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Objective Assessment of Macular Function at Retinal and Cortical Levels

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ClinicalTrials.gov Identifier: NCT03517241
Recruitment Status : Not yet recruiting
First Posted : May 7, 2018
Last Update Posted : May 7, 2018
Sponsor:
Information provided by (Responsible Party):
Markus Ritter, MD, Medical University of Vienna

Brief Summary:

Research questions/hypotheses: About 15% of the population over 40 years of age are affected by diseases of the retina. Accurate measurement of the extent of visual field impairment is of highest importance for disease subtype diagnosis and severity classification. The current gold-standard approach for the assessment of macular sensitivity is microperimetry (MP) where the patient is asked to report whether or not visual stimuli presented at different positions within the visual field are detected. While this technique is a very straightforward approach and simple in its application, it is important to note that MP is psychophysical in nature and requires constantly high attentional performance of the patient throughout the examination period. As many patients suffering from retinal diseases are well over 65 years of age, they are unable to maintain such high levels of attention over longer periods and, thus, MP results may be biased. Retinotopic assessment using population receptive field (pRF) mapping based on functional magnetic resonance imaging (fMRI) offers an alternative by allowing for objective visual field testing, independent of patient performance. We have shown previously in healthy subjects that pRF allows for accurate detection of simulated central scotomata down to 2.35 degrees radius. Also, pilot data in patients with retinal scotomata showed strong correspondence between pRF and MP results, i.e. macular regions with reduced macular sensitivity and atrophy of outer retinal layers correlated well with pRF coverage maps showing reduced density of activated voxels. The aim of this project is to determine whether pRF mapping could serve as an alternative visual field testing method by: (1) assessing test-retest reproducibility of pRF and MP in clinical populations with stable retinal diseases (Stargardt disease, geographic atrophy) over a four-week period; (2) assessing visual field changes over a one-year period in patients suffering from acute retinal scotomata (branch retinal artery occlusions, full-thickness macular holes). All pRF mapping will be accompanied by MP measurements to allow for a direct comparison of the two techniques.

Scientific/scholarly innovation/originality of the project: The present project applies a novel approach for linking retinal function assessed with MP and pRF mapping in a representative patient population with acute and chronic retinal diseases. The project seeks to contribute to best practice methods for using fMRI to assess macular dysfunction both for documentation of the natural course of the disease and during therapy in a study setting.

Methods: fMRI uses pRF mapping to provide retinotopic data (pRF coverage maps) that are then correlated with the results of conventional ophthalmic testing including MP, visual acuity and contrast sensitivity testing, reading performance, optical coherence tomography and autofluorescence imaging.


Condition or disease Intervention/treatment
Macula; Degeneration, Congenital or Hereditary Retina Disorder Diagnostic Test: functional magnetic resonance imaging (fMRI) Diagnostic Test: Microperimetry (MP) Diagnostic Test: Optical coherence tomography (OCT) Diagnostic Test: Blue light fundus autofluorescence imaging (FAF) Diagnostic Test: Visual testing

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Study Type : Observational
Estimated Enrollment : 100 participants
Observational Model: Case-Control
Time Perspective: Prospective
Official Title: A Multimodal Approach Towards an Objective Assessment of Macular Function at Retinal and Cortical Levels
Estimated Study Start Date : May 15, 2018
Estimated Primary Completion Date : March 16, 2020
Estimated Study Completion Date : June 15, 2020

Resource links provided by the National Library of Medicine


Group/Cohort Intervention/treatment
Geographic atrophy secondary to AMD
20 patients clinically diagnosed with geographic atrophy (GA) secondary to AMD.
Diagnostic Test: functional magnetic resonance imaging (fMRI)
Retinotopic mapping using functional magnetic resonance imaging (fMRI) is based on MR images acquired with blood-oxygenation-level-dependent (BOLD) contrast to reveal areas of neuronal activity in the visual cortex

Diagnostic Test: Microperimetry (MP)
MP allows localized testing of retinal sensitivity of foveal, parafoveal and even more peripheral macular regions

Diagnostic Test: Optical coherence tomography (OCT)
Optical Coherence Tomography (OCT) is a non-invasive diagnostic technique that renders an in vivo cross sectional view of the retina.

Diagnostic Test: Blue light fundus autofluorescence imaging (FAF)
Fundus autofluorescence imaging (FAF), is a non-invasive diagnostic technique focusing on the fluorescent properties of pigments in the retina to generate images.

Diagnostic Test: Visual testing
Best-corrected visual acuity will be measured using Early Treatment Diabetic Retinopathy Study (ETDRS) charts. Reading acuity and reading speed will be examined using Radner Reading Charts. Reading acuity is measured in logRAD unit (= reading equivalent of logMAR) and in critical font size (critical reading size), reading speed is measured in words per minute (wpm). Contrast sensitivity will be determined using Pelli-Robson contrast sensitivity charts.

