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2. Recent advances in neuro-ophthalmology

Author

Bassi, Shikha T, Newman, Nancy J, Chen, John J, Tisavipat, Nanthaya Yui, Mollan, Susan P, Moss, Heather E, and Milea, Dan

Subjects
Innovations, Neuroophthalmology -- Innovations, Neuro-ophthalmology -- Innovations
Abstract

Author(s): Shikha T Bassi (corresponding author) [1]; Nancy J Newman [2]; John J Chen [3,4]; Nanthaya Yui Tisavipat [4]; Susan P Mollan [5,6]; Heather E Moss [7]; Dan Milea [8,9] [...], This review article represents a collaborative effort across continents, bringing together the latest developments in neuro-ophthalmology with a focus on innovative diagnostic and therapeutic modalities that are shaping the future of the field. Among the most significant advancements is the rise of optical coherence tomography (OCT), now recognized as an indispensable tool in neuro-ophthalmological research, providing unparalleled insights into optic nerve and central nervous system pathologies. Gene therapy, particularly for conditions such as Lebers hereditary optic neuropathy, marks a new frontier in personalized medicine, offering hope for previously untreatable conditions. The article also examines the transformative role of telemedicine and artificial intelligence (AI) in clinical practice, which are revolutionizing patient care and enhancing diagnostic precision. Furthermore, it highlights the impact of novel serological biomarkers on the understanding and management of immune-mediated optic neuritis, and discusses the introduction of new therapeutic agents like Tocilizumab and Teprotumumab, which are redefining treatment paradigms. Collectively, these advancements reflect the profound influence of modern medicine on neuro-ophthalmology, paving the way for improved patient outcomes and fostering new avenues for research and clinical practice. Keywords: Artificial intelligence, AQP4 antibody, collapsin response mediator protein 5 antibody, gene therapy, giant cell arteritis, glial fibrillary acidic protein antibody, myelin oligodendrocyte glycoprotein antibody, optical coherence tomography, teleophthalmology, teprotumumab, thyroid eye disease, tocilizumab

Published
2024
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5. Randomized trial of bilateral gene therapy injection for m.11778G>A MT-ND4 Leber optic neuropathy

Author

Newman, Nancy J, Yu-Wai-Man, Patrick, Subramanian, Prem S, Moster, Mark L, Wang, An-Guor, Donahue, Sean P, Leroy, Bart P, Carelli, Valerio, Biousse, Valerie, Vignal-Clermont, Catherine, Sergott, Robert C, Sadun, Alfredo A, Rebolleda Fernández, Gema, Chwalisz, Bart K, Banik, Rudrani, Bazin, Fabienne, Roux, Michel, Cox, Eric D, Taiel, Magali, Sahel, José-Alain, Giulia, Amore, Shweta, Anand, Rudrani, Banik, Piero, Barboni, Valérie, Biousse, Hayley, Boston, Asma, Burale, Michele, Carbonelli, Valerio, Carelli, Celia, Chen, Hui-Chen, Cheng, Steve, Cho, Manuela, Contin, Pietro, D’Agati, DeBusk, Adam A, Julie, De Zaeytijd, Jannah, Dobbs, Lindreth, DuBois, Simona, Esposti, Alcides, Fernandes Filho, Elizabeth, Fortin, Sapna, Gangaputra, Deborah, Gibbs, François, Girmens Jean, Rabih, Hage, Haller, Julia A, Gad, Heilweil, George Baker, Hubbard III, Jeong-Min, Hwang, Laia, Jaumendreu Urquijo, Neringa, Jurkute, Rustum, Karanjia, Wahiba, Khemliche, La Chiara, Morgia, Maria, Massini, Marc, Mathias, Memon, Muhammad A, Susan, Mohamed, Muñoz Negrete, Francisco J, Ghazala, O’Keefe, Shriji, Patel, Paula, Pecen, Peragallo, Jason H, Lise, Plaine, Mary, Preston, Gema, Rebolleda Fernández, Martina, Romagnoli, José-Alain, Sahel, Melissa, SantaMaria, Chuanbin, Sun, Katy, Tai, Heather, Tollis, Irena, Tsui, Tucker, William R, Catherine, Vignal-Clermont, An-Guor, Wang, Saige, Wilkins, and Patrick, Yu-Wai-Man

