Myofibroblastic Transformation Secondary to Epithelial-stromal Interactions in the Keratoconus

NCT ID: NCT03990740

Last Updated: 2020-05-14

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

WITHDRAWN

Study Classification

OBSERVATIONAL

Study Start Date

2019-11-01

Study Completion Date

2020-05-12

Brief Summary

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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

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Conditions

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Keratoconus

Study Design

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Observational Model Type

CASE_CONTROL

Study Time Perspective

PROSPECTIVE

Study Groups

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Cases

Patients suffering from keratoconus and requiring a first optical corneal transplant

Corneal sampling

Intervention Type 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.

Controls

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

Corneal sampling

Intervention Type 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.

Interventions

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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.

Intervention Type PROCEDURE

Eligibility Criteria

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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
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Fondation Ophtalmologique Adolphe de Rothschild

NETWORK

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Other Identifiers

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EGN_2017_22

Identifier Type: -

Identifier Source: org_study_id

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