ixt cotter denmark 2018 handoutchildhood intermittent exotropia financial disclosures no financial...
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Childhood Intermittent Exotropia
Financial Disclosures
No financial interestin materials or methods discussed herein
Grant Support NIH/NEI: EY011751 & EY022595
Intermittent Exotropia (IXT)
What We Don’t Know
What We
Know
• Most common form of childhood-onset XT • Normal alignment & sensory fusion sometimes• Good stereoacuity at near (generally)• Amblyopia is rare
• Natural history• Best form of treatment
Course Objectives: PEDIG Findings• IXT treatment based on randomized clinical trials� Overminus lenses � Part-time patching� Surgery
• Natural history of IXT based on 3-year observational study• Define / describe outcome measures
What Should We Measure?
Outcome Measure for Studies of IXT?
Magnitude ?Stereoacuity ?
% Time of Alignment
Control of IXT
Outcome Measure for Studies of IXT?
% Time of Alignment or Frequency
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Ways of Assessing Control of IXT
• Patient and parental report• Cover testing–Proportion of time XT is manifest – Speed of recovery - see video
• PEDIG IXT control scale
PEDIG IXT Control Scale
Mohney BG, Holmes JM. Strabismus 2006;14(3):147–150
�
4321
5 Constant XT
XT >50% of time
XT <50% of time
> 5 seconds to recover
1-5 seconds to recover 0 < 1 second to recover
Observationfor
30 seconds
�
No XT unless dissociated 10 sec;
Worst of 3 consecutive 10-sec dissociations
Step 1: 30 sec observation before dissociation at distance
1..2..3..4..5..6..7..8..9..10..11..12..13..14..15..16..17..18..19..20..
21..22..23..24..25..26..27..28..29..30
Spontaneously XT for 10 of 30 seconds (33% of 30 seconds)
Control of XT: Start at Distance PEDIG IXT Control Scale
Mohney BG, Holmes JM. Strabismus 2006;14(3):147–150
�4321
5 Constant XT
XT >50% of time
XT <50% of time
> 5 seconds to recover
1-5 seconds to recover 0 < 1 second to recover
Tropia Observed
�No XT Unless Dissociated
Step 2: Near - 30 second observation before dissociation
1..2..3..4..5..6..7..8..9..10..11..12..13..14..15..16..17..18..19..20..21..22..23..24..25..26..27..28..29..30
No spontaneous tropia at nearControl score must be <3
(so….must dissociate at near)
Control of XT: Near
1..2..3..4..5..6..7..8..9..10
1..2..3..
4NOTE: If recovery >5 seconds for OD, control score = 2
& no further testing needed
Dissociate (occlude) for 10 sec; Uncover & observe recovery 3X: OD, OS, Worst eye
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1..2..3..4..5..6..7..8..9..10
1..2..3..4..5..6
7NOTE: If recovery >5 seconds for OD, control score = 2
& no further testing needed
Dissociate (occlude) for 10 sec; Uncover & observe recovery 3X: OD, OS, Worst eye
Near Control = 2
PEDIG IXT Control Scale
Mohney BG, Holmes JM. Strabismus 2006;14(3):147–150
�
4321
5 Constant XT
XT >50% of time
XT <50% of time
> 5 seconds to recover
1-5 seconds to recover 0 < 1 second to recover
Tropia Observed
�
No XT Unless Dissociated
Distance Control = 3
Near Control = 2
PEDIG IXT Control Scale
Outcome Measure for PEDIG IXT Studies
% Time of Alignment•At present, taking the mean of 3 measures during
exam vs. using a single measure*• Better represents overall control than single
measure*Hatt et al. Am J Ophthalmol 2011;152:872–876.
Cover Testing: Clinical TipTest distance at far can make a difference
Use remote test distance
Divergence Excess XT 3m vs. 6m
Increased angle 5-15Δ 64%
Surgery (yes/no) 32%
Surgical dose different 32%
Kushner & Morton. Ann Ophthalmol 1982;14:86-9.