Subjects
Biomedical and Clinical Sciences, Ophthalmology and Optometry, Clinical Research, Genetics, Neurosciences, Clinical Trials and Supportive Activities, Eye Disease and Disorders of Vision, 6.1 Pharmaceuticals, Evaluation of treatments and therapeutic interventions, Eye, Humans, DNA, Mitochondrial, Genetic Therapy, Inflammation, Mutation, Optic Atrophy, Hereditary, Leber, LHON REFLECT Study Group, NADH dehydrogenase 4, leber hereditary optic neuropathy, lenadogene nolparvovec, mitochondrial DNA, recombinant adeno-associated virus vector 2, Medical and Health Sciences, Psychology and Cognitive Sciences, Neurology & Neurosurgery, Biomedical and clinical sciences, Health sciences, Psychology
Abstract

Leber hereditary optic neuropathy (LHON) is an important example of mitochondrial blindness with the m.11778G>A mutation in the MT-ND4 gene being the most common disease-causing mtDNA variant worldwide. The REFLECT phase 3 pivotal study is a randomized, double-masked, placebo-controlled trial investigating the efficacy and safety of bilateral intravitreal injection of lenadogene nolparvovec in patients with a confirmed m.11778G>A mutation, using a recombinant adeno-associated virus vector 2, serotype 2 (rAAV2/2-ND4). The first-affected eye received gene therapy; the fellow (affected/not-yet-affected) eye was randomly injected with gene therapy or placebo. The primary end point was the difference in change from baseline of best-corrected visual acuity (BCVA) in second-affected/not-yet-affected eyes treated with lenadogene nolparvovec versus placebo at 1.5 years post-treatment, expressed in logarithm of the minimal angle of resolution (LogMAR). Forty-eight patients were treated bilaterally and 50 unilaterally. At 1.5 years, the change from baseline in BCVA was not statistically different between second-affected/not-yet-affected eyes receiving lenadogene nolparvovec and placebo (primary end point). A statistically significant improvement in BCVA was reported from baseline to 1.5 years in lenadogene nolparvovec-treated eyes: -0.23 LogMAR for the first-affected eyes of bilaterally treated patients (P < 0.01); and -0.15 LogMAR for second-affected/not-yet-affected eyes of bilaterally treated patients and the first-affected eyes of unilaterally treated patients (P < 0.05). The mean improvement in BCVA from nadir to 1.5 years was -0.38 (0.052) LogMAR and -0.33 (0.052) LogMAR in first-affected and second-affected/not-yet-affected eyes treated with lenadogene nolparvovec, respectively (bilateral treatment group). A mean improvement of -0.33 (0.051) LogMAR and -0.26 (0.051) LogMAR was observed in first-affected lenadogene nolparvovec-treated eyes and second-affected/not-yet-affected placebo-treated eyes, respectively (unilateral treatment group). The proportion of patients with one or both eyes on-chart at 1.5 years was 85.4% and 72.0% for bilaterally and unilaterally treated patients, respectively. The gene therapy was well tolerated, with no systemic issues. Intraocular inflammation, which was mostly mild and well controlled with topical corticosteroids, occurred in 70.7% of lenadogene nolparvovec-treated eyes versus 10.2% of placebo-treated eyes. Among eyes treated with lenadogene nolparvovec, there was no difference in the incidence of intraocular inflammation between bilaterally and unilaterally treated patients. Overall, the REFLECT trial demonstrated an improvement of BCVA in LHON eyes carrying the m.11778G>A mtDNA mutation treated with lenadogene nolparvovec or placebo to a degree not reported in natural history studies and supports an improved benefit/risk profile for bilateral injections of lenadogene nolparvovec relative to unilateral injections.

