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Home , Ocular ischemic syndrome

4/12/21

INTRAVITREAL INJECTIONS

Marcus Altman, MD PGY3, Casey Eye Institute OAO 2021

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OBJECTIVES

• Understand indications for use of intravitreal injections in common ophthalmic conditions

• List two classes of medications used for intravitreal injections and their basic mechanisms of action

• Discuss a general technique/procedure for administering intravitreal injections, and their potential risks/complications

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INTRAVITREAL INJECTIONS

• accounted for ~11% of total Medicare Part B spending among medical specialties in 2017 • >4 million injections performed in the U.S. in 2013

• 96% performed for retinal vascular diseases

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INTRAVITREAL INJECTIONS

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ANTI-VEGF AGENTS

• Anti-vascular endothelial growth factor (anti-VEGF) agents

• Bevacizumab (Avastin) • Ranibizumab (Lucentis) • Aflibercept (Eyelea)

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ANTI-VEGF INDICATIONS

• Wet/exudative age-related • —proliferative and diabetic • Retinal vein occlusion

• Neovascularization related to other conditions – ocular ischemic syndrome, radiation retinopathy, /inflammatory disease, myopic choroidal neovascularization, etc

Hanna et al 2019 6

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ANTI-VEGF INDICATIONS

• Neovascularization related to: • Wet/exudative age-related macular degeneration • Proliferative • Retinal vein occlusion

• Other: high , uveitis/inflammatory disease, ocular ischemic syndrome, etc • Macular edema related to: • Diabetes • Retinal vein occlusion

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ANTI-VEGF AGENTS

• Wet/exudative age-related macular degeneration

• Diabetes—proliferative retinopathy and diabetic macular edema • Retinal vein occlusion

• Neovascularization related to other conditions – ocular ischemic syndrome, radiation retinopathy, uveitis/inflammatory disease, myopic choroidal neovascularization, etc

Baumal et al 2020, AJMC 8

Holekamp 2019 9

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NEOVASCULARIZATION

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AGE-RELATED MACULAR DEGENERATION

Non-exudative (“Dry”) AMD

BCSC 11

AGE-RELATED MACULAR DEGENERATION

Non-exudative (“Dry”) AMD

BCSC Retina 12

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AGE-RELATED MACULAR DEGENERATION

Exudative (“Wet”) AMD

BCSC Retina 13

WET AGE-RELATED MACULAR DEGENERATION

Solomon et al 2019 14

TREATMENT APPROACHES

• Treat and extend (T&E)

• As needed (PRN)

Arai et al 2020 15

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DIABETIC RETINOPATHY

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NONPROLIFERATIVE DIABETIC RETINOPATHY

The Retinal Atlas 17

PROLIFERATIVE DIABETIC RETINOPATHY

VEGF

Complications: -Tractional -Vitreous hemorrhage The Retinal Atlas -Neovascular 18

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PROLIFERATIVE DIABETIC RETINOPATHY - TREATMENT

Pan-retinal photocoagulation Anti-VEGF

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PROLIFERATIVE DIABETIC RETINOPATHY - TREATMENT

Diabetic Retinopathy Clinical Research Network (DRCR.net) studies

BCSC Retina 20

RETINAL VEIN OCCLUSION

Branch retinal vein occlusion (BRVO) Central retinal vein occlusion (CRVO)

The Retinal Atlas 21

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RETINAL VEIN OCCLUSION WITH NEOVASCULARIZATION

Neovascularization

VEGF

The Retinal Atlas 22

RETINAL VEIN OCCLUSION WITH NEOVASCULARIZATION - TREATMENT

Pan-retinal photocoagulation Anti-VEGF

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MACULAR EDEMA

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MACULAR EDEMA

• Diabetes – nonproliferative or proliferative • Retinal vein occlusion

BCSC Retina The Retinal Atlas 25

MACULAR EDEMA – ANTI-VEGF TREATMENT

Diabetes - DRCR.net Protocol I Retinal vein occlusion – BRAVO (A) and CRUISE (B) BCSC Retina; Gerding et al 2015 26

