Endothelial Treatment Info
The cornea is the clear, outer surface of the eye. It allows light to pass through and come to focus on the retina. The cornea must remain clear and properly shaped to provide good vision. If the cornea becomes cloudy or if the cornea becomes irregular in shape, vision can be impaired.
Cataract surgery is the most common surgical procedure in the US with over 4.5 million procedures performed annually. While a cataract is not considered a corneal condition, the health of the cornea is a major determinant in the outcome of cataract surgery. The innermost endothelial layer of the cornea is the primary determinant of corneal health. If the endothelial layer is damaged during the surgery the cornea will experience edema (swelling) and over time persistent edema can lead to opacification of the cornea. Cataract surgery is one of the most successful procedures, and for most patients visual recovery occurs within days of the surgery. However, for approximately 7% of patients with compromised corneal health it is possible to have long term edema that leads to lifelong visual impairment and in some cases may require a corneal transplant to recover vision.
For patients at risk of corneal decompensation, surgeons will take extra precautions by using viscoelastic substances that protect the endothelial layer. To the extent they can, they will utilize the lowest power settings on the surgical instrument that removes the existing lens. However, even healthy eyes will lose endothelial cells during the surgery and it is the extent of cell loss relative to the pre-surgical state that determines if there will be complications.
Trefoil is developing TTHX1114 as an agent that will stimulate the inherent regenerative properties of existing endothelial cells to protect and trigger the proliferation and migration of endothelial cells. In the STORM study, patients that were treated with a higher dose TTHX1114 experienced faster visual recovery and more significant reduction in edema than patients who were treated with a low dose of TTHX1114.
While there are numerous conditions that can affect the health of the cornea, more than 4% of the people over the age of 40 experience a decline in the number of endothelial cells on the inner surface of the cornea. When this decline in cells reaches a certain point, it is characterized as Fuchs dystrophy, an inheritable disease that causes the cornea to swell. Endothelial cells regulate the correct amount of fluid in the eye by pumping out fluid. When fewer of these cells line the inside surface of the eye, fluid begins to build up in the cornea. As the cornea swells with the extra fluid, vision declines. As the disease progresses the cornea can develop blisters on the cornea, a condition called bullous keratopathy.
There is currently no means to prevent Fuchs’ dystrophy. Doctors treat the disease based on its stage. Removing excess water from the cornea with hypertonic eye drops is often suggested in the early stage of the disease, but it is not a long-term solution.
If a patient has high eye pressure and Fuchs’ dystrophy, glaucoma eye drops may help to decrease eye pressure. High eye pressure can cause Fuchs’ dystrophy to progress further, so maintaining a low eye pressure is important for patients with both conditions.
Once Fuchs’ dystrophy reaches a point where it significantly impairs a patient’s vision, then a cornea transplant can restore vision.
Different Treatment Techniques
Cornea Transplant Overview
A cornea transplant is a surgical procedure where a surgeon replaces all or part of a patient’s diseased cornea, creating the opportunity for restored vision. Patients with a damaged cornea that prevents acceptable vision are candidates for corneal transplantation. This procedure allows patients to receive clear vision through a full or partial replacement of the cornea with a donor cornea.
Donor tissue comes from individuals who have donated their eyes upon passing for the benefit of others. The donor is carefully screened for infections and diseases including hepatitis, syphilis and AIDS. An eye bank network is used to obtain a donor cornea and ensure the safe use of the tissue. Donor cornea tissue in the United States is provided by a network of eye banks in the United States, which are regulated by the FDA.
There are a number of different cornea transplant procedures which may be offered depending on the stage of the disease as well as patient preference. There are advantages and disadvantages with each procedure which should be discussed with your surgeon.
One of the most recent advances to treat the decreased vision and swollen, cloudy corneas seen in Fuchs Dystrophy is a technique called Descemet Stripping Only (DSO), also referred to as Descemetorhexis Without Endothelial Keratoplasty (DWEK). This innovative procedure strips away the damaged membrane in a small 4mm circular area on the back of the cornea. Then, instead of implanting donor cornea tissue, the person’s own endothelial cells redistribute across the treated area to restore the normal functioning of the cornea.
One of the most exciting aspects of this new technique is that it eliminates the potential for vision-threatening rejection episodes that can occur after a cornea transplant. The procedure is most suited for patients where the progression of the disease is primarily in the central portion of the cornea.
Compared with implanting a thin layer of donor tissue, the visual recovery may be somewhat slower with the DSO/DWEK procedure, due to the time it takes for the person’s own cells to repopulate the surgical area; however, an advantage is that because no donor tissue is transplanted, there is no need for long term use of immune-suppressing steroid eye drops to mitigate the risk of transplant rejection.
