1. 1 Evidence Based Treatment of Amblyopia in 2005 What we have learnt from the Pediatric Eye Disease Investigator Group [PEDIG] Lionel Kowal

2. 2 Amblyopia is the most common cause of monocular visual impairment in children. Existing data on the treatment of amblyopia largely retrospective / uncontrolled. Rationale for PEDIG Amblyopia Studies

3. 3 PEDIG : Network of community & university- based ophthalmologists and optometrists A Randomized Trial of Atropine Versus Patching for Treatment of Moderate Amblyopia in Children - ATS 1 A Randomized Trial Comparing Part-time Versus Full-time Patching for Severe Amblyopia - ATS 2A A Randomized Trial Comparing Part-time Versus Minimal- time Patching for Moderate Amblyopia - ATS 2B Prospective Study of Recidivism After Cessation of Amblyopia Treatment - ATS 2C An Evaluation of Treatment of Amblyopia in Children 7-<18 Years Old – ATS3 A Randomized Trial of Atropine Regimens for Treatment of Moderate Amblyopia in Children – ATS4

4. ATS14 Amblyopia Treatment Study ATS 1 A Randomized Trial of Atropine Versus Patching for Treatment of Moderate Amblyopia in Children The Pediatric Eye Disease Investigator Group. A randomized trial of atropine vs patching for treatment of moderate pamblyopia Archives of Ophthalmology 2002;120:268-278

5. ATS15 To compare patching and atropine as treatments for moderate amblyopia in children 3 to <7 years old To develop estimates of the success rates of treatment To identify factors that may be associated with successful treatment Objectives

6. ATS16 A randomized, controlled single-masked multi-center clinical trial 2 treatment groups Primary outcome: VA @ 6 mo Treatment after 6 mo: investigator discretion Patching Atropine Study Design

7. ATS17 Eligibility Able to measure VA with single surrounded HOTV Strabismic and/or anisometropic amblyopia Visual Acuity: –Amblyopic eye: 6/12 to 6/30 –Sound eye: 6/12 or better –3 lines or more interocular difference < 2 mo of amblyopia therapy in prior 2 y

8. ATS18 Electronic Visual Acuity Tester 20/40020/20020/10020/5020/25 Holmes, JM, Beck, RW, et al The Amblyopia Treatment Study Visual Acuity Testing Protocol Archives of Ophthalmology 2001:119;1345-1353.

9. ATS19 Patching Treatment Initial –6 h/d up to all waking hours at investigator’s discretion Subsequent (@ 17 w) –If <6/9 and <3 line improvement, increase up to all or all but one waking hours –If >6/9 or >3 line improvement, investigator could decrease patching to a minimum of 1 h/d

10. ATS110 Atropine Treatment Initial –1 drop atropine 1% daily in sound eye Subsequent (@ 17 w) –If <6/9 and <3 line improvement, replace hypermetropic lens of sound eye with plano –If >6/9 or >3 line improvement, investigator could decrease atropine to 2/w

11. ATS111 Amblyopia Treatment Index Questionnaire of 18 items, each scored from 1 to 5, with 5 representing the most difficult Three subscales measured  adverse effects of treatment  difficulties with compliance  social stigma of treatment Items are summed to create each subscale score, then scaled to a common range The Pediatric Eye Disease Investigator Group Impact of Patching and Atropine Treatment on the Child and Family in the Amblyopia Treatment Study Archives of Ophthalmology 2003:121;1625-1632

12. ATS112 Patient Characteristics Female47% Caucasian83% African American5% Hispanic6% Asian2% Mixed2% Other2% N=419

13. ATS113 <3 y2% 3 to <4 y15% 4 to <5 y 20% 5 to <6 y33% 6 to <7 y30% Mean Age5.3 y Age n=419

14. ATS114 Strabismus38% Anisometropia37% Combined-mechanism24% Cause of Amblyopia n=419 Prior Treatment 26% received previous treatment for amblyopia

