Determination of the Sensitivity and Specificity of a Smartphone Application to Detect Retinoblastoma

This study seeks to determine whether a smartphone application called CRADLE (ComputeR Assisted Detection of LEukocoria) has the potential to improve the detection of leukocoria. There will be no impact on participants' health outcome.

This study will be performed in two parts, each with a distinct cohort of patients.

Part 1 will assess the feasibility of various techniques/conditions for using CRADLE within patients known to have leukocoria.

Part 2 will estimate the sensitivity and specificity of CRADLE to detect leukocoria (using the techniques selected from information gathered in Part 1) as compared to an ophthalmoscope, within patients referred to the clinic for suspected leukocoria.

PRIMARY OBJECTIVES:

• To determine the most effective usage of a camera phone application (CRADLE) to maximize detection of leukocoria in patients with retinoblastoma, congenital cataracts, and glaucoma.
• To estimate the sensitivity and specificity of a camera phone application (CRADLE) in detecting leukocoria.

Study Overview

• Status: Recruiting
• Conditions: Glaucoma, Congenital; Retinoblastoma; Cataracts Infantile; Leucocoria
• Intervention / Treatment: Other: CRADLE; Other: Red reflex testing

Detailed Description

This study will utilize three strata called Stratum I, Stratum II and Stratum III.

STRATUM I - Infants and children known to have leukocoria who have been diagnosed with retinoblastoma, cataracts or glaucoma or other eye conditions.

Participants enrolled on Stratum I of the study will have the CRADLE application used by the doctor during their appointment.

The participant will look straight forward while the doctor stands about 1-3 feet away holding the device that has the CRADLE application. He or she will slowly move the device up, down, middle, right, and left - both in a lit and dimmed room.

The participant will be videotaped and photographed during this appointment. The doctor will record the results as determined by CRADLE ("normal" or no leukocoria versus "abnormal" or positive for leukocoria).

STRATUM II - Infants and children who are referred to an eye doctor to evaluate for leukocoria.

Participants enrolled on Stratum II of the study will be asked to look straight forward while he or she uses the CRADLE application (using the best method determined from Stratum I). The doctor will also examine the participant's eyes with the ophthalmoscope method. The results from both CRADLE and the ophthalmoscope method will be recorded and compared (white eye present versus absent, and normal versus abnormal as described above).

STRATUM III - Infants and children receiving treatment for retinoblastoma. For participants enrolled on Stratum III, he or she will have the same procedures as described in Stratum II.

After receiving informed consent, participants will undergo evaluation by ophthalmoscope and CRADLE on Day 1. Stratum III participants only will also undergo CRADLE evaluation on Days 2, 3, and 4.

• Study Type: Interventional
• Enrollment (Estimated): 290
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Carlos Rodriguez-Galindo, MD; Phone Number: 866-278-5833; Email: referralinfo@stjude.org

Study Locations

• United States
  • Tennessee
    • Memphis, Tennessee, United States, 38105-2794
      • Recruiting
      • St. Jude Children's Research Hospital
      • Principal Investigator: Carlos Rodriguez-Galindo, MD
      • Contact: Carlos Rodriguez-Galindo; Phone Number: 866-278-5833; Email: referralinfo@stjude.org

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: No older than 7 years (Child)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria - Stratum I:

• Patient has been diagnosed with congenital or infantile cataracts, congenital glaucoma, or retinoblastoma, and is scheduled for a visit with an ophthalmologist at St. Jude Children's Research Hospital or University of Tennessee Hamilton Eye Institute.
• Patient with retinoblastoma is newly diagnosed, or has received < 2 cycles of chemoreductive therapy, and has not undergone enucleation.
• Patient with cataracts or glaucoma has not received any prior therapy.

Inclusion Criteria - Stratum II:

• Patient without prior diagnosis has been referred for ophthalmological evaluation, including leukocoria or other conditions.

Inclusion Criteria - Stratum III:

• Patient with retinoblastoma undergoing ocular salvage treatment.