Stargards disease
20 patients clinically and genetically diagnosed with Stargards disease (STGD)
Diagnostic Test: functional magnetic resonance imaging (fMRI)
Retinotopic mapping using functional magnetic resonance imaging (fMRI) is based on MR images acquired with blood-oxygenation-level-dependent (BOLD) contrast to reveal areas of neuronal activity in the visual cortex

Diagnostic Test: Microperimetry (MP)
MP allows localized testing of retinal sensitivity of foveal, parafoveal and even more peripheral macular regions

Diagnostic Test: Optical coherence tomography (OCT)
Optical Coherence Tomography (OCT) is a non-invasive diagnostic technique that renders an in vivo cross sectional view of the retina.

Diagnostic Test: Blue light fundus autofluorescence imaging (FAF)
Fundus autofluorescence imaging (FAF), is a non-invasive diagnostic technique focusing on the fluorescent properties of pigments in the retina to generate images.

Diagnostic Test: Visual testing
Best-corrected visual acuity will be measured using Early Treatment Diabetic Retinopathy Study (ETDRS) charts. Reading acuity and reading speed will be examined using Radner Reading Charts. Reading acuity is measured in logRAD unit (= reading equivalent of logMAR) and in critical font size (critical reading size), reading speed is measured in words per minute (wpm). Contrast sensitivity will be determined using Pelli-Robson contrast sensitivity charts.

Branch retinal artery occlusion
20 patients clinically diagnosed with branch retinal artery occlusion (BRAO)
Diagnostic Test: functional magnetic resonance imaging (fMRI)
Retinotopic mapping using functional magnetic resonance imaging (fMRI) is based on MR images acquired with blood-oxygenation-level-dependent (BOLD) contrast to reveal areas of neuronal activity in the visual cortex

Diagnostic Test: Microperimetry (MP)
MP allows localized testing of retinal sensitivity of foveal, parafoveal and even more peripheral macular regions

Diagnostic Test: Optical coherence tomography (OCT)
Optical Coherence Tomography (OCT) is a non-invasive diagnostic technique that renders an in vivo cross sectional view of the retina.

Diagnostic Test: Blue light fundus autofluorescence imaging (FAF)
Fundus autofluorescence imaging (FAF), is a non-invasive diagnostic technique focusing on the fluorescent properties of pigments in the retina to generate images.

Diagnostic Test: Visual testing
Best-corrected visual acuity will be measured using Early Treatment Diabetic Retinopathy Study (ETDRS) charts. Reading acuity and reading speed will be examined using Radner Reading Charts. Reading acuity is measured in logRAD unit (= reading equivalent of logMAR) and in critical font size (critical reading size), reading speed is measured in words per minute (wpm). Contrast sensitivity will be determined using Pelli-Robson contrast sensitivity charts.

Full thickness macular hole
20 patients clinically diagnosed with acute full thickness macular hole (FTMH) before and after macular surgery
Diagnostic Test: functional magnetic resonance imaging (fMRI)
Retinotopic mapping using functional magnetic resonance imaging (fMRI) is based on MR images acquired with blood-oxygenation-level-dependent (BOLD) contrast to reveal areas of neuronal activity in the visual cortex

Diagnostic Test: Microperimetry (MP)
MP allows localized testing of retinal sensitivity of foveal, parafoveal and even more peripheral macular regions

Diagnostic Test: Optical coherence tomography (OCT)
Optical Coherence Tomography (OCT) is a non-invasive diagnostic technique that renders an in vivo cross sectional view of the retina.

Diagnostic Test: Blue light fundus autofluorescence imaging (FAF)
Fundus autofluorescence imaging (FAF), is a non-invasive diagnostic technique focusing on the fluorescent properties of pigments in the retina to generate images.

Diagnostic Test: Visual testing
Best-corrected visual acuity will be measured using Early Treatment Diabetic Retinopathy Study (ETDRS) charts. Reading acuity and reading speed will be examined using Radner Reading Charts. Reading acuity is measured in logRAD unit (= reading equivalent of logMAR) and in critical font size (critical reading size), reading speed is measured in words per minute (wpm). Contrast sensitivity will be determined using Pelli-Robson contrast sensitivity charts.

Healthy controls
20 healthy control subjects. Visual acuity of 20/16- 20/32
Diagnostic Test: functional magnetic resonance imaging (fMRI)
Retinotopic mapping using functional magnetic resonance imaging (fMRI) is based on MR images acquired with blood-oxygenation-level-dependent (BOLD) contrast to reveal areas of neuronal activity in the visual cortex

Diagnostic Test: Microperimetry (MP)
MP allows localized testing of retinal sensitivity of foveal, parafoveal and even more peripheral macular regions

Diagnostic Test: Optical coherence tomography (OCT)
Optical Coherence Tomography (OCT) is a non-invasive diagnostic technique that renders an in vivo cross sectional view of the retina.

