About Us

Treating Corneal Blindness Through Tissue Engineering

There is severe shortage of human cadaver corneas for corneal transplants. Cornea Biosciences (www.corneabio.com) created a bioengineered cornea to aid with solving world blindness. The company’s cornea is the result of ten years of research and development conducted at the University of Ottawa in Canada and Linkoping University in Sweden. The company was founded in 2011 and incorporated in Singapore with the express objective of furthering development of the bioengineered cornea, and providing this cornea to the millions of people unilaterally or bilaterally blind from corneal disease or injury and unable to obtain a corneal transplant due to a severe shortage of human donor corneas.

As a not-for-profit foundation established by Cornea Biosciences, the mission of The Corneal Transplant Foundation is to provide information on corneal transplantation, support corneal transplant research and assist economically disadvantaged patients in obtaining corneal transplants.

The Need

The World Health Organization estimates over 10 million people in the world are blind in one or both eyes due to corneal disease or injury

This is due to corneal injury or disease and many of these people could benefit from corneal transplants. According to data from eye banks and government health agencies, less than 150,000 corneal transplants are done annually worldwide due to a shortage of human cadaver corneas.

 

WHAT RESEARCH HAS SHOWN US

The Solution

Corneal Biosciences is helping to meet that need with its bioengineered corneas. The company’s corneas are the result of over ten years of research conducted at the University of Ottawa, Canada and Linkoping University in Sweden. This type of cornea is made from Type III recombinant human collagen cross-linked with biopolymers, and has been extensively tested for biocompatability in rabbits, dogs, and pigs. After four years in a human clinical trial conducted in Sweden, the bioengineered cornea has shown a remarkable compatibility with no signs of rejection. This cornea behaves in many ways like a human cornea – epithelial cells quickly regrow over the surface and cornea nerves regrow into the matrix of the cornea. Thus, patients report the sensation of touch is restored. The company’s cornea is expected to have a minimal shelf life of six months; whereas, human cadaver corneas quickly deteriorate after 15 days. The new tissue engineered corneas will not replace human tissue rather they will be supplemental.  As such, they could restore sight to millions of people who have suffered debilitating loss of vision due to corneal disease or injury.  Many of these people will be able to once again lead normal, productive lives.
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Procedures

What is a corneal transplant?

Rejection of Corneal Transplants

Types of Corneal Transplants

Future Approaches – Research & Development

What is a corneal transplant?

Anatomy

The cornea is the clear window on the front of the eye similar to the crystal on a watch.

It is the first part of the eye through which light enters.  The cornea is about 0.5mm thick and about 11 x 12 mm in diameter. The cornea consists of three (3) main layers:

  1. The epithelium consists of 6-7 layers of cells over which the tears sit to keep the surface of the eye moist and allow for the lids to move over the eye’s surface.
  2. The stroma accounts for about 90% of the cornea’s thickness and consists of collagen fibers and cells called keratocytes. The collagen fibers are in a multi-layered mesh that gives the cornea a defined shape and the ability to absorb some direct trauma.  The multi-layers are referred to as “lamellae”.   The defined curved shape of the cornea is important since the cornea bends and focuses light as it enters the eye.
  3.  The endothelium is on the back of the cornea and consists of a single layer of cells. The endothelial cells are normally hexagonal in shape and have a “water pump” function to maintain the proper water level in the stroma. This function is important to keep the cornea clear so that light can pass through.
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Cross section of the human eye showing the location of the cornea and its various layers
Courtesy of Cornea Research Foundation of America – www.cornea.org

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Image of the human corneal endothelium. Note that this single layer of cells have a hexagonal shape under normal, healthy conditions.

Corneal Transplants, or Keratoplasty

The word keratoplasty comes from the Greek words “kerato” for “horn-like” or “referring to the cornea” and “plastia” for molding or surgical repair of the body — so “cornea repair”.
If a cornea becomes cloudy or even opaque through disease, infection or traumatic injury, light cannot pass through the cornea so that the vision is the eye becomes impaired or totally blind.