Published
2023

11. Application of a Deep Learning System to Detect Papilledema on Nonmydriatic Ocular Fundus Photographs in an Emergency Department

Author

Fraser, Clare L., Micieli, Jonathan A., Costello, Fiona, Bénard-Séguin, Étienne, Yang, Hui, Chan, Carmen Kar Mun, Cheung, Carol Y, Chan, Noel CY, Hamann, Steffen, Gohier, Philippe, Vautier, Anaïs, Rougier, Marie-Bénédicte, Chiquet, Christophe, Vignal-Clermont, Catherine, Hage, Rabih, Khanna, Raoul Kanav, Tran, Thi Ha Chau, Lagrèze, Wolf Alexander, Jonas, Jost B, Ambika, Selvakumar, Fard, Masoud Aghsaei, La Morgia, Chiara, Carbonelli, Michele, Barboni, Piero, Carelli, Valerio, Romagnoli, Martina, Amore, Giulia, Nakamura, Makoto, Fumio, Takano, Petzold, Axel, Wenniger lj, Maillette de Buy, Kho, Richard, Fonseca, Pedro L., Bikbov, Mukharram M., Milea, Dan, Najjar, Raymond P, Ting, Daniel, Tang, Zhiqun, Loo, Jing Liang, Tow, Sharon, Singhal, Shweta, Vasseneix, Caroline, Wong, Tien Yin, Lamoureux, Ecosse, Yu Chen, Ching, Aung, Tin, Schmetterer, Leopold, Sanda, Nicolae, Thuman, Gabriele, Hwang, Jeong-Min, Vanikieti, Kavin, Suwan, Yanin, Padungkiatsagul, Tanyatuth, Yu-Wai-Man, Patrick, Jurkute, Neringa, Hong, Eun Hee, Biousse, Valerie, Newman, Nancy J., Peragallo, Jason H., Datillo, Michael, Kedar, Sachin, Lin, Mung Yan, Patil, Ajay, Aung, Andre, Boyko, Matthew, Alsakran, Wael Abdulraman, Zayani, Amani, Bouthour, Walid, Banc, Ana, Mosley, Rasha, Labella, Fernando, Miller, Neil R., Chen, John J., Mejico, Luis J., Kilangalanga, Janvier Ngoy, Biousse, Valérie, Najjar, Raymond P., Wright, David W., Keadey, Matthew T., Wong, Tien Y., and Bruce, Beau B.

Published
2024
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13. Therapeutic benefit of idebenone in patients with Leber hereditary optic neuropathy: The LEROS nonrandomized controlled trial

Author

Yu-Wai-Man, Patrick, Carelli, Valerio, Newman, Nancy J., Silva, Magda Joana, Linden, Aki, Van Stavern, Gregory, Szaflik, Jacek P., Banik, Rudrani, Lubiński, Wojciech, Pemp, Berthold, Liao, Yaping Joyce, Subramanian, Prem S., Misiuk-Hojło, Marta, Newman, Steven, Castillo, Lorena, Kocięcki, Jarosław, Levin, Marc H., Muñoz-Negrete, Francisco Jose, Yagan, Ali, Cherninkova, Sylvia, Katz, David, Meunier, Audrey, Votruba, Marcela, Korwin, Magdalena, Dziedziak, Jacek, Jurkutė, Neringa, Harvey, Joshua P., La Morgia, Chiara, Priglinger, Claudia, Llòria, Xavier, Tomasso, Livia, and Klopstock, Thomas

Published
2024
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14. The BONSAI (Brain and Optic Nerve Study with Artificial Intelligence) deep learning system can accurately identify pediatric papilledema on standard ocular fundus photographs

Author

Fraser, Clare L., Micieli, Jonathan A., Costello, Fiona, Étienne Bénard-Séguin, Yang, Hui, Mun Chan, Carmen Kar, Cheung, Carol Y., Chan, Noel CY., Hamann, Steffen, Gohier, Philippe, Vautier, Anaïs, Rougier, Marie-Bénédicte, Chiquet, Christophe, Vignal-Clermont, Catherine, Hage, Rabih, Khanna, Raoul Kanav, Chau Tran, Thi Ha, Lagrèze, Wolf Alexander, Jonas, Jost B., Ambika, Selvakumar, Fard, Masoud Aghsaei, La Morgia, Chiara, Carbonelli, Michele, Barboni, Piero, Carelli, Valerio, Romagnoli, Martina, Amore, Giulia, Nakamura, Makoto, Fumio, Takano, Petzold, Axel, de Buy Wenniger L.J., Maillette, Kho, Richard, Fonseca, Pedro L., Bikbov, Mukharram M., Milea, Dan, Najjar, Raymond P., Ting, Daniel, Tang, Zhiqun, Loo, Jing Liang, Tow, Sharon, Singhal, Shweta, Vasseneix, Caroline, Wong, Tien Yin, Lamoureux, Ecosse, Chen, Ching Yu, Aung, Tin, Schmetterer, Leopold, Sanda, Nicolae, Thuman, Gabriele, Hwang, Jeong-Min, Vanikieti, Kavin, Suwan, Yanin, Padungkiatsagul, Tanyatuth, Yu-Wai-Man, Patrick, Jurkute, Neringa, Hong, Eun Hee, Biousse, Valerie, Newman, Nancy J., Peragallo, Jason H., Datillo, Michael, Kedar, Sachin, Lin, Mung Yan, Patil, Ajay, Aung, Andre, Boyko, Matthew, Alsakran, Wael Abdulraman, Zayani, Amani, Bouthour, Walid, Banc, Ana, Mosley, Rasha, Labella, Fernando, Miller, Neil R., Chen, John J., Mejico, Luis J., Kilangalanga, Janvier Ngoy, Cioplean, Daniela, Dragomir, Mihaela, Chia, Audrey, and Biousse, Valérie

