Myofibroblastic Transformation Secondary to Epithelial-stromal Interactions in the Keratoconus

NCT03990740 | Withdrawn

• 1 other identifier: EGN_2017_22
• Study Type: observational
• Target: N/A
• Locations: 0 countries
• Sites: N/A

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.

Conditions

Keratoconus

Keywords

Metalloproteinase; Glycoprotein; Cornea; Direct epithelial-stromal interactions; Fibroblasts; Myofibroblasts

Outcome Measures

Primary Outcomes (1)

• 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

Study Arms (2)

Cases

Patients suffering from keratoconus and requiring a first optical corneal transplant

Procedure: Corneal sampling

Controls

Patients with an indication of orbital exenteration operation due to an orbital tumor

Procedure: Corneal sampling

Interventions

Corneal sampling PROCEDURE

Corneal samples will be taken during corneal transplants for cases and orbital exenterations for controls. The mRNA (messenger ribonucleic acid) will be extracted and a retrotranscription will be made to obtain cDNA (complementary DNA). A qPCR (quantitative polymerase chain reaction) will be able to quantify the expression of alpha-SMA, MMP 1-2-3 and 9, and EMMPRIN.

Cases; Controls

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

Keratoconus patients requiring first optical corneal transplantation and controls with indication of orbital exenteration due to an orbital tumor.

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Fondation Ophtalmologique Adolphe de Rothschild: lead

MeSH Terms

Conditions

Keratoconus; Corneal Diseases

Condition Hierarchy (Ancestors)

Eye Diseases

Study Design

• Study Type: observational
• Observational Model: CASE CONTROL
• Time Perspective: PROSPECTIVE
• Sponsor Type: NETWORK
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 11, 2019
• First Posted: June 19, 2019
• Study Start: November 1, 2019
• Primary Completion: May 12, 2020
• Study Completion: May 12, 2020
• Last Updated: May 14, 2020

Record last verified: 2020-05

Data Sharing

• IPD Sharing: Will not share