Type of corneal transplant

Cornea transplant is the most common tissue transplant with donor in   France . Almost 5,000 patients benefit from it each year. More than 300 cornea transplants are performed each year at the Rothschild Foundation in Paris .

Type of corneal transplant

What should you know about the surgery?

There are different types of keratoplasties:

  • Penetrating Keratoplasty in which the entire cornea is replaced.

  • Anterior Lamellar Keratoplasty (DALK, PDALK)) in which the entire cornea is replaced except a small layer called endothelium.

  • Endothelial Keratoplasty (DMEK) in which only the corneal endothelium is replaced.

greffe de cornée paris
 

Which Keratoplasty is indicated for you ?

 

  • In more than 60% of the cases, only the corneal endothelium is abnormal (Fuchs dystrophy, Pseudophakic bullous keratopathy).  A DMEK (Descemet Membrane Endothelial Keratoplasty) is indicated.

  • In 20% of the cases, the anterior part of the cornea is abnormal (as in Keratoconus). A DALK (Deep Anterior Lamellar Keratoplasty) is indicated.

  • When the entire cornea is abnormal, a penetrating keratoplasty aimed to replace the complete cornea is indicated.

Cornea transplant - DMEK

The first penetrating keratoplasties were developed more than a hundred years ago to replace opaque corneas with clear ones of full thickness. Since the early 1990s, penetrating grafts were gradually replaced with new techniques involving anterior and posterior lamellar grafts. This was possible because for most patients needing keratoplasty only a specific layer of the cornea is damaged. For example, over 35% of patients undergoing grafts suffer from endothelial damage such as Fuchs dystrophy or pseudophakic bullous keratopathy.
 

A posterior lamellar keratoplasty (PLK) was first attempted by Barraquer in 1950. A corneal flap was cut and lifted on the anterior side allowing for the trephination on the posterior side. A donor posterior lamellar button was then sutured in situ. This technique has gone by several names: Endothelial lamellar keratoplasty (Jones and Culbertson), endokeratoplasty (Busin), and microkeratome-assisted posterior keratoplasty (Azar). In 1998 Melles modernized the technique by performing a posterior lamellar keratoplasty, making a scleral-limbal incision to access the recipient endothelium.

In another major development, a descemetorhexis technique was devised in order to remove only the unhealthy endothelium. The name Descemet’s Stripping Endothelial Keratoplasty (DSEK) was thus proposed. The donor graft was then manually prepared by dissection from the donor cornea.
 

The preparation of the donor cornea was subsequently automated and performed using a microkeratome on artificial chamber, resulting in the name Descemet's Stripping Automated Endothelial Keratoplasty (DSAEK).

These techniques somewhat succeeded in rehabilitating the patient’s vision but they still had limitations with regard to the perfect anatomical reconstruction because a stroma-stroma interface of variable thickness persisted and prevented a 10/10 postoperative visual acuity from being achieved in the majority of cases.

DMEK (Descemet's Membrane Endothelial Keratoplasty) was developed to restore the anatomy of the cornea. The Descemet endothelium alone is removed from the donor cornea and grafted to the posterior surface of the recipient cornea.

 

Surgical technique  

 

Three distinct operating steps are individualized to perform DMEK.

 

  • The first step consists of separating the Descemet endothelium of the donor. The thin endothelial layer is gently peeled from the posterior stroma of the donor cornea while avoiding all contact between the surgical instruments and the endothelium in the central 9 mm (Figure 1).

Figure 1: Endothelio-Descemet peeling from the donor cornea

Then a 9-mm trephine is used to obtain the final endothelial graft, which instantly curls up with the endothelial cells exposed to the outside of the roll that just formed (Figures 2, 3, and 4).

Greffe de cornée DMEK paris : Roll endothelio Descemetique

Figure 2: Endothelial-descemetic roll. Endothelial cells are at the outside of the roll

Greffe de cornée paris : propriété membrane de Descemet

Figure 4: Presence of elastin fiber within Descemet's membrane

Greffe de cornée paris : Propriété de la membrane de Descemet

Figure 3: Characteristics of the Descemet membrane .

