We Pursue Eye Research
Cornea Transplant Database
The Foundation maintains the largest cornea transplant database in the Western Hemisphere. This database contains up to 20 years of information on over 5000 grafts, including over 4000 traditional full thickness grafts and over 1600 small incision endothelial keratoplasty grafts (known as DSEK, DSAEK, DMEK or DMAEK). We have carefully analyzed patient outcomes to document long-term graft survival rates and identify risk factors for graft failure.
The patients in this study all received their transplants at Price Vision Group in Indianapolis, IN.
Use of small incision endothelial keratoplasty increased 10-fold between 2005 and 2008. Endothelial keratoplasty now accounts for over 85% of the transplants performed to treat corneal endothelial problems and it represents over 1/3 of all transplants performed in the USA. We are proud that the Cornea Research Foundation’s transplant database and sharing of information through presentations at eye meetings, publications in leading eye journals, and surgical training courses directly contributed to the widespread adoption of this transplant technique, which is safer than a traditional full thickness transplant.
Although endothelial keratoplasty, or targeted replacement of dysfunctional corneal endothelium, had been attempted in various forms for decades, it was not widely adopted until recently. Between 1998 and 2003, Dr. Gerritt Melles reported a series of breakthroughs that improved and simplified the technique.
Dr. Francis Price, founder of the Cornea Research Foundation, learned endothelial keratoplasty from Dr. Melles in 2001. In 2002, Dr. Price and the Cornea Research Foundation began offering endothelial keratoplasty courses in the USA. In late 2003, Dr. Price adopted the iteration now known as DSEK. In 2004, we began teaching the DSEK technique (which is also known as DSAEK when the donor cornea is prepared with a microkeratome), and we shared DSEK outcomes at major eye meetings. In 2005 we published the findings from our first 50 consecutive DSEK cases, showing that it was safer than traditional penetrating keratoplasty and provided faster visual recovery. Due to the growing interest in DSEK / DSAEK, the Eye Bank Association of America began to track the number of corneas being used for endothelial keratoplasty in 2005. Since then the use of DSEK /DSAEK has continued to increase by over 10-fold. We have now trained over 500 cornea transplant surgeons from 23 countries in the DSEK / DSAEK procedure. We have also written the first book describing the DSEK procedure in detail along with patient outcomes. We are also evaluating the outcomes of newer endothelial keratoplasy procedures known as DMEK and DMAEK. These techniques use ultra-thin donor tissue for optimal visual outcomes.
The Cornea Research Foundation has the largest database on DSEK / DSAEK procedures in the world. We feel very honored to have helped change the way that transplants are performed. Following are some of our key findings about DSEK / DSAEK and newer endothelial keratoplasty techniques.
Advantages of Endothelial Keratoplasty
Compared with standard penetrating keratoplasty, endothelial keratoplasty (DSEK, DSAEK, DMEK and DMAEK):
- Is safer and requires minimal restrictions in normal activities
- Provides faster visual recovery
- Does not require any sutures
- Causes minimal change in glasses prescription
The most important advantage of endothelial keratoplasty is safety. While the cornea is removed during a full thickness transplant procedure, sometimes a hemorrhage can develop and cause permanent vision loss. Also, standard penetrating keratoplasty requires a very large incision, and afterwards patients have 5% lifetime risk of breaking open the incision with minor trauma, potentially losing the eye. In over 1600 endothelial keratoplasty procedures, we have not had any patients lose vision due to hemorrhage during surgery or minor trauma after surgery. We allow endothelial keratoplasty patients to resume normal daily activities within 2 months, much sooner than after a full thickness graft.
Most DSEK / DSAEK patients recover vision of 20/40 or better (the level required to pass the driving test) within a couple of months, and some have recovered 20/25 vision within a week. Younger patients are likely to recover the best vision. Patients who postpone treatment of endothelial dysfunction for too long may develop scarring in the front part of the cornea, which could delay full visual recovery since the front part of the cornea is not replaced with endothelial keratoplasty.
Endothelial keratoplasty does not require any sutures to hold the new transplant in place, so problems with loose sutures or infection at the suture sites are avoided. Patients also retain corneal sensation after endothelial keratoplasty so this helps promote normal blinking and tear production, which are important for keeping the surface of the cornea healthy. In contrast, corneal sensation over the area of the grafted tissue is lost for a prolonged period after penetrating keratoplasty and this can lead to ocular surface problems such as ulcerations or scarring of the surface of the eye.
