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Cochrane Database of Systematic Reviews

Anti‐vascular endothelial growth factor (VEGF) drugs for treatment of retinopathy of prematurity

Información

DOI:
https://doi.org/10.1002/14651858.CD009734.pub3Copiar DOI
Base de datos:
  1. Cochrane Database of Systematic Reviews
Versión publicada:
  1. 08 enero 2018see what's new
Tipo:
  1. Intervention
Etapa:
  1. Review
Grupo Editorial Cochrane:
  1. Grupo Cochrane de Neonatología

Copyright:
  1. Copyright © 2018 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.

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Autores

  • Mari Jeeva Sankar

    Correspondencia a: Newborn Health Knowledge Centre, WHO Collaborating Centre for Training and Research in Newborn Care, Department of Pediatrics, All India Institute of Medical Sciences, Delhi, India

    [email protected]

  • Jhuma Sankar

    Department of Pediatrics, All India Institute of Medical Sciences, New Delhi, India

  • Parijat Chandra

    Dr. R. P. Centre for Ophthalmic Sciences, All India Institute of Medical Sciences (AIIMS), New Delhi, India

Contributions of authors

MJS and JS updated the literature with the help of the Cochrane Neonatal Review Group Information Specialist. MJS and JS independently extracted data and assessed included studies for risk of bias. MJS conducted the data analysis and wrote the final draft with inputs from the remaining authors (JS and PC).

Sources of support

Internal sources

  • None, Other.

    The authors did not receive any support from either external or internal resources

External sources

  • No sources of support supplied

Declarations of interest

Mari Jeeva Sankar: no conflict of interest

Jhuma Sankar: no conflict of interest

Parijat Chandra: no conflict of interest

Acknowledgements

The review authors (MJS and JS) acknowledge the contributions of the three authors (Dr Vishnu Bhat and Dr Renuka Srinivasan from JIPMER, Puducherry, India and Dr Manisha Mehta, New Delhi, India) of the earlier review (Sankar 2016).

Version history

Published

Title

Stage

Authors

Version

2018 Jan 08

Anti‐vascular endothelial growth factor (VEGF) drugs for treatment of retinopathy of prematurity

Review

Mari Jeeva Sankar, Jhuma Sankar, Parijat Chandra

https://doi.org/10.1002/14651858.CD009734.pub3

2016 Feb 27

Anti‐vascular endothelial growth factor (VEGF) drugs for treatment of retinopathy of prematurity

Review

Mari Jeeva Sankar, Jhuma Sankar, Manisha Mehta, Vishnu Bhat, Renuka Srinivasan

https://doi.org/10.1002/14651858.CD009734.pub2

2012 Mar 14

Anti‐vascular endothelial growth factor (VEGF) drugs for treatment of retinopathy of prematurity

Protocol

Mari Jeeva Sankar, Jhuma Sankar, Vishnu Bhat, Renuka Srinivasan

https://doi.org/10.1002/14651858.CD009734

Differences between protocol and review

We have listed the differences between the protocol and review below.

a. Secondary outcomes

Added: One additional outcome, recurrence of ROP requiring retreatment up to 6 months of age, that was not planned in the protocol.

b. Dealing with missing data

Deleted: “For dichotomous data, if drop‐outs exceed 10% for any trial, we will assign the worse outcomes to those who were lost to follow‐up and assess the impact in the study results in sensitivity analyses (Higgins 2011).”

c. Assessment of heterogeneity

Deleted: “If statistical heterogeneity is detected, we will explore the possible causes. We intend to use the fixed‐effect model if the I2 statistic is less than 60%; in the event that the I2 is more than 60%, we will use the random effects.”

d. Data synthesis

Deleted: “For ordinal outcomes (as in Likert scale for parental satisfaction), we will summarize the data using methods for continuous variables ‐ as a difference in means or standardized difference in means. Depending upon the heterogeneity, we plan to use either fixed‐effect or random effects models with inverse variance weighting for the meta‐analyses.”

e. Measures of treatment effect

Deleted: “We used the fixed‐effect model for pooling the results of individual studies.”

f. Unit of analysis issues

Added: “However, had a given study randomised eyes and not infants, we intended to use the study data but refrained from pooling these data with data of studies that had randomised infants. We decided a priori to use the eye‐level data (and not infant‐level data) in these studies, that is incidence of outcomes in eyes randomised to anti‐VEGF versus incidence of outcomes in eyes randomised to the control group; consequently, we did not consider individual‐level outcomes such as mortality or long‐term neurodevelopment in these studies. We a priori assumed that the beneficial effect, if any, would be diluted in these studies, that is the effect size would be closer to the null effect, if systemic absorption of anti‐VEGF agents were to occur (because the eye randomised to control group would be exposed to both anti‐VEGF agents and 'control' treatment).

