Thursday, 27 September 2012

Lamellar keratoplasty : Growing acceptance By Anurag Mathur,MS; Sonu Goel ,DNB; Sonai Mukherjee,MBBS

Dr Sudhir Singh
Prof. P.K Mathur
Dr  Pavan Shorey
Editorial Board
Dr Anshoo Choudhary
Dr Arun Kshetrapal
Dr L S Jhala
Dr Mayank Agrawal
Dr Mukesh Sharma
Dr Sandeep Arora
Dr Sonu Goel
Dr Subodh Saraf
Dr Sukesh Tandon
Dr Sunil Gupta
Dr Suresh Kumar Pandey
Dr Swati Tomar
Dr Virendra Agrawal

Lamellar keratoplasty :  Growing acceptance
Anurag Mathur,MS; Sonu Goel ,DNB; Sonai Mukherjee,MBBS
Corresponding Author
Dr. Anurag Mathur
M.S. (ophthalmology)
Consultant - Cornea and Anterior Segment
Anand hospital & eye centre
Jaipur (Rajasthan)
Article Code RJO20110107
“Could not a small piece of cornea be excised with a trephine, the size of a small bristle or a large quill and would it not heal with a transparent scar?”
- Erasmus Darwin 1760
Since the first inception of the idea of penetrating keratoplasty, the world has seen a sea of change with respect to concept of the modern day corneal surgery. Penetrating Keratoplasty (PK) is a 100 year old technique. It is well established and routinely performed in large numbers across the globe but there are certain issues associated with this procedure. In PK long term survival depend on endothelial cells transplanted at the time of surgery. Structural and immunological integrity of the eye is breached.Allograft rejection is still a major cause for graft failureContinuous loss of endothelium is another concern.
Due to these complications there was a compelling need to find procedures whereby these issues could be minimized. Lamellar procedures like DLK, DLEK, DSEK, DMEK etc. are comparatively safe and risk of rejection and subsequent failure, endothelial cell loss and damage to the structural integrity of the eye are less than full thickness procedure. Also these procedures ensure more efficient utilization of available tissues.

Deep lamellar keratoplasty (DLK)
Lamellar keratoplasty was first described by von Walther
in 1830. 1
Stromal pathologies not involving endothelium accounts for about 1/3rd keratoplasties . In DLK the
advantage is of retaining host DM, therefore risk of allograft rejection is substantially low. DLK also offers advantage of  shorter postoperative steroid therapyreduced risk of anterior synechiae  and reduced risk of intraocular infection due to a “closed eye” procedure.
DLK is a technically difficult procedure. Goal is to reach to the level of DM in every case so as to leave minimal stromal tissue behind which may be responsible for delayed and suboptimal visual recovery and increased interface haze. various techniques have been described to bare DM which include manual dissection by Anwar in 19722, using air injection by Archilla3, Rostron4 and Anwar5 (Big bubble technique) independently with slight modifications in the technique, hydrodelamination by Sugita6, visco dissection by Teichmann and others7, Peeling techniqueMalbran8 1965, Polack9 1971,and Gasset10 in 1979 and Divide and conquer technique described by Tsubota11 1998 etc.
Anwar Big bubble technique of DALK  is the preferred technique these days as it is easier, safer and speedier than other methods of lamellar dissection.  Visual recovery  comparable to PK and endothelial cell loss is significantly less than PK have been reported by various studies.
Major complications associated with this procedure are perforation of DM (10- 30%) and formation of pseudo anterior chamber.
Management of Descemet’s membrane perforation depends upon the size and location of the defect. Microperforations in the periphery  can be managed by air injection into the anterior chamber at the end of surgery. The air bubble acts as a tamponade to seal the hole. Larger tears, usually spanning from rim to rim or along the circumference of the trephine excision are more difficult to manage.
Pseudo anterior chambers occur secondary to breaks in Descemet’s membrane. A shallow separation between donor tissue and host DM often resolves spontaneously but for larger separations require air or gas injection intracamerally.
 Endothelial Keratoplasty
 Endothelial keratoplasty refers to selective replacement of the diseased endothelium. At present, over 50% of corneal transplants are performed primarily to treat endothelial dysfunction.
Terry et al have described 5 goals for the ideal EK procedure12
(1) a smooth surface
topography without significant change in astigmatism from
preoperative to postoperative status;
 (2) a highly predictable and stable corneal power;
(3) a healthy donor endothelium that resolves all edema;
(4) a tectonically stable globe, safe from injury and infection; and
(5) an optically pure cornea.
Evolution of endothelial keratoplasty:
Full-thickness corneal transplantation
Posterior lamellar keratoplasty [ PLK]. Melles, 199813
Deep lamellar endothelialkeratoplasty (DLEK). Terry and Ousley, 200114
Descemet-stripping endothelial keratoplasty. Price, 200515
Descemet-stripping automated endothelial keratoplasty (DSAEK). Gorovoy 200616
Descemets membrane endothelial keratoplasty ( DMEK).17
Cultured endothelial cells transplantation. Melles, 200618

