Corneal transplant

A corneal transplant is a surgical procedure in which a damaged or diseased cornea is replaced with donated corneal tissue (the graft). When the whole cornea is replaced it is called penetrating keratoplasty, and when only part of the cornea is replaced it is called lamellar keratoplasty. Keratoplasty simply means surgery on the cornea. The graft is taken from a person who has recently died with no known eye disease or other factors that could affect the survival prospects of the donated tissue or the health of the recipient.

The cornea is the clear front part of the eye covering the iris, the pupil and the anterior chamber. The surgical procedure is performed by ophthalmologists who specialise in corneal transplantation and is often done on an inpatient basis in Israel, whereas in North America it is a day-surgery procedure. Donors can be of any age, although a minimum age of two years is generally accepted, with no limit after that (Shimon Peres donated his corneas after he died). A corneal transplant is performed when non-invasive treatment such as medication, or less invasive surgery (such as corneal cross-linking in keratoconus), cannot heal the cornea adequately.

Historical background

The first corneal transplant was performed in 1905 by Eduard Zirm (the eye clinic of Olomouc, today in the Czech Republic), making it one of the first types of transplant surgery of any organ to be performed successfully. The Russian eye surgeon Vladimir Filatov's attempts at corneal transplantation began with a first attempt in 1912 and continued, improving gradually, until on 6 May 1931 he successfully transplanted a cornea into a patient using corneal tissue from a person who had died. He reported extensively on a further transplant in 1936, and shared his technique in full detail. In 1936, Castroviejo performed a first transplant in an advanced case of keratoconus, achieving a significant improvement in the patient's vision.

Tudor Thomas, a clinical teacher at the Welsh National School of Medicine, conceived the idea of a donor system for corneal transplants, and the East Grinstead bank was established in 1955. Advances in the use of microscopes allowed surgeons to operate with a more magnified view, while advances in materials science allowed them to use sutures finer than a human hair.

What brought about the success of corneal transplantation was the establishment of eye banks. These are organisations located around the world to coordinate the distribution of donated corneas to surgeons, as well as to supply eyes for research. In Israel, as of 2020, there is no single central eye bank for the whole country, and most hospitals supply corneas for themselves, with collaborations between different hospitals at times as well.

Indications for a corneal transplant

The general indications for a corneal transplant can be classified into 4 categories:

Optical: to improve visual acuity by replacing unhealthy or abnormal tissue with healthy donor tissue. The most common indication in this category is pseudophakic bullous keratopathy, followed by keratoconus, Fuchs' dystrophy, and scarring due to keratitis and trauma.

Tectonic: to preserve the normal anatomy of the cornea and its integrity in patients with stromal thinning, or after perforation of the cornea following a penetrating injury.

Therapeutic: to remove inflamed or infected corneal tissue that is not responding to conservative treatment such as antibiotics, anti-inflammatory treatment or antiviral treatment.

Cosmetic: to improve the appearance of patients with corneal scars or opacities (this accounts for a minority of cases, because of the risks of corneal transplantation and because of the shortage of tissue).

Types of corneal transplant

Full-thickness corneal transplant: penetrating keratoplasty. An operation in which all the layers of the cornea are removed from the patient and all the layers of a donor's cornea are transplanted in their place. Today this type of corneal transplant is becoming less common, because there are now partial-thickness corneal transplants that carry lower risks and, in the right indications, produce better visual acuity results. Today the main indications for penetrating keratoplasty are: full-thickness central corneal scars resulting from trauma or infections, degenerative diseases of the cornea involving all the layers, severe chemical injuries of the cornea, repeat corneal transplantation, and failure to perform an anterior lamellar corneal transplant such as DALK.

Partial-thickness corneal transplant: there are several types of common corneal transplant that involve partial endothelial corneal transplants such as DMEK and DSAEK. There are also anterior partial corneal transplants such as DALK (more common, and described in detail below) and SALK (less common, mentioned briefly).

DMEK corneal transplant: this is the most advanced partial corneal transplant (as of 2020). The initials stand for Descemet membrane endothelial keratoplasty. In this operation the endothelial layer and Descemet's membrane are removed from the patient and replaced with those same layers from a donor who has died. The main indications for this operation today are pseudophakic bullous keratopathy and Fuchs' dystrophy. This operation has a faster recovery of visual acuity, better final visual acuity and a lower chance of graft rejection compared with DSAEK. Even so, it is a procedure that is technically harder to perform and is not suitable for complex eyes (long eyes, eyes after vitrectomy, eyes with no lens (aphakic) or with a large iris defect (aniridia)). In addition, there is a higher rate of the need for rebubbling (filling the anterior chamber with air) after surgery compared with DSAEK.

