Given that the definitive pathogenesis of Mooren's ulcer has not been fully clarified and clinical relapse occurs frequently, natural killer (NK)-cells demonstrate unique therapeutic potential. Since NK cells do not express T-cell receptors (TCRs), they exert biological functions through a specific self-versus-non-self recognition pathway and hardly induce graft-versus-host disease (GVHD) after transplantation. Therefore, NK-cells serve as an ideal cellular therapeutic vehicle for such autoimmune diseases. This project targets refractory Mooren's ulcer by taking advantage of the distinctive immunological properties of NK-cells for disease intervention. Its core merits consist of eliminating the risk of GVHD and conferring immunomodulatory effects. From a clinical perspective, this study fills the research gap of cell-based therapies focused on the relapse mechanism of Mooren's ulcer and delivers a minimally-invasive and safe novel therapeutic option for intractable patients.
Clinically confirmed as a corneal ulcer with undermining characteristics, meeting the clinical diagnostic criteria for undermining corneal ulcers (infiltration and ulceration appearing at the peripheral cornea, or showing progressive development accompanied by ciliary injection; other corneal lesions have been ruled out).
The ulcerative lesion covers an area no greater than half the circumference of the cornea, with stromal infiltration depth not exceeding 1/3 to 2/3 of the corneal thickness; no severe complications such as corneal perforation or endophthalmitis have occurred.
There are obvious symptoms such as eye pain, photophobia, tearing, and a foreign-body sensation, and conventional conservative medical treatments have shown poor efficacy.
The intraocular pressure of the affected eye is within the normal range (10-21 mmHg), and there are no associated ocular conditions such as severe blepharitis or dacryocystitis. The contralateral eye has no history of corneal ulceration due to keratitis or active lesions.
Those who do not meet any of the above selection criteria.
Exclusion criteria related to corneal lesions: The corneal ulcer has already developed severe complications such as perforation, endophthalmitis, or corneal hydrops; the ulcer area exceeds half of the corneal circumference, or the depth of corneal stromal infiltration exceeds two-thirds of the corneal thickness; or the patient has concurrent other corneal diseases (such as infectious keratitis, keratoconus, corneal dystrophy, etc.).
Exclusion of systemic diseases: Individuals with severe cardiovascular and cerebrovascular diseases, hepatic or renal dysfunction (hepatic function-ALT/AST exceeding 1.5 times the upper limit of normal; renal function-creatinine exceeding 1.2 times the upper limit of normal), hematopoietic dysfunction, or uncontrolled autoimmune diseases (such as rheumatoid arthritis, systemic lupus erythematosus, etc.); individuals with active infections, malignant tumors, or a history of surgery within the past 3 months; and diabetic patients with poor glycemic control (HbA1C above 8.5%).
Exclusion of special populations: pregnant women and breastfeeding women; individuals (both men and women) who have plans to conceive and are not using effective contraception; individuals with alcohol dependence or substance abuse.
Single group
Allogeneic natural killer (NK)-cell transplantation
Biological/VaccineInvestigational allogeneic NK-cells will be delivered via subconjunctival injection for patients with refractory Mooren's ulcer under strict sterile conditions. After cell transplantation, patients will receive routine topical ophthalmic medications and regular slit-lamp examinations. Participants are followed-up for 48-weeks to evaluate corneal recovery, visual changes and safety profiles of this cell-based intervention.
Change in central corneal thickness compared with baseline at 48 weeks after NK-cell transplantation
Central corneal thickness, measured in micrometers (μm), will be assessed in patients with refractory Mooren's ulcer before treatment and at the 48-week follow-up after subconjunctival injection of allogeneic NK-cells. The change in central corneal thickness from baseline to 48 weeks, expressed in μm, will be calculated to assess therapeutic efficacy.
Change of best-corrected visual acuity (BCVA) from baseline at week 48
Best-corrected visual acuity, measured as the number of correctly identified letters on a standardized ETDRS chart, will be assessed in patients with refractory Mooren's ulcer before treatment and at the 48-week follow-up after subconjunctival injection of allogeneic NK-cells. The change in best-corrected visual acuity from baseline, expressed as the number of ETDRS letters gained, will be calculated to evaluate the improvement in visual function following NK-cell intervention.
Change in corneal endothelial cell density from baseline at 48 weeks after NK-cell transplantation
Corneal endothelial cell density, measured in cells per square millimeter (cells/mm²), will be assessed in patients with refractory Mooren's ulcer before treatment and at the 48-week follow-up after subconjunctival injection of allogeneic NK-cells. The change in corneal endothelial cell density from baseline to 48 weeks, expressed in cells/mm², will be calculated to evaluate the effect of NK-cell transplantation on corneal endothelial function.
Incidence of adverse events throughout the 48-week observation period
Ocular local reactions, including conjunctival hyperemia, chemosis, anterior chamber inflammation, and corneal epithelial defects, as well as ocular infections, will be recorded and graded according to standardized grading scales (e.g., the Common Terminology Criteria for Adverse Events \[CTCAE\]) in patients with refractory Mooren's ulcer following subconjunctival injection of allogeneic NK-cells. The incidence and severity of ocular local reactions and infections will be summarized to evaluate the ocular safety of NK-cell transplantation.
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Suxia Li
Lead sponsor
Shandong Eye Hospital
Sponsor institution
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