Clinical Review

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1. Background

Vision is limited by two main factors: (a) the quality of the image that is transferred from the eye, and (b) the neural processing in the brain, which needs to integrate information between different neurons located at neighboring brain locations  (space).  Cortical cells (neurons) are highly specialized and optimized as image analyzers. Thus, to characterize an image, visual processing involves  the cooperative activity of many  neurons—those neuronal interactions contributing to both excitation and inhibition.  The integration of image parts should be performed very quickly, since the time-window in which the first percept is formed is very short. Thus, visual information processing may be limited if the first  percept representation is inefficient either due  to slow neural processing or  to  the lack of effective interactions between the neurons.

1.1. Contrast sensitivity

Contrast sensitivity (CS), i.e., the ability to discriminate between shades of gray, is one of the main determinants of how well people see. It is assumed that the contrast sensitivity function (CSF) describes the combined response of the classical receptive fields of simple cells that have been selectively tuned for location, orientation, and spatial frequency and constitute the fundamental units of analysis. (Wilson, 1991; Wilson & Wilkinson, 1997). Thus, CSF describes the output of an early stage that provides the building blocks for the succeeding steps of visual processing.

During  the  last  two  decades,  it  was  demonstrated  that  contrast  response  is  also determined by lateral interactions in the visual cortex of humans (Bonneh & Sagi, 1999; Cass & Alais, 2006; Cass & Spehar, 2005; Ellenbogen, Polat, & Spitzer, 2006; Polat & Norcia, 1996; Polat & Sagi, 1993, 1994a, 1994b, 2006; Shani & Sagi, 2006; Solomon & Morgan,  2000;  Tanaka  &  Sagi,  1998;  Woods,  Nugent,  &  Peli,  2002) and of  animals (Crook, Engelmann, & Lowel, 2002; Kapadia, Ito, Gilbert, & Westheimer, 1995; Mizobe, Polat,) Visual acuity (VA) is the most common clinical measurement of visual function and is considered  as  the  gold  standard  measure  of  visual  functions.  VA  measures the ability to identify black symbols on a white background at a standardized distance as the size of the symbols  is varied. A person with standard (normal) VA can recognize a letter that is specified as 6/6 (20/20).

1.2. Neural plasticity and perceptual learning

Visual plasticity is the  ability of the visual system to change its  responses in order  to adapt to changes in the visual input. Evidence for plasticity in the adult visual system has been reported in human studies that have demonstrated that  training in specific  visual tasks  leads  to  improvement  in  performance  or  sensitivity  (for  a  review,  see (Fahle & Poggio, 2002)). Perceptual learning has a major  influence on our understanding of the development and plasticity of the visual system. Improvement after perceptual learning was demonstrated using a variety of visual tasks showing that the adult visual system can change according to behavioral demands (Fahle, 2005; Fiorentini & Berardi, 1980; Polat & Sagi, 1994b; Sagi & Tanne, 1994). (For a review, see Fahle (2002), Fahle and Poggio (2002), Gilbert, Sigman, and Crist (2001), Sagi and Tanne (1994).

1.3. Plasticity in amblyopia

Amblyopia is a reduction of visual functions that cannot be directly attributed to  the effect of any structural abnormality of the eye or the posterior visual pathway. It is caused by abnormal binocular visual experience early in life, during the ‘critical  period’  that prevents normal development of the visual  system. A generally practiced  principle of treatment is that therapy can only be effective during the critical period,  usually considered to end around the age of 8–9 (Greenwald & Parks, 1999; Prieto-Diaz, 2000; von Noorden, 1981), when the visual system is considered sufficiently plastic for cortical modifications to occur. The standard amblyopia therapy is thus traditionally  directed toward children and consists of penalizing the preferred eye by using an eye  patch or atropine, thus forcing the brain to use the visual input from the amblyopic eye. However, in adults, the visual deficiencies are thought to be irreparable after the first decade of life, once the developmental maturation window has been terminated;  thus the standard treatment is usually not offered.  However, recovery of visual  functions in adults with amblyopia after occlusion therapy (Birnbaum, Koslowe, & Sanet, 1977; Simmers, Gray, McGraw, & Winn, 1999; Wick, Wingard, Cotter, &  Scheiman, 1992) or after loss of vision in the good eye (El Mallah, Chakravarthy, & Hart, 2000) was reported. The first step in a series of controlled studies that provided evidence for plasticity, after perceptual learning, in adults with amblyopia used training for the vernier acuity task (Levi & Polat, 1996; Levi, Polat, & Hu, 1997b). Repetitive practice led to a substantial improvement in vernier acuity in the  amblyopic eyes  of  adults with amblyopia. In two observers, the improvement in vernier acuity was accompanied by a commensurate improvement in VA reaching up to normal vision. These studies provided an optimistic possibility for future treatment of amblyopia  based on perceptual learning. Recent studies have provided additional evidence for  plasticity in adults with amblyopia  (Chung,  Li,  &  Levi,  2006; Fronius,  Cirina,  Cordey,  &  Ohrloff,  2005;  Fronius,  Cirina,  Kuhli,  Cordey,  &  Ohrloff, 2006; Levi, 2005; Li & Levi, 2004; Polat et al., 2004; Zhou et al., 2006).

