FDA label 44eadfd6-9d30-e343-e063-6294a90a4ae6

5 WARNINGS AND PRECAUTIONS Endophthalmitis, retinal detachments, and retinal vasculitis with or without occlusion may occur following intravitreal injections. Patients and/or caregivers should be instructed to report any signs and/or symptoms suggestive of endophthalmitis, retinal detachment, or retinal vasculitis without delay and should be managed appropriately. ( 5.1 ) Increases in intraocular pressure have been seen within 60 minutes of an intravitreal injection. ( 5.2 ) There is a potential risk of arterial thromboembolic events following intravitreal use of VEGF inhibitors. ( 5.3 ) 5.1 Endophthalmitis, Retinal Detachments, and Retinal Vasculitis with or without Occlusion Intravitreal injections, including those with aflibercept products, have been associated with endophthalmitis and retinal detachments [see Adverse Reactions (6.1) ] and, more rarely, retinal vasculitis with or without occlusion [see Adverse Reactions (6.2) ]. Proper aseptic injection technique must always be used when administering OPUVIZ. Patients and/or caregivers should be instructed to report any signs and/or symptoms suggestive of endophthalmitis, retinal detachment, or retinal vasculitis without delay and should be managed appropriately [see Dosage and Administration (2.7) and Patient Counseling Information (17) ]. 5.2 Increase in Intraocular Pressure Acute increases in intraocular pressure have been seen within 60 minutes of intravitreal injection, including with aflibercept products [see Adverse Reactions (6.1) ]. Sustained increases in intraocular pressure have also been reported after repeated intravitreal dosing with vascular endothelial growth factor (VEGF) inhibitors. Intraocular pressure and the perfusion of the optic nerve head should be monitored and managed appropriately [see Dosage and Administration (2.7) ] . 5.3 Thromboembolic Events There is a potential risk of arterial thromboembolic events (ATEs) following intravitreal use of VEGF inhibitors, including aflibercept products. ATEs are defined as nonfatal stroke, nonfatal myocardial infarction, or vascular death (including deaths of unknown cause). The incidence of reported thromboembolic events in wet AMD studies during the first year was 1.8% (32 out of 1824) in the combined group of patients treated with aflibercept compared with 1.5% (9 out of 595) in patients treated with ranibizumab; through 96 weeks, the incidence was 3.3% (60 out of 1824) in the aflibercept group compared with 3.2% (19 out of 595) in the ranibizumab group. The incidence in the DME studies from baseline to week 52 was 3.3% (19 out of 578) in the combined group of patients treated with aflibercept compared with 2.8% (8 out of 287) in the control group; from baseline to week 100, the incidence was 6.4% (37 out of 578) in the combined group of patients treated with aflibercept compared with 4.2% (12 out of 287) in the control group. There were no reported thromboembolic events in the patients treated with aflibercept in the first six months of the RVO studies.

6 ADVERSE REACTIONS The following potentially serious adverse reactions are described elsewhere in the labeling: Hypersensitivity [see Contraindications (4.3) ] Endophthalmitis, Retinal detachments, and Retinal Vasculitis with or without Occlusion [see Warnings and Precautions (5.1) ] Increase in intraocular pressure [see Warnings and Precautions (5.2) ] Thromboembolic events [see Warnings and Precautions (5.3) ] The most common adverse reactions (≥5%) reported in patients receiving aflibercept were conjunctival hemorrhage, eye pain, cataract, vitreous detachment, vitreous floaters, and intraocular pressure increased. ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Biogen MA Inc. at 1-866-MED-INFO (1-866-633-4636) or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch. See 17 for PATIENT COUNSELING INFORMATION *Biosimilar means that the biological product is approved based on data demonstrating that it is highly similar to an FDA-approved biological product, known as a reference product, and that there are no clinically meaningful differences between the biosimilar product and the reference product. Biosimilarity of OPUVIZ has been demonstrated for the condition(s) of use (e.g., indication(s), dosing regimen(s)), strength(s), dosage form(s), and route(s) of administration described in its Full Prescribing Information. 6.1 Clinical Trials Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in other clinical trials of the same or another drug and may not reflect the rates observed in practice. A total of 2980 adult patients treated with aflibercept constituted the safety population in eight phase 3 studies. Among those, 2379 patients were treated with the recommended dose of 2 mg. Serious adverse reactions related to the injection procedure have occurred in <0.1% of intravitreal injections with aflibercept including endophthalmitis and retinal detachment. The most common adverse reactions (≥5%) reported in patients receiving aflibercept were conjunctival hemorrhage, eye pain, cataract, vitreous detachment, vitreous floaters, and intraocular pressure increased. Neovascular (Wet) Age-Related Macular Degeneration (AMD) The data described below reflect exposure to aflibercept in 1824 patients with wet AMD, including 1223 patients treated with the 2-mg dose, in 2 double-masked, controlled clinical studies (VIEW1 and VIEW2) for 24 months (with active control in year 1) [see Clinical Studies (14.1) ]. Safety data observed in the aflibercept group in a 52-week, double-masked, Phase 2 study were consistent with