Clinical trial NCT02263690: Comparison of Three Different Anesthetic Approaches for Intravitreal Injections
Official title: Comparison of Three Different Anesthetic Approaches for Intravitreal Injections: A Prospective Randomized Trial
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Pain
Lead sponsor: Retina Clinic, Sao Paulo, Brazil
Sponsor class: OTHER
First posted: 2014-10-13
Enrollment: 92
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief summary: 92 patients in treatment with intravitreal injections were randomized to 1 of 3 groups: proparacaine 0.5% drops (Group Drops), proparacaine 0.5% drops plus subconjunctival lidocaine (Group SC), or 2% lidocaine gel (Group Gel). Patients were asked to score their pain experience using a visual analogue scale (VAS), a scale of 0 to 10, immediately following the injections as well as 10 minutes, 1 hour, 6 hours and 24 hours after. Patients also graded the overall injection experience as Excellent, Very Good, Fair, Poor or Awful. The physician evaluated the patient's eye movement during intravitreal injection in three levels: none or minimal (0), not compromising the injection (1), compromising the injection (2).

Detailed description: This prospective, randomized, triple-armed trial compared the effectiveness of three different anesthetic approaches for intravitreal injections. Were included 92 consecutive patients scheduled to receive intravitreal injection of bevacizumab (Avastin, Genentech, Inc.) in one eye, from June 2014 to September 2014, evaluated at at a single center - Retina Clinic, Osasco, São Paulo, Brazil. The same ophthalmologist (CGA) administered both, anesthetic and therapeutic, injections. A masked nurse collected patient assessment responses and a masked statistician performed statistical analyses. The research followed the tenets of the Declaration of Helsinki and was approved by the Committee of Ethics in Research. All participants gave written informed consent prior to their participation.

Patients were randomized to 1 of 3 groups before injection: proparacaine 0.5% drops (Anestalcon®, Alcon Lab. do Brasil Ltda, São Paulo, Brazil), (Group Drops), proparacaine plus subconjunctival lidocaine 1% (Xylestesin®, Cristália, São Paulo, Brazil) (Group SC), or 2% lidocaine gel (Xylestesin®, Cristália, São Paulo, Brazil) (Group Gel).

A standardized method was used to prepare the injection site and disinfect the skin using povidone iodine 10%. Patients from groups Drops and SC received a drop of proparacaine 0.5% before receiving a drop of povidone iodine 5%. For the patients from Group Gel, the gel was placed on the eye before receiving the drop of povidone iodine 5%. Patients from Group Drops received a second drop of proparacaine 0.5%, 5 minutes after the drop of povidone iodine 5%. For the patients from Group SC, a subconjunctival bleb of anesthesia was created by injecting 0.4 ml of lidocaine 1% into the subconjunctival space, posteriorly to the superotemporal limbus with a 30-gauge, 1/2-inch needle attached to a 1-ml syringe. After 5 minutes of the drop of povidone iodine 5%, sterile field and a lid speculum were placed. The injection site was measured with calipers to be 3.5 mm or 4.0 mm posterior to the superotemporal limbus, for pseudophakic and phakic eyes, respectively. A 30-gauge 1/2-inch needle was used to inject 0.05 ml of bevacizumab (Avastin, Genentech, Inc.). After the injection, mild pressure was applied with a swabstick over the injection site to reduce vitreous reflux and subconjunctival hemorrhage another a drop of povidone iodine 5% was applied.

Immediately following the injection, a nurse, who was masked to the treatment, explained the 100-mm visual analog scale (VAS) for pain (Figure 1) and questioned the patients' level of pain perceived during the injection. This assessment was repeated 10 minutes, 1 hour, 6 hours and 24 hours later, without visualization of their prior responses. Patients were also asked to grade their overall experience with the injection procedure as Excellent (5), Very good (4), Fair (3), Poor (2) or Awful (1). The physician evaluated the patients' eye movement during intravitreal injection into three levels: none or minimal (0), not compromising the injection (1), compromising the injection (2). Complications that occurred during or after the procedures were also recorded.

Eligibility criteria: Inclusion Criteria:

* Age: 18 years or older
* Indications for injection included neovascular AMD, DME and cystoid macular edema (CME) secondary to RVO.

