A new counter-intuitive therapy for adult amblyopia

Abstract

Visual cortex plasticity is high during a critical period of early postnatal development, but rapidly diminishes with the transition to adulthood. Accordingly, visual disorders such as amblyopia (lazy eye), can be treated early in life by long-term occlusion of the non-amblyopic eye, but may become irreversible in adults, because of the decline in brain plasticity. Here we show that a novel counter-intuitive approach can promote the recovery of visual function in adult amblyopic patients: short-term occlusion of the amblyopic (not the fellow) eye, combined with physical exercise (cycling). After six brief (2h) training sessions, visual acuity improved in all ten patients (0.15±0.02 LogMar), and six of them also recovered stereopsis. The improvement was preserved for up to one year after training. A control experiment revealed that physical activity was crucial for the recovery of visual acuity and stereopsis. Thus, we propose a non-invasive therapeutic strategy for adult human amblyopia based an inverse-occlusion and physical exercise procedure.

Response to short-term deprivation of the human adult visual cortex measured with 7T BOLD

“…Particularly important is Ocular Dominance plasticity in amblyopia (Webber and Wood, 2005), a cortical deficit still without cure in adults, although recent advancements in training procedures are opening new hopes (Levi and Li, 2009; Sengpiel, 2014). Endorsing plasticity may increase the effectiveness of these treatments and preliminary data from our laboratory suggest that monocular deprivation of the amblyopic eye may indeed boost sensitivity of the deprived eye and improve its acuity (Lunghi et al, 2018) – just like an acuity change is revealed by the present BOLD measurements in normally sighted participants. Our data demonstrate that two hours of abnormally unbalanced visual experience is sufficient to induce a functional reorganization of cortical circuits, particularly of the parvocellular pathway, leading to an alteration of basic visual perceptual abilities.…”

“…Only in rare occasions does adaptation induce effects that last over days (McCollough, 1965), yet our recent work shows that deprivation effects of short-term monocular deprivation is retained across 6 hr sleep (Menicucci et al, 2018), consistent with plasticity reinforcement during sleep (Raven et al, 2018; Timofeev and Chauvette, 2017). Most importantly, in adult amblyopic patients, short-term monocular deprivation is able to induce improvement of visual acuity and stereovision (Lunghi et al, 2018) for up to one year. All this evidence supports the concept that homeostatic plasticity in the human adult cortex may be linked with or may promote more stable forms of Hebbian-like plasticity.…”

“…For example, in patients with keratoconus (adult-onset corneal dystrophia, often monocular), best corrected visual acuity is worse than in emmetropic eyes, but it is better than predicted by the corneal dystrophy (Sabesan and Yoon, 2009; Sabesan and Yoon, 2010): when corneal aberrations of the keratoconic (KC) eyes are simulated in the emmetropic eyes, visual acuity is worse than in the KC eyes, demonstrating a permanent perceptual boost of the deprived information. Moreover, in adult amblyopes (Lunghi et al, 2018), short-term monocular deprivation (of the amblyopic eye) may lead to permanent partial recovery of acuity (of the amblyopic eye). This observation resonates with the idea – introduced in the context of work at the cellular level – that homeostatic plasticity and Hebbian plasticity may be fundamentally linked (Maffei and Turrigiano, 2008) and may open important new pathways for the therapy of amblyopia and, in general, for the rehabilitation of early-onset visual dysfunctions (Legge and Chung, 2016).…”