Descemet stripping automated endothelial keratoplasty.

Endothelial keratoplasty is at present the gold standard for surgical treatment of corneal endothelial pathologies not associated with significant corneal scar. Tremendous progress has been made in recent years in improving the technology of endothelial keratoplasty techniques, such as descemet stripping automated endothelial keratoplasty (DSAEK) and descemet membrane endothelial keratoplasty. In this review, we discuss the current techniques and outcomes of DSAEK.

Endothelial keratoplasty has evolved significantly in the past few decades. It has now become the surgery of choice for endothelial failure without stromal scarring. At its inception, endothelial keratoplasty was performed from the anterior route, and now, the approach is gradually shifted toward the posterior route. The first case of posterior lamellar keratoplasty (PLK) was performed by Tillett in 1956 using manual lamellar dissection of posterior recipient stroma and attachment of donor lenticule with sutures and air tamponade.[1] Melles et al. were first to describe endothelial keratoplasty through the posterior approach, and this technique was known as PLK.[2] A 9 mm scleral tunnel was made to dissect posterior stroma, descemet membrane (DM), and endothelium and same-sized posterior donor lenticule were implanted with air tamponade without suture fixation.[3] PLK was introduced in the United States by Terry and Ousley, who called it as deep lamellar endothelial keratoplasty (DLEK).[4] Later, Melles et al. described technique, in which the dissection of diseased DM (descemetorrhexis) was done without dissecting posterior stroma and transplanting donor's DM through 5 mm incision.[56] However, maintaining apposition of graft in anterior chamber (AC) was difficult with rolling of the graft. In 2005, Price and Price. performed refined technique wherein the recipient's DM was dissected using Melles' technique and donor tissue was manually dissected similar to PLK/DLEK technique and donor posterior lenticule with DM was folded 60/40 over fold and transplanted through 5-mm incision. The posterior graft was apposed using air tamponade without sutures.[7] This technique was known as descemet stripping endothelial keratoplasty (DSEK). As the technique involved manual dissection, obtaining uniformly thick and smooth surface of donor posterior stroma was surgically challenging. This issue was solved by Gorovoy, who modified DSEK technique using automated microkeratome to dissect donor lenticule, and this technique was popularized as descemet stripping automated endothelial keratoplasty (DSAEK).[8] As per Eye Bank Association of America, DSAEK is the most frequently utilized keratoplasty procedure in the United States.[9] This article reviews the current indications, surgical techniques, and outcomes of DSAEK with an aim to provide up-to-date information to the experienced as well as beginners of endothelial keratoplasty (EK).

Indications

Patients with endothelial dysfunction causing visual loss or visual disability in the form of glare and fluctuating vision affecting day-to-day activities such as reading, writing, or driving are suitable candidates for EK. The only absolute contraindication is significant corneal scarring and high irregular astigmatism. The diseases where DSAEK is indicated are summarized in Table 1.[789101112]

Table 1

Indications of descemet stripping automated endothelial keratoplasty

Surgical Technique

The surgery involves three principal steps, which includes donor preparation, recipient preparation, and donor lenticule insertion.[10] Various techniques have been described in literature for these three major steps.

Donor preparation

The aim of the surgeon in donor preparation is to achieve the thinnest lenticule possible. All the methods described for donor cut employ the use of an artificial AC which the corneoscleral rim is mounted. The central corneal thickness (with the epithelium on) of the donor tissue is measured using an ultrasonic pachymeter.[13] The donor tissue can be prepared in the following manner.

Manual method

Preset depth calibrated blades are used to make a vertical lamellar incision in the cornea at the desired depth. The dissection is then carried out at this depth to create an interface between the anterior and posterior layers of the cornea. This technique avoids the use of expensive equipment. However, uniformity of the dissection is difficult to reproduce, often leading to an irregular stromal bed and a reduced final visual acuity.

