Corneal Collagen Cross-linking Study
Victorian Eye and Ear Hospital (RVEEH)
Centre for Eye Research Australia (CERA)
Update June 2011
Centre for Eye Research Australia (CERA) in Melbourne has provided
the Association with an update on its corneal collagen crosslinking
trial. Started in 2006, the CERA trial was the world's first randomized
clinical trial of corneal crosslinking and is being followed closely
by corneal surgeons and keratoconus patients in Australia and overseas.
including up to 4-year findings were presented at the International
Congress of Collagen Crosslinking in Milan in January 2011. Data analysis including up to 4 year findings were presented at the 6th International Congress of Collagen Cross Linking in Milan in January 2011.
At the time of the last interim analysis, nine treated patients and ten patients from the control group had completed their four year follow-up. While there are considerable individual differences in the initial post-operative period, follow-up at the 4 year mark indicates that patients who receive CXL remain stable or show a slight improvement in either vision, corneal steepness, or both.
Participants in the control group on average experienced a slight worsening of their condition. In cases where marked progression was noted, patients in the control group were offered the treatment on compassionate grounds. To date, 13 patients have received CXL for this reason.
It should be emphasized that this trial only involves patients with progressive keratoconus who are 16 years or older. While there is increasing interest in CXL for younger patients, there is currently only limited research data available to support this. Therefore any decision to treat a patient under 16 years of age with CXL would need to be carefully considered and can only be made on an individual basis.
The conference highlighted the high level of interest internationally of the Australian trial. During the congress, two major variations of the current recommended protocol were the subject of lively discussion. These were:
1) the potential to achieve effective CXL treatment without removing the corneal epithelium (outer skin of the cornea) and 2) variations in the treatment parameters intended to achieve comparable results with shorter treatment times.
While these amendments would be equally appealing to both people undergoing
the treatment and clinicians performing CXL, doubts were expressed
about the efficacy of the currently trialed ‘epithelium on’ options.
Although the concept of a shorter treatment time might hold great future
potential, the majority of Congress delegates agreed that there is
a need for thorough scientific evaluation of any treatment variation
and that a formally structured protocol should be developed.
full update can be downloaded here.
Interested in becoming a study participant?
Patients who are interested in participating in the ‘thin cornea’ pilot
study, keratectasia pilot, or in being involved in future trials are advised
to contact their eye care specialist or Tony Wu (Trial Coordinator) on 03 9929
8618 or email@example.com.
Funding to continue these important trials is still required. If you would
like to donate, please contact Fiona Slocombe (CERA Fundraising Administrator)
on 03 9929 8426 or firstname.lastname@example.org.
Update July 2009
Update December 2008
update on the corneal
collagen crosslinking study can be found on the RVEEH website here
of the RVEEH Study
FAQ bulletin below has been posted by Keratoconus Australia in the interests
of public information. Keratoconus Australia has relied on information
provided by the trial conveners in preparing this FAQ bulletin. Keratoconus
Australia and its officers cannot be held responsible for any claims about
the treatment, the trial, its risks and outcomes. Nor will it accept responsibility
for inaccuracies or misunderstandings arising from this bulletin. Patients
interested in the trial are strongly advised to make their own inquiries
about this treatment, the trial and its suitability and risks for them.
Australia supports research into treatments for keratoconus and its effects
on vision. As part of its commitment to research in this field, the Association
is providing assistance to the trial organizers. However as a patient support
group, we are not qualified to make judgments about the safety or usefulness
of experimental treatments like the collagen crosslinking treatment for
keratoconus. Nor do we stand to make any financial gain from the trial.
people have been asking us about the new treatment for keratoconus
publicized first in
There has been
much confusion about the nature of the treatment, who it can
help and when it will be available.
information has been prepared to explain the new collagen cross-linking
treatment being trialed at Melbourne’s Royal Victorian
Eye & Ear Hospital.
held on 30 May
2006 in Melbourne to provide an opportunity for keratoconus patients
and their families to hear more about the treatment, the trial and
to ask questions about how this could affect them. The video of
this seminar is now available.
