KeratoconusNCT01403129
Keratoconus Detection by Ultrasound
An observational study of Keratoconus, run by Columbia University at 2 sites in 2 countries.
Trial summary
Keratoconus (KC) is a corneal disease which will in many cases ultimately require corneal transplantation to maintain vision. Early detection, which is not possible with current technology, would allow early treatment and prevent severe damage to KC corneas inadvertently operated upon for correction of vision. Read more about this study
- Who is it for?
- Ages 6 to 65 yearsHealthy volunteers can take part
- Conditions the study is for
- Keratoconus
- What is being tested?
- Artemis Ultrasound Exam and Optical Coherence Tomography (OCT) Exam
- Type of treatment
- Surgery or procedure
- How many people
- 250 participants
- Where
- 2 sitesin 2 countries
- Study dates
- Dec 2010to Jan 2020
- Phase
- Observational
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 6 to 65 years
- All sexes
- Healthy volunteers accepted
- Child, Adult, Older adult
Study population: Patients presenting to CUMC associated physicians and the London Vision Clinic.
Who may be able to join
- Clinical diagnosis of keratoconus (KC) or keratoconus-suspect
- Blood relation of person with KC
- Age-matched normal of KC subjects
- Ability to sit still in front of ultrasound unit and lie on exam table
Who cannot join
- Other eye disease
Trial locations and contacts
2 sites in 2 countries.
2 sites in 2 countries
United States1 site
Columbia University Medical Center
New York, New York, 10032
About this study
Official title: Early Detection of Keratoconus Using Ultrasound
Keratoconus (KC) is a corneal disease which will in many cases ultimately require corneal transplantation to maintain vision. Early detection, which is not possible with current technology, would allow early treatment and prevent severe damage to KC corneas inadvertently operated upon for correction of vision. The investigators' aim is to combine measurements of different properties of the cornea to develop means for early detection of KC.
Read the detailed description
Keratoconus is the most common degenerative disease affecting the cornea. As keratoconus develops, the cornea thins and bulges. Eventually, a corneal transplant may be needed to maintain vision. In its earliest stages, the disease is particularly difficult to detect. This is of great importance to the corneal refractive surgeon because surgical treatment of a keratoconic cornea will weaken it and greatly accelerate the occurrence of symptoms. Early detection of keratoconus will benefit patients because of the recent development of methods for strengthening the corneal stroma and preventing disease progression.
The investigators have developed a technique based on the use of high resolution ultrasound for imaging the cornea and measuring the thickness of its component layers, including the epithelium and the stroma. In early keratoconus, as the anterior stromal surface begins to bulge forward, the epithelium will thin above the apex of the bulge and thicken around it, to maintain a smooth anterior surface. The investigators have also developed methods for characterizing the elastic properties of the cornea by inducing and measuring surface displacements in response to a pulse of acoustic radiation force.
The investigators' goal is to reduce the percentage of screened cases deemed keratoconus-suspect by at least a factor of two by allowing an unambiguous diagnosis of early keratoconus. This would provide two major benefits; (1) to be able to predict eyes with higher risk of developing ectasia after corneal refractive surgery, and (2) early diagnosis would allow earlier treatment of the condition with collagen crosslinking, preserving the cornea from disease progression.
- Conditions
- Keratoconus
- Being tested
- Artemis Ultrasound Exam, Optical Coherence Tomography (OCT) Exam
- Keywords
- keratoconus, keratoconus-suspect, ultrasound exam, acoustic radiation force ultrasound exam
- Medical subject headings
- Keratoconus
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Artemis Ultrasound ExamProcedure or surgery
Also called Ultrasound biomicroscope (UBM), High frequency ultrasound
Ultrasound exam of both eyes using an Artemis-2 device. Exam will be performed once. Exam duration is 20 minutes per eye.
