Identification of Cellular Biomarkers of Rare Eye Diseases in Adults

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

NOT_YET_RECRUITING

Clinical Phase

NA

Total Enrollment

110 participants

Study Classification

INTERVENTIONAL

Study Start Date

2026-01-20

Study Completion Date

2027-01-20

Brief Summary

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The cornea is the outermost transparent 'window' of the eye allowing light to enter and serving as the first-line immune and mechanical barrier. It is a complex avascular tissue composed of cells, stem cells, nerves, and collagen layers organized in an exquisite manner to maintain its transparency and self-healing capacity. This delicately balanced interplay of corneal elements is disrupted in rare diseases of the cornea, resulting in non-healing wounds, corneal ulceration, inflammation, new vessel ingrowth (neovascularization), defective innervation, scarring, oedema and loss of transparency. For many Rare Eye Diseases (REDs), drug development has been relatively unsuccessful, delivering few to no new therapies. Current management is often prohibitively expensive, has low efficacy and leads to debilitating side effects. The RESTORE VISION project (https://restorevision-project.eu/) aims to improve eye health by using cutting-edge models for each rare disease to test novel and repurposed compounds (9 in total) and determine drug mechanisms of action, formulating compounds as safe eye drop suspensions, and performing several first-in-human trials of novel therapies. Thes drugs have solid preliminary data showing beneficial effects in restoring the cell physiology, immune, avascular, neural and signaling environment in the cornea.

The current clinical study is part of Work package 2 within the RESTORE VISION EU grant agreement (''Validation of human drug targets of repurposed drugs and novel therapies'') and aims to ascertain the expression levels of genes and proteins and investigate pathways of interest in human tissue and fluid samples of REDs, that are targeted by the proposed experimental/repurposed substances. Therapeutic target gene and/or protein expression will be verified in human blood, tears and conjunctival cells collected from 7 RED patient groups. The RESTORE VISION Consortium know multiple putative genes and proteins involved in the REDs and/or affected by the drugs to be tested in RED models. These will be analyzed in patient samples from the 7 REDs to see if they are 1) expressed at all; 2) differ in expression between patient and control group and 3) are correlated with clinical endpoints and/or symptoms of REDs.

The 7 REDs under investigation are briefly explained as follows:

1. AAK: genetic progressive limbal stem cell degeneration leading to corneal neovascularization, inflammation, recurrent erosions, chronic pain and vision loss.
2. OCP: autoimmune scarring of the conjunctiva leads to deficient wound healing, inflammation, scarring, blindness and pain.
3. EEC Syndrome: Ectodermal Dysplasia causes pathological corneal scarring and blindness.
4. NK: involves a corneal nerve deficit leading to reduction or loss of corneal sensitivity, impaired wound healing, corneal ulceration and loss of vision.
5. LSCD: acquired or hereditary stem cell deficiency inducing epithelial breakdown, neovascularization, scarring and inflammation leading to decreased vision, tearing and pain.
6. oGvHD: a severe side-effect of successful bone-marrow transplantation leads to painful and blinding ocular surface inflammation, neovascularization and delayed wound healing.
7. CN: in high-risk transplantation, pathologic inflammation, corneal blood and lymphatic vessels are key risk factors for high-risk corneal graft failure, leading to graft rejection and blindness.

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Detailed Description

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The expression levels of the genes/proteins that are investigated in this study will be differentially expressed (up/down regulated) between patient and control groups and furthermore there will be associations between the expression levels of these genes/proteins\* and clinical endpoints/symptoms in patients with the 7 REDs. The analysis that will be performed in this study will provide key insights into mechanisms of disease in the 7 REDs and the pathways targeted by the RESTORE VISION drugs.

\*Restore Vision REDs and gene/protein targets :

Impression cytology :

* For AAK : PAX6, IRS-1, MR, GR, HSD1, HSD2
* For OCP : IRS-1,MR, GR
* For EEC : IRS-1, MR, GR, HSD1, HSD2
* For NK : IRS-1, MR, GR, HSD1, HSD2
* For LSCD : IRS-1, MR, GR, HSD1, HSD2, DCN/LRG-1
* For oGvHD : IRS-1, MR, GR, HSD1, HSD2
* For CN : IRS-1, MR, GR, HSD1, HSD2, DCN/LRG-1

Tear fluid :

* For AKK : PAX6
* For EEC : SPRR1A
* For LSCD :DCN/LRG

Conditions

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Rare Diseases Ophthalmology

Study Design

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Allocation Method

NON_RANDOMIZED

Intervention Model

PARALLEL

This is a cross-sectional interventional research with minimal risks and constraints, national and multi-center clinical study carried out as part of the overall EU project. This WP2 study will be performed in two other countries: Germany (UKK) and Italy (OSR). Each partner will have the responsibility for the clinical study carried out in its country.

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Control group

In France, two groups of participants will be recruited (110 participants). 55 of subjects in a control group, will be selected to match the two groups with regard to possible confounding variables, such as gender and age (±5). Patients in the control group will be recruited from the ophthalmology clinics of the Cochin and Necker hospitals, as these patients are already being treated in these hospitals for other pathologies unrelated to rare diseases.

