A New Dichoptic Training Strategy Leads to Better Cooperation Between the Two Eyes in Amblyopia

Zitian Liu, Zidong Chen, Le Gao, Manli Liu, Yiru Huang, Lei Feng, Junpeng Yuan, Daming Deng, Chang-Bing Huang, Minbin Yu, Zitian Liu, Zidong Chen, Le Gao, Manli Liu, Yiru Huang, Lei Feng, Junpeng Yuan, Daming Deng, Chang-Bing Huang, Minbin Yu

Abstract

Recent clinical trials failed to endorse dichoptic training for amblyopia treatment. Here, we proposed an alternative training strategy that focused on reducing signal threshold contrast in the amblyopic eye under a constant and high noise contrast in the fellow eye (HNC), and compared it to a typical dichoptic strategy that aimed at increasing the tolerable noise contrast in the fellow eye (i.e., TNC strategy). We recruited 16 patients with amblyopia and divided them into two groups. Eight patients in Group 1 received the HNC training, while the other eight patients in Group 2 performed the TNC training first (Phase 1) and then crossed over to the HNC training (Phase 2). We measured contrast sensitivity functions (CSFs) separately in the amblyopic and fellow eyes when the untested eye viewed mean luminance (monocularly unmasked) or noise stimuli (dichoptically masked) before and after training at a particular frequency. The area under the log contrast sensitivity function (AULCSF) of masked and unmasked conditions, and dichoptic gain (the ratio of AULCSF of masked to unmasked condition) were calculated for each eye. We found that both dichoptic training paradigms substantially improved masked CSF, dichoptic gain, and visual acuity in the amblyopic eye. As opposed to the TNC paradigm, the HNC training produced stronger effects on masked CSFs, stereoacuity, dichoptic gain, and visual acuity in the amblyopic eye. Interestingly, the second-phase HNC training in Group 2 also induced further improvement in the masked contrast sensitivity and AULCSF in the amblyopic eye. We concluded that the HNC training strategy was more effective than the TNC training paradigm. Future design for dichoptic training should not only focus on increasing the tolerable noise contrast in the fellow eye but should also "nurture" the amblyopic eye under normal binocular viewing conditions and sustained interocular suppression.

Keywords: amblyopia; contrast sensitivity functions; dichoptic masking; dichoptic training; interocular suppression.

Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Copyright © 2020 Liu, Chen, Gao, Liu, Huang, Feng, Yuan, Deng, Huang and Yu.

Figures

FIGURE 1
FIGURE 1
(A) Two strategies of dichoptic training used in this study. Left: High noise contrast (HNC) protocol; Sinusoidal gratings were presented to one eye, while a mean background luminance (monocular unmasked condition) or a Gaussian white noise mask (dichoptic masked condition) was presented to the untested eye. From top to bottom: the contrast of gratings in an amblyopic eye (AE) was manipulated from high to low, while noise mask in a fellow eye (FE) was fixed at high contrast (σ = 0.33). With training, the contrast of grating was adjusted (usually decreased) to maintain stable performance. Right: tolerable noise contrast (TNC) protocol; grating contrast in AE was fixed while mask contrast in FE was manipulated from low to high to maintain stable performance. (B) Four conditions of CSFs were measured: unmasked fellow eye (FEU), unmasked amblyopic eye (AEU), masked fellow eye (FEM), and masked amblyopic eye (AEM).
FIGURE 2
FIGURE 2
Learning curves for the two different training protocols in amblyopic participants from (A) Group 1 with constant and high noise contrast in the fellow eye (HNC), (B) Group 2 (Phase 1) with progressively elevated noise contrast in the fellow eye (TNC); (C) Group 2 (Phase 2), HNC training.
FIGURE 3
FIGURE 3
(A) Pre- and post-training contrast sensitivity functions (CSFs) under different conditions in Group 1. (B) Dichoptic gains for the two eyes before HNC training (x-axis) are plotted against those after training (y-axis). The diagonal unity line represents unchanged dichoptic gain between pre- and post-training assessment.
FIGURE 4
FIGURE 4
(A) CSFs under different conditions in Group 2 before (Pre, circle) and after (Post, triangle) the TNC training (Phase 1). (B) CSFs under different conditions in Group 2 after the TNC training (Post, triangle) and after crossed over to the HNC training (Cross, square) (Phase 2). (C) Dichoptic gains for the two eyes in Group 2 before training (x-axis) is plotted against those after training (y-axis) for the two phases. The diagonal unity line represents unchanged dichoptic gain between pre- and post-training assessment.
FIGURE 5
FIGURE 5
Improvements in visual function after HNC vs. TNC training. Error bars represent SEM. *p < 0.05; **p < 0.01; ***p < 0.001.
FIGURE 6
FIGURE 6
Summary of training effects. Groups were represented by different colors: black (Group 1), dark gray (Group 2, Phase 1), and light gray (Group 2, Phase 2). Error bars represent SEM. *p < 0.05.

