Endothelial Keratoplasty: Targeted Treatment for Corneal Endothelial Dysfunction






Definition


Endothelial keratoplasty has significant advantages over penetrating keratoplasty as a targeted method to replace endothelial cells in the treatment of endothelial dysfunction.




Key Feature





  • Targeted replacement of corneal endothelium through a small 2–5 mm incision.





Associated Features





  • Rapid visual recovery.



  • Few activity restrictions.



  • No significant increase in astigmatism.



  • Minimal disruption of corneal innervation.



  • Lower risk of immunological rejection than with penetrating keratoplasty.



  • Rapid sequential surgery.





Introduction


Penetrating keratoplasty (PKP) was long considered the gold standard for the treatment of endothelial dysfunction. Advances in endothelial keratoplasty (EKP) techniques, coupled with the many advantages it offers to patients, have made it the preferred treatment for endothelial dysfunction ( Fig. 4.29.1 ).




Fig. 4.29.1


Slit-lamp images of penetrating keratoplasty (A) and Descemet’s membrane endothelial keratoplasty (C), with corresponding anterior segment optical coherence tomography images (B,D).

(A,B from Anshu A, Price MO, Tan DTH, et al. Endothelial keratoplasty: a revolution in evolution. Surv Ophthalmol 2012;57:236–52, Fig. 1.)








After PKP, it generally takes 6 months to several years for the refraction to stabilize ; 10%–15% of the patients typically require a hard contact lens for best vision ; and a final mean refractive cylinder of 4–5 D is common. Furthermore, PKP incision severs all corneal nerves, so the inclination to blink and produce tears is reduced postoperatively. This, together with the prolonged presence of corneal sutures to hold the graft in place, increases the risk that ocular surface complications will interfere with recovery. Moreover, because of the PKP wound, the cornea never regains the full strength of a virgin cornea, so an eye that has undergone PKP is forever at increased risk of loss from a traumatic injury.


In contrast, EKP involves selective removal of dysfunctional recipient corneal endothelium and replacement with donor tissue consisting of healthy endothelium, with or without posterior stroma. EKP is performed through a small incision and spares the majority of the host cornea, so corneal strength and surface topography are minimally altered, and the technique is essentially refractive–neutral. Furthermore, corneal innervation is retained, and corneal sutures are not required, so ocular surface complications are minimal. Finally, the small incision allows rapid healing and visual recovery, and patients can resume normal activities within weeks of surgery.




Evolution of EKP Techniques


Originally described by Tillett in 1956, EKP has evolved rapidly, particularly since 1998, when Melles reported successful replacement of dysfunctional endothelium through a scleral–limbal approach, using an air bubble rather than sutures to secure the donor tissue, in a technique he called posterior lamellar keratoplasty (PLK). Later renamed deep lamellar endothelial keratoplasty (DLEK), this technique required lamellar dissection of the recipient and donor corneal tissue. Both dissections were originally done manually by using a series of curved blades of increasing length.


Melles subsequently eliminated the challenging recipient stromal dissection and excision steps by peeling the Descemet’s membrane (DM) and dysfunctional endothelium from the recipient cornea before implanting the donor tissue. This EKP modification became known as Descemet’s stripping with endothelial keratoplasty (DSEK). Use of a microkeratome was introduced to facilitate the donor lamellar dissection, and this technique variation was referred to as either DSEK or Descemet’s stripping automated endothelial keratoplasty (DSAEK). In 2005, eye banks began performing the donor lamellar dissection with a microkeratome and providing “precut” tissue to surgeons.


Even though DSEK provides 20/40 or better vision more reliably compared with PKP, fewer patients than expected achieve 20/20 vision, and variations in the donor stromal thickness increase the higher order aberrations of the posterior corneal surface. Over time, surgeons have gravitated toward use of thinner DSEK tissue, which seems to provide better vision with less risk of rejection than thicker tissue, although the rate of tissue loss is greater with ultra-thin DSEK.


