Download Amblyopia as a Window to Neural Plasticity in the Visual System 2010

Amblyopia as a Window to
Neuroplasticity in the Visual System
Leonard J. Press, O.D., FCOVD, FAAO
Observational Data Is
Necessary But Insufficient
Yet Data Can Be Manipulated to
Draw One’s Own Conclusions
NEI Sponsored Research: Clinical
Trials
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PEDIG: Pediatric Eye Disease Investigator
Group – www.nei.nih.gov/ats3
OSU, SCCO, UAB, PCO, NECO, SUNY, IU,
SCO
Diane Tucker OD Cleveland Clinic
Foundation
Melissa Rice OD Mayo Clinic
Wilmer, Bascom Palmer
Michael Gallaway OD
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PCO & Private Practice, NJ
NEI Sponsored Research: Putting
Clinical Trials into Context
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PEDIG: The Pediatric Eye Disease
Investigator Group – mixed group of ODs and
MDs in multicenter private and institutional
practice. www.nei.nih.gov/ats3
A Randomized Trial of Patching Regimens
for Treatment of Severe Amblyopia in
Children.
Ophthalmology 2003;110:2075-2087.
Study Results
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Children age 3 – 7
Entering VA 20/100 – 20/400
No patching treatment prior 6 mos.
No amblyopia treatment any type prior mo.
Outcome: 6 hrs. daily patching produces
increased VA similar to full-time patching
PEDIG Study Results on Use of
Atropine in Moderate Amblyopia
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PEDIG. The course of moderate amblyopia
treated with atropine in children: experience
of the Amblyopia Treatment Study. Am J
Ophthalmol 2003;136:639-639.
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Children Age 3 – 7
Entering VA 20/40 – 20/100
Patching group > 6 hrs/day
Atropine group 1 drop daily
Outcome of ATS for Atropine in
Moderate Amblyopia
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Improvement initially faster with occlusion
than atropine
At 6 months both groups equal
Mean improvement was 3 lines of VA (20/60
to 20/30)
But … is atropine necessary daily?
PEDIG Daily Atropine versus
Weekend Atropine
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PEDIG. A Randomized Trial of Atropine
Regimens for Treatment of Moderate
Amblyopia in Children. Ophthalmology
2004;111:2076-2085.
Daily atropine group vs. weekend atropine
group (Sat. and Sun.)
Outcome after 17 wks. similar results
Treatment of Amblyopia
in Older Children
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PEDIG. Randomized trial of treatment of amblyopia
in children aged 7 to 17 years. Arch Ophthalmol
2005;123:437-447.
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NEI background: “Most eye care practitioners
believe that there is an age beyond which
attempting to treat amblyopia is futile. It is generally
held that the response to treatment is best when it is
instituted at an early age and is poor when
attempted after 8 years of age.”
Editorial Accompanying 2005
PEDIG Amblyopia Study
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“As physicians we pride ourselves in our use
of scientific method to give the best care to
our patients. Yet many of our daily decisions
reveal us more as apprentices than
scientists. We choose a particular treatment
not because a clinical trial determined that it
worked better, but because that is the way
our mentors did it.”
Outcome of Treatment for Older
Children from PEDIG Study
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Age 7 – 12: 2 - 6 hrs. per day of patching
with near activities and atropine can improve
VA even if the amblyopia has been previously
treated.
Age 13 – 17: 2 – 6 hrs. per day of patching
with near activities may improve visual acuity
when amblyopia has not been previously
treated.
Treatment of anisometropic
amblyopia in children with
refractive correction
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Ophthalmology 2006;113:895-903.
Phase one of a two-part study
Children ages 3 – 7
No prior Rx or treatment of any kind
Entering VA 20/40 to 20/250
Spectacle Rx was only treatment
Study Results of
Anisometropic Amblyopia
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Followed for 30 wks; VA ck every 5 wks
For 77% VA improved >/= 2 lines
For 60% VA improved >/= 3 lines
Conclusion: Rx alone is a powerful tx modality
for young children with aniso, and in
moderate cases may be the only treatment
necessary.
