Trial Detail





Hong Kong Eye Hospital

Hong Kong Eye Hospital


Miss Wong Sin Ting Janice

Department of Ophthalmology & Visual Sciences The Chinese University of Hong Kong 3/F Hong Kong Eye Hospital 147K Argyle Street, Mongkok, Hong Kong SAR


The Chinese University of Hong Kong

Dr. Chow Wing See Vanissa

3/F, Hong Kong Eye Hospital, 147K, Argyle Street, Mongkok, Kowloon, Hong Kong


Hong Kong Eye Hospital, The Chinese University of Hong Kong

Repeat Collagen Cross-Linking for Keratoconus

Repeat Collagen Cross-Linking for Keratoconus


Repeat Cross-linking

Hong Kong





Drug and device and surgery

1. UV-A 3mW
2. 1% riboflavin
(The steroid, contact lens are routine postop medications)

1. UV-A 3mW : 30 minutes
2. 1% riboflavin : q2min x 15

Collagen crosslinking (CXL) has emerged for the past ten years as another treatment option for keratoconus. It involves application of riboflavin 0.1% as a photosensitizer and ultraviolet-A (UV-A) light on the affected corneal surface after removal of corneal epithelium. UV-A induces a photo-oxidative reaction resulting in additional covalent bond formation between collagen filaments in the cornea, thereby increasing the cornea’s strength and stability. This treatment differs from all above treatment options as it targets directly at the pathology of the ectatic cornea, by stabilizing the corneal structure.

The conventional CXL protocol of 3mW/cm2 UV-A irradiance for 30 minutes has extensive evidence demonstrating promising clinical and topographic results.2-8 Stabilisation is seen in most eyes, and regression is also seen with steepest curvature reduced by two diopters in 21.3-80% of eyes and improvement of one Snellen line in best-corrected visual acuity in more than 50% of eyes9. There is improvement in the corneal shape, as suggested by improvement in topographic indices10. Patients’ subjective visual function11 and quality of life1 also improve after CXL. It is also safe, in both paediatric12 and adult populations. Loss of two or more Snellen lines of visual acuity is reported at a rate of 2.9-3.5%9, which may be due to infective keratitis, endothelial damage, stromal scarring or progression of disease (7.6%13). Risk of damage to the endothelium, lens or retina from the UV-A irradiation is prevented by strict adherence to the suggested amount of irradiation and selecting patients with more than 400micron of corneal thickness9, 14, 15.

Based on the Bunsen-Roscoe law of reciprocity16, using a constant radiant exposure of 5.4 J/cm2, accelerated CXL has been developed as an alternative treatment protocol with higher illumination intensity but shorter duration. Clinical results in the literature, though promising, are small-scaled and short-term.17-21 In vitro results, on the other hand, question its efficacy as corneas treated by accelerated CXL were less biochemically stiff than when treated with conventional CXL.22 We have also performed accelerated CXL in 36 eyes since 2012, and one-year results showed that 22% (4/18) suffered from progression of disease still.

Currently there is only one case report that showed additional topographic improvement with accelerated CXL after conventional CXL23, with no adverse outcome on the vision or endothelium. The current study wishes to explore the outcome of retreatment with conventional CXL on eyes that have failed to respond to accelerated CXL.

a. Previously treated with accelerated CXL
b. Progressive keratoconus after treatment, as defined by
i. worsened best-corrected visual acuity not accountable by corneal scarring (or other lenticular or posterior segment diseases), and/or
ii. 1D increase in steepest curvature, >1D increase in manifest cylinder and >0.5D increase in manifest spherical equivalent observed at two consecutive occasions

a. Central ECD ≤ 2000
b. Corneal pachymetry <400um at thinnest point (on Pentacam)
c. Corneal scarring
d. History of corneal surgery, herpetic eye disease, severe DES, LSCD, delayed epithelial healing
e. Underlying autoimmune disease, pregnancy, nursing

13 years of age

999 years of age

Both Male and Female



Historical control

Open label

Single group




1. Topography: Kmax, Kmean, anterior elevation, posterior elevation

1. Visual acuity
2. Refraction
3. Endothelial cell density
4. Axial length
5. Pachymetry
6. Complications





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