1. CATT objectives To determine whether off-lable “Avastin” works as well as approved medication for neovascular AMD- “Lucentis” To evaluate how often treatment needs to be given

2. Single blind 1208 patients 44 centers in U.S. Age > 50 Active CNV (leakage on FA, Fluid within or bellow the retina or bellow RPE on TD-OCT) NO previous treatment for AMD VA 20/25- 20/320 CATT study patients

3. 4 treatment groups Lucentis every 28 days Lucentis as needed Avastin every 28 days Avastin as needed CATT treatment methods first mandatory intravitreal injection 0.50 mg Lucentis 1.25 mg Avastin

4. “as needed” (signs of CNV) : Leakage on FA Fluid on TD-OCT (within or bellow the retina or bellow RPE) New or persistent hemorrhage Decreased VA (compared with previous) Dye leakage Increased lesion size on FA CATT treatment methods

5. CATT Baseline characteristics Mean age : + 80 Sex: + 180 female, + 110 male (every group) Race: + 98% white Characteristic Lucentis Monthly (n=301) Avastin Monthly (n=286) Lucentis PRN (n=298) Avastin PRN (n=300)

6. Lucentis Monthly (n=301) Avastin Monthly (n=286) Lucentis PRN (n=298) Avastin PRN (n=300) Characteristic CATT Baseline characteristics

7. CATT main results- Visual acuity Avastin monthly =Lucentis monthly Avastin PRN= Lucentis PRN Avastin PRN? Avastin monthly Avastin PRN? Lucentis monthly Avastin monthly = Lucentis PRN Lucentis PRN= Lucentis monthly

8. CATT main results Lucentis monthly Avastin monthly Lucentis PRN Avastin PRN Lucentis monthly Avastin monthly Lucentis PRN Avastin PRN

9. CATT secondary results- Retinal thickness Pvalue Avastin PRN (n=271)(n=285) Avastin monthly (n= 265) (n=284) Characteristic <0.0017.7 + 3.56.9 + 3.011.9 + 1.211.7 + 1.5Mean no. of treatments Total thickness at fovea- μm 0.002308 + 127294 + 139300 + 149226 + 125 Mean 0.03-152 + 178-164 + 181 Mean change at from baseline Retinal thickness plus subfoveal- fluid thickness at fovea- μm 0.001172 + 68166 + 66172 + 81152 + 57 Mean 0.18-79 + 123-79 + 132 Mean change at from baseline -196 + 176-168 + 186 -100 + 130 -81 + 134 Lucentis monthly Lucentis PRN

10. CATT secondary results- Retinal fluid Pvalue Avastin PRN (n=271) (n=285) Avastin monthly (n= 265)(n=284) Characteristic Fluid on optic coherence tomography- no. (%) <0.00152(19.2)69(26.0)Absent 214(79.0)188(70.9)Present 5(1.8)14(4.9)8(3.0)9(3.2)Data missing 124(43.7) 151(53.2) 68(23.9) 203(71.2) Lucentis monthly Lucentis PRN

11. CATT secondary results- Adverse Events Pvalue Avastin PRN (n=300) Lucentis PRN (n=298) Avastin monthly (n= 286) Lucentis monthly (n=301) Charachretistic Between groups Among groups 0.040.1177 (22.7)61 (20.5)64 (22.4)53 (17.6) >1 Serious systemic event (MI, Stroke, THI, HTN) 0.020.119 (3.0)2 (0.7)6 (2.1)3 (1.0)Gastrointestinal disorder 0.030.1428 (9.30)16 (5.4)26 (9.1)18 (6.0) Any other system organ class 0.450.03004 (1.4)2 (0.7)Ocular event in the study eye- Endophthalmitis

12. During 1 Yr period the drugs had equivalent effect on VA PRN dosing results in 4 -5 fewer injections over 1 year than monthly dosing Both drugs reduced fluid in or under the retina. Complete resolution was greater with Lucentis Serious systemic adverse events (primarily hospitalizations) was higher with Avastin than with Lucentis (24.1% vs. 19.0%) CATT summery