A Randomized trial to evaluate 2
hours of daily patching for
strabismic and anisometropic
amblyopia in children
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Ophthalmology 2006;113:904-912
Second part of two phase study
Children ages 3 – 7
Entering VA 20/40 – 20/400
Patients requiring Rx had to complete phase
1 (see previous study)
Mixed Study of Strab & Aniso
Amblyopia
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After Rx phase completed, subgroup
assigned patching/near activities
2 hrs of daily patching and >/= 1 hr of near
activities while patched
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Near eye/hand such as crafts; connect dots;
hidden pix; video games – monitored via log
These activities resulted in additional
improvement of half to one line
Personal observations
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To obtain >3 lines of VA improvement,
patching/near activities were necessary (21%
of this group had at least 4 lines improvement
vs. 5% of control group)
When VA was in range of 20/125 – 20/400,
43% of patching/near activities group
improved at least 3 lines, vs. 7% of control
group
Management of Patients
with Amblyopia
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Appropriate Rx if any
Quality time patching if moderate
“Belt and suspenders” approach to atropine
and patching if moderate
Refractive amblyopes OK with primarily
home-based procedures
Strabismic amblyopes require more vigilance
in-office and prone to regression (need
“fortified amblyopia therapy”)
Tips for Successful Management
(Undoing Occlusion Confusion)
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Severe Amblyopia < 20/100
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Moderate Amblyopia (20/60 – 20/100)
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Minimal occlusion
Shallow Amblyopia > 20/60
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Direct maximal occlusion (factor in function)
No occlusion
Value of Rx and nearpoint activities
Issues in Compliance with
Patching
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Young children resist patching because it
doesn’t make any sense to occlude better
eye
Children of all ages are concerned about their
appearance
Children are adept at beating the system
Methods of Occlusion
Methods of Occlusion
Methods of Occlusion
Patchees (www.bernell.com)
Patchees (works like Colorforms)
Broadening the View of
Amblyopia
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Levi, Ciuffreda,
Selenow – text on
Amblyopia (1991)
Best visual acuity
less than 20/40?
Two line difference
in best visual acuity?
BVA < 20/20?
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Amblyopia is a
developmental
disorder of spatial
vision
Functional Abnormalities in
Amblyopia Beneath the Surface of
Reduced Acuity
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Contrast Sensitivity
Spatial Distortion
Spatial Interaction
Crowding
Accommodation
Eye Movements
Suppression
Interaction of spatial
and temporal functions
Functional Consequences of Amblyopia
Kurt Simons PhD JAAPOS 2008;12:429-30
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Amblyopic subjects’ binocular reading speed is
significantly slower than that of normal subjects, despite
the amblyopic subjects having the same levels of
binocular visual acuity and reading acuity as the normal
subjects.
It appears then that amblyopia, although it has its onset
in childhood, has a major functional effect at the other
end of the lifespan.
Is there additional ophthalmologic literature that
acknowledges amblyopia results in functional deficits
through the lifespan that should be treated?
The Effect of Amblyopia on Fine Motor Skills
in Children. Webber AI, Wood JM, Gole GA, Brown B. Invest
Ophthalmol Vis Sci 2008;49:594–603
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Fine motor skills were reduced in children with
amblyopia, particularly those with strabismus, compared
with control subjects. The deficits in motor performance
were greatest on manual dexterity tasks requiring speed
and accuracy.
Clinicians may want to make parents of children with
amblyopia aware of this more global impact when
discussing the consequences of the condition.
From the School of Optometry & Institute of Health & Biomedical
Innovation, Queensland University of Technology; Department of
Paediatrics & Child Health, University of Queensland, AU.
Presented in part at ARVO 2007
Grasping Deficits and Adaptations in Adults with
Stereo Vision Losses. Melmoth DR, Finlay AL, Morgan MJ,
Grant S. Invest Ophthalmol Vis Sci 2009;50: 3711–3720
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High-grade binocular stereo vision is essential for skilled precision
grasping. Reduced disparity sensitivity results in an inaccurate
grasp-point selection and greater reliance on nonvisual information
from object contact to control grip stability.
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Prioritizing the recovery of high-grade binocularity, rather than just
vision in the affected eye, should provide generalized benefits for
visuomotor control in this disorder.
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From the Department of Optometry and Visual Science, The Henry
Wellcome Laboratories for Visual Sciences, City University, London,
United Kingdom.
Visual Motion Processing by Neurons in Area MT of
Macaque Monkeys with Experimental Amblyopia. ElShamayleh Y et al. J Neurosci 2010;20(36):12198-12209.
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Amblyopia is a developmental visual disorder that
manifests as loss of acuity without obvious organic
cause.
Commonly associated with deficits in spatial vision, but
behavioral studies also uncover significant impairments
in visual motion processing.
