Dr Laurence Sullivan
Bayside Eye Specialists
Keratoconus may be characterised as a disorder of young people.1 There is a bimodal distribution of the age of onset with typical keratoconus beginning in the late teens or early twenties, and a later onset in middle age for the pellucid marginal corneal degeneration subtype. The earlier the onset of keratoconic keratectasia, the higher the chance of progression necessitating eventual corneal transplantation. Early onset keratoconus typically progresses for a decade or so before stabilising (relatively) in the early thirties. This is thought to be due to physiological collagen cross-linking that occurs with ageing.
What causes keratoconus?
Despite continuing research, the exact cause of keratoconus remains unknown. Research indicates that keratoconus may be caused by an excess of proteolytic enzymes that break down the proteins within the cornea, causing the cornea to become thin and stretched.
The genetic inheritance of keratoconus has not clearly been determined although sometimes it runs in families. It appears that it may involve a number of different genes—27 at last count. Blood relatives of someone affected with keratoconus have minor changes in their corneas that may indicate that keratoconus probably varies both in the specific genetic cause as well as in its expression within a family.
Vigorous eye-rubbing can contribute to the disease process. People with keratoconus should absolutely avoid rubbing their eyes. This is sometimes difficult because atopy is commonly associated with keratoconus. Anti-allergy drops such as Patanol or Zaditen can help. Another association is sleep apnoea.
Until recently, the only option for a keratoconus patient who was intolerant of a rigid contact lens was a corneal transplant, lamellar or full-thickness. About 20 per cent of keratoconus patients need corneal transplants during their life-times;2 however, pioneering work by a group in Dresden, Germany, under the direction of Theo Seiler MD PhD has provided a new treatment option to significantly delay or prevent the need for transplants in these patients.3
Corneal collagen crosslinking
When Professor Seiler originally introduced corneal collagen crosslinking (CXL) in 2003 as a therapeutic option to delay or prevent the progression of keratoconus, it was viewed with a healthy degree of scepticism but preclinical experiments and a large body of literature supporting its efficacy have since convinced us that this is a safe and effective treatment.4
The first randomised trial of this treatment, which was conducted in Melbourne at the Royal Victorian Eye and Ear Hospital, showed definite benefits5 (Figure 1). These results have been replicated many times and CXL has now become solidly established as a therapy. A minority of treated corneas also show significant flattening and improved best spectacle corrected visual acuity. (Figure 2)
Figure 1. Week 1 postoperative. Left arrow indicates residual scar from removal
of apical nodule, right arrow indicates anterior one-third corneal haze
In a clinical trial, Rabinowitz and colleagues have followed 300 cases done to date with three-year follow-up. They have noted minimal progression in only two per cent of patients. They have also treated 43 patients younger than 18 years of age using CXL. In these 51 eyes, even though keratoconus progression was rapid preoperatively, they have not seen any progression to date. Long-term follow-up studies suggest that the effect of CXL lasts at least eight years.6
Figure 2. Results of the Melbourne trial. Untreated eyes (A)
deteriorated while treated eyes (B) stabilised or improved
Based on Seiler's recommendations,7 we have adopted the following inclusion criteria for CXL:
- Progression of astigmatism by refraction of at least 1.00 D and confirmed by topographic evidence of progressive keratoconus in the year preceding treatment
- Corneal thickness, as measured by ultrasound, of no less than 400 µm
- Central K readings not exceeding 58 D
- No central or paracentral corneal scarring.
In selected eyes in which corneal thickness is between 350 and 400 µm, we have started performing CXL after using hypotonic solution to swell the cornea. Treating without epithelial removal has also been studied and seems to have about 30 per cent of the effect of treatment with removal of epithelium.8-10
If we believe that outcomes will be less than optimal because of severe central corneal irregularity, we recommend penetrating keratoplasty or deep anterior lamellar keratoplasty instead of CXL to avoid performing an additional procedure prior to proceeding to a transplant.
Young age is not now thought of as an exclusion criterion for CXL. Recent publications with paediatric patients have shown significant and rapid functional improvement in these young patients with progressive keratoconus who underwent CXL.11-19
Caporossi and colleagues found a good functional response and stability of the keratoconus with three years of follow-up.14
Vinciguerra and colleagues reported improved UCVA and BSCVA in patients up to 18 years of age with progressive keratoconus who underwent CXL.15 They felt that this improvement was most likely to be due to significant reduction of corneal asymmetry, and corneal as well as total wavefront aberrations. Gaster and colleagues reported in 2012 on 31 eyes of teenagers who underwent CXL and found significant improvement in UCVA and BSCVA and decreased pachymetry along with no significant complications.16 They concluded that CXL in young patients is safe and efficacious, and should be performed earlier rather than later.
A large Swiss study reported by Chatzis and Hafezi followed 59 eyes of children and adolescents aged nine to 19 years.17 They found significant corneal flattening up to two years post-treatment but observed some possible loss of effect at three years. Other recent papers18,19 suggest a similar positive response in younger patients as is seen in adults.
Treating children can introduce logistical and other difficulties. In adults the procedure is usually performed under topical anaesthesia, with 30 minutes of soaking with riboflavin solution followed by 30 minutes of focused UVA irradiation. This is not always well tolerated in children. We have treated a number of unco-operative patients at the RVEEH under general anaesthesia.
The future for keratoconus patients looks good and hopefully, in the not too distant future, the need for corneal transplantation will be significantly reduced. Unfortunately, this relatively new procedure is not yet covered by the Australian Medicare Benefits Schedule.
References available on request. Email email@example.com, Subject: Sullivan Corneal crosslinking