  • Fuchs endothelial dystrophy
  • Pseudophakic bullous keratopathy
  • Aphakic bullous keratopathy
  • Failed graft
  • Iridocorneo endothelial syndrome
  • Argon Laser Iridotomy induced bullous keratoplasty
  • Descemet Membrane Breaks After Forceps Delivery
  • Congenital Hereditary Endothelial Dystrophy
  • Bee sting injury
          Retention of normal corneal topography
          Faster wound healing- faster visual rehabilitation
          Stable globe intraoperatively- risk for deadly expulsive suprachoroidal hemorrhage is minimized.
          More resistant to injury after surgery
          Reduced chances of graft failure from ocular surface disease
          Reduced suture related complications
          Preservation of corneal sensation may provide another advantage of DSAEK over traditional penetrating keratoplasty.
          Two lamellar procedures can be done with help of single donor cornea

Comparing DSEK with penetrating keratoplasty:
DSEK appears similar to PK in terms of:
          Surgical risks
          Complication rates
          Graft survival (clarity)
          Visual acuity and
          Endothelial cell loss.
DSAEK superior to Penetrating Keretoplasty in terms of:
          Earlier visual recovery
          Refractive stability
          Postoperative refractive outcomes
          Wound and suture-related complications and
          Intraoperative and late suprachoroidal hemorrhage risk.
 The tissues can be precut in the eye bank using the Moria microkeratome system or the manual dissection using the artificial anterior chamber. The results of the precut tissue were comparable with that during the surgery.
Similarly, when comparing the results of microkeratome assisted tissue dissection compared to manual dissection, the visual recovery was faster with microkeratome assisted tissue dissection.19
 Femtosecond assisted dissection of the tissue gives a more predictable cut and planar configuration with a center to periphery ratio of lenticule close to 1, which helps in avoiding any refractive surprises and post operative hyperopia in cases where DSEK is combined with phacoemulsification and IOL implantation.
With respect to the donor tissue selection for DSEK, any donor tissue with a good endothelial cell count and a good sclera rim is preferred. With respect to use of pediatric donor tissue for DSEK, pediatric donor tissue may be very flaccid and would give an unpredictable cut on the moria microkeratome system. For such cases it is preferable to use the manual dissection.
Surgical procedure of DSEK
The surgical procedure includes making a standard sclera or corneal tunnel to enter the anterior chamber. A 7 to 8 mm mark is made using a trephine on the cornea. This helps in guiding the descemetorrhexis. The descemetorrhexis is performed using a reverse sinskey hook. This process can be assisted by improving the visibility of the anterior chamber using air, trypan blue or chandelier illumination system. In case phacoemulsification is to be done as a combined surgery, first the phacoemulsification is completed and then descemetorrhexis is carried out.
Having scored the descemets membrane the diseased descemets membrane can be peeled off using a forceps or a descemets stripper or using an automated irrigation and aspiration canula.
After the removal of the descemets membrane, a few surgeons prefer to scrape the edges of the scored area. This helps in improving the adhesion of the graft to the stroma.
It is essential that all the viscoelastic is removed from the eye after the desecemts has been scored. Any viscoelastic in the eye can result in the post operative increased chance of dislocation of the lenticule.
Methods of insertion of the donor lenticule:
A number of methods have been devised to insert the lenticule in the anterior chamber
The taco fold20 was once the most famous technique for the donor lenticule insertion. This involved folding the donor lenticule into a 60:40 taco fold followed by insertion using a non coapting forceps. This was however associated with a  high complications rates related to the difficulty in unfolding in the anterior chamber and eventual trauma to the endothelial cells. A modification of the technique was using a Hitch suture21 which is a 10-0 MFN suture that is passed through the graft loop made on one side of the graft.  The suture is passed on the 40 % fold which is placed inferiorly and the lenticule is unfolded using a sinskey hook that pulls on the suture.
