Corneal collagen crosslinking (CXL) appears to be a beneficial therapy that stops progression of keratoconus in children, according to Dr William J. Johnson, an ophthalmologist in Tifton, Georgia, United States. This is good news because keratoconus is generally more aggressive in paediatric 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 paediatric patients preoperatively, sedation requirements and insurance coverage barriers.
Dr Erin D. Stahl, section chief and paediatric ophthalmologist at University of Missouri-Kansas City School of Medicine and associate professor of ophthalmology at the University of Kansas School of Medicine, joined Dr Johnson in conducting the study at Children’s Mercy Hospital in Kansas City, Missouri, US.
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. In patients whose corneas were too thin for endothelial protection despite application of hypotonic vitamin B2 to induce corneal oedema, 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.
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. In 2019, at age 19, the cylinder had stabilised, the myopia in the left eye had decreased and the BCVA was 20/25.
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,” Dr 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 in patients with keratometry beyond typical contact lens therapeutic ranges and an effort to manage their, often irregular, astigmatism. 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 and the pachymetry was stable. The topographic/tomographic data improved, although not significantly.
Dr Johnson emphasised 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.
“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. “At the very least, the idea is to shepherd them through their younger years, during which time there is a higher risk of corneal transplantation side effects.”
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, Dr Johnson explained. He pointed out that although shorter protocols may be desirable to decrease anaesthetic exposure or operating room utilisation, efficiency should not override efficacy in these protocol assessments going forward.
Moreover, Dr 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.
The short-term results suggested the effectiveness of CXL. One patient who lived a fair distance from the surgical centre did not have access to a practitioner who was 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 one has occurred,” Dr Johnson said.
Dr Johnson pointed out that CXL in a paediatric population has been a safe procedure at their institution. “Many findings in the FDA [Food and Drug Administration]-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 paediatric keratoconus and CXL because of the difficulty in obtaining definitive data in this patient population.”
William J. Johnson, MD
This article is adapted from Dr Johnson’s presentation at the 2020 virtual annual meeting of the American Academy of Ophthalmology. Dr Johnson has no financial interest in this subject matter.
Erin Stahl, MD
Dr Stahl is a consultant for Glaukos.