Adv Ther (2014) 31:494–511 DOI 10.1007/s12325-014-0121-0

REVIEW

New Perspectives on Lamellar Keratoplasty George D. Kymionis • Dimitrios G. Mikropoulos • Dimitra M. Portaliou

•

Kostantinos G. Boboridis Irini C. Voudouragkaki Nikolaos D. Dragoumis •

•

•

Anastasios G. P. Konstas

To view enhanced content go to www.advancesintherapy.com Received: March 26, 2014 / Published online: May 21, 2014 Ó Springer Healthcare 2014

ABSTRACT

resistance

Lamellar (anterior and posterior) keratoplasty

approach of ‘‘partial corneal transplantation’’ may be divided into anterior and posterior:

entails the surgical replacement of diseased-only

techniques including superficial and deep

corneal tissue, while healthy host corneal tissue is preserved. Selective keratoplasty offers several

anterior lamellar keratoplasty (SALK and DALK, respectively) and endothelial keratoplasty as well

advantages in comparison to penetrating keratoplasty such as a lower rate of graft

as Descemet stripping automated endothelial keratoplasty (DSAEK) and Descemet membrane

rejection, less endothelial cell loss, faster/

endothelial keratoplasty (DMEK). These novel

superior visual rehabilitation and enhanced

surgical procedures are rapidly becoming the preferred therapy option for specific corneal

Electronic supplementary material The online version of this article (doi:10.1007/s12325-014-0121-0) contains supplementary material, which is available to authorized users. G. D. Kymionis
D. M. Portaliou Vardinoyiannion Eye Institute of Crete (VEIC), Faculty of Medicine, University of Crete, Heraklion, Crete, Greece G. D. Kymionis
D. M. Portaliou Bascom Palmer Eye Institute, Miller School of Medicine, University of Miami, Miami, FL, USA D. G. Mikropoulos
A. G. P. Konstas 3rd University Department of Ophthalmology, Aristotle University of Thessaloniki, Thessaloniki, Greece K. G. Boboridis
I. C. Voudouragkaki
N. D. Dragoumis
A. G. P. Konstas (&) 1st University Department of Ophthalmology, Aristotle University of Thessaloniki, 1 Kyriakidi Street, 546 36 Thessaloniki, Greece e-mail: [email protected]

to

closed

injury.

The

surgical

dysfunctions involving the corneal stroma (SALK, DALK), or corneal endothelium (DSAEK, DMEK). During the past decade, the continuing advancement of surgical techniques and the development of innovative surgical instruments have significantly enhanced corneal transplantation. Lamellar keratoplasty techniques facilitate corneal surgery, provide patients with superior outcomes and can successfully restore vision in corneal-related blindness. Nevertheless, more long-term evidence is needed to better evaluate these promising new techniques.

Keywords: Corneal anterior

lamellar

transplantation; keratoplasty;

Deep

Descemet

Adv Ther (2014) 31:494–511

495

stripping automated endothelial keratoplasty;

automated endothelial keratoplasty (DSAEK)

Descemet membrane endothelial keratoplasty; Lamellar keratoplasty; Ophthalmology;

[6]

Penetrating keratoplasty (PKP); Superficial anterior lamellar keratoplasty; Surgery

and

Descemet

membrane

endothelial

keratoplasty (DMEK) [7]. Here, the authors provide a brief review of current anterior and posterior lamellar keratoplasty approaches and their outcomes, along with some recent developments in the field of selective lamellar

INTRODUCTION

transplantation.

Penetrating keratoplasty (PKP) was the gold standard of care for rehabilitation of cornealrelated visual impairment throughout the

METHODS

second half of the twentieth century, irrespective of the corneal pathology being

A computerized review of the literature and

treated

(e.g.

keratoconus,

endothelial

dystrophies and corneal infections) [1]. However, although PKP has been an effective procedure for the majority of corneal blinding disorders, it requires a whole corneal replacement

and

consequently

is

citation tracking was performed up to March 2014 using PubMed, and 112 case reports and full-length studies met the inclusion criteria and were included in our review article. Compliance with Ethics

not

infrequently associated with a spectrum of surgical complications such as increased

This article does not contain any new studies with human or animal subjects performed by

rejection risk, infection and high postoperative astigmatism related to the need to

any of the authors.

ensure a tight seal for the donor graft tissue [2–4].

