Statistics from Altmetric.com
If you wish to reuse any or all of this article please use the link below which will take you to the Copyright Clearance Center’s RightsLink service. You will be able to get a quick price and instant permission to reuse the content in many different ways.
- medical education
- wound healing
- eye (tissue) banking
- treatment surgery
- treatment medical
- stem cells
Modern lamellar corneal grafting has done to penetrating keratoplasty what phacoemulsification did to extracapsular cataract extraction a few decades ago. Although, in a global context, both extracapsular cataract extraction and penetrating keratoplasty are probably more often performed than their modern counterparts, an irreversible change for better and for good has occurred. The concept of replacing only the diseased ‘layer(s)’ of the cornea, instead of replacing the whole (full thickness) cornea is not new. The earliest attempts at corneal grafting were indeed lamellar.1 Modern instrumentation and technology, in particular the operating microscope, have enabled surgeons to revisit the old concept and succeed where their predecessors had failed. When the stroma is affected with ectasia, scars or dystrophies such as granular or lattice, but the endothelium is normal, it makes sense to leave the recipient Descemet's membrane and endothelium behind. This considerably reduces the risk of immune rejection and graft failure. A collective term used to describe this approach is deep anterior lamellar keratoplasty (DALK).2 3 On the other hand, when the endothelium is affected, as in endothelial dystrophies, in particular Fuch's dystrophy and pseudophakic bullous keratopathy, it makes sense to replace only the endothelium while retaining the recipient's stroma and epithelium. This not only maintains corneal integrity and curvature, conferring a huge advantage, but for reasons not yet fully understood, also reduces the incidence of endothelial rejection.4 Endothelial keratoplasty has evolved rapidly over the last decade leaving in its wake a trail of new and at times confusing terminology. Descemet's lamellar endothelial keratoplasty,5 posterior lamellar keratoplasty,6 Descemet's stripping endothelial keratoplasty (DSEK),7 Descemet's stripping automated endothelial keratoplasty,8 Descemet's membrane endothelial keratoplasty (DMEK)9 and Descemet's membrane automated keratoplasty10 all refer to approaches towards the same objective and are more representative of the phases through which the procedure has travelled while being refined and perfected. The journey is by no means over.
The popularity of any new surgical procedure is directly related to the advantage it offers to the patient and the ease with which it can be performed. As different surgeons take on the procedure and experience builds, modifications, adaptations and nuances are introduced by individuals who often zealously guard the ownership of such refinements. With DALK and DSEK/DMEK the advantages are undisputed, but both are technically challenging requiring skill and dexterity. Several refinements have indeed been introduced and as expected led to some acrimonious debate. The following paragraphs deal with such refinements involving the use of air bubble(s) in the DALK and DMEK procedures.
In DALK, the challenge is in the separation of the entire stroma from the anterior surface of Descemet's membrane. Of the various techniques on offer, the one that provides the deepest and most desirable plane is the ‘big bubble’ technique first introduced by Anwar.11 Air is injected into the stroma with a 27–30-gauge hypodermic needle. The air forms a big bubble in the plane between Descemet's membrane and the stroma affecting a clean cleavage between the two. In the process, a number of tiny small bubbles may ‘fill’ the stroma rendering it opaque. When this occurs, the view through the recipient cornea is obscured making it difficult to ascertain whether a big bubble has formed or not. In October 2007, the journal published a paper describing the injection of small bubbles into the anterior chamber to help detect the formation of a big bubble in DALK.12 This was also accompanied by an editorial emphasising the usefulness of this tip.13 Confronted with an opaque recipient cornea, the authors had injected air into the anterior chamber in the form of a few small bubbles. These bubbles remained in the periphery of the anterior chamber and when the eye was moved with a forceps, the bubbles moved along the periphery of the anterior chamber indicating that the central part of the anterior chamber was occupied by the cleaved Descemet's and that a big bubble had been successfully achieved. This was a simple but useful tip.
