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By James Hoekel OD FAAO
 St. Louis Children’s Hospital Eye Center
Washington University School of Medicine
   None
   Amblyopia treatment

    ◦ Eliminate the obstacle to vision (i.e.
      cataract etc)

    ◦ Correct refractive error

    ◦ Force the poorer eye by limiting use of
      the better eye
Full time vs Part time occlusion
   google.images for amblyopia therapy
   Gold std for amblyopia Tx
                   Adhesives work best
                     Costly
                     Some skin irritation
                     Alternative use- felt patch
                     Easier to peak in non
                      adhesive patch
                     Always use specs if
google.images         significant Rx
                     Occasionally covered by
                      insurance
                     Use of splints and restraints?
   Why isn’t patching successful?
        Compliance?

   How to enhance compliance?
   Why are children not
    compliant?
        social stigma
        skin irritation
        just don’t like it
        sensory abnormality

   Awan et al report compliance
    rates of 58 and 41% when
    patching rx for 3hr or 6hr.



                                     google.images
   Used daily to weekly
   Better with hyperopes
   Nearly ineffective in
    myopic children
   Blurs to about 20/120
   Often tolerated better
    than patching
   Works best to remove
    any plus in glasses




                             google.images
Penalization Pearls

•Best  used for those with patching
failure

•Hyperopes



•Old   enough to watch sound eye
                                            vistakon
•Maybe less regression when stopping
treatment
   Reduce or eliminate
    necessary refractive
    power to blur the
    sound eye
   Mostly used in
    hyperopia
   Works synergistically
    with atropine
   Very effective in high
    ametropia
   Occlusive contact
                    lens
                   Often used as final
                    means of treatment
                   Costly, risks of
                    infection to sound
                    eye, easy to rub out
                   Able to custom make
                    any base curve or
                    diameter


google.images
   Bangerter filter
    ◦ Degrades image
     May allow child
       binocularity
     Improved tolerance
       over complete
       occlusion
     Unfortunately, many
       look over specs in liu
       of using specs



        coopereyecare
   Part time occlusion is labor
    intensive
   Constant monitoring is
    sometimes required
   Two parents working; who is
    monitoring PTO compliance?
   Refractive surgery may benefit
    children with spectacle non-
    compliance
   Currently WUSM is one of only a
    few centers in North America
    offering pediatic refractive
    surgery for amblyopia
   In office and home
    based therapy
   Utilized for
    improvements of
    amblyopia
   Met with some
    debate yet merits
   Few pediatric specialists in North America offer this
    treatment in children
   Multiple challenges include fixation, discomfort, long term
    changes, testing, compliance
   Able to treat refractive error in children intolerant to
    glasses and contact lenses
   Neurobehavioral abnormalities create increased challenges
   14 month old with
    eye misaligment X4 -
    6 mos
   Left eye goes to the
    nose
   FFM OD FFU OS
   30 LET
   Cycloplegic refraction
    reveals
   +3.50 OD and +5.00
    OS

                             volunteer model
You have access to
Spatial Sweep
 VEP, Flash
 VEP, Pattern
 VEP,Multifocal
 ERG,Traditional ERG
 Cardiff, OKN, Plus
 Optix, EOG, OKN
 recording, OKN
 tracing, HRT and      google.images

 Pupillography
 recording
Follow Up? Treatment
 ?
   Full cycloplegic RX
   6 week follow up
   PTO 50% of
    waking hours
   Spec wear
    recommend full
    time (>80%)
   +3.50 OD and
    +5.00 OS
   Wears specs fairly
    well
   Patching 5 hours per
    day
   10 PD LET
   Tx option now?
   Wears specs fairly
    well
   Patching 5 hours per
    day
   10 PD LET
   Tx option now?
   Reduce PTO to 2 hrs
    day and follow up 3
    months
   FFM OD and OS
   NO Longer
    crossing
   Patching 3 hrs a
    day
   Clinical Follow up
    demonstrates
    good alignment
    and tracking
                         Washington University School of
                             Medicine and Barnes Jewish
                                                Hospital
   So D/C PTO and
    order SSVEP
   (is VA better with
    grating charts
    than letter charts?)