Exclusion Criteria:

* Previous known allergic response to the topical anesthetics to be used.
* Previous intravitreal injections of drugs other than anti-VEGF agents
* Previous pars plana vitrectomy
* Anterior segment conditions that could affect pain sensation, such as conjunctival irritation, active conjunctivitis or keratitis or bullous keratopathy
* Patients using systemic analgesic or sedative medications

Primary outcomes:
measure: Pain experience and patient satisfaction after 3 different anesthetic approaches for intravitreal injections
timeFrame: immediately after injection, 10 minutes, 1 hour, 6 hours and 24 hours later
Secondary outcomes:
Other outcomes:
Locations:
city: Osasco
country: Brazil
facility: Retina Clinic
state: São Paulo
Study officials:
affiliation: Vitreo-retinal Fellow
name: Gabriel C Andrade, M.D.
role: PRINCIPAL_INVESTIGATOR
References:
citation: Aiello LP, Brucker AJ, Chang S, Cunningham ET Jr, D'Amico DJ, Flynn HW Jr, Grillone LR, Hutcherson S, Liebmann JM, O'Brien TP, Scott IU, Spaide RF, Ta C, Trese MT. Evolving guidelines for intravitreous injections. Retina. 2004 Oct;24(5 Suppl):S3-19. doi: 10.1097/00006982-200410001-00002.
citation: Ulrich JN. Topical nepafenac after intravitreal injection: a prospective double-masked randomized controlled trial. Retina. 2014 Mar;34(3):509-11. doi: 10.1097/IAE.0b013e3182a0e611.
citation: Brynskov T, Kemp H, Sorensen TL. No cases of endophthalmitis after 20,293 intravitreal injections in an operating room setting. Retina. 2014 May;34(5):951-7. doi: 10.1097/IAE.0000000000000071.
citation: Nuzzi R, Tridico F. Local and systemic complications after intravitreal administration of anti-vascular endothelial growth factor agents in the treatment of different ocular diseases: a five-year retrospective study. Semin Ophthalmol. 2015 Mar;30(2):129-35. doi: 10.3109/08820538.2013.835833. Epub 2013 Oct 30.
citation: 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 Jan-Feb;40(1):13-8. doi: 10.3928/15428877-20090101-05.
citation: Kaderli B, Avci R. Comparison of topical and subconjunctival anesthesia in intravitreal injection administrations. Eur J Ophthalmol. 2006 Sep-Oct;16(5):718-21. doi: 10.1177/112067210601600509.
citation: Bartfield JM, Holmes TJ, Raccio-Robak N. A comparison of proparacaine and tetracaine eye anesthetics. Acad Emerg Med. 1994 Jul-Aug;1(4):364-7. doi: 10.1111/j.1553-2712.1994.tb02646.x.
citation: Blaha GR, Tilton EP, Barouch FC, Marx JL. Randomized trial of anesthetic methods for intravitreal injections. Retina. 2011 Mar;31(3):535-9. doi: 10.1097/IAE.0b013e3181eac724.
citation: Davis MJ, Pollack JS, Shott S. Comparison of topical anesthetics for intravitreal injections : a randomized clinical trial. Retina. 2012 Apr;32(4):701-5. doi: 10.1097/IAE.0b013e31822f27ca.
citation: Kozak I, Cheng L, Freeman WR. Lidocaine gel anesthesia for intravitreal drug administration. Retina. 2005 Dec;25(8):994-8. doi: 10.1097/00006982-200512000-00007.
citation: Friedman SM, Margo CE. Topical gel vs subconjunctival lidocaine for intravitreous injection: a randomized clinical trial. Am J Ophthalmol. 2006 Nov;142(5):887-8. doi: 10.1016/j.ajo.2006.06.033.
citation: Page MA, Fraunfelder FW. Safety, efficacy, and patient acceptability of lidocaine hydrochloride ophthalmic gel as a topical ocular anesthetic for use in ophthalmic procedures. Clin Ophthalmol. 2009;3:601-9. doi: 10.2147/opth.s4935. Epub 2009 Nov 2.
citation: 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 Oct;34(10):1773-5. doi: 10.1016/j.jcrs.2008.05.056.
citation: Inman ZD, Anderson NG. Incidence of endophthalmitis after intravitreal injection of antivascular endothelial growth factor medications using topical lidocaine gel anesthesia. Retina. 2011 Apr;31(4):669-72. doi: 10.1097/IAE.0b013e3181ef463d.
citation: Charles S, Rosenfeld PJ, Gayer S. Medical consequences of stopping anticoagulant therapy before intraocular surgery or intravitreal injections. Retina. 2007 Sep;27(7):813-5. doi: 10.1097/IAE.0b013e318154b9f2. No abstract available.
citation: Meyer CH, Callizo J, Mennel S, Kussin A. Perioperative management of anticoagulated patients undergoing repeated intravitreal injections. Arch Ophthalmol. 2007 Jul;125(7):994. doi: 10.1001/archopht.125.7.994. No abstract available.