Eye transplantation comprises a range of cutting-edge surgical procedures intended to restore or improve vision and ocular function. Some of the most well-known practices include corneal transplantation, amniotic membrane transplantation, eyelash transplantation, and eyelid and tear duct transplantation.
While highly innovative, each of these surgeries offers unique benefits along with potential risks.
Common corneal transplantations
Table 1: Corneal transplantation procedures with uses and risk factors.1,2
| Corneal Transplantations | Procedure | Use | Potential Complications |
|---|---|---|---|
| Penetrating keratoplasty (PK) | This procedure involves a complete cornea replacement with a donor full-thickness cornea graft. | It used to be considered the gold standard for corneal replacement until new procedures emerged. It still remains the procedure of choice for combined stromal and endothelial pathologies. | There is an increased risk of expulsive suprachoroidal hemorrhage, primary graft failure, worsening glaucoma, microbial keratitis, and wound dehiscence. |
| Descemet stripping endothelial keratoplasty (DSEK) | This is one of two procedures involving the removal of the innermost layer of the cornea, specifically the endothelium and Descemet membrane, which is then replaced with up to one-third of donor corneal tissue. | This procedure is chosen for endothelial corneal dysfunction and dystrophy. | Risk factors include graft rejection, post-operative glaucoma, endothelial graft failure, and glaucoma. |
| Descemet membrane endothelial keratoplasty (DMEK) | This is one of two procedures involving the removal of the back layer of the cornea, specifically the endothelium and Descemet membrane, which is then replaced with a much thinner layer of donor corneal tissue. | This procedure is chosen for endothelial dysfunction and dystrophy. It is sometimes the surgeon’s preference to perform DMEK vs. DSEK. | Potential complications include graft detachment, epithelial defect or erosion, raised intraocular pressure (IOP), Descemet graft folds, and cystoid macular edema (CME). |
| Deep anterior lamellar keratoplasty (DALK) | This procedure replaces the anterior corneal tissue with donor corneal tissue, leaving the endothelial layer intact. | This procedure is a less invasive treatment for conditions with a healthy endothelial layer, such as keratoconus. | Due to this procedure’s less invasive nature, complications such as glaucoma, endophthalmitis, and expulsive hemorrhage are less likely to develop when compared to PK. However, it is technically more challenging than PK, and if the cornea is too thin, it may perforate during attempted DALK and PKP will be needed instead. |
Table 1: Courtesy of Gardin et al. and Mayo Clinic.
Overview of other ocular transplantations
Amniotic membrane transplantation (AMT)
Amniotic membrane transplantation treats conditions affecting the ocular surface by utilizing placental membrane for its accelerated healing, analgesic, and anti-inflammatory properties.3
Multiple AMT procedures are available, depending on the patient’s needs and presentation:
- Sutured AMT: With absorbable or nonabsorbable sutures, is used in more stable cases requiring long-term graft placement. The sutures provide a scaffold for epithelial cell migration, maintaining the membrane's position to allow for healing. This procedure is commonly used to treat chemical burns and corneal ulcers.4
- Glued AMT: Uses fibrin glue, or another type of tissue adhesive, to stabilize the membrane on the ocular surface when sutures are impractical. The gluing method is less invasive, faster, and more comfortable for the patient than sutures, but it does not provide the same level of stability. This procedure is most commonly used for small defects or post-operative cases.5
- Bandage lenses: Another method of AMT that allows a contact lens to be placed on the eye, instead of sutures or glue, to protect the amniotic membrane and cornea while the eye heals. This procedure is most commonly used for dry eyes or mild corneal defects.6,7
Each application method of AMT has its advantages and disadvantages. Donor screening processes are in place to minimize risk factors; however, as with most medical procedures, there remains a risk of infection.8
Eyelash transplantation
Eyelash transplantation can relieve patients with cosmetic concerns or those requiring reconstructive surgery due to avulsions, burns, or infections. The procedure is similar to hair transplantation and offers more permanent results; however, there are still risks of post-operative infection, poor aesthetic outcomes, and corneal irritation.9
Eyelid transplantation
Eyelid transplantation is a reconstructive surgery used following trauma or tumor excision. This procedure involves autologous transplantation, where the individual's stem cells are harvested and subsequently used to support healing.10,11 Local tissue flaps are preferred over grafts due to their tissue resemblance and decreased risk of post-operative complications.