However, due to the high endothelial cell loss, up to 34.3%, associated with the forceps technique there has been a search for development of non traumatic techniques for the donor lenticule insertion.
The first step towards this was the development of the Busin glide22 for the donor insertion. Busin glide consists of a specialised instrument that can load and carry the lenticule with the endothelial side up and helps in inserting the lenticule using the pull through technique using a specialised forceps. This technique is associated with an endothelial cell loss of up to 25%.
Another technique involved the use of cartridge for the insertion of the donor lenticule. This further decreased the endothelial cell loss to 9 %.
The sheet glide described in the cataract surgery has been used for donor lenticule insertion. The donor lenticule is placed on healon smeared sheet glide with the endothelial side down and the donor lenticule can then be inserted into the anterior chamber using either needle push through or forceps pull through technique. The endothelial damage by this method is 9%.  Recently, a number of devices have been developed which act as both carrier and injector systems for insertion of the donor lenticule into the anterior chamber. The latest among these is the Tan’s endoglide which is specially designed to avoid any endothelial surface rubbing against each other with an endothelial cell loss of only 5 % in one series.
After insertion of the donor lenticule into the anterior chamber it is important to secure the donor into position to allow adequate apposition with the stroma of the host. This is achieved using air tamponade. Many surgeons believe in complete air fill only for a period of 7 to 10 minutes followed by partial air removal, in order to prevent any undue increase in intraocular pressure and related optic nerve damage.
This is followed by suturing the wound watertight.
A few surgeons also prefer to give venting incisions, around 4 to 5 incision in order to drain out any fluid from the interface.
During the post operative period the patient is kept on frequent doses of topical steroids and antibiotics. Antiglaucoma medications may be added as per need.
Non descemets stripping endothelial keratoplasty:
Recently, Kobayashi A et al 23suggested that not stripping the descemets membrane provides a better and smoother interface with comparable dislocation rates.  Histopathological studies on the corneas undergoing keratoplasty following failed DSEK have proved that even in areas with retained host descemets membrane, the adhesion of the donor lenticule is equally good. Thus, adhesion of the donor to the host stroma does not appear to involve significant scarring or keratocyte proliferation. Contrary to previous assumptions, retained DM does not appear to hinder graft adhesion, raising the possibility that removal of DM may be unnecessary for endothelial transplantation.
New triple procedure:24
Phcoemulsification with DSEK has become the new triple procedure. In cases of Fuchs endotheial dystrophy with cataract, phacoemulsification with simultaneous DSEK has become the procedure of choice. The combined surgery has similar dislocation rates, with no iatrogenic graft failures, a rapid visual recovery and similar rates of endothelial cell loss. Special considerations during the combined surgery includes, use of viscocohesive viscoelastics during the phacoemulsification, small anterior capsulorhexis [~ 4mm]-to stabilize 6-mm optic IOL, complete removal of viscoelastic after descemetorhexis, IOL power 1.25 myopic- to compensate for post DSAEK hyperopia.
Complications of DSEK:
A recent report by the American Academy of Ophthalmology has given a review of available literature on DSEK. According to this report the Best-corrected Snellen visual acuity (mean, 9 months; range, 3–21 months) -20/34 to 20/66 with an induced hyperopia -0.7 to 1.5 diopters (D; mean, 1.1 D), and astigmatism ranging from 0.4 to 0.6 D.
Major complications of DSAEK include
          Posterior graft dislocations (mean, 14%; range, 0%–82%)
          Endothelial graft rejection (mean, 10%; range, 0%– 45%)
