Theranostic Guided Riboflavin/UV-A Corneal Cross-linking

NCT05457647 | Completed Results

• 1 other identifier: RSKC001
• Study Type: interventional
• Target: 50
• Locations: 1 country
• Sites: 3

Brief Summary

This is a clinical study consisting of a study arm to validate accuracy and precision of the combined use of theranostic imaging biomarkers, riboflavin score and theranostic score, to assess and predict efficacy of corneal cross-linking in flattening the corneal topography Kmax value at 12-months postoperatively. The objective of the study is 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.

Conditions

Keratoconus

Keywords

theranostics; riboflavin; UV-A light; corneal cross-linking

Outcome Measures

Primary Outcomes (1)

• Validation of the Theranostic Scores

  The aim of this study is to validate the combined use of theranostic imaging biomarkers in predicting the propsensity of corneal corneal cross-linking (CXL) in flattening the Kmax at 1-year. The accuracy and precision (95% CI) of the combined use of the theranostic imaging biomarkers to predict CXL treatment outcome are determined by calculating the percentage of correctly classified eyes and the positive predictive value (PPV) respectively.

  12 months

Secondary Outcomes (2)

• Corneal Topography

  12 months

• Endothelial Cell Density

  12 months

Other Outcomes (5)

• Manifest Refraction

  12 months

• Corrected Distance Visual Acuity

  12 months

• Uncorrected Distance Visual Acuity

  12 months

Study Arms (1)

Riboflavin/UV-A corneal cross-linking monitored by theranostic software module

EXPERIMENTAL

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

Interventions

Riboflavin/UV-A corneal cross-linking DEVICE

Corneal cross-linking procedure is performed using the C4V CHROMO4VIS™ medical device equipped with theranostic software module in all participants. Participants will receive a single dose of the 0.22% riboflavin ophthalmic solution, RitSight™. Application of the riboflavin eye drop is done for 15 minutes for the epi-off CXL treatment and 20 minutes for the epi-on CXL treatment. Estimates of riboflavin concentration into the cornea are monitored by the C4V CHROMO4VIS™ system during the dosing phase of treatment. Once the pre-set dosing phase is completed, the C4V CHROMO4VIS™ system provides the Operator the access to the UV-A light irradiation of the cornea with 5.4 J/cm2 total energy dose (10 mW/cm2 for 9 min.) and 7.00 mm light beam diameter in all participants. Estimates of treatment efficacy by calculation of theranostic score are performed by the C4V CHROMO4VIS™ system during UV-A light irradiation.

Riboflavin/UV-A corneal cross-linking monitored by theranostic software module

Eligibility Criteria

• Age: 18 Years - 40 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• 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.
• 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.
• at least two central corneal thickness (CCT) measurements showing at least -10 µm change in in the last year or longer interval period.

You may not qualify if:

• Anterior corneal curvature steeper than 63 D;
• Corneal thickness thinner than 400 µm;
• Corneal scarring;
• Descemetocele;
• History of herpetic keratitis;
• Concomitant eye diseases;
• Inflammatory eye diseases;
• Glaucoma;
• Cataract;
• Nistagmus;
• Pregnancy;
• Breast feeding.

Sponsors & Collaborators

• Regensight: lead
• University of Roma La Sapienza: collaborator

Study Sites (3)

Azienda Ospedaliera Universitaria Mater Domini - Università Magna Graecia di Catanzaro

Catanzaro, 88100, Italy

Location

Azienda Ospedaliera Universitaria Careggi, Università di Firenze

Florence, 50134, Italy

Location

Azienda Ospedaliera Universitaria Policlinico G. Martino, Università di Messina

Messina, 98124, Italy

Location

Related Publications (8)

• 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.

  PMID: 29451741 BACKGROUND

• 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.

  PMID: 30360937 BACKGROUND

• 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.

  PMID: 31900647 BACKGROUND

• 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.

  PMID: 26868750 BACKGROUND

• 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.

  PMID: 25542349 BACKGROUND

• Lombardo G, Bernava GM, Serrao S, Lombardo M. Theranostic-guided corneal cross-linking: Preclinical evidence on a new treatment paradigm for keratoconus. J Biophotonics. 2022 Dec;15(12):e202200218. doi: 10.1002/jbio.202200218. Epub 2022 Sep 16.

  PMID: 36059083 BACKGROUND

• Roszkowska AM, Lombardo G, Mencucci R, Scorcia V, Giannaccare G, Vestri A, Alunni Fegatelli D, Bernava GM, Serrao S, Lombardo M. A randomized clinical trial assessing theranostic-guided corneal cross-linking for treating keratoconus: the ARGO protocol. Int Ophthalmol. 2023 Jul;43(7):2315-2328. doi: 10.1007/s10792-022-02628-4. Epub 2022 Dec 31.

  PMID: 36587174 BACKGROUND

• Roszkowska AM, Scorcia V, Mencucci R, Giannaccare G, Lombardo G, Alunni Fegatelli D, Vestri A, Bifezzi L, Bernava GM, Serrao S, Lombardo M. Assessment of the Predictive Ability of Theranostics for Corneal Cross-linking in Treating Keratoconus: A Randomized Clinical Trial. Ophthalmology. 2024 Dec;131(12):1403-1415. doi: 10.1016/j.ophtha.2024.06.012. Epub 2024 Jun 20.

  PMID: 38908553 RESULT

Related Links

• Updates on clinical trial RSKC001

MeSH Terms

Conditions

Keratoconus

Condition Hierarchy (Ancestors)

Corneal Diseases; Eye Diseases

Limitations and Caveats

This study assessed CXL efficacy by measuring the change of the Kmax index, which was aligned with commonly used approaches in the field. The list of adverse events may not be fully comprehensive as the first postoperative visit was scheduled at 7 days after treatment, excluding immediate postoperative events, such as eye pain, stromal oedema, corneal striae and conjunctival hyperaemia, from the assessment.

Results Point of Contact

• Title: Dr. Marco Lombardo, Study Director
• Organization: Studio Italiano di Oftalmologia

studiolombardo@visioeng.it

+393313438300

Study Officials

• Vincenzo Scorcia, MD

  Azienda Ospedaliera Universitaria Mater Domini - Università Magna Graecia di Catanzaro

  PRINCIPAL INVESTIGATOR

• Marco Lombardo, MD, PhD

  Studio Italiano di Oftalmologia

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Masking Details: Outcome assessor is masked. Statistician is masked. Participant receives stratification to either corneal cross-linking protocol after consent form signature. All participants wear contact lens after treatment until first postoperative eye examination at 1 week, when the corneal epithelium is completely healed.
• Purpose: OTHER
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: 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. If both eyes of a study participant are eligible, the eye with worst CDVA is enrolled and treated.

Study Record Dates

• First Submitted: July 11, 2022
• First Posted: July 14, 2022
• Study Start: April 27, 2022
• Primary Completion: January 26, 2024
• Study Completion: January 26, 2024
• Last Updated: February 11, 2025
• Results First Posted: February 11, 2025

Record last verified: 2025-02

Data Sharing

• IPD Sharing: Will not share

Locations

IT (3)