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Retinal Microperimetry as a Means to Assess Visual Field Expansion in Visual Restoration Therapy

Retinal Microperimetry as a Means to Assess Visual Field
Expansion in Visual Restoration Therapy
Mohamad Chmayssani, Brandon Minzer, Nina Saxena, Roy Arogyasami, Ronald Lazar, Vivienne C Greenstein,
Randolph Marshall
Columbia University Medical Center, New York, NY
Although several studies have reported t hat Visual Restoration Therapy (VRT) expands
visual fields,1
questions have been raised as to whether th e results are explained by
intermittent saccades or eccentric fixation into the “blind”
field rather than restored vision in
the previously non-seeing region. W e used Micropermetry (MP-1) to test the hypothesis
that expansion of visual field following VRT is independent of eye movements.
VRT is a computerized, home-based treatm ent for patients with homonymous visual
field defects aimed at reducing the size of the defect through repetitive stimulation of
the visual borderzone adjacent to the blind f ield. VRT targets the borderzone while
central fixation is maintained through fixating o n a central stimulus. Patient responds to
either a central fixation stimulus color change or a n eccentric stimulus appearing in the
peripheral field.
MP-1 (Fig-1) has an automated tracking system that controls for eye movement s. MP-1
has an infrared camera that uses the retinal v essel as a reference frame. With any shift
or movement between this reference image a nd the real-time fundus image the
stimulus position is corrected. The MP-1 also all ows stimulus parameters, e.g. size,
duration and luminance, to be chosen by the examiner to be similar to those used for
VRT training and HRP visual field mapping .
-10 -8 -6 -4 -2 0 2 4 6 8 10
Retinal Microperimetry
Eccentricity (deg of visual angle)
= seen
= not seen
HRP map, eyes still
Microperimetry (MP-1). The Nidek
MP-1 (Nidek
Technologies, Padova, Italy) uses a refe rence
frame for stimulus presentation based on a photograph of the retinal vessels, adjusting the
location of stimuli based on the referenced vessels. P recise stimulus presentation to known
locations on the retina is therefore possible. Follo wing pupil dilation (1% tropicamide
and 2.5%
hydrochloride) and adaptation to di m room illumination for 30 minutes the patient
maintained fixation on a centrally placed re d cross (2°
in diameter) while responding to
suprathreshold “white”
test lights (stimulus size Goldman I, duratio n 200 msecs, 0 dB) presented
on a dim “white”
background (1.27 cd/m2). The non-tested e ye was occluded throughout the
procedure. Sixty-eight locations covering a n area 20°
in diameter were tested. Stimulus l ocations
were spaced 2 degrees apart from each othe r and were centered around the fovea. The results of
the microperimetry tests and the location of fixation during stimulus presentation were displayed
on color digital photographs acquired b y the MP-1 color camera.
Patients: Six patients (25-79) with retro-chiasmatic
brain injury producing homonymous visual f ield
defects underwent VRT >6 months following stroke.
Visual Restoration Therapy. Therapy was done at home twice-daily for 20-30 minutes, 6 days a
week. VRT targets specific regions of the visual f ield while the
patient maintains central fixation.
With the chin supported on a frame 15 inches from an LCD screen,
the patient fixates on a central
stimulus (size=0.5deg) and presses a single mouse button when either the central fixation stimulus
changes color or an eccentric stimulus appe ars in the peripheral
field. The color change (yellow to
green) was designed to be subtle enough to require foveal vision
for discrimination, thus maximizing
central fixation. During therapy, stimuli consisted of suprathreshold white squares 2 degrees in
width which appeared sequentially alo ng a horizontal path from a
position in the seeing field 6
degrees from the border of the blind fiel d, into the blind field
6 degrees, and then back into the
seeing field. The luminance of the back ground was<1cd/m2, room lights off for the therapy. The
interval varied between 1000 and 1 800 msec
to minimize anticipation of the next
stimulus. Eighty percent of the eccentric stimuli appeared in the visual borderzone; 20% appeared
at random locations in the seeing and blin d fields to reduce the
predictability of target location..
