Proteomic Study of Tears From Patients With a PAX6 Mutation (PLAPAX6)

This is a single-center prospective pilot study involving the ophthalmology and medical genetics departments of the Montpellier University Hospital, and the proteomics platform of the Montpellier University Hospital.

5 patients with PAX6 pathogenic variation will be included in order to determine the proteomic profile in a tear sample associated with different pathogenic variations of the PAX6 gene.

Participation in the study for the patients consists of a single visit with an ophthalmological examination and a tear collection.

Study Overview

• Status: Completed
• Conditions: Aniridia
• Intervention / Treatment: Other: Tear collection

Detailed Description

The transcription factor PAX6 is required for the normal development of all elements constituting the eyeball, including the lacrimal gland.

In patients with PAX6 gene mutations, the cornea presents a limbal anomaly that has been evolving since childhood and is responsible for variable damage. It evolves from a simple peripheral keratopathy to an advanced stage with complete corneal opacification and fibrosis. Chronic inflammation, associated with tear film damage is very common and promotes keratopathy. The current treatment of dry eye in patients with ocular malformation related to a PAX6 mutation is non specific: it aims to palliate the quantitative tear defect and uses tear substitutes, cyclosporine eye drops, meatus plugs, scleral lenses.

The identification of specific qualitative abnormalities constitutes the indispensable preliminary step necessary in order to be able to consider in the long term an adapted treatment, of tear protein supplementation, aiming at preserving the cornea of patients with an ocular malformation related to a PAX6 gene mutation.

In this study, patients will be recruited from the active file of patients and patients previously treated in the ophthalmology or medical genetics departments of Montpellier University Hospital for an ocular malformation related to a PAX6 mutation.

Participation in the study will consist of a single visit of up to 3 hours.

During the pre-inclusion visit, the existence of a pathogenic variation of the PAX6 gene identified in each patient will be verified.

Once the inclusion is achieved, the same day, it is planned to:

• data collection: demographic (age, sex), clinical (weight, height, head circumference, blood pressure, associated neurodevelopmental disorder, neurological examination, extraocular damage, description of the ocular malformation, previous surgical interventions) and genetic (description of the pathogenic variation of the PAX6 gene),
• an ophthalmological examination,
• the collection of tears by Schirmer strip (2 to 4 mm) will be performed by the ophthalmologist.

The data for each protein in the spectrum will be compared with the previously established reference proteomic profile range. Significant variations (50% change) will be retained.

The discovery of tear film abnormalities in the pathophysiological context of a PAX6 gene alteration will allow a better understanding of the progressive tear and corneal damage in these complex ocular malformations. This is an essential preliminary step in the perspective of a better management of the patients, by the creation of specific adapted eye drops allowing to palliate more specifically the identified anomalies, following the example of the treatment by eye drops containing NGF developed in the United States in order to treat the attacks of the corneal innervation.

• Study Type: Interventional
• Enrollment (Actual): 5
• Phase: Not Applicable

Contacts and Locations

Study Locations

• France
  • Montpellier, France
    • University Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Patients with an isolated pathogenic variation of PAX6
2. Age: 18-60 years
3. Subject affiliated to a French social security system or beneficiary of such a system
4. Written consent given by the subject

Exclusion Criteria:

1. Ophthalmologic procedure less than 3 months old
2. Chromosomal abnormality not limited to the PAX6 gene
3. Being under court protection, guardianship or curatorship
4. To be deprived of liberty by administrative decision
5. Be in a period of exclusion in relation to another protocol
6. Pregnant or breastfeeding woman

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Patients treated for an ocular malformation linked to a PAX6 mutation.	Other: Tear collection; Collection of tears by Schirmer strip (2 to 4 mm).

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Proteomic profile of tears associated with different pathogenic variations of the PAX6 gene.	Proteomic profile (quantitative and qualitative analysis of global protein expression after gel prefractionation) of tears associated with different pathogenic variations of the PAX6 gene.	Through study completion, an average of 18 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Types of changes relative to the previously established reference tear profile range.	Types of changes (protein expression deficiency or excess, defined as greater than 50% change) relative to the previously established reference tear profile range.	Through study completion, an average of 18 months

Collaborators and Investigators

• Sponsor: University Hospital, Montpellier
• Investigators: Principal Investigator: Marjolaine WILLEMS, PH, University Hospital, Montpellier

Study record dates

Study Major Dates

• Study Start (Actual): February 9, 2023
• Primary Completion (Actual): November 22, 2023
• Study Completion (Actual): November 22, 2023

Study Registration Dates

• First Submitted: September 21, 2022
• First Submitted That Met QC Criteria: September 29, 2022
• First Posted (Actual): September 30, 2022

Study Record Updates

• Last Update Posted (Actual): August 9, 2024
• Last Update Submitted That Met QC Criteria: August 7, 2024
• Last Verified: August 1, 2024

More Information

Terms related to this study

• Keywords: aniridia; PAX6; tear proteomics
• Additional Relevant MeSH Terms: Eye Diseases; Congenital Abnormalities; Eye Abnormalities; Genetic Diseases, Inborn; Uveal Diseases; Eye Diseases, Hereditary; Iris Diseases; Aniridia
• Other Study ID Numbers: RECHMPL22_0050

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No