Morphological and functional retinal impairment in Alzheimer's disease patients
Introduction
A depletion of optic nerve ganglion cells and their axons has been histologically observed in Alzheimer's Disease (AD) patients (Hinton et al., 1986). Further morphometric analyses performed by the paraphenilene–diamine technique confirmed this finding and showed a predominant involvement of the largest retinal ganglion cells (M-cells) that contribute with large caliber fibers to the optic nerve (Sadun and Bassi, 1990). However, more recent studies (Rizzo et al., 1992, Curcio and Druker, 1993) failed to confirm the above-mentioned findings. This discrepancy has been, at least partially, attributed to methodological bias such as a different postmortem delay in axon count and/or difficulties in obtaining well-preserved myelinated axons.
An objective method of quantifying in vivo the optic nerve axons and retinal thickness has been proposed. This method consists of a new non-invasive technology allowing cross-sectional imaging of the eye by optical coherence tomography (OCT) (Huang et al., 1991, Hee et al., 1995a, Hee et al., 1995b, Puliafito et al., 1995, Schuman, 1997), and so far has been widely employed in assessing the nerve fiber layer (NFL) thickness in ocular hypertension or glaucoma (Parisi et al., 1999a, Parisi et al., 2001, Manni et al., 1999, Schuman et al., 1995) and multiple sclerosis (Parisi et al., 1999b). Recently, Chauhan and Marshall (1999) raised some criticism regarding the accuracy of the OCT in the NFL thickness measurement. However, in the same report, they showed a good correlation between excimer-laser induced ablation of the inner retina and the signal recorded by OCT, stating that ‘… the thickness of the inner band was reduced by the same amount as the ablation step height’. Therefore, although the accuracy of OCT in quantifying NFL thickness is still a matter of debate, we can assume that progressive changes in the OCT signal coming from the inner retina (including NFL, inner plexiform layer and ganglion cell layer) are paralleled by similar changes occurring in the tissue.
The bioelectrical activity of ganglion cells and their fibers can be objectively assessed by recording electroretinographic signals in response to patterned stimuli (PERG) (Maffei and Fiorentini, 1981, Maffei et al., 1990). Several studies have shown the presence of an abnormal PERG in AD patients and this finding was considered as further evidence of retinal ganglion cell dysfunction (Katz et al., 1989, Trick et al., 1989).
A group of AD patients was evaluated by means of combined morphometric (OCT) and electrophysiological (PERG) analyses in order to assess: (a) the optic nerve fiber layer thickness in vivo; (b) the function of the innermost retinal layer; (c) whether a correlation exists between morphological and functional parameters. Preliminary results have been previously published as an abstract (Parisi et al., 2000).
Section snippets
Subjects
According to the inclusion criteria (see above), 17 subjects (mean age 70.37±6.1 years) were selected from a group of 40 patients with diagnosis of AD. The diagnosis was performed using the established criteria of the National Institute of Neurological and Communicative Disorders and Stroke-Alzheimer's Disease and Related Disorders Association (NINCDS-ADRDA) (McKhann et al., 1984). For this study, we included patients with a mild severity of cognitive impairment, according to criteria described
Results
The clinical characteristics of AD patients are shown in Table 1.
Discussion
AD patients showed a reduction in NFL thickness significantly correlated to abnormal PERG responses.
Our OCT results show an NFL reduced thickness in each quadrant examined indicating that an involvement of the neuroretinal tissue occurs in AD patients. An age-related reduction of NFL thickness in normal subjects has been reported (Gramer and Dirmeyer, 1998); however, the reduction in NFL thickness observed in our AD patients was significantly greater than that observed in the age-matched
Acknowledgements
We thank Drs Fiermonte, Manni, Coco, Ripandelli, Coppè, Scassa, Olzi, Coppola, and Gregori for their helpful cooperation in the selection of the patients and in the morphological and electrophysiological evaluations.
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