Survey of Intravitreal Injection Techniques Among
`Retinal Specialists in the United States
`
`AMY E. GREEN-SIMMS, NOHA S. EKDAWI, AND SOPHIE J. BAKRI
`
`● PURPOSE: To describe the intravitreal injection tech-
`nique practice patterns of retinal specialists in the United
`States from April 8, 2010 to April 21, 2010.
`● DESIGN: Questionnaire survey.
`● METHODS: All members of the American Academy of
`Ophthalmology who self-categorized as “Retinal/Vitre-
`ous Surgery” were contacted by e-mail to complete an
`anonymous, 20-question, internet-based survey.
`● RESULTS: A total of 765 retinal specialists (44%)
`responded to the survey. Most respondents wear gloves
`(58%) and use an eyelid speculum (92%) when per-
`forming an intravitreal injection. More than 99% use
`povidone-iodine preinjection. The majority measure
`the injection site from the limbus (56%) and inject
`straight into the vitreous cavity (96%). Most do not
`displace the conjunctiva (83%). Seventy-two percent
`routinely assess postinjection optic nerve perfusion,
`primarily by gross visual acuity measurement (32%).
`While nearly one third of participants use prophylactic
`topical antibiotics preinjection, more than two thirds
`use topical antibiotics postinjection. Forty-six percent
`perform bilateral simultaneous intravitreal injections.
`The majority of respondents use a 30-gauge needle for
`the injection of ranibizumab (78%) and bevacizumab
`(60%). However, respondents use both a 27- and
`30-gauge needle for the injection of triamcinolone
`acetonide.
`● CONCLUSIONS: Retinal specialists in the United States
`participate in a range of techniques for the care before,
`during, and after intravitreal injections. Further study is
`needed to elucidate best practice patterns.
`(Am J Oph-
`thalmol 2011;151:329 –332. © 2011 by Elsevier Inc.
`All rights reserved.)
`
`D ESPITE THE WIDESPREAD ACCEPTANCE OF INTRA-
`
`vitreal injections for the treatment of a variety of
`ocular diseases, there is no current consensus
`upon injection technique or preinjection or postinjection
`care. Serious adverse effects of intravitreal injection in-
`clude endophthalmitis, retinal detachment, ocular hyper-
`tension, and cataract.1–5 With the increasing occurrence
`of patients receiving bilateral simultaneous injections,
`
`Accepted for publication Aug 25, 2010.
`From the Department of Ophthalmology, Mayo Clinic, Rochester,
`Minnesota.
`Inquiries to Sophie J. Bakri, Department of Ophthalmology, Mayo
`Clinic, 200 First Street SW, Rochester, MN 55905; e-mail: bakri.sophie@
`mayo.edu
`
`there remains a need to evaluate best practice pattern
`techniques to increase patient safety.6 There have been
`reports summarizing the risks of intravitreal injections1
`and describing guidelines based on current best evidence
`and practice.7–12 However, few elements regarding in-
`travitreal
`injection technique or peri-injection care
`stem from evidence-based medicine. This study aims to
`describe the intravitreal injection practice patterns of
`retinal specialists in the United States from April 8,
`2010 to April 21, 2010.
`
`METHODS
`
`ALL MEMBERS OF THE AMERICAN ACADEMY OF OPHTHAL-
`mology (AAO) who self-categorized as “Retina/Vitreous
`Surgery” were contacted by e-mail to complete an anony-
`mous, 20-question, internet-based survey. In March 2010,
`there were 2058 AAO members who self-categorized as
`“Retina/Vitreous Surgery.” Among those physicians, 253
`did not list an e-mail address. Seventeen e-mail addresses
`were recorded for more than 1 physician. Therefore, 1788
`surveys were e-mailed on April 8, 2010. Sixty-eight e-mails
`were returned to sender as the addresses were no longer
`valid. This study, therefore, included 1720 total survey
`participants. Three reminder e-mails were sent to partici-
`pants who had not yet completed the survey. Study data
`were collected and managed using REDCap electronic data
`capture tools hosted at the Mayo Clinic. REDCap (Re-
`search Electronic Data Capture) is a secure, web-based
`application designed to support data capture for research
`studies, providing: 1) an intuitive interface for validated
`data entry; 2) audit trails for tracking data manipulation;
`and 3) automated export procedures for seamless data
`downloads to common statistical packages. Results were
`tabulated on April 21, 2010.