Anterior Lamellar Keratoplasty (ALK)

The need to circumvent the PKP-related

The concept of lamellar keratoplasty is not new,

complications has led to the development of innovative surgical techniques of partial

but the manual dissection of both host and donor tissues employed in past decades created

replacement of the damaged corneal layer or tissue. Depending upon the site of pathology to

irregular surfaces that often resulted in post-

be

operative corneal opacification, or scarring, thus compromising visual outcome [8]. Recent

categorized into anterior and posterior corneal transplantations. In particular, anterior lamellar

advances in surgical techniques and instrument refinement have facilitated wider adoption of

keratoplasty involves the replacement of the corneal stroma to beneath the level of the

anterior lamellar keratoplasty with visual results

be

treated,

lesion,

but

the

new

techniques

without

can

involving

the

comparable, or even superior to the standard penetrating keratoplasty [9].

endothelium, thus eliminating the risk of endothelial rejection [5]. Conversely, posterior

Indications

lamellar keratoplasty aims to replace the diseased endothelium and includes two

The indications for anterior keratoplasty (ALK) include five

distinct

categories [10–16].

techniques:

Descemet

stripping

lamellar principal

Adv Ther (2014) 31:494–511

496

(a)

Corneal ectasias [11], dystrophies and

with post-operative corrected distance visual

degenerations [12]. ALK can be considered as the ideal treatment option for all forms

acuities C20/40 in 7 of the 9 eyes within the first

of stromal dystrophy accompanied by a healthy corneal endothelium. (b)

(c)

Post-operative complications of refractive

vision post-operatively (CDVA remained 20/400) and another patient with post-stromal

surgery [13, 14]. ALK is often indicated in post-refractive surgery ectasias

melt scar improved from 20/200 to 20/100 postoperatively. Finally, Taka´cs and Nagy [19]

accompanied by thinning, or scarring. Ocular surface diseases [15]. These less

describe a case report of microkeratome-

common indications include stem cell deficiency as a result of Stevens–Johnson syndrome, ocular cicatricial pemphigoid, and chemical or thermal burns. (d) Corneal trauma [16]. ALK is indicated after trauma (e)

month. One of the nine patients with poststromal melt scar showed no improvement in

resulting

in

anterior

stromal

assisted lamellar keratoplasty to remove a central corneal scar of the anterior stroma caused by pterygium excision with optimistic outcomes. Uncorrected distance visual acuity (UDVA) improved from 0.15 to 0.6 and the topographical cylinder decreased from 7.98 to 3.79 D. Further long-term evidence is needed to

scarring or opacification. Infections [16]. This technique can be

evaluate this technique.

employed in infectious keratitis cases that do not respond to standard topical/

Complications

systemic antibiotic therapies.

noted in any of the small case series described above.

Microkeratome-Assisted ALK A Laser in situ keratomileusis microkeratome can be used to

No intraoperative complications and no graft failure or immunologic rejection episodes were

(LASIK) perform

automated dissection of both the donor and host corneas [17]. In a non-comparative

Femtosecond Laser-Assisted ALK (FALK)

interventional case series conducted by Wiley

The first in vitro study comparing two different techniques for predissection of human anterior

et al. [17], five consecutive microkeratomeassisted lamellar keratoplasties were performed

and posterior lamellar corneal grafts for eye bank storage with the use of a mechanical

on five eyes of four patients with lattice corneal dystrophy. There were no post-operative

microkeratome or a Femtosecond Laser was

complications in this case series while mean

described in 2006 by Suwan-Apichon et al. [20]. FALK is a technique first described by Yoo

post-operative corrected distance visual acuity (CDVA) improved significantly from 20/100

et al. [21] in which a donor corneal graft was created using the 30-kHz femtosecond laser

pre-operatively to 20/34 after a mean followup of 9 months. In a similar study by Patel et al.

(IntraLase, Abbott Laboratories Inc, Illinois,

[18], superficial ALK was performed in nine eyes

USA). Donor corneal cut was calibrated according to the depth of the lesions to be

of 8 consecutive patients with recurrence of anterior stromal dystrophy (n = 3), post

removed in the recipient cornea, when visualized pre-operatively by anterior segment

photorefractive keratectomy (PRK) haze (n = 2), and scarring after stromal melt (n = 4)

ocular coherence tomography (AS-OCT; Visante OCT, model 1000, Carl Zeiss Meditec, Dublin,

Adv Ther (2014) 31:494–511

497

California, USA). An additional 10–20% depth

after photorefractive keratectomy (PRK) and

was allowed to compensate for donor tissue

granular dystrophy recurred in the graft.

swelling. A recipient corneal lenticule was created using similar femtosecond laser

Adjunctive surgeries including phototherapeutic keratectomy, PRK, cataract

settings except that the recipient corneal lenticule was set to be 0.1 mm smaller in

extraction, debridement

and were

diameter than the donor graft diameter. The

management

of

host corneal button was then removed and replaced with the donor lenticule being inserted

development and epithelial ingrowth. The results of the FALK studies are summarized in

into the recipient residual corneal stromal bed and, after adhesion was checked, a soft bandage

