Residency · Residency · Ophthalmology

Corneal Transplantation: PK, DALK, DSAEK, and DMEK

Overview and Evolution

Corneal transplantation is the most commonly performed solid organ transplant worldwide. Over the past two decades, the field has undergone a fundamental paradigm shift from full-thickness penetrating keratoplasty toward selective lamellar techniques that replace only the diseased layer while preserving healthy tissue. This evolution has brought significant advantages, including reduced rejection risk, better tectonic integrity, and faster visual recovery.

Indications by Layer of Disease

The choice of transplant technique depends on which corneal layer is primarily affected. Anterior disease -- including keratoconus, stromal scarring, and anterior stromal dystrophies -- is best addressed with deep anterior lamellar keratoplasty (DALK) or penetrating keratoplasty (PK). Endothelial disease, such as Fuchs dystrophy or pseudophakic bullous keratopathy, is treated with DSAEK or DMEK. Full-thickness disease involving all corneal layers, or failed prior grafts, requires PK. Therapeutic PK is also performed for perforated or medically refractory infectious keratitis.

Penetrating Keratoplasty (PK)

Surgical Principles

PK involves full-thickness replacement of all corneal layers. The host cornea is trephined using a vacuum trephine or femtosecond laser, and the donor button -- typically sized 0.25-0.50 mm larger than the host bed to reduce postoperative intraocular pressure issues -- is sutured into place. Suture techniques include 16 interrupted 10-0 nylon sutures, a single continuous 10-0 nylon suture, or a combination of both. Postoperative suture adjustment is an important tool for managing residual astigmatism.

Advantages

PK is suitable for virtually any corneal pathology and has the longest track record of long-term outcomes data. It is the only technique that can simultaneously address combined anterior and posterior corneal disease.

Disadvantages

As an open-sky procedure, PK carries the risk of expulsive suprachoroidal hemorrhage. Postoperative astigmatism is typically high and irregular, averaging 3-5 diopters. Visual rehabilitation is prolonged, often requiring 12-18 months before stable refraction is achieved. The rejection rate is higher than with lamellar techniques, and the wound remains vulnerable to traumatic dehiscence for years after surgery.

Outcomes

Five-year graft survival ranges from approximately 75-90% for low-risk indications such as keratoconus and Fuchs dystrophy, but is considerably lower for high-risk scenarios including neovascularized corneas, repeat grafts, and chemical injuries. Rejection remains the leading cause of graft failure.

Deep Anterior Lamellar Keratoplasty (DALK)

Concept

DALK selectively replaces the epithelium, Bowman layer, and stroma while preserving the host's own Descemet membrane and endothelium. It is ideal for diseases limited to the anterior stroma in patients with a healthy endothelium.

Indications

The primary indication for DALK is keratoconus. Other indications include anterior stromal dystrophies, anterior stromal scarring, and post-infectious stromal opacity in eyes with confirmed healthy endothelium.

Surgical Techniques

The most widely used technique is the big-bubble method described by Anwar, in which air is injected into the deep stroma to create a large separation between the stroma and Descemet membrane. Two types of bubbles can form: a Type 1 bubble (between the stroma and Dua's layer or pre-Descemet stroma) and a Type 2 bubble (between Dua's layer and Descemet membrane, which is smaller and more fragile). Alternative approaches include manual layer-by-layer dissection, which is slower and less predictable in depth, and the Melles technique using viscoelastic-assisted dissection.

Advantages over PK

The most significant advantage is the elimination of endothelial rejection, since the host endothelium is preserved. DALK also provides superior tectonic integrity because Descemet membrane remains intact, removes the risk of open-sky complications, and offers longer graft survival.

Disadvantages

The procedure is technically demanding, with a steep learning curve for the big-bubble technique. Descemet membrane perforation -- either macro or micro -- can occur and may necessitate conversion to PK. If the dissection does not reach bare Descemet membrane, interface haze may develop and limit visual outcomes. Sutures are still required, and prolonged astigmatism management remains necessary.

Outcomes

Five-year graft survival exceeds 90% for keratoconus. Visual acuity is comparable to PK when the dissection successfully exposes bare Descemet membrane. Rejection episodes are limited to stromal and epithelial types (never endothelial), resulting in a lower overall rate and severity.

Descemet Stripping Automated Endothelial Keratoplasty (DSAEK)

Concept

DSAEK is a selective posterior lamellar transplant in which the donor tissue consists of Descemet membrane, endothelium, and a thin layer of posterior stroma. Only the diseased endothelial layer is replaced while the host stroma and epithelium remain intact. The donor tissue is prepared using a microkeratome (hence "automated").

Indications

DSAEK is indicated for Fuchs endothelial corneal dystrophy, pseudophakic bullous keratopathy, failed prior endothelial keratoplasty, ICE syndrome (with limited success), and post-cataract surgery endothelial decompensation.