References

    1. Astle A. T., Webb B. S., McGraw P. V. (2011). The pattern of learned visual improvements in adult amblyopia. Invest. Ophthalmol. Vis. Sci. 52 7195–7204. 10.1167/iovs.11-7584
    1. Birch E. E., Jost R. M., De La Cruz A., Kelly K. R., Beauchamp C. L., Dao L., et al. (2019). Binocular amblyopia treatment with contrast-rebalanced movies. J. AAPOS 23 160 e161–160 e165. 10.1016/j.jaapos.2019.02.007
    1. Birch E. E., Li S. L., Jost R. M., Morale S. E., De La Cruz A., Stager D., et al. (2015). Binocular iPad treatment for amblyopia in preschool children. J. AAPOS 19 6–11. 10.1016/j.jaapos.2014.09.009
    1. Bossi M., Tailor V. K., Anderson E. J., Bex P. J., Greenwood J. A., Dahlmann-Noor A., et al. (2017). Binocular therapy for childhood amblyopia improves vision without breaking interocular suppression. Invest. Ophthalmol. Vis. Sci. 58 3031–3043. 10.1167/iovs.16-20913
    1. Brainard D. H. (1997). The psychophysics toolbox. Spat. Vis. 10 433–436. 10.1163/156856897X00357
    1. Campana G., Camilleri R., Pavan A., Veronese A., Lo Giudice G. (2014). Improving visual functions in adult amblyopia with combined perceptual training and transcranial random noise stimulation (tRNS): a pilot study. Front. Psychol. 5:1402. 10.3389/fpsyg.2014.01402
    1. Chen G., Hou F., Yan F. F., Zhang P., Xi J., Zhou Y., et al. (2014). Noise provides new insights on contrast sensitivity function. PLoS One 9:e90579. 10.1371/journal.pone.0090579
    1. Chen Z., Li J., Liu J., Cai X., Yuan J., Deng D., et al. (2016). Monocular perceptual learning of contrast detection facilitates binocular combination in adults with anisometropic amblyopia. Sci. Rep. 6:20187. 10.1038/srep20187
    1. Cotter S. A., Pediatric Eye Disease Investigator Group, Edwards A. R., Wallace D. K., Beck R. W., Arnold R. W., et al. (2006). Treatment of anisometropic amblyopia in children with refractive correction. Ophthalmology 113 895–903. 10.1016/j.ophtha.2006.01.068
    1. Dobson V., Miller J. M., Clifford-Donaldson C. E., Harvey E. M. (2008). Associations between anisometropia, amblyopia, and reduced stereoacuity in a school-aged population with a high prevalence of astigmatism. Invest. Ophthalmol. Vis. Sci. 49 4427–4436. 10.1167/iovs.08-1985
    1. Dosher B. A., Lu Z. L. (2005). Perceptual learning in clear displays optimizes perceptual expertise: learning the limiting process. Proc. Natl. Acad. Sci. U.S.A. 102 5286–5290. 10.1073/pnas.0500492102
    1. Gao T. Y., Anstice N., Babu R. J., Black J. M., Bobier W. R., Dai S., et al. (2018a). Optical treatment of amblyopia in older children and adults is essential prior to enrolment in a clinical trial. Ophthalm. Physiol. Opt. 38 129–143. 10.1111/opo.12437
    1. Gao T. Y., Guo C. X., Babu R. J., Black J. M., Bobier W. R., Chakraborty A., et al. (2018b). effectiveness of a binocular video game vs placebo video game for improving visual functions in older children, teenagers, and adults with amblyopia: a randomized clinical trial. JAMA Ophthalmol. 136 172–181. 10.1001/jamaophthalmol.2017.6090