A corneal transplant can then be performed by an ophthalmic surgeon who uses a round cookie-cutter like blade called a “trephine” to remove the central part of the affected cornea and then replace it with a clear, healthy piece of donor cornea.   The donor corneal tissue is obtained from a deceased person whose had pledged to donate their eyes or corneas when they died.  The family of the donor cannot also make this anatomical gift.

Some typical conditions that may require corneal transplantation:

Keratoconus – the cornea becomes cone-shaped rather than having a gentle curvature:

How the world may look to a patient with keratoconus

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Note the pronounced cone shape on the image
on the right

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Note the pronounced cone shape on the image
on the right
Courtesy of Cornea Research Foundation of America – www.cornea.org

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Types of Infections

Corneal Ulcer/Infection – an infection of the cornea that can be caused by bacteria or fungi

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Bacterial corneal ulcer

Viral infections – can be caused by herpes simplex or herpes zoster viruses

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Herpes simplex virus keratitis

Stromal Corneal Dystrophies

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Granular corneal dystrophy

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Herpes simplex virus keratitis

Endothelial diseases – these conditions are where the endothelium becomes diseased and the pump function decreases so that too water gets into the stroma causing swelling (“corneal edema”). The swelling causes the cornea to become cloudy so that light does not pass through normally, with a decrease in vision.

Examples of these conditions include:

Fuchs’ endothelial dystrophy (FED)

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Fuchs Endothelial Dystrophy

Pseudophakic bullous keratopathy (PBK)

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Pseudophakic bullous keratopathy

This condition can occur sometimes after cataract surgery if the endothelial cell density is low along so that there is not enough pump function. “Bullae” refer to painful “blisters” that can form on the surface of the cornea.

Rejection of Corneal Transplants

Corneal transplants may be rejected by the recipient.  Since the cornea has no blood vessels, there is generally less chance of rejection as compared with organ transplants, such as kidneys and livers, that have large blood supplies. The incidence of rejection varies with the type of corneal disease.  Steroid eye drops are used to control rejection in the recipient eye after a corneal transplant.

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Eye Banks – from where donor corneas come

The donated corneas are generally recovered by an “eye bank” who has specially trained personnel that recover, inspect, preserve and evaluate the donor corneal tissue to determine whether it is suitable for the various types of corneal transplant.  The cause of death and medical history of the donor are checked to make sure that the donated tissue is safe to transplant.  These donor screening procedures also test the donor’s blood for infectious diseases.  Eye banks may also pre-prepare donor corneas for the corneal surgeon for the various types of corneal transplants.

An eye bank technician working in the eye bank laboratory at the National Eye Bank of Ethiopia in Addis Ababa

An eye bank technician working in the eye bank laboratory at the National Eye Bank of Ethiopia in Addis Ababa

An eye bank in Italy

An eye bank in Italy

Types of Corneal Transplants

Penetrating Keratoplasty (PK) – full thickness

The majority of corneal transplants have generally been “penetrating keratoplasty” in which the full thickness of the cornea is replaced with healthy donor cornea tissue. The first full thickness corneal transplants using human tissue were performed in the early 1900s. The surgery was improved so that penetrating keratoplasty began to be performed on a more regular basis during the 1930s and 1940s in various countries.

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Schematic diagram of a full thickness penetrating corneal transplant (PK)
Courtesy of Cornea Research Foundation of America – www.cornea.org

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Examples of corneal trephines (round, cookie cutter-like blades). These can range is size from 2.0 to over 10.0mm in diameter.

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Note how very thin sutures are used to secure the corneal transplant in place.

