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Cornea transplant approximately one week after surgery. Multiple light reflections indicate folds in the cornea, which later resolved.
Corneal transplantation, also known as corneal grafting, is a surgical procedure where a damaged or diseased cornea is replaced by donated corneal tissue (the graft) in its entirety (penetrating keratoplasty) or in part (lamellar keratoplasty). (Keratoplasty is surgery to the cornea.) The graft is taken from a recently deceased individual with no known diseases or other factors that may affect the viability of the donated tissue or the health of the recipient.
The cornea is the transparent front part of the eye that covers the iris, pupil and anterior chamber. The surgical procedure is performed by ophthalmologists, physicians who specialize in eyes, and is often done on an outpatient basis. Donors can be of any age, as is shown in the case of Janis Babson, who donated her eyes at age 10. The corneal transplantation is performed when medicines, keratoconus conservative surgery and cross-linking can not heal the cornea anymore.
- 1 Indications
- 2 Pre-operative examination
- 3 Procedure
- 4 Risks
- 5 Prognosis
- 6 History
- 7 Synthetic corneas
- 8 Alternatives
- 9 New technology
- 10 Epidemiology and economics
- 11 References
- 12 External links
Indications for corneal transplantation include the following:
- Optical: To improve visual acuity by replacing the opaque or distorted host tissue by clear healthy donor tissue. The most common indication in this category is pseudophakic bullous keratopathy, followed by keratoconus, corneal degeneration, keratoglobus and dystrophy, as well as scarring due to keratitis and trauma.
- Tectonic/reconstructive: To preserve corneal anatomy and integrity in patients with stromal thinning and descemetoceles, or to reconstruct the anatomy of the eye, e.g. after corneal perforation.
- Therapeutic: To remove inflamed corneal tissue unresponsive to treatment by antibiotics or anti-virals.
- Cosmetic: To improve the appearance of patients with corneal scars that have given a whitish or opaque hue to the cornea.
In most instances, the patient will meet with their ophthalmologist for an examination in the weeks or months preceding the surgery. During the exam, the ophthalmologist will examine the eye and diagnose the condition. The doctor will then discuss the condition with the patient, including the different treatment options available. The doctor will also discuss the risks and benefits of the various options. If the patient elects to proceed with the surgery, the doctor will have the patient sign an informed consent form. The doctor might also perform a physical examination and order lab tests, such as blood work, X-rays, or an EKG.
The surgery date and time will also be set, and the patient will be told where the surgery will take place. Within the United States, the supply of corneas is sufficient to meet the demand for surgery and research purposes. Therefore, unlike other tissues for transplantation, delays and shortages are not an issue.
On the day of the surgery, the patient arrives to either a hospital or an outpatient surgery center, where the procedure will be performed. The patient is given a brief physical examination by the surgical team and is taken to the operating room. In the OR, the patient lies down on an operating table and is either given general anesthesia, or local anesthesia and a sedative.
With anesthesia induced, the surgical team prepares the eye to be operated on and drapes the face around the eye. An eyelid speculum is placed to keep the lids open, and some lubrication is placed on the eye to prevent drying. In children, a metal ring is stitched to the sclera which will provide support of the sclera during the procedure.
A trephine (a circular cutting device) is used by the surgeon to cut the donor cornea, which removes a circular disc of cornea. A second trephine is then used to remove a similar sized portion of the patient's cornea. The donor tissue is then sewn in place with sutures.
Antibiotic eyedrops placed, the eye is patched, and the patient is taken to a recovery area while the effects of the anesthesia wear off. The patient typically goes home following this and sees the doctor the following day for the first post operative appointment.
Encompasses several techniques which selectively replace diseased layers of the cornea while leaving healthy layers in place. Advantage includes improved tectonic integrity of the eye. Disadvantages include the technically challenging nature of these procedures which replace portions of a structure only 500 µm thick, and reduced optical performance of the donor/recipient interface compared to full thickness keratoplasty.
Deep Anterior Lamellar Keratoplasty
In this procedure, the anterior layers of the central cornea are removed and replaced with donor tissue. Endothelial cells and Descemets membrane are left in place. This technique is used in cases of anterior corneal opacifications, scars, and ectatic diseases such as keratoconus.
Replaces the patient's endothelium with a transplanted disc of posterior stroma/Descemets/endothelium (DSEK) or Descemets/endothelium (DMEK).
