Egyptian Retina Journal

ORIGINAL ARTICLE
Year
: 2018  |  Volume : 5  |  Issue : 1  |  Page : 6--11

Bevacizumab as an adjunct to vitrectomy for diabetic retinopathy: A retrospective study


Balbir Khan1, Rajwinder Kaur2, Mandeep Kaur2, Prithpal Singh Matreja3,  
1 Department of Ophthalmology, Adesh Medical College and Hospital, Ambala, Haryana, India
2 Department of Ophthalmology, Gian Sagar Medical College and Hospital, Patiala, Punjab, India
3 Department of Pharmacology, Teerthanker Mahaveer University, Moradabad, Uttar Pradesh, India

Correspondence Address:
Dr. Rajwinder Kaur
Department of Ophthalmology, Gian Sagar Medical College and Hospital, Ram Nagar, Rajpura, Patiala - 140 601, Punjab
India

Abstract

Purpose: The purpose of this study is to evaluate the effect of a single preoperative injection of intravitreal bevacizumab (IVB) on the visual and anatomical outcome of patients undergoing 23-gauge pars plana vitrectomy (23G PPV) for proliferative diabetic retinopathy (PDR). Materials and Methods: Medical record from patients undergoing vitrectomy for PDR were retrospectively analyzed for the last 3 years. IVB has been a routine procedure for patients fulfilling eligibility criteria for the past 3 years. Patients who did not receive IVB preoperatively were assigned as control group (Group A). Patients who received a single IVB injection (1.25 mg in 0.05 ml) preoperatively were assigned to Group B. Medical record of 100 patients who had completed 12-month follow-up were included in each group. Results: The primary outcome measure was visual outcome which was better in Group B as compared to Group A, anatomical outcome observed was 65% patients in Group A and 85% patients in Group B. The secondary outcomes were intraoperative hemorrhage and postoperative vitreous hemorrhage (VH). Intraoperative hemorrhage was seen in 40% patients in Group A and 20% patients in Group B, whereas postoperative VH was seen in 45% patients in Group A and 15% patients in Group B. Conclusion: Preoperative use of bevacizumab achieves excellent anatomical and functional success in majority of patients undergoing PPV for PDR and significantly reduced occurrence of postoperative VH. The results are encouraging when combined with transconjunctival 23 GPPV.



How to cite this article:
Khan B, Kaur R, Kaur M, Matreja PS. Bevacizumab as an adjunct to vitrectomy for diabetic retinopathy: A retrospective study.Egypt Retina J 2018;5:6-11


How to cite this URL:
Khan B, Kaur R, Kaur M, Matreja PS. Bevacizumab as an adjunct to vitrectomy for diabetic retinopathy: A retrospective study. Egypt Retina J [serial online] 2018 [cited 2019 Apr 26 ];5:6-11
Available from: http://www.egyptretinaj.com/text.asp?2018/5/1/6/239454


Full Text



 Introduction



India is set to emerge as the diabetic capital of the world, as per the WHO estimates 31.7 million people were affected by diabetes mellitus (DM) in India in the year 2000. This figure is estimated to rise to 79.4 million by 2030, the largest number in any nation in the world. Almost two-third of all Type 2 DM and almost all Type 1 DM patients are expected to develop diabetic retinopathy (DR) over time.[1],[2],[3],[4] The prevalence of developing any DR in patients with Type 1 diabetes was 56.0%, and 30.3% in Type 2 diabetes according to the UK National DR screening service.[5]

Tractional retinal detachment (TRD) and nonclearing vitreous hemorrhage (VH) are two potentially blinding complications associated with DR. The first goal of diabetic vitrectomy is to restore useful vision. The second important goal of surgery is to stabilize the diabetic neovascular process, thereby producing long-term anatomic and visual success. Eyes in which these surgical objectives are achieved and which have a good 6-month outcome tend to remain stable for many years.[6],[7] The incidence of postoperative VH after vitrectomy is 12%–63% in patients with DR.[8],[9]

The various causes of early or persistent postoperative VH include dispersion of residual blood from the peripheral vitreous skirt or retinal surface or oozing of blood from dissected fibrovascular tissue or directly from the sclerotomies. Intraocular neovascularization in patients with DM also correlates with retinal ischemia, which stimulates vascular endothelial growth factor (VEGF), a key molecule responsible for ocular neovascularization, and anti-VEGF pharmacotherapy is one therapeutic option for intraocular neovascularization. Panretinal photocoagulation (PRP) represents the mainstay in the treatment of proliferative diabetic disease.[10],[11],[12]

Bevacizumab, a full-length humanized monoclonal antibody to VEGF was approved by the US Food and Drug Administration for the treatment for metastatic colorectal cancer.[13] Recent reports on the intravitreal injection of bevacizumab have shown promising result in targeting VEGF-implicated intraocular neovascularization seen in proliferative DR (PDR).[14] Bevacizumab has also shown to enhance the clearance of VH, induce involution of retinal neovascularization and anterior segment neovascularization with no reported complications.[15],[16],[17]

We retrospectively evaluated patients with DM who underwent 23-gauge pars plana vitrectomy (23G PPV) for PDR to study the effect of preoperative intravitreal bevacizumab (IVB) injection on the visual and anatomical outcome.

