Table 1.

Summary of characteristics of the included studies

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

G group, IVI intravitreal injection, SC, subconjunctival, RNZ, ranibizumab, BVZ bevacizumab, AFL aflibercept, TAC triamcinolone acetonide