Group Type OTHER

Ophthalmological visit

Intervention Type OTHER

Uncorrected visual acuity (UCVA), best-corrected visual acuity (BSCVA), corneal topography, corneal pachymetry, ocular surface pictures (to evaluate disease status of the eye with and without fluorecein), Schirmer's test, Corneal esthesiometry, Tear film break-up time test, Intraocular pressure.

Below is a summary of steps to perform ocular surface pictures of the cornea.

1. Ensure slit lamp cleaning and appropriate magnification and light settings.
2. Ensure comfortable positioning of both the operator and the patient.
3. Examine external orbital structures and adnexa for inflammation, irritation, or lesions.
4. Examine lids and lashes for abnormalities.
5. Examine both bulbar and palpebral conjunctiva for signs of irritation and injection.
6. Examine the cornea for clarity and the presence of any defect.
7. Examine the anterior chamber depth and evaluate abnormalities that might affect its transparency (blood, purulent material, cells and flare).
8. Examine the surface of the iris an

Questionnaires

Intervention Type OTHER

Ocular Surface Disease Index (OSDI) questionnaire, Visual Analog Pain Scale (VAS) questionnaire

Blood sample collection

Intervention Type OTHER

Blood samples from RED patients or control group are collected in BD Vacutainer K2 EDTA.

Impression cytology

Intervention Type OTHER

Put one drop of oxybuprocaine hydrochloride 0.4% in patients' eyes and wait 10 seconds. Gently apply both side of one sterile nitrocellulose membrane onto the unexposed bulbar conjunctiva, superotemporally, inferotemporally, superonasally, and inferonasally, for approximately 20 seconds, please, keep the eyes separated.

Tear fluid

Intervention Type OTHER

One sterile minisponge per eye will be placed over the lids margin at the junction of the lateral and middle thirds of the lower eyelids and kept in place for 2 minutes. During application of sponges the patient needs to look up to facilitate the procedure. To avoid excessive tear reflex, as well as a mild discomfort, it is recommended that patients close their eyes during the collection. Remove sponge using sterile tweezers and put it into empty 0.5mL tube (pierced at the bottom with a sterile needle) placed into another empty 1.5 mL tube and keep it on ice until processing.

Patient group

In France, two groups of participants will be recruited (110 participants). 55 subjects with REDs in an experimental group. This group is divided into subgroups. Indeed, 15 patients will be affected by AAK, 5 by NK, 5 by LSCD, 10 by OCP, 5 by Oc GvHD, 10 by EEC and 5 by CNV (the 7 different rare eye diseases)

Group Type OTHER

Ophthalmological visit

Intervention Type OTHER

Uncorrected visual acuity (UCVA), best-corrected visual acuity (BSCVA), corneal topography, corneal pachymetry, ocular surface pictures (to evaluate disease status of the eye with and without fluorecein), Schirmer's test, Corneal esthesiometry, Tear film break-up time test, Intraocular pressure.

Below is a summary of steps to perform ocular surface pictures of the cornea.

1. Ensure slit lamp cleaning and appropriate magnification and light settings.
2. Ensure comfortable positioning of both the operator and the patient.
3. Examine external orbital structures and adnexa for inflammation, irritation, or lesions.
4. Examine lids and lashes for abnormalities.
5. Examine both bulbar and palpebral conjunctiva for signs of irritation and injection.
6. Examine the cornea for clarity and the presence of any defect.
7. Examine the anterior chamber depth and evaluate abnormalities that might affect its transparency (blood, purulent material, cells and flare).
8. Examine the surface of the iris an

Questionnaires

Intervention Type OTHER

Ocular Surface Disease Index (OSDI) questionnaire, Visual Analog Pain Scale (VAS) questionnaire

Blood sample collection

Intervention Type OTHER

Blood samples from RED patients or control group are collected in BD Vacutainer K2 EDTA.

Impression cytology

Intervention Type OTHER

Put one drop of oxybuprocaine hydrochloride 0.4% in patients' eyes and wait 10 seconds. Gently apply both side of one sterile nitrocellulose membrane onto the unexposed bulbar conjunctiva, superotemporally, inferotemporally, superonasally, and inferonasally, for approximately 20 seconds, please, keep the eyes separated.

Tear fluid

Intervention Type OTHER

One sterile minisponge per eye will be placed over the lids margin at the junction of the lateral and middle thirds of the lower eyelids and kept in place for 2 minutes. During application of sponges the patient needs to look up to facilitate the procedure. To avoid excessive tear reflex, as well as a mild discomfort, it is recommended that patients close their eyes during the collection. Remove sponge using sterile tweezers and put it into empty 0.5mL tube (pierced at the bottom with a sterile needle) placed into another empty 1.5 mL tube and keep it on ice until processing.

Interventions

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Ophthalmological visit

Uncorrected visual acuity (UCVA), best-corrected visual acuity (BSCVA), corneal topography, corneal pachymetry, ocular surface pictures (to evaluate disease status of the eye with and without fluorecein), Schirmer's test, Corneal esthesiometry, Tear film break-up time test, Intraocular pressure.

