Clinical trial NCT05676580: Risk Factors and Progression of Keratoconus
Official title: Risk Factors and Progression of Keratoconus
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Keratoconus
Lead sponsor: University Hospital, Montpellier
Sponsor class: OTHER
First posted: 2023-01-09
Enrollment: 200
Sex: ALL
Minimum age (years): 10
Maximum age (years): 40
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: HEALTH_SERVICES_RESEARCH

Brief summary: 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.

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)

Primary outcomes:
measure: Keratoconus clinical progression (Keratometry map)
timeFrame: Baseline vs Visit at 1 month/6 months/12 months/24 months
measure: Keratoconus clinical progression (Pachymetric map)
timeFrame: Baseline vs Visit at 1 month/6 months/12 months/24 months
measure: Keratoconus clinical progression (Visual acuity test)
timeFrame: Baseline vs Visit at 1 month/6 months/12 months/24 months
measure: Keratoconus clinical progression (Biomicroscopic examination of the cornea)
timeFrame: Baseline vs Visit at 1 month/6 months/12 months/24 months
measure: ABCD grading of keratoconus
timeFrame: Baseline vs Visit at 1 month/6 months/12 months/24 months
measure: Keratoconus histological progression - Confocal microscopy (tissue thickness)
timeFrame: Baseline vs Visit at 1 month/6 months/12 months/24 months
measure: Keratoconus histological progression - Confocal microscopy (Cellular organization)
timeFrame: Baseline vs Visit at 1 month/6 months/12 months/24 months
measure: Keratoconus histological progression - Confocal microscopy (Cellular density)
timeFrame: Baseline vs Visit at 1 month/6 months/12 months/24 months
measure: Keratoconus histological progression - Confocal microscopy (Light scattering)
timeFrame: Baseline vs Visit at 1 month/6 months/12 months/24 months
measure: Risk factors - Questionnaire
timeFrame: Baseline vs 24 months
measure: Tears proteomics
timeFrame: Baseline vs Visit at 1 month/6 months
Secondary outcomes:
measure: ABCD class worsening between consultations
timeFrame: Baseline vs Visit at 1 month/6 months - Baseline vs 12 months - Baseline vs 24 months
measure: Keratoconus histological evolution
timeFrame: Baseline vs Visit at 1 month/6 months
measure: Proteomic profile evolution
timeFrame: Baseline vs Visit at 1 month/6 months
Other outcomes:
Locations:
city: Montpellier
country: France
facility: CHU Gui de Chauliac - Service d'Ophtamologie
state: Occitanie
Study officials:
affiliation: CHU Monptellier
name: Vincent DAIEN, PR
role: PRINCIPAL_INVESTIGATOR
References: