Table 4.
Randomized clinical trials and observational studies that compare disease recurrence, disease regression and need for retreatment 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 |
|---|---|---|---|---|---|---|
| Kang et al. [10] | Observational study | 2019 | 52 eyes of 27 infants with TR-ROP |
IVB (0.625 mg/0.025 ml), IVR (0.2 mg/0.02 ml), Diode LPC |
No differences between groups in: ROP recurrence requiring retreatment (P = 0.120) |
Serious overall risk of bias due to bias in measuring of the outcome |
| Roohipoor et al. [13] | Randomized clinical trial | 2019 | 232 eyes of 116 infants with type 1 ROP in zone II (stage 2 or 3 ROP with plus disease) |
IVB (0.625 mg/0.025 ml), Diode LPC |
No differences between groups in: Rate of complete vascularization of non-ablated retina and ROP regression at 90 weeks PMA (P = 0.200) |
High overall risk of bias (“High” in the RoB 2 tool) |
| 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: Higher rate of eyes with additional treatment due to ROP resistance, ROP reactivation, ROP progression and due to avascularity in zone 1 or zone 2 (P = 0.040) No differences between groups at: Rates of regression of acute ROP after primary treatment (P = 0.330) |
Serious overall risk of bias due to baseline confounding |
| Zhang et al. [44] | Observational study | 2019 | 283 infants with TR-ROP |
IVB (dose unspecified), LPC (type unspecified) |
Anti-VEGF group had: Greater odds of having a second procedure (P < 0.001) |
Serious overall risk of bias due to bias in measurement of the outcome |
| Kang et al. [36] | Observational study | 2019 | 314 eyes of 165 infants with type 1 ROP |
IVR (0.25 mg/0.025 ml), Diode LPC |
Diode LPC group had: Higher rate of infants that underwent additional laser (P = 0.010) Higher rate of additional scleral encircling (scleral buckling (P = 0.040) No differences between groups at: Infants requiring addition IVR injection (P = 0.010) Need for vitrectomy (P = 0.660) |
Serious overall risk of bias due to bias in the measurement of the outcomes |
| 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) |
No differences between groups in: Rate of retreatment within the period of 8 weeks (P = 0.140, Fisher’s exact test) |
Serious overall risk of bias due to bias in measurement of the outcome |
| Ling et al. [48] | Observational study | 2019 | 340 eyes of 176 infants with type 1 ROP |
IVB (0.625 mg/0.025 ml), IVR (0.25 mg/0.025 ml), Diode LPC |
At 75 weeks PMA, no differences between groups in: ROP recurrence rate (P = 0.050) Rate of need for vitrectomy (P = 0.270) Both anti-VEGF groups had: Higher mean interval of recurrence from initial treatment than the LPC group (P < 0.001) ROP recurrence at a later age compared to LPC group (P = 0.005) |
Moderate overall risk of bias |
| 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 |
IVB group had: Higher rate of disease activity (P = 0.040) Lower mean time to complete regression (P = 0.001) No differences between groups at: Rates of retreatment (P = 0.060) Time between treatment and retreatment (P = 0.270) |
The two first outcomes are at serious overall risk of bias due to bias in measurement of the outcome. The next two are at moderate overall risk of bias |
| 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 |
IVB group FA findings 4 years after treatment: All eyes had abnormalities at the periphery (shunts, vessel leakage, avascular area, tangles, abnormal vessel branching/abnormalities at the posterior pole, such as hyperfluorescent lesions and absence of foveal avascular zone LPC group FA findings 4 years after treatment: leakage (1 eye), tangles and shunts (3 eyes), macular abnormalities (3 eyes) |
High overall risk of bias (“High” in the RoB 2 tool) |
| Blair et al. [40] | Observational study | 2018 | 36 eyes of 19 patients with APROP |