Greffe de cornée paris : Tapis de bain versus roll endothélial

Figure 5: We can compare endothelio-Descemet to a bath carpet where the small circles on the bath mat represent endothelial cells. In the anterior chamber, the graft must be oriented as in the photo on the right with the endothelial cells facing the anterior chamber (and not as in the photo on the left (crossed out by a red cross)

  • The second step involves removing the Descemet endothelium of the recipient. This is done through an air bubble in the anterior chamber by using an inverted Sinskey hook, which makes a descemetorhexis.

  • The third step involves injecting and positioning the graft onto the posterior surface of the recipient stroma. The graft is first aspirated into a dedicated injector by a so-called “no touch” technique and injected into the anterior chamber through a 3-mm incision (Figures 5, 6).

  • An alternating injection of balanced salt solution and air allows the graft to be unrolled and positioned on the posterior surface of the recipient stroma (Figure 6). The graft’s tendency to curl up with the endothelial cells to the outside is an important indicator that ensures that the graft is properly oriented during surgery. An air bubble is then injected to fill the anterior chamber and press the graft onto the posterior stromal surface (Figure 7). The air bubble is maintained for 30 minutes then 50% of it emptied.

Greffe de cornée paris : Déroulement d'un greffon DMEK en chambre antérieur

Figure 6: Unfolding of the graft in the anterior chamber

Greffe de cornée Paris : Injection d'une bulle d'air sous un greffon de DMEK déroulé

Figure 7: Injection of an air bubble under the graft

The advantages of DMEK

  • One major “theoretical” advantage of DMEK is the pure anatomical reconstruction, meaning that only the unhealthy tissue is replaced by identical healthy tissue. In practice, this solves the problem without creating another one. The corneal curvature is not changed and no additional stroma is added. DMEK restores the physical and functional characteristics of the cornea.

  • DMEK preserves eyeball integrity: the procedure involves performing a micro-incision (3 mm) that is similar to a cataract surgery incision. This causes little or no corneal denervation. In addition, the post-operative refraction is unchanged because the surgery is most often performed without sutures, resulting in little induced astigmatism.  

  • There is no doubt that DMEK provides the best vision result and does so more quickly than any other type of graft: According to studies, more than 90% of eyes that undergo surgery achieve a postoperative AV of 5/10 or better and more than 80% of them achieve an AV of 8/10 or better. Rarely does the postoperative AV come out lower than the preoperative AV. Therefore DMEK is a very safe surgery.

  • Compared to other graft techniques, studies report a low rejection rate: less than 1% for DMEK, about 8% for DSAEK, and 20-30% for penetrating grafts.

  • Reversals are easy. The primary graft can be replaced if it fails.

Descemet Membrane Endothelial Keratoplasty (DMEK) is therefore certainly the surgical technique of choice for endothelial pathologies. The development of optical coherence tomography integrated to surgical microscopes allows the direct viewing of the graft orientation and significantly simplifies the procedure (Figure 8, A and B).

Greffe de cornée paris : OCT intra-opératoire (iOCT) d'un greffon de DMEK à l'envers en chambre antérieur

Figure 8A: Intraoperative OCT showing the inverted graft in the anterior chamber

greffe de cornée paris : OCT intra opératoire (iOCT) d'un greffon de DMEK dans le bon sens en chambre antérieure

Figure 8B: Intraoperative OCT showing the graft well oriented in the anterior chamber

To learn more about DMEK in videos or DMEK in complex cases , visit the dedicated pages by clicking on the links.

Patient information - Cornea transplant - DMEK

What Should I Know About My Surgery? Descemet Membrane Endothelial Keratoplasy: DMEK

 

 

Surgery:

  • The operation usually occurs under local / loco regional anesthesia.  One night admission is sometime needed.

  • There is no pain during the surgery or after the surgery.

  • It’s primordial to keep a supine position during the first 5 hours after the surgery. It’s also important to sleep on the back the first 2 nights.  

  • In case of intense pain and nausea, it’s important to have your eye checked by your doctor. Pain is usually caused by an increase in intra ocular pressure that might occur in the first hours after the surgery. Adequate treatment need to be started.

