Lindstrom's Perspective

Array of technologies and techniques under evaluation for keratoconus treatment

The OSN New York round table discussions are great learning experiences for the audience and the participants. I participated in the round table featured in the cover story of this issue of Ocular Surgery News, so in this commentary I will simply expand on one personal area of interest.

Collagen cross-linking is now FDA approved in the U.S. using the Avedro KXL system. The FDA indication label is for progressive keratoconus and utilizes an epithelium-off approach with continuous ultraviolet light application. Over nearly 15 years, our cornea group at Minnesota Eye Consultants has participated in the Peschke, Topcon and CXLUSA epithelium-off CXL clinical trials. We then evolved to an epithelium-on approach while participating in further CXLUSA clinical trials.

While controversial to many, we have become convinced that epithelium-on CXL can be safe and effective with less patient morbidity and good outcomes. While off label, we continue to utilize this approach in most patients. We use the Avedro UV light delivery system but have developed our own method of epithelium-on CXL that allows us to treat most patients in a simultaneous bilateral same-day approach. Avedro will be initiating a clinical trial to evaluate the safety and efficacy of epithelium-on CXL, and we are hopeful this will lead to FDA approval in the future.

An epithelium-on CXL approach nearly eliminates the epithelial wound healing problems discussed in the accompanying round table, which can result in sight-threatening corneal scarring or even infection with corneal perforation. As I mentioned above, the FDA-approved method of treatment uses mechanical removal of the epithelium followed by riboflavin loading and UV light application. When I use this approach, I prefer to treat one eye at a time because it is painful, complications can occur, and visual recovery is often slow.

As mentioned in the round table, poor epithelial would healing can be problematic. My preferred approach to a nonhealing epithelial defect with no sign of infection is to discontinue the contact lens and all potentially toxic medications and treat with frequent non-preserved tears alone. If an antibiotic is needed, Vigamox (moxifloxacin, Alcon/Novartis) is preservative free. Loteprednol ointment is also preservative free if a steroid is needed. Custom preservative-free topical medications can be obtained from several compounding pharmacies.

I have had success in tough cases of persistent epithelial defects with a “Botox”-induced ptosis. I find this simpler and more acceptable to patients than a suture or glue tarsorrhaphy.

Many of my colleagues around the world prefer combined same-day PRK/PTK treatment immediately followed by CXL. For me, this approach has generated more corneal haze than desired despite applying mitomycin C on the table and using intense postoperative topical steroids. So, in the face of great enthusiasm by many respected colleagues, I have personally abandoned this approach.

In keratoconus patients with 20/40 or better BCVA, I perform epithelium-on CXL, and in select cases have done a PTK/PRK with 30 seconds of MMC 0.2 mg/mL 1 or more years later to reduce astigmatism and surface scarring and enhance uncorrected vision. I have found the outcomes with this approach to be quite remarkable for many patients. I have not yet seen the keratoconus progress after the PRK/PTK, and haze is similar to a standard treatment. There are no hard and fast guidelines, but I like to have a residual corneal thickness of at least 400 µm including epithelium after the treatment.

In patients who have more severe keratoconus and do not refract to 20/40 or better, I have helped many by combining the placement of Intacs (Addition Technology) with conductive keratoplasty placed under intraoperative keratoscopic control 2 to 4 weeks before epithelium-on CXL. This is my version of the “triple procedure” for keratoconus (Intacs, CK and CXL), and in some patients a PTK/PRK 1 year later makes it a “quadruple procedure” (Intacs, CK, CXL and PTK/PRK). We have many tools that can now be applied alone or together to help the keratoconus patient. These include CXL, Intacs, CK, PTK/PRK, tissue addition procedures and of course, when needed, lamellar or penetrating keratoplasty.

Having performed keratoplasty for 45 years, I have seen many keratoconus patients develop so-called “recurrent keratoconus” in their grafts 20-plus years after keratoplasty. In most patients, I believe this is progression of disease in the recipient cornea outside the keratoplasty. We may learn that CXL before PK is helpful in reducing this late recurrence of irregular astigmatism, especially when keratoplasty is required at an earlier age.

Studies in the Nordic countries suggest that the number of keratoconus patients requiring keratoplasty is declining since CXL has become available. It would be laudable to see keratoconus disappear as an indication for keratoplasty in the annual Eye Bank Association of America statistics. I believe it is in our patients’ best interest to treat them at the very first sign of keratoconus, rather than waiting for evidence of progression, which will usually mean treatment at a very young age. We and our optometric colleagues will need to be on the lookout for these patients as they present for contact lens fitting in their early teens. Additional diagnostic technology to screen for abnormal corneal biomechanics and elasticity will be critical to know who to treat early and who might be safely followed. I believe Brillouin spectroscopy, currently in early clinical evaluation by Theo Seiler, MD, PhD, and Mr. Julian Stevens, may be a valuable adjunct in this regard. In addition, contact lens technology will continue to advance, providing the keratoconus patient even after surgical treatment with the best possible vision.

Many innovative surgeons around the world are using these and other tools in different combinations to advance the art and science of treating the patient with keratoconus. As we all openly share our outcomes, we can expect to make great progress to the benefit of these long-suffering patients in the next decade. I see the innovation cycle again working its magic but also see some cause for concern that third-party reimbursement may be absent or inadequate. If so, these young patients may not be able to afford the technologies now evolving that can preserve and enhance their vision for a lifetime. A truly tragic outcome would be ever-better treatments for keratoconus that are outside the reach financially for many of our patients.

Disclosure: Lindstrom reports relevant financial disclosures for Avedro, CXLO, Imprimis, Allergan, Alcon/Novartis and Bausch + Lomb.

