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 < 0.001) and placebo (−0.194 logMAR; 95% CI: −0.254 to −0.133; p < 0.001) groups. While this study failed to provide evidence that fluoxetine enhances neuroplasticity, our data support other recent clinical studies suggesting that improvement of vision can be accomplished in adults with amblyopia.

The effect of combined patching and citalopram on visual acuity in adults with amblyopia: a randomized, crossover, placebo-controlled trial

“…In agreement with Huttunen et al [51], we found no effect of SSRI treatment on VEP parameters. This is in contrast to other emerging potential approaches to amblyopia treatment in adulthood such as the non-invasive brain stimulation technique anodal transcranial direct current stimulation that increases VEP amplitude [28].…”

“…Pattern Reversal VEP (1°checks) found no effect of the SSRI citalopram combined with two weeks of patching on amblyopic eye visual acuity or a range of secondary outcome measures in adults with amblyopia. These results are broadly consistent with another recent study with a similar duration treatment period (10 days) that reported no advantage of combining fluoxetine with perceptual learning compared to perceptual learning alone in adults with amblyopia [51]. A preliminary study of donepezil [54] and a randomized clinical trial of levodopa [55] have also found no benefit of drug treatment in amblyopia therapy.…”

“…It is possible that larger doses and longer treatment times are required to replicate the effects found in non-human animals. Supporting this idea, Sharif et al [50] found a significant effect of combined fluoxetine and patching with dose of 0.5 mg/kg/day and a 3-month treatment period whereas Huttunen et al [51] found no effect with 20 mg per day over 10 days. The parameter space for dosing and treatment duration is large for drug intervention studies of this type and further work is required to identify optimal values.…”

Cortical Tuning is Impaired After Perceptual Experience in Primary Visual Cortex of Serotonin Transporter-Deficient Mice

“…SF and contrast processing were also impaired after perceptual learning. Although fluoxetine was shown to improve visual acuity in adult rats, recent clinical trials in humans report diverse findings regarding the efficacy of the antidepressants in managing amblyopia ( Huttunen et al. 2018 ; Lagas et al.…”

From Basic Visual Science to Neurodevelopmental Disorders: The Voyage of Environmental Enrichment-Like Stimulation

“…Adult amblyopic rats chronically treated with fluoxetine display robust recovery of visual cortex plasticity and visual functions, together with increased BDNF and a reduced GABAergic tone in the primary visual cortex [96]. A very recent study examined the effect of fluoxetine in adult amblyopic human subjects, without a significant improvement in visual performance compared to that obtained in subjects treated with placebo [97]. Since all patients did also perform, during the 10 weeks of pharmacological treatment, an intense perceptual training therapy, it remains unclear whether the lack of a specific effect of fluoxetine in this study was due to a ceiling effect of the training paradigm.…”