Neuro-Ophthalmologic Hurdles in Whole-Eye Transplantation


Purpose of Review

Anatomical and functional successes have extended into the field of vascularized composite allotransplantation. However, the goal of whole-eye transplantation continues as an unfinished effort, primarily because of difficulties accomplishing optic nerve repair and regeneration. This review provides a summary of neuro-ophthalmological findings regarding eye donors and recipients, based on ocular function in donors and neurophysiological events known to occur in blind people.

Recent Findings

Experimental advances regarding regeneration of the optic nerve in lower mammals have demonstrated anatomical success, but little is known regarding functional capacity. Modern imaging and functional studies in patients with brain death and patients with blindness have provided useful information concerning possible scenarios in whole-eye transplantation.


Some questions remain regarding the functionality of an eye in a hypothetical donor, as well as the ability of the recipient’s visual pathway to perform adequately. A multidisciplinary approach, involving both clinical and basic research, is necessary to address the challenges of whole-eye transplantation.

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Papers of particular interest, published recently, have been highlighted as: • Of importance

  1. 1.

    Shores JT, Malek V, Lee WPA, Brandacher G. Outcomes after hand and upper extremity transplantation. J Mater Sci Mater Med. 2017;28(5):72.

    CAS  Article  PubMed  Google Scholar 

  2. 2.

    Siemionow M. The decade of face transplant outcomes. J Mater Sci Mater Med. 2017;28(5):64.

    CAS  Article  PubMed  Google Scholar 

  3. 3.

    Aycart MA, Kiwanuka H, Krezdorn N, et al. Quality of life after face transplantation: outcomes, assessment tools, and future directions. Plast Reconstr Surg. 2017;139(1):194–203.

    CAS  Article  PubMed  Google Scholar 

  4. 4.

    Bramstedt KA, Plock JA. Looking the world in the face: the benefits and challenges of facial transplantation for blind patients. Prog Transplant. 2017;27(1):79–83.

    Article  PubMed  Google Scholar 

  5. 5.

    Hendrickx H, Blondeel PN, Van Parys H, Roche NA, Peeters PC, Vermeersch HF, et al. Facing a new face: an interpretative phenomenological analysis of the experiences of a blind face transplant patient and his partner. J Craniofac Surg. 2018;29(4):826–31.

    Article  PubMed  Google Scholar 

  6. 6.

    Carty MJ, Bueno EM, Lehmann LS, Pomahac B. A position paper in support of face transplantation in the blind. Plast Reconstr Surg. 2012;130(319):319–24.

    CAS  Article  PubMed  Google Scholar 

  7. 7.

    Coffman KL, Gordon C, Siemionow M. Favorable psychological and social advantages have been documented in blind patients with face transplant, as well as new findings in non visual routes in rehabilitative purposes. Curr Opin Organ Transplant. 2010;15(2):236–40.

    Article  PubMed  Google Scholar 

  8. 8.

    Suchyta MA, Sharp R, Amer H, Bradley E, Mardini S. Ethicists’ opinions regarding the permissibility of face transplant. Plast Reconstr Surg. 2019;144(1):212–24.

    CAS  Article  PubMed  Google Scholar 

  9. 9.

    Pomahac B, Pribaz J, Eriksson E, et al. Three patients with full facial transplantation. N Engl J Med. 2012;366(8):715–22.

    CAS  Article  PubMed  Google Scholar 

  10. 10.

    Roche NA, Vermeersch HF, Stillaert FB, et al. Complex facial reconstruction by vascularized composite allotransplantation: the first Belgian case. J Plast Reconstr Aesthet Surg. 2015;68(3):362–71.

    Article  PubMed  Google Scholar 

  11. 11.

    Bravo MG, Granoff MD, Johnson AR, Lee BT. Development of a new large-animal model for composite face and whole-eye transplantation: a novel application for anatomical mapping using indocyanine green and liquid latex. Plast Reconstr Surg. 2020;145(1):67e–75e.

    CAS  Article  PubMed  Google Scholar 

  12. 12.

    Zor F, Polat M, Kulahci Y, Sahin H, Aral AM, Erbas VE, et al. Demonstration of technical feasibility and viability of whole eye transplantation in a rodent model. J Plast Reconstr Aesthet Surg. 2019;72(10):1640–50.

    Article  PubMed  Google Scholar 

  13. 13.