    1. Gardner J. L., Sun P., Waggoner R. A., Ueno K., Tanaka K., Cheng K. (2005). Contrast adaptation and representation in human early visual cortex. Neuron 47 607–620. 10.1016/j.neuron.2005.07.016
    1. Hess R. F., Bradley A. (1980). Contrast perception above threshold is only minimally impaired in human amblyopia. Nature 287 463–464. 10.1038/287463a0
    1. Hess R. F., Campbell F. W., Greenhalgh T. (1978). On the nature of the neural abnormality in human amblyopia; neural aberrations and neural sensitivity loss. Pflugers. Arch. 377 201–207. 10.1007/BF00584273
    1. Hess R. F., Howell E. R. (1977). The threshold contrast sensitivity function in strabismic amblyopia: evidence for a two type classification. Vis. Res. 17 1049–1055. 10.1016/0042-6989(77)90009-8
    1. Hess R. F., Mansouri B., Thompson B. (2010). A new binocular approach to the treatment of amblyopia in adults well beyond the critical period of visual development. Restor. Neurol. Neurosci. 28 793–802. 10.3233/RNN-2010-0550
    1. Holmes J. M., Clarke M. P. (2006). Amblyopia. Lancet 367 1343–1351. 10.1016/S0140-6736(06)68581-4
    1. Holmes J. M., Levi D. M. (2018). Treatment of amblyopia as a function of age. Vis. Neurosci. 35:E015. 10.1017/S0952523817000220
    1. Holmes J. M., Manh V. M., Lazar E. L., Beck R. W., Birch E. E., Kraker R. T., et al. (2016). Effect of a binocular iPad game vs Part-time patching in children aged 5 to 12 years with Amblyopia: a randomized clinical trial. JAMA Ophthalmol. 134 1391–1400. 10.1001/jamaophthalmol.2016.4262
    1. Holmes J. M., Repka M. X., Kraker R. T., Clarke M. P. (2006). The treatment of amblyopia. Strabismus 14 37–42. 10.1080/09273970500536227
    1. Hou F., Huang C. B., Tao L., Feng L., Zhou Y., Lu Z. L. (2011). Training in contrast detection improves motion perception of sinewave gratings in amblyopia. Invest. Ophthalmol. Vis. Sci. 52 6501–6510. 10.1167/iovs.11-7541
    1. Huang C., Tao L., Zhou Y., Lu Z. L. (2007). Treated amblyopes remain deficient in spatial vision: a contrast sensitivity and external noise study. Vis. Res. 47 22–34. 10.1016/j.visres.2006.09.015
    1. Huang C. B., Zhou J., Lu Z. L., Feng L., Zhou Y. (2009). Binocular combination in anisometropic amblyopia. J. Vis. 9 11–16. 10.1167/9.3.17
    1. Huang C. B., Zhou J., Lu Z. L., Zhou Y. (2011). Deficient binocular combination reveals mechanisms of anisometropic amblyopia: signal attenuation and interocular inhibition. J. Vis. 11:10.1167/11.6.44 10.1167/11.6.4
    1. Huang C. B., Zhou Y., Lu Z. L. (2008). Broad bandwidth of perceptual learning in the visual system of adults with anisometropic amblyopia. Proc. Natl. Acad. Sci. U.S.A. 105 4068–4073. 10.1073/pnas.0800824105
    1. Jia W., Lan F., Zhao X., Lu Z. L., Huang C. B., Zhao W., et al. (2018). The effects of monocular training on binocular functions in anisometropic amblyopia. Vis. Res. 152 74–83. 10.1016/j.visres.2017.02.008