Surgical Technique

The host is prepared by performing a descemetorhexis -- a circular stripping of the host's Descemet membrane and endothelium. The donor tissue, typically 100-130 micrometers thick (or less than 100 micrometers for ultrathin DSAEK), is pre-cut by the eye bank or the surgeon. The tissue is inserted into the anterior chamber through a small incision using a folding technique or an insertion device such as a Busin glide or EndoGlide. An air bubble is injected to tamponade the graft against the posterior stroma, and the patient is positioned supine for one to two hours. Sutures are generally unnecessary because the small wound is self-sealing.

Advantages

As a closed-globe procedure, DSAEK eliminates the open-sky risk. It produces minimal suture-induced astigmatism and offers faster visual recovery than PK (weeks to months rather than 12-18 months). The rejection rate is lower than PK, and the procedure can be combined with cataract surgery in a triple procedure.

Disadvantages

The interface between the donor and host stroma introduces some optical limitation, with a hyperopic shift from the posterior stromal curvature that caps best-corrected visual acuity. Graft dislocation occurs in 1-14% of cases (more commonly in early surgical experience) and requires rebubbling. Endothelial cell loss is significant, reaching 35-50% at five years. DSAEK typically achieves best-corrected visual acuity of 20/30-20/40, compared with 20/20-20/25 achievable with DMEK.

Ultrathin DSAEK

Ultrathin DSAEK uses donor tissue thinner than 100 micrometers, producing visual outcomes that approach those of DMEK with reduced hyperopic shift. It serves as a bridging technique between standard DSAEK and DMEK.

Descemet Membrane Endothelial Keratoplasty (DMEK)

Concept

DMEK transplants only the isolated donor Descemet membrane and endothelium, with no stromal tissue attached. At approximately 10-15 micrometers thick, it is the thinnest possible corneal graft and represents the most anatomically precise replacement of the diseased endothelial layer.

Indications

The indications mirror those for DSAEK -- primarily Fuchs dystrophy and pseudophakic bullous keratopathy -- but DMEK is preferred when the best possible visual outcomes are the priority.

Surgical Technique

The donor Descemet membrane is peeled from the donor stroma, during which the tissue naturally scrolls with the endothelium facing outward. After performing a descemetorhexis on the host eye, the donor tissue is loaded into an injector and inserted through a small 2.5-3.0 mm clear corneal incision into the anterior chamber. The scrolled tissue is then unrolled using gentle tapping maneuvers on the corneal surface with air-BSS exchanges (the "no-touch" technique). An 80-100% air fill provides tamponade, which is partially vented at the conclusion. The patient remains supine for several hours postoperatively.

Advantages over DSAEK

DMEK delivers superior visual outcomes, with 75-90% of patients achieving 20/25 or better compared with approximately 50% following DSAEK. There is negligible hyperopic shift because no stromal interface exists. The rejection rate is the lowest of any corneal transplant technique, approximately 1% at two years compared with 5-10% for DSAEK. Visual recovery is also faster, typically measured in weeks.

Disadvantages

The surgical learning curve is steeper than for DSAEK. The rebubbling rate is higher, ranging from 5-30% during the learning phase and 5-15% even in experienced hands. The fragile donor tissue can fail during preparation. Complex eyes -- including aphakic eyes, those with anterior chamber IOLs, or those with glaucoma tubes -- present particular technical challenges. Graft tissue availability can also be limited due to preparation failures.

Outcomes

Two-year graft survival exceeds 95%. Five-year endothelial cell density stabilizes at approximately 1,000-1,200 cells/mm2. The rejection rate is the lowest among all corneal transplant types.

Corneal Transplant Techniques Comparison

Graft Rejection

Immunology

The cornea is an immune-privileged site owing to its avascularity and anterior chamber-associated immune deviation (ACAID). Despite this privilege, rejection remains the leading cause of graft failure. Risk factors include corneal neovascularization (the single greatest risk factor), prior failed grafts, large graft size, young recipient age, and active inflammation at the time of surgery. Unlike solid organ transplants, ABO blood group matching and HLA matching are not routinely performed for corneal transplants, except in high-risk cases.

Types of Rejection

Three types of rejection are recognized. Epithelial rejection produces an elevated epithelial rejection line known as the Kaye-Baer line; it is generally mild and self-limited. Subepithelial (stromal) rejection manifests as subepithelial infiltrates similar in appearance to adenoviral subepithelial infiltrates. Endothelial rejection is the most common and most visually significant form. Its hallmark is the Khodadoust line -- a linear endothelial rejection line composed of keratic precipitates migrating across the graft endothelium. Other manifestations include diffuse endothelial keratic precipitates, localized or diffuse corneal edema, and an anterior chamber inflammatory reaction.