`
`RESULTS
`
`BY APRIL 21, 2010, 765 OF 1720 RETINAL SPECIALISTS (44%)
`responded to the survey. Among participants, 279 (37%)
`worked in a retina-only group practice, 225 (29%) worked
`in a multispecialty group practice, 126 (16%) worked in a
`solo practice, 109 (14%) worked in a university setting, 19
`(2%) worked in a combination of the above settings, and
`6 (1%) described their setting as “other.” The participants
`
`0002-9394/$36.00
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`
`© 2011 BY ELSEVIER INC. ALL RIGHTS RESERVED.
`
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`were nearly evenly divided in terms of length of time
`practicing, after the completion of a retina/vitreous fellow-
`ship. Twenty-four percent (180/761) have practiced be-
`tween 1 and 7 years post-fellowship, 26% (196/761) have
`practiced between 8 and 15 years post-fellowship, 28%
`(216/761) have practiced between 16 and 25 years post-
`fellowship, and 22% (169/761) have practiced for over 25
`years since fellowship completion. Sixty-seven percent of
`respondents (513/762) performed 10 to 50 intravitreal
`injections per week. Eighteen percent (138/762) per-
`formed 0 to 10 injections per week, and 15% (111/762)
`performed ⬎50 injections per week.
`
`● PREINJECTION CONSIDERATIONS: Fifty-eight percent
`(439/762) of respondents don gloves to perform an intra-
`vitreal injection. Among those who wear gloves, 58%
`(254/439) wear sterile gloves and 42% (185/439) wear
`clean gloves. The majority of respondents do not use a
`sterile drape (88%; 668/759), yet do use an eyelid speculum
`(92%; 700/760). Nearly all respondents use povidone-
`iodine preinjection (758/761). One third of retinal special-
`ists use prophylactic topical antibiotics either
`for a
`multiday course preinjection or immediately prior to an
`injection (34%; 257/758).
`
`● INJECTION TECHNIQUE: Approximately half of the
`survey respondents (56%; 424/762) measure the distance
`from the limbus to the injection site. Among those who
`measure, 66% use calipers (280/424), 28% use a tuberculin
`syringe (119/424), and 6% use another device (25/424).
`Few respondents displace the conjunctiva prior to injec-
`tion (17%; 129/761) or tunnel the needle during injection
`(4%; 33/758). Among the 59% of participants (448/757)
`who consider the speed of the jet of fluid they inject, a
`majority (76%; 340/448) inject quickly. A majority of
`survey participants use a 30-gauge needle for the intravit-
`real injection of ranibizumab (Lucentis; Genentech, South
`San Francisco, California; USA) and bevacizumab (Avas-
`tin; Genentech) (78%; 581/745 and 60%; 455/759 respec-
`tively). Most respondents use a 27-gauge needle for the
`intravitreal injection of triamcinolone acetonide (Kena-
`log) (57%; 418/738). A similar amount of retinal special-
`ists use a 27-gauge vs a 30-gauge needle for the injection of
`triamcinolone acetonide (Triesence) (43%; 301/697 and
`44%; 310/697 respectively).
`
`● POSTINJECTION CONSIDERATIONS: Nearly three quarters
`of the survey respondents routinely assess postinjection optic
`nerve perfusion (72%; 546/759). Among those who assess
`optic nerve perfusion, 32% (176/546) perform a gross visual
`acuity examination (finger count or hand motion assess-
`ment), 21% (116/546) visualize the optic nerve, 15% (83/
`546) measure the intraocular pressure, and 31% (171/546)
`use a combination of the above techniques. A majority of
`retinal specialists (81%; 608/753) use prophylactic topical
`antibiotics postinjection. Nearly half of the survey respon-
`
`dents (46%; 348/763) perform bilateral simultaneous in-
`travitreal injections.
