Best Practice Intravitreal injections in a safe and

sustainable way
Author: Project Group Sustainable Ophthalmology, Redmer van Leeuwen

Approved by the Working Group on Medical Retina and chair of the Quality
Committee of the Dutch Ophthalmology Society, March 2021

Final version, approved by the Medical Retina working group

1. Introduction

2. What do the current guidelines say?

3. Advice

4. Conclusion

5. Worked out example

6. References

7. Figure

1. Introduction
The injection of medication into the vitreous humor of the eye, the intravitreal
injection (IVI), was developed in 2003, later the number of injections has
exploded worldwide. In the Netherlands, the number of IVIs has increased from
100,000 injections in 2012 to 300,000 injections in 2019 (NZa figures). For the
time being, there seems to be no alternative for this successful labour-intensive
therapy.

The first guideline for the IVI procedure in 2004 (Aiello, 2004), which was
revised in 2014 (Avery, 2014). In Dutch practice, this guideline appears to have
been worked out well in essence. There does appear to be a diversity in the
materials used (see Figure 1).

1 Introduction

The main complications of an IVI are endophthalmitis, lens perforation, corneal

erosion, and conjunctival hemorrhage. Endophthalmitis is the most serious
complication and has an incidence of 0.01 – 0.26% (Menchini, 2018). An IVI
guideline should aim to prevent this complication. This requires optimal
disinfection of the eye and rapid and sterile introduction of the needle into the
eye.

The aim of this Best Practice is to advise on how ophthalmologists in the

Netherlands can perform the IVIs as safely and sustainably as possible. Not using
unnecessary materials has the most impact on sustainability, fully through reuse
and finally recycling waste from (reduce-reuse-recycle principle). Given the
enormous quantities, a small saving per procedure can lead to significant gains in
terms of costs, waste, and carbon footprint (see point 5). Therefore, the aim
should be to use only the essential parts with an IVI and to leave unnecessary
gestures.
2. What do the current Guidelines say?

This Best Practice is based on the 'Updated Guidelines of an Expert Panel' from
the US (Avery 2014, see Figure 2), the 'Euretina Expert Consensus
Recommendations' from 2018 (Gryzbowski 2018, see Figure 3) and the Dutch
guideline AMD from 2014. In these recommendations by American and
European experts, all steps of the IVI procedure are substantiated with the most
recent scientific literature and the opinion of retina experts. The text below quotes
from these recommendations. In exceptional cases, references are made to
specific publications. Sometimes reference is made to other guidelines or
literature.

Setting/Space

The legal requirements in this regard differ between countries and so does clinical
practice. In the US and Canada, most IVIs are performed in the doctor's office,
while in other countries the OR or treatment room is used. The question is this
difference is reflected in the risk of endophthalmitis. Studies in the US report
incidence rates of 0.029% to 0.057%. In countries where the IVI takes place in
the OR, an incidence of 0.009% to 0.021% is found. Comparative studies could
not find any difference in risk between office-based and OR-based procedures.
The effect of air control was also not demonstrable (Dossarps 2015).

Euretina expert panel: “In conclusion, operating theatre, adequate room or in-
office settings are recommended for IVI.”

Anesthetics

Usually proparacaine or lidocaine drops are used. There is no evidence for

superiority of any particular type of anesthetic. The added value of a cotton swab
soaked in anesthetic has also not been demonstrated. A retrospective analysis of a
US clinic found that the use of lidocaine gel was associated with an increased risk
of endophthalmitis (Stern et al 2019).
Topicale antisepsis

It is recommended by both guidelines to disinfect the fornix and conjunctiva with

povidone iodine eye drops, preferably 2 times, and leave on for 30 seconds.
Usually the 5% concentration is used. Brushing the eyelids is not recommended
because this can release bacteria from the meibomian glands. Dropping povidone
iodine on the eyelids is recommended by some. Chlorhexidine is a safe
alternative.

Perioperative antibiotics

A systematic review and meta-analysis showed that antibiotic prophylaxis is not

associated with a reduction in endotalmitis risk (Benoist d'Azy et al, 2016). Also,
a recent large study from Japan showed again that topical antibiotic prophylaxis
does not reduce the risk of endophthalmitis (Morioka et al 2020). Unnecessary
use of antibiotics will lead to resistance. For this reason, the use of antibiotic
drops is not recommended, both before and after the IVI procedure.

