Reopening the ‘Window to the Soul’?: The Ethics of Eye Transplantation Now and in the Future

This article refers to:

First-in-Human Whole-Eye Transplantation: Ensuring an Ethical Approach to Surgical Innovation

Of all the five senses losing sight is the one that individuals fear the most. Worldwide blindness has afflicted tens of millions of people each year. Historically, this has inspired researchers and doctors to try whole eye transplants (WET).

In the early twentieth century efforts were made to transplant eyes in salamanders, tadpoles, toads and frogs including across species with mixed success. Some of these cold-blooded invertebrates did regain some transient vision but most did not. Efforts in mammals including rabbits, pigs, sheep and dogs saw restoration of blood flow and muscle movement but none regained vision (Bourne et al. 2017).

A human cadaveric donor WET was attempted in 1969 at Methodist Hospital in Houston. The cornea, lens, and iris were transplanted but failed to restore vision (Bourne et al. 2017).

The immediate future of eye transplantation both single and dual is likely to be very limited. Despite the remarkable technical achievement of the NYULangone team (Laspro et al. 2024), transplant experts and ophthalmology researchers know of a number of huge challenges that continue to make successful WET so difficult.

The capability of nerves in general and the optic nerve in particular to regenerate continues to be poorly understood and at best uncertain. The optic nerve must regenerate to permit light stimuli to reach the appropriate visual centers of the brain and the brain must be able to provide the correct interpretation of these somewhat novel signals from a new eye for eye transplantation to be functionally effective.

An immunosuppressive protocol that hinders rejection with minimal side effects profile is required. A proven protocol for surveillance for allograft rejection of the eye remains undefined. Immunosuppression carries well known dangers (Fishman 2017) including dangerous viral, fungal and bacterial infections, and damage to the kidneys and other vital organs. The NYU group avoided this challenge by transplanting an eye as part of a total face transplant which required immunosuppression. But simply transplanting an eye leaves the issues of risks from inadequate detection of rejection, immunosuppression itself and immunosuppressive failure unresolved.

Moreover, the risk evaluation involving immunosuppression is different from many other traditional forms of transplantation in that eye transplants are not life-saving. Those facing certain death due to heart, lung or liver failure are not prone to be risk averse about immunosuppressive risks. But transplants done for reasons of quality of life and esthetic considerations when vision restoration is hugely unlikely shift the equation about life threatening and debilitating risks for both a candidate and the surgical transplant team (Caplan and Purves 2017).

Even “rescue” should immunosuppression lead to uncontrolled fatal organ damage is different for the eye. Retransplantation is possible and well-known for kidneys and hearts with some success but poorer results than initial transplants. Efficacy and adverse event rates are completely unknown for WET. Even the availability of potential donors to attempt necessary second or third transplants is uncertain.

Surgery for WET outside of face transplantation has some challenges. The optimal surgical technique used in cadaver procurement must be very efficient with short ischemia time from procurement to implantation in order to avoid cellular damage (Bourne et al. 2017).

In addition, the prevailing standard of care in ophthalmology is that intraocular surgery is inappropriate in an eye with no light perception (NLP). These eyes are believed to be in a uniquely vulnerable state; most NLP eyes have endured a prior injury that confers a high risk of surgical complications. Beyond the risk to the NLP eye, the contralateral eye is vulnerable to the rare but potentially devastating outcome of blindness—sympathetic ophthalmic (SO) (Anderson, Caplan, and Schuman 2019). Although immunosuppressive treatments for SO exist, they are associated with serious side effects and toxicities, with the potential to reduce resistance to infection creating lethal risks, causing systemic illnesses such as diabetes and hypertension, and increasing the likelihood of hepatitis, kidney failure, and certain cancers (Anderson, Caplan, and Schuman 2019). Treatment is often lifelong and not uniformly effective. In a monocular patient, Surgery continues to have the potential of causing bilateral blindness.

How this bears on operations aimed at improving the quality of life of a person with one injured eye is not known. But risking blindness again shifts the equation when quality of life not functional restoration is at issue.

For someone simply in need of WET there are prosthetic options. Many find these unsatisfactory (Laspro et al. 2024) but the option is perhaps more attractive given the current risks and unknowns of undertaking WET for quality of life considerations.

Research on WET as a part of face transplantation, when conducted by experienced teams following stringent moral guidelines has a future, albeit limited (Laspro et al. 2024). WET by itself still requires more animal, computer-based and lab research to become a viable program for clinical research much less therapy.*

*Thanks to Linda C. Cendales, M.D., Director, Vascularized Composite Allotransplantation, Duke University Department of Surgery, for useful feedback.

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The authors declare there is no complete of interest at this study.

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The author(s) reported there is no funding associated with the work featured in this article.