Optical Coherence Tomography (OCT) ExamProcedure or surgery
Also called OCT
OCT exam of both eyes. Exam will be performed once, duration is 10. I utes per eye.
| Study group | Role | What they receive |
|---|---|---|
| Keratoconus-Suspect | A person who has or is suspected of having keratoconus. Will have either or both Artemis-2 exam and OCT exam. Receives: Procedure: Artemis Ultrasound Exam; Procedure: Optical Coherence Tomography (OCT) Exam | |
| Keratoconus-Related | A person who is genetically related to someone with keratoconus. Will have either or both Artemis-2 exam and OCT exam. Receives: Procedure: Artemis Ultrasound Exam; Procedure: Optical Coherence Tomography (OCT) Exam | |
| Age-Matched Normal | A person who is approximately the same age as subjects who have been enrolled in the study.
Will have either or both Artemis-2 exam and OCT exam. Receives: Procedure: Artemis Ultrasound Exam; Procedure: Optical Coherence Tomography (OCT) Exam |
What is being measured
The primary outcome is the main question the study is designed to answer.
Differences in elastic parameters between normal and KC corneas.
The undamped vibrational frequency and damping time-constant for the anterior and posterior corneal surfaces and for Bowman's membrane will be measured. The elastic modulus will be calculated form the change in corneal thickness resulting from known radiation force.
Measured: Up to 1 year after enrollment
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted27 Jul 2011 (estimated)
- Study startDec 2010
- Primary completionJan 2020
- Study completionJan 2020
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (7)Papers the sponsor has linked to this study.
- Other trials for KeratoconusStudies of the same condition, open and under way.
- More trials run by Columbia UniversityThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Case-control
- Time perspective
- Cross-sectional
- Enrolment
- 250 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Columbia University
- Sponsor type
- University, hospital or other
- Collaborators
- National Eye Institute (NEI)
- Responsible party
- Principal investigator, Ronald H Silverman, Columbia University
- Investigators
- Ronald H Silverman, PhD, Principal investigator, Columbia University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01403129
- Sponsor's protocol ID
- AAAF1497
- Other IDs
- R01EY019055
- Status last verified
- Aug 2021
- First submitted
- 25 Jul 2011
- Last updated
- 3 Aug 2021
- Results posted
- No
- Data monitoring committee
- No
- Individual data sharing
- No
Publications
Urs R, Lloyd HO, Silverman RH. Acoustic radiation force for noninvasive evaluation of corneal biomechanical changes induced by cross-linking therapy. J Ultrasound Med. 2014 Aug;33(8):1417-26. doi: 10.7863/ultra.33.8.1417.
PubMed 25063407Silverman RH, Urs R, Roychoudhury A, Archer TJ, Gobbe M, Reinstein DZ. Epithelial remodeling as basis for machine-based identification of keratoconus. Invest Ophthalmol Vis Sci. 2014 Mar 13;55(3):1580-7. doi: 10.1167/iovs.13-12578.
PubMed 24557351Ursea R, Feng M, Urs R, RoyChoudhury A, Silverman RH. Comparison of artemis 2 ultrasound and Visante optical coherence tomography corneal thickness profiles. J Refract Surg. 2013 Jan;29(1):36-41. doi: 10.3928/1081597X-20121126-01. Epub 2012 Nov 30.
PubMed 23205905Urs R, Lloyd HO, Reinstein DZ, Silverman RH. Comparison of very-high-frequency ultrasound and spectral-domain optical coherence tomography corneal and epithelial thickness maps. J Cataract Refract Surg. 2016 Jan;42(1):95-101. doi: 10.1016/j.jcrs.2015.07.038.
PubMed 26948783Reinstein DZ, Archer TJ, Urs R, Gobbe M, RoyChoudhury A, Silverman RH. Detection of Keratoconus in Clinically and Algorithmically Topographically Normal Fellow Eyes Using Epithelial Thickness Analysis. J Refract Surg. 2015 Nov;31(11):736-44. doi: 10.3928/1081597X-20151021-02.
PubMed 26544561Reinstein DZ, Yap TE, Archer TJ, Gobbe M, Silverman RH. Comparison of Corneal Epithelial Thickness Measurement Between Fourier-Domain OCT and Very High-Frequency Digital Ultrasound. J Refract Surg. 2015 Jul;31(7):438-45. doi: 10.3928/1081597X-20150623-01.