`
`DISCUSSION
`
`THE INTRAVITREAL INJECTION OF MEDICATION HAS
`gained tremendous acceptance among retinal specialists for
`the treatment of a number of conditions including age-
`related macular degeneration, diabetic retinopathy, and
`macular edema. Variations, however, remain on injection
`technique and preinjection and postinjection care. We
`report upon a survey of techniques employed by retinal
`specialists across the United States from April 8, 2010 to
`April 21, 2010.
`
`study finds
`● PREINJECTION CONSIDERATIONS: This
`that one third of survey participants (33%; 254/762) wear
`sterile gloves for intravitreal injections. In comparison,
`90% of medical retina specialists and 85% of vitreoretinal
`specialists surveyed in the United Kingdom in 2004 reported
`wearing sterile gloves.10 Bhavsar and associates recently
`reported a low rate of endophthalmitis among patients en-
`rolled in the Diabetic Retinopathy Clinical Research Net-
`work Laser-Ranibizumab-Triamcinolone (DRCR Network
`LRT) clinical trials, whereupon the study protocol did not
`mandate sterile gloves.13 Since the syringe containing the
`drug may not be sterile, it is therefore not necessary to use
`sterile gloves, as long as the tip of any instrument touching
`the eye remains sterile.
`Preinjection treatment with topical antibiotics was used
`by approximately one third of survey respondents. Moss
`and associates recently reported that the frequency of
`conjunctival bacterial growth was similar with a preinjec-
`tion povidone-iodine cleaning either with or without a
`3-day course of topical antibiotic.14 With the increasing
`frequency of injections given per patient per year, physi-
`cians should be aware of the risk of inducing antibiotic
`resistance. In addition, despite preinjection antibiotics and
`povidone-iodine preparation, studies have reported rare
`bacterial contamination of intravitreal injection needle
`points.15,16
`
`● INJECTION TECHNIQUE: In order to measure the site of
`the injection from the limbus, 66% of study respondents
`used calipers, 28% used a tuberculin syringe, and 6% used
`another method. Nearly half (44%) of participants, how-
`ever, used no method of measurement to ensure an
`injection through the pars plana. Large study protocols
`have specified that intravitreal injections are to be made in
`the inferotemporal quadrant 3.5 to 4 mm from the lim-
`bus.17 There remains an increased risk of retinal detach-
`ment with a more posterior approach and an increased risk
`of traumatic cataract formation with a more anterior
`approach. There is also a risk of hemorrhage if the needle
`penetrates the ciliary body.
`
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`Most survey respondents (83%) did not displace the
`conjunctiva prior to injection. There have been several
`studies, however, examining the construction of wound
`entry for maximal vitreal retention of medication. Ro-
`drigues and associates reported that a tunneled scleral
`incision, performed by inserting the needle in a 30-degree
`angle parallel to the limbus with a subsequent perpendic-
`ular repositioning halfway during scleral insertion, resulted
`in significantly less subconjunctival reflux of medication as
`measured by width of the postinjection subconjunctival
`bleb.18 In their study, however, needle gauge was not re-
`ported. Upward mobilization of the conjunctiva was per-
`formed before the straight injection technique; no mention of
`conjunctival manipulation was reported before tunneled in-
`cisions. Lopez-Guajardo and associates similarly reported a
`significant reduction in intravitreal drug loss after an oblique
`injection technique.19 After grasping limbal conjunctiva to
`stabilize the globe, a 27-gauge needle was inserted at a 30- to
`40-degree angle to the scleral plane and aimed equatorially
`towards the six-o’clock position. Thirty minutes after injec-
`tion, a significantly smaller subconjunctival bleb as measured
`by ultrasound biomicroscopy was found in eyes that were
`injected at an oblique angle vs a straight injection. Other
`techniques to reduce drug reflux include holding a sterile
`cotton-tipped applicator over the injection site for a period of
`seconds.