15. ATS115 Patient Follow Up Patching Group 215 Atropine Group 204 6 Month Exam Completed 208 (97%) Patients Randomized 419 6 Month Exam Completed 194 (95%) 2 Year Exam Completed 176 (86%) 2 Year Exam Completed 187 (87%)

16. ATS116 Patching Group: Number of Hours of Patching Prescribed 6 hours 8 hours 10 hours >=12 hours At Enrollment 6-7 hours 8-9 hours >=12 hours Maximum 10-11 hours The number of hours prescribed at baseline was the maximum for 80% of patients

17. ATS117 Atropine Group All patients prescribed one drop of 1% atropine daily A plano spectacle lens was prescribed for the sound eye during follow up for 56 /194 patients

18. ATS118 Amblyopic Eye Acuity at 6 Months PatchingAtropine (N=208) (N=194) Mean improvement from 3.16 lines 2.84 lines baseline Mean acuity at 6 months 6/9 6/9 -2 (Snellen approximation) >6/9 or >3 line improvement from baseline 79% 74%

19. ATS119 Amblyopic Eye at 6 Months Amblyopic Eye Visual Acuity Cumulative Distribution 6-month Amblyopic Eye Visual Acuity >20/16>20/20>20/25>20/32>20/40>20/50>20/63>20/80>20/100>20/125>20/160 N=208 N=194

20. ATS120 Amblyopic Eye Mean Acuity at Each Visit 20/20 20/25 20/30 20/40 20/50 20/60 20/80 20/60 - 20/40 20/30 - 20/30 20/50 + 20/40 + 20/30 -2 5 wks6 mos0 wks16 wks

21. ATS121 Treatment Effect in Subgroups at 6 Months Effect of treatment was similar in subgroups based on: Age: – 5 years old Cause of amblyopia: –strabismus, anisometropia, combined Baseline visual acuity in amblyopic eye –20/80 to 20/100, 20/40 to 20/60

22. ATS122 Effect of Treatment on Sound Eye at 6 Months A decrease in visual acuity of 1 or more lines at 6 months:  patching - 17 patients (8%)  atropine - 47 patients (23%) Some cases were due to improper refractive correction In other cases there likely was residual cycloplegia from atropine not having been discontinued

23. ATS123 Ocular Side Effects Any ocular side effect26% Types of ocular side effects Lid/conjunctival irritation 4% Light sensitivity 18% Eye pain/headache 2% Other 2% Facial Flushing 2% Systemic Side Effects 3% * Reported at any visit in first 6 months Atropine Side Effects* N=208

24. ATS124 Skin Irritation Mild 41% Moderate/Severe 6% * Reported at any visit in first 6 months Patching Side Effects* N=215

25. ATS125 Amblyopia Treatment Index Both treatments were well tolerated All 3 subscale scores were consistently worse in the patching group Median Score SubscalePatchingAtropine Adverse Effects 2.25 2.00 Difficulty with Compliance 2.20 1.80 Social Stigma 3.00 2.00

26. ATS126 Amblyopic Eye Acuity at 2 Years PatchingAtropine (N=188) (N=179) Mean improvement from 3.7 lines 3.6 lines baseline Mean acuity at 2 years 20/32 +2 20/32 +1 (Snellen approximation) >20/32 or >3 line improvement from baseline 86% 84% Two-year follow-up of a 6-month randomized trial of atropine vs patching for treatment of moderate amblyopia in children. Arch Ophthalmol. 2005 Feb;123(2):149-57.

