Survey of intravitreal injection techniques among retina specialists in Israel.

PURPOSE: The purpose of this study was to describe antivascular endothelial growth factor intravitreal injection techniques of retinal specialists in order to establish a cornerstone for future practice guidelines.
METHODS: All members of the Israeli Retina Society were contacted by email to complete an anonymous, 19-question, Internet-based survey regarding their intravitreal injection techniques.
RESULTS: Overall, 66% (52/79) completed the survey. Most (98%) do not instruct patients to discontinue anticoagulant therapy and 92% prescribe treatment for patients in the waiting room. Three quarters wear sterile gloves and prepare the patient in the supine position. A majority (71%) use sterile surgical draping. All respondents apply topical analgesics and a majority (69%) measure the distance from the limbus to the injection site. A minority (21%) displace the conjunctiva prior to injection. A majority of the survey participants use a 30-gauge needle and the most common quadrant for injection is superotemporal (33%). Less than half routinely assess postinjection optic nerve perfusion (44%). A majority (92%) apply prophylactic antibiotics immediately after the injection.
CONCLUSION: The majority of retina specialists perform intravitreal injections similarly. However, a relatively large minority performs this procedure differently. Due to the extremely low percentage of complications, it seems as though such differences do not increase the risk. However, more evidence-based medicine, a cornerstone for practice guidelines, is required in order to identify the intravitreal injection techniques that combine safety and efficacy while causing as little discomfort to the patients as possible.

Introduction

Intravitreal injections have become a widely accepted treatment modality for several ophthalmic diseases.1 In recent years, new indications for the recurring use of anti-vascular endothelial growth factor (anti-VEGF) intravitreal injections have risen.2–5 Despite the potential risks of intravitreal injections,6 there is little agreement among clinicians and researchers regarding acceptable injection techniques.7,8

Attempts have been made to draft recommendations and guidelines for clinicians,9–12 a difficult task considering the scarce amount of high-quality evidence comparing different peri-injection practices.7

The purpose of this study was to describe the personal anti-VEGF intravitreal injection techniques of retinal specialists in Israel.

Materials and methods

All members of the Israeli Retina Society were contacted by email to complete an anonymous, 19-question, Internet-based survey regarding the intravitreal injection techniques they use when injecting anti-VEGF materials (Supplementary material). In November 2013, there were 79 Israeli Retina Society members. All of the physicians listed a unique email address. Therefore, 79 surveys were emailed on November 7, 2013. Three reminder emails were sent to participants in order to maximize the response rate. Study data were collected using an online Google Form and automatically saved to a Google Spreadsheet as previously described.13 Google Inc. (Mountain View, CA, USA) has several web-based services that support data capture for research studies, providing both an intuitive interface for data entry and automated export procedures for data collection.13 All the results were tabulated on November 28, 2013. The ethic committee approval was unnecessary for this study as the questionnaire was conducted via emails.

Results

By November 28, 2013, 52 of 79 retinal specialists (66%) responded to the survey. Ninety percent (47/52) of the respondents perform intravitreal injections on a regular basis. Six of the 52 (12%) work in operating room settings, while the rest work in an outpatient retina clinic.

Preinjection practices

Ninety-eight percent (51/52) of the respondents do not instruct patients to discontinue anticoagulant or antiplatelet therapy. Preinjective treatments prescribed to the patient in the waiting room are depicted in Table 1. Briefly, 92% (48/52) prescribe at least one treatment for patients while they are in the waiting room, with topical anesthetics and mydriatics being the most common treatments. Seventy-nine percent (41/52) of the respondents wear gloves. Among those who wear gloves, 95% (39/41) wear sterile gloves and 5% (2/41) wear clean gloves. Seventy-five percent (39/52) prepare the patient in the supine position, while the rest do so in a sitting position. Table 2 depicts the characteristics of the operating field in which the injections are performed. Briefly, all but one use a speculum and 71% (37/52) use sterile surgical draping.