The OSN New York round table discussions are great learning experiences for the audience and the participants. I participated in the round table featured in the cover story of this issue of Ocular Surgery News, so in this commentary I will simply expand on one personal area of interest.

Collagen cross-linking is now FDA approved in the U.S. using the Avedro KXL system. The FDA indication label is for progressive keratoconus and utilizes an epithelium-off approach with continuous ultraviolet light application. Over nearly 15 years, our cornea group at Minnesota Eye Consultants has participated in the Peschke, Topcon and CXLUSA epithelium-off CXL clinical trials. We then evolved to an epithelium-on approach while participating in further CXLUSA clinical trials.

While controversial to many, we have become convinced that epithelium-on CXL can be safe and effective with less patient morbidity and good outcomes. While off label, we continue to utilize this approach in most patients. We use the Avedro UV light delivery system but have developed our own method of epithelium-on CXL that allows us to treat most patients in a simultaneous bilateral same-day approach. Avedro will be initiating a clinical trial to evaluate the safety and efficacy of epithelium-on CXL, and we are hopeful this will lead to FDA approval in the future.

An epithelium-on CXL approach nearly eliminates the epithelial wound healing problems discussed in the accompanying round table, which can result in sight-threatening corneal scarring or even infection with corneal perforation. As I mentioned above, the FDA-approved method of treatment uses mechanical removal of the epithelium followed by riboflavin loading and UV light application. When I use this approach, I prefer to treat one eye at a time because it is painful, complications can occur, and visual recovery is often slow.

As mentioned in the round table, poor epithelial would healing can be problematic. My preferred approach to a nonhealing epithelial defect with no sign of infection is to discontinue the contact lens and all potentially toxic medications and treat with frequent non-preserved tears alone. If an antibiotic is needed, Vigamox (moxifloxacin, Alcon/Novartis) is preservative free. Loteprednol ointment is also preservative free if a steroid is needed. Custom preservative-free topical medications can be obtained from several compounding pharmacies.

I have had success in tough cases of persistent epithelial defects with a “Botox”-induced ptosis. I find this simpler and more acceptable to patients than a suture or glue tarsorrhaphy.

Many of my colleagues around the world prefer combined same-day PRK/PTK treatment immediately followed by CXL. For me, this approach has generated more corneal haze than desired despite applying mitomycin C on the table and using intense postoperative topical steroids. So, in the face of great enthusiasm by many respected colleagues, I have personally abandoned this approach.

PAGE BREAK

In keratoconus patients with 20/40 or better BCVA, I perform epithelium-on CXL, and in select cases have done a PTK/PRK with 30 seconds of MMC 0.2 mg/mL 1 or more years later to reduce astigmatism and surface scarring and enhance uncorrected vision. I have found the outcomes with this approach to be quite remarkable for many patients. I have not yet seen the keratoconus progress after the PRK/PTK, and haze is similar to a standard treatment. There are no hard and fast guidelines, but I like to have a residual corneal thickness of at least 400 µm including epithelium after the treatment.

In patients who have more severe keratoconus and do not refract to 20/40 or better, I have helped many by combining the placement of Intacs (Addition Technology) with conductive keratoplasty placed under intraoperative keratoscopic control 2 to 4 weeks before epithelium-on CXL. This is my version of the “triple procedure” for keratoconus (Intacs, CK and CXL), and in some patients a PTK/PRK 1 year later makes it a “quadruple procedure” (Intacs, CK, CXL and PTK/PRK). We have many tools that can now be applied alone or together to help the keratoconus patient. These include CXL, Intacs, CK, PTK/PRK, tissue addition procedures and of course, when needed, lamellar or penetrating keratoplasty.

Having performed keratoplasty for 45 years, I have seen many keratoconus patients develop so-called “recurrent keratoconus” in their grafts 20-plus years after keratoplasty. In most patients, I believe this is progression of disease in the recipient cornea outside the keratoplasty. We may learn that CXL before PK is helpful in reducing this late recurrence of irregular astigmatism, especially when keratoplasty is required at an earlier age.

Studies in the Nordic countries suggest that the number of keratoconus patients requiring keratoplasty is declining since CXL has become available. It would be laudable to see keratoconus disappear as an indication for keratoplasty in the annual Eye Bank Association of America statistics. I believe it is in our patients’ best interest to treat them at the very first sign of keratoconus, rather than waiting for evidence of progression, which will usually mean treatment at a very young age. We and our optometric colleagues will need to be on the lookout for these patients as they present for contact lens fitting in their early teens. Additional diagnostic technology to screen for abnormal corneal biomechanics and elasticity will be critical to know who to treat early and who might be safely followed. I believe Brillouin spectroscopy, currently in early clinical evaluation by Theo Seiler, MD, PhD, and Mr. Julian Stevens, may be a valuable adjunct in this regard. In addition, contact lens technology will continue to advance, providing the keratoconus patient even after surgical treatment with the best possible vision.

PAGE BREAK

Many innovative surgeons around the world are using these and other tools in different combinations to advance the art and science of treating the patient with keratoconus. As we all openly share our outcomes, we can expect to make great progress to the benefit of these long-suffering patients in the next decade. I see the innovation cycle again working its magic but also see some cause for concern that third-party reimbursement may be absent or inadequate. If so, these young patients may not be able to afford the technologies now evolving that can preserve and enhance their vision for a lifetime. A truly tragic outcome would be ever-better treatments for keratoconus that are outside the reach financially for many of our patients.

Disclosure: Lindstrom reports relevant financial disclosures for Avedro, CXLO, Imprimis, Allergan, Alcon/Novartis and Bausch + Lomb.