Abstract
Amblyopia is a developmental disorder that results in a wide range of visual deficits. One proven approach to recovering vision in adults with amblyopia is perceptual learning (PL). Recent evidence suggests that neuromodulators can enhance adult plasticity. In this pilot study, we asked whether donepezil, a cholinesterase inhibitor, enhances visual PL in adults with amblyopia. Nine adults with amblyopia were first trained on a low-contrast single-letter identification task while taking a daily dose (5 mg) of donepezil throughout training. Following 10,000 trials of training, participants showed improved contrast sensitivity for identifying single letters. However, the magnitude of improvement was no greater than, and the rate of improvement was slower than, that obtained in a previous study in which six adults with amblyopia were trained using an identical task and protocol but without donepezil (Chung et al., 2012). In addition, we measured transfer of learning effects to other tasks and found that for donepezil, the post-pre performance ratios in both a size-limited (acuity) and a spacing-limited (crowding) task were not significantly different from those found in the previous study without donepezil administration. After an interval of several weeks, six participants returned for a second course of training on identifying flanked (crowded) letters, again with concurrent donepezil administration. Although this task has previously been shown to be highly amenable to PL in adults with amblyopia (Chung et al., 2012; Hussain et al., 2012), only one observer in our study showed significant learning over 10,000 trials of training. Auxiliary experiments showed that the lack of a learning effect on this task during donepezil administration was not due to either the order of training of the two tasks or the use of a sequential training paradigm. Our results reveal that cholinergic enhancement with donepezil during training does not improve or speed up PL of single-letter identification in adults with amblyopia, and importantly, it may even halt learning and transfer related to a crowding task.Clinical Trial Registration: This study was registered with ClinicalTrials.gov (NCT03109314).
Highlights
Amblyopia is a developmental disorder of spatial vision that reflects the neural impairment that occurs when normal visual development is disrupted, and it is an ideal model for understanding when and how brain plasticity may be harnessed for recovery of function
Our results reveal that cholinergic enhancement with donepezil during training does not improve or speed up perceptual learning (PL) of single-letter identification in adults with amblyopia, and importantly, it may even halt learning and transfer related to a crowding task
We have previously shown that adults with amblyopia were able to improve on a low-contrast single letter identification task, as well as on a flanked letter task designed to reduce crowding, following 10 sessions (10,000 trials) of PL of the respective tasks (Chung et al, 2012)
Summary
Amblyopia is a developmental disorder of spatial vision that reflects the neural impairment that occurs when normal visual development is disrupted, and it is an ideal model for understanding when and how brain plasticity may be harnessed for recovery of function. Amblyopia is generally treated in young children by patching or penalizing the stronger eye. It is rarely treated in older children or adults because it is commonly assumed that there is limited visual system plasticity after the “critical period” of visual development has ended. One approach to recovering vision in human adults with amblyopia is perceptual learning (PL), in which patients practice a challenging visual task. The reduction in visual acuity deficits, the sine qua non of amblyopia, following PL is limited to about 1 to 2 lines on a visual acuity chart (Levi and Li, 2009; Tsirlin et al, 2015)
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