Visual field defects that arise from eye disease are increasing as human life spans lengthen. The consequences of visual field defects on the central visual pathways are important to assess, particularly in light of potential treatments of eye disease that restore function to the retina. For individuals with field defects arising from congenital eye disease, primary visual cortex (V1) appears to remap, whereas this form of reorganization is not present in individuals with field defects that arise later in life as a result of inherited or acquired eye disease. However, research has revealed that the areas of V1 that normally map the visual field defect are active under specific circumstances. This review attempts to resolve whether or not this activity reflects reorganization of the central visual pathways. Alongside the measures of function are measures of anatomical properties of the human visual pathway, which demonstrate transneuronal degeneration in individuals with eye disease. These results are concerning because degeneration of the central visual pathways may ultimately limit the success of sight-restoring treatments of eye disease.


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Literature Cited

  1. Abishiha J, Dubis AM, Cowing J, Fahy RT, Sundaram V. et al. 2014. A prospective longitudinal study of retinal structure and function in achromatopsia. Invest. Ophthalmol. Vis. Sci. 55:5733–43 [Google Scholar]
  2. Ackerman CJ, Tolhurst DJ, Morgan JE, Baker GE, Thompson ID. 2003. The relay of visual information to the lateral geniculate nucleus and the visual cortex in albino ferrets. J. Comp. Neurol. 20:1253–60 [Google Scholar]
  3. Alexander JJ, Umino Y, Everhart D, Chang B, Min SH. et al. 2007. Restoration of cone vision in a mouse model of achromatopsia. Nat. Med. 13:685–87 [Google Scholar]
  4. Andrews TJ, Halpern SD, Purves D. 1997. Correlated size variations in human visual cortex, lateral geniculate nucleus, and optic tract. J. Neurosci. 17:2859–68 [Google Scholar]
  5. Angelucci A, Levitt JB, Walton EJ, Hupe JM, Bullier J, Lund JS. 2002. Circuits for local and global signal integration in primary visual cortex. J. Neurosci. 22:8633–46 [Google Scholar]
  6. Baker CI, Dilks DD, Peli E, Kanwisher N. 2008. Reorganization of visual processing in macular degeneration: replication and clues about the role of foveal loss. Vis. Res. 48:1910–19 [Google Scholar]
  7. Baker CI, Peli E, Knouf N, Kanwisher NG. 2005. Reorganization of visual processing in macular degeneration. J. Neurosci. 25:614–18 [Google Scholar]
  8. Baseler HA, Brewer AA, Sharpe LT, Morland AB, Jagle H, Wandell BA. 2002. Reorganization of human cortical maps caused by inherited photoreceptor abnormalities. Nat. Neurosci. 5:364–70 [Google Scholar]
  9. Baseler HA, Gouws A, Haak KV, Racey C, Crossland MD. et al. 2011. Large-scale remapping of visual cortex is absent in adult humans with macular degeneration. Nat. Neurosci. 14:649–55 [Google Scholar]
  10. Baseler HA, Gouws A, Morland AB. 2009. The organization of the visual cortex in patients with scotomata resulting from lesions of the central retina. Neuro-Ophthalmology 33:149–57 [Google Scholar]
  11. Binda P, Thomas JM, Boynton GM, Fine I. 2013. Minimizing biases in estimating the reorganization of human visual areas with BOLD retinotopic mapping. J. Vis. 13:713 [Google Scholar]