Published
2024
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17. Indirect Comparison of Lenadogene Nolparvovec Gene Therapy Versus Natural History in Patients with Leber Hereditary Optic Neuropathy Carrying the m.11778G>A MT-ND4 Mutation

Author

Carelli, Valerio, Newman, Nancy J., Yu-Wai-Man, Patrick, Biousse, Valerie, Moster, Mark L., Subramanian, Prem S., Vignal-Clermont, Catherine, Wang, An-Guor, Donahue, Sean P., Leroy, Bart P., Sergott, Robert C., Klopstock, Thomas, Sadun, Alfredo A., Rebolleda Fernández, Gema, Chwalisz, Bart K., Banik, Rudrani, Girmens, Jean François, La Morgia, Chiara, DeBusk, Adam A., Jurkute, Neringa, Priglinger, Claudia, Karanjia, Rustum, Josse, Constant, Salzmann, Julie, Montestruc, François, Roux, Michel, Taiel, Magali, and Sahel, José-Alain

Published
2023
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19. Safety of Lenadogene Nolparvovec Gene Therapy Over 5 Years in 189 Patients With Leber Hereditary Optic Neuropathy

Author

VIGNAL-CLERMONT, CATHERINE, YU-WAI-MAN, PATRICK, NEWMAN, NANCY J., CARELLI, VALERIO, MOSTER, MARK L., BIOUSSE, VALERIE, SUBRAMANIAN, PREM S., WANG, AN-GUOR, DONAHUE, SEAN P., LEROY, BART P., SADUN, ALFREDO A., KLOPSTOCK, THOMAS, SERGOTT, ROBERT C., REBOLLEDA FERNANDEZ, GEMA, CHWALISZ, BART K., BANIK, RUDRANI, TAIEL, MAGALI, ROUX, MICHEL, and SAHEL, JOSÉ-ALAIN

Published
2023
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20. Hereditary Optic Neuropathies

Author

Karanjia, Rustum, Yu-Wai-Man, Patrick, Newman, Nancy J., Levin, Leonard, Section editor, Cestari, Dean, Section editor, Albert, Daniel M., editor, Miller, Joan W., editor, Azar, Dimitri T., editor, and Young, Lucy H., editor

Published
2022
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28. Remote Diagnosis of Retinal Detachment in an Emergency Department Using Nonmydriatic Hybrid Ocular Imaging.

Author

Shanmugam, Nithya, Benard-Seguin, Etienne, Arepalli, Sruthi, Alencastro, George, McHenry, Jessica G., Rodriguez Duran, Mariana, Torres Soto, Mariam, Pendley, Andrew M., Wright, David W., Newman, Nancy J., and Biousse, Valérie

Subjects
OPHTHALMOLOGIC emergencies, OPTICAL coherence tomography, RETINAL detachment, MEDICAL triage, EYE care
Abstract

