1/18/22, 5:21 AM
`
`Intravitreal Injections - EyeWiki
`
`AMERICAN ACADEMY
`OF OPHTHALMOLOGY®
`
`Protecting Sight. Empowering Lives . EyeWiki®
`
`Intravitreal Injections
`
`Enroll in the Residents and Fellows contest Enroll in the International Ophthalmologists contest
`
`Residents and Fellows contest rules | International Ophthalmologists contest rules
`
`Original article
`contributed by:
`
`All contributors:
`
`Sami Kamjoo, MD
`
`Theodore Leng, MD, MS, Alexander Barash, MD, Koushik Tripathy, MD (AIIMS), FRCS (Glasgow), Jason Hsu, MD, Sami
`Kamjoo, MD, Jennifer I Lim MD
`
`Assigned editor:
`
`Jason Hsu, MD
`
`Review:
`
`Assigned status Update Pending
`
` by Jason Hsu, MD on July 14, 2021.
`
`Intravitreal drug delivery has become the gold standard for treatment of many retinal diseases, including neovascular age-related macular degeneration
`(AMD), diabetic retinopathy, and retinal vein occlusion.  The frequency of intravitreal injections has signicantly increased since the introduction of anti-
`vascular endothelial growth factor (VEGF) medications.  The technique involved in properly performing this procedure is important to master in order to
`optimize patient safety and reduce the risk of complications. 
`Contents
`1 Common Diseases Treated by Intravitreal Injections
`2 Informed Consent and Risks of Intravitreal Injections
`3 Common Intravitreal Medications
`4 Anesthesia
`5 Preparation for Intravitreal Injection
`6 Injection Site
`7 Asepsis
`8 Injection Technique
`9 Post-Injection Care Tips
`10 Bilateral Intravitreal Anti-VEGF Injections
`11 Follow up
`12 Similar safety and efcacy of intravitreal bevacizumab compared to ranibizumab
`13 Additional Resources
`14 References
`
`Common Diseases Treated by Intravitreal Injections
`
`1. Neovascular AMD
`2. DME/NPDR/PDR (diabetic macular edema/non-proliferative diabetic retinopathy/proliferative diabetic retinopathy)
`3. RVO (retinal vein occlusions)
`4. Endophthalmitis
`5. Uveitis
`6. CME (cystoid macular edema)
`7. CNVM (choroidal neovascular membrane) secondary to multiple retinal diseases
`
`Informed Consent and Risks of Intravitreal Injections
`
`Discuss the indications, risks, benets, and alternatives with patients.  Obtain informed consent and have the patient's signature on the consent form
`witnessed. 
`
`The RISKS of intravitreal injections include:
`
`Pain / foreign body sensation / epiphora (possibly due to dry eye, corneal abrasion, infection)
`•
`Bleeding (subconjunctival, vitreous hemorrhage)
`•
`Retinal tear / detachment
`•
`Cataract (from inadvertently hitting the lens)
`•
`Infection (endophthalmitis)
`•
`Uveitis / retinal vasculitis (higher risk with brolucizumab)
`•
`Loss of vision (from any of above)
`•
`Loss of the eye (from a severe infection)
`•
`Increased intraocular pressure with damage to optic nerve (primarily with steroids but may also occur after higher numbers of anti-VEGF injections)
`•
`•
`Need for surgery (to address some of the complications above)
`Stroke/heart attack (with anti-VEGF medications, controversial)
`•
`Off-label use (for bevacizumab, triamcinolone, other medications)
`•
`Need for additional injections in future (patients need to understand this)
`•
`
`The Academy uses cookies to analyze performance and provide relevant personalized content to users of our website. Learn more
`Accept
`.______________I L---1 ____ J
`
`https://eyewiki.aao.org/Intravitreal_Injections
`
`1/5
`
`Novartis Exhibit 2306.001
`Regeneron v. Novartis, IPR2021-00816
`
`

`

`1/18/22, 5:21 AM
`lntravitreal Injections - EyeWiki
`BENEFITS of intravitreal injections depend on the ocular pathology being treated, but typically include improvement in vision or prevention of worsening
`vision (in the case of AMD, DR, RVO). In the case of an infection, the benefit is also direct delivery of the antibiotic/antifungal into the eye close to the nidus of
`the infection.
