AI-Assisted Interpretation of Ultra-Widefield Retinal Images

Prospective Multi-Center Evaluation of AI-Assisted Interpretation of Ultra-Widefield Retinal Images in a Multi-Reader Crossover Study

The goal of this prospective observational study is to evaluate the impact of artificial intelligence (AI) assistance on clinician interpretation of ultra-widefield (UWF) retinal images.

The main questions it aims to answer are:

whether AI assistance improves the diagnostic performance of ophthalmologists in detecting retinal findings on UWF retinal images; whether AI assistance improves sensitivity, specificity, and inter-reader agreement across clinicians with different levels of experience.

Approximately 600 UWF retinal images prospectively collected from multiple ophthalmic centers in China will be included. Images will be independently annotated by expert retinal specialists to establish reference labels for retinal finding categories.

Four ophthalmologists with different levels of clinical experience, including one senior retinal specialist and three junior ophthalmologists, will participate in a crossover multi-reader study.

For each clinician, the dataset will be randomly divided into two equal subsets. During the first reading session, clinicians will evaluate one subset without AI assistance and the other subset with AI assistance. After a washout interval of at least two weeks, the reading conditions will be reversed in a second reading session with independently randomized image order.

Under the AI-assisted condition, clinicians will be provided with category-level AI prediction probabilities for retinal findings. No localization maps, heatmaps, segmentation overlays, or automated diagnostic recommendations will be displayed. Clinicians will retain full autonomy over final decisions.

Reader performance under AI-assisted and unaided conditions will be compared using expert reference annotations as the ground truth.

Study Overview

• Status: Completed
• Conditions: Retinal Disease
• Intervention / Treatment: Device: AI-Assisted Interpretation; Device: Unaided Interpretation

Detailed Description

This study is a prospective multi-center observational reader study designed to evaluate the impact of artificial intelligence (AI) assistance on clinician interpretation of ultra-widefield (UWF) retinal images.

Approximately 600 UWF retinal images will be prospectively collected from multiple ophthalmic centers in China. Images will be acquired using clinically routine UWF retinal imaging systems and will include a broad spectrum of retinal diseases and retinal findings encountered in real-world clinical practice.

All images will undergo independent expert annotation by retinal specialists to establish reference labels for retinal finding categories. These expert annotations will serve as the reference standard for subsequent performance evaluation.

Four ophthalmologists with different levels of clinical experience will participate in the reader study, including:

one senior retinal specialist with approximately five years of retinal clinical experience; three junior ophthalmologists with approximately two years of ophthalmology residency training.

A randomized crossover multi-reader design will be implemented to minimize recall bias and balance reading conditions.

For each clinician, the image dataset will be randomly divided into two equal subsets (subset A and subset B; approximately 300 images each).

During Round 1:

subset A will be interpreted without AI assistance; subset B will be interpreted with AI assistance.

After a washout interval of at least two weeks, the reading conditions will be reversed during Round 2:

subset A will be interpreted with AI assistance; subset B will be interpreted without AI assistance.

Image order will be independently randomized for each session and each clinician.

Under the unaided condition, clinicians will evaluate retinal images using standard clinical interpretation without AI output.

Under the AI-assisted condition, clinicians will receive category-level AI prediction probabilities for retinal finding categories. The AI output will provide probabilistic confidence scores only and will not include lesion localization maps, heatmaps, segmentation overlays, or automated binary recommendations.

Clinicians will remain blinded to the expert reference labels and to the interpretations of other readers. Final diagnostic decisions will be independently determined by each clinician.

The primary analysis will compare diagnostic performance between unaided and AI-assisted conditions, including sensitivity, specificity, area under the receiver operating characteristic curve (AUC), and inter-reader agreement.

