Theranostic Guided Riboflavin/UV-A Corneal Cross-linking
Condition: Keratoconus
MeSH terms: Keratoconus
Study type: Interventional

Summary: 
      This is a clinical study consisting of a study arm to assess the performance of the
      theranostic software module (Research Use Only) of a CE marked (CE1936) UV-A medical device,
      C4V CHROMO4VIS™, in order to validate its use for theranostic-guided corneal cross-linking
      treatment of keratoconus and corneal ectasia. The study hypothesis is that theranostic-guided
      riboflavin/UV-A corneal cross-linking with the C4V CHROMO4VIS™ system is safe and can
      estimate treatment efficacy during operation, regardless of treatment protocol, i.e., either
      with or without epithelial removal.
    

Detailed description: 
      Keratoconus is a naturally-occurring ocular condition characterized by progressive thinning
      and steepening of the central cornea, resulting in corneal optical irregularities with
      increasing myopia, irregular astigmatism, corneal opacity and consequential loss of visual
      acuity. Riboflavin/UV-A corneal cross-linking is a procedure used to biomechanically
      stabilize the weak cornea in keratoconus and to slow down or halt the clinical progression of
      this disease. Theranostics is an emerging therapeutic paradigm that enables monitoring of
      image-guided therapy in clinic through the use of a theranostic module that makes use of
      real-time non-invasive molecular analysis of the tissue being treated to achieve optimal
      treatment outcomes in the management of disease.

      The theranostic software module of the C4V CHROMO4VIS™ medical device is able to measure the
      concentration of riboflavin into the cornea during treatment (i.e., the riboflavin score) and
      to provide the surgeon with an objective assessment of treatment efficacy (i.e., the
      theranostic score).

      The scope of this study is to validate the theranostic imaging biomarkers by assessing the
      change of corneal topography Kmax value at 1-year postoperatively. The 1-year follow-up is
      long enough to provide scientific evidence of the safety and efficacy of the theranostic UV-A
      medical device in question. A pre-operative examination will ensure that every interested and
      willing participant fulfils the inclusion criteria of this study. Post-operative examinations
      will be carried out after 1 week, 1 month, 3 months, 6 months and 12 months.

      This is a multi-center clinical trial. Eligible participants will be stratified with
      allocation ratio 1:1 into either treatment protocol (EpiOn and EpiOFF Thera-CXL) using a
      computer-generated stratification plan with blocks. Two different blocks are created, which
      include eyes with Kmax steeper or flatter than 54.0 D to allocate patients with comparable
      baseline Kmax values in either treatment protocol.
    

Intervention name(s): Riboflavin/UV-A corneal cross-linking
Intervention type(s): Device
Intervention description(s): Corneal cross-linking procedure will be performed using the theranostic software module of the C4V CHROMO4VIS™ system in all participants. Participants will receive a single dose of the 0.22% riboflavin ophthalmic solution, RitSight™. Application of the riboflavin eye drop will be done for 15 minutes for the EpiOFF CXL treatment and 20 minutes for the EpiON CXL treatment. Estimates of riboflavin concentration into the cornea will be monitored by the C4V CHROMO4VIS™ system during the dosing phase of treatment. Once the dosing phase is completed, the C4V CHROMO4VIS™ system provides the Operator the access to the UV-A irradiation of the cornea with 5.4 J/cm2 total energy dose and 7.00 mm light beam diameter in all participants. Estimates of treatment efficacy by calculation of theranostic score will be performed by the C4V CHROMO4VIS™ system during UV-A irradiation.
Intervention MeSH terms: Riboflavin
Intervention model: Single Group Assignment
Intervention model description: One study arm receiving riboflavin/UV-A corneal cross-linking with either standard, Epi-OFF, or transepithelial, Epi-ON, treatment protocol. Only one eye of each participant is designated as the study eye.
Masking: None (Open Label)
Primary purpose: Other
Keywords: theranostics; riboflavin; UV-A light; corneal cross-linking