Longitudinal Natural History Study of Retinal Function in Eyes of Patients With Diabetes

NCT ID: NCT07270133

Last Updated: 2025-12-08

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

NOT_YET_RECRUITING

Total Enrollment

450 participants

Study Classification

OBSERVATIONAL

Study Start Date

2025-12-02

Study Completion Date

2032-12-31

Brief Summary

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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.

Detailed Description

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Conditions

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Diabetic Retinal Disease

Study Design

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Observational Model Type

COHORT

Study Time Perspective

PROSPECTIVE

Study Groups

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Non-diabetic controls

Aged-matched people without a diagnosis of diabetes. At least one eye must be eligible without retinal pathology.

Optical coherence tomography- Angiography

Intervention Type OTHER

non-invasive, dye-free imaging method that maps retinal and choroidal vasculature, allowing both qualitative and quantitative assessment of microvascular health. Quantitative metrics like vessel density, perfusion, FAZ size, and non-perfusion area serve as functional "scales" for disease severity and progression.

Visual Acuity

Intervention Type DIAGNOSTIC_TEST

Visual Acuity measured with the Electronic Early Treatment Diabetic Retinopathy Study (E-ETDRS) visual acuity test on a scale from 100 letters (Snellen equivalent of 20/10) to 0 letters (Snellen equivalent of \<20/800). Higher scores indicate better visual acuity, and lower scores indicate worse visual acuity

Reading Speed

Intervention Type DIAGNOSTIC_TEST

The MNREAD (Minnesota Low-Vision Reading) test is a standardized test that measures reading performance in people with normal or impaired vision.

Visual Field testing

Intervention Type DIAGNOSTIC_TEST

The objectiveFIELD Analyzer is a perimetry tool that measures visual fields using electroencephalography-based brain responses to flickering light. Higher sensitivity = better function, Lower sensitivity (more negative deviations from normal) = worse function; Global indices (MD, PSD-like values) indicate overall field loss and pattern of damage.

Contrast sensitivity

Intervention Type DIAGNOSTIC_TEST

A clinical device that utilizes the quick Contrast Sensitivity Function (qCSF) methodology to assess visual function. The qCSF method is a Bayesian adaptive algorithm designed to efficiently estimate a patient's contrast sensitivity across a wide range of spatial frequencies. Higher curve / higher AULCSF = better contrast sensitivity (normal vision). Lower curve / lower Area Under the Log Contrast Sensitivity Function = reduced contrast sensitivity (seen in early AMD, glaucoma, diabetic retinopathy, etc.).

Electroretinography (ERG) and pupillography in light- and dark-adapted states

Intervention Type DIAGNOSTIC_TEST

The RETeval® is a portable, handheld electroretinography (ERG) and visual evoked potential (VEP) device. It enables clinicians to assess the retinal and optic nerve.

Ultrawide field-color photograph

Intervention Type DIAGNOSTIC_TEST

Ultrawide field color photography is a high-resolution, wide-angle retinal imaging technique that captures both central and peripheral retina in natural color. Grading is typically based on the Diabetic Retinopathy Severity Scale or DRSS, which is a standardized grading scale from 10 (no DR) to 85 (severe PDR)

Ultrawide field-Fluorescein angiogram

Intervention Type DIAGNOSTIC_TEST

a high-resolution, wide-angle retinal vascular imaging technique that allows clinicians to see both central and peripheral retina blood flow, detect ischemia, leakage, and neovascularization, and guide diagnosis and treatment

Optical coherence tomography

Intervention Type DIAGNOSTIC_TEST

non-invasive retinal imaging tool that produces detailed cross-sectional images. Disease-specific grading systems (like macular thickness for DME or RNFL thickness for glaucoma) are used to quantify severity and monitor progression

Subclinical (No diabetic retinopathy on the diabetic retinopathy severity scale)

Eyes of patients with a diagnosis of diabetes, Diabetic Retinopathy Severity Scale = 10, and no diabetic macular edema. Lower limit on duration of disease for Type 1 is 5 years, for Type 2 is 1 year

Optical coherence tomography- Angiography

Intervention Type OTHER

non-invasive, dye-free imaging method that maps retinal and choroidal vasculature, allowing both qualitative and quantitative assessment of microvascular health. Quantitative metrics like vessel density, perfusion, FAZ size, and non-perfusion area serve as functional "scales" for disease severity and progression.

