|Year : 2014 | Volume
| Issue : 1 | Page : 5-9
Clinical outcome of preoperative and intraoperative intravitreal injection of bevacizumab as an adjunct to vitrectomy in the treatment of proliferative diabetic retinopathy
Mohamed Farouk Sayed Othman, Hossam M Moharram, Raafat Mohy Eldin
Department of Ophthalmology, El-Minia University, Minia, Egypt
|Date of Submission||02-Feb-2013|
|Date of Acceptance||10-Dec-2013|
|Date of Web Publication||21-Jun-2014|
Mohamed Farouk Sayed Othman
MD, Alsafwa Hospital, Almageedyst, Mallawy, Minia, Postal code 61111
Source of Support: None, Conflict of Interest: None
The aim of this study was to evaluate the safety and clinical efficacy of an intravitreal injection of bevacizumab in pars plana vitrectomy (PPV) for complicated proliferative diabetic retinopathy (PDR).
Patients and methods
The study included 20 eyes of 20 patients (25-68 years old) with complicated PDR. All patients underwent 23-G PPV, and all of them received an intravitreal injection of 1.25 mg bevacizumab 1 week before planned vitrectomy and at the end of surgery.
The mean surgical time was 60.5 ± 20.2 min (range 40-95 min). Iatrogenic breaks were reported in four eyes (20%) and silicone oil was used in these cases (20%). Final visual acuity showed improvement in 17 eyes (85%), whereas postoperative best-corrected visual acuity remained unchanged in three eyes (15%). The mean preoperative corrected visual acuity was 1.47 ± 0.73 logMAR units. A statistically significant increase in the mean corrected visual acuity was observed in all study eyes at 3 months after surgery (0.60 ± 0.48 logMAR units; P < 0.001). There were no cases with postoperative bleeding.
Injection of bevacizumab, 1.25 mg (0.05 ml), 1 week before PPV and at the end of operation is safe and effective, resulting in a decrease in the operation time, iatrogenic retinal breaks, intraoperative and postoperative bleeding, and improved visual acuity in PDR patients.
Keywords: Intravitreal bevacizumab, pars plana vitrectomy, proliferative diabetic retinopathy
|How to cite this article:|
Othman MF, Moharram HM, Eldin RM. Clinical outcome of preoperative and intraoperative intravitreal injection of bevacizumab as an adjunct to vitrectomy in the treatment of proliferative diabetic retinopathy. J Egypt Ophthalmol Soc 2014;107:5-9
|How to cite this URL:|
Othman MF, Moharram HM, Eldin RM. Clinical outcome of preoperative and intraoperative intravitreal injection of bevacizumab as an adjunct to vitrectomy in the treatment of proliferative diabetic retinopathy. J Egypt Ophthalmol Soc [serial online] 2014 [cited 2017 Aug 22];107:5-9. Available from: http://www.jeos.eg.net/text.asp?2014/107/1/5/134924
| Introduction|| |
Proliferative diabetic retinopathy (PDR) is one of the most prevalent and severe ocular disorders, which is a major cause of adult blindness . Vitrectomy is a predominant treatment for PDR , whereas the risk of complications is of particular concern because of the bleeding from the fibrovascular membrane (FVM) .
Bevacizumab (Avastin) is a recombinant humanized monoclonal IgG1 antibody that inhibits human vascular endothelial growth factor (VEGF) . Recently, numerous studies have reported clinical outcomes of intravitreal bevacizumab (IVB) as an adjunct to vitrectomy in the management of diabetic retinopathy ,,,,,,,. Bevacizumab can induce regression of retinal neovascularization in patients with diabetes; therefore, it was suggested that a presurgical administration of IVB may reduce intraoperative bleeding during vitrectomy in PDR ,,. However, the presurgical administration of IVB remains controversial. Some studies have reported that bevacizumab pretreatment for diabetic vitrectomy did not influence the rates of postoperative vitreous hemorrhage or final visual acuity ,.
The aim of this study is to evaluate the clinical outcome after an IVB injection before vitrectomy and at the end of surgery in the management of complications associated with PDR.
| Patients and methods|| |
Twenty eyes of 20 patients with PDR were enrolled and underwent pars plana vitrectomy (PPV) between January 2011 and June 2011 at the Ophthalmology Department, El-Minia University Hospital. All patients were administered two IVB injections (Avastin; Roche, Bafel, Switzerland) 1.25 mg (0.05 ml). The first injection was administered 1 week before vitrectomy and the second at the end of the surgery.
Patients with PDR indicated for PPV because of vitreous hemorrhage and/or tractional retinal detachment were included in this study.