`
`ALTERNATIVES to intravitreal injections can include observation, surgery (pars plana vitrectomy), or laser treatment (e.g., laser photocoagulation or
`photodynamic therapy) depending on the ocular disease.
`
`Common lntravitreal Medications
`• Bevacizumab (Avastin, off-label) 1.25mg/0.05ml (0.675mg/0.03ml if considering using for treatment of Zone I+ ROP in an infant)
`• Ranibizumab (lucentis) 0.5mg/0.05ml (for neovascular AMD, RVO, myopic CNVM) or 0.3mg/0.05ml (for diabetic retinopathy/DME)
`• Aflibercept (Eylea) 2.0 mg /0.05 ml
`• Brolucizumab (Beovu) 6 mg/0.05 ml
`• Triamcinolone acetonide (Kenalog, off-label) 2mg/0.05ml or 4mg/0.1ml (Triesence/Trivaris is alcohol-free preparation that is FDA-approved for
`intraocular use)
`
`• Ganciclovir 4mg/0.1ml - administer 2 mg in 0.05 ml (twice weekly for cytomegalovirus retinitis for 14 days for induction)
`• Clindamycin 1mg/0.1ml
`• Foscarnet 2.4mg/0.1ml - administer 1.2 mg in 0.05 ml
`• Fomivirsen - 330 micrograms/0.05ml
`• Methotrexate - 400 micrograms/0.1ml
`• Vancomycin 1mg/0.1ml
`• Ceftazidime 2.25mg/0.1ml
`• Amikacin 0.4mg/0.1ml
`• Amphotericin B 5 micrograms/0. lml
`• Voriconazole 50-100 micrograms/0. lml
`• Dexamethasone 0.4mg/0.1ml
`
`Anesthesia
`Topical, subconjunctival, or pledgets are commonly used routes of local anesthesia for in-office intravitreal injections. The choice of anesthetic depends on
`physician preference, and is also dictated by how the patient tolerated prior injections. Retrobulbar block may need to be used for an inflamed eye, such as in
`the case of endophthalmitis requiring a tap and injection. However, subconjunctival anesthetic is usually adequate and less painful than a retrobulbar block in
`an already inflamed eye. An acute inflamed eye is generally a contraindication for intravitreal anti-VEGF injections, especially with brolucizumab.
`
`Several studies have looked at the different anesthetic choices for intravitreal injections. One randomized controlled trial found that topical anesthesia was
`effective for most patients.111 In this study, patients felt the least pain with the actually injection when a subconjunctival anesthetic was given. However,
`patients felt more pain when the actual anesthetic was being administered subconjunctivally. Therefore the collective pain score (anesthesia pain+ intravitreal
`injection pain) was greater for the subconjunctival group compared to the topical group (in which patients had less pain during the administration of the
`anesthetic, but slightly higher pain score during the actual intravitreal injection).
`
`Topical tetracaine or proparacaine eyedrops can be effective. In a similar fashion, pledgets soaked with proparacaine or tetracaine can be placed in the fornix
`and allowed to rest on the globe over the area of planned injection for a short period of time. Another option is to use a gel type anesthetic, such as lidocaine
`2% or 4% jelly or Tetravisc. Some recent reports indicate that the gel may result in trapping of microbes on the ocular surface, so if gel is used it may be best to
`apply betadine before and after the gel is placed. For subconjunctival anesthesia, typically lidocaine 1% or 2% without epinephrine is effective.
`
`Other points to remember:
`
`• Subconjunctival anesthesia has a higher risk of causing subconjunctival hemorrhage
`• Allow adequate time for anesthetic to take effect (can be as fast as 1- 2 minutes for subconj, but would wait longer for topical lidocaine jelly, such as 5 min)
`• If a patient is very nervous or "jumpy" consider a subconjunctival injection so that the injection itself is not felt or minimally felt. Still use topical anesthetics
`prior to performing the subconjunctival injection to minimize discomfort.
`• If using topical anesthesia (since patients feel the injection more), remind them immediately before the injection that they will feel pressure, so that they do
`not move with the unanticipated sensation.
