The problems of the cornea and lens in aniridia

.   The cornea  has a disorder in 90% of patients with aniridia .  A normal, healthy cornea is a clear, avascular (lacking blood vessels) transparent tissue that allows light to pass through.  Most individuals with anirdia are born with a clear, healthy corner.  However, unlike the iris, the cornea is one area of the aniridic eye that degrades and causes vision to degenerate over time.

Impact on vision:  In order to understand the impact on vision, it is helpful to understand a high-level ‘biology’ of the cornea and the adjacent limbus region:

The limbus (see diagram) is the border of the cornea and the sclera (whites of the eye).  The limbus region is responsible for creating stem cells that ‘refresh’ the clear epithelium of cornea (think of the epithelium as the ‘skin’ on the cornea, much like the skin on our bodies, but this skin is clear, not opaque).  In individuals with aniridia these stem cells do not function properly.  For some unknown reason, the mutated PAX 6 gene in people with aniridia disrupts the signal for the cornea to refresh itself. Over time the opaque epithelial cells and vascularization (veins) from the conjunctive begin to grow over the clear cornea and cover the cornea starting from the periphery of the cornea and working its way into the center.  The result is that the ‘clear window’ of the cornea changes into the transparency of wax paper.

 The cornea is made up of 5 layers.  Each layer needs to be healthy to maximize vision and keep the other layers intact.  Most individuals with aniridia are born with a clear, healthy cornea.

However, by their early teens, the cornea begins to show evidence of the opacification (think of wax paper growing over the cornea) caused by the malfunctioning stem cells.  This is called corneal pannus (also called corneal keratopathy or aniridic keratopathy).  Corneal pannus is scarring of the corneal tissue. Left untreated, this opacification and vasularization can pass through the epithelial layer (the outermost layer, or the ‘skin’ of the cornea) and cause damage to the stroma layer of the cornea.

The impact on vision of corneal pannus is profound in individuals with aniridia.  An individual’s baseline vision is further reduced by having a layer of ‘wax paper’ cover the “windshield”.  The result is very little vision.

Current medical/surgical treatments:  Treatment of corneal pannus depends on the stage of the disease.  In the early stages when the central vision has not yet been affected because the central cornea still has a normal epithelium, the treatment is to keep the surface of the eye as healthy as possible. (Indeed, one way to prolong the health of the aniridic cornea is to keep the surface as healthy as possible by protecting it and making sure it stays lubricated and not dry or inflammed.)  However, once the pannus has significantly affected the central vision, the current treatment is surgery.

Because the culprit of the pannus (scarring) is the limbus region (the area generating stem cells to refresh the cornea), this region needs to be addressed with a limbal stem cell transplantation.  The most-commonly used technique for addressing the malfunctioning limbus region is keratolimbal allograft (KLAL).  During the KLAL procedure, limbal tissue from a cadaver or a living-related donor (“allo-” means other) is grafted (“-graft”) onto the aniridic eye. (The scarred tissue is first removed and then the new tissue is grafted).  While this procedure has regained sight for thousands of people it has associated risk because of the required systemic immunosuppression drugs (so that the body does not reject the foreign tissue) and if not properly monitored post-surgically, has a high risk of failure.  In addition, individuals have a very high incidence of post-surgical glaucoma.

If the scarring has penetrated the stroma layer of the cornea (later stages of the disease), then in addition to the KLAL treatment (or other treatment used to address the limbus region), the individual with aniridia must also have a cornea transplant.

In recent years, some individuals with aniridia have opted for artificial corneas (keratoprosthesis), especially when the individual has had multiple KLAL failures or they cannot tolerate immunosuppression drugs.  The benefit to an artificial cornea is that it does not require immunosuppression drugs.  However, complications can include glaucoma and retinal detachment.  Also, any foreign object in the anridic eye can lead to aniridic fibrosis (described below).

Future treatments or prevention:  Hope for the future includes treatments that do not require immunosuppression by using stem cells from an individuals own body or, even better, preventing corneal keratopathy altogether.

 The lens is a transparent, biconvex structure in the eye whose function is to focus light onto the macula.  Problems that can occur in the lens include cataracts (clouding of the lens), microphakia (abnormal smallness of the lens), and lens subluxation (displaced or malpositioned lens).

Impact on vision:  Some individuals with aniridia are born with small cataracts, which are little “dots” clouding the lens. Typically, these small dots do not impact one’s vision. However, as the aniridic eye becomes more affected by the other associated eye problems, such as glaucoma, the cataracts can grow and begin to impact vision.  Cataracts typically grow very slowly.  Cataracts and lens subluxation typically cause a high degree of astigmatism (vision is blurred due to the inability of the optics of the eye to focus a point object into a sharp focused image on the retina).  Astigmatism can be helped using properly-prescribed refractive glasses.

Current medical/surgical treatments:  In the early stages of cataracts when vision is not significantly impacted, the use of corrective glasses or contact lenses can improve vision.  However, contact lens use in individuals with aniridia must be closely monitored because contacts can harm the cornea (see above).  The type of contact lens and frequency of use is very important.

Once vision is significantly impacted, cataract extraction surgery may be necessary.  An intra-ocular lens may be implanted but carries the risk of aniridic fibrosis.