Objectively Diagnose and Monitor Treatment of Light Sensitivity

Use of Facial Feature to Objectively Diagnose and Monitor Treatment of Light Sensitivity

The purpose of this project is to provide a new framework for diagnosing and monitoring treatment of light sensitivity and headache by objective measurement of facial features, pupil responses, retinal electrical responses and autonomic nerve responses to light.

Study Overview

• Status: Recruiting
• Conditions: Migraine; Traumatic Brain Injury; Photophobia
• Intervention / Treatment: Device: Pupillography; Device: Ocular Coherence Tomography (OCT); Device: Wrist-watch sensor device; Device: Videography; Device: Electrophysiology

Detailed Description

Using objecting measurement of facial features, pupil responses, retinal electrical responses and autonomic nerve responses to light this project aims to provide a new framework for diagnosing and monitoring treatment of light sensitivity. The patient's responses will be measured with videography facial muscle electrical responses Electromyogram (EMG) measured from surface skin electrodes and retinal electrical responses (EMG) or electroretinogram (ERG) recorded from a portable hand-held device). Simultaneously, patient's will have their heart rate and skin conductance objectively monitored using wristwatch devices (E4, Empatica). If successful, this will open an immediate new way to objectively assess the mechanisms that lead to light sensitivity, and provide an approach to effectively treat, and manage the symptoms of light sensitivity and headache from different causes, including traumatic brain injury (TBI) and migraine.

• Study Type: Interventional
• Enrollment (Estimated): 120
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Julie Nellis, BSN; Phone Number: 319-356-2780; Email: julie-nellis@uiowa.edu
• Study Contact Backup: Name: Jan Full, BSN; Phone Number: 3193562780; Email: jan-full@uiowa.edu

Study Locations

• United States
  • Iowa
    • Iowa City, Iowa, United States, 52242
      • Recruiting
      • University of Iowa Health Care

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes

Description

Healthy Control subjects:

Inclusion Criteria

• Healthy individuals with normal eye exam in the previous year
• Age 18-80

Exclusion Criteria

• History of eye or systemic disorder that affect the retina, optic nerve, visual pathway, or pupil defect: including glaucoma, optic neuropathy, or retinal disease, diabetes and/or hypertension that are not well controlled, history of head trauma, concussion, or TBI, history of cervical or spinal injury/surgery
• Medications or eyedrops that would confound measuring the pupil light reflex and EMG: including topical autonomic drugs that could influence pupil size, ocular pharmacologic agents, sedative agents (e.g. benzodiazepines or barbiturates), opioid narcotics
• Must not be light sensitive or get migraine headaches

TBI patients without photosensitivity or headache:

Inclusion Criteria

• Age 18-80
• Traumatic Brain Injury (TBI)

Exclusion Criteria

• History of eye or systemic disorder that affect the retina, optic nerve, visual pathway, or pupil defect: including glaucoma, optic neuropathy, or retinal disease, diabetes and/or hypertension that are not well controlled
• Medications or eyedrops that would confound measuring the pupil light reflex and EMG: including topical autonomic drugs that could influence pupil size, ocular pharmacologic agents, sedative agents (e.g. benzodiazepines or barbiturates), opioid narcotics - Must not be light sensitive or get migraine headaches (use headache criteria from Ana if we are including headaches)

Patients with photosensitivity from non-TBI causes Inclusion Criteria

• Age 18-80
• Photosensitivity: determined by patient reporting symptoms and there may or may not be an identified cause associated with their light sensitivity (i.e. history of uveitis, childhood exotropia, meningitis, radiation, tumor)

Exclusion Criteria

• History of eye or systemic disorder that affect the retina, optic nerve, visual pathway, or pupil defect: including glaucoma, optic neuropathy, or retinal disease, diabetes and/or hypertension that are not well controlled, history of head trauma, concussion, or TBI, history of cervical or spinal injury/surgery
• Medications or eyedrops that would confound measuring the pupil light reflex and EMG: including topical autonomic drugs that could influence pupil size, ocular pharmacologic agents, sedative agents (e.g. benzodiazepines or barbiturates), opioid narcotics

TBI patients with photosensitivity Inclusion Criteria

• Age 18-80
• Photosensitivity: determined by patient reporting symptoms and cause associated with their light sensitivity is post TBI
• TBI