`
`Preparation for I ntravitreal Injection
`• Patient should be at least slightly supine with neck well supported
`• Ensure that the headrest is secure and will not unlock during the injection (as patients have a tendency to get nervous, extending their necks and pushing
`back on the headrest)
`• Close the door and make sure there are no distractions during the injection which could cause the patient to have an ocular saccade
`• Ensure that you have all required instruments before starting, as it is very uncomfortable for patient to wait once Betadine is instilled into the eye
`• Do a surgical "timeout" before the procedure to confirm the correct patient, correct eye, and any allergies. Preferably the timeout should be done with a
`technician or a nurse to help confirm with the patient prior to the procedure.
`
`Injection Site
`• Superotemporally or inferotemporal for ease of access, though any quadrant can be used.
`• Some retina specialists prefer the superotemporal quadrant, since should a complication such as a retinal detachment occur, it can be treated with a
`pneumatic retinopexy. Others prefer the inferior quadrant as patients tend to look up with any squeezing of the lids (Bell's phenomenon).
`
`Asepsis
`• Most important is povidone-iodine 5% solution as it has evidence based data showing risk reduction for endophthalmitis in ocular surgery.
`• Antibiotic use is controversial, and most retina specialists do not pre-treat with antibiotics.121 Historically, post-procedure antibiotics were given for
`approximately 3 days (likely for medico-legal reasons). Several studies have demonstrated that post-injection antibiotics do not reduce the incidence of
`endophthalmitis_l3ll4ll5ll6l More importantly, studies show increased antibiotic resistance with the use of post-procedure antibiotics.171181
`• 5% povidone-iodine solution should be placed on the globe and allowed to sit on the eye for at least 30-60 seconds. One may also use 10% Betadine swabs
`to gently clean the eye and eyelashes. However, 10% Betadine is associated with more corneal toxicity so care should be taken to avoid getting it in the
`
`The Academy uses cookies to analyze performance and provide relevant personalized content to users of our website. !Learn mor, I Accept I
`
`https://eyewiki.aao.org/lntravitreal_lnjections
`
`2/5
`
`Novartis Exhibit 2306.002
`Regeneron v. Novartis, IPR2021-00816
`
`

`

`1/18/22, 5:21 AM
`•
`Gloves are optional. However, patients may feel more comfortable if the surgeon uses gloves.
`•
`Do not talk (or cough or sneeze) while preparing or performing the intravitreal injection as studies suggest that there may be a higher risk of oral ora-
`[9][10][11]
`associated endophthalmitis during intravitreal injections due to talking .
`  If you must talk, turn your head away from the surgical eld and speak
`before uncapping the needle.  
`•
`Consider wearing a mask if there is a need to speak or instruct the patient during the injection as one study suggested that this may yield equivalent
`[12]
`outcomes to a no talking policy with potentially a lower incidence of oral ora-associated endophthalmitis.
` However, if wearing a surgical mask it may
`be best to face the surgical eld as exhalations will exit the mask to the sides and back of the surgical mask.
`
`Intravitreal Injections - EyeWiki
`
`Injection Technique
`
`Many variations in technique exist, and the following is one example:
`
`1. Conrm informed consent obtained
`2. Surgical time-out to conrm correct medication and correct eye
`3. Place patient in near supine position; make sure the headrest of the chair is stable
`4. Topical proparacaine (wait 10-15 seconds before placing povidone-iodine)
`5. 5% povidone-iodine drops; ask patient to blink multiple times to spread the povidone-iodine
`6. If necessary, place 2% lidocaine gel on the eye, focusing on the planned injection quadrant.  (Note:  use povidone-iodine prior to lidocaine gel to sterilize the
`globe prior to placing the gel so as not to have bacteria trapped in the gel and possibly increase risk of endophthalmitis).
`7. Ask patient to close their eyes, and return in 2-5 minutes.
`8. Apply 5% povidone-iodine drops again to planned injection quadrant and inferior cul-de-sac.
`9. Place sterile closed-blade eyelid speculum (be careful not to cause a corneal abrasion) or have an assistant retract both lids. 
`10. Mark the location of injection:  3-3.5mm for pseudophakes, 3.5-4.0 mm for phakic patients.  Tip:  Can use the end of a TB syringe (without needle attached)
`to mark 3.5-4.0 mm.  After marking and causing an indentation with the TB syringe, consider placing 5% povidone-iodine again. It will slightly pool in the
`indentation ring and nicely highlight the injection site. 
`11. Have the patient look away from the injection site.  For example, if injecting the right eye in the superotemporal quadrant, ask the patient to look down and
`to the left. 
