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NCT Number: NCT05676580

Risk Factors and Progression of Keratoconus

Primary objective :

Description of keratoconus at baseline and during progression in 200 participants followed by the ophthalmology departments of CHU Montpellier, CHU Bordeaux and CHU Toulouse during a 2-year period. Clinical outcome, histology of the cornea and tears proteomics will be assessed in 4 groups at different points in time:

* At 6 months in participants with no intervention (risk reduction instructions: not to rub their eyes) * At 6 months in participants with no intervention that didn't comply with the risk reduction instructions * At 1 month in participants assigned to cross-linking surgery * At 1 month in participants assigned to intra corneal ring surgery If both eyes are affected, both will be evaluated with their own visit agenda. Visits for no surgery participants will be set at 6 months, 12 months and 24 months in the absence of intervention (apart from the behavioral risk reduction).

Visits for surgery participants will be set at D7, 1 month, 6 months, 12 months and 24 months after the procedure: cross-linking or placement of the intra corneal ring.

Secondary objective :

Description of the association between clinical outcomes, histological progression of the cornea and tears proteomics in time, 2 years period.

Comparison of tears proteomics in 36 participants with keratoconus followed at CHU of Montpellier and healthy participants at baseline .

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Key information

Conditions

Keratoconus Corneal Diseases Eye Diseases

Age range

10 year–40 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Not applicable

Primary location

CHU Gui de Chauliac - Service d'Ophtamologie

Montpellier, Occitanie, 34295, France

Location status: Recruiting

Location contact

David Touboul, Pr

PRINCIPAL_INVESTIGATOR

Fanny Babeau, Dr

SUB_INVESTIGATOR

Pierre Fournié, Pr

PRINCIPAL_INVESTIGATOR

Vincent DAIEN, Pr

CONTACT

[email protected]

Vincent Daien, Pr

PRINCIPAL_INVESTIGATOR

About this study

This trial is a prospective cohort study of 200 participants with keratoconus followed by the ophthalmology departments of CHU Montpellier, CHU Bordeaux and CHU Toulouse during a 2-year period. If both eyes are affected, each will be evaluated considering their own visit agenda. Histological and proteomic evaluations will be performed in 36 participants's eyes whose initial management is abstention of surgery (12 participants), cross-linking (12 participants) or intra corneal ring (12 participants).

The target population consist of participants with clinical keratoconus (topographic Rabinowitz criteria with slit lamp abnormalities and visual impairment), preclinical or crude keratoconus (abnormal or suspicious topography with normal slit lamp examination and normal visual acuity). They will be aged between 10 and 40 years included.

The follow-up will be taken care off by the ophthalmology departments of the Montpellier University Hospital, Bordeaux University Hospital or Toulouse University Hospital Collection of written informed consent, after a period of reflection, will be necessary for adult participants. For minors: informed consent will have to be signed by at least one of the 2 parents or legal guardians, and approval from the child will be asked after a period of reflection. All participants will have to be affiliated to the French social security system or beneficiary of such a system.

Description of the study course:

No therapeutic intervention outside of routine care will be performed. Depending on the therapeutic orientation, the follow-up is carried out as follows:

  • Visits at 6 months, 12 months and 24 months in the absence of intervention (apart from the behavioral risk reduction management).
  • Visits at day 7, 1 month, 6 months, 12 months and 24 months after the procedure: cross-linking or placement of the intra corneal ring.

In this study, participants will be followed for a maximum of 2.5 years. In addition to the description of keratoconus progression, we will take a tear sample using the Schirmer test to create a biobank. This tears collection will be performed in 36 participants followed at the Montpellier University Hospital, at inclusion and at short-term follow-up visit (6 months if abstention, 1 month if surgery).

