October 2006

CComplications ofomplications ofAAge-related Macular ge-related Macular Degeneration Degeneration PPreventionreventionTTrialrial

Sponsored by the National Eye InstituteSponsored by the National Eye Institute

CComplications ofomplications ofAAge-related Macular ge-related Macular Degeneration Degeneration PPreventionreventionTTrialrial

Sponsored by the National Eye InstituteSponsored by the National Eye Institute

October 2006

Study QuestionStudy Question Study QuestionStudy Question

Can low-intensity Can low-intensity macular laser macular laser treatment reduce treatment reduce the incidence of the incidence of vision loss in vision loss in eyes with large eyes with large drusendrusen??

October 2006

Design SummaryDesign SummaryDesign SummaryDesign Summary

Major Eligibility Criteria – > 10 large drusen

(>125) in each eye– Visual acuity

>20/40 in each eye– Age > 50 years– No other ocular

disease

October 2006

Design SummaryDesign Summary

Randomization SchemeRandomization Scheme

CAPT Eligible PatientCAPT Eligible Patient

Randomization of eyesRandomization of eyes

One EyeTreated

One EyeObserved

5Initial Treatment (1500-2500 µ)

Barely visible burns60 burns15 burns/quadrant 100 µ burns0.1 second1500-2500 µ

2500 µ 1500 µ

6

October 2006

Design SummaryDesign Summary Design SummaryDesign Summary

• Sample Size: 1052 people Sample Size: 1052 people

2104 eyes2104 eyes

Length of Follow-Up: Length of Follow-Up: ≥≥5 years 5 years

October 2006

Design SummaryDesign Summary Design SummaryDesign Summary

Outcome Measures Outcome Measures PrimaryPrimary

Change in visual acuityChange in visual acuity SecondarySecondary

Incidence of Advanced AMD Incidence of Advanced AMD (CNV, GA, SPED)(CNV, GA, SPED)

Contrast thresholdContrast thresholdReading (critical print size)Reading (critical print size)Side effects of treatmentSide effects of treatment

October 2006

Description of Follow-upDescription of Follow-up Description of Follow-upDescription of Follow-up

• Overall missed visits:Overall missed visits: 3%3%

• 87% of the 1052 patients 87% of the 1052 patients completed the 5-year examinationcompleted the 5-year examination

9% patient deaths9% patient deaths

4% missed the 5-year exam4% missed the 5-year exam

October 2006

Percentage of Eyes with 50% Percentage of Eyes with 50% Reduction of Baseline Drusen by Reduction of Baseline Drusen by

Treatment GroupTreatment Group

19%

34% 37%41% 42%

46%

1% 3%9%

16%

25%

31%36%

14%

0%

10%

20%

30%

40%

50%

60%

70%

80%

90%

100%

6 12 24 36 48 60 72

Months of Follow-up

Treated

Observed

October 2006

Percentage of Eyes with Visual Percentage of Eyes with Visual Acuity Loss of Three Acuity Loss of Three LinesLines or or

MoreMore

3%5%

10%

15%

21%

24%

2% 3%

6%

13%

16%

21%

24%

2%

0%

10%

20%

30%

6 12 24 36 48 60 72

Months of Follow-up

Treated

Observed

October 2006

Incidence of AdvancedIncidence of Advanced Age-related Macular Age-related Macular

DegenerationDegeneration

0%

5%

10%

15%

20%

25%

30%

0 6 12 18 24 30 36 42 48 54 60 66 72 78

Months of Follow-up

Treated

Observed

p=0.51

20%

October 2006

Incidence of Choroidal Incidence of Choroidal NeovascularizationNeovascularization

0%

5%

10%

15%

20%

25%

30%

0 6 12 18 24 30 36 42 48 54 60 66 72 78

Months of follow-up

Treated

Observed

P=0.95

13%

October 2006

Incidence of Geographic Incidence of Geographic AtrophyAtrophy

0%

5%

10%

15%

20%

25%

30%

0 6 12 18 24 30 36 42 48 54 60 66 72 78

Months of follow-up

..