Aiming for exact anatomical replacement with the thinnest possible tissue, Melles developed a technique for peeling DM and healthy endothelium from a donor cornea and implanting it into a recipient eye in a method he called DM endothelial keratoplasty (DMEK). The extremely thin DMEK graft is more challenging to handle compared with a thicker DSEK graft ( Fig. 4.29.2 ), leading to the development of hybrid techniques with a narrow rim of donor stromal tissue ringing a central area of bare endothelium without stroma. The hybrid techniques, known as DMEK-S and DMAEK, were not widely adopted because the risk of tissue loss was greater than with DMEK.




Fig. 4.29.2


Diagram illustrating the differences between Descemet’s stripping endothelial keratoplasty (DSEK) and Descemet’s membrane endothelial keratoplasty (DMEK). The host cornea epithelial and endothelial layers are depicted in sky blue, the host stroma in pale blue, the donor endothelium in dark blue, and the donor stroma in medium blue.


A variation of DMEK, called pre-Descemet’s endothelial keratoplasty (PDEK), utilizes a big bubble to separate the donor Descemet’s membrane and endothelium from the donor stroma. With a type 1 big bubble, a pre-Descemet’s layer remains attached to Descemet’s membrane, thereby providing slightly thicker tissue than in standard DMEK. This results in easier unfolding and the ability to utilize tissue from younger donors who have a thinner Descemet’s membrane. The disadvantages of PDEK are that the graft diameter is limited by the big bubble diameter to about 7–7.5 mm and the donor tissue must be cut from the underlying stroma with scissors. Time will tell which of these technique variations become dominant for standard noncomplicated cases, such as Fuchs’ dystrophy.




Indications


EKP is an excellent option for any type of endothelial dysfunction ( Box 4.29.1 ). With appropriate modifications, EKP can be performed in eyes with peripheral anterior synechiae, glaucoma filtration surgery, and iris abnormalities, including aniridia. If anterior stromal scarring from long-standing corneal edema is significant, replacement of the full corneal thickness with a PKP may provide better visual acuity. However, in many cases, patients who have tolerated long-standing corneal edema also have other visual limitations (e.g., retinal problems). In such cases, EKP is an attractive alternative because it quickly resolves the corneal edema and bullae while maintaining much of the structural integrity of the eye. In eyes with significant iris defects, aniridia, and/or aphakia, DSEK is preferable to DMEK, which can more easily escape into the posterior chamber or be damaged by contact with an intraocular lens (IOL) or artificial iris during unfolding.



Box 4.29.1

Endothelial Keratoplasty: Indications and Contraindications


Indications





  • Essentially all forms of endothelial dysfunction



  • Fuchs’ endothelial dystrophy



  • Pseudo-phakic or aphakic bullous keratopathy



  • Previous failed penetrating keratoplasty



  • Posterior polymorphous dystrophy



  • Congenital hereditary endothelial dystrophy



  • Iridocorneal endothelial (ICE) syndrome



  • Endothelial failure from trauma, previous surgery, angle closure or glaucoma drainage devices



Contraindications





  • Advanced keratoconus and anterior stromal dystrophies



  • Hypotony



  • Stromal opacities that would preclude acceptable postoperative vision






Surgical Technique


Anesthesia and Recipient Preparation


EKP is readily performed with topical or local anesthesia. With local anesthesia (using a retrobulbar or peribulbar block), it is important to ensure that there is no back pressure from periorbital swelling because back pressure can cause the anterior chamber to forcefully shallow while the donor tissue is being inserted and may even push the donor tissue back out of the eye.


A 2–5 mm clear corneal or scleral tunnel incision is made in the recipient eye. Temporal placement of the incision has several advantages compared with superior placement: Donor button insertion is facilitated because the corneal diameter is longer horizontally; the superior conjunctiva is preserved for future glaucoma surgery, if needed; and orbital anatomy, such as large brows or sunken globes, is not as important. If the recipient epithelium is hazy or scarred, it can be removed, generally improving the view into the eye.


