Amblyopia as a Window to Neuroplasticity in the Visual System Leonard J. Press, O.D., FCOVD, FAAO

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Amblyopia as a Window to Neuroplasticity in the
Visual System Leonard J. Press, O.D., FCOVD,
FAAO
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Observational Data Is Necessary But Insufficient
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Yet Data Can Be Manipulated to Draw Ones Own
Conclusions
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NEI Sponsored Research Clinical Trials

• 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
• PCO Private Practice, NJ

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NEI Sponsored Research Putting Clinical Trials
into Context

• 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 20031102075-2087.

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Study Results

• 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

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PEDIG Study Results on Use of Atropine in
Moderate Amblyopia

• PEDIG. The course of moderate amblyopia treated
  with atropine in children experience of the
  Amblyopia Treatment Study. Am J Ophthalmol
  2003136639-639.
• Children Age 3 7
• Entering VA 20/40 20/100
• Patching group gt 6 hrs/day
• Atropine group 1 drop daily

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Outcome of ATS for Atropine in Moderate Amblyopia

• 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?

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PEDIG Daily Atropine versusWeekend Atropine

• PEDIG. A Randomized Trial of Atropine Regimens
  for Treatment of Moderate Amblyopia in Children.
  Ophthalmology 20041112076-2085.
• Daily atropine group vs. weekend atropine group
  (Sat. and Sun.)
• Outcome after 17 wks. similar results

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Treatment of Amblyopiain Older Children

• PEDIG. Randomized trial of treatment of
  amblyopia in children aged 7 to 17 years. Arch
  Ophthalmol 2005123437-447.
• 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.

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Editorial Accompanying 2005 PEDIG Amblyopia Study

• 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.

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Outcome of Treatment for Older Children from
PEDIG Study

• 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.

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Treatment of anisometropic amblyopia in children
with refractive correction

• Ophthalmology 2006113895-903.
• 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

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Study Results of Anisometropic Amblyopia

• Followed for 30 wks VA ck every 5 wks
• For 77 VA improved gt/ 2 lines
• For 60 VA improved gt/ 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.

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A Randomized trial to evaluate 2 hours of daily
patching for strabismic and anisometropic
amblyopia in children

• Ophthalmology 2006113904-912
• 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)

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Mixed Study of Strab Aniso Amblyopia

• After Rx phase completed, subgroup assigned
  patching/near activities
• 2 hrs of daily patching and gt/ 1 hr of near
  activities while patched
• 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

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Personal observations

• To obtain gt3 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

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Management of Patientswith Amblyopia

• 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)

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Tips for Successful Management (Undoing Occlusion
Confusion)

• Severe Amblyopia lt 20/100
• Direct maximal occlusion (factor in function)
• Moderate Amblyopia (20/60 20/100)
• Minimal occlusion
• Shallow Amblyopia gt 20/60
• No occlusion
• Value of Rx and nearpoint activities

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Issues in Compliance with Patching

• Young children resist patching because it doesnt
  make any sense to occlude better eye
• Children of all ages are concerned about their
  appearance
• Children are adept at beating the system

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Methods of Occlusion
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Methods of Occlusion
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Methods of OcclusionPatchees (www.bernell.com)
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Patchees (works like Colorforms)
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Broadening the View of Amblyopia

• Amblyopia is a developmental disorder of spatial
  vision

• Levi, Ciuffreda, Selenow text on Amblyopia
  (1991)
• Best visual acuity less than 20/40?
• Two line difference in best visual acuity?
• BVA lt 20/20?

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Functional Abnormalities in Amblyopia Beneath the
Surface of Reduced Acuity

• Contrast Sensitivity
• Spatial Distortion
• Spatial Interaction
• Crowding
• Accommodation
• Eye Movements
• Suppression
• Interaction of spatial
• and temporal functions

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Functional Consequences of AmblyopiaKurt Simons
PhD JAAPOS 200812429-30

• 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?

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The Effect of Amblyopia on Fine Motor Skillsin
Children. Webber AI, Wood JM, Gole GA, Brown B.
Invest Ophthalmol Vis Sci 200849594603

• 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

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Grasping Deficits and Adaptations in Adults with
Stereo Vision Losses. Melmoth DR, Finlay AL,
Morgan MJ, Grant S. Invest Ophthalmol Vis Sci
200950 37113720

• 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.
• 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.
• From the Department of Optometry and Visual
  Science, The Henry Wellcome Laboratories for
  Visual Sciences, City University, London, United
  Kingdom.

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Visual Motion Processing by Neurons in Area MT of
Macaque Monkeys with Experimental Amblyopia.
El-Shamayleh Y et al. J Neurosci
201020(36)12198-12209.

• 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.

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Reading Strategies in Mild to Moderate
StrabismicAmblyopia An Eye Movement
Investigation. Kanonidou E, Proudlock FA, Gottlob
I. Invest Ophthalmol Vis Sci 20105135023508.

