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

Purpose

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.

Condition

  • Diabetic Retinal Disease

Eligibility

Eligible Ages
Over 18 Years
Eligible Sex
All
Accepts Healthy Volunteers
No

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

Study Design

Phase
Study Type
Observational
Observational Model
Cohort
Time Perspective
Prospective

Arm Groups

ArmDescriptionAssigned Intervention
Non-diabetic controls Aged-matched people without a diagnosis of diabetes. At least one eye must be eligible without retinal pathology.
  • Diagnostic Test: 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
    Other names:
    • Early treatment diabetic retinopathy study visual acuity ETDRS
  • 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.
    Other names:
    • MNREAD (Minnesota Low-Vision Reading)
  • 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.
    Other names:
    • objectiveFIELD analyzer
  • 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.).
    Other names:
    • AST Manifold qCSF
  • 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.
    Other names:
    • RETeval device
  • 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)
    Other names:
    • UWF-Photo
  • 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
    Other names:
    • UWF-FA
  • 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
    Other names:
    • OCT
  • Other: 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.
    Other names:
    • OCT-A
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
  • Diagnostic Test: 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
    Other names:
    • Early treatment diabetic retinopathy study visual acuity ETDRS
  • 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.
    Other names:
    • MNREAD (Minnesota Low-Vision Reading)
  • 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.
    Other names:
    • objectiveFIELD analyzer
  • 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.).
    Other names:
    • AST Manifold qCSF
  • 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.
    Other names:
    • RETeval device
  • 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)
    Other names:
    • UWF-Photo
  • 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
    Other names:
    • UWF-FA
  • 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
    Other names:
    • OCT
  • Other: 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.
    Other names:
    • OCT-A
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
  • Diagnostic Test: 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
    Other names:
    • Early treatment diabetic retinopathy study visual acuity ETDRS
  • 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.
    Other names:
    • MNREAD (Minnesota Low-Vision Reading)
  • 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.
    Other names:
    • objectiveFIELD analyzer
  • 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.).
    Other names:
    • AST Manifold qCSF
  • 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.
    Other names:
    • RETeval device
  • 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)
    Other names:
    • UWF-Photo
  • 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
    Other names:
    • UWF-FA
  • 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
    Other names:
    • OCT
  • Other: 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.
    Other names:
    • OCT-A
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
  • Diagnostic Test: 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
    Other names:
    • Early treatment diabetic retinopathy study visual acuity ETDRS
  • 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.
    Other names:
    • MNREAD (Minnesota Low-Vision Reading)
  • 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.
    Other names:
    • objectiveFIELD analyzer
  • 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.).
    Other names:
    • AST Manifold qCSF
  • 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.
    Other names:
    • RETeval device
  • 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)
    Other names:
    • UWF-Photo
  • 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
    Other names:
    • UWF-FA
  • 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
    Other names:
    • OCT
  • Other: 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.
    Other names:
    • OCT-A
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
  • Diagnostic Test: 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
    Other names:
    • Early treatment diabetic retinopathy study visual acuity ETDRS
  • 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.
    Other names:
    • MNREAD (Minnesota Low-Vision Reading)
  • 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.
    Other names:
    • objectiveFIELD analyzer
  • 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.).
    Other names:
    • AST Manifold qCSF
  • 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.
    Other names:
    • RETeval device
  • 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)
    Other names:
    • UWF-Photo
  • 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
    Other names:
    • UWF-FA
  • 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
    Other names:
    • OCT
  • Other: 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.
    Other names:
    • OCT-A
Proliferative diabetic retinopathy Eyes of patients with a diagnosis of diabetes, Diabetic Retinopathy Severity Scale > 60, and no center-involved diabetic macular edema
  • Diagnostic Test: 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
    Other names:
    • Early treatment diabetic retinopathy study visual acuity ETDRS
  • 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.
    Other names:
    • MNREAD (Minnesota Low-Vision Reading)
  • 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.
    Other names:
    • objectiveFIELD analyzer
  • 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.).
    Other names:
    • AST Manifold qCSF
  • 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.
    Other names:
    • RETeval device
  • 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)
    Other names:
    • UWF-Photo
  • 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
    Other names:
    • UWF-FA
  • 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
    Other names:
    • OCT
  • Other: 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.
    Other names:
    • OCT-A

Recruiting Locations

Boston Medical Center Corporation
Boston, Massachusetts 02118
Contact:
Steven D Ness, MD
617-414-4020
sreevardhan.alluri@bmc.org

More Details

Status
Recruiting
Sponsor
Jaeb Center for Health Research

Study Contact