Myofibroblastic Transformation Secondary to Epithelial-stromal Interactions in the Keratoconus

Keratoconus Clinical Trial

— MYKE  

Official title:

Myofibroblastic Transformation Secondary to Epithelial-stromal Interactions in the Keratoconus (MYKE)

Clinical Trial Details — Status: Withdrawn

Administrative data

• NCT number: NCT03990740
• Other study ID #: EGN_2017_22
• Status: Withdrawn
• Start date: November 1, 2019
• Est. completion date: May 12, 2020

Study information

• Verified date: May 2020
• Source: Fondation Ophtalmologique Adolphe de Rothschild
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial 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.

Recruitment information / eligibility

• Status: Withdrawn
• Enrollment: 0
• Est. completion date: May 12, 2020
• Est. primary completion date: May 12, 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Keratoconus

Intervention

Procedure:
• Corneal sampling
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.

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
Fondation Ophtalmologique Adolphe de Rothschild

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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