• Study Type: Observational
• Enrollment (Actual): 462

Contacts and Locations

Study Locations

• China
  • Chongqing Municipality
    • Chongqing, Chongqing Municipality, China
      • Chongqing Huaxia Eye Hospital
  • Fujian
    • Fuzhou, Fujian, China, 361000
      • Fuzhou Eye Hospital
    • Xiamen, Fujian, China, 361000
      • Xiamen Eye Center of Xiamen University
  • Hebei
    • Hengshui, Hebei, China
      • Hengshui Tongrui Eye Hospital
  • Shandong
    • Heze, Shandong, China
      • Heze Huaxia Eye Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: Yes

• Sampling Method: Non-Probability Sample

Study Population

Participants undergoing clinically indicated ultra-widefield retinal imaging at participating ophthalmic centers in China, including individuals with diverse retinal diseases and retinal findings encountered in real-world clinical practice.

Description

Inclusion Criteria:

• Participants undergoing ultra-widefield retinal imaging at participating ophthalmic centers;

Exclusion Criteria:

• Poor-quality or ungradable retinal images;

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
AI-Assisted Interpretation; Clinicians interpret ultra-widefield retinal images with access to AI-generated category-level prediction probabilities for retinal findings.	Device: AI-Assisted Interpretation; Clinicians interpret ultra-widefield retinal images with access to AI-generated category-level prediction probabilities for retinal findings.
Unaided Interpretation; Clinicians interpret ultra-widefield retinal images without AI assistance using routine retinal image interpretation alone.	Device: Unaided Interpretation; Clinicians interpret ultra-widefield retinal images without AI assistance using routine retinal image interpretation alone.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Sensitivity for retinal finding detection	Sensitivity of clinicians in detecting retinal finding categories under AI-assisted and unaided conditions using expert annotations as the reference standard.	through study completion, an average of 2 months
Specificity for retinal finding detection	Specificity of clinicians in detecting retinal finding categories under AI-assisted and unaided conditions.	through study completion, an average of 2 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Area under the receiver operating characteristic curve (AUC)	The AUC quantifies the overall ability to correctly distinguish the presence versus absence of predefined retinal findings on ultra-widefield retinal images. AUC values range from 0.5 (no discriminative ability) to 1.0 (perfect discrimination). Clinician interpretations will be compared with an expert-adjudicated reference standard under AI-assisted and unaided conditions.	through study completion, an average of 2 months
Inter-reader agreement	Agreement among participating clinicians in classifying predefined retinal findings on ultra-widefield retinal images. Agreement will be quantified using Cohen's kappa coefficient (for pairwise comparisons) or Fleiss' kappa coefficient (for multiple readers). Kappa values range from 0 (no agreement beyond chance) to 1 (perfect agreement).	At study completion (up to 3 months)
Diagnostic performance improvement among junior ophthalmologists	Improvement in diagnostic performance of junior ophthalmologists when interpreting ultra-widefield retinal images with AI assistance compared with unaided interpretation, measured by changes in sensitivity, specificity, accuracy, and AUC using the expert-adjudicated reference standard.	At study completion (up to 3 months)

Collaborators and Investigators

• Sponsor: Xiamen Ophthalmology Center Affiliated to Xiamen University
• Investigators: Principal Investigator: Xiuju Chen, Xiamen Eye Center of Xiamen University

Study record dates

Study Major Dates

• Study Start (Actual): January 1, 2026
• Primary Completion (Actual): February 1, 2026
• Study Completion (Actual): February 10, 2026

Study Registration Dates

• First Submitted: June 5, 2026
• First Submitted That Met QC Criteria: June 10, 2026
• First Posted (Actual): June 16, 2026

Study Record Updates

• Last Update Posted (Actual): June 16, 2026
• Last Update Submitted That Met QC Criteria: June 10, 2026
• Last Verified: June 1, 2026

More Information

Terms related to this study

• Keywords: Artificial Intelligence; Retinal Imaging; Reader Study; Diagnostic Performance; AI-Assisted Diagnosis; Ultra-Widefield Imaging
• Additional Relevant MeSH Terms: Eye Diseases; Retinal Diseases
• Other Study ID Numbers: XMYKZX-KY-2026-008

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: De-identified individual participant data underlying the results reported in this study, including retinal imaging data and associated annotations, may be made available upon reasonable request to the corresponding investigator following publication, subject to institutional ethics approval, data-sharing agreements, and applicable data governance and privacy regulations.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No