The Diabetic Retinopathy Clinical Research Network 5-Year Follow-up of a Randomized Trial Evaluating Ranibizumab Plus Prompt versus Deferred Laser for.

The Diabetic Retinopathy Clinical Research Network


5-Year Follow-up of a Randomized Trial Evaluating Ranibizumab Plus Prompt versus Deferred Laser for

Diabetic Macular Edema

Background: Protocol IBackground: Protocol IPreviously reported intravitreous ranibizumab

with prompt or deferred laser more effective through at least 2 years compared with laser

3-year comparison of ranibizumab groups concluded prompt laser was no better and possibly worse than deferred laser

Study extended to 5 years to assess longer-term course of DME treated with ranibizumab

To report the comparison of ranibizumab groups through 5 years

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3

Completion of 5 Year VisitCompletion of 5 Year Visit

Ranibizumab+ Prompt Laser

Ranibizumab + Deferred Laser

Eyes originally randomized N = 180 N = 181Completed 5 Year (excl deaths) 69% (76%) 61% (74%)

Death prior to 5 Year 9% 17%Discontinued/Dropped prior to 5 YearIncludes pts who did not consent to extension

21% 22%

Eyes in the extension study N = 132 N = 136Completed 5 Year (excl deaths) 94% (97%) 82% (92%)

Death prior to 5 Year 3% 11%

Dropped prior to 5 Year 3% 7%

Ranibizumab

+ prompt laserRanibizumab

+ deferred laser

CompletersNon-

completers CompletersNon-

completers

N = 124 N = 56 N = 111 N = 70

Median Age 63 65 63 65

Prior PRP 33% 11% 21% 20%

Lens Status Phakic 73% 61% 75% 63%

Median VA (letter score) 65 65 67 62

Median CST (µm) 375 372 394 378

Mild/Moderate/HR PDR 34% 27% 24% 37% 4

Baseline Characteristics of Completers vs Non-Completers

Baseline Characteristics of Completers vs Non-Completers

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Visits Prior to 5 Year*Visits Prior to 5 Year*

Ranibizumab+ Prompt

LaserN=124

Ranibizumab + Deferred

LaserN=111

Median # of visits in year 1 13 13





Median # of visits prior to 5 year visit 38 40

* Only eyes that completed 5 year visit

TreatmentsTreatments

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7

Injections Prior to 5 Year*Injections Prior to 5 Year*

*Only eyes that completed 5 year visit

Ranibizumab+ Prompt

LaserN=124


LaserN=111

Median # of injections in year 1 8 9





Median # of injections prior to 5 year visit 13 17

% of eyes that received >1 injection in year 4 46% 55%% of eyes that received >1 injection in year 5 38% 48%

8

Focal/Grid Laser Prior to 5 Years*Focal/Grid Laser Prior to 5 Years*

Ranibizumab+ Prompt

LaserN = 124


LaserN = 111

% of eyes that did NOT receive laser treatments prior to the 5 year visit

0 56%

Median # laser treatments prior to the 5 year visit 3 0

* Only eyes that completed 5 year visit

Visual AcuityVisual Acuity

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Mean Change in Visual Acuity* at Follow-up Visits

Mean Change in Visual Acuity* at Follow-up Visits

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+7.2

+9.8

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Change in Visual Acuity at 5 YearsChange in Visual Acuity at 5 Years

Change in Visual Acuity (letters)

Ranibizumab+ PromptLaser N = 124


Laser N = 111

Estimated Means* +7.2 +9.8Estimated Diff*(95% CI)*[P-Value]*[adjusted P-Value]†

-2.6 (-5.5 to +0.4)

[P = 0.09] [P = 0.15]

*truncated to ± 30 letters, based on longitudinal analyses adjusting for baseline VA†Additional adjustment for potential confounders (baseline lens status, CSF, DR severity, prior PRP, age)

Distribution of VA Change at 5 YearsDistribution of VA Change at 5 Years

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Change in Visual Acuity (letters)

Ranibizumab+ PromptN = 124


N = 111>15 letter gain 27% 38%

RR (95%CI)P value

1.47 (1.04, 2.09)0.03

>10 letter gain 46% 58%

RR (95%CI)P value

1.27 (1.01, 1.60)0.04

>15 letter loss 6% 5%

RR (95%CI)P value

0.96 (0.34, 2.72)0.94

>10 letter loss 9% 8%

RR (95%CI)P value

0.91 (0.40, 2.10)0.83

Change in VA Over 5 Years Stratified by Baseline VA

Change in VA Over 5 Years Stratified by Baseline VA

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• Test for interaction at 5 Year time point: P = 0.001• Test for interaction from longitudinal model: P = 0.004

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Percent of Eyes with VA 20/40 (Letter Score 69) or Better

Percent of Eyes with VA 20/40 (Letter Score 69) or Better

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Percent of Eyes with VA 20/200 (Letter score 38) or Worse

Percent of Eyes with VA 20/200 (Letter score 38) or Worse

Retinal ThickeningRetinal Thickening

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Mean Change in CSF Thickeningat Follow-up Visits

Mean Change in CSF Thickeningat Follow-up Visits

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Change in Retinal Thickness at 5 Years*Change in Retinal Thickness at 5 Years*

*Based on a longitudinal model adjusting for baseline CSF and VA†Additional adjustment for potential confounders (baseline lens status, DR severity, prior PRP, age)

Ranibizumab+

PromptLaser N = 124

Ranibizumab +

DeferredLaser N = 111

Estimated Mean change* -167 -165

Estimated Difference* (95% CI)[P-Value][adjusted P-Value]†

-8 (-30 to +15)[P = 0.48][P = 0.53]

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Reduced VA and Thickened at 5 Years

Reduced VA and Thickened at 5 Years

Ranibizumab+ PromptLaser N = 124


Laser N = 111

VA 20/32 or worse and

CSF >250 µm 23% 24%

EndophthalmitisEndophthalmitis

Ranibizumab + Prompt Laser

treatment

Ranibizumab + Deferred Laser

treatment

N = 187 eyes N = 188 eyesNumber (%) cases 1 (1%) 2 (1%)

N=2557 injections N=3176 injectionsRate per injection 0.04% 0.06%

20N’s include ALL randomized eyes

SummarySummary

VA gain at 1 year was maintained to 5 years concomitant with diminishing need for treatment over time

Adding laser at initiation of ranibizumab was no better than deferring laser at least 24 weeks

Deferring laser may be associated with more VA gain through 5 years, especially in eyes with worse VA at baseline

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SummarySummary

Over half assigned to deferral never received laser through 5 years

Eyes assigned to prompt laser needed fewer injections over 5 years

Few eyes in either group had substantial VA loss About 1/3 still thickened more work to be done

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ConclusionsConclusions Differences in VA may be real, in particular for

eyes with worse baseline VA, but deferral may require more injections over 5 years to achieve results seen in this report, and thus may entail greater costs (cost effectiveness analysis is beyond scope of study)

Results apply to patients similar to those enrolled in this trial and following same retreatment criteria.

Eyes initiating ranibizumab (with prompt or deferred laser) can maintain vision gains obtained by first year through 5 years with minimal treatment after 3 years 25



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The Diabetic Retinopathy Clinical Research Network 5-Year Follow-up of a Randomized Trial Evaluating Ranibizumab Plus Prompt versus Deferred Laser for.

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