1 Macular Morphology and Visual Acuity in the Comparison of Age-related Macular Degeneration Treatments Trial (CATT) Jaffe GJ, Martin DF, Toth CA, Daniel E, Maguire, MG, Ying G-S, Grunwald JE, Huang J for the CATT Research Team Jaffe GJ, Martin DF, Toth CA, Daniel E, Maguire, MG, Ying G-S, Grunwald JE, Huang J for the CATT Research Team Supported by Cooperative Agreements from the National Eye Institute, National Institutes of Health, DHHS Available through

Presence and Type of Fluid on OCT Over Time 2 Jaffe et al. Macular Morphology and Visual Acuity in the Comparison of Age-related Macular Degeneration Treatments Trials Ophthalmology Epub 2013 May 03

Impact Over Time of Drug & Dosing Regimen on OCT–Determined Thickness Measurements 3 Jaffe et al. Macular Morphology and Visual Acuity in the Comparison of Age-related Macular Degeneration Treatments Trials Ophthalmology Epub 2013 May 03

Retinal thickness category over time by treatment group Retinal thickness category over time by treatment group 4 Jaffe et al. Macular Morphology and Visual Acuity in the Comparison of Age-related Macular Degeneration Treatments Trials Ophthalmology Epub 2013 May 03

Lesion Components Under the Foveal Center by Drug and Dosing Regimen 5 Jaffe et al. Macular Morphology and Visual Acuity in the Comparison of Age-related Macular Degeneration Treatments Trials Ophthalmology Epub 2013 May 03 Week Foveal Intraretinal Fluid Present Retinal Thickness Category (µ)Ranibizumab MonthlyBevacizumab MonthlyRanibizumab PRN Bevacizumab PRN 0 Yes <1203(2.0%)3(2.1%)7(5.3%)5(3.4%) 120 to 21256(38.1%)47(33.1%)35(26.7%)50(33.6%) >21288(59.9%)92(64.8%)89(67.9%)94(63.1%) No <12028(19.2%)22(16.4%)24(15.3%)25(17.5%) 120 to (71.9%)95(70.9%)110(70.1%)100(69.9%) >21213(8.9%)17(12.7%)23(14.6%)18(12.6%) 4 Yes <1205(7.4%)3(4.1%)4(6.1%)5(6.6%) 120 to 21247(69.1%)43(58.9%)48(72.7%)48(63.2%) >21216(23.5%)27(37.0%)14(21.2%)23(30.3%) No <12055(25.7%)45(22.6%)51(23.4%)41(20.4%) 120 to (69.2%)139(69.8%)153(70.2%)139(69.2%) >21211(5.1%)15(7.5%)14(6.4%)21(10.4%) 12 Yes <1206(10.2%)6(10.0%)5(7.7%)8(8.2%) 120 to 21241(69.5%)35(58.3%)33(50.8%)57(58.2%) >21212(20.3%)19(31.7%)27(41.5%)33(33.7%) No <12050(24.4%)34(17.8%)44(21.5%)32(18.7%) 120 to (72.2%)148(77.5%)154(75.1%)127(74.3%) >2127(3.4%)9(4.7%)7(3.4%)12(7.0%) 24 Yes <1203(6.5%)6(9.5%)3(5.3%)8(10.1%) 120 to 21230(65.2%)34(54.0%)34(59.6%)43(54.4%) >21213(28.3%)23(36.5%)20(35.1%)28(35.4%) No <12046(21.7%)36(20.0%)53(25.6%)36(20.8%) 120 to (75.0%)134(74.4%)142(68.6%)128(74.0%) >2127(3.3%)10(5.6%)12(5.8%)9(5.2%) 52 Yes <1202(7.7%)6(11.8%)4(8.7%)4(7.0%) 120 to 21217(65.4%)23(45.1%)27(58.7%)33(57.9%) >2127(26.9%)22(43.1%)15(32.6%)20(35.1%) No <12069(28.4%)42(20.8%)49(22.0%)49(24.0%) 120 to (67.1%)146(72.3%)161(72.2%)139(68.1%) >21211(4.5%)14(6.9%)13(5.8%)16(7.8%)

Foveal Lesion Composition Foveal Lesion Composition 6 Jaffe et al. Macular Morphology and Visual Acuity in the Comparison of Age-related Macular Degeneration Treatments Trials Ophthalmology Epub 2013 May 03 Baseline Week 52

