An Assistant Model for IRD Care Needs: A Randomized Control Trial (IRD)

A Multi-stage Evaluation Foundation Model for Inherited Retinal Diseases Care Needs: A Randomized Control Trial

we present FM-IRD（also designated as Retina4IRD）, the first foundation model-based AI system specifically designed for genotype diagnosis of IRD by emulating clinician decision-making reasoning process. Retina4IRD is capable of processing multimodal input including color fundus photography (CFP), optical coherence tomography (OCT), and descriptive medical metadata. Trained and validated on genetically confirmed cases from centers across China, South Korea, and Poland, the system generates a ranked list of candidate pathogenic genetic variants. Retina4IRD also can generated attention heatmaps to enhance decision-making interpretability. To validate its clinical impact, we conducted a prospective multicenter RCT involving 295 participants, rigorously assessing Retina4IRD's diagnostic accuracy and real-world utility. This will improve the standardized diagnosis of IRD diseases, effectively transforming the traditional time-consuming and resource-intensive diagnostic pathway into an efficient intelligent workflow

Study Overview

• Status: Completed
• Conditions: Inherited Retinal Diseases
• Intervention / Treatment: Other: FM-IRDs assisted; Other: without FM-IRDs

Detailed Description

A randomized, controlled validation trial was conducted to evaluate the effectiveness of Retina4IRD (also designated as FM-IRD) in clinical settings. This trail was conducted at seven centers in China with large outpatient IRDs care .

Participants were recruited from the outpatient of IRD clinics of the participating centers, or through referrals from collaborating retinal specialists. Given that genetic testing results were unavailable at enrollment, and to prioritize the model's ability to identify patients with actionable therapeutic targets, genotypes of our randomized controlled trial were categorized into 17 classes, including mutations with available gene therapies or ongoing clinical trials. All participants provided written informed consent before enrolment assessments. All participants subsequently underwent WES testing to confirm the causative genetic mutations, which served as the gold standard for IRD gene mutation diagnosis.

• Study Type: Interventional
• Enrollment (Actual): 300
• Phase: Not Applicable

Contacts and Locations

Study Locations

• China
  • Shanghai, China
    • Shanghai General Hospital
  • Shanghai, China, 200080
    • Shanghai General Hospital, Shanghai Jiao Tong University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Presenting with clinical features suggestive of suspected IRD based on the initial assessment by the physician

Exclusion Criteria:

• Refusal to undergo WES genetic testing.
• Screening for a history of intraocular surgery in both eyes within the past 6 months;
• Subjects with severe systemic diseases, intellectual developmental disorders, psychiatric illnesses, etc.
• Patient data that the investigator deems necessary to exclude.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Retina4IRD(also designated as FM-IRDs) assisted arm; Arm A: In the diagnostic process of IRD, retinal specialists make diagnostic decision with the assistance of FM-IRDs.	Other: FM-IRDs assisted; A Foundation Model for Assisting the precision Diagnosis of Inherited Retinal Diseases: FM-IRDs
Active Comparator: specialist-only without AI assisted arm; Arm B: In the diagnostic process of IRD, retinal specialists make independent decision-making without the assistance of FM-IRDs.	Other: without FM-IRDs; without FM-IRDs

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The diagnostic accuracy of IRDs	The top-5 gene mutation prediction accuracy, which will be assessed after all participants of the study have had WES test	21 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Quality of the health management strategy	The secondary endpoint is defined as the quality of the health management strategy formulated for the top-one predicted genotype, which encompassed four dimensions: available interventions, recommended follow-up intervals, fertility counseling recommendations, and the necessity of multidisciplinary consultation. The quality of the strategy is evaluated using a comprehensive scoring system, which was developed by a panel of multiple experts. This system has a score range of 0 to 40, with higher scores indicating better outcomes. The final assessment is conducted independently by two senior IRD experts.	7 days

Collaborators and Investigators

• Sponsor: Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine
• Investigators: Principal Investigator: Xiaodong Sun, PhD, Shanhai General Hopsital

Study record dates

Study Major Dates

• Study Start (Actual): February 27, 2025
• Primary Completion (Actual): June 7, 2025
• Study Completion (Actual): July 1, 2025

Study Registration Dates

• First Submitted: February 11, 2025
• First Submitted That Met QC Criteria: February 20, 2025
• First Posted (Actual): February 21, 2025

Study Record Updates

• Last Update Posted (Actual): March 16, 2026
• Last Update Submitted That Met QC Criteria: March 12, 2026
• Last Verified: March 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Eye Diseases; Retinal Diseases
• Other Study ID Numbers: EyeFM-IRDs; 2022YFC2502800 (Other Grant/Funding Number: National Key R & D Program of China)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

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