Methods Cont’d
We defined relative-defect as cells where det ection occurred 25% or 50% out of 4 trials at pre-treatment, whereas c ells
detected zero times were defined as absol ute-defect. We excluded locations seen 3 out of 4 times to evaluate for
improvement only in more severely aff ected resions.
We quantified performance within each c ell and compared change over time for both relative and absolute zones among
the six patients using a paired t-test. Furtherm ore, we translated the performance, stimulus detection rate, into a visu al
map using the following color code:
1) Black voxels represent all blind (absolute d efect) fields (0)
that did not improve.
2) Grey voxels represent blind field (0) that im proved either to
1 or 2
3) Lime voxels represent relative defect zones (1,2) that improved.
4) Lavendor
voxels represent relative defect zone (1,2) t hat worsened or did not improve.
5) White voxels represent normal detection (3, 4 ) at baseline.
For the group, there was improvement in stimuli detection at both absolute and relative defect zones (P<0.038).
Improvement was seen in each patient, in co ntiguous cells along the borderzone and blind regions. Table 1 repr esents the
stimulus detection rate at baseline and follo w up including both absolute and relative defect cells.
Fig-1 (a, b) illustrates one run of microperimetr y tests at each of the time points (pre and post-VRT respectively) for pati ent
1.Location of fixation during stimulus pre sentation is also displayed on the color digital photographs acq uired by the MP-1
color camera (cluster of blue dots), indicating consist ent fixation within 1 degree of the central fixation spot. Fig-1 (C)
summarizes the improvement in the visual fiel d using the color code described above.
Figure 2 (a, b) illustrates one run of the Microper imetry at each of the time points for patient 2. Again consistent fixati on is
demonstrated. Figure 2 C is the constructed v isual map demonstrating the visual field expansion for patient 2 2nd to VRT.
Using the same color code, Figures 3-6 dis play the expansion in the visual filed in contiguous cells along the border zone
and the blind region for patients (3-6).
Fig1a Fig1b Fig1c
Fig2a Fig2b Fig2c
Using microperimetry we showed that visual field maps improved in 6 patients
undergoing VRT. Our data suggest that wit h the use of microperimetry, visual field
expansion can be demonstrated to be indepe ndent of eye movements.
Although the mechanism of visual field e xpansion following visual field training
with VRT is not addressed by this study, our f indings of visual field expansion are
consistent with animal models showing chan ges in cellular receptive fields after
injury2. Other animal studies have shown that trainin g of the visual system may
result in plasticity at the cellular level3. In hum ans, we previously showed that 1
month of training by hemianopic
stroke patients on the VRT program resulted in
increases in the BOLD signal in regions relate d to visual processing, and these
changes were specific to stimuli In the trained (bor derzone) field compared with the
untrained field4. The biological basis for the rea ssignment of new RFs
to neurons
within a previously silent cortical regi on is thought to be long-range horizontal
connections in superficial layers of primary vis ual cortex2.
1) Kasten, E., Wust, S., Behrens-Baumann, W. & Sabel, B. A. Computer-based trainingfor
the treatment of partial blindness treatment. Nat Med 4, 1083-7 (1998).
2) Gilbert, C. D. & Wiesel, T. N. Receptive field dynamics in adult primary visual cortex.
Nature 356, 150-2 (1992).
3) Yang T, Manusell
JH. The effect of perceptual learning on neuronal responses in
monkey visual area V4. J Neurosci
24, 1617-26 (2004)
4) Marshall RS, Ferrera JJ, Barnes A, Xian Zhang, O’Brien KA, Chmayssani M, Hirsch J,
Lazar RM. Brain activity associated with stimulation therapy
of the visual borderzone
in hemianopic
stroke patients. Neurorehabil
Neural Repair.