Diagnostic Test: Blue light fundus autofluorescence imaging (FAF)
Fundus autofluorescence imaging (FAF), is a non-invasive diagnostic technique focusing on the fluorescent properties of pigments in the retina to generate images.

Diagnostic Test: Visual testing
Best-corrected visual acuity will be measured using Early Treatment Diabetic Retinopathy Study (ETDRS) charts. Reading acuity and reading speed will be examined using Radner Reading Charts. Reading acuity is measured in logRAD unit (= reading equivalent of logMAR) and in critical font size (critical reading size), reading speed is measured in words per minute (wpm). Contrast sensitivity will be determined using Pelli-Robson contrast sensitivity charts.




Primary Outcome Measures :
  1. Correspondence between coverage maps originating from microperimetry and population-receptive field mapping of the primary visual cortex measured by functional magnetic resonance imaging. [ Time Frame: 2 years ]
    Qualitative and quantitative assessment of the correspondence between conventional functional assessment of retinal scotomata (microperimetry) and population-receptive field (pRF) mapping of the primary visual cortex measured by functional magnetic resonance imaging in patients clinically diagnosed with geographic atrophy secondary to age-related macular degeneration, Stargardts disease, branch retinal artery occlusions and full thickness macular holes before and after macular surgery. The microperimetry test grid (retinal sensitivity measured in Decibel, dB) willl be correlated with the pRF coverage maps calculated from fMRI data. Each dot represents the centre of a receptive field of a single voxel and every pRF centre is associated with a 2D Gaussian which together constitute the coverage map. Correspondence between coverage maps will be quantified by calculating the matching coefficient.


Secondary Outcome Measures :
  1. Correspondence between coverage maps originating from structural imaging (optical coherence tomography and autofluorescence imaging) and population-receptive field mapping of the primary visual cortex measured by functional magnetic resonance imaging. [ Time Frame: 2 years ]
    Qualitative and quantitative assessment of the correspondence between conventional structural assessment of retinal scotomata (optical coherence tomography and autofluorescence imaging) and population-receptive field (pRF) mapping of the primary visual cortex measured by functional magnetic resonance imaging in patients clinically diagnosed with geographic atrophy secondary to age-related macular degeneration, Stargardts disease, branch retinal artery occlusions and full thickness macular holes before and after macular surgery. The retinal layer thickness maps (measured in micometer, µm) willl be correlated with the pRF coverage maps calculated from fMRI data. Each dot represents the centre of a receptive field of a single voxel and every pRF centre is associated with a 2D Gaussian which together constitute the coverage map.Correspondence between coverage maps will be quantified by calculating the matching coefficient.

  2. Reproducibility assessment [ Time Frame: 1 year ]
    Reproducibility of population-receptive field mapping of the primary visual cortex and of conventional ophthalmic assessment (microperimetry, visual acuity and contrast sensitivity testing, reading performance, optical coherence tomography and autofluorescence imaging) in patients with retinal scotomata secondary to Stargardt disease and geographic atrophy compared with normal control participants with artificial scotomata.



Information from the National Library of Medicine

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Ages Eligible for Study:   Child, Adult, Older Adult
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Sampling Method:   Non-Probability Sample
Study Population
Consecutive enrollment from the Macular Disease Unit of the Dept. of Ophthalmology, Medical University of Vienna.
Criteria

Inclusion Criteria:

  • 20 patients clinically diagnosed with GA secondary to AMD.
  • 20 patients clinically and genetically diagnosed with STGD.
  • 20 patients clinically diagnosed with BRAO.
  • 20 patients clinically diagnosed with acute FTMH before and after macular surgery.
  • 20 healthy control subjects. Visual acuity of 20/16- 20/32

Exclusion Criteria:

  • Presence of any other ophthalmological or neurological disease affecting visual function
  • Cataract > grade 2 (according to lens opacities system)
  • All routine exclusion criteria that apply to MRI scans including pacemakers, metallic implants, prostheses or coils, claustrophobia
  • Pregnancy
  • Dyslexia

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03517241


Contacts
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Contact: Markus Ritter, MD +4314040079400 markus.ritter@meduniwien.ac.at

Sponsors and Collaborators
Medical University of Vienna

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Responsible Party: Markus Ritter, MD, Associate Professor, Medical University of Vienna
ClinicalTrials.gov Identifier: NCT03517241     History of Changes
Other Study ID Numbers: EK1816/2014
First Posted: May 7, 2018    Key Record Dates
Last Update Posted: May 7, 2018
Last Verified: May 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Retinal Diseases
Eye Diseases