Overview of Corneal Endothelial Transplantation
The cornea has five layers and plays a primary role in the focus of the eye. Previously, if a disease affected any layer, a surgery known as penetrating keratoplasty (PK) was the key treatment. However, with technological improvements, a new operation known as endothelial keratoplasty (EK), which involves transplanting parts of the cornea, has been introduced. Compared to PK, EK brings fewer foreign substances into the body, speeds up visual recovery, has less risk of the wound reopening, improves eye stability, and reduces vision distortion.
The history of EK dates back to 1956 when the first transplant was carried out by Dr. Tillett. This early version involved a large incision and implantation of a partial graft from a donor’s cornea. In the 1960s, Dr. Barraquer improved this method by using a very fine surgical instrument for a top-down approach similar to LASIK (a common laser eye surgery) and suturing (stitching) the graft. However, these techniques were complex and could not solve the problems associated with PK.
A breakthrough came in 1998 when Melles and colleagues introduced an innovative method that involved dissecting out a pocket in the corneal tissue, inserting the graft there, and securing it with air instead of stitches. This eliminated a significant source of tension and the risk of the graft being displaced.
This technique was further refined over the years. The term deep lamellar endothelial keratoplasty (DLEK) was coined by Dr. Terry. However, due to its technical complexity, it remained challenging to adopt universally.
In 2004, Melles and colleagues patented a new technique now known as Descemet stripping endothelial keratoplasty (DSEK), which involves removal of a small portion of the diseased cornea and replacing it with a thin layer of healthy tissue. This technique gradually replaced DLEK due to its better visual outcomes and continued refinements.
DSEK later evolved to Descemet stripping automated endothelial keratoplasty (DSAEK) and ultrathin DSAEK (UT-DSAEK), both providing improved visual outcomes and faster recovery times.
Later on, Descemet membrane endothelial keratoplasty (DMEK) was developed. This procedure involves placing an even thinner graft, without any stroma (the thicker, middle layer of the cornea). A similar technique called pre-Descemet Endothelial Keratoplasty (PDEK) was also developed.
While DMEK showed better visual outcomes and faster recovery time, it was not widely adopted due to the increased surgical skill required and higher rates of complications.
On another note, femtosecond laser technology has been used in EK procedures to aid in obtaining a thin graft and smoothing it with laser light. Studies show that it can help reduce some complications associated with DMEK.
Finally, in areas where donor tissue is limited, variations of DMEK involving smaller or differently shaped grafts have been explored as promising solutions.
Anatomy and Physiology of Corneal Endothelial Transplantation
The cornea is the outer layer of the eye that shields it from injury and contributes to most of the eye’s refractive power, or ability to focus light, accounting for almost 70% of this total function. The cornea is composed of five layers, listed from outermost to innermost: the epithelium, Bowman layer, stroma, Descemet membrane, and the endothelium.
The epithelium acts like a shield for the eye and smooths the surface where tears form atop the cornea. Bowman layer aids in keeping the cornea’s shape. The stroma, which is the primary layer that bends light, provides structural strength to the cornea. The stroma’s fibers are designed in layers at different angles, making the inner part of it more prone to swelling. The cornea has many nerves provided by the ophthalmic nerve. The Descemet membrane, produced by endothelial cells, attaches the endothelium to the stroma.
The endothelium, or the inner layer of the cornea, consists of specialized cells arranged in a honeycomb pattern. This layer works like a pump to keep the cornea clear by moving nutrients and fluids in and out of the stroma. The number of these cells decreases as we age, which can affect the clearness of the cornea.
There are various diseases related to the corneal endothelium, leading to surgical procedures. Fuchs Endothelial Corneal Dystrophy (FECD) is the most common of these, often occurring in both eyes from a young age due to genetic factors. FECD can cause blurry vision and can be painful.
Pseudophakic and Aphakic Bullous Keratopathy can occur as a side effect of cataract surgery. Iridocorneal Endothelial Syndrome (ICE) is a rare condition where corneal endothelial cells travel and block other eye components, possibly due to a viral trigger. This can lead to issues with eye pressure and corneal clarity.
