yong Loo Lin School of Medicine (R.P.N., T.A.), and Department of Statistics and Applied Probability (A.H.T.), National University of Singapore; and Save Sight Institute (C.F.), Faculty of Health and Medicine, The University of Sydney, New South Wales, Australia.
MD, PhD
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Elisabeth A. Wibroe
From the Ophthalmic Engineering & Innovation Laboratory (M.J.A.G., S.P.), Singapore Eye Research Institute (T.A.T., R.P.N., T.A., D.M.), Singapore National Eye Centre; Duke-NUS Graduate Medical School (M.J.A.G., T.A.T., R.P.N., T.A., D.M.), Singapore; Institute for Molecular and Clinical Ophthalmology (M.J.A.G.), Basel, Switzerland; Department of Ophthalmology (E.A.W., S.H.), Rigshospitalet, University of Copenhagen, Denmark; Yong Loo Lin School of Medicine (R.P.N., T.A.), and Department of Statistics and Applied Probability (A.H.T.), National University of Singapore; and Save Sight Institute (C.F.), Faculty of Health and Medicine, The University of Sydney, New South Wales, Australia.
MD
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Raymond P. Najjar
From the Ophthalmic Engineering & Innovation Laboratory (M.J.A.G., S.P.), Singapore Eye Research Institute (T.A.T., R.P.N., T.A., D.M.), Singapore National Eye Centre; Duke-NUS Graduate Medical School (M.J.A.G., T.A.T., R.P.N., T.A., D.M.), Singapore; Institute for Molecular and Clinical Ophthalmology (M.J.A.G.), Basel, Switzerland; Department of Ophthalmology (E.A.W., S.H.), Rigshospitalet, University of Copenhagen, Denmark; Yong Loo Lin School of Medicine (R.P.N., T.A.), and Department of Statistics and Applied Probability (A.H.T.), National University of Singapore; and Save Sight Institute (C.F.), Faculty of Health and Medicine, The University of Sydney, New South Wales, Australia.
PhD
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Tin Aung
From the Ophthalmic Engineering & Innovation Laboratory (M.J.A.G., S.P.), Singapore Eye Research Institute (T.A.T., R.P.N., T.A., D.M.), Singapore National Eye Centre; Duke-NUS Graduate Medical School (M.J.A.G., T.A.T., R.P.N., T.A., D.M.), Singapore; Institute for Molecular and Clinical Ophthalmology (M.J.A.G.), Basel, Switzerland; Department of Ophthalmology (E.A.W., S.H.), Rigshospitalet, University of Copenhagen, Denmark; Yong Loo Lin School of Medicine (R.P.N., T.A.), and Department of Statistics and Applied Probability (A.H.T.), National University of Singapore; and Save Sight Institute (C.F.), Faculty of Health and Medicine, The University of Sydney, New South Wales, Australia.
MD, PhD
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Alexandre H. Thiéry
From the Ophthalmic Engineering & Innovation Laboratory (M.J.A.G., S.P.), Singapore Eye Research Institute (T.A.T., R.P.N., T.A., D.M.), Singapore National Eye Centre; Duke-NUS Graduate Medical School (M.J.A.G., T.A.T., R.P.N., T.A., D.M.), Singapore; Institute for Molecular and Clinical Ophthalmology (M.J.A.G.), Basel, Switzerland; Department of Ophthalmology (E.A.W., S.H.), Rigshospitalet, University of Copenhagen, Denmark; Yong Loo Lin School of Medicine (R.P.N., T.A.), and Department of Statistics and Applied Probability (A.H.T.), National University of Singapore; and Save Sight Institute (C.F.), Faculty of Health and Medicine, The University of Sydney, New South Wales, Australia.
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Steffen Hamann
From the Ophthalmic Engineering & Innovation Laboratory (M.J.A.G., S.P.), Singapore Eye Research Institute (T.A.T., R.P.N., T.A., D.M.), Singapore National Eye Centre; Duke-NUS Graduate Medical School (M.J.A.G., T.A.T., R.P.N., T.A., D.M.), Singapore; Institute for Molecular and Clinical Ophthalmology (M.J.A.G.), Basel, Switzerland; Department of Ophthalmology (E.A.W., S.H.), Rigshospitalet, University of Copenhagen, Denmark; Yong Loo Lin School of Medicine (R.P.N., T.A.), and Department of Statistics and Applied Probability (A.H.T.), National University of Singapore; and Save Sight Institute (C.F.), Faculty of Health and Medicine, The University of Sydney, New South Wales, Australia.
MD, PhD
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Clare Fraser
From the Ophthalmic Engineering & Innovation Laboratory (M.J.A.G., S.P.), Singapore Eye Research Institute (T.A.T., R.P.N., T.A., D.M.), Singapore National Eye Centre; Duke-NUS Graduate Medical School (M.J.A.G., T.A.T., R.P.N., T.A., D.M.), Singapore; Institute for Molecular and Clinical Ophthalmology (M.J.A.G.), Basel, Switzerland; Department of Ophthalmology (E.A.W., S.H.), Rigshospitalet, University of Copenhagen, Denmark; Yong Loo Lin School of Medicine (R.P.N., T.A.), and Department of Statistics and Applied Probability (A.H.T.), National University of Singapore; and Save Sight Institute (C.F.), Faculty of Health and Medicine, The University of Sydney, New South Wales, Australia.
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Dan Milea
From the Ophthalmic Engineering & Innovation Laboratory (M.J.A.G., S.P.), Singapore Eye Research Institute (T.A.T., R.P.N., T.A., D.M.), Singapore National Eye Centre; Duke-NUS Graduate Medical School (M.J.A.G., T.A.T., R.P.N., T.A., D.M.), Singapore; Institute for Molecular and Clinical Ophthalmology (M.J.A.G.), Basel, Switzerland; Department of Ophthalmology (E.A.W., S.H.), Rigshospitalet, University of Copenhagen, Denmark; Yong Loo Lin School of Medicine (R.P.N., T.A.), and Department of Statistics and Applied Probability (A.H.T.), National University of Singapore; and Save Sight Institute (C.F.), Faculty of Health and Medicine, The University of Sydney, New South Wales, Australia.
MD, PhD
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Citation
Discriminating Between Papilledema and Optic Disc Drusen Using 3D Structural Analysis of the Optic Nerve Head
Michaël J.A. Girard, Satish Panda, Tin Aung Tun, Elisabeth A. Wibroe, Raymond P. Najjar, Tin Aung, Alexandre H. Thiéry, Steffen Hamann, Clare Fraser, Dan Milea
Neurology Jan 2023, 100 (2) e192-e202; DOI: 10.1212/WNL.0000000000201350

