ARGO: Theranostic Guided Riboflavin/UV-A Corneal Cross-linking
Study Details
Study Description
Brief 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.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
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N/A |
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 and to provide the surgeon with an objective assessment of treatment efficacy.
The scope of this study is to validate the theranostic imaging biomarker score 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.
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: Riboflavin/UV-A corneal cross-linking monitored by theranostic software module 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. |
Device: Riboflavin/UV-A corneal cross-linking
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.
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Outcome Measures
Primary Outcome Measures
- Validation of the theranostic score [12 months]
The aim of this study is to validate the Theranostic Imaging Biomarker for theranostic-guided corneal corneal cross-linking (CXL) in patients with keratoconus
Secondary Outcome Measures
- Corneal topography outcome [12 months]
Change of Maximum Simulated Keratometry
- Treatment safety [12 months]
Change of Endothelial Cell Density
Other Outcome Measures
- Manifest Refraction change [12 months]
Change of Manifest Refraction
Eligibility Criteria
Criteria
Inclusion Criteria:
criteria for inclusion in the clinical trial are those currently referred to as the golden standard for the treatment of corneal cross-linking. The criterion to determine progression of keratoconus is based on providing at least one of the following evidences:
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at least two Placido disk corneal topography measurements showing at least +1.00 D steepening of the Kmax value in the last year or longer interval period.
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at least two manifest refraction measurements showing at least -0.50 D change in spherical equivalent refraction in the last year or longer interval period.
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at least two central corneal thickness (CCT) measurements showing at least -10 µm change in in the last year or longer interval period.
Exclusion Criteria:
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Anterior corneal curvature steeper than 63 D;
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Corneal thickness thinner than 400 µm;
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Corneal scarring;
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Descemetocele;
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History of herpetic keratitis;
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Concomitant eye diseases;
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Inflammatory eye diseases;
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Glaucoma;
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Cataract;
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Nistagmus;
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Pregnancy;
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Breast feeding.
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Azienda Ospedaliera Universitaria Mater Domini - Università Magna Graecia di Catanzaro | Catanzaro | Italy | 88100 | |
| 2 | Azienda Ospedaliera Universitaria Careggi, Università di Firenze | Firenze | Italy | 50134 | |
| 3 | Azienda Ospedaliera Universitaria Policlinico G. Martino, Università di Messina | Messina | Italy | 98124 |
Sponsors and Collaborators
- Regensight
Investigators
- Principal Investigator: Vincenzo Scorcia, MD, Azienda Ospedaliera Universitaria Mater Domini - Università Magna Graecia di Catanzaro
Study Documents (Full-Text)
None provided.More Information
Additional Information:
Publications
- Lombardo G, Micali NL, Villari V, Serrao S, Lombardo M. All-Optical Method to Assess Stromal Concentration of Riboflavin in Conventional and Accelerated UV-A Irradiation of the Human Cornea. Invest Ophthalmol Vis Sci. 2016 Feb;57(2):476-83. doi: 10.1167/iovs.15-18651.
- Lombardo G, Serrao S, Lombardo M. Comparison between standard and transepithelial corneal crosslinking using a theranostic UV-A device. Graefes Arch Clin Exp Ophthalmol. 2020 Apr;258(4):829-834. doi: 10.1007/s00417-019-04595-6. Epub 2020 Jan 3.
- Lombardo G, Villari V, Micali NL, Leone N, Labate C, De Santo MP, Lombardo M. Non-invasive optical method for real-time assessment of intracorneal riboflavin concentration and efficacy of corneal cross-linking. J Biophotonics. 2018 Jul;11(7):e201800028. doi: 10.1002/jbio.201800028. Epub 2018 Apr 10.
- Lombardo M, Lombardo G. Noninvasive real-time assessment of riboflavin consumption in standard and accelerated corneal crosslinking. J Cataract Refract Surg. 2019 Jan;45(1):80-86. doi: 10.1016/j.jcrs.2018.07.062. Epub 2018 Oct 22.
- Lombardo M, Pucci G, Barberi R, Lombardo G. Interaction of ultraviolet light with the cornea: clinical implications for corneal crosslinking. J Cataract Refract Surg. 2015 Feb;41(2):446-59. doi: 10.1016/j.jcrs.2014.12.013. Epub 2014 Dec 23. Review.
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