This relatively new procedure has revolutionized treatment of disorders of the innermost layer of the cornea (endothelium). Unlike a full thickness corneal transplant, the surgery can be performed with one or no sutures. Patients may recover functional vision in days to weeks, as opposed to up to a year with full thickness transplants.However, an australian study has shown that despite its benefits, the loss of endothelial cells that maintain transparency is much higher in DSEK compared to a full thickness corneal transplant.The reason may be greater tissue manipulation during surgery, the study concluded. 
During surgery the patient's corneal endothelium is removed and replaced with donor tissue. With DSEK, the donor includes a thin layer of stroma, as well as endothelium, and is commonly 100–150 µm thick. With DMEK only the endothelium is transplanted. In the immediate post operative period the donor tissue is held in position with an air bubble placed inside the eye (the anterior chamber). The tissue self adheres in a short period and the air is adsorbed into the surrounding tissues.
Complications include displacement of the donor tissue requiring repositioning ('refloating'). This is more common with DMEK than DSEK. Folds in the donor tissue may reduce the quality of vision requiring repair. Rejection of the donor tissue may require repeating the procedure. Gradual reduction in endothelial cell density over time can lead to loss of clarity and require repeating the procedure.
Patients with endothelial transplants frequently achieve best corrected vision in the 20/30 to 20/40 range, although some reach 20/20. Optical irregularity at the graft/host interface may limit vision below 20/20.
The risks are similar to other intraocular procedures, detachment or displacement of lamellar transplants.
There is also a risk of infection. Since the cornea has no blood vessels (it takes its nutrients from the aqueous humor) it heals much more slowly than a cut on the skin. While the wound is healing, it is possible that it might become infected by various microorganisms. This risk is minimized by antibiotic prophylaxis (using antibiotic eyedrops, even when no infection exists).
There is a risk of cornea rejection, which occurs in about 20% of cases.
The prognosis for visual restoration and maintenance of ocular health with corneal transplants is generally very good. Risks for failure or guarded prognoses are multifactorial. The type of transplant, the disease state requiring the procedure, the health of the other parts of the recipient eye and even the health of the donor tissue may all confer a more or less favorable prognosis.
The majority of corneal transplants result in significant improvement in visual function for many years or a lifetime. In cases of rejection or transplant failure, the surgery generally can be repeated.
The first cornea transplant was performed in 1905 by Eduard Zirm (Olomouc Eye Clinic, now Czech Republic), making it one of the first types of transplant surgery successfully performed. Another pioneer of the operation was Ramon Castroviejo. Russian eye surgeon Vladimir Filatov's attempts at transplanting cornea started with the first try in 1912 and were continued, gradually improving until on 6 May 1931 he successfully grafted a patient using corneal tissue from a deceased person. He widely reported of another transplant in 1936, disclosing his technique in full detail. In 1936, Castroviejo did a first transplantation in an advanced case of keratoconus, achieving significant improvement in patient's vision.
Instrumental in the success of cornea transplants were the establishment of eye banks. These are organizations located throughout the world to coordinate the distribution of donated corneas to surgeons, as well as providing eyes for research. Some eye banks also distribute other anatomical gifts.
The Boston keratoprosthesis is the most widely used 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 Claes Dohlman, MD, PhD.
In cases where there have been several graft failures or the risk for keratoplasty is high, synthetic corneas can substitute successfully for donor corneas. Such a device contains a peripheral skirt and a transparent central region. These two parts are connected on a molecular level by an interpenetrating polymer network, made from poly-2-hydroxyethyl methacrylate (pHEMA). AlphaCor is a U.S. FDA-approved type of synthetic cornea measuring 7.0 mm in diameter and 0.5 mm in thickness. The main advantages of synthetic corneas are that they are biocompatible, and the network between the parts and the device prevents complications that could arise at their interface. The probability of retention in one large study was estimated at 62% at 2 years follow-up.
In a very rare and complex multi-step surgical procedure, employed to help the most disabled patients, a lamina of the patient's tooth is grafted into the eye, with an artificial lens installed in the transplanted piece.
Phototherapeutic keratectomy (PTK)
Diseases that only affect the surface of the cornea can be treated with an operation called phototherapeutic keratectomy. With the precision of an excimer laser and a modulating agent coating the eye, irregularities on the surface can be removed. However, in most of the cases where corneal transplantation is recommended, PTK would not be effective.