Pupil dilation

In some countries, ophthalmologists want the pupil to be dilated to allow

visualization of the lens and papilla. However, this is not essential and is not
recommended as standard procedure. Informing the patient about light perception
is a good alternative.

Injection location

There is agreement on the location of the injection: 3.5 to 4 mm from the limbus.
In the US, only 56% of respondents measured this distance for the IVI, mostly
using a marker. No statement is made about the necessity of using a compass or
marker.

Eyelid spreader

The usefulness of an eyelid dilator has been demonstrated in a prospective,

placebo-controlled trial with pegabtanib, in the early years of the IVIs (Mansour
et al 2012). Alternatives have been studied, but there seems to be a consensus
about the standard use of an eyelid dilator in IVIs. No statement is made about
the type of spreader or the choice between reusable or disposable spreader.

Gloves, clothing, and drapes

The WHO prescribes the use of surgical gloves in surgical interventions in
general (WHO guidelines on hand hygiene in health care, 2009). There are no
prospective randomized studies on the use of sterile or non-sterile gloves or drape
in an IVI.

The US expert panel (Avery 2014) stated that the use of sterile or non-sterile
gloves fits into modern clinical practice, in combination with hand washing. In
addition, these experts argued that the use of a sterile drape is optional. Applying
a hole cloth to the face can cause stress and discomfort, takes time, and was found
to even lead to more infections in a Cochrane review of 5 randomized trials
(Tailor 2011; Webster 2013). For this reason, it seems better not to use a drape.

US expert panel: “Although the use of gloves has not been shown to reduce the
risk of endophthalmitis, sterile or nonsterile gloves may be used as consistent
with modern office practice. There is no evidence to support the routine use of a
drape when performing IVT injections.”

Euretina expert panel: “In summary, there is no significant evidence that the use
of sterile gloves or drape reduces endophthalmitis rates or adverse events, as
prospective and randomized controlled trials are lacking. From the available data
we conclude to consider gloves, sterile or nonsterile, appropriate for IVI; draping,
however, may not be essential. Appropriate clothing depending on the IVI setting
is advised.”

Face mask

Several studies have shown that wearing a mask as well as being silent by the
surgeon significantly reduces the spread of bacteria from the oral flora. It is
therefore recommended that the doctor and nurse wear a mask during the IVI
procedure. Recently, through experimental research has shown that wearing a
mouth mask by the patient can actually increase the risk of endophthalmitis
(Hadayer et al, 2020).

No statement is made about hat and jacket, but there seems to be no hard
indication to recommend this personal protection in this setting.

Eye bandage/eye pad

In the guidelines of the American and European experts, no statement is made

about an eye bandage after the IVI. There doesn't seem to be any medical
argument for this either. The wound is closed and does not leak. Patient comfort
could well be an argument.
3. Advice

Based on the above, the following advice applies to the requirements for an IVI:

Essential:Mouth mask (operator and assistant)Gloves (sterile or non-sterile,

operator only) Anesthetic eye dropsPovidone iodine dropsSterile eyelid spreader
(single use or reusable)

Optional: Compass/marker (preferably reusable) Cotton swabs for iodine fornix

Non-sterile gauze and non-sterile fluid for removing iodine Eye ointment (usable
for several patients)

Not necessary:

Hole cloth Swab for anesthesia and massage

Tweezers

Hat

Jacket (for doctor and patient)

Tablecloth

Antibiotics Pre and Post Injection

Savings can be made by omitting optional and unnecessary parts (Reduce). An

option that needs further investigation is the reuse of gloves (Reuse), for example
by washing the hands with alcohol while wearing gloves between procedures.

Tips:

- Use a non-sterile tray of iodine for multiple patients

- Iodine can also be poured into the packaging/bag of the cotton swabs, instead of
in a container

- Bottles of oxy/tetracaine/cocaine instead of minims

- Use sterile (crepe) paper wrapping paper, instead of plastic coated paper

4. Conclusion
In order to realize savings in costs, waste and CO2 emissions, it makes sense to
critically assess the material you are currently using for the IVI and to adjust it if
necessary. This Best Practice, based on the literature, can help with that.

