© 2018 by Trefoil Therapeutics, Inc.

Trefoil is dedicated to pursuing novel pharmacologic treatments for corneal diseases and disorders based on cutting edge university based research to enhance to  and maintain our most precious sense - sight.

The Visual System

There are four fundamental elements to the human visual system.

  1. Cornea

  2. Crystalline lens

  3. Retina

  4. Brain

 

The cornea is the clear outermost portion of the eye and it is the transparent cornea that allows light to enter the eye where it is focused by the lens on the retina and subsequently transmitted to the brain for processing.

 

Any compromise to the clarity and health of the cornea leads to degradation of sight and the other visual components of the eye cannot compensate for a lack of input.  In some cases disease of the cornea can be treated with a cornea transplant; however, as with any form of tissue transplantation there are risks of serious infection or rejection of the donor tissue.

Cornea Anatomy

 

The cornea contains no blood vessels to nourish or protect it against infection; instead the cornea receives nourishment from the tears and aqueous humor (a fluid in the front of the eye) that fills the chamber behind it.  The tear film is comprised of three distinct layers (an oily lipid layer, an aqueous layer and a mucin layer) that act in an interdependent manner to protect the cornea and provide an element of the refractive function of the eye.

 

The cornea must remain transparent to refract light properly and to see well, all layers of the cornea must be free of any cloudy or opaque areas.

While the visual system that we know as the eye is impressive, the cornea is itself a remarkable individual system that is comprised of five primary components, each of which has a unique contribution to the transmission of light into the eye:

Epithelium

 

The epithelium is the cornea’s outermost region which is the element exposed to the external environment, protected by the team film and the eyelids. The epithelium layer represents about 10% of the total corneal thickness. The epithelium functions primarily to:

  • Block the effects of the external environment such as dust, water, and bacteria, into the eye

  • Provide a smooth surface that absorbs oxygen and nutrients from tears and then distributes these nutrients to the rest of the cornea

 

The epithelium has thousands of tiny nerve endings that make the cornea extremely sensitive to pain.  In fact, the cornea is 300-600 times as sensitive to pain as skin. The basement membrane is the part of the epithelium that serves as the foundation on which the epithelial cells anchor and organize themselves.

 

Bowman’s Layer

 

Below the basement membrane of the epithelium is a transparent sheet of tissue known as Bowman’s layer. This layer is composed of collagen, strong layered protein fibers. Once injured, Bowman’s layer can form a scar as it heals and if these scars are large and centrally located, vision loss can occur.

 

Stroma

 

The next layer of the cornea is the stroma, which comprises about 90 percent of the cornea’s thickness. It consists of water (78 percent) and collagen (16 percent). Collagen gives the cornea its strength, elasticity, and form. The collagen’s unique shape, arrangement, and spacing are essential in producing the cornea’s light-conducting transparency.

Descemet’s Membrane

Under the stroma is Descemet’s membrane, a thin but strong layer of tissue that serves as a protective barrier against infection and injuries. Descemet’s membrane is composed of collagen fibers (different from those of the stroma) and is made by the corneal endothelial cells that lie below it. Descemet’s membrane will regenerate after injury.

 

Endothelium

 

The endothelium is the very thin, inner cellular monolayer of the cornea. Corneal endothelial cells are essential in keeping the cornea clear. Normally, fluid is transferred slowly from inside the eye into the middle corneal layer (stroma). The role of the endothelium is to pump excess fluid out of the stroma. Without the balancing effect of the endothelium layer the stroma would become hazy, and ultimately opaque due to the excess water. In a normal healthy eye, a balance is maintained between the transfer of fluid into and out of the stromal layer of the cornea. The loss of endothelial cells through disease or trauma is permanent and if too many endothelial cells are destroyed, corneal edema will occur leading to blindness. 

 

The only treatment available today for endothelium disease or trauma is a corneal surgery - either a corneal transplantation or in some cases endothelial keratoplasty (EK) which selectively replaces only the innermost layer of the cornea (endothelium) and leaves the overlying healthy corneal tissue intact.

In EK, the surgeon makes a tiny incision and places a thin disc of donor tissue containing a healthy endothelial cell layer on the back surface of the cornea. The small incision is self-sealing and typically no sutures are required. The most common type of EK procedure is called Descemet's Stripping Endothelial Keratoplasty (DSEK).The American Academy of Ophthalmology in 2009 endorsed DSEK as superior to the conventional full thickness corneal transplant procedure for its better vision outcomes and stability, as well as reduced surgical risk factors.

EK has several advantages over the traditional corneal transplantation procedure. These include:

 

  • Faster recovery of vision

  • Less operating time

  • Minimal removal of corneal tissue which results in reduced impact on the structural integrity of the eye and less susceptibility to post-surgical injury

  • Reduced risk of astigmatism after surgery.

 

Since 2009, the DSEK procedure has become the preferred technique for patients with Fuchs' dystrophy and other endothelial disorders of the cornea.  However, traditional corneal transplantation remains the preferred option when the majority of the cornea is diseased.