Retinal Imaging in Neurodegenerative Disease

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.

• Retinal and Choroidal Imaging (Device): Non-invasive OCT, OCTA, and UWF fundus photography of retina

Primary outcomes

• 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 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 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 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 capillary flux index (CFI) [Baseline, 1 year]: Capillary flux index as measured on peripapillary 4.5mm optical coherence tomography angiography scan

Secondary outcomes

• 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 width gradient [Baseline, 1 year]: Retinal vessel width gradient 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

Sex: All, ages: 18 Years to any, accepts healthy volunteers

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.

• Results publication: Zhao W, Robbins CB, Grewal DS, Patel H, Soundararajan S, Liu AJ, Johnson KG, Agrawal R, Petrella JR, Stinnett SS, Parker D, Fekrat S. Correlating retinal and choroidal vascular parameters with volumetric MRI in Alzheimer's disease and amnestic mild cognitive impairment. BMC Ophthalmol. 2025 Jul 1;25(1):365. doi: 10.1186/s12886-025-04157-x. PMID 40598011
• Results publication: Robbins CB, Akrobetu D, Ma JP, Stinnett SS, Soundararajan S, Liu AJ, Johnson KG, Grewal DS, Fekrat S. ASSESSMENT OF RETINAL MICROVASCULAR ALTERATIONS IN INDIVIDUALS WITH AMNESTIC AND NONAMNESTIC MILD COGNITIVE IMPAIRMENT USING OPTICAL COHERENCE TOMOGRAPHY ANGIOGRAPHY. Retina. 2022 Jul 1;42(7):1338-1346. doi: 10.1097/IAE.0000000000003458. PMID 35723922

• Sharon Fekrat, MD FACS FASRS, Principal investigator, Duke University
• Dilraj Grewal, MD, Principal investigator, Duke University