IVB (0.5–0.625 mg /0.02–0.025 cc), Diode LPC |
No differences between groups at: Rate of eyes with acute reactivation requiring retreatment (P > 0.050) Mean age of the treatment-requiring recurrence (P = 0.080) |
Serious overall risk of bias due to baseline and time-varying confounding |
| Zhang et al. [39] | Randomized clinical trial | 2017 | 100 eyes of 50 infants with Zone 2 TR-ROP (i.e., zone 2 stage 2 or 3 ROP with plus disease) |
IVR (0.3 mg/0.03 ml), Diode LPC |
The IVR group had: Greater rates of ROP recurrence (P = 0.001) |
Medium overall risk of bias (“Some Concerns” in the RoB 2.0 tool) |
| Sukgen et al. [45] | Observational study | 2017 | 31 eyes in 16 patients with stage 4A ROP |
IVR (0.25 mg/0.025 ml), Diode LPC |
No differences between groups at: Rates of requirement for vitreoretinal surgery due to ROP progression (P = 0.230) |
Moderate overall risk of bias |
| Toy et al. [51] | Observational study | 2016 | 58 eyes of 30 patients with type 1 ROP |
IVB (0.625 mg/0.025 ml), Diode LPC |
Rate of recurrence or angiographic demonstration of ischemia, leakage, or both requiring rescue laser was 91% in IVB group vs 0% in diode LPC | Serious overall risk of bias |
| Nicoară et al. [50] | Observational study | 2016 | 46 eyes of 23 infants with APROP |
IVB (0.625 mg/0.025 ml), Diode LPC |
IVB group had: Greater rates of APROP regression (P < 0.001, McNemar test) |
Moderate overall risk of bias |
| Karkhaneh et al. [38] | Randomized clinical trial | 2016 | 158 eyes of 79 infants with zone 2/stage 2 or 3 ROP |
IVB (0.625 mg/0.025 ml), Diode LPC |
IVB group had: Higher rate of stage 3 ROP recurrence and retreatment (P = 0.020) No differences between groups in: Need for PPV (P = 0.540) Time between treatment and retreatment (P = 0.290) |
Medium overall risk of bias (“Some Concerns” in the RoB 2.0 tool) |
| Kong et al. [22] | Observational study | 2015 | 80 eyes of 42 patients with type 1 ROP |
IVB (0.625 mg/0.025 ml), LPC (type unspecified) |
No differences between groups at: Rate of retreated eyes (P = 0.330) |
Serious overall risk of bias due to baseline confounding |
| Hwang et al. [29] | Observational study | 2015 | 54 eyes of 28 infants with type 1 ROP |
IVB (0.625 mg/0.025 ml), Diode LPC |
No differences between groups at: Rates of ROP recurrence (P = 1.000) |
Moderate overall risk of bias |
| Warren et al. [33] | Observational study | 2015 | 47 infants with threshold ROP |
IVB (dose unspecified), LPC (type unspecified) |
Anti-VEGF group had: Longer time to maturation (P < 0.050) No differences between groups at: Rates of patients requiring retreatment (P > 0.050) Patients requiring vitrectomy (P > 0.050) |
Serious overall risk of bias due to baseline and time-varying confounding |
| Moran et al. [49] | Randomized clinical trial | 2014 | 28 eyes of 14 infants with symmetrical zone 1 or posterior zone 2 Stage 3+ ROP |
IVB (1.25 mg/0.1 ml), Diode LPC |
Recurrence requiring retreatment: 3 eyes (21.42%) of the IVB group, 1eye (7.14%) of the diode LPC group IVB group had Longer time until recurrence (measured in weeks PMA) (P < 0.050) |
High overall risk of bias (“High” in the RoB 2 tool) |
| Mintz-Hittner et al. [5] | Randomized clinical trial | 2011 | 300 eyes of 150 infants with ROP (zone 1 or zone 2 posterior stage 3+) |
IVB (0.625 mg/0.025 ml), Diode LPC |
IVB group had: Lower rates of ROP recurrence compared to the LPC group (OR = 0.17, 95% CI: 0.05–0.53; P = 0.002, for zones 1 and 2 combined) Other outcomes: Performance of PPV: 2 eyes (IVB group), 13 eyes (LPC group) |
Medium overall risk of bias (“Some Concerns” in the 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, OR odds ratio, CI confidence interval, PPV pars plana vitrectomy, IVR intravitreal ranibizumab, PMA postmenstrual age, FA fluorescent angiography, APROP aggressive posterior retinopathy of prematurity