Nonpenetrating artificial cornea might help fight corneal blindness globally
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A novel nonpenetrating artificial cornea may help fight global corneal blindness, addressing the problem of corneal tissue shortage. It could also disrupt dominant paradigms and become a first-line less invasive alternative to human graft penetrating surgery, according to the inventor.
Yichieh Shiuey, MD, has a long-time interest in artificial corneas. During his residency training at Harvard Medical school, his mentor, Claes Dohlman, MD, PhD, taught him how to use the Boston artificial cornea (KPro). The device had the capacity for excellent vision but also had the potential for serious complications. All commercially available artificial corneas until now required penetration into the anterior chamber, with the consequent risks for leakage, endophthalmitis and glaucoma.
“Traditionally we thought that glaucoma related to corneal transplantation and penetrating artificial cornea was caused by changes in the angle structure, but Dr. Dohlman’s group has discovered another fundamental issue. Once you penetrate the cornea, you create an inflammatory response that goes all the way down to the retina and optic nerve, with consequent death of retinal ganglion cells,” Shiuey said.
Because penetration is the cause of most problems, Shiuey thought that a nonpenetrating artificial cornea might be the way to overcome them and created KeraKlear (KeraMed), an artificial cornea that is implanted into a partial-thickness corneal pocket made by a femtosecond laser and requires removal of less than 10% of the corneal tissue.
“By using a method that does not penetrate the anterior chamber, we prevent complications such as endophthalmitis, glaucoma and retroprosthetic membrane. Another advantage is that by using a nonpenetrating technique, the KeraKlear can actually be implanted in an office setting, and requirements are the same as for any laser procedure,” he said.
This is important in the many parts of the world where there is limited access to sterile ophthalmic operating rooms.
Procedure, indications and outcomes
The femtosecond laser is used to create an 8 mm diameter corneal pocket at a depth that is approximately 100 µm above the endothelium and a vertical trephination of a 3.5 mm to 3.7 mm diameter to the depth of the corneal pocket. In this way, most of the diseased tissue is removed, but at least 100 µm of posterior corneal stroma is left in place to serve as a protective layer. The KeraKlear is then inserted into the corneal pocket.
“The most common causes of corneal blindness around the world affect the anterior cornea. Therefore, the KeraKlear is an excellent solution for the majority of corneal blindness globally. With corneal edema, which affects the entire cornea, even though we leave 100 µm of not perfectly transparent tissue, there is still enough clarity to provide functional vision,” Shiuey said.
In a patient with multiple previous corneal transplants and an edematous cornea, vision improved from hand motion to 20/60, which he called “no less than a miracle.”
Patients who perform best with this artificial cornea are those with noninflammatory conditions such as corneal scars, keratoconus and corneal dystrophies. In these eyes, KeraKlear showed a high rate of success in studies, with 90% retention at 4 to 5 years. On the other hand, it should not be used in inflammatory conditions such as Stevens-Johnson syndrome, ocular cicatricial pemphigoid or atopic keratoconjunctivitis because of a high risk for corneal melting and extrusion.
With all artificial corneas, there is some risk for infection and corneal melt. Studies with KeraKlear showed that the rate of these complications was relatively low in patients who have noninflammatory conditions. In a study performed in Venezuela, only one of 26 patients developed corneal melting and one developed infectious keratitis due to noncompliance with the antibiotic regimen. No eyes were lost in this study.
“If you have a severe melt with the Boston KPro, you have a hole in the eye, which is a very dangerous situation. An infection with KeraKlear is bacterial keratitis, while with penetrating procedures it is endophthalmitis. To be fair, there are potential complications, but also PKP has complications, like graft failure, occurring in 17% to 20% of the cases, while in our study there were only two patients who were not able to retain the KeraKlear,” Shiuey said.
A paradigm shift
Currently, 99% of cases of corneal blindness are treated with tissue transplantation, while keratoprostheses are commonly associated with the most severe conditions and are only used as the last resort when everything else has failed.
“This is the wrong approach because there is only enough tissue available to treat about 1% of the cornea blind in the world. Thanks to the high safety profile, KeraKlear can be used as a primary procedure and used as an alternative to tissue transplantation for most cases of cornea blindness,” Shiuey said.
He proposed to “reverse the paradigm,” using nonpenetrating artificial corneas for just about everybody, while still having the option of doing keratoplasty as a secondary procedure in the unlikely event of a failure. Moving entirely toward artificial corneas would require a big change in thinking, but he believes that there will be much broader acceptance as more surgeons try this new option.
“With PKP, postoperative astigmatism heavily affects results for at least 6 months to 1 year because of the healing process, while with KeraKlear most patients are better immediately after surgery. There are no problems of suture-induced astigmatism,” he said. “I always think back of one patient with keratoconus in whom I did PKP and was seeing very well, but over time the sutures loosened and when I removed them, he had 9 D of astigmatism, which was about the same as preop.”
In patients with keratoconus, the KeraKlear has the function of an implanted rigid contact lens without the drawbacks of discomfort, poor fitting and intolerance.
“Eventually, patients with severe keratoconus may want to have a KeraKlear instead,” he said.
There are cases that are best suited for tissue transplantation, such as Fuchs’ dystrophy, and he believes that tissue should be reserved for those indications, while using artificial corneas for everyone else.
“If we do this, we can solve the global problem of corneal blindness,” he said.
Fighting corneal blindness
Bilateral corneal blindness affects approximately 10 million people and is the third leading cause of blindness worldwide. In addition, 29 million people have unilateral corneal blindness. Nearly 13 million are on a corneal transplant waiting list worldwide, while fewer than 200,000 grafts are available annually.
“Due to tissue shortage, only 2% of the bilaterally corneal blind and less than 1% of the unilaterally corneal blind are treated each year,” Shiuey said.
Developing a solution for this specific cause of avoidable blindness was his inspiration and his goal for the last 20 years.
“With KeraKlear, we have the alternative to human tissue. We have the safety, we have the ability to implant it in places that do not have the OR for corneal transplantation, and also, very importantly, the learning curve for the surgery is straightforward. Ophthalmologists who do LASIK or cataract surgery already have the skill set they need to implant the KeraKlear. I know that, for myself, doing corneal transplantation required 2 years of additional training beyond residency to feel comfortable, and that is a long time. Globally, there is not enough tissue, but also not enough trained corneal transplant surgeons,” he said.
KeraKlear has received the CE mark and is sold in Europe and other parts of the world where the CE mark is accepted for market authorization. It is not cleared for use in the United States, but its development was partly financed with a $3 million grant from the National Institutes of Health. – by Michela Cimberle
- For more information:
- Yichieh Shiuey, MD, can be reached at PAMF Munnerlyn Eye Institute, 1085 W. El Camino Real, Level 3, Sunnyvale, CA 94087; email: shiuey@yahoo.com.
Disclosure: Shiuey reports he is the inventor of KeraKlear and has a financial interest in the device.