Exclusion Criteria

- History of eye or systemic disorder that affect the retina, optic nerve, visual pathway, or pupil defect: including glaucoma, optic neuropathy, or retinal disease, diabetes and/or hypertension that are not well controlled

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Screening
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

5

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Healthy Control subjects	Device: Pupillography; A hand-held pupillometer/electroretinogram device (RETeval, LKC) will be held in front of the subject's eye, but will not touch the eye. The device will provide a brief, a series of brief light stimuli and then record the pupil response and the elicited electrical response from the retina from a surface skin patch (electrode) placed below each eye, from the light as a measure of whether the inherent sensitivity of the eye in the retina is normal. The investigators will repeat this in the left eye. The visible light stimulus is safe and is given at an intensity experienced in normal daily light exposures. The test takes about 2 minutes per eye.; Other Names: Reteval, LKC; Device: Ocular Coherence Tomography (OCT); The thickness of the optic nerve and macula will also be measured inside of the eye using a special camera that forms an image of the layers of the retina without pupil dilation. The imaging is harmless and measures the structural health of the optic nerve and retinal layers. This test takes 5-10 minutes per eye.; Device: Wrist-watch sensor device; A wrist-watch sensor device (E4, Empatica) will be place on each wrist to measure skin conductance, heart rate, skin temperature and arm movement during testing. These wrist-watch devices are being used to monitor changes in sympathetic nerve activity to light intensity, (the sympathetic nerves supply the blood vessels to the skin and heart).; Other Names: (E4, Empatica); Device: Videography; The subject will sit comfortably in front of miniature combination infrared/visible light video cameras and infrared diode light source located within 1 meter to provide video recording of the face during testing with light and during darkness, described next. After the 10 minutes of dark-adapting, the subject will put his/her chin on a chin rest in front of the video cameras and a light emitting diode (LED) array give diffuse red, blue, and white stimuli over a range of intensities. None of the stimuli are as bright as a flash from a camera and are in the range of intensities normally experienced during daily activities. At the end of the test the investigators will add filters over the glasses: orange (blue-blocking) filters and neutral density filters. Subjects will grade independently, both the brightness and discomfort they feel from each light stimulus intensity.; Device: Electrophysiology; Next, electrodes will be placed above, below and to the side of the test eye to record the electromyogram (EMG) for measuring eyelid opening and blink rate.
Active Comparator: TBI Patients without photosensitivity	Device: Pupillography; A hand-held pupillometer/electroretinogram device (RETeval, LKC) will be held in front of the subject's eye, but will not touch the eye. The device will provide a brief, a series of brief light stimuli and then record the pupil response and the elicited electrical response from the retina from a surface skin patch (electrode) placed below each eye, from the light as a measure of whether the inherent sensitivity of the eye in the retina is normal. The investigators will repeat this in the left eye. The visible light stimulus is safe and is given at an intensity experienced in normal daily light exposures. The test takes about 2 minutes per eye.; Other Names: Reteval, LKC; Device: Ocular Coherence Tomography (OCT); The thickness of the optic nerve and macula will also be measured inside of the eye using a special camera that forms an image of the layers of the retina without pupil dilation. The imaging is harmless and measures the structural health of the optic nerve and retinal layers. This test takes 5-10 minutes per eye.; Device: Wrist-watch sensor device; A wrist-watch sensor device (E4, Empatica) will be place on each wrist to measure skin conductance, heart rate, skin temperature and arm movement during testing. These wrist-watch devices are being used to monitor changes in sympathetic nerve activity to light intensity, (the sympathetic nerves supply the blood vessels to the skin and heart).; Other Names: (E4, Empatica); Device: Videography; The subject will sit comfortably in front of miniature combination infrared/visible light video cameras and infrared diode light source located within 1 meter to provide video recording of the face during testing with light and during darkness, described next. After the 10 minutes of dark-adapting, the subject will put his/her chin on a chin rest in front of the video cameras and a light emitting diode (LED) array give diffuse red, blue, and white stimuli over a range of intensities. None of the stimuli are as bright as a flash from a camera and are in the range of intensities normally experienced during daily activities. At the end of the test the investigators will add filters over the glasses: orange (blue-blocking) filters and neutral density filters. Subjects will grade independently, both the brightness and discomfort they feel from each light stimulus intensity.; Device: Electrophysiology; Next, electrodes will be placed above, below and to the side of the test eye to record the electromyogram (EMG) for measuring eyelid opening and blink rate.
Active Comparator: Migraine patients without photosensitivity	Device: Pupillography; A hand-held pupillometer/electroretinogram device (RETeval, LKC) will be held in front of the subject's eye, but will not touch the eye. The device will provide a brief, a series of brief light stimuli and then record the pupil response and the elicited electrical response from the retina from a surface skin patch (electrode) placed below each eye, from the light as a measure of whether the inherent sensitivity of the eye in the retina is normal. The investigators will repeat this in the left eye. The visible light stimulus is safe and is given at an intensity experienced in normal daily light exposures. The test takes about 2 minutes per eye.; Other Names: Reteval, LKC; Device: Ocular Coherence Tomography (OCT); The thickness of the optic nerve and macula will also be measured inside of the eye using a special camera that forms an image of the layers of the retina without pupil dilation. The imaging is harmless and measures the structural health of the optic nerve and retinal layers. This test takes 5-10 minutes per eye.; Device: Wrist-watch sensor device; A wrist-watch sensor device (E4, Empatica) will be place on each wrist to measure skin conductance, heart rate, skin temperature and arm movement during testing. These wrist-watch devices are being used to monitor changes in sympathetic