Given the large numbers of IVIs, the use of only essential materials during this
procedure leads to significant savings in costs, waste and CO2 emissions. Based
on this Best Practice, based on the literature, you can critically assess your IVI
procedure: you can omit optional and unnecessary parts. Finally, the choice of
materials from which the IVI set is built can also contribute to a saving in costs
and CO2 emissions.

5. Saving example

In the UMC Utrecht, a disposable IVI set has been used for many years with a
plasticized tablecloth, metal spreader, 2 plastic swabs for iodination of the fornix,
1 plastic swab for anaesthesia, a plastic measuring stick, a container for the
iodine, and a plastic container. for the sturdiness. All together this set weighs
135.5 grams. This IVI set was adapted on the basis of the above Best Practice.
After removing the two plastic containers, replacing the plasticized tablecloth
with a much smaller crepe paper sheet, and a much smaller packaging, this
weight had decreased to 66.5 grams. In combination with recycling of the clean
paper and plastic, a reduction in the carbon footprint from 0.68 kilograms of CO2
to 0.17 kilograms of CO2 could be achieved. See Figure 4 for the exact dates. If
this reduction of 75% is extended to the 300,000 injections that take place
annually in the Netherlands, based on approximately identical disposable IVI
sets, a gain of 153,000 kg CO2 is possible. This carbon footprint corresponds to
695,461 kilometers of driving.

References

- Menchini et al. Antibiotic prophylaxis for preventing endophthalmitis

after intravitreal injection: a systematic review. Eye 32:1423-1431, 2018

- Aiello et al, Evolving guidelines for intravitreal injections. Retina 24:S3-

S19, 2004
- Avery et al, Intravitreal injection technique and monitoring. Updated
guidelines of an
expert panel. Retina 34:S1-S18, 2014

- Mansour et al, Insight into 144 patients with ocular vascular events
during VEGF
antagonist injections. Clin Ophthalmol 2012;6:343-363

- Grzybowski et al, 2018 Update on intravitreal injections: Euretina expert

consensus
recommendations. Ophthalmologica 2018 (http://dx.doi.org/
10.1159%2F000486145)

- Webster et al. Use of plastic adhesive drapes during surgery for

preventing surgical
site infection. Cochrane Database Syst Rev 2013;1:CD006353

- Hadayer et al. Patients wearing face masks during intravitreal injections

may be at a
higher risk of endophthalmitis. Retina 40(9):1651-1656, 2020

- Siu et al. Systematic review of reusable versus disposable laparoscopic

instruments:
costs and safety. ANZ J Surg 87 (2017) 28-33

- Dossarps D, et al. Endophthalmitis after intravitreal injections: incidence,

presentation,
management, and visual outcome. Am J Ophthalmol 2015;160:17-25

- Morioka et al. Incidence of endophthalmitis after intravitreal injection of

an anti -VEGF
agent with or without topical antibiotics. Scientific Reports 2020; 10:22122
 - Nederlandse Zorgautoriteit https://www.opendisdata.nl/msz/
zorgactiviteit/039810

- WHO guidelines on hand hygiene in health care 2009

https://apps.who.int/iris/bitstream/handle/
10665/44102/9789241597906_eng.pdf?seq
uence=1&isAllowed=y&ua=1

- Benoist d’Azy et al. Antibioprophylaxis in prevention of endopthalmitis

in intravitreal injection: a systematic review and meta-analysis. PLoS One
2016 https://doi.org/10.1371/journal.pone.0156431

- Stern et al. Predictors of endophthalmitis after intravitreal injection. A

multivariable analysis based on injection protocol and povidone iodine
strength. Ophthalmology Retina 2019;3:3-7

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Figuur 1. Various IVI sets in the Netherlands.

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Figuur 2. From Avery et al., 2014

Figuur 3. From Grzybowski et al, 2018

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Figuur 4. Waste from disposable intravitreal sets at UMC Utrecht, broken down
by weight of total waste, residual waste (hospital specific waste) and CO2
emissions.

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