Judging criteria:

  • Paraclinical examination of the participants
  • Ophthalmological paraclinical data
  • Confocal microscopy examination
  • ABCD classification of keratoconus
  • Composition and evolution of tears determined by proteomic analysis
  • Survey on risk factors: allergies, atopy, ocular friction, family history, ethnic origin, smoking, dry eye syndrome, low pachymetry

Prevalence of risk factors: a survey will measure the prevalence of risk factors for keratoconus:

  • Presence of atopy/allergy
  • Eye rubs
  • Family history
  • Ethnic origin
  • Tobacco use
  • Dry eye syndrome (survey + clinical examination)
  • Low pachymetry

This self-survey will be completed at the inclusion visit and at the last follow-up visit (M24). The time to complete this questionnaire is approximately 10 minutes.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

  • Participants with clinical keratoconus (Rabinowitz criteria with topographic slit lamp abnormalities and visual impairment), preclinical or crude keratoconus (abnormal or suspicious topography with normal slit lamp examination and normal visual acuity, visual acuity)
  • Followed by the ophthalmology services of the CHU Montpellier, CHU Bordeaux or CHU Toulouse
  • For adult Participants: collection of written informed consent, after a period of reflection period
  • For minors: informed consent signed by at least one of the 2 parents or legal representatives legal representatives, and assent of the child after a period of reflection
  • Affiliation to the French social security system or beneficiary of such a system

Exclusion criteria

  • Person under legal supervision, guardianship or curator
  • History of corneal implant on both eyes
  • Planned relocation before the end of the first stage of treatment (abstention, cross-linking, intra-corneal ring depending on the participant)

Treatment and study plan

cross-linking surgery or intra corneal ring

Procedure

After keratoconus diagnosis the patient was assigned to surgery

abstention

Other

No surgery

Primary outcomes

  1. Keratoconus clinical progression (Keratometry map)

    Time frame: Baseline vs Visit at 1 month/6 months/12 months/24 months

    Modelisation of refraction measurements in diopters, by corneal elevation topography (Orbscan and Pentacam), giving an additional indicator of the corneal deformity. High values of diopter correspond to positive bulges of the cornea. A topographic axial map will be acquired to monitor minimal and maximal keratometry.

    These measurements will be taken at baseline and compared for reference of progression at each visit for each eye.

    Keratoconus definition according to Rabinowitz (Rabinowitz YS, 1989) criteria:

    • Corneal asymmetry greater than 1.5 diopters (D), between the upper and lower part of the cornea, on the median vertical axis.
    • Central corneal power (Kmax) > 47.2 D, measured at the top of the cone.
    • Asymmetry of central keratometry > 1D between the two eyes

  2. Keratoconus clinical progression (Pachymetric map)

    Time frame: Baseline vs Visit at 1 month/6 months/12 months/24 months

    Thickness of the cornea will be assessed in microns (µm) at several locations and will be presented as a map by corneal elevation topography (Orbscan and Pentacam).

    The pachymetric map will be acquired at baseline and compared for reference of progression at each visit for each eye. The higher and lower thickness points will be notified for the anterior and posterior parts of the eye.

  3. Keratoconus clinical progression (Visual acuity test)

    Time frame: Baseline vs Visit at 1 month/6 months/12 months/24 months

    Visual acuity test with and without correction: decimal and Parinaud scales secondarily translated in LogMar.

  4. Keratoconus clinical progression (Biomicroscopic examination of the cornea)

    Time frame: Baseline vs Visit at 1 month/6 months/12 months/24 months

    A biomicroscopic examination of the cornea in search of signs that may modify the therapeutic indications i.e : Fleischer rings (iron deposits in the lower part of the bulge, due to the stagnation of tears), visible corneal nerves, corneal opacities (due to scar tissue)

  5. ABCD grading of keratoconus

    Time frame: Baseline vs Visit at 1 month/6 months/12 months/24 months

    Grading of the keratoconus, according to the ABCD classification :

    • A: keratometry of the anterior surface of the cornea (Anterior radius of curvature (ARC)), in the area of 3 mm centered by the thinnest point.
    • B: keratometry of the posterior surface of the cornea (Back or posterior radius of curvature PRC), in the 3mm area centered by the thinnest point.
    • C: thinnest point of the Cornea, i.e. minimum pachymetry.
    • D: Distance best corrected vision: visual acuity with the best correction, measured in 10° or in the Parinaud scale.