`12. Hold syringe in dominant hand, and a cotton-tipped applicator in the non-dominant hand
`13. Do not talk and ask patient not to talk during the injection. Alternatively, wear a mask.  Make sure the needle tip (which is usually a short 30g) is always kept
`absolutely sterile.
`14. Using your dominant hand, rest your wrist or pinky nger on the patient's face (forehead for superior and cheek for inferior injection sites) for hand
`stabilization
`15. Insert the needle at the marked site in a smooth and single motion, aiming for the mid-vitreous cavity
`16. Insert the short 30g needle about 1/2 length in (to make sure you are in the vitreous cavity and not in the suprachoroidal space)
`17. Swing over with your non-dominant hand to push down on the plunger in a smooth fashion.  (Note:  some surgeons prefer to inject with one-hand; the
`author feels that using two hands is more stable).  Do not move the needle while inside the eye so as to not cause traction on the vitreous and potentially
`cause a retinal tear/detachment.
`18. As you remove the needle, cover the injection site with a cotton-tipped applicator that is in your non-dominant hand
`19. Rinse the povidone-iodine out of the patient's eye
`20. Ensure optic nerve perfusion (patient should be at least light perception).  Paracentesis is usually not required unless a large volume of medication is
`injected.  Some physicians prefer to check and document the IOP and do not let the patient leave until the IOP has reduced to an acceptable level. 
`Glaucoma patients may need an anterior chamber paracentesis as their outow may be compromised. Injecting Kenalog or Triesence 0.1cc causes a rapid
`and high IOP and it is not uncommon for patients to be temporarily NLP after the injection.  Warn patients about this.  Tip:  One can try to place pressure
`on the globe (e.g., anesthetic solution on a cotton-tipped applicator at the proposed injection site) to squeeze some aqueous out of the eye and lower the
`IOP prior to injection and possibly prevent transient NLP vision.  
`
`Post-Injection Care Tips
`Make sure to wash off povidone-iodine well so the patient does not have irritation/corneal toxicity
`•
`Reassure patients that they may see oaters which are due to air bubbles or the medication itself (in the case of Kenalog, Triesence, or Dexamethasone
`•
`implant)
`Review endophthalmitis and retinal detachment symptoms and precautions
`•
`Consider a follow-up phone call with patients 3-7 days after the injection
`•
`A one week in-ofce follow-up is at the physician's discretion, but is not typically needed.
`•
`Bilateral Intravitreal Anti-VEGF Injections
`
`Intravitreal injections of anti-VEGF are traditionally given unilaterally. More recently, there has been an increase in the use of these medications in a bilateral
`fashion in patients with pathology in both eyes. Common diseases that may need bilateral injections include diabetic macular edema and neovascular AMD, and
`[13]
`there is evidence that the rate of bilateral involvement increases with the follow-up and disease duration.
` A survey of retina specialists in the US in 2011
`[14]
`found that 46% of retina specialists perform bilateral same-day injections.
` The purpose of bilateral same-day injections is to decrease both physician and
`[15]
`patient burden in terms of ofce visits. In one study, more than 90% of patients strongly preferred bilateral injections to unilateral injections.
` However,
`some physicians will avoid bilateral injections for fear of bilateral endophthalmitis. Other local complications should be considered when administering
`bilateral injections, including inammation/uveitis, raised intraocular pressure, retinal detachment and subretinal hemorrhages. Separate eyedrops, speculum,
`needle, and syringe are typically used for each eye to minimize risks.
`
`There have been several large-scale studies of endophthalmitis in bilateral same-day intravitreal anti-VEGF injections. Overall, bilateral injections appear to
`have a similar safety prole to unilateral injections. The largest study of 101,932 same-day bilateral intravitreal anti-VEGF injections in 5890 patients at a large
`[16]
`academic private practice over 5 years found 28 cases of endophthalmitis (0.027% of total injections) with no cases of bilateral endophthalmitis.
` Other
`[17] [18] [19][20][21]
`similar studies have found the incidence of endophthalmitis from 0-0.01% to 0.065%.
`
`
`
`Follow up
`Depends on the disease being treated and duration of treatment. Early on, patients may require monthly injections and follow-up. Later in the course as the
`•
`disease is stabilized, some advocate extending the interval between injections permitting less frequent injections and follow-up visits.