Posterior Polymorphous Dystrophy (PPCD) and Congenital Hereditary Endothelial Dystrophy (CHED) are also rare genetic conditions affecting the cornea starting from the early years of life. They are both characterized by irregularities in the cornea that potentially cause vision problems.
Why do People Need Corneal Endothelial Transplantation
If a person struggles with impaired vision and issues with their cornea (the transparent front part of the eye), they may be suitable candidates for a specific eye procedure. The most common reasons for needing this procedure are conditions like Fuchs endothelial corneal dystrophy (an eye disease that affects the cornea), aphakic or pseudophakic bullous keratopathy (swelling and clouding of the cornea after cataract surgery), and when previous cornea transplants have failed.
Other less common reasons for the procedure include damage to the cornea due to injury, iridocorneal endothelial syndrome (a rare disorder that changes the shape of the cornea and iris), posterior polymorphous dystrophy (an inherited eye disorder which affects the cornea), and congenital hereditary endothelial dysfunction (an inherited disorder of the cornea).
This procedure, known as DMEK, also successfully treats failed penetrating keratoplasty (PK, a cornea transplant) with superior visual results compared to repeating PK or using another method called DSEK (a form of cornea transplant). The survival rate, or how long the new cornea lasts in the eye, is also similar over a four-year period for these different procedures.
When a Person Should Avoid Corneal Endothelial Transplantation
Sometimes, if someone has a serious eye disease that causes thick scarring, like advanced bullous keratopathy, one treatment option might be a PK, or a full thickness cornea transplant. This is because the scars and cloudiness on the cornea can make it hard for doctors to see properly and for the patient to see better.
However, there are some circumstances where another type of surgery, called DMEK (Descemet’s Membrane Endothelial Keratoplasty), might not be the best option. This might be the case for patients who have a condition called glaucoma, where pressure builds up in the eyes, people who don’t have a lens in one or both eyes (aphakia), or people who have defects in the colored part of their eyes (the iris). This is because the very thin grafts used in this type of surgery might be lost. In such cases, doctors might recommend DSAEK (Descemet’s Stripping Automated Endothelial Keratoplasty) or a mix of DMEK and DSAEK.
Also, sometimes, doctors need to increase the pressure in the eyes to make the graft stick properly. But if a person’s eyes are very soft (hypotonic eyes) or in a condition called pre-phthisic (where the eye is on the verge of becoming shrunken or blind), this could make that condition worse.
Equipment used for Corneal Endothelial Transplantation
The equipment required to perform eye surgery can vary in accordance with the techniques being used. A device known as a microkeratome, which is used for precision cutting of the cornea, may be needed. If the procedures involve DSEK (Descemet’s Stripping Endothelial Keratoplasty) or DMEK (Descemet’s Membrane Endothelial Keratoplasty), donor tissue will be used. This tissue might be prepared by the eye surgeon on the day of the operation or it can be sourced from an eye bank.
Special devices, often referred to as glide or mechanical injection devices, are used to insert the donor grafts during DSEK. In contrast, an intraocular lens injector, which is a device used to insert replacement lenses into the eye, may be utilized for the placement of the DMEK graft.
To enhance visibility during these procedures, a gel-like substance known as viscoelastic or air might be injected into the eye. Additionally, for the maintenance of the anterior chamber (the front part of the eye) depth, the surgical team might irrigate, or wash out, this section of the eye.
Who is needed to perform Corneal Endothelial Transplantation?
These medical operations require a team of healthcare professionals. This includes an anesthesiologist, who is a doctor specialized in giving medicines to help you sleep or relieve pain during surgery. There’s also a circulating nurse, who prepares the operating room and provides instruments to the other staff. A scrub tech helps to maintain a clean environment by washing and sterilizing equipment. The assistant helps the main surgeon during the operation. Finally, the operating ophthalmologist is a special type of eye doctor who performs the actual surgery. They are experienced in managing complex methods that may be needed for your case.