these results. Table 1: Most Common Adverse Reactions (≥1%) in Wet AMD Studies Adverse Reactions Baseline to Week 52 Baseline to Week 96 Aflibercept (N=1824) Active Control (ranibizumab) (N=595) Aflibercept (N=1824) Control (ranibizumab) (N=595) Conjunctival hemorrhage 25% 28% 27% 30% Eye pain 9% 9% 10% 10% Cataract 7% 7% 13% 10% Vitreous detachment 6% 6% 8% 8% Vitreous floaters 6% 7% 8% 10% Intraocular pressure increased 5% 7% 7% 11% Ocular hyperemia 4% 8% 5% 10% Corneal epithelium defect 4% 5% 5% 6% Detachment of the retinal pigment epithelium 3% 3% 5% 5% Injection site pain 3% 3% 3% 4% Foreign body sensation in eyes 3% 4% 4% 4% Lacrimation increased 3% 1% 4% 2% Vision blurred 2% 2% 4% 3% Intraocular inflammation 2% 3% 3% 4% Retinal pigment epithelium tear 2% 1% 2% 2% Injection site hemorrhage 1% 2% 2% 2% Eyelid edema 1% 2% 2% 3% Corneal edema 1% 1% 1% 1% Retinal detachment <1% <1% 1% 1% Less common serious adverse reactions reported in <1% of the patients treated with aflibercept were hypersensitivity, retinal tear, and endophthalmitis. Macular Edema Following Retinal Vein Occlusion (RVO) The data described below reflect 6 months exposure to aflibercept with a monthly 2 mg dose in 218 patients following central retinal vein occlusion (CRVO) in 2 clinical studies (COPERNICUS and GALILEO) and 91 patients following branch retinal vein occlusion (BRVO) in one clinical study (VIBRANT) [see Clinical Studies (14.2) , (14.3) ]. Table 2 : Most Common Adverse Reactions (≥1%) in RVO Studies Adverse Reactions CRVO BRVO Aflibercept (N=218) Control (N=142) Aflibercept (N=91) Control (N=92) Eye pain 13% 5% 4% 5% Conjunctival hemorrhage 12% 11% 20% 4% Intraocular pressure increased 8% 6% 2% 0% Corneal epithelium defect 5% 4% 2% 0% Vitreous floaters 5% 1% 1% 0% Ocular hyperemia 5% 3% 2% 2% Foreign body sensation in eyes 3% 5% 3% 0% Vitreous detachment 3% 4% 2% 0% Lacrimation increased 3% 4% 3% 0% Injection site pain 3% 1% 1% 0% Vision blurred 1% <1% 1% 1% Intraocular inflammation 1% 1% 0% 0% Cataract <1% 1% 5% 0% Eyelid edema <1% 1% 1% 0% Less common adverse reactions reported in <1% of the patients treated with aflibercept in the CRVO studies were corneal edema, retinal tear, hypersensitivity, and endophthalmitis. Diabetic Macular Edema (DME) and Diabetic Retinopathy (DR) The data described below reflect exposure to aflibercept in 578 patients with DME treated with the 2-mg dose in 2 double-masked, controlled clinical studies (VIVID and VISTA) from baseline to week 52 and from baseline to week 100 [see Clinical Studies (14.4) ]. Table 3 : Most Common Adverse Reactions (≥1%) in DME Studies Adverse Reactions Baseline to Week 52 Baseline to Week 100 Aflibercept (N=578) Control (N=287) Aflibercept (N=578) Control (N=287) Conjunctival hemorrhage 28% 17% 31% 21% Eye pain 9% 6% 11% 9% Cataract 8% 9% 19% 17% Vitreous floaters 6% 3% 8% 6% Corneal epithelium defect 5% 3% 7% 5% Intraocular pressure increased 5% 3% 9% 5% Ocular hyperemia 5% 6% 5% 6% Vitreous detachment 3% 3% 8% 6% Foreign body sensation in eyes 3% 3% 3% 3% Lacrimation increased 3% 2% 4% 2% Vision blurred 2% 2% 3% 4% Intraocular inflammation 2% <1% 3% 1% Injection site pain 2% <1% 2% <1% Eyelid edema <1% 1% 2% 1% Less common adverse reactions reported in <1% of the patients treated with aflibercept were hypersensitivity, retinal detachment, retinal tear, corneal edema, and injection site hemorrhage. Safety data observed in 269 patients with nonproliferative diabetic retinopathy (NPDR) through week 52 in the PANORAMA trial were consistent with those seen in the phase 3 VIVID and VISTA trials (see Table 3 above). 6.2 Postmarketing Experience The following adverse reactions have been identified during postapproval use of aflibercept. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure. Eye disorders : Retinal vasculitis and occlusive retinal vasculitis related to intravitreal injection with aflibercept (reported at a rate of 0.6 and 0.2 per 1 million injections, respectively, based on postmarketing experience from November 2011 until November 2023). Scleritis.

<table width="96%" border="1" cellspacing="0" cellpadding="0" styleCode="TableNormal1"><col width="32%"/><col width="17%"/><col width="17%"/><col width="17%"/><col width="17%"/><tbody><tr><td rowspan="2" align="center" styleCode="Botrule Lrule Rrule Toprule" valign="top"><paragraph styleCode="First TableParagraph"><content styleCode="bold">Adverse Reactions</content></paragraph></td><td colspan="2" align="center" styleCode="Botrule Lrule Rrule Toprule"><paragraph styleCode="First TableParagraphCxSpMiddle"><content styleCode="bold">Baseline to Week 52</content></paragraph></td><td colspan="2" align="center" styleCode="Botrule Lrule Rrule Toprule"><paragraph styleCode="First TableParagraphCxSpLast"><content styleCode="bold">Baseline to Week 96</content></paragraph></td></tr><tr><td align="center" styleCode="Botrule Lrule Rrule Toprule" valign="top"><paragraph styleCode="First TableParagraphCxSpFirst"><content styleCode="bold">Aflibercept</content></paragraph><paragraph styleCode="TableParagraphCxSpMiddle"><content styleCode="bold">(N=1824)</content></paragraph></td><td align="center" styleCode="Botrule Lrule Rrule Toprule" valign="top"><paragraph styleCode="First TableParagraphCxSpMiddle"><content styleCode="bold">Active Control (ranibizumab) (N=595)</content></paragraph></td><td align="center" styleCode="Botrule Lrule Rrule Toprule" valign="top"><paragraph styleCode="First TableParagraphCxSpMiddle"><content styleCode="bold">Aflibercept</content></paragraph><paragraph styleCode="TableParagraphCxSpMiddle"><content