Keratoconus: Epidemiology, treatment effects and economic evaluation

DA Godefrooij

    Research output: ThesisDoctoral thesis 1 (Research UU / Graduation UU)

    5 Downloads (Pure)


    Keratoconus is a disease of the cornea that usually has its onset during puberty or early adulthood. The annual incidence of keratoconus is 1 per 7500 and the estimated prevalence in the general population is 1 per 375. These values are five-fold to ten-fold higher than previously reported values in population studies. In advanced keratoconus cases a corneal transplantation is often warranted to restore visual function. Receiving a corneal transplant has a substantial impact on quality of life, especially when visual acuity deteriorates or if a corneal transplantation must be performed to restore visual acuity. Preventing the need for corneal transplantation is one of the priorities in keratoconus care. In the Netherlands, the annual number of corneal transplantations decreased after the introduction of corneal crosslinking, suggesting that crosslinking can reduce the need for corneal transplantation. Lamellar transplantation techniques were increasingly performed over the last decade, accounting for approximately 35% of keratoplasties in 2010 and thereafter. The classic penetrating keratoplasty is still common, with a stable frequency form 2010 onwards. This thesis provided evidence for the stabilizing effect of crosslinking in children up to five years. An interesting finding was that the chance of progression despite crosslinking treatment is much higher in children (22%) then in adults (2-10%). The prognosis after treatment is related to the location of the cornea that is most affected by keratoconus; patients with more central cones benefitting more from treatment in terms of cone flattening and patients with lower pre-treatment visual acuity are more likely to benefit from crosslinking with respect to visual acuity. Although the transepithelial crosslinking technique was initially lauded by many for its potential beneficial effects, head-to-head comparison between the transepithelial technique and the (original) epithelium-off technique demonstrated that transepithelial crosslinking was less effective in halting keratoconus progression than epithelium-off crosslinking. Furthermore, there was no clinically relevant difference between the two techniques on higher-order aberration, which are optical disturbances of the cornea that are not correctable by glasses and that are much more frequent in keratoconic eyes than in normal eyes.

    The cost of the crosslinking treatment, including pre-treatment screening and one year follow-up are €1759.06 ($1929.47). In order to investigate the rational of investing money in crosslinking treatments in order to prevent future corneal transplantations and loss of visual acuity, we performed a cost-effectiveness analysis. Cost-effectiveness turned out to be strongly influenced by the assumption of crosslinking effectiveness duration. The longest documented stabilizing effect of crosslinking in literature is ten years. When assuming no effect of crosslinking after ten years, the benefits in terms of gain in quality of life and prevented transplantations would be relatively small in relation to the costs of crosslinking (€54,384 per quality-adjusted life year). However, long term follow-up studies on crosslinking efficacy showed no trend towards a diminishing effect over time, and a stabilizing effect beyond ten years is regarded probable and reasonable. If a lifetime stabilizing effect of crosslinking was assumed crosslinking would be very cost-effective compared to standard management (€10,149 per quality-adjusted life year).
    Original languageEnglish
    Awarding Institution
    • University Medical Center (UMC) Utrecht
    • Imhof, Saskia, Primary supervisor
    • Wisse, RPL, Co-supervisor
    • de Wit, Ardine, Co-supervisor
    Award date2 Feb 2017
    Print ISBNs978-94-6233-490-8
    Publication statusPublished - 2 Feb 2017


    • Keratoconus
    • crosslinking
    • transplantation
    • keratoplasty
    • quality of life
    • costs
    • cost-effectiveness
    • higher-order aberrations


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