Retina specialists worldwide have adopted intravitreal injections into their armamentarium for treatment of various retinal diseases.1-3 Experience with intravitreal injections began with the treatment of endophthalmitis, in which a vitreous tap was performed followed by injection of intravitreal antibiotics.4
Further experience with intravitreal injections was gained through the use of pneumatic retinopexy in which a long-acting gas bubble was injected into the vitreous to facilitate retinal detachment repair.5 For the treatment of CMV retinitis, intravitreal ganciclovir and foscarnet injections were utilized in the early 1990s.6 More recently, injection of intravitreal methotrexate has been shown to be useful in the treatment of intraocular lymphoma.7
In this article, we'll review the recommendations of a panel convened in mid-2004 that looked at current practices in an attempt to reach a consensus on the safe use of intravitreal injections.
Triamcinolone Driving the Trend
Over the past five years, triamcinolone acetonide injections have been used increasingly for a variety of retinal diseases8-11 and anti-VEGF intravitreal injections are being investigated for treatment of choroidal neovascularization.12-13 Although results of definitive randomized clinical trials are still pending, preliminary evidence from case series supported by frequent clinical use has given hope for these treatments in reversing visual loss from many otherwise blinding retinal diseases. Just when we all thought that outcomes of photodynamic therapy (PDT) were disappointing, the combination of intravitreal steroids with PDT has been shown to produce a greater patient benefit in terms of visual acuity outcomes and reduced number of re-treatments for wet age-related macular degeneration.14 In using intravitreal injections, controversies exist regarding patient selection, frequency of re-treatments, and the actual injection procedure itself.1,2 Multicenter clinical trials are under way but the many issues surrounding the injection procedure may not be fully answered. Meanwhile, the practitioner is left asking the question, "How should I perform this injection procedure?"
Protocol Review
Figure 1. The importance of povidone-iodine application to the conjunctiva, lashes and lid margins is one area of agreement among a recently convened expert panel studying intravitreal injection safety issues.
In May 2004, a group of experienced investigators met to create a document with best practices guidelines in an attempt to minimize complications and optimize outcomes following intravitreal injections of retinal pharmacotherapies.1 Representatives from pharmaceutical companies based in the United States and known to be involved in the research and development of retinal pharmacotherapies administered by intravitreal injection were invited to participate in this meeting. The meeting was sponsored by an unrestricted educational grant to the journal Retina from Eyetech/Pfizer Ophthalmics, New York. Over two days, the participants reviewed the risks of intravitreal injections both in published manuscripts and articles about to be published from clinical trials.
Protocols from various studies were reviewed, including anti-VEGF therapies for wet AMD and anti-viral therapies for CMV retinitis. These study protocols varied greatly regarding use of topical antibiotics, drug injection technique and follow-up requirements.
An attempt was made to achieve consensus, but there was often disagreement among participants as to the value of a particular maneuver when there was little scientific data to support use or non-use.
 |
| Figure 2. A sterile lid speculum is used to maintain lid position and to direct lashes out of the injection field. |
Perhaps the strongest area of agreement was for the use of povidone-iodine on the conjunctiva as well as on the lid margins and lashes. Povidone-iodine is well-recognized as the most effective means of bacterial prophylaxis for intraocular surgery.15,16 The committee developed a set of guidelines, some of which (See Table 1) had consensus agreement, such as: use of povidone-iodine (See Figure 1); use of a lid speculum (See Figure 2); avoidance of extensive massage of the eyelids; avoidance of injecting patients with active eyelid or ocular adnexal infection; dilatation of the pupil in order to view the posterior segment immediately after injection; use of adequate anesthesia; and general avoidance of prophylactic or post-injection anterior chamber paracentesis.
Others (See Table 2) had less agreement: Most of the investigators did not use a sterile drape; most advocated the use of gloves; most preferred topical povidone-iodine drops over flush; there was no agreement on the use of pre- or post-injection topical antibiotics, no agreement on specific intraocular pressure levels at which the physicians are comfortable discharging the patient, and disagreement on when to see the patient back for follow-up after injection. Most investigators ask the patient to return for follow-up within one week of the injection but many preferred a one- to three-day follow-up. Others ask their nurse assistant to call the patient within one week of the treatment regarding symptoms of visual loss, pain, or red eye, which would necessitate the need for a prompt return for follow-up.
| Table 1. Guidelines with More Agreement |
| Apply povidone-iodine to ocular surface, eyelids and eye lashes |
| Use lid speculum |
| Avoid contamination of the needle with eyelashes or eyelid margin |
| Avoid extensive massage of eyelids either pre-or post-injection (to avoid expressing meibomian glands) |
| Avoid injecting patients who have active eyelid or ocular adnexal infection |
| Dilate pupil (to view posterior segment after injection) |
| Use adequate anesthetic for a given patient (topical drops and/or subconjunctival injection) |
| Avoid prophylactic or post-injection anterior chamber paracentesis |
Drs. Flynn and Scott are in the Department of Ophthalmology at Bascom Palmer Eye Institute, University of Miami School of Medicine. Contact Dr. Flynn at 900 NW 17th St., Miami, Fla. 33136. Phone:
(305) 326-6118; Fax: (306) 326-6417; or e-mail:
hflynn@med.miami.edu.
Table 2. Areas with No Clear Consensus
Most did not want to use a povidone-iodine flush, and preferred drops; (no benefits attributed to allowing the povidone-iodine to dry)
Most did not use a sterile drape
Most advocated use of gloves
Use of pre- or post-injection topical antibiotics little published scientific data to support reduction in endophthalmitis rates)
Intraocular pressure should be checked following injection (no agreement on IOP level at which physicians are comfortable to discharge patient)
No consensus regarding the need for clinic follow-up examination versus telephone interchange with physician or nurse
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10. Ip MS, Gottlieb JL, Kahana et al. Intravitreal triamcinolone acetonide for the treatment of macular edema associated with central retinal vein occlusion. Arch Ophthalmol 2004:122;1131-1136.
11. Jonas JB, Kriest I, Hugger P et al. Intravitreal triamcinolone acetonide for exudative age related macular degeneration. Br J Ophthalmol 2003;87:462-468.
12. The Eyetech Study Group. Preclinical and phase 1A clinical evaluation of an anti-VEGF pegylated aptamer (EYE001) for the treatment of exudative age-related macular degeneration. Retina 2002:22;143-152.
13. The Eyetech Study Group. Anti-vascular endothelial growth factor therapy for subfoveal choroidal neovascularization secondary to age-related macular degeneration: phase II study results. Ophthalmology 2003;110:979-986.
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15. Apt L, Isenberg S, Yoshimori R, et al. Chemical preparation of the eye in ophthalmic surgery: Effect of povodine-iodine on the conjunctiva. Arch Ophthalmol 1984;102:728.
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