Study Question

1. Complications ofAge-related Macular Degeneration PreventionTrialSponsored by the National Eye Institute

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

3. 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

4. Design Summary Randomization Scheme CAPT Eligible Patient Randomization of eyes One Eye Treated One Eye Observed

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

7. Design Summary • Sample Size: 1052 people 2104 eyes • Length of Follow-Up: ≥5 years

8. 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

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

10. Percentage of Eyes with 50% Reduction of Baseline Drusen by Treatment Group

11. Percentage of Eyes with Visual Acuity Loss of Three Lines or More

12. Incidence of Advanced Age-related Macular Degeneration 20%

13. Incidence of Choroidal Neovascularization 13%

14. Incidence of Geographic Atrophy 7.5% P=0.64

15. VA Loss – All Patients • Mean VA score • Baseline: 20/25(+2) • 5 years: 20/40(+3) • Mean loss ~ 2 lines • Eyes with 20/20 or better • Baseline: 50% • 5 years: 31%

16. VA Loss at 5 Years by Advanced AMD Status and Treatment Group Advanced AMD ≥ 3 Line Loss at 5 Years Treated Observed Present 60% 54% Absent 10% 11%

17. Secondary Vision Outcomes5-Year Results from CAPT

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

19. Summary • 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 effect

20. 5-Year Results from CAPT

21. 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 Principal Investigators of Clinical Centers

22. 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 Principal Investigators of Clinical Centers

23. Chairman’s Office Stuart L. Fine, MD Reading Center Judith Alexander Coordinating Center Maureen G. Maguire, PhD CAPT Resource Centers at the University of Pennsylvania

24. Appendix

25. Serous PED Without Apparent CNV • Not common • 2 treated eyes • 5 untreated eyes • Included as part of Advanced AMD

26. Prophylactic Treatment of AMD (PTAMD) Multi-Centered Trial - Design • Bilateral Study reported by Friberg at ARVO 2006 • Eligibility 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 visit • 639 patients (1278 eyes) enrolled

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

28. PTAMD – Subgroup Results • Eyes with initial VA 20/32 to 20/63 (n=?) • At 2 yrs Treated Observed • ≥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 yrs • ≥2 line gain: 7% 5% • ≥2 line loss: 11% 14% • CAPT subgroup at 5 yrs • ≥2 line loss: 33% 33%

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

30. Observed Eye - <50% Drusen Reduction at 12 months Initial Visit 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. Treated Eye- <50% Drusen Reduction at 12 months Initial Visit 12 Months

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

37. Treated Eye - <50% Drusen Reduction at 12 months Initial Visit 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