Samantha: IAXT (50%) 14Δ at 3m; CAXT 25Δ at 50ft
Evidence in Relation to Treatment of Childhood IXT
PEDIG RCT’s
Part-timePatching
OverminusLenses
IXTRCT’s
RCT: Patching vs Observation• 3 to <11 years• 12 to 35 months
Surgical Procedure
RCT: Over-minus vs Observation• 3 to <7 years
RCT: Bil LR Recession vs Unilateral Recess-Resect for Basic IXT• 3 to <11 years
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Effectiveness of part-time patching in reducing risk of deterioration of
IXT over 6 months?
IXT: Part-time Patching Background• Reported benefits� Eliminates suppression � Reduces magnitude +/or frequency� Changes character of deviation
• Commonly prescribed by peds ophthalmology� Varying dosages, duration, outcomes� Retrospective, small samples, no comparison group
Intermittent Exotropia-2 (IXT-2)
RCT’s Comparing Part-time Patching with Observation for
Children with IXT
Cotter S. et al. PEDIG. Ophthalmology 2014;121(12):2299-310 & Mohney B. et al. PEDIG Ophthalmology 2015;122:1718-25.
Study Objective• Determine effectiveness of prescribed part-time patching for
reducing risk of deterioration of IXT over 6 months among children:� 3 to <11 years old� 12 to 35 months old
Major Eligibility Criteria• Age: 3 to < 11 years; 12 months to 35 months• Previously untreated IXT (any type)
� IXT or CXT at distance; & IXT or XP at near
� ≥ 10∆ at distance � ≥ 15∆ at distance +/or near
• Near stereoacuity of 400” (only older cohort)• No amblyopia or amblyopia treatment in last year
• Investigator / child / parent willing forgo all other IXT treatment until deterioration criteria met
Observation(SRx if needed)
Patching3 hours / day
Previously Untreated Children with IXTYounger: 12 to 35 months
Older: 3 to <11 years
6-month Primary Outcome
3-months 3-months
6-month Primary Outcome
IXT-2 Study Overview
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* Masked assessment (Retest ≥10 min IF deterioration) of: - Stereoacuity- XT control (PEDIG office control score)- Ocular alignment
* *1-month wash out; stop patching at 5 months
ObservationRefractive correction if needed
Patching3 hrs/day
RandomizedPreviously Untreated IXT
3-months*
6-month Primary Outcome* *
3-months*
6-month Primary Outcome**
IXT-2 Study OverviewPrimary Outcome: Deterioration by 6 Months
Formal Deterioration Criteria:
• Constant XT ≥10∆ at Dist & Near*
or
• Near stereopsis: drop ≥ 2 octaves from baseline*
*Masked examiner with retest
Preschool Randot Stereoacuity
Baseline Stereoarc sec
Stereo at FU visit to meet
deterioration*
40 200 or worse
60 400 or worse
100 400 or worse
200 800 or worse
400 Nil
Also Considered DeteriorationIf non-protocol treatment started without meeting formal deterioration criteria:
1. And no allowed exceptions2. Even if allowed exceptions of”−Debilitating diplopia −Overwhelming social concern (parent/child)−Failure to keep up with stereo age-norms
Part-Time Patching Results?
3 to <10 year olds
• Difference in proportions = 5.4% • Lower limit of 1-sided exact 95% CI = 2.0%; P = 0.003
Deterioration by 6 Months Was Uncommon
6.0%
Deteriorated
Not Deteriorated
0.6%Observation Patching
6% 0.6%
94% 99.4%
Cotter S. et al. PEDIG. Ophthalmology 2014;121(12):2299-310.
