October 2006 Complications of Age-related Macular Degeneration Prevention Trial Sponsored by the National Eye Institute

October 2006 Study Question Can low-intensity macular laser treatment reduce the incidence of vision loss in eyes with large drusen ?

October 2006 Design 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 Summary Randomization Scheme CAPT Eligible Patient Randomization of eyes One Eye Treated One Eye Observed

5 Initial Treatment ( µ) Barely visible burns 60 burns 15 burns/quadrant 100 µ burns 0.1 second µ 2500 µ 1500 µ

6

October 2006 Design Summary Sample Size: 1052 peopleSample Size: 1052 people 2104 eyes 2104 eyes Length of Follow-Up: ≥5 years Length of Follow-Up: ≥5 years

October 2006 Design Summary Outcome Measures  Primary  Change in visual acuity  Secondary  Incidence of Advanced AMD (CNV, GA, SPED)  Contrast threshold  Reading (critical print size)  Side effects of treatment

October 2006 Description of Follow-up Overall missed visits:3%Overall missed visits:3% 87% of the 1052 patients completed the 5-year examination 87% of the 1052 patients completed the 5-year examination  9% patient deaths  4% missed the 5-year exam

October 2006 Percentage of Eyes with 50% Reduction of Baseline Drusen by Treatment Group Percentage of Eyes with 50% Reduction of Baseline Drusen by Treatment Group

October 2006 Percentage of Eyes with Visual Acuity Loss of Three Lines or More Percentage of Eyes with Visual Acuity Loss of Three Lines or More

October 2006 Incidence of Advanced Age-related Macular Degeneration 20%

October 2006 Incidence of Choroidal Neovascularization 13%

October 2006 Incidence of Geographic Atrophy P= %

October 2006 VA Loss – All Patients Mean VA scoreMean VA score  Baseline: 20/25 (+2)  5 years: 20/40 (+3)  Mean loss ~ 2 lines Eyes with 20/20 or betterEyes with 20/20 or better  Baseline: 50%  5 years: 31%

October 2006 VA Loss at 5 Years by Advanced AMD Status and Treatment Group Advanced AMD ≥ 3 Line Loss at 5 YearsTreated Observed at 5 YearsTreated Observed Present 60%54% Absent 10%11%

October 2006 Secondary Vision Outcomes 5-Year Results from CAPT

October 2006 Adverse Events No immediate complications of treatment at either initial or 12-month treatmentNo immediate complications of treatment at either initial or 12-month treatment (burns to foveal avascular zone, breaks in Bruch’s membrane, hemorrhage) (burns to foveal avascular zone, breaks in Bruch’s membrane, hemorrhage) Loss of ≥6 lines of VA not due to AMD or cataractLoss of ≥6 lines of VA not due to AMD or cataract  Treated eyes:0.6%  Observed eyes: 1.3%

October 2006 Summary Treated and observed eyes were very similar at 5 years after enrollment on:Treated and observed eyes were very similar at 5 years after enrollment on:  3-line loss in VA  Incidence of Advanced AMD (CNV & GA)  Change in contrast threshold  Change in critical print size  Adverse events Laser treatment as applied in CAPT had no clinically significant beneficial or harmful effectLaser treatment as applied in CAPT had no clinically significant beneficial or harmful effect

October Year Results from CAPT

October 2006 Principal Investigators of Clinical 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 Clinical 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 Office Stuart L. Fine, MD Reading Center Judith Alexander Coordinating Center Maureen G. Maguire, PhD

October 2006 Appendix

Serous PED Without Apparent CNV Not commonNot common  2 treated eyes  5 untreated eyes Included as part of Advanced AMDIncluded as part of Advanced AMD

October 2006 Prophylactic Treatment of AMD (PTAMD) Multi-Centered Trial - Design Bilateral Study reported by Friberg at ARVO 2006Bilateral Study reported by Friberg at ARVO 2006 Eligibility criteriaEligibility criteria  ≥5 drusen ≥63 microns in each eye  VA ≥20/63 Randomized assignment of one eye to a single treatment of 48 subthreshold diode laser burns at initial visitRandomized assignment of one eye to a single treatment of 48 subthreshold diode laser burns at initial visit 639 patients (1278 eyes) enrolled639 patients (1278 eyes) enrolled

October 2006 PTAMD – Overall Results CNV incidenceCNV incidence  No difference between treated and observed eyes at 3 years Mean VA at 2 yearsMean VA at 2 years  Treated eyes 1.5 letters better than observed (p=0.04) Percentage with ≥2 line VA gain at 2 yearsPercentage with ≥2 line VA gain at 2 years  12% Treated vs 8% Observed

October 2006 PTAMD – Subgroup Results Eyes with initial VA 20/32 to 20/63 (n=?)Eyes with initial VA 20/32 to 20/63 (n=?) At 2 yrs TreatedObservedAt 2 yrs TreatedObserved  ≥2 line gain: 31% 19% p=0.02  ≥2 line loss: 13% 22% p=0.04 CAPT subgroup: initial VA 20/32-20/40 in 1 or both eyes (n= 385) at 2 yrsCAPT subgroup: initial VA 20/32-20/40 in 1 or both eyes (n= 385) at 2 yrs  ≥2 line gain: 7% 5%  ≥2 line loss: 11% 14% CAPT subgroup at 5 yrsCAPT subgroup at 5 yrs  ≥2 line loss: 33% 33%

29 Initial Visit 12 Months Observed Eye - <50% Drusen Reduction at 12 months

30 Initial Visit12 Months Observed Eye - <50% Drusen Reduction at 12 months

31 Observed Eye - <50% Drusen Reduction at 12 months Initial Visit12 Months

32 Observed Eye - <50% Drusen Reduction at 12 months Initial Visit12 Months

33 Observed Eye - >50% Drusen Reduction at 12 months Initial Visit12 Months

34 Observed Eye - >50% Drusen Reduction at 12 months Initial Visit12 Months

35 Initial Visit12 Months Treated Eye - <50% Drusen Reduction at 12 months

36 Initial Visit12 Months Treated Eye - <50% Drusen Reduction at 12 months

37 Initial Visit12 Months Treated Eye - <50% Drusen Reduction at 12 months

38 Treated Eye - >50% Drusen Reduction at 12 months Initial Visit12 Months

39 Treated Eye - >50% Drusen Reduction at 12 months Initial Visit12 Months

40 Treated Eye - >50% Drusen Reduction at 12 months Initial Visit12 Months

41 Treated Eye - >50% Drusen Reduction at 12 months Initial Visit12 Months

42 Treated Eye - >50% Drusen Reduction at 12 months Initial Visit12 Months