Effect of PAE Hydrogel Loaded With tRF-ASO-Exo on Patients With Diabetic Ocular Surface Diseases

NCT07382453 | Not Yet Recruiting Phase 2 DMC

• 1 other identifier: 2025-L236
• Study Type: interventional
• Target: 30
• Locations: 0 countries
• Sites: N/A

Brief Summary

The purpose of this study is to determine whether poly（β-amino ester）(PAE)hydrogel loaded with tRNA-derived fragments-antisense oligonucleotides-exosomes(tRF-ASO-Exo) could alleviate symptoms in patients with diabetic ocular surface diseases(DOSD).

Conditions

Diabetic Keratopathy

Outcome Measures

Primary Outcomes (6)

• corneal and conjunctival nerve density

  In vivo confocal microscopy (IVCM) examination: All subjects underwent IVCM to assess corneal and conjunctival nerve density. Instruct the patient to fixate on a target, and the examiner slowly moves the objective lens until the vortex structure of the subbasal nerve plexus of the cornea can be seen.

  1day, 2 weeks, 6 weeks, 12 weeks

• Corneal sensitivity

  Corneal sensitivity of the operated eye was evaluated by one examiner via a French Cochet-Bonnet aesthesiometer (Luneau Ophthalmologie), which consists of a calibrated nylon filament on a retractable shaft with a length scale. Longer filaments (lower bending force, weaker stimulus) indicate higher sensitivity. The sensitivity threshold was the maximum filament length evoking a reliable blink response. All tests were conducted in a standardized quiet indoor setting; patients kept eyes open with stable gaze during testing. Starting at 60 mm, the filament was perpendicularly applied to the central cornea, then shortened by 5 mm increments until consistent blinks occurred. Three measurements were taken, and corneal sensitivity was defined as the mean length of positive responses.

  1day, 2 weeks, 6 weeks, 12 weeks

• conjunctival goblet cell density

  All participants underwent in vivo confocal microscopy (IVCM) assessment of conjunctival goblet cell density. Prior to imaging, subjects were instructed to maintain steady fixation on a standardized external target. The examiner systematically scanned the temporal bulbar conjunctiva approximately 3 mm from the corneal limbus, using the "section" scanning mode to acquire high-resolution images of the conjunctival epithelium-including the vortex region and its surrounding tissue within a 2-3 mm radius. To ensure optimal image quality and anatomical coverage, four non-overlapping image fields were captured per eye, each centered on a distinct location within a predefined small target zone. A sterile, single-use plastic cap was gently applied to the conjunctival surface prior to scanning to stabilize the ocular surface and minimize motion artifact. A total of 100-200 well-focused, artifact-free images were acquired for each examined eye.

  1day, 2 weeks, 6 weeks, 12 weeks

• Changes in Ocular Surface Staining

  Ocular surface integrity was checked with a non-toxic dye at the slit lamp. Corneal and conjunctival staining were graded with the NEI photo atlas; lower scores mean less dry-eye damage. Change-from-baseline numbers were calculated for each eye, so a negative value equals improvement.

  1day, 2 weeks, 6 weeks, 12 weeks

• conjunctival vessel density and number of branches

  AS-OCTA examination was performed to quantify conjunctival vasculature using anterior segment optical coherence tomography angiography. The anterior segment AS Angio 9×9 mm scan pattern with a resolution of 256×256 A-scans was selected for imaging and motion tracking. The scanning frame was positioned to intersect the corneal limbus, and the focal plane was adjusted until optimal visualization of the conjunctival layer was achieved. Superficial and deep conjunctival vascular plexuses were analyzed at depth ranges of 0-50 μm and 50-100 μm, respectively, with partial overlap between the two layers to account for transitional vascular networks. Vessel density and branching index were quantified using the device-integrated analytical software. Additionally, en face images were exported and further processed using ImageJ software (National Institutes of Health, USA) for supplementary image analysis.

  1day, 2 weeks, 6 weeks, 12 weeks

• Changes in Ocular Surface Disease Index (OSDI) Score

  The Ocular Surface Disease Index (OSDI) is a validated 12-item questionnaire specifically designed to quantify the severity of dry eye symptoms in clinical settings. Its scoring range spans from 0 to 100, with lower scores correlating with a greater alleviation of dry eye-related discomfort. Baseline-adjusted OSDI scores were calculated, and a reduction of more than 10 points from the baseline value was defined as a clinically meaningful improvement in symptoms.

  1day, 2 weeks, 6 weeks, 12 weeks

Secondary Outcomes (4)

• Changes in tear secretion amount by Schirmer's Test

  1day, 2 weeks, 6 weeks, 12 weeks

• Changes in Tear break time

  1day, 2 weeks, 6 weeks, 12 weeks

• Changes in best corrected visual acuity (BCVA)

  1day, 2 weeks, 6 weeks, 12 weeks

• Changes in conjunctiva redness score

  1day, 2 weeks, 6 weeks, 12 weeks

Study Arms (3)

Exo treatment

EXPERIMENTAL

Following a 14-day placebo run-in period-during which all subjects receive bilateral placebo eye drops (one drop per eye, twice daily, approximately 12 hours apart)-participants will receive active treatment for 84 days: Group 1 (Exo) receives 10 μg/drop of unmodified MSC-Exos.

Drug: Exosomes

tRF-ASO-Exo treatment

EXPERIMENTAL

Following a 14-day placebo run-in period-during which all subjects receive bilateral placebo eye drops (one drop per eye, twice daily, approximately 12 hours apart)-participants will receive active treatment for 84 days:Group 2 (tRF-ASO-Exo) receives 10 μg/drop of tRF-ASO-engineered MSC-Exos.

