Is the RAPDx Pupillograph Able to Distinguish Between Glaucoma Subjects and Healthy Subjects?

• Sponsor: Wills Eye (Other)
• Overall Status: Completed
• CT.gov ID: NCT02526693
• Collaborator: (none)
• Enrollment: 104
• Arms: 2
• Duration (Months): 14

Study Details

Study Description

Brief Summary

The Konan RAPDx (Konan Medical USA, Irvine, CA) is a newly patented pupillography device.The aims of this study are to assess the ability of the RAPDx to distinguish between healthy subjects and patients with confirmed glaucoma using standard testing sequences developed for use at the Wills Eye Hospital Glaucoma Research Center and to determine the combination of demographic, clinical, and RAPDx testing parameters which allow for maximum sensitivity and specificity.

Condition or Disease	Intervention/Treatment	Phase
Glaucoma	Diagnostic Test: Pupillometer	N/A

Detailed Description

The RAPDx utilizes noninvasive digital, high-definition, infrared machine-vision with eye-tracking and automated blink detection technology to analyze and quantify the pupillary response to light.

During the scheduled appointment, all patients will receive an undilated fundus examination by the attending ophthalmologist. The following data will be collected; Demographic information, Visual acuity, Intraocular pressure (IOP) measured by Goldmann applanation tonometry, Disc damage likelihood scale (DDLS), Vertical cup/disc ratio, Gonioscopy (if not documented in the chart within the past 2 years) and Humphrey visual field examination.

Each participant will undergo RAPDx testing with two different testing sequences. They are separated by a 10-second resting period during which the patient is instructed to close his or her eyes. The exam may be paused at any time and re-alignment may be performed during any pause. The two testing sequences are:

1. Standard Factory Setting: 0.1-second stimuli with 2-second inter-stimuli pauses;

2. Custom Setting: 3-second stimuli with 1-second inter-stimuli pauses

Study Design

• Study Type: Interventional
• Actual Enrollment: 104 participants
• Allocation: Non-Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Diagnostic
• Official Title: RAPDx Pupillography for Early Detection of Glaucoma
• Study Start Date: Jun 1, 2014
• Actual Primary Completion Date: Aug 1, 2015
• Actual Study Completion Date: Aug 1, 2015

Arms and Interventions

Arm	Intervention/Treatment
Other: Glaucoma Patients Glaucoma patients recruited from Wills Eye Hospital Glaucoma Service will be tested with the relative afferent pupillary defect test (RAPDx) Pupillometer. The noninvasive RAPDx measures the pupils response during light stimulation.	Diagnostic Test: Pupillometer; The Konan RAPDx (relative afferent pupillary defect) (Konan Medical USA, Irvine, CA) pupillometer utilizes digital, high-definition, infrared machine-vision with eye-tracking and automated blink detection technology to analyze and quantify pupillary response to light.; Other Names: Relative afferent pupillary defect pupillometer
Other: Healthy Controls Healthy subjects with no eye diseases recruited from Wills Eye Hospital Glaucoma Service staff, family and friends will be tested with the relative afferent pupillary defect test (RAPDx) Pupillometer. The noninvasive RAPDx measures the pupils response during light stimulation.	Diagnostic Test: Pupillometer; The Konan RAPDx (relative afferent pupillary defect) (Konan Medical USA, Irvine, CA) pupillometer utilizes digital, high-definition, infrared machine-vision with eye-tracking and automated blink detection technology to analyze and quantify pupillary response to light.; Other Names: Relative afferent pupillary defect pupillometer

Outcome Measures

Primary Outcome Measures

1. Amplitude Asymmetry of Pupil Constriction [1 examination, one hour]

   Pupil size changes when light shines into the eyes making the diameter of the pupil smaller (constriction). The size of the pupil's reaction to light, measured in millimeters, is the amplitude or change in diameter. Amplitude of maximum pupil constriction (pupil size) when light is shone is compared between the right and left eyes. Asymmetry is the difference between maximum pupil size of the two eyes.

2. Latency Asymmetry of Pupil Constriction [1 examination, one hour]

   Pupil size changes at different speeds when light shines into the eyes making the diameter of the pupil smaller (constriction). The speed of the pupil's reaction to light is the latency or amount of time. Latency of maximum pupil constriction when light is shone is compared between the right and left eyes. Asymmetry is the difference in time it takes for maximum pupil constriction between the two eyes.

3. Maximum Constriction Asymmetry Duration [1 examination, one hour]

   Log difference between duration of maximum pupil constriction when light is shone into the right versus the left eye. The duration of maximum constriction is calculated as time in milliseconds between point of maximum constriction and time when pupil amplitude has reached 50% of peak amplitude of dilation.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

Inclusion Criteria:

Glaucoma patients:

• optic nerve damage (neuroretinal rim notch, asymmetric inter-eye cup to disc (c/d_ ratio >0.2 or disc damage likelihood scale (DDLS) >2, or absence of neuroretinal rim not due to other cause)

• glaucomatous visual field (VF) deficits (cluster of 3 or more points on pattern deviation plot depressed below 5% level, at least 1 depressed below 1% level; OR corrected pattern standard deviation/pattern standard deviation significant at P <0.05; or glaucoma hemifield test "outside normal limits") with good reliability indices (fixation losses, false-positive rate, false-negative rate each < 33%).

