Macular Thickness as a Potential Biomarker of Mild Alzheimer's Disease (original) (raw)

Although several postmortem findings in the retina of patients with Alzheimer's disease (AD) are available, 1 new biomarkers for early diagnosis and follow-up of AD are still lacking. It has been postulated that the defects in the retinal nerve fiber layer (RNFL) may be the earliest sign of AD, even before damage to the hippocampal region that affects memory. 2 This fact may reflect retinal neuronal-ganglion cell death and axonal loss in the optic nerve in addition to aging. 1 Changes in longitudinal optical coherence tomography (OCT) measurements of RNFL can act as a surrogate marker of axonal health, making OCT an invaluable tool for measuring axonal loss as a biomarker. 2 The goal of this study was to examine the thickness of the macular and peripapillary RNFL with OCT to determine the most predictive area affected in patients with mild AD, Geriatric Depression Scale-4, Reisberg scale, and make comparisons using normal subjects. Twenty patients with mild AD and 28 age-matched control subjects from the Geriatric Unit in the Hospital Clínico San Carlos, Madrid, Spain, were studied. The AD patients met the criteria for AD according to the National Institute of Neurological and Communicative Disorders and StrokeeAlzheimer's Disease and Related Disorders Association and the Diagnostic and Statistical Manual of Mental Disorders IV, having mild cognitive impairment according to the Clinical Dementia Rating scale. Informed consent was obtained from both groups. The research followed the tenets of the Declaration of Helsinki, and the protocol was approved by the local ethics committee. The inclusion criteria for patients were: being free of ocular disease and systemic disorders affecting vision; best-corrected visual acuity (BCVA) of 20/40; AE5 spherocylindrical refractive error; and intraocular pressure of <20 mmHg. All the subjects underwent a complete ophthalmologic examination, including visual acuity, refraction, anterior and posterior segment biomicroscopy, intraocular pressure measurement, dilated fundus examination, and OCT. The RNFL thickness and macular thickness were measured by OCT Model 3D OCT-1000 (Topcon, Japan) after pupil dilatation. The analysis area was centered manually and the absence of segmentation errors was confirmed for each scan. One eye of each patient assigned at random was analyzed. In the peripapillary area the average thickness (360) and the temporal (316 e45), superior (46 e135), nasal (136 e225), and inferior (226 e315) quadrant thicknesses were evaluated. Macular RNFL thickness data were displayed in 3 concentric rings centered in the foveola, distributed as follows: A central macular ring, 1 mm from the fovea; an inner macular ring, 3 mm from the fovea; and an outer macular ring, 6 mm from the fovea. The inner and outer rings were each divided into 4 quadrants (superior, inferior, nasal, and temporal (Fig 1). The data are reported as mean values AE standard deviations. The differences between groups were analyzed using the Manne Whitney U test. Sensitivity at 90% specificity and receiver operating characteristics (ROCs) analysis for discriminating between healthy and mild AD patients were calculated for the RNFL thickness in all the areas studied. Data were processed in a SPSS 19.0. P < 0.05 was considered statistically significant.