PRoTECT: Corneal Wavefront Guided PRK + Epi-off CXL vs. PTK+Epi-off CXL in Keratoconus (PRoTECT)

January 20, 2026 updated by: Instituto de Oftalmología Fundación Conde de Valenciana

Corneal Wavefront Guided PRK Combined With Epi-off Corneal Cross-Linking Versus Epi-off Corneal Cross-Linking With PTK Epithelial Removal in Keratoconus: A Randomized Clinical Trial

Keratoconus causes irregular astigmatism and reduced vision. Epi-off corneal crosslinking (CXL) stabilizes the cornea but often leaves higher-order aberrations uncorrected. This randomized, parallel-group trial compares corneal wavefront guided photorefractive keratectomy (corneal wavefront guided PRK, 50 µm therapeutic ablation) combined with accelerated epi-off CXL versus epi-off CXL with epithelial removal by phototherapeutic keratectomy (PTK) using a Schwind AMARIS excimer laser, in adults with keratoconus. The primary endpoint is change in best-corrected distance visual acuity (logMAR) at 12 months. Key secondary endpoints include Kmax, corneal higher-order aberrations, manifest refraction, Scheimpflug densitometry (haze) and Fantes grade, Corvis ST biomechanics, NEI VFQ-25, and endothelial cell density by non-contact specular microscopy at 1, 3, 6 and 12 months.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Recruiting

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Estimated)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
50

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Mexico
    • Mexico City
      • Mexico City, Mexico City, Mexico, 06800
        • Recruiting
        • Instituto de Oftalmología FAP Conde de Valenciana, IAP Sede Centro
        • Contact:

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • Age 18-40 years
  • Diagnosis of keratoconus, ABCD Belin stage I-III at baseline
  • Minimum (thinnest) corneal pachymetry ≥ 450 µm pre-op
  • Written informed consent
  • Age-stratified progression requirements:
  • 18-25 y: keratoconus stage I-III (progression not mandatory)
  • 25-35 y: documented progression (meet ≥ 2 Table-1 criteria below) or, if recent documentation is absent, high-risk features for future progression: Kmax > 53 D, strong family history, severe atopy with persistent eye rubbing, or any of the following over 12 months: ΔKmax ≥ 1.0 D, thinnest pachymetry decrease ≥ 10 µm, or increase in manifest cylinder ≥ 1.0 D
  • 35-40 y: clear, unequivocal recent progression (meet ≥ 2 Table-1 criteria); late-onset documented progression may be considered

Exclusion Criteria:

  • Central corneal scars or opacities
  • Prior ocular surgery or trauma (exception: prior LASIK if it is the cause of post-surgical ectasia, per protocol text)
  • Autoimmune disease or uncontrolled diabetes mellitus
  • Pregnancy or lactation
  • Contact lens wear within 2 weeks before baseline evaluation

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Double

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Experimental: Corneal Wavefront Guided PRK + CXL
Corneal wavefront guided therapeutic PRK (50 µm) with Schwind AMARIS, followed by accelerated epi-off CXL. Intensity: 30 mW/cm² (pulsed 1 s on / 1 s off; 50% duty cycle). Total energy (fluence): 5.4 J/cm². Total time (elapsed): 6 minutes [equivalent to 3 minutes "on" time].
Device: Schwind AMARIS excimer laser
Used for corneal wavefront guided PRK therapeutic ablation (50 µm) or for PTK epithelial removal, according to arm assignment.
Procedure: Corneal collagen crosslinking epi-off accelerated
Riboflavin-UVA crosslinking performed after epithelial removal (corneal wavefront guided PRK arm via PRK; comparator arm via PTK). Intensity: 30 mW/cm² (pulsed 1 s on / 1 s off; 50% duty cycle). Total energy (fluence): 5.4 J/cm². Total time (elapsed): 6 minutes [equivalent to 3 minutes "on" time].
Active Comparator: PTK + CXL
Epithelial removal by PTK using Schwind AMARIS, followed by accelerated epi-off CXL. Intensity: 30 mW/cm² (pulsed 1 s on / 1 s off; 50% duty cycle). Total energy (fluence): 5.4 J/cm². Total time (elapsed): 6 minutes [equivalent to 3 minutes "on" time].
Device: Schwind AMARIS excimer laser
Used for corneal wavefront guided PRK therapeutic ablation (50 µm) or for PTK epithelial removal, according to arm assignment.
Procedure: Corneal collagen crosslinking epi-off accelerated
Riboflavin-UVA crosslinking performed after epithelial removal (corneal wavefront guided PRK arm via PRK; comparator arm via PTK). Intensity: 30 mW/cm² (pulsed 1 s on / 1 s off; 50% duty cycle). Total energy (fluence): 5.4 J/cm². Total time (elapsed): 6 minutes [equivalent to 3 minutes "on" time].