Healthy subjects:

• normal optic nerve exam

• normal reliable VF (Humphrey mean deviation (MD) >-2 or Octopus MD ≤0.8; fixation losses, false-positive rate, and false-negative rate each < 33%)

• open angles gonioscopy.

Exclusion Criteria:

• Abnormal ocular motility preventing binocular fixation (e.g. strabismus, nystagmus).

• Any condition preventing adequate visualization and examination of pupil or optic nerve (e.g. dense corneal opacities or lens opacities).

• Active infection of anterior or posterior segments of the eye.

• Any intraocular surgical or laser procedure within previous 4 weeks.

• Any non-glaucomatous condition causing RAPD, anisocoria or corectopia (ex. optic neuropathy, Horner's syndrome, previous iris injury due to trauma or surgery, etc.).

• Subjects under age 18 or subjects presently housed in correctional facility.

Contacts and Locations

Locations

No locations specified.

Sponsors and Collaborators

• Wills Eye

Investigators

• Principal Investigator: George Spaeth, MD, Wills Eye Hospital

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: George L. Spaeth MD, Principal Investigator, Wills Eye
• ClinicalTrials.gov Identifier: NCT02526693
• Other Study ID Numbers: 14-400E
• First Posted: Aug 18, 2015
• Last Update Posted: Oct 23, 2019
• Last Verified: Oct 1, 2019

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No
• Keywords provided by George L. Spaeth MD, Principal Investigator, Wills Eye: glaucoma; relative afferent pupillary defect; pupillography
• Additional relevant MeSH terms: Glaucoma

Study Results

Participant Flow

Arm/Group Title	Glaucoma Patients	Healthy Controls
Arm/Group Description	50 Glaucoma patients recruited from Wills Eye Hospital Glaucoma Service will be tested with RAPDx Pupillometer machine. RAPDx Pupillometer: Konan relative afferent pupillary defect RAPDx (Konan Medical USA, Irvine, CA) utilizes digital, high-definition, infrared machine-vision with eye-tracking and automated blink detection technology to analyze and quantify pupillary response to light.	50 Healthy subjects with no eye diseases from Wills Eye Hospital Glaucoma Service staff, family and friends will be tested with RAPDx Pupillometer machine. RAPDx Pupillometer: Konan relative afferent pupillary defect RAPDx (Konan Medical USA, Irvine, CA) utilizes digital, high-definition, infrared machine-vision with eye-tracking and automated blink detection technology to analyze and quantify pupillary response to light.
Period Title: Overall Study
STARTED	53	51
COMPLETED	50	50
NOT COMPLETED	3	1

Baseline Characteristics

Arm/Group Title	Glaucoma	Healthy Control	Total
Arm/Group Description	Glaucoma patients are recruited from Wills Eye Hospital glaucoma service, who will be tested with the RAPDx Pupillography machine. RAPDx Pupillography: The Konan RAPDx (Konan Medical USA, Irvine, CA) utilizes digital, high-definition, infrared machine-vision with eye-tracking and automated blink detection technology to analyze and quantify the pupillary response to light.	Healthy subjects are recruited from Wills Eye Hospital primary care service, who will be tested with the RAPDx Pupillography machine. RAPDx Pupillography: The Konan RAPDx (Konan Medical USA, Irvine, CA) utilizes digital, high-definition, infrared machine-vision with eye-tracking and automated blink detection technology to analyze and quantify the pupillary response to light.	Total of all reporting groups
Overall Participants	50	50	100
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%
Between 18 and 65 years	23 46%	34 68%	57 57%
>=65 years	27 54%	16 32%	43 43%
Sex: Female, Male (Count of Participants)
Female	31 62%	33 66%	64 64%
Male	19 38%	17 34%	36 36%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 0%
Asian	2 4%	3 6%	5 5%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%
Black or African American	37 74%	14 28%	51 51%
White	9 18%	29 58%	38 38%
More than one race	2 4%	4 8%	6 6%
Unknown or Not Reported	0 0%	0 0%	0 0%
Region of Enrollment (participants) [Number]
United States	50 100%	50 100%	100 100%

Outcome Measures

1. Primary Outcome

Title	Amplitude Asymmetry of Pupil Constriction
Description	Pupil size changes when light shines into the eyes making the diameter of the pupil smaller (constriction). The size of the pupil's reaction to light, measured in millimeters, is the amplitude or change in diameter. Amplitude of maximum pupil constriction (pupil size) when light is shone is compared between the right and left eyes. Asymmetry is the difference between maximum pupil size of the two eyes.
Time Frame	1 examination, one hour