However, they are only used for minor pre-septal defects and often contain hair follicles, making them non-viable for transplantation due to the risk of keratopathy.12 Since the anterior and posterior lamellae are composed of different tissues, graft and flap choices vary.12
Anterior lamellar reconstruction commonly uses advancement flaps that share one border with the lid crease. Alternatively, a full-thickness graft from the contralateral eye may be used or from the posterior auricular, preauricular, or supraclavicular regions containing no hair. Split-thickness grafts are rarely used.12
Posterior lamellar reconstruction must use tissue with a stable lid margin,12 with graft options usually including conjunctival, transconjunctival, mucosal, palatal, or cartilaginous tissue, often combined with local flaps.10
The grafts and flaps used in transplantation must have sufficient wound-healing abilities. Therefore, tissue previously treated with radiation is not viable for this procedure.12 Potential risks include infection and graft rejection.10,11
Tear duct transplantation
Tear duct transplantation is a surgical procedure to address dry eye disease in patients with damaged or absent tear ducts, as seen in conditions like Stevens-Johnson syndrome and Sjögren’s syndrome. Initially, the procedure involved transplanting the parotid duct or sublingual gland.
However, the submandibular gland has recently become preferred due to its higher survival rate and more effective relief of dry eye symptoms. Common complications include issues related to limited vascularization, which can be mitigated by using computed tomographic venography to improve blood supply to the transplanted tissue.13
Exploring whole-eye transplantation
The concept of whole-eye transplantation (WET) has been explored for over a century, with early experiments in animal models proving unsuccessful. These mammal studies were deemed failures because, despite successfully extracting and transplanting the donor's eye, the vision was not restored in the recipient. The primary challenge was reconnecting the severed optic nerve, which, once cut, could not regenerate.14
Vision depends on the precise transmission of signals from the retina to subcortical target areas through the optic nerve, a white-matter pathway composed of axon bundles originating from retinal ganglion cells (RGCs).13 Unlike mammals, cold-blooded vertebrates only experience partial death of RGCs, allowing them to regenerate their optic nerve spontaneously. In mammals, however, RGC damage is far more extensive, presenting significant challenges for regeneration.15
Advancements in animal models of WET
In 1928, a monumental study known as The Degeneration and Regeneration of the Nervous System proved through experiments with adult rabbits that using a peripheral nerve graft strategy allows for RGC regeneration. This series of experiments served as the first evidence that, under certain conditions, it is possible to restore central nervous system (CNS) neurons to their proper functions. Still, regeneration through the mature optic nerve remains a challenge.15
Despite these setbacks, advancements in immunology and technology and developments in corneal transplantation and other groundbreaking ophthalmologic treatments have renewed interest in whole-eye transplantation. In the 21st century, new animal studies have focused on stem cell therapy and axonal regrowth, offering a novel approach to restoring vision.16
The United States Department of Defense has played a crucial role in supporting whole-eye transplantation research, motivated by its potential to assist military veterans suffering from severe eye injuries.17
The first successful WET and partial face transplant
A groundbreaking case at NYU Langone Health made headlines in May of 2023 as the first and only whole-eye and partial face transplant. The recipient, a military veteran from Arkansas, received the entire left eye and skin graft from a single donor following a high-voltage electrical accident.
The procedure involved harvesting the donor’s bone marrow for stem cells, which were injected into the optic nerve to support regeneration. The eye transplantation was a success from a cosmetic standpoint and showed promise due to the healthy blood flow to the retina.