Visual Acuity

Intervention Type DIAGNOSTIC_TEST

Visual Acuity measured with the Electronic Early Treatment Diabetic Retinopathy Study (E-ETDRS) visual acuity test on a scale from 100 letters (Snellen equivalent of 20/10) to 0 letters (Snellen equivalent of \<20/800). Higher scores indicate better visual acuity, and lower scores indicate worse visual acuity

Reading Speed

Intervention Type DIAGNOSTIC_TEST

The MNREAD (Minnesota Low-Vision Reading) test is a standardized test that measures reading performance in people with normal or impaired vision.

Visual Field testing

Intervention Type DIAGNOSTIC_TEST

The objectiveFIELD Analyzer is a perimetry tool that measures visual fields using electroencephalography-based brain responses to flickering light. Higher sensitivity = better function, Lower sensitivity (more negative deviations from normal) = worse function; Global indices (MD, PSD-like values) indicate overall field loss and pattern of damage.

Contrast sensitivity

Intervention Type DIAGNOSTIC_TEST

A clinical device that utilizes the quick Contrast Sensitivity Function (qCSF) methodology to assess visual function. The qCSF method is a Bayesian adaptive algorithm designed to efficiently estimate a patient's contrast sensitivity across a wide range of spatial frequencies. Higher curve / higher AULCSF = better contrast sensitivity (normal vision). Lower curve / lower Area Under the Log Contrast Sensitivity Function = reduced contrast sensitivity (seen in early AMD, glaucoma, diabetic retinopathy, etc.).

Electroretinography (ERG) and pupillography in light- and dark-adapted states

Intervention Type DIAGNOSTIC_TEST

The RETeval® is a portable, handheld electroretinography (ERG) and visual evoked potential (VEP) device. It enables clinicians to assess the retinal and optic nerve.

Ultrawide field-color photograph

Intervention Type DIAGNOSTIC_TEST

Ultrawide field color photography is a high-resolution, wide-angle retinal imaging technique that captures both central and peripheral retina in natural color. Grading is typically based on the Diabetic Retinopathy Severity Scale or DRSS, which is a standardized grading scale from 10 (no DR) to 85 (severe PDR)

Ultrawide field-Fluorescein angiogram

Intervention Type DIAGNOSTIC_TEST

a high-resolution, wide-angle retinal vascular imaging technique that allows clinicians to see both central and peripheral retina blood flow, detect ischemia, leakage, and neovascularization, and guide diagnosis and treatment

Optical coherence tomography

Intervention Type DIAGNOSTIC_TEST

non-invasive retinal imaging tool that produces detailed cross-sectional images. Disease-specific grading systems (like macular thickness for DME or RNFL thickness for glaucoma) are used to quantify severity and monitor progression

Minimal to Mild non-proliferative diabetic retinopathy

Eyes of patients with a diagnosis of diabetes, Diabetic Retinopathy Severity Scale = 20-35, and no center-involved diabetic macular edema

Optical coherence tomography- Angiography

Intervention Type OTHER

non-invasive, dye-free imaging method that maps retinal and choroidal vasculature, allowing both qualitative and quantitative assessment of microvascular health. Quantitative metrics like vessel density, perfusion, FAZ size, and non-perfusion area serve as functional "scales" for disease severity and progression.

Visual Acuity

Intervention Type DIAGNOSTIC_TEST

Visual Acuity measured with the Electronic Early Treatment Diabetic Retinopathy Study (E-ETDRS) visual acuity test on a scale from 100 letters (Snellen equivalent of 20/10) to 0 letters (Snellen equivalent of \<20/800). Higher scores indicate better visual acuity, and lower scores indicate worse visual acuity

Reading Speed

Intervention Type DIAGNOSTIC_TEST

The MNREAD (Minnesota Low-Vision Reading) test is a standardized test that measures reading performance in people with normal or impaired vision.

