# Using multimodal imaging to improve the diagnostic accuracy and confidence in distinguishing non-arteritic anterior ischemic optic neuropathy from optic disc drusen

**Authors:** Min Young Kim, Anas Alkhabaz, Miaomiao Yu, Rishita Pujari, Yaping Joyce Liao

PMC · DOI: 10.3389/fneur.2026.1653402 · Frontiers in Neurology · 2026-02-10

## TL;DR

This study shows that using multiple types of eye imaging improves doctors' ability to correctly diagnose optic nerve swelling and distinguish it from similar-looking conditions.

## Contribution

The study demonstrates that multimodal imaging significantly improves diagnostic accuracy and confidence in differentiating NAION from ODD and controls.

## Key findings

- Multimodal imaging achieved 93.4% accuracy for NAION, 90.5% for ODD, and 99.5% for controls.
- Combining color fundus and RNFL imaging improved NAION accuracy to 88.1%.
- Diagnostic confidence for NAION increased from 3-37% with single modality to 28-82% with multimodal imaging.

## Abstract

Optic nerve head elevation (ONHE) is a common diagnostic challenge in the general eye clinic. When caused by optic disc edema (ODE), ONHE may signal a neuro-ophthalmic emergency requiring urgent and invasive evaluation, whereas pseudoedema typically does not. This study evaluated whether multimodal oph¬thalmic imaging improves diagnostic accuracy and confidence in distinguishing nonarteritic anterior ischemic optic neuropathy (NAION), used as a model of true ODE, from optic disc drusen (ODD), a common cause of pseudoedema.

We prospectively collected multimodal ophthalmic images using fundus color, near-infrared reflectance (NIR), fundus autofluorescence (FAF), and spectral-domain optical coherence tomography (OCT) optic nerve head and retinal nerve fiber layer (RNFL) analysis from 98 subjects (149 eyes: 60 NAION, 59 ODD, 30 controls). After a two-hour training session with a neuro-ophthalmologist, two masked medical trainees (a senior medical student and a recent medical gradu¬ate) independently reviewed single-, dual-, or multimodal image sets using a 0–5 confidence-weighted scale to assess for NAION, ODD, and control. Diagnostic accuracy was calculated using a weighted scoring system that penalized uncer¬tainty and misclassification. Confidence levels were categorized as high (defi¬nite), medium (likely), or low (maybe).

Among single imaging modalities, NAION diagnostic accuracy was highest with RNFL (83.2%) and color fundus imaging (80.9%), and lowest with FAF (65.4%). Combining color + RNFL improved accu¬racy to 88.1%. For ODD, FAF alone yielded the highest accuracy of 82.3%. The diagnostic accuracy of control images was consistently high across all single modalities (84.2 to 93.8%). Multimodal imaging produced the highest accuracy overall (NAION 93.4%, ODD 90.5%, controls 99.5%). The highest improvement using multimodal imaging was in NAION diagnostic confidence, which improved from 3 to 37% with single modality to 28 to 82% with multimodal imaging. We used mixed ANOVA and chi-square tests to evaluate diagnostic accuracy and grader confidence across modalities.

Brief training combined with multimodal imaging significantly improved diagnostic accuracy and confidence in differentiating NAION, ODD, and healthy controls. These findings support the potential clinical value of multimodal imaging in urgent-care settings where rapid and reliable evaluation of ONHE is essential.

## Linked entities

- **Diseases:** nonarteritic anterior ischemic optic neuropathy (MONDO:0000499)

## Full-text entities

- **Genes:** USP9X (ubiquitin specific peptidase 9 X-linked) [NCBI Gene 8239] {aka DFFRX, FAF, FAF-X, FAM, MRX99, MRXS99F}
- **Diseases:** medium to (MESH:C536038), neurologic deficit (MESH:D009461), pseudopapilledema (MESH:C562401), congenital optic disc anomalies (MESH:C566924), obstructive sleep apnea (MESH:D020181), hemorrhage (MESH:D006470), myopic degeneration (MESH:D001251), glaucoma (MESH:D005901), optic neuritis (MESH:D009902), infection (MESH:D007239), ODD (MESH:D015594), tumor (MESH:D009369), ischemic (MESH:D002545), ischemic damage (MESH:D017202), IIH (MESH:D011559), vascular conditions (MESH:D002561), edema (MESH:D004487), headache (MESH:D006261), ODE (MESH:D010211), optic nerve edema (MESH:D000080344), vessel vasculitis (MESH:D014657), AION (MESH:D018917), anomalous optic discs (MESH:D009901), vision loss (MESH:D014786), drusen (MESH:D015593), ONHE (MESH:D006259), giant cell arteritis (MESH:D013700)
- **Species:** Homo sapiens (human, species) [taxon 9606]

## Full text

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## Figures

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## References

46 references — full list in the complete paper: https://tomesphere.com/paper/PMC12929115/full.md

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Source: https://tomesphere.com/paper/PMC12929115