Exclusion criteria included the following:
- patients who are not fit for general anesthesia,
- patients who were pregnant,
- patients with ischemic heart disease,
- patients with a history of thromboembolic events,
- patients with a history of previous intraocular surgery,
- patients with best-corrected visual acuity (BCVA) of 0.15 or better and patients with visual acuity less than perception of light with good projection.
For all patients, the following were performed:
- Complete assessment of history.
- General examination.
- Complete ophthalmic examination including slit-lamp examination of the anterior segment, indirect ophthalmoscopic fundus examination in patients with clear media, tonometry, and examination of the visual acuity.
- Fluorescein angiography was performed whenever the media were clear enough to obtain good-quality images.
- Ultrasonography was performed in patients with opaque media.
Patients were examined preoperatively, on the first postoperative day, at the end of the first week, 2 weeks, and then monthly for 3 months.
Preoperative intravitreal Avastin was administered in the operative theater under complete aseptic conditions 3.50 mm from the limbus about 1 week before PPV. After the injection of bevacizumab, patients were instructed to instill one drop of gatifloxacin into the injected eye four times daily.
Phacoemulsification with acrylic posterior chamber intraocular lens in the capsular bag was performed before vitrectomy in eyes with coexistent cataract.
Three-port PPV (23 G) was performed with removal of epiretinal FVMs, further endolaser panretinal photocoagulation, and gas tamponade (SF6, C2F6). Bevacizumab was injected into the vitreous cavity using a 30-G needle inserted through the inferotemporal pars plana 3.0-3.5 mm posterior to the limbus. After the injection, central retinal artery perfusion was confirmed by indirect ophthalmoscopy.
Postoperatively, patients were administered gatifloxacin, prednisolone acetate, and tear substitute eye drops and dexamethasone with tobramycin ointment at night.
BCVA and complete ophthalmic evaluation were performed before, 1 week after injections, on the first postoperative day, and 1 week, 2 weeks, 1 month, and 3 months after vitrectomy. BCVA was measured using Snellens' visual acuity chart and was analyzed on a logarithm of minimal angle of resolution (logMAR) scale .
For statistical analysis, the SPSS (IBM corporation, Nevada, Las Vegas, USA) package for statistical analysis version 10.0 was used. Values were expressed as mean ± SD and range, or number and percent. The Wilcoxon test was used to compare preoperative and postoperative dependent nonparametric variables such as visual acuity. P value less than 0.05 was considered statistically significant.
| Results|| |
Preoperative data are shown in [Table 1]. The age of the patients ranged between 25 and 68 years, with a mean of 47 ± 13 years. Four patients (20%) had diabetes mellitus type 1 and 16 patients (80%) had type 2. Among the patients, there were 11 men (55%) and nine women (45%). Ophthalmic examination of the other eye of the 20 patients showed six eyes with non-PDR and 13 eyes with PDR treated by panretinal photocoagulation.
|Table 1: Preoperative data of 20 patients who underwent pars plana vitrectomy with an intravitreal injection of bevacizumab|
Click here to view
The indications for surgery were tractional retinal detachment with vitreous hemorrhage in eight cases (40%), tractional retinal detachment in seven cases (35%), and dense vitreous hemorrhage in five cases (25%). Cataract was present in 11 eyes (55%).
Intraoperative and postoperative data are shown in [Table 2]. The mean surgical time was 60.5 ± 20.2 min (range 40-95 min). Iatrogenic breaks were reported in four eyes (20%) and silicone oil 2000 was used in these cases (20%). For retinal tamponade, gas was used in 11 eyes (55%), air was used in five eyes (25%), and silicone oil was used in four eyes (20%). Final visual acuity showed improvement in 17 eyes (85%), whereas postoperative BCVA remained unchanged in three eyes (15%).
|Table 2: Intraoperative and postoperative data of 20 patients who underwent pars plana vitrectomy with an intravitreal injection of bevacizumab|
Click here to view
The mean preoperative visual acuity was 1.47 ± 0.73 logMAR units. Postoperatively, the mean final visual acuity (3 months after surgery) reached 0.60 ± 0.48 logMAR units. This improvement in the mean visual acuity was highly significant (P < 0.001) [Figure 1]. No cases of postoperative bleeding or endophthalmitis were observed.
Postoperative mild corneal edema occurred in six eyes (33%), which resolved in 2 weeks. Increased intraocular pressure occurred in four eyes (20%), which was controlled by a combination of b-blocker and carbonic anhydrase inhibitor.
