Anti‐vascular endothelial growth factor for proliferative diabetic retinopathy

Abstract

BackgroundProliferative diabetic retinopathy (PDR) is an advanced complication of diabetic retinopathy that can cause blindness. It consists of thepresence of new vessels in the retina and vitreous haemorrhage. Although panretinal photocoagulation (PRP) is the treatment of choicefor PDR, it has secondary effects that can affect vision. Anti-vascular endothelial growth factor (anti-VEGF), which produces an inhibitionof vascular proliferation, could improve the vision of people with PDR.ObjectivesTo assess the effectiveness and safety of anti-VEGFs for PDR and summarise any relevant economic evaluations of their use.Search methodsWe searched CENTRAL (which contains the Cochrane Eyes and Vision Trials Register; 2022, Issue 6); Ovid MEDLINE; Ovid Embase; the ISRCTNregistry; ClinicalTrials.gov, and the WHO ICTRP. We did not use any date or language restrictions. We last searched the electronic databaseson 1 June 2022.Selection criteriaWe included randomised controlled trials (RCTs) comparing anti-VEGFs to another active treatment, sham treatment, or no treatment forpeople with PDR. We also included studies that assessed the combination of anti-VEGFs with other treatments. We excluded studies thatused anti-VEGFs in people undergoing vitrectomy. Data collection and analysisTwo review authors independently selected studies for inclusion, extracted data, and assessed the risk of bias (RoB) for all included trials.We calculated the risk ratio (RR) or the mean difference (MD), and 95% confidence intervals (CI). We used GRADE to assess the certaintyof evidence.Main resultsWe included 15 new studies in this update, bringing the total to 23 RCTs with 1755 participants (2334 eyes). Forty-five per cent of participantswere women and 55% were men, with a mean age of 56 years (range 48 to 77 years). The mean glycosylated haemoglobin (Hb1Ac) was8.45% for the PRP group and 8.25% for people receiving anti-VEGFs alone or in combination. Twelve studies included people with PDR,and participants in 11 studies had high-risk PDR (HRPDR).Twelve studies were of bevacizumab, seven of ranibizumab, one of conbercept, two of pegaptanib, and one of aflibercept. The meannumber of participants per RCT was 76 (ranging from 15 to 305). Most studies had an unclear or high RoB, mainly in the blinding ofinterventions and outcome assessors. A few studies had selective reporting and attrition bias.No study reported loss or gain of 3 or more lines of visual acuity (VA) at 12 months. Anti-VEGFs ± PRP probably increase VA comparedwith PRP alone (mean difference (MD) -0.08 logMAR, 95% CI -0.12 to -0.04; I2 = 28%; 10 RCTS, 1172 eyes; moderate-certainty evidence).Anti-VEGFs ± PRP may increase regression of new vessels (MD -4.14 mm2, 95% CI -6.84 to -1.43; I2 = 75%; 4 RCTS, 189 eyes; low-certaintyevidence) and probably increase a complete regression of new vessels (RR 1.63, 95% CI 1.19 to 2.24; I2 = 46%; 5 RCTS, 405 eyes; moderate-certainty evidence). Anti-VEGFs ± PRP probably reduce vitreous haemorrhage (RR 0.72, 95% CI 0.57 to 0.90; I2 = 0%; 6 RCTS, 1008 eyes;moderate-certainty evidence). Anti-VEGFs ± PRP may reduce the need for vitrectomy compared with eyes that received PRP alone (RR 0.67,95% CI 0.49 to 0.93; I2 = 43%; 8 RCTs, 1248 eyes; low-certainty evidence). Anti-VEGFs ± PRP may result in little to no difference in the qualityof life compared with PRP alone (MD 0.62, 95% CI -3.99 to 5.23; I2 = 0%; 2 RCTs, 382 participants; low-certainty evidence). We do not knowif anti-VEGFs ± PRP compared with PRP alone had an impact on adverse events (very low-certainty evidence). We did not find differencesin visual acuity in subgroup analyses comparing the type of anti-VEGFs, the severity of the disease (PDR versus HRPDR), time to follow-up(< 12 months versus 12 or more months), and treatment with anti-VEGFs + PRP versus anti-VEGFs alone.The main reasons for downgrading the certainty of evidence included a high RoB, imprecision, and inconsistency of effect estimates.Authors' conclusionsAnti-VEGFs ± PRP compared with PRP alone probably increase visual acuity, but the degree of improvement is not clinically meaningful.Regarding secondary outcomes, anti-VEGFs ± PRP produce a regression of new vessels, reduce vitreous haemorrhage, and may reduce theneed for vitrectomy compared with eyes that received PRP alone. We do not know if anti-VEGFs ± PRP have an impact on the incidence ofadverse events and they may have little or no effect on patients' quality of life. Carefully designed and conducted clinical trials are required,assessing the optimal schedule of anti-VEGFs alone compared with PRP, and with a longer follow-up.