Had a given study randomised infants but provided the outcome data for eyes, we planned to contact the authors to obtain infant‐level data so as to avoid unit of analysis error; using eyes as the denominator without adjusting for non‐independence between the eyes can result in spuriously precise results, that is narrow confidence intervals similar to those seen in cluster randomised trials when the clusters are randomised but the outcomes are analysed at the individual level without adjusting for 'cluster' effect (Higgins 2011). If we could not obtain that information, we used the data for eyes but mentioned up‐front that the analysis refers to eyes and not infants.”

Keywords

MeSH

PICO

Population
Intervention
Comparison
Outcome

El uso y la enseñanza del modelo PICO están muy extendidos en el ámbito de la atención sanitaria basada en la evidencia para formular preguntas y estrategias de búsqueda y para caracterizar estudios o metanálisis clínicos. PICO son las siglas en inglés de cuatro posibles componentes de una pregunta de investigación: paciente, población o problema; intervención; comparación; desenlace (outcome).

Para saber más sobre el uso del modelo PICO, puede consultar el Manual Cochrane.

Study flow diagram: review update.
Figuras y tablas -
Figure 1

Study flow diagram: review update.

Risk of bias summary: review authors' judgements about each risk of bias item for each included study.
Figuras y tablas -
Figure 2

Risk of bias summary: review authors' judgements about each risk of bias item for each included study.

Comparison 1 Anti‐vascular endothelial growth factor therapy versus cryo/laser therapy, Outcome 1 Structural outcome ‐ partial or complete retinal detachment.
Figuras y tablas -
Analysis 1.1

Comparison 1 Anti‐vascular endothelial growth factor therapy versus cryo/laser therapy, Outcome 1 Structural outcome ‐ partial or complete retinal detachment.

Comparison 1 Anti‐vascular endothelial growth factor therapy versus cryo/laser therapy, Outcome 2 Structural outcome ‐ complete retinal detachment (unit of analysis: eyes).
Figuras y tablas -
Analysis 1.2

Comparison 1 Anti‐vascular endothelial growth factor therapy versus cryo/laser therapy, Outcome 2 Structural outcome ‐ complete retinal detachment (unit of analysis: eyes).

Comparison 1 Anti‐vascular endothelial growth factor therapy versus cryo/laser therapy, Outcome 3 Refractive error ‐ very high myopia ‐ at or after 12 months of age (unit of analysis: eyes).
Figuras y tablas -
Analysis 1.3

Comparison 1 Anti‐vascular endothelial growth factor therapy versus cryo/laser therapy, Outcome 3 Refractive error ‐ very high myopia ‐ at or after 12 months of age (unit of analysis: eyes).

Comparison 1 Anti‐vascular endothelial growth factor therapy versus cryo/laser therapy, Outcome 4 Refractive error ‐ spherical equivalent refractions ‐ at 30 months of age (unit of analysis: eyes).
Figuras y tablas -
Analysis 1.4

Comparison 1 Anti‐vascular endothelial growth factor therapy versus cryo/laser therapy, Outcome 4 Refractive error ‐ spherical equivalent refractions ‐ at 30 months of age (unit of analysis: eyes).

Comparison 1 Anti‐vascular endothelial growth factor therapy versus cryo/laser therapy, Outcome 5 Mortality before discharge from primary hospital.
Figuras y tablas -
Analysis 1.5

Comparison 1 Anti‐vascular endothelial growth factor therapy versus cryo/laser therapy, Outcome 5 Mortality before discharge from primary hospital.

Comparison 1 Anti‐vascular endothelial growth factor therapy versus cryo/laser therapy, Outcome 6 Mortality at 30 months of age.
Figuras y tablas -
Analysis 1.6

Comparison 1 Anti‐vascular endothelial growth factor therapy versus cryo/laser therapy, Outcome 6 Mortality at 30 months of age.

