Download Mean Change in Visual Acuity * 2 - Jaeb Center for Health Research

Factors Associated with Changes
in Visual Acuity and OCT Thickness
at 1 Year after Treatment for
Diabetic Macular Edema
Sponsored by the National Eye Institute,
National Institutes of Health, U.S. Department of Health and Human Services
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Laser-Ranibizumab-Triamcinolone Randomized
Clinical Trial for DME: Mean Change in Visual Acuity*
11
10
Sham+prompt
laser
9
Letters Improved
8
Ranibizumab+
prompt laser
7
6
Ranibizumab+
deferred laser
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4
Triamcinolone
+prompt laser
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2
1
0
0
4
8 12 16 20 24 28 32 36 40 44 48 52 56 60 64 68 72 76 80 84 88 92 96 100 104
weeks
that were ±30 letters were assigned a value of 30
P-values for difference in mean change in visual acuity from sham+prompt laser at the 52-week visit: ranibizumab+prompt
laser <0.001; ranibizumab+deferred laser <0.001; and triamcinolone+prompt laser=0.31.
* Values
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Purpose
 To identify factors associated with improvement
of visual acuity, and those associated with
improvement in OCT CSF at 1 year in the
ranibizumab treated eyes
 Because 1-year outcomes were similar, data
from the two ranibizumab arms in the trial (361
eyes) were pooled for this analysis
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Statistical Methods: Model 1
Poisson regression models adjusted for
baseline* were used to evaluate the association
of 37 assorted baseline factors:
 Demographic
 Clinical
 OCT
 Fundus photographic variables
with visual acuity/OCT CSF improvement
from baseline to 1 year
*Vision analyses adjusted for baseline VA; OCT analyses adjusted for baseline CSF
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Statistical Methods: Model 2
OCT improvement at various time points
and VA at 1 year was evaluated to explore
the impact of anatomic changes during
ranibizumab treatment on the visual
outcome at 1 year.
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Methods: Factors Evaluated in Model 2
Included Select Follow-up Variables
OCT CSF improvement*
• Improved at all times (4, 8, and 12 months) : “early
and consistent”
• Improved at 4 month but not sustained at both 8
and 12 month: “early but inconsistent”
• Not improved at 4 month but improved at 8 and/or
12 month: “late bloomers”
• Not improved at any time (4, 8, and 12 months):
“never/evers”
*improvement of ≥20% reduction in CSF vs. baseline
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Methods: Factors Evaluated
Model 1 and Model 2
Participant Characteristics at Baseline
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Race/Ethnicity
Gender
Diabetes type
Diabetes duration
Age
Insulin use
Mean arterial blood pressure*
HbA1c*
* obtained on exam
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Methods: Factors Evaluated
Model 1 and Model 2
Participant Characteristics obtained by
History at Baseline (continued)
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Hypertension
Elevated cholesterol
Cardiovascular disease
Renal disease
Neurologic disease
Prescribed glitazones
Prescribed statins
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Methods: Factors Evaluated
Model 1 and Model 2
Historical Ocular Characteristics present at
Baseline
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Prior DME treatment
Timing of most recent prior DME treatment
Prior laser for DME
Timing of prior laser for DME
Prior PRP
Timing of prior PRP
Timing of prior cataract extraction
History of YAG capsulotomy
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Methods: Factors Evaluated
Model 1 and Model 2
Baseline Ocular Characteristics on exam:
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Visual acuity
Visual acuity in non-study eye
Lens status
Diabetic Retinopathy Severity on clinical exam
(investigator assessment)
 Type of DME on clinical exam (investigator
assessment)
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Methods: Factors Evaluated
Model 1 and Model 2
Baseline OCT Characteristics per
Reading Center
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Central subfield thickness
Retinal volume
Cystoid abnormalities
Subretinal fluid
Vitreoretinal abnormalities
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Methods: Factors Evaluated
Model 1 and Model 2
Baseline Ocular Characteristics
provided by Photograph Reading Center
 Diabetic Retinopathy Severity Level
 Hemorrhages/Microaneurysms severity in
macular grid
 Hard exudates
 Surface wrinkling retinopathy
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Outcome Measures at 1 Year
Model 1 and Model 2
Visual Acuity:
 Continuous outcome: VA change from baseline
 Binary outcomes
• ≥10 letter improvement
• ≥15 letter improvement
• ≥ 20/32 (restricted to eyes < 20/32 at baseline)
OCT:
 Continuous outcome: CSF change from baseline
 Binary outcomes
• 20% or more reduction in CSF
• 50% or more reduction in CSF
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• CSF < 250 and decrease of ≥ 25 µm from baseline
Results of
Multivariate Model 1
for Vision or CSF Change
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Median Change in VA (Letter Score)
from Baseline
Baseline Characteristics Associated with
1 Year Visual Acuity Change
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13
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10
10
8
8
7
6
6
4
2
0
Baseline Visual Acuity*
P<.001
*p < .001
Age**
** p<.01
Surface Wrinkling Retinopathy*
*p < .001
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Association between Baseline CSF and
1 Yr Change in CSF
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Baseline Factors Associated
with CSF Change
(continuous variable)
Baseline OCT CSF (P < 0.001)
• For every 100 µm thicker baseline
OCT CSF, 1 year CSF decreased an
additional 70 µm on average
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Baseline Factors Associated with
Binary CSF Outcomes
Thicker baseline OCT CSF was associated with
20% or 50% reduction in thickness (P < 0.001)
No baseline factors were associated with
CSF < 250 and decrease of ≥ 25 µm from
baseline
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Results of
Multivariate Model 2
for Vision or CSF Change
(Includes Select Ocular Factors
During Follow -Up)
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Relationship between CSF Improvement
During Follow-up and Vision Outcome
(p<0.001)
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Baseline or Select Follow-up Factors
Associated with
Visual Acuity Change
(continuous variable)
Baseline Visual Acuity (P < 0.001)
• Similar magnitude to model 1
CSF improvement during follow-up
(P < 0.001)
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Factors Associated with
VA Binary Outcomes
Model 1 and Model 2
Baseline visual acuity (P < 0.001)
• Lower (worse) levels of initial VA more
likely to improve at least 10 or 15 letters
• Higher (better) levels of initial VA more
likely to achieve 20/32 or better
• VA of >20/32 at 1-year was achieved by 76% of
eyes with ≥ 66 letters at baseline compared to
38% of eyes with < 66 letters
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Summary
Baseline visual acuity was the only consistent
baseline predictor of 1 year vision outcomes
Baseline CSF was the only consistent baseline
predictor of 1 year CSF outcomes
Results may be due to ceiling and floor effects
of these variables
 Highlights importance of noting baseline values
of cohort to understand magnitude of vision and
OCT outcomes
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Summary
CSF improvement prior to 1 year was also
associated with 1 year vision outcomes
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Thank you!
Susan B. Bressler
Haijing Qin
The Diabetic Retinopathy Clinical
Research Network
• Subjects
• Investigators
• Staff
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