`
`The Academy uses cookies to analyze performance and provide relevant personalized content to users of our website. Learn more
`
`Accept
`
`https://eyewiki.aao.org/Intravitreal_Injections
`
`3/5
`
`Novartis Exhibit 2306.003
`Regeneron v. Novartis, IPR2021-00816
`
`

`

`1/18/22, 5:21 AM
`
`Intravitreal Injections - EyeWiki
`
`Similar safety and efficacy of intravitreal bevacizumab compared to
`ranibizumab
`
`[22]
`[23]
`[24]
`[25]
`[26]
`Numerous trials (CATT
`, IVAN , GEFAL
`, MANTA , LUCAS
`) conducted worldwide have shown intravitreal bevacizumab to be non-inferior to
`ranibizumab in terms of efcacy and safety in AMD. Bevacizumab has the advantage of signicantly reducing the cost of therapy. However, intravitreal
`bavacizumab injection has not been approved by the Food and Drug Administration (FDA) and the use in the eye is hence 'off label'. All patients need to be
`clearly informed of this when obtaining written consent for intravitreal bevacizumab injection.
`
`Additional Resources
`Video:  Univeristy of Iowa, Intravitreal Injection Technique:  http://video.google.com/videoplay?docid=-4029538953224029219
`•
`Article: Preventing infections: injection technique: http://dx.doi.org/10.4172/2327-5073.1000118
`•
`®
`Boyd K, Janigian RH. Eye Injections (https://www.aao.org/eye-health/treatments/eye-injections-list). American Academy of Ophthalmology. EyeSmart
`•
`Eye health. https://www.aao.org/eye-health/treatments/eye-injections-list. Accessed March 11, 2019.
`
`References
`
`1. Blaha GR, Tilton EP, Barouch FC, Marx JL.Randomized trial of anesthetic
`methods for intravitreal injections. Retina. 2011 Mar;31(3):535-9.
`2. Uhr JH, Xu D, Rahimy E, Hsu J. Current Practice Preferences and Safety
`Protocols for Intravitreal Injection of Anti-Vascular Endothelial Growth
`Factor Agents. Ophthalmol Retina. 2019 Aug;3(8):649-655. doi:
`10.1016/j.oret.2019.03.013. Epub 2019 Mar 22. PMID: 31068264.
`3. Storey P, Dollin M, Pitcher J, Reddy S, Vojtko J, Vander J, Hsu J, Garg SJ;
`Post-Injection Endophthalmitis Study Team. The role of topical antibiotic
`prophylaxis to prevent endophthalmitis after intravitreal injection.
`Ophthalmology. 2014 Jan;121(1):283-289. doi:
`10.1016/j.ophtha.2013.08.037. Epub 2013 Oct 18. PMID: 24144453.
`4. Rumya R. Rao, Golnaz Javey, Philip J. Rosenfeld, William J. Feue. 
`Elimination of Post-Injection Topical Antibiotics after Intravitreal
`Injections.  ARVO May, 2011
`5. Reibaldi M, Pulvirenti A, Avitabile T, Bonglio V, Russo A, Mariotti C,
`Bucolo C, Mastropasqua R, Parisi G, Longo A. POOLED ESTIMATES OF
`INCIDENCE OF ENDOPHTHALMITIS AFTER INTRAVITREAL
`INJECTION OF ANTI-VASCULAR ENDOTHELIAL GROWTH FACTOR
`AGENTS WITH AND WITHOUT TOPICAL ANTIBIOTIC PROPHYLAXIS.
`Retina. 2018 Jan;38(1):1-11. doi: 10.1097/IAE.0000000000001583.
`PMID: 28267115.
`6. Cheung CS, Wong AW, Lui A, Kertes PJ, Devenyi RG, Lam WC. Incidence of
`endophthalmitis and use of antibiotic prophylaxis after intravitreal
`injections. Ophthalmology. 2012 Aug;119(8):1609-14. doi:
`10.1016/j.ophtha.2012.02.014. Epub 2012 Apr 4. PMID: 22480743.
`7. 3. Kim SJ, Toma HS.  Ophthalmic antibiotics and antimicrobial resistance a
`randomized, controlled study of patients undergoing intravitreal
`injections.Ophthalmology. 2011 Jul;118(7):1358-63. Epub 2011 Mar 21.