27. ATS127 Amblyopic Eye at 2 Years Amblyopic Eye Visual Acuity Cumulative Distribution 6-month Amblyopic Eye Visual Acuity >20/16>20/20>20/25>20/32>20/40>20/50>20/63>20/80>20/100>20/125>20/160 N=188 N=176

28. ATS128 Summary There was substantial improvement in amblyopic eye visual acuity with both treatments Improvement was more rapid in the patching group The difference between groups in amblyopic eye acuity at six months was small (about a third of a line) There was no difference between groups in amblyopic eye acuity after 2 years

29. ATS229 Amblyopia Treatment Study ATS 2A, 2B, 2C AN EVALUATION OF PATCHING REGIMENS

30. ATS230 Patching is most commonly prescribed. However, controversy exists concerning how much treatment is necessary. Most data on the response according to the daily dosage of patching are retrospective and uncontrolled. There is no standard of care once initial treatment of amblyopia is completed. Rationale

31. ATS231 Randomized Trials Patching 2 hours versus 6 hours daily for moderate amblyopia (20/40 to 20/80) Patching 6 hours versus full-time for severe amblyopia (20/100 to 20/400)

32. ATS232 Eligibility Age < 7 years Able to measure visual acuity with single surrounded HOTV optotypes Strabismic and/or anisometropic amblyopia Visual acuity: –Amblyopic eye: 20/40 to 20/400 –Sound eye: 20/40 or better –3 lines or more interocular difference No more than 2 months of amblyopia therapy in prior 2 years

33. ATS233 Severe Amblyopia Trial 20/100-20/400 Moderate Amblyopia Trial 20/40-20/80 Randomize Full-time patching all or all but 1 hr per day Part-time patching 6 hrs per day Part-time patching 6 hrs per day Minimal-time patching 2 hrs per day Visit A: 5 ± 1 week Visual acuity testing both eyes Ocular alignment assessment Amblyopia Treatment Index Visit B: 17 ± 1 week Visual acuity testing (masked) both eyes Ocular alignment assessment Stereoacuity Testing Study Design

34. ATS234 Treatment Protocol Severe amblyopia: 6 hours of patching Full time patching Moderate amblyopia: 2 hours of patching 6 hours of patching All treatment groups were prescribed at least 1 hour of near activities while patching. Investigator - Patching decreased to no less than 7 hours per week Investigator - Patching could be continued, reduced, or stopped

35. ATS2B35 Results ATS 2B 2 vs. 6 hours of patching for moderate amblyopia (20/40 – 20/80) The Pediatric Eye Disease Investigator Group A Randomized Trial of Patching Regimens for Treatment of Moderate Amblyopia in Children Archives Of Ophthalmology 121:2003;603-611

36. ATS2B36 Patient Characteristics N=189 Female44% Caucasian85% Age (mean)5.2 years Cause of Amblyopia Strabismus40% Anisometropia33% Combined27% Prior Amblyopia Treatment14%

37. ATS2B37 Patient Follow Up 2 Hour Group n=95 6 Hour Group n=94 Patients Randomized N=189 4-MONTH MASKED EXAM Completed n=92 (97%) Completed n=89 (95%)

38. ATS2B38 Amblyopic Eye Acuity at 4 Months 2 Hours Patching N=92 6 Hours Patching N=89 Mean improvement from baseline 2.4 lines Mean acuity at 4 months (Snellen approximation) 20/32 -2 >20/32 or >3 line improvement from baseline 62%

39. ATS2B39 Amblyopic Eye Mean Acuity at Each Visit 20/32 20/40 20/50 20/63 20/80 20/63 + Mean Visual Acuity Score 2 Hours N=95 6 Hours N=94 Baseline 20/40 + 2 Hours N=87 6 Hours N=85 5 Weeks 20/32 -2 2 Hours N=92 6 Hours N=89 4 Months

40. ATS2B40 Amblyopia Treatment Index Both treatments were well tolerated. The subscale scores were similar between the groups on the adverse event and treatment compliance subscales. On the social stigma subscale, which includes questions related to the patch making the child feel different, the 6- hour group was worse. Median Score Subscale2 Hours6 Hours Adverse Effects 2.13 2.13 Difficulty with Compliance 2.33 2.33 Social Stigma 2.67 3.00

41. ATS2B41 Summary 2 vs. 6 hours for moderate amblyopia Amblyopia improved with both patching regimens, when combined with prescribing 1 hour of near activities There was no demonstrable advantage to the greater number of hours either in the rapidity or magnitude of improvement after 4 months of treatment

