May 2011, Issue 51

A Comparison of Local Anesthesia Techniques for Intravitreal Injections

Robert J. Courtney, MD Casey Eye Institute Retina - Vitreous Service Department of Ophthalmology Oregon Health & Science University	Andreas K. Lauer, MD Casey Eye Institute Retina - Vitreous Service Department of Ophthalmology Oregon Health & Science University

Intravitreal therapy represents an efficient and common means to deliver therapeutics to the posterior segment and the use of anti-vascular endothelial growth factor agents in this context has revolutionized the treatment of exudative age-related macular degeneration. However, intravitreal injection can be associated with significant patient anxiety and discomfort, and carries some risk of complications such as infection, hemorrhage, retinal detachment and lens damage.^1,2 Until intravitreal pharmacologic agents with sustained therapeutic effects become more common place, many patients will require ongoing treatment with monthly or near-monthly injections.³ An ocular anesthetic technique that minimizes patient discomfort and risk of complication is important to consider when using intravitreally administered agents.

Numerous methods of anesthesia for intravitreal injection have been compared including peribulbar and subconjunctival anesthetic injections as well as the use of anesthetic eye drops, gels, and anesthetic-soaked pledgets. When 0.5% proxymetacaine plus an anesthetic-soaked cotton tip held to the eye for 30 seconds was compared to subconjunctival 2% lidocaine, Cintra et al found no significant difference in patient pain scores for both the intravitreal injection and total procedure.⁴ Kaderli and Avci also compared topical anesthetic to subconjunctival 4% lidocaine and while there was a significantly lower pain score during the intravitreal injection in the subconjunctival group, the overall procedure pain scores were similar.⁵ Kozak et al and Friedman et al each compared topical lidocaine gel and subconjunctival lidocaine.^6,7 Both studies found no significant difference in pain between the groups and concluded that topical lidocaine gel was superior. In another study, Blaha and coworkers found no significant difference between topical 0.5% tetracaine, 0.5% proparacaine, 4% lidocaine-soaked pledget and subconjunctival 2% lidocaine with each patient experiencing each method in four randomized sequential treatments.¹ Each of the previous authors noted a significant increase in subconjunctival hemorrhage in the subconjunctival lidocaine group. In a review of the literature, Yau and associates concluded that topical anesthetics were the preferred method. In their own comparison of topical entities, they found no significant difference between 4% tetracaine, 4% tetracaine with a lidocaine-soaked cotton swab held to the eye for 10 seconds and 4% cocaine.⁸

While topical drop forms of anesthetic do not appear to increase the risk of infection, the use of lidocaine gel as an ocular anesthetic has been challenged by a theoretical increased risk of infection. In vitro studies have indicated that lidocaine gel may interfere with the antiseptic mechanism of iodine preparations and a large retrospective review of cases of acute post-operative endophthalmitis suggested lidocaine gel as a possible risk factor.^9,10 However, a retrospective review of 4690 consecutive intravitreal injections performed using 2% lidocaine gel found no cases of endophthalmitis; the authors reported that application of povidone-iodine solution directly before and following application of lidocaine gel may explain their favorable results.¹¹ Peribulbar injection of 2% lidocaine was evaluated by Cintra and colleagues and while patients reported significantly lower pain during the intravitreal injection, the overall procedure pain score was significantly higher in this group as it related to the administration of the peribulbar ansthetic.⁴ Peribulbar injection also raises the risks of globe perforation, retrobulbar hemorrhage and persistent diplopia.¹

In summary, the majority of studies to date have demonstrated no significant difference in pain score between topical anesthetics and subconjunctival lidocaine during the time of injection. Non-vision threatening concerns relating to the increased frequency of subconjunctival hemorrhage is a more common feature with subconjunctival anesthesia. Lidocaine gel was found to be useful but the question of increased risk of infection remains. Gel formulations are also more expensive than liquid anesthetic preparations.⁴ For patient comfort, safety, efficiency and cost, current evidence supports the use of topical anesthetics alone with consideration given to lidocaine gel and subconjunctival lidocaine when deemed appropriate by the treating physician. If using an anesthetic pledget, remember to take it out before the patient leaves the office.

REFERENCES
1. Blaha GR, Tilton EP, Barouch FC, Marx JL. Randomized trial of anesthetic methods for intravitreal injections. Retina. 2010;X:1-5. 
2. Meyer CH, Rodrigues EB, Michels S, Mennel S, Schmidt JC, Helb HM, Hager A, Martinazzo M, Farah ME. Incidence of damage to the crystalline lens during intravitreal injections. J Ocul Pharmacol Ther. 2010;26(5):491-5.
3. Lalwani GA, Rosenfeld PJ, Fung AE, Dubovy SR, Michels S, Feuer W, Davis JL, Flynn HW Jr, Esquiabro M. A variable-dosing regimen with intravitreal ranibizumab for neovascular age-related macular degeneration: year 2 of the PrONTO Study. Am J Ophthalmol. 2009;148(1):43-58.e1.
4. Cintra LP, Lucena LR, Da Silva JA, Costa RA, Scott IU, Jorge R. Comparative study of analgesic effectiveness using three different anesthetic techniques for intravitreal injection of bevacizumab. Ophthalmic Surg Lasers Imaging. 2009;40(1):13-8.
5. Kaderli B, Avci R. Comparison of topical and subconjunctival anesthesia in intravitreal injection administrations. Eur J Ophthalmol. 2006 Sep-Oct; 16 (5) :718-21.
6. Kozak I, Cheng L, Freeman WR. Lidocaine gel anesthesia for intravitreal drug administration. Retina. 2005;25(8):994-8.
7. Friedman SM, Margo CE. Topical gel vs subconjunctival lidocaine for intravitreous injection: a randomized clinical trial. Am J Ophthalmol. 2006;142(5):887-8.
8. Yau GL, Jackman CS, Hooper PL, Sheidow TG. Intravitreal injection anesthesia-comparison of different topical agents: a prospective randomized controlled trial. Am J Ophthalmol. 2011;151(2):333-337.e2.
9. Boden JH, Myers ML, Lee T, Bushley DM, Torres MF. Effect of lidocaine gel on povidone-iodine antisepsis and microbial survival. J Cataract Refract Surg. 2008;34(10):1773-1775.
10. Miller JJ, Scott IU, Flynn HW Jr, Smiddy WE, Newton J, Miller D. Acute-onset endophthalmitis after cataract surgery (2000-2004): incidence, clinical settings, and visual acuity outcomes after treatment. Am J Ophthalmol. 2005;139(6):983-7.
11. Inman ZD, Anderson NG. Incidence of endophthalmitis after intravitreal injection of antivascular endothelial growth factor medications using topical lidocaine gel anesthesia. Retina. 2010;X:1-4.