NCT07063719

Identification of Cellular Biomarkers of Rare Eye Diseases in Adults

• Status: Not Yet Recruiting
• Phase: N/A
• Study type: Interventional
• Enrollment: 110 (estimated)
• Sponsor: Institut National de la Santé Et de la Recherche Médicale, France · Other Government
• Sex: All
• Age: 18 Years
• Healthy volunteers: Accepted

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. 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.

Detailed description

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

• Rare Diseases
• Ophthalmology

Interventions

Type	Name	Description
OTHER	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
OTHER	Questionnaires	Ocular Surface Disease Index (OSDI) questionnaire, Visual Analog Pain Scale (VAS) questionnaire
OTHER	Blood sample collection	Blood samples from RED patients or control group are collected in BD Vacutainer K2 EDTA.
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.
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.

Timeline

• Start date: 2026-01-20
• Primary completion: 2027-01-20
• Completion: 2027-01-20
• First posted: 2025-07-14
• Last updated: 2025-12-05

Locations

2 sites across 1 country: France