The History of Corneal Transplantation




© Springer International Publishing Switzerland 2016
Jesper Hjortdal (ed.)Corneal Transplantation10.1007/978-3-319-24052-7_1


1. The History of Corneal Transplantation



Gabriël van Rij  and Bart T. H. van Dooren2


(1)
Department of Ophthalmology, Erasmus Medical Center, Rotterdam, The Netherlands

(2)
Department of Ophthalmology, Amphia Hospital, Breda, The Netherlands

 



 

Gabriël van Rij



Abstract

The concept of corneal transplantation is very old. However, it took many centuries before this miraculous operation could be performed with some success in both animals and humans. Knowledge of the history of keratoplasty is obligatory for a better understanding of modern corneal transplantation.

In the second half of the twentieth century, penetrating keratoplasty became the gold standard in corneal transplantation. Good results became more or less routine, due to a better knowledge of indications for treatment, a better understanding and hence prevention and treatment of allograft rejection and improvements in eye banking, operating microscopes, instruments and suture materials.

The recent two decades have once more seen a paradigm shift towards the selective replacement of only the diseased layers of the cornea. This has resulted in a rapid rise in the popularity of (deep) anterior lamellar and endothelial keratoplasty.


Keywords
History of keratoplastyCorneal transplantationPenetrating keratoplastyDeep anterior lamellar keratoplasty (DALK)Endothelial keratoplasty (EK)



History of Keratoplasty


In ancient times, cosmetical treatment of corneal scars had been performed by means of a tattoo-like coloration of the scar. Lampblack or soot was used in old Egypt (±1500 BC), and copper sulphate reduced with nutgall was applied to achieve reasonable cosmesis by Galenus (131–200 AD). In the eighteenth century, superficial removal of scars was widely performed by surgeons in France and Germany [1]. The idea of removing scars from the cornea using a trephine was first proposed by Erasmus Darwin (the grandfather of Charles Darwin) in 1796 [2]. In 1789 Pellier De Quengsy introduced his ideas on treating corneal opacification with what would now be called keratoprosthesis, i.e. the replacement of opaque corneal tissue by man-made material. His concept entailed an artificial cornea made from glass framed in silver [3]. Attempts in the second half of the nineteenth century to actually treat patients with artificial corneas, among others by von Hippel and by Nussbaum, were not successful [4, 5]. The artificial cornea concept was in fact not developed into a useful technique until 1963, when among others Strampelli published on successful clinical application of keratoprostheses. In Strampelli’s case, this was the osteo-odonto-keratoprosthesis, in which the optical element was embedded in a biocompatible carrier made out of the patient’s own tooth and jawbone [1, 6]. Recently the application of keratoprostheses made of artificial materials has increased, with variable results in patient groups with significant high-risk eyes [7].

The first widely known experiments with full-thickness tissue corneal transplantations in animals, conducted in 1818, either heterologous (between species a.k.a. xenografting) or homologous (within species), are attributed to Reisinger. He also introduced the term “keratoplasty” for corneal transplantation [8]. Wars at the end of the eighteenth and the beginning of the nineteenth centuries made corneal blindness from smallpox, venereal disease and “Egyptian ophthalmia” (trachoma) prevalent. With this background, Bigger performed the first successful corneal transplantation in animals. In 1837, during his captivity in Egypt by Sahara Bedouins, he performed a homograft on his captor’s pet gazelle which had been blinded by a corneal wound [9].

Heterologous transplantations of animal tissue into humans were then attempted. In 1838, the New York ophthalmologist and general practitioner Richard Sharp Kissam transplanted a pig’s cornea into a human patient. Kissam operated without any anaesthesia. Ether anaesthesia was not introduced until 1846, chloroform anaesthesia in 1847 and topical cocaine anaesthesia in 1858. His patient initially received more light in his eye, but the cornea opacified and absorbed over a 2-week period [10]. The experiments on corneal transplantation in humans and animals conducted by Power, described in 1872, suffered the same fate [11].

Success in heterografting remained elusive until the first successful lamellar heterograft in a human by Von Hippel. A leucoma corneae was excised from a young girl’s eye with Descemet’s membrane and endothelium remaining, and a rabbit cornea was transplanted into the wound bed. This procedure was performed in 1886 and was described in 1888 as the first in a series of 8 lamellar operations, of which 4 were successful [4]. Von Hippel performed anterior lamellar keratoplasty because he felt that corneal transparency depended on the integrity of the corneal endothelium and Descemet’s membrane. Therefore, he abandoned full-thickness corneal grafts.