  12. Boucard CC, Hernowo AT, Maguire RP, Jansonius NM, Roerdink JBTM. et al. 2009. Changes in cortical grey matter density associated with long-standing retinal visual field defects. Brain 132:1898–906 [Google Scholar]
  13. Boucard CC, Hoogduin JM, van der Grond J, Cornelissen FW. 2007. Occipital proton magnetic resonance spectroscopy (1H-MRS) reveals normal metabolite concentrations in retinal visual field defects. PLOS ONE 2:e222 [Google Scholar]
  14. Brindley GS, Lewin WS. 1968. The sensations produced by electrical stimulation of the visual cortex. J. Physiol. 196:479–93 [Google Scholar]
  15. Carvalho LS, Xu J, Pearson RA, Smith AJ, Bainbridge JW. et al. 2011. Long-term and age-dependent restoration of visual function in a mouse model of CNGB3-associated achromatopsia following gene therapy. Hum. Mol. Genet. 20:3161–75 [Google Scholar]
  16. Chaturvedi N, Hedley-Whyte ET, Dreyer EB. 1993. Lateral geniculate nucleus in glaucoma. Am. J. Ophthalmol. 116:182–88 [Google Scholar]
  17. Chen Z, Lin F, Wang J, Li Z, Dai H. et al. 2013. Diffusion tensor magnetic resonance imaging reveals visual pathway damage that correlates with clinical severity in glaucoma. Clin. Exp. Ophthalmol. 41:43–49 [Google Scholar]
  18. Cheung S-H, Legge GE. 2005. Functional and cortical adaptations to central vision loss. Vis. Neurosci. 22:187–201 [Google Scholar]
  19. Crossland MD, Culham LE, Rubin GS. 2004. Fixation stability and reading speed in patients with newly developed macular disease. Ophthalmic Physiol. Opt. 24:327–33 [Google Scholar]
  20. Daniel PM, Whitteridge D. 1961. The representation of the visual field on the cerebral cortex in monkeys. J. Physiol. 159:203–21 [Google Scholar]
  21. DeYoe EA, Bandettini P, Neitz J, Miller D, Winans P. 1994. Functional magnetic resonance imaging (fMRI) of the human brain. J. Neurosci. Methods 54:171–87 [Google Scholar]
  22. Dilks DD, Baker CI, Peli E, Kanwisher N. 2009. Reorganization of visual processing in macular degeneration is not specific to the “preferred retinal locus.”. J. Neurosci. 29:2768–73 [Google Scholar]
  23. Dilks DD, Julian JB, Peli E, Kanwisher N. 2014. Reorganization of visual processing in age-related macular degeneration depends on foveal loss. Optom. Vis. Sci. 91:e199–206 [Google Scholar]
  24. Duncan RO, Sample PA, Bowd C, Weinreb RN, Zangwill LM. 2012. Arterial spin labeling fMRI measurements of decreased blood flow in primary visual cortex correlates with decreased visual function in human glaucoma. Vis. Res. 60:51–60 [Google Scholar]
  25. Duncan RO, Sample PA, Weinreb RN, Bowd C, Zangwill LM. 2007a. Retinotopic organization of primary visual cortex in glaucoma: a method for comparing cortical function with damage to the optic disk. Investig. Ophthalmol. Vis. Sci. 48:733–44 [Google Scholar]
  26. Duncan RO, Sample PA, Weinreb RN, Bowd C, Zangwill LM. 2007b. Retinotopic organization of primary visual cortex in glaucoma: comparing fMRI measurements of cortical function with visual field loss. Prog. Retinal Eye Res. 26:38–56 [Google Scholar]
  27. Engel SA, Glover GH, Wandell BA. 1997. Retinotopic organization in human visual cortex and the spatial precision of functional MRI. Cereb. Cortex 7:181–92 [Google Scholar]
