Intravitreal Injection for Wet (Exudative) Age-Related Macular Degeneration (AMD)
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Intravitreal injection with anti-vascular endothelial growth factor (anti-VEGF) therapy has become the criterion standard for treatment of choroidal neovascular membranes (CNVs) associated with age-related macular degeneration (AMD or ARMD). [1, 2] Treatment options in wet AMD include bevacizumab (Avastin, Genentech, San Francisco, CA), which is a full-length anti-VEGF antibody, ranibizumab (Lucentis, Genentech), which is an affinity-matured fragment, pegaptanib (Macugen, OSI/Eyetech Inc.), and aflibercept (Eylea, Regeneron, Tarrytown, NY), another anti-VEGF trap. [3, 4, 5] With the exception of bevacizumab, which is used on an off-label basis, all of the other aforementioned drugs are FDA approved for AMD.
The image below illustrates wet age-related macular degeneration.
Absolute contraindications to intravitreal injection are as follows:
Relative contraindications to intravitreal injection are as follows:
Many patients take anti-platelet or anti-coagulant agents. It is not necessary to stop these before injection.
Equipment for intravitreal injection is as follows:
Various sterile packs with required equipment are available.
In many countries, including United States, Canada, and Australia, performing intravitreal injection in a minor procedure room or examination room under sterile conditions is common practice. However, some countries or centers recommend this procedure in an operating room.
Currently, preinjection antibiotics are not used in most cases. The frequency of conjunctival bacterial growth was found to be similar with preinjection povidone-iodine, with or without a 3-day course of topical antibiotic. [8]
Commonly used methods for local anesthesia include the following [9] :
Topical anesthetic drops
Application of cotton swabs soaked in tetracaine or lidocaine
Lidocaine 2% gel
Subconjunctival lidocaine following the instillation of topical anesthetic
Confirm the eye undergoing treatment.
Apply anesthetic of choice.
Instill povidone-iodine solution. The authors use Povidine-iodine 5%. It is applied to the conjunctival sac, lids, and lashes following the instillation of anesthetic. After a few minutes, another drop is instilled over the site. As an alternative to povidone-iodine solution, chlorhexidine may be used. This is useful in patients who have an allergy or intolerance to povidone-iodine. [10]
Insert speculum (see image below). This is optional but prevents the lids from closing during the injection. If no lid speculum is to be used, the location of injection should be the inferior quadrants to reduce the likelihood of the lids touching the needle.
Use the scleral marker to mark the injection site at 3.5 mm for a pseudophakic eye and 4 mm for a phakic eye. The author prefers the superotemporal quadrant, although some protocols describe an inferotemporal approach.
Inject gently into the mid-vitreous. An oblique entry (tunneled approach) may reduce the risk of reflux and aid in the construction of a self-sealing wound. [11] This can be particularly relevant in vitrectomized eyes.
Gently apply the sterile cotton tip to tamponade the injection site following withdrawal of the needle for 10 seconds with a gentle rub. This helps reduce reflux.
Check vision and central retinal artery perfusion.
Flush the eye with lubricants/balance salt solution to remove any residual povidone-iodine to reduce postinjection irritation. Topical antibiotics are optional, although evidence is growing that they are unnecessary and potentially increase the risk of bacterial resistance. [12, 13, 14]
The patient needs to be aware that severe pain, visual loss, or marked hyperemia of the globe requires urgent re-assessment by the ophthalmologist. A mechanism must be in place to allow the patient to contact the treating ophthalmologist or a member of the team urgently after hours.
A recent survey of intravitreal techniques by retinal specialists in the United States found only one third of participants wear sterile gloves for intravitreal injections. [15] Most (83%) did not displace the conjunctiva prior to injection, and most used a 30-gauge needle for injection of ranibizumab or bevacizumab. Although most respondents in this study did not use prophylactic topical antibiotics pre-injection, 81% used topical antibiotics post injection.
Allow sufficient time for the anesthetic to take effect.
Aim to reduce the time between speculum insertion and injection to reduce corneal exposure time. This may reduce the amount of corneal desiccation and epitheliopathy.
Eye washout with normal saline following the procedure may reduce discomfort in patients sensitive to povidone-iodine and/or anesthetic.
Warn patients about subconjunctival hemorrhage, which can otherwise be anxiety provoking.
Reduce the risk of endophthalmitis by wearing a mask or by not speaking during the procedure.
Bilateral injections increase efficiency and convenience to the patient with no apparent risk increase. [16]
Potential complications of intravitreal injection for age-related macular degeneration (AMD) are summarized as follows [6, 17, 18] :
Overview
What is an intravitreal injection for wet (exudative) age-related macular degeneration (AMD)?
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Boyle J, Vukicevic M, Koklanis K, Itsiopoulos C. Experiences of patients undergoing anti-VEGF treatment for neovascular age-related macular degeneration: A systematic review. Psychol Health Med. 2014 Jul 18. 1-15. [Medline].
Pinheiro-Costa J, Freitas-da-Costa P, Falcão MS, Brandão EM, Falcão-Reis F, Carneiro AM. Switch from Intravitreal Ranibizumab to Bevacizumab for the Treatment of Neovascular Age-Related Macular Degeneration: Clinical Comparison. Ophthalmologica. 2014 Aug 29. [Medline].
Gibson JM, Gibson SJ. A safety evaluation of ranibizumab in the treatment of age-related macular degeneration. Expert Opin Drug Saf. 2014 Sep. 13(9):1259-70. [Medline].
