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Heather E Whitson, Sina Farsiu, Sandra Stinnett, Sung Lee, Leon Kwark, Guy Potter, James Burke, Scott W Cousins, Eleonora Lad; Retinal imaging biomarkers for early diagnosis of Alzheimer’s disease. Invest. Ophthalmol. Vis. Sci. 2015;56(7 ):389.
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This project is based on the concept that retinas of people with Alzheimer's Disease (AD) may experience neuroinflammation similar to the brain. Inflammatory injury may cause atrophy of the ganglion cell layer (GCL) in the retina and its axonal projections which may manifest during the prodromal stage of AD. In this interim analysis of an ongoing case-control study, our objective is to determine whether GCL or nerve fiber layer (NFL) thickness may serve as non-invasive, inexpensive biomarkers to help diagnose AD. A second objective is to create retinal imaging processing software useful for the development of novel retinal biomarkers of AD.
NCT01937221 is enrolling 18 patients with mild cognitive impairment (MCI)/prodromal AD, 18 patients with mild-to-moderate AD and 18 cognitively normal, age-matched adults. All behavioral, imaging, and laboratory data are reviewed by a neurologist and neuropsychologist for consensus diagnosis regarding assignment to cognitive group. We carefully exclude any eyes with major eye diseases and diagnoses that may cause GCL or NFL thinning (e.g. normal tension glaucoma). Study participants undergo a full ophthalmic examination, ultra-high-resolution spectral domain optical coherence tomography (SD-OCT), wide-field fundus color and autofluorescence photography and stereo disc photography. Location-specific NFL and GCL thicknesses are measured using the Duke Optical Coherence Tomography Retinal Analysis Program (DOCTRAP) software, which has been validated in numerous large-scale clinical trials. The extent of peripheral drusen and amyloid plaques are graded by blinded investigators and quantified using the DOCTRAP software.
Preliminary analysis showed a statistically significant difference between neurocognitive status of 14 control subjects and 10 mild-moderate AD subjects but did not reveal a reduction in NFL or GCL in AD patients. Analysis of all data collected from control, MCI and AD subjects will be presented.
Careful exclusion of normal tension glaucoma may account for our preliminary, negative findings, which controvert a previous group’s finding of thinner NFL among persons with moderate-to-severe AD. Comparison of retinal images between normal subjects and subjects with different stages of cognitive impairment, prodromal and mild-moderate AD, will allow evaluation of the most promising retinal-based imaging biomarkers for diagnosing early AD.
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