Topical Insulin for Glaucoma (TING2)

A Phase 1/2 Dose Escalation Followed by a Masked, Randomized, Placebo-Controlled Study to Evaluate Topical Insulin for Neuroprotection in Open Angle Glaucoma

This study evaluates the safety and preliminary efficacy of topical sterile human insulin eye drops (EYED-002) in patients with open-angle glaucoma. The study uses a phase 1/2 dose-escalation design followed by a masked, randomized, placebo-controlled phase. Insulin is formulated as preservative-free eye drops and delivered once daily. The primary objective is to determine the safety profile of topical insulin; secondary objectives assess effects on retinal structure, visual field, visual acuity, contrast sensitivity, and quality of life.

Study Overview

• Status: Not yet recruiting
• Conditions: Primary Open Angle Glaucoma; Open Angle Glaucoma; Low Tension Glaucoma; Pseudoexfoliation Glaucoma; Pigmentary Glaucoma
• Intervention / Treatment: Drug: EYED-002 Low Dose (721 U/mL topical insulin); Drug: EYED-002 High Dose (1442 U/mL topical insulin); Drug: EYED-002 (highest tolerated dose, 12-month); Drug: Vehicle Placebo

• Study Type: Interventional
• Enrollment (Estimated): 90
• Phase: Phase 2; Phase 1

Contacts and Locations

• Study Contact: Name: Study Team; Phone Number: 650-497-5942; Email: glaucomatrials@stanford.edu

Study Locations

• United States
  • California
    • Palo Alto, California, United States, 94303
      • Byers Eye Institute at Stanford University
      • Principal Investigator: Jeffrey Goldberg, MD PhD
      • Contact: Study Team; Phone Number: 6504975942; Email: glaucomatrials@stanford.edu

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Limited Inclusion Criteria - All Groups:

• Provide written informed consent approved by the appropriate ethics committee
• Age 18 years or older
• Understand study procedures and have the ability and willingness to abide by all procedures during the study
• Capable of providing informed consent
• Diagnosis of glaucoma
• Only one eye per patient will be selected as the study eye; if both eyes meet inclusion criteria, the eye with worse visual acuity and/or visual field will be selected

Limited Exclusion Criteria - All Groups:

• Pregnant or breastfeeding
• Presence of any ocular pathology other than glaucoma that contributes to severe vision loss (retinopathy, maculopathy, severe uveitis, keratopathy, etc.)
• Diagnosis of glucose intolerance, type 1 or type 2 diabetes mellitus
• Inability to perform reliable visual field testing
• Unable to provide informed consent
• Unable to complete the tests and follow-ups required by the study

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Sequential Assignment
• Masking: Triple

Number of Arms

5

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Group 1: Low-Dose EYED-002; N=5 participants with open-angle glaucoma. Low-dose topical insulin (EYED-002), administered as one drop to the study eye once daily in-clinic for 5 consecutive days. Open-label.	Drug: EYED-002 Low Dose (721 U/mL topical insulin); Sterile, preservative-free suspension of Human Insulin USP. One drop to study eye for duration of study group.; Other Names: Topical Sterile Human Insulin
Experimental: Group 2: High-Dose EYED-002; N=5 participants with open-angle glaucoma. High-dose topical insulin (EYED-002), administered as one drop to the study eye once daily in-clinic for 5 consecutive days.	Drug: EYED-002 High Dose (1442 U/mL topical insulin); Sterile, preservative-free suspension of Human Insulin USP. One drop to study eye once daily in-clinic for duration of study group.; Other Names: Topical Sterile Human Insulin
Experimental: Group 3: Active EYED-002 (Randomized); N=40 participants randomized to active EYED-002 at the highest tolerated dose from Groups 1 or 2, administered once daily at home for 12 months. Double -masked.	Drug: EYED-002 (highest tolerated dose, 12-month); Highest tolerated dose of EYED-002 (721 U/mL or 1442 U/mL, determined from Groups 1 and 2 safety review). Once daily at home for 12 months in single-use vials, dispensed at quarterly visits.; Other Names: Topical Sterile Human Insulin
Placebo Comparator: Group 3: Vehicle Placebo (Randomized); N=20 participants randomized to vehicle-only placebo, administered once daily at home for 12 months. double-masked. Eligible participants may roll over to open-label active EYED-002 for an additional 12 months after Month 12.	Drug: Vehicle Placebo; Vehicle-only formulation without active insulin. Single-use vials identical in appearance to active EYED-002. Once daily at home for 12 months.; Other Names: Placebo eye drop
Experimental: Group 4: Open-Label Access; N=20 participants ineligible for randomization due to glaucoma severity. Receive highest tolerated dose of EYED-002 once daily for 12 months in an open-label access arm.	Drug: EYED-002 (highest tolerated dose, 12-month); Highest tolerated dose of EYED-002 (721 U/mL or 1442 U/mL, determined from Groups 1 and 2 safety review). Once daily at home for 12 months in single-use vials, dispensed at quarterly visits.; Other Names: Topical Sterile Human Insulin

