Optic Nerve Head Structural Response to IOP Elevation in Patients With Keratoconus

The mechanism by which vision loss in glaucoma occurs is still unknown, but it is clear that increased Intraocular Pressure (IOP) is a major risk factor. It is also thought that the lamina cribrosa (LC) is a site of primary damage during the pathogenesis of the disease. The changes caused by intraocular pressure (IOP) modulation at the level of the optic nerve head and LC will be evaluated in the present study. Subjects with keratoconus exhibit abnormal collagen properties that can impair their LC behavior. By evaluating their lamina biomechanical response we can advance our understanding on the role of the lamina in glaucoma pathogenesis. A better understanding of the process will ultimately lead to improved detection and management of glaucoma.

It is hypothesized that subjects with keratoconus have an abnormal biomechanical response of the lamina cribrosa in response to IOP modulation.

Study Overview

• Status: Recruiting
• Conditions: Glaucoma; Keratoconus
• Intervention / Treatment: Device: Ophthalmodynamometer; Device: Goldmann applanation tonometer; Device: Pentacam; Device: ORA; Device: Optical Coherence Tomography (OCT)

• Study Type: Interventional
• Enrollment (Estimated): 130
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Jamika Singleton-Garvin; Phone Number: 929-455-5522; Email: Jamika.Singleton-Garvin@nyulangone.org

Study Locations

• United States
  • New York
    • New York, New York, United States, 10016
      • Recruiting
      • New York University School of Medicine
      • Contact: Jamika Singleton-Garvin; Phone Number: 929-455-5522; Email: Jamika.Singleton-Garvin@nyulangone.org
      • Principal Investigator: Chaim Wollstein, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 90 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

Candidates must meet the following inclusion criteria in order to participate in the study.

• Ability to provide informed consent and to understand the study procedures

Keratoconus:

• Clinical diagnosis of keratoconus
• Central thinning of the cornea
• Abnormal posterior ectasia.

Glaucoma:

• Glaucomatous ONH abnormality: rim thinning, notching, undermining (excavation) or diffuse or localized RNFL defects that are characteristic of glaucoma.
• Two consecutive abnormal SITA standard perimetry tests with GHT outside normal limits.

Exclusion Criteria:

Candidates that meet any of the exclusion criteria at baseline will be excluded from study participation.

• Media opacity (e.g. lens, vitreous, cornea).
• Strabismus, nystagmus or a condition that would prevent fixation.
• Diabetes with evidence of retinopathy.
• Previous intraocular surgery or ocular trauma (with the exception of laser procedures and subjects that have undergone uneventful cataract surgery more than 6 months from enrollment date).
• Neurological and non-glaucomatous causes for visual field damage.
• Any intraocular non-glaucomatous ocular disorders.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Subjects With Keratoconus	Device: Ophthalmodynamometer; The ODM (Baillart ophthlmodynamometer) is a disc attached to a piston that induces a controlled force on a fixed area. The device will be used to apply a pressure within the range of 10 mmHg - 50 mmHg 4 times to each eye. Each increase of pressure will last approximately 30 seconds. The device is FDA approved and will be used as routinely used in clinical practice; Device: Goldmann applanation tonometer; The Goldmann applanation tonometer (Haag-Streit, Basel, Switzerland) measures the IOP after the eye is numbed with a drop of anesthetic (proparacaine), which is approved by the FDA. Proparacaine is part of routine patient care using a tonometer regardless of participation in this study. The instrument's tip lightly touches the surface of the cornea and the IOP is measured. The device is FDA approved is routinely used in clinical practice.; Device: Pentacam; This device maps the cornea and provides pachymetry, topography and corneal aberration maps. The device is FDA approved and routinely used in clinical practice.; Device: ORA; ORA is an air puff tonometer that applies controlled force to flattens the cornea and provides the corneal hysteresis and corneal resistance factor. The device is FDA approved and routinely used in clinical practice.; Device: Optical Coherence Tomography (OCT); OCT is a non-contact,real-time, high resolution, and reproducible imaging modality that provides in-vivo optical cross-sectional scanning of the retina, the ONH and of the anterior segment structures including the cornea. Clinical staff will perform subject testing, not research coordinators. Information about these non-FDA approved OCTs and the multi-modal adaptive optics system can be found in appendices A, B, C, and D. With all devices, the participant sits in a slit lamp like frame. A low power laser light is projected toward the back of their eyes while the subject fixates on a target. None of the systems produce harmful radioactive radiation.
Active Comparator: Subjects with Glaucoma	Device: Ophthalmodynamometer; The ODM (Baillart ophthlmodynamometer) is a disc attached to a piston that induces a controlled force on a fixed area. The device will be used to apply a pressure within the range of 10 mmHg - 50 mmHg 4 times to each eye. Each increase of pressure will last approximately 30 seconds. The device is FDA approved and will be used as routinely used in clinical practice; Device: Goldmann applanation tonometer; The Goldmann applanation tonometer (Haag-Streit, Basel, Switzerland) measures the IOP after the eye is numbed with a drop of anesthetic (proparacaine), which is approved by the FDA. Proparacaine is part of routine patient care using a tonometer regardless of participation in this study. The instrument's tip lightly touches the surface of the cornea and the IOP is measured. The device is FDA approved is routinely used in clinical practice.; Device: Pentacam; This device maps the cornea and provides pachymetry, topography and corneal aberration maps. The device is FDA approved and routinely used in clinical practice.; Device: ORA; ORA is an air puff tonometer that applies controlled force to flattens the cornea and provides the corneal hysteresis and corneal resistance factor. The device is FDA approved and routinely used in clinical practice.; Device: Optical Coherence Tomography (OCT); OCT is a non-contact,real-time, high resolution, and reproducible imaging modality that provides in-vivo optical cross-sectional scanning of the retina, the ONH and of the anterior segment structures including the cornea. Clinical staff will perform subject testing, not research coordinators. Information about these non-FDA approved OCTs and the multi-modal adaptive optics system can be found in appendices A, B, C, and D. With all devices, the participant sits in a slit lamp like frame. A low power laser light is projected toward the back of their eyes while the subject fixates on a target. None of the systems produce harmful radioactive radiation.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
LC measurements measured in microns	These micron measurements will be obtained from in vivio OCT images	1 Day
Anterior laminar displacement measured in microns	These micron measurements will be obtained from in vivio OCT images	1 Day

Collaborators and Investigators

• Sponsor: NYU Langone Health
• Investigators: Principal Investigator: Chaim Wollstein, NYU Langone Health

Study record dates

Study Major Dates

• Study Start (Actual): November 15, 2018
• Primary Completion (Estimated): July 31, 2024
• Study Completion (Estimated): July 31, 2024

Study Registration Dates

• First Submitted: June 6, 2018
• First Submitted That Met QC Criteria: June 6, 2018
• First Posted (Actual): June 18, 2018

Study Record Updates

• Last Update Posted (Actual): October 4, 2023
• Last Update Submitted That Met QC Criteria: October 3, 2023
• Last Verified: October 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Eye Diseases; Corneal Diseases; Keratoconus
• Other Study ID Numbers: 17-01360

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Deidentified data will be shared upon request.
• IPD Sharing Time Frame: Data is available upon reasonable request indefinitely
• IPD Sharing Access Criteria: Requests should be directed to Gadi.wollstein@nyulangone.org. To gain access, data requestors will need to sign a data access agreement.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; ICF

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