Keratoconus is a disorder in which the paracentral and central cornea undergo progressive thinning and steepening, almost always initially presenting to optometrists. Even very early disease can be detected by corneal topography, a Placido-based imaging technique which demonstrates thinning, steepening and irregularity of corneal curvature. In its early stages, keratoconus causes worsening of vision on account of increasing myopia and irregular astigmatism. Spectacle correction provides good visual acuity in early disease only, until increasing irregular astigmatism requires correction with rigid contact lenses for best vision. Patients with more advanced keratoconus lose contact lens-corrected visual acuity on account of corneal opacification and eventually require corneal transplant surgery: in one large multicentre report, transplantation was eventually necessary in at least one eye of 21% of patients.
CXL
Irrespective of the age at onset, keratoconus progresses until the age of around 30 to 35 years before spontaneously stabilising. The concept of stabilising keratoconus and arresting its progression at a stage when there is still good unaided or spectacle-corrected vision is relatively recent. Corneal collagen cross-linking (CXL) increases the stiffness of the cornea, which can stop the progression of early keratoconus. It is the only current intervention for this purpose. CXL has been reported to be efficacious in the majority of treated adult eyes in a number of non-randomised studies and two randomised controlled trials. At Moorfields Eye Hospital in a 2016 audit, 381 of 406 eyes had clinically defined stabilisation of keratoconus progression at 12 months post-CXL (personal communication, Daniel Gore). CXL has been approved by the National Institute for Health and Care Excellence (NICE) in the UK and has become widely available across most regions as a NHS-funded procedure.
Paediatric challenge
Young age at presentation, before 20 years, is accepted as a prognostic indicator of high risk of progression to rigid contact lens wear and later corneal transplantation. A number of studies have reported an inverse correlation between age and keratoconus severity. Indeed, keratoconus is one of the most common causes of corneal transplantation in the under 17 year age group.
In younger subjects, only two observational studies of CXL in keratoconus patients of under 19 years have been published, each reporting effectiveness. Findings included improved visual acuity, reduced myopic spherical equivalent on refraction testing, and flattening on keratometry readings compared to pre-CXL. Although the above studies suggested a beneficial effect of CXL, no randomised trial has been undertaken in young patients. In the United Kingdom, NICE has requested more robust evidence before recommending CXL in the paediatric age group.
One consequence of increasing availability of corneal topography, not least in optometrists’ practices, is definitive diagnosis of keratoconus at an earlier age and stage of disease. Increasing numbers of young keratoconus patients are being referred to hospital clinics. If such patients have progression of keratoconus, this may be the optimum time to use CXL – in order to halt progression in one or both eyes while unaided or spectacle-corrected visual acuity remains good. Research on effectiveness of CXL in the paediatric age group is needed now and the results will be of sustained interest.
Keralink trial
The Keralink trial has been designed to investigate efficacy and safety of the established technique of CXL in the paediatric age group. This is a trial funded by the National Institute for Health Research, in which patients aged 16 or less with progressive keratoconus in one or both eyes will be randomised to receive either CXL or standard care with spectacles and/or contact lenses. The trial will directly address these questions:
- What is the efficacy of CXL in the early stage of keratoconus in children?
- If effective, what is the duration of CXL benefit, particularly in young patients?
- Is there a measurable improvement in quality of life following CXL?
Funding for 21-month follow-up is in place in the first instance, although the Keralink team will seek funding for longer follow-up of recruited patients.
The trial will commence recruitment in October 2016 and be conducted in Moorfields Eye Hospital in London, St Paul’s Eye Unit in Liverpool and the Royal Hallamshire Hospital in Sheffield. As young patients with early keratoconus are the ideal recruits for the trial, it is from optometrists that Keralink
investigators particularly need to recruit patients. The chief investigator is Mr Frank Larkin at Moorfields, assisted by consultant colleagues Mr Stephen Tuft (also Moorfields), Mr Matthew Edwards and Mr Mathew Raynor (Sheffield) and Prof Colin Willoughby (Liverpool). Patients aged 16 or younger with a confirmed diagnosis should be referred to any of the centres via their GP, with a copy of the corneal topography if this has been done.
For further information please contact Mr Larkin, consultant ophthalmologist, c/o Judy.Carpenter@moorfields.nhs.uk or Seetal Savania Dholakia, clinical research optometrist, seetaldholakia@hotmail.com.