Table 1. A modified FALK method has also been

contact lens was applied. In 12 eyes of 12

presented

[23]

who

patients, preliminary results showed improvement in UDVA. One eye (8%)

employed the Ziemer Femtosecond (Ziemer Ophthalmic Systems AG,

laser Port,

maintained the pre-FALK CDVA, whereas the remaining 11 eyes (92%) experienced a gain of 1

Switzerland) with two different dissection depths: midstromal ([250 lm of posterior

to 8 lines at the last follow-up examination [21].

residual

No graft rejection, displacement, infection or epithelial ingrowth was found in this series of

Descemet (approximately 50 lm of posterior residual corneal bed thickness) with the same

patients. In one eye, due to residual corneal scarring, phototherapeutic keratectomy (PTK;

principals described above. The six patients included in the study underwent treatment

40-lm deep) was performed (10 months after FALK) after lifting the FALK graft. In another

with a 1,000-kHz FEMTO LDV laser (Ziemer Ophthalmic Systems AG, Port, Switzerland),

patient

by

epithelial necessary

haze

formation,

Bonfadini

corneal

bed

ingrowth for the

et

al.

thickness)

cataract

and

pre-

hyperopic

creating a horizontal lamellar bed interface in

photorefractive keratectomy (PRK) over the graft was performed 4 months after FALK. Six

the cornea of the donor and recipient eyes. A manual partial-thickness vertical trephination

patients developed dry eye that was treated with artificial tears and punctual occlusion with

was used to complete the excisions. The mean difference between pre-operative and post-

subjective improvement of symptoms [21].

operative UCVAs was a gain of 4.3 lines (range

Long-term FALK results by the same group of scientists mentioned above, as reported by

3–8 lines). CDVAs were improved in all eyes compared with pre-operative levels. No

Shousha et al. [22], show significant CDVA improvement over pre-operative values at the

intraoperative complications occurred. Larger studies with long-term follow-up are needed to

12-, 18-, 24-, and 36-month visits. Importantly,

further evaluate this technique.

54% of all patients had CDVA greater than 20/30 at the 12-month follow-up. At the

Complications

12-month visit, the mean spherical equivalent and refractive astigmatism were -0.4 ± 3.4 D

Residual corneal pathology, mild interface haze, anisometropia, recurrence of pathology, haze

(range 5.4 to -6.8 D) and 2.2 ± 2.3 D (range 0.3

after adjunctive photorefractive keratectomy, dry eye, epithelial ingrowth, and suspicious

due

to

anisometropia,

to 8 D), respectively. Two patients lost a mean of 1.5 lines of best spectacle-corrected visual acuity (BSCVA) because surface haze developed

ectasia were noted in the long-term study of Shousha et al. [22]. Further, Bonfadini et al. [23]

12

13

6

Retrospective noncomparative, interventional case series

Yoo et al. [21]

Shusha Retrospective, et al. [22] noncomparative, interventional case series

Bonfadini Retrospective, et al. [23] noncomparative, interventional case series

2 patients trauma

10 patients post infection corneal scar

Pathology

Complications: Residual corneal pathology, mild interface haze, anisometropia, recurrence of pathology, haze after adjunctive photorefractive keratectomy, dry eye, epithelial ingrowth, and suspicious ectasia

12 months post-op 0.3 ± 0.2 (0.1–0.6) (n = 12)

UCVA: mean gain of 4.3 lines No intraoperative complications, graft rejection, (range 3–8 lines) or infection

36 months post-op 3.8 ± 2.9 (1–6) (n = 5)

12 months post-op 5 ± 7.1 (1–27) (n = 12)

Mean gain or loss of lines:

36 months post-op 0.2 ± 0.2 (0–0.4) (n = 5)

Adjuvant procedures: PTK, PRK, cataract extraction, epithelial ingrowth debridement

CDVA (LogMar): pre-op 0.8 ± 0.7 (0.2–3) (n = 13)

CDVA: pre-op 0.4 or worse (0.4–3), post-op 0.4 or better (range 0.1–0.6) in 10/12 patients

CDVA: mean gain of 8.0 lines Complications: 1 case of epithelial ingrowth, 1 case of irregular astigmatism keratoconjunctivitis (range 4–13 lines)

1 post-pterygium excision

1

1 herpetic disease

3 infectious keratitis

Remarks

UCVA (LogMar): pre-op 0.54 Adjuvant procedures: PTK, PRK or worse (range, 0.54–3), Transient dry eye in 50% of patients post-op 0.4 or better (range No intraoperative complications 0.18–1)

Outcomes

CDVA corrected distance visual acuity, PRK photorefractive keratectomy, PTK phototherapeutic keratectomy, UDVA uncorrected distance visual acuity

12

2 patients granular dystrophy

11 patients post 12–69 (mean infection corneal 31 months) scar

12.7 (range 6–24)