    Li Y, Chiaki K, Wang B, et al. Evaluation of viability, structural integrity and functional outcome after whole eye transplantation. Plast Reconstr Surg. 2015;135(5S):82.

    Article  Google Scholar 

  14. 14.

    Sosin M, Mundinger GS, Dorafshar AH, Fisher M, Bojovic B, Christy MR, et al. Eyelid transplantation: lessons from a total face transplant and the importance of blink. Plast Reconstr Surg. 2015;135(1):167e–75e.

    CAS  Article  PubMed  Google Scholar 

  15. 15.

    Bourne RRA, Flaxman SR, Braithwaite T, et al. Vision Loss Expert Group. Magnitude, temporal trends, and projections of the global prevalence of blindness and distance and near vision impairment: a systematic review and meta-analysis. Lancet Glob Health. 2017;5(9):e888–97.

    Article  PubMed  Google Scholar 

  16. 16.

    Flaxman SR, Bourne RRA, Reskikoff S, et al. The Vision Loss Expert Group of the Global Burden of Disease Study. Global causes of blindness and distance vision impairment 1990–2020: a systematic review and meta-analysis. Lancet Glob Health. 2017;5(12):e1221–34.

    Article  PubMed  Google Scholar 

  17. 17.

    • Sánchez-Migallón MC, Valiente-Soriano FJ, Salinas-Navarro M, et al. Nerve fibre layer degeneration and retinal ganglion cell loss long term after optic nerve crush or transection in adult mice. Exp Eye Res. 2018;170:40–50. Study that highlights the temporality of the changes in the RGC and its axons after axotomy in mice.

  18. 18.

    • Rovere G, Nadal-NicolaÌs FM, Agudo-Barriuso M, et al. Comparison of retinal nerve fiber layer thinning and retinal ganglion cell loss after optic nerve transection in adult albino rats. IOVS. 2015;56:4487–98. This study demonstrates through optic coherence tomography and immunoreactants the changes in RGC and RNFL after ON transection in rats.

  19. 19.

    Muller PL, Wolf S, Dolz-Marco R, et al. Ophthalmic diagnostic imaging: retina. 2019 Aug 14. In: Bille JF, editor. High resolution imaging in microscopy and ophthalmology: new frontiers in biomedical optics [Internet]. Cham (CH): Springer; 2019. Chapter 4. Available from:

  20. 20.

    Andries L, De Groef L, Moons L. Neuroinflammation and optic nerve regeneration: where do we stand in elucidating underlying cellular and molecular players? Curr Eye Res. 2020;45(3):397–409.

    Article  PubMed  Google Scholar 

  21. 21.

    Bollaerts I, Van Houcke J, Andries L, et al. Neuroinflammation as fuel for axonal regeneration in the injured vertebrate central nervous system. Mediat Inflamm. 2017.

  22. 22.

    Böhm RR, Prokosch V, Brückner M, et al. ßB-2 Crystallin promotes axonal regeneration in the injured optic nerve in adult rats. Transplantation. 2015;24:1829–44.

    Article  Google Scholar 

  23. 23.

    Yin Y, Cui Q, Gilbert H, et al. Oncomodulin links inflammation to optic nerve regeneration. PNAS. 2009;106(46):19587–92.

    Article  PubMed  Google Scholar 

  24. 24.

    Duan X, Qiao M, Bei F, Kim IJ, He Z, Sanes JR. Subtype-specific regeneration of retinal ganglion cells following axotomy: effects of osteopontin and mTOR signaling. Neuron. 2015;85(6):1244–56.

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  25. 25.

    Patel AK, Park KK, Hackam AS. Wnt signaling promotes axonal regeneration following optic nerve injury in the mouse. Neuroscience. 2017;343:372–83.

    CAS  Article  PubMed  Google Scholar 

  26. 26.

    Li S, Qinghai H, HaoWang, Xuming T, Ho KW, Gao X, et al. Subtype-specific regeneration of retinal ganglion cells following axotomy: effects of osteopontin and mTOR signaling. Neuron. 2015;85(6):1244–56.

    CAS  Article  Google Scholar 

  27. 27.

    Donahue RJ, Maes ME, Grosser JA, Nickells RW. BAX-depleted retinal ganglion cells survive and become quiescent following optic nerve damage. Mol Neurobiol. 2020;57(2):1070–84.

    CAS  Article  PubMed  Google Scholar 

  28. 28.

