Comparison of Three Different Anesthetic Approaches for Intravitreal Injections

Study Overview
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Brief Summary
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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
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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.

Official Title
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Comparison of Three Different Anesthetic Approaches for Intravitreal Injections: A Prospective Randomized Trial

Conditions
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Pain

Intervention / Treatment
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* Procedure: Group Drops
* Procedure: Group SC
* Procedure: Group gel


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Group Drops<br>proparacaine 0.5% drops (Group Drops) Patients from group Drops received a drop of proparacaine 0.5% before receiving a 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%. | Procedure: Group Drops<br>* The patients in the group Drops received a drop of proparacaine 0.5% before receiving a peri-ocular drop of povidone iodide 5%. The patients in the group Drops received a second drop of proparacaine 0.5% 5 minutes after the drop of povidone iodide 5%<br>* Other names: Proparacaine 0.5% drops;|
| Active Comparator: Group SC<br>proparacaine 0.5% drops plus subconjunctival lidocaine (Group SC) Patients from group SC received a drop of proparacaine 0.5% before receiving a 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. | Procedure: Group SC<br>* The patients in the group SC received a drop of proparacaine 0.5% before receiving a peri-ocular drop of povidone iodide 5%. In the patients in the group SC, a subconjunctival bleb of anesthesia was created by injecting 0,4 mL of lidocaine 1% into the subconjunctival space 4 mm posterior to the superotemporal limbus with a 30-gauge, 1/2-inch needle attached to a 1-mL syringe.<br>* Other names: Subconjunctival 1% Lidocaine;|
| Active Comparator: Group Gel<br>Lidocaine gel 2% on the eye (Group Gel) Patients from Group Gel received 1 mL of 2% lidocaine gel on the eye before receiving the drop of povidone iodine 5%. For the patients from Group Gel, 1 mL of 2% lidocaine gel was applied on the eye before receiving the drop of povidone iodine 5%. | Procedure: Group gel<br>* For the patients in group gel, the gel was placed on the eye before receiving the peri-ocular drop of povidone iodide 5%.<br>* Other names: Lidocaine 2% gel;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pain experience and patient satisfaction after 3 different anesthetic approaches for intravitreal injections | Pain experience according the visual analogue scale (VAS), a scale of 0 to 10 (0 = no pain, 10 = worst pain ever). Patient satisfaction according the overall injection experience, graded by the patient as Excellent, Very Good, Fair, Poor, or Awful. | immediately after injection, 10 minutes, 1 hour, 6 hours and 24 hours later |