Eyes Follow-up (months)

References Study design

Table 1 Summary of femtosecond laser-assisted anterior lamellar keratoplasty (ALK)

498 Adv Ther (2014) 31:494–511

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499

observed one case of epithelial ingrowth at the

1996 and February 2013, the survival rate of

graft–host interface 2 weeks after FALK. The

DALK grafts was worse than the survival of

epithelial ingrowth was debrided surgically, and the graft was sutured into position. No

PKP grafts performed for the same indications over the same timeframe.

recurrence was noted 1 year post-operatively. To date, no graft failures or immunologic rejection

Surgical Techniques

episodes have been described in these 3 case series of patients who underwent FALK for a variety of pathological conditions (see Table 1).

Several surgical techniques and modifications of DALK have been described to date to accomplish removal of all, or virtually all, of the corneal stroma by means of lamellar dissection. Malbran [8] was one of the first to

Deep Anterior Lamellar Keratoplasty (DALK)

report lamellar dissection and intra-stromal air injection followed by lamellar dissection

DALK comprises near total, or total stromal

techniques for ALK. Anwar [27] was the first to

replacement while preserving intact the Descemet’s membrane (DM) and corneal

describe a method of partial trephination followed by lamellar dissection accomplished

endothelium. Several advantages of DALK over PKP exist, the most important being

using a rounded 69 Beaver blade (Beaver-Visitec International, Inc., Waltham, Massachusetts,

that

corneal

USA), which was replaced recently with a

endothelium is not seen; the procedure is extraocular and not intraocular, topical

Martinez dissecting spatula, or a variety of dissecting blades. The major drawback of this

corticosteroids can usually be discontinued earlier, the average 5-year post-operative

technique is the risk of rapture of DM limiting its use.

immune

rejection

of

the

endothelial cell loss is less in DALK compared to PKP [24], there may be superior

Sugita and Kondo [28] introduced the

resistance to rupture of the globe after blunt

concept of hydrodelamination to obtain stromal removal. Stromal collagen fibers are

trauma compared to a penetrating keratoplasty and sutures can be removed

cut across and down to the requisite depth, and a saline solution is injected with a blunt 27

earlier [23]. Furthermore, fewer intraoperative and post-operative complications have been

gauge needle at the bottom of this incision. The

DALK

solution penetrates between the collagen fibers, which whiten and swell making deeper

procedure (including expulsive hemorrhage, anterior synechiae, post-operative

dissection safer with respect to DM capture that, however, can still occur (39.2% in this

endophthalmitis, and glaucoma) in comparison to PKP [25]. On the other hand,

study by Sugita and Kondo).

observed

in

association

with

a

DALK requires a substantial learning curve as

In the Melles technique [29], the aqueous is exchanged for air, to visualize the posterior

it is surgically challenging and many of its complications are linked to intraoperative

corneal surface. Through a 5.0-mm scleral incision, a deep stromal pocket is created

technical difficulties. In a recent observational, prospective registry study by

across the cornea, using the air to visualize the endothelium interface as the reference plane for

Coster et al. [26] involving a large number of

dissection depth. The pocket is filled with

transplantations performed between January

viscoelastic, and an anterior corneal lamella is

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500

excised. A full thickness donor button is sutured

This DM baring technique has a variety of

into the recipient bed after having stripped its

modifications such as the ‘‘small bubble’’ [33],

DM. A small modification of technique was described a year later by the same group of

the ‘‘large bubble’’ [34] and the ‘‘double bubble’’ [35] techniques that aim to facilitate the

surgeons in which, using the interface as a reference plane, a 30 gauge needle is inserted

procedure and therefore procedure’s success rate.

increase

the

directly into the cornea just anterior to DM to

The use of a femtosecond laser for the

facilitate the procedure [30]. The Archila technique [31] is considered the

dissection of anterior lamella during ‘‘big bubble’’ DALK was first described by Price Jr.

predecessor of other techniques of maximum depth dissection, such as Anwar’s big bubble

et al. [36] in 2009 and later reiterated by other investigators [36–38]. This surgical technique

technique

partial-thickness

offers customized wound construction for

trephination, intra-stromal air is injected until the cornea becomes opaque and then manual

patient and donor, offering the advantage of less induced astigmatism, improved wound

deep dissection is carried out down to the DM, which appears clear using either a sharp

strength, and allowing earlier suture removal. The ‘‘big bubble’’ technique has been also

crescent or a blunt spatula. This step can be

applied with promising results in uncommon

repeated as long as microbubbles are visible; making sure that there is still a layer of stroma

corneal conditions such as in 16 radial keratotomy incisions [39], descemetocele [40]

that protects the DM against perforation. The big bubble technique [32] described by

and healed hydrops [41].