    Sagawa H, Teresaki H, Naanishi K, Tokita Y, Watanabe M. Regeneration of optic nerve fibers with unoprostone, a prostaglandin-related antiglaucoma drug, in adult cats. Jpn J Ophthalmol. 2014;58:100–9.

    Article  PubMed  Google Scholar 

  29. 29.

    Yin H, Yin H, Zhang W, et al. Transcorneal electrical stimulation promotes survival of retinal ganglion cells after optic nerve transection in rats accompanied by reduced microglial activation and TNF-α expression. Brain Res. 2016.

  30. 30.

    • De Lima S, Koriyama Y, Kurimoto T, et al. Full-length axon regeneration in the adult mouse optic nerve and partial recovery of simple visual behaviors. PNAS. 2012;109(23):9149–54. Key study that confirms ON regeneration to brain visual target zones and funcional recovery in mice.

  31. 31.

    Lim JH, Stafford BK, Nguyen PL, Lien BV, Wang C, Zukor K, et al. Neural activity promotes long-distance, target-specific regeneration of adult retinal axons. Nat Neurosci. 2016;19(8):1073–84.

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  32. 32.

    Yang SG, Li CP, Peng XQ, Teng ZQ, Liu CM, Zhou FQ. Strategies to promote long-distance optic nerve regeneration. Front Cell Neurosci. 2020;14:119.

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  33. 33.

    Blackiston DJ, Vien K, Levin M. Serotonergic stimulation induces nerve growth and promotes visual learning via posterior eye grafts in a vertebrate model of induced sensory plasticity. npj Regen Med. 2017;2:8.

    Article  PubMed  PubMed Central  Google Scholar 

  34. 34.

    Davidson EH, Wang EW, Yu JY, et al. Total human eye allotransplantation: developing surgical protocols for donor and recipient procedures. Plast Reconstr Surg. 2016;138(6):1297–308.

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  35. 35.

    Siemionow M, Bozkurt M, Zor F, et al. A new composite eyeball-periorbital transplantation model in humans: an anatomical study in preparation for eyeball transplantation. Plast Reconstr Surg. 2018;141(4):1011–8.

    CAS  Article  PubMed  Google Scholar 

  36. 36.

    Wainright JL, Wholley CL, Rosendale J, Cherikh WS, Di Battista D, Klassen DK. VCA deceased donors in the United States. Transplantation. 2019;103(5):990–7.

    Article  PubMed  Google Scholar 

  37. 37.

    Wong-Riley MT. Energy metabolism of the visual system. Eye Brain. 2010;2:99–116.

    Article  PubMed  PubMed Central  Google Scholar 

  38. 38.

    Feke GT, Tagawa H, Deupree DM, Goger DG, Sebag J, Weiter JJ. Blood flow in the normal human retina. Invest Ophthalmol Vis Sci. 1989;30(1):58–65.

    CAS  PubMed  Google Scholar 

  39. 39.

    Tobalem S, Schutz JS, Chronopoulos A. Central retinal artery occlusion-rethinking retinal survival time. BMC. 2018;18:101.

    Article  Google Scholar 

  40. 40.

    Bertelli E, Regoli M, Bracco S. An update on the variations of the orbital blood supply and hemodynamic. Surg Radiol Anat. 2017;39(5):485–96.

    Article  PubMed  Google Scholar 

  41. 41.

    • Riggs BJ, Cohen JS, Shivakumar B, et al. Doppler ultrasonography of the central retinal vessels in children with brain death. Pediatr Crit Care Med. 2017;18(3):258–64. This study on Doppler US, proves potentially useful as anciliary test to diagnose brain dead in children, and provides information in ocular hemodynamics in these patients.

  42. 42.

    Murali K, Kang D, Nazari H, et al. Spatial variations in vitreous oxygen consumption. PLoS One. 2016;11(3):e0149961.

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  43. 43.

    Kumar V. Eye is the window to the brain pathology. Curr Adv Ophthalmol. 2018;1(1):3–4.

    Article  PubMed  Google Scholar 

  44. 44.

    Evans LP, Newell EA, Mahajan M, Tsang SH, Fergunson PJ, Mahoney J, et al. Acute vitreoretinal trauma and inflammation after traumatic brain injury in mice. Ann Clin Transl Neurol. 2018;5(3):240–51.

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  45. 45.