A few months later, the editor of the journal received a letter from the authors of a paper published in another journal in January 200714 wherein it was described that air injected into the anterior chamber after achieving a big bubble remained in the periphery of the anterior chamber. Although the authors had used the small bubbles for a different purpose, the principle of the anterior chamber bubbles being retained on the periphery in the presence of a central big bubble was clearly demonstrated. The authors claimed priority in the description of the technique. They were invited to write a Letter to the journal to defend their claim, but one did not arrive. A scrutiny of the literature revealed that yet another author had claimed originality of this technique of using small bubbles in the anterior chamber to detect the presence of a big bubble.15 All three papers were published in the same year (2007) and submitted, accepted or published online the previous year (2006). It is highly likely that the three sets of authors independently conceived, tested and published the idea.
DSEK and Descemet's stripping automated endothelial keratoplasty have proven to be very successful procedures, but long term follow-up has revealed that most patients do not recover visual acuity of more than approximately 6/12.16 This has been attributed to the residual stroma used as a carrier for the Descemet's membrane and endothelium. DMEK, wherein a disc of Descemet's membrane without the posterior stroma is transplanted, was introduced by Melles9 to overcome this problem. This is reported to give visual acuity of 6/6 or better in 6–12 months after the procedure.17 One technical challenge with DMEK is the harvesting of a 8 mm or so disc of Descemet's membrane/endothelium with minimal endothelial cell loss.
In August 2010, Zarei-Ghanavati et al published a letter in the journal18 demonstrating and claiming a novel technique wherein air was injected into the stroma of a cadaver sclero-corneal disc to separate the Descemet's membrane, like in the big bubble technique described above. The air was then aspirated and the deflated Descemet's/endothelium was punched with a trephine from the endothelial side to yield a separated sheet of Descemet's/endothelium. This was a simple adaptation of the original idea to obtain tissue for DMEK.
Soon after publication the editor of the journal received an email from the corresponding author, S Zarei-Ghanavati, stating that another surgeon, Dr M Busin, had written to him claiming that the idea was originally his. In support, Dr Busin had presented evidence to show that he had presented this idea at an American Academy of Ophthalmology (AAO) meeting in Atlanta, Georgia, in 2008 and the paper was in press. Dr S Zarei-Ghanavati, however, claimed that he had no knowledge of this presentation and a literature search had not revealed any previous publication on the proposed modification.
In this journal (see page 1172), we publish the letter written by Dr Busin et al19 who have indeed demonstrated that the use of air to cleave the Descemet's membrane towards preparation of the DMEK button was an idea they had developed and presented at the AAO meeting in 2008 and subsequently published in Ophthalmology.20 We also publish the reply by Dr S Zarei-Ghanavati et al21 who contend that they arrived at the same idea independently and also show that their technique is different to that described by Busin et al although the principle is the same.
Another set of authors22 reported their novel use of the principle of a big bubble to obtain a DMEK button. Their paper was accepted for publication in October 2009 and had patients that were followed for 12–24 months, indicating that the authors had conceived and implemented the idea around 2006–2007.
It is quite possible that, like with the use of small bubbles to detect the presence of a big bubble in DALK, for DMEK as well, the three groups of authors independently conceived the same idea and developed it for clinical use.
Equally it is possible that an idea or part of it, presented at one meeting, is carried ‘on the wind’ and germinates into another idea at a distant site. The issue assumes considerable importance when intellectual property rights and patents are at stake. Here, of course, this is not the case as ‘air’ is available in plenty and difficult to sell, or is it?
A pint of beer must technically contain 568 ml of liquid. The ‘head’ or froth on a glass of beer usually occupies 10% of the volume of the container. Considering the global sale of beer this amounts to underselling of thousands of gallons of beer, making bubbles worth a small fortune!
On a more positive note, modern lamellar corneal surgery has changed the face of corneal transplantation. Many have contributed to its development (M Anwar, M Busin, G Melles, F Price, M Terry), but one stands tall. History will recall Gerrit Melles of the Netherlands Institute of Innovative Ocular Surgery, whose innovations and perseverance brought about this phenomenal revolution in corneal surgery.
Competing interests None.
Provenance and peer review Not commissioned; internally peer reviewed.