[32].

After

Anwar and Teichmann in 2002 continues to gain popularity and currently is the technique

RESULTS AND DISCUSSION

most commonly used. The cornea is trephined and dissected to a depth of approximately 60–80%. A convenient point in the

There is cumulative evidence in the literature

circumference of the cut is chosen as the entry site for the needle. The tip is introduced, bevel

[42] concluded that between the several different surgical techniques employed, the highest

down, into the central corneal stroma at the

success rate of DM exposure (60%) was seen with the ‘‘big bubble’’ technique [32]. Several

chosen entry site, deep in the trephination groove. Air is injected paracentrally through a

concerning the efficacy of DALK. Sarnicola et al.

studies have reported visual acuity outcomes of

27- or 30-gauge needle or by a specially designed cannula producing a so-called ‘‘big

20/40, or better ranging from 77.8% to 100% of study patients [24, 43–45]. In a prospective non-

bubble’’ separation of DM from the overlying

comparative case series of 81 patients with keratoconus performed by Fontana et al. [46]

stroma. After the ‘‘big bubble’’ is realized, an anterior lamellar keratectomy is performed, a

with mean follow-up 17.9 ± 10.6 months (range

small opening is created into the air bubble and the remaining stromal layers are lifted with an

2–34 months), mean pre-operative CDVA was 20/100 while post-operative was 20/30 at the end

iris spatula, severed with a blade, and excised

of the follow-up period. Mean keratometry and spherical equivalent refraction improved from

with scissors. This procedure requires a significant learning curve and failure to achieve the ‘‘big bubble’’ is not uncommon.

62.1 ± 6.7 D and -10.76 ± 5 D to 47.51 ± 4.73 D and -1.81 ± 3.2 D, respectively, after surgery.

Adv Ther (2014) 31:494–511

501

Similar visual acuity and refractive results were

perforation of DM (12 months: 27.7% ± 11.1%

also observed by Kubaloglu et al. [47] who

vs. 12.9% ± 17.6%). Van Dooren et al. [51]

reported the long-term results of DALK using the ‘‘big bubble’’ technique in 241 eyes of patients

observed a rate of EC loss of 14.3% over a 2-year period after DALK with the Melles’

with keratoconus. In this study, UDVA was lower than 20/100 in all eyes pre-operatively and better

technique. It is worthwhile noting that EC loss was mostly the result of intraoperative

than

post-

manipulations, and that in the immediate

operatively. CDVA was 20/40 or better in 187 eyes (79.9%) and 20/20 or better in 38 eyes

post-operative period, endothelial cell density (ECD) stabilized without further endothelial cell

(16.2%). Similar success was documented by Noble et al. [48] who carried out the larger

decrease [52]. Ashar et al. [53] explored the possibility of

DALK series (80 eyes of 68 patients) in the

lamellar keratoplasty in children less than

published literature employing the Melles technique in a heterogeneous group of patients.

16 years old with a variety of corneal pathological conditions such as keratoconus,

Mean follow-up was 21.2 months (range 6–48 months). This group established that the

microbial keratitis, corneal scar, corneal keloid, and chemical injury with limbal stem cell

mean post-operative refractive cylinder was

deficiency and dermoid. In their group of

3.31 ± 2.59 D (range from -4 to 12 D), and the mean spherical equivalent was -2.54 ± 3.61 D

patients, the success rate in terms of visual outcomes was comparable to the adult case

(range from -13.25 to 7 D); significantly, 52.2% of their cases exhibited a refractive cylinder less

series. Alterations in the density and distribution of

than ±3 D and 49.3% of the eyes had a spherical equivalent less than ±3 D.

keratocytes after DALK have been reported by different studies by means of confocal

20/100

in

191

eyes

(81.6%)

DALK is also successful in patients with

microscopy.

Balestrazzi

et

al.

[54],

using

stromal scars. In a pertinent study [49] conducted in 79 patients with corneal scarring

confocal microscopy in seven patients with a history of keratoconus, reported a slightly

and mean follow-up of 28.1 ± 17.9 months, a CDVA of 20/40 or better was documented in 59

reduced density of keratocytes with irregular distribution in the anterior stroma and highly

eyes (82%) post-operatively. The mean spherical

reflective particles and linear hyporeflective

equivalent and topographic astigmatism were -3.32 ± 2.13 (range -9.13 to ?4.75) and

microfolds at the interface 18 months after airguided manual DALK. Marchini et al. [55]

-2.97 ± 1.94 (range -8.0 to ?4.50) D, respectively. There were two instances of

reported changes in the deep stromal interface characterized by discontinuity of tissue and

stromal graft rejection, which responded well

cellular stromal architecture, absent or reduced

to medical therapy. Endothelial cell (EC) loss is considered one of

keratocyte density and variable background extracellular reflectivity. Interestingly,

the most important predictors of graft survival. In a randomized clinical trial by Cheng et al.

statistically significant changes in anterior and posterior mean keratocyte density, or visible

[50] comparing endothelial cell loss after DALK

scarring at the interface was not observed. Two

and PKP, the investigators concluded that cell loss was significantly higher after PKP compared

other investigations [56, 57] reported a lower density of keratocytes after DALK using the ‘‘big

with the DALK procedure performed without

bubble’’

technique

in

patients

with

Adv Ther (2014) 31:494–511

502

keratoconus.