Visual Field testing

Intervention Type DIAGNOSTIC_TEST

The objectiveFIELD Analyzer is a perimetry tool that measures visual fields using electroencephalography-based brain responses to flickering light. Higher sensitivity = better function, Lower sensitivity (more negative deviations from normal) = worse function; Global indices (MD, PSD-like values) indicate overall field loss and pattern of damage.

Contrast sensitivity

Intervention Type DIAGNOSTIC_TEST

A clinical device that utilizes the quick Contrast Sensitivity Function (qCSF) methodology to assess visual function. The qCSF method is a Bayesian adaptive algorithm designed to efficiently estimate a patient's contrast sensitivity across a wide range of spatial frequencies. Higher curve / higher AULCSF = better contrast sensitivity (normal vision). Lower curve / lower Area Under the Log Contrast Sensitivity Function = reduced contrast sensitivity (seen in early AMD, glaucoma, diabetic retinopathy, etc.).

Electroretinography (ERG) and pupillography in light- and dark-adapted states

Intervention Type DIAGNOSTIC_TEST

The RETeval® is a portable, handheld electroretinography (ERG) and visual evoked potential (VEP) device. It enables clinicians to assess the retinal and optic nerve.

Ultrawide field-color photograph

Intervention Type DIAGNOSTIC_TEST

Ultrawide field color photography is a high-resolution, wide-angle retinal imaging technique that captures both central and peripheral retina in natural color. Grading is typically based on the Diabetic Retinopathy Severity Scale or DRSS, which is a standardized grading scale from 10 (no DR) to 85 (severe PDR)

Ultrawide field-Fluorescein angiogram

Intervention Type DIAGNOSTIC_TEST

a high-resolution, wide-angle retinal vascular imaging technique that allows clinicians to see both central and peripheral retina blood flow, detect ischemia, leakage, and neovascularization, and guide diagnosis and treatment

Optical coherence tomography

Intervention Type DIAGNOSTIC_TEST

non-invasive retinal imaging tool that produces detailed cross-sectional images. Disease-specific grading systems (like macular thickness for DME or RNFL thickness for glaucoma) are used to quantify severity and monitor progression

Moderate non-proliferative diabetic retinopathy

Eyes of patients with a diagnosis of diabetes, Diabetic Retinopathy Severity Scale = 43-47, and no center-involved diabetic macular edema

Optical coherence tomography- Angiography

Intervention Type OTHER

non-invasive, dye-free imaging method that maps retinal and choroidal vasculature, allowing both qualitative and quantitative assessment of microvascular health. Quantitative metrics like vessel density, perfusion, FAZ size, and non-perfusion area serve as functional "scales" for disease severity and progression.

Visual Acuity

Intervention Type DIAGNOSTIC_TEST

Visual Acuity measured with the Electronic Early Treatment Diabetic Retinopathy Study (E-ETDRS) visual acuity test on a scale from 100 letters (Snellen equivalent of 20/10) to 0 letters (Snellen equivalent of \<20/800). Higher scores indicate better visual acuity, and lower scores indicate worse visual acuity

Reading Speed

Intervention Type DIAGNOSTIC_TEST

The MNREAD (Minnesota Low-Vision Reading) test is a standardized test that measures reading performance in people with normal or impaired vision.

Visual Field testing

Intervention Type DIAGNOSTIC_TEST

The objectiveFIELD Analyzer is a perimetry tool that measures visual fields using electroencephalography-based brain responses to flickering light. Higher sensitivity = better function, Lower sensitivity (more negative deviations from normal) = worse function; Global indices (MD, PSD-like values) indicate overall field loss and pattern of damage.