Comparison 1 Anti‐vascular endothelial growth factor therapy versus cryo/laser therapy, Outcome 7 Local adverse effects ‐ corneal opacity requiring corneal transplant (unit of analysis: eyes).
Figuras y tablas -
Analysis 1.7

Comparison 1 Anti‐vascular endothelial growth factor therapy versus cryo/laser therapy, Outcome 7 Local adverse effects ‐ corneal opacity requiring corneal transplant (unit of analysis: eyes).

Comparison 1 Anti‐vascular endothelial growth factor therapy versus cryo/laser therapy, Outcome 8 Local adverse effects ‐ lens opacity requiring cataract removal (unit of analysis: eyes).
Figuras y tablas -
Analysis 1.8

Comparison 1 Anti‐vascular endothelial growth factor therapy versus cryo/laser therapy, Outcome 8 Local adverse effects ‐ lens opacity requiring cataract removal (unit of analysis: eyes).

Comparison 1 Anti‐vascular endothelial growth factor therapy versus cryo/laser therapy, Outcome 9 Local adverse effects ‐ endophthalmitis.
Figuras y tablas -
Analysis 1.9

Comparison 1 Anti‐vascular endothelial growth factor therapy versus cryo/laser therapy, Outcome 9 Local adverse effects ‐ endophthalmitis.

Comparison 1 Anti‐vascular endothelial growth factor therapy versus cryo/laser therapy, Outcome 10 Local adverse effects ‐ vitreous haemorrhage.
Figuras y tablas -
Analysis 1.10

Comparison 1 Anti‐vascular endothelial growth factor therapy versus cryo/laser therapy, Outcome 10 Local adverse effects ‐ vitreous haemorrhage.

Comparison 1 Anti‐vascular endothelial growth factor therapy versus cryo/laser therapy, Outcome 11 Recurrence of ROP.
Figuras y tablas -
Analysis 1.11

Comparison 1 Anti‐vascular endothelial growth factor therapy versus cryo/laser therapy, Outcome 11 Recurrence of ROP.

Comparison 1 Anti‐vascular endothelial growth factor therapy versus cryo/laser therapy, Outcome 12 Recurrence of ROP (unit of analysis: eyes).
Figuras y tablas -
Analysis 1.12

Comparison 1 Anti‐vascular endothelial growth factor therapy versus cryo/laser therapy, Outcome 12 Recurrence of ROP (unit of analysis: eyes).

Comparison 2 Anti‐vascular endothelial growth factor therapy plus cryo/laser therapy versus cryo/laser therapy, Outcome 1 Structural outcome ‐ retinal detachment (unit of analysis: eyes).
Figuras y tablas -
Analysis 2.1

Comparison 2 Anti‐vascular endothelial growth factor therapy plus cryo/laser therapy versus cryo/laser therapy, Outcome 1 Structural outcome ‐ retinal detachment (unit of analysis: eyes).

Comparison 2 Anti‐vascular endothelial growth factor therapy plus cryo/laser therapy versus cryo/laser therapy, Outcome 2 Local adverse effects ‐ perioperative retinal haemorrhages (unit of analysis: eyes).
Figuras y tablas -
Analysis 2.2

Comparison 2 Anti‐vascular endothelial growth factor therapy plus cryo/laser therapy versus cryo/laser therapy, Outcome 2 Local adverse effects ‐ perioperative retinal haemorrhages (unit of analysis: eyes).

Comparison 2 Anti‐vascular endothelial growth factor therapy plus cryo/laser therapy versus cryo/laser therapy, Outcome 3 Recurrence of ROP by 55 weeks' postmenstrual age.
Figuras y tablas -
Analysis 2.3

Comparison 2 Anti‐vascular endothelial growth factor therapy plus cryo/laser therapy versus cryo/laser therapy, Outcome 3 Recurrence of ROP by 55 weeks' postmenstrual age.

