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How to Give Intravitreal Injections

by michelle e. wilson, bs, and adrienne w. scott, md edited by ingrid u. scott, md, mph, and sharon fekrat, md

ntravitreal injection enables hemorrhage, sustained ocular hyper- highly targeted drug therapy, tension, and hypotony.1 maximizing therapeutic drug Of all postinjection complications, delivery to the posterior pole has greatest potential while minimizing systemic to be visually devastating. According Itoxicity. With the increasing use of to studies assessing the safety profile intravitreal anti-VEGF agents in the of intravitreal injection, the rate of en- treatment of neovascular age-related dophthalmitis has been found to be as (AMD), dia- low as 0.05 percent per injection.2 betic , retinal vein Contraindications. Active external occlusion, and various other retinal eye infection (including conjuncti- vascular disorders, intravitreal injec- vitis, meibomianitis, and significant tion has become the most common blepharitis) is a contraindication to ophthalmic procedure performed in intravitreal injection and should be the United States. treated prior to injection.3 Glaucoma is This review offers practical guid- common among patients requiring in- PATIENT PREP. The patient should be ance for the delivery of intravitreal travitreal injection and is not a contra- instructed to direct his gaze away from injections based on published, peer- indication to therapy despite the tran- the site of needle entry. reviewed literature, and expert consen- sient rise in (IOP) sus where evidence is lacking. that may occur following injection. show no significant difference in injec- Despite the theoretical increased risk tion-related pain with the use of topi- Overview of intraocular hemorrhage in patients cal drops, subconjunctival anesthesia, Background and indications. Intra- on long-term anticoagulation who or topical gel. There is some vitreal injection was first described receive intravitreal injection, that risk concern that viscous anesthetic gel in 1911 with the use of an air bubble has not been substantiated in studies. may prevent adequate sterilization of to tamponade a . the ocular surface. (Kenalog) Preinjection Risk Management Povidone-iodine. Povidone-iodine became the first intravitreal agent We recommend the following steps: is the only agent shown to decrease with widespread application, used as a 1) Apply a topical anesthetic; 2) apply bacterial colonization as well as the treatment for macular edema associ- 5 percent or 10 percent povidone- risk of endophthalmitis. Application ated with a variety of etiologies, such iodine drops and/or periocular povi- of povidone-iodine to the conjunctival as and retinal vein done-iodine eyelid preparation; 3) in- surface, eyelids, and lashes is recom- occlusion. It also was used as an ad- sert a sterile speculum to separate the mended prior to introducing the sterile junct to photodynamic therapy in the lids; and 4) reapply povidone-iodine speculum. (The speculum prevents treatment of choroidal neovasculariza- immediately over the injection site the needle tip from touching the lids tion (CNV) related to AMD. prior to injection. or lashes prior to needle insertion.) Potential complications. These Local anesthetic. Nearly all injec- Studies have found that a 5 percent include intraocular , tions are performed with local anes- povidone-iodine solution is as effec- retinal detachment or perforation, thesia, with topical anesthetic drops tive as 10 percent and is less irritating

Natalie Loyacano, COMT, ROUB, OSA, OCS traumatic lens damage, intraocular employed most commonly. Studies to the eye. There is controversy as to