    Ankamah E, Sebag J, Ng E, Nolan JM. Vitreous antioxidants, degeneration, and vitreo-retinopathy: exploring the links. Antioxidants (Basel). 2019;9(1):7.

    CAS  Article  Google Scholar 

  46. 46.

    Stefansson E, Olafsdottir OB, Eliasdottir TS, Vehmeijer W, Einarsdottir AB, Bek T, et al. Retinal oximetry: metabolic imaging for diseases of the retina and brain. Prog Retin Eye Res. 2019;70:1–22.

    Article  PubMed  Google Scholar 

  47. 47.

    Machado C, Santiesteban R, GarciÌa O, et al. Visual evoked potentials and electroretinography in brain-dead patients. Doc Ophthalmol. 1993;84(1):89–96.

    CAS  Article  Google Scholar 

  48. 48.

    Yazar MA. Bedside ultrasonography of the optic nerve sheath in brain death. Transplant Proc. 2019;51:2180–2.

    Article  PubMed  Google Scholar 

  49. 49.

    Topcuoglu MA, Arsava EM, Bas DF, Kozak HH. Transorbital ultrasonographic measurement of optic nerve sheath diameter in brain death. J Neuroimaging. 2015;25(6):906–9.

    Article  PubMed  Google Scholar 

  50. 50.

    Vashist P, Senjam SS, Gupta V, Gupta N, Kumar A. Definition of blindness under National Programme for Control of Blindness: do we need to revise it? Indian J Ophthalmol. 2017;65(2):92–6.

    Article  PubMed  PubMed Central  Google Scholar 

  51. 51.

    Guntinas-Lichius O, Finkensieper M. Three patients with full facial transplantation. N Engl J Med. 2012;366(19):1841–2.

    CAS  Article  PubMed  Google Scholar 

  52. 52.

    Bridge H, Watkins KE. Structural and functional brain reorganisation due to blindness: the special case of bilateral congenital anophthalmia. Neurosci Biobehav Rev. 2019;107:765–74.

    Article  PubMed  Google Scholar 

  53. 53.

    Reislev NH, Dyrby TB, Siebner HR, Lundell H, Ptito M, Kupers R. Thalamocortical connectivity and microstructural changes in congenital and late blindness. Neural Plast. 2017;2017:9807512.

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  54. 54.

    Zhou Z, Xu J, Shi L, Liu X, Hou F, Zhou J, et al. Alterations of the brain microstructure and corresponding functional connectivity in early-blind adolescents. Neural Plast. 2019;2019:2747460.

  55. 55.

    Hardman J, Halpin SF, Hourihan MD, Mars S, Lane C. MRI of the anterior optic pathways following enucleation. Neuroradiology. 1997;39(11):815–7.

    CAS  Article  PubMed  Google Scholar 

  56. 56.

    Abramoff MD, Ramos LP, Jansen GH, Mourits MP. Patients with persistent pain after enucleation studied by MRI dynamic color mapping and histopathology. Invest Ophthalmol Vis Sci. 2001;42(10):2188–92.

    CAS  PubMed  Google Scholar 

  57. 57.

    Wang WL, Xu H, Li Y, Ma ZZ, Sun XD, Hu YT. Dose response and time course of manganese-enhanced magnetic resonance imaging for visual pathway tracing in vivo. Neural Regen Res. 2016;11(7):1185–90.

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  58. 58.

    Zor F, Karagoz H, Kapucu H, et al. Immunological considerations and concerns as pertinent to whole eye transplantation. Curr Opin Organ Transplant. 2019;24(6):726–32.

    CAS  Article  PubMed  Google Scholar 

  59. 59.

    Zuo KJ, Saffari TM, Chan K, Shin AY, Borschel GH. Systemic and local FK506 (Tacrolimus) and its application in peripheral nerve surgery. J Hand Surg [Am]. 2020;45(8):759–65.

    Article  Google Scholar 

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Correspondence to Mariana Mayorquín-Ruiz MD.

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Mayorquín-Ruiz, M., Gómez-Villegas, T., Ramírez-Cedillo, C.G. et al. Neuro-Ophthalmologic Hurdles in Whole-Eye Transplantation. Curr Transpl Rep 8, 28–33 (2021).

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  • Whole-eye transplant
  • Optic nerve regeneration
  • Blindness
  • Visual restoration
  • Vascularized composite allotransplantation
  • Retinal ganglion cells