  28. Engel SA, Rumelhart DE, Wandell BA, Lee AT, Glover GH. et al. 1994. fMRI of human visual cortex. Nature 369:525 [Google Scholar]
  29. Felleman DJ, Van Essen DC. 1991. Distributed hierarchical processing in the primate cerebral cortex. Cereb. Cortex 1:1–47 [Google Scholar]
  30. Gandhi SP, Heeger DJ, Boynton GM. 1999. Spatial attention affects brain activity in human primary visual cortex. PNAS 96:3314–19 [Google Scholar]
  31. Glickstein M, Heath GG. 1975. Receptors in the monochromat eye. Vis. Res. 15:633–36 [Google Scholar]
  32. Gupta N, Ang L-C, Noël de Tilly L, Bidaisee L, Yücel YH. 2006. Human glaucoma and neural degeneration in intracranial optic nerve, lateral geniculate nucleus, and visual cortex. Br. J. Ophthalmol. 90:674–78 [Google Scholar]
  33. Haak KV, Cornelissen FW, Morland AB. 2012. Population receptive field dynamics in human visual cortex. PLOS ONE 7:e37686 [Google Scholar]
  34. Harrison LM, Stephan KE, Rees G, Friston KJ. 2007. Extra-classical receptive field effects measured in striate cortex with fMRI. NeuroImage 34:1199–208 [Google Scholar]
  35. Hernowo AT, Boucard CC, Jansonius NM, Hooymans JM, Cornelissen FW. 2011. Automated morphometry of the visual pathway in primary open-angle glaucoma. Investig. Ophthalmol. Vis. Sci. 52:2758–66 [Google Scholar]
  36. Hernowo AT, Prins D, Baseler HA, Plank T, Gouws AD. et al. 2014. Morphometric analyses of the visual pathways in macular degeneration. Cortex 56:99–110 [Google Scholar]
  37. Hoffmann MB, Dumoulin SO. 2015. Congenital visual pathway abnormalities: a window onto cortical stability and plasticity. Trends Neurosci. 38:155–65 [Google Scholar]
  38. Hoffmann MB, Kaule FR, Levin N, Masuda Y, Kumar A. et al. 2012. Plasticity and stability of the visual system in human achiasma. Neuron 75:393–401 [Google Scholar]
  39. Hoffmann MB, Tolhurst DJ, Moore AT, Morland AB. 2003. Organization of the visual cortex in human albinism. J. Neurosci. 23:8921–30 [Google Scholar]
  40. Holmes G. 1918. Disturbances of vision by cerebral lesions. Br. J. Ophthalmol. 2:353–84 [Google Scholar]
  41. Hubel DH, Wiesel TN. 1971. Aberrant visual projections in the Siamese cat. J. Physiol. 218:33–62 [Google Scholar]
  42. Iwata F, Patronas NJ, Caruso RC, Podgor MJ, Remaley NA. et al. 1997. Association of visual field, cup-disc ratio, and magnetic resonance imaging of optic chiasm. Arch. Ophthalmol. 115:729–32 [Google Scholar]
  43. Kashiwagi K, Tsukahara S. 2004. Examination and treatment of patients with angle-closure glaucoma in Japan: results of a nationwide survey. Jpn. J. Ophthalmol. 48:133–40 [Google Scholar]
  44. Klein R, Blodi BA, Meuer SM, Myers CE, Chew EY, Klein BE. 2010a. The prevalence of macular telangiectasia type 2 in the Beaver Dam eye study. Am. J. Ophthalmol. 150:55–62e2 [Google Scholar]
  45. Klein R, Cruickshanks KJ, Nash SD, Krantz EM, Nieto FJ. et al. 2010b. The prevalence of age-related macular degeneration and associated risk factors. Arch. Ophthalmol. 128:750–58 [Google Scholar]
  46. Kohl S, Baumann B, Broghammer M, Jagle H, Sieving P. et al. 2000. Mutations in the CNGB3 gene encoding the β-subunit of the cone photoreceptor cGMP-gated channel are responsible for achromatopsia (ACHM3) linked to chromosome 8q21. Hum. Mol. Genet. 9:2107–16 [Google Scholar]
