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.

Trial Health

At Risk

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Trial has exceeded expected completion date

Enrollment

100

participants targeted

Target at P50-P75 for all trials

Timeline

Completed

Started May 2018

Typical duration for all trials

Status

unknown

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

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Study Timeline

Key milestones and dates

2.1 years study duration

First Submitted

Initial submission to the registry

April 17, 2018

Completed

20 days until next milestone

First Posted

Study publicly available on registry

May 7, 2018

Completed

8 days until next milestone

Study Start

First participant enrolled

May 15, 2018

Completed

1.8 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

March 16, 2020

Completed

3 months until next milestone

Study Completion

Last participant's last visit for all outcomes

June 15, 2020

Completed

Last Updated

May 7, 2018

Status Verified

May 1, 2018

Enrollment Period

1.8 years

First QC Date

April 17, 2018

Last Update Submit

May 3, 2018

Conditions

Macula; Degeneration, Congenital or Hereditary Retina Disorder

Outcome Measures

Primary Outcomes (1)

Correspondence between coverage maps originating from microperimetry and population-receptive field mapping of the primary visual cortex measured by functional magnetic resonance imaging.
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.
2 years

Secondary Outcomes (2)

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.
2 years
Reproducibility assessment
1 year

Study Arms (5)

Geographic atrophy secondary to AMD

20 patients clinically diagnosed with geographic atrophy (GA) secondary to AMD.

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

Stargards disease

20 patients clinically and genetically diagnosed with Stargards disease (STGD)

Branch retinal artery occlusion

20 patients clinically diagnosed with branch retinal artery occlusion (BRAO)

Full thickness macular hole

20 patients clinically diagnosed with acute full thickness macular hole (FTMH) before and after macular surgery

Healthy controls

20 healthy control subjects. Visual acuity of 20/16- 20/32

Interventions

functional magnetic resonance imaging (fMRI)DIAGNOSTIC_TEST

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