                           google.images for amblyopia
                                               therapy
   SSVEP reveals 20/50 and 20/85
   Regression noted
   Treated with 2 hours a day PTO and 4
    month follow up
   20/20 and
    20/25++
   9/9 circles
    (Titmus)
   Wears+2.50,+3.7
    5
   Still esotropic sin
    Rx
Patch 2 hrs a day or Atropine


  Not
Resolved
                     Improved           Not Improved            Switch
                                                               Treatment




      Amblyopia                   Good
       Resolved                 Compliance               Poor
                                                       Compliance
                                 Increase
                                INTENSITY
      +/- Taper
      then D/C
                                Not Improved
                                  (residual
                                 amblyopia)                  Consider
       Not Improved                                         final push
   Spectacles are widely accepted form of
    amblyopia treatment
   Visual acuity improves in some amblyopic
    children
   This improvement in vision is now referred
    to as refractive adaptation; PEDIG refers to
    this as ‘optical treatment’
   Most ECP Rx glasses then follow up VA after
    few months of spec wear (PEDIG 18 weeks)



                          google.images for amblyopia
                                              therapy
   7y/o wm referred
    because he often
    closes one eye
   UCVA 20/20 and
    20/160
   +fly and orthophoria
   (no refractive ET)
   Cycloplegic refraction
    is +1.00 and +6.00 -
    0.75 X 063 20/160++
   Tx options: ?????

                             Patients evidence of patching
   Specs rx -1D over
    cyclo
   PTO: 2 hours OD
   4 month f/u VA
    ◦   20/50+
    ◦   Continue as previous
    ◦   4 mo later 20/40+
    ◦   4 mo later 20/30-
    ◦   4 mo later 20/30+
    ◦   Pt cuts PTO 20/40+2



                               Happily shows his work!
NAVP Treatment of Amblyopia
Eligibility
 Age 10 to <18 years
 Amblyopic eye acuity of 20/40 to 20/160

Treatment
 >2 hours daily patching
 At least one hour of near activities during
  patching
Outcome: Visual acuity after two months of
 treatment
Results:   Visual acuity improved >2 lines in 18
 (27%)
            of 66 patients
   PEDIG ATS studies
    include:
   6 hours vs full
    time for severe
    (20/100 to
    20/400)
   Or in older
    children 2 to 6
    hours per day
    +Atropine + near
                        google.images for amblyopia
                                            therapy
   CLs are well tolerated in anisometropia
   More equal retinal image sizes
   Improved binocularity and stereopsis
   Improved compliance if sound eye has refractive
    error
   Infants with high amounts of
    anisometropia require contact lenses to
    reduce risk of dense amblyopia
   CJ Roberts study shows successful use of
    CL for 6 diopters of myopic aniso
    improved 3-4 lines. Not as successful in
    >10 diopters of anisometropia.
    Improvement in VA w/in 6 months
   Occasionally sound eye is reduced
   Mostly at risk if child is very young
   Skin irritation is typically temporary
   Cholinergic side effects of A1%
   Hypothetical increase in UV rays (A1%)
   Decreased academics (?) due to reading
    dysfunction or struggles associated with
    reading through amblyopic eye
   PEDIG ATS 3
    ◦   Children 7-18 yo
    ◦   Optical correction alone
    ◦   Optical correction plus patching
    ◦   And Daily A1% <12 yo
    ◦   53% improved at least 2 lines
    ◦   47% of 13-17 yo improved if no
        prior tx
   Isoametropia        Diopters
    ◦ Astigmatism       >2.50 D
    ◦ Hyperopia         >5.00 D
    ◦ Myopia            >8.00 D
    Anisometropia
    ◦ Astigmatism       >1.50 D
    ◦ Hyperopia         >1.00 D
    ◦ Myopia            >3.00 D




                    google.images for amblyopia
                                        therapy
   Animals with early onset
    amblyopia have
    predominately
    monocular connections
   Cytochrome oxidase
    highlights metabolic
    activity in ocular
    dominance columns
    which is reduced in
    amblyopia