Table 1

Preinjection treatments prescribed to patients in the waiting room

Treatment	n	%
Topical anesthetics	46/52	88
Mydriatics	24/52	46
Disinfective treatment	19/52	37
Sedative treatment when necessary	1/52	2

Table 2

Characteristics of the operating field in which injections are performed

Characteristic	n	%
Use of speculum	51/52	98
Sterile surgical draping	37/52	71
Surgeon wears surgical mask	19/52	37
Assistant wears surgical mask	15/52	29
Surgeon wears surgical head cover	13/52	25
Assistant wears surgical head cover	7/52	13

Injection practices

All the survey respondents apply topical analgesics in one of the following forms: gel only (8%, 4/52), drops only (25%, 13/52), or both (67%, 35/52). Two respondents (4%) verify that the analgesic effect is sufficient before proceeding to the injection. Sixty-nine percent (36/52) measure the distance from the limbus to the injection site. Among those who measure, 56% use calipers (20/36) and 44% use another device (16/36) such as the plastic cover of a 30-gauge needle (4 mm diameter). Twenty-one percent of the respondents displace the conjunctiva prior to injection (11/52). A majority of the survey participants use a 30-gauge needle for intravitreal injections of anti-VEGF (90%, 47/52); the rest use either a 27-gauge needle (4%, 2/52) or a 31-gauge needle (4%, 2/52). The most common quadrant for injection is the superotemporal (33%, 17/52), followed by the inferotemporal (17%, 9/52), superonasal (6%, 3/52), and inferonasal (4%, 2/52), while the rest (40%, 21/52) stated that they do not prefer a specific quadrant.

Postinjection practices

Less than half of the survey respondents (44%, 23/52) routinely assess postinjection optic nerve perfusion. Among those who assess optic nerve perfusion, 48% (11/23) perform a gross visual acuity examination (finger count or hand motion assessment), 30% (7/23) visualize the optic nerve, and 26% (6/23) measure the intraocular pressure. The majority (73%, 38/52) do not perform an anterior chamber tap in order to prevent a rise in intraocular pressure (IOP), while the rest perform a tap in cases of end-stage glaucoma. Table 3 depicts the postinjection treatments prescribed immediately after the injection. Briefly, 92% (48/52) of the retinal specialists apply some form of prophylactic antibiotics immediately after the injection. A majority (77%, 40/52) apply prophylactic topical antibiotic drops immediately afterward. The majority of physicians do not prescribe prophylactic drops for the patients to continue putting in their eyes at home after receiving the injection. Half of the survey respondents (56%, 26/52) perform bilateral simultaneous intravitreal injections. Of those who do not perform bilateral injections, one half stated that they avoid doing so only in cases of steroidal injections as the chances of endophthalmitis are increased, while the other half stated that the minute chance of bilateral endophthalmitis is unacceptable.

Table 3

Postinjection treatment prescribed immediately after injection

Treatment	n	%
Topical antibiotic drops	40	77
Antibiotic cream	9	17
Topical analgesic drops	7	13
Use of eye patch	6	11.5
Topical treatment to lower intraocular pressure	2	4

Discussion

In this study, we have shown the wide variety of personal intravitreal injection techniques of retina specialists based on a national survey.

The amount of intravitreal injections performed has increased to a point of being second only to cataract surgery as the most common treatment in most tertiary ophthalmic centers. It has been speculated that intravitreal injections of anti-VEGF will become the most common intraocular procedure worldwide.14 Still, despite the attempts made, well-defined guidelines and recommendations based on high-quality evidence have yet to be formulated.9–13 We herein discuss the different practices of retina specialists during the different phases of intravitreal injection (preinjection, injection, and postinjection) and compare the findings to previous reports from other countries.

In this study, all but one of the specialists instructed patients to continue anticoagulant/antiplatelet therapy. Indeed, the risk of hemorrhagic complications following intravitreal injections in such patients is extremely low, while the risk of stopping such therapy carries an increased thromboembolic risk.15 However, different diseases may have different chances of hemorrhagic complications, and therefore, each case should be treated individually. In terms of working in a sterile environment, a majority of the survey participants wear sterile gloves (39/52) for intravitreal injections. In comparison, 33% of medical retina specialists in USA7 reported wearing sterile gloves, while 90% did so in UK.8 The syringe containing bevacizumab is not sterile, as the emphasis is on the tip of the instrument which must remain sterile. Therefore, one may argue against the necessity of sterile gloves. However, one cannot entirely rule out the possibility that injecting without sterile gloves may lead to an increase in the number of infective complications. Preinjection treatment with topical antibiotics or povidone-iodine was used by approximately one-third of the survey respondents (19/52), similar to the survey conducted in USA.7 As repeated use of topical antibiotics increases the antibiotic resistance of the ocular surface flora,16 the habit of routinely instilling antibiotics should be approached with caution.