It was not until 1905 that the first successful penetrating homologous corneal graft was performed in a human patient. The Moravian ophthalmologist Eduard Konrad Zirm transplanted a donor cornea obtained from an enucleated eye of a young boy into the eye of a 45-year-old labourer, suffering from corneal scars caused by a chemical lye injury. Zirm used general anaesthesia (chloroform) and strict asepsis [12].

Shortly thereafter, the concept of auto-keratoplasty or homograft was initiated. In this concept the donor cornea was harvested from the patient itself: from the fellow, blind eye, as described by Plange [1], or as a rotational graft in which a small corneal scar can be rotated out of the visual axis in the diseased eye, as described by Kraupa [5].

Allografting, in which the donor cornea is harvested from another individual of the same species, is currently the most commonly practised form of corneal transplantation. However, it took quite some time after Zirm, before reproducible results with penetrating corneal allografts were obtained. First the operative technique and donor tissue preservation and preparation had to be further developed and standardised. Much work in this respect was done and published in the 1920s and 1930s by Elschnig from Tsjechia, Filatov from Russia, Tudor Thomas in the UK and Castroviejo in the USA [1318]. Improvements in lamellar transplant technique were achieved by the French ophthalmologists Paufique et al. [19] and Switzerland’s Franceschetti [20], from the 1930s through the 1950s, leading to a temporarily renewed popularity of this treatment modality.

The biggest hazard to a successful penetrating corneal graft is allograft rejection. Paufique described the concept of “maladie du greffon”, i.e. opacification of a previously clear cornea, which he attributed to sensitisation to the donor by the recipient [19]. This seminal concept of immunological rejection of the donor graft was proven by Maumenee in 1951 [21]. Much important work in the field of corneal allograft rejection was done by Khodadoust and Silverstein [22, 23]. The use of corticosteroids realised a breakthrough in the treatment and prevention of corneal transplant rejection and opacification. This concurred with the introduction of antibiotics, the introduction of the operation microscope, the development of microsurgical techniques and of newer suture materials that ensued. Other important developments included the better understanding of endothelial physiology and of donor cornea preservation. US-based ophthalmologists and scientists such as Paton, Troutman, Maurice, McCarey and Kaufman played important roles in these developments [24, 25]. All these developments led to a substantial improvement in the popularity of penetrating keratoplasty and hence in the number of cases operated with this technique.


Recent and Current Developments in Penetrating and Lamellar Keratoplasty



Penetrating Keratoplasty


In the past, penetrating keratoplasty was considered the gold standard in corneal transplantation. In penetrating keratoplasty (PK), a full-thickness button of diseased cornea is replaced by full-thickness corneal donor tissue. A successful outcome after a penetrating keratoplasty is a clear graft with low astigmatism, providing a good visual acuity. Irregular and high regular astigmatism are the most frequent visual acuity impairing complications after penetrating keratoplasty.

At present there are three forms of penetrating keratoplasty: traditional penetrating keratoplasty; anterior mushroom keratoplasty, with a wider anterior than posterior diameter; and top-hat (or posterior mushroom) keratoplasty, with a wider posterior than anterior diameter. A top-hat keratoplasty is indicated in patients with both endothelial failure and secondary stromal opacities. Anterior mushroom keratoplasty has better astigmatic properties and can be applied in patients with relatively healthy endothelium [26, 27].

Femtosecond lasers have recently been applied to more reproducibly fashion several types of (mushroom and other) shaped corneal incisions in both donor and recipient corneas [28].

The graft survival in all types of PK is good in low-risk cases, with a success rate of 80 % or more of having a clear graft after 10 years. The cornea enjoys a relative immune privilege being avascular tissue, and furthermore immunosuppressive treatment can be directly applied in high concentrations using eye drops. Therefore, HLA matching of donor tissue to recipient status is usually not performed in low-risk cases, and still good graft survival rates are obtained. Allograft rejection however is still one of the major causes of corneal transplant failure in PK [29]. When a cornea becomes vascularised, the risk for corneal graft rejection is elevated. High-risk cases include repeat transplantations, especially after previous allograft rejection, and corneas with extensive deep blood (and lymph) vessel ingrowth [29, 30].

Other important reasons for graft failure in PK are (secondary) glaucoma, ocular surface problems and late endothelial failure [29]. The concept of late endothelial failure is an intriguing problem. After PK, grafts lose endothelial cells at a faster than physiological rate, even in the absence of overt endothelial allograft rejection. The exact cause for the elevated endothelial cell loss rate needs yet to be determined. Hypothetically it may arise from prolonged cell redistribution onto the recipient cornea or from chronic pro-apoptotic changes in the anterior chamber [3133].


