Mobile Medical Application for Cost-effective Strabismus Screening

Develop and evaluate a new smartphone based app to screen for and measure eye misalignment (strabismus). The investigators will validate the app against simulated strabismus of known magnitude and common clinical tests. They will evaluate the app as a screening tool in high risk populations, to determine the sensitivity and specificity. They hypothesize that the app can measure to within 2 units (prism diopters) of the ground truth, and that it will be correlated with gold standard tests.

Study Overview

• Status: Completed
• Conditions: Strabismus
• Intervention / Treatment: Other: EyeTurn App

Detailed Description

The goal of the proposed project is the development and evaluation of a novel mobile medical application for the detection and monitoring of strabismus (eye misalignment). The image analysis technology necessary to measure strabismus using the corneal reflection technique (Photographic Hirschberg Test) has been available for many decades, however it has never been deployed using a smart phone. A smart phone platform will eliminate barriers of cost (since the hardware is maintained and updated by the smart phone industry), leading to rapid wide spread application and allowing the technology to finally reach its potential level of impact for children's eye care in the detection and management of strabismus. Strabismus causes visual confusion and double vision which ultimately results in the brain suppressing vision from the deviated eye. In children this results in under-development (amblyopia) with permanent vision loss in the deviated eye if not detected and treated at a young age. Strabismus in children is also associated with coordination problems such as postural instability and severe social disadvantages. Strabismus develops in an estimated 3-8% of children in the U.S. The prototype smart phone app (Referred to here as the Mobile Eye Alignment App - MEAA), uses photographic analysis of the corneal reflection (Purkinjie image) generated by the smart phone camera flash. The corneal reflection method uses the displacement of the reflection from the center of the pupil in the deviated eye to calculate the amount of eye misalignment. This measurement technique will be deployed for the proposed project using the hardware of the iPhone, a popular phone with an iOS operating system. Preliminary results suggest the app can measure differences in eye alignment of 1.6° (2.8 prism diopters). If successfully developed, the app has potential to be utilized to advance pediatric strabismus research by facilitating and reducing the cost of collecting enormous amounts of data from the general population and under-served or remote populations for epidemiological studies, and allowing researchers to capture eye alignment data much more frequently than is currently possible. Such a tool could better delineate the natural history of strabismus and perhaps help determine its causes. While devices are available which could make these measurements, the costs are prohibitively high (>$3,000 ea.) and will not reach the widespread availability of smart phones. Clinical goals for the app are to provide eye doctors with an objective measurement tool in the exam room, allow daily monitoring of treatment effects, and eventually to be used as a screening tool by school nurses, pediatricians, and parents. The barriers to market success of stand-alone devices is not the accuracy sensitivity or specificity of photographic analysis technique which has been reported with sensitivity from 53% to near 90% and specificity ranging from 76% to 94% for strabismus detection. Impact of strabismus screening for the young - Early detection for strabismus in young children, especially during the critical period up to 2 years of age, is important to ensure that treatment is administered as soon as possible. The success of amblyopia treatment depends on several factors, but principally on the age of onset and the age at which the treatment is initiated. Therapy for amblyopia is maximally effective if started before age 3 and can be initiated as early as 8 months, underscoring the critical need for early and widespread access to strabismus screening. Indeed, countries with long-standing early vision screening programs have reported significantly reduced rates of amblyopia. Access to strabismus screening is also important for older, school age children (age 7-17) suffering from amblyopia, for whom treatment can lead to significant improvements in visual acuity ranging from 20%-70% of patients, depending on their age bracket.

Aims

AIM 1:

Develop and test key functionality of the strabismus app by comparing measurements with successive versions of the prototype app to known angles of eye deviation (non-strabismic volunteers will gaze at off axis targets of known eccentricity).

AIM 2:

Evaluate the strabismus app accuracy and feasibility in participants with strabismus tested with both the app and clinical methods and analyzed for levels of agreement.

Primary Hypothesis: For strabismus ranging from 1 to 30 prism diopters (target range), the optimized version of the app will provide measurements which are highly correlated with the ground truth (simulated strabismus) or clinical tests of eye alignment.

• Study Type: Observational
• Enrollment (Actual): 91
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • Massachusetts
    • Boston, Massachusetts, United States, 021141
      • Ophthalmology of Clinical Research Office, Mass Eye and Ear

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years to 84 years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes

• Sampling Method: Non-Probability Sample

Study Population

Normal vision participants with simulated strabismus and participants with strabismus.

Description

Inclusion Criteria:

Ground Truth Aim Study:

• Age 18 to 88 years
• Normal or corrected to normal vision

Clinical Aim Study:

• Ages 18 to 88
• Strabismus
• Able to keep looking at a visual target for 30-60 seconds

Exclusion Criteria:

Ground Truth Aim Study:

• Age less than 18 years or greater than 88.

Clinical Study:

• Age less than 18 or greater than 88
• Inability to keep looking at a visual target for 30-60 seconds

Study Plan

How is the study designed?