Furthermore,

hyporeflective

striae

in

the

representing microfolds and moderateto high-reflective

there rear

were stroma

sheets of amorphous

long-term evidence for the success of DALK and associated complications. Posterior Lamellar Keratoplasties (PLK)

deposits at the interface [58]. The attempt to deal with endothelial pathology Complications

has led to the development of posterior lamellar keratoplasty (PLK). This technique was first

Reported DALK complications include DM

described by Melles et al. [68] in human

perforation, which ranges in incidence between 4% and 39.2% depending on surgical

cadaver eyes and animal models. This group [68] experimented with the creation of a deep

experience and the specific technique used [29, 43, 45, 58, 59]. Intraoperative difficulty in DM

stromal pocket across the cornea through a superior scleral incision and later described a

exposure and rupture occurs approximately in

case report of a sutureless PLK with the use of an

50% of cases even when performed by experienced surgeons [60]. Breaks in DM can

air bubble for graft fixation [69]. Deep lamellar endothelial keratoplasty (DLEK) [70, 71] was

lead to the formation of a secondary pseudoanterior chamber [61]. Graft rejection can occur

achieved through a 5.0-mm self-sealing scleral incision using a 9.0-mm folded donor, which

in between 3% and 14.3% [61–63] in correlation

led to DSEK [72] and an attempt to automate

with the underlying pathology (keratoconus patients have lower rejection rates [61]) and

the procedure to DSAEK [6] when a microkeratome is used for preparation of the

the high-risk factors such as herpetic infection or stromal neovascularization, but it is usually

donor tissue. DSAEK is widely used and constantly evolving and the need to further

successfully managed with the use of topical steroids. Maurino et al. [64] reported three rare

enhance endothelial transplantation has led to DMEK as described by Melles et al. [7].

cases of fixed dilated pupil and iris ischaemia (Urrets-Zavalia syndrome) after DALK surgery associated with the DM microperforation

Indications Posterior lamellar keratoplasty in the form of

intraoperatively and introduction of air/gas into the anterior chamber intraoperatively or

DSAEK or DMEK is particularly beneficial in treating patients with Fuchs’ endothelial

post-operatively, whereas Niknam and Rajabi

dystrophy

[65] reported another four cases that developed fixed dilated pupil after performing DALK for

decompensation resulting from endothelial cell loss [73], including iridocorneal

keratoconus and granular corneal dystrophy. In those four cases after microperforation, air was

endothelial syndrome [74, 75] and congenital hereditary endothelial dystrophy [7].

and

other

forms

of

corneal

left in the anterior chamber for a couple of days. Finally, two cases of Candida keratitis following DALK for keratoconus have also been described

DSAEK: Surgical Technique

in the literature [66]. Most studies, except Krumeich et al. [67] who report a 5-year

The classic DSAEK technique consists of a 4- to 5-mm limbal or corneo-scleral incision used for

follow-up after DALK, report short-term results

insertion of the donor tissue [6]. Descemet stripping is performed over an 8.0-mm

and complications In the future we need to see

Adv Ther (2014) 31:494–511

503

diameter circle with a reverse-bent Sinskey hook

Femtosecond laser technology have also been

corresponding

epithelial

tried but producing reliably thin and smooth

trephine marker. The recipient’s endothelium and DM are carefully removed [6, 76, 77].

posterior lenticules is not always easy [84]. Despite the thin graft technique difficulties,

Preparation of the donor tissue is performed with the aid of automated means

Neff et al. [85] found that thinner DSAEK grafts (equal or less to 131 lm) had better visual

(microkeratome or Femtosecond laser). Tissue

outcomes than thicker grafts 1 year after

preparation can be performed by the operating surgeon prior to surgery, or by an eye bank

surgery.

technician (pre-cut tissue). After the donor tissue is prepared, it is cut with a trephine to

DSAEK: Results Over the last few years, DSAEK has become

the desired diameter, usually 8–9 mm and the

established as the technique of choice in many centers worldwide, as it provides superior and

to

the

8.0-mm

posterior lenticule is inserted into the recipient’s anterior chamber using a variety of

predictable visual recovery compared to PKP

different surgical instruments (forceps, glides, inserters) [78]. Once properly unfolded, the