Deterioration by 6 MonthsObservation
(N=165)Patching(N=159)
Number (%) Deteriorated 10 (6.0%) 1 (0.6%)
• Formal deterioration criteria met 7 (4.2%) 1 (0.6%)
Constant XT ≥10∆ D&N 1 (0.6%) ** 0
Stereo worsened ≥ 2 octaves 6 (3.6%) 1 (0.6%)
Both criteria 0 0
• Started treatment against protocol 3 (1.8%) 0
**Had 40 sec RDS on Randot Preschool; protocol-required UCT not performed
3 to <10 Years Small Difference in Deterioration By 6 Months
• Difference in proportions = 5.4% ; Lower limit of 1-sided exact 95% CI = 2.0%; P = 0.003
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Deterioration by 6 MonthsObservation
(N=165)
Patching
(N=159)
Number (%) Deteriorated 10 (6.0%) 1 (0.6%)
• Formal deterioration criteria met 7 (4.2%) 1 (0.6%)
Constant XT ≥10∆ D&N 1 (0.6%) * 0
Stereo worsened ≥ 2 octaves 6 (3.6%) 1 (0.6%)
Both criteria 0 0
• Started treatment against protocol 3 (1.8%) 0
*Had 40 sec RDS on Randot Preschool; protocol-required UCT not performed
• Difference in proportions = 5.4% ; Lower limit of 1-sided exact 95% CI = 2.0%; P = 0.003
3 to <10 Years Only 1 Subject Developed Constant XT
Part-Time Patching 12 to 35 month olds
Results?
Deterioration by 6 Months Observation(N=87)
Patching(N=90)
TOTAL Number (%) Deteriorated 4 (4.6%) 2 (2.2%)• Formal deterioration criteria met 2 (2.3%) 2 (2.2%)
Constant XT ≥10∆ D&N• Started treatment against protocol 2 (2.3%) 0
Difference in proportions = 2.4%1-sided exact 95% CI = -3.8% to +9.4%; P = 0.27
No Difference in Deterioration By 6 Monthsin 12 to 35-Month-Old Children
Mohney B et al. PEDIG. Ophthalmology 2015;122(8):1718-1725 Mohney B et al. PEDIG. Ophthalmology 2015 Aug;122(8):1718-1725
Deterioration by 6 Months Observation(N=87)
Patching(N=90)
TOTAL Number (%) Deteriorated 4 (4.6%) 2 (2.2%)• Formal deterioration criteria met 2 (2.3%) 2 (2.2%)
Constant XT ≥10∆ D&N• Started treatment against protocol 2 (2.3%) 0
Difference in proportions = 2.4%1-sided exact 95% CI = -3.8% to +9.4%; P = 0.27
No Difference in Deterioration By 6 Monthsin 12 to 35-Month-Old Children
Part-time Patching for the Treatment of Childhood IXT
Take Home Message
•Deterioration of IXT over 6 months was uncommon
•3 to <11 yrs: Observation or PT-patching both reasonable management approaches
•12 to 35 mo: Insufficient evidence to recommend PT patching
Cotter S. et al. PEDIG. Ophthalmology 2014;121(12):2299-310 & Mohney B. et al. PEDIG Ophthalmology 2015;122:1718-25.
Overminus Lens Therapy for IXT
What We Don’t Know
What We
Know
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Overminus Lens Therapy for IXT
• Rx more minus (or less plus) than distance refraction•Mechanism?�Magnitude reduced by stimulating A/C�A/C triggers reflex fusional vergence�May allow clear distance vision, facilitating fusion• Stimulation of accommodation by:• Excessive convergence required for fusion (convergence
accommodation)?• Reliance on excessive AC to overcome XT?
Intermittent Exotropia Study 3 (IXT3)
A Pilot Randomized Clinical Trial of Overminus Spectacle Therapy for Intermittent Exotropia
Chen A & PEDIG. Ophthalmology. 2016;123(10):2127-36 .
Assess initial short-term response of IXT to overminus lenses
Intermittent Exotropia Study-3: Study Objective Major Eligibility Criteria
• Age: 3 to <7 years
• IXT
�Distance control score ≥ 2 (mean of 3)
�Near control score ≠ 5 (mean of 3)
�≥ 15∆ exo at distance by PACT
�Near not exceed distance by >10 ∆ (PACT)
• SE between +1.00 D and -6.00 D OD & OS
IXT-3 Study: 3 to < 7 Years
Randomization
Overminus GroupSpectacles with full CR plus 2.50D overminus
Enrollment
Observation GroupNon-overminus spectacles
or no spectacles
2-week Phone Call from Site
8-Week Primary Outcome Exam (Masked Exam)
Control assessed 3 times
throughout a single exam
Baseline XT Control at Distance
42%
23%
35%
44%
22%
33%
0%
10%
20%
30%
40%
50%
60%
0 to <1 1 to <2 2 to <3 3 to <4 4 to 5
Observation (N=31) Mean = 3.2Overminus (N=27) Mean = 3.2
N/A N/APerc
enta
ge o
f Pa
tient
s
Control Score
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8
35%
29%
19%
10%6%
26%
44%
19%
7%4%
0%
10 %
20 %
30 %
40 %
50 %
0 to <1 1 to <2 2 to <3 3 to <4 4 to 5
Perc
enta
ge o
f Pat
ient
s
Observation (N=31) Mean = 1.5Overminus (N=27) Mean = 1.3
Baseline XT Control at Near
43
Over-Minus LensesResults?