          Primary graft failure (mean, 5%; range, 0%–29%)
          Iatrogenic glaucoma (mean, 3%; range, 0%–15%).
          Average endothelial cell loss
          At 6 months :37%,
          At 12 months: 42%
Intraopertive complications:
  1. Inversion of the donor lenticule:
Rarely during the insertion the donor tissue may be inverted and may lie with the endothelial side lying at the stromal side of the tissue. This is corrected by flipping the lenticule in the anterior chamber.
Post operative complications:
  1. Donor dislocation:
Factors contributing to donor dislocation:
  • Residual ophthalmic viscosurgical device in the graft–host interface.
  • Trapped fluid in the graft–host interface.
  • Wrong orientation of graft.
  • Mechanical trauma to the donor material during insertion
  • Excessive manipulation [loss of donor viability]
  • Excessive  eye rubbing
Precautions to prevent donor dislocation:
  • No viscoelastic should be used as far as possible. If required Only viscocohesive agents should be used- and should be removed out of AC before graft insertion
  • Complete removal of Fluid between the Graft and Host
  • Massage of corneal surface
  • Four stab incision to drain out fluid
  • Minimal manipulation during surgery.
  • 8-9 mm air left at the end of procedure/ patient advised to lie down in Supine Position.
  • Grafts with Good Pre-Operative Specular Count to be used
Management of Dislocated lenticule
SF6 or C3F8 descemetopexy is done to achieve the adhesion between the lenticule and the host stroma. Recently, fibrin glue has been used in conjunction with the C3F8 gas in management of dislocated donor lenticule.
Another method to prevent dislocation includes presoaking of the donor lenticule in BSS plus solution. It has been postulated to work by making the presoaked tissue less lubricious for handling, more adherent to the stroma, and less likely to slide and become decentered. Also, presoaked tissues are thicker, more rigid grafts facilitating the folding, insertion, and unfolding of the graft. The glucose in BSS Plus also provides the energy source critical for endothelial cells
2.Primary graft failure:
          Primary Graft failure – graft edema never cleared after surgery. Corneal grafts that have not cleared after 2 months are classified as primary graft failures.
Incidence – 4% - 45 %
Factors for Graft Failure include:
          Lack of endothelial function
     From unhealthy tissue, unhealthy recipient circumstances
     (Blood, interface foreign bodies, infection, flat chamber
  • Persistent detachment of the graft
  • Retained descemet’s membrane
  • Traumatic loss of endothelial cells
  • Following graft rejection episode
  • Graft Loss [ dislocated to posterior segment]
Histopathological analysis of graft failure in DSEK:
Various histopatholical features of graft failure in DSEK include:
  • Chronic inflammatory infiltrate in the stroma. Collections of epithelioid histiocytes and lymphocytes are present on the posterior corneal surface.
  • Acute and chronic stromal inflammation, edema, and endothelial hypocellularity. Fibrous membrane that distorts graft’s surface
  • Folded segment of DM is incorporated into fibrous membrane
  • Marked donor stromal hypocellularity, severe endothelial atrophy, and peripheral anterior synechiae
  • Peripheral retrocorneal fibrous membrane is sometimes present, likely of stromal origin. In such cases stroma is edematous and paucicellular. Severe endothelial hypocellularity is present.
  1. Glaucoma:
Mechanism :
Acute glaucoma:
  1. Air in anterior chamber –pupillary block.
  2. Air migrating posterior to iris – peripheral iridocorneal adhesion
  3. Malignant glaucoma.
  1. Distortion of the angle leading to increased IOP
Delayed glaucoma induced by topical corticosteroids
Precautions to prevent pupillary block
  • Placing a freely mobile air bubble.
  • Cycloplegics at the end of the procedure.
  • Large iridectomy in aphakia
  1. Air in anterior chamber –pupillary block: Pupil dialation
  2. Air migrating posterior to iris – peripheral iridocorneal adhesion
  3. Malignant glaucoma: Pupil Dilatation
                                              Air removal from AC
                                             Anterior chamber reformation with/ without PI.
  1. Patient predisposed to glaucoma: Posterior vitrectomy