Intrastromal corneal ring segments
The implants manufactured under the trade name Intacs are the only patented intrastromal corneal implant that has US FDA approval and European CE Mark for both Myopia and Keratoconus. There are over one-hundred clinical articles at  for clinical reference (search for Intacs and they all are arranged in chronological order) and are a well documented clinical solution for treating keratoconus. Another version of intrastromal cornea ring segments is manufactured under the trade name KeraRing and is available in South America and Europe.
With this procedure, the implants are placed in the stroma to reshape the cornea into a more natural shape. In mild myopia, this corrects a patients vision. In keratoconus, the goal is to reshape the cornea to where contact lens intolerant patients are able to achieve functional vision with contact lenses or glasses. Although, surgical procedure don't carry a guarantee, one clinically proven benefit of Intacs is that they can be safely removed and the cornea returns to its pre-operative state. Future treatment options are not affected.
In the early stages and up to the more advanced stages of keratoconus, contact lenses are often used to improve vision. Contact lenses improve visual acuity for the majority of keratoconus patients. The majority of patients need to use hard contact lenses. Only 10 to 20% will need cornea transplants during their lifetime due to progression of the disease.
This procedure aims at stabilizing and strengthening the cornea by activating a riboflavin solution throughout 30 minutes with UV-A light.
High speed lasers
Blades are being replaced by high speed lasers in order to make surgical incisions more precise. These improved incisions allow the cornea to heal more quickly and the sutures to be removed sooner. The cornea heals more strongly than with standard blade operations. Not only does this dramatically improve visual recovery and healing, it also allows the possibility for improvement in visual outcomes.
Since 2004, Amnitrans Eyebank in Rotterdam, The Netherlands, provides donor corneas pre-cut for advanced keratoplasty procedures, such as DSEK, DSAEK, FS-DSEK and DMEK. In 2007, Seattle-based SightLife, one of the leading corneal tissue banks in the world, introduced a process for the preparation of donated corneal tissue using a Femtosecond Laser. This process is known as Custom Corneal Tissue.
Endothelial keratoplasty (EK) has been introduced by Melles et al. in 1998. Today there are three forms of EK. Deep Lamellar Endothelial Keratoplasty (DLEK) in which the posterior part of the recipient cornea is replaced by donor tissue. Descemet's Stripping (Automated) Endothelial Keratoplasty (DSEK/DSAEK) in which the diseased Descemet's membrane is removed and replaced by a healthy donor posterior transplant. The transplant tissue can be prepared by a surgeon's hand or ordered already prepared for surgery. Ocular Systems Inc. was the first organization to deliver prepared grafts for surgery in 2005. DSEK/DSAEK uses only a small incision that is either self-sealing or may be closed with a few sutures. The small incision offers several benefits over traditional methods of corneal transplant such as Penetrating Keratoplasty. Because the procedure is less invasive, DSAEK leaves the eye much stronger and less prone to injury than full-thickness transplants. New medical devices such as the EndoSaver (patent pending) are designed to ease process of inserting endothelial tissue into the cornea. Additionally, DSAEK has a more rapid rate of visual recovery. Vision is typically restored in one to six months rather than one to two years. Descemet Membrane Endothelial Keratoplasty (DMEK)] is the most recent EK technique in which an isolated Descemet membrane is transplanted. The DMEK procedure is a 'like for like' replacement of the diseased part of the cornea with visual rehabilitation to 20/40 or better in 90% of cases and 20/25 or better in 60% of cases within the first three months. Rejection rates are lower (1%) and visual recovery is faster than any other form of corneal transplantation. In the UK (2013) DMEK is available to patients under the National Health Service at the Royal Shrewsbury Hospital and the Calderdale and Huddersfield NHS Trust.
Not all patients with diseased corneas are candidates for endothelial keratoplasty. These procedures correct corneal endothelial failure, but are not able to correct corneal scarring, thinning, or surface irregularity. There is currently limited data on long-term survival of DMEK grafts however the early indications are very positive.