Treatment of Rejection

Treatment must be urgent and aggressive. Topical prednisolone acetate 1% is administered hourly, then slowly tapered over weeks to months. Severe cases may require subconjunctival or periocular dexamethasone injection. For refractory or repeatedly rejected grafts, systemic immunosuppression with intravenous methylprednisolone, oral prednisone, or mycophenolate may be necessary. Timing is critical: graft survival is markedly better when rejection is treated within 24-48 hours of symptom onset.

Prophylaxis

Topical corticosteroid prophylaxis (prednisolone acetate or fluorometholone) should continue for at least 12 months after PK, and many surgeons maintain a low-dose regimen indefinitely. Long-term daily topical steroids are particularly important for high-risk grafts.

Eye Bank and Donor Tissue

Donor Screening

Donor age typically ranges from 2 to 75 years, with younger donors providing higher endothelial cell counts. Exclusion criteria include death from unknown cause, active systemic infection, prior ocular surgery (for endothelial grafts), and positive testing for CJD, HIV, or hepatitis B/C. The minimum acceptable endothelial cell density for transplantation is generally 2,000-2,500 cells/mm2.

Tissue Preservation

In North America, the standard preservation medium is Optisol-GS, stored at 4 degrees Celsius, which permits storage for up to 14 days. In Europe, organ culture at 31-37 degrees Celsius is standard, allowing storage for up to four weeks with quality checks. Eye banks now routinely prepare pre-cut tissue for DSAEK and DMEK procedures, which has standardized the quality of lamellar grafts and reduced intraoperative tissue preparation failures.

<image>Comparative diagram of four corneal transplantation techniques shown in cross-section. Each panel shows the corneal layers (epithelium, Bowman layer, stroma, Descemet membrane, endothelium) with the replaced portion highlighted. Panel A: PK — entire full-thickness cornea replaced with donor-to-host junction shown with sutures. Panel B: DALK — epithelium and stroma replaced, host Descemet and endothelium preserved (big-bubble air space shown). Panel C: DSAEK — only posterior stroma, Descemet membrane, and endothelium replaced (donor tissue ~100 um thick). Panel D: DMEK — only Descemet membrane and endothelium replaced (~15 um thick). Label each layer and technique clearly.</image>

<image>Slit lamp photographs of corneal graft rejection. Panel A: Khodadoust line — a linear endothelial rejection line of keratic precipitates migrating across the donor endothelium with adjacent corneal edema on one side and clear cornea on the other. Panel B: Diffuse endothelial rejection showing scattered KPs across the graft endothelium with diffuse corneal edema. Panel C: Epithelial rejection line (Kaye-Baer line) — an elevated linear opacity in the epithelium. Include annotations identifying the rejection line direction, KPs, corneal edema, and graft-host junction.</image>

<image>Surgical technique illustration for DMEK. Sequential steps: (1) Donor Descemet membrane being peeled from the donor stroma with the tissue scrolling into a roll, endothelium-out; (2) Descemetorhexis on the host eye with stripping of host Descemet membrane using a reverse Sinskey hook; (3) Donor tissue loaded into an injector and inserted through a 2.5 mm clear corneal incision into the anterior chamber; (4) Unscrolling the donor tissue using tapping maneuvers on the corneal surface with air-BSS exchanges; (5) Air bubble tamponade filling the anterior chamber with the donor tissue flat against the posterior stroma. Show the correct orientation (endothelium facing down toward the anterior chamber).</image>

Key Clinical Pearls

DMEK provides the best visual outcomes and lowest rejection rate for endothelial disease but demands the steepest learning curve and has the highest rebubbling rate. DALK eliminates endothelial rejection in keratoconus, which is its most important advantage over PK. The big-bubble technique in DALK achieves bare Descemet membrane dissection in approximately 70-80% of cases, with a perforation rate of 4-10%. Graft rejection can occur years after transplantation, so patients must be educated about the warning signs, remembered by the mnemonic RSVP: Redness, Sensitivity to light, decreased Vision, and Pain. Intraocular pressure must always be monitored in graft patients on chronic topical steroids, as steroid-induced glaucoma is a common complication. Corneal neovascularization is the single greatest risk factor for graft rejection. The triple procedure (phacoemulsification + IOL + DSAEK/DMEK) is efficient but requires careful patient selection and surgical planning. Pre-cut donor tissue from eye banks has standardized lamellar keratoplasty and reduced intraoperative tissue preparation failures.

References

• Price MO, Price FW. Endothelial keratoplasty — a review. Clin Exp Ophthalmol. 2010;38(2):128-140.
• Anshu A, et al. Risk of corneal transplant rejection significantly reduced with DMEK. Ophthalmology. 2012;119(3):536-540.
• Anwar M, Teichmann KD. Big-bubble technique to bare Descemet's membrane in anterior lamellar keratoplasty. J Cataract Refract Surg. 2002;28(3):398-403.
• Gain P, et al. Global survey of corneal transplantation and eye banking. JAMA Ophthalmol. 2016;134(2):167-173.
• AAO BCSC Section 8: External Disease and Cornea. 2023-2024.

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