  1. Endothelial cell loss:
Following table suggest the mean endothelial cell loss in cases of DSEK vs PK25

  1. Graft rejection:
  • Probability of a rejection episode - 7.6%  (by 1 year) and 12%  (by 2 years)
  • Independent risk factor of rejection:
1. Pre-existing glaucoma or
2. Steroid responsive ocular hypertension.
3. Race African-American graft recipients.
  • Relative risk of graft rejection episodes not higher when the fellow eye had been grafted with DSEK within the prior year. Recommended time for second eye grafting : 1 months after primary surgery/ when vision stabilizes.
  1. Epithelial downgrowth:
Appear as large, whitish opacities seen at the graft-host interface and along the posterior corneal surface.
Melles et al  present the first published report of a successful pure Descemet’s membrane transplantation through a small 3.5–mm corneal incision, and have extended the EK lexicon to ‘‘Descemet membrane endothelial keratoplasty’’ (DMEK). While the visual recovery was reported to be rapid and complete due to the exquisitely smooth surface on both sides of the interface, also the early donor endothelial cell survival measured at 2350 cells/mm.
Method of DMEK : (as described by Melles)

Courtesy : Gerrit R.J. Melles et al. (Cornea 2006;25:987–990)

Compared with DSAEK, DMEK provided a significantly higher rate of 20/20 and 20/25 vision,with comparable endothelial cell loss. Descemet’s membrane endothelial keratoplasty restored physiologic pachymetry, but donor preparation and attachment currently are more challenging than with DSAEK.
Recently a modifications of the original technique was proposed26. In this technique which is known as DMEK-S new type of lamella consisting of bare DM-endothelium with a supporting stromal rim was used. Long term results from larger studies are still awaited for this technique.
1.Mühlbauer FX. Über Transplantation der Cornea. Gekrönte Preis- schrift. Munich. Jos. Lindauer, 1840. Abstract in Zeis: Schmidt CC(ed): Jahrbücher der in und ausländischen gesammten Medizin.Leipzig, Otto Wigand, 1842;267–8.
2. Anwar M. Dissection technique in lamellar keratoplasty. Br J Oph-thalmol 1972;56:711–33. Archila EA. Deep lamellar keratoplasty dissection of host tissue withintrastromal air injection. Cornea 1984-85;3:217–84. Chau GK, Dilly SA, Sheard CE, Rostron CK. Deep lamellar kerato-plasty on air with lyophilized tissue. Br J Ophthalmol 1992;76:646–505. Anwar M, Teichmann KD. Big-bubble technique to bare Descemet’smembrane in anterior lamellar keratoplasty. J Cataract Refract Surg2002;286. Sugita J, Kondo J. Deep lamellar keratoplasty with complete removalof pathologic stroma for vision improvement. Br J Ophthalmol 1997;81:184–87. Morris E, Kirwan JF, Sujatha S, et al. Corneal endothelial specularmicroscopy following deep lamellar keratoplasty with lyophilized tis-sue. Eye 1998;12:619–228. Malbran E. Lamellar keratoplasty in keratoconus. In: King JH, Mc-Tigue JW, eds. The Cornea-World Congress. London/WashingtonDC, Butterworths, 1965:511–189. Polack FM. Lamellar keratoplasty: Malbran’s “peeling off” technique.Arch Ophthalmol 1971;86:293–5.10. Gasset AR. Lamellar keratoplasty in the treatment of keratoconus:conoectomy. Ophthalmic Surg 1979;10:26–3311. Tsubota K, Kaido M, Monden Y, et al. A new surgical technique fordeep lamellar keratoplasty with single running suture adjustment. AmJ Ophthalmol 1998;126:1–812. Endothelial Keratoplasty:History, Current State, and Future DirectionsMark A. Terry, MD. Cornea  Volume 25, Number 8, September 200613. Melles GR, Eggink FA, Lander F, et al. A surgical technique for posteriorlamellar keratoplasty. Cornea. 1998;17:618–626
14 Terry MA, Ousley PJ. Deep lamellar endothelial keratoplasty in the firstUnited States patients: early clinical results. Cornea. 2001;20:239–243.
15 Price FW, PriceMO. Descemet’s stripping with endothelial keratoplasty in50 eyes: a refractive neutral corneal transplant. J Refract Surg. 2005;21:339–345.
16 Gorovoy MS. Descemet-stripping automated endothelial keratoplasty.Cornea. 2006;25:886–889
17 Melles GRJ, Ong TS, Ververs B, van der Wees J. Descemet membrane endothelial keratoplasty (DMEK). Cornea. 2006;25:987–990 18 McAlister JC, Joyce NC, Harris DL, et al. Induction of replication in human corneal endothelial cells by E2F2 transcription factor cDNAtransfer. Invest Ophthalmol Vis Sci. 2005;46:3597–3603 19 Farid M, Steinert RF femtosecond laser assisted corneal surgery.Curr Opin Ophthalmol. 2010 Jul;21(4):288-92
20. Mehta JS, Por YM, Poh R, Beuerman RW, Tan D Comparison of donor insertion techniques for descemet stripping automated endothelial keratoplasty. Arch Ophthalmol. 2008 Oct;126(10):1383-8
21. Macsai MS, Kara-Jose AC. Suture technique for Descemet stripping and endothelial keratoplasty.Cornea. 2007 Oct;26(9):1123-6
 24. Terry MA, Shamie N, Chen ES, Phillips PM, Shah AK, Hoar KL, Friend DJ. Endothelial keratoplasty for Fuchs' dystrophy with cataract: complications and clinical results with the new triple procedure. Ophthalmology. 2009 Apr;116(4):631-9
25. Price O et al.Descemet’s Stripping Automated Endothelial Keratoplasty Outcomes Compared with Penetrating Keratoplasty from the Cornea Donor Study. Ophthalmology 2009
 26. Pavel Studeny, Andrej Farkas, Magdalena Vokrojova, et al. Descemet's membrane endothelial keratoplasty with a stromal rim (DMEK-S). Br J Ophthalmol published online October 22, 2009 Br J Ophthal
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