42. ATS2B42 Summary - Adverse Effects We found no indication that 6 hours of patching compared with 2 hours of patching was associated with a higher rate of adverse effects on the sound eye acuity New heterotropias were rare

43. ATS2B43 Conclusions When combined with prescribing 1 hour of near activities, 2 hours of daily patching appears to be as effective as 6 hours of daily patching in treating moderate amblyopia in children 3 to < 7 years of age A shorter duration of patching may ease the implementation of patching therapy and monitoring compliance for some parents

44. ATS2A44 Results ATS 2A 6 hours vs. full time patching for severe amblyopia (20/100 – 20/400) The Pediatric Eye Disease Investigator Group A Randomized Trial of Prescribed Patching Regimens for Treatment of Severe Amblyopia in Children Ophthalmology 2003:11;2075-2087

45. ATS2A45 Patient Characteristics N= 175 Female46% Caucasian83% Age (mean)4.8 years Cause of Amblyopia Strabismus27% Anisometropia34% Combined38% Prior Amblyopia Treatment14%

46. ATS2A46 Patient Follow Up 6 Hour Group n=85 Full-time Group n=90 Patients Randomized N=175 4-MONTH MASKED EXAM Completed n=73 (86%) Completed n=84 (93%)

47. ATS2A47 Amblyopic Eye Acuity at 4 Months 6 Hours Patching N=73 Full-time Patching N=84 Mean improvement from baseline 4.8 lines4.7 lines Mean acuity at 4 months (Snellen approximation) 20/5020/50 -2

48. ATS2A48 Amblyopic Eye Mean Acuity at Each Visit 20/160 20/200 20/125 20/063 20/080 20/100 20/250 20/050 20/040 Mean Visual Acuity Score Full- time N=90 Six- hrs N=85 Baseline Exam 20/16020/160 +1 Full- time N=77 Six- hrs N=75 Five-week Exam 20/63 -2 Full- time N=84 Six- hrs N=73 Four-month Exam 20/50 20/50 -2

49. ATS2A49 Treatment Effect in Subgroups at 4 Months Effect of treatment was similar in subgroups based on: Age: – 5 years old Cause of amblyopia: –strabismus, anisometropia, combined Baseline visual acuity in amblyopic eye –20/100 to 20/160, 20/200 to 20/400

50. ATS2A50 Amblyopia Treatment Index Both treatments were well tolerated The subscale scores were similar between the groups on the adverse event, treatment compliance, and social stigma subscale subscales Median Score Subscale6 HoursFull-Time Adverse Effects 2.25 2.50 Difficulty with Compliance 2.33 2.42 Social Stigma 3.00 3.00

51. ATS2A51 Summary 6 hrs vs. full-time for severe amblyopia Amblyopia improved with both prescribed patching regimens, when combined with prescribing 1 hour of near activities Compared to 6-hour patching, there was no demonstrable advantage to full-time patching in the rapidity or the magnitude of improvement after 4 months of treatment

52. 52 Amblyopia Recurrence ATS 2C Prospective observational study 156 children with successfully treated amblyopia – ready to stop treatment Treatment STOPPED at enrollment Risk of amblyopia recurrence after cessation of treatment. J AAPOS. 2004 Oct;8(5):420-8.