Treated

Observed

P=0.64

7.5%

October 2006

VA Loss – All PatientsVA Loss – All Patients

• Mean VA score Mean VA score Baseline:Baseline: 20/25 20/25(+2)(+2)

5 years:5 years: 20/40 20/40(+3)(+3)

Mean loss Mean loss ~~ 2 lines 2 lines

• Eyes with 20/20 or betterEyes with 20/20 or betterBaseline:Baseline: 50% 50%

5 years:5 years: 31% 31%

October 2006

VA Loss at 5 Years by Advanced VA Loss at 5 Years by Advanced AMD Status and Treatment AMD Status and Treatment

GroupGroup

Advanced AMD Advanced AMD ≥ 3 Line Loss≥ 3 Line Loss

at 5 Yearsat 5 Years Treated Treated ObservedObserved

PresentPresent 60% 60%54%54%

AbsentAbsent 10% 10%11%11%

October 2006

Secondary Vision OutcomesSecondary Vision Outcomes5-Year Results from CAPT5-Year Results from CAPT

24%

30%

21%

28%

0%

5%

10%

15%

20%

25%

30%

35%

Contrast Needed Doubled Reading Print Size Doubled

Treated

Observed

October 2006

Adverse EventsAdverse Events

• No immediate complications of No immediate complications of treatment at either initial or 12-treatment at either initial or 12-month treatment month treatment

(burns to foveal avascular zone, breaks in (burns to foveal avascular zone, breaks in Bruch’s membrane, hemorrhage)Bruch’s membrane, hemorrhage)

• Loss of Loss of ≥6 lines of VA ≥6 lines of VA notnot due to due to AMD or cataractAMD or cataract

Treated eyes:Treated eyes: 0.6%0.6%Observed eyes: Observed eyes: 1.3%1.3%

October 2006

SummarySummary

• Treated and observed eyes were very Treated and observed eyes were very similar at 5 years after enrollment on:similar at 5 years after enrollment on:3-line loss in VA3-line loss in VAIncidence of Advanced AMD (CNV & Incidence of Advanced AMD (CNV &

GA)GA)Change in contrast thresholdChange in contrast thresholdChange in critical print sizeChange in critical print sizeAdverse eventsAdverse events

• Laser treatment as applied in CAPT had Laser treatment as applied in CAPT had no clinically significant beneficial or no clinically significant beneficial or harmful effectharmful effect

October 2006

5-Year Results from CAPT5-Year Results from CAPT

21%

13%

7%

24%

30%

21%

13%

8%

21%

28%

0%

5%

10%

15%

20%

25%

30%

35%

3 or MoreLine Loss in

VisualAcuity

DevelopedCNV

DevelopedGeographic

Atrophy

ContrastNeededDoubled

ReadingPrint SizeDoubled

TreatedUntreated

October 2006

Principal Investigators of Principal Investigators of Clinical CentersClinical Centers

• Donald W. Park, MD Mesa, AZ

• Robert N. Johnson, MD San Francisco, CA

• Peter Reed Pavan, MD Tampa, FL

• Baker Hubbard III, MD Atlanta, GA

• Alice Lyon, MD Chicago, IL

• David Orth, MD Harvey, IL

• James C. Folk, MD Iowa City, IA

• Charles C. Barr, MD Louisville, KY

• Jeffrey Heier, MD Boston, MA

• Susan B. Bressler, MD Baltimore, MD

October 2006

Principal Investigators of Principal Investigators of Clinical CentersClinical Centers

• Michael Trese, MD Royal Oak, MI

• Colin A. McCannel, MD Rochester, MN

• Gilbert Grand, MD St. Louis, MO

• Andrew N. Antoszyk, MD Charlotte, NC

• Steven R. Leff, MD Edison, NJ

• Lawrence J. Singerman, MD Cleveland, OH

• Frederick H. Davidorf, MD Columbus, OH

• Richard F. Dreyer, MD Portland, OR

• Michael L. Klein, MD Portland, OR

• Juan E. Grunwald, MD Philadelphia, PA

• Gary Edd Fish, MD Dallas, TX

• Suresh R. Chandra, MD Madison, WI

October 2006

CAPT Resource Centers at the University of Pennsylvania

• Chairman’s OfficeStuart L. Fine, MD

• Reading CenterJudith Alexander

• Coordinating Center Maureen G. Maguire, PhD

October 2006

AppendixAppendix

October 2006

Serous PED Without Apparent Serous PED Without Apparent CNVCNV

• Not commonNot common2 treated eyes2 treated eyes5 untreated eyes5 untreated eyes