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Corneal transplant surgery is performed under an operating microscope

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Corneal transplant surgery as seen by the ophthalmic surgeon through the operating microscope

The previous images of corneal diseases are those that require full thickness, penetrating corneal transplants (PK).
Another example of a corneal diseases that requires a full thickness transplant is interstitial keratitis:

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Interstitial keratitis

However, in the late 1990s and through the first decade of the 21st century, corneal transplant surgery has improved so that only that portion of the cornea that was diseased or injured could be replaced instead of the full thickness. These newer procedures are known as lamellar keratoplasty of which there are several types.

Lamellar Keratoplasty
“Lamellar” refers to “being arranged in “lamellae” with lamellae being defined as “thin plates”.

Anterior Lamellar Keratoplasty (ALK)
If only front portion of the cornea needs to be replaced, then an anterior lamellar keratoplasty is performed.

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Deep Anterior Lamellar Keratoplasty (DALK)
If the entire stroma, or middle section, of the cornea needs to be replaced, then a deep anterior lamellar keratoplastyis performed. DALK is performed when the endothelium remains healthy and has not been affected by the corneas disease or injury.

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Corneal conditions are diseases that can be treated by anterior lamellar grafts include:

Superficial cornea scar – a scar may be caused after a bacterial infection or following trauma to the cornea. If the scar is superficial and does not involve the entire corneal thickness, then an anterior lamellar keratoplasty can be performed.

Keratoconus – the cornea becomes cone-shaped due to changes in the stroma but the endothelium may not be affected. As a result, a deep anterior lamellar keratoplasty (DALK) can be performed.

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The DALK procedure can also be used to treat superficial corneal scars.

Posterior Lamellar Keratoplasty
If only the endothelium is diseased or damaged and needs to be replaced, a posterior lamellar keratoplasty (PLK) can be performed. These corneal transplant procedures are also called endothelial keratoplasty (EK).
The first PLK involved the corneal surgeon entering the area behind the cornea, known as the anterior chamber, to dissect a layer of the stroma with the dysfunctional endothelium. A similar sized graft was prepared from the donor cornea using the same surgical maneuvers and then placed into the anterior chamber and then on back of the cornea. In this manner, a non-functioning endothelium is replaced with a healthy donor endothelium.
This approach was very challenging to learn, was time-consuming and technically challenging. It was simplified by a corneal surgeon in the Netherlands figuring out that the dysfunctional endothelium could be “stripped” off the back on the cornea along with Descemet’s membrane, a very thin layer on which the single cell of endothelial cells sit. This procedure was much simpler to learn and fairly simple.

As a result of this discovery, the current most common types of EK are:

Descemet’s Stripping Endothelial Keratoplasty (DSEK)

DSEK involves stripping the non-working endothelium from the back of the cornea and then replacing it with a thin layer of donor stroma with the donor endothelial layer. A device called a microkeratome is used to prepare the DSEK corneal transplant.

Courtesy of Cornea Research Foundation of America – www.cornea.org

Descemet’s Membrane Endothelial Keratoplasty (DMEK)
There is also an approach to replacing a dysfunctional endothelium by stripping off the patient’s endothelium and then just dissecting the donor’s healthy endothelium with its underlying Descemet’s membrane.

Image of DMEK graft being unfolded in the anterior chamber of the patient’s eye. The graft has been dyed blue so that the corneal surgeon can see it when placed in the anterior chamber of the eye.

OCT cross section image of patient transplanted corneas comparing DSEK and DMEK. Note that the donor stromal layer can easily be seen on the back of the cornea on the DSEK image as where the DMEK graft is so thin that it can really be seen on the back of the lower image
Courtesy of Price Vision Group – www.pricevisiongroup.com

Corneal diseases for which DSEK or DMEK are performed include:

Fuchs Endothelial Dystrophy (FED)

Fuchs Endothelial Dystrophy

Pseudophakic bullous keratopathy (PBK)

Pseudophakic Bullous Keratopathy

Failed or repeat full thickness penetrating corneal transplants (PK)

Failed penetrating keratoplasty (PK)

Limbal Stem Cell Grafts or Keratolimbal Allografts (KLAL)

In some situations, a special type of corneal transplant needs to be performed to replace limbal stem cells. These cells are at the limbus, which is where the clear cornea and sclera, or the white part of the eye meets. These cells are the source of new corneal epithelial cells, which divide and then grow across the surface of the cornea so that the epithelium remains intact and healthy. This thin area of cells, as shown on the diagram below, can be damaged by various diseases such as aniridia, Stevens-Johnson syndrome, or damage from chemical burns.

