Table 3.
Randomized clinical trials and observational studies comparing the adverse events, complications, and unfavorable outcomes between intravitreal anti-VEGF and LPC treatment modalities for TR-ROP
| Authors/first author | Study Type | Year | Participants | Treatment modalities being compared | Outcomes | Risk-of-bias assessment with RoB 2 tool8 or with ROBINS-I tool9 |
|---|---|---|---|---|---|---|
| Stahl et al. [6] | Randomized clinical trial | 2019 | 225 infants with zone 1 stage 1+, 2+, 3 or 3+ ROP, or APROP |
0.2 mg IVR, 0.1 mg IVR, Diode LPC |
Infants with unfavorable structural outcome (retrolental membrane obscuring the view of the posterior pole, substantial temporal retinal vessel dragging causing abnormal structural features or macular ectopia, posterior retinal fold involving the macula, or retinal detachment involving the macula.): 1(0.2 mg IVR group), 5 (0.1 mg IVR group), 7 (LPC group) No differences between groups in: Death Serious AEs Non-serious systemic AEs |
Low overall risk of bias (“Low” in RoB 2.0 tool) |
| Shah et al. [43] | Observational study | 2019 | 398 eyes of 199 infants with APROP |
Anti-VEGF (type and dose unspecified), LPC (type unspecified) |
LPC group had a: Greater rate of eyes with RD (P = 0.002) |
Serious overall risk of bias due to baseline and time-varying confounding |
| Zhang et al. [44] | Observational study | 2019 | 283 infants with TR-ROP |
IVB (dose unspecified), LPC (type unspecified) |
No differences between groups in rate of RD (P = 0.190) Other adverse events (vitreous hemorrhage, corneal opacities, cataract, glaucoma, strabismus) |
Serious overall risk of bias because of missing information in two bias assessment domains |
| Kang et al. [10] | Observational study | 2019 | 52 eyes of 27 infants with TR-ROP |
Anti-VEGF (either IVB 0.625 mg/0.025 ml, or IVR 0.2 mg/0.02 mL), Diode LPC |
No differences between groups in: Rates of complications (systemic complications, death, strabismus requiring operation) (P = 0.160) |
Moderate overall risk of bias |
| Roohipoor et al. [13] | Randomized clinical trial | 2019 | 232 eyes of 116 infants with type 1 zone 2 ROP |
IVB(0.625 mg/0.025 ml), Diode LPC |
IVB group had: Cataract formation in one eye of 159 injected (0.63%) Diode LPC group had: Retinal fold and traction in 2 eyes (2.6%) |
Medium overall risk of bias (“Some Concerns” in RoB 2.0 tool) |
| Kang et al. [36] | Observational study | 2019 | 314 eyes from 165 infants with type 1 ROP | IVR (0.25 mg/0.025 ml), diode LPC |
Diode LPC group had a higher incidence rate of: Retinal detachment (P = 0.040) Macular dragging (P = 0.040) No differences were found between the groups in incidence rate of: Vitreous hemorrhage (P = 0.610) Cataract (P = 0.730) Glaucoma (P = 0.400) Adverse neurodevelopmental outcomes (P = 0.490) Strabismus requiring operation (P = 0.630) |
Moderate overall risk of bias |
| Barry et al. [46] | Observational study | 2019 | 222 eyes of 115 infants with type 1 ROP |
IVB (0.375 to 0.625 mg per eye), LPC (type unspecified) |
LPC group of infants before 36 weeks PMA had a higher rate of: RD (P = 0.011) No differences between groups in rate of: RD for the whole cohort (treated before, at or after 36 weeks PMA, P = 0.373) Death within 8 weeks after treatment (P = 1.000) |
Serious overall risk of bias due to baseline confounding, time-varying confounding and selection bias |
| Lyu et al. [42] | Observational study | 2019 | 27 eyes of 14 infants with type 1 ROP |
IVR (0.25 mg/0.025 ml), Diode LPC |
IVR group had: Greater rate of eyes with unfavorable outcomes (temporally dragged retina over the nerve, retinal detachment, or fold) (P = 0.510, Fisher’s exact test) |
Serious overall risk of bias due to baseline and time-varying confounding |
| Blair et al. [40] | Observational study | 2018 | 36 eyes of 19 infants with APROP |
IVB (0.5–0.625 mg/ 0.02–0.025 cc), Diode LPC |
Diode LPC group had: Higher rate of eyes with poor structural outcome (P = 0.002) |
Serious overall risk of bias due to baseline and time-varying confounding |
| Walz et al. [41] | Observational study | 2018 | 166 infants with TR-ROP |
Anti-VEGF (type and dose unspecified), LPC (type unspecified) |