DSAEK corneal transplant: this is a posterior partial corneal transplant, and the initials stand for Descemet stripping automated endothelial keratoplasty. In this operation the endothelial layer and Descemet's membrane are removed from the patient and replaced with endothelium, Descemet's membrane and a little posterior stroma from the donor tissue. If the thickness of the stroma taken from the donor is under 100 microns, it is called ultra-thin DSAEK. If it is under 60 microns, it is called nano-thin DSAEK. The indications for this operation are identical to those for DMEK, and when the eye is very complex, as mentioned above, DSAEK is preferable to DMEK. It is a procedure with a lower chance of complications, including graft rejection, compared with penetrating keratoplasty.

DALK corneal transplant: this is an anterior partial corneal transplant, and the initials stand for deep anterior lamellar keratoplasty. In this operation all the layers of the cornea are removed except the endothelium, Descemet's membrane and Dua's layer (the most posterior part of the stroma), and they are replaced with donor tissue from which the endothelial layer and Descemet's membrane have been removed. The main indications for this operation are keratoconus and corneal scars that are not full thickness. It is a procedure with a lower chance of the complications associated with the open-sky stage of penetrating keratoplasty, and a lower chance of rejection as well.

SALK corneal transplant: this is an anterior corneal transplant, and the initials stand for superficial anterior lamellar keratoplasty. In this operation only part of the anterior stroma is removed and replaced with similar tissue from a donor. The main indication is a very superficial scar. It is a procedure that is not performed much today.

Artificial corneal transplant

Boston keratoprosthesis

Boston KPro type 1 — titanium back plate: the Boston keratoprosthesis is the most common synthetic cornea to date, with over 900 procedures performed worldwide in 2008. The Boston KPro was developed at the Massachusetts Eye and Ear Infirmary under the leadership of Dr Claes Dohlman.

AlphaCor: in cases where there have been several graft failures, or where the risk of keratoplasty is high, synthetic corneas can successfully replace donor corneas. Such a device contains a peripheral skirt and a clear central zone. These two parts are joined at the molecular level by an interpenetrating polymer network made of poly(2-hydroxyethyl methacrylate) (pHEMA). AlphaCor is a type of synthetic cornea approved by the American FDA, 7.0 mm in diameter and 0.5 mm thick. The main advantages of synthetic corneas are that they are biocompatible, and that the network between the parts of the device prevents complications that could arise at their interface. The probability of graft survival in one large study was estimated at around 60% at two years of follow-up.

Osteo-odonto-keratoprosthesis (OOKP): in a rare and extremely complex multi-stage surgical procedure, used to help the most complex patients, part of the layers of the patient's own tooth is used and implanted into the patient's eye with an artificial lens fitted inside the tooth tissue.

The risks of a corneal transplant

The risks are similar to those of other intraocular procedures, but in addition include graft rejection (lifelong), detachment of a lamellar or partial graft, and primary or secondary graft failure. Topical treatment (drops) alone is usually needed in order to prevent and treat graft rejection. Even so, the use of other immunosuppressive drugs including cyclosporine A, tacrolimus, mycophenolate mofetil and sirolimus to prevent graft rejection is increasing, but there is not enough evidence to establish which immunosuppressive treatment is better. In a literature review that included low- to moderate-quality evidence, side effects were found to be common with systemic mycophenolate mofetil treatment, but less common with topical treatments such as cyclosporine A and tacrolimus.

There is also a risk of infection. Because the cornea has no blood vessels (it obtains the substances it needs from the fluid in the anterior chamber and from the tear film), it heals far more slowly than an incision in the skin. While the wound is healing, it may become infected with various micro-organisms. This risk is minimised by preventive antibiotic treatment (using antibiotic eye drops, even when there is no infection) in the period immediately after surgery.

There is a risk of corneal rejection, which occurs in about 10% of cases. Graft failure can occur at any time after a corneal transplant, even years or decades later. The reasons can vary, although it is usually because of endothelial failure of the graft over the years, infection in the graft, trauma, or recurrence of the underlying disease.