[86]. In the report published by the American Academy of Ophthalmology [87], the average

endothelial graft is attached to the recipient

post-operative CDVA measured in Snellen (mean 9 months, range 3–21 months) ranged

stroma using an air bubble. More recently, thin DSAEK techniques [79,

from 20/34 to 20/66. A mean CDVA of 20/40

80] are becoming increasingly popular in order to overcome issues related to endothelial graft

was generally achieved by 3–6 months after surgery [88–90]. A review of post-operative

thickness as this directly influences the posterior radius of the curvature and thus, the

refractive results found induced hyperopia ranging from 0.7 to 1.5 D, (mean 1.1 D), with

refractive power of the cornea, leading to a post-

minimal-induced astigmatism ranging from -

operative hyperopic shift correlated to the thickness of the graft (thicker grafts induce

0.4 to 0.6 D and a mean refractive shift of 0.11 D [91]. It has clearly been demonstrated by these

more hyperopia) [80]. Yoo et al. [81] reported the 1-year results of anterior segment optical

studies that DSAEK does not induce astigmatism and this is considered a major

coherence tomography after DSAEK combined

advantage with respect to PKP. In contrast,

with phacoemulsification in patients with Foch’s dystrophy. A significant correlation

Coster et al. [26] reported visual outcomes significantly better for penetrating grafts than

between the ratio of central graft thickness to mean peripheral donor corneal lenticule

for DSAEK performed for Fuchs’ dystrophy (P\0.001), but DSAEK achieved better visual

thickness at 3 mm and induced hyperopic

outcomes

shift (R(2) = 0.65, P\0.001) was observed. In an attempt to improve visual outcomes a

pseudophakic bullous keratopathy (P\0.001). The Coster registry study is mostly based on

trend towards thinner grafts has been developed. A double pass with the standard

results by low volume surgeons who may be inferior to those reported by high volume

non-disposable microkeratome system on the

surgeons worldwide. With regard to DSAEK graft survival, the

donor lenticule has been successfully described but the risk of perforation can be a possible drawback [82, 83]. Thin grafts employing

than

penetrating

grafts

for

American Academy of Ophthalmology report concluded that the rate of clear grafts varies

Adv Ther (2014) 31:494–511

504

between 55% and 100%, with an average of

endothelial

94% graft survival at 1 year post-operatively [87,

intraocular lens (IOL), treated with DSAEK.

failure

implanted

with

toric

91–93]. Price and Price [93] reported a 2-year graft survival of 99% in a cross-sectional and

Three months post-operatively the cornea was clear with no edema. UDVA was 20/40 and

longitudinal retrospective analysis of 263 eyes. The 3-year survival rate as reported by the same

corrected distance visual acuity was 20/25 with ?1.50 - 1.00 9 20.

research group did not differ significantly between DSAEK and PKP procedures performed for either Fuchs’ dystrophy (96%

DSAEK: Complications

for both; P = 0.81) or non-Fuchs’ cases (86% vs. 84%, respectively; P = 0.41) [94]. In the Coster

following DSAEK surgery are graft dislocation and primary graft failure, both significantly

et al. [26] study, graft survival performed for

associated with the learning curve and surgical skill. The prevalence of graft dislocation

Fuchs’ dystrophy or pseudophakic bullous keratopathy was poorer than survival of

The

most

common

early

complications

requiring additional air to attach the lenticule

penetrating grafts for the same indications over the same era (P\0.001).

ranges between 1% and 82% [99]. Reported rates of primary graft failure (PGF) after DSAEK

An important advantage of DSAEK that

vary between 0% and 29% [94]. Graft rejection rates following DSEK range from 0% to 45.5%,

contributes to the low failure rates is the concept of anterior chamber immune privilege

with follow-up from 3 months to 2 years, were

and deviation [95]. A full thickness graft exposes the endothelium to superficial lymphatic

significantly lower as compared to PKP [94, 95]. Other potential complications following DSAEK

drainage and antigen processing, whereas endothelial grafting does so to a much lesser

surgery include iatrogenic pupillary block glaucoma from the residual air bubble [99],

degree, or not at all, where the antigen

interface epithelial downgrowth [100], corneal

processing is privileged through blood born lymphocytes and the spleen.

infection [101] and endophthalmitis [102]. Lastly, Suh et al. [99] reported a case of limited

The 6-month EC loss for DSAEK ranges between 13% and 54% and at 1 year it ranges

intraoperative suprachoroidal hemorrhage that was managed successfully; the DSAEK small

from 15.6% to 61% [88]. Most of the EC

incision surgery, in contrast to PKP which is

diminution occurs in the first 6 months after the procedure.

open sky, permitted a readily closure and a second step completion of the transplantation.