  47. Kohl S, Marx T, Giddings I, Jagle H, Jacobson SG. et al. 1998. Total colourblindness is caused by mutations in the gene encoding the α-subunit of the cone photoreceptor cGMP-gated cation channel. Nat. Genet. 19:257–59 [Google Scholar]
  48. Komaromy AM, Alexander JJ, Rowlan JS, Garcia MM, Chiodo VA. et al. 2010. Gene therapy rescues cone function in congenital achromatopsia. Hum. Mol. Genet. 19:2581–93 [Google Scholar]
  49. Kriegeskorte N, Simmons WK, Bellgowan PS, Baker CI. 2009. Circular analysis in systems neuroscience: the dangers of double dipping. Nat. Neurosci. 12:535–40 [Google Scholar]
  50. Lagrèze WA, Gaggl M, Weigel M, Schulte-Mönting J, Bühler A. et al. 2009. Retrobulbar optic nerve diameter measured by high-speed magnetic resonance imaging as a biomarker for axonal loss in glaucomatous optic atrophy. Investig. Ophthalmol. Vis. Sci. 50:4223–28 [Google Scholar]
  51. Lipinski DM, Thake M, MacLaren RE. 2013. Clinical applications of retinal gene therapy. Prog. Retinal Eye Res. 32:22–47 [Google Scholar]
  52. Little DM, Thulborn KR, Szlyk JP. 2008. An fMRI study of saccadic and smooth-pursuit eye movement control in patients with age-related macular degeneration. Investig. Ophthalmol. Vis. Sci. 49:1728–35 [Google Scholar]
  53. Liu J, Wandell BA. 2005. Specializations for chromatic and temporal signals in human visual cortex. J. Neurosci. 25:3459–68 [Google Scholar]
  54. Liu T, Cheung S-H, Schuchard RA, Glielmi CB, Hu X. et al. 2010. Incomplete cortical reorganization in macular degeneration. Investig. Ophthalmol. Vis. Sci. 51:6826–34 [Google Scholar]
  55. Masuda Y, Dumoulin SO, Nakadomari S, Wandell BA. 2008. V1 projection zone signals in human macular degeneration depend on task, not stimulus. Cereb. Cortex 18:2483–93 [Google Scholar]
  56. Masuda Y, Horiguchi H, Dumoulin SO, Furuta A, Miyauchi S. et al. 2010. Task-dependent V1 responses in human retinitis pigmentosa. Investig. Ophthalmol. Vis. Sci. 51:5356–64 [Google Scholar]
  57. Michalakis S, Mühlfriedel R, Tanimoto N, Krishnamoorthy V, Koch S. et al. 2010. Restoration of cone vision in the CNGA3−/− mouse model of congenital complete lack of cone photoreceptor function. Mol. Ther. 18:2057–63 [Google Scholar]
  58. Morland AB, Baseler HA, Hoffmann MB, Sharpe LT, Wandell BA. 2001. Abnormal retinotopic representations in human visual cortex revealed by fMRI. Acta Psychol. 107:229–47 [Google Scholar]
  59. Morland AB, Hoffmann MB, Neveu M, Holder GE. 2002. Abnormal visual projection in a human albino studied with functional magnetic resonance imaging and visual evoked potentials. J. Neurol. Neurosurg. Psychiatry 72:523–26 [Google Scholar]
  60. Ogawa S, Takemura H, Horiguchi H, Terao M, Haji T. et al. 2014. White matter consequences of retinal receptor and ganglion cell damage. Investig. Ophthalmol. Vis. Sci. 55:6976–86 [Google Scholar]
  61. Pang J, Deng W-T, Dai X, Lei B, Everhart D. et al. 2012. AAV-mediated cone rescue in a naturally occurring mouse model of CNGA3-achromatopsia. PLOS ONE 7:e35250 [Google Scholar]
  62. Plank T, Frolo J, Brandl-Rühle S, Renner AB, Hufendiek K. et al. 2011. Gray matter alterations in visual cortex of patients with loss of central vision due to hereditary retinal dystrophies. NeuroImage 56:1556–65 [Google Scholar]
  63. Plank T, Frolo J, Farzana F, Brandl-Ruhle S, Renner AB, Greenlee MW. 2013. Neural correlates of visual search in patients with hereditary retinal dystrophies. Hum. Brain Mapp. 34:2607–23 [Google Scholar]