`8. Storey P, Dollin M, Rayess N, Pitcher J, Reddy S, Vander J, Hsu J, Garg S;
`Post-Injection Endophthalmitis Study Team. The effect of prophylactic
`topical antibiotics on bacterial resistance patterns in endophthalmitis
`following intravitreal injection. Graefes Arch Clin Exp Ophthalmol. 2016
`Feb;254(2):235-42. doi: 10.1007/s00417-015-3035-x. Epub 2015 May 5.
`PMID: 25940556.
`9. Wen JC, McCannel CA, Mochon AB, Garner OB. Bacterial dispersal
`associated with speech in the setting of intravitreous injections. Arch
`Ophthalmol. 2011 Dec;129(12):1551-4. doi:
`10.1001/archophthalmol.2011.227. Epub 2011 Aug 8. PMID: 21825179.
`10. Chen E, Lin MY, Cox J, Brown DM. Endophthalmitis after intravitreal
`injection: the importance of viridans streptococci. Retina. 2011
`Sep;31(8):1525-33. doi: 10.1097/IAE.0b013e318221594a. Erratum in:
`Retina. 2011 Nov;31(10):2139. PMID: 21878800.
`11. Garg SJ, Dollin M, Storey P, Pitcher JD 3rd, Fang-Yen NH, Vander J, Hsu J;
`Post-Injection Endophthalmitis Study Team. MICROBIAL SPECTRUM
`AND OUTCOMES OF ENDOPHTHALMITIS AFTER INTRAVITREAL
`INJECTION VERSUS PARS PLANA VITRECTOMY. Retina. 2016
`Feb;36(2):351-9. doi: 10.1097/IAE.0000000000000694. PMID:
`26200514.
`12. Patel SN, Hsu J, Sivalingam MD, Chiang A, Kaiser RS, Mehta S, Park CH,
`Regillo CD, Sivalingam A, Vander JF, Ho AC, Garg SJ; Wills Post-Injection
`Endophthalmitis (PIE) Study Group. The Impact of Physician Face Mask
`Use on Endophthalmitis After Intravitreal Anti-Vascular Endothelial
`Growth Factor Injections. Am J Ophthalmol. 2020 Sep 2;222:194-201.
`doi: 10.1016/j.ajo.2020.08.013. Epub ahead of print. PMID: 32888902;
`PMCID: PMC7462768.
`
`13. Giocanti-Auregan A, Tadayoni R, Grenet T, et al. Estimation of the need for
`bilateral intravitreal anti-VEGF injections in clinical practice. BMC
`Ophthalmol. 2016;16:142. Published 2016 Aug 9. doi:10.1186/s12886-
`016-0317-y
`14. Survey of intravitreal injection techniques among retinal specialists in the
`United States Am J Ophthalmol, 151 (2) (2011), pp. 329-332).
`15. Mahajan VB, Elkins KA, Russell SR, et al. Bilateral intravitreal injection of
`antivascular endothelial growth factor therapy. Retina. 2011;31(1):31‐35.
`doi:10.1097/IAE.0b013e3181ed8c80
`16. Borkar DS, Obeid A, Su DC, et al. Endophthalmitis Rates after Bilateral
`Same-Day Intravitreal Anti-Vascular Endothelial Growth Factor
`Injections. Am J Ophthalmol. 2018;194:1‐6.
`doi:10.1016/j.ajo.2018.06.022
`17. Juncal VR, Francisconi CLM, Altomare F, et al. Same-Day Bilateral
`Intravitreal Anti-Vascular Endothelial Growth Factor Injections:
`Experience of a Large Canadian Retina Center. Ophthalmologica.
`2019;242(1):1‐7. doi:10.1159/000499115
`18. Ruão M, Andreu-Fenoll M, Dolz-Marco R, Gallego-Pinazo R. Safety of
`bilateral same-day intravitreal injections of anti-vascular endothelial
`growth factor agents. Clin Ophthalmol. 2017;11:299‐302. Published
`2017 Feb 1. doi:10.2147/OPTH.S124282
`19. Chao DL, Gregori NZ, Khandji J, Goldhardt R. Safety of bilateral
`intravitreal injections delivered in a teaching institution. Expert Opin
`Drug Deliv. 2014;11(7):991‐993. doi:10.1517/17425247.2014.909806
`20. Lima LH, Zweifel SA, Engelbert M, et al. Evaluation of safety for bilateral
`same-day intravitreal injections of antivascular endothelial growth factor
`therapy. Retina. 2009;29(9):1213‐1217.