Contrast sensitivity

Intervention Type DIAGNOSTIC_TEST

A clinical device that utilizes the quick Contrast Sensitivity Function (qCSF) methodology to assess visual function. The qCSF method is a Bayesian adaptive algorithm designed to efficiently estimate a patient's contrast sensitivity across a wide range of spatial frequencies. Higher curve / higher AULCSF = better contrast sensitivity (normal vision). Lower curve / lower Area Under the Log Contrast Sensitivity Function = reduced contrast sensitivity (seen in early AMD, glaucoma, diabetic retinopathy, etc.).

Electroretinography (ERG) and pupillography in light- and dark-adapted states

Intervention Type DIAGNOSTIC_TEST

The RETeval® is a portable, handheld electroretinography (ERG) and visual evoked potential (VEP) device. It enables clinicians to assess the retinal and optic nerve.

Ultrawide field-color photograph

Intervention Type DIAGNOSTIC_TEST

Ultrawide field color photography is a high-resolution, wide-angle retinal imaging technique that captures both central and peripheral retina in natural color. Grading is typically based on the Diabetic Retinopathy Severity Scale or DRSS, which is a standardized grading scale from 10 (no DR) to 85 (severe PDR)

Ultrawide field-Fluorescein angiogram

Intervention Type DIAGNOSTIC_TEST

a high-resolution, wide-angle retinal vascular imaging technique that allows clinicians to see both central and peripheral retina blood flow, detect ischemia, leakage, and neovascularization, and guide diagnosis and treatment

Optical coherence tomography

Intervention Type DIAGNOSTIC_TEST

non-invasive retinal imaging tool that produces detailed cross-sectional images. Disease-specific grading systems (like macular thickness for DME or RNFL thickness for glaucoma) are used to quantify severity and monitor progression

Severe non-proliferative diabetic retinopathy

Eyes of patients with a diagnosis of diabetes, Diabetic Retinopathy Severity Scale = 53, and no center-involved diabetic macular edema

Optical coherence tomography- Angiography

Intervention Type OTHER

non-invasive, dye-free imaging method that maps retinal and choroidal vasculature, allowing both qualitative and quantitative assessment of microvascular health. Quantitative metrics like vessel density, perfusion, FAZ size, and non-perfusion area serve as functional "scales" for disease severity and progression.

Visual Acuity

Intervention Type DIAGNOSTIC_TEST

Visual Acuity measured with the Electronic Early Treatment Diabetic Retinopathy Study (E-ETDRS) visual acuity test on a scale from 100 letters (Snellen equivalent of 20/10) to 0 letters (Snellen equivalent of \<20/800). Higher scores indicate better visual acuity, and lower scores indicate worse visual acuity

Reading Speed

Intervention Type DIAGNOSTIC_TEST

The MNREAD (Minnesota Low-Vision Reading) test is a standardized test that measures reading performance in people with normal or impaired vision.

Visual Field testing

Intervention Type DIAGNOSTIC_TEST

The objectiveFIELD Analyzer is a perimetry tool that measures visual fields using electroencephalography-based brain responses to flickering light. Higher sensitivity = better function, Lower sensitivity (more negative deviations from normal) = worse function; Global indices (MD, PSD-like values) indicate overall field loss and pattern of damage.

Contrast sensitivity

Intervention Type DIAGNOSTIC_TEST

A clinical device that utilizes the quick Contrast Sensitivity Function (qCSF) methodology to assess visual function. The qCSF method is a Bayesian adaptive algorithm designed to efficiently estimate a patient's contrast sensitivity across a wide range of spatial frequencies. Higher curve / higher AULCSF = better contrast sensitivity (normal vision). Lower curve / lower Area Under the Log Contrast Sensitivity Function = reduced contrast sensitivity (seen in early AMD, glaucoma, diabetic retinopathy, etc.).

Electroretinography (ERG) and pupillography in light- and dark-adapted states

Intervention Type DIAGNOSTIC_TEST

The RETeval® is a portable, handheld electroretinography (ERG) and visual evoked potential (VEP) device. It enables clinicians to assess the retinal and optic nerve.