Fernandez et al. [96] were the first to report the results of DSAEK in a 9-year-old child with

DMEK: Surgical Technique

promising results. Kymionis et al. [97] reported the first case of DSAEK in a 4-year-old boy for the management of irreversible endothelial

DMEK allows transplantation of an isolated endothelium DM layer without adherent corneal stroma [7]. It is a relatively difficult

rejection after penetrating keratoplasty. Three months after the procedure, the cornea

technique requiring high surgical dexterity and therefore its use is currently limited. Donor

remained clear with the donor button in

tissue preparation includes the use of corneoscleral buttons excised and stored by organ

place. Kymionis and Kontadakis [98] also presented an interesting case of an adult patient with penetrating keratoplasty graft

culture in modified minimum essential medium at 31 °C or cold storage medium. After 1 week of

Adv Ther (2014) 31:494–511

505

culture, EC morphology and viability were

109] and Laaser et al. [110] at 6 months post-

evaluated and the corneo-scleral buttons are

operatively. The average 6-month endothelial

mounted endothelial side up on a custom-made holder with a suction cup. DM is stripped from

cell loss after DMEK was 32% in three different patient series [104, 109, 110] while the 12- and

the posterior stroma, so that a 9.0- to 10.0-mm diameter flap of posterior DM with its

24-month follow-up showed further ECD decrease but with no statistical significance

endothelial monolayer was obtained [103].

[111]. These data are short term and therefore

Owing to the elastic properties membrane, a ‘Descemet-roll’

of the forms

longer follow-up is necessary for further critical appraisal of this novel technique.

spontaneously, with the endothelium on the outer side. Each Descemet-roll is then stored in

DMAEK data although limited are equally promising. Early results demonstrate a mean

organ culture medium until the time of

CDVA at 1 month of 20/30 (range 20/15–20/50)

transplantation. Price et al. [104] describe an alternative

with approximately 90% of patients achieving 20/40 or better [105]. Nevertheless, further

technique in which the peripheral DM of the donor is gently scored, and then the scored edge

refinements in the technique are needed before it can begin to replace DSAEK.

of DM is grasped with a non-toothed forceps and slowly stripped away from the stroma approximately half way to the center for 360°.

DMEK/DMAEK Complications

A central partial-thickness trephination is then performed endothelial side up on the donor

DSAEK. Rejection episodes have been reported, but it is interesting to point out that in a study

cornea, and the separation of the central punched DM is completed using non-toothed

by Anshu et al. [112] investigating the relative risk of rejection following DMEK in a

forceps.

comparative study evaluating DMEK, DSEK,

In DMAEK, lamellar dissection is automated and performed using a microkeratome as for

and PK performed for similar indications and with the same steroid regimen, it seems that the

DSAEK [105, 106]. Kymionis et al. [107] have described DMAEK with the use of an

Kaplan–Meier cumulative probability of a rejection episode at 2 years was only 1% for

epikeratome.

DMEK versus 12% for DSEK and 18% for PKP.

DMEK and DMAEK: Results

Primary graft failure of 8% has been reported in a consecutive series of 60 cases [104]. Glaucoma

Visual rehabilitation with DMEK occurs fast and can be very successful. In particular, early

or persistent ocular hypertension after DMEK has also been reported [7].

DMEK complications are similar to those with

results with DMEK in a study by Price et al. [104] showed that mean CDVA was 20/30 at 1 month (range 20/20–20/60). At 3 months,

CONCLUSIONS

26% of patients had 20/20 vision, 63% 20/25 or better, and 94% 20/40 or better. The

Continuing

refractive cylinder remained unchanged at 0.9 D, but a statistically significant hyperopic

transplantation techniques have led to a growing tendency towards selective

shift of 0.50 D was evident. Similarly promising

replacement of the diseased area of the cornea. This evolving approach appears to provide

results were reported by both Ham et al. [108,

improvements

in

corneal

Adv Ther (2014) 31:494–511

506

considerable advantages compared to the older, open-sky corneal procedures. Anterior stromal and posterior endothelial keratoplasties continue to evolve in order to minimize the risk of graft rejection, accelerate recovery times and offer patients superior visual outcomes. On

Conflict of interest. G. D. Kymionis, D. G. G.

Mikropoulos, Boboridis, I.

D. C.

M. Portaliou, Voudouragkaki,

K. N.

D. Dragoumis and A. G. P. Konstas declare no conflict of interest.

the other hand, these lamellar procedures are

Compliance with ethics guidelines. This

more technically demanding and time consuming, and interface irregularity arising

article does not contain any new studies with human or animal subjects performed by any of

from manual lamellar dissection may result in suboptimal visual outcomes.

the authors.

In the future, ophthalmic surgeons need to become familiar with these new techniques in order to incorporate them into their

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