                               google.images for amblyopia
                                                   therapy
   Mosaic of ocular
    dominance columns
    in striate cortex
    revealed by
    processing the tissue
    for cytochrome
    oxidase in a patient
    who lost sight in one
    eye prior to his death




                             Jonathan horton’s lab pub at ucsf
   Many children left with 20/30 or worse
   Regression is common in >40% of amblyopic
    treatments
   Prescribe Polycarbonate lenses
   Caution with soft contact lenses
    ◦ Especially extended wear
   Probably two-thirds of
    amblyopes are purely
    refractive and probably one
    third are associated with
    microtropia
   Microtropia likely results in
    poorer vision at the time of
    presentation
   Does anisometropia create
    loss of bifoveal fixation or
    does loss of foveal fixation
    cause the secondary
    amblyopia?
   Factors thought to affect treatment outcomes
    ◦ Compliance: significant role in outcome
    ◦ Age at commencement of treatment
    ◦ Density of the amblyopia
       Severity of vision loss at time of presentation
       Specs or CLs and 2-3 hours of daily patching
        should solve a great deal of amblyopic needs
       If specs or contact lenses fail then consider
        non traditional treatments



                               google.images for amblyopia
                                                   therapy
   Horton, J. Stryker, M. Amblyopia induced by anisometropia without shrinkage of
    ocular dominance columns in human striate cortex. Proc. Natl. Acad. Sci. USA Vol.
    90. p. 594-5498, June 1993 Neurobiology
   Braverman, R. Diagnosis and treatment of refractive errors in the pediatric
    population. Current Opinion in Ophthalmology Vol 18 (5) September 2007. 379-
    383.
   Steinman, S. Steinman, B. Garzia, R. Foundations of Binocular Vision: A Clinical
    Perspective. 2000 McGraw Hill Publishing
   Pediatric Eye Disease Investigational Group (2005) Randomized trial of treatment of
    amblyopia in children aged 7-17 years. Arch Ophthalmol 123: 437-447.
   Donahue, S. The Relationship between anisometropia, patient, age, and the
    development of amblyopia. Trans Am Ophthalmol Soc 2005; 103:313-336.
   Pediatric Eye Disease Investigator Group. A randomized trial of patching regimens
    for treatment of severe amblyopia in children. Ophthalmology 2003; 110:2075-
    87.
   Pediatric Eye Disease Investigator Group. Randomized trial of treatment of
    amblyopia in children aged 7 to 17 years. Arch Ophthalmol 2005; 123:437-47.
   Sakatani, K. Jabbur, N. O’Brien, T. Improvement in best corrected visual acuity in
    amblyopic adult eyes after laser in situ keratomileusis. J Cataract Refract Surg
    2004; 30:2517-2521.
   Wallace, D. ( 2009)Pediatric Ophthalmology: Current
    Thought and a Practical Guide. Springer. M. Edward
    Wilson ed. Pp33-46.
   Awan M, Proudlock FA, Gottlob I (2005) A
    randomized controlled trial of unilateral strabismic
    and mixed amblyopia using occlusion dose monitors
    to record compliance. Invest Ophthal Vis Sci 46:
    1435-1439.