There are currently a number of clinical trials underway to investigate whether different drugs may accelerate recovery and resumption of normal activities following the DSO procedure. For a list of all clinical trials related to Fuchs Dystrophy please visit the Clinical Trials site here.
Trefoil Therapeutics has an active clinical trial (STORM) investigating the use of TTHX1114 in conjunction with DSO.
If you are interested in obtaining more information regarding the STORM clinical trial please submit a request for information here: STORM Clinical Trial page.
More recently DMEK has been developed and in this procedure a thinner layer of transplant tissue is used. DMEK replaces only the interior layer of the cornea, called the endothelium. With DMEK, patients are less likely to reject the donor tissue than with the thicker DSEK, and the visual clarity after surgery can be better, with many patients achieving 20/25 vision or better within the first six months after surgery. Patients can resume normal activities quickly and avoid vision-threatening rejection episodes. This is because compared to (penetrating keratoplasty, PKP) and DSEK options, DMEK is the most anatomical repair possible – just one cell layer (the endothelial cells) and a thin membrane all of which is only 15 to 20 microns thick.
DMEK provides the lowest risk of graft rejection; fewer than 1 in 100 of DMEK patients have experienced a graft rejection episode.
Descemet’s Stripping Endothelial Keratoplasty surgery improves vision by removing the damaged cells and replacing them with healthy endothelial donor tissue. It is a partial-thickness corneal transplant that uses a much thinner donor tissue than a complete transplant.
DSEK, is a thicker posterior corneal transplant than DMEK. The advantage of the thicker graft is that it is easier for the surgeon to position the tissue behind the patient’s cornea and it adheres easier. There is less likelihood of the patient needing additional air injections to get the tissue to adhere, so there may be fewer post-operative visits for the patient.
After DSEK surgery, you should be able to see better within 2 – 3 months. By the fifth or sixth month, you can expect to have 20/40 vision. DSEK has a very high success rate with only 1 in 10 patients experiencing donor tissue rejection after the first year. If the donor cornea is rejected, the procedure can be performed again.
Partial-Thickness Corneal Transplant+
Advances in technology and surgical technique have led to the development of alternative transplantation procedures that involve transplantation of only the inner endothelial layer of the eye. The procedure options, DSEK (Descemet’s Stripping Endothelial Keratoplasty) or DMEK (Descemet’s Membrane Endothelial Keratoplasty), replace the affected cells while keeping the outer layer of the eye intact and providing better visual recovery.
More recently a procedure known as DSO (Descemet’s Stripping Only) has been developed which does not require the transplantation of donor cornea tissue. In this procedure the affected cells are stripped away (as with a traditional transplant) and the cornea is left to heal through the regeneration of the patient’s own endothelial cells. In some cases, a drug will be prescribed to stimulate faster regeneration of the endothelial cells. Each of these procedures is described in more detail below:
(DSEK) and (DMEK) are procedures for replacing only the two most posterior or inner layers of the cornea with donor tissue. Partial-thickness corneal transplants provide a transplant technique for patients when the interior endothelial layer of the cornea has broken down.
Surgery is performed in an outpatient surgery center which means it is not necessary to enter or be admitted to a hospital. Anesthesia is given intravenously and with eye drops (topical anesthesia). The diseased innermost layer of the cornea is removed carefully and the corresponding thin layer from a healthy donor cornea is put in its place. The transplant is held in place by only an air bubble, requiring patients to lay flat on their backs with their faces directed upwards immediately after surgery to float the bubble into place. The bubble goes away within the first week and as it does, patients do not need to lay flat as much. The surgery can be combined with cataract surgery for patients who require both.
Full Thickness Corneal Transplant+
If the whole thickness of the cornea is unhealthy, a full thickness corneal transplant called a Penetrating Keratoplasty (PK) will be required. During the PK procedure a circle of corneal tissue is removed and replaced with the donor tissue. The new corneal tissue will be stitched into place for a comfortable and smooth healing process.
There is a long-term 22% rate of rejection due to the more complicated nature of the procedure to replace the full thickness cornea and this will only be recommended when the surgeon determines another procedure is unlikely to be successful.
Fuchs Patients and DSO Candidates
Trefoil Therapeutics is currently enrolling interested candidates in a clinical trial evaluating corneal cell regeneration to restore vision. We will help match you with a local site – for more information, please visit our STORM Clinical Trial page.
Have Other Questions?