Identification of Cellular Biomarkers of Rare Eye Diseases in Adults

NCT07063719 | Not Yet Recruiting

• 1 other identifier: C24-15
• Study Type: interventional
• Target: 110
• Locations: 1 country
• Sites: 2

Brief Summary

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. 1.AAK: genetic progressive limbal stem cell degeneration leading to corneal neovascularization, inflammation, recurrent erosions, chronic pain and vision loss.
2. 2.OCP: autoimmune scarring of the conjunctiva leads to deficient wound healing, inflammation, scarring, blindness and pain.
3. 3.EEC Syndrome: Ectodermal Dysplasia causes pathological corneal scarring and blindness.
4. 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. 5.LSCD: acquired or hereditary stem cell deficiency inducing epithelial breakdown, neovascularization, scarring and inflammation leading to decreased vision, tearing and pain.
6. 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. 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.

Conditions

Rare Diseases; Ophthalmology

Keywords

Rare occular disease

Outcome Measures

Primary Outcomes (1)

• The expression levels of the genes and proteins

  The primary endpoint will be the expression levels of the genes and proteins listed in the Study description. These genes and proteins are expected to be differentially expressed (upregulated or down regulated) compared to the control group. The investigators will arbitrarily set at 1 the target level in the control group and the RED group will be expressed in relation to the control group. While sample collection occurs in 4 Clinical centers (2 in Inserm, France, 1 in Klinikum der Universitaet zu Koeln (UKK, Germany) and 1 in San Raffaele Hospital OSR, Italy), following any initial required processing all samples will be shipped to OSR in Italy who will perform the qPCR, Elisa and/or Mass Spectrometry analysis. Laboratory tests (qPCR, Elisa and/or Mass Spectrometry) will be performed at the Eye Repair lab of the Department of Neuroscience at IRCCS at OSR.

  At the inclusion visit

Secondary Outcomes (1)

• The expression levels of the genes and proteins

  At the inclusion visit

Study Arms (2)

Control group

OTHER

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.

Other: Ophthalmological visit; Other: Questionnaires; Other: Blood sample collection; Other: Impression cytology; Other: Tear fluid

Patient group

OTHER

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)

Other: Ophthalmological visit; Other: Questionnaires; Other: Blood sample collection; Other: Impression cytology; Other: Tear fluid

Interventions

Ophthalmological visit 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

Control group; Patient group

Questionnaires OTHER

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

Control group; Patient group

Blood sample collection OTHER

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

Control group; Patient group

Impression cytology 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.

Control group; Patient group

Tear fluid 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.

Control group; Patient group

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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
• confocal microscopy findings
• RED 3 - LSCD Diagnosis criteria

You may not qualify if:

• 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)

Sponsors & Collaborators

• Institut National de la Santé Et de la Recherche Médicale, France: lead

Study Sites (2)

Hôpital Universitaire Cochin, APHP

Paris, France

Location

Hôpital Universitaire Necker Enfants malades, APHP

Paris, France

Location

Related Publications (2)

• Stachon T, Fecher-Trost C, Latta L, Yapar D, Fries FN, Meyer MR, Kasmann-Kellner B, Seitz B, Szentmary N. Protein profiling of conjunctival impression cytology samples of aniridia subjects. Acta Ophthalmol. 2024 Jun;102(4):e635-e645. doi: 10.1111/aos.16614. Epub 2023 Dec 21.

  PMID: 38130099 BACKGROUND

• Lasagni Vitar RM, Bonelli F, Atay A, Triani F, Fonteyne P, Di Simone E, Rama P, Mondino A, Ferrari G. Topical neurokinin-1 receptor antagonist Fosaprepitant ameliorates ocular graft-versus-host disease in a preclinical mouse model. Exp Eye Res. 2021 Nov;212:108825. doi: 10.1016/j.exer.2021.108825. Epub 2021 Nov 3.

  PMID: 34740637 BACKGROUND

MeSH Terms

Conditions

Rare Diseases

Interventions

Surveys and Questionnaires

Condition Hierarchy (Ancestors)

Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Data Collection; Epidemiologic Methods; Investigative Techniques; Health Care Evaluation Mechanisms; Quality of Health Care; Health Care Quality, Access, and Evaluation; Public Health; Environment and Public Health

Central Study Contacts

Francine Behar-Cohen, PU-PH

CONTACT

+33 01 44 27 81 64; Francine.behar@gmail.com

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER GOV
• Responsible Party: SPONSOR

Model Details: 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.

Study Record Dates

• First Submitted: June 24, 2025
• First Posted: July 14, 2025
• Study Start: January 20, 2026
• Primary Completion (Estimated): January 20, 2027
• Study Completion (Estimated): January 20, 2027
• Last Updated: December 5, 2025

Record last verified: 2025-12

Locations

FR (2)