eyenet 45 Ophthalmic Pearls whether using drops or a flush is more cinolone acetonide and 30-gauge nee- perimental evidence suggests insuf- effective. We recommend reapplication dles commonly used for the anti-VEGF ficient penetration into the vitreous of povidone-iodine immediately over agents , , to prevent infection. There is also an the injection site prior to injection. and . Studies suggest that increase in resistant bacterial strains . The use of preinjection smaller, sharper needles require less with repeated use. antibiotics is controversial. There is force for penetration and result in less IOP measurement. Postinjection evidence showing decreased coloniza- drug reflux. Some physicians have IOP may be measured, especially tion of the ocular surface with the use begun using 31-gauge needles (the size for patients who have glaucoma, of preinjection antibiotics, particularly commonly used by diabetic patients to who are receiving large injection vol- in conjunction with povidone-iodine; test blood sugar and inject insulin), as umes, or who complain of pain or however, there is no evidence to sug- smaller needle size may decrease pa- reduced vision. Some guidelines rec- gest that the use of preinjection anti- tient discomfort. ommend a funduscopic examination biotics actually decreases the risk of Needle length between 0.5 and after each injection to assess central endophthalmitis. Moreover, repeat 0.62 inches (12.7 to 15.75 mm) is rec- retinal artery perfusion and identify injections are associated with more ommended, as longer needles may injection-related hemorrhage or retinal resistant flora. increase risk of retinal injury if the detachment. Instead, many physicians Using a face mask. The use of a patient accidentally moves forward employ functional tests such as a de- face mask for the injecting physician, during the procedure. termination of at least counting fingers injection assistants, and the patient is Injection site. The patient should vision or assessment of absence of light not currently considered standard of be instructed to direct his or her gaze perception. care.4 However, recovery of common away from the site of needle entry (Fig. Central retinal artery occlusion is respiratory flora from vitreous culture 1). The injection is placed 3 to 3.5 mm indicated by the absence of light per- aspirates in patients diagnosed with posterior to the limbus for an aphakic ception. In this case, paracentesis is in- endophthalmitis after intravitreal or pseudophakic eye, and 3.5 to 4 mm dicated in an attempt to restore central injection strongly supports efforts to posterior to the limbus for a phakic retinal artery perfusion immediately. minimize talking, coughing, or sneez- eye. Injection in the inferotemporal Vision is typically recovered quickly ing during the injection procedure.5 quadrant is common, although any after decreasing IOP with rapid para- Bilateral injections. For bilateral quadrant may be used. centesis. Routine pre- or postinjection injections, we recommend separate Sterile ophthalmic calipers or the paracentesis is not recommended for preparation of each eye. Separate in- hub of a sterile tuberculin syringe may standard 0.05 mL intravitreal injec- struments and medication vials should be used to mark the injection site and tions. be used for each eye to decrease the risk to verify that adequate anesthesia has Complications. Transient, mild of potential bilateral contamination. been achieved. elevations of IOP are common, al- IOP rise. A transient, volume-relat- Injection technique. Some guide- though IOP usually drops below 30 ed rise in IOP is common following in- lines suggest pulling the mmHg 15 to 20 minutes postinjection jection. There is no evidence to suggest over the injection site with forceps or a and returns to within 4 to 5 mmHg that prophylactic IOP-lowering agents sterile cotton swab to create a steplike of baseline after 30 minutes. IOP nor- are effective in preventing the post­ entry path. While this approach may, malization may take slightly longer in injection volume-mediated IOP spike, in theory, decrease reflux and risk of patients with glaucoma. and their use is not recommended. infection, a straight injection path is As noted above, endophthalmitis is most commonly employed.6 the most feared complication of intra- Peri-injection Risk Management After the sclera is penetrated, the vitreal injection, because of the poten- Injection volume. An injection volume needle is advanced toward the center tial for severe vision loss. of 0.05 mL is most commonly used. of the globe and the solution is gently If postinjection endophthalmitis is The maximum safe volume to inject injected into the midvitreous cavity. suspected, recommended management without preinjection paracentesis is The needle is removed, and a sterile includes immediate vitreous tap (for believed to be 0.1 mL to 0.2 mL. Larger cotton swab is immediately placed over culture) and injection of intravitreal injection volumes are uncommon, the injection site to prevent reflux. antibiotics ( 1 mg/0.1 mL with two exceptions: the injection of and 2.25 mg/0.1 mL). Ur- gas for pneumatic retinopexy and the Postinjection Risk Management gent vitrectomy may be considered. injection of multiple intravitreal agents Antibiotics. These are used by many Pseudoendophthalmitis is a sterile in one session. physicians postinjection and often inflammatory reaction that does not Needle selection. Needle size varies consist of a fourth-generation fluoro- involve true microbial infection. This according to the substance injected, quinolone. However, as with preinjec- has been reported most commonly with 27-gauge needles often used for tion antibiotics, there is no evidence following injection of triamcinolone crystalline substances such as triam- showing clinical benefit of use. Ex- acetonide and bevacizumab. Unlike

46 april 2013 true endophthalmitis, pseudoendo- phthalmitis occurs earlier, typically within one day of injection, and often subsides without specific treatment. Follow-up. After the injection, all patients should be provided with information regarding the signs and symptoms of complications, such as eye pain or discomfort, redness, pho- tophobia, and diminished vision. Pa- tients should be instructed to contact the physician’s office immediately if symptoms develop.

NOTE: For a slideshow of images illustrating the steps outlined in this article, go to www. eyenet.org. It will be available in mid-April.

1 Jager RD et al. . 2004;24(5):676-698. 2 Bhavsar AR et al. Am J Ophthalmol. 2007; 144(3):454-456. 3 Aiello LP et al. Retina. 2004;24(5 suppl): S3-S19. 4 Schimel AM et al. Arch Ophthalmol. 2011; 129(12):1607-1609. 5 McCannel CA. Retina. 2011;31(4):654-661. 6 Knecht PB et al. Retina. 2009;29(3):1175- 1181.

Ms. Wilson is a medical student and research assistant, and Dr. Scott is assistant professor of ; both are at the Wilmer Eye Institute. The authors report no related finan- cial interests.

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