Summary of findings for the main comparison. Anti‐vascular endothelial growth factor therapy compared to conventional laser/cryotherapy in preterm infants with type 1 retinopathy of prematurity

Anti‐vascular endothelial growth factor (anti‐VEGF) therapy compared to conventional laser/cryotherapy in preterm infants with type 1 retinopathy of prematurity (ROP)

Patient or population: preterm infants with type 1 ROP
Setting: neonatal units
Intervention: anti‐VEGF therapy
Comparison: conventional laser/cryotherapy

Outcomes

Anticipated absolute effects* (95% CI)

Relative effect
(95% CI)

No. of participants
(studies)

Quality of the evidence
(GRADE)

Comments

Risk with conventional laser/cryotherapy

Risk with anti‐VEGF therapy

Structural outcome ‐ retinal detachment

Study population

RR 1.04
(0.21 to 5.13)

272
(3 RCTs)

⊕⊝⊝⊝
VERY LOW 1 2 3

15 per 1000

16 per 1000
(3 to 77)

Structural outcome ‐ complete retinal detachment

(unit of analysis: eyes)

Study population

RR 0.33
(0.01 to 7.50)

26
(1 RCT)

⊕⊝⊝⊝
VERY LOW 2 3 4 5

77 per 1000

25 per 1000
(1 to 577)

Refractive error ‐ very high myopia ‐ at 30 months of age

(unit of analysis: eyes)

Study population

RR 0.06
(0.02 to 0.20)

211
(1 RCT)

⊕⊕⊝⊝
LOW 1 4

416 per 1000

25 per 1000
(8 to 83)

Mortality before discharge from primary hospital

Study population

RR 1.50
(0.26 to 8.75)

229
(2 RCTs)

⊕⊕⊝⊝
LOW 2 3 5

18 per 1000

27 per 1000
(5 to 158)

Mortality at 30 months of age

Study population

RR 0.86
(0.30 to 2.45)

150
(1 RCT)

⊕⊕⊝⊝
LOW 2 3 5

93 per 1000

80 per 1000
(28 to 229)

Local adverse effects ‐ corneal opacity requiring corneal transplant

(unit of analysis: eyes)

Study population

RR 0.34
(0.01 to 8.26)

286
(1 RCT)

⊕⊝⊝⊝
VERY LOW 1 2 3 4

7 per 1000

2 per 1000
(0 to 57)

Local adverse effects ‐ lens opacity requiring cataract removal

(unit of analysis: eyes)

Study population

RR 0.15
(0.01 to 2.79)

544
(3 RCTs)

⊕⊝⊝⊝
VERY LOW 1 2 3 4

11 per 1000

2 per 1000
(0 to 31)

Recurrence of ROP (up to 6 months of age)

Study population

RR 0.88
(0.47 to 1.63)

193
(2 RCTs)

⊕⊝⊝⊝
VERY LOW 1 2 6

204 per 1000

180 per 1000
(96 to 333)

Recurrence of ROP

(unit of analysis: eyes)

Study population

RR 5.36
(1.22 to 23.50)

188
(2 RCTs)

⊕⊝⊝⊝
VERY LOW 1 3 7

23 per 1000

123 per 1000
(28 to 540)

*The risk in the intervention group (and its 95% confidence interval) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI).
CI: confidence interval; RCT: randomised controlled trial; RR: risk ratio

GRADE Working Group grades of evidence
High quality: We are very confident that the true effect lies close to that of the estimate of the effect.
Moderate quality: We are moderately confident in the effect estimate: the true effect is likely to be close to the estimate of the effect, but there is a possibility that it is substantially different.
Low quality: Our confidence in the effect estimate is limited: the true effect may be substantially different from the estimate of the effect.
Very low quality: We have very little confidence in the effect estimate: the true effect is likely to be substantially different from the estimate of effect.

1Outcome assessment not masked.
295% CI around the pooled estimate includes both 1) no effect and 2) appreciable benefit or appreciable harm.
3Number of events too small.
4Serious risk of bias in analysis (unit of analysis error) in one or more of the included studies.
5Outcome assessment not masked, but outcome is objective.
6Evidence of large heterogeneity (I2 = 86%).
7Unclear risk of selection bias (details of allocation concealment not provided in the individual studies).