Endothelial keratoplasty causes minimal change in glasses prescription, and hard contact lenses are not required for best vision afterwards. In contrast, penetrating keratoplasty can cause large and unpredictable changes in glasses prescription and about 15% of patients require hard contact lenses for optimal vision after a full thickness graft.
These advantages have greatly improved the benefit-to-risk ratio for patients, so many endothelial keratoplasty patients now choose to have their second eye treated within a few months after the first eye, and patients are more willing to have a transplant before their visual problems become so debilitating.
Who can benefit from endothelial keratoplasty?
Patients with Fuchs dystrophy or corneal decompensation following cataract surgery were the initial candidates for endothelial keratoplasty. Dr. Price expanded the number of patients who could be helped by DSEK by pioneering its use to rehabilitate failed penetrating keratoplasties and as a treatment for patients with iridocorneal endothelial (ICE) syndrome. He also developed special techniques to allow DSEK / DSAEK to be performed safely in eyes where the iris and lens are missing.
Transplant rejection after DSEK / DSAEK
To determine the rate and risk factors for graft rejection after DSEK / DSAEK, we monitored outcomes in almost 600 DSEK / DSAEK eyes. We found that the risk of experiencing a graft rejection episode was about 9% within the first year and about 12% within 2 years of DSEK / DSAEK, which was similar or slightly lower than the rate we’ve seen in eyes with a full thickness graft. We were able to successfully treat DSEK / DSAEK graft rejection episodes with eye drops in 9 out of 10 eyes, while about 1 in 10 eyes failed to clear and required a regraft.
Early detection of a rejection episode is the key to successful treatment. However, one third of the DSEK / DSAEK patients who experienced a rejection episode did not notice any symptoms, such as a change in vision or eye irritation. These patients were diagnosed during a regularly scheduled eye exam. This shows how important it is for you to have regular eye examinations after a transplant.
We found that African American patients were 5-times more likely to experience a graft rejection episode than Caucasians after DSEK / DSAEK. We think this is because darkly pigmented eyes may be more prone to develop inflammation and a strong immune response. We recommend increased use of topical steroids to prevent rejection in patients with darkly pigmented eyes.
A side effect of the steroid eye drops commonly used to prevent graft rejection is that they sometimes lead to increased pressure inside the eye. To control the eye pressure we often have to reduce the steroid eye drops and introduce use of glaucoma medications. We found that DSEK / DSAEK patients who had problems with increased eye pressure were twice as likely to experience a graft rejection episode as those who did not experience pressure problems. The increased risk of rejection was related to the need to reduce the steroids in the eyes with pressure problems.
Monitoring intraocular pressure after DSEK / DSAEK
It is important to have the pressure inside your eye checked regularly, particularly as you get older, to avoid developing permanent vision loss from glaucoma. The most common method of measuring eye pressure (called Goldmann applanation) tends to give artificially high readings in normal eyes with thick corneas. Since DSEK / DSAEK substantially increases central corneal thickness, we were concerned about whether an adjustment to Goldmann readings would be needed in DSEK / DSAEK eyes.
In collaboration with glaucoma specialists from the University of Illinois, we measured the pressure in 50 DSEK / DSAEK eyes using the Goldmann technique and two other techniques that are relatively insensitive to corneal thickness. We found that the Goldmann technique did not require a thickness adjustment after DSEK / DSAEK – high Goldmann readings were indicative of truly elevated pressure. Interestingly, we found that the 3 techniques had somewhat different reading levels and should not be used interchangeably.
Glaucoma and DSEK / DSAEK
In studies of full thickness grafts, glaucoma has been associated with poorer visual outcomes, so we were interested in finding out how glaucoma patients do after DSEK / DSAEK. In collaboration with glaucoma specialists from University of Illinois, we studied the vision and intraocular pressure outcomes in 400 DSEK / DSAEK patients (315 without prior glaucoma, 64 with medically managed glaucoma and 21 with prior glaucoma surgery). We found that our glaucoma patients achieved excellent visual outcomes after DSEK / DSAEK, which was very good news. Interestingly, between 30% and 40% of the patients in all 3 groups developed elevated eye pressure at some point during the first year, probably in response to the steroid eye drops used to prevent transplant rejection. In most cases, the pressure was controlled by reducing the steroid eye drops and introducing or increasing the use of glaucoma medications.