Automated microkeratomes

Donor lenticule is prepared using a microkeratome with the cutting head of 350 or 400 μm. Different types of microkeratomes are available in the market. The microkeratome head is either passed straight or in a rotational manner over the mounted cornea. The Moria Surgical (Antony, France) offers two types of blade attachments; one has a rotational and the other has a translational effect. Gebauer SLc Original and SLc Expert Microkeratomes offer to provide ultrathin lenticules (<100 μm) with a single-pass or double-pass technique.

Single-pass technique

Vajpayee et al. using a 400 μm microkeratome head slowed the speed of the pass to achieve a thinner donor lenticule without any complications during the donor preparation.[13] A single, slow pass of 400 μm microkeratome yielded thin donor lenticules in all the cases, and the mean graft thickness achieved at the end of 6 months was 111 ± 17.62 μm (range 70–134 μm). Excellent visual outcomes were obtained in the majority of the patients.

Nahum et al. have described a nomogram for choosing the appropriate microkeratome head size in single pass microkeratome-assisted dissection of donor tissue.[14] The authors reported mean postoperative donor graft central thickness of 63 ± 29 μm in 42 eyes using this nomogram. Thus, creation of ultra-thin DSAEK lenticules has been made possible with a single microkeratome pass.

Double-pass technique

In this technique, an initial debulking cut is performed using a microkeratome with a 300-μm head. A second cut (refinement cut) is carried out from the direction opposite to the one of the first cut.[15] The size of the head used for this step is selected such that a residual bed with a central thickness of approximately 100 μm is left. Intraoperative pachymetry or anterior segment optical coherence tomography helps in deciding the residual stromal thickness during the procedure.

The double-pass technique, in experienced hands and when successful, results in excellent outcome.[15] However, it has some issues such as the potential higher risk of donor tissue perforation (microkeratome is passed twice), difficult manipulation of a thinner graft which may lead to increased endothelial loss, prolonged time for second cut, chances of second pass creating a smaller diameter cut, and unpredictability when donor thickness exceeds 600 μm.[131516]

Precut tissue

Tissue preparation is done either in advance by the operating surgeon or by an eye bank technician before surgery.[1718] This precut tissue is then shipped to surgeons when needed. This has the advantage of reducing the cost as well as the time of surgery. Moreover, in countries like India where every corneal surgeon does not have the microkeratome, it will be extremely useful.

Femtosecond laser-assisted endothelial keratoplasty

Femtosecond laser-assisted EK is another addition to the existing techniques of EK donor lenticule preparation. In this technique, the donor cornea undergoes a lamellar cut from the epithelial side with the femtosecond laser at the desired depth. This may be followed by excimer laser photoablation of the stromal tissue to achieve a smooth surface. While femtosecond laser dissection yields a thin and reproducible endothelial graft cut with a high level of safety and accuracy, excimer photoablation provides a smooth, high-quality interface.[1920]

Few studies have shown disappointing results when the grafts have been cut from the epithelial side using femtosecond laser.[2122] This has been attributed to the attenuation of the laser beam in a swollen donor cornea and an uneven surface when applanated from the epithelial side. These can be alleviated by mounting the graft endothelial side up on the artificial AC (ZeimerPort, Switzerland) followed by creation of the lenticule with femtosecond laser cut by applanating the surface from the endothelial side.[23] One of the major concerns with this technique is the endothelial cell loss attributed to direct applanation of the endothelial side. This can be minimized by the use of visco dispersive agent (Viscoat) as the interface fluid.[24]

Recipient preparation

The donor can be inserted either through a scleral tunnel or clear corneal incision.

Scleral tunnel

A limited fornix-based peritomy is fashioned in the superotemporal or superonasal quadrant. A “reverse smile” scleral tunnel of 3.5 mm length partial scleral thickness incision is created such that it is 1.5 mm from the limbus centrally and 3.0 mm from the limbus at the edges and extends 1.0 mm into the clear cornea.

