Retinal Imaging in Neurodegenerative Disease

Recruiting

• Conditions: Amyotrophic Lateral Sclerosis (ALS); Neuro-Degenerative Disease; Normal Cognition; Post-Traumatic Stress Disorder; Alzheimer's Disease; Parkinson's Disease; Multiple Sclerosis; Huntington Disease; Concussion; Down Syndrome
• Interventions: Device: Retinal and Choroidal Imaging

• Registration Number: NCT03233646
• Lead Sponsor: Duke University

Brief Summary

This study aims to develop and evaluate biomarkers using non-invasive optical coherence tomography (OCT) and OCT angiography (OCTA) as well as ultra-widefield (UWF) fundus photography to assess the structure and function of the retinal and choroidal microvasculature and structure in persons with mild cognitive impairment (MCI) and Alzheimer's Disease (AD), Parkinson's Disease (PD), or other neurodegenerative disease, diseases as outlined.

Detailed Description

Using a multidisciplinary approach, this study aims to yield new insight into the vascular and structural pathophysiology of neurodegenerative disease. The investigators propose to develop and evaluate imaging biomarkers from OCT, OCTA, and UWF fundus photos to assess the structure and function of the retinal and choroidal microvasculature and structure in these individuals.

The investigators hypothesize that microvascular and structural network alterations in the retina and choroid may mirror and possibly precede changes in the cerebral microcirculation seen in these neurodegenerative diseases. Using advanced image analysis and machine learning techniques, the investigators aim to evaluate markers of reduced capillary blood flow and non-perfusion in the superficial retinal vascular plexus and choriocapillaris imaged using OCT and OCTA, in a resolution not previously possible, that would complement already established retinal structural markers and increase their sensitivity and specificity in the earlier detection of these neurodegenerative diseases.

This study looks to provide a proof of concept for retinal and choroidal imaging-based microvascular and structural biomarkers as an effective screening tool for neurodegenerative disease, particularly during in cognitive aging.

The protocol for this study was amended and the record was updated accordingly.

Study Timeline

• Study Start: 2017-07-20
• Study First Submitted: 2017-07-26
• Study First Submitted QC: 2017-07-26
• Study First Posted: 2017-07-28
• Status Verified: 2025-01
• Last Update Submitted: 2025-01-24
• Last Update Posted: 2025-01-27
• Primary Completion: 2025-12-31
• Study Completion: 2025-12-31

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 2000

Inclusion Criteria

• Adults with neurodegenerative disease ((MCI, PD, AD, FTD, DLB, ALS, MS, HD, TBI, concussion, PTSD and other neurodegenerations as well as Down Syndrome)
• Adults without neurodegenerative disease

Exclusion Criteria

• Inability to cooperate with or complete testing or other neurologic or age- related ocular conditions that would impact image acquisition.
• Eyes that have had intraocular surgery, other than cataract surgery.

If two eyes satisfy the inclusion criteria, both eyes will be included in the study. If one eye satisfies the inclusion criteria, the eye that qualifies will be included in the study.

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Arm && Interventions

Group	Intervention	Description
Controls	Retinal and Choroidal Imaging	Controls will be recruited from the relatives/attendants of study participants or will be patients themselves and will not have a neurodegenerative disease diagnosis.
Case	Retinal and Choroidal Imaging	Patients with (MCI, PD, AD, FTD, DLB, ALS, MS, HD, TBI, concussion, PTSD and other neurodegenerations as well as Down Syndrome)

Primary Outcome Measures

Name	Time	Method
Change in retinal nerve fiber layer (RNFL) thickness	Baseline, 1 year	Retinal nerve fiber layer thickness as measured on optical coherence tomography scan of macula
Change in central subfield thickness (CST)	Baseline, 1 year	Central subfield thickness as measured on optical coherence tomography scan of macula
Change in choroidal vascularity index (CVI)	Baseline, 1 year	Choroidal vascularity index as measured using the COIN software in 1500 um area centered on the fovea
Change in foveal avascular zone (FAZ) area	Baseline, 1 year	Foveal avascular zone area as measured in the superficial capillary plexus on 3mm optical coherence tomography angiography scan of the macula
Change in ganglion cell-inner plexiform layer (GCIPL) thickness	Baseline, 1 year	Ganglion cell inner plexiform layer thickness as measured on optical coherence tomography scan of macula
Change in average vessel density (VD)	Baseline, 1 year	Average vessel density as measured in the ETDRS 3mm and 6mm circle and rings on optical coherence tomography angiography scan of the macula
Change in average capillary perfusion density (CPD)	Baseline, 1 year	Capillary perfusion density as measured on peripapillary 4.5mm optical coherence tomography angiography scan
Change in average perfusion density (PD)	Baseline, 1 year	Average perfusion density as measured in the ETDRS 3mm and 6mm circle and rings on optical coherence tomography angiography scan of the macula
Change in average capillary flux index (CFI)	Baseline, 1 year	Capillary flux index as measured on peripapillary 4.5mm optical coherence tomography angiography scan

Secondary Outcome Measures

Name	Time	Method
Change in retinal vessel width gradient	Baseline, 1 year	Retinal vessel width gradient measured on ultra-widefield scanning laser ophthalmoscopy image using VAMPIRE software
Change in retinal vessel tortuosity	Baseline, 1 year	Retinal vessel tortuosity measured on ultra-widefield scanning laser ophthalmoscopy image using VAMPIRE software
Change in retinal vessel fractal dimension	Baseline, 1 year	Retinal vessel fractal dimension measured on ultra-widefield scanning laser ophthalmoscopy image using VAMPIRE software

Trial Locations

Locations (1)

Duke University Medical Center; 🇺🇸 Durham, North Carolina, United States