DMEK and DMAEK
DSEK / DSAEK provides 20/40 or better vision to almost all patients who do not have other eye problems. However, not as many patients achieve 20/20 vision as we would expect after DSEK / DSAEK. Dr. Gerritt Melles found that using ultra-thin donor tissue, consisting of only endothelium and Descemet membrane, could provide higher rates of 20/20 vision.
The Cornea Research Foundation set up a multi-center study to evaluate DMEK. We have found that it does provide significantly more patients with 20/20 and 20/25 vision. However, it is more difficult to get the graft to attach and it
is more likely than in DSEK / DSAEK surgery that additional air will need to be injected into the eye sometime in the first few weeks to securely attach the donor tissue to the recipient cornea. The biggest hurdle with DMEK is preparing and handling the extremely thin donor graft. To facilitate the procedure, we have also been evaluating a hybrid technique, which we call DMAEK, in which the center of the graft is extremely thin, like DMEK, but the edges are thicker, like DSEK/ DSAEK, for easier handling.
The Cornea Research Foundation of America, Price Vision Group, and a number of eye banks are working on improving techniques for DSEK / DSAEK, DMEK, and DMAEK. We are not sure which technique will ultimately be used
the most. Both DMEK and DMAEK are providing superior visual results compared with DSEK / DSAEK, and in DMEK eyes it is difficult to even tell that a transplant was performed. In fact, Price Vision Group doctors make a point of telling DMEK patients to expect that an eye doctor may tell them some day that they couldn’t have had a transplant, because if the doctor does not look very closely, he may not be able to detect the slight edge of the thin DMEK graft. Currently, the donor preparation issues for both DMEK and DMAEK and difficulty with orienting the DMEK tissue correctly during surgery limits widespread acceptance of these two procedures, so we are continuing to work on ways to make it easier so that all patients can enjoy the best possible vision.
Penetrating Keratoplasty Outcomes
Cornea Transplant Survival
Patients who received a traditional full thickness transplant at Price Vision Group had an outstanding 80% graft survival rate 10-years after their transplant. This is among the highest long-term survival rate reported in any of the studies conducted around the world, and is only equaled by the 10-year survival rate reported by the Mayo Clinic in Rochester, Minnesota. Our Fuchs’ dystrophy patients had even higher 10-year survival rate of 90%. Our keratoconus patients had the highest 10-year survival rate of 95%. (Figure – transplant survival rates)
Risk factors for cornea transplant failure
The graft survival rate was twice as high for first-time grafts as it was for regrafts. This shows how important it is to identify risk factors in order to anticipate and prevent failure of the initial transplant.
We found that the risk of cornea transplant failure is highest in the first year after transplantation, and drops to a low but steady rate over longer time periods. We now know that for the first six months after receiving a full thickness cornea transplant, the major risk is ocular surface disease, such as infection or ulcer. There is also a continuing risk over the long term that you might reject you graft. Fortunately, medications are available to treat either ocular surface disease or rejection. Therefore, if you are a transplant patient, you should receive frequent follow-up examinations, and you should come in immediately for a checkup if you notice any problems developing with your graft.
Causes of cornea transplant failure
We found that a major cause of graft failure is endothelial cell failure. The endothelial cells line the inner surface of the cornea and continuously pump fluid to keep the cornea clear. There are a finite number of these cells and they do not get replaced. If the endothelial cells become diseased or damaged or if there are too few of the cells to keep up with the job, the cornea becomes cloudy. Our analysis identified several risk factors for endothelial failure, including small graft size, as well as pre-existing conditions such as diabetes.
Cornea transplants and glaucoma
One of our most significant findings was that glaucoma increased the risk of all three major types of graft failure, including endothelial failure, rejection, and ocular surface disease. Glaucoma is a leading cause of blindness in the United States. Glaucoma affects nearly 1 out of 20 Americans and it targets any age group, even newborns. Scientific literature had previously recognized that elevated intraocular eye pressures associated with glaucoma could cause endothelial cell damage. However, it was surprising to find that glaucoma also increased the risk of rejection and ocular surface disease. This is likely due to the preservatives in the glaucoma eye drops. This finding is important because it may help doctors to more effectively manage their glaucoma patients and the glaucoma medications they prescribe.
