Keratoconus is a progressive degenerative disease of the cornea which often leads to progressive steepening and thinning of the cornea, increased irregular astigmatism, and decreased vision. Typically presenting in the second or third decade of life, keratoconus has been estimated to have a prevalence of 1:2000, but more recent estimates have suggested a much higher prevalence.

Initially, the condition may lead to rapidly worsening refractive error and inability to attain full correction with spectacles. Rigid contact lenses are often needed to fully correct vision, but eventually, even contact lenses may not be effective. If left untreated, many patients eventually advance to needing corneal transplantation.

While corneal transplantation—whether as a full thickness graft or anterior lamellar graft—may allow for excellent vision, it also exposes the patient to significant risks. Being that most of these patients are relatively young, and the burden of a corneal graft lasts a lifetime, there has been significant effort to prevent the need for grafting as much as possible. In recent years, numerous advancements in keratoconus management have developed to significantly improve the quality of life for patients with the disease.

Corneal Crosslinking

There are 2 primary goals with keratoconus management: limiting progression and optimizing vision. For limitation of progression, corneal crosslinking has become the gold standard. Corneal crosslinking was first approved in the United States in 2016, using the epithelial-off (epi-off) Dresden Protocol. In the pivotal clinical trials for approval, when comparing treated patients to those receiving a sham treatment, there was found to be a greater than 2.5 diopter difference in change of maximum K reading (Kmax) favoring the treatment group after 12 months. The treated arm showed greater than 1.5 diopters of flattening, while the sham arm steepened by 1.0 diopters. Based on these results, epi-off crosslinking was approved.

While these results are impressive and have led to a dramatic decrease in the number of grafts needed, epi-on crosslinking is not without its drawbacks. Due to the epithelial defect created, patients are subject to discomfort, infection, delayed wound healing, scarring, haze, and delayed visual recovery. Therefore, investigation into crosslinking without epithelial removal (epi-on) is underway. One protocol by Glaukos, using supplemental oxygen, has been submitted to the FDA for approval with a PDUFA date later this year.

Another protocol, by Epi-On therapeutics, using a unique formulation of riboflavin that allows for production of oxygen during the crosslinking reaction, is still in the clinical trial phase. Due to the decreased risks of epi-on treatment, it is expected that once approved, epi-on crosslinking will become the standard of care.

Scleral Lenses

While crosslinking has demonstrated the ability to slow or halt progression, it may not necessarily improve vision. Certainly, many patients have had significant flattening in the cornea after treatment, leading to improvement in vision, but this is not always the case. Therefore, other avenues needed to be developed to allow for visual rehabilitation.

Rigid contact lenses have long been the standard to improve vision in patients with corneal irregularities like keratoconus. Unfortunately, due to the irregularity in shape and often tremendous steepening of the cornea, standard gas-permeable lenses are not always sufficient.

In recent years, improvement in contact lens design and development of the scleral lens have led to many more keratoconus patients attaining excellent vision. Scleral lenses have improved to the point that almost any keratoconus patient can be fitted, allowing for an opportunity to attain excellent vision unless they have visually significant central scarring.

Thanks to our ability to stop progression and to correct vision with scleral lenses, the need for transplantation has decreased dramatically. Of course, it is important to remember that merely improving vision with contact lenses, even to 20/20, does not slow progression. Therefore, patients may still need crosslinking, despite visual correction with contacts.

Early Treatment

While the combination of crosslinking and scleral lenses has improved the lives of many patients, one of the keys to success is early treatment. In the past, when crosslinking was not available, patients were monitored until they needed a transplant. Now, the onus is on the gatekeepers (optometrists and comprehensive ophthalmologists) to look for keratoconus early and to send patients for evaluation and possible treatment upon diagnosis, to avoid progression. Crosslinking may stop progression even in advanced cases, but it may not improve vision. Ideally, it would be most beneficial to treat patients while they are still functional in spectacles, so that they do not even need to resort to scleral lenses.

New Procedures

Still, many patients cannot wear contact lenses for a variety of reasons. Even if their progression has been halted with crosslinking and their vision is excellent with contact lenses, they may have other issues limiting their ability to wear contacts. Therefore, procedures to make the cornea more regular and less dependent upon contacts are also being developed.

Initially, intrastromal corneal ring segments were used to neutralize some of the corneal astigmatism and lead to a more spherical shape, which could be better corrected with spectacles. Of course, this is a plastic foreign body within the cornea that has potential to extrude or cause visual aberrations.

In recent years, 2 new procedures have been used to achieve the same effect, but with the potential for more success: CAIRS and CTAK.

CAIRS (corneal allogenic intrastromal ring segments) is a procedure developed by Dr. Soosan Jacob involving the implantation of arc-shaped segments of donor corneal tissue into the patient cornea to reshape it. CTAK (corneal tissue addition keratoplasty) is a similar procedure involving the placement of arc-shaped segments made from donor corneas into the patient cornea to reshape it. Both procedures are much less invasive than transplantation, with much less risk. The segments are also removable, if needed.

Conclusion

In summary, keratoconus is no longer a condition that patients must live with until they progress to transplant surgery. With corneal crosslinking, progression may be slowed or halted completely. If treated early enough, patients may be stabilized while they still have excellent vision, limiting their dependency on contacts. Even if the condition is advanced, many patients may be able to avoid transplants with the use of scleral lenses. For those patients unable to use scleral lenses, newer surgical techniques, such as CAIRS and CTAK, may correct vision to allow for much better function and to avoid corneal transplantation. OM

Kenneth Beckman, MD, FACS, is director of cornea services at Comprehensive EyeCare of Central Ohio in Westerville, and clinical assistant professor of ophthalmology at The Ohio State University in Columbus.