¡¡¡¡DISCUSSION

¡¡¡¡VEGF has been shown to contribute significantly to proliferative diabetic retinopathy. Retinal ischemia leads to an increased production of intravitreal VEGF by pigment epithelial cells, pericytes and endothelial cells. Inhibition of VEGF activity such as IVB and panretinal photocoagulation may decrease VEGF levels and inhibit retinal neovascularization. Bevacizumab can induce regression of retinal neovascularization in diabetic patients and AMD patients[6,7]. The effects of bevacizumab in patients with retinal neovascularization secondary to diabetic retinopathy have been evaluated in a number of studies. In a study by Averyl[8], fluorescein angiography revealed reduction of leakage from the foci of neovascularization within 1 week after IVB in 45 eyes with PDR. Moradian et al[9] reported regression of the neovascularization in eyes with active progressive PDR.

¡¡¡¡Our current study revealed the efficacy of IVB in reducing the rate of iatrogenic breaks, intraocular and postoperative bleeding after vitrectomy in PDR patients. In this study, we found that IVB was helpful in quieting down the fibrovascular proliferation before vitrectomy, making surgery easier. In PPV group, 18 cases of iatrogenic breaks and 10 cases of multiple breaks were reported. It was often observed the presence of strong adhesion between the fibrovascular membranes and the retina. This leads to higher incidence of retinal iatrogenic breaks due to difficulty in peeling the clotted blood that adhered tightly to the retina. It was also difficult to completely remove the vitreous cortex around the breaks when the iatrogenic breaks occurred. The residual vitreous cortex in the iatrogenic break area may exert strong tractional force to the retina causing the retinal breaks to enlarge into bigger hole after vitrectomy. Only 4 cases in which iatrogenic breaks occurred in IVB group may reveal that IVB quiets down the fibrovascular proliferation and makes membraneª²peeling easier. Hence, IVB reduced the rate of iatrogenic break and repeat surgery. Our result was supported by findings from Ishikawa et al[2] who reported IVB 7 days before PPV reduced the risk of increasing tissue traction due to excessive fibrosis in patients with severe PDR and tractional retinal detachment. It also demonstrated that there were decreased surgical time and less intraoperative bleeding in patients who received IVB 5 to 7 days before vitrectomy[10].

¡¡¡¡Intraoperative bleeding is one of the main complications associated with PPV in PDR[11]. We determined intraocular bleeding by direct observation during surgery. Intraoperative bleeding was observed in all cases of PPV group. Intraoperative bleeding interferes with fundus examination and detection of iatrogenic breaks. The removal of bleeding not only may create iatrogenic breaks, but also may extent the breaks and create much more bleeding. Often, surgery will not continue due to excessive intraoperative bleeding and there is a need to do the repeat surgery. Intraoperative bleeding also increases the risk of postoperative haemorrhage and should be avoided whenever possible. It is suggested that IVB is a good alternative to avoid haemorrhage. Intraocular bleeding was encountered in 7 cases of IVB group where there was minimum bleeding observed during surgical dissection of fibrovascular membranes and tissues. The use of IVB reduced intraoperative bleeding and iatrogenic breaks compare to the control group in our study. The use of IVB prior to PPV induced regression of new vessels, reduced intraoperative bleeding and made the surgery technically easier[8,12].

¡¡¡¡Postoperative bleeding was reported in 9 eyes (32.1%) and a repeat surgery in 1 case in PPV group. The sources of hemorrhage are often difficult to determine in the early postoperative period. In our findings, the postoperative bleeding was often from severed fibrovascular membranes that may induce a repeat surgery. No postoperative bleeding was reported in all the IVBª²treated cases in our study. IVB may provide complete VEGF blockade and prevent recurrence of bleeding in the early postoperative period. A single dose of bevacizumab could provide complete pharmacological blockage of VEGF for a minimum of 4 weeks[13]. Although some studies showed better visual results in the cases treated by IVB, there was no significant difference in our study.

¡¡¡¡In conclusion, preoperative IVB was helpful in reducing intraoperative and postoperative complication, with increase in safety of surgery. The combination of therapies offers the potential to revolutionize the approach to the complications of diabetic eye disease. It is necessary for our future study to increase the number of participants and observe the IVBª²related complication.