Eylea (aflibercept intravitreal) [package insert]. Tarrytown, NY: Regeneron Pharmaceutical, Inc. August, 2018. Available at [Full Text].
Scott IU, Flynn HW Jr. Reducing the risk of endophthalmitis following intravitreal injections. Retina. 2007 Jan. 27(1):10-2. [Medline].
Yamashiro K, Tsujikawa A, Miyamoto K, et al. Sterile endophthalmitis after intravitreal injection of bevacizumab obtained from a single batch. Retina. 2010 Mar. 30(3):485-90. [Medline].
Moss JM, Sanislo SR, Ta CN. A prospective randomized evaluation of topical gatifloxacin on conjunctival flora in patients undergoing intravitreal injections. Ophthalmology. 2009 Aug. 116(8):1498-501. [Medline].
Prenner JL. Anesthesia for intravitreal injection. Retina. 2011 Mar. 31(3):433-4. [Medline].
Merani R, McPherson ZE, Luckie AP, Gilhotra JS, Runciman J, Durkin S, et al. Aqueous Chlorhexidine for Intravitreal Injection Antisepsis: A Case Series and Review of the Literature. Ophthalmology. 2016 Dec. 123 (12):2588-2594. [Medline].
Rodrigues EB, Grumann A, Penha FM, et al. Effect of needle type and injection technique on pain level and vitreal reflux in intravitreal injection. J Ocul Pharmacol Ther. 2011 Apr. 27(2):197-203. [Medline].
Bhavsar AR, Googe JM Jr, Stockdale CR, et al. Risk of endophthalmitis after intravitreal drug injection when topical antibiotics are not required: the diabetic retinopathy clinical research network laser-ranibizumab-triamcinolone clinical trials. Arch Ophthalmol. 2009 Dec. 127(12):1581-3. [Medline]. [Full Text].
Dave SB, Toma HS, Kim SJ. Changes in ocular flora in eyes exposed to ophthalmic antibiotics. Ophthalmology. 2013 May. 120 (5):937-41. [Medline].
Yin VT, Weisbrod DJ, Eng KT, Schwartz C, Kohly R, Mandelcorn E, et al. Antibiotic resistance of ocular surface flora with repeated use of a topical antibiotic after intravitreal injection. JAMA Ophthalmol. 2013 Apr. 131 (4):456-61. [Medline].
Green-Simms AE, Ekdawi NS, Bakri SJ. Survey of intravitreal injection techniques among retinal specialists in the United States. Am J Ophthalmol. 2011 Feb. 151(2):329-32. [Medline].
Chao DL, Gregori NZ, Khandji J, Goldhardt R. Safety of bilateral intravitreal injections delivered in a teaching institution. Expert Opin Drug Deliv. 2014 Jul. 11 (7):991-3. [Medline].
Yamashiro K, Tsujikawa A, Miyamoto K, et al. Sterile endophthalmitis after intravitreal injection of bevacizumab obtained from a single batch. Retina. 2010 Mar. 30(3):485-90. [Medline].
Sampat KM, Garg SJ. Complications of intravitreal injections. Curr Opin Ophthalmol. 2010 May. 21(3):178-83. [Medline].
Csaky K, Do DV. Safety implications of vascular endothelial growth factor blockade for subjects receiving intravitreal anti-vascular endothelial growth factor therapies. Am J Ophthalmol. 2009 Nov. 148(5):647-56. [Medline].
US Food and Drug Administration. FDA alerts health care professionals of infection risk from repackaged Avastin intravitreal injections. Available at http://www.fda.gov/Drugs/DrugSafety/ucm270296.htm. Accessed: August 31, 2011.
David T Wong, MD, FRCSC Associate Professor of Ophthalmology and Vision Sciences, Department of Ophthalmology and Vision Sciences, University of Toronto Faculty of Medicine; Ophthalmologist-in-Chief, St Michael’s Hospital, Canada
David T Wong, MD, FRCSC is a member of the following medical societies: Alpha Omega Alpha, American Academy of Ophthalmology, American Society of Retina Specialists, Association for Research in Vision and Ophthalmology, Canadian Medical Association, Canadian Ophthalmological Society, College of Physicians and Surgeons of Ontario, Ontario Medical Association, Royal College of Physicians and Surgeons of Canada
Disclosure: Serve(d) as a speaker or a member of a speakers bureau for: Novartis, Alcon, Bayer<br/>Received research grant from: Novartis, Alcon, Bayer, Genetech<br/>Received consulting fee from Alcon for consulting; Received consulting fee from Novartis for consulting; Received consulting fee from Bayer for consulting; Received consulting fee from Allergan for consulting; Received consulting fee from B & L for consulting.
Andrew A Dahl, MD, FACS Assistant Professor of Surgery (Ophthalmology), New York College of Medicine (NYCOM); Director of Residency Ophthalmology Training, The Institute for Family Health and Mid-Hudson Family Practice Residency Program; Staff Ophthalmologist, Telluride Medical Center
Andrew A Dahl, MD, FACS is a member of the following medical societies: American Academy of Ophthalmology, American College of Surgeons, American Intraocular Lens Society, American Medical Association, American Society of Cataract and Refractive Surgery, Contact Lens Association of Ophthalmologists, Medical Society of the State of New York, New York State Ophthalmological Society, Outpatient Ophthalmic Surgery Society
Disclosure: Nothing to disclose.
Intravitreal Injection for Wet (Exudative) Age-Related Macular Degeneration (AMD)
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