Efficacy of Customized Corneal Cross-linking vs. Standard Corneal Cross-linking

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Brief Title

Efficacy of Customized Corneal Cross-linking vs. Standard Corneal Cross-linking

Official Title

Efficacy of Customized Corneal Cross-linking Versus Standard Corneal Cross-linking in Patients With Progressive Keratoconus

Brief Summary

      The standard or Dresden protocol was established in 2003 and treats the entire cornea.
      However, recent ultra-structural research showed that keratoconus is localized. Therefore,
      treating only the affected zone and minimalizing the risk of damaging surrounding tissues
      would be beneficial.

      The objective of this study is to evaluate whether the effectiveness of customized
      cross-linking (cCXL) is non-inferior to standard accelerated cross-linking (sCXL) in terms of
      flattening of the cornea and halting keratoconus progression.
    

Detailed Description

      In 2003 Wollensak et al used corneal cross-linking (CXL) in humans to halt the progression of
      keratoconus. During the procedure the top layer of the cornea, the epithelium, is debrided.
      Then the cornea is soaked with riboflavin, a photosensitizer. Hereafter a 9.0 mm diameter
      Ultraviolet-A (UVA) beam radiates the cornea for 30 minutes with a fluence of 3 mW/cm2
      resulting in a total energy of 5,4 J/cm2. This protocol is called the Dresden protocol.
      Currently, accelerated versions of the Dresden protocol are used in common practice. There
      are different accelerated protocols with fluences of 9mW/cm2, 10mW/cm2 and 15 mW/cm2. The
      higher the fluence, the shorter the treatment time, however according to the Bunsen-Roscoe
      reciprocity law the total amount of energy stays the same.During the procedure oxygen
      radicals are formed that interact with the surrounding molecules, leading to the formation of
      new chemical bounds between the collagen fibrils (i.e. corneal crosslinks). The final goal of
      the procedure is to cause the cornea to stiffen and achieve flattening of the treated region.

      For any treatment, it is imperative that the unaffected region of the tissue is not
      unnecessarily treated by an intervention or drug application. To minimalize the risk of
      damage to surrounding tissues it would be beneficial that the UVA beam is restricted to the
      affected, keratoconic zone in the patient's cornea. This can be achieved by customizing the
      beam shape and size in a way that only the degenerated zone is treated, i.e. by customized
      cross-linking (cCXL). Recently published studies provide clinical evidence that similar
      clinical outcomes (amount of corneal flattening) can be achieved when only the cone is
      treated instead of the entire cornea.They also show the potential benefits of cCXL, e.g. the
      treatment is patient-specific, a smaller surface of the cornea is irradiated, lower incidence
      of corneal haze, a faster reepithelialisation and a shorter procedure time. However, none of
      these studies are randomized and study results are limited by using small sample sizes.
      Therefore, we feel that there is a great need for a randomized controlled trial with an
      appropriate design and sample size to confirm these findings.

      The aim of this study is to investigate if cCXL is non-inferior to sCXL (10 mW/cm2) in terms
      of flattening of the corneal surface and halting the disease progression.
    


Study Type

Interventional


Primary Outcome

Change in maximum keratometry (Kmax)

Secondary Outcome

 Visual acuity

Condition

Keratoconus

Intervention

Customized crosslinking

Study Arms / Comparison Groups

 Customized crosslinking
Description:  In the customized corneal cross-linking protocol (cCXL) a patient-specific treatment pattern, based on the patient's Pentacam images, will be used to treat the cornea. The CXL pattern exists out of 3 concentric circles and is centered on the cone. To estimate the cone location a combination of the thinnest corneal point, maximum anterior elevation and maximum posterior elevation is used. The epithelium is debrided with alcohol within the marked zone. After the application of riboflavin each circle receives a different amount of energy, which gradually decreases with increasing circle size.
The procedure is done with the Avedro Mosaic CXL device (Avedro, Inc. Waltham, Massachusetts, United States).

Publications

* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.

Recruitment Information


Recruitment Status

Procedure

Estimated Enrollment

124

Start Date

March 1, 2021

Completion Date

July 2023

Primary Completion Date

July 2023

Eligibility Criteria

        Inclusion Criteria:

          -  Progressive keratoconus based on an increase of maximum keratometry (Kmax) of 1
             diopter (D) over a time period of 12 months

        Exclusion Criteria:

          -  Corneal scarring

          -  Corneal disease other than keratoconus

          -  History of corneal surgery (e.g. refractive surgery, corneal transplantation,
             intracorneal ring segments)

          -  Patient unwilling or unable to give informed consent, unwilling to accept
             randomization or inability to complete follow-up (e.g. hospital visits) or comply with
             study procedures

          -  Insufficient corneal thickness including epithelium < 375 µm

          -  Pregnancy

          -  Among patients in whom both eyes are eligible only the first eye which is undergoing
             corneal cross-linking is enrolled in the study

          -  Participation in another clinical study
      

Gender

All

Ages

16 Years - 45 Years

Accepts Healthy Volunteers

No

Contacts

R.M.M.A. Nuijts, MD, PhD, 433877229, [email protected]

Location Countries

Netherlands

Location Countries

Netherlands

Administrative Informations


NCT ID

NCT04532788

Organization ID

NL73003.068.20


Responsible Party

Sponsor

Study Sponsor

Maastricht University Medical Center

Collaborators

 ZonMw: The Netherlands Organisation for Health Research and Development

Study Sponsor

R.M.M.A. Nuijts, MD, PhD, Principal Investigator, Department of Ophthalmology, Maastricht University Medical Center (MUMC+)


Verification Date

August 2021