Ultrawide field-color photograph

Intervention Type DIAGNOSTIC_TEST

Ultrawide field color photography is a high-resolution, wide-angle retinal imaging technique that captures both central and peripheral retina in natural color. Grading is typically based on the Diabetic Retinopathy Severity Scale or DRSS, which is a standardized grading scale from 10 (no DR) to 85 (severe PDR)

Ultrawide field-Fluorescein angiogram

Intervention Type DIAGNOSTIC_TEST

a high-resolution, wide-angle retinal vascular imaging technique that allows clinicians to see both central and peripheral retina blood flow, detect ischemia, leakage, and neovascularization, and guide diagnosis and treatment

Optical coherence tomography

Intervention Type DIAGNOSTIC_TEST

non-invasive retinal imaging tool that produces detailed cross-sectional images. Disease-specific grading systems (like macular thickness for DME or RNFL thickness for glaucoma) are used to quantify severity and monitor progression

Proliferative diabetic retinopathy

Eyes of patients with a diagnosis of diabetes, Diabetic Retinopathy Severity Scale \> 60, and no center-involved diabetic macular edema

Optical coherence tomography- Angiography

Intervention Type OTHER

non-invasive, dye-free imaging method that maps retinal and choroidal vasculature, allowing both qualitative and quantitative assessment of microvascular health. Quantitative metrics like vessel density, perfusion, FAZ size, and non-perfusion area serve as functional "scales" for disease severity and progression.

Visual Acuity

Intervention Type DIAGNOSTIC_TEST

Visual Acuity measured with the Electronic Early Treatment Diabetic Retinopathy Study (E-ETDRS) visual acuity test on a scale from 100 letters (Snellen equivalent of 20/10) to 0 letters (Snellen equivalent of \<20/800). Higher scores indicate better visual acuity, and lower scores indicate worse visual acuity

Reading Speed

Intervention Type DIAGNOSTIC_TEST

The MNREAD (Minnesota Low-Vision Reading) test is a standardized test that measures reading performance in people with normal or impaired vision.

Visual Field testing

Intervention Type DIAGNOSTIC_TEST

The objectiveFIELD Analyzer is a perimetry tool that measures visual fields using electroencephalography-based brain responses to flickering light. Higher sensitivity = better function, Lower sensitivity (more negative deviations from normal) = worse function; Global indices (MD, PSD-like values) indicate overall field loss and pattern of damage.

Contrast sensitivity

Intervention Type DIAGNOSTIC_TEST

A clinical device that utilizes the quick Contrast Sensitivity Function (qCSF) methodology to assess visual function. The qCSF method is a Bayesian adaptive algorithm designed to efficiently estimate a patient's contrast sensitivity across a wide range of spatial frequencies. Higher curve / higher AULCSF = better contrast sensitivity (normal vision). Lower curve / lower Area Under the Log Contrast Sensitivity Function = reduced contrast sensitivity (seen in early AMD, glaucoma, diabetic retinopathy, etc.).

Electroretinography (ERG) and pupillography in light- and dark-adapted states

Intervention Type DIAGNOSTIC_TEST

The RETeval® is a portable, handheld electroretinography (ERG) and visual evoked potential (VEP) device. It enables clinicians to assess the retinal and optic nerve.

Ultrawide field-color photograph

Intervention Type DIAGNOSTIC_TEST

Ultrawide field color photography is a high-resolution, wide-angle retinal imaging technique that captures both central and peripheral retina in natural color. Grading is typically based on the Diabetic Retinopathy Severity Scale or DRSS, which is a standardized grading scale from 10 (no DR) to 85 (severe PDR)

Ultrawide field-Fluorescein angiogram

Intervention Type DIAGNOSTIC_TEST

a high-resolution, wide-angle retinal vascular imaging technique that allows clinicians to see both central and peripheral retina blood flow, detect ischemia, leakage, and neovascularization, and guide diagnosis and treatment

Optical coherence tomography

Intervention Type DIAGNOSTIC_TEST

non-invasive retinal imaging tool that produces detailed cross-sectional images. Disease-specific grading systems (like macular thickness for DME or RNFL thickness for glaucoma) are used to quantify severity and monitor progression

Interventions

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Optical coherence tomography- Angiography

non-invasive, dye-free imaging method that maps retinal and choroidal vasculature, allowing both qualitative and quantitative assessment of microvascular health. Quantitative metrics like vessel density, perfusion, FAZ size, and non-perfusion area serve as functional "scales" for disease severity and progression.