PubMed 26186562Silverman RH, Urs R, RoyChoudhury A, Archer TJ, Gobbe M, Reinstein DZ. Combined tomography and epithelial thickness mapping for diagnosis of keratoconus. Eur J Ophthalmol. 2017 Mar 10;27(2):129-134. doi: 10.5301/ejo.5000850. Epub 2016 Aug 8.
PubMed 27515569
Study at a glance
From the registry record, last updated by the sponsor on 3 Aug 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Early Detection of Keratoconus Using Ultrasound
- ClinicalTrials.gov ID
- NCT01403129
- Acronym / sponsor ID
- AAAF1497
- Conditions
- Keratoconus
- Keywords
- keratoconus, keratoconus-suspect, ultrasound exam, acoustic radiation force ultrasound exam
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 250 participants (estimated)
- Lead sponsor
- Columbia UniversityUniversity, hospital or other
- Collaborators
- National Eye Institute (NEI)
- Study start
- Dec 2010
- Primary completion
- Jan 2020 (actual)
- Study completion
- Jan 2020 (actual)
- First posted
- 27 Jul 2011 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Keratoconus (KC) is a corneal disease which will in many cases ultimately require corneal transplantation to maintain vision. Early detection, which is not possible with current technology, would allow early treatment and prevent severe damage to KC corneas inadvertently operated upon for correction of vision. The investigators' aim is to combine measurements of different properties of the cornea to develop means for early detection of KC.
Detailed description
Keratoconus is the most common degenerative disease affecting the cornea. As keratoconus develops, the cornea thins and bulges. Eventually, a corneal transplant may be needed to maintain vision. In its earliest stages, the disease is particularly difficult to detect. This is of great importance to the corneal refractive surgeon because surgical treatment of a keratoconic cornea will weaken it and greatly accelerate the occurrence of symptoms. Early detection of keratoconus will benefit patients because of the recent development of methods for strengthening the corneal stroma and preventing disease progression.
The investigators have developed a technique based on the use of high resolution ultrasound for imaging the cornea and measuring the thickness of its component layers, including the epithelium and the stroma. In early keratoconus, as the anterior stromal surface begins to bulge forward, the epithelium will thin above the apex of the bulge and thicken around it, to maintain a smooth anterior surface. The investigators have also developed methods for characterizing the elastic properties of the cornea by inducing and measuring surface displacements in response to a pulse of acoustic radiation force.
The investigators' goal is to reduce the percentage of screened cases deemed keratoconus-suspect by at least a factor of two by allowing an unambiguous diagnosis of early keratoconus. This would provide two major benefits; (1) to be able to predict eyes with higher risk of developing ectasia after corneal refractive surgery, and (2) early diagnosis would allow earlier treatment of the condition with collagen crosslinking, preserving the cornea from disease progression.
Study design
- Observational model
- Case-control
- Time perspective
- Cross-sectional
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Keratoconus-Suspect | – | Procedure: Artemis Ultrasound Exam, Procedure: Optical Coherence Tomography (OCT) ExamA person who has or is suspected of having keratoconus. Will have either or both Artemis-2 exam and OCT exam. |
| Keratoconus-Related | – | Procedure: Artemis Ultrasound Exam, Procedure: Optical Coherence Tomography (OCT) ExamA person who is genetically related to someone with keratoconus. Will have either or both Artemis-2 exam and OCT exam. |
| Age-Matched Normal | – | Procedure: Artemis Ultrasound Exam, Procedure: Optical Coherence Tomography (OCT) ExamA person who is approximately the same age as subjects who have been enrolled in the study. Will have either or both Artemis-2 exam and OCT exam. |
Who may qualify
- Ages
- 6 to 65 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Child, Adult, Older adult
- Study population
- Patients presenting to CUMC associated physicians and the London Vision Clinic.