    1. Kelly K. R., Jost R. M., Dao L., Beauchamp C. L., Leffler J. N., Birch E. E. (2016). Binocular iPad Game vs Patching for treatment of amblyopia in children: a randomized clinical trial. JAMA Ophthalmol. 134 1402–1408. 10.1001/jamaophthalmol.2016.4224
    1. Kelly K. R., Jost R. M., Wang Y. Z., Dao L., Beauchamp C. L., Leffler J. N., et al. (2018). Improved binocular outcomes following binocular treatment for childhood Amblyopia. Invest. Ophthalmol. Vis. Sci. 59 1221–1228. 10.1167/iovs.17-23235
    1. Kiorpes L., Kiper D. C., O’Keefe L. P., Cavanaugh J. R., Movshon J. A. (1998). Neuronal correlates of amblyopia in the visual cortex of macaque monkeys with experimental strabismus and anisometropia. J. Neurosci. 18 6411–6424. 10.1523/JNEUROSCI.18-16-06411.1998
    1. Kiorpes L., Tang C., Movshon J. A. (1999). Factors limiting contrast sensitivity in experimentally amblyopic macaque monkeys. Vis. Res. 39 4152–4160. 10.1016/s0042-6989(99)00130-3
    1. Knox P. J., Simmers A. J., Gray L. S., Cleary M. (2012). An exploratory study: prolonged periods of binocular stimulation can provide an effective treatment for childhood amblyopia. Invest. Ophthalmol. Vis. Sci. 53 817–824. 10.1167/iovs.11-8219
    1. Kohn A. (2007). Visual adaptation: physiology, mechanisms, and functional benefits. J. Neurophysiol. 97 3155–3164. 10.1152/jn.00086.2007
    1. Lesmes L. A., Lu Z. L., Baek J., Albright T. D. (2010). Bayesian adaptive estimation of the contrast sensitivity function: the quick CSF method. J. Vis. 10 17.1–1721. 10.1167/10.3.17
    1. Levi D. M. (2006). Visual processing in amblyopia: human studies. Strabismus 14 11–19. 10.1080/09273970500536243
    1. Levi D. M., Klein S. A. (1985). Vernier acuity, crowding and amblyopia. Vis. Res. 25 979–991. 10.1016/0042-6989(85)90208-1
    1. Levi D. M., Klein S. A., Sharma V. (1999). Position jitter and undersampling in pattern perception. Vis. Res. 39 445–465. 10.1016/s0042-6989(98)00125-4
    1. Levi D. M., Knill D. C., Bavelier D. (2015). Stereopsis and amblyopia: a mini-review. Vis. Res. 114 17–30. 10.1016/j.visres.2015.01.002
    1. Levi D. M., Li R. W. (2009). Perceptual learning as a potential treatment for amblyopia: a mini-review. Vis. Res. 49 2535–2549. 10.1016/j.visres.2009.02.010
    1. Levi D. M., Polat U., Hu Y. S. (1997). Improvement in Vernier acuity in adults with amblyopia. practice makes better. Invest. Ophthalmol. Vis. Sci. 38 1493–1510.
    1. Levitt H. (1971). Transformed up-down methods in psychoacoustics. J. Acoust. Soc. Am. 49:467 10.1121/1.1912375
    1. Li J., Hess R. F., Chan L. Y., Deng D., Yang X., Chen X., et al. (2013a). Quantitative measurement of interocular suppression in anisometropic amblyopia: a case-control study. Ophthalmology 120 1672–1680. 10.1016/j.ophtha.2013.01.048
    1. Li J., Thompson B., Deng D., Chan L. Y., Yu M., Hess R. F. (2013b). Dichoptic training enables the adult amblyopic brain to learn. Curr. Biol. 23 R308–R309. 10.1016/j.cub.2013.01.059
    1. Li J., Spiegel D. P., Hess R. F., Chen Z., Chan L. Y., Deng D., et al. (2015). Dichoptic training improves contrast sensitivity in adults with amblyopia. Vis. Res. 114 161–172. 10.1016/j.visres.2015.01.017