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NAVP Treatment of Amblyopia

  • 1. By James Hoekel OD FAAO St. Louis Children’s Hospital Eye Center Washington University School of Medicine
  • 2. None
  • 3. Amblyopia treatment ◦ Eliminate the obstacle to vision (i.e. cataract etc) ◦ Correct refractive error ◦ Force the poorer eye by limiting use of the better eye
  • 4. Full time vs Part time occlusion google.images for amblyopia therapy
  • 5. Gold std for amblyopia Tx  Adhesives work best  Costly  Some skin irritation  Alternative use- felt patch  Easier to peak in non adhesive patch  Always use specs if google.images significant Rx  Occasionally covered by insurance  Use of splints and restraints?
  • 6. Why isn’t patching successful?  Compliance?  How to enhance compliance?  Why are children not compliant?  social stigma  skin irritation  just don’t like it  sensory abnormality   Awan et al report compliance rates of 58 and 41% when patching rx for 3hr or 6hr. google.images
  • 7. Used daily to weekly  Better with hyperopes  Nearly ineffective in myopic children  Blurs to about 20/120  Often tolerated better than patching  Works best to remove any plus in glasses google.images
  • 8. Penalization Pearls •Best used for those with patching failure •Hyperopes •Old enough to watch sound eye vistakon •Maybe less regression when stopping treatment
  • 9. Reduce or eliminate necessary refractive power to blur the sound eye  Mostly used in hyperopia  Works synergistically with atropine  Very effective in high ametropia
  • 10. Occlusive contact lens  Often used as final means of treatment  Costly, risks of infection to sound eye, easy to rub out  Able to custom make any base curve or diameter google.images
  • 11. Bangerter filter ◦ Degrades image May allow child binocularity Improved tolerance over complete occlusion Unfortunately, many look over specs in liu of using specs coopereyecare
  • 12. Part time occlusion is labor intensive  Constant monitoring is sometimes required  Two parents working; who is monitoring PTO compliance?  Refractive surgery may benefit children with spectacle non- compliance  Currently WUSM is one of only a few centers in North America offering pediatic refractive surgery for amblyopia
  • 13. In office and home based therapy  Utilized for improvements of amblyopia  Met with some debate yet merits
  • 14. Few pediatric specialists in North America offer this treatment in children  Multiple challenges include fixation, discomfort, long term changes, testing, compliance  Able to treat refractive error in children intolerant to glasses and contact lenses  Neurobehavioral abnormalities create increased challenges
  • 15. 14 month old with eye misaligment X4 - 6 mos  Left eye goes to the nose  FFM OD FFU OS  30 LET  Cycloplegic refraction reveals  +3.50 OD and +5.00 OS volunteer model
  • 16. You have access to Spatial Sweep VEP, Flash VEP, Pattern VEP,Multifocal ERG,Traditional ERG Cardiff, OKN, Plus Optix, EOG, OKN recording, OKN tracing, HRT and google.images Pupillography recording Follow Up? Treatment ?
  • 17. Full cycloplegic RX  6 week follow up  PTO 50% of waking hours  Spec wear recommend full time (>80%)  +3.50 OD and +5.00 OS
  • 18. Wears specs fairly well  Patching 5 hours per day  10 PD LET  Tx option now?
  • 19. Wears specs fairly well  Patching 5 hours per day  10 PD LET  Tx option now?  Reduce PTO to 2 hrs day and follow up 3 months
  • 20. FFM OD and OS  NO Longer crossing  Patching 3 hrs a day  Clinical Follow up demonstrates good alignment and tracking Washington University School of Medicine and Barnes Jewish Hospital
  • 21. So D/C PTO and order SSVEP  (is VA better with grating charts than letter charts?) google.images for amblyopia therapy
  • 22. SSVEP reveals 20/50 and 20/85  Regression noted  Treated with 2 hours a day PTO and 4 month follow up
  • 23. 20/20 and 20/25++  9/9 circles (Titmus)  Wears+2.50,+3.7 5  Still esotropic sin Rx
  • 24. Patch 2 hrs a day or Atropine Not Resolved Improved Not Improved Switch Treatment Amblyopia Good Resolved Compliance Poor Compliance Increase INTENSITY +/- Taper then D/C Not Improved (residual amblyopia) Consider Not Improved final push
  • 25. Spectacles are widely accepted form of amblyopia treatment  Visual acuity improves in some amblyopic children  This improvement in vision is now referred to as refractive adaptation; PEDIG refers to this as ‘optical treatment’  Most ECP Rx glasses then follow up VA after few months of spec wear (PEDIG 18 weeks) google.images for amblyopia therapy
  • 26. 7y/o wm referred because he often closes one eye  UCVA 20/20 and 20/160  +fly and orthophoria  (no refractive ET)  Cycloplegic refraction is +1.00 and +6.00 - 0.75 X 063 20/160++  Tx options: ????? Patients evidence of patching