styleCode="bold">(N=1824)</content></paragraph></td><td align="center" styleCode="Botrule Lrule Rrule Toprule" valign="top"><paragraph styleCode="First TableParagraphCxSpLast"><content styleCode="bold">Control (ranibizumab) (N=595)</content></paragraph></td></tr><tr><td styleCode="Botrule Lrule Rrule Toprule"><paragraph styleCode="First TableParagraph">Conjunctival hemorrhage</paragraph></td><td align="center" styleCode="Botrule Lrule Rrule Toprule"><paragraph styleCode="First TableParagraphCxSpMiddle">25%</paragraph></td><td align="center" styleCode="Botrule Lrule Rrule Toprule"><paragraph styleCode="First TableParagraphCxSpMiddle">28%</paragraph></td><td align="center" styleCode="Botrule Lrule Rrule Toprule"><paragraph styleCode="First TableParagraphCxSpMiddle">27%</paragraph></td><td align="center" styleCode="Botrule Lrule Rrule Toprule"><paragraph styleCode="First TableParagraphCxSpLast">30%</paragraph></td></tr><tr><td styleCode="Botrule Lrule Rrule Toprule"><paragraph styleCode="First TableParagraph">Eye pain</paragraph></td><td align="center" styleCode="Botrule Lrule Rrule Toprule"><paragraph styleCode="First TableParagraphCxSpMiddle">9%</paragraph></td><td align="center" styleCode="Botrule Lrule Rrule Toprule"><paragraph styleCode="First TableParagraphCxSpMiddle">9%</paragraph></td><td align="center" styleCode="Botrule Lrule Rrule Toprule"><paragraph styleCode="First TableParagraphCxSpMiddle">10%</paragraph></td><td align="center" styleCode="Botrule Lrule Rrule Toprule"><paragraph styleCode="First TableParagraphCxSpLast">10%</paragraph></td></tr><tr><td styleCode="Botrule Lrule Rrule Toprule"><paragraph styleCode="First TableParagraph">Cataract</paragraph></td><td align="center" styleCode="Botrule Lrule Rrule Toprule"><paragraph styleCode="First TableParagraphCxSpMiddle">7%</paragraph></td><td align="center" styleCode="Botrule Lrule Rrule Toprule"><paragraph styleCode="First TableParagraphCxSpMiddle">7%</paragraph></td><td align="center" styleCode="Botrule Lrule Rrule Toprule"><paragraph styleCode="First TableParagraphCxSpMiddle">13%</paragraph></td><td align="center" styleCode="Botrule Lrule Rrule Toprule"><paragraph styleCode="First TableParagraphCxSpLast">10%</paragraph></td></tr><tr><td styleCode="Botrule Lrule Rrule Toprule"><paragraph styleCode="First TableParagraph">Vitreous detachment</paragraph></td><td align="center" styleCode="Botrule Lrule Rrule Toprule"><paragraph styleCode="First TableParagraphCxSpMiddle">6%</paragraph></td><td align="center" styleCode="Botrule Lrule Rrule Toprule"><paragraph styleCode="First TableParagraphCxSpMiddle">6%</paragraph></td><td align="center" styleCode="Botrule Lrule Rrule Toprule"><paragraph styleCode="First TableParagraphCxSpMiddle">8%</paragraph></td><td align="center" styleCode="Botrule Lrule Rrule Toprule"><paragraph styleCode="First TableParagraphCxSpLast">8%</paragraph></td></tr><tr><td styleCode="Botrule Lrule Rrule Toprule"><paragraph styleCode="First TableParagraph">Vitreous floaters</paragraph></td><td align="center" styleCode="Botrule Lrule Rrule Toprule"><paragraph styleCode="First TableParagraphCxSpMiddle">6%</paragraph></td><td align="center" styleCode="Botrule Lrule Rrule Toprule"><paragraph styleCode="First TableParagraphCxSpMiddle">7%</paragraph></td><td align="center" styleCode="Botrule Lrule Rrule Toprule"><paragraph styleCode="First TableParagraphCxSpMiddle">8%</paragraph></td><td align="center" styleCode="Botrule Lrule Rrule Toprule"><paragraph styleCode="First TableParagraphCxSpLast">10%</paragraph></td></tr><tr><td styleCode="Botrule Lrule Rrule Toprule"><paragraph styleCode="First TableParagraph">Intraocular pressure increased</paragraph></td><td align="center" styleCode="Botrule Lrule Rrule Toprule"><paragraph styleCode="First TableParagraphCxSpMiddle">5%</paragraph></td><td align="center" styleCode="Botrule Lrule Rrule Toprule"><paragraph styleCode="First TableParagraphCxSpMiddle">7%</paragraph></td><td align="center" styleCode="Botrule Lrule Rrule Toprule"><paragraph styleCode="First TableParagraphCxSpMiddle">7%</paragraph></td><td align="center" styleCode="Botrule Lrule Rrule Toprule"><paragraph styleCode="First TableParagraphCxSpLast">11%</paragraph></td></tr><tr><td styleCode="Botrule Lrule Rrule Toprule"><paragraph styleCode="First TableParagraph">Ocular hyperemia</paragraph></td><td align="center" styleCode="Botrule Lrule Rrule Toprule"><paragraph styleCode="First TableParagraphCxSpMiddle">4%</paragraph></td><td align="center" styleCode="Botrule Lrule Rrule Toprule"><paragraph styleCode="First TableParagraphCxSpMiddle">8%</paragraph></td><td align="center" styleCode="Botrule Lrule Rrule Toprule"><paragraph styleCode="First TableParagraphCxSpMiddle">5%</paragraph></td><td align="center" styleCode="Botrule Lrule Rrule Toprule"><paragraph styleCode="First TableParagraphCxSpLast">10%</paragraph></td></tr><tr><td styleCode="Botrule Lrule Rrule Toprule"><paragraph styleCode="First TableParagraph">Corneal epithelium defect</paragraph></td><td align="center" styleCode="Botrule Lrule Rrule Toprule"><paragraph styleCode="First TableParagraphCxSpMiddle">4%</paragraph></td><td align="center" styleCode="Botrule Lrule Rrule Toprule"><paragraph styleCode="First TableParagraphCxSpMiddle">5%</paragraph></td><td align="center" styleCode="Botrule Lrule Rrule Toprule"><paragraph styleCode="First TableParagraphCxSpMiddle">5%</paragraph></td><td align="center" styleCode="Botrule Lrule Rrule Toprule"><paragraph styleCode="First TableParagraphCxSpLast">6%</paragraph></td></tr><tr><td styleCode="Botrule Lrule Rrule Toprule"><paragraph styleCode="First TableParagraph">Detachment