Background: Ocular emergencies are commonly evaluated in general emergency departments (ED) where ophthalmologists are rarely available. Nonmydriatic ocular imaging combining color fundus photographs and optical coherence tomography (NMFP-OCT) can help with rapid remote triage by ophthalmologists. We evaluated the rate at which retinal detachments (RDs) can be diagnosed with NMFP-OCT in the ED. Methods: Quality improvement project with prospective collection of data on RD patients who had NMFP-OCT obtained by ED staff over 1 year. Photographs were interpreted remotely by ophthalmologists and all patients underwent an in-person ophthalmologic examination in the ED to confirm the presence of a RD. Results: A total of 63 eyes (58 patients) had a RD, among which 53 (84.1%) had strong suggestion of RD on ocular imaging (34 [54%] were seen on both color and OCT nerve/macula; 11 [17.5%] were seen on color but missed on OCT; 8 [12.7%] were missed on color but seen on OCT). Ten RDs (15.9%) were missed on both color and OCT because of peripheral location of the RD (4, 40%), vitreous hemorrhage (4, 40%), or poor image quality (2, 20%). A total of 40 out of 58 patients were not seen by an eye care provider prior to reaching our ED and 10 had an inappropriate stroke workup for acute vision loss of presumed vascular origin. Conclusion: NMFP-OCT of the posterior pole obtained by ED staff revealed the RD in 84.1% of eyes, allowing for rapid remote triage of patients with visual symptoms and avoiding unnecessary testing when the diagnosis of RD is confirmed. [ABSTRACT FROM AUTHOR]

Published
2025
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30. Natural history of patients with Leber hereditary optic neuropathy—results from the REALITY study

Author

Yu-Wai-Man, Patrick, Newman, Nancy J., Carelli, Valerio, La Morgia, Chiara, Biousse, Valérie, Bandello, Francesco M., Clermont, Catherine Vignal, Campillo, Lorena Castillo, Leruez, Stephanie, Moster, Mark L., Cestari, Dean M., Foroozan, Rod, Sadun, Alfredo, Karanjia, Rustum, Jurkute, Neringa, Blouin, Laure, Taiel, Magali, and Sahel, José-Alain

Published
2022
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31. Deep Learning System Outperforms Clinicians in Identifying Optic Disc Abnormalities

Author

Vasseneix, Caroline, Nusinovici, Simon, Xu, Xinxing, Hwang, Jeong-Min, Hamann, Steffen, Chen, John J., Loo, Jing Liang, Milea, Leonard, Tan, Kenneth B.K., Ting, Daniel S.W., Liu, Yong, Newman, Nancy J., Biousse, Valerie, Wong, Tien Ying, Milea, Dan, Najjar, Raymond P., Gohier, Philippe, Miller, Neil, Vanikieti, Kavin, La Morgia, Chiara, Rougier, Marie-Bénédicte, Ambika, Selvakumar, Fonseca, Pedro, Lagrèze, Wolf Alexander, Sanda, Nicolae, Chiquet, Christophe, Yang, Hui, Chan, Carmen K. M., Cheung, Carol Y., Ha Chau, Tran Thi, Jurkute, Neringa, Yu-Wai-Man, Patrick, Kho, Richard, Jonas, Jost B, Vignal-Clermont, Catherine, Kim, Dong Hyun, Yang, Hee Kyung, Aung, Tin, Singhal, Shweta, Tow, Sharon, Nongpiur, Monisha Esther, Perera, Shamira, Narayanaswamy, Arun, Thirugnanam, Umapathi N., Fraser, Clare L., Mejico, Luis J., and Fard, Masoud Aghsaei

Published
2023
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32. Acute Visual Loss

Author

Lock, Jane H., Lamirel, Cédric, Newman, Nancy J., Biousse, Valérie, and Roos, Karen L., editor

Published
2021
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37. Efficacy and Safety of Intravitreal Gene Therapy for Leber Hereditary Optic Neuropathy Treated within 6 Months of Disease Onset

