Objective Assessment of Macular Function at Retinal and Cortical Levels

A Multimodal Approach Towards an Objective Assessment of Macular Function at Retinal and Cortical Levels

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.

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