1.4. Improving normal visual functions

Some insight into the mechanism underlying neural plasticity, which may improve  the contrast sensitivity, comes from lateral masking experiments (Polat & Sagi, 1994b, 1995; Polat et al., U. Polat / Vision Research 49 (2009) 2566–2573 2567 2004). These studies suggest that practice on lateral interactions increases the efficacy of the  collinear interactions between neighboring neurons, an effect that  enables connectivity with remote neurons via a cascade of local interactions. Thus,  the results suggest a possible tool for the use of lateral interactions for improving CS in people with normal vision and in people with impaired lateral interactions such as amblyopia.  Polat has developed a perceptual learning procedure that was designed  to improve the abnormal lateral interactions in amblyopia by stimulating the deficient  neuronal populations and effectively promoting their collinear interactions (Polat,  2006, 2008; Polat et al., 2004). Since the amblyopic deficit is not identical among subjects (Bonneh, Sagi, & Polat, 2004; Bonneh et al., 2007; Polat, 2008; Polat et al., 2005), the treatment was tailored and specifically designed for each individual’s deficiencies.

1.5. Improvement of lateral interactions in amblyopia

Amblyopes exhibit abnormal lateral interactions (Bonneh et al., 2004, 2007; Ellemberg et al., 2002; Levi et al., 2002; Polat, 2006, 2008; Polat et al., 2004). The lateral interaction function of the amblyopes at the beginning of the treatment showed no facilitation and in fact, increased the amount of suppression. However, after the treatment, the amount of suppression was significantly reduced to a normal level (Polat, 2008; Polat et al., 2004).

1.6. Improvement of CSF in amblyopia

In the study of Polat et al. (2004), the amblyopic eyes exhibit the typical lower CS before treatment, as compared with normal sighted eyes, with the low spatial frequencies near the normal values and the high spatial frequencies showing a worse deficit. The treatment produced a significant improvement in sensitivity, by about a factor of two, in all spatial frequencies including the high spatial frequency range, raising the function to within the normal  (lower) range. Most interesting is the result that after 12 months, CSF was not only retained, but it also increased toward an average range at the high spatial frequencies. This result suggests that the  high spatial frequencies are used after the treatment in daily tasks and thus are naturally practiced.

1.7. Improvement of CSF in non-amblyopic groups

The  procedure  of  Polat  et  al.  (2004),  when  applied  to  people  with  normal  vision  or corrected to normal vision, improved their visual acuity to better than 66.  It has  been recently applied to improve the vision of people with low myopia (Tan & Fong, 2008). The vision of myopic (short  sighted) subjects is blurred without optical  correction. Therefore, the CSF is reduced, especially at the higher spatial frequencies,  when compared with people with corrected vision. This reduction in CS is reminiscent of the CS of amblyopic subjects. This study used a protocol similar to the one used for  the amblyopia (Polat et al., 2004); it showed that when subjects practiced with  uncorrected moderate myopia it improved their CS. Thus, even in cases when the lateral interactions are normal (low myopia), training improves CS.

1.8. Improvement of VA

The VA was found to improve after training on contrast detection  of amblyopes (Polat et al.,  2004), anisometropic amblyopes  (Huang  et  al.,  2008;  Zhou  et  al.,  2006), and  after training on verneir acuity (Levi & Polat, 1996; Levi, Polat, & Hu, 1997a). The training of low myopia on lateral interactions also shows improvement of VA (Tan & Fong, 2008). Thus, the training  can be generalized to the letter recognition task (VA), an effect that supports the relationships between these perceptual tasks and letter recognition.

1.9. Transfer to improvement of binocular vision

In the studies of Polat and colleagues, during the treatment, the fellow eye was covered; thus the treatment was monocular, targeting the abnormal lateral  interactions of the amblyopic eye. Very surprisingly, after treatment, the binocular  functions improved, indicating that both the binocular fusion and the stereo acuity  improved (Polat, 2006, 2008). A significant improvement in stereoacuity was also found in a retrospective study (Lichter, 2007).

1.10. Additional indications for function improvement.

In addition to Amblyopia and Myopia, several other conditions that cause reduced VA were studied. Presbyopic patients showed an increase of 1.5 to 2 lines and an increase of close to 100% in CS following treatment (Polat 2009; Tan 2005; Stahl & Durrie 2008;  Durrie & McMinn, 2007). Patients who have undergone refractive surgery have shown  similar results (Tan 2005, Waring IV et al., unpublished data). Patients who have  undergone intra-ocular-lens (IOL) implant surgery following cataract extraction  showed high CS improvement and an increase of 1 to 1.5 lines of VA in a variety of  monofocal and multifocal or accommodating IOLs (Waring IV et al. 2010). A possible positive treatment outcome in myopia control is suggested by seminal work done on school children (Chua et al. 2007), and although this is yet to be determined by a randomized double blind controlled study, over several years, the current  findings suggest optimistic outcomes.

Due to the promising findings in the above studies and in light of the fact that  the treatment is safe and non-invasive, several practitioners have used this treatment  in managing several types of ocular pathologies. Among others these include:  congenital nystagmus  (CN)  (Morad 2012), age related macular degeneration, retinitis  pigmentosa (Lyra,  2009) pathological myopia and congenital stationary  night blindness. A retrospective multicenter study which is being carried out during this year has already showing positive results in cases of CN.

1.11. Persistence of the improved functions

Different studies measured the persistence of the results over a retention period. While amblyopia  showed  a  surprising  increase  in  CS  function  over  time  (Polat  et  al  2004), others showed a mild regression of about 15% of the treatment effect over the first six months post treatment. However, in the following eighteen months of retention no further regression  was  noted  (Siow  &  Tan,  2008).  Studies  aimed  at  presbyopia  and  post refractive correction procedures have shown no regression over twelve months retention (Tan et al. 2005, Ng et al. 2007)


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