Preparing for Corneal Endothelial Transplantation
During a specific type of eye surgery called DSEK, a surgeon needs to prepare a graft, which is a piece of healthy tissue that they’ll use to replace the damaged tissue. This graft can be collected by hand or using a special eye surgery tool called a microkeratome. The use of this tool often produces smoother, thinner grafts which tend to result in better recovery.
For another type of surgery called DMEK, the graft is collected in a different way. The surgeon may either score (make shallow cuts) and peel it off the back of the cornea or use a method called pneumodissection, which uses air pressure to help loosen the tissue. The risk with pneumodissection is that it may lead to a smaller graft and more loss of the innermost cells of the cornea. This method can also be used to retain a layer of the cornea called the pre-Descemet layer, which makes the graft easier to handle.
Grafts obtained from diabetic donors have been linked to graft failure, so these should be used with caution or avoided. Other risks for decreased graft survival in DSEK include having prior glaucoma surgery or a history of rejecting previous grafts.
In some cases, if a patient is also suffering from foggy lenses, a procedure to remove cataracts and insert a clear, artificial lens can be done at the same time as the DSEK or DMEK, and it doesn’t increase the risk of complications. However, DSEK and DMEK can increase early cataract development in patients, especially those over 50 years old. For older patients with clear lenses, it’s important to discuss the risks and benefits of combining these surgeries.
How is Corneal Endothelial Transplantation performed
Deep Lamellar Endothelial Keratoplasty (DELK) involves a challenging operation which starts with making a 9.0-mm cut in the sclera (the white outer coating of the eye), about 1.0-mm away from the superior limbus (the border area where the cornea, the clear front part of the eye, meets the sclera). Viscoelastic, a special gel-like substance, is then injected to the operation area. Then, a deep cavity is skillfully designed beneath the entire cornea using a set of specialized tools such as curved blades and scissors. This process is also applied when obtaining the graft (donated tissue) which is later placed in the created gap in the cornea. After cleaning out the viscoelastic, air is pumped into the patient’s anterior chamber (the front part of the eye) and the graft is carefully placed and stuck to the cornea using a flat tool coated in viscoelastic.
Descemet Stripping Endothelial Automated Keratoplasty (DSAEK) is a different procedure where a smaller 3-5 mm cut is made in the eye. The diseased Descemet membrane (the thin layer of tissue behind the cornea) and endothelium (innermost layer of the cornea) are removed using a special hook and forceps. To get a clearer view, the surgeon may inject viscoelastic or air into the anterior chamber. The graft is then introduced using various methods. Initial methods used forceps to pull in the folded graft but it was found to cause loss of cells, particularly in patients with shallower anterior chambers. To reduce graft insertion damage, several specialized devices were developed that either glide the graft into place or mechanically inject it. Once the graft is in place, an air bubble is used to make it stick to the cornea. After around 10-30 minutes, some of this air is replaced with a liquid (balanced salt solution) to avoid blockage in the pupil.
Descemet Membrane Endothelial Keratoplasty (DMEK) modifies steps from DSEK but with a thinner graft. The thin graft makes it necessary to achieve a smooth surface on the recipient’s eye. Once the donor tissue is in the eye, it rolls up by itself with the innermost layer of the cornea facing out, which can be seen more clearly when stained with a blue dye. The graft is first put in an injector and then flushed into the eye. Insertion and unrolling of the graft are skillfully done using bursts of either liquid or air, followed by an air bubble to stick the graft to the cornea. It’s crucial that the graft is positioned correctly, and so several techniques are used to check this. Once the graft is in place, some air is removed after 30 minutes to 2 hours or before insertion, a small hole is created at the bottom of the iris (the colored part of the eye) to prevent pupil blockage.
Descemet Stripping Only (DSO) is a more straightforward procedure. It only involves removal of the Descemet membrane by a method similar to the ones used in DSEK and DMEK. By dilating the pupil before the operation, the surgeon gets a better view of the Descemet membrane. Postoperative recovery and improvement of endothelial cell density (the number of cells in a specific area) can be aided by the use of rho-associated kinase inhibitors, which are particular types of drugs.
