Parkinson disease, Alzheimer disease, and multiple sclerosis are progressive neurodegenerative disorders affecting distinctive collections of central nervous system neurons. Despite the progressive nature of these diseases, there are no objective, reliable, noninvasive diagnostic measures for their activity, progression, or response to treatment. In addition to motor and cognitive abnormalities, symptoms in Parkinson, Alzheimer and multiple sclerosis patients often include blurred vision, color vision abnormalities and decreased contrast sensitivity. These visual disturbances may be accompanied by distinctive structural changes within the eye and, in particular, within the retina. The retina, as a direct extension of the central nervous system (CNS), may offer a unique, quantifiable location to noninvasively investigate pathophysiology and to monitor disease activity in these disorders.
A recent literature search on PubMed identified a total of 63 published studies in multiple sclerosis, six in Alzheimer disease, and six in Parkinson disease involving the use of optical coherence tomography (OCT). As a comparison, in the last 10 months alone, there were 161 publications in age-related macular degeneration and 43 in diabetic macular edema dealing specifically with OCT. Most studies in neurodegenerative disorders are led by neurologists, with minimal input from ophthalmologists or retina specialists, with no standardized protocols or quality measures for retinal scanning, in relatively small numbers of patients, with limited control data and inadequate longitudinal follow-up.
MULTIPLE SCLEROSIS
Multiple sclerosis (MS) is an autoimmune disorder characterized
by progressive axonal degeneration with resultant
neurological deterioration. Most patients, at the time of
their first clinically apparent symptoms, have occult MRI activity, signifying that sentinel clinical events do not necessarily
represent the beginning of the disease process.1 Optic
neuritis (ON) may be a presenting sign of MS or may occur
during an exacerbation of the disease. While most patients
return to baseline visual acuity, contrast sensitivity and color
vision abnormalities may persist, signifying more permanent
retinal or optic nerve dysfunction. Anatomic correlates to
this lasting dysfunction include optic-disc pallor and focal
retinal nerve fiber layer (RNFL) defects as observed on dilated
fundus examination.2
The first use of OCT in MS, published in 1999, reported a 46% reduction in average RNFL thickness in eyes affected by ON compared with controls and a 28% reduction in MS patients even without history of ON.3 Since then, several groups have shown a reduction in both RNFL thickness and macular volume in patients with and, interestingly, even without a history of ON.3 Based on these limited published reports, an expert panel concluded that OCT could be an appropriate adjunct to the diagnosis of MS and may serve as a measure of treatment effects of disease-modifying drugs compared with placebo in patients with MS. However, the same panel cautioned that more data are necessary to determine whether RNFL loss measured by OCT directly correlates with CNS axonal loss in patients with MS.4
PARKINSON DISEASE
Parkinson disease (PD) is a progressive neurodegenerative
disorder with selective dopaminergic neuronal loss principally
in the substantia nigra. The retina also contains dopaminergic
neurons that modulate the receptive fields of ganglion
cells and PD may have a degenerative effect on these retinal
neurons as well.5 Not surprisingly, in addition to motor dysfunction,
PD patients often report decreased vision, diminished spatial contrast sensitivity, and dyschromatopsia.6
There have been several reports of RNFL thinning and
decreased macular volume in PD patients compared with
controls using the Stratus OCT (Carl Zeiss Meditec, Dublin,
CA).7,8 Given the paucity of OCT data, the relationship
between RNFL and macular thickness in patients with PD
compared with control patients remains uncertain.
ALZHEIMER DISEASE
Alzheimer disease (AD) is the most common degenerative
dementia, causing a progressive decline in cognitive function.
Visual disturbances noted in AD patients include decreased
or blurred vision and impairment of spatial contrast sensitivity,
motion perception, and color discrimination.9 Reports
have attributed this visual dysfunction to damage in the primary
visual cortex and to degeneration of the higher cortical
area.10 However, studies have also shown evidence of precortical
involvement, with a reduction in the number of retinal
ganglion cells and optic nerve axons.11-15 As a substantiation
of retinal dysfunction in AD patients, five published reports
have indicated that there may be a reduction of peripapillary
and macular RNFL thickness and macular volume.15
CASE PRESENTATION
A 38 year-old woman with a history of MS was referred
by her neurologist for peripapillary RNFL evaluation. Her
visual acuity was 20/20 in each eye. Although she reported
some red color desaturation in her left eye, the patient had
no afferent pupillary defect. Ocular history was significant
for a distant history of ON in the left eye (at least 5 years
previous, although the patient was unsure exactly how long
ago). The patient underwent a circular scan OCT using the
3D OCT 2000 (Topcon, Paramus, NJ). The scan was centered centered
on the optic nerve as is
done in a glaucoma protocol.
Despite the patient's lack of
visual symptoms, the RNFL in
the affected left eye was thinner
compared with that in the right
eye (Figures 1, 2). The RNFL in
the right eye was also borderline
thin compared with agematched
controls.
CONCLUSIONS
Although there is an indication
of potential clinical utility
of OCT in neurodegenerative
disorders, especially in MS, at
this time it is still premature to
use OCT measurements as primary
or secondary endpoints
in clinical decision-making in these patients. Importantly,
observations using the Spectralis OCT (Heidelberg
Instruments, Vista, CA) must be confirmed with the newer
generation high-resolution spectral-domain systems in larger
cohorts, perhaps even in a prospective manner.
Szil´rd Kiss, MD, is an Assistant Professor of Ophthalmology at Weill Cornell Medical College and an Assistant Attending Physician at the New York Presbyterian Hospital. Dr. Kiss states that he has no financial arrangements relevant to the products and companies discussed in this article. He may be reached at 646-962-2020; or via e-mail at szk7001@med.cornell.edu.
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