Retinal Ganglion Cell Analysis Using High-Definition Optical Coherence Tomography in Patients with Mild Cognitive Impairment and Alzheimer's Disease

Article type: Research Article

Authors: Cheung, Carol Yim-lui^{a; b; c; 1; *} | Ong, Yi Ting^{a; b; d; 1} | Hilal, Saima^{b; e; h} | Ikram, M. Kamran^{a; b; c; e} | Low, Sally^a | Ong, Yi Lin^a | Venketasubramanian, N.^e | Yap, Philip^f | Seow, Dennis^g | Chen, Christopher Li Hsian^{e; h; 2} | Wong, Tien Yin^{a; b; c; 2}

Affiliations: [a] Singapore Eye Research Institute, Singapore National Eye Centre, Singapore | [b] Department of Ophthalmology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore | [c] Office of Clinical Sciences, Duke-NUS Graduate Medical School, Singapore | [d] NUS Graduate School for Integrative Sciences and Engineering, National University of Singapore, Singapore | [e] Memory Aging and Cognition Centre, National University Health System, Singapore | [f] Department of Geriatric Medicine, Khoo Teck Puat Hospital, Singapore | [g] Department of Geriatric Medicine, Singapore General Hospital, Singapore | [h] Department of Pharmacology, National University of Singapore, Singapore

Correspondence: [*] Correspondence to: Dr. Carol Y. Cheung, Singapore Eye Research Institute, The Academia, 20 College Road, Discovery Tower Level 6, Singapore 169856. Tel.: +65 6576 7233; E-mail: [email protected].

Note: [1] These authors contributed equally to this work as first authors.

Note: [2] These authors contributed equally to the work as last authors.

Abstract: Background:Alzheimer’s disease (AD) is a neurodegenerative disorder with emerging evidence that it is associated with retinal ganglion cell loss; however, few data exist to establish this association. Objective:To determine whether macular ganglion cell-inner plexiform layer (GC-IPL) and retinal nerve fiber layer (RNFL), as quantitatively measured by non-invasive in vivo spectral-domain optical coherence tomography (SD-OCT), are altered in patients with AD and mild cognitive impairment (MCI). Methods:Patients with AD and MCI were recruited from dementia/memory clinics, and cognitively normal controls were selected from the Singapore Epidemiology of Eye Disease program. SD-OCT (Cirrus HD-OCT, software version 6.0.2, Carl Zeiss Meditec Inc, Dublin, CA) was used to measure the GC-IPL and RNFL thicknesses. Results:Compared with cognitively normal controls (n = 123), patients with AD (n = 100) had significantly reduced GC-IPL thicknesses in all six (superior, superonasal, inferonasal, inferior, inferotemporal, and superotemporal) sectors (mean differences from –3.42 to –4.99 µm, all p < 0.05) and reduced RNFL thickness in superior quadrant (–6.04 µm, p = 0.039). Patients with MCI (n = 41) also had significantly reduced GC-IPL thicknesses compared with controls (mean differences from –3.62 to –5.83 µm, all p < 0.05). Area under receiver operating characteristic curves of GC-IPL were generally higher than that of RNFL to discriminate AD and MCI from the controls. Conclusions:Our data strengthens the link between retinal ganglion cell neuronal and optic nerve axonal loss with AD, and suggest that assessment of macular GC-IPL can be a test to detect neuronal injury in early AD and MCI.

Keywords: Alzheimer's disease, mild cognitive impairment, neurodegenerative disorder, optic nerve, retinal ganglion cell, spectral-domain optical coherence tomography

DOI: 10.3233/JAD-141659

Journal: Journal of Alzheimer's Disease, vol. 45, no. 1, pp. 45-56, 2015