No differences between the two treatment groups in: Incidence of systemic complications (P > 0.050) |
Serious overall risk of bias due to baseline confounding |
| Lepore et al. [37] | Randomized clinical trial | 2018 | 42 eyes of 21 infants with type 1 zone 1 ROP |
IVB (0.5 mg/0.02 ml), Diode LPC |
Eyes with complete RD 4 weeks after treatment: 1 (IVB group) vs 0 (LPC group) | High overall risk of bias (“High” in RoB 2.0 tool) |
| Roohipoor et al. [19] | Observational study | 2018 | 986 eyes of 493 infants with type 1 ROP |
IVB (0.625 mg/0.025 ml), Diode LPC |
Diode LPC group had a higher rate of: Macular dragging (P = 0.020) No differences between groups in rate of: RD (P = 0.620) |
moderate overall risk of bias |
| Peyton et al. [47] | Observational study | 2018 | 22 infants with type 1 ROP |
IVB (dose unspecified), LPC (type unspecified) |
No differences between groups in rate of: Death in the period of 12- and 24-month PTA (P = 1.000) |
Serious overall risk of bias due to baseline confounding |
| Zhang et al. [39] | Randomized clinical trial | 2017 | 100 eyes of 50 infants with Zone 2 Stage 2 or 3 ROP with plus disease |
IVR (0.3 mg/0.03 ml), Diode LPC |
No complications (anterior segment ischemia, pupillary membrane, lens opacity, vitreous hemorrhage, retinal detachment, endophthalmitis) between groups | Medium overall risk of bias (“Some Concerns” in RoB 2.0 tool) |
| Sukgen et al. [45] | Observational study | 2017 | 31 eyes of 16 infants with stage 4A ROP |
IVR (0.25 mg/0.025 ml), Diode LPC |
No differences between the two treatment groups in: Mean width of partial RD (P = 0.806) |
Moderate overall risk of bias |
| Karkhaneh et al. [38] | Randomized clinical trial | 2016 | 158 eyes of 79 infants with Type 1 Zone 2 ROP |
IVB (0.625 mg/0.025 ml), Diode LPC |
Absence of complications (death, cataract, endophthalmitis, vitreous hemorrhage, retinal detachment) at 54 weeks PMA in both groups | Medium overall risk of bias (“Some Concerns” in RoB 2.0 tool) |
| Kong et al. [22] | Observational study | 2015 | 80 eyes of 42 infants with type 1 ROP |
IVB (0.625 mg/0.025) ml, LPC (type unspecified) |
LPC group had: Higher rate of unfavorable structural outcomes at 1 year of chronological age (P = 0.020) |
Serious overall risk of bias due to baseline and time-varying confounding |
| Gunay et al. [27] | Observational study | 2015 | 78 eyes of 40 infants with APROP |
IVB (0.625 mg/0.025) ml, Diode LPC |
Diode LPC group had: Greater rate of strabismus at 2 years CA (P = 0.040) |
Serious overall risk of bias due to selection bias |
| Isaac et al. [31] | Observational study | 2015 | 45 eyes of 25 infants with type 1 ROP |
IVB (0.625 mg/0.025) ml, Diode LPC |
No differences between the two treatment groups in: Favorable outcomes (P = 0.080) |
moderate overall risk of bias |
| Warren et al. [33] | Observational study | 2015 | 47 infants with threshold ROP |
IVB (dose unspecified), Diode LPC |
No differences between the two treatment groups in: Rate of infants with strabismus requiring surgery (P > 0.050) |
Serious overall risk of bias due to baseline and time-varying confounding |
| Mintz-Hittner et al. [5] | Randomized clinical trial | 2011 | 300 eyes of 150 infants with zone 1 or zone 2 posterior stage 3 + ROP |
IVB (0.625 mg/0.025 ml), Diode LPC |
Eyes with macular dragging: 1 (IVB group) vs 22 (LPC group) Eyes with RD: 2 (IVB group) vs 2 (LPC group) Eyes with corneal opacity requiring corneal transplant: 1 (LPC group) Lens opacity requiring cataract removal: 3 (LPC group) Infants with Death: 5 (IVB group) 2 (LPC group) |
Low overall risk of bias (“Low” in RoB 2.0 tool) |
anti-VEGF anti-vascular endothelial growth factor, LPC laser photocoagulation, TR-ROP treatment-requiring retinopathy of prematurity, RoB 2: version 2 of the Cochrane risk-of-bias tool for randomized trials, ROBINS-I: risk of bias in non-randomized studies of interventions, ROP retinopathy of prematurity, IVB intravitreal bevacizumab, RD retinal detachment, APROP aggressive posterior retinopathy of prematurity, IVR intravitreal ranibizumab, AE adverse event, CA corrected age, PMA postmenstrual age, PTA post term age