Clear corneal incision

A clear corneal incision of 4 mm in width is fashioned either nasally or temporally by first making a corneal tunnel with the help of crescent blade followed by AC entry with keratome.

Donor insertion

Numerous techniques have been described for the insertion of donor lenticule within the eye. They can either be categorized into “push-in” or “pull-through” techniques.

“Pull-through” techniques

In pull-through techniques, the donor is docked into the main incision and pulled within the eye from the opposite small clear corneal incision with the help of forceps/suture. One of the most commonly performed pull-through techniques is the use of Busin glide (Asico, Westmont, IL, USA). The glide with the donor tissue is docked into the scleral tunnel/clear corneal incision. The donor lenticule is pulled into the AC by grasping the edge of the donor lenticule with a bent disposable 23-gauge vitreous forceps from the opposite side port. After the donor lenticule gets unfolded, AC is filled with air.

The other pull-through technique used often is the “suture pull-through” technique, in which a prolene suture is passed through the graft before inserting it and pulling it within the eye. The suture is then hitched on to the recipient cornea.

Push-in techniques

In push in techniques, the donor is pushed in through the main incision with forceps/glides and injectors. The various donor insertion techniques include forceps: Taco with 60/40 over fold, trifold, 40/60 under fold, glides: Busin glide, Sheets glide, Tan EndoGlide and inserters: Endoserter (Winston-Salem, NC, USA), Endoshield/Endoinjector (Keramed, San Jose, CA, USA), Neusidl Corneal Inserter (Fischer Surgical, Arnold, MO, USA).[1025262728] In general, these glides allow better maintenance of AC during the procedure, better unfolding, and being bimanual allow the surgeon for better hold during the procedure.[2829303132] Endoserter requires 4–5.5 mm incision size and no AC maintainer is needed. Reported endothelial loss at 6 months is 13%–33%.[33] Endoglide is based on pull-in and pull-out technique. It requires 4–5.0 mm incision size and an AC maintainer. Reported endothelial loss at 6 months with Endoglide is 13%–26%.[34] In a randomized study comparing these two insertion devices, in 20 cases of fuchs endothelial corneal dystrophy and PBK, no difference was seen in the endothelial loss at 12 months. The mean endothelial cell loss, including that in the rebubbled eyes, was 41.2% and 31.4% at 12 months in the Tan EndoGlide and EndoSerter groups, respectively.[35]

Outcomes of Descemet Stripping Automated Endothelial Keratoplasty

The outcomes and complications of DSAEK reported from various studies are summarized in the Table 2.[3536373839404142434445464748495051525354555657585960616263646566676869707172] Figs. 1 and 2 show the postoperative outcomes after DSAEK and ultrathin DSAEK, respectively. Fig. 3 shows intraoperative optical coherence tomography showing complete attachment of the donor lenticule.

Table 2

Outcomes and complications of descemet stripping automated endothelial keratoplasty

Figure 1

(a) Postoperative photograph of a patient 1 month after descemet stripping automated endothelial keratoplasty with a clear graft. (b) The anterior segment optical coherence tomography shows a postoperative graft thickness of 165 μm at 1 month

Figure 2

(a) Postoperative photograph of a patient 1-month after ultrathin descemet stripping automated endothelial keratoplasty (double-pass technique) with a clear graft. (b) The anterior segment optical coherence tomography shows a postoperative graft thickness of 57 μm at 1 month

Figure 3

Intraoperative optical coherence tomography showing complete attachment of the donor lenticule

Graft survival

Graft clarity

The reported long-term graft clarity of DSAEK reported in studies, including a large number of cases with follow-up ranging from 6 months to 3 years ranges from 90% to 99%.[10384969]

Primary graft failure

Primary graft failure (PGF) is characterize by the clinical situation, in which a corneal graft does not clear as expected after surgery usually by 2 months. It can result mostly from poor quality donor tissue, unhealthy recipient circumstances (blood, interface foreign bodies, infection, and flat chamber), or poor surgical technique.[10] The published studies showed rates from 0% to 29%, with an average PGF rate of 1%.[104273]

