Objective Assessment of Macular Function at Retinal and Cortical Levels

• Conditions: Retina Disorder; Macula; Degeneration, Congenital or Hereditary
• Interventions: 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

• Registration Number: NCT03517241
• Lead Sponsor: 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.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2018-04-17
• Status Verified: 2018-05
• Study First Submitted QC: 2018-05-03
• Last Update Submitted: 2018-05-03
• Study First Posted: 2018-05-07
• Last Update Posted: 2018-05-07
• Study Start: 2018-05-15
• Primary Completion: 2020-03-16
• Study Completion: 2020-06-15

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: All
• Target Recruitment: 100

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

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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

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Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Arm && Interventions

Group	Intervention	Description
Geographic atrophy secondary to AMD	Visual testing	20 patients clinically diagnosed with geographic atrophy (GA) secondary to AMD.
Geographic atrophy secondary to AMD	Blue light fundus autofluorescence imaging (FAF)	20 patients clinically diagnosed with geographic atrophy (GA) secondary to AMD.
Geographic atrophy secondary to AMD	functional magnetic resonance imaging (fMRI)	20 patients clinically diagnosed with geographic atrophy (GA) secondary to AMD.
Geographic atrophy secondary to AMD	Optical coherence tomography (OCT)	20 patients clinically diagnosed with geographic atrophy (GA) secondary to AMD.
Geographic atrophy secondary to AMD	Microperimetry (MP)	20 patients clinically diagnosed with geographic atrophy (GA) secondary to AMD.
Stargards disease	Optical coherence tomography (OCT)	20 patients clinically and genetically diagnosed with Stargards disease (STGD)
Stargards disease	Blue light fundus autofluorescence imaging (FAF)	20 patients clinically and genetically diagnosed with Stargards disease (STGD)
Healthy controls	Blue light fundus autofluorescence imaging (FAF)	20 healthy control subjects. Visual acuity of 20/16- 20/32
Stargards disease	functional magnetic resonance imaging (fMRI)	20 patients clinically and genetically diagnosed with Stargards disease (STGD)
Stargards disease	Visual testing	20 patients clinically and genetically diagnosed with Stargards disease (STGD)
Branch retinal artery occlusion	Blue light fundus autofluorescence imaging (FAF)	20 patients clinically diagnosed with branch retinal artery occlusion (BRAO)
Stargards disease	Microperimetry (MP)	20 patients clinically and genetically diagnosed with Stargards disease (STGD)
Full thickness macular hole	Blue light fundus autofluorescence imaging (FAF)	20 patients clinically diagnosed with acute full thickness macular hole (FTMH) before and after macular surgery
Branch retinal artery occlusion	functional magnetic resonance imaging (fMRI)	20 patients clinically diagnosed with branch retinal artery occlusion (BRAO)
Branch retinal artery occlusion	Microperimetry (MP)	20 patients clinically diagnosed with branch retinal artery occlusion (BRAO)
Branch retinal artery occlusion	Visual testing	20 patients clinically diagnosed with branch retinal artery occlusion (BRAO)
Full thickness macular hole	Microperimetry (MP)	20 patients clinically diagnosed with acute full thickness macular hole (FTMH) before and after macular surgery
Healthy controls	Microperimetry (MP)	20 healthy control subjects. Visual acuity of 20/16- 20/32
Branch retinal artery occlusion	Optical coherence tomography (OCT)	20 patients clinically diagnosed with branch retinal artery occlusion (BRAO)
Full thickness macular hole	functional magnetic resonance imaging (fMRI)	20 patients clinically diagnosed with acute full thickness macular hole (FTMH) before and after macular surgery
Full thickness macular hole	Optical coherence tomography (OCT)	20 patients clinically diagnosed with acute full thickness macular hole (FTMH) before and after macular surgery
Healthy controls	Optical coherence tomography (OCT)	20 healthy control subjects. Visual acuity of 20/16- 20/32
Healthy controls	Visual testing	20 healthy control subjects. Visual acuity of 20/16- 20/32
Full thickness macular hole	Visual testing	20 patients clinically diagnosed with acute full thickness macular hole (FTMH) before and after macular surgery
Healthy controls	functional magnetic resonance imaging (fMRI)	20 healthy control subjects. Visual acuity of 20/16- 20/32

Primary Outcome Measures

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

Name	Time	Method
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	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.
Reproducibility assessment	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.