  • 27. Specs rx -1D over cyclo  PTO: 2 hours OD  4 month f/u VA ◦ 20/50+ ◦ Continue as previous ◦ 4 mo later 20/40+ ◦ 4 mo later 20/30- ◦ 4 mo later 20/30+ ◦ Pt cuts PTO 20/40+2 Happily shows his work!
  • 29. Eligibility  Age 10 to <18 years  Amblyopic eye acuity of 20/40 to 20/160 Treatment  >2 hours daily patching  At least one hour of near activities during patching Outcome: Visual acuity after two months of treatment Results: Visual acuity improved >2 lines in 18 (27%) of 66 patients
  • 30. PEDIG ATS studies include:  6 hours vs full time for severe (20/100 to 20/400)  Or in older children 2 to 6 hours per day +Atropine + near google.images for amblyopia therapy
  • 31. CLs are well tolerated in anisometropia  More equal retinal image sizes  Improved binocularity and stereopsis  Improved compliance if sound eye has refractive error
  • 32. Infants with high amounts of anisometropia require contact lenses to reduce risk of dense amblyopia  CJ Roberts study shows successful use of CL for 6 diopters of myopic aniso improved 3-4 lines. Not as successful in >10 diopters of anisometropia. Improvement in VA w/in 6 months
  • 33. Occasionally sound eye is reduced  Mostly at risk if child is very young  Skin irritation is typically temporary  Cholinergic side effects of A1%  Hypothetical increase in UV rays (A1%)  Decreased academics (?) due to reading dysfunction or struggles associated with reading through amblyopic eye
  • 34. PEDIG ATS 3 ◦ Children 7-18 yo ◦ Optical correction alone ◦ Optical correction plus patching ◦ And Daily A1% <12 yo ◦ 53% improved at least 2 lines ◦ 47% of 13-17 yo improved if no prior tx
  • 35. Isoametropia Diopters ◦ Astigmatism >2.50 D ◦ Hyperopia >5.00 D ◦ Myopia >8.00 D Anisometropia ◦ Astigmatism >1.50 D ◦ Hyperopia >1.00 D ◦ Myopia >3.00 D google.images for amblyopia therapy
  • 36. Animals with early onset amblyopia have predominately monocular connections  Cytochrome oxidase highlights metabolic activity in ocular dominance columns which is reduced in amblyopia google.images for amblyopia therapy
  • 37. Mosaic of ocular dominance columns in striate cortex revealed by processing the tissue for cytochrome oxidase in a patient who lost sight in one eye prior to his death Jonathan horton’s lab pub at ucsf
  • 38. Many children left with 20/30 or worse  Regression is common in >40% of amblyopic treatments  Prescribe Polycarbonate lenses  Caution with soft contact lenses ◦ Especially extended wear
  • 39. Probably two-thirds of amblyopes are purely refractive and probably one third are associated with microtropia  Microtropia likely results in poorer vision at the time of presentation  Does anisometropia create loss of bifoveal fixation or does loss of foveal fixation cause the secondary amblyopia?
  • 40. Factors thought to affect treatment outcomes ◦ Compliance: significant role in outcome ◦ Age at commencement of treatment ◦ Density of the amblyopia  Severity of vision loss at time of presentation  Specs or CLs and 2-3 hours of daily patching should solve a great deal of amblyopic needs  If specs or contact lenses fail then consider non traditional treatments google.images for amblyopia therapy
  • 41. Horton, J. Stryker, M. Amblyopia induced by anisometropia without shrinkage of ocular dominance columns in human striate cortex. Proc. Natl. Acad. Sci. USA Vol. 90. p. 594-5498, June 1993 Neurobiology  Braverman, R. Diagnosis and treatment of refractive errors in the pediatric population. Current Opinion in Ophthalmology Vol 18 (5) September 2007. 379- 383.  Steinman, S. Steinman, B. Garzia, R. Foundations of Binocular Vision: A Clinical Perspective. 2000 McGraw Hill Publishing  Pediatric Eye Disease Investigational Group (2005) Randomized trial of treatment of amblyopia in children aged 7-17 years. Arch Ophthalmol 123: 437-447.  Donahue, S. The Relationship between anisometropia, patient, age, and the development of amblyopia. Trans Am Ophthalmol Soc 2005; 103:313-336.  Pediatric Eye Disease Investigator Group. A randomized trial of patching regimens for treatment of severe amblyopia in children. Ophthalmology 2003; 110:2075- 87.  Pediatric Eye Disease Investigator Group. Randomized trial of treatment of amblyopia in children aged 7 to 17 years. Arch Ophthalmol 2005; 123:437-47.  Sakatani, K. Jabbur, N. O’Brien, T. Improvement in best corrected visual acuity in amblyopic adult eyes after laser in situ keratomileusis. J Cataract Refract Surg 2004; 30:2517-2521.
  • 42. Wallace, D. ( 2009)Pediatric Ophthalmology: Current Thought and a Practical Guide. Springer. M. Edward Wilson ed. Pp33-46.  Awan M, Proudlock FA, Gottlob I (2005) A randomized controlled trial of unilateral strabismic and mixed amblyopia using occlusion dose monitors to record compliance. Invest Ophthal Vis Sci 46: 1435-1439.