Update April 2007
by Dr Christine Wittig,
Research Fellow CERA
In October 2006, a second site joined the trial. Professor
Lawrie Hirst is the leading investigator in Queensland and can be contacted
at the Queensland Eye Institute in Brisbane on 07 3010 3360 (phone) or 07 3010
there are 35 patients (48 eyes) enrolled in the trial – 27 patients
(38 eyes) at the RVEEH and 8 patients (10 eyes) at the Queensland Eye Institute
in Brisbane. The early results are promising, suggesting a treatment effect
at 3 months. It is important that the trial continues to confirm these early
trends and confirm that the effect is maintained.
Until recently, involvement in the trial has
been limited to patients with a cornea thicker than 400 microns. However, many
patients with progressive keratoconus have corneas thinner than this threshold.
In order to allow these patients to participate in the trial, the procedure
has been modified in a way causes the cornea to swell (thicken) temporarily
for the duration of the treatment (approximately 45 minutes). Although worldwide
the number of eyes treated in this way remains small, early results indicate
that this strategy provides a similar level of protection of the deeper ocular
tissues. In February 2007, the RVEEH Human Research
Ethics Committee approved this amendment to the original protocol which allows
eyes with a corneal thickness of at least 330 microns to be enrolled in the
now being sought to continue recruitment for this study for at least the
next six months. Anyone in a position to assist in the financial support
of this project may do so through and every support is greatly appreciated.
For details please contact the Fundraising
Manager at the Centre for Eye Research Australia, on (phone) 03 9929 8360
, (fax) 03 9662 8423 or Email: email@example.com
FREQUENTLY ASKED QUESTIONS
What is keratoconus?
The cornea is the clear window on the front of
the eye. It provides the majority of the focussing power of the eye.
Keratoconus is a common bilateral corneal condition, occurring in more than 1
in 2000 people. It is characterised by progressive corneal thinning and
stretching which gradually progresses in both eyes allowing the corneas to
bulge forward and adopt
an irregular cone shape. As a result, the eye develops astigmatism and the vision may become
condition typically starts in adolescence and early adulthood. Initial
management is with glasses or rigid contact lenses. Replacement of the central
cornea by corneal transplantation surgery becomes necessary in a minority of
affected individuals when vision can no longer be improved with glasses or
What is collagen cross-linking?
Although current treatments can improve vision in
keratoconus, they do not treat the underlying cause of the corneal weakness and
distortion. They do not stop the progression of keratoconus.
new technique of collagen cross-linking using the photosensitizer
riboflavin (vitamin B2) and ultraviolet light (UVA) has been developed in
Europe. In extensive experimental studies in animal eyes (including
biomechanical stress & strain measurements) researchers have demonstrated
a significant increase in corneal rigidity or stiffness after collagen
cross-linking using this riboflavin/UVA treatment.
A pilot clinical study in humans evaluated the effect of the
new cross-linking method in patients with keratoconus and showed that, in all
treated eyes, progression of the condition was halted. To date there are over
100 patients with more than 2 years follow-up after cross-linking treatment and
some eyes have been followed for 5 years with encouraging results.
the treatment done?
treatment involves removing the skin (epithelium) from the surface of the
cornea and then applying Riboflavin
eye drops. The eye is then exposed to UVA light for 30 minutes. After
the treatment, an eye-pad is worn for 1-3 days and antibiotic ointment is
applied to the treated eye four times a day until the surface of the eye has
Who can benefit from this
important to understand that collagen cross-linking treatment is not a cure for
keratoconus. Rather, it aims to slow or even halt the progression of the
condition. After the treatment, it is expected that it will continue to be
necessary to wear spectacles or contact lenses (although a change in the
prescription may be required). However, it is hoped that the treatment will
prevent further deterioration in vision and the need for corneal
A person whose keratoconus is already so bad that it
cannot be corrected by contact lenses is unlikely to gain any benefit from this
treatment. In this situation a corneal transplant is usually required.
Initially the treatment would be offered only to patients in
whom there is clear evidence of progression of their keratoconus.
When would this treatment become more widely available to
other keratoconus patients?
Should the treatment prove safe and effective, it is likely
that it will be made more widely available. It is possible that other centers
will offer this treatment before the trial is concluded.
What is the trial being conducted at the RVEEH?
The trial is
a randomized control trial designed to test the hypothesis that Riboflavin/UVA
treatment may be useful in maintaining and improving corneal rigidity in
keratoconus, and may retard or even stop progression of the disease.
the clinical usefulness and efficacy of Riboflavin/UVA treatment in
those with progressive keratoconus.
the safety profile of this treatment.