Key inclusion criteria (4 listed)
- Clinical diagnosis of keratoconus (KC) or keratoconus-suspect
- Blood relation of person with KC
- Age-matched normal of KC subjects
- Ability to sit still in front of ultrasound unit and lie on exam table
Key exclusion criteria (1 listed)
- Other eye disease
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Artemis Ultrasound ExamAlso: Ultrasound biomicroscope (UBM), High frequency ultrasoundUltrasound exam of both eyes using an Artemis-2 device. Exam will be performed once. Exam duration is 20 minutes per eye. | Procedure or surgery | Age-Matched Normal, Keratoconus-Related, Keratoconus-Suspect |
| Optical Coherence Tomography (OCT) ExamAlso: OCTOCT exam of both eyes. Exam will be performed once, duration is 10. I utes per eye. | Procedure or surgery | Age-Matched Normal, Keratoconus-Related, Keratoconus-Suspect |
Primary outcome
Differences in elastic parameters between normal and KC corneas.
Time frame: Up to 1 year after enrollment
The undamped vibrational frequency and damping time-constant for the anterior and posterior corneal surfaces and for Bowman's membrane will be measured. The elastic modulus will be calculated form the change in corneal thickness resulting from known radiation force.
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 3 Aug 2021.
- Results publication: PubMed 25063407Urs R, Lloyd HO, Silverman RH. Acoustic radiation force for noninvasive evaluation of corneal biomechanical changes induced by cross-linking therapy. J Ultrasound Med. 2014 Aug;33(8):1417-26. doi: 10.7863/ultra.33.8.1417.
- Results publication: PubMed 24557351Silverman RH, Urs R, Roychoudhury A, Archer TJ, Gobbe M, Reinstein DZ. Epithelial remodeling as basis for machine-based identification of keratoconus. Invest Ophthalmol Vis Sci. 2014 Mar 13;55(3):1580-7. doi: 10.1167/iovs.13-12578.
- Results publication: PubMed 23205905Ursea R, Feng M, Urs R, RoyChoudhury A, Silverman RH. Comparison of artemis 2 ultrasound and Visante optical coherence tomography corneal thickness profiles. J Refract Surg. 2013 Jan;29(1):36-41. doi: 10.3928/1081597X-20121126-01. Epub 2012 Nov 30.
- Results publication: PubMed 26948783Urs R, Lloyd HO, Reinstein DZ, Silverman RH. Comparison of very-high-frequency ultrasound and spectral-domain optical coherence tomography corneal and epithelial thickness maps. J Cataract Refract Surg. 2016 Jan;42(1):95-101. doi: 10.1016/j.jcrs.2015.07.038.
- Results publication: PubMed 26544561Reinstein DZ, Archer TJ, Urs R, Gobbe M, RoyChoudhury A, Silverman RH. Detection of Keratoconus in Clinically and Algorithmically Topographically Normal Fellow Eyes Using Epithelial Thickness Analysis. J Refract Surg. 2015 Nov;31(11):736-44. doi: 10.3928/1081597X-20151021-02.
- Results publication: PubMed 26186562Reinstein DZ, Yap TE, Archer TJ, Gobbe M, Silverman RH. Comparison of Corneal Epithelial Thickness Measurement Between Fourier-Domain OCT and Very High-Frequency Digital Ultrasound. J Refract Surg. 2015 Jul;31(7):438-45. doi: 10.3928/1081597X-20150623-01.
- Results publication: PubMed 27515569Silverman RH, Urs R, RoyChoudhury A, Archer TJ, Gobbe M, Reinstein DZ. Combined tomography and epithelial thickness mapping for diagnosis of keratoconus. Eur J Ophthalmol. 2017 Mar 10;27(2):129-134. doi: 10.5301/ejo.5000850. Epub 2016 Aug 8.
- Ronald H. Silverman HomepageLink provided by the sponsor.
- Dan Z. Reinstein HomepageLink provided by the sponsor.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Ronald H Silverman, PhD principal investigator
Columbia University
2 sites in 2 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Keratoconus, run by Columbia University at 2 sites in 2 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 1 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 3 Aug 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in United States, United Kingdom. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Differences in elastic parameters between normal and KC corneas. (time frame: Up to 1 year after enrollment). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01403129, which also lists 7 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 3 Aug 2021.