Author

Vignal, Catherine, Hage, Rabih, Catarino, Claudia B., Priglinger, Claudia, Priglinger, Siegfried, Thurau, Stephan, von Livonius, Bettina, Muth, Daniel, Wolf, Armin, Al-Tamami, Jasmina, Pressler, Angelika, Schertler, Cosima, Hildebrandt, Martin, Neuenhahn, Michael, Heilweil, Gad, Tsui, Irena, Hubbard, G. Baker, Hendrick, Andrew, Dattilo, Michael, Peragallo, Jason, Hawy, Eman, DuBois, Med, Lindreth, Gibbs, Deborah, Filho, Alcides Fernandes, Dobbs, Jannah, Carbonelli, Michele, Di Vito, Lidia, Contin, Manuela, Mohamed, Susan, La Morgia, Chiara, Silvestri, Sara, Acheson, James, Eleftheriadou, Maria, Esposti, Simona, Gemenetzi, Maria, Leitch-Devlin, Lauren, Tucker, William R., Jurkute, Neringa, SantaMaria, Melissa, Tollis, Heather, Haller, Julie A., Massini, Maria, Newman, Nancy J., Yu-Wai-Man, Patrick, Carelli, Valerio, Moster, Mark L., Biousse, Valerie, Vignal-Clermont, Catherine, Sergott, Robert C., Klopstock, Thomas, Sadun, Alfredo A., Barboni, Piero, DeBusk, Adam A., Girmens, Jean François, Rudolph, Günther, Karanjia, Rustum, Taiel, Magali, Blouin, Laure, Smits, Gerard, Katz, Barrett, and Sahel, José-Alain

Published
2021
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41. The Increasing Burden of Emergency Department and Inpatient Consultations for "Papilledema".

Author

Ray, Hetal J., Okrent Smolar, Avital Lily, Dattilo, Michael, Bouthour, Walid, Berman, Gabriele, Peragallo, Jason H., Kedar, Sachin, Pendley, Andrew M., Greene, James G., Keadey, Matthew T., Wright, David W., Bruce, Beau B., Newman, Nancy J., and Biousse, Valérie

Abstract

Background: Increasing incidence of idiopathic intracranial hypertension (IIH), overreported radiologic signs of intracranial hypertension, difficult access to outpatient neuro-ophthalmology services, poor insurance coverage, and medicolegal concerns have lowered the threshold for emergency department (ED) visits for "papilledema." Our objective was to examine referral patterns and outcomes of neuro-ophthalmology ED and inpatient consultations for concern for papilledema. Methods: At one university-based quaternary care center, all adults referred for "papilledema" over one year underwent a standardized ED "papilledema protocol." We collected patient demographics, final diagnoses, and referral patterns. Results: Over 1 year, 153 consecutive patients were referred for concern for papilledema. After papilledema protocol, 89 of 153 patients (58%) had bilateral optic disc edema, among whom 89% (79/89) had papilledema (intracranial hypertension). Of the 38 of 153 (25%) consultations for suspected disorder of intracranial pressure without previous fundus examination (Group 1), 74% (28/38) did not have optic disc edema, 21% (8/38) had papilledema, and 5% (2/38) had other causes of bilateral disc edema. Of the 89 of 153 (58%) consultations for presumed papilledema seen on fundus examination (Group 2), 58% (66/89) had confirmed papilledema, 17% (15/89) had pseudopapilledema, and 9% (8/89) had other causes of bilateral optic disc edema. Of the 26 of 153 (17%) patients with known IIH (Group 3), 5 had papilledema and 4 required urgent intervention. The most common diagnosis was IIH (58/79). Compared with IIH, patients with secondary causes of intracranial hypertension were older (P = 0.002), men (P < 0.001), not obese (P < 0.001), and more likely to have neurologic symptoms (P = 0.002). Conclusions: Inpatient and ED consultations for "papilledema" are increasing. Of the 153 ED and inpatient neuro-ophthalmology consultations seen for "papilledema" over 1 year, one-third of patients with optic disc edema of unknown cause before presentation to our ED had new vision- or life-threatening disease, supporting the need for prompt identification and evaluation of optic disc edema in the ED. In the face of limited access to neuro-ophthalmologists, this study supports the need for emergency department access to expert eye-care evaluation or ocular fundus camera for prompt identification of optic disc edema and standardized evaluation for neurologic emergencies. [ABSTRACT FROM AUTHOR]

Published
2024
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42. A Deep Learning Approach for Accurate Discrimination Between Optic Disc Drusen and Papilledema on Fundus Photographs.