of the retinal pigment epithelium</paragraph></td><td align="center" styleCode="Botrule Lrule Rrule Toprule"><paragraph styleCode="First TableParagraphCxSpMiddle">3%</paragraph></td><td align="center" styleCode="Botrule Lrule Rrule Toprule"><paragraph styleCode="First TableParagraphCxSpMiddle">3%</paragraph></td><td align="center" styleCode="Botrule Lrule Rrule Toprule"><paragraph styleCode="First TableParagraphCxSpMiddle">5%</paragraph></td><td align="center" styleCode="Botrule Lrule Rrule Toprule"><paragraph styleCode="First TableParagraphCxSpLast">5%</paragraph></td></tr><tr><td styleCode="Botrule Lrule Rrule Toprule"><paragraph styleCode="First TableParagraph">Injection site pain</paragraph></td><td align="center" styleCode="Botrule Lrule Rrule Toprule"><paragraph styleCode="First TableParagraphCxSpMiddle">3%</paragraph></td><td align="center" styleCode="Botrule Lrule Rrule Toprule"><paragraph styleCode="First TableParagraphCxSpMiddle">3%</paragraph></td><td align="center" styleCode="Botrule Lrule Rrule Toprule"><paragraph styleCode="First TableParagraphCxSpMiddle">3%</paragraph></td><td align="center" styleCode="Botrule Lrule Rrule Toprule"><paragraph styleCode="First TableParagraphCxSpLast">4%</paragraph></td></tr><tr><td styleCode="Botrule Lrule Rrule Toprule"><paragraph styleCode="First TableParagraph">Foreign body sensation in eyes</paragraph></td><td align="center" styleCode="Botrule Lrule Rrule Toprule"><paragraph styleCode="First TableParagraphCxSpMiddle">3%</paragraph></td><td align="center" styleCode="Botrule Lrule Rrule Toprule"><paragraph styleCode="First TableParagraphCxSpMiddle">4%</paragraph></td><td align="center" styleCode="Botrule Lrule Rrule Toprule"><paragraph styleCode="First TableParagraphCxSpMiddle">4%</paragraph></td><td align="center" styleCode="Botrule Lrule Rrule Toprule"><paragraph styleCode="First TableParagraphCxSpLast">4%</paragraph></td></tr><tr><td styleCode="Botrule Lrule Rrule Toprule"><paragraph styleCode="First TableParagraph">Lacrimation increased</paragraph></td><td align="center" styleCode="Botrule Lrule Rrule Toprule"><paragraph styleCode="First TableParagraphCxSpMiddle">3%</paragraph></td><td align="center" styleCode="Botrule Lrule Rrule Toprule"><paragraph styleCode="First TableParagraphCxSpMiddle">1%</paragraph></td><td align="center" styleCode="Botrule Lrule Rrule Toprule"><paragraph styleCode="First TableParagraphCxSpMiddle">4%</paragraph></td><td align="center" styleCode="Botrule Lrule Rrule Toprule"><paragraph styleCode="First TableParagraphCxSpLast">2%</paragraph></td></tr><tr><td styleCode="Botrule Lrule Rrule Toprule"><paragraph styleCode="First TableParagraph">Vision blurred</paragraph></td><td align="center" styleCode="Botrule Lrule Rrule Toprule"><paragraph styleCode="First TableParagraphCxSpMiddle">2%</paragraph></td><td align="center" styleCode="Botrule Lrule Rrule Toprule"><paragraph styleCode="First TableParagraphCxSpMiddle">2%</paragraph></td><td align="center" styleCode="Botrule Lrule Rrule Toprule"><paragraph styleCode="First TableParagraphCxSpMiddle">4%</paragraph></td><td align="center" styleCode="Botrule Lrule Rrule Toprule"><paragraph styleCode="First TableParagraphCxSpLast">3%</paragraph></td></tr><tr><td styleCode="Botrule Lrule Rrule Toprule"><paragraph styleCode="First TableParagraph">Intraocular inflammation</paragraph></td><td align="center" styleCode="Botrule Lrule Rrule Toprule"><paragraph styleCode="First TableParagraphCxSpMiddle">2%</paragraph></td><td align="center" styleCode="Botrule Lrule Rrule Toprule"><paragraph styleCode="First TableParagraphCxSpMiddle">3%</paragraph></td><td align="center" styleCode="Botrule Lrule Rrule Toprule"><paragraph styleCode="First TableParagraphCxSpMiddle">3%</paragraph></td><td align="center" styleCode="Botrule Lrule Rrule Toprule"><paragraph styleCode="First TableParagraphCxSpLast">4%</paragraph></td></tr><tr><td styleCode="Botrule Lrule Rrule Toprule"><paragraph styleCode="First TableParagraph">Retinal pigment epithelium tear</paragraph></td><td align="center" styleCode="Botrule Lrule Rrule Toprule"><paragraph styleCode="First TableParagraphCxSpMiddle">2%</paragraph></td><td align="center" styleCode="Botrule Lrule Rrule Toprule"><paragraph styleCode="First TableParagraphCxSpMiddle">1%</paragraph></td><td align="center" styleCode="Botrule Lrule Rrule Toprule"><paragraph styleCode="First TableParagraphCxSpMiddle">2%</paragraph></td><td align="center" styleCode="Botrule Lrule Rrule Toprule"><paragraph styleCode="First TableParagraphCxSpLast">2%</paragraph></td></tr><tr><td styleCode="Botrule Lrule Rrule Toprule"><paragraph styleCode="First TableParagraph">Injection site hemorrhage</paragraph></td><td align="center" styleCode="Botrule Lrule Rrule Toprule"><paragraph styleCode="First TableParagraphCxSpMiddle">1%</paragraph></td><td align="center" styleCode="Botrule Lrule Rrule Toprule"><paragraph styleCode="First TableParagraphCxSpMiddle">2%</paragraph></td><td align="center" styleCode="Botrule Lrule Rrule Toprule"><paragraph styleCode="First TableParagraphCxSpMiddle">2%</paragraph></td><td align="center" styleCode="Botrule Lrule Rrule Toprule"><paragraph styleCode="First TableParagraphCxSpLast">2%</paragraph></td></tr><tr><td styleCode="Botrule Lrule Rrule Toprule"><paragraph styleCode="First TableParagraph">Eyelid edema</paragraph></td><td align="center" styleCode="Botrule Lrule Rrule Toprule"><paragraph styleCode="First TableParagraphCxSpMiddle">1%</paragraph></td><td align="center" styleCode="Botrule Lrule Rrule Toprule"><paragraph styleCode="First TableParagraphCxSpMiddle">2%</paragraph></td><td