Effects Of Bevacizumab Plus Panretinal Photocoagulation On Proliferative Diabetic Retinopathy

Although in the past 25 years, great progress has been reached in the pathogenesis and management of diabetes retinopathy(DR),proliferative diabetic retinopathy(PDR) remains the most common cause of loss of visual in patients with diabetes mellitus(DM). Nearly 25% of the patients with DM present with retinopahthy more or less,5% of which are PDR. The occurrence of retinal neovascularization(RNV)in PDR is a significant factor for severe vision loss in the patients with DM,while vascular endothelial growth factor (VEGF) is one of the key factors which precipitate the formation of RNV. At the current time , the management of PDR includes: panretinal photocoagulation(PRP),pars plana vitrectomy(PPV) and medication. PRP currently is the principal therapy for PDR, however it is a destructive therapy,with adverse side effects such as loss of peripheral visual field and night vision as well as exacerbation of macular edema and subsequent reduction of central vision acuity. Although 60% of patients with PDR respond to PRP with regression of RNV within 3 months,however,many patients require additional laser treatment and 4.5% ultimately require PPV despite PRP. While PPV is also challenging,expensive with unsatisfying outcomes what patients can't accept,anti-VEGF therapy turns to be the hot spot and main stream for the management of neovascularization. Nowadays ,bevacizumab is the most common anti-VEGF agents used clinically, which is a full-length humanized monoclonal antibody directed against all isoforms of VEGF-A. Bevacizumab is safe,low toxic and cheap so that it could be a promising medication for PDR. Therefore,the purpose of the current study was to evaluate the therapeutic effects of intravitreal injection of bevacizumab(IVB) when used in combination with PRP for the treatment of PDR. Purpose: To evaluate the effects of IVB on RNV in eyes with PDR. To evaluate the effects of IVB plus PRP compared with PRP on best corrected visual acuity (BCVA),total area of fluorescein leakage from active RNV,laser energy of PRP and change of electroretinography (ERG) in patients with PDR. To evaluate the safety of this combined therapy.Methods: A prospective clinical trial was conducted on 44 eyes of 38 patients with PDR type 2 diabetics and no prior laser treatment. Bevacizumab-assigned eyes received 1.25mg IVB first,7d later underwent fundus fluorescein angiography (FFA),and the same day first session of PRP was given. Then PRP was finished in three sessions once a week during a month. All 44 cases received standard laser treatment in 4 sessions once a week according to Early Treatment Diabetic Retinopathy Study protocol. Standardized ophthalmic evaluation including BCVA, stereoscopic fundus photography,intraocular pressure (IOP),and FFA were performed at baseline and at weeks 4,8,and 12 after PRP was finished,while ERG was taken at baseline and 12w after PRP. Main outcome measures include change in FFA leakage of the RNV,BCVA, laser energy of PRP,change of wave b in ERG.Results:1 Thirty-eight (n=44 eyes) patients completed the 12-week follow-up after PRP. There was no significant difference between the combined therapy group and PRP group with respect to age, gender, type or duration of diabetes.2 1 week after IVB,BCVA improved from 4.10±0.35 at baseline to 4.41±0.35and a total of 77.27% show a better BCVA while 22.73% with a stable BCVA. RNV leaking area decreased from (26.56±26.06)mm2 at baseline to (3.47±1.98) mm2(P <0.01), 45.45% showed complete regression of RNV and 54.55% partial regression. Lessen of the RNV leaking with no change in the area could been seen in 6 of the no-IVB eyes, while lessen of the RNV leaking with change in the area could been seen in 3 of the no-IVB eyes.3 Laser energy of IVB plus PRP group was (149.09±25.80)mW lower than that of sham group significantly,which was (222.73±36.15)mW(P <0.01).4. At week 4, 8 and 12 after PRP, BCVA in IVB plus PRP group was 4.39±0.33,4.38±0.34,4.34±0.34 and RNV leaking area was (1.90±1.21) mm2,(1.35±2.15) mm2,(3.12±3.06)mm2. BCVA in sham group was 4.12±0.38,4.23±0.34,4.18±0.33, and RNV leaking area was (17.23±13.68) mm2,(13.71±10.83) mm2,(11.66±10.44) mm2.At weeks 4 after PRP, 54.55% in IVB plus PRP group showed complete regression and 45.45% partial regression. At weeks 8 after PRP, 3 eyes (13.64%) of Group combined therapy showed increase of RNV leakage area compare to that at 1w after IVB, although lower than that at 4w after PRP. At weeks 12 after PRP, 13 eyes (59.09%) showed increase of RNV leakage area compare to that at 1w after IVB. The RNV leakage area in the Group combined therapy was lower than that at baseline remarkably at every visiting point.After PRP, BCVA and regression of RNV in the IVB plus PRP group are far better than that in sham group. And the change of ERG of the IVB plus PRP group was lower than that in sham group(P <0.01).5. No significant ocular of systemic adverse events were observed.Conclusions: In the short-term,IVB remarkably reduced the area of active leaking RNV and improved the visual acuity. The synergistic action of IVB and PRP was obvious. IVB remarkably augmented the short term response to PRP in PDR and IVB significantly lessened the retinal edema leading to lower energy of PRP, so that protect the function of retina. While IVB plus PRP avoided the short term effects of IVB and postponed the recurrence of RNV. The adjunctive use of IVB with PRP was associated with a greater reduction in the area of active leaking RNV and better visual acuity than PRP alone in PDR patients.