Figuras y tablas -
Summary of findings for the main comparison. Anti‐vascular endothelial growth factor therapy compared to conventional laser/cryotherapy in preterm infants with type 1 retinopathy of prematurity
Summary of findings 2. Anti‐vascular endothelial growth factor therapy combined with laser/cryotherapy compared to laser/cryotherapy in preterm infants with type 1 retinopathy of prematurity

Anti‐vascular endothelial growth factor (anti‐VEGF) therapy combined with laser/cryotherapy compared to laser/cryotherapy in preterm infants with type 1 retinopathy of prematurity (ROP)

Patient or population: preterm infants with type 1 ROP
Settings: neonatal units
Intervention: anti‐VEGF combined with laser/cryotherapy
Comparison: laser/cryotherapy

Outcomes*

Anticipated absolute effects* (95% CI)

Relative effect
(95% CI)

No. of participants
(studies)

Quality of the evidence
(GRADE)

Comments

Risk with conventional laser/cryotherapy

Risk with anti‐VEGF therapy

Structural outcome ‐ retinal detachment

(unit of analysis: eyes)

Study population

RR 0.26
(0.12 to 0.55)

152
(1 RCT)

⊕⊕⊝⊝
LOW 1,2,3

393 per 1000

102 per 1000
(47 to 216)

Local adverse effects ‐ perioperative retinal haemorrhages

(unit of analysis: eyes)

Study population

RR 0.62
(0.24 to 1.56)

152
(1 RCT)

⊕⊝⊝⊝
VERY LOW 1,2,3,4

143 per 1000

89 per 1000
(34 to 223)

Recurrence of ROP by 55 weeks' postmenstrual age

Study population

RR 0.29
(0.12 to 0.7)

76
(1 RCT)

⊕⊕⊝⊝
LOW 1,3

500 per 1000

145 per 1000
(60 to 350)

*Only the outcomes for which data are available are reported here.

#The basis for the assumed risk (e.g. the median control group risk across studies) is provided in footnotes. The corresponding risk (and its 95% confidence interval) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI).
CI: Confidence interval; RCT: randomised controlled trial; RR: risk ratio

GRADE Working Group grades of evidence
High quality: We are very confident that the true effect lies close to that of the estimate of the effect.
Moderate quality: We are moderately confident in the effect estimate: the true effect is likely to be close to the estimate of the effect, but there is a possibility that it is substantially different.
Low quality: Our confidence in the effect estimate is limited: the true effect may be substantially different from the estimate of the effect.
Very low quality: We have very little confidence in the effect estimate: the true effect is likely to be substantially different from the estimate of effect.

1Outcome assessment not masked.
2Serious risk of bias in analysis (unit of analysis error).
3Unclear risk of selection bias
495% CI around the pooled estimate includes both 1) no effect and 2) appreciable benefit or appreciable harm.

Figuras y tablas -
Summary of findings 2. Anti‐vascular endothelial growth factor therapy combined with laser/cryotherapy compared to laser/cryotherapy in preterm infants with type 1 retinopathy of prematurity
Comparison 1. Anti‐vascular endothelial growth factor therapy versus cryo/laser therapy

Outcome or subgroup title

No. of studies

No. of participants

Statistical method

Effect size

1 Structural outcome ‐ partial or complete retinal detachment Show forest plot

3

272

Risk Ratio (M‐H, Fixed, 95% CI)

1.04 [0.21, 5.13]

1.1 Zone I

1

64

Risk Ratio (M‐H, Fixed, 95% CI)

0.21 [0.01, 4.26]

1.2 Zone II

3

208

Risk Ratio (M‐H, Fixed, 95% CI)

5.13 [0.25, 103.45]

2 Structural outcome ‐ complete retinal detachment (unit of analysis: eyes) Show forest plot

1

26

Risk Ratio (M‐H, Fixed, 95% CI)

0.33 [0.01, 7.50]

3 Refractive error ‐ very high myopia ‐ at or after 12 months of age (unit of analysis: eyes) Show forest plot

1

211

Risk Ratio (M‐H, Fixed, 95% CI)

0.06 [0.02, 0.20]

3.1 Zone I

1

87

Risk Ratio (M‐H, Fixed, 95% CI)

0.07 [0.02, 0.30]

3.2 Zone II posterior

1

124

Risk Ratio (M‐H, Fixed, 95% CI)

0.05 [0.01, 0.34]

4 Refractive error ‐ spherical equivalent refractions ‐ at 30 months of age (unit of analysis: eyes) Show forest plot

1

211

Mean Difference (IV, Fixed, 95% CI)

5.68 [4.33, 7.02]

4.1 Zone I

1

87

Mean Difference (IV, Fixed, 95% CI)

6.93 [4.26, 9.60]