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort
Strabismus; Participants with strabismus had measurement with the app and compared to the cover test with prism neutralization (gold standard) or eye turning to know eccentricity.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Comparison of App-measured Eye Deviation Angles to Gold Standard	Linear regression analysis was used to compare the app measurements of strabismus angle to ground truth and gold standard measures. The outcome measure is the difference between the two methods, in terms of least square mean (LSM).	15 minutes

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Perceived Value Survey	A 10 point likert-type rating scale to quantify the perceived value (1 low value to 10 high value) of the app tele-strabismus consultation (a subaim in the clinical evaluation aim)	5 minutes after completion of the tele-strabismus consult
Test-Retest repeatability of the app	Strabismus angle	3 app measurements taken over approximately 1 minute
Robustness	calculation of the percentage of capture failures (capture failures/ total number of attempted image captures)	1 year

Collaborators and Investigators

• Sponsor: Massachusetts Eye and Ear Infirmary
• Collaborators: National Eye Institute (NEI)
• Investigators: Principal Investigator: Gang Luo, PhD, Massachusetts Eye and Ear

Publications and helpful links

General Publications

• Loudon SE, Rook CA, Nassif DS, Piskun NV, Hunter DG. Rapid, high-accuracy detection of strabismus and amblyopia using the pediatric vision scanner. Invest Ophthalmol Vis Sci. 2011 Jul 7;52(8):5043-8. doi: 10.1167/iovs.11-7503.
• Brodie SE. Photographic calibration of the Hirschberg test. Invest Ophthalmol Vis Sci. 1987 Apr;28(4):736-42.
• Rowe, F.J., Clinical Orthoptics. 3rd ed. 2012: Wiley and Sons. 486.
• Taylor K, Elliott S. Interventions for strabismic amblyopia. Cochrane Database Syst Rev. 2011 Aug 10;(8):CD006461. doi: 10.1002/14651858.CD006461.pub3.
• Barnard, S. and E. Johnson, Detecting strabismus. Optician, 2013.
• Klaver P, Marcar V, Martin E. Neurodevelopment of the visual system in typically developing children. Prog Brain Res. 2011;189:113-36. doi: 10.1016/B978-0-444-53884-0.00021-X.
• Williams C, Northstone K, Harrad RA, Sparrow JM, Harvey I; ALSPAC Study Team. Amblyopia treatment outcomes after screening before or at age 3 years: follow up from randomised trial. BMJ. 2002 Jun 29;324(7353):1549. doi: 10.1136/bmj.324.7353.1549.
• Epelbaum M, Milleret C, Buisseret P, Dufier JL. The sensitive period for strabismic amblyopia in humans. Ophthalmology. 1993 Mar;100(3):323-7. doi: 10.1016/s0161-6420(13)32170-8.
• Eibschitz-Tsimhoni M, Friedman T, Naor J, Eibschitz N, Friedman Z. Early screening for amblyogenic risk factors lowers the prevalence and severity of amblyopia. J AAPOS. 2000 Aug;4(4):194-9. doi: 10.1067/mpa.2000.105274.
• Lions C, Bui-Quoc E, Bucci MP. Postural control in strabismic children versus non strabismic age-matched children. Graefes Arch Clin Exp Ophthalmol. 2013 Sep;251(9):2219-25. doi: 10.1007/s00417-013-2372-x. Epub 2013 May 9.
• Scheiman MM, Hertle RW, Beck RW, Edwards AR, Birch E, Cotter SA, Crouch ER Jr, Cruz OA, Davitt BV, Donahue S, Holmes JM, Lyon DW, Repka MX, Sala NA, Silbert DI, Suh DW, Tamkins SM; Pediatric Eye Disease Investigator Group. Randomized trial of treatment of amblyopia in children aged 7 to 17 years. Arch Ophthalmol. 2005 Apr;123(4):437-47. doi: 10.1001/archopht.123.4.437.
• Hertle RW, Scheiman MM, Beck RW, Chandler DL, Bacal DA, Birch E, Chu RH, Holmes JM, Klimek DL, Lee KA, Repka MX, Weakley DR Jr; Pediatric Eye Disease Investigator Group. Stability of visual acuity improvement following discontinuation of amblyopia treatment in children aged 7 to 12 years. Arch Ophthalmol. 2007 May;125(5):655-9. doi: 10.1001/archopht.125.5.655.
• Lukman H, Kiat JE, Ganesan A, Chua WL, Khor KL, Choong YF. Negative social reaction to strabismus in school children ages 8-12 years. J AAPOS. 2011 Jun;15(3):238-40. doi: 10.1016/j.jaapos.2011.01.158. Epub 2011 Jun 16.
• Cotter SA, Tarczy-Hornoch K, Song E, Lin J, Borchert M, Azen SP, Varma R; Multi-Ethnic Pediatric Eye Disease Study Group. Fixation preference and visual acuity testing in a population-based cohort of preschool children with amblyopia risk factors. Ophthalmology. 2009 Jan;116(1):145-53. doi: 10.1016/j.ophtha.2008.08.031. Epub 2008 Oct 29.

Study record dates

Study Major Dates

• Study Start (Actual): February 1, 2018
• Primary Completion (Actual): December 30, 2019
• Study Completion (Actual): January 30, 2025

Study Registration Dates

• First Submitted: February 7, 2018
• First Submitted That Met QC Criteria: February 23, 2018
• First Posted (Actual): March 1, 2018

Study Record Updates

• Last Update Posted (Actual): July 14, 2025
• Last Update Submitted That Met QC Criteria: June 21, 2025
• Last Verified: June 1, 2025

More Information

Terms related to this study

• Keywords: Double Vision, Amblyopia
• Additional Relevant MeSH Terms: Nervous System Diseases; Eye Diseases; Cranial Nerve Diseases; Ocular Motility Disorders; Strabismus
• Other Study ID Numbers: 15-061H; 2R44EY025902-02 (U.S. NIH Grant/Contract)

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