Amblyopia affects extrastriate processing in area MT by
influencing integration time of motion perception and
effects further downstream on coherence sensitivity.
The development of visual neuronal response properties
in extrastriate cortex, like that of striate cortex, is
modified by visual experience.
Reading Strategies in Mild to Moderate Strabismic
Amblyopia: An Eye Movement Investigation. Kanonidou
E, Proudlock FA, Gottlob I. Invest Ophthalmol Vis Sci
2010;51:3502–3508.
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In strabismic amblyopia, reading is impaired, not only during
monocular viewing with the amblyopic eye, but also with the nonamblyopic eye and binocularly, even though normal visual acuity
pertains to the latter two conditions.
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The impaired reading performance is associated with differences in
both the saccadic and fixational patterns, most likely as adaptation
strategies to abnormal sensory experiences such as crowding and
suppression.
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From the Ophthalmology Group, University of Leicester, Faculty of
Medicine & Biological Sciences, Leicester Royal Infirmary, UK.
Here’s the conclusion of the IOVS article. Good
points, but what’s missing?
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In clinical practice, the visual impairments and improvements in
visual function in amblyopes are usually tracked with high-contrast
visual acuity charts.
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Amblyopes may exhibit significant deficits in visual function after
treatment, in parameters such as contour integration, stability of
fixation, low contrast perception, and motion detection - despite
minor or absent deficits in high-contrast visual acuity.
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Our findings support previous suggestions that there may be some
benefit in including standardized reading charts in the assessment of
visual function in patients with strabismic amblyopia.
Amblyopia As A
Developmental Disorder
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Relative to the “normal” eye, the eye with
Amblyopia is developmentally disabled (DD)
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Any approach that aids visual processing in
DD aids visual processing in amblyopia
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The mainstay of optometric therapy for DD is
what vision scientists now refer to as
perceptual learning
VT As Supervised Perceptual
Learning
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Haidinger Brush/MIT
Accommodative stimulation
Ocular motor precision with small detail
Reduce crowding
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Hart Chart Saccadics
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Vary viewing distance
Modify the chart
Spatial localization
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pointer in straw x – y – z dimensions
effects of lenses/prism: SILO and JNDs
Monocular Fixation in a
Binocular Field (MFBF)
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Amblyopic eye
functions centrally while
the normally preferred
eye functions
peripherally
Analogy to picture-inpicture TV screen
Unsupervised/Passive Learning
Under MFBF Conditions
Occlusion foils to fog non-amblyopic
eye to a level of function below
the amblyopic eye
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Atropine penalization
Cholinergic antagonist to paralyze accommodation
 Dilation of pupil reduces depth of focus
at all distances and induces aberrations
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The Elegance of Atropine
Penalization
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Titrated amblyopia therapy
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Cycloplegically induced blur is maximal after 1-3
hours and begins to wane after 42 hours.
Blur increases with near fixation distance
Supervised perceptual learning during active
VT procedures potentiates the MFBF
properties of atropine
Superivsed Perceptual Learning
under MFBF Conditions
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Anaglyphic (red/green) or polarized filters to
control which part of the stimulus is seen
exclusively by the amblyopic eye
Feedback when amblyopic eye is suppressed
or de-tuned is immediately apparent
MFBF Procedure - Letter Tracking:
Letters printed in red ink seen by
amblyopic eye through green filter.
Non-amblyopic eye sees only where
guided by amblyopic eye
MFBF Vectogram
Applying Computerized
Therapy to Amblyopia
Amblyopia iNet
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VT program based on NIH studies
Hand-eye coordination program using
principles of operant conditioning and
behavior modification from HTS & PTS
Encourages compliance
www.visiontherapysolutions.net
Find The Target (“Crowding”)
Find The Target (reduced size)
Windows of Opportunity in
Treating Amblyopia
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Is it ever too late to treat a lazy eye?
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Optometry has maintained that age alone should
not be used as a limiting factor for amblyopia
therapy.
1977 article in American Academy of Optometry
journal by Birnbaum et al established this in a
review of the literature
Cortical Plasticity and Adult
Amblyopia
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The Jane Fonda influence
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The Christopher Reeve influence
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Forget age limitations
Forget poor prognosis for rehab
Implications from Alzheimer’s research
Accept cognitive challenges at
older ages (old dogs/new tricks)
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http://www.revophth.com/index.asp?page=1_14594.htm
Ophthalmology “Discovers”
Neuroplasticity and Neuroadaptation
Concepts of Plasticity as Related
to Amblyopia: Periods of Visual
Development
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Critical period
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Sensitive period
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6 months to 8 years
Susceptible period
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Birth to 6 months
8 – 18 years
Residual plasticity period
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18 years through adulthood
“Stereo Sue”
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Sue Barry, Ph.D.