4.2 Zone II posterior

1

124

Mean Difference (IV, Fixed, 95% CI)

5.25 [3.69, 6.81]

5 Mortality before discharge from primary hospital Show forest plot

2

229

Risk Ratio (M‐H, Fixed, 95% CI)

1.50 [0.26, 8.75]

5.1 Zone I

1

67

Risk Ratio (M‐H, Fixed, 95% CI)

1.03 [0.07, 15.80]

5.2 Zone II

2

162

Risk Ratio (M‐H, Fixed, 95% CI)

1.95 [0.18, 20.71]

6 Mortality at 30 months of age Show forest plot

1

150

Risk Ratio (M‐H, Fixed, 95% CI)

0.86 [0.30, 2.45]

6.1 Zone I

1

67

Risk Ratio (M‐H, Fixed, 95% CI)

0.62 [0.16, 2.38]

6.2 Zone II posterior

1

83

Risk Ratio (M‐H, Fixed, 95% CI)

1.46 [0.26, 8.31]

7 Local adverse effects ‐ corneal opacity requiring corneal transplant (unit of analysis: eyes) Show forest plot

1

286

Risk Ratio (M‐H, Fixed, 95% CI)

0.34 [0.01, 8.26]

7.1 Zone I

1

128

Risk Ratio (M‐H, Fixed, 95% CI)

0.0 [0.0, 0.0]

7.2 Zone II posterior

1

158

Risk Ratio (M‐H, Fixed, 95% CI)

0.34 [0.01, 8.26]

8 Local adverse effects ‐ lens opacity requiring cataract removal (unit of analysis: eyes) Show forest plot

3

544

Risk Ratio (M‐H, Fixed, 95% CI)

0.15 [0.01, 2.79]

8.1 Zone I

1

128

Risk Ratio (M‐H, Fixed, 95% CI)

0.0 [0.0, 0.0]

8.2 Zone II

3

416

Risk Ratio (M‐H, Fixed, 95% CI)

0.15 [0.01, 2.79]

9 Local adverse effects ‐ endophthalmitis Show forest plot

2

129

Risk Ratio (M‐H, Fixed, 95% CI)

0.0 [0.0, 0.0]

10 Local adverse effects ‐ vitreous haemorrhage Show forest plot

2

129

Risk Ratio (M‐H, Fixed, 95% CI)

0.0 [0.0, 0.0]

11 Recurrence of ROP Show forest plot

2

193

Risk Ratio (M‐H, Fixed, 95% CI)

0.88 [0.47, 1.63]

11.1 Zone I

1

64

Risk Ratio (M‐H, Fixed, 95% CI)

0.15 [0.04, 0.62]

11.2 Zone II

2

129

Risk Ratio (M‐H, Fixed, 95% CI)

2.53 [1.01, 6.32]

12 Recurrence of ROP (unit of analysis: eyes) Show forest plot

2

188

Risk Ratio (M‐H, Fixed, 95% CI)

5.36 [1.22, 23.50]

12.1 Zone I or zone II

1

30

Risk Ratio (M‐H, Fixed, 95% CI)

3.0 [0.35, 25.68]

12.2 Zone II

1

158

Risk Ratio (M‐H, Fixed, 95% CI)

7.53 [0.98, 58.07]

Figuras y tablas -
Comparison 1. Anti‐vascular endothelial growth factor therapy versus cryo/laser therapy
Comparison 2. Anti‐vascular endothelial growth factor therapy plus cryo/laser therapy versus cryo/laser therapy

Outcome or subgroup title

No. of studies

No. of participants

Statistical method

Effect size

1 Structural outcome ‐ retinal detachment (unit of analysis: eyes) Show forest plot

1

152

Risk Ratio (M‐H, Fixed, 95% CI)

0.26 [0.12, 0.55]

2 Local adverse effects ‐ perioperative retinal haemorrhages (unit of analysis: eyes) Show forest plot

1

152

Risk Ratio (M‐H, Fixed, 95% CI)

0.62 [0.24, 1.56]

3 Recurrence of ROP by 55 weeks' postmenstrual age Show forest plot

1

76

Risk Ratio (M‐H, Fixed, 95% CI)

0.29 [0.12, 0.70]

Figuras y tablas -
Comparison 2. Anti‐vascular endothelial growth factor therapy plus cryo/laser therapy versus cryo/laser therapy