2008 Mar-Apr;22(2):136-
44. Epub
2007 Aug
The objective of this study was to determine the effect of a visual rehabilitation intervention on visual field defects in a US cohort. Vision Restoration Therapy (VRT) consists of a specific pattern of stimulation that is directed at the border of the blind field. This retrospective study evaluated individuals with homonymous visual field defect from retrochiasmatic lesions treated with 6 modules of VRT. Suprathreshold visual field testing of the central 43x32 was obtained at baseline and after each module. The main outcome measures were the change in stimuli detection and the shift in the position of the border of the blind field. The impact of age, time from injury and type of visual field defect were analyzed. Among 161 patients, the mean absolute improvement in stimuli detection was 12.8%. The average border shift was 4.87. Improvements of > or =3% was noted in 76% of patients. Absolute change in stimulus detection of > or =3% at mid-therapy was associated with a greater final improvement. Age, time from lesion and type of visual field defect did not influence the degree of field expansion. VRT improves stimulus detection and results in a shift of the position of the border of the blind field as measured on suprathreshold visual field testing. These results support prior reports and support VRT as a useful rehabilitative intervention for a proportion of patients with visual field defects from retrochiasmatic lesions.
Full-text available
Partial blindness after brain injury has been considered non-treatable. To evaluate whether patients with visual-field defects can profit from computer-based visual restitution training (VRT), two independent clinical trials were conducted using patients with optic nerve (n = 19) or post-chiasmatic brain injury (n = 19). In post-chiasma patients, VRT led to a significant improvement (29.4%) over baseline in the ability to detect visual stimuli; in optic nerve patients, the effects were even more pronounced (73.6% improvement). Visual-field enlargements were confirmed by the observation of a visual-field expansion of 4.9 degrees-5.8 degrees of visual angle and improved acuity in optic nerve patients. Ninety five percent of the VRT-treated patients showed improvements, 72.2% confirmed visual improvements subjectively. Patients receiving a placebo training did not show comparable improvements. In conclusion, VRT with a computer program improves vision in patients with visual-field defects and offers a new, cost-effective therapy for partial blindness.
Full-text available
Previous studies have shown that perceptual learning can substantially alter the response properties of neurons in the primary somatosensory and auditory cortices. Although psychophysical studies suggest that perceptual learning induces similar changes in primary visual cortex (V1), studies that have measured the response properties of individual neurons have failed to find effects of the size described for the other sensory systems. We have examined the effect of learning on neuronal response properties in a visual area that lies at a later stage of cortical processing, area V4. Adult macaque monkeys were trained extensively on orientation discrimination at a specific retinal location using a narrow range of orientations. During the course of training, the subjects achieved substantial improvement in orientation discrimination that was primarily restricted to the trained location. After training, neurons in V4 with receptive fields overlapping the trained location had stronger responses and narrower orientation tuning curves than neurons with receptive fields in the opposite, untrained hemifield. The changes were most prominent for neurons that preferred orientations close to the trained range of orientations. These results provide the first demonstration of perceptual learning modifying basic neuronal response properties at an intermediate level of visual cortex and give insights into the distribution of plasticity across adult visual cortex.
The adult brain has a remarkable ability to adjust to changes in sensory input. Removal of afferent input to the somatosensory, auditory, motor or visual cortex results in a marked change of cortical topography. Changes in sensory activity can, over a period of months, alter receptive field size and cortical topography. Here we remove visual input by focal binocular retinal lesions and record from the same cortical sites before and within minutes after making the lesion and find immediate striking increases in receptive field size for cortical cells with receptive fields near the edge of the retinal scotoma. After a few months even the cortical areas that were initially silenced by the lesion recover visual activity, representing retinotopic loci surrounding the lesion. At the level of the lateral geniculate nucleus, which provides the visual input to the striate cortex, a large silent region remains. Furthermore, anatomical studies show that the spread of geniculocortical afferents is insufficient to account for the cortical recovery. The results indicate that the topographic reorganization within the cortex was largely due to synaptic changes intrinsic to the cortex, perhaps through the plexus of long-range horizontal connections.
Brain activity associated with stimulation therapy of the visual borderzone in hemianopic stroke patients
  • R S Marshall
  • J J Ferrera
  • A Barnes
  • Xian Zhang
  • O 'brien
  • K A Chmayssani
  • M Hirsch
  • J Lazar
Marshall RS, Ferrera JJ, Barnes A, Xian Zhang, O'Brien KA, Chmayssani M, Hirsch J, Lazar RM. Brain activity associated with stimulation therapy of the visual borderzone in hemianopic stroke patients. Neurorehabil Neural Repair. 2008 Mar-Apr;22(2):136-44. Epub 2007 Aug 14.