Similar to previous reports,7,8 nearly two-third of the participants measure the distance of the site of the injection from the limbus (36/52), with a majority of them using calipers (20/36). Previous studies have identified that sclerotomies anterior to 3.5 mm from the limbus may damage the crystalline lens,17 while those posterior to 4.5 mm may damage the peripheral retina inducing a retinal tear and consecutive development of retinal detachment.18 Therefore, precise measurement of the distance of the injection from the limbus is warranted. Only a minority of the participants (21%) reported displacing the conjunctiva prior to injection and a majority used a 30-gauge needle (47/52), a finding that is consistent with those from USA and UK.7,8 Reflux and conjunctival bleb formation is often noted at the intravitreal injection site19 and is a cause for concern among physicians because of the potential loss of drug.20 This has led to several studies evaluating factors that may influence the amount of reflux from intravitreal injections.21–24 Though vitreous prolapse may be observed after intravitreal injection with both 27- and 30-gauge needles,25 27-gauge needles require twice the force to penetrate the sclera than a 30/31-gauge needle,26 potentially leading to more discomfort during intravitreal injections.27 Though most participants in this study stated that they do not prefer a specific quadrant (21/52), the superotemporal one was the most frequent among those who did (17/52). This is interesting, considering a recent report showed that injections in the inferior half may be associated with less pain.28

Less than half of the survey respondents routinely assessed optic nerve perfusion following intravitreal injections (as opposed to three-quarters of their USA counterparts).7 A short-term increase in IOP following intravitreal injections has been well-documented,29 leading some to recommend routine assessment for ischemic optic nerve damage.9 Despite the fact that majority of the respondents did not use prophylactic topical antibiotics in the preinjection phase, an overwhelming majority (92%) did so in the postinjection phase. Despite a recent study reporting higher rates of endophthalmitis when immediate postinjection antibiotics were not instilled,30 others have shown that the addition of preinjection or postinjection topical antibiotics to povidone-iodine antisepsis offers little to no benefit31–33 while leading to the development of resistant strains of bacteria.34

This study had several limitations. First, the response rate was 66%, and therefore, response bias may have played a role in this study. Second, this study surveyed Israeli retina specialists, and therefore, its findings may differ significantly from those for the retina specialists worldwide. Due to good communication between practicing retina specialists in Israel, an impressive amount of versatility exists when performing this relatively “simple” procedure. This may imply a similar versatility in the way specialists from other countries perform this procedure as well as more complex ones. One must take into consideration that not all injection techniques are suitable for every surgeon, and therefore, diversity may, in fact, be required. These differences in techniques must be taken into consideration when performing retrospective studies in order to study the efficacy and safety of intravitreal injections. Finally, more evidence-based medicine, a cornerstone for practice guidelines, is required in order to identify the intravitreal injection techniques that combine safety and efficacy while causing as little discomfort to the patients as possible.

Supplementary material

Questionnaire regarding intravitreal injection of anti-vascular endothelial growth factor (VEGF)

Do you regularly perform intravitreal injections of anti-VEGF?

No

Yes

Do you provide instructions to the patient before they arrive to the clinic for the injection?

No

Yes

Does the patient receive any treatment while waiting to receive the injection?

No

Topical anesthetics

Topical mydriasis

Where do you perform injections?

Office-based clinic

Operating room

How do you position the patient while injecting?

Sitting

Supine

How do you prepare a sterile field before the injection?

Speculum – yes/no

Sterile draping – yes/no

Hair cover for surgeon – yes/no

Mouth cover for surgeon – yes/no

Do you use gloves when performing injections?

No

Regular gloves

Sterile surgical gloves

Which anesthetic do you add before performing the injection?

Topical drops

Topical gel

Both

None

Do you perform a test for sufficient anesthesia before the injection?

No

Yes

How do you measure and mark the distance from the limbus before the injection?

None

Caliper

Another method

At which site do you perform the injection itself?

No specific site

Inferior temporal

Inferior nasal

Superior temporal

Superior nasal

What is the gauge of the needle you use?

Do you displace the conjunctiva before inserting the needle?

No

Yes

How do you verify adequate optic nerve perfusion after the injection?

I do not

Check tonus of the globe

Check visual acuity for finger count

Pulsation of the optic nerve

Do you perform paracentesis of the anterior chamber in order to prevent a rise in intraocular pressure?

I do not as the danger outweighs the benefits

I do in cases of end-stage glaucoma

Do you perform bilateral injections at the same visit?

No

Yes

What treatment do you provide immediately after the injection itself?

Topical antibiotic drops – yes/no

Topical antibiotic ointment – yes/no

Topical anesthetics – yes/no

Dressing eye with bandage – yes/no

Do you prescribe topical antibiotics for use at home afterwards?

No

Yes

Do you have any general comments or ideas that you would like to suggest?