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Table 1 Summary of characteristics of the included studies

From: Patient pain during intravitreal injections under topical anesthesia: a systematic review

Study background Participants Interventions Outcomes
References (country) Objective Cases, n Mean age, years Groups according to anesthetic technique Pain grading Drug Average pain score Main conclusion
Blaha et al. [16] (USA) To compare pain scores during injection versus total procedure for four anesthetic techniques 96 80 G1: 0.5% topical proparacaine Pain was graded on a 0 to 10 scale RNZ, BVZ G1: 3.0 No statistical difference in pain scores for the four anesthetic techniques. Topical drops provided excellent anesthesia in a quick, comfortable, and safe manner for IVI
G2: 0.5% topical tetracaine G2: 2.8
G3: topical proparacaine + 4% lidocaine pledget G3: 2.3
G4: topical proparacaine + SC injection of 2% lidocaine G4: 3.1
p = 0.28
Yau et al. [11] (Canada) To compare the anesthetic effectiveness of three topical agents used for IVIs 93 Group 1: 83.6 G1: 0.5% tetracaine hydrochloride drops + 4% lidocaine pledget for 10 Patients graded pain on a 100-mm VAS, or by saying a number from 0 to 100 RNZ G1: 19 (12–26) No clinical (statistical) difference in patient pain between the three topical agents tested. The addition of a 4% lidocaine pledget for 10” offered no clinical advantage in pain relief compared to 0.5% tetracaine or 4% cocaine drops alone
Group 2: 79.5 G2: 0.5% tetracaine hydrochloride drops G2: 21 (13–29)
Group 3: 82.1 G3: 4% cocaine + epinephrine 1/100.000 drops G3: 21 (16–27)
Örnek et al. [14] (Turkey) To compare the efficacy of topical 0.75% levobupivacaine and 0.5% proparacaine 96 63.97 G1: 0.75% levobupivacaine drops Patients graded pain on a 100-mm VAS RNZ, TAC G1: 44.77 ± 16.42 0.5% topical proparacaine was more effective than 0.75% topical levobupivacaine in preventing pain during IVI
G2: 0.5% proparacaine drops G2: 34.18 ± 14.83
p = 0.003
Shiroma et al. [1] (Brazil) To investigate the safety and anesthetic efficacy of five concentrations of lidocaine gel 260 70.1 G1: 2% lidocaine gel Patients graded pain on a 0 to 10 scale RNZ G1: 2.63 ± 1.68 Lidocaine gel at concentrations from 2% to 12% induced similar anesthetic effect for IVI
G2: 3.5% lidocaine gel G2: 2.08 ± 1.35
G3: 5% lidocaine gel G3: 2.00 ± 1.65
G4: 8% lidocaine gel G4: 1.93 ± 1.40
G5: 12% lidocaine gel G5: 1.83 ± 1.35
p = 0.077
Andrade et al. [6] (Brazil) To compare the anesthetic effectiveness of topical proparacaine drops, SC lidocaine, and 2% lidocaine gel 92 66.4 G1: proparacaine Patients graded pain on a 0 to 10 scale BVZ G1: 3.2 ± 1.7 SC injection of lidocaine was most effective in preventing pain during IVI compared to proparacaine or 2% lidocaine gel
G2: proparacaine + SC injection of 2% lidocaine G2: 1.0 ± 1.0
G3: 2% lidocaine gel G3: 1.0 ± 1.1
Kumar et al. [15] (UK) To compare patient comfort during IVI after SC anesthesia or topical eye drops 30 G1: 72 G1: 0.5% proximetacaine Patients graded pain on a 0 to 10 scale TAC G1: 0.87 ± 0.83 There was no significant difference in pain scores or overall satisfaction scores between the two groups
G2: 74 G2: SC injection of 2% lidocaine G2: 0.93 ± 0.96
p = 0.84
Davis et al. [2] (USA) To compare the anesthetic effect among topical proparacaine drops, 4% lidocaine solution, and 3.5% lidocaine gel 120 80.18 G1: 0.5% topical proparacaine Patients graded pain on a 0 to 10 scale BVZ, RNZ, TAC G1: 1.78 ± 1.44 There was no significant difference in pain scores or overall satisfaction scores between the different groups
G2: topical proparacaine + 4% lidocaine pledget G2: 1.75 ± 1.46
G3: 3.5% lidocaine gel G3: 1.48 ± 1.58
p = 0.38
Rifkin and Schaal [5] (USA) To determine factors associated with patient comfort during in-office IVI 60 65 G1: 0.5% TetraVisc Patients graded pain on a 0 to 10 scale BVZ, RNZ, TAC G1: 3.39 ± 2.26 The tetracaine group reported the lowest pain
G2: proparacaine G2: 3.17 ± 2.18
G3: tetracaine G3: 3.05 ± 2.01
p < 0.01
  1. G group, IVI intravitreal injection, SC, subconjunctival, RNZ, ranibizumab, BVZ bevacizumab, AFL aflibercept, TAC triamcinolone acetonide