INVITED REVIEW The case from animal studies for balanced binocular treatment strategies for human amblyopia Donald E. Mitchell and Kevin R. Duffy Department of Psychology and Neuroscience, Dalhousie University, Halifax, Canada Citation information: Mitchell DE & Duffy KR. The case from animal studies for balanced binocular treatment strategies for human amblyopia. Ophthalmic Physiol Opt 2014, 34, 129–145. doi: 10.1111/opo.12122 Keywords: amblyopia, critical period, stereopsis, visual acuity Correspondence: Donald E Mitchell E-mail address: d.e.mitchell@dal.ca Received: 9 January 2014; Accepted: 15 January 2014 Abstract Although amblyopia typically manifests itself as a monocular condition, its origin has long been linked to unbalanced neural signals from the two eyes during early postnatal development, a view confirmed by studies conducted on animal models in the last 50 years. Despite recognition of its binocular origin, treatment of amblyopia continues to be dominated by a period of patching of the non-amblyo- pic eye that necessarily hinders binocular co-operation. This review summarizes evidence from three lines of investigation conducted on an animal model of deprivation amblyopia to support the thesis that treatment of amblyopia should instead focus upon procedures that promote and enhance binocular co-operation. First, experiments with mixed daily visual experience in which episodes of abnor- mal visual input were pitted against normal binocular exposure revealed that short exposures of the latter offset much longer periods of abnormal input to allow normal development of visual acuity in both eyes. Second, experiments on the use of part-time patching revealed that purposeful introduction of episodes of binocular vision each day could be very beneficial. Periods of binocular exposure that represented 30–50% of the daily visual exposure included with daily occlu- sion of the non-amblyopic could allow recovery of normal vision in the amblyo- pic eye. Third, very recent experiments demonstrate that a short 10 day period of total darkness can promote very fast and complete recovery of visual acuity in the amblyopic eye of kittens and may represent an example of a class of artificial envi- ronments that have similar beneficial effects. Finally, an approach is described to allow timing of events in kitten and human visual system development to be scaled to optimize the ages for therapeutic interventions. Introduction Exactly fifty years have elapsed since publication of the ini- tial three papers of David Hubel and Torstein Wiesel that paved the way to an understanding of the anatomical and physiological basis of amblyopia. 1–3 This milestone makes it a propitious time to consider the impact of research on animal models of amblyopia on clinical treatment. Because Hubel and Wiesel’s initial work had such an impact it is important to summarize first their major findings and the important principles of development that they enunciated. Subsequent work by others is then reviewed in the context of its impact on treatment of human amblyopia. For the sake of economy, only selected primary articles will be cited and for more detailed summaries the reader is directed to a number of extensive reviews 4–10 that have been published over the last 35 years. Shortly after publication of their landmark description of the functional properties of neurones in the adult cat visual cortex, 11 Hubel and Wiesel demonstrated that many of these characteristics were already established in young visu- ally inexperienced kittens. 2 Notably, this was true for one of the definitive characteristics of cortical cells, the fact that they could be excited, but not necessarily equally, by visual stimulation of either eye. However, the relative weighting of the two eyes on individual cortical cells evident in the © 2014 The Authors Ophthalmic & Physiological Optics © 2014 The College of Optometrists Ophthalmic & Physiological Optics 34 (2014) 129–145 129 Ophthalmic & Physiological Optics ISSN 0275-5408