and Complications

Elias Reichel

INTRODUCTION

Intravitreal injections are becoming an increasingly common part of clinical practice. In the past, indications for injection of substances into the vitreous cavity were relatively limited. The advent of new therapies targeting the posterior pole has resulted in an exponential rise in the number of injections performed. As the number of these procedures increases, careful technique becomes a more important part of producing safe and effective results.

Today, there are a host of pharmaceuticals used to treat retinal diseases via intravitreal injection, with many more under investigation. The most commonly injected medications are those used to treat exudative macular degeneration. Ranibizumab (Lucentis, Genentech, San Francisco, CA) has been the subject of large clinic trials and may be administered at a minimum interval of 4 weeks. The use of bevacizumab (Avastin, Genentech) has also been well studied. In addition, bevacizumab is also used to treat other forms of retinal neovascularization as well as macular edema. Trials for use of ranibizumab for a number of these conditions are currently under way.

Another commonly injected medication is triamcinolone acetate (Kenalog, Bristol Myers Squibb, New York, NY). Used off label, this steroid preparation has been used for treating macular edema, uveitis, and as an adjunct to macular degeneration therapy. Other applications of intravitreal injections include antiviral medications of cytomegalovirus (CMV) or herpetic infections, antibiotics for endophthalmitis, and tissue plasminogen activator for submacular hemorrhage. In-office injections of intravitreal gas are also used to treat retinal detachments with pneumatic retinopexy.

As the role of intravitreal injections in office-based practice has expanded, basic guidelines for the technique have been discussed.¹ Since then, our knowledge of the risks and complications of injections have also expanded. While intravitreal injections are most often safe and relatively pain-free procedures, they are still associated with risk, while rare, serious complications such as endophthalmitis, retinal detachment, traumatic cataract, and vitreous hemorrhage have been reported. This chapter discusses injection protocol and issues related to peri-injection management.

Injection Protocol

While injection protocol is subject to minor variation between clinicians, the general technique remains the same.

Preinjection

1. Prior to the day of the injection, some clinicians elect to pretreat the affected eye with a topical antibiotic, usually for a period of 3 days.

Injection

1. The patient is examined. Injection is contraindicated in the presence of active ocular or periocular infection.
   
2. Informed consent is obtained, and the eye to be injected is verified.
   
3. The eye to be injected is dilated.
   
4. The lid and eyelashes are cleaned with 5% povidone-iodine.
   
5. Five percent povidone-iodine is placed on the conjunctiva prior to subconjunctival injection of anesthetic.
   
6. If T/topical anesthesia is administered, the conjunctiva is then flushed with 5% povidone-iodine to clean the conjunctiva and remove any anesthetic vehicle that may be on the ocular surface.
   
7. Some clinicians elect to use a sterile drape, use of gloves is recommended.
   
8. A sterile lid speculum is placed.
   
9. The injection site is marked 3.5 mm posterior to limbus in pseudophakic eyes and 4.0 mm posterior to limbus in phakic eyes.
   
10. Five percent povidone iodine is instilled into the eye at the injection site, most commonly inferotemporally.
    
11. The drug is injected using either a 30- or 27-gauge needle directed toward the center of the vitreous cavity. Care is taken to avoid contact with the eyelashes or lid margin.
    
12. The injection is performed slowly, but firmly.
    
13. A cotton-tipped applicator is used to apply brief pressure at the injection site to prevent reflux.
    
14. The lid speculum is removed and topical antibiotic is administered.
    
15. The patient’s vision is checked to confirm hand motions.
    
16. Perfusion of the optic nerve is confirmed using indirect ophthalmoscopy.
    
17. The intraocular pressure is checked 10 minutes following the injection and the patient is discharged if the IOP is within safe levels, usually 35 mm Hg or below.
    
18. If the intraocular pressure is high, topical glaucoma drops are administered and the pressure is rechecked. Rarely, an anterior chamber paracentesis may be required.

Postinjection

1. The patient is instructed to use topical antibiotics for 3 to 7 days following the injection.
   
2. A telephone follow-up is usually done the week following the injection. The patient should be examined if there is significant pain or decrease in vision.

Techniques

Although the rate of complications following intravitreal injections is low, meticulous antisepsis should be maintained to minimize serious sequelae such as endophthalmitis.

Gloves and Draping

Prior to the procedure, it is common practice to wear gloves. While the gloves need not be sterile, they are a part of universal safety precautions. Some physicians also drape the eyelids and lashes prior to the injection. Draping may help to prevent contamination of the needle with eyelid flora but is optional.

Eyelid Speculum and Povidone Iodine

Possible sources for bacterial contamination of the needle include the eyelashes and the conjunctiva. To minimize contact with the eyelashes, the use of a sterile eyelid speculum is recommended. In addition, the application of 5% to 10% povidone iodine to the periorbita and 5% to the injection site itself is critical. The use of povidone iodine has been shown to reduce the number of conjunctival bacteria.² Furthermore, the application of povidone iodine reduces the risk of endophthalmitis following cataract surgery.^3–7 Just prior to the injection, the povidone iodine may be applied as drops, a swab, or an irrigating flush.⁵

Antibiotic Prophylaxis

Many clinicians also choose to use preinjection and/or postinjection antibiotics for prophylaxis. The role of preinjection antibiotics remains controversial. Previous studies have shown that, prior to cataract surgery, a 3-day course of topical antibiotics provides a further decrease in bacterial colonization than povidone iodine prep. alone.² However, recent data suggest that a fourth-generation fluoroquinolone does not provide additional benefit over povidone iodine alone.¹⁴ For cataract surgery, preoperative antibiotics are possibly relevant but do not definitely alter clinical outcomes.⁷ Preinjection antibiotics were not used in the SCORE of DRCRnet clinical trials and a low incidence of endophthalmitis was observed,³ suggesting that they may not be necessary. In contrast, most clinicians prescribe topical antibiotic prophylaxis following an injection. However, there have been reported case series with a low incidence of endophthalmitis in which a significant portion of patients were not given postinjection antibiotics.¹¹

Anesthesia

A variety of methods are employed to provide anesthesia for intravitreal injections. The most common method is to employ a topical anesthetic. Some clinicians elect to apply proparacaine- or tetracaine-soaked pledgets to the injection site prior to delivery of the medication. An alternative is to use viscous tetracaine or 2% lidocaine jelly.⁶ Our current practice is to use two administrations of 3.5% lidocaine gel,¹⁰ separated by a 5-minute interval, which provides adequate anesthesia. Subconjunctival injection of 2% lidocaine solution is less commonly employed and may be associated with more chemosis, hemorrhage, and accidental perforation of the eye wall.

Complications

In general, intravitreal injections are well tolerated and rates of complications are low. In large studies, the most common adverse events were benign and included subconjunctival hemorrhage and keratoconjunctivitis sicca. However, serious adverse events such as endophthalmitis, retinal detachment, vitreous hemorrhage, and traumatic cataract can occur. Anticoagulation or the use of platelet inhibitors does not appear to increase the risk of vitreous hemorrhage in conjunction with intravitreal injections. Table 19.1 summarizes the complication rates seen during several large clinical trials of anti-VEGF agents.

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