align="center" styleCode="Botrule Lrule Rrule Toprule"><paragraph styleCode="First TableParagraphCxSpMiddle">2%</paragraph></td><td align="center" styleCode="Botrule Lrule Rrule Toprule"><paragraph styleCode="First TableParagraphCxSpLast">3%</paragraph></td></tr><tr><td styleCode="Botrule Lrule Rrule Toprule"><paragraph styleCode="First TableParagraph">Corneal edema</paragraph></td><td align="center" styleCode="Botrule Lrule Rrule Toprule"><paragraph styleCode="First TableParagraphCxSpMiddle">1%</paragraph></td><td align="center" styleCode="Botrule Lrule Rrule Toprule"><paragraph styleCode="First TableParagraphCxSpMiddle">1%</paragraph></td><td align="center" styleCode="Botrule Lrule Rrule Toprule"><paragraph styleCode="First TableParagraphCxSpMiddle">1%</paragraph></td><td align="center" styleCode="Botrule Lrule Rrule Toprule"><paragraph styleCode="First TableParagraphCxSpLast">1%</paragraph></td></tr><tr><td styleCode="Botrule Lrule Rrule Toprule"><paragraph styleCode="First TableParagraph">Retinal detachment</paragraph></td><td align="center" styleCode="Botrule Lrule Rrule Toprule"><paragraph styleCode="First TableParagraphCxSpMiddle">&lt;1%</paragraph></td><td align="center" styleCode="Botrule Lrule Rrule Toprule"><paragraph styleCode="First TableParagraphCxSpMiddle">&lt;1%</paragraph></td><td align="center" styleCode="Botrule Lrule Rrule Toprule"><paragraph styleCode="First TableParagraphCxSpMiddle">1%</paragraph></td><td align="center" styleCode="Botrule Lrule Rrule Toprule"><paragraph styleCode="First TableParagraphCxSpLast">1%</paragraph></td></tr></tbody></table>

<table width="98%" border="1" cellspacing="0" cellpadding="0" styleCode="TableNormal1"><col width="32%"/><col width="17%"/><col width="17%"/><col width="17%"/><col width="17%"/><tbody><tr><td styleCode="Botrule Lrule Rrule Toprule"><paragraph styleCode="First TableParagraph"><content styleCode="bold">Adverse Reactions</content></paragraph></td><td colspan="2" align="center" styleCode="Botrule Lrule Rrule Toprule"><paragraph styleCode="First TableParagraph"><content styleCode="bold">CRVO</content></paragraph></td><td colspan="2" align="center" styleCode="Botrule Lrule Rrule Toprule"><paragraph styleCode="First TableParagraph"><content styleCode="bold">BRVO</content></paragraph></td></tr><tr><td align="center" styleCode="Botrule Lrule Rrule Toprule" valign="top"/><td align="center" styleCode="Botrule Lrule Rrule Toprule"><paragraph styleCode="First TableParagraph"><content styleCode="bold">Aflibercept</content></paragraph><paragraph styleCode="TableParagraph"><content styleCode="bold">(N=218)</content></paragraph></td><td align="center" styleCode="Botrule Lrule Rrule Toprule"><paragraph styleCode="First TableParagraph"><content styleCode="bold">Control</content></paragraph><paragraph styleCode="TableParagraph"><content styleCode="bold">(N=142)</content></paragraph></td><td align="center" styleCode="Botrule Lrule Rrule Toprule"><paragraph styleCode="First TableParagraph"><content styleCode="bold">Aflibercept</content></paragraph><paragraph styleCode="TableParagraph"><content styleCode="bold">(N=91)</content></paragraph></td><td align="center" styleCode="Botrule Lrule Rrule Toprule"><paragraph styleCode="First TableParagraph"><content styleCode="bold">Control</content></paragraph><paragraph styleCode="TableParagraph"><content styleCode="bold">(N=92)</content></paragraph></td></tr><tr><td styleCode="Botrule Lrule Rrule Toprule"><paragraph styleCode="First TableParagraph">Eye pain</paragraph></td><td align="center" styleCode="Botrule Lrule Rrule Toprule"><paragraph styleCode="First TableParagraph">13%</paragraph></td><td align="center" styleCode="Botrule Lrule Rrule Toprule"><paragraph styleCode="First TableParagraph">5%</paragraph></td><td align="center" styleCode="Botrule Lrule Rrule Toprule"><paragraph styleCode="First TableParagraph">4%</paragraph></td><td align="center" styleCode="Botrule Lrule Rrule Toprule"><paragraph styleCode="First TableParagraph">5%</paragraph></td></tr><tr><td styleCode="Botrule Lrule Rrule Toprule"><paragraph styleCode="First TableParagraph">Conjunctival hemorrhage</paragraph></td><td align="center" styleCode="Botrule Lrule Rrule Toprule"><paragraph styleCode="First TableParagraph">12%</paragraph></td><td align="center" styleCode="Botrule Lrule Rrule Toprule"><paragraph styleCode="First TableParagraph">11%</paragraph></td><td align="center" styleCode="Botrule Lrule Rrule Toprule"><paragraph styleCode="First TableParagraph">20%</paragraph></td><td align="center" styleCode="Botrule Lrule Rrule Toprule"><paragraph styleCode="First TableParagraph">4%</paragraph></td></tr><tr><td styleCode="Botrule Lrule Rrule Toprule"><paragraph styleCode="First TableParagraph">Intraocular pressure increased</paragraph></td><td align="center" styleCode="Botrule Lrule Rrule Toprule"><paragraph styleCode="First TableParagraph">8%</paragraph></td><td align="center" styleCode="Botrule Lrule Rrule Toprule"><paragraph styleCode="First TableParagraph">6%</paragraph></td><td align="center" styleCode="Botrule Lrule Rrule Toprule"><paragraph styleCode="First TableParagraph">2%</paragraph></td><td align="center" styleCode="Botrule Lrule Rrule Toprule"><paragraph styleCode="First TableParagraph">0%</paragraph></td></tr><tr><td styleCode="Botrule Lrule Rrule Toprule"><paragraph styleCode="First TableParagraph">Corneal epithelium defect</paragraph></td><td align="center" styleCode="Botrule Lrule Rrule Toprule"><paragraph styleCode="First TableParagraph">5%</paragraph></td><td align="center" styleCode="Botrule Lrule Rrule Toprule"><paragraph styleCode="First TableParagraph">4%</paragraph></td><td