53. 53 Previous Rx Enrollment 156 children 5w 13w 26w 52w Study period – off treatment Study Design Treatment STOPPED

54. 54 Recurrence overall during 1-year follow-up Recurrence ( 2 logMAR - Confirmed by repeat testing) 21% (95% CI 14% to 28%) Alternative Definition – Non replicated 2 logMAR VA No recurrence All recurrences - 24% (95% CI 17% to 32%) 21% 3%

55. 55 Timing of the 35 recurrences Pts Weeks 14 (40%) 10 (29%) 5 (14%) 6 (17%)

56. 56 Patching vs Atropine Patching Stopped (77% pts) Atropine Stopped (23% pts) 25% Recurrence (95% CI 17% to 34%) 21% Recurrence (95% CI 7% to 35%)

57. 57 Patching hours stopped Patching hours stopped at enrollment Recurrence 15% 18% 43% 43% P=0.008

58. 58 Conclusions of Amblyopia Recurrence Study ¼ of successfully amblyopic children experience a recurrence over 1 year of f/u Recurrence risk is similar for stopping patching and atropine Most recurrences occur within 3 months – early follow-up is critical – but long term follow-up is also important If 6 or more hours of patching stopped – recurrence risk is lower if patching is reduced to 2 hours per day before cessation – suggests “weaning” is beneficial

59. ATS359 An Evaluation of Treatment of Amblyopia in Children 7-<18 Years Old – ATS3 Supported by the National Eye Institute

60. ATS3PS60 PEDIG Pilot Study 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 A prospective, pilot study of treatment of amblyopia in children 10 to <18 years old. Am J Ophthalmol. 2004:137;581-583.

61. ATS361 To determine the response rate to amblyopia treatment in children from 7 to <18 years To determine the frequency of recidivism of successfully-treated amblyopia in children 7 to <18 years Objectives

62. ATS362 Eligibility Age 7 years to <18 years Amblyopia associated with strabismus, anisometropia, or both Best corrected visual acuity in the amblyopic eye 20/40 to 20/400 Best corrected visual acuity in the sound eye 20/25 or better No myopia in amblyopic eye >-6.00 D spherical equivalent No amblyopia treatment (other than spectacles) in the past month and no more than one month of amblyopia treatment in the last 6 months

63. ATS363 Randomized, controlled multi-center clinical trial Sample size: >360 children (>90 in each of 4 age groups) Treatment groups: Control Group: Optical correction only Active Group: Optical correction Patching plus near activities Atropine (patients <13 yrs only) Primary analysis: Comparison of proportion of treatment responders between treatment groups Study Design

64. ATS364 Enrollment Prescription of spectacles Randomization (within 30 days of enrollment) Visual acuity testing in new spectacles Randomized Trial Follow Up Post-randomized Trial Follow Up Observation Phase Follow Up Treatment is discontinued End of Study Nonresponders Responders Active GroupControl Group Study Flow

65. ATS365 Enrollment/Randomization Screening/Enrollment Visit: Patients are prescribed new spectacles (if needed) Randomization Visit (within 1 month): New spectacles are placed on patient for the first time Visual acuity is tested using E-ETDRS protocol, which yields a letter score Patient is randomized as long as visual acuity still meets eligibility criteria

66. ATS366 Treatment Groups Patients are randomized to one of the following treatment groups: Control Group: Optical correction only Active Treatment Group: Optical correction Patching 2-6 hours daily At least 1 hour of near activities daily during patching Atropine 1% one drop daily (pts <13 yrs only)

67. ATS367 Randomized Trial Follow Up Follow-up visits occur every 6 weeks up to 24 weeks Visual acuity is tested with the E-ETDRS protocol Using the best of two measured amblyopic eye visual acuities, the patient is classified as a responder, nonresponder or neither When the patient meets criteria for either responder or non-responder and this is confirmed by masked exam, the randomized trial is over

68. ATS368 Responder/Nonresponder Criteria Responder Criteria: 10 letter (2 line) or more improvement in amblyopic eye acuity compared with acuity at randomization Nonresponder Criteria: minimal improvement that is visit specific, but less than 10 letters by 24 weeks

69. ATS369 Post-Randomized Trial Nonresponders: –End study follow up –Control group patients may start on active treatment outside study Responders: –Continue assigned treatment until no further improvement –Once improvement has stopped: Control Group patients end study, but may start on active treatment outside study Active Treatment Group patients discontinue treatment and enter the Observation Phase