There is a bioengineering technique that uses stem cells to create corneas or part of corneas that can be transplanted into the eyes. Corneal stem cells are removed from a healthy cornea. They are collected and, through laboratory procedures, made into five to ten layers of cells that can be stitched into a patient’s eye. The stem cells are placed into the area where the damaged cornea tissue has been removed. This is a good alternative for those that cannot gain vision through regular cornea transplants. A new development, announced by the University of Cincinnati Medical School in May 2007, would use bone marrow stem cells to regrow the cornea and its cells. This technique, which proved successful in mouse trials, would be of use to those suffering from inherited genetic degenerative conditions of the cornea, especially if other means like a transplant aren't feasible. It works better than a transplant because these stem cells keep their ability to differentiate and replicate, and so keep the disease from recurring, longer and better.
Limbal stem cells
In a further development, in a Wednesday, July 2, 2014 news release from Harvard University's web page (from the online edition of the Harvard Gazette university newspaper, authored by Massachusetts Eye and Ear Communications), it was stated that,: "Researchers have identified a way to enhance regrowth of human corneal tissue to restore vision, using a molecule that acts as a marker for hard-to-find limbal stem cells". A photograph next to the article states that human donor corneal tissue contained the stem cells and that they led to fully functional mouse corneas. The second paragraph goes on to state,: "This work, a collaboration among the Harvard-affiliated Massachusetts Eye and Ear/Schepens Eye Research Institute, Boston Children’s Hospital, Brigham and Women’s Hospital, and the VA Boston Healthcare System, holds promise for burn patients, victims of chemical injury, and others with damaging eye diseases. The research, published this week in the journal Nature, is also one of the first examples of constructing a tissue from an adult-derived human stem cell." Antibodies were used to find the molecule used as a marker, named ABCB5. The article goes on to state that the "co-senior authors of the study are Bruce Ksander of Mass. Eye and Ear and postdoctoral fellow Paraskevi Kolovou". Lastly, it is important to note, as Ksander and others go on to state, that it was an example of basic research able to be moved relatively quickly to translational applications (by definition, one that can be used relatively quickly by the pharmaceutical industry once the methods have been verified and receive governmental regulatory approval). This had to be supported by a number of collaborators, listed at the end of the article, including several universities and multiple other agencies, such as the VA Department, the National Cancer Institute, and the NIH (the National Institutes of Health, specifically its National Institute of Neurological Disorders and Stroke) in order to hope to be carried out. 
On 25 August 2010 investigators from Canada and Sweden reported results from the first 10 people in the world treated with the biosynthetic corneas. Two years after having the corneas implanted, six of the 10 patients had improved vision. Nine of the 10 experienced cell and nerve regeneration, meaning that corneal cells and nerves grew into the implant. To make the material, the researchers placed a human gene that regulates the natural production of collagen into specially programmed yeast cells. They then molded the resulting material into the shape of a cornea. This research shows the potential for these bioengineered corneas but the outcomes in this study were not nearly as good as those achieved with human donor corneas. This may become an excellent technique, but right now it is still in the prototype stage and not ready for clinical use. The results were published in the journal Science Translational Medicine.
Epidemiology and economics
Corneal transplant is one of the most common transplant procedures. Although approximately 100,000 procedures are performed worldwide each year, some estimates report that 10,000,000 people are affected by various disorders that would benefit from corneal transplantation.
In Australia, approximately 1,500 grafts are performed each year.  According to the NHS Blood and Transplant, over 2,300 corneal transplant procedures are performed each year in the United Kingdom.  Between April 1, 2005 and March 31, 2006, 2,503 people received corneal transplants in the UK. 
In the United States, the cost is usually covered in part by Medicare and health insurers. Reimbursement depends on the patient's personal healthcare provider. Usually 80% of the cost will be covered by the patient's health insurance. Those on Medicare will be reimbursed up to $1,200 while the remainder is left up to the patient. The average cost of the procedure ranges from $7,500 to $11,000.
In 2005, there were about 32,840 corneal transplant recipients. The estimated first year billed charges per patient, including medications, was $19,100. There were a larger number of transplants for patients over 65 than under, 18,000 compared to 14,840. There were 41,652 corneal transplants performed in the United States in 2008.
In Sweden and many other european countries, corneal transplants are paid by taxes. Every year about six hundred of these operations are performed.
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||This article includes a list of references, but its sources remain unclear because it has insufficient inline citations. (October 2009)|
- Facts About the Cornea and Corneal Disease The National Eye Institute (NEI)