Similar sections of a donor cornea can be removed and then transplanted with healthy limbal stem cells, again as shown in the diagrams. KLAL can be challenging to manage since they require the recipient to be on long-term steroid drops to prevent graft rejection.

Courtesy of Cornea Research Foundation of America – www.cornea.org

Limbal stem cell transplants are sometimes combined with full thickness penetrating corneal transplants (PK):

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Aniridia

Stevens-Johnson Syndrome

Chemical Burn

Artificial Corneas – Keratprostheses

Corneal transplants can fail after time due to rejection and/or increased rate of loss of endothelial cells. Corneal disease conditions that result in scarring, with formation of blood vessels, tend to very prone to rejection – the presence of blood vessels make the cornea transplant similar to an organ transplant, for which control of rejection can be a challenge. Diseases that may require a keratoprostheses include severe chemical burns and those that prevent formation of a healthy corneal epithelium, even if a KLAL is performed.
In some cases, after failed repeat corneal transplants using donor corneal tissue, the only option to restore sight may be to use an artificial cornea, or keratoprosthesis. These are medical devices that are synthetic, non-biologic material that are placed in the front of the eye to replace the cornea. Keratoprosthses can be made of plastic or metal materials.
The most common keratoprosthesis is called the Boston “K-Pro”. It is a full thickness cornea replacement. Patients that receive these devices need to receive long-term antibiotic and steroid eye drops. The medical management of these patients can be very intensive.

Failed corneal transplant on left with Boston K-Pro in place after additional surgery

Boston K-Pro with back plate made of titanium

Diagram of Boston K-Pro parts and assembly

There is also a partial thickness keratoprosthsis available that can be used to treat corneas with severe diseases on the corneal surface that would be at high-risk for rejection:

Use of Femtosecond Lasers In Corneal Transplant Surgery

Femtosecond lasers are being used in some cases to make very precise incisions in the donor cornea and in the recipient eye to make wound shapes that better anchor the corneal transplant in the eye. Shapes include:

Femtosecond laser “top hat” corneal transplant
Courtesy of Cornea Research Foundation of America – www.cornea.org

Corneal transplants performed with the FS laser may result in both faster healing and improvement in vision. The laser can be used for full thickness penetrating and anterior lamellar grafts (ALK, DALK). Experiments are underway so that the FS laser could be used to prepare very thin DSEK grafts.

Penetrating keratoplasty made with femtosecond laser. White scar-like circle indicates where the laser incision was made.

Future Approaches – Research & Development

Future advances in corneal transplantation and the treatment of corneal diseases include:

Bioengineered corneas: Bioengineered corneas are made from materials that are biocompatible when placed into the corneas and mimic the collagen of which human corneas are comprised. These materials will address the worldwide shortage of donor corneas that exist in most countries, except for the USA and a few European nations.

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Bioengineered corneas act as a “scaffold” that allows the cornea to repair itself.
These materials can also be used as a scaffold or “carrier” for stem cells that can be used to transplant into the cornea to treat specific corneal diseases:

– Cultured, bioengineered human corneal endothelial cells may be used in place of donor eye tissue to perform endothelial keratoplasty (EK) such as DSEK and DMEK.

– Cultured, bioengineered limbal stem cells grafts can be created for KLAL procedures.

– Cultured, bioengineered stromal stem cells can be added to scaffold material to repair corneal scars.

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Improved artificial corneas

Keratoprostheses may be improved so that can be attached better into the front of the eye.

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