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Glaucoma Patients	Healthy Controls
Arm/Group Description	Glaucoma patients recruited from Glaucoma Service at Wills Eye Hospital will be tested with RAPDx Pupillography machine Relative afferent pupillary defect RAPDx Pupillography: The Konan RAPDx (Konan Medical USA, Irvine, CA) utilizes digital, high-definition, infrared with eye-tracking and automated blink detection to analyze and quantify pupillary response to light and dark with a standard testing sequence and a custom sequence.	Healthy subjects are recruited from the Wills Eye clinic, who will be tested with the RAPDx Pupillography machine Relative afferent pupillary defect RAPDx Pupillography: The Konan RAPDx (Konan Medical USA, Irvine, CA) utilizes digital, high-definition, infrared with eye-tracking and automated blink detection to analyze and quantify pupillary response to light and dark with a standard testing sequence and a custom sequence.
Measure Participants	50	50
Custom sequence	0.8 (0.75)	0.29 (0.27)
Standard sequence	0.5 (0.52)	0.16 (0.12)

2. Primary Outcome

Title	Latency Asymmetry of Pupil Constriction
Description	Pupil size changes at different speeds when light shines into the eyes making the diameter of the pupil smaller (constriction). The speed of the pupil's reaction to light is the latency or amount of time. Latency of maximum pupil constriction when light is shone is compared between the right and left eyes. Asymmetry is the difference in time it takes for maximum pupil constriction between the two eyes.
Time Frame	1 examination, one hour

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Glaucoma	Healthy Controls
Arm/Group Description	50 Glaucoma patients recruited from Wills Eye Hospital Glaucoma Service will be tested with RAPDx Pupillometer. RAPDx Pupillometer: The Konan relative afferent pupillary defect RAPDx (Konan Medical USA, Irvine, CA) utilizes digital, high-definition, infrared machine-vision with eye-tracking and automated blink detection technology to analyze and quantify pupillary response to light and dark with a standard testing sequence and a custom sequence.	50 Healthy subjects with no eye diseases recruited from Wills Eye Hospital Glaucoma Service staff, family and friends will be tested with the relative afferent pupillary defect test (RAPDx) Pupillometer. Pupillometer: The Konan RAPDx (relative afferent pupillary defect) (Konan Medical USA, Irvine, CA) pupillometer utilizes digital, high-definition, infrared machine-vision with eye-tracking and automated blink detection technology to analyze and quantify pupillary response to light and dark with a standard testing sequence and a custom sequence.
Measure Participants	50	50
Custom sequence	0.22 (0.23)	0.14 (0.14)
Standard sequence	0.2 (0.21)	0.13 (0.11)

3. Primary Outcome

Title	Maximum Constriction Asymmetry Duration
Description	Log difference between duration of maximum pupil constriction when light is shone into the right versus the left eye. The duration of maximum constriction is calculated as time in milliseconds between point of maximum constriction and time when pupil amplitude has reached 50% of peak amplitude of dilation.
Time Frame	1 examination, one hour

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Glaucoma Patients	Healthy Controls
Arm/Group Description	50 Glaucoma patients recruited from Wills Eye Hospital Glaucoma Service will be tested with relative afferent pupillary defect (RAPDx) Pupillometer. Pupillometer: The Konan RAPDx (relative afferent pupillary defect) (Konan Medical USA, Irvine, CA) pupillometer utilizes digital, high-definition, infrared machine-vision with eye-tracking and automated blink detection technology to analyze and quantify pupillary response to light and dark with a standard testing sequence and a custom sequence.	50 Healthy subjects with no eye diseases recruited from Wills Eye Hospital Glaucoma Service staff, family and friends will be tested with relative afferent pupillary defect (RAPDx) Pupillometer. Pupillometer: The Konan RAPDx (relative afferent pupillary defect) (Konan Medical USA, Irvine, CA) pupillometer utilizes digital, high-definition, infrared machine-vision with eye-tracking and automated blink detection technology to analyze and quantify pupillary response to light and dark with a standard testing sequence and a custom sequence.
Measure Participants	50	50
Mean (Standard Deviation) [milliseconds]	2.23 (0.64)	1.92 (0.54)

Adverse Events

Time Frame	1 examination, one hour
Arm/Group Title	Glaucoma Patients		Healthy Controls
Arm/Group Description	50 Glaucoma patients recruited from Wills Eye Hospital Glaucoma Service were tested with RAPDx Pupillometer. Konan (Konan Medical USA, Irvine, CA) RAPDx (relative afferent pupillary defect) test utilizes digital, high-definition, infrared machine-vision with eye-tracking and automated blink detection technology to analyze and quantify pupillary response to light.		50 Healthy controls recruited from Wills Eye Hospital Glaucoma Service staff, family and friends were tested with RAPDx Pupillometer. Konan (Konan Medical USA, Irvine, CA) RAPDx (relative afferent pupillary defect) test utilizes digital, high-definition, infrared machine-vision with eye-tracking and automated blink detection technology to analyze and quantify pupillary response to light.
All Cause Mortality
	Glaucoma Patients		Healthy Controls
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/50 (0%)		0/50 (0%)
Serious Adverse Events
	Glaucoma Patients		Healthy Controls
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/50 (0%)		0/50 (0%)
Other (Not Including Serious) Adverse Events
	Glaucoma Patients		Healthy Controls
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/50 (0%)		0/50 (0%)

Limitations/Caveats

Small sample size. Single site design. Single light design limits pupil stimulus.

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.