An Update on the Safety and Efficacy of Corneal Collagen Cross-Linking in Pediatric Keratoconus

Abstract

Keratoconus is a degenerative disease that affects adolescents and young adults and presents with variable thinning and conical deformation of the corneal apex. The resultant irregular astigmatism can progress to levels that can significantly affect everyday activities and overall quality of life. Therefore, stopping the progression of the disease is an essential part in managing patients with keratoconus. Corneal collagen cross-linking is a minimally invasive procedure that stiffens the anterior corneal stroma by creating strong covalent bonds between collagen fibrils. Over the past decade, many studies have proved its safety and efficacy in halting keratoconus progression in adults. This review of the literature highlights the growing trend towards using this treatment in pediatric keratoconic patients. In children, keratoconus tends to be more severe and fast progression is often encountered requiring closer follow-up intervals. Standard cross-linking shows comparable results in children with a good safety-efficacy profile during follow-up periods of up to three years. Further research is needed to standardize and evaluate transepithelial and accelerated cross-linking protocols as these could be of tremendous help in a population where cooperation and compliance are major issues.

Pediatric keratoconus: a review of the literature

“…The prevalence of keratoconus varies among populations with an estimate of the disease occurring in 1/2000 individuals [4]. More recent studies since 2009 in the Middle East and Asia use videokeratography to estimate the prevalence of keratoconus ranging from 0.9 to 3.3% [7–14].…”

“…Previously, it has been documented that a non-inflammatory process is involved in the pathogenesis of the disease [4]; however, recent studies found evidence of inflammatory markers, and cytokines including interleukins (IL-1, IL-6, IL-8), TNF-α in the tears of patients with keratoconus [21–23]. Proposed mechanisms include increased kinetics of cyclooxygenase with a tenfold increase in maximal reaction rate and 10 times greater PGE2 production.…”

“…Eye rubbing increases the level of tear metalloproteinase-13, IL-6 and TNF-α in normal and keratoconic eyes, and it is the release of inflammatory mediators that contributes to the development of keratoconus [33]. Additionally, it has been documented that 10% of pediatric patients diagnosed with keratoconus have a positive family history [4, 19, 34, 35]. When accounting for subclinical forms, there is estimated 15–67 times higher prevalence of keratoconus in first-degree relatives than the general population [4, 35].…”

“…Additionally, it has been documented that 10% of pediatric patients diagnosed with keratoconus have a positive family history [4, 19, 34, 35]. When accounting for subclinical forms, there is estimated 15–67 times higher prevalence of keratoconus in first-degree relatives than the general population [4, 35]. However, recent studies reported lower incidences of keratoconus with vernal keratoconjunctivitis in the pediatric population of 0.61%, as compared to previously documented [36].…”

“…Higher rates of corneal collagen remodeling were observed in pediatric corneas when compared to adults. It is thought that the weak ectatic lamellae may exceed the capacity of the cross-linking process [4, 38] leading to more rapid ectasia progression [39] and a sevenfold higher risk of needing corneal transplantation [40] in keratoconus patients. Biochemically, Kotecha et al [41] suggested stiffening of the cornea with age as they report a negative correlation between corneal viscoelastic properties with advancing age.…”