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Fluoxetine does not enhance the effect of perceptual learning on visual function in adults with amblyopia.

ABSTRACT: Amblyopia is a common visual disorder that is treatable in childhood. However, therapies have limited efficacy in adult patients with amblyopia. Fluoxetine can reinstate early-life critical period-like neuronal plasticity and has been used to recover functional vision in adult rats with amblyopia. We conducted a Phase 2, randomized (fluoxetine vs. placebo), double-blind, multicenter clinical trial examined whether or not fluoxetine can improve visual acuity in amblyopic adults. This interventional trial included 42 participants diagnosed with moderate to severe amblyopia. Subjects were randomized to receive either 20?mg fluoxetine (n?=?22) or placebo (n?=?20). During the 10-week treatment period, all subjects performed daily computerized perceptual training and eye patching. At the primary endpoint, the mean treatment group difference in visual acuity improvement was only 0.027 logMAR units (95% CI: -0.057 to 0.110; p?=?0.524). However, visual acuity had significantly improved from baseline to 10 weeks in both fluoxetine (-0.167 logMAR; 95% CI: -0.226 to -0.108; p?

SUBMITTER: Huttunen HJ

PROVIDER: S-EPMC6110780 | biostudies-literature | 2018 Aug

REPOSITORIES: biostudies-literature

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Fluoxetine does not enhance the effect of perceptual learning on visual function in adults with amblyopia.

Huttunen Henri J HJ Palva J Matias JM Lindberg Laura L Palva Satu S Saarela Ville V Karvonen Elina E Latvala Marja-Leena ML Liinamaa Johanna J Booms Sigrid S Castrén Eero E Uusitalo Hannu H

Scientific reports 20180827 1

Amblyopia is a common visual disorder that is treatable in childhood. However, therapies have limited efficacy in adult patients with amblyopia. Fluoxetine can reinstate early-life critical period-like neuronal plasticity and has been used to recover functional vision in adult rats with amblyopia. We conducted a Phase 2, randomized (fluoxetine vs. placebo), double-blind, multicenter clinical trial examined whether or not fluoxetine can improve visual acuity in amblyopic adults. This intervention ...[more]

PMID: 30150750

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Project description: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).

Project description:PurposeDevelop a paradigm to map binocular perceptual visual distortions in adult amblyopes and visually normal controls, measure their stability over time, and determine the relationship between strength of binocular single vision and distortion magnitude.MethodsPerceptual visual distortions were measured in 24 strabismic, anisometropic, or microtropic amblyopes (interocular acuity difference ≥ 0.200 logMAR or history of amblyopia treatment) and 10 controls (mean age 27.13 ± 10.20 years). The task was mouse-based target alignment on a stereoscopic liquid crystal display monitor, measured binocularly five times during viewing dichoptically through active shutter glasses, amblyopic eye viewing cross-hairs, fellow eye viewing single target dots (16 locations within central 5°), and five times nondichoptically, with all stimuli visible to either eye. Measurements were repeated over time (1 week, 1 month) in eight amblyopic subjects, evaluating test-retest reliability. Measurements were also correlated against logMAR visual acuity, horizontal prism motor fusion range, Frisby/Preschool Randot stereoacuity, and heterophoria/heterotropia prism cover test measurement.ResultsSixty-seven percent (16/24) of amblyopes had significant perceptual visual distortions under dichoptic viewing conditions compared to nondichoptic viewing conditions and dichoptic control group performance. Distortions correlated with the strength of motor fusion (r = -0.417, P = 0.043) and log stereoacuity (r = 0.492, P = 0.015), as well as near angle of heterotropic/heterophoric deviation (r = 0.740, P < 0.001), and, marginally, amblyopia depth (r = 0.405, P = 0.049). Global distortion index (GDI, mean displacement) remained, overall, consistent over time (median change in GDI between baseline and 1 week = -0.03°, 1 month = -0.08°; x-axis Z = 4.4256, P < 0.001; y-axis Z = 5.0547, P < 0.001).ConclusionsPerceptual visual distortions are stable over time and associated with poorer binocular function, greater amblyopia depth, and larger angles of ocular deviation. Assessment of distortions may be relevant for recent perceptual learning paradigms specifically targeting binocular vision.

Dataset Information

Fluoxetine does not enhance the effect of perceptual learning on visual function in adults with amblyopia.

Publications

Fluoxetine does not enhance the effect of perceptual learning on visual function in adults with amblyopia.

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