Multimodal Characterization of Radiation-Induced Optic Neuropathy after Proton Radiotherapy
Abstract
Purpose: To evaluate the performance of multimodal ophthalmologic assessment compared with current visual acuity (VA)-based on Common Terminology Criteria for Adverse Events classification evaluation of radiation-induced optic neuropathy (RION) severity grade and to describe the relative prominence of functional, electrophysiological, and structural changes across postradiotherapy time windows. Design: Prospective cohort study. Subjects: Patients treated with proton radiotherapy for brain, skull base, or head-and-neck tumors between 2018 and 2023 who underwent standardized baseline and longitudinal ophthalmologic evaluations. Eyes with preexisting optic neuropathy were excluded. Of 238 patients, 89 met inclusion criteria (full assessment, no baseline deficit); 39 developed clinically diagnosed RION during follow-up. Methods: Participants underwent repeated assessments including best-corrected VA (ETDRS), visual field (VF) perimetry (mean deviation [MD] and pattern standard deviation [PSD]), spectral-domain OCT retinal nerve fiber layer (RNFL) thickness, and pattern-reversal visual evoked potentials (VEPs) (P100 latency and amplitude). The median follow-up after proton radiotherapy was 3.83 (2.94-4.75) years. Single-variable and multivariable decision tree models were constructed to identify RION. Random forest models quantified feature importance and temporal dynamics across predefined postradiotherapy intervals (0-0.5, 0.5-1, 1-2, and 2-5 years). Main Outcome Measures: Model performance (accuracy and F1 score) for identification of clinically diagnosed RION and relative importance of ophthalmologic parameters over time. Results: Of 39 patients with RION and 50 without, VF MD and PSD demonstrated the strongest individual performance for RION identification (accuracy 75%-79%; F1 score 0.78-0.81), outperforming VA, RNFL thickness, and VEP measures. The multimodal model combining all assessments achieved higher apparent-sample performance (accuracy 81.7% [95% confidence interval (CI), 73.9%-88.1%]; F1 score 0.83 [95% CI, 0.75-0.89]); cross-validated performance was more modest (mean area under the curve 0.64). Random forest analyses identified VF MD as the most influential parameter, followed by VEP measures and longitudinal RNFL change. Within the first year after radiotherapy, functional (VF) and electrophysiological (VEP) abnormalities were more prominent, whereas structural RNFL thinning became more evident between 1 and 2 years. Cross-sectional differences in VA were limited. Conclusions: In patients with clinically diagnosed RION after proton radiotherapy, functional alterations predominated during the first year after treatment, whereas structural RNFL thinning became evident in the second year. Visual field-based assessment demonstrated greater sensitivity than VA-based grading alone; the cross-validated multimodal model achieved modest performance and did not clearly outperform VF testing alone. These findings should be considered hypothesis-generating. Prospective validation in larger cohorts is warranted. Financial Disclosures: The author has no/the authors have no proprietary or commercial interest in any materials discussed in this article.
Related
- Characterization of Radiation-Induced Errors in Superconducting Qubits Protected with Various Gap-Engineering Strategies
- Impact of phantom design on fetal radiation exposure assessment in pregnant women undergoing head and neck 6MV photon radiotherapy
- Radiation therapy quality assurance (RT QA) of adjuvant fractionated radiotherapy for WHO grade 2 atypical meningioma in the ROAM/EORTC1308 trial
- GammaTile® Brachytherapy as Spatially Fractionated Radiation Therapy for Postoperative Brain Cancer: A Paradigm for Precision Intracranial Radiotherapy
- Characterization and Validation of MicroDiamond Detectors in Patient-specific Quality Assurance of Magnetic Resonance-guided Stereotactic Radiotherapy
BibTeX
@article{thariat2026multimodal,
title = {{Multimodal Characterization of Radiation-Induced Optic Neuropathy after Proton Radiotherapy}},
author = {Juliette Thariat and Thao-Nguyen Pham and Thibaud Mathis and Dorothee Lebhertz and Jean-Claude Quintyn},
journal = {Ophthalmology Science},
year = {2026},
month = sep,
doi = {10.1016/j.xops.2026.101359},
url = {https://hal.science/hal-05762847v1},
note = {CC BY},
}
RIS
TY - JOUR
TI - Multimodal Characterization of Radiation-Induced Optic Neuropathy after Proton Radiotherapy
AU - Juliette Thariat
AU - Thao-Nguyen Pham
AU - Thibaud Mathis
AU - Dorothee Lebhertz
AU - Jean-Claude Quintyn
PY - 2026
DA - 2026/09/24
JO - Ophthalmology Science
DO - 10.1016/j.xops.2026.101359
UR - https://hal.science/hal-05762847v1
AB - Purpose: To evaluate the performance of multimodal ophthalmologic assessment compared with current visual acuity (VA)-based on Common Terminology Criteria for Adverse Events classification evaluation of radiation-induced optic neuropathy (RION) severity grade and to describe the relative prominence of functional, electrophysiological, and structural changes across postradiotherapy time windows. Design: Prospective cohort study. Subjects: Patients treated with proton radiotherapy for brain, skull base, or head-and-neck tumors between 2018 and 2023 who underwent standardized baseline and longitudinal ophthalmologic evaluations. Eyes with preexisting optic neuropathy were excluded. Of 238 patients, 89 met inclusion criteria (full assessment, no baseline deficit); 39 developed clinically diagnosed RION during follow-up. Methods: Participants underwent repeated assessments including best-corrected VA (ETDRS), visual field (VF) perimetry (mean deviation [MD] and pattern standard deviation [PSD]), spectral-domain OCT retinal nerve fiber layer (RNFL) thickness, and pattern-reversal visual evoked potentials (VEPs) (P100 latency and amplitude). The median follow-up after proton radiotherapy was 3.83 (2.94-4.75) years. Single-variable and multivariable decision tree models were constructed to identify RION. Random forest models quantified feature importance and temporal dynamics across predefined postradiotherapy intervals (0-0.5, 0.5-1, 1-2, and 2-5 years). Main Outcome Measures: Model performance (accuracy and F1 score) for identification of clinically diagnosed RION and relative importance of ophthalmologic parameters over time. Results: Of 39 patients with RION and 50 without, VF MD and PSD demonstrated the strongest individual performance for RION identification (accuracy 75%-79%; F1 score 0.78-0.81), outperforming VA, RNFL thickness, and VEP measures. The multimodal model combining all assessments achieved higher apparent-sample performance (accuracy 81.7% [95% confidence interval (CI), 73.9%-88.1%]; F1 score 0.83 [95% CI, 0.75-0.89]); cross-validated performance was more modest (mean area under the curve 0.64). Random forest analyses identified VF MD as the most influential parameter, followed by VEP measures and longitudinal RNFL change. Within the first year after radiotherapy, functional (VF) and electrophysiological (VEP) abnormalities were more prominent, whereas structural RNFL thinning became more evident between 1 and 2 years. Cross-sectional differences in VA were limited. Conclusions: In patients with clinically diagnosed RION after proton radiotherapy, functional alterations predominated during the first year after treatment, whereas structural RNFL thinning became evident in the second year. Visual field-based assessment demonstrated greater sensitivity than VA-based grading alone; the cross-validated multimodal model achieved modest performance and did not clearly outperform VF testing alone. These findings should be considered hypothesis-generating. Prospective validation in larger cohorts is warranted. Financial Disclosures: The author has no/the authors have no proprietary or commercial interest in any materials discussed in this article.
SN - 2666-9145
ER -