`A majority of participants in this study reported using a
`30-gauge needle for the intravitreal
`injection of both
`ranibizumab and bevacizumab. There was less of a consen-
`sus among retinal specialists, however, in the injection
`technique of triamcinolone acetonide. Both 27-gauge and
`30-gauge needles were used with frequency for the injec-
`tion of Kenalog and Triesence. The use of a larger-
`diameter needle likely relates to steroid drug preparation
`in which particles may clog a finer needle. Our survey
`did not specifically poll retinal specialists regarding
`needle choice for medications prepared by compounding
`pharmacies. Chen and associates report that vitreous
`prolapse was observed after intravitreal injection with
`both 27- and 30-gauge needles.20 Furthermore, Pulido
`and associates
`report
`that 27-gauge needles
`require
`almost twice the force to penetrate the sclera as 30- or
`31-gauge needles, which require a similar force for
`scleral penetration.21 This has implications for patient
`comfort during intravitreal injections; a 31-gauge needle
`may induce less pain.22
`Our survey reports that a majority of retinal specialists
`consider the speed with which they inject medication into
`
`the vitreous cavity. Among those who consciously manipu-
`late the syringe plunger, most inject quickly. In Aiello and
`associates’ guidelines for intravitreal injection, they recom-
`mend a “moderately slow injection” to reduce excessive drug
`dispersion in the vitreous cavity and to prevent the needle
`from displacing off of the syringe.7 Peyman and associates
`report using a slow technique to “avoid jet formation or
`cavitary flow.”23 In addition, there is a theoretical risk of
`causing a retinal break with a fast injection of fluid (especially
`through a larger-bore needle).
`
`● POSTINJECTION CONSIDERATIONS: Nearly three quarters
`of survey respondents routinely assessed optic nerve perfu-
`sion after intravitreal injection. We did not specifically
`survey if retinal specialists alter their practice based on
`volume of fluid injected. Several reports have charac-
`terized a short-term increase in intraocular pressure
`(IOP) after intravitreal injection, with pressures return-
`ing to baseline after a maximum of 30 minutes.24 –28 These
`studies were performed using straight injection techniques.
`Knecht and associates compared changes in IOP with
`straight and tunneled intravitreal injections.29 They re-
`ported no significant difference in IOP 5 minutes postin-
`jection, even though the tunneled injection sites had
`significantly less vitreal reflux. Aiello and associates
`recommend monitoring IOP and checking for perfusion
`of the optic nerve postinjection to assess for ischemic
`optic nerve damage.7 It should also be noted that reports
`exist of persistent intraocular pressure elevation follow-
`ing even a single injection of ranibizumab30 or triam-
`cinolone acetonide.31
`While a majority of respondents in this study did not use
`prophylactic topical antibiotics preinjection, 81% used
`topical antibiotics postinjection. A recent analysis of the
`participants of the DRCR Network LRT trials, where
`topical antibiotic use was not part of the protocol for
`intravitreal
`injections, reported a low rate of endoph-
`thalmitis.13 However, reports of the development of en-
`dophthalmitis do remain.32,33 Topical antibiotics should
`be used no more than 3 days postinjection to limit drug
`resistance in the community.7
`Limitations of this study include a survey response rate
`of 44%. Bias may be introduced depending on the partic-
`ipants who chose to reply. Despite our limitations, we are
`able to report current practice variations in the United
`States regarding intravitreal injection techniques among
`retinal specialists.
`
`PUBLICATION OF THIS ARTICLE WAS SUPPORTED BY FUNDING RECEIVED FROM RESEARCH TO PREVENT BLINDNESS, NEW YORK,
`New York, USA. The Center for Translational Science Activities, Bethesda, Maryland, USA, provided grant support (NIH/NCRR CTSA UL1 RR024150).
`Sophie J. Bakri receives grant support from Regeneron - VIEW 1 trial, NEI - CATT trial, and NEI - AREDS 2 trial. Sophie J. Bakri discloses financial
`relationships (consulting fees or paid advisory boards) with Allergan and Genentech. Involved in design of the study (A.G., N.E., S.B.); conduct of the study
`and collection and management of data (A.G.); analysis and interpretation of data (A.G., S.B.); and preparation (A.G.), review, and approval of manuscript
`(A.G., N.E., S.B.). This study received Mayo Clinic IRB approval.
`
`VOL. 151, NO. 2
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`SURVEY OF INTRAVITREAL INJECTION TECHNIQUES
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