100 volunteers will participate in the trial. Approximately 50% of the eyes
that qualify will be randomly allocated to receive the treatment; the other 50%
will act as the control group and will not receive the treatment. Subjects in
both groups will undergo regular detailed clinical examinations over the course
of the trial.
will be analyzed at regular intervals during the course of the study. If there
is a significant effect observed in treated patients (relative to the control
group), those patients in the control group will also be offered the treatment
(free of charge). The trial will be continued for up to 5 years in order to
gather valuable long-term data.
Am I eligible to participate in the trial?
To be eligible to participate in the trial, you will need to
meet two essential criteria:
diagnosis of keratoconus must be confirmed based on clinical examination
findings and corneal topography (mapping), and
must be evidence of progression of the keratoconus occurring over the
last 12 months. This would be determined in conjunction with the treating
optometrist and/or ophthalmologist based on changes in contact lens
prescription, spectacle prescription and measurements of corneal shape
(keratometry or computerized corneal mapping).
You will NOT be eligible to participate in the trial
if any of the following apply:
are aged less than 16 or older than 50 years
are pregnant or breastfeeding
is a past history of Herpes Simplex Keratitis or corneal surgery
cornea is too thin (less than 330 microns)
corneal disease or scarring is present
is a history of chemical burns to the cornea or healing problems.
is a known allergy to Riboflavin
note that patients MUST be able and willing to attend regular examinations
at the Royal Victorian Eye & Ear Hospital in East Melbourne.
There could be as many as 8 visits during the first 12
months and annual checkups thereafter for up to five years.
who have had a corneal transplant in one eye may be able to participate
if their un-operated eye satisfies these requirements. Those who have
had transplants in BOTH eyes will not be able to take part in the study.
What are the risks?
are a number of potential risks associated with this treatment although very
few complications have been reported so far.
light is potentially harmful to the eye and some damage does occur to the cells
in the front part of the cornea where the treatment has its effect. However,
the dose used is designed to prevent observable damage to the cells that line
the back of the cornea or the other structures within the eye. No lens
opacities (cataracts) have been attributed to this treatment in European
treatment involves the scraping away of the outer layer (skin or epithelium)
of the cornea. There
is therefore a risk that the surface of the cornea will be slow or fail to
Infection may occur which could lead to the development of corneal scarring. Antibiotics
are routinely used to prevent this complication. Corneal scarring might
necessitate further surgical procedures (including corneal transplantation).
lesser but more common risks include:
to wear contact lenses for several weeks after the treatment
in the shape of the cornea necessitating a refitting of a contact lens or a
change in the spectacle correction.
As is the case with any experimental
treatment, there may also be long-term risks that have not yet been
corneal rigidity induced by exposure to UVA and riboflavin may wear off
over time and further
periodic treatments may be required, raising the possibility of other side
effects from repeat doses of the treatment.
Who will conduct the trial?
trial is being conducted by the Corneal Unit of the RVEEH in Melbourne
led by Dr Grant Snibson. Dr Christine Wittig, the principal researcher,
is a German doctor who participated in the early trials
of collagen cross-linking at the Dresden Hospital, Germany.
study has been approved by the Hospital’s Human Research Ethics Committee.
Will I be paid for participating
in the trial?
payments will be made to subjects for their participation in the trial
or to cover any expenses related to their attendance for examinations.
All treatments and examinations related to the trial will be provided
free of charge to participants.
If I can’t participate in the
trial, how can I assist?
Funding is still required for the
study and contributions can be made by contacting the Centre for Eye Research
:03 9929 8360 Fax:
03 9662 3859 Email:
How can I get more information
about participating in this trial and the collagen cross-linking treatment?
you have evidence from your optometrist that you may be a suitable candidate
for this trial (see above), you can contact the trial organizers by faxing
reports from your optometrist on the progression of your keratoconus and
your corneal thickness to 03 9662 3859 or emailing the
trial organizers .
Australia and the trial organizers held a
public seminar on May 30, 2006 in Melbourne to provide an opportunity for
keratoconus patients and their families to hear more about this treatment,
its benefits and risks and the trial itself. A video
of the seminar is now available. Go to Events for
information bulletin has been prepared by Keratoconus Australia in conjunction with Dr.
Christine Wittig Research Fellow, Centre for Eye Research Australia.