Anterior Lamellar Keratoplasty


In anterior lamellar keratoplasty (ALK), only the diseased epithelium, Bowman’s membrane and (anterior) corneal stroma are removed and transplanted, leaving the unaffected but vulnerable endothelium of the patient in place. Indications for ALK include many cases of keratoconus, epithelial and (anterior) stromal corneal dystrophies and partial-thickness post-infective (i.e. non-active, of herpetic and non-herpetic origin) and non-infective (e.g. traumatic) corneal scars.

In the 1960s and 1970s, the frequency with which anterior lamellar keratoplasty was performed sank inversely with the increase in PK’s success and hence popularity. This was mainly caused by ALK’s disappointing visual results. A large part of these poor results stem from the irregular scattering of light (diffraction) at the recipient-donor wound interface. The need for a very smooth recipient and host surface at the wound interface, which was to be obtained more readily at a deeper corneal plane, was recognised early on. However, to attain this goal required both surgical skills and time [34]. Yet, the advantages of ALK over PK in suitable indications remained tempting. There were less complications to be expected, as ALK was not truly an intraocular surgery. There was no risk of postoperative endothelial rejection and probably less risk of late endothelial failure and open globe after traumatic wound dehiscence.

In spite of this, comparative studies from the late 1970s kept on showing that visual results were better after PK than after ALK for keratoconus – one of the most apt indications for ALK [3436]. However, good visual results were actually shown to be obtainable, when the lamellar dissection could be made at or just above the level of Descemet’s membrane which presented a natural, very smooth opticalinterface [37]. It was not until the introduction of the “big-bubble” technique by Anwar, however, that Descemet’s membrane could reproducibly be bared. In this technique an air bubble is used to dissect through the corneal stroma and to split the stroma from Descemet’s membrane. A nearly full-thickness donor cornea, devoid of donor endothelium, is sutured in. Visual results after deep ALK with the big-bubble technique proved to be as good as or even better than PK [38]. Injecting viscoelastic material into the deep stroma can also be used to bare Descemet’s membrane [39].

Microkeratome and femtosecond laser-assisted approaches towards ALK have recently gained some interest. Especially with the microkeratome, both the recipient and donor lamellar interfaces can be cut very smoothly. For selected cases, the results are promising [40].


Endothelial Keratoplasty


Endothelial keratoplasty (EK) is a treatment concept aimed at replacing only the diseased endothelium and posterior corneal layers, which have caused corneal clouding through oedema. Disorders that may be treated with EK include endothelial dystrophies, especially Fuchs endothelial dystrophy, iridocorneal endothelial (ICE) syndrome and pseudophakic bullous keratopathy. The main advantage of this concept is an untouched anterior corneal curvature, resulting in much less suture-induced high and irregular astigmatism, as can be seen after PK. Other suture- and full-thickness wound-related complications such as infections and wound dehiscence can also be avoided.

Barraquer was the first to publish on the concept of selective transplantation of an endothelium-containing posterior corneal lamella for the treatment of corneal oedema. In 1951 he reported for the first time on such a design, which involved the (manual) cutting of a hinged anterior lamellar corneal flap, followed by the excision and replacement of a deep corneal stroma lamella including the endothelium [41]. In 1964 he reported on the first results obtained with this technique in two patients, who obtained clear grafts and good visual acuities. In 1983 he introduced the motor-driven microkeratome in EK for the cutting of the anterior flap in both donor and recipient and reported a good result in one patient [42].

Apparently unaware of Barraquer’s work, Tillet published a report in 1956 on the selective transplantation of a posterior donor corneal lamella with endothelium, performed successfully in a patient with Fuchs’ endothelial dystrophy, in 1954. The posterior recipient disc had been excised after a manual lamellar dissection through a 180° superior corneal incision. The half-thickness donor posterior disc was positioned onto the posterior surface of the recipient’s anterior cornea and fixated with silk sutures. The graft remained clear for at least 1 year. However, the visual results were disappointing because of a poorly controlled glaucoma [43].

In the late 1970s, the concept of selective endothelial transplantation gained new interest, when experimental models were developed for the transplantation of cultured human and heterologous corneal endothelial cells. Experiments were performed with seeding the endothelial cells on animal and human donor corneas, Descemet’s membranes, amnion membranes and artificial carrier devices [44]. Experiments on bioengineered corneal constructs with cultured human corneal endothelial cells have continued into the present time [45]. Although progress has been made, none of these techniques has reached the clinical phase yet.

Only gold members can continue reading. Log In or Register to continue

Stay updated, free articles. Join our Telegram channel

Mar 20, 2017 | Posted by in OPHTHALMOLOGY | Comments Off on The History of Corneal Transplantation

Full access? Get Clinical Tree

Get Clinical Tree app for offline access