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. 2017 Jun 22;2017(6):CD007419. doi: 10.1002/14651858.CD007419.pub5

REVEAL 2015

Methods Parallel group RCT
One eye per person, eye with worse VA selected unless other eye more suitable for treatment
Participants Country: Asian population from 52 centres across 6 countries, or regions: China, Hong Kong, Japan, South Korea, Singapore, and Taiwan.
Number of people randomised: 396 (396 eyes)
Average age: 61 years
Sex: 44% women
Inclusion criteria:

  • 18 years or older

  • diabetes mellitus (according to the American Diabetes Association or World Health Organization guidelines)

  • HbA1c ≤ 10%

  • visual impairment due to DMO

  • stable medication for the management of diabetes within 3 months before randomisation and expected to remain stable during the study

  • visual impairment due to focal or diffuse DMO in at least 1 eye that was eligible for laser treatment in the opinion of the investigator

  • BCVA letter score between 78‐39, both inclusive, based on ETDRS‐like VA testing charts administered at a starting distance of 4 m (approximate Snellen equivalent 20/32‐20/160)

  • decreased vision due to DMO and not other causes, in the investigator’s opinion (at visit 1)


Exclusion criteria:

  • concomitant conditions in the study eye that could prevent the improvement in VA on the study treatment in the investigator’s opinion

  • active intraocular inflammation or infection in either eye

  • uncontrolled glaucoma in either eye (e.g. IOP > 24 mmHg on medication, or from the investigator’s judgement)

  • laser PRP (within 6 months) or focal/grid laser photocoagulation (within 3 months) before study entry

  • treatment with antiangiogenic drugs in the study eye within 3 months before randomisation

  • history of stroke

  • systolic BP > 160 mmHg or diastolic BP > 100 mmHg

  • untreated hypertension

  • change in antihypertensive treatment within 3 months preceding baseline
Interventions "Patients were randomised in a 1:1:1 ratio to 1 of 3 treatment arms: intravitreal ranibizumab 0.5 mg injection + sham laser, intravitreal ranibizumab 0.5 mg injection + active laser, or active laser + sham injections for 12 months" Page 1404
Number in each group: ranibizumab + sham laser (n = 133), ranibizumab + active laser (n =132), or sham injection + active laser (n = 131).
Outcomes Primary outcome:

  • mean average change in BCVA from baseline over 12 months


Secondary outcomes:

  • several BCVA expressions

  • mean change in central retinal (subfield) thickness

  • safety


Follow‐up: 12 months
Notes Dates participants enrolled: not reported
Funding: Novartis
Conflict of interest: authors reported financial support of Novartis or were Novartis employees
Trial registration: NCT00989989
Risk of bias
Bias Authors' judgement Support for judgement
Random sequence generation (selection bias) Low risk "At Visit 2, all patients who fulfilled all the inclusion/exclusion criteria were given the lowest available number on the randomization list. This number assigned them to one of the treatment arms. The investigator entered the randomization number on the electronic case report form. A randomization list was produced by, or under the responsibility of Novartis Drug Supply Management using a validated system that automated the random assignment of treatment arms to randomization numbers in the specified ratio"
Allocation concealment (selection bias) Low risk See above
Blinding of participants and personnel (performance bias) All outcomes Low risk "To ensure successful masking in this double‐masked study, at the start of the study and at each study site, the following site personnel were required to demonstrate their role: BCVA assessor and evaluating investigator (masked to the treatment assignment) and treating investigator (unmasked to the treatment assignment" Page 1404
Blinding of outcome assessment (detection bias) All outcomes Low risk See above
Incomplete outcome data (attrition bias) All outcomes High risk Higher proportion of loss to follow‐up in the laser group; this can decrease the benefit with anti‐VEGF (see below).
"Overall, 345 (87.1%) patients completed the study. The proportion of patients who discontinued the study was 7.5% in the ranibizumab arm, 13.6% in the ranibizumab þ active laser treatment arm, and 17.6% in the laser treatment arm (Fig 2, available at www.aaojournal.org). Adverse events (range, 3.0%‐6.8%) were the most common reason for discontinuation across all treatment arms (Fig 2, available at www.aaojournal.org). Unsatisfactory therapeutic effect (n= 7 [5.3%]) was reported only in the laser arm." Page 1405
Selective reporting (reporting bias) Unclear risk No protocol available
Other bias Low risk No other bias identified
Overall risk of bias Low risk Low risk for most items