Steven Markow, O.D.
Theresa Ruggiero, O.D.
Oliver Sacks, M.D.
Stereoscopic photograph taken by Oliver Sacks,
aged 12, from his bedroom window in London
Fixing My Gaze
Susan R. Barry, Ph.D. 2009/2010
www.fixingmygaze.com
The Mind’s Eye
Oliver Sacks, M.D., 2010
www.oliversacks.com/books/the-minds-eye
Patient Case
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MDS, female age 6
Had been examined by O.D. 12/04 and
detected to have amblyopia OS of 20/400
Referred to Ped O-M.D. who Rxed
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OD +1.00 sph
OS +5.00 – 0.50 cx 180
• Uncooperative with patching
Initial Findings 3/2/05
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VA cc: OD 20/20 OS 20/70
CT (cc): Orthophoria D & N
Ret: OD +1.25
OS +5.25 – 1.50 cx 15
Subj: OD +1.00, 20/20
OS +5.00 -1.25 cx 15, 20/60
Stereo (cc): Randot 100 seconds of arc
Findings Continued
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Worth 4-dot (cc): Normal Fusion
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Cycloplegia: OD +2.00
OS +6.00 – 1.50x15
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DFE: all structures normal
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Fixation: OS central, steady
Diagnosis?
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Refractive amblyopia OS
Rx: OD +1.00
OS +5.25 – 1.25 cx 15
- Continue with full-time wear
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Discussed CLs, but child averse, and mother
declines
Implement Atropine Therapy
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Plan: parent to instill i gt 1% atropine OD on
Friday night.
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Check on Saturday AM to see if pupil OD
dilated. If not, instill one more drop.
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Come to office Monday to for instruction on
home VT activities: dot-to-dot; mazes.
Progress Evaluation #1
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4 wk F/U
VAcc OS D: 20/40-3
Plan: continue home therapy and weekend
atropine instillation OD.
Progress Evaluation #2
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8 wk F/U, good compliance with atropine
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VA: OS = 20/40+1WL 20/30L
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Stereo: Randot 80 seconds of arc
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Plan: Continue atropine therapy, adding “Jump
Start” computer learning activities
Progress Evaluation #3
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12 wk F/U
VA: OS 20/30-2WL 20/30L
Stereo: Randot 60 seconds of arc
School performance starting to decrease
(reading difficulties)
Plan: discontinue atropinization in favor of 2
hrs “quality time patching” daily after school
(e.g. Michigan Letter Tracking)
Progress Evaluation #4
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16 wk F/U
VA: OS 20/30-2WL 20/25L
Stereo: Randot 60 seconds of arc
Plan: continue “quality time patching” after
school and on weekends
Progress Evaluation #5
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20 wk F/U
VA: OS 20/25WL 20/20L
Stereo: Randot 40 seconds of arc
Plan: taper “quality time patching” after
school and on weekends
Final Progress Evaluation
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24 wk F/U
VA: OS 20/25WL 20/20L
Stereo: Randot 40 seconds of arc
Assessment: stable acuity OS
Plan: continue full-time wear of Rx
Monitor at 6 mo intervals
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Not concerned about recidivism if Rx used f/t
Continue to recommend CLs
VEP (Visual Evoked Potential)
www.diopsys.com
VEP (Visual Evoked Potential)
www.diopsys.com
http://www.diopsys.com/opt-prac-study.php
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4 ½ yo – Rx: OD +2.00 OS +5.25
Aided VA OS 20/40-2; unaided VA 20/200
Office based VT able to reduce aniso Rx
BVA ultimately equal OD and OS
BVA OS ultimately same cc or sc
VEP used to help objectively determine if Rx
still advisable
RESOURCES
• www.nei.nih.gov/ats3
• www.aoa.org: Clinical Practice Guidelines on
Treatment of Amblyopia
 www.covd.org: Applied Concepts Course on
Amblyopia and Annual Meeting
 www.oepf.org: Regional Clinical Seminars and
Therapist materials
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Press LJ. Applied Concepts in Vision Therapy
2008 (http://oep.excerpo.com/)
Thank You