Corneal crosslinking outcomes look good for pediatric keratoconus

This article is reviewed by William J. Johnson, MD

Corneal collagen crosslinking (CXL) appears to be a beneficial therapy that stops progression of keratoconus in children, according to William J. Johnson, MD, an ophthalmologist in Tifton, Georgia.

This is good news because keratoconus generally is more aggressive in pediatric patients. In addition, he noted, penetrating keratoplasties performed in children are associated with a guarded prognosis.

“CXL has provided a mechanism to arrest progression and avoid end-stage disease,” he said.

However, caveats for CXL include the ability to adequately test pediatric patients preoperatively, sedation requirements, and insurance coverage barriers.

Related: COVID-19 impacts keratoconus patients waiting for corneal crosslinking

Retrospective analysis
Erin D. Stahl, MD, section chief and pediatric ophthalmologist at University of Missouri-Kansas City School of Medicine and associate professor of ophthalmology at the University of Kansas School of Medicine, joined Johnson in conducting the study at Children’s Mercy Hospital in Kansas City, Missouri.

The medical records of the patients who had undergone CXL at Children’s Mercy Hospital were reviewed retrospectively. CXL was performed in all patients using the KXL system (Avedro) with Photrexa riboflavin preparations (Glaukos).

Following a superficial keratectomy and application of topical vitamin B2 every 2 minutes for 30 minutes, ultraviolet (UV)-A light (365 nm, 3 mW/cm2) was applied for 30 minutes with vitamin B2 continuing to be applied every 2 minutes during the UV light exposure.

Related: Is the time right for crosslinking?

In patients whose corneas were too thin for endothelial protection despite application of hypotonic vitamin B2 to induce corneal edema, the UV light was blocked for part of the treatment, he explained.

The primary outcomes were the best-corrected visual acuity (BCVA), complications, treatment failure, and length of follow-up; if available, the tomographic and topographic data also were reviewed.

Representative case
In 2015, a 13-year-old patient received a diagnosis of keratoconus based on retinoscopy reflex and topography and a marked increase in cylinder in the left eye (+2.25 x 075).

Later that year, the cylinder again increased (-7.50+4.00 x 080) and the VA decreased to a BCVA of 20/30. In 2017, the patient underwent bilateral CXL; the central corneal thicknesses were 439 µm and 478 µm in the right and left eyes, respectively.

Related: More than meets the eye with corneal dystrophies

In 2019, at age 19, the cylinder had stabilized, the myopia in the left eye had decreased, and the BCVA was 20/25.

Study results
The study included 43 eyes of 27 patients (mean age at surgery, 15 years; median follow-up, 328 days).

“The logarithm of the minimum angle of resolution BCVA improved modestly from 0.3 preoperatively to 0.1 postoperatively,” Johnson said. Due to the small sample size, this was not statistically significant.

Postoperatively, many patients were fitted with a scleral contact lens, a particularly helpful adjunct when trying to provide optical rehabilitation and manage often irregular astigmatism in patients with keratometry beyond typical contact lens therapeutic ranges.

Related: CXL imperative in treatment of pediatric keratoconus

The pachymetry and the topographic and tomographic data remained largely stable overall from preoperative to postoperative measurements.

When the investigators evaluated cases with a minimum of 6 months of follow-up, 26 eyes were included, the median preoperative and postoperative BCVA had a similar trend, the pachymetry was stable, and the topographic/tomographic data improved, although not significantly.

Consideration
Johnson emphasized the need to follow the cohort over the long term despite the encouraging short-term safety and efficacy results. Although the treatment is designed to arrest progression of keratoconus, continued observation is needed, he said.

“The goal is to reach a point where a penetrating keratoplasty or even a partial-thickness deep anterior lamellar keratoplasty is not necessary at all,” he said. “The idea is to shepherd them through their younger years, during which time there is a higher risk of corneal transplantation [adverse] effects.”

Related: Estimating the total corneal power key in keratoconus patients

A secondary outcome in these patients was a determination of whether CXL provided a safe and effective treatment that delayed progression to corneal transplantation and also strengthened the potential future graft-host junction to decrease the risk of recurrence in any future grafts, Johnson explained.

Johnson pointed out that although shorter protocols may be desirable to decrease anesthetic exposure or operating room utilization, efficiency should not override efficacy in these protocol assessments going forward.

Moreover, Johnson believes the safety of the treatment was demonstrated. One surgical complication resulted from an aggressive postoperative healing response that caused scarring.

One episode of hydrops was likely progression of the keratoconus, given that it was more than a year after the surgery, which may occur in a small percentage of patients after CXL.

Related: SARS-CoV-2 genomic RNA in corneal transplantation: Are corneal transplantations safe?

The short-term results suggested the effectiveness of CXL. One patient who lived a distance from the surgical center did not have access to a practitioner able to fit a scleral contact lens, so they underwent a penetrating keratoplasty to facilitate RGP fitting.

“There may be a need for more penetrating keratoplasties or partial-thickness transplants in this cohort in the future, but, to date, only 1 has occurred,” Johnson said.

Conclusion
Johnson pointed out that CXL in a pediatric population has been a safe procedure at the institution.

“Many findings in the FDA-approved CXL studies are similar to our current results, including stability, modest although nonsignificant BCVA improvement, and few complications,” he concluded. “Clinical judgment is a fixture in managing pediatric keratoconus and CXL because of the difficulty in obtaining definitive data in this patient population.”

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William J. Johnson, MD
e:johnsonwilliam67@gmail.com
This article is adapted from Johnson’s presentation at the American Academy of Ophthalmology’s 2020 virtual annual meeting. Johnson has no financial interest in this subject matter.

Erin D. Stahl, MD
e:edstahl@mch.edu
Stahl is a consultant for Glaukos.