Gonzalez 2014.

Study characteristics
Methods	Study design: randomised, open‐label, parallel (three arms) clinical trial Unit of randomisation: participant Unit of analyses: eye/participant Follow‐up: baseline, week 3, week 6, and every 6 weeks until week 52 (12 months)
Participants	Country: USA Setting: Valley Retina Institute PA, Edinburg, Texas Number of participants: 30 Exclusions post‐randomisation: not reported Losses to follow‐up: 4 Age (mean (SD)): older than 18 years. No more information specified. Gender: both. No more information specified. Inclusion criteria: people with proliferative diabetic retinopathy with high‐risk characteristics. All eyes must meet at least one or both of the following criteria: mild neovascularisation of the disc (NVD) of at least 1/4 to 1/3 disc area as shown in standard photograph 10A of the DRS. Moderate neovascularisation of the retina elsewhere (NVE) of at least 1/2 disc area as shown in standard photograph 7 of the DRS. 2. ETDRS visual acuity score greater than or equal to 24 letters (approximately 20/320) and less than or equal to 85 letters (approximately 20/20) by the ETDRS visual acuity protocol at the screening visit. 3. Eyes with mild pre‐retinal haemorrhage (PRH) or mild vitreous haemorrhage (VH) that does not interfere with clear visualisation of the macula and optic disc are eligible for this study. 4. Evaluating physician believes that PRP can be safely withheld for 3 weeks. Exclusion criteria: 1. Presence of moderate or dense PRH or VH that prevents clear visualisation of the macula and/or optic disc. 2. Presence of either: significant epiretinal membranes involving the macula, OR proliferative diabetic membranes along the major retinal arcades that are extensive enough to cause either: significant vitreomacular traction, OR significant impairment in visual acuity. 3. Presence of any tractional retinal detachment. 4. Severe ischaemia involving the foveal avascular zone as determined by fluorescein angiography performed at the initial screening visit. 5. Significant media opacity (due to cornea, anterior chamber, or lens) precluding clear visualisation of the macula or optic disc. 6. Presence of neovascular glaucoma with or without hyphema. 7. Previous treatment with intravitreal steroid injections in the study eye within 6 months of baseline. 8. Previous treatment with peribulbar steroid injections in the study eye within 90 days of baseline 9. Previous PRP laser treatment in the study eye within 90 days of baseline visit.
Interventions	Treatments Three intravitreal pegaptanib (IVP) injections every 6 weeks, then additional injections every 12 weeks. Three IVP every 6 weeks followed by selective laser treatment. Control: Standard PRP Duration: 12 months
Outcomes	Primary: regression of high‐risk proliferative diabetic retinopathy. Treatment failure was defined as: 1) Development of increased neovascularisation 2) neovascularisation that is not regressed at least 50% compared to the baseline amount within 3 weeks; 3) Development of significant vitreous haemorrhage that is sufficient in quantity to obscure visualisation of the entire macula, optic disc, and the major temporal arcade vessels. Secondary: loss of BCVA measured by comparing the percentages of participants that lost 3 or more lines on ETDRS chart in the study arms. Humphrey Visual Fields, dark adaptation, ETDRS, BCVA, FA, and OCT were performed in all groups at baseline and at variable pre‐determined times.
Notes	Funding: Pfizer MPDRS‐ED Trial registration: NCT01486771 Date conducted: not reported Conflict of interest: specified (the authors have collaborated with Allergan, Ampio, Genentech, Kalvista, Ophthotec, Pfizer, Regeneron and Valeant).
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	Quote: "Patients were randomised into three arms" Comment: not described.
Allocation concealment (selection bias)	Unclear risk	Comment: not described.
Blinding of participants and personnel (performance bias) All outcomes	High risk	Quote in the protocol: "open label"
Blinding of outcome assessment (detection bias) All outcomes	High risk	Quote in the protocol: "open label"
Incomplete outcome data (attrition bias) All outcomes	Low risk	Comment: only four participants were lost.
Selective reporting (reporting bias)	High risk	There are not details of regression of PDR.