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Functional and Structural Imaging for Glaucoma (FSOCT)

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ClinicalTrials.gov Identifier: NCT01957267
Recruitment Status : Recruiting
First Posted : October 8, 2013
Last Update Posted : May 2, 2019
Sponsor:
Collaborator:
National Eye Institute (NEI)
Information provided by (Responsible Party):
David Huang, Oregon Health and Science University

Tracking Information
First Submitted Date September 11, 2013
First Posted Date October 8, 2013
Last Update Posted Date May 2, 2019
Study Start Date September 2013
Estimated Primary Completion Date December 2022   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures
 (submitted: April 30, 2019)
  • Measure of retinal non-perfusion areas in mm2 [ Time Frame: 5 years ]
  • Measure vessel density in percentage (%) [ Time Frame: 5 years ]
  • Determine accuracy of sector visual field progression in OCT-based sector visual field simulation compared to actual visual field results. Measured in dB change over time. [ Time Frame: 5 years ]
Original Primary Outcome Measures
 (submitted: September 30, 2013)
Developing glaucoma or progression with glaucoma as defined by study criteria [ Time Frame: 5 years ]
Change History Complete list of historical versions of study NCT01957267 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures Not Provided
Original Secondary Outcome Measures Not Provided
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title Functional and Structural Imaging for Glaucoma
Official Title Longitudinal Observational Study Using Functional and Structural Optical Coherence Tomography to Diagnose and Guide Treatment of Glaucoma
Brief Summary

The specific aims of the clinical studies are to:

  • Develop quantitative wide-field OCT angiography.
  • Simulate visual field results by combining structural and angiography OCT data.
  • Establish or validate age-adjusted normal reference ranges for above OCT-derived parameters.
  • Establish criteria for glaucoma diagnosis based on above imaging-derived parameters.
  • Evaluate the sensitivity and specificity of above OCT-derived parameters
  • Measure the rate of normal age-related change in above OCT-derived parameters.
  • Assess the reproducibility of above OCT-derived parameters.
  • Assess abilities of above OCT-derived parameters on predicting glaucoma conversion and progression.
Detailed Description

Glaucoma is the second leading cause of blindness in the US. The diagnosis and monitoring of glaucoma are important problems, not only because of its prevalence, but also because of its silent and irreversible nature. However all of the current diagnostic tests have serious limitations. Although elevated intraocular pressure (IOP) is a risk factor, most glaucoma patients actually have IOP within normal range. Visual field (VF) tests are poorly reproducible, and a series of 3 tests are needed to establish diagnosis or confirm progression. Although ophthalmoscopic examination can detect optic nerve head (ONH) and nerve fiber layer (NFL) defects, reliability in diagnosis and tracking is hampered by its subjective and semi-quantitative nature. Although quantitative imaging with optical coherence tomography (OCT), scanning laser polarimetry (SLP), and confocal scanning laser ophthalmoscopy (cSLO) can more objectively detect ONH and NFL defects, their diagnostic accuracies are still not sufficient to be relied on alone for diagnostic screening. It has been estimated that about half of glaucoma patients in the US do not know that they have the disease. Thus, there is a need for improvements in glaucoma diagnostic technologies. One approach that deserves further exploration is blood flow imaging.

There is much circumstantial evidence that vascular factors play important roles in the pathophysiology of glaucoma:

  1. Systemic vasculopathy increases the risk of developing glaucoma. Hypertension, diabetes, and vasospastic conditions are all known risk factors. Normal tension glaucoma has also been linked to peripheral endothelial dysfunction and erectile dysfunction. This suggests that poor circulation may be a causative factor or a facilitative factor that predisposes the ONH to damage by elevated IOP.
  2. Decrease or fluctuation in ocular perfusion pressure was identified as an independent risk factor for progression in the Collaborative Normal-Tension Glaucoma Study and other studies. Nocturnal hypotension is also a risk factor for glaucoma progression.
  3. Medications that improve ocular perfusion appear to have protective effects that are not explained by the lowering of IOP.
  4. Optic disc hemorrhage and peripapillary atrophy are both associated with accelerated glaucoma progression. These finding may support a role for focal ischemia.
  5. Animal experiments show that increased IOP causes decreased ONH blood flow in the presence of low systemic blood pressure.

Despite the evidence, the management of glaucoma remains focused on the lowering of IOP, the one causative factor that responds to treatment and can be easily measured. Blood flow measurement is a research topic, but currently has no clinical role in the diagnosis, prognostic evaluation, or treatment of glaucoma. Therapies aimed at improving ocular circulation cannot be effectively developed without a practical method for quantitative and reproducible evaluation of ONH and retinal perfusion. Thus there is a great need to develop better technology for the evaluation of ocular circulation.

