1. Primary open-angle glaucoma (POAG) is a
neurodegenerative visual disorder that can result in
blindness. Typically, increased intraocular pressure causes
degeneration of retinal ganglion cells, which affects
neurons in the lateral geniculate nucleus (LGN) and
primary visual cortex (V1). Although the cause is unknown,
POAG results in cell loss and shrinkage of tissue in the LGN.
Despite this evidence, there are no studies demonstrating
functional loss in the LGN. Consequently, this study
measured functional activity in the LGN in POAG. Neuronal
activity in ten subjects was inferred using functional
magnetic resonance imaging (fMRI). Subjects participated
up to 8 functional scans and one anatomical scan. Subjects
were presented with flickering checkerboard stimuli
alternating between the left and right visual fields or the
superior and inferior visual fields. The fMRI signal for each
voxel was correlated with the stimulus timing using a
threshold of p = 0.001. Large clusters of significantly
correlated activity were found in V1. However, similar
activity could not be detected in the LGN. To confirm the
sensitivity of our measure, one healthy control subject was
analyzed. LGN could be localized using the same threshold
parameters as for the POAG patients. Our study provides
further evidence that the LGN degenerates in individuals
with POAG.
Abstract
Results
Methods
Ten patients with POAG volunteered for this study and
participated in 6 to 8 functional scans each. All subjects
possessed abnormal fields of vision and were provided a
consent form which explained the purpose and possible
consequences of the study.
All subjects were administered a complete ophthalmologic
examination and were screened for standard MRI exclusion
criteria (Duncan, 2012). Individuals who had metal in their
body that could not be removed and/or were taking
medications known to effect cerebral metabolism could
not participate in this study (Duncan, 2007). In addition,
individuals with conditions that elevated intraocular
pressure such as pituitary lesions, diabetic retinopathy or
demyelinating diseases were excluded.
FMRI images were acquired at the Center for Brain Imaging
at New York University using a Siemens Allegra 3.0 Tesla
scanner with an 8-channel brain coil.
Visual stimuli were presented with checkerboard stimuli
that flickered at 8 Hz. Stimuli were presented alternately
between the left versus right visual fields and the superior
versus inferior visual fields every 15 seconds.
CONCLUSIONS
Introduction
Glaucoma is an irreversible disease that has become the
second leading cause of blindness around the world. There
are many kinds of glaucoma, the most prevalent being
primary open angle glaucoma (POAG).
Although the ultimate underlying cause of POAG is
unknown, POAG appears to be the result of the improper
drainage of aqueous humor in the eye. The lack of clear
symptoms, together with the slow progression of the
disease, makes it difficult to determine the
pathophysiology of POAG. Contrary to popular belief,
damage associated with glaucoma is not limited to the eye
(Songs, 2014).
Functional Magnetic Resonance Imaging (FMRI) is an
imaging method that locates neuronal activity by
measuring changes of oxygenated and deoxygenated
hemoglobin (Chen, 2012). In addition, FMRI is a non-
invasive technique that helps assess anatomical and
functional changes of the central nervous system, including
the functional changes in POAG patients.
Previous studies indicate that POAG causes an anatomical
degeneration in the LGN (Gupta et al., 2006). However,
due to the fact that the functional degeneration in the LGN
has not been researched, this study uses fMRI to
investigate the loss of functional capabilities between the
LGN and the primary visual cortex in human glaucoma
patients.
Evidence of Diminished Neuronal Activity in the Lateral
Geniculate Nucleus of Patients with Primary Open-Angle Glaucoma
Ariel Rosario and Robert O. Duncan
Department of Behavioral Sciences
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doi:10.1371/journal.pone.0089493
Figure 3: Functional activity in the in LGN and
V1 of a healthy control subject
Figure 2: Saggittal image of Superior-Inferior
differences in activity for all glaucoma patients
Figure 1: Saggittal image of Superior-
Inferior differences in activity for all
glaucoma patients • Significant functional data was selected from
regions of interest corresponding to LGN and V1
using a threshold of p = 0.001.
• Large clusters of significantly correlated activity
were found in the superior and the inferior regions
of V1 in each hemisphere of subjects with POAG.
However, similar activity could not be detected in
the LGN of the same POAG subjects.
• To confirm the sensitivity of our measure, one
healthy control subject (not age-matched) was
analyzed. LGN could be localized using the same
threshold parameters as for the POAG patients.
Figure 4: Functional activity in LGN and V1
of a representative glaucoma patient
Due to the lack of detectable functional activity in LGN,
our study provides further evidence that the LGN
undergoes morphological and functional changes in
individuals with POAG. Despite clear activity in V1, no
signal was detected in the LGN of subjects with POAG.
This information can possibly lead to new treatments and
the cause of POAG.