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Wet Macular Degeneration Injection

  • Author: David T Wong, MD, FRCSC; Chief Editor: Hampton Roy, Sr, MD  more...
 
Updated: Apr 04, 2016
 

Overview

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 (ARMD).[1, 2] Treatment options in wet ARMD 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 sodium (Macugen, OSI/Eyetech Inc.), and aflibercept (Eylea, Regeneron, Tarrytown, NY), another anti-VEGF trap.[3, 4] With the exception of bevacizumab, which is used on an off-label basis, all of the other aforementioned drugs are FDA approved for ARMD.

The image below illustrates wet age-related macular degeneration.

Wet age-related macular degeneration (ARMD). Wet age-related macular degeneration (ARMD).
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Contraindications

Absolute contraindications are as follows:

  • Active blepharitis or external ocular surface infection is an absolute contraindication for intravitreal injections. These conditions should be treated appropriately first. [5]

Relative contraindications are as follows:

  • History of significant acute inflammation related to the agent injected. [6]
  • Recent history of adverse thromboembolic event such as stroke.

Many patients take anti-platelet or anti-coagulant agents. It is not necessary to stop these before injection.

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Equipment

Equipment is as follows:

  • Povidine/iodine 5% and/or 10%
  • Speculum
  • Scleral marker (calipers)
  • Tuberculin syringe
  • 30- or 32-gauge needle (27-gauge for triamcinolone)
  • Cotton swab
  • Sterile gloves (optional)
  • Sterile drape (optional)
  • Mask (optional)

Various sterile packs with required equipment are available.

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Preparation

In many countries, including United States, Canada, and Australia, performing this procedure 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.[7]  

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Anesthesia

Commonly used methods for local anesthesia include the following[8] :

  • Topical anesthetic drops
  • Application of cotton swabs soaked in tetracaine or lidocaine
  • Lidocaine 2% gel
  • Subconjunctival lidocaine following the instillation of topical anesthetic
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Technique

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, a further drop is instilled over the site.

Insert speculum (see image below).

After a subconjunctival injection of lidocaine 1% After a subconjunctival injection of lidocaine 1% and topical anesthesia, a lid speculum is placed. A 5% povidone iodine solution is used to clean the conjunctival surface.

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.[9] 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.[10, 11, 12]

The patient needs to be aware that severe pain, visual loss, or injection 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.[13] 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.

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Pearls

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 Povidine-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.[14]

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Complications

Complications are summarized as follows[5, 15, 16] :

  • Endophthalmitis: In recent multicenter clinical trials of anti-VEGF therapy, the incidence of endophthalmitis has ranged from 0.7% to 1.6%. Non-infectious (sterile) endophthalmitis occurs in response to anti-VEGF.
  • Retinal detachment: This complication is rare. ANCHOR and MARINA demonstrated a 0.01% per-injection detachment rate.
  • Cataract
  • Transient raised IOP and possible progression of glaucoma damage in susceptible eyes
  • Hypotony
  • Adverse thromboembolic events [17]
  • Infection: The FDA issued a safety alert regarding repackaged intravitreal injections of bevacizumab (Avastin), an anti-VEGF antibody. Serious eye infections caused by Streptococcus endophthalmitis have been reported in 12 patients who received the injections. The infections were the result of contamination that occurred during the repackaging of bevacizumab from 100 mg/4 mL single-use, preservative-free vials into individual 1-mL syringes for off-label use to treat wet macular degeneration. [18]
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Contributor Information and Disclosures
Author

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<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.

Chief Editor

Hampton Roy, Sr, MD Associate Clinical Professor, Department of Ophthalmology, University of Arkansas for Medical Sciences

Hampton Roy, Sr, MD is a member of the following medical societies: American Academy of Ophthalmology, American College of Surgeons, Pan-American Association of Ophthalmology

Disclosure: Nothing to disclose.

References
  1. Barthelmes D, Walton R, Campain AE, Simpson JM, Arnold JJ, McAllister IL, et al. Outcomes of persistently active neovascular age-related macular degeneration treated with VEGF inhibitors: observational study data. Br J Ophthalmol. 2014 Sep 23. [Medline].

  2. 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].

  3. 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].

  4. 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].

  5. Scott IU, Flynn HW Jr. Reducing the risk of endophthalmitis following intravitreal injections. Retina. 2007 Jan. 27(1):10-2. [Medline].

  6. 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].

  7. 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].

  8. Prenner JL. Anesthesia for intravitreal injection. Retina. 2011 Mar. 31(3):433-4. [Medline].

  9. 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].

  10. 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].

  11. Dave SB, Toma HS, Kim SJ. Changes in ocular flora in eyes exposed to ophthalmic antibiotics. Ophthalmology. 2013 May. 120 (5):937-41. [Medline].

  12. 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].

  13. 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].

  14. 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].

  15. 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].

  16. Sampat KM, Garg SJ. Complications of intravitreal injections. Curr Opin Ophthalmol. 2010 May. 21(3):178-83. [Medline].

  17. 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].

  18. 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.

 
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After a subconjunctival injection of lidocaine 1% and topical anesthesia, a lid speculum is placed. A 5% povidone iodine solution is used to clean the conjunctival surface.
Wet age-related macular degeneration (ARMD).
 
 
 
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