Involvement of the foveal center by CNV or sequelae of CNV at week 52 7 (A) Ranibizumab Monthly (B) Bevacizumab Monthly (C) Ranibizumab PRN (D) Bevacizumab PRN Fluid Only 10.9% CNV 21.5% SPED 0.4% Scar 16.2% RPE Tears 1.5% Other 2.3% No Pathology 17.7% Can't Grade 3.0% Blocked Fluorescence 5.3% Non-geographic Atrophy 18.5% Geographic Atrophy 2.6% Fluid Only 8.2% CNV 21.2% SPED 0.4% Scar 20.4% RPE Tears 0.8% Other 4.9% No Pathology 24.9% Can't Grade 1.6% Blocked Fluorescence 4.9% Non-geographic Atrophy 11.8% Geographic Atrophy 0.8% Fluid Only 4.5% CNV 26.5% SPED 1.1% Scar 19.0% Hemorrhage 0.7% RPE Tear 0.7% Other 4.8% No Pathology 20.1% Can't Grade 3.4% Blocked Fluorescence 3.4% Non-geographic Atrophy 14.5% Geographic Atrophy 1.1% Fluid Only 9.4% CNV 29.8% SPED 0.4% Scar 18.8% Hemorrhage 0.4% RPE Tears 0.8% Other 3.9% No Pathology 16.1% Can't Grade 2.4% Blocked Fluorescence 1.6% Non-geographic Atrophy 13.3% Geographic Atrophy 3.1%

Mean visual acuity by status of fluid 8 Jaffe et al. Macular Morphology and Visual Acuity in the Comparison of Age-related Macular Degeneration Treatments Trials Ophthalmology Epub 2013 May 03

Retinal thickness and Visual Acuity at Baseline and Follow-up Retinal thickness and Visual Acuity at Baseline and Follow-up 9 Jaffe et al. Macular Morphology and Visual Acuity in the Comparison of Age-related Macular Degeneration Treatments Trials Ophthalmology Epub 2013 May 03

Nonlinear relationship of visual acuity with foveal total thickness during follow-up Nonlinear relationship of visual acuity with foveal total thickness during follow-up 10 Jaffe et al. Macular Morphology and Visual Acuity in the Comparison of Age-related Macular Degeneration Treatments Trials Ophthalmology Epub 2013 May 03

Mean VA by Neovascular Lesion Area and Pathology in Foveal Center at Week 52 (N=1053) 11 Jaffe et al. Macular Morphology and Visual Acuity in the Comparison of Age-related Macular Degeneration Treatments Trials Ophthalmology Epub 2013 May 03 Fundus Feature at Week 52N Unadjusted Mean Visual Acuity Score (Standard Error) P values* Neovascular lesion area (mm 2 ) < ≥0 to ≤ (1.11) >1.92 to ≤ (1.10) >4.96 to ≤ (1.10) > (1.11) Missing (1.98) Pathology in foveal center < None (1.20) Fluid only (1.85) Choroidal neovascularization or serous pigment epithelium detachment (1.06) Non-geographic atrophy (1.39) Geographic atrophy, hemorrhage, RPE § tear, blocked fluorescence (2.01) Scar (1.25) Other § or missing (1.75) *1-way analysis of variance RPE = retinal pigment epithelium § Other includes pigment, drusenoid pigment epithelial detachment and non-leaking choroidal neovascularization

Adjusted Mean Visual Acuity for OCT and Fundus Features at Week 52 (n=1004) ∗ 12 Jaffe et al. Macular Morphology and Visual Acuity in the Comparison of Age-related Macular Degeneration Treatments Trials Ophthalmology Epub 2013 May 03 *Subjects (n=49) with missing data for fluid or retinal thickness were excluded. CNV= choroidal neovascularization RPE = retinal pigment epithelium

Conclusions Anti–vascular endothelial growth factor (VEGF) therapy reduced lesion activity and improved VA in all treatment groups. Anti–vascular endothelial growth factor (VEGF) therapy reduced lesion activity and improved VA in all treatment groups. At all time points, eyes with residual IRF had worse VA than those without. At all time points, eyes with residual IRF had worse VA than those without. Eyes with abnormally thin or thick retinas, residual large lesions, and scar also had worse VA. Eyes with abnormally thin or thick retinas, residual large lesions, and scar also had worse VA. Monthly ranibizumab dosing yielded more eyes with no fluid and an abnormally thin retina, although the long-term significance is unknown. Monthly ranibizumab dosing yielded more eyes with no fluid and an abnormally thin retina, although the long-term significance is unknown. These results have important treatment implications in eyes undergoing anti-VEGF therapy for neovascular These results have important treatment implications in eyes undergoing anti-VEGF therapy for neovascular Jaffe et al. Macular Morphology and Visual Acuity in the Comparison of Age-related Macular Degeneration Treatments Trials Ophthalmology Epub 2013 May 03