70. ATS370 Observation Phase Visits occur at 13 wks, 26 weeks, and 52 weeks after treatment discontinuation Visual acuity is assessed at each visit Recurrence: acuity 10 or more letters worse than acuity at treatment discontinuation

71. 71 RESULTS 507 patients 49 sites –1 to 33 patients/per site

72. 72 Patient Characteristics 7 < 13 YRS N=404 (%) TREATMENT (N = 201)OPTICAL CORRECTION (N = 203) AGE9.8 (1.6)9.5 (1.7) FEMALE89 (44)87 (43) NO PRIOR TREATMENT96 (48)99 (49) CAUSE OF AMBLYOPIA Strabismus52 (26) Anisometropia75 (38)81 (41) Combined73 (37)66 (33) ACUITY IN AMBLYOPIC EYE 20/200 - 40016 (8)18 (9) 20/100 – 16044 (22)48 (24) 20/40 – 80141 (70)137 (67)

73. 73 Patient Characteristics 13 < 18 YRS N=103 (%) TREATMENT (N = 55)OPTICAL CORRECTION (N = 48) AGE14.7 (1.4)14.9 (1.2) FEMALE31 (56)25 (52) NO PRIOR TREATMENT36 (65)33 (69) CAUSE OF AMBLYOPIA Strabismus11 (20)14 (29) Anisometropia20 (36)17 (35) Combined24 (44)17 (35) ACUITY IN AMBLYOPIC EYE 20/200 - 4002 (4)3 (6) 20/100 – 16020 (36)16 (33) 20/40 – 8033 (60)29 (60)

74. 74 Responder Rate 7 < 13 YRS TREATMENT (N = 201)OPTICAL CORRECTION (N = 203) TOTAL106 (53)50 (25) AMBLYOPIA LEVEL 20/40 – 80 (N 141/137)70 (50)30 (22) 20/100-400 (N 60/66)36 (60)20 (30) PRIOR AMBLYOPIA TREATMENT Yes (N 105/104)42 (40)14 (13) No (N 96/99)64 (67)36 (36) N (%) * All Statistically Different

75. 75 Responder Rate 13 < 18 YRS TREATMENT (N = 55)OPTICAL CORRECTION (N = 48) TOTAL14 (25)11 (23) AMBLYOPIA LEVEL 20/40 – 80 (N 33/29)7 (21)6 (21) 20/100-400 (N 22/19)7 (32)5 (26) PRIOR AMBLYOPIA TREATMENT Yes (N 38/28)6 (16)7 (25) No (N 17/20) *8 (47) *4 (20) * N (%) * Suggestive of Difference

76. 76 Conclusions Amblyopic vision improves with optical correction alone in about ¼ of all 7 to 17 Year Olds and ½ of 7 to 12 years olds with additional treatment. Amblyopic vision improves in 7 to < 13 year old children but not 13 to < 18 year olds who have been treated previously. All amblyopic eyes have remaining visual deficit. Persistence of effect after treatment cessation is unknown.

77. 77 Amblyopia Treatment Study 4 (ATS4) A Randomized Trial of Atropine Regimens for Treatment of Moderate Amblyopia in Children

78. 78 Study Objectives To compare daily versus weekend atropine (two- days) for moderate amblyopia (20/40 to 20/80) in children 3 to <7 years old To determine the maximum amount of improvement that could be achieved with these atropine schedules.

79. 79 Study Design A randomized, controlled, single-masked multi- center clinical trial 2 treatment groups: Primary outcome: Visual acuity at 4 months Secondary outcome: Maximum visual acuity improvement daily atropine weekend atropine

80. 80 Eligibility Age < 7 years Able to measure visual acuity with single surrounded HOTV optotypes Strabismic and/or anisometropic amblyopia No amblyopia treatment in the past month and no more than 1 month of amblyopia treatment in the past six months

81. 81 Eligibility Visual Acuity Amblyopic eye - 20/40 to 20/80 Sound eye - > 20/40 Inter-eye acuity difference - > 3 lines