Our Publications on Penetrating Keratoplasty
The Foundation’s corneal transplant database helps us learn more and more each day about how to more effectively treat patients who have lost their vision. As listed below, our findings have been published in leading ophthalmology journals so that doctors and patients worldwide can benefit from our research.
- Price FW, Price DA, Ngakeng V, Price MO. Survey of steroid usage patterns during and after low-risk penetrating keratoplasty. Cornea 2009;28:865-70.
- Sugar A, Tanner JP, Dontchev M, Tennant B, Schultze RL, Dunn SP, Lindquist TD, Gal RL, Beck RW, Kollman C, Mannis M, Holland E, for the Cornea Donor Study Investigator Group. Recipient risk factors for graft failure in the cornea donor study.. Ophthalmology 2009; 116: 1023-1028.
- Dunn SP, Stark WJ, Stulting RD, Lass JH, Sugar A, Pavilack MA, Smith PW, Tanner JP, Dontchev M, Gal RL, Beck RW, Kollman C, Mannis MJ, Holland EJ; Cornea Donor Study Investigator Group. The effect of ABO blood incompatibility on corneal transplant failure in conditions with low-risk of graft rejection. Am J Ophthalmol. 2009;147:432-8.
- Price FW, Price MO, Jordan CS. Safety of incomplete incision patterns in femtosecond laser-assisted penetrating keratoplasty. Journal of Cataract and Refractive Surgery 2008; 34:2099-2013.
- Price FW, Price MO. Femtosecond laser shaped penetrating keratoplasty: one-year results utilizing a top-hat configuration. Am J Ophthalmol 2008;145:210-214.
- Price FW, Price, MO. Adult keratoplasty: has the prognosis improved in the last 25 years? Ophthalmology International, 2008; 28:141-146.
- Ngakeng V, Hauck MJ, Price MO, Price FW. AlphaCor keratoprosthesis: a novel approach to minimize the risks of long-term postoperative complications. Cornea 2008;27:905-910.
- Cornea Donor Study Investigator Group. Donor age and corneal endothelial cell loss 5 years after successful corneal transplantation. Specular microscopy ancillary study results. Ophthalmology. 2008 Apr;115(4):627-632.e8.
- Cornea Donor Study Investigator Group. The effect of donor age on corneal transplantation outcome results of the cornea donor study. Ophthalmology. 2008 Apr;115(4):620-626.e6.
- Price MO, Price FW. Efficacy of topical cyclosporine 0.05% for prevention of cornea transplant rejection episodes. Ophthalmology 2006;113:1785-90.
- Riddle HK, Price MO, Price FW. Topical anesthesia for penetrating keratoplasty. Cornea, 2004; 23:712-714
- Thompson RW, Price MO, Bowers PJ, Price FW. Long-term graft survival after penetrating keratoplasty. Ophthalmology, 2003; 121:1087-1092
- Price MO, Thompson RW, Price FW. Risk factors for various causes of failure in initial corneal grafts. Archives of Ophthalmology, 2003; 121:1087-1092.
- Dobbins K, Price FW, Whitson WE. Trends in the indications for penetrating keratoplasty in the midwestern United States. Cornea 2000 19(6): 813-816.
- Loden JC, Price FW Jr. Price graft-over-host technique to manage positive pressure during penetrating keratoplasty. J Cataract Refract Surg. 1998 Jun;24(6):736-8.
- Riddle HK, Parker DAS, Price FW. Management of post keratoplasty astigmatism. Current Opinion in Ophthalmology 1998;9(IV):15-28.
- Price FW, Whitson WE, Johns SK, Gonzales JS. Risk factors for corneal graft failure. J Refract Surg 1996;12:133-146.
- Price FW, Whitson WE, Collins KS. Five-year corneal graft survival. A large, single-center patient cohort. Arch Ophthalmol 1993;111:799-805.
- Price FW, Whitson WE. Graft survival in four common groups of patients undergoing penetrating keratoplasty. Ophthalmology 1991;98:322-328.
- Price FW, Whitson WE, Marks RG. Progression of visual acuity after penetrating keratoplasty. Ophthalmology 1991;98:1177-1185.