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Change in best-corrected distance visual acuity (logMAR)
Time Frame: Baseline to 12 months
ETDRS-based CDVA in logMAR; change from baseline at 12 months; primary analysis by ANCOVA adjusted for baseline; one study eye per participant.
Baseline to 12 months

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Change in Kmax (Diopters)
Time Frame: Baseline; 3; 6; 12 months
Pentacam Scheimpflug tomography; maximum keratometry (D); change from baseline at each time point.
Baseline; 3; 6; 12 months
Change in corneal higher-order aberrations (µm RMS)
Time Frame: Baseline; 3,6,12 months
Wavefront/aberrometry total HOAs RMS (µm) over 6-mm pupil; change from baseline.
Baseline; 3,6,12 months
Change in manifest refraction spherical equivalent (Diopters)
Time Frame: Baseline; 3;6;12 months
Manifest refraction SE (D); change from baseline.
Baseline; 3;6;12 months
Corneal haze (Scheimpflug densitometry units)
Time Frame: Baseline; 3;6;12 months
CCT and corneal haze as measured by Pentacam Corneal Densitometry. Unit of measure: gray units.
Baseline; 3;6;12 months
Corvis ST metric: Ambrosio Relational Thickness horizontal (ART-h)
Time Frame: Baseline; 3,6; 12 months
ART-h as measured by Corvis ST. Unit of measure: microns
Baseline; 3,6; 12 months
Visual Functioning Questionnaire (NEI VFQ-25)
Time Frame: Baseline; 6;12 months
NEI VFQ-25 composite and subscale scores computed per scoring manual; change from baseline. 0 to 100, where higher scores indicate better vision-related quality of life.
Baseline; 6;12 months
Endothelial cell density (cells/mm²; specular microscopy)
Time Frame: Baseline; 1; 3; 6; 12 months
Non-contact specular microscopy; primary metric = endothelial cell density (cells/mm²); secondary metrics (if collected) = coefficient of variation and hexagonality; change from baseline; one study eye per participant.
Baseline; 1; 3; 6; 12 months
Serious corneal adverse events
Time Frame: Baseline to 12 months
Incidence of protocol-defined serious ocular AEs ( infectious keratitis, perforation, persistent epithelial defect >14 days, ≥20% endothelial cell density loss, visually significant stromal scarring requiring surgery).
Baseline to 12 months
Corneal haze (Fantes grade)
Time Frame: Baseline; 3; 6; 12 months
Fantes clinical haze grade (ordinal); recorded at each visit. Units: Fantes grade. Scale: 0-4 scale, higher scores = worse haze.
Baseline; 3; 6; 12 months
Corvis ST metric: Inverse Concavity Radius
Time Frame: Baseline; 3; 6; 12 months
Inverse Concavity Radius as measured by Corvis ST. Unit of measure: mm
Baseline; 3; 6; 12 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Instituto de Oftalmología Fundación Conde de Valenciana

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
September 1, 2025

Primary Completion (Estimated)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
September 1, 2026

Study Completion (Estimated)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
December 30, 2027

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
November 16, 2025

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
January 20, 2026

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
January 28, 2026

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
January 28, 2026

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
January 20, 2026

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
November 1, 2025

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • PRoTECT-CXL-TGPRK-MX

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

UNDECIDED

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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