TABLE 4.
Moderate and strong signals of anti-VEGF drugs in ocular adverse events.
| SMQs/PTs | Ranibizumab | Aflibercept | Brolucizumab | ||||||
|---|---|---|---|---|---|---|---|---|---|
| N | ROR (95%CI) | IC (IC-2SD) | N | ROR (95%CI) | IC (IC-2SD) | N | ROR (95%CI) | IC (IC-2SD) | |
| Retinal disorders | |||||||||
| Retinal pigment epithelial tear | 356 | 836.54 (706.72, 990.22) | 7.39 (7.19) | 55 | 58.67 (44.42, 77.50) | 4.78 (4.37) | 10 | 77.05 (41.18, 144.16) | 3.28 (2.40) |
| Detachment of retinal pigment epithelium | 292* | 440.01 (376.16, 514.69) | 7.03 (6.82) | 63 | 61.35 (47.27, 79.61) | 4.90 (4.52) | 18 | 127.85 (79.88, 204.63) | 4.05 (3.38) |
| Vitreous haemorrhage | 333* | 133.70 (118.43, 150.94) | 6.32 (6.14) | 157* | 60.00 (50.86, 70.78) | 5.33 (5.09) | 14* | 38.10 (22.48, 64.57) | 3.45 (2.70) |
| Retinal haemorrhage | 660* | 97.72 (89.83, 106.31) | 6.16 (6.04) | 307* | 44.37 (39.47, 49.88) | 5.17 (5.00) | 72 | 77.97 (61.55, 98.76) | 5.21 (4.87) |
| Retinal scar | 122* | 377.92 (298.95, 477.77) | 6.30 (5.98) | 25* | 52.95 (35.12, 79.83) | 4.10 (3.51) | / | / | / |
| Macular hole | 117* | 95.96 (78.73, 116.97) | 5.59 (5.30) | 101* | 88.06 (71.35, 108.68) | 5.45 (5.14) | / | / | / |
| Vitreous floaters | 401 | 50.89 (45.89, 56.44) | 5.36 (5.21) | 386 | 53.28 (47.96, 59.20) | 5.41 (5.26) | 453 | 599.32 (538.71, 666.74) | 7.80 (7.65) |
| Subretinal fibrosis | 59* | 375.82 (268.40, 526.22) | 5.56 (5.11) | / | / | / | 6* | 196.41 (86.59, 445.50) | 2.76 (1.64) |
| Retinal tear | 132* | 62.55 (52.18, 74.98) | 5.30 (5.03) | 21 | 9.79 (6.36, 15.08) | 2.79 (2.17) | 9 | 32.64 (16.92, 62.95) | 2.97 (2.05) |
| Retinal ischaemia | 56* | 89.16 (67.10, 118.47) | 5.03 (4.62) | 18* | 27.89 (17.37, 44.79) | 3.50 (2.82) | 23* | 285.66 (187.01, 436.37) | 4.46 (3.85) |
| Retinal detachment | 261 | 30.46 (26.86, 34.53) | 4.69 (4.50) | 119 | 14.58 (12.15, 17.50) | 3.67 (3.40) | 8 | 122.31 (60.51, 247.23) | 3.08 (2.10) |
| Vitreous detachment | 72 | 37.96 (29.87, 48.25) | 4.58 (4.23) | 31 | 17.07 (11.94, 24.41) | 3.48 (2.96) | 9 | 38.09 (19.74, 73.50) | 3.01 (2.09) |
| Retinal artery occlusion | 76* | 29.52 (23.41, 37.21) | 4.37 (4.03) | 74* | 31.31 (24.76, 39.58) | 4.42 (4.08) | 110 | 391.11 (320.55, 477.19) | 6.39 (6.10) |
| Retinal depigmentation | 27* | 112.60 (74.20, 170.88) | 4.43 (3.84) | 9* | 35.64 (18.16, 69.95) | 2.98 (2.03) | / | / | / |
| Macular ischaemia | 23* | 205.27 (126.46, 333.18) | 4.37 (3.70) | / | / | / | / | / | / |
| Retinal vascular thrombosis | 24* | 36.12 (23.87, 54.66) | 3.87 (3.27) | / | / | / | / | / | / |
| Vitreous haze | 17* | 154.38 (89.70, 265.70) | 3.97 (3.22) | 29* | 365.83 (228.87, 584.76) | 4.73 (4.10) | 25 | 2285.46 (1407.06, 3712.23) | 4.68 (4.02) |
| Retinal vasculitis | 28* | 23.82 (16.30, 34.81) | 3.70 (3.15) | 51* | 49.29 (37.00, 65.65) | 4.61 (4.19) | 237 | 2930.41 (2480.17, 3462.39) | 7.70 (7.47) |
| Photopsia | 68* | 10.81 (8.50, 13.75) | 3.21 (2.86) | 28* | 4.79 (3.30, 6.94) | 2.07 (1.53) | 35* | 47.60 (34.03, 66.57) | 4.36 (3.87) |
| Vitreal cells | / | / | / | 28* | 361.41 (224.49, 581.84) | 4.68 (4.05) | 37* | 4799.11 (3007.42, 7658.20) | 5.22 (4.64) |
| Ocular infections | |||||||||
| Endophthalmitis | 590 | 109.11 (99.74, 119.36) | 6.26 (6.13) | 805 | 178.27 (164.51, 193.19) | 6.82 (6.70) | 38 | 49.60 (35.94, 68.46) | 4.45 (3.98) |