First day after the surgery:

  • An eye exam will be done and can assess graft positioning and adherence.

  • There is no pain. It’s possible to have dry eye and foreign body sensations.

  • Vision is still blurry.

 

First week after the surgery:

  • Dry eye and foreign body sensations will slowly decrease. You should respect your treatment (usually 4 to 6 times per day of steroids eyedrops).

  • Visual Acuity improves slowly.

  • An eye exam confirms the adherence of the graft. In case of peripheral graft detachment, (3 to 10% of the cases) and dependent on its severity, an air bubble is reintroduced in the eye. This can be done in the clinic and doesn’t need an operative room in most cases.

First month after the surgery:

  • Visual Acuity is improved and will continue to improve in the next few months.

  • Post-operative treatment need to be continued, more specifically, steroids eye drops should never be stopped without your surgeon authorization.

 

Patient information - Cornea transplant - DMEK

What Should I Know About My Surgery? Descemet Membrane Endothelial Keratoplasy: DMEK

 

 

Surgery:

  • The operation usually occurs under local / loco regional anesthesia.  One night admission is sometime needed.

  • There is no pain during the surgery or after the surgery.

  • It’s primordial to keep a supine position during the first 5 hours after the surgery. It’s also important to sleep on the back the first 2 nights.  

  • In case of intense pain and nausea, it’s important to have your eye checked by your doctor. Pain is usually caused by an increase in intra ocular pressure that might occur in the first hours after the surgery. Adequate treatment need to be started.

First day after the surgery:

  • An eye exam will be done and can assess graft positioning and adherence.

  • There is no pain. It’s possible to have dry eye and foreign body sensations.

  • Vision is still blurry.

 

First week after the surgery:

  • Dry eye and foreign body sensations will slowly decrease. You should respect your treatment (usually 4 to 6 times per day of steroids eyedrops).

  • Visual Acuity improves slowly.

  • An eye exam confirms the adherence of the graft. In case of peripheral graft detachment, (3 to 10% of the cases) and dependent on its severity, an air bubble is reintroduced in the eye. This can be done in the clinic and doesn’t need an operative room in most cases.

First month after the surgery:

  • Visual Acuity is improved and will continue to improve in the next few months.

  • Post-operative treatment need to be continued, more specifically, steroids eye drops should never be stopped without your surgeon authorization.

 

DMEK in videos

DMEK, a real revolution in the world of keratoplasties - Prize for best film (2nd) from the French Society of Ophthalmology. This video quickly traces the evolution of corneal transplantation and the advent of pure endothelial graft (DMEK) for Fuchs dystrophy and other endothelial decompensations.
DMEK: An unedited surgery (graft unfolding) of the learning curve period. It is important to control the preparation / peeling of the endothelial graft even if in the future, this step will undoubtedly be carried out in the eye banks. The unfolding of the graft involves precise management of intracameral fluidics, each movement / injection having a direct impact on the endothelial graft.
DMEK corneal transplant: The integration of OCT (Optical Coherence Tomography) technology in surgical microscopes (here a RESCAN microscope) has made surgery safer, especially when it is performed at an advanced stage with severe corneal edemas limiting visualization. Here is one of the first surgeries performed with this technology allowing the verification of the orientation of the endothelial graft live peroperatively.
DMEK corneal transplant: The main difficulty in DMEK endothelial transplant surgery is unfolding the DMEK graft in the anterior chamber. This step is now well standardized and there are specific techniques to apply depending on the configuration of the endothelial graft in the anterior chamber.
 

DMEK in the presence of an Anterior Chamber IOL

The main indications for DMEK (Descemet Membrane Endothelial Keratoplasty) are “simple” corneal edemas secondary to Fuchs dystrophy. However, the indications have now broadened and include decompensated penetrating keratoplasties, the Descemet Stripping Automated Endothelial Keratoplasty (DSAEK) which did not work well or the more complex eyes, vitrectomized, aphakic, history of glaucoma surgery, or even in the presence of anterior or posterior stromal fibrosis. If the surgery is more complex in these latter indications, the results can be spectacular.

