With the emergence of significant number of recent clinical trials on different indications of anti-vascular endothelial growth factor (anti-VEGF) in diabetic eye disease, it is time to re-think whether anti-VEGF therapy is the be all and end all treatment for complications of diabetic retinopathy (DR) [1,2,3,4,5]. Initial studies of anti-VEGF therapy for visual impairment due to diabetic macular oedema (DMO) highlighted the importance of aggressive therapy or treat to stability [5]. In addition, anti-VEGF therapy also resulted in two-step improvement in severity of DR in about 35% of patients [6]. Given these very encouraging results, in China, the Chinese clinical guidelines state that anti-VEGF therapy should be chosen as the first-line treatment when DMO involves the macular centre [7]. However, with the popularity of anti-VEGF therapy in China, this therapy tends to be used far more commonly than this indication for DMO. For example, it is used in DMO threatening the fovea and also for DMO with no visual impairment.

Recent data from Protocol V indicates that anti-VEGF do not need to be initiated aggressively in eyes with DMO with minimal visual impairment and that we could patiently wait until the patient experiences a loss of at least five ETDRS letters before initiating anti-VEGF therapy [1]. This requires a change in culture and behaviour of the retinal specialists in China as anti-VEGF is now considered a magic bullet for any macular oedema.

Secondly, as visual field loss is a concern in eyes with proliferative DR (PDR) treated with panretinal photocoagulation (PRP), the short terms results from Protocol S and the CLARITY studies were also very encouraging and resulted in widespread use of anti-VEGF for PDR [2, 3]. However, the 5-year results of Protocol S question the long-term benefit of anti-VEGF in PDR as the dramatic visual field loss after 2 years of follow-up indicate that anti-VEGF is actually not a magic bullet and that we require further studies to understand the deterioration of visual field after 2 years [4]. The research question that needs to be asked is why does visual field loss occur quite abruptly after 2 years and does this worsening correlate with increasing area of non-perfusion as the natural history of the disease progresses over time? Moreover, there is now sufficient evidence that anti-VEGF treatment itself does not reverse the pathological process of non-perfusion in DR [8].

Considering the new evidence on anti-VEGF in DMO and PDR, the rising prevalence of DMO and PDR with the diabetes epidemic and the fact that many people in China cannot afford anti-VEGF treatment, we recently published an editorial in the Chinese Journal of Ophthalmology, putting forward the strategies of anti-VEGF therapy in DR, emphasizing that anti-VEGF therapies cannot replace PRP and one should not exaggerate its clinical indication [9]. Specific treatment strategies include: (1) for visual impairment due to centre-involving DMO in eyes with non-PDR (NPDR), anti-VEGF therapy is the first choice of treatment. When DR progresses to severe NPDR and PDR, PRP is the standard of care and anti-VEGF therapy should be used as an adjuvant or to prevent the aggravation of DMO after PRP; (2) for high-risk PDR, anti-VEGF therapy may be used to inhibit neovascularization prior to completion of PRP within the effective period of drug action, so as to avoid the disease progression caused by the slow uptake of PRP; (3) for patients in whom PRP is indicated but cannot complete PRP immediately, anti-VEGF therapy may be used or even repeated as a temporary measure. Anti-VEGF therapy can be terminated after completion of PRP; (4) for patients with advanced PDR, anti-VEGF therapy is recommended before vitrectomy to reduce the probability of intraoperative and postoperative haemorrhage, to create a bloodless field for the operation and to avoid postoperative complications. However, it is necessary to strictly adhere to the timing of anti-VEGF injection; (5) for neovascular glaucoma secondary to DR, a comprehensive treatment strategy of anti-VEGF treatment, completion of PRP and anti-glaucoma surgery has to be adopted.