 Materials and Methods



This retrospective, comparative study was conducted in the vitreoretinal clinic at a Tertiary Care Teaching Hospital in North India. All patients with DM who underwent vitreoretinal surgery between January 2012 and January 2014 were identified from medical records and reviewed. All patients visiting the vitreoretinal clinic between January 2012 and January 2013 were placed in Group A (i.e. patients who had not received IVB), whereas patients who underwent surgery between January 2013 and January 2014 were placed in Group B (patients received IVB 1.25 mg in 0.05 ml 3 days preoperatively). Patients in both groups were matched as possible as according to the surgical indication and preoperative best-corrected visual acuity (BCVA). All patients who were included in the study were having metabolic and hypertension control and had undergone the following laboratory investigations: hemoglobin, glycosylated hemoglobin, fasting blood sugar, postprandial blood sugar, lipid profile, 24 h urinary protein, blood urea, and serum creatinine.

Only those patients who underwent vitreoretinal surgery as a consequence of PDR were included in the study. The indications for surgery included TRD threatening the macula, TRD with vitreous hemorrhage, nonclearing vitreous hemorrhage (NCVH) of at least 3-month duration, and massive retinal subhyaloid bleeding covering posterior pole [Figure 1]. All patients who had previously undergone vitreoretinal surgery, except laser surgery, or intraocular surgery of any type within the prior 6 months were excluded from the study. Patients who had previously received IVB were also excluded from the study.{Figure 1}

The following data were recorded from medical records: patient demographics, duration of diabetes, lens status, intraocular pressure, preoperative PRP, and BCVA and fundus biomicroscopy. Gonioscopy and ultrasonography (if fundus was not visible) was done in both the groups. All the patients included had data of postoperative examination at day 1, 7, 30, and thereafter monthly up to the end of follow-up to 12 months. The primary outcome assessed was visual and anatomical outcome where anatomical outcome means flat retina. The secondary outcomes assessed were intraoperative vitreous hemorrhage and early postoperative vitreous hemorrhage. TRD was defined as elevated retina visible or detected on ultrasound preoperatively or if that was a predominant pathology found at the time of operation. NCVH was defined as vitreous hemorrhage, which was persistent (for at least 3 months) or recurrent requiring surgery.

Intravitreal bevacizumab

A 10% povidone-iodine swabstick was then used to paint the injection site. Bevacizumab in dose of 1.25 mg in 0.05 ml was injected intravitreally 3.5 mm posterior to the superotemporal corneoscleral limbus through the pars plana in phakic patients, 3 mm away from the limbus in pseudophakic patients under complete sterile preparation in operation theater in usual sterile fashion using topical anesthesia.[18]

The surgical procedure was similar for both groups under local anesthesia. All patients underwent 23-gauge 3-port PPV by Feros Oertli vitrectomy unit by a single vitreoretinal surgeon. A binocular indirect ophthalmomicroscope (BIOM) was used in all cases, following sufficient clearance of the vitreous hemorrhage to allow visualization of the posterior pole when necessary; dissection of the preretinal fibrovascular proliferation was carried out. High-speed 23-gauge cutter (up to 2500 cuts/min) was used to cut membranes very close to the retina. With careful elevation of the posterior hyaloids by depressing the periphery with muscle hook, meticulous shaving of the vitreous base under a wide-angle viewing system (BIOM) was performed with careful attention to remove as much residual blood as possible. For macula, central Lander's lens was used to remove if any membrane at the macula. Fill-in pan retinal endolaser photocoagulation (PRP) was administered to any area of the previously untreated retina. Full attention was directed to relieving all traction. Hemostasis was maintained by raising intraocular pressure or by administering endolaser or endodiathermy. Intraoperative bleeding, any iatrogenic break, use of endodiathermy, and endotamponade used was documented. The decision to use endotamponade (either Air, C3F8 or Silicon Oil) was taken intra operatively. Criteria for silicone oil (a) intraoperatively found combined RD, (b) multiple iatrogenic breaks, (c) iatrogenic break in TRD, and (d) break near disc. Criteria for gas (a) in eyes with superior breaks with no proliferative vitroretinopathy, (b) inferior breaks with on or off the retina. At the end of surgery, single raw of cryotherapy is applied to the anterior retinal and around the sclerotomy sites in an attempt to quell fibrovascular in growth and subsequent hemorrhage. No internal limiting membrane peeling was done in any of the surgeries.

Postoperatively, the following data were recorded: intraoperative complications, tamponade use, postoperative complications, vitreoretinal reoperations, and BCVA. Primary outcomes of this study were BCVA at 6 months, the incidence of intraoperative and postoperative complications, incidence of additional vitreoretinal surgery including the removal of silicon oil, and the restoration of useful vision to previously blind eyes.

 Results



Patient demographics

As shown in [Table 1]: A total of 200 eyes of 180 patients (106 male and 94 female) were included in this study.{Table 1}

Median follow-up of the patients was 12 months. Cases of both groups were matched as possible as according to the surgical indication and preoperative BCVA [Table 1].

Group A

A total of 52 patients were male and 48 were female. History of the duration of diabetes was more than 15 years. Indication to do 23 GPPV was combined RD in 10% cases, TRD in 20% cases, VH and TRD were present in 30% cases, preretinal hemorrhage covering the macula in 20% cases, and dense VH in 20% cases. History of previous incomplete PRP was positive in 55% cases, and neovascularization of iris was present in 12% cases.

Group B

A total of 54 patients were male and 46 were female. History of duration of diabetes was more than 16 years. Indication to do 23 GPPV was CRD in 12% cases, TRD in 25% cases, VH [Figure 2] and TRD were present in 25% cases, preretinal hemorrhage covering the macula in 20% cases, and dense VH