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

Overview

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.

Interventions

• 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
• 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.
• 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.
• 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 retinopa
• 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.
• 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)
• 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
• 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 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.

Primary outcome measures

• Does the performance of the objectiveFIELD Analyzer at baseline worsen as the Diabetic Retinopathy Severity Score increases [Time frame: 4 Years]
• Does the performance of the Contrast sensitivity (AST Manifold qCSF) at baseline worsen as the Diabetic Retinopathy Severity Score increases [Time frame: 4 Years]
• Does the performance of the Electroretinography (ERG) at baseline worsen as the Diabetic Retinopathy Severity Score increases [Time frame: 4 Years]
• Does the performance of the Ultrawide field-color photograph at baseline worsen as the Diabetic Retinopathy Severity Score increases [Time frame: 4 Years]
• Does the performance of the Ultrawide field-Fluorescein angiogram at baseline worsen as the Diabetic Retinopathy Severity Score increases [Time frame: 4 Years]
• Does the performance of the Optical coherence tomography at baseline worsen as the Diabetic Retinopathy Severity Score increases [Time frame: 4 Years]
• Does the performance of the Optical Coherence Tomography- Angiography at baseline worsen as the Diabetic Retinopathy Severity Score increases [Time frame: 4 Years]
• Does the performance of Visual Acuity at baseline worsen as the Diabetic Retinopathy Severity Score increases [Time frame: 4 Years]

Eligibility criteria

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

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Observational model

Cohort

Study locations

Center list to be confirmed — check the primary protocol.

Identifiers

NCT: NCT07270133 · Protocol AR · UG1EY014231

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