Below is a summary of steps to perform ocular surface pictures of the cornea.

1. Ensure slit lamp cleaning and appropriate magnification and light settings.
2. Ensure comfortable positioning of both the operator and the patient.
3. Examine external orbital structures and adnexa for inflammation, irritation, or lesions.
4. Examine lids and lashes for abnormalities.
5. Examine both bulbar and palpebral conjunctiva for signs of irritation and injection.
6. Examine the cornea for clarity and the presence of any defect.
7. Examine the anterior chamber depth and evaluate abnormalities that might affect its transparency (blood, purulent material, cells and flare).
8. Examine the surface of the iris an

Intervention Type OTHER

Questionnaires

Ocular Surface Disease Index (OSDI) questionnaire, Visual Analog Pain Scale (VAS) questionnaire

Intervention Type OTHER

Blood sample collection

Blood samples from RED patients or control group are collected in BD Vacutainer K2 EDTA.

Intervention Type OTHER

Impression cytology

Put one drop of oxybuprocaine hydrochloride 0.4% in patients' eyes and wait 10 seconds. Gently apply both side of one sterile nitrocellulose membrane onto the unexposed bulbar conjunctiva, superotemporally, inferotemporally, superonasally, and inferonasally, for approximately 20 seconds, please, keep the eyes separated.

Intervention Type OTHER

Tear fluid

One sterile minisponge per eye will be placed over the lids margin at the junction of the lateral and middle thirds of the lower eyelids and kept in place for 2 minutes. During application of sponges the patient needs to look up to facilitate the procedure. To avoid excessive tear reflex, as well as a mild discomfort, it is recommended that patients close their eyes during the collection. Remove sponge using sterile tweezers and put it into empty 0.5mL tube (pierced at the bottom with a sterile needle) placed into another empty 1.5 mL tube and keep it on ice until processing.

Intervention Type OTHER

Eligibility Criteria

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Inclusion Criteria

Patient group:

* Women and men with age equal or higher than 18 years (patients planning to conceive may be included in the study)
* Willingness and ability to read and understand the informed consent.
* Diagnosis (including genotype, if needed) of REDs.
* Affiliation with a social security scheme or beneficiary of such a scheme.

RED 1 - AAK Diagnosis criteria

* Compatible slit lamp examination (iris/pupillary abnormalities, with or without corneal opacification, vascularization, cataract, glaucoma). with or without:
* Foveal hypoplasia and optic disc malformations as detected through fundus examination or OCT tomography
* Compatible anterior segment OCT or high-frequency ultrasound biomicroscopy (UBM)
* Positive genetic testing

RED 2 - NK Diagnosis criteria

* Compatible history and slit lamp findings of one of the three stages of the Mackie classification (I - punctate keratopathy; II - persistent epithelial defect; III - stromal involvement)
* Reduced/absent corneal sensitivity
* Exclusion of infectious or toxic etiologies with or without:
* confocal microscopy findings

RED 3 - LSCD Diagnosis criteria

* Compatible history and slit lamp examination (e.g. corneal conjunctivalization with persistent epithelial defects, loss of limbal anatomy or irregular staining with fluorescein) with or without:
* confocal microscopy findings

RED 4 - OCP Diagnosis criteria

* Compatible slit lamp examination
* Exclusion of infectious or toxic etiologies with or without:
* conjunctival /oral biopsy with characteristic mucous pemphigoid findings

RED 5 - OC GVHD Diagnosis criteria • Compatible history and slit lamp examination consistent with one of 4 grades of ocular GVHD (1 - conjunctival hyperemia, 2 - fibrovascular changes \<25% of palpebral conjunctiva, 3 - fibrovascular changes \>25%, 4 - \>75% or cicatricial entropion)

RED 6 - EEC Diagnosis criteria

* Compatible slit lamp examination
* Compatible systemic findings with or without:
* Positive genetic testing

RED 7- CNV Diagnosis criteria

* Compatible slit lamp examination of corneal stromal neovascularization (1-4 quadrants)
* Exclusion of infectious or toxic etiologies with or without:
* confocal microscopy findings

Control group:

* Women and men with age equal or higher than 18 years (patients planning to conceive may be included in the study).
* Willingness and ability to read and understand the informed consent.
* Non-diagnosis of REDs.
* Affiliation with a social security scheme of beneficiary of such a scheme.

Exclusion Criteria

Patient group:

* Pregnancy, breastfeeding (in case any stress was caused to the woman by the biological sampling).
* Descemetocele/impending corneal perforation.
* Recent (less than 3 months) ocular surgery.
* Recent (less than 1 month) change in topical medications type and frequency of the ocular pathology.
* Persons subject to a legal protection measure (under guardianship, curatorship or safeguard of justice)

Control group:

* Pregnancy, breastfeeding.
* Active ocular infection.
* Descemetocele/impending corneal perforation.
* Recent (less than 3 months) ocular surgery.
* Recent (less than 1 month) change in topical medications type and frequency of the ocular pathology.
* Persons subject to a legal protection measure. (under guardianship, curatorship or safeguard of justice)

Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

Yes