Longitudinal Study of Retinal Function in Eyes Treated for Diabetic Macular Edema With Anti-VEGF Agents (AS)

A considerable hurdle to the development of novel, more effective therapies for diabetic retinal disease is the limited number of primary endpoints available for use in regulatory trials. Current endpoints necessitate long trial durations and a greater number of participants to show efficacy. Thus, a better understanding of the structural and functional changes in the retina occurring in people with diabetes is essential for developing primary endpoints and validating surrogate and clinical endpoints.

Study Overview

• Status: Not yet recruiting
• Conditions: Diabetic Retinal Disease
• Intervention / Treatment: Drug: Anti-Vascular Endothelial Growth Factor

• Study Type: Interventional
• Enrollment (Estimated): 100
• Phase: Phase 4

Participation Criteria

Eligibility Criteria

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

Description

Key inclusion criteria:

• Age ≥18 years
• Diagnosed with Type 1 or Type 2 diabetes
• Best corrected visual acuity 20/320 or better (Snellen) (≥24 ETDRS letters)
• At least 1 eye with CI-DME requiring treatment
• Able and willing to provide informed consent.

Key exclusion criteria:

• Ocular or systemic condition, aside from diabetes mellitus (DM), that is likely to affect the assessment of DRSS, DME, or the functioning of the neural retina.
• Previous treatment of any kind for diabetic retinopathy or DME
• Any condition that may preclude adequate imaging of the macula (e.g. dense cataract or other media opacity, ptosis)
• History of rhegmatogenous retinal detachment or macular hole
• History of vitrectomy
• Intraocular surgery (including cataract surgery) within 4 months prior to enrollment or anticipated within the next 6 months

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: Non-Randomized
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Mild center-involved diabetic macular edema; Eyes with optical coherence tomography central subfield thickness <75 µm above DRCR standard thresholds of Zeiss Cirrus central subfield: ≥ 290µm in women or ≥ 305µm in men • Heidelberg Spectralis central subfield: ≥ 305µm in women or ≥ 320µm in men	Drug: Anti-Vascular Endothelial Growth Factor; All study eyes will receive an injection of anti-VEGF at baseline, 4, and 8 weeks. The participant will then be assessed for treatment every 8 weeks. At and after the 16-week visit, an injection will only be given if the eye has center-involved DME or visual acuity worse than 20/20 (presumed to be due to DME). Otherwise, an injection will not be given. The follow-up interval remains 8 weeks regardless of whether an injection is given or deferred. However, if an injection is deferred and the participant experiences vision issues or other symptoms, they may return for evaluation prior to 8 weeks (e.g., in 4 weeks) and can receive an injection (provided it has been at least 21 days since the last injection).; Other Names: Anti-VEGF
Active Comparator: Moderate Center-involved diabetic macular edema; Eyes with OCT central subfield thickness 75 to <175 µm above DRCR standard thresholds of: Zeiss Cirrus central subfield: ≥ 290µm in women or ≥ 305µm in men • Heidelberg Spectralis central subfield: ≥ 305µm in women or ≥ 320µm in men	Drug: Anti-Vascular Endothelial Growth Factor; All study eyes will receive an injection of anti-VEGF at baseline, 4, and 8 weeks. The participant will then be assessed for treatment every 8 weeks. At and after the 16-week visit, an injection will only be given if the eye has center-involved DME or visual acuity worse than 20/20 (presumed to be due to DME). Otherwise, an injection will not be given. The follow-up interval remains 8 weeks regardless of whether an injection is given or deferred. However, if an injection is deferred and the participant experiences vision issues or other symptoms, they may return for evaluation prior to 8 weeks (e.g., in 4 weeks) and can receive an injection (provided it has been at least 21 days since the last injection).; Other Names: Anti-VEGF
Active Comparator: Severe Center-involved diabetic macular edema; Severe CI-DME: Eyes with OCT central subfield thickness >=175µm above DRCR standard thresholds of Zeiss Cirrus central subfield: ≥ 290µm in women or ≥ 305µm in men • Heidelberg Spectralis central subfield: ≥ 305µm in women or ≥ 320µm in men	Drug: Anti-Vascular Endothelial Growth Factor; All study eyes will receive an injection of anti-VEGF at baseline, 4, and 8 weeks. The participant will then be assessed for treatment every 8 weeks. At and after the 16-week visit, an injection will only be given if the eye has center-involved DME or visual acuity worse than 20/20 (presumed to be due to DME). Otherwise, an injection will not be given. The follow-up interval remains 8 weeks regardless of whether an injection is given or deferred. However, if an injection is deferred and the participant experiences vision issues or other symptoms, they may return for evaluation prior to 8 weeks (e.g., in 4 weeks) and can receive an injection (provided it has been at least 21 days since the last injection).; Other Names: Anti-VEGF

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in multifocal pupillographic objective perimetry (mfPOP) response delays	mfPOP response delays measured using the Objective Field Analyzer (OFA)	Baseline to 1 year
Change in area under the log contrast sensitivity function (AULCSF)	AULCSF as measured by the Adaptive Sensory Testing (AST) Manifold contrast sensitivity testing system	Baseline to 1 year
Change in electroretinography parameter	Measured by the RETeval device	Baseline to 1 year
Change in reading performance	Measured by the MNREAD test	Baseline to 1 year
Change in visual field function	Measured by Humphrey Visual Field testing	Baseline to 1 year
Change in diabetic retinopathy severity	Assessed by ultra-widefield (UWF) color fundus photography	Baseline to 1 year
Change in retinal vascular pathology	Assessed by ultra-widefield fluorescein angiography (UWF-FA)	Baseline to 1 year
Change in retinal structure	measured by optical coherence tomography (OCT)	Baseline to 1 year
Change in retinal microvascular parameter	Measured by optical coherence tomography angiography (OCTA)	Baseline to 1 year

Collaborators and Investigators

• Sponsor: Jaeb Center for Health Research
• Collaborators: National Eye Institute (NEI)

Study record dates

Study Major Dates

• Study Start (Estimated): May 1, 2026
• Primary Completion (Estimated): December 1, 2027
• Study Completion (Estimated): May 1, 2033

Study Registration Dates

• First Submitted: February 9, 2026
• First Submitted That Met QC Criteria: April 28, 2026
• First Posted (Actual): May 5, 2026

Study Record Updates

• Last Update Posted (Actual): May 5, 2026
• Last Update Submitted That Met QC Criteria: April 28, 2026
• Last Verified: April 1, 2026

More Information

Terms related to this study

• Other Study ID Numbers: Protocol AS (1); UG1EY014231 (U.S. NIH Grant/Contract)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No