• In strabismic amblyopia, reading is impaired, not
  only during monocular viewing with the amblyopic
  eye, but also with the non-amblyopic eye and
  binocularly, even though normal visual acuity
  pertains to the latter two conditions.
• 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.
• From the Ophthalmology Group, University of
  Leicester, Faculty of Medicine Biological
  Sciences, Leicester Royal Infirmary, UK.

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Heres the conclusion of the IOVS article. Good
points, but whats missing?

• In clinical practice, the visual impairments and
  improvements in visual function in amblyopes are
  usually tracked with high-contrast visual acuity
  charts.
• 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.
• 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.

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Amblyopia As A Developmental Disorder

• Relative to the normal eye, the eye with
  Amblyopia is developmentally disabled (DD)
• Any approach that aids visual processing in DD
  aids visual processing in amblyopia
• The mainstay of optometric therapy for DD is what
  vision scientists now refer to as perceptual
  learning

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VT As Supervised Perceptual Learning

• Haidinger Brush/MIT
• Accommodative stimulation
• Ocular motor precision with small detail
• Reduce crowding
• Hart Chart Saccadics
• Vary viewing distance
• Modify the chart
• Spatial localization
• pointer in straw x y z dimensions
• effects of lenses/prism SILO and JNDs

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Monocular Fixation in a Binocular Field (MFBF)

• Amblyopic eye functions centrally while the
  normally preferred eye functions peripherally
• Analogy to picture-in-picture TV screen

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Unsupervised/Passive Learning Under MFBF
Conditions

• Occlusion foils to fog non-amblyopic
• eye to a level of function below
• the amblyopic eye
• 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

• Titrated amblyopia therapy
• 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

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Superivsed Perceptual Learning under MFBF
Conditions

• 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

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MFBF Procedure - Letter TrackingLetters
printed in red ink seen by amblyopic eye through
green filter.Non-amblyopic eye sees only where
guided by amblyopic eye
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MFBF Vectogram
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Applying Computerized Therapy to Amblyopia
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Amblyopia iNet

• 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

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Find The Target (Crowding)
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Find The Target (reduced size)
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Windows of Opportunity in Treating Amblyopia

• Is it ever too late to treat a lazy eye?
• 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

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Cortical Plasticity and Adult Amblyopia

• The Jane Fonda influence
• Forget age limitations
• The Christopher Reeve influence
• Forget poor prognosis for rehab
• Implications from Alzheimers research
• Accept cognitive challenges at
• older ages (old dogs/new tricks)

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http//www.revophth.com/index.asp?page1_14594.ht
mOphthalmology Discovers Neuroplasticity and
Neuroadaptation
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Concepts of Plasticity as Related to Amblyopia
Periods of Visual Development

• Critical period
• Birth to 6 months
• Sensitive period
• 6 months to 8 years
• Susceptible period
• 8 18 years
• Residual plasticity period
• 18 years through adulthood

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Stereo Sue

• Sue Barry, Ph.D.
• Steven Markow, O.D.
• Theresa Ruggiero, O.D.
• Oliver Sacks, M.D.

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Stereoscopic photograph taken by Oliver Sacks,
aged 12, from his bedroom window in London
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Fixing My GazeSusan R. Barry, Ph.D.
2009/2010www.fixingmygaze.comThe Minds
EyeOliver Sacks, M.D., 2010www.oliversacks.com/b
ooks/the-minds-eye
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Patient Case

• 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
• OD 1.00 sph
• OS 5.00 0.50 cx 180

• Uncooperative with patching

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Initial Findings 3/2/05

• 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

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Findings Continued

• Worth 4-dot (cc) Normal Fusion
• Cycloplegia OD 2.00
• OS 6.00 1.50x15
• DFE all structures normal
• Fixation OS central, steady

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Diagnosis?

• Refractive amblyopia OS
• Rx OD 1.00
• OS 5.25 1.25 cx 15
• - Continue with full-time wear
• Discussed CLs, but child averse, and mother
  declines

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Implement Atropine Therapy

• Plan parent to instill i gt 1 atropine OD on
  Friday night.
• Check on Saturday AM to see if pupil OD dilated.
  If not, instill one more drop.
• Come to office Monday to for instruction on home
  VT activities dot-to-dot mazes.

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Progress Evaluation 1

• 4 wk F/U
• VAcc OS D 20/40-3
• Plan continue home therapy and weekend atropine
  instillation OD.

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Progress Evaluation 2

• 8 wk F/U, good compliance with atropine
• VA OS 20/401WL 20/30L
• Stereo Randot 80 seconds of arc
• Plan Continue atropine therapy, adding Jump
  Start computer learning activities

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Progress Evaluation 3

• 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)

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Progress Evaluation 4

• 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

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Progress Evaluation 5

• 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

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Final Progress Evaluation

• 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
• Not concerned about recidivism if Rx used f/t
• Continue to recommend CLs

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VEP (Visual Evoked Potential) www.diopsys.com
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VEP (Visual Evoked Potential) www.diopsys.com
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http//www.diopsys.com/opt-prac-study.php

• 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

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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
• Press LJ. Applied Concepts in Vision Therapy
  2008 (http//oep.excerpo.com/)

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Thank You