  6. Keratoconus histological progression - Confocal microscopy (tissue thickness)

    Time frame: Baseline vs Visit at 1 month/6 months/12 months/24 months

    Histological degradation of the cornea taken at baseline for reference. The confocal microscope allows longitudinal analysis making it possible to carry out comparative qualitative and quantitative analyzes of the corneal tissue during time. In keratoconus, this technique is possible to highlight a reduction in basal plexus nerve density and poorer anterior stromal cell density compared to healthy subjects.

    Tissue thickness in microns (µm)

  7. Keratoconus histological progression - Confocal microscopy (Cellular organization)

    Time frame: Baseline vs Visit at 1 month/6 months/12 months/24 months

    Histological degradation of the cornea taken at baseline for reference. The confocal microscope allows longitudinal analysis making it possible to carry out comparative qualitative and quantitative analyzes of the corneal tissue during time. In keratoconus, this technique is possible to highlight a reduction in basal plexus nerve density and poorer anterior stromal cell density compared to healthy subjects.

    Cell organization and morphology. Image acquisition.

    • Colonization by inflammatory cells (yes/no), increased nucleo/cytoplasmic ratio (yes/no), hyperreflectivity of the nuclei (yes/no).
    • Nerve density of the basal plexuses of normal appearance (yes/no), straight with branches (yes/no), normal hyperreflectivity (yes/no)

  8. Keratoconus histological progression - Confocal microscopy (Cellular density)

    Time frame: Baseline vs Visit at 1 month/6 months/12 months/24 months

    Histological degradation of the cornea taken at baseline for reference. The confocal microscope allows longitudinal analysis making it possible to carry out comparative qualitative and quantitative analyzes of the corneal tissue during time. In keratoconus, this technique is possible to highlight a reduction in basal plexus nerve density and poorer anterior stromal cell density compared to healthy subjects.

    Cellular density (number). Image acquisition.

    • Cell count in the different layers, corneal nerve count from the basal plexus to the corneal apex

  9. Keratoconus histological progression - Confocal microscopy (Light scattering)

    Time frame: Baseline vs Visit at 1 month/6 months/12 months/24 months

    Histological degradation of the cornea taken at baseline for reference. The confocal microscope allows longitudinal analysis making it possible to carry out comparative qualitative and quantitative analyzes of the corneal tissue during time. In keratoconus, this technique is possible to highlight a reduction in basal plexus nerve density and poorer anterior stromal cell density compared to healthy subjects.

    Light scattering in vivo, measurement of corneal deformity. Diopter.

  10. Risk factors - Questionnaire

    Time frame: Baseline vs 24 months

    • Presence of atopy/allergy
    • Eye rubbing
    • Family medical history
    • Ethnicity
    • Smoking habits
    • Dry eye syndrome

  11. Tears proteomics

    Time frame: Baseline vs Visit at 1 month/6 months

    For 36 participants from Montpellier. Composition and evolution of tears determined by proteomic analysis

Secondary outcomes

  1. ABCD class worsening between consultations

    Time frame: Baseline vs Visit at 1 month/6 months - Baseline vs 12 months - Baseline vs 24 months

    At baseline and during follow-up

  2. Keratoconus histological evolution

    Time frame: Baseline vs Visit at 1 month/6 months

    Comparison of confocal microscopy results from primary outcomes through time.

  3. Proteomic profile evolution

    Time frame: Baseline vs Visit at 1 month/6 months

    Difference between the composition of tears from healthy participants and from keratoconus patients from baseline to short term follow up.

Study contacts

Contact information is provided by the study sponsor or research team.

Vincent DAIEN, PR

CONTACT

[email protected]

0673055877 ext. +33

Sponsors and collaborators

Lead sponsor

University Hospital, Montpellier

Other

Registry information

Acronym: FRPK

Important dates

Study start
2023
Primary completion
2027
Study completion
2028
First posted
Jan 9, 2023
Registry last updated
Sep 5, 2025

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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