Ganglion cell analysis detects early neurodegenerative disease
OCT imaging gives optometrists an opportunity to provide timely intervention and comanagement with neurologists.
Optometrists are positioned to investigate neurodegenerative conditions such as Alzheimer’s disease, multiple sclerosis and Parkinson’s disease by examining the ganglion cell complex through optical coherence tomography.
Looking past the eye
“With the advent of ganglion cell analysis (GCA) looking at the ganglion cell complex (GCC), we’ve opened up a new pathway to look beyond the eye itself and begin to analyze structural and functional change within the cerebral cortex,” J. James Thimons, OD, of Ophthalmic Consultants of Connecticut and a Primary Care Optometry News Editorial Board member, explained in an interview.
Optical coherence tomography (OCT) is used to detect a loss in peripapillary retinal nerve fiber layer (RNFL) and a reduction in macular thickness and volume, which occurs in people with mild cognitive impairment, he said. The RNFL, which is the basic diagnostic element for glaucoma, avails valuable information about cellular activity in the eye itself.
“GCA is, to a large degree, a measure of the cortex pathways, so anywhere along the pathway where damage has occurred we are able to define it and understand how to connect the patient, the GCA and the RNFL and try to go forward from an assessment perspective to come up with a working diagnosis,” Thimons said.
Thimons has participated in two multiple sclerosis (MS) drug trials, during which the number of patients with MS at his practice rose dramatically over 3 years and has remained steady. He found that frequently patients would be symptomatic of physical change, but they could not find an abnormality in the visual field or RNFL.
“What really stood out was that the GCA would always match the patient’s clinical symptomatology. If they had MS and they had an MRI level-diagnosed disease, they always ended up with some form of ganglion cell damage that was consistent with their diagnosis,” Thimons added.
Some neurology practices are looking at OCT as a way to amplify their diagnostic acumen, he added.
He also uses this tool to make a “backward” diagnosis. When he sees a patient who lacks an MS diagnosis with an abnormal GCA, and systemic symptoms are consistent with the possibility for demyelinating disease, he will either image the patient himself or refer them, depending on modality, to a neurology group. Inevitably, they come back with some level of cognitive impairment confirmed.
Challenges with imaging
“The caveat,” Jarett Mazzarella, OD, a staff optometrist in the Salisbury VA Health Care System, explained, “is that we do have tracking technology [within the OCT] to reduce blink or motion artifact, but to get an accurate reading in this particular patient population may be more difficult. Patients with Parkinson’s may have tremors or difficulty with head position or fixation. Alzheimer’s patients may not be able to take a subjective response well and may need further direction. In all, it may hamper the reliability of the test, which we, as practitioners, need to be aware of.”
“The device has opened up the diagnosis potential of the practice,” Thimons continued. “And when we talk to patients and neurologists, the response is genuinely remarkable. Some will say, ‘This is amazing. Do you do this [testing] for everyone?’”
Eneh Jones-Odeh, MBBS, BSc, an ophthalmology specialist who previously worked at King’s College in London and is currently working at Torbay Hospital, is investigating whether RNFL thickness is associated with cognitive function in healthy individuals and whether RNFL thinning is secondary to cortical loss or if the same disease process affects both.
In a 2015 review in Eye, she reported the association between Alzheimer’s and multiple sclerosis and the RNFL and ganglion cell layer (GCL) ocular structures to determine their potential as biomarkers of neurodegeneration.
A previous study from Parisi and colleagues showed thinning of the RNFL in all quadrants in Alzheimer’s patients using OCT when compared with age-matched normal controls. The thinning correlated with abnormal retinal function tested with pattern electroretinogram, according to Jones-Odeh.
“These data suggest that the RNFL may be affected in early Alzheimer’s disease and, therefore, may be a useful biomarker of probable development of cognitive impairment in the future,” she wrote.
Another study highlighted in the review, from Iseri and colleagues, found that total macular thickness and volume of Alzheimer’s patients were significantly reduced and related to the degree of cognitive impairment.
“Further work from the same group corroborated the findings, reporting a 25% total reduction in the GCL in the foveal and parafoveal retina, with the greatest reduction of 52% being observed in the temporal region of the fovea,” according to Jones-Odeh.
“A limitation of most studies investigating this link is their small sample size and cross-sectional study design,” Jones-Odeh told PCON. “Therefore, further studies face the challenge of producing longitudinal data assessing sensitivity and specificity of a specific ocular biomarker in larger sample sizes. OCT provides an inexpensive, noninvasive approach for visualizing the central nervous system and obtaining quantitative measurements of ocular morphologies that have been implicated in neurodegenerative processes.”
She has also explored whether there is phenotypic sharing between RNFL thickness and cognitive traits and whether potential sharing is due to genetic factors using a twin model study design.
She is currently involved in research investigating the heritability, epidemiological and ophthalmic factors influencing GCC thickness in a healthy aging population. – by Abigail Sutton
- Iseri PK, et al. J Neuroophthalmol. 2006;26(1):18–24.
- Jones-Odeh E, Hammond CJ. Eye. 2015; doi:10.1038/eye.2015.158.
- Parisi V, et al. Clin Neurophysiol. 2001;112(10):1860–1867.
- For more information:
- Jarett Mazzarella, OD, is a staff optometrist in the Salisbury VA Health Care System and can be reached at email@example.com.
- Eneh Jones-Odeh, MBBS, BSc, can be reached at Torbay Hospital in South Devon, U.K., at firstname.lastname@example.org.
- J. James Thimons, OD, practices at Ophthalmic Consultants of Connecticut and is a Primary Care Optometry News Editorial Board member. He can be reached at email@example.com.
Disclosures: Jones-Odeh and Mazzarella reported no relevant financial disclosures. Thimons speaks for Zeiss and Optovue.