Overminus Group Had Better Mean Distance Control at 8 Weeks
45
0
1
2
3
4
5
2.8 points
2.0 points
Mea
n 8-
wee
k Dist
ance
Con
trol
Difference = -0.80 (-1.49 to -0.11)P = 0.01 for one-sided test
Observation Over-minus Chen A & PEDIG. Ophthalmology. 2016;123(10):2127-36. 3.2
Overminus Lenses for 3 to <7 Year Old Children With IXT
Take Home Message
Chen A & PEDIG. Ophthalmology. 2016;123(10):2127-36 .
Improved distance control at 8 weeks
Larger & longer RCT needed to assess effectiveness of overminus lenses
on and off treatment
Currently Recruiting
Intermittent Exotropia Study 5 (IXT-5)
RCT of Overminus Spectacle Therapy for IXT
Currently Recruiting:12 months on treatment, then wean off treatment
Overminus Lens Tx: Cotter Clinical Impressions• Patient profile�Age?�Accommodative function?�AC/A ratio? (Basic or DE; not CI)
• Determination of overminus power?�Decrease in IXT magnitude?�Decrease in IXT frequency? Look for improvement in this--
-�What if results in eso at near? Rx a bifocal
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Overminus Lens Therapy• Length of treatment? • Parental education – very important• Myopia progression: no evidence of this yet� Retrospective chart reviews
*Group Initial RE Change After 5 Y Change After 10 YControl (62) 0.00 ± 1.40 -1.40 ± 2.00 -2.41 ± 2.20
6-mo Tx (74) 0.00 ± 1.50 -1.52 ± 1.80 -2.34 ± 2.405-yr Tx (34) -0.10 ± 1.50 -1.54 ± 1.90 -2.36 ± 2.10
*Kushner BJ. Arch Ophthalmol 1999. 117:638-642; Rutstein RP et al. OVS 1989; 66:487-491
Natural History of IXT in Children?
For Example: Surgery - Balance of Possibilities
ü Improvement of social concerns
ü Possibility of improving distance &
retaining near stereoacuity
Pros Cons
ü Possibility of spontaneous improvement
ü Surgical complications & high rate of
reoperations
ü Possibility of loss of stereoacuity through surgical overcorrection*
*21% overcorrection 6-mo post-surgery;
Buck et al. BMC Ophthalmology 2012
IXT-2 Study OverviewRandomized
3-Months
12, 18, 24, 30 month FU Visits 36 months: Natural History Outcome
Observation: No Treatment
6-Month Outcome for RCT
Patching
3-Months
12, 18, 24, 30 month FU Visits36 months - Study Completed
6-Month Primary Outcome -RCT
Masked Examinations•Ocular alignment• Stereoacuity•XT control
Natural History of IXT in Young Children
Objective
PEDIG. Unpublished data
Deterioration of IXT Over 3-Year Period in Children with Untreated IXT Ages
3 to 10 Years Old
Baseline IXT Characteristics
§ 183 children randomized to observation
§ 83% completed the study
§ Mean age = 6.1 years
§ 63% female; 61% white
§ 40-60 arc sec stereo at near: 62%
§ Type of IXT: 69% basic exo; 21% pseudo-DE
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Baseline: Character of the Exodeviation
5%
95%
Distance Deviation Type Near Deviation Type1%
70%
27%
2%
Constantexotrop iaIntermittentexotrop iaExophoria
Noexodeviation
Calculates cumulative probability of motor deterioration by 3 yrs
Primary Analysis: Kaplan-Meier Survival Analysis
• Dichotomous outcome: deteriorated or not deteriorated� Once deteriorated, always deteriorated
• Subjects lost to follow up: contribute to analysis for time in study� If deteriorated before lost, counted when deterioration occurred
� If not deteriorated before lost, “censored” at last study visit; credit for time
not deteriorated• Subjects who started treatment w/o meeting motor deterioration:
“censored” at that visit
Primary Outcome - Deterioration by 3 Years
§ Unpublished data presented§ Abstract available
§ Cotter SA, Mohney BG, Chandler DL, Holmes JM, Petersen DB, Kraker RT, Wallace DK, for the Pediatric Eye Disease Investigator Group. Natural history of childhood intermittent exotropia over a 3-year period. Investigative Ophthalmology and Visual Science 2016 57: E-abstract 984.