align="center" styleCode="Botrule Lrule Rrule Toprule"><paragraph styleCode="First TableParagraph">2%</paragraph></td><td align="center" styleCode="Botrule Lrule Rrule Toprule"><paragraph styleCode="First TableParagraph">0%</paragraph></td></tr><tr><td styleCode="Botrule Lrule Rrule Toprule"><paragraph styleCode="First TableParagraph">Vitreous floaters</paragraph></td><td align="center" styleCode="Botrule Lrule Rrule Toprule"><paragraph styleCode="First TableParagraph">5%</paragraph></td><td align="center" styleCode="Botrule Lrule Rrule Toprule"><paragraph styleCode="First TableParagraph">1%</paragraph></td><td align="center" styleCode="Botrule Lrule Rrule Toprule"><paragraph styleCode="First TableParagraph">1%</paragraph></td><td align="center" styleCode="Botrule Lrule Rrule Toprule"><paragraph styleCode="First TableParagraph">0%</paragraph></td></tr><tr><td styleCode="Botrule Lrule Rrule Toprule"><paragraph styleCode="First TableParagraph">Ocular hyperemia</paragraph></td><td align="center" styleCode="Botrule Lrule Rrule Toprule"><paragraph styleCode="First TableParagraph">5%</paragraph></td><td align="center" styleCode="Botrule Lrule Rrule Toprule"><paragraph styleCode="First TableParagraph">3%</paragraph></td><td align="center" styleCode="Botrule Lrule Rrule Toprule"><paragraph styleCode="First TableParagraph">2%</paragraph></td><td align="center" styleCode="Botrule Lrule Rrule Toprule"><paragraph styleCode="First TableParagraph">2%</paragraph></td></tr><tr><td styleCode="Botrule Lrule Rrule Toprule"><paragraph styleCode="First TableParagraph">Foreign body sensation in eyes</paragraph></td><td align="center" styleCode="Botrule Lrule Rrule Toprule"><paragraph styleCode="First TableParagraph">3%</paragraph></td><td align="center" styleCode="Botrule Lrule Rrule Toprule"><paragraph styleCode="First TableParagraph">5%</paragraph></td><td align="center" styleCode="Botrule Lrule Rrule Toprule"><paragraph styleCode="First TableParagraph">3%</paragraph></td><td align="center" styleCode="Botrule Lrule Rrule Toprule"><paragraph styleCode="First TableParagraph">0%</paragraph></td></tr><tr><td styleCode="Botrule Lrule Rrule Toprule"><paragraph styleCode="First TableParagraph">Vitreous detachment</paragraph></td><td align="center" styleCode="Botrule Lrule Rrule Toprule"><paragraph styleCode="First TableParagraph">3%</paragraph></td><td align="center" styleCode="Botrule Lrule Rrule Toprule"><paragraph styleCode="First TableParagraph">4%</paragraph></td><td align="center" styleCode="Botrule Lrule Rrule Toprule"><paragraph styleCode="First TableParagraph">2%</paragraph></td><td align="center" styleCode="Botrule Lrule Rrule Toprule"><paragraph styleCode="First TableParagraph">0%</paragraph></td></tr><tr><td styleCode="Botrule Lrule Rrule Toprule"><paragraph styleCode="First TableParagraph">Lacrimation increased</paragraph></td><td align="center" styleCode="Botrule Lrule Rrule Toprule"><paragraph styleCode="First TableParagraph">3%</paragraph></td><td align="center" styleCode="Botrule Lrule Rrule Toprule"><paragraph styleCode="First TableParagraph">4%</paragraph></td><td align="center" styleCode="Botrule Lrule Rrule Toprule"><paragraph styleCode="First TableParagraph">3%</paragraph></td><td align="center" styleCode="Botrule Lrule Rrule Toprule"><paragraph styleCode="First TableParagraph">0%</paragraph></td></tr><tr><td styleCode="Botrule Lrule Rrule Toprule"><paragraph styleCode="First TableParagraph">Injection site pain</paragraph></td><td align="center" styleCode="Botrule Lrule Rrule Toprule"><paragraph styleCode="First TableParagraph">3%</paragraph></td><td align="center" styleCode="Botrule Lrule Rrule Toprule"><paragraph styleCode="First TableParagraph">1%</paragraph></td><td align="center" styleCode="Botrule Lrule Rrule Toprule"><paragraph styleCode="First TableParagraph">1%</paragraph></td><td align="center" styleCode="Botrule Lrule Rrule Toprule"><paragraph styleCode="First TableParagraph">0%</paragraph></td></tr><tr><td styleCode="Botrule Lrule Rrule Toprule"><paragraph styleCode="First TableParagraph">Vision blurred</paragraph></td><td align="center" styleCode="Botrule Lrule Rrule Toprule"><paragraph styleCode="First TableParagraph">1%</paragraph></td><td align="center" styleCode="Botrule Lrule Rrule Toprule"><paragraph styleCode="First TableParagraph">&lt;1%</paragraph></td><td align="center" styleCode="Botrule Lrule Rrule Toprule"><paragraph styleCode="First TableParagraph">1%</paragraph></td><td align="center" styleCode="Botrule Lrule Rrule Toprule"><paragraph styleCode="First TableParagraph">1%</paragraph></td></tr><tr><td styleCode="Botrule Lrule Rrule Toprule"><paragraph styleCode="First TableParagraph">Intraocular inflammation</paragraph></td><td align="center" styleCode="Botrule Lrule Rrule Toprule"><paragraph styleCode="First TableParagraph">1%</paragraph></td><td align="center" styleCode="Botrule Lrule Rrule Toprule"><paragraph styleCode="First TableParagraph">1%</paragraph></td><td align="center" styleCode="Botrule Lrule Rrule Toprule"><paragraph styleCode="First TableParagraph">0%</paragraph></td><td align="center" styleCode="Botrule Lrule Rrule Toprule"><paragraph styleCode="First TableParagraph">0%</paragraph></td></tr><tr><td styleCode="Botrule Lrule Rrule Toprule"><paragraph styleCode="First TableParagraph">Cataract</paragraph></td><td align="center" styleCode="Botrule Lrule Rrule Toprule"><paragraph styleCode="First TableParagraph">&lt;1%</paragraph></td><td align="center" styleCode="Botrule Lrule Rrule Toprule"><paragraph styleCode="First TableParagraph">1%</paragraph></td><td align="center" styleCode="Botrule