Author

Sathianvichitr, Kanchalika, Najjar, Raymond P., Zhiqun, Tang, Fraser, J. Alexander, Yau, Christine W. L., Girard, Michael J. A., Costello, Fiona, Lin, Mung Y., Lagrèze, Wolf A., Vignal-Clermont, Catherine, Fraser, Clare L., Hamann, Steffen, Newman, Nancy J., Biousse, Valérie, Milea, Dan, Petzold, Axel, Gohier, Philippe, Miller, Neil R., Vanikieti, Kavin, and Milea, Leonard

Abstract

Supplemental Digital Content is Available in the Text. Background: Optic disc drusen (ODD) represent an important differential diagnosis of papilledema caused by intracranial hypertension, but their distinction may be difficult in clinical practice. The aim of this study was to train, validate, and test a dedicated deep learning system (DLS) for binary classification of ODD vs papilledema (including various subgroups within each category), on conventional mydriatic digital ocular fundus photographs collected in a large international multiethnic population. Methods: This retrospective study included 4,508 color fundus images in 2,180 patients from 30 neuro-ophthalmology centers (19 countries) participating in the Brain and Optic Nerve Study with Artificial Intelligence (BONSAI) Group. For training and internal validation, we used 857 ODD images and 3,230 papilledema images, in 1,959 patients. External testing was performed on an independent data set (221 patients), including 207 images with ODD (96 visible and 111 buried), provided by 3 centers of the Optic Disc Drusen Studies Consortium, and 214 images of papilledema (92 mild-to-moderate and 122 severe) from a previously validated study. Results: The DLS could accurately distinguish between all ODD and papilledema (all severities included): area under the receiver operating characteristic curve (AUC) 0.97 (95% confidence interval [CI], 0.96–0.98), accuracy 90.5% (95% CI, 88.0%–92.9%), sensitivity 86.0% (95% CI, 82.1%–90.1%), and specificity 94.9% (95% CI, 92.3%–97.6%). The performance of the DLS remained high for discrimination of buried ODD from mild-to-moderate papilledema: AUC 0.93 (95% CI, 0.90–0.96), accuracy 84.2% (95% CI, 80.2%–88.6%), sensitivity 78.4% (95% CI, 72.2%–84.7%), and specificity 91.3% (95% CI, 87.0%–96.4%). Conclusions: A dedicated DLS can accurately distinguish between ODD and papilledema caused by intracranial hypertension, even when considering buried ODD vs mild-to-moderate papilledema. [ABSTRACT FROM AUTHOR]

Published
2024
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45. Young Adults With Anterior Ischemic Optic Neuropathy: A Multicenter Optic Disc Drusen Study

Author

Hamann, Steffen, Malmqvist, Lasse, Wegener, Marianne, Fard, Masoud Aghsaei, Biousse, Valérie, Bursztyn, Lulu, Citirak, Gülsenay, Costello, Fiona, Crum, Alison V., Digre, Kathleen, Fraser, J. Alexander, Huna-Baron, Ruth, Katz, Bradley, Lawlor, Mitchell, Newman, Nancy J., Peragallo, Jason H., Petzold, Axel, Sibony, Patrick A., Subramanian, Prem S., Warner, Judith E.A., Wong, Sui H., and Fraser, Clare L.

Published
2020
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46. Application of a Deep Learning System to Detect Papilledema on Nonmydriatic Ocular Fundus Photographs in an Emergency Department