nerve activity to light intensity, (the sympathetic nerves supply the blood vessels to the skin and heart).; Other Names: (E4, Empatica); Device: Videography; The subject will sit comfortably in front of miniature combination infrared/visible light video cameras and infrared diode light source located within 1 meter to provide video recording of the face during testing with light and during darkness, described next. After the 10 minutes of dark-adapting, the subject will put his/her chin on a chin rest in front of the video cameras and a light emitting diode (LED) array give diffuse red, blue, and white stimuli over a range of intensities. None of the stimuli are as bright as a flash from a camera and are in the range of intensities normally experienced during daily activities. At the end of the test the investigators will add filters over the glasses: orange (blue-blocking) filters and neutral density filters. Subjects will grade independently, both the brightness and discomfort they feel from each light stimulus intensity.; Device: Electrophysiology; Next, electrodes will be placed above, below and to the side of the test eye to record the electromyogram (EMG) for measuring eyelid opening and blink rate.
Active Comparator: Migraine patients with photosensitivity	Device: Pupillography; A hand-held pupillometer/electroretinogram device (RETeval, LKC) will be held in front of the subject's eye, but will not touch the eye. The device will provide a brief, a series of brief light stimuli and then record the pupil response and the elicited electrical response from the retina from a surface skin patch (electrode) placed below each eye, from the light as a measure of whether the inherent sensitivity of the eye in the retina is normal. The investigators will repeat this in the left eye. The visible light stimulus is safe and is given at an intensity experienced in normal daily light exposures. The test takes about 2 minutes per eye.; Other Names: Reteval, LKC; Device: Ocular Coherence Tomography (OCT); The thickness of the optic nerve and macula will also be measured inside of the eye using a special camera that forms an image of the layers of the retina without pupil dilation. The imaging is harmless and measures the structural health of the optic nerve and retinal layers. This test takes 5-10 minutes per eye.; Device: Wrist-watch sensor device; A wrist-watch sensor device (E4, Empatica) will be place on each wrist to measure skin conductance, heart rate, skin temperature and arm movement during testing. These wrist-watch devices are being used to monitor changes in sympathetic nerve activity to light intensity, (the sympathetic nerves supply the blood vessels to the skin and heart).; Other Names: (E4, Empatica); Device: Videography; The subject will sit comfortably in front of miniature combination infrared/visible light video cameras and infrared diode light source located within 1 meter to provide video recording of the face during testing with light and during darkness, described next. After the 10 minutes of dark-adapting, the subject will put his/her chin on a chin rest in front of the video cameras and a light emitting diode (LED) array give diffuse red, blue, and white stimuli over a range of intensities. None of the stimuli are as bright as a flash from a camera and are in the range of intensities normally experienced during daily activities. At the end of the test the investigators will add filters over the glasses: orange (blue-blocking) filters and neutral density filters. Subjects will grade independently, both the brightness and discomfort they feel from each light stimulus intensity.; Device: Electrophysiology; Next, electrodes will be placed above, below and to the side of the test eye to record the electromyogram (EMG) for measuring eyelid opening and blink rate.
Active Comparator: TBI patients with photosensitivity	Device: Pupillography; A hand-held pupillometer/electroretinogram device (RETeval, LKC) will be held in front of the subject's eye, but will not touch the eye. The device will provide a brief, a series of brief light stimuli and then record the pupil response and the elicited electrical response from the retina from a surface skin patch (electrode) placed below each eye, from the light as a measure of whether the inherent sensitivity of the eye in the retina is normal. The investigators will repeat this in the left eye. The visible light stimulus is safe and is given at an intensity experienced in normal daily light exposures. The test takes about 2 minutes per eye.; Other Names: Reteval, LKC; Device: Ocular Coherence Tomography (OCT); The thickness of the optic nerve and macula will also be measured inside of the eye using a special camera that forms an image of the layers of the retina without pupil dilation. The imaging is harmless and measures the structural health of the optic nerve and retinal layers. This test takes 5-10 minutes per eye.; Device: Wrist-watch sensor device; A wrist-watch sensor device (E4, Empatica) will be place on each wrist to measure skin conductance, heart rate, skin temperature and arm movement during testing. These wrist-watch devices are being used to monitor changes in sympathetic nerve activity to light intensity, (the sympathetic nerves supply the blood vessels to the skin and heart).; Other Names: (E4, Empatica); Device: Videography; The subject will sit comfortably in front of miniature combination infrared/visible light video cameras and infrared diode light source located within 1 meter to provide video recording of the face during testing with light and during darkness, described next. After the 10 minutes of dark-adapting, the subject will put his/her chin on a chin rest in front of the video cameras and a light emitting diode (LED) array give diffuse red, blue, and white stimuli over a range of intensities. None of the stimuli are as bright as a flash from a camera and are in the range of intensities normally experienced during daily activities. At the end of the test the investigators will add filters over the glasses: orange (blue-blocking) filters and neutral density filters. Subjects will grade independently, both the brightness and discomfort they feel from each light stimulus intensity.; Device: Electrophysiology; Next, electrodes will be placed above, below and to the side of the test eye to record the electromyogram (EMG) for measuring eyelid opening and blink rate.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Correlation of facial responses to light sensitivity	Hand held pupillography/videography, electroretinogram, and electrophysiology measurements are correlated to develop of an objective biological marker of light sensitivity.	1 Day
Difference in objective biological markers of light sensitivity between light sensitive and normal subjects	The correlation of facial responses to light sensitivity is compared between groups to test whether the measure can accurately distinguish light sensitivity.	1 Day