82. 82 Atropine Treatment weekend or daily atropine 1% solution was prescribed For patients in the daily atropine group, if the amblyopic eye acuity improved to be the same as or better than the sound eye acuity, atropine could be decreased to no less than twice per week

83. 83 Visit Schedule 5-week visit Masked outcome visit at 4 months –Amblyopic eye at 17 weeks, sound eye and binocularity at 19 weeks Additional visits at investigator discretion Partial responders returned every 8 weeks

84. 84 Patient Characteristics N=168 Female39% Caucasian79% Age (mean)5.3 years Cause of Amblyopia Strabismus33% Anisometropia41% Combined23% Prior Amblyopia Treatment18%

85. 85 Patient Follow-Up Weekend Group n=85 Daily Group n=83 Patients Randomized N=168 4-MONTH MASKED EXAM Completed n=83 (98%) Completed n=77 (93%)

86. 86 Amblyopic Eye at 4 Months Weekend atropine N=83 Daily atropine N=77 Mean improvement from baseline 2.3 lines Mean acuity at 4 months (Snellen approximation) 20/32 -1 >20/32 or >3 line improvement from baseline 66%

87. 87 Amblyopic Eye at 4 Months Amblyopic Eye Visual Acuity Cumulative Distribution 4-month Amblyopic Eye Visual Acuity >20/16>20/20>20/25>20/32>20/40>20/50>20/63>20/80>20/100>20/125>20/160 N=92 N=89 N=77 N=83

88. 88 5 Weeks 20/40 +1 20/40 Amblyopic Eye Mean Acuity at Each Visit 20/32 20/40 20/50 20/63 Mean Visual Acuity Score Daily N=83 Weekend N=85 Baseline Daily N=78 Weekend N=81 Daily N=77 Weekend N=83 20/63 +2 4 Months 20/32 -1

89. 89 Acuity at Study Completion 20/25 or better OR equal to sound eye –Daily - 39 (47%) –Weekend - 45 (53%) Mean Amblyopic eye acuity –Daily – 0.23 logMAR (20/32 -3 ) 2.3 lines of improvement –Weekend – 0.21 log MAR (20/32 -1 ) 2.5 lines of improvement

90. 90 Treatment Effect in Subgroups Effect of treatment was similar in subgroups based on: Age: – 5 years old Cause of amblyopia: –strabismus, anisometropia, combined Baseline visual acuity in amblyopic eye – 20/50

91. 91 Effect of Treatment on the Sound Eye A decrease in sound eye visual acuity of 2 or more lines at 4 months:  Weekend atropine - 2 patients (2.4%)  Daily atropine - 2 patients (2.6%) Further Follow-up Testing: One in each group same as or better than baseline One in each group 20/32 compared with 20/20 at baseline

92. 92 Other adverse effects Light sensitivity (no treatment changes) –Daily group – 13 (16%) –Weekend group – 25 (29%) Facial flushing / fever –2 patients in daily group – 1 stayed on treatment and 1 switched to homatropine

93. 93 Ocular alignment 2 in daily and none in weekend developed > 8  deviation 2 in daily, 3 in weekend had disappearance of a microstrabismus 10% developed new strabismus or a preexisting angle of strabismus that had increased by at least 10  8% had their strabismus resolved or reduced by at least 10 

94. 94 Amblyopia Treatment Index Both treatments were well tolerated. The subscale scores were similar between the groups on the adverse event and social stigma subscales. On the compliance subscale the weekend group was slightly worse. Median Score SubscaleWeekendDaily Adverse Effects 2.00 2.00 Difficulty with Compliance 2.10 2.00 Social Stigma 2.00 2.00

95. 95 Conclusions Weekend atropine appears to be as effective as daily atropine in treating moderate amblyopia in children 3 to < 7 years of age A reduced frequency is another alternative treatment for amblyopia. The magnitude of the visual acuity improvement was similar to that seen for 2- hour and 6-hour prescribed patching regimens for moderate amblyopia.