Natural History of IXT in Young Children
Objective
PEDIG. Unpublished data
Deterioration of IXT Over 3-Year Period in Children with Untreated IXT Ages
12 to 35-Month Old Childrern
Natural History of IXT in Young Children
PEDIG. Unpublished data
Deterioration of IXT Over 3-Year Period in Children with Untreated IXT Ages
12 to 35-Month Old Children
Unpublished dataAbstract found at: Cotter SA, Mohney B, Chandler D, Holmes J, Wallace D, Crouch E, Kraker R, SupersteinR, Paysse E for the Pediatric Eye Disease Investigator Group. Development of Constant Exotropia Over 3 Years in Children 12 to 35-Month-Old with Untreated IXT. Optometry and Vision Science 2016; 93: E-abstract 160026.
A Randomized Trial Comparing Bilateral Lateral Rectus Recession
versus Unilateral Recession-Resection for Basic Type IXT
PEDIG. Unpublished data
Intermittent Exotropia Study 1 (IXT-1)
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Study Objective•Determine long term effectiveness of BLRc (bilateral lateral rectus recession) vs. R/R (unilateral lateral rectus recession with medial rectus resection) for treatment of basictype and pseudo-DE type IXT
Table 2: Surgical Dose* Bilateral Lateral Rectus Recession (BLRc) Angle of Largest Deviation
by PACT Amount to Recess Each Lateral Rectus (LR)*
16 PD 4.0 mm 18 PD 5.0 mm 20 PD 5.0 mm 25 PD 6.0 mm 30 PD 7.0 mm 35 PD 7.5 mm 40 PD 8.0 mm 45 PD 8.5 mm 50 PD 9.0 mm
Unilateral Lateral Rectus Recession with Medial Rectus Resection (R&R):
Angle of Largest Deviation
by PACT Amount to Recess
Lateral Rectus (LR)* Amount to Resect
Medial Rectus (MR)** 16 PD 4.0 mm 3.0 mm 18 PD 5.0 mm 4.0 mm 20 PD 5.0 mm 4.0 mm 25 PD 6.0 mm 5.0 mm 30 PD 7.0 mm 5.5 mm 35 PD 7.5 mm 6.0 mm 40 PD 8.0 mm 6.5 mm 45 PD 8.5 mm 6.5 mm 50 PD 9.0 mm 7.0 mm
•Suboptimal surgical outcome criteria (exotropia, constant ET or stereo loss) met at ANY visit
OR
•Reoperation without meeting suboptimal surgical outcome criteria
Primary Outcome Suboptimal Surgical Outcome BY 3 Years
Suboptimal Surgical Outcome
BY 3 Years (Primary Outcome)
PEDIG. Unpublished data
To be published soon
Abstract found at:
Chen AM, Cotter SA, Chandler DL, Holmes JM, Donahue SP, on behalf of PEDIG.
“A Randomized Trial Comparing Bilateral Lateral Rectus Recession versus
Unilateral Recess-Resect for Basic Type Intermittent Exotropia.”
Optometry and Vision Science 2017; 93: E-abstract 175227
Treatments for IXT•Monitor; watchful waitingü Part-time patchingü Over-minus lenses• BI Prism• Vision therapyü Surgery
Non-surgical
Thank You
Susan [email protected]