If the host Descemet’s membrane has any guttae or other abnormalities, then it should be removed before implanting the donor tissue for optimal visual results. The anterior chamber is filled with air or viscoelastic to facilitate visualization of DM during its removal. A blunt Sinskey hook is used to score DM in a circular pattern to outline the area of planned membrane removal. The far edge of DM is grasped with a stripping instrument or infusion/aspiration tip and carefully is peeled off and removed from the eye ( Fig. 4.29.3 ). Trypan blue can be injected into the anterior chamber immediately after stripping DM to facilitate visualization of loose pieces of Descemet’s membrane or stroma. After the membrane is removed, it can be spread on the surface of the cornea to determine whether removal was complete or whether some fragment might remain in the eye. If viscoelastic material was used, care should be taken to completely remove it from the anterior chamber and back surface of the cornea because retained viscoelastic material on the stromal surface can impede attachment of the donor tissue and impair vision.




Fig. 4.29.3


Stripping of host Descemet’s membrane using a 90° angled stripper.


Donor Tissue Preparation and Insertion


Donor tissue preparation involves three steps: dissection; sizing to the appropriate diameter with a trephine (usually 8–9 mm); and insertion. Preparing the donor tissue before opening the patient’s eye allows the surgeon to ensure that the tissue will be suitable for transplantation.


Descemet’s Stripping With Endothelial Keratoplasty


The lamellar dissection usually is done with a microkeratome either at the eye bank or at the time of surgery ( Fig. 4.29.4 ). A donor corneal/scleral shell is mounted on an artificial anterior chamber designed to accompany the microkeratome being used. The artificial anterior chamber can be filled with viscoelastic material, balanced salt solution, or tissue storage solution. The donor thickness is measured, and a microkeratome head of appropriate depth is selected to provide a posterior donor button of approximately 0.08–0.15 mm thickness, according to the surgeon’s preference.




Fig. 4.29.4


Lamellar dissection of the donor tissue with a microkeratome in Descemet’s stripping endothelial keratoplasty (DSEK).


The donor tissue is carefully transferred from the artificial anterior chamber and placed endothelial side up on a standard punch trephine block, where it is punched to an appropriate diameter, taking into consideration the horizontal white-to-white dimensions of the recipient cornea and the anterior chamber depth. The donor tissue is covered with tissue storage solution while the recipient eye is prepared.


A variety of insertion techniques are available, including forceps, glides, and inserters. When using forceps, the posterior donor button is folded over on itself like a “taco” with approximately 60% anterior and 40% posterior, and the folded tissue is gently grasped at the leading edge with forceps that only compress at the tip as the tissue is guided into the eye. A disadvantage of this method is that it can be difficult to unfold the donor correctly in the eye, especially for surgeons early in the learning curve. Another method is to fixate the edge of the donor with a suture, thread the suture across the anterior chamber and out through a stab incision nasally, and pull the tissue into the eye.


A third method is to place the tissue on a glide or insertion cartridge, insert retina/vitreal intraocular forceps through a nasal stab incision, reach across the eye and grasp the tip of the donor through the 5-mm temporal incision, and pull the tissue into the eye ( ). The tissue also can be inserted with a single-use inserter. Use of a funnel glide or insertor helps the donor tissue curl with the endothelium inward for protection as it is inserted.



Once the donor tissue is in the eye and unfolded stromal side up, the anterior chamber is filled with air to press the donor button up against the recipient cornea ( Fig. 4.29.5 ). While the anterior chamber is completely filled with air, a LASIK (laser-assisted in situ keratomileusis) roller can be used to help center the donor tissue and massage fluid out of the donor/recipient interface ( Fig. 4.29.6 ). Several small incisions can be made in the peripheral recipient cornea down to the graft interface to help drain any fluid trapped between the donor and recipient tissue. Intraoperative optical coherence tomography (OCT) can help identify fluid in the interface. After 8–10 minutes, many surgeons remove most of the air to prevent pupillary block, and leave the anterior chamber approximately one third full. Some surgeons then have the patients lay face up with a partial air bubble for 30–60 minutes. Other surgeons leave the anterior chamber completely filled for 1–2 hours. At the completion of surgery, antibiotics, corticosteroids, dilating drops, and nonsteroidal anti-inflammatory drugs (NSAIDs) are applied to the treated eye.