¡¡¡¡¡¾²Î¿¼ÎÄÏס¿

¡¡¡¡1 Patel JI, Hykin PG, Gregor ZJ, Boulton M, Cree IA. Angiopoietin concentrations in diabetic retinopathy. Br J Ophthalmol 2005;89(4):480ª²483

¡¡¡¡2 Ishikawa K, Honda S, Tsukahara Y, Negi A. Preferable use of intravitreal bevacizumab as a pretreatment of vitrectomy for severe proliferative diabetic retinopathy. Eye 2009;23(1):108ª²111

¡¡¡¡3 da R Lucena D, Ribeiro JA, Costa RA, Barbosa JC, Scott IU, de Figueiredoª²Pontes LL, Jorge R. Intraoperative bleeding during vitrectomy for diabetic tractional retinal detachment with versus without preoperative intravitreal bevacizumab (IBeTra study). Br J Ophthalmol 2009;93(5):688ª²691

¡¡¡¡4 Ahmadieh H, Moradian S, Malihi M. Rapid regression of extensive retinovitreal neovascularization secondary to branch retinal vein occlusion after a single intravitreal injection of bevacizumab. Int Ophthalmol 2005;26(4ª²5):191ª²193

¡¡¡¡5 Jorge R, Costa RA, Calucci D, Cintra LP, Scott IU. Intravitreal bevacizumab (Avastin) for persistent new vessels in diabetic retinopathy (IBEPE study). Retina 2006;26(9):1006ª²1013

¡¡¡¡6 Giammaria D, Cinque B, Di Lodovico D, Savastano MC, Cifone MG, Spadea L. Antiª²vascular endothelial growth factor activity in the bevacizumab and triamcinolone acetonide combination for intravitreal use. Eur J Ophthalmol 2009;19(5):842ª²847

¡¡¡¡7 Baeteman C, Hoffart L, Galland F, Ridings B, Conrath J. Subretinal hemorrhage after intravitreal injection of antiª²VEGF for ageª²related macular degeneration: a retrospective study. J Fr Ophtalmol 2009;32(5):309ª²313

¡¡¡¡8 Avery RL, Pearlman J, Pieramici DJ, Rabena MD, Castellarin AA, Nasir MA, Giust MJ, Wendel R, Patel A. Intravitreal bevacizumab (Avastin) in the treatment of proliferative diabetic retinopathy. Ophthalmology 2006;113(10):1695ª²1696

¡¡¡¡9 Moradian S, Ahmadieh H, Malihi M, Soheilian M, Dehghan MH, Azarmina M. Intravitreal bevacizumab in active progressive proliferative diabetic retinopathy. Graefes Arch Clin Exp Ophthalmol 2008;246(12):1699ª²1705

¡¡¡¡10 Rizzo S, Genovesiª²Ebert F, Di Bartolo E, Vento A, Miniaci S, Williams G. Injection of intravitreal bevacizumab (Avastin) as a preoperative adjunct before vitrectomy surgery in the treatment of severe proliferative diabetic retinopathy (PDR). Graefes Arch Clin Exp Ophthalmol 2008;246(6):837ª²842

¡¡¡¡11 Oshima Y, Shima C, Wakabayashi T, Kusaka S, Shiraga F, Ohji M, Tano Y. Microincision vitrectomy surgery and intravitreal bevacizumab as a surgical adjunct to treat diabetic traction retinal detachment. Ophthalmology 2009;116(5):927ª²938

¡¡¡¡12 Chen E, Park CH. Use of intravitreal bevacizumab as a preoperative adjunct for tractional retinal detachment repair in severe proliferative diabetic retinopathy. Retina 2006;26(6):699ª²700

¡¡¡¡13 di Lauro R, De Ruggiero P, di Lauro R, di Lauro MT, Romano MR. Intravitreal bevacizumab for surgical treatment of severe proliferative diabetic retinopathy. Graefes Arch Clin Exp Ophthalmol 2010;248(6):785ª²791

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