 

The integrity of the anterior segment is an important element to consider preoperatively, since its impairment can complicate the technical procedure. This assumes that the anterior chamber is present and that there is a functional iris separating the anterior segment from the posterior segment. These elements are important in order to be able to perform a DMEK in good conditions, while minimizing the intraoperative risks. The unfolding of the endothelial graft in the anterior chamber is sometimes carried out by pressing the graft to the iris, and the absence of the latter can lead to the passage of the endothelial graft in the vitreous cavity.

When an endothelial keratoplasty is indicated, the finding of a bullous keratopathy in the presence of an anterior chamber implant raises several questions:

  1. Should a DMEK be performed, which may be technically difficult in the presence of an anterior chamber implant and severe corneal edema limiting visualization? Or is it preferable to carry out a DSAEK (Descemet Stripping Automated Endothelial Keratoplasty) "guaranteeing" an acceptable postoperative visual acuity and less important operative risks.

  2. Should the anterior chamber implant be removed and replaced with an implant fixed to the sclera?

It is currently difficult to provide a consensual answer to these questions and the experience of each practitioner certainly weighs in the decision, which must be made on a case-by-case basis.

Melles' team showed that DMEK could be performed in the presence of an anterior chamber implant and that the loss of endothelial cells at 6 months was not greater compared to DSEK on an anterior chamber implant. Technically, surgery is therefore feasible and our experience is consistent with the results of Melles' work.

 

To the first question, that of the choice between DMEK or DSAEK in the presence of an anterior chamber implant, the answer to be provided therefore seems relatively simple: DMEK should be preferred if it is well mastered since it can give the best visual acuity. In DSAEK, and depending on the thickness of the graft, the corneal endothelium is found closer to the anterior chamber implant, with therefore carry a risk of faster secondary decompensation.

 

However, the second question is also of importance: does it make sense to renew the corneal endothelium while the cause of the endothelial decompensation (the anterior chamber implant) is still in place? To answer it, it is necessary to differentiate:

 

a) bullous keratopathies occurring on "old" anterior chamber implants of an elderly pseudophakic patient who had undergone complicated cataract surgery more than 15 or 20 years ago, and whose endothelium eventually decompensated .

b) bullous keratopathies of the young phakic subject, who had benefited less than 15 years ago from the placement of an anterior chamber implant with refractive aim.

c) the presence of other complications caused by the anterior chamber implant such as ocular hypertension (HTO) or glaucoma.

In the presence of an anterior chamber implant causing HTO and / or bullous keratopathy in the young subject, it is preferable to remove the implant and perform an endothelial keratoplasty. The visual potential is generally good because visual function is preserved, and the presence of an anterior chamber implant would risk compromising the long-term survival of the graft, hence the need to remove it.

 

When an elderly subject (> 75 years old) presents with bullous keratopathy and an anterior chamber implant, it is important to inquire about the date of onset of the symptoms. If the implant has been in place for more than 20 years and the visual discomfort started a few months ago, the question of maintaining the implant is legitimate. Indeed, the removal of the implant often requires a wide incision, and the placement of stitches. The resulting astigmatism can affect the visual outcome significantly. In addition, the removal of the implant must be accompanied by the placement of an implant fixed to the sclera and this intervention is delicate, especially in conditions of poor visualization.

 

In these patients whose native endothelium has "tolerated" the presence of an implant in the anterior chamber for more than ten years, graft survival seems a plausible hypothesis, provided that the pool of endothelial cells provided is sufficient to obtain a clear cornea for a long time.

 

Conversely, several studies have shown the occurrence of greater long-term endothelial loss in subjects having benefited from DSAEK in the presence of an anterior chamber implant. And it makes sense to extrapolate these results to the DMEK. For this reason, the maintenance of the implant in the anterior chamber must remain reserved for precise indications, when the morbidity of major surgery outweighs the necessary lifespan of the graft.

Example: DMEK in the presence of an anterior chamber implant:

70-year-old patient, operated in 1983 for a bilateral cataract with placement of an anterior chamber implant.

