Intravitreal Bevacizumab as anti-vascular endothelial growth factor in the management of complications of diabetic retinopathy

[摘要] ENGLISH ABSTRACT: Bevacizumab is a complete full-length humanized antibody that binds to all subtypes ofvascular endothelial growth factor (VEGF) and is used successfully in tumor therapy as a systemicdrug. Recent studies have demonstrated the usefulness of an intravitreal injection of bevacizumab(IVB) in the reduction of macular edema secondary to central retinal vein occlusion,and choroidal neovascularization secondary to age-related macular degeneration (AMD). The drugis extremely cost-effective compared to similar anti-VEGF drugs on the market, hence the need toexamine its effect in diabetic eye disease (the ever-growing global health epidemic challenge) forapplication in middle to low income countries.The purpose of the current research is to determine if intravitreal bevacizumab (IVB) as anti-VEGF ishelpful in the management of complications of diabetic retinopathy. We conducted several multicenterretrospective studies of eyes with complications from diabetic retinopathy treated with off-label IVB.Ten previously published studies (one prospective), and one unpublished prospective study are includedhere on the management of diabetic macular edema (DME) and proliferative diabetic retinopathy (PDR).We progressively reported over the years our experienced as we followed patients with DME treatedwith IVB at 6 months, 12 months, and 24 months of follow up. In addition, 5 year follow up data wasadded later on. We found that primary IVB at doses of 1.25 to 2.5 mg seem to provide stability orimprovement in best correct visual acuity (BCVA), optical coherence tomography (OCT), andfluorescein angiography (FA) in diffuse DME at 24 months. The results show no evident differencebetween IVB at doses of 1.25 or 2.5 mg. However, the early visual gains due to IVB were not maintained5 years after treatment. Later, we provide evidence to support the use of primary IVB with or withoutgrid laser photocoagulation (GLP) as treatment of diffuse DME. Primary IVB without GLP seems to besuperior to GLP alone to provide stability or improvement in best-corrected visual acuity in patientswith diffuse diabetic macular edema at 24 months. We showed first that IVB resulted in markedregression of retinal neovascularization (RN) in patients with PDR and previous pan retinalphotocoagulation (PRP), and rapid resolution of vitreous hemorrhage in three naive eyes. Six-monthsresults of intravitreal bevacizumab at doses of 1.25 or 2.5 mg in patients with PDR did not reveal anysafety concerns. Later, we published that IVB resulted in marked regression of RN in patients with PDRand previous pan-retinal photocoagulation at 2 years. Intravitreal bevacizumab in naive eyes resulted in control or regression of 42.1% of eyes without adjunctive laser or vitrectomy during 24 months offollow-up. Meaning that a large number of patients (almost 58%) needed PRP or vitrectomy. Anotherone of our studies demonstrated the usefulness of using preoperative IVB during small-gaugevitreoretinal surgery in eyes with tractional retinal detachment (TRD) in PDR. This was a prospectivenon-comparative study and patients had significant anatomic and functional success. In addition, wereported for the first time ever that TRD may occur or progress shortly following administration of IVBin patients with severe PDR (5.2% and 3.2% in two studies). Based on our data, we now believe thatextreme care must be taken in using a dose of 2.5 mg or more of bevacizumab in patients with PDR. In addition, to have more than 15 years with a diagnosis of diabetes can increase the risk of TRD.Physicians must be prepared to perform the vitrectomy preferably before 13 days after the applicationof IVB and to perform a vitrectomy immediately on those patients in whom a TRD occurs. Werecommend less than 5 days after injection as more than 80% of the retinal detachments developed afterthat period of time. Finally, in our prospective randomized clinical trial, pre-operative intravitrealbevacizumab therapy as adjuvant to PPV may be helpful and beneficial for patients with TRD secondaryto severe PDR. Pre-operative IVB seems to reduce intraoperative bleeding, improving surgical visualfield visualization, and reducing intraoperative and postoperative complications including iatrogenicretinal breaks and postoperative hemorrhage. In summary, IVB as anti-VEGF agent is helpful in themanagement of complications of diabetic retinopathy to prevent blindness with a more accessible drugworldwide.

[发布机构] Stellenbosch University