| Vitritis | 97 | 67.92 (54.93, 83.99) | 5.22 (4.91) | 237* | 225.79 (194.06, 262.71) | 6.58 (6.37) | 196 | 1469.04 (1244.90, 1733.54) | 7.37 (7.13) |
| Hypopyon | 41* | 44.51 (32.34, 61.26) | 4.39 (3.93) | 66* | 82.67 (63.81, 107.10) | 5.12 (4.75) | 18* | 160.07 (99.84, 256.63) | 4.09 (3.41) |
| Eye infection | 160* | 19.64 (16.76, 23.01) | 4.08 (3.85) | 127* | 16.85 (14.12, 20.12) | 3.86 (3.60) | 18* | 18.26 (11.47, 29.06) | 3.25 (2.58) |
| Blepharitis | 22 | 7.77 (5.10, 11.84) | 2.57 (1.96) | 17* | 6.53 (4.04, 10.53) | 2.31 (1.62) | / | / | / |
| Glaucoma | |||||||||
| Ocular hypertension | 102* | 68.17 (55.42, 83.85) | 5.25 (4.95) | 62* | 42.87 (33.10, 55.53) | 4.62 (4.24) | 7* | 35.49 (16.85, 74.75) | 2.74 (1.71) |
| Intraocular pressure increased | 310 | 21.58 (19.24, 24.19) | 4.27 (4.10) | 402 | 31.09 (28.10, 34.41) | 4.76 (4.61) | 80 | 47.01 (37.58, 58.81) | 4.87 (4.54) |
| Glaucoma | 182* | 9.85 (8.50, 11.42) | 3.20 (2.98) | 100* | 5.83 (4.79, 7.11) | 2.46 (2.17) | 27* | 12.32 (8.43, 18.01) | 3.12 (2.57) |
| Lens disorders | |||||||||
| Cataract | 430 | 9.41 (8.54, 10.36) | 3.16 (3.01) | 261 | 6.14 (5.43, 6.94) | 2.56 (2.38) | 62 | 11.47 (8.91, 14.76) | 3.27 (2.90) |
| Posterior capsule opacification | 19 | 90.31 (55.43, 147.14) | 4.00 (3.31) | 7* | 32.61 (15.21, 69.90) | 2.70 (1.65) | 6* | 217.69 (95.79, 494.71) | 2.77 (1.64) |
| Posterior capsule rupture | 8* | 63.54 (30.46, 132.53) | 2.98 (1.96) | / | / | / | / | / | / |
| Lenticular opacities | 9* | 23.34 (11.96, 45.54) | 2.83 (1.90) | / | / | / | / | / | / |
| Toxic anterior segment syndrome | / | / | / | 20* | 24.17 (15.45, 37.83) | 3.49 (2.85) | / | / | / |
| Corneal disorders | |||||||||
| Corneal abrasion | 41* | 33.83 (24.65, 46.42) | 4.19 (3.73) | 28* | 24.67 (16.89, 36.03) | 3.73 (3.18) | / | / | / |
| Corneal erosion | 22* | 37.93 (24.59, 58.51) | 3.82 (3.20) | 10* | 18.06 (9.62, 33.91) | 2.81 (1.92) | / | / | / |
| Corneal oedema | 35* | 14.46 (10.33, 20.24) | 3.37 (2.88) | 53 | 24.26 (18.42, 31.95) | 4.04 (3.64) | 9* | 31.18 (16.17, 60.14) | 2.95 (2.03) |
| Keratic precipitates | 14* | 44.49 (25.76, 76.84) | 3.48 (2.70) | 36* | 144.85 (100.34, 209.09) | 4.81 (4.29) | 121* | 10432.45 (7534.69, 14444.65) | 6.87 (6.53) |
| Corneal opacity | / | / | / | 14* | 12.58 (7.41, 21.38) | 2.81 (2.06) | 9* | 63.07 (32.62, 121.94) | 3.13 (2.20) |
| Conjunctival disorders | |||||||||
| Conjunctival haemorrhage | 70 | 16.73 (13.18, 21.23) | 3.74 (3.39) | 53 | 13.70 (10.43, 17.99) | 3.44 (3.04) | / | / | / |
| Conjunctival hyperaemia | 22 | 6.64 (4.36, 10.11) | 2.40 (1.79) | 19* | 6.24 (3.97, 9.81) | 2.29 (1.64) | 21 | 54.52 (35.39, 84.00) | 3.98 (3.36) |
| Conjunctivitis | 63* | 4.38 (3.42, 5.62) | 2.05 (1.68) | / | / | / | / | / | / |
| Lacrimal disorders | |||||||||
| Lacrimation increased | 183 | 8.04 (6.95, 9.31) | 2.92 (2.71) | 136 | 6.48 (5.47, 7.68) | 2.62 (2.37) | 70 | 26.57 (20.94, 33.73) | 4.25 (3.90) |
| Dry eye | / | / | / | / | / | / | 46* | 12.48 (9.32, 16.71) | 3.30 (2.88) |
Abbreviations: PTs, Preferred Terms; SMQs, Standardised MedDRA Queries; N, Number of target adverse events of target drug.
/indicates that IC-2SD value of the adverse event is less than 1.5.
*indicates that this adverse reaction is not in the instructions.