What caused a patient in her 70s to develop complications after she received an intravitreal Injection (IVI) in her left eye? That’s what K. Bailey Freund, MD, of Vitreous Retina Macula Consultants of New York in New York City, and colleagues needed to figure out.

The patient reported seeing numerous small floaters starting the day after receiving an injection of pegcetacoplan (Empaveli, 15 mg per 0.1 mL), a recently approved C3 targeting agent for geographic atrophy.

Pretreatment examination revealed bilateral center-involving geographic atrophy and bilateral posterior vitreous detachments, evidenced by Weiss rings, according to the research letter in JAMA Ophthalmology. Best-corrected visual acuities were 20/50 in the left eye and 20/40 in the right eye. She had not received any previous treatments such as intraocular surgery or IVIs.

The injection of pegcetacoplan had been prepared and administered by an ophthalmologist experienced in IVI. The injection was administered “using a 1-mL Luer lock Syringe [Becton Dickinson] attached to a 5-μm filter needle to withdraw the drug from its vial, maintaining the filter needle within the vial while inverting the syringe, and moving the plunger down and up to remove gas bubbles before injection,” the clinicians noted.

At a follow-up assessment 2 weeks later, the patient told the team that since the day following the injection, many small spots had appeared in her vision.

On examination, clinicians noted that the patient’s visual acuity was stable, intraocular pressure was normal, and there was no evidence of anterior segment or vitreous inflammation.

They observed multiple Sods in the anterior vitreous in the patient’s left eye. They performed a B-scan ultrasound examination which revealed “multiple hyperechogenic areas within a detached vitreous in the left eye,” they said.

When the patient returned for another follow-up assessment 2 month later, she told clinicians that there were fewer floaters affecting her vision. However, the team noted that SODs continued to be visible in the anterior vitreous.

Discussion

The researchers reporting this case of a patient who developed floaters after an IVI treatment with pegcetacoplan noted that “intravitreal SODs, seen clinically as translucent spherical bodies appearing hyperechogenic on B-scan ultrasonography, were first reported in 2006 following IVI of pegaptanib sodium [now off the U.S. market].”

The team noted a 2016 alert issued by the American Society of Retina Specialists that outlined similar descriptions of symptomatic SODs following intravitreal bevacizumab treatments administered using siliconized insulin syringes.

A 2017 study comparing various syringes used in IVI showed that SODs appeared at the end of injections with fixed-needle insulin syringes when the plunger was completely depressed. However, this effect did not occur when treatment was delivered using detachable needle syringes that contained dead space at the syringe tip, or with silicone-free syringes.

The full prescribing information for pegcetacoplan advises that in preparing the injection, gas bubbles may collect in the dead space in the syringe tip and needle before the medication, and be retained near the plunger as a result of the drug’s comparatively higher viscosity. Furthermore, the label instructs: “Do not tap the syringe to remove air bubbles. While maintaining the filter needle within the vial, invert the syringe and move the plunger down and up until bubbles move to the top.”

However, this may cause injection of SODs into the eye “despite the use of a Luer lock syringe,” the study authors noted. The considerable force that must be used to draw the medication into the syringe results in a large excursion of the plunger. Thereafter, repeated up and down movements may dislodge silicone oil from the syringe’s wall, they suggested, causing the silicone oil to become mixed with the medication. As a result, the SODs are not trapped in the dead space and end up being injected into the eye.

“Ophthalmologists could consider using silicone-free Luer lock syringes, which might mitigate this occurrence,” Freund’s group suggested. Or, using a filtered vial adaptor to draw the medication into the syringe with the vial inverted would allow the gas bubbles to remain at the tip of the syringe, where they can be expelled more easily before the treatment is administered. This approach was used in the phase III studies of pegcetacoplan, they pointed out.

In addition to syringe-related SODs, gas bubbles and vitreous hemorrhage have also been linked to floaters following IVI of anti-vascular endothelial growth factor agents.

In an analysis of complication rates across over 44,000 IVIs performed from 2012 to 2016, researchers found that “no injection protocol parameter, such as type of anesthesia, preparation, or post-injection medication, increased the risk of a complication.” However, patient’s gender, age, number of previous injections, and IVI provider did influence the risk of serious complications requiring medical intervention or close observation.