    1. Li S. L., Reynaud A., Hess R. F., Wang Y. Z., Jost R. M., Morale S. E., et al. (2015). Dichoptic movie viewing treats childhood amblyopia. J. AAPOS 19 401–405. 10.1016/j.jaapos.2015.08.003
    1. Li J., Thompson B., Lam C. S., Deng D., Chan L. Y., Maehara G., et al. (2011). The role of suppression in amblyopia. Invest. Ophthalmol. Vis. Sci. 52 4169–4176. 10.1167/iovs.11-7233
    1. Li R. W., Klein S. A., Levi D. M. (2008). Prolonged perceptual learning of positional acuity in adult amblyopia: perceptual template retuning dynamics. J. Neurosci. 28 14223–14229. 10.1523/JNEUROSCI.4271-08.2008
    1. Li R. W., Young K. G., Hoenig P., Levi D. M. (2005). Perceptual learning improves visual performance in juvenile amblyopia. Invest. Ophthalmol. Vis. Sci. 46 3161–3168. 10.1167/iovs.05-0286
    1. Liu X. Y., Zhang J. Y. (2018). Dichoptic training in adults with amblyopia: additional stereoacuity gains over monocular training. Vis. Res. 152 84–90. 10.1016/j.visres.2017.07.002
    1. Liu X. Y., Zhang J. Y. (2019). Dichoptic de-masking learning in adults with Amblyopia and its mechanisms. Invest. Ophthalmol Vis. Sci. 60 2968–2977. 10.1167/iovs.18-26483
    1. Lunghi C., Morrone M. C., Secci J., Caputo R. (2016). Binocular rivalry measured 2 hours after occlusion therapy predicts the recovery rate of the amblyopic eye in anisometropic children. Invest. Ophthalmol. Vis. Sci. 57 1537–1546. 10.1167/iovs.15-18419
    1. McKee S. P., Levi D. M., Movshon J. A. (2003). The pattern of visual deficits in amblyopia. J. Vis. 3 380–405. 10.1167/3.5.5
    1. Mitchell D. E., Kind P. C., Sengpiel F., Murphy K. (2003). Brief daily periods of binocular vision prevent deprivation-induced acuity loss. Curr. Biol. 13 1704–1708. 10.1016/j.cub.2003.09.026
    1. Moseley M. J., Neufeld M., McCarry B., Charnock A., McNamara R., Rice T., et al. (2002). Remediation of refractive amblyopia by optical correction alone. Ophthalm. Physiol. Opt. 22 296–299. 10.1046/j.1475-1313.2002.00034.x
    1. Mou T. (2005). The 5-grade notation of the standard logarithmic visual acuity chart. Chin. J. Optomet. Ophthalmol. 7 217–219. 10.3760/cma.j.issn.1674-845X.2005.04.001
    1. Murphy K. M., Roumeliotis G., Williams K., Beston B. R., Jones D. G. (2015). Binocular visual training to promote recovery from monocular deprivation. J. Vis. 15:15.1.2 10.1167/15.1.2
    1. Ooi T. L., Su Y. R., Natale D. M., He Z. J. (2013). A push-pull treatment for strengthening the ‘lazy eye’ in amblyopia. Curr. Biol. 23 R309–R310. 10.1016/j.cub.2013.03.004
    1. Pediatric Eye Disease Investigator Group, J. M., Manny R. E., Lazar E. L., Birch E. E., Kelly K. R., et al. (2019). A Randomized trial of binocular dig rush game treatment for amblyopia in children aged 7 to 12 Years. Ophthalmology 126 456–466. 10.1016/j.ophtha.2018.10.032
    1. Pelli D. G. (1997). The VideoToolbox software for visual psychophysics: transforming numbers into movies. Spat. Vis. 10 437–442. 10.1163/156856897X00366