Fig. 4.29.5


Air injection to lift and press the donor tissue up against the host cornea.



Fig. 4.29.6


Massaging the surface of the recipient cornea to center the Descemet’s stripping endothelial keratoplasty (DSEK) donor tissue and remove fluid from the donor/recipient interface, while the anterior chamber is completely filled with air.


Descemet’s Membrane Endothelial Keratoplasty


The most common donor tissue dissection technique consists of gently peeling off DM and endothelium ( ). First, the DM periphery is scored all the way around. The tissue is stained with trypan blue to enhance visualization. The peripheral edge is lifted all the way around by using a microfinger or hockey stick–shaped instrument. With the tissue submerged in tissue storage solution, an edge of the membrane is grasped with forceps and peeled about halfway to the center, quadrant by quadrant, with replacement of each section on the stromal base ( Fig. 4.29.7 ). The tissue is partially trephined, cutting through DM but not completely through the stroma. An edge is grasped with nontoothed forceps, and the central DM is gently peeled from the underlying stroma and replaced in tissue storage solution. Donor DM and endothelium also can be isolated using air, fluid, or viscoelastic. However, using a type 1 big bubble to detach DM limits the graft diameter to about 7–7.5 mm, and the graft must be cut from the stroma with scissors.




Fig. 4.29.7


Descemet’s Membrane Endothelial Keratoplasty (DMEK) Donor Tissue Preparation.

A nontoothed forceps is being used to peel Descemet’s membrane and endothelium from a donor corneal/scleral rim that is submerged in corneal storage solution in a cornea viewing chamber. The corneal/scleral rim was stained with trypan blue to enhance visualization of the scored edge of the membrane.


Immediately before insertion into the recipient eye ( ), the donor tissue is stained again with trypan blue to improve visualization. The donor tissue naturally curls up endothelium-outward and can be placed in a glass pipette or inserter, such as an IOL injector, for placement in the recipient eye. The donor DM is gently unfolded in the correct orientation with a combination of balanced salt solution and air injections. Then air or a long-acting gas (20% sulfur hexafluoride) is injected beneath the donor tissue to completely fill the anterior chamber and press the graft up against the host cornea.



Instead of allowing the donor tissue to naturally curl with the endothelium facing outward, opposite sides can be folded over the middle (trifold technique), with the endothelium facing inward. The folded tissue is pulled into an IOL cartridge and injected into the eye or pulled in with forceps. Both the PDEK donor preparation method and the trifold DMEK insertion technique facilitate unfolding the donor tissue inside the recipient eye. Thus both allow use of younger donor tissue, which otherwise can be more challenging to unfold.




Anesthesia and Recipient Preparation


EKP is readily performed with topical or local anesthesia. With local anesthesia (using a retrobulbar or peribulbar block), it is important to ensure that there is no back pressure from periorbital swelling because back pressure can cause the anterior chamber to forcefully shallow while the donor tissue is being inserted and may even push the donor tissue back out of the eye.


A 2–5 mm clear corneal or scleral tunnel incision is made in the recipient eye. Temporal placement of the incision has several advantages compared with superior placement: Donor button insertion is facilitated because the corneal diameter is longer horizontally; the superior conjunctiva is preserved for future glaucoma surgery, if needed; and orbital anatomy, such as large brows or sunken globes, is not as important. If the recipient epithelium is hazy or scarred, it can be removed, generally improving the view into the eye.


If the host Descemet’s membrane has any guttae or other abnormalities, then it should be removed before implanting the donor tissue for optimal visual results. The anterior chamber is filled with air or viscoelastic to facilitate visualization of DM during its removal. A blunt Sinskey hook is used to score DM in a circular pattern to outline the area of planned membrane removal. The far edge of DM is grasped with a stripping instrument or infusion/aspiration tip and carefully is peeled off and removed from the eye ( Fig. 4.29.3 ). Trypan blue can be injected into the anterior chamber immediately after stripping DM to facilitate visualization of loose pieces of Descemet’s membrane or stroma. After the membrane is removed, it can be spread on the surface of the cornea to determine whether removal was complete or whether some fragment might remain in the eye. If viscoelastic material was used, care should be taken to completely remove it from the anterior chamber and back surface of the cornea because retained viscoelastic material on the stromal surface can impede attachment of the donor tissue and impair vision.