Using high-speed OCT systems, we have developed new methods to image and measure optic nerve head (ONH) and retinal blood flow. Preliminary results showed that VF loss was more highly correlated with retinal blood flow as measured by OCT than any neural structure measured by OCT or other imaging modality. Accordingly, the goal of the proposed project is to improve the diagnostic and prognostic evaluation of glaucoma by further developing novel functional OCT measurements using ultrahigh-speed (70-100 kHz) OCT technology.

Retinal blood flow, ONH circulation, optic disc rim volume, peripapillary nerve fiber layer volume, and macular ganglion cell complex volume are all pieces of the same glaucoma puzzle. This project will develop novel imaging methods that allow us to look at the whole picture using one tool - ultrahigh-speed OCT.

Study Type Observational
Study Design Observational Model: Cohort
Time Perspective: Prospective
Target Follow-Up Duration Not Provided
Biospecimen Not Provided
Sampling Method Non-Probability Sample
Study Population The study will enroll both males and females and include all ethnic and racial groups through clinical practices in the centers. The study will enroll subjects in the older adult age range commonly affected by glaucoma - 40 years or older. The study will exclude people with life-threatening or debilitating illness that would make 5-year participation unlikely or cooperation with tests difficult. For similar reasons those older than 80 years are excluded. The study also excludes those with any disease that might confound the diagnosis of glaucoma. Otherwise people with any health status are eligible for enrollment. Two groups of participants are recruited in the study: healthy controls or participants with confirmed glaucoma.
Condition Glaucoma
Intervention Not Provided
Study Groups/Cohorts
  • Glaucoma Group
    Patients with clinically confirmed glaucomatous ONH or NFL defects, with or without VF abnormalities
  • Normal Group
    Volunteers with healthy eyes
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status Recruiting
Estimated Enrollment
 (submitted: April 10, 2018)
160
Original Estimated Enrollment
 (submitted: September 30, 2013)
150
Estimated Study Completion Date December 2022
Estimated Primary Completion Date December 2022   (Final data collection date for primary outcome measure)
Eligibility Criteria

Inclusion Criteria: Normal Subjects (both eyes must meet all criteria)

  1. No history or evidence of retinal pathology or glaucoma
  2. Normal Humphrey 24-2 VF: A mean defect (MD), corrected pattern standard deviation (CPSD) within 95% limits of normal reference, and glaucoma hemifield test (GHT) within normal limits (97%).
  3. Intraocular pressure < 21 mm Hg
  4. Central corneal pachymetry > 500 microns
  5. No chronic ocular or systemic corticosteroid use
  6. Open angle (gonioscopy must show 75% or more of the angle to be Grade 2 or more by Shaffer's grading system)
  7. Normal appearing ONH and NFL: vertical and horizontal cup/disc ratio (CDR) ≤ 0.5 and intact neuroretinal rim without peripapillary hemorrhages, notches, localized pallor, or NFL defect
  8. Symmetric ONH between left and right eyes: CDR difference < 0.2 in both vertical and horizontal dimensions

Inclusion criteria: Glaucoma Group

  1. ONH or NFL defect visible on slit-lamp biomicroscopy defined as one of following:

    1. diffuse or localized thinning of the rim
    2. disc (splinter) hemorrhage
    3. notch in the rim
    4. vertical cup/disc ratio greater than the fellow eye by > 0.2
  2. Presence or absence of VF defects as measured by Humphrey SITA 24-2 VF.

Exclusion Criteria: All Groups

  1. Best-corrected visual acuity less than 20/40
  2. Age < 40 or >80 years
  3. Refractive error of > +3.00 D or < -7.00 D
  4. Previous intraocular surgery except for uncomplicated cataract extraction with posterior chamber intraocular lens implantation
  5. Diabetic retinopathy
  6. Other diseases that may cause VF loss or optic disc abnormalities
  7. Inability to clinically view or photograph the optic discs due to media opacity or poorly dilating pupil
  8. Inability to perform reliably on automated VF testing
  9. Life-threatening or debilitating illness making it unlikely patient could successfully complete the study.
  10. Refusal of informed consent or of commitment to the full length of the study
Sex/Gender
Sexes Eligible for Study: All
Ages 40 Years to 80 Years   (Adult, Older Adult)
Accepts Healthy Volunteers Yes
Contacts
Contact: Humberto Martinez, COT 503-494-7712 martinhu@ohsu.edu
Contact: Denzil Romfh, OD 503-494-4351 romfhd@ohsu.edu
Listed Location Countries United States
Removed Location Countries  
 
Administrative Information
NCT Number NCT01957267
Other Study ID Numbers OHSU IRB #00009729
1R01EY023285 ( U.S. NIH Grant/Contract )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement Not Provided
Responsible Party David Huang, Oregon Health and Science University
Study Sponsor Oregon Health and Science University
Collaborators National Eye Institute (NEI)
Investigators
Principal Investigator: John Morrison, MD Oregon Health and Science University
PRS Account Oregon Health and Science University
Verification Date April 2019