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Abstract

Background and Objectives The distinction of papilledema from other optic nerve head (ONH) lesions mimicking papilledema, such as optic disc drusen (ODD), can be difficult in clinical practice. We aimed the following: (1) to develop a deep learning algorithm to automatically identify major structures of the ONH in 3-dimensional (3D) optical coherence tomography (OCT) scans and (2) to exploit such information to robustly differentiate among ODD, papilledema, and healthy ONHs.

Methods This was a cross-sectional comparative study of patients from 3 sites (Singapore, Denmark, and Australia) with confirmed ODD, those with papilledema due to raised intracranial pressure, and healthy controls. Raster scans of the ONH were acquired using OCT imaging and then processed to improve deep-tissue visibility. First, a deep learning algorithm was developed to identify major ONH tissues and ODD regions. The performance of our algorithm was assessed using the Dice coefficient. Second, a classification algorithm (random forest) was designed to perform 3-class classifications (1: ODD, 2: papilledema, and 3: healthy ONHs) strictly from their drusen and prelamina swelling scores (calculated from the segmentations). To assess performance, we reported the area under the receiver operating characteristic curve for each class.

Results A total of 241 patients (256 imaged ONHs, including 105 ODD, 51 papilledema, and 100 healthy ONHs) were retrospectively included in this study. Using OCT images of the ONH, our segmentation algorithm was able to isolate neural and connective tissues and ODD regions/conglomerates whenever present. This was confirmed by an averaged Dice coefficient of 0.93 ± 0.03 on the test set, corresponding to good segmentation performance. Classification was achieved with high AUCs, that is, 0.99 ± 0.001 for the detection of ODD, 0.99 ± 0.005 for the detection of papilledema, and 0.98 ± 0.01 for the detection of healthy ONHs.

Discussion Our artificial intelligence approach can discriminate ODD from papilledema, strictly using a single OCT scan of the ONH. Our classification performance was very good in the studied population, with the caveat that validation in a much larger population is warranted. Our approach may have the potential to establish OCT imaging as one of the mainstays of diagnostic imaging for ONH disorders in neuro-ophthalmology, in addition to fundus photography.

Glossary

3D=
3-dimensional;
AI=
artificial intelligence;
AUC=
area under the receiver operating characteristic curve;
BOSAI=
Brain and Optic Nerve Study;
BMO=
Bruch membrane open;
CNN=
convolutional neural network;
ICP=
intracranial pressure;
OCT=
optical coherence tomography;
ODD=
optic disc drusen;
ONH=
optic nerve head;
RF=
random forest;
RPE=
retinal pigment epithelium;
SNAI=
Singapore National Eye Center

Footnotes

  • Go to Neurology.org/N for full disclosures. Funding information and disclosures deemed relevant by the authors, if any, are provided at the end of the article.

  • Previously published: https://arxiv.org/abs/2112.09970.

  • Submitted and externally peer reviewed. The handling editor was Rebecca Burch, MD.

  • Received February 4, 2022.
  • Accepted in final form August 19, 2022.
  • © 2022 American Academy of Neurology
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