Lrule Rrule Toprule"><paragraph styleCode="First TableParagraph">5%</paragraph></td><td align="center" styleCode="Botrule Lrule Rrule Toprule"><paragraph styleCode="First TableParagraph">0%</paragraph></td></tr><tr><td styleCode="Botrule Lrule Rrule Toprule"><paragraph styleCode="First TableParagraph">Eyelid edema</paragraph></td><td align="center" styleCode="Botrule Lrule Rrule Toprule"><paragraph styleCode="First TableParagraph">&lt;1%</paragraph></td><td align="center" styleCode="Botrule Lrule Rrule Toprule"><paragraph styleCode="First TableParagraph">1%</paragraph></td><td align="center" styleCode="Botrule Lrule Rrule Toprule"><paragraph styleCode="First TableParagraph">1%</paragraph></td><td align="center" styleCode="Botrule Lrule Rrule Toprule"><paragraph styleCode="First TableParagraph">0%</paragraph></td></tr></tbody></table>

<table width="98%" border="1" cellspacing="0" cellpadding="0" styleCode="TableNormal1"><col width="32%"/><col width="17%"/><col width="17%"/><col width="17%"/><col width="17%"/><tbody><tr><td styleCode="Botrule Lrule Rrule Toprule"><paragraph styleCode="First TableParagraph"><content styleCode="bold">Adverse Reactions</content></paragraph></td><td colspan="2" align="center" styleCode="Botrule Lrule Rrule Toprule"><paragraph styleCode="First TableParagraph"><content styleCode="bold">Baseline to Week 52</content></paragraph></td><td colspan="2" align="center" styleCode="Botrule Lrule Rrule Toprule"><paragraph styleCode="First TableParagraph"><content styleCode="bold">Baseline to Week 100</content></paragraph></td></tr><tr><td align="center" styleCode="Botrule Lrule Rrule Toprule" valign="top"/><td align="center" styleCode="Botrule Lrule Rrule Toprule"><paragraph styleCode="First TableParagraph"><content styleCode="bold">Aflibercept (N=578)</content></paragraph></td><td align="center" styleCode="Botrule Lrule Rrule Toprule"><paragraph styleCode="First TableParagraph"><content styleCode="bold">Control</content></paragraph><paragraph styleCode="TableParagraph"><content styleCode="bold">(N=287)</content></paragraph></td><td align="center" styleCode="Botrule Lrule Rrule Toprule"><paragraph styleCode="First TableParagraph"><content styleCode="bold">Aflibercept (N=578)</content></paragraph></td><td align="center" styleCode="Botrule Lrule Rrule Toprule"><paragraph styleCode="First TableParagraph"><content styleCode="bold">Control</content></paragraph><paragraph styleCode="TableParagraph"><content styleCode="bold">(N=287)</content></paragraph></td></tr><tr><td styleCode="Botrule Lrule Rrule Toprule"><paragraph styleCode="First TableParagraph">Conjunctival hemorrhage</paragraph></td><td align="center" styleCode="Botrule Lrule Rrule Toprule"><paragraph styleCode="First TableParagraph">28%</paragraph></td><td align="center" styleCode="Botrule Lrule Rrule Toprule"><paragraph styleCode="First TableParagraph">17%</paragraph></td><td align="center" styleCode="Botrule Lrule Rrule Toprule"><paragraph styleCode="First TableParagraph">31%</paragraph></td><td align="center" styleCode="Botrule Lrule Rrule Toprule"><paragraph styleCode="First TableParagraph">21%</paragraph></td></tr><tr><td styleCode="Botrule Lrule Rrule Toprule"><paragraph styleCode="First TableParagraph">Eye pain</paragraph></td><td align="center" styleCode="Botrule Lrule Rrule Toprule"><paragraph styleCode="First TableParagraph">9%</paragraph></td><td align="center" styleCode="Botrule Lrule Rrule Toprule"><paragraph styleCode="First TableParagraph">6%</paragraph></td><td align="center" styleCode="Botrule Lrule Rrule Toprule"><paragraph styleCode="First TableParagraph">11%</paragraph></td><td align="center" styleCode="Botrule Lrule Rrule Toprule"><paragraph styleCode="First TableParagraph">9%</paragraph></td></tr><tr><td styleCode="Botrule Lrule Rrule Toprule"><paragraph styleCode="First TableParagraph">Cataract</paragraph></td><td align="center" styleCode="Botrule Lrule Rrule Toprule"><paragraph styleCode="First TableParagraph">8%</paragraph></td><td align="center" styleCode="Botrule Lrule Rrule Toprule"><paragraph styleCode="First TableParagraph">9%</paragraph></td><td align="center" styleCode="Botrule Lrule Rrule Toprule"><paragraph styleCode="First TableParagraph">19%</paragraph></td><td align="center" styleCode="Botrule Lrule Rrule Toprule"><paragraph styleCode="First TableParagraph">17%</paragraph></td></tr><tr><td styleCode="Botrule Lrule Rrule Toprule"><paragraph styleCode="First TableParagraph">Vitreous floaters</paragraph></td><td align="center" styleCode="Botrule Lrule Rrule Toprule"><paragraph styleCode="First TableParagraph">6%</paragraph></td><td align="center" styleCode="Botrule Lrule Rrule Toprule"><paragraph styleCode="First TableParagraph">3%</paragraph></td><td align="center" styleCode="Botrule Lrule Rrule Toprule"><paragraph styleCode="First TableParagraph">8%</paragraph></td><td align="center" styleCode="Botrule Lrule Rrule Toprule"><paragraph styleCode="First TableParagraph">6%</paragraph></td></tr><tr><td styleCode="Botrule Lrule Rrule Toprule"><paragraph styleCode="First TableParagraph">Corneal epithelium defect</paragraph></td><td align="center" styleCode="Botrule Lrule Rrule Toprule"><paragraph styleCode="First TableParagraph">5%</paragraph></td><td align="center" styleCode="Botrule Lrule Rrule Toprule"><paragraph styleCode="First TableParagraph">3%</paragraph></td><td align="center" styleCode="Botrule Lrule Rrule Toprule"><paragraph styleCode="First TableParagraph">7%</paragraph></td><td align="center" styleCode="Botrule Lrule Rrule Toprule"><paragraph styleCode="First TableParagraph">5%</paragraph></td></tr><tr><td