Myofibroblastic Transformation Secondary to Epithelial-stromal Interactions in the Keratoconus

Withdrawn

• Conditions: Keratoconus
• Interventions: Procedure: Corneal sampling

• Registration Number: NCT03990740
• Lead Sponsor: Fondation Ophtalmologique Adolphe de Rothschild

Brief Summary

Keratoconus is characterized by a thinning of the cornea, which causes a decrease in visual acuity due to astigmatism.

Publications suggest that keratoconus is linked to chronic inflammation (increase in pro-inflammatory cytokines and metalloproteinases (MMP). Direct epithelial-stromal interactions (D-ESI) have a role in the induction of metalloproteinases (MMP) and the differentiation of fibroblasts into myofibroblasts via an EMMPRIN membrane glycoprotein (extracellular matrix membran MMP inducer - CD 147). On a healthy cornea, EMMPRIN's effects are prevented by a lack of contact between epithelial and stromal cells through a basement membrane, which is altered in the keratoconus The hypothesis is that stromal thinning of the keratoconus could be related to increased expression of EMMPRIN by epithelial and stromal cells (resulting in increased MMP synthesis), with a preponderance at the most deformed areas.

The main objective is to demonstrate a transformation of fibroblasts to myofibroblasts in the corneal stroma of keratoconus patients.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2019-06-11
• Study First Submitted QC: 2019-06-18
• Study First Posted: 2019-06-19
• Study Start: 2019-11-01
• Status Verified: 2020-05
• Primary Completion: 2020-05-12
• Study Completion: 2020-05-12
• Last Update Submitted: 2020-05-12
• Last Update Posted: 2020-05-14

Recruitment & Eligibility

• Status: WITHDRAWN
• Sex: All
• Target Recruitment: Not specified

Inclusion Criteria

• For the cases :

  • Suffering from keratoconus and requiring a first optical corneal transplant

• For the controls:

  • Orbital exenteration operation due to an orbital tumor
  • Absence of any anomaly of the ocular surface observed during the slit lamp examination at the last preoperative consultation

Exclusion Criteria

• For the cases:

  • Keratoconus patient requiring a tectonic corneal transplant
  • Known pregnancy, or breastfeeding

• For the controls:

  • History of orbital radiotherapy
  • History of corneal surgery
  • History of corneal surface tumour
  • Eye surface abnormality noted in the preoperative period
  • Known keratoconus
  • Known pregnancy, or breastfeeding
  • Secondary exclusion if a keratoconus is diagnosed during the immunohistochemical analysis by visualization of Bowman membrane interruption

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Arm && Interventions

Group	Intervention	Description
Cases	Corneal sampling	Patients suffering from keratoconus and requiring a first optical corneal transplant
Controls	Corneal sampling	Patients with an indication of orbital exenteration operation due to an orbital tumor

Primary Outcome Measures

Name	Time	Method
Comparison of alpha-SMA's (Smooth Muscle Actin) messenger RNA expression evaluated by quantitative PCR (RT-qPCR) in corneal stroma in keratoconus patients compared to non-keratoconus controls	12 hours