Author

Biousse, Valérie, primary, Najjar, Raymond P., additional, Tang, Zhiqun, additional, Lin, Mung Yan, additional, Wright, David W., additional, Keadey, Matthew T., additional, Wong, Tien Y., additional, Bruce, Beau B., additional, Milea, Dan, additional, Newman, Nancy J., additional, Fraser, Clare L., additional, Micieli, Jonathan A., additional, Costello, Fiona, additional, Bénard-Séguin, Étienne, additional, Yang, Hui, additional, Chan, Carmen Kar Mun, additional, Cheung, Carol Y, additional, Chan, Noel CY, additional, Hamann, Steffen, additional, Gohier, Philippe, additional, Vautier, Anaïs, additional, Rougier, Marie-Bénédicte, additional, Chiquet, Christophe, additional, Vignal-Clermont, Catherine, additional, Hage, Rabih, additional, Khanna, Raoul Kanav, additional, Tran, Thi Ha Chau, additional, Lagrèze, Wolf Alexander, additional, Jonas, Jost B, additional, Ambika, Selvakumar, additional, Fard, Masoud Aghsaei, additional, La Morgia, Chiara, additional, Carbonelli, Michele, additional, Barboni, Piero, additional, Carelli, Valerio, additional, Romagnoli, Martina, additional, Amore, Giulia, additional, Nakamura, Makoto, additional, Fumio, Takano, additional, Petzold, Axel, additional, Wenniger lj, Maillette de Buy, additional, Kho, Richard, additional, Fonseca, Pedro L., additional, Bikbov, Mukharram M., additional, Najjar, Raymond P, additional, Ting, Daniel, additional, Loo, Jing Liang, additional, Tow, Sharon, additional, Singhal, Shweta, additional, Vasseneix, Caroline, additional, Wong, Tien Yin, additional, Lamoureux, Ecosse, additional, Yu Chen, Ching, additional, Aung, Tin, additional, Schmetterer, Leopold, additional, Sanda, Nicolae, additional, Thuman, Gabriele, additional, Hwang, Jeong-Min, additional, Vanikieti, Kavin, additional, Suwan, Yanin, additional, Padungkiatsagul, Tanyatuth, additional, Yu-Wai-Man, Patrick, additional, Jurkute, Neringa, additional, Hong, Eun Hee, additional, Biousse, Valerie, additional, Peragallo, Jason H., additional, Datillo, Michael, additional, Kedar, Sachin, additional, Patil, Ajay, additional, Aung, Andre, additional, Boyko, Matthew, additional, Alsakran, Wael Abdulraman, additional, Zayani, Amani, additional, Bouthour, Walid, additional, Banc, Ana, additional, Mosley, Rasha, additional, Labella, Fernando, additional, Miller, Neil R., additional, Chen, John J., additional, Mejico, Luis J., additional, and Kilangalanga, Janvier Ngoy, additional

Published
2024
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48. The BONSAI (Brain and Optic Nerve Study with Artificial Intelligence) deep learning system can accurately identify pediatric papilledema on standard ocular fundus photographs

Author

Lin, Mung Yan, Najjar, Raymond P., Tang, Zhiqun, Cioplean, Daniela, Dragomir, Mihaela, Chia, Audrey, Patil, Ajay, Vasseneix, Caroline, Peragallo, Jason H., Newman, Nancy J., Biousse, Valérie, Milea, Dan, Lin, Mung Yan, Najjar, Raymond P., Tang, Zhiqun, Cioplean, Daniela, Dragomir, Mihaela, Chia, Audrey, Patil, Ajay, Vasseneix, Caroline, Peragallo, Jason H., Newman, Nancy J., Biousse, Valérie, and Milea, Dan

Abstract

Background: Pediatric papilledema often reflects an underlying severe neurologic disorder and may be difficult to appreciate, especially in young children. Ocular fundus photographs are easy to obtain even in young children and in nonophthalmology settings. The aim of our study was to ascertain whether an improved deep-learning system (DLS), previously validated in adults, can accurately identify papilledema and other optic disk abnormalities in children. Methods: The DLS was tested on mydriatic fundus photographs obtained in a multiethnic pediatric population (<17 years) from three centers (Atlanta-USA; Bucharest-Romania; Singapore). The DLS's multiclass classification accuracy (ie, normal optic disk, papilledema, disks with other abnormality) was calculated, and the DLS's performance to specifically detect papilledema and normal disks was evaluated in a one-vs-rest strategy using the AUC, sensitivity and specificity, with reference to expert neuro-ophthalmologists. Results: External testing was performed on 898 fundus photographs: 447 patients; mean age, 10.33 (231 patients ≤10 years of age; 216, 11-16 years); 558 normal disks, 254 papilledema, 86 other disk abnormalities. Overall multiclass accuracy of the DLS was 89.6% (range, 87.8%-91.6%). The DLS successfully distinguished “normal” from “abnormal” optic disks (AUC 0.99 [0.98-0.99]; sensitivity, 87.3% [84.9%-89.8%]; specificity, 98.5% [97.6%-99.6%]), and “papilledema” from “normal and other” (AUC 0.99 [0.98-1.0]; sensitivity, 98.0% [96.8%-99.4%]; specificity, 94.1% (92.4%-95.9%)]. Conclusions: Our DLS reliably distinguished papilledema from normal optic disks and other disk abnormalities in children, suggesting it could be utilized as a diagnostic aid for the assessment of optic nerve head appearance in the pediatric age group.

Published
2024

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