As of September 2024, the recipient remains healthy, and the donor eye shows no signs of organ rejection. Despite the positive outcome, the patient has not regained sight in the donor's eye, highlighting the significant gap in the ability to restore vision through this procedure.18
Addressing the main challenges of WET
Vision restoration has been the greatest challenge in whole-eye transplantation, as none of the animal studies or human trials have been successful. This issue arises from the inability to reconnect the optic nerve, which, once severed, does not naturally regenerate. A transplanted eye remains non-functional without a proper connection to the brain’s visual cortex.14
Stem cell therapy has been a significant focus of investigation for aiding optic nerve regeneration. In animal studies, scientists successfully induced some optic nerve restoration in mice by combining stem cell injections with growth factors such as fibroblast growth factor-2 (FGF2) and neurotrophic factor brain-derived neurotrophic factor (BDNF). Despite this breakthrough, the number of regenerated axons was insufficient to restore vision.15
Stem cell therapy is also being researched for retinal cell transplantation. Retinal degenerative diseases are known to cause partial and complete vision loss. Emerging preclinical studies and clinical trials have shown promise in restoring vision in cases of age-related macular degeneration, Parkinson’s disease, and traumatic brain injury.19,20
Preventing graft rejection in whole-eye transplants
Graft rejection is a common concern in all transplantation surgeries, and it is particularly significant in whole-eye transplantation. The eye is an immune-privileged site, and introducing many new tissue types can lead to inflammation, rejection, and neuronal damage.
To prevent graft rejection, patients are prescribed immunosuppressive drugs, which come with their potential side effects. WET post-operative care thus becomes a balancing act between preventing graft rejection and preserving the eye's immune-privileged state.14
Future advancements for whole-eye transplantation
To preserve the viability of the optic nerve, the NIH-funded Bascom Palmer whole eye transplant project has focused on further investigating the use of gene therapy and stem cells to regenerate vision.
Dr. Alfonso and his team have collaborated with biomedical engineers to biologically modify the donor tissue while keeping the donor eye in an extracorporeal membrane oxygenation (ECMO) device to improve blood flow and increase the chances of preserving viable donor tissue.21
If the optic nerve may never be viable enough to restore vision, the Bascom Palmer project has also been exploring the implantation of computer chips in both the eye and the brain to facilitate direct image transmission between the two organs. However, this advancement in technology brings its own set of risks.
In addition to the concerns of graft rejection and immune response, a significant challenge is the need to somehow “retrain” the brain to interpret images transmitted from the new eye and implant.21
Ongoing efforts to improve WET techniques
Eyes On Eyecare is proud to announce that David RP Almeida, MD, MBA, PhD, the Chief Medical Editor for ophthalmology content at Eyes On Eyecare, was recently selected as a finalist for the Advanced Research Projects Agency for Health (ARPA-H) Transplantation of Human Eye Allografts (THEA) program.
Dr. Almeida represented the only private practice from the 20 finalists (which were selected from over 4,000 applicants) and continues to advance cutting-edge care in ophthalmology with his research. Take an exclusive look at the abstract for his poster presentation below!
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Whole-Eye Transplantation Poster Abstract
Read through Dr. Almeida's poster abstract for the Transplantation of Human Eye Allografts (THEA) program to gain insights into an innovative surgical approach to restore sight through WET.
Conclusion
WET has been one of the most groundbreaking yet perplexing efforts in ophthalmology. Although complete vision restoration has not yet been achieved, innovations in gene therapy, stem cell research, surgical techniques, and bioengineering have brought us closer to this once-distant goal.
The primary challenge remains the regeneration of the optic nerve, though some studies are exploring alternative approaches, such as computer chip technology, to circumvent this issue. With ongoing advancements in technology and medicine, the restoration of vision could become one of the most outstanding achievements in ophthalmology and transplant medicine.