Exclusion Criteria

• Prior treatment for cataracts or glaucoma
• Inability or unwillingness of research participant or legal guardian to consent.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Diagnostic
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Stratum I: Initial Evaluation Group; Initially, a small group of patients diagnosed with congenital or infantile cataracts, congenital glaucoma or retinoblastoma and who meet the eligibility criteria will undergo testing with CRADLE on Day 1.	Other: CRADLE; A smartphone software application designed to detect leukocoria using a sophisticated photoluminic analysis. The investigator or designee will perform tests with CRADLE in separate patient cohorts with known diagnosis of retinoblastoma, congenital glaucoma, or cataracts.; Other Names: Smartphone application; ComputeR Assisted Detection of LEukocoria
Experimental: Stratum II: Leukocoria Evaluation Group; A separate group of participants who are referred for evaluation of leukocoria or any other eye condition will undergo red reflex testing testing with CRADLE on Day 1.	Other: CRADLE; A smartphone software application designed to detect leukocoria using a sophisticated photoluminic analysis. The investigator or designee will perform tests with CRADLE in separate patient cohorts with known diagnosis of retinoblastoma, congenital glaucoma, or cataracts.; Other Names: Smartphone application; ComputeR Assisted Detection of LEukocoria; Other: Red reflex testing; Traditional red reflex testing for leukocoria using a direct ophthalmoscope on routine eye examination. Red reflex testing via direct ophthalmoscope will be performed before dilation, using the ophthalmoscope held close to the examiner's eye, focused on the pupil, viewed at 12 to 18 inches from the patient's eyes, with the room lights dimmed, in accordance with the American Academy of Pediatrics guidelines.; Other Names: Ophthalmoscopic exam
Experimental: Stratum III: Retinoblastoma Group; A separate group of participants with known retinoblastoma and who are undergoing ocular salvage treatments will be screened with red reflex testing using direct ophthalmoscopy on Day 1. They will also undergo testing with the CRADLE software application defined as the most effect in Stratum I on Day 1 then for three additional consecutive visits which typically occur every 3 to 4 weeks.	Other: CRADLE; A smartphone software application designed to detect leukocoria using a sophisticated photoluminic analysis. The investigator or designee will perform tests with CRADLE in separate patient cohorts with known diagnosis of retinoblastoma, congenital glaucoma, or cataracts.; Other Names: Smartphone application; ComputeR Assisted Detection of LEukocoria; Other: Red reflex testing; Traditional red reflex testing for leukocoria using a direct ophthalmoscope on routine eye examination. Red reflex testing via direct ophthalmoscope will be performed before dilation, using the ophthalmoscope held close to the examiner's eye, focused on the pupil, viewed at 12 to 18 inches from the patient's eyes, with the room lights dimmed, in accordance with the American Academy of Pediatrics guidelines.; Other Names: Ophthalmoscopic exam

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Rate of detection of leukocoria using CRADLE	This outcome will assess the feasibility of various techniques and conditions for using CRADLE in participants with retinoblastoma, congenital cataracts, and glaucoma. The most effective usage of CRADLE to maximize detection of leukocoria will be determined by review of all images, and the most effective and efficient technique will be selected based on the findings and the clarity of the images. This technique will be used for completion of the subsequent objectives using a new cohort of participants.	Day 1
Sensitivity of CRADLE versus ophthalmoscope to detect leukocoria	The test results obtained by CRADLE will be compared to those obtained by ophthalmoscopic examination to determine the effectiveness of detection of leukocoria by CRADLE. The results will be reported as number of true positive. An ideal test for sensitivity has no false positives.	Up to Day 4
Specificity of CRADLE versus ophthalmoscope to detect leukocoria	The test results obtained by CRADLE will be compared to those obtained by ophthalmoscopic examination to determine the effectiveness of detection of leukocoria by CRADLE. The results will be reported as number of false negatives (specificity). An ideal test for sensitivity has no false negatives.	Up to Day 4

Collaborators and Investigators

• Sponsor: St. Jude Children's Research Hospital
• Investigators: Principal Investigator: Carlos Rodriguez-Galindo, MD, St. Jude Children's Research Hospital

Publications and helpful links

Helpful Links

• St. Jude Children's Research Hospital
• Clinical Trials Open at St. Jude

Study record dates

Study Major Dates

• Study Start (Actual): March 15, 2018
• Primary Completion (Estimated): July 30, 2025
• Study Completion (Estimated): July 30, 2026

Study Registration Dates

• First Submitted: December 28, 2016
• First Submitted That Met QC Criteria: January 6, 2017
• First Posted (Estimated): January 10, 2017

Study Record Updates

• Last Update Posted (Actual): August 16, 2023
• Last Update Submitted That Met QC Criteria: August 14, 2023
• Last Verified: August 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Neoplasms by Site; Neoplasms, Glandular and Epithelial; Eye Diseases; Congenital Abnormalities; Ocular Hypertension; Eye Abnormalities; Glaucoma, Open-Angle; Infant, Newborn, Diseases; Retinal Diseases; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms, Nerve Tissue; Eye Diseases, Hereditary; Lens Diseases; Eye Neoplasms; Retinal Neoplasms; Glaucoma; Hydrophthalmos; Cataract; Retinoblastoma
• Other Study ID Numbers: RBAPP; NCI-2021-05557 (Registry Identifier: NCI)

Drug and device information, study documents

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