Partial-thickness corneal transplant — further information

Surgical options for a partial-thickness corneal transplant

In certain cases, a full-thickness corneal transplant may not be needed in order to treat disease or damage in the cornea. Some patients can have a partial-thickness corneal transplant (endothelial keratoplasty), in which only the affected layers of corneal tissue are replaced with donor tissue and the patient's healthy, properly functioning corneal layers remain in place.

The layers of the cornea

Starting from the front of the eye, the cornea is made up of five main tissue layers:

• Epithelium. This outer, clear, membrane-like layer helps prevent foreign material, such as dust and bacteria, from entering the eye. It absorbs oxygen and nutrients from the tear film so that they are available to the rest of the cornea. The epithelium also contains nerve endings that make the cornea sensitive to injury or pain.
• Bowman's layer. Directly behind the epithelium, Bowman's layer is a relatively strong structure that helps protect the cornea from injury.
• Stroma. The stroma is located behind Bowman's layer. It is the thickest layer of the cornea. Like Bowman's layer, it contains collagen fibres that give the cornea both strength and flexibility.
• Descemet's membrane. This layer also helps protect the internal structures of the eye. It is very thin and made of collagen, but a different type of collagen from the stroma. Descemet's membrane is produced by the cells of the corneal layer behind it, the endothelium.
• Endothelium. This single layer of cells is the innermost layer of the cornea. It performs a pumping function that maintains the correct balance of fluid in the cornea in order to keep it clear. If the endothelium is not working properly because of injury or disease, the cornea may swell and become cloudy or opaque, preventing clear vision.

Types of partial-thickness corneal transplant

Several types of partial corneal transplant can be performed.

DSAEK partial corneal transplant

Descemet's stripping endothelial keratoplasty (DSAEK) is used when Descemet's membrane and the endothelium are the corneal layers responsible for the vision problems. Common causes of disease or dysfunction of the endothelium include previous eye surgery, various infectious, inflammatory or traumatic conditions, and an inherited condition such as Fuchs' corneal dystrophy.

How DSAEK is performed

A DSAEK corneal transplant is usually performed under local anaesthesia, with the addition of intravenous or oral sedation as needed. Descemet's membrane and the endothelium are replaced with a corneal graft (including a small amount of stroma), but the rest of the cornea remains in place. The graft is obtained from a donor who died recently and is carefully screened to confirm that it is suitable for transplantation.

After the eye has been anaesthetised, a small incision is made near the edge of the cornea. Through the incision, Descemet's membrane and the endothelium are removed and replaced with the graft. A bubble of air or gas is placed beneath the graft to hold it in position. Sutures are not used to hold the graft in place, but the small incision is sutured closed. If the graft does not adhere sufficiently, a procedure to inject a further air bubble may be needed during the first weeks after the initial procedure.

The "automated" in the name DSAEK refers to the way the donor tissue is prepared. It is shaved from the donor eye with a microkeratome, a precise oscillating blade.

The advantages of DSAEK over a full-thickness corneal transplant

Recovery from a corneal transplant is faster after DSAEK than after a full-thickness transplant, provided the eye has no other problems that would limit potential visual acuity. Although it is fairly blurred immediately after DSAEK surgery, vision usually begins to improve within one to two months after surgery. Patients can usually be fitted with glasses within 4 to 6 months (compared with 12 to 18 months after a full-thickness transplant). In addition, because only the thinnest inner layers of the patient's cornea are replaced, the integrity of the cornea is less affected than in a full-thickness transplant.

DMEK partial corneal transplant

Descemet membrane endothelial keratoplasty (DMEK) is the least invasive of the partial-thickness corneal transplants, since the smallest amount of tissue — Descemet's membrane and the endothelium, with no stroma — is removed and replaced with a graft of donor tissue. As with DSAEK, DMEK can be used when Descemet's membrane and the endothelium are the corneal layers responsible for the vision problems.

How DMEK is performed

DMEK is usually performed under local anaesthesia, with the addition of intravenous or oral sedation as needed. As with the other types of corneal transplant, the corneal tissue graft used in DMEK is obtained from a donor who has died, after careful screening to confirm that it is suitable for transplantation.