  64. Rosengarth K, Keck I, Brandl-Rühle S, Frolo J, Hufendiek K. et al. 2013. Functional and structural brain modifications induced by oculomotor training in patients with age-related macular degeneration. Front. Psychol. 4:428 [Google Scholar]
  65. Schoups A, Vogels R, Qian N, Orban G. 2001. Practising orientation identification improves orientation coding in V1 neurons. Nature 412:549–53 [Google Scholar]
  66. Schumacher EH, Jacko JA, Primo SA, Main KL, Moloney KP. et al. 2008. Reorganization of visual processing is related to eccentric viewing in patients with macular degeneration. Restor. Neurol. Neurosci. 26:391–402 [Google Scholar]
  67. Sereno MI, Dale AM, Reppas JB, Kwong KK, Belliveau JW. et al. 1995. Borders of multiple visual areas in humans revealed by functional magnetic resonance imaging. Science 268:889–93 [Google Scholar]
  68. Shao Y, Keliris GA, Papanikolaou A, Fischer MD, Zobor D. et al. 2013. Visual cortex organisation in a macaque monkey with macular degeneration. Eur. J. Neurosci. 38:3456–64 [Google Scholar]
  69. Sharpe LT, Nordby K. 1990. The photoreceptors in the achromat. Night Vision: Basic, Clinical and Applied Aspects RF Hess, LT Sharpe, K Nordby 335–89 Cambridge, UK: Cambridge Univ. Press [Google Scholar]
  70. Shipp S, Zeki S. 1989. The organization of connections between areas V5 and V2 in macaque monkey visual cortex. Eur. J. Neurosci. 1:333–54 [Google Scholar]
  71. Sundaram V, Wilde C, Aboshiha J, Cowing J, Han C. et al. 2014. Retinal structure and function in achromatopsia: implications for gene therapy. Ophthalmology 121:234–45 [Google Scholar]
  72. Sunness JS, Liu T, Yantis S. 2004. Retinotopic mapping of the visual cortex using functional magnetic resonance imaging in a patient with central scotomas from atrophic macular degeneration. Ophthalmology 111:1595–98 [Google Scholar]
  73. Szlyk JP, Little DM. 2009. An fMRI study of word-level recognition and processing in patients with age-related macular degeneration. Investig. Ophthalmol. Vis. Sci. 50:4487–95 [Google Scholar]
  74. Timberlake GT, Peli E, Essock EA, Augliere RA. 1987. Reading with a macular scotoma. II. Retinal locus for scanning text. Investig. Ophthalmol. Vis. Sci. 28:1268–74 [Google Scholar]
  75. Wandell BA, Dumoulin SO, Brewer AA. 2007. Visual field maps in human cortex. Neuron 56:366–83 [Google Scholar]
  76. Wandell BA, Smirnakis SM. 2009. Plasticity and stability of visual field maps in adult primary visual cortex. Nat. Rev. Neurosci. 10:873–84 [Google Scholar]
  77. Weaver KE, Richards TL, Saenz M, Petropoulos H, Fine I. 2013. Neurochemical changes within human early blind occipital cortex. Neuroscience 252:222–33 [Google Scholar]
  78. Zeki S, Shipp S. 1988. The functional logic of cortical connections. Nature 335:311–17 [Google Scholar]
  79. Zhang Y, Chen X, Wen G, Wu G, Zhang X. 2013. Proton magnetic resonance spectroscopy (1H-MRS) reveals geniculocalcarine and striate area degeneration in primary glaucoma. PLOS ONE 8:e73197 [Google Scholar]
  80. Zohary E, Dilks DD, Kanwisher N, Pascual-Leone A. 2009. Cortical reorganization without readout change in macular degeneration. Soc. Neurosci. Abstr.215.7 [Google Scholar]

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