Possible Complications of Corneal Endothelial Transplantation
After eye surgeries like DSAEK and DMEK, the most common issue people face early on is graft detachment, where the transplanted cornea tissue separates from the eye. This can sometimes get better on its own, especially after DSEK surgery. But if the detachment is complete, the area needs to be reinflated with gas – this procedure is called ‘rebubbling’. To prevent graft detachment, doctors make sure that the recipient site in the eye is larger than the graft, advise patients to avoid rubbing their eyes, use a special gas that lasts longer in the eye, and use real-time imaging during surgery to remove any fluid between the graft and the eye.
While the rate of graft detachment after DMEK surgery can vary, some studies report it could be as high as 74%. Detachment after DMEK is less likely to improve without medical intervention because the transplant has a tendency to roll up. If the detachment includes a large part of the graft, doctors usually resort to rebubbling. In extreme cases where the graft is completely detached or rolled up, the patient may need to have the transplant redone.
Primary graft failure refers to a situation where there’s no improvement in the swollen cornea, requiring another transplant. This could be due to the quality of the donor tissue or it could also be because of damage from the transplant process. Your surgeon’s skill and experience can play a huge role in this. That’s because surgeons who are more familiar with these techniques and do these surgeries more often have lower failure rates.
Also, there is a risk of pupillary block, a condition where the pupil of the eye is blocked by air, which can damage the eye. This is more likely in DMEK surgeries, and if one has symptoms like increased eye pressure, pain, or vision loss. Preventive measures include making a small hole to allow fluid flow and reducing the amount of air used in surgery. Additionally, increased eye pressure can be a common post-surgery issue often because of a reaction to steroids used in treatment. Reducing the steroid dose may help manage this.
Rejection can also happen after these surgeries, which means your body’s immune system can resist the donor graft. This is more subtle than after other kinds of eye surgeries. Yet, it’s often detected by chance during follow-ups. People of African descent, those with glaucoma, and individuals who react to steroids are at a higher risk. Additionally, a condition called hyphema, where blood collects inside the eye, can happen during DMEK surgery especially when it is combined with cataract surgery. However, this does not typically cause severe issues like vision loss.
What Else Should I Know About Corneal Endothelial Transplantation?
Research comparing different types of corneal transplant surgeries, DMEK (Descemet’s Membrane Endothelial Keratoplasty) and DSAEK (Descemet’s Stripping Automated Endothelial Keratoplasty), shows that patients receiving DMEK tend to have better vision and satisfaction. However, DMEK could lead to more complications, which are usually easy to manage. A study comparing these two techniques found that DMEK offered better eyesight at 3, 6, and 12 months post-operation, despite a slight decrease in the number of healthy cells at the back of the cornea.
Scientists aren’t totally sure why DMEK provides better vision, as there is no difference in the level of cloudiness or scattered light caused by DMEK and DSAEK procedures. Higher-order aberrations (distortions in the eye that cause problems like halos around lights or double vision) in the back of the cornea might be one reason.
The average 5-year graft survival rate (how long the transplanted tissue remains healthy) and the decrease of healthy cells at the back of the cornea are similar for both DMEK and DSAEK. For DMEK, it ranges between 90-96%, and for DSAEK, it’s between 85-96%. However, patients who had previous surgeries to lower eye pressure (glaucoma) have lower success rates with DSAEK procedures.
Meanwhile, corneal transplants are generally better compared to full-thickness corneal transplants (PK or Penetrating Keratoplasty) for many cases of endothelial disease (a condition that affects the inner layer of your cornea). Researchers are trying to determine the most effective method among the many available options. While most research compares DSEAK and DMEK techniques, there’s a need for more broad-ranging studies to understand which techniques work better for different conditions – with the ultimate goal of helping patients.
It’s significant for eye surgeons to learn these new techniques properly before using them, as the learning process can be challenging. However, the benefits that patients receive from these advances are well worth the effort.