INTRAVITREAL STEROIDS

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INTRAVITREAL STEROIDS

• Triamcinolone acetonide (Triescence) • Dexamethasone pellet (Ozurdex)

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INTRAVITREAL STEROIDS - INDICATIONS

• Macular edema related to: • Diabetes

• Retinal vein occlusion Triam cinolone • Uveitis comparable to ranibizumab specifically in pseudophakic patients

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Doshi et al 2011 30

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TECHNIQUE FOR INTRAVITREAL INJECTIONS

• Anesthesia • To p ic a l p ro p a r a c a in e • Subconjunctival lidocaine • /lash retraction • Lid-speculum, cotton-tip applicator, bimanual • Sterilization • 5% povidone-iodine; ideally waiting 60- 90 seconds after application to inject • Face-mask and/or no-talk policy should be used – possible contamination of oral flora • Injection • 3-4mm posterior to the corneal limbus BCSC Retina 31

Chaturvedi et al 2019 32

COMPLICATIONS OF INTRAVITREAL INJECTIONS

• Subconjunctival hemorrhage - ~11% incidence • Local irritation – good irrigation after to remove betadine! • Increased intraocular pressure – acute and chronic • Vitreous hemorrhage • Retinal detachment • – 0.02-0.2% incidence • 5% betadine • Consider mask and/or no-talk technique

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COMPLICATIONS OF INTRAVITREAL INJECTIONS

• Subconjunctival hemorrhage - ~11% incidence Anti-VEGF agents • Local irritation – good irrigation after to remove betadine! • Thromboembolic events such as heart attack and • Increased intraocular pressure – acute and chronic when used systemically; • Vitreous hemorrhage theoretical risk with intravitreal injections • Retinal detachment • Endophthalmitis – 0.02-0.2% incidence Steroid agents • Increased intraocular pressure, • 5% betadine glaucoma • Consider mask and/or no-talk technique •

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SUMMARY

• Many indications and uses for intravitreal agents, particularly anti-VEGF agents

• Practices vary for injection technique, but goal is to maximize patient comfort and reduce risk of complications, particularly endophthalmitis

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REFERENCES

• Colin A. McCannel, MD. 2020-2021 Basic and Clinical Science Course, Section 12: Retina and Vitreous. American Academy of Ophthalmology, 2020.

• H. Nida Sen, MD. 2020-2021 Basic and Clinical Science Course, Section 9: Uveitis and Ocular Inflammation. American Academy of Ophthalmology, 2020.

• The Retinal Atlas - Yannuzzi

• Williams GA. IVT Injections: Health Policy Implications, 2014

• Medicare Part B Drugs: Trends in Spending and Utilization, 202006-2017; ASPE Office of Health Policy

• “Liposomes and nanotechnology in drug development: Focus on ocular targets” Honda et al 2013; Int J Nanomedicine 8:495-503

• “W et Age-Related Macular Degeneration: Treatment Advances to Reduce the Injection Burden” Baumal 2020; The American Journal of Managed Care

• “Review of Age-Related Macular Degeneration Treatment Options” Holekamp 2019; The American Journal of Managed Care

• “Nephrotoxicity induced by intravitreal vascular endothelial growth factor inhibitors: emerging evidence” Hanna et al 2019; Kidney International 96:572-580

• “Anti-vascular endothelial growth factor for neovascular age-related macular degeneration (Review)” Solomon et al 2019; Cochrane Database of Systematic Reviews

• “Efficacy of Modified Treat-and-Extend Aflibercept Regimen for Macular Edema Due to Branch Retinal Vein Occlusion: 1-Year Prospective Study” Arai et al 2020; Journal of Clinical Medicine

• “Ranibizumab in retinal vein occlusion: treatment recommendations by an expert panel” Gerding et al 2015; Br J Ophthalmol 99:297-304

• ”Intravitreal injection technique” Doshi et al 2011; Seminars in Ophthalmology 26(3) 104-113

• ”Real-World Trends in Intravitreal Injection Practices among American Retina Specialists” Chaturvedi et al 2019; Ophthalmology Retina 3(8);656-662

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