[Figure 2] shows the preoperative and postoperative results of some cases.
| Discussion|| |
Retinal neovascularization represents an important risk factor for severe vision loss in patients with diabetes mellitus . Bevacizumab can induce regression of retinal neovascularization in diabetic patients . The effects of bevacizumab in patients with retinal neovascularization secondary to diabetic retinopathy have been evaluated in a number of studies. Rizzo et al.  reported that IVB administered before vitrectomy was well tolerated and reduced active neovascularization, thus facilitating PPV. In a study by Yeh et al.  bevacizumab injections induced regression of neovascularization after 1 week.
In the current study, we advocated administration of two IVB injections (preoperative and intraoperative) in an effort to quiet down the fibrovascular proliferation before vitrectomy, making surgery easier. The reduced risk of intraoperative bleeding facilitated removal of the FVMs. A bloodless field allows for better visibility, facilitating completion of surgery.
Preoperatively, we administered IVB at a dose of 1.25 mg (0.05 ml) 1 week before vitrectomy. There is a controversy about the timing of preoperative IVB. The study by Di Lauro et al.  showed that the effect of IVB was efficacious at both 7 and 20 days before PPV, with their 7-day group having slightly better outcomes. A single dose of bevacizumab could provide complete pharmacological blockage of VEGF for a minimum of 4 weeks. A recent study by Gupta et al.  found a significantly greater beneficial effect of IVB in eyes subjected to surgery within the first 2 weeks after the IVB injection than in those subjected to PPV more than 2 weeks after the IVB injection.
Our current findings showed the efficacy of bevacizumab in reducing the rate of iatrogenic breaks, bleeding, and complications after PPV in patients with PDR. These findings are in agreement with those of recent studies in the literature ,,.
Postoperative vitreous hemorrhage is common within the first few days following PPV for PDR , with two-third occurring within the first 6 months . No postoperative bleeding was reported in our study. IVB may provide complete VEGF blockade causing transient vasoconstriction, which clinically mimics vascular regression and prevents recurrence of bleeding in the early postoperative period .
Our data are in agreement with previous reports in the literature. Ahn et al.  compared the effects of preoperative (1-14 days) and intraoperative IVB injection and they preferred an intraoperative administration of bevacizumab than preoperative administration as an adjunct for reducing postoperative vitreous hemorrhage. Zhao et al.  reported excellent outcomes with preoperative IVB in vitrectomy for severe PDR. The incidence of intraoperative bleeding, frequency of endodiathermy, surgical time, postoperative bleeding, and reabsorption time of blood were significantly reduced. A study by Jirawison and Ittipunkul  showed that patients administered an IVB injection of 1.25 mg at the end of diabetic vitrectomy had the lowest incidence of early postoperative vitreous hemorrhage, with no statistical significance when compared with patients who underwent vitrectomy but did not receive this injection.
The reasons for better visual outcome after pretreatment with IVB can at best be speculative and may include shorter operative time, fewer intraoperative manipulations, and minimal use of intraoperative diathermy. A similar improvement in visual acuity with the use of preoperative IVB has been reported previously in a number of series of patients at variable intervals after surgery up to 6 months ,,,,, whereas others have shown either comparable results , or at least no detrimental effects on visual acuity ,,.
| Conclusion|| |
When IVB was used as an additive to PPV for the management of complications associated with PDR, it was helpful in reducing intraoperative and postoperative complications, with an increase in the safety of surgery.
| Acknowledgements|| |
Conflicts of interest
There are no conflicts of interest.