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Correlation of objective biological marker of light sensitivity to optic nerve structures	Bio marker score will be correlated to optic nerve structure measurements made using Optical Coherence Tomography (OCT) to evaluate structural loss of the optic nerve.	1 Day
Correlation of objective biological marker of light sensitivity to macula (structure found in the back of the eye).	Bio marker score will be correlated to macula structure measurements made using Optical Coherence Tomography (OCT) to examine to evaluate structural loss of the macula (structure found in the back of the eye).	1 Day

Collaborators and Investigators

• Sponsor: Randy Kardon

Study record dates

Study Major Dates

• Study Start (Actual): July 11, 2019
• Primary Completion (Estimated): January 1, 2028
• Study Completion (Estimated): January 1, 2028

Study Registration Dates

• First Submitted: July 17, 2018
• First Submitted That Met QC Criteria: October 1, 2018
• First Posted (Actual): October 3, 2018

Study Record Updates

• Last Update Posted (Actual): November 24, 2025
• Last Update Submitted That Met QC Criteria: November 18, 2025
• Last Verified: May 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neurologic Manifestations; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Wounds and Injuries; Eye Diseases; Headache Disorders, Primary; Headache Disorders; Vision Disorders; Sensation Disorders; Craniocerebral Trauma; Trauma, Nervous System; Brain Injuries; Pathological Conditions, Signs and Symptoms; Signs and Symptoms; Brain Injuries, Traumatic; Migraine Disorders; Photophobia
• Other Study ID Numbers: 201604763

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED
• IPD Plan Description: We will determine a plan to share IPD closer to time of completion of the study.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: Yes
• product manufactured in and exported from the U.S.: Yes