`doi:10.1097/IAE.0b013e3181b32d27
`21. Woo SJ, Han JM, Ahn J, et al. Bilateral same-day intravitreal injections
`using a single vial and molecular bacterial screening for safety
`surveillance. Retina. 2012;32(4):667‐671.
`doi:10.1097/IAE.0b013e31822c296b
`22. Comparison of Age-related Macular Degeneration Treatments Trials
`(CATT) Research Group, Martin DF, Maguire MG, Fine SL, Ying GS, Jaffe
`GJ, Grunwald JE, Toth C, Redford M, Ferris FL 3rd. Ranibizumab and
`bevacizumab for treatment of neovascular age-related macular
`degeneration: two-year results. Ophthalmology. 2012 Jul;119(7):1388-
`98. doi: 10.1016/j.ophtha.2012.03.053. Epub 2012 May 1. PMID:
`22555112; PMCID: PMC3389193.
`23. IVAN Study Investigators, Chakravarthy U, Harding SP, Rogers CA,
`Downes SM, Lotery AJ, Wordsworth S, Reeves BC. Ranibizumab versus
`bevacizumab to treat neovascular age-related macular degeneration: one-
`year ndings from the IVAN randomized trial. Ophthalmology. 2012
`Jul;119(7):1399-411. doi: 10.1016/j.ophtha.2012.04.015. Epub 2012 May
`11. Erratum in: Ophthalmology. 2012 Aug;119(8):1508. Erratum in:
`Ophthalmology. 2013 Sep;120(9):1719. PMID: 22578446.
`24. Kodjikian L, Souied EH, Mimoun G, Mauget-Faÿsse M, Behar-Cohen F,
`Decullier E, Huot L, Aulagner G; GEFAL Study Group. Ranibizumab versus
`Bevacizumab for Neovascular Age-related Macular Degeneration: Results
`from the GEFAL Noninferiority Randomized Trial. Ophthalmology. 2013
`Nov;120(11):2300-9. doi: 10.1016/j.ophtha.2013.06.020. Epub 2013 Aug
`2. PMID: 23916488.
`
`The Academy uses cookies to analyze performance and provide relevant personalized content to users of our website. Learn more
`
`Accept
`
`https://eyewiki.aao.org/Intravitreal_Injections
`
`4/5
`
`Novartis Exhibit 2306.004
`Regeneron v. Novartis, IPR2021-00816
`
`

`

`1/18/22, 5:21 AM
`
`Intravitreal Injections - EyeWiki
`
`25. Krebs I, Schmetterer L, Boltz A, Told R, Vécsei-Marlovits V, Egger S,
`Schönherr U, Haas A, Ansari-Shahrezaei S, Binder S; MANTA Research
`Group. A randomised double-masked trial comparing the visual outcome
`after treatment with ranibizumab or bevacizumab in patients with
`neovascular age-related macular degeneration. Br J Ophthalmol. 2013
`Mar;97(3):266-71. doi: 10.1136/bjophthalmol-2012-302391. Epub 2013
`Jan 3. PMID: 23292928.
`27. Intravitreal Injections, Focal Points, Volume XXVII, Number 8, September 2009.
`
`26. Berg K, Pedersen TR, Sandvik L, Bragadóttir R. Comparison of
`ranibizumab and bevacizumab for neovascular age-related macular
`degeneration according to LUCAS treat-and-extend protocol.
`Ophthalmology. 2015 Jan;122(1):146-52. doi:
`10.1016/j.ophtha.2014.07.041. Epub 2014 Sep 13. PMID: 25227499.
`
`Retrieved from "https://eyewiki.org/w/index.php?title=Intravitreal_Injections&oldid=70830"
`
`This page was ast edited on Ju y 14, 2021, at 06:32.
`
`This page has been accessed 461,838 times.
`
`The Academy uses cookies to analyze performance and provide relevant personalized content to users of our website. Learn more
`
`Accept
`
`https://eyewiki.aao.org/Intravitreal_Injections
`
`5/5
`
`Novartis Exhibit 2306.005
`Regeneron v. Novartis, IPR2021-00816
`
`