 

Best Corrected Visual Acuity on 07/04/2013:

OD: Count Fingers

 

Central pachymetry OD: 740 microns

 

LAF: Severe corneal edema on OD with angular support AC-IOL OD

DMEK in December 2013: Unfolding of the endothelial graft in the anterior chamber. It is sometimes difficult in these eyes to unfold the graft by a classic "no touch" technique. Here unfolding of the graft is performed by inserting a cannula in the endothelial roll. The injection of BSS on the sides allows the graft to unfold. The use of a special cannula (Geuder, DMEK unfolder cannula) or a C-Press technique can facilitate this surgery.

Cornée claire post DMEK avec ICA en place

January 2014: BCVA OD: 4/10; Clear cornea; central pachymetry: 539 microns

 

November 2014: BCVA OD: 8/10; Clear cornea (top right); central pachymetry: 544 microns (bottom right); Specular microscopy: 1728c / mm2 (left bottom).

Microscopie spéculaire un an post DMEK sur implant de chambre antérieure
Carte pachymetrique post-DMEK sur implant de chambre antérieure

Endothelial Keratoplasty using a C-Press technique in the presence of an anterior chamber implant

Here unfolding the graft using a C-Press technique: On the video on the left, insertion of a cannula inside the graft (after checking the correct orientation of the graft) through the main incision. It is usually not advisable to use the main incision to manipulate the graft for fear of expelling the graft, but on a vitrectomized eye (as in this case with an anterior chamber implant) this risk is very low. At the same time, use the left hand to press on the cornea (Cornea Press) and keep the graft open. The OCT images (right) clearly show this step with the cornea invaginating into the anterior chamber and preventing the graft from rolling. The pressure on the cornea must be sufficient to prevent the rolling of the graft but not too strong in order to limit the contact between the graft and the implant (here visible slightly on the OCT images).

Anterior chamber implant removal, secondary implantation fixated to the sclera (Yamanee) and DMEK - Triple procedure

When the anterior chamber implant (AC-IOL) is recent, in a young subject, and it is directly the cause of endothelial decompensation, it may be advisable to proceed with its removal before DMEK surgery. In this case, it is recommended to first remove the ICA and perform a DMEK, then plan for secondary implantation surgery as a second step.

Indeed, the staging of interventions limits the per- and post-operative risks and increases the success rate. However, for practical reasons, it is sometimes necessary to perform a triple procedure (ICA removal, implantation fixed to the sclera and DMEK) at the same operating time. In the video above, the Yamanee technique for secondary implantation fixated to the sclera after AC-IOL removal.

In this specific case, in the presence of an asymmetric dilated pupil, it is preferable to carry out a pupilloplasty in order to be in the best conditions to perform the DMEK surgery, hence reducing the risk of dislocation of the graft in the vitreous cavity. In addition, pupilloplasty limits the phenomena of postoperative photophobia.

DMEK is then performed (video below) and the C-Press technique is used here to unfold the graft. The implant attached to the sclera remains stable despite the pressure on the cornea and, in our series, no case of implant dislocation was reported during these triple procedures. After ensuring the correct orientation of the graft, a cannula is inserted into the graft while a second presses on the cornea in order to artificially flatten the anterior chamber.

Simple descemethorhexis without transplant

What is a simple Descemethorhexis (DWEK Descemthorhexis Without Endothelial Keratoplasty)?

 

 

A simple Descemethorhexis involves removing a central diameter of the Descemet membrane from the recipient cornea without grafting an endothelium and a Descemet membrane from a donor. The idea behind this approach came from several observations during the follow-up of patients who had benefited from DMEK (Descemet Membrane Endothelial Keratoplasty).

 

  • First, it was noted in the early postoperative period that corneal clearance was faster at the periphery compared to the corneal center.

  • Then, and in the presence of a postoperative decentration of the endothelial graft, the area virgin of endothelial cells (between the edges of the descemethorhexis and the edges of the graft) thinned relatively quickly and there was no edema at this level.

  • Finally, in cases of incomplete DMEK with the impossibility of positioning and / or unrolling the endothelial graft during the operation, the bare stromal bed cleared up spontaneously in some cases with no residual edema. This surprising result occurred when the indication for surgery was Fuchs' dystrophy but never when it was a bullous keratopathy.

