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Current treatments for macular degenerative diseases can stabilize or slow disease progression but generally cannot provide a ‘cure’. As a result, a significant number of individuals with macular degeneration suffer from a loss of central vision that forces them to rely on para-central peripheral vision. Most patients with macular degeneration (84% of 1339 eyes) [
] develop a preferred retinal locus (PRL): a specific para-central retinal region that is used for visual tasks in place of the fovea. However, the para-central retina is more susceptible to crowding (an inability to differentiate visual objects presented in ‘visual clutter’) [
]. This means that visual processing remains poor, even after spatial resolution limitations are addressed with appropriate magnification. Therefore, the reduction of crowding could be an effective rehabilitation strategy. Perceptual learning studies in individuals with normal vision [
] have reported improvements in peripheral visual function with training. However, perceptual learning requires extensive training and gains are typically specific to the trained stimulus. Nevertheless, these findings indicate that the neural mechanisms contributing to crowding in peripheral vision are plastic.
Non-invasive brain stimulation techniques such as anodal direct current stimulation (a-tDCS) offer an alternative approach to improving peripheral visual function [
]. Collinear inhibition refers to the impaired detectability of a visual target when it is flanked by similarly oriented high contrast targets and is one of the low-level mechanisms involved in visual crowding [
]. Building on this previous work, in this case series of three patients with central vision loss, we tested whether a-tDCS could be used to modulate the neural mechanisms that contribute to crowding in a clinical population.
5 participants (4 females; age: 55 ± 22 years) diagnosed with macular degeneration agreed to participate in this study. Participants were excluded if they had multiple PRLs and any contraindications to transcranial electrical stimulation. Two participants were excluded due to a history of epilepsy and a preexisting heart condition. Data for the remaining three participants were collected at the School of Optometry and Vision Science, University of Waterloo, Waterloo, Canada (n = 2) and the Envision Research Institute, Wichita, USA (n = 1). All participants provided written, informed consent. The study was approved by the University of Waterloo and Wichita State University research ethics committees. All the procedures involved in this research adhered to the tenets of the Declaration of Helsinki. A sham controlled, single-blind study design was used to test the effect of visual cortex a-tDCS on collinear inhibition.
Patients with macular degeneration performed a 2AFC contrast detection task with collinear flankers positioned at a distance of 3λ from the target (collinear inhibition) or 6λ (collinear facilitation). Participants were encouraged to adopt their habitual head position so that they could see the fixation cross clearly and fixation was monitored using an infrared video-based eyetracker. Each patient completed two randomized sessions: real anodal-tDCS or sham tDCS. tDCS was administered using a commercially available DC Stimulator (NeuroConn MC). The electrical current was administered using two 5 cm × 5 cm rubber electrodes placed inside saline soaked sponges. The electrodes were secured using a head strap and placed over Oz (anodal electrode) and Cz (cathodal electrode) based on the 10–20 EEG electrode positioning system. Active stimulation involved 2 mA of anodal tDCS for 20 minutes. Sham stimulation involved a 5 second ramp up of current immediately followed by a 5 second ramp down with the electrodes left in place for 20 minutes. Active and sham stimulation visits took place on two different days and each visit was separated by at least 48 hours. The order of stimulation was also randomized. During each visit, all participants completed 4 sessions of contrast threshold measurements: pre-, during-, 5min post- and 30min post-stimulation (Supplementary Figure 1).
All participants completed the two study sessions without reporting any adverse effects. However, participant S3 could not complete the 6λ viewing condition. Fig. 1 shows the mean normalized contrast thresholds for the collinear inhibition condition for the active and sham stimulation sessions. The mean contrast threshold values and staircase reversal standard deviations for every participant for the collinear inhibition and facilitation viewing conditions are provided in Supplementary Table 1. A reduction of collinear inhibition is apparent for the active but not the sham stimulation conditions for all participants. With a single session of a-tDCS, an average 56% (38%–76%) reduction of collinear inhibition was sustained after 30min of stimulation.
Fig. 1Changes in contrast threshold for the anodal and sham tDCS conditions.
The solid line with circular markers represenst the active anodal stimulation condition whereas the dotted line with square markers represents sham stimulation. Abbreviations: DS – during-stimulation; PS – post-stimulation.
Our preliminary case series results indicate that it may be possible to alleviate lateral inhibition and perhaps other components of crowding in patients with macular degeneration by directly altering cortical processing with non-invasive brain stimulation. These observations provide a foundation for larger studies into the use of visual cortex a-tDCS to improve visual function in patients with central vision loss. Recent technological advances have enabled tDCS to be delivered as a home based therapy (for instance, https://soterixmedical.com/research/remote) meaning that such studies can be more easily accomplished.
Declaration of competing interest
The authors confirm there are no known conflicts of interest associated with this publication and there has been no significant financial support for this work that influenced its outcome.
Acknowledgement
This research was funded by the LCI Foundation (RNR), CFI grant 34095(BT) and NSERC grants RPIN-05394 and RGPAS-477166 (BT).
Appendix A. Supplementary data
The following is the Supplementary data to this article:
We wish to confirm that there are no known conflicts of interest associated with this publication and there has been no significant financial support for this work that could have influenced its outcome.
We confirm that the manuscript has been read and approved by all named authors and that there are no other persons who satisfied the criteria for authorship but are not listed. We further confirm that the order of authors listed in the manuscript has been approved by all of us.
We further confirm that any aspect of the work covered in this manuscript that has involved either experimental animals or human patients has been conducted with the ethical approval of all relevant bodies and that such approvals are acknowledged within the manuscript.
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References
Fletcher D.C.
Schuchard R.A.
Preferred retinal loci relationship to macular scotomas in a low-vision population.
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This article has been withdrawn at the request of the author(s) and/or editor. The Publisher apologizes for any inconvenience this may cause. The full Elsevier Policy on Article Withdrawal can be found at https://www.elsevier.com/about/our-business/policies/article-withdrawal .
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