    1. Polat U., Ma-Naim T., Belkin M., Sagi D. (2004). Improving vision in adult amblyopia by perceptual learning. Proc. Natl. Acad. Sci. U.S.A. 101 6692–6697. 10.1073/pnas.0401200101
    1. Polat U., Ma-Naim T., Spierer A. (2009). Treatment of children with amblyopia by perceptual learning. Vis. Res. 49 2599–2603. 10.1016/j.visres.2009.07.008
    1. Shooner C., Hallum L. E., Kumbhani R. D., Garcia-Marin V., Kelly J. G., Majaj N. J., et al. (2017). Asymmetric dichoptic masking in visual cortex of amblyopic macaque monkeys. J. Neurosci. 37 8734–8741. 10.1523/JNEUROSCI.1760-17.2017
    1. Sloper J. (2016). New treatments for amblyopia-to patch or play? JAMA Ophthalmol. 134 1408–1410. 10.1001/jamaophthalmol.2016.4296
    1. Subramanian V., Jost R. M., Birch E. E. (2013). A quantitative study of fixation stability in amblyopia. Invest. Ophthalmol. Vis. Sci. 54 1998–2003. 10.1167/iovs.12-11054
    1. Tailor V., Bossi M., Greenwood J. A., Dahlmann-Noor A. (2016). Childhood amblyopia: current management and new trends. Br. Med. Bull. 119 75–86. 10.1093/bmb/ldw030
    1. Vedamurthy I., Nahum M., Bavelier D., Levi D. M. (2015a). Mechanisms of recovery of visual function in adult amblyopia through a tailored action video game. Sci. Rep. 5:8482. 10.1038/srep08482
    1. Vedamurthy I., Nahum M., Huang S. J., Zheng F., Bayliss J., Bavelier D., et al. (2015b). A dichoptic custom-made action video game as a treatment for adult amblyopia. Vis. Res. 114 173–187. 10.1016/j.visres.2015.04.008
    1. Wang J., Feng L., Wang Y., Zhou J., Hess R. F. (2018). Binocular benefits of optical treatment in anisometropic amblyopia. J. Vis. 18:6 10.1167/18.4.6
    1. Xi J., Jia W. L., Feng L. X., Lu Z. L., Huang C. B. (2014). Perceptual learning improves stereoacuity in amblyopia. Invest. Ophthalmol. Vis. Sci. 55 2384–2391. 10.1167/iovs.13-12627
    1. Xie X. Y., Yu C. (2019). Perceptual learning of Vernier discrimination transfers from high to zero noise after double training. Vis. Res. 156 39–45. 10.1016/j.visres.2019.01.007
    1. Xu P., Lu Z. L., Qiu Z., Zhou Y. (2006). Identify mechanisms of amblyopia in Gabor orientation identification with external noise. Vis. Res. 46 3748–3760. 10.1016/j.visres.2006.06.013
    1. Zhao W., Jia W. L., Chen G., Luo Y., Lin B., He Q., et al. (2017). A complete investigation of monocular and binocular functions in clinically treated amblyopia. Sci. Rep. 7:10682. 10.1038/s41598-017-11124-0
    1. Zhou J., Reynaud A., Yao Z., Liu R., Feng L., Zhou Y., et al. (2018). Amblyopic suppression: passive attenuation, enhanced Dichoptic masking by the fellow eye or reduced Dichoptic masking by the amblyopic eye? Invest. Ophthalmol. Vis. Sci. 59 4190–4197. 10.1167/iovs.18-24206
    1. Zhou Y., Huang C., Xu P., Tao L., Qiu Z., Li X., et al. (2006). Perceptual learning improves contrast sensitivity and visual acuity in adults with anisometropic amblyopia. Vis. Res. 46 739–750. 10.1016/j.visres.2005.07.031

Source: PubMed

3
Abonnieren