Keratoconus
Conditions
Keywords
Keratoconus, Corneal ectasia, Corneal cross-linking, Corneal collagen crosslinking (CXL), Epi-off CXL, Riboflavin UV-A, Topography-guided PRK, TG-PRK, Phototherapeutic keratectomy (PTK), PTK epithelial removal, Schwind AMARIS excimer laser, Excimer laser, Athens Protocol (TG-PRK + CXL), Crete protocol (PTK + CXL), Pentacam Scheimpflug tomography, Kmax, Higher-order aberrations (HOAs), Corneal haze, Specular microscopy, Endothelial cell density, NEI VFQ-25, Visual acuity (logMAR), Randomized clinical trial, Parallel assignment
Brief summary
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.
Interventions
DEVICESchwind AMARIS excimer laser
Used for corneal wavefront guided PRK therapeutic ablation (50 µm) or for PTK epithelial removal, according to arm assignment.
PROCEDURECorneal 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 \[equivalent to 3 minutes "on" time\].
Sponsors
Instituto de Oftalmología Fundación Conde de Valenciana
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in best-corrected distance visual acuity (logMAR) | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in Kmax (Diopters) | Baseline; 3; 6; 12 months | Pentacam Scheimpflug tomography; maximum keratometry (D); change from baseline at each time point. |
| Change in corneal higher-order aberrations (µm RMS) | Baseline; 3,6,12 months | Wavefront/aberrometry total HOAs RMS (µm) over 6-mm pupil; change from baseline. |
| Change in manifest refraction spherical equivalent (Diopters) | Baseline; 3;6;12 months | Manifest refraction SE (D); change from baseline. |
| Corneal haze (Scheimpflug densitometry units) | Baseline; 3;6;12 months | CCT and corneal haze as measured by Pentacam Corneal Densitometry. Unit of measure: gray units. |
| Corvis ST metric: Ambrosio Relational Thickness horizontal (ART-h) | Baseline; 3,6; 12 months | ART-h as measured by Corvis ST. Unit of measure: microns |
| Visual Functioning Questionnaire (NEI VFQ-25) | 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. |
| Endothelial cell density (cells/mm²; specular microscopy) | 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. |
| Serious corneal adverse events | 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). |
| Corneal haze (Fantes grade) | 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. |
| Corvis ST metric: Inverse Concavity Radius | Baseline; 3; 6; 12 months | Inverse Concavity Radius as measured by Corvis ST. Unit of measure: mm |
Countries
Mexico
Outcome results
None listed