Late graft failure

Late endothelial failure is due to progressive endothelial cell loss. Analysis of the available studies suggests endothelial cell loss in the range of 25%–61% at 3-year follow-up.[1035447273] At 5 years follow-up, it has been reported to be around 51.9%.[52]

Functional outcomes

Visual acuity

The greatest advantage of DSAEK over penetrating keratoplasty (PKP) is early and predictable visual recovery. The procedure is usually sutureless and the anterior corneal surface is not affected. Both these factors allow for rapid and better uncorrected as well as best-corrected visual acuity (BCVA). Mean BCVA of 20/40 or better is achieved in more than 70% of cases.[51525354737475]

Hyperopia

The hyperopia induced ranges from 0.7 to 1.5 D with an average induced hyperopia of 1 D.[103776] The induced hyperopia is primarily due to nonuniform thickness profiles of donor lenticules.[1050] Donor lenticules prepared with the microkeratome are thinner centrally and thicker in the periphery, resulting in a reduced radius of curvature of the posterior corneal surface and reduced effective corneal power.[7376] The hyperopic shift from DSAEK must be considered while calculating intraocular lens (IOLs) power in cases undergoing triple procedure. Target refraction should be aimed at 0.5–1.0 D of myopia in these cases.

Astigmatism

The average postoperative astigmatism after DSAEK is 1.5 D.[105273] The amount of astigmatism often depends on the type of incision.

Higher order aberration

DSAEK does not change the anterior corneal curvature but the posterior corneal curvature is altered due to differences in curvatures between the host and the donor lenticule as well as an uneven thickness of donor lenticule. These changes can induce posterior corneal higher order aberrations after DSAEK.[7778]

Complications

The complications of DSAEK can be categorized into intraoperative and postoperative complications and are summarized as follows:

Graft detachment and dislocation

Early postoperative graft detachment/dislocation remains one of the most common complications of DSAEK surgery. It manifests as interface fluid, significant graft displacement, or a graft that is completely dislocated into the AC. The reported average dislocation rate is around 14.5% [Table 1].[1073]

Graft rejection

The incidence of graft rejection following DSAEK is relatively less compared to PKP. The reported rates range from 0% to 45.5% with an average rate of 10% with follow-up ranging from 3 months to 2 years.[10363773] The factors accounting for this low incidence are limited exposure of donor cells to host immune surveillance, absence of graft sutures, a lesser donor derived antigen presenting cells, and less disruption to the blood-aqueous barrier compared to PKP.[7980]

Symptoms are relatively less serious such as small drop in vision or mild photophobia or at times patient may be completely asymptomatic.[8081] The signs also differ and include scattered keratic precipitates unlike an endothelial rejection line, a localized corneal edema, or simple conjunctival hyperemia.[81]

Endothelial cell loss

Endothelial cell loss is still a major concern in DSAEK. Surgical trauma related to graft insertion appears to be the primary cause for this loss. The endothelial loss reported from larger series (involving ≥100 eyes) ranges from 14.9% to 59% with follow-up ranging from 6 months to 3 years [Table 1].[103545]

Raised intraocular pressure and glaucoma

Glaucoma following DSAEK can occur due to pupillary block, inflammation, or steroid use.[107382] The reported incidence of glaucoma after DSAEK ranges from 0% to 15%, with an average rate of 3.0%.[1073] Pupillary block is a rare but serious immediate postoperative complication after DSAEK, with a reported incidence of 0%–10%.[394357]

Epithelial ingrowth

Epithelial ingrowth is a rare complication of DSAEK.[83] The source of these epithelial cells can be host epithelial cells transported during donor insertion, donor epithelial cells transferred after eccentric trephination that has included full-thickness tissue beyond the microkeratome dissection and epithelial ingrowth related to the use of mid-peripheral full-thickness venting incisions.[1083848586]

