What per-injection rate of endophthalmitis after intravitreal injection do large series and meta-analyses report?

About 0.02 to 0.06 percent Reported rates are about 0.02 to 0.06 percent per injection; the risk applies to every injection, so patients on monthly treatment are exposed repeatedly.

Which organisms are the commonest cause of post-injection endophthalmitis?

Coagulase-negative staphylococci Coagulase-negative staphylococci from the skin and lids are the commonest cause; S. aureus and other bacteria are a minority and fungi are rare.

Where do the viridans streptococci causing post-injection endophthalmitis usually come from?

Oral flora, from talking or breathing over the field Viridans streptococci come from the mouth and are linked to talking or breathing over the field without a mask; these infections progress fast and often end with poor vision.

Contaminated povidone-iodine solution

The patient's nasolacrimal duct

Hematogenous spread from the gut

When does post-injection endophthalmitis usually present after the injection?

Within two to seven days, often three to five Onset is usually within two to seven days of injection, often at three to five days, with increasing pain, redness and falling vision.

Which presentation favors sterile intraocular inflammation over infectious post-injection endophthalmitis?

Less pain, better vision and often a white eye Sterile inflammation is a noninfectious drug reaction with less pain, better vision and often a white eye; when in doubt, treat as infection because delay is costly.

Vitreous haze hiding the retina

Which intravitreal antibiotic doses are commonly used for post-injection endophthalmitis?

Vancomycin 1 mg and ceftazidime 2.25 mg After a vitreous tap for Gram stain, culture and PCR, vancomycin 1 mg and ceftazidime 2.25 mg are commonly injected, adapted to local guidance.

Vancomycin 2.25 mg and ceftazidime 1 mg

Gentamicin 0.1 mg and cefazolin 1 mg

Moxifloxacin 0.5 mg and amikacin 0.4 mg

In endophthalmitis after intravitreal injection, which presenting vision favors immediate pars plana vitrectomy?

Light perception vision The Endophthalmitis Vitrectomy Study found immediate vitrectomy benefited post-cataract eyes presenting with light perception vision, and many surgeons apply this to post-injection disease.

What povidone-iodine concentration is applied to the conjunctiva and lashes before intravitreal injection to prevent endophthalmitis?

5 percent Povidone-iodine 5 percent is applied to the conjunctiva and lashes and left to dry, with a speculum keeping the lashes away from the field.

What is the role of topical antibiotics in preventing post-injection endophthalmitis?

Avoided, as studies show no reduction in infection Topical antibiotics are avoided because studies have not shown that they reduce the infection rate; antisepsis, masking and sterile technique matter instead.

Mandatory for three days after each injection

Given only to patients on monthly injections

Required before injection instead of povidone-iodine

A cluster of post-injection endophthalmitis cases should prompt investigation of what?

The drug supply, compounding pharmacy and technique Clusters can reveal contamination, so investigate the drug supply, the compounding pharmacy and the technique, and report to infection control and, for compounded drugs, the regulator.

The patients' systemic immune status

The anti-VEGF agent's molecular class

The interval between injections

Post-Injection Endophthalmitis: Signs and Treatment

Post-injection endophthalmitis is an infection of the vitreous that develops after an intravitreal injection.

It is also the most feared complication of anti-VEGF therapy.

It is rare, with reported rates of a few cases per ten thousand injections, but the number of injections performed each year is so large that every retina clinic will see cases.

Early recognition and rapid treatment decide whether the eye keeps useful vision.

How Often Post-Injection Endophthalmitis Occurs

Large series and meta-analyses report rates between about 0.02 and 0.06 percent per injection, which is roughly one case for every 2,000 to 5,000 injections.

The risk applies to each injection, so a patient on monthly treatment is exposed repeatedly over the years.

Most cases occur after an injection that seemed routine, which is why every injection needs the same level of care (see intravitreal injection technique).

Organisms

Coagulase-negative staphylococci, the commonest cause, from the skin and lids
Streptococcus species, particularly viridans streptococci from the mouth, linked to talking or breathing over the field without a mask, and often more severe
Staphylococcus aureus, and other bacteria in a minority
Fungi, rarely

Streptococcal infections tend to progress fast and have a poor visual outcome, so they deserve particular urgency.

Test your knowledge 10 questions from this article

Presentation

The usual onset is within two to seven days of the injection, and often at three to five days.

Increasing pain and redness
Blurred vision or a sudden drop in acuity
Light sensitivity
Lid swelling and discharge in some patients
Hypopyon, which is less common in the early stage than after cataract surgery
Cells in the vitreous, with haze that hides the retina

Mild discomfort and a few cells in the anterior chamber can occur after injection and may be sterile inflammation, but increasing pain and loss of vision call for urgent assessment.

Differential Diagnosis of Post-Injection Endophthalmitis

Sterile intraocular inflammation: a noninfectious reaction to the drug, with less pain and a better vision, and often a white eye (see anti-VEGF therapy)
Postoperative or endogenous endophthalmitis in a patient with other risk factors (see acute postoperative endophthalmitis and endogenous endophthalmitis)
Vitreous hemorrhage and retinal tear
Retinal detachment, retinal vein occlusion, and neovascular glaucoma

When in doubt, treat as infection, because the cost of delay is high.

