Purpose of the Study/Objectives
The objective of this reliability study is to successfully develop a mechanism for diagnostics of Relative Afferent Pupillary Defect (RAPD) using pupil measurement values and pathologic response. The diagnostics of this test will later be compared with the traditional swinging flashlight test results. The physiological basis of the study is that the reaction of the pupils in the right and left eyes are linked. When a bright light is shone into one eye, it will lead to an equal constriction of both pupils. When the light source is removed from the eye, the pupils will enlarge equally.
Our hypothesis is difference between pupil measurement values of two eyes when the light source moves from one eye to the other is an indicator of RAPD. This reliability study is to use a commercially-available, off-the-shelf virtual reality (VR) head-mounted display (HMD) and machine learning (ML) algorithms to detect RAPD at an earlier stage with small differences in pupil measurement values. The RAPD is a critically important sign in patients with unexplained visual loss because it is an objective finding of afferent pupillary dysfunction. The research question is if the proposed use of VR and ML to replace the swinging flashlight test provides a more reliable and objective pupil measurement to detect RAPD.
Background
A relative afferent pupillary defect (RAPD) is a critically important ophthalmologic examination finding that defines a defect (lesion) in the pupil pathway on the afferent side. A RAPD is relative to the fellow eye and occurs because of the bilateral and equal innervation of the pupils in normal individuals. The RAPD manifests as a difference in pupillary light reaction between the two eyes. The test requires two eyes but only one working pupil.
In a normal patient without afferent pupillary disease, shining a light in either eye will produce constriction of both eyes equally. In the case of an afferent pupillary pathway lesion, the light response is tested individually in each eye and then the light swings between the two eyes to detect RAPD. The normal pupillary response is characterized by equal constriction of the pupils in both eyes when the light stimulus is applied to each eye individually and no dilation or pupillary escape when the light swings from the one eye to the fellow eye. The pathologic response that characterizes the RAPD includes the following: (1) the light reaction causes pupil constriction in both eyes when the light shines in the normal eye, and (2) dilatation of the pupils in both eyes when the light stimulus is rapidly transferred from the normal eye to the pathologic eye.
Study Design
The study design is a reliability study evaluating the performance of the HTC Vive Pro Eye, to detect RAPD. The HTC Vive Pro Eye (product name) is not an experimental device. It is a consumer-grade VR HMD available as an off-the-shelf VR Headset. To validate the ability of the VR HMD to detect RAPD in patients, a reliability study will be performed by using the device on patients with known RAPD and patients without RAPD. Participants will undergo manual pupil measurement in the eye clinic via penlight for direct and swinging light test reflexes. Patients then will undergo the VR HMD eye measurements as discussed previously.
The anticipated total number of participants for this study is 120 patients aged 18 to 85, consisting of 60 participants in the control group (no known RAPD) and 60 participants in the experimental group (known RAPD). Both groups will undergo the traditional swinging flashlight test and testing with the VR HMD.
Medical Records will be used to obtain ocular imaging, pupil measurements, past medical history and past ocular history. Demographic information will be obtained through a self-reporting survey for age, gender and ethnicity. Data will be acquired by using the VR HMD. The protocol presents light through the VR HMD displays to each eye individually and will use participants' pupil diameters via its integrated eye tracking cameras to collect information about pupillary reflex deficit. Data from visual function tests such as visual acuity, visual field, chromatic sensitivity, etiology of RAPD etc. will be taken from the EPIC (product name) electronic medical record (EMR) to compare with current study findings.
This research will include records of participants' voices or images. Video of the pupils of the participant and their gaze location may be recorded via VR device for research purpose. Audio, video or photographs may be recorded for publication purposes. Subject identity will be removed from the audio, video and photographs. Informed Consent Form will ask the subject for their permission to be photographed or audio/video recorded.
Principal Investigator (PI) and researchers will ensure that all study personnel are informed about the research plan and their research-related duties by routine meetings, regular communication via email and phone. All researchers will take the human subject protection training sanctioned by the university via Collaborative Institutional Training Initiative (CITI) Program training.
A counterbalanced repeated measures experimental design will be used to compare participant performance in two conditions: using traditional swinging flashlight test versus using pupil measurement head-mounted display. The independent variable in the study will be modes (2 conditions) and the measured dependent variables (1 condition) will be RAPD.
Study Intervention
The study intervention that is being evaluated is whether virtual reality testing through a VR HMD device can adequately diagnose RAPD.
Each participant will undergo the standard of care swinging flashlight test to diagnose RAPD by their treating ophthalmologist, an IRB approved study team member, at their regular clinic visit, prior to participation in the study. If the patient elects to participate in the study, participates in the consent process and signs the Informed Consent Form, he or she will undergo a repeat of the standard of care swinging flashlight test, then participant will undergo testing with the VR HMD. Data on each participant's pupil sizes in both light and dark simulations is measured and coded. The VR HMD pupil measurement device is a consumer-grade virtual reality headset available as an off-the-shelf gaming product. The risk of using the device is minimal and no greater than the standard of care swinging flashlight test. The device uses illumination of less than 90 cd/m2 which is below and in accordance with the typical flashlight exposure of 100 cd/m2. There is therefore no disproportionate increase in risk. The device's maximum illumination is well below the threshold which would be of potential risk of harm. Risk of loss of private health information (PHI) is minimized by the manner with which the data will be stored.
At the acquisition time, subjects will be assigned a study identification number. That number will be recorded on a subject identity master key, along with the subject's medical record number (MRN). Once the subject identity master key has been created and stored separately from study data in a password protected file on the University of Texas Medical Branch's (UTMB's) secure server behind a firewall. All identifying information will then be removed from the subject's data. The deidentified data will then be stored in a secure folder on the UTMB secure server behind a firewall and that of the collaborating site (University of Nevada, Reno) computer behind a firewall.
The total testing should take approximately 10-30 minutes. After each participant has their standard of care ophthalmology visit with their treating ophthalmologist, an Institutional Review Board- (IRB-) approved study team member, consent will be obtained by an IRB-approved study team member, who has been properly trained and designated by the PI to obtain consent. If the patient consents, they will undergo a repeat of the swinging light test and their pupil measurements recorded manually. Then the subject will undergo testing with the VR HMD during which the device will take pupillary measurements lasting approximately five minutes. No follow-up appointments for research purposes are necessary.
Subjects will be recruited from the UTMB eye clinic. Subjects' participation is limited to one visit. Study enrollment is anticipated to take six months. The duration of the study is estimated to be two years.