After the eye has been anaesthetised, a small incision is made near the edge of the cornea. Through the incision, Descemet's membrane and the endothelium are removed and replaced with the graft. A bubble of air or gas is placed beneath the graft to hold it in position. Sutures are not used to hold the graft in place, but the small incision is sutured closed. If the graft does not adhere sufficiently, a procedure to inject a new air bubble may be needed during the first weeks after the initial procedure.

The advantages of DMEK over DSAEK and a full-thickness corneal transplant

Recovery from a corneal transplant is faster after DMEK than after a DSAEK transplant or a full-thickness transplant, provided the eye has no other problems that would limit the best potential vision. Despite fairly blurred vision immediately after DMEK, vision usually begins to improve within one to two weeks after surgery. Patients can usually be fitted with glasses within one to two months (compared with 4 to 6 months after DSAEK and 12 to 18 months after a full-thickness transplant). In addition, because only a very thin tissue graft is used for DMEK, the possibility of graft rejection may be lower than in a DSAEK transplant and a full-thickness transplant, and there is a higher chance that the final vision after surgery can reach 20/20 with glasses.

Risks associated with corneal transplants

As with any kind of surgical procedure, a corneal transplant carries some risks and possible complications. Graft rejection is one of the possible risks. If graft rejection or another problem occurs, but the eye retains its visual potential, a repeat transplant procedure can be performed. The procedure may be the same as the first operation, a different partial-thickness corneal transplant option, or a full-thickness transplant.

Private corneal transplant surgery

Can a corneal transplant be done privately?

The answer is yes. A corneal transplant can be performed privately as well as in a public hospital. Private corneal transplant surgery is possible because corneas for transplantation can be imported from an accredited cornea bank abroad. If you have private medical insurance or supplementary insurance services through your health fund, they will cover a substantial part of the cost of importing the cornea for private corneal transplant surgery. In addition, if you have chosen to have the operation with a doctor or centre with whom they have an arrangement, they will cover the cost of the surgeon's fee and the cost of the operating theatre.

With whom is it best to have a private corneal transplant?

It is right to have a private corneal transplant with a corneal transplant specialist who is experienced in the surgical technique suited to your eye. There are today various advanced methods of performing a corneal transplant, and each of them has its own learning curve, so it is best to have the operation with someone who has had the appropriate training for it:

• Full corneal transplant — PKP — in which all the layers of the cornea are replaced — for example after trauma
• DALK corneal transplant — in which the innermost, most posterior layer is left in place — for example for keratoconus
• DSAEK posterior corneal transplant — in which the endothelium, Descemet's membrane and a little posterior stroma are replaced or transplanted — for example for complex eyes with failure of the endothelial layer
• DMEK posterior corneal transplant — in which only the endothelium and Descemet's membrane are replaced — an advanced operation usually performed in patients with Fuchs' dystrophy, or those with failure of the endothelial layer after cataract surgery

What makes up the cost of private corneal transplant surgery?

The cost of private corneal transplant surgery is made up of the cost of the cornea, the cost of the surgeon's fee and the cost of the operating theatre at the medical centre where you have the operation. The cost of the cornea can range from NIS 5,000 to NIS 10,000, depending on the requirements of the tissue: tissue that requires extensive preparation by the cornea bank it is bought from will cost more than tissue that arrives unprocessed or unprepared. The surgeon's fee is at the surgeon's discretion, or in accordance with their agreement with insurance companies and supplementary insurance services (if they have one), and broadly speaking it can range from NIS 7,500 to NIS 20,000 (and even more). The cost of the operating theatre varies from one medical centre to another, but can likewise range from NIS 3,000 to NIS 10,000, depending on the type of surgery, the length of surgery, the medical staff required and the need for an anaesthetist to be present. Private corneal transplant surgery can therefore range from NIS 15,000 up to NIS 40,000–50,000 per eye.

What is the waiting list for a private corneal transplant?

The waiting list for a corneal transplant generally depends on tissue from donors. When you have private corneal transplant surgery, because the cornea is ordered from an accredited cornea bank abroad, the wait itself is usually a matter of a few weeks, depending on the surgeon's availability.

Is there an advantage to private corneal transplant surgery over the public system?

As noted, the availability of tissue will be higher with private corneal transplant surgery, since it is purchased from abroad and matched precisely to the patient's needs. In addition, you will have the option of choosing your surgeon and making sure you are getting a cornea specialist experienced in the corneal transplant technique best suited to your eye.

— Prof. Mimouni performs all types of corneal transplant in private settings as well — contact us for details.