Risk Factors and Progression of Keratoconus

Overview

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 .

Detailed description

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.

Interventions

• Procedure cross-linking surgery or intra corneal ring
  After keratoconus diagnosis the patient was assigned to surgery
• Other abstention
  No surgery

Primary outcome measures

• Keratoconus clinical progression (Keratometry map) [Time frame: Baseline vs Visit at 1 month/6 months/12 months/24 months]
• Keratoconus clinical progression (Pachymetric map) [Time frame: Baseline vs Visit at 1 month/6 months/12 months/24 months]
• Keratoconus clinical progression (Visual acuity test) [Time frame: Baseline vs Visit at 1 month/6 months/12 months/24 months]
• Keratoconus clinical progression (Biomicroscopic examination of the cornea) [Time frame: Baseline vs Visit at 1 month/6 months/12 months/24 months]
• ABCD grading of keratoconus [Time frame: Baseline vs Visit at 1 month/6 months/12 months/24 months]
• Keratoconus histological progression - Confocal microscopy (tissue thickness) [Time frame: Baseline vs Visit at 1 month/6 months/12 months/24 months]
• Keratoconus histological progression - Confocal microscopy (Cellular organization) [Time frame: Baseline vs Visit at 1 month/6 months/12 months/24 months]
• Keratoconus histological progression - Confocal microscopy (Cellular density) [Time frame: Baseline vs Visit at 1 month/6 months/12 months/24 months]
• Keratoconus histological progression - Confocal microscopy (Light scattering) [Time frame: Baseline vs Visit at 1 month/6 months/12 months/24 months]
• Risk factors - Questionnaire [Time frame: Baseline vs 24 months]

Secondary outcome measures (3)

• ABCD class worsening between consultations [Time frame: Baseline vs Visit at 1 month/6 months - Baseline vs 12 months - Baseline vs 24 months]
• Keratoconus histological evolution [Time frame: Baseline vs Visit at 1 month/6 months]
• Proteomic profile evolution [Time frame: Baseline vs Visit at 1 month/6 months]

Eligibility criteria

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)

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Non-randomized

Model

Parallel assignment

Masking

Open label

Primary purpose

Health services research

Study locations

France · 1 center

• CHU Gui de Chauliac - Service d'Ophtamologie — Montpellier

Identifiers

NCT: NCT05676580 · RECHMPL20_0450 / UF8090

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