• Included as part of Advanced AMDIncluded as part of Advanced AMD

October 2006

Prophylactic Treatment of AMD Prophylactic Treatment of AMD (PTAMD) Multi-Centered Trial - (PTAMD) Multi-Centered Trial -

DesignDesign

• Bilateral Study reported by Friberg at Bilateral Study reported by Friberg at ARVO 2006ARVO 2006

• Eligibility criteriaEligibility criteria

≥≥5 drusen ≥635 drusen ≥63 microns in each eye microns in each eye

VA VA ≥20/63≥20/63

• Randomized assignment of one eye to a Randomized assignment of one eye to a single treatment of 48 subthreshold single treatment of 48 subthreshold diode laser burns at initial visitdiode laser burns at initial visit

• 639 patients (1278 eyes) enrolled639 patients (1278 eyes) enrolled

October 2006

PTAMD – Overall ResultsPTAMD – Overall Results

• CNV incidence CNV incidence

No difference between treated and No difference between treated and observed eyes at 3 yearsobserved eyes at 3 years

• Mean VA at 2 yearsMean VA at 2 years

Treated eyes 1.5 letters better than Treated eyes 1.5 letters better than observed (p=0.04) observed (p=0.04)

• Percentage with Percentage with ≥2 line VA gain at 2 ≥2 line VA gain at 2 yearsyears

12% Treated vs 8% Observed12% Treated vs 8% Observed

October 2006

PTAMD – PTAMD – SubgroupSubgroup Results Results

• Eyes with initial VA 20/32 to 20/63 (n=?)Eyes with initial VA 20/32 to 20/63 (n=?)

• At 2 yrsAt 2 yrs TreatedTreated ObservedObserved

≥≥2 line gain:2 line gain: 31% 31% 19% p=0.02 19% p=0.02

≥≥2 line loss: 13% 2 line loss: 13% 22% p=0.04 22% p=0.04

• CAPT subgroup: initial VA 20/32-20/40 in 1 or both CAPT subgroup: initial VA 20/32-20/40 in 1 or both eyes (n= 385) at 2 yrseyes (n= 385) at 2 yrs

≥≥2 line gain: 7% 2 line gain: 7% 5% 5%

≥≥2 line loss: 11% 2 line loss: 11% 14% 14%

• CAPT subgroup at 5 yrsCAPT subgroup at 5 yrs

≥≥2 line loss: 33% 2 line loss: 33% 33% 33%

29

Initial Visit 12 Months

Observed Eye - <50% Drusen Reduction at 12 months

30

Initial Visit 12 Months

Observed Eye - <50% Drusen Reduction at 12 months

31

Observed Eye - <50% Drusen Reduction at 12 months

Initial Visit 12 Months

32

Observed Eye - <50% Drusen Reduction at 12 months

Initial Visit 12 Months

33

Observed Eye - >50% Drusen Reduction at 12 months

Initial Visit 12 Months

34

Observed Eye - >50% Drusen Reduction at 12 months

Initial Visit 12 Months

35

Initial Visit 12 Months

Treated Eye - <50% Drusen Reduction at 12 months

36

Initial Visit 12 Months

Treated Eye - <50% Drusen Reduction at 12 months

37

Initial Visit 12 Months

Treated Eye - <50% Drusen Reduction at 12 months

38

Treated Eye - >50% Drusen Reduction at 12 months

Initial Visit 12 Months

39

Treated Eye - >50% Drusen Reduction at 12 months

Initial Visit 12 Months

40

Treated Eye - >50% Drusen Reduction at 12 months

Initial Visit 12 Months

41

Treated Eye - >50% Drusen Reduction at 12 months

Initial Visit 12 Months

42

Treated Eye - >50% Drusen Reduction at 12 months

Initial Visit 12 Months