Murat V. Kalayoglu, M.D., Ph.D.
Each year, more than 40,000 corneas are transplanted successfully in the United States. Most patients receiving a corneal transplant suffer from corneal scarring or decompensation due to keratoconus, bullous keratopathy, corneal scars from trauma, Fuchs endothelial dystrophy, and stromal corneal dystrophies such as lattice, granular or macular dystrophy. However, several types of corneal and external diseases prevent sustained corneal clarity following transplantation. Diseases such as ocular cicatricial pemphigoid, chemical burns, and Stevens – Johnson syndrome have dismal corneal transplant success rates.
Furthermore, even though the corneal eye bank program is extremely effective in providing transplanted tissue in the United States, there is an overwhelming need for transplantable cadaveric corneas in the developing world. According to the World Health Organization, over 10 million individuals are blinded from corneal scarring. In much of the developing world, religious and cultural factors, lack of general education and the absence of eye banking facilities prevent widespread cadaveric donation for corneal transplantation. Clearly, there is an enormous need - and potential - for an alternative to cadaveric corneal transplantation.
Advances in surgical technique and material design, coupled with a better understanding of the pathophysiology of immune rejection, have allowed the development of “artificial corneas”, or keratoprostheses. In many ways, the keratoprosthesis is the “holy grail” of corneal surgery; implanting an “artificial cornea” that would restore a patient’s vision would reach millions and save vision in countless individuals. The ideal keratoprosthesis would be inert and not be rejected by the patient’s immune system, be inexpensive and maintain long-term clarity. In addition, it would be quick to implant, easy to examine and allow an excellent view of the retina.
To date, no keratoprosthesis meets these gold standards. In fact, none even come close; the history of keratoprosthetics is riddled with failures and surgical complications. However, a set of keratoprostheses have shown surprising success over the past several years, and are routinely used for some diseases. Commercially available keratoprostheses may be the only viable option to restore vision in patients with severe ocular cicatricial pemphigoid, Stevens – Johnson syndrome, or severe chemical burns.
Stevens – Johnson syndrome is an acute polymorphic disease that affects the skin and mucous membranes. The disease affects men and women equally, and can affect individuals of all ages. Stevens – Johnson syndrome is a severe disease that can have mortality rates of 15%. About half of all afflicted patients develop eye problems, which can range in severity from mild conjunctivitis to severe perforating ulcerations. The exact pathogenesis of the disease is not known, but there are strong associations with certain medications and infections. Ocular cicatrizing pemphigoid is a chronic autoimmune cicatrizing conjunctivitis. The disease usually affects women older than 30. The disease progresses from development of conjunctival bullae to subepithelial fibrosis and loss of conjunctival goblet cells. Mucous tear deficiency, symblepheron formation and scarring may follow. In these diseases, the chances that a corneal transplant will be successful approach 0%. With a keratoprosthesis, however, success rates can be over 80% after 1 year – a remarkable achievement considering the severity of disease and absence of alternatives.
Despite these success rates, a high rate of complications continues to plague keratoprosthetic surgery. Endophthalmitis, glaucoma and extrusion of the implant are serious complications that continue to occur even with newer generation materials. Other complications include sterile vitritis and the formation of a retrolental fibrotic membrane that blocks the visual axis and reduces visual acuity. Sometimes, these membranes can be disrupted with YAG laser surgery; however, others are too thick to do so with laser and need to be removed with intraocular procedures. Due to these complications, most surgeons do not perform keratoprosthesis surgery unless the patient is blinded bilaterally from a select few diseases for which corneal transplantation is not an option.
Commercially available keratoprostheses are made from several different types of materials. Polymethylmethacrylate (PMMA) remains a popular material and is used in collar-button designs and KPro optics. Poly (2-hydroxyethylmethacrylate) (PHEMA) is also used in keratoprostheses. Ongoing work continues to optimize biocompatibility between the keratoprosthesis material and host cornea and sclera. Recently, scientists from the University of Ottawa Eye Institute in Ontario, Canada implanted an artificial extracellular matrix to a pig model and demonstrated successful in vivo regeneration of host corneal epithelium, stroma and nerves. Such research will continue to refine the currently available keratoprostheses and enable the development of more biocompatible artificial corneas.