Corneal disease ranks as the fifth leading cause of blindness in the world.[1] Keratoplasty is the most common and successful transplantation in humans with the first transplant completed in 1905.[2]

History of Corneal Transplantation

Modern corneal transplantation techniques represent the culmination of centuries of ideas, experimentation, and perseverance. The French surgeon Pellier de Quengsy was the first to suggest the use of a transparent material to replace an opaque cornea in 1789.[3] Transplantation with xenografts was first postulated by Karl Himley in 1813 and attempted, experimentally and without success, by his student Franz Reisinger in 1824. Richard Kissam performed the first therapeutic corneal xenograft with a porcine cornea in 1838. The first successful human allograft and penetrating keratoplasty (PK) followed developments in anesthetics and antiseptic surgery and was performed by Eduard Zirm in December 1905 on a 45-year-old farm laborer with lime burns.[4][5]

Recent Developments

Scientific advances in immunology, surgical technique, and tissue banking have shaped corneal transplantation into the field it is today.[6][7] The last 20 years have brought significant developments in selective endothelial replacement that have brought about considerable shifts in the field.

Gerrit Melles described a posterior lamellar keratoplasty (PLK), whereby only a portion of the cornea was transplanted. Following an incision at the limbus, the endothelium, Descemet’s membrane (DM) and posterior stroma were dissected out and replaced by a donor button consisting of the same corneal layers that were held in place by an air bubble.[8] Mark Terry modified the PLK in 2001, including the use of viscoelastic material instead of an air bubble and renamed the procedure deep lamellar endothelial keratoplasty (DLEK).[9] In 2004 Gerrit Melles modified the technique further by only removing the host endothelium and DM (i.e., descemetorhexis), obviating the need for stromal dissection, and replacing with a donor button of endothelium, DM and stroma (Descemet’s stripping endothelial keratoplasty; DSEK) with further modification for automated donor dissection using a microtome (Descemet’s stripping automated endothelial keratoplasty; DSAEK).[10][11][12] In 2006 the technique was further developed by only transplanting a donor button of endothelium and DM without the posterior stroma (Descemet’s membrane endothelial keratoplasty; DMEK).[13] Minor modifications include automated posterior lamella dissection similar to DSEK (Descemet’s membrane automated endothelial keratoplasty; DMAEK).[14]

A selective keratoplasty technique that relates to the anterior cornea is the deep anterior lamellar keratoplasty (DALK), whereby a donor button replaces the epithelium, Bowman's layer, and stroma.[15]

Macroanatomy

The cornea is a transparent avascular structure that protects structures inside the eye and contributes to two-thirds of its refractive power. The cornea is convex, has a diameter of approximately 11.5 mm, and increases in thickness from the center (550-565 μm) to the periphery (610-640 μm).[16] The cornea is densely innervated by long ciliary nerves that originate in the ophthalmic division of the trigeminal nerve. 

Microanatomy

The layers anteroposteriorly include the epithelium, Bowman’s layer, stroma, Descemet’s membrane, and endothelium.[17]

The epithelium is the main barrier to the eye, provides a smooth optical surface and performs immunological functions. It consists of 5 to 7 cell layers in the center and 7 to 10 cell layers in the periphery, with an approximate thickness of 50 μm. The limbal stem cell hypothesis suggests the proliferation of stem cells and transient amplifying cells in the periphery with central migration to replace cells lost on the surface.[18]

Bowman’s layer is a tough tissue composed of primarily type I and V collagen and is an acellular condensate of the stroma. It contributes to the corneal shape. 

The corneal stroma provides mechanical strength and refractive power and consists of regularly arranged collagen fibers, glycosaminoglycans, and interconnected keratocytes, in packed layers or lamellae.  At the corneal center, there are 200 lamellae, with a much higher packing density and interconnectivity in the anterior area compared to the posterior. In DSEK/DSAEK, when the air bubble is introduced to separate the endothelium and DM part of the posterior stroma adheres to the DM, suggesting a natural cleavage plane in the stroma ten μm above the DM.[19] There have been suggestions that this area of the posterior stroma is anatomically distinct and has been named pre-Descemet’s layer or Dua’s layer.[20]

DM is a 7-10 micrometer structure that consists of Type IV collagen and laminin and is secreted by endothelial cells continuously.[21] The corneal endothelium is a simple cuboidal monolayer of cells that are rich in mitochondria and are responsible for maintaining transparency.

Penetrating keratoplasty indications include keratoconus, ectasias, corneas degenerations, dystrophies, keratitis, congenital opacities, chemical/mechanical corneal trauma, and re-grafts. The reported leading indications in a region are dependent on sociopolitical, geographical and economic factors and may not accurately reflect the most common aetiologies of corneal pathology.[22]

Endothelial keratoplasty (EK) includes PLK, DLEK, DSEK, DSAEK, DMEK, and DMAEK. EK procedures are not appropriate for patients with healthy corneal endothelium such as keratoconus. EK indications include: Fuch’s endothelial dystrophy, posterior polymorphous dystrophy, congenital hereditary endothelial dystrophy, bullous keratopathy, iridocorneal endothelial syndrome, and failed EKs.

Deep anterior lamellar keratoplasty (DALK) indications include those that relate to the pathology of the anterior cornea (epithelium, Bowman’s layer, and stroma), such as keratoconus and corneal scars.

There are absolute and relative contraindications for corneal transplantation in each country that are highly region-dependant. The National Health Services (NHS) Blood and Transplant Agency in the United Kingdom (UK) has the following absolute contraindications: transplant unlikely to restore corneal function or integrity or remove tissue that would otherwise have led to further damage to the eye.

Basic operating room equipment is usually necessary with the arrangement for local anesthesia (e.g., retrobulbar block) alongside intravenous sedation or general anesthesia.