Drug: tRNA-derived fragments-antisense oligonucleotides-exosomes

tRF-ASO-Exo-PAE treatment

EXPERIMENTAL

Following a 14-day placebo run-in period-during which all subjects receive bilateral placebo eye drops (one drop per eye, twice daily, approximately 12 hours apart)-participants will receive active treatment for 84 days:Group 3 (tRF-ASO-Exo-PAE) receives 10 μg/drop of tRF-ASO-engineered MSC-Exos delivered via PAE hydrogel.

Drug: poly（β-amino ester）hydrogel loaded with tRNA-derived fragments-antisense oligonucleotides-exosomes

Interventions

Exosomes DRUG

Participants will receive artificial tears for 2 weeks to get the normalized baseline, followed by Exosomes 10ug/drop, two times a day for 84 days. The follow-up visit will be 12 weeks.

Also known as: Exo

Exo treatment

tRNA-derived fragments-antisense oligonucleotides-exosomes DRUG

Participants will receive artificial tears for 2 weeks to get the normalized baseline, followed by tRF-ASO-Exo 10ug/drop, two times a day for 84 days. The follow-up visit will be 12 weeks.

Also known as: tRF-ASO-Exo

tRF-ASO-Exo treatment

poly（β-amino ester）hydrogel loaded with tRNA-derived fragments-antisense oligonucleotides-exosomes DRUG

Participants will receive artificial tears for 2 weeks to get the normalized baseline, followed by tRF-ASO-Exo-PAE 10ug/drop, two times a day for 84 days. The follow-up visit will be 12 weeks.

Also known as: tRF-ASO-Exo-PAE

tRF-ASO-Exo-PAE treatment

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• \. Patients with fasting blood glucose ≥ 7.0 mmol/L or 2-hour postprandial blood glucose ≥ 11.1 mmol/L.
• \. Those who clearly understand and voluntarily participate in this study, and sign the written informed consent form themselves, and are able and willing to follow the instructions to participate in all trial evaluations and visits.
• \. Male subjects and female subjects of childbearing age must agree to use medically approved contraceptive measures during the trial and for 90 days after the trial. For female subjects who have not reached menopause or have been menopausal for less than two years, the pregnancy test must be negative.
• \. A history of severe dry eye symptoms (including one or more of the following subjective symptoms: dryness, foreign body sensation, burning sensation, fatigue, discomfort, redness, sudden eye pain, photophobia, tearing, blurred vision, and decreased corneal sensation) in both eyes for at least 180 days before the screening visit (Visit 0).
• \. Currently (within 30 days before Visit 0) using artificial tears to relieve dry eye-related symptoms, and artificial tears must be discontinued 72 hours before Visit 0.
• \. At Visit 0, the Chinese Dry Eye Questionnaire score is \> 7 points or the total score of the Ocular Surface Disease Index is \> 13 points.
• \. At Visit 0 and Visit 1, the dryness score is \> 40 points. 8. At Visit 0, the best corrected visual acuity of both eyes is ≥ 4.3 (5-meter reading on the international standard logarithmic visual acuity chart, 5-point recording method).
• \. At Visit 0 and Visit 1, the corneal fluorescein staining score of at least one area of at least one eye is ≥ 2 points.
• \. At Visit 0 and Visit 1, the conjunctival redness score of at least one eye is ≥ 1 point.
• \. At the screening visit and baseline visit (Visit 0 and Visit 1), at least one eye of the same subject meets the following criteria: a. The corneal lower zone fluorescein staining score is ≥ 0.5 points; b. The Schirmer's test without anesthesia is ≥ 1 and ≤ 10 mm/5 min.

You may not qualify if:

• Any past or current malignancy in or around the eye.
• Dry eye traced to scarring (radiation, alkali burn, Stevens-Johnson, cicatricial pemphigoid) or goblet-cell loss (vitamin-A deficiency).
• Active ocular allergy now or expected during the study.
• Ocular or systemic infection at screening/baseline-fever, herpetic keratitis, or on antibiotics.
• Prior immunodeficiency, HIV, hep B/C, active hep A, organ or bone-marrow transplant.
• Any serious chronic illness the PI thinks could mess with endpoints-severe heart/lung disease, uncontrolled hypertension or diabetes.
• Blood donation or major blood loss within 8 weeks of screening.
• Active ocular rosacea, periorbital acne, or pterygium.
• Lid problems-lagophthalmos, entropion, ectropion, or abnormal blink.
• Clinically relevant slit-lamp findings needing treatment (conjunctivitis, trichiasis, conjunctivochalasis) that could skew results.
• Eye surgery or laser (including YAG, meibomian thermopulsation, IPL) within 6 months of screening, or any such plan during the trial.
• Punctal plugs (non-dissolvable within 90 days; dissolvable within 180 days) or planned plug procedures during the study.
• Systemic steroids, immunomodulators, oral doxy/tetracycline within 90 days, or on-and-off use planned.
• Topical glaucoma meds within 90 days.
• Cyclosporine-A or lifitegrast drops within 42 days.

Sponsors & Collaborators

• Affiliated Hospital of Nantong University: lead

Central Study Contacts

Min Ji

CONTACT

0513(81160554); amyji1234@hotmail.com

Xi Zhu

CONTACT

0513-81160554; 806549014@qq.com

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 27, 2026
• First Posted: February 2, 2026
• Study Start: February 15, 2026
• Primary Completion (Estimated): December 30, 2028
• Study Completion (Estimated): June 30, 2029
• Last Updated: February 4, 2026

Record last verified: 2026-01

Data Sharing

• IPD Sharing: Will not share