| References|| |
|1.||Fong DS, Aiello LP, Ferris III FL, Klein R. Diabetic retinopathy. Diabetes Care 2004; 27:2540-2553. |
|2.|| Joussen AM, Joeres S. Benefits and limitations in vitreoretinal surgery for proliferative diabetic retinopathy and macular edema. Dev Ophthalmol 2007; 39:69-87. |
|3.|| Ishikawa K, Honda S, Tsukahara Y, Negi A. Preferable use of intravitreal bevacizumab as a pretreatment of vitrectomy for severe proliferative diabetic retinopathy. Eye (Lond) 2009; 23:108-111. |
|4.|| Gandhi JS, Tan LT, Pearce I, Charles SJ. Bevacizumab (Avastin) as a surgical adjunct in diabetic vitrectomy for fibrovascular disease. Eye 2009; 23:742-743. |
|5.|| Rizzo S, Genovesi-Ebert F, Di Bartolo E. 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; 246:837-842. |
|6.|| Yang CM, Yeh PT, Yang CH. Bevacizumab pretreatment and long-acting gas infusion on vitreous clear-up after diabetic vitrectomy. Am J Ophthalmol 2008;146:211-217. |
|7.|| Yeoh J, Williams C, Allen P. Avastin as an adjunct to vitrectomy in the management of severe proliferative diabetic retinopathy: a prospective case series. Clin Experiment Ophthalmol 2008; 36:449-454. |
|8.|| Ahmadieh H, Shoeibi N, Entezari M. Intravitreal bevacizumab for prevention of early postvitrectomy hemorrhage in diabetic patients: a randomized clinical trial. Ophthalmology 2009; 116:1943-1948. |
|9.|| Lo WR, Kim SJ, Aaberg TM. Visual outcomes and incidence of recurrent vitreous hemorrhage after vitrectomy in diabetic eyes pretreated with bevacizumab (Avastin). Retina 2009; 29:926-931. |
|10.||1Romano MR, Gibran SK, Marticorena J. Can an intraoperative bevacizumab injection prevent recurrent postvitrectomy diabetic vitreous hemorrhage? Eur J Ophthalmol 2009; 19:618-621. |
|11.||1Yeh PT, Yang CM, Lin YC, Chen MS, Yang CH. Bevacizumab pretreatment in vitrectomy with silicone oil for severe diabetic retinopathy. Retina 2009; 29:768-774. |
|12.||1Di Lauro R, De Ruggiero P, Di Lauro R. Intravitreal bevacizumab for surgical treatment of severe proliferative diabetic retinopathy. Graefes Arch Clin Exp Ophthalmol 2010; 248:785-791. |
|13.||1Holladay JT. Proper method for calculating average visual acuity. J Refract Surg 1997; 13:388-391. |
|14.||1Giammaria D, Cinque B, Di Lodovico D, Savastano MC, Cifone MG, Spadea L. Anti-vascular endothelial growth factor activity in the bevacizumab and triamcinolone acetonide combination for intravitreal use. Eur J Ophthalmol 2009; 19:842-847. |
|15.||1Gupta A, Bansal R, Gupta V, Dogra MR. Six-month visual outcome after pars plana vitrectomy in proliferative diabetic retinopathy with or without a single preoperative injection of intravitreal bevacizumab. Int Ophthalmol 2012; 32:135-144. |
|16.||1Ahn J, Woo SJ, Chung H, Park KH. The effect of adjunctive intravitreal bevacizumab for preventing postvitrectomy hemorrhage in proliferative diabetic retinopathy. Ophthalmology 2011; 118:2218-2226. |
|17.||1Zhao LQ, Zhu H, Zhao PQ, Hu YQ. A systematic review and meta-analysis of clinical outcomes of vitrectomy with or without intravitreal bevacizumab pretreatment for severe diabetic retinopathy. Br J Ophthalmol 2011; 95:1216-1222. |
|18.||1Liggett PE, Lean JS, Barlow WE, Ryan SJ. Intraoperative argon endophotocoagulation for recurrent vitreous hemorrhage after vitrectomy for diabetic retinopathy. Am J Ophthalmol 1987; 103:146-149. |
|19.||1Lee MS, Abrams GW. Membrane dissection in proliferative diabetic retinopathy. In: Peyman GA, Ameffert S, Conway MD, editors. Vitreoretinal surgical techniques. London: Martin Dunitz Ltd; 2001. 251-266. |
|20.||2Beer PM, Wong S, Hammad AM, Falk NS, O′Malley MR. Vitreous levels of unbound bevacizumab and unbound vascular endothelial growth factor in two patients. Retina. 2006; 26:871-876. |
|21.||2Jirawison C, Ittipunkul N. Intravitreal bevacizumab at the end of diabetic vitrectomy for prevention of postoperative vitreous hemorrhage: a comparative study. J Med Assoc Thai 2012; 95:S136-S142. |
|22.||2El-Batarny AF. Intravitreal bevacizumab as an adjunctive therapy before diabetic vitrectomy. Clin Ophthalmol 2008; 2:709-716. |
|23.||2Farahvash MS, Majidi AR, Roohipoor R, Ghassemi F. Preoperative injection of intravitreal bevacizumab in dense diabetic vitreous hemorrhage. Retina 2011; 31:1254-1260. |
|24.||2Pokroy R, Desai UR, Du E, Li Y, Edwards P. Bevacizumab prior to vitrectomy for diabetic tractional retinal detachment. Eye 2011; 25:989-997. |
|25.||2Aiello LP, Avery RL, Arrigg PG, et al. Vascular endothelial growth factor in ocular fluid of patients with diabetic retinopathy and other retinal disorders. N Engl J Med 1994; 331:1480-1487. |
[Figure 1], [Figure 2]
[Table 1], [Table 2]