Editor's Notes

  1. Oto et al reported non compliance rate of 47% with patching programs
  2. Inconspicuous in some children and frighteningly obvious in others.Generally well tolerated
  3. In our office this language translates as discontinue part time occlusion and order spatial sweep visual evoked potential. Some believe due to motor control component, gratings are redundant and so make less demands on gaze control. Some severe amblyopes like those of congenital cataracts may have a difficult time holding steady vision
  4. Pattern of ocular dominance columns along the medial face of the right human occipital lobe. The dashed line
  5. Figure 20: Mosaic of ocular dominance columns in striate cortex revealed by processing the tissue for cytochromeoxidase in a patient who lost sight in one eye prior to his death. The image above shows the actual tissue montage; the image below is a sketch of the columns. Note the partial reconstruction of dark and pale cytochromeoxidase stripes in V2. BS = blind spot; MC = monocular crescent.We have examined the ocular dominance columns in a patient with strabismic amblyopia and in a patient with anisometropic amblyopia (see: Horton JC &amp; Stryker MP, Anisometropia induces amblyopia without shrinkage of ocular dominance columns in human striate cortex. Proc. Natl Acad. Sci, 90:5494-5498, 1993 and Horton JC &amp; Hocking DR, Pattern of ocular dominance columns in human striate cortex in strabismic amblyopia. Visual Neuroscience, 13:787-795, 1996). Neither case showed evidence of shrinkage of the amblyopic eye’s ocular dominance columns. From these findings, we conclude that amblyopia is not always associated with reduction in the size of ocular dominance columns. It is possible that when amblyopia begins at a later age it is not accompanied by a change in the dimensions of ocular dominance columns. Presumably abnormalities in intracortical wiring, yet to be revealed, are responsible for amblyopia in these cases.From our studies, it is apparent that many anatomical features of the macaque visual cortex are also present in the human visual cortex. Their similarity gives us confidence that our research findings in the macaque are applicable to the human. This is gratifying, because our ultimate goal is to understand how the human visual system functions. Continuing studies in the macaque, therefore, will allow us to make further advances in understanding the human visual system. In turn, human studies will continue to help shape our experiments in the macaque.