Infectious keratitis

Bacterial, fungal and herpetic, all form of keratitis have been reported following DSAEK.[8788] The most commonly isolated causative organism is Candida albicans.[10] Source of infection is often the donor tissue and rarely from late inoculation from conjunctiva and adnexa microflora. The infiltrate at the onset is often small and involves the donor lenticule or the interface. In addition, the effectiveness of topical antifungal agents may be reduced by posterior lamellar location of infiltrate. All these factors result in a poor prognosis of such cases. Majority of cases may require the removal of the lenticule with a therapeutic PKP.[878889]

Interface haze

Interface abnormalities can occur in any form of lamellar keratoplasty, including DSAEK. The source of interface haze may include blood, retained ophthalmic viscoelastic, inflammatory cells, debris, and irregular cut of the donor tissue by the microkeratome, retained fragments of DM, microkeratome-generated plastic particles, and epithelial cells.[109091] Most such cases cause minimal effect on BCVA or resolve with time, repeat DSAEK is required for the treatment of refractory cases.[91]

Other less-common complications

Other less frequent complications of DSAEK include endophthalmitis[92] and folds in donor tissue.[9293]

Descemet Stripping Automated Endothelial Keratoplasty in Special Situations

Descemet stripping automated endothelial keratoplasty in the presence of anterior chamber intraocular lens

The primary concerns of performing DSAEK in the presence of an anterior chamber intraocular lens (ACIOL) are increased tissue manipulation, reduced AC depth (ACD), difficulty in graft manipulation, more difficult air-bubble management, and intermittent postoperative IOL touch.[56] In the presence of a well-centered ACIOL and an ACD >3 mm, DSAEK can be performed successfully in such cases.[56]

Descemet stripping automated endothelial keratoplasty in aphakia

The difficulties in performing DSAEK in aphakic eyes are difficulty of air retention in the AC, migration of air posteriorly, chances of graft dislocation into vitreous cavity, and chances of host DM dislocation posteriorly. The various modifications that can be employed to overcome these difficulties are simultaneous DSAEK and IOLs implantation,[94] insertion of an infusion cannula through pars plana route,[95] or placement of temporary anchor sutures to prevent donor dislodgement and improve graft adherence.[96]

Descemet stripping automated endothelial keratoplasty in aniridia

Congenital aniridia or aniridia associated with trauma along with aphakia poses a risk of posterior migration of air into vitreous cavity. This problem can be overcome by performing an aniridia IOLs implantation followed by DSAEK in stepwise manner or placing an anchor suture in the peripheral edge of the donor tissue and securing it to the overlying recipient cornea.[93]

Descemet stripping automated endothelial keratoplasty with previous trabeculectomy or tube shunt implantation

The problems encountered in such cases includes loss of the remaining field of vision due to the transient intraocular pressure (IOP) rise, difficulty in surgery due to presence of tube of the glaucoma valve, tube position contributing to corneal decompensation, and possibility of air escaping through the sclerostomy or tube or large iridotomy.[1097] The various technical modifications that can be helpful in such cases include trimming of the tube if it extends centrally,[97] placement viscoelastic between the graft and the iris to block the escape of air from the AC,[98] suture closure of the iridotomy opening and meticulous monitoring of IOP.[10]

With the recent advancements in the techniques of EK, the surgery has become faster and safer with better visual outcomes. Further, an early rehabilitation of patients with DSAEK has made it the procedure of choice over full-thickness PKP to be used in patients with endothelial dysfunction. The creation of ultra-thin lenticules has further led to a reduction in the interface haze with improved visual outcomes and results close to those of DM endothelial keratoplasty. With the added advantages of DSAEK such as a lower rate of graft rejection, preservation of ocular surface, absence of suture-related problems, and the broader spectrum of ocular disorders where it can be safely used, DSAEK will surpass PKP as the first-line surgical treatment modality for cases with endothelial disorders.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.