Management for Post-Injection Endophthalmitis

Same-day referral to a retina service, and avoid delay for tests
Vitreous tap or biopsy for Gram stain, culture, and PCR
Intravitreal antibiotics, commonly vancomycin 1 milligram and ceftazidime 2.25 milligrams, with the choice adapted to local guidance
Pars plana vitrectomy in eyes with severe disease, particularly those with light perception vision or a poor response
Topical steroids and cycloplegics as supportive treatment, and consider intravitreal steroids in selected cases
Repeat injections at 48 to 72 hours if there is no improvement

The Endophthalmitis Vitrectomy Study, which examined post-cataract cases, found that immediate vitrectomy benefited eyes presenting with light perception vision.

Many surgeons apply this approach to post-injection disease (see the reference below).

Clinical eye photograph illustrating Post Injection Endophthalmitis

Prevention

Povidone-iodine 5 percent on the conjunctiva and lashes, left to dry
A speculum to hold the lids, and avoidance of contact with the lashes
A mask for the operator and the patient, or silence during the procedure, to reduce oral flora
Sterile gloves and instruments, and single-dose vials
Avoidance of topical antibiotics, which studies have not shown to reduce the infection rate
Careful teaching of patients about the symptoms and a clear route for urgent contact

Clusters of cases should lead to an investigation of the drug supply, the compounding pharmacy, and the technique.

Counselling

Explain to every patient on injection therapy that pain, redness, and falling vision in the week after injection are an emergency and must not wait until the next appointment.

Also, give a telephone number that is answered, and make sure the patient has access to rapid care at weekends.

After a Case: What to Review

When endophthalmitis occurs after an injection, look at the technique used on that day, the lot of the drug, the number of injections done in the session, and the person who performed the procedure.

Review whether staff masked the patient, whether the antisepsis was complete, and whether staff handled the speculum and instruments properly.

Report the case to the local infection control team and, if the clinic used a compounded drug, to the pharmacy and the regulator, since clusters can reveal contamination.

Post-Injection Endophthalmitis: Follow-Up of Treated Eyes

Review the patient daily in the early days, with acuity, pressure, and the view of the fundus.

Many eyes with coagulase-negative staphylococci recover useful vision with prompt treatment, while streptococcal infections more often end with poor vision despite aggressive treatment.

Plan retinal detachment surveillance after infection, and discuss with the patient whether to continue the injection program and under what changes.

For the latest studies, see the PubMed results for post-injection endophthalmitis.

References

McCannel CA. Meta-analysis of endophthalmitis after intravitreal injection of anti-vascular endothelial growth factor agents: causative organisms and possible prevention strategies. Retina. 2011;31:654-661.
Endophthalmitis Vitrectomy Study Group. Results of the Endophthalmitis Vitrectomy Study: a randomized trial of immediate vitrectomy and of intravenous antibiotics for the treatment of postoperative bacterial endophthalmitis. Arch Ophthalmol. 1995;113:1479-1496.
Avery RL, Bakri SJ, Blumenkranz MS, et al. Intravitreal injection technique and monitoring: updated guidelines of an expert panel. Retina. 2014;34(Suppl 12):S1-S18.
American Academy of Ophthalmology. Basic and Clinical Science Course, Section 12: Retina and Vitreous. AAO; current edition.

Test yourself

A few questions straight from this article.

1 / 10 0 correct

What per-injection rate of endophthalmitis after intravitreal injection do large series and meta-analyses report?
Reported rates are about 0.02 to 0.06 percent per injection; the risk applies to every injection, so patients on monthly treatment are exposed repeatedly.
Which organisms are the commonest cause of post-injection endophthalmitis?
Coagulase-negative staphylococci from the skin and lids are the commonest cause; S. aureus and other bacteria are a minority and fungi are rare.
Where do the viridans streptococci causing post-injection endophthalmitis usually come from?
Viridans streptococci come from the mouth and are linked to talking or breathing over the field without a mask; these infections progress fast and often end with poor vision.
When does post-injection endophthalmitis usually present after the injection?
Onset is usually within two to seven days of injection, often at three to five days, with increasing pain, redness and falling vision.
Which presentation favors sterile intraocular inflammation over infectious post-injection endophthalmitis?
Sterile inflammation is a noninfectious drug reaction with less pain, better vision and often a white eye; when in doubt, treat as infection because delay is costly.
Which intravitreal antibiotic doses are commonly used for post-injection endophthalmitis?
After a vitreous tap for Gram stain, culture and PCR, vancomycin 1 mg and ceftazidime 2.25 mg are commonly injected, adapted to local guidance.
In endophthalmitis after intravitreal injection, which presenting vision favors immediate pars plana vitrectomy?
The Endophthalmitis Vitrectomy Study found immediate vitrectomy benefited post-cataract eyes presenting with light perception vision, and many surgeons apply this to post-injection disease.
What povidone-iodine concentration is applied to the conjunctiva and lashes before intravitreal injection to prevent endophthalmitis?
Povidone-iodine 5 percent is applied to the conjunctiva and lashes and left to dry, with a speculum keeping the lashes away from the field.
What is the role of topical antibiotics in preventing post-injection endophthalmitis?
Topical antibiotics are avoided because studies have not shown that they reduce the infection rate; antisepsis, masking and sterile technique matter instead.
A cluster of post-injection endophthalmitis cases should prompt investigation of what?
Clusters can reveal contamination, so investigate the drug supply, the compounding pharmacy and the technique, and report to infection control and, for compounded drugs, the regulator.

Ahmed Ophthalmologist

Writes and reviews the clinical articles on Educate. Every post is checked against peer-reviewed sources before it goes live.