Fig. 4.29.3


Stripping of host Descemet’s membrane using a 90° angled stripper.




Donor Tissue Preparation and Insertion


Donor tissue preparation involves three steps: dissection; sizing to the appropriate diameter with a trephine (usually 8–9 mm); and insertion. Preparing the donor tissue before opening the patient’s eye allows the surgeon to ensure that the tissue will be suitable for transplantation.


Descemet’s Stripping With Endothelial Keratoplasty


The lamellar dissection usually is done with a microkeratome either at the eye bank or at the time of surgery ( Fig. 4.29.4 ). A donor corneal/scleral shell is mounted on an artificial anterior chamber designed to accompany the microkeratome being used. The artificial anterior chamber can be filled with viscoelastic material, balanced salt solution, or tissue storage solution. The donor thickness is measured, and a microkeratome head of appropriate depth is selected to provide a posterior donor button of approximately 0.08–0.15 mm thickness, according to the surgeon’s preference.




Fig. 4.29.4


Lamellar dissection of the donor tissue with a microkeratome in Descemet’s stripping endothelial keratoplasty (DSEK).


The donor tissue is carefully transferred from the artificial anterior chamber and placed endothelial side up on a standard punch trephine block, where it is punched to an appropriate diameter, taking into consideration the horizontal white-to-white dimensions of the recipient cornea and the anterior chamber depth. The donor tissue is covered with tissue storage solution while the recipient eye is prepared.


A variety of insertion techniques are available, including forceps, glides, and inserters. When using forceps, the posterior donor button is folded over on itself like a “taco” with approximately 60% anterior and 40% posterior, and the folded tissue is gently grasped at the leading edge with forceps that only compress at the tip as the tissue is guided into the eye. A disadvantage of this method is that it can be difficult to unfold the donor correctly in the eye, especially for surgeons early in the learning curve. Another method is to fixate the edge of the donor with a suture, thread the suture across the anterior chamber and out through a stab incision nasally, and pull the tissue into the eye.


A third method is to place the tissue on a glide or insertion cartridge, insert retina/vitreal intraocular forceps through a nasal stab incision, reach across the eye and grasp the tip of the donor through the 5-mm temporal incision, and pull the tissue into the eye ( ). The tissue also can be inserted with a single-use inserter. Use of a funnel glide or insertor helps the donor tissue curl with the endothelium inward for protection as it is inserted.



Once the donor tissue is in the eye and unfolded stromal side up, the anterior chamber is filled with air to press the donor button up against the recipient cornea ( Fig. 4.29.5 ). While the anterior chamber is completely filled with air, a LASIK (laser-assisted in situ keratomileusis) roller can be used to help center the donor tissue and massage fluid out of the donor/recipient interface ( Fig. 4.29.6 ). Several small incisions can be made in the peripheral recipient cornea down to the graft interface to help drain any fluid trapped between the donor and recipient tissue. Intraoperative optical coherence tomography (OCT) can help identify fluid in the interface. After 8–10 minutes, many surgeons remove most of the air to prevent pupillary block, and leave the anterior chamber approximately one third full. Some surgeons then have the patients lay face up with a partial air bubble for 30–60 minutes. Other surgeons leave the anterior chamber completely filled for 1–2 hours. At the completion of surgery, antibiotics, corticosteroids, dilating drops, and nonsteroidal anti-inflammatory drugs (NSAIDs) are applied to the treated eye.


Oct 3, 2019 | Posted by in OPHTHALMOLOGY | Comments Off on Endothelial Keratoplasty: Targeted Treatment for Corneal Endothelial Dysfunction

Full access? Get Clinical Tree

Get Clinical Tree app for offline access