Intervention Type OTHER

Visual Acuity

Visual Acuity measured with the Electronic Early Treatment Diabetic Retinopathy Study (E-ETDRS) visual acuity test on a scale from 100 letters (Snellen equivalent of 20/10) to 0 letters (Snellen equivalent of \<20/800). Higher scores indicate better visual acuity, and lower scores indicate worse visual acuity

Intervention Type DIAGNOSTIC_TEST

Reading Speed

The MNREAD (Minnesota Low-Vision Reading) test is a standardized test that measures reading performance in people with normal or impaired vision.

Intervention Type DIAGNOSTIC_TEST

Visual Field testing

The objectiveFIELD Analyzer is a perimetry tool that measures visual fields using electroencephalography-based brain responses to flickering light. Higher sensitivity = better function, Lower sensitivity (more negative deviations from normal) = worse function; Global indices (MD, PSD-like values) indicate overall field loss and pattern of damage.

Intervention Type DIAGNOSTIC_TEST

Contrast sensitivity

A clinical device that utilizes the quick Contrast Sensitivity Function (qCSF) methodology to assess visual function. The qCSF method is a Bayesian adaptive algorithm designed to efficiently estimate a patient's contrast sensitivity across a wide range of spatial frequencies. Higher curve / higher AULCSF = better contrast sensitivity (normal vision). Lower curve / lower Area Under the Log Contrast Sensitivity Function = reduced contrast sensitivity (seen in early AMD, glaucoma, diabetic retinopathy, etc.).

Intervention Type DIAGNOSTIC_TEST

Electroretinography (ERG) and pupillography in light- and dark-adapted states

The RETeval® is a portable, handheld electroretinography (ERG) and visual evoked potential (VEP) device. It enables clinicians to assess the retinal and optic nerve.

Intervention Type DIAGNOSTIC_TEST

Ultrawide field-color photograph

Ultrawide field color photography is a high-resolution, wide-angle retinal imaging technique that captures both central and peripheral retina in natural color. Grading is typically based on the Diabetic Retinopathy Severity Scale or DRSS, which is a standardized grading scale from 10 (no DR) to 85 (severe PDR)

Intervention Type DIAGNOSTIC_TEST

Ultrawide field-Fluorescein angiogram

a high-resolution, wide-angle retinal vascular imaging technique that allows clinicians to see both central and peripheral retina blood flow, detect ischemia, leakage, and neovascularization, and guide diagnosis and treatment

Intervention Type DIAGNOSTIC_TEST

Optical coherence tomography

non-invasive retinal imaging tool that produces detailed cross-sectional images. Disease-specific grading systems (like macular thickness for DME or RNFL thickness for glaucoma) are used to quantify severity and monitor progression

Intervention Type DIAGNOSTIC_TEST

Other Intervention Names

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Early treatment diabetic retinopathy study visual acuity ETDRS MNREAD (Minnesota Low-Vision Reading) objectiveFIELD analyzer AST Manifold qCSF RETeval device UWF-Photo UWF-FA OCT OCT-A

Eligibility Criteria

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Inclusion Criteria

* Age ≥ 18 years
* Diagnosed with Type 1 or Type 2 diabetes or non-diabetic control patients
* Best corrected visual acuity 20/32 or better (Snellen) (≥74 ETDRS letters)
* Meets criteria for one of the defined observational groups below
* Able and willing to provide informed consent

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
* Requiring treatment for DR/DME in the next 6 months
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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National Eye Institute (NEI)

NIH

Sponsor Role collaborator

Jaeb Center for Health Research

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Other Identifiers

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UG1EY014231

Identifier Type: NIH

Identifier Source: secondary_id

View Link

Protocol AR

Identifier Type: -

Identifier Source: org_study_id

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