styleCode="Botrule Lrule Rrule Toprule"><paragraph styleCode="First TableParagraph">Intraocular pressure increased</paragraph></td><td align="center" styleCode="Botrule Lrule Rrule Toprule"><paragraph styleCode="First TableParagraph">5%</paragraph></td><td align="center" styleCode="Botrule Lrule Rrule Toprule"><paragraph styleCode="First TableParagraph">3%</paragraph></td><td align="center" styleCode="Botrule Lrule Rrule Toprule"><paragraph styleCode="First TableParagraph">9%</paragraph></td><td align="center" styleCode="Botrule Lrule Rrule Toprule"><paragraph styleCode="First TableParagraph">5%</paragraph></td></tr><tr><td styleCode="Botrule Lrule Rrule Toprule"><paragraph styleCode="First TableParagraph">Ocular hyperemia</paragraph></td><td align="center" styleCode="Botrule Lrule Rrule Toprule"><paragraph styleCode="First TableParagraph">5%</paragraph></td><td align="center" styleCode="Botrule Lrule Rrule Toprule"><paragraph styleCode="First TableParagraph">6%</paragraph></td><td align="center" styleCode="Botrule Lrule Rrule Toprule"><paragraph styleCode="First TableParagraph">5%</paragraph></td><td align="center" styleCode="Botrule Lrule Rrule Toprule"><paragraph styleCode="First TableParagraph">6%</paragraph></td></tr><tr><td styleCode="Botrule Lrule Rrule Toprule"><paragraph styleCode="First TableParagraph">Vitreous detachment</paragraph></td><td align="center" styleCode="Botrule Lrule Rrule Toprule"><paragraph styleCode="First TableParagraph">3%</paragraph></td><td align="center" styleCode="Botrule Lrule Rrule Toprule"><paragraph styleCode="First TableParagraph">3%</paragraph></td><td align="center" styleCode="Botrule Lrule Rrule Toprule"><paragraph styleCode="First TableParagraph">8%</paragraph></td><td align="center" styleCode="Botrule Lrule Rrule Toprule"><paragraph styleCode="First TableParagraph">6%</paragraph></td></tr><tr><td styleCode="Botrule Lrule Rrule Toprule"><paragraph styleCode="First TableParagraph">Foreign body sensation in eyes</paragraph></td><td align="center" styleCode="Botrule Lrule Rrule Toprule"><paragraph styleCode="First TableParagraph">3%</paragraph></td><td align="center" styleCode="Botrule Lrule Rrule Toprule"><paragraph styleCode="First TableParagraph">3%</paragraph></td><td align="center" styleCode="Botrule Lrule Rrule Toprule"><paragraph styleCode="First TableParagraph">3%</paragraph></td><td align="center" styleCode="Botrule Lrule Rrule Toprule"><paragraph styleCode="First TableParagraph">3%</paragraph></td></tr><tr><td styleCode="Botrule Lrule Rrule Toprule"><paragraph styleCode="First TableParagraph">Lacrimation increased</paragraph></td><td align="center" styleCode="Botrule Lrule Rrule Toprule"><paragraph styleCode="First TableParagraph">3%</paragraph></td><td align="center" styleCode="Botrule Lrule Rrule Toprule"><paragraph styleCode="First TableParagraph">2%</paragraph></td><td align="center" styleCode="Botrule Lrule Rrule Toprule"><paragraph styleCode="First TableParagraph">4%</paragraph></td><td align="center" styleCode="Botrule Lrule Rrule Toprule"><paragraph styleCode="First TableParagraph">2%</paragraph></td></tr><tr><td styleCode="Botrule Lrule Rrule Toprule"><paragraph styleCode="First TableParagraph">Vision blurred</paragraph></td><td align="center" styleCode="Botrule Lrule Rrule Toprule"><paragraph styleCode="First TableParagraph">2%</paragraph></td><td align="center" styleCode="Botrule Lrule Rrule Toprule"><paragraph styleCode="First TableParagraph">2%</paragraph></td><td align="center" styleCode="Botrule Lrule Rrule Toprule"><paragraph styleCode="First TableParagraph">3%</paragraph></td><td align="center" styleCode="Botrule Lrule Rrule Toprule"><paragraph styleCode="First TableParagraph">4%</paragraph></td></tr><tr><td styleCode="Botrule Lrule Rrule Toprule"><paragraph styleCode="First TableParagraph">Intraocular inflammation</paragraph></td><td align="center" styleCode="Botrule Lrule Rrule Toprule"><paragraph styleCode="First TableParagraph">2%</paragraph></td><td align="center" styleCode="Botrule Lrule Rrule Toprule"><paragraph styleCode="First TableParagraph">&lt;1%</paragraph></td><td align="center" styleCode="Botrule Lrule Rrule Toprule"><paragraph styleCode="First TableParagraph">3%</paragraph></td><td align="center" styleCode="Botrule Lrule Rrule Toprule"><paragraph styleCode="First TableParagraph">1%</paragraph></td></tr><tr><td styleCode="Botrule Lrule Rrule Toprule"><paragraph styleCode="First TableParagraph">Injection site pain</paragraph></td><td align="center" styleCode="Botrule Lrule Rrule Toprule"><paragraph styleCode="First TableParagraph">2%</paragraph></td><td align="center" styleCode="Botrule Lrule Rrule Toprule"><paragraph styleCode="First TableParagraph">&lt;1%</paragraph></td><td align="center" styleCode="Botrule Lrule Rrule Toprule"><paragraph styleCode="First TableParagraph">2%</paragraph></td><td align="center" styleCode="Botrule Lrule Rrule Toprule"><paragraph styleCode="First TableParagraph">&lt;1%</paragraph></td></tr><tr><td styleCode="Botrule Lrule Rrule Toprule"><paragraph styleCode="First TableParagraph">Eyelid edema</paragraph></td><td align="center" styleCode="Botrule Lrule Rrule Toprule"><paragraph styleCode="First TableParagraph">&lt;1%</paragraph></td><td align="center" styleCode="Botrule Lrule Rrule Toprule"><paragraph styleCode="First TableParagraph">1%</paragraph></td><td align="center" styleCode="Botrule Lrule Rrule Toprule"><paragraph styleCode="First TableParagraph">2%</paragraph></td><td align="center" styleCode="Botrule Lrule Rrule Toprule"><paragraph styleCode="First TableParagraph">1%</paragraph></td></tr></tbody></table>