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence and severity of ocular and systemic adverse events (AEs) and serious adverse events (SAEs)	Safety of topical sterile human insulin (EYED-002) in patients with open-angle glaucoma. AEs and SAEs classified using MedDRA nomenclature, assessed for severity (mild, moderate, severe) and causality. Safety monitoring includes glycemia measurements before and 2 hours after in-clinic insulin administration, and serial serum electrolyte (potassium) measurements.	From informed consent through end of participation (up to 27 months)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in retinal nerve fiber layer (RNFL) and ganglion cell complex (GCC) thickness by SD-OCT	Change in retinal thickness as measured by spectral domain optical coherence tomography (SD-OCT).	Baseline to 12 months (Groups 3 and 4); Baseline to Day 5 (Groups 1 and 2)
Change in visual field by Humphrey 24-2 (mean deviation, VFI, pointwise analysis)	Change in visual field as measured by mean deviation, visual field index, and pointwise analysis on Humphrey 24-2 testing.	Baseline to 12 months (Groups 3 and 4); Baseline to Day 5 (Groups 1 and 2)
Change in best corrected visual acuity (BCVA) by ETDRS	Change in visual acuity as measured by ETDRS chart.	Baseline to 12 months (Groups 3 and 4); Baseline to Day 5 (Groups 1 and 2)
Change in contrast sensitivity by FrACT contrast test	Change in contrast sensitivity as measured by the computer-based FrACT contrast test.	Baseline to 12 months (Groups 3 and 4); Baseline to Day 5 (Groups 1 and 2)
Change in quality of life by GQL-15 questionnaire	Change in patient-reported quality of life as measured by the Glaucoma Quality of Life-15 (GQL-15) questionnaire.	Baseline, 6 months, and 12 months (Group 3)

Collaborators and Investigators

• Sponsor: Stanford University
• Investigators: Principal Investigator: Jeffrey L Goldberg, MD PhD, Stanford University

Publications and helpful links

General Publications

• Agostinone J, Alarcon-Martinez L, Gamlin C, Yu WQ, Wong ROL, Di Polo A. Insulin signalling promotes dendrite and synapse regeneration and restores circuit function after axonal injury. Brain. 2018 Jul 1;141(7):1963-1980. doi: 10.1093/brain/awy142.
• Saludares M, Wennberg-Smith Z, Beykin G, Khatib TZ, Nunez M, Wang Q, Di Polo A, Goldberg JL. A Phase I Randomized Trial of Topical Insulin for Glaucoma: Safety and Efficacy Outcomes. Ophthalmol Sci. 2025 Dec 6;6(2):101032. doi: 10.1016/j.xops.2025.101032. eCollection 2026 Feb.

Study record dates

Study Major Dates

• Study Start (Estimated): June 1, 2026
• Primary Completion (Estimated): October 1, 2028
• Study Completion (Estimated): October 1, 2029

Study Registration Dates

• First Submitted: May 26, 2026
• First Submitted That Met QC Criteria: May 26, 2026
• First Posted (Actual): June 2, 2026

Study Record Updates

• Last Update Posted (Actual): June 2, 2026
• Last Update Submitted That Met QC Criteria: May 26, 2026
• Last Verified: May 1, 2026

More Information

Terms related to this study

• Keywords: glaucoma; neuroprotection; retinal ganglion cell; topical insulin; EYED-002
• Additional Relevant MeSH Terms: Eye Diseases; Optic Nerve Diseases; Uveal Diseases; Ocular Hypertension; Iris Diseases; Glaucoma; Glaucoma, Open-Angle; Low Tension Glaucoma; Exfoliation Syndrome; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Peptide Hormones; Peptides; Amino Acids, Peptides, and Proteins; Insulins; Pancreatic Hormones; Proinsulin; Insulin
• Other Study ID Numbers: 73339

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No