Fuchs Dystrophy:

How to explain such results? To obtain some answers, it is necessary to try to understand certain aspects of the pathophysiology of Fuchs' dystrophy and endothelial scarring.

 

Little is known about the pathophysiology of Fuchs' dystrophy, but a genetic mutation associated with environmental factors appears to be at the root of the disease. Rare mutations have been identified (SLC4A11, TCF4, TCF8, CLU, LOXHD1) without however being present in all affected patients. Therefore, in the majority of cases, Fuchs "dystrophy" is not caused by a specific genetic mutation, but rather by a defective defense mechanism against oxidative stress which can arise from ultraviolet radiation, changes in temperature or aqueous humor. Faced with a permanent oxidative stress exceeding the defense mechanisms of endothelial cells (more fragile in the presence of a Fuchs dystrophy), the latter become senile and die by apoptosis. The corneal center is the most subject to oxidative stress, hence the damage is central at an early stage of the disease. However, it is not yet proven that this same oxidative stress is the direct cause of the drops visible in "Fuchs' dystrophies".

 

Until recently, all studies agreed that endothelial cells had no regenerative potential but that the defect was filled by enlargement and migration of adjacent cells. New studies challenge this precept and have suggested that endothelial stem cells are present at the corneal periphery and that they could replace dead cells by centripetal migration. This healing mechanism could be defective in Fuchs' "dystrophy" with the presence of endothelial drops which would form a physical barrier to the migration of endothelial stem cells. Therefore the only way to fill the void left by central cell apoptosis in a Fuchs is the elongation of adjacent cells.

 

From these elements of pathophysiology, it is easy to imagine that the removal of the physical barrier created by the drops in Fuchs "dystrophies" (descemethorhexis) should allow peripheral endothelial cells (stem?) Of the host to migrate and colonize the posterior corneal surface left blank. This would call into question the name of Fuchs' “dystrophy”, the term dystrophy meaning irreversible cellular pathology, while the clinic seems to prove possible reversibility in some cases.

 

Faced with these theoretical principles, clinical work has come to corroborate or invalidate the stated hypotheses. Thus in the series of simple Descemethorhexis presented by Colby et al, 25% of the corneas did not clear up and subsequently required an endothelial graft. The other patients had a clear cornea between 1 and 3 months postoperatively and visual acuity measured at 10/10. Therefore, the difficulty today consists in being able to evaluate the predictive factors of a good result preoperatively in order to intervene only on the "good" candidates.

 

As of January 2015, five patients have benefited from this treatment at the Rothschild Foundation in Paris. They presented with Fuchs dystrophy and moderate corneal edema, whether or not associated with nuclear cataracts. Combined cataract surgery when needed and central descemethorhexis were performed. Figures 1 and 2 show the improvement in corneal condition in parallel with the recovery of visual acuity. More than a 3 years later, the corneas are still perfectly clear with an acceptable endothelial load. Visual acuity in 4 of the 5 patients was 10/10 at 6 months postoperatively (preoperatively between 1 and 3/10). The fifth patient presented visual acuity measured at 4/10 at 4 months post descemethorhexis with very slow visual improvement. A DMEK was  performed and the surgery allowed to recover 9/10 of visual acuity.

 
 

Slit lamp image of central corneal edema early postoperatively (top) and clear cornea late postoperatively (right, 6 months post descmethorhexis). We can visualize on the right image the limits of the Descemetic rhexis.

Video of a simple descemethorhexis under OCT. The size of this descemethorhexis should be around 4mm, taking care not to damage the posterior stroma in order to allow its colonization by peripheral endothelial cells.

OCT 3 semaines post Descemethorhexis - d

OCT 1 week after Descemethorhexis showing severe corneal edema (left) and 3 weeks later showing slight decrease of the corneal edema.

OCT 6 semaines post Descemthorhexis.jpg

OCT, 6 weeks after Descemethorhexis with a significant decrease in corneal edema. There, persists a slight paracentral edema (left) and right, OCT 1 year after descemethorhexis showing a cornea of normal thickness.