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Corneal Collagen Cross-linking in Keratectasia
mOsmol/l). Hypo-osmolar riboflavin solution does not contain Figure 2: Regression of Keratoconus After Corneal
dextrane T500. The solution is protected from light and used within
two hours. After removal of the corneal epithelium and 30 minutes
of instillation of iso-osmolar riboflavin solution, the corneal stromal
thickness was measured using ultrasound pachymetry. In cases
where the remaining stromal bed was thinner than 400µm, hypo-
osmolar riboflavin was applied every 20 seconds for five more
minutes, and the corneal thickness is checked again. Hypo-osmolar
riboflavin solution is administered repeatedly until the minimal
corneal thickness reaches 400µm, which usually occurs within five
to 15 minutes.
The absolute increase in corneal thickness that can be achieved
using this modified protocol ranges between 36 and 110µm. The
technique has been used successfully with primary progressive
keratoconus and iatrogenic keratectasia after refractive laser
surgery; the results are similar to those in patients in whom the
standard protocol (i.e. an iso-osmolar solution) was used. Scheimpflug true net power analysis of the anterior corneal surface pre-operatively and at six
months after corneal collagen cross-linking. The difference map shows the decrease in the
maximal K-readings (arrows).
Removing or Not Removing the Epithelium
Recently, Pinelli and co-workers suggested a modification of the colleagues analysed 241 eyes of 272 patients with progressive
technique in which no epithelium is removed. They claim that this keratectasia with a maximum follow-up of six years. The maximal
modification is an enhancement of the technique for several K-readings decreased significantly by 2.68D in the first year, by
reasons: first, the procedure is painless for the patient, and second, 2.21D in the second year and by 4.84D in the third year (see Figure
the complications of epithelial healing are avoided. However, 2). The best corrected visual acuity (BCVA) improved significantly
Wollensak et al. have recently unambiguously shown in rabbit (≥1 line) in 53% of 142 eyes in the first year, in 57% of 66 eyes in the
corneas that the increase in biomechanical strength in corneas second year and in 58% of 33 eyes in the third year, and remained
where the epithelium had not been removed is only one-fifth that stable (no lines lost) in 20, 24 and 29%, respectively.
of corneas in which the epithelium had been removed prior to
Mazzotta and co-workers presented a six-month follow-up after CXL
for keratoconus including in vivo confocal microscopy in 10 eyes of
Corneal Collagen Cross-linking in 10 patients.
Confocal microscopic analysis at one month after CXL
Primary Keratectasia – Keratoconus and using the standard parameters showed that the outer 270–350µm of
Pellucid Marginal Degeneration the stroma were free of keratocytes. This confirms the experimental
Between 1999 and 2002, 22 patients with progressive keratectasia results of Wollensak et al., who detected keratocyte apoptosis up
were treated in a phase I clinical study and were followed for an to 300µm depth following CXL.
At six months after treatment,
average of two years (range three months to four years).
The re-population by activated keratocytes led to an even higher density
distinction between clinical subentities such as keratoconus and than that seen pre-operatively. An increase of approximately 20% of
pellucid marginal degeneration was not performed. The progression corneal thickness was attributed to corneal oedema; this gradually
halted in every case, and no side effects were observed except for returned to pre-operative levels at six months after treatment.
slight corneal oedema, photophobia and minimal intrastromal Although not numerically documented, the authors did not observe
a change in endothelial cell counts or appearance (morphometry) at
any time after treatment.
To investigate potential long-term side
Corneal Collagen Cross-linking in Secondary
effects and complications of corneal
Keratectasia – Iatrogenic Keratectasia After
Refractive Laser Surgery
collagen cross-linking, prospective
Kohlhaas and co-workers reported the first CXL in a case of
studies with a follow-up of at least
iatrogenic keratectasia after laser-assisted in situ keratomileusis
The keratectasia occurred one month after LASIK, and the
eight to 10 years will be necessary.
progression was documented for the following 10 months. Within a
follow-up of 18 months after CXL, corneal topography, K-readings
and refraction were stable. No side effects regarding corneal
scarring in the early post-operative phase. Sixteen eyes showed a endothelium were reported. Hafezi and co-workers presented
regression of the keratectasia with a reduction of the maximal 10 cases of CXL after iatrogenic keratectasia with a follow-up of
K-readings by 2D.
Endothelial cell counts were unaffected by the up to 25 months.
Their results show that CXL can distinctly reverse
treatment. In the follow-up five-year study, 48 patients were otherwise progressive iatrogenic keratectasia after LASIK. The
included and, again, no patient showed further progression of observed reduction of maximal K-values is probably due to
keratoconus. Regression was observed in 31 patients by an average the increased biomechanical stability of the cornea after cross-
In a long-term follow-up study, Raiskup-Wolf and linking and is in line with similar findings in keratoconus patients
EUROPEAN OPHTHALMIC REVIEW 59