Are You Side Effect Savvy?

Intravitreal injections (IVIs) made their debut in the eye care world in 2004 with the approval of pegaptanib sodium (Macugen, Eyetech/Pfizer) for the treatment of neovascular age-related macular degeneration. Since then, use of IVIs has grown exceptionally, and they are now the most performed ophthalmic procedure in the United States.¹

IVIs are most frequently used to deliver anti-vascular endothelial growth factor drugs for the treatment of wet age-related macular degeneration, macular edema following retinal vein occlusion, diabetic macular edema, myopic choroidal neovascularization, retinopathy of prematurity, and diabetic retinopathy. Other IVIs include steroids, antibiotics, antivirals, and gene therapy agents. The most recent FDA-approved IVI is a complement inhibitor for geographic atrophy. Although the targeted drug delivery approach that IVIs provide is unparalleled, their use is not without risk. Both optometrists and retina specialists play important roles in the health care of patients receiving IVIs.

This article discusses tips for optimizing the care of these patients when complications are encountered, specifically for the comanaging optometrist.

SETTING THE STAGE

In our experience, patients tend to be more amenable to treatment when they are counseled by their referring optometrist on the possibility of receiving an IVI. Anxiety about a needle in the eye is understandable, but reassuring patients that the procedure is common and efficient can be comforting. Additionally, highlighting the vision-saving features of the injection on referral can further facilitate patient compliance.

Despite all the reassurances in the world, patients may ask about side effects and complications, so it behooves the comanaging optometrist to be well-versed in identifying and managing the most common of these. Here’s a rundown.

THE SIDE EFFECTS

Below are the most frequent side effects encountered by our patients who receive IVIs.

Dry Eye and Irritation

Povidone-iodine ophthalmic solution is the most commonly used antiseptic for injections due to its efficacy and availability,² but it is known to be irritating to the corneal epithelium.³ To address this issue, most retina specialists will rinse the eye with an eye wash solution immediately after injection. This rinse is often incomplete, however, due to poor physician or assistant technique, poor patient cooperation (keeping your eye open while being rinsed is not an easy task), and individual patient anatomy (eg, deep orbit; small, tight eyelids). As a result, povidone-iodine often remains trapped on the palpebral conjunctiva and conjunctival fornix.

Additionally, povidone-iodine acts as an extrinsic factor to dysregulate the homeostasis of a normal tear film. When introduced to the ocular surface, the solution triggers the inflammatory cascade of dry eye, potentially causing the patient to have worsening symptoms of their baseline dry eye disease.⁴ After IVI, patients may complain of irritation, sandiness, and pain. In our practice, we have patients return to the office for an additional rinse when possible. We also always recommend that patients start frequent use of preservative-free artificial tears with special instructions to use a new, unopened vial to limit infection. Placing a cool compress on the closed eye can also be beneficial. Symptoms typically subside 24 hours after injection. Optimizing the ocular surface of patients who receive IVIs has been beneficial, with our mutual patients being served by optometry-owned dry eye centers.

Red Eye

When an IVI is given, a 30-g needle is placed through the conjunctiva and sclera 3.5 mm to 4 mm behind the corneal limbus. As a result, patients may develop a red eye from a subconjunctival hemorrhage (Figure 1), which may cause blood-tinged tears for a few hours post injection. In addition, patients can develop some localized chemosis in the area of the injection, which may be due to reflux vitreous trapped under the conjunctiva or from a subconjunctival anesthetic used prior to the injection. Reassurance and lubrication as needed is typically all that is warranted. We usually recommend individual vialed preservative-free artificial tears.

Figure 1. This image shows a classic example of subconjunctival hemorrhage-induced red eye in a patient who received an IVI.

Floaters

As the injected medication enters the vitreous cavity, air bubbles within the drug may enter the vitreous, resulting in the patient experiencing floaters, which are usually perfectly circular and noted to be in the patient’s inferior visual field. These will self-dissipate. Some patients may have an increase in vitreous syneresis or a new posterior vitreous detachment, which develops after the injection.⁵ Thorough peripheral retinal examination with scleral depression is useful to evaluate for any retinal breaks. However, not all floaters are created equally; thus, persistent and numerous floaters should necessitate immediate evaluation for endophthalmitis.

IOP Spikes

Elevations in IOP can be expected immediately after an injection, due to the volume of fluid that enters the eye (typically between 0.05 mL and 0.1 mL, depending on the medication). This spike can result in transient visual changes, which normally resolve by the time the patient leaves the office. Chronic IVIs have not conclusively illustrated a rise in IOP.⁶ Optometrists comanaging patients receiving IVIs should monitor their IOP regularly to identify possible trends towards elevation. One caveat, of course, would be ocular hypertension from a steroid IVI with steroid response.

Endophthalmitis

The most serious and vision-threatening complication of an IVI is iatrogenic endophthalmitis (Figure 2). Fortunately, this side effect is rare, with reports of less than 0.05%.⁷ The pneumonic “RSVP” can be helpful to remember how most patients will present with endophthalmitis (see Don’t Forget to RSVP).

Figure 2. Patients with anterior cell, hypopyon, vitritis, ciliary flush, and decreased visual acuity should be immediately referred to the treating retina specialist for suspected iatrogenic endophthalmitis.

Examination findings may include decreased visual acuity, anterior cell, hypopyon, vitritis, and ciliary flush. If suspected, it is ideal to err on the side of caution and refer to the treating retina specialist urgently. Most infectious endophthalmitis presents 48 to 72 hours post injection.⁷ The most common culprits behind infectious endophthalmitis following IVIs include coagulase-negative Staphylococcus and Staphylococcus aureus.⁷

Two major risk factors for developing endophthalmitis include significant blepharitis and talking during the injection, which releases oral flora onto the injection site. Although both patient and retina specialists wearing masks during injections help, I often rely on my optometric colleagues to manage a patient’s blepharitis during the course of their treatment with IVIs. Immediate treatment with broad-spectrum antibiotics, usually intravitreal vancomycin and ceftazidime, is indicated. The visual prognosis of an infectious endophthalmitis can vary depending on the virulence of microbe.⁷

COLLABORATE AND COUNSEL

As the number of patients receiving IVIs continues to grow, the collaborative relationship between retina specialists and optometrists will only strengthen. It is useful to counsel patients on what to expect when undergoing an IVI and to recognize common side effects so that they can be effectively dealt with.

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2. Mulcahy LT, Schimansky S, Fletcher E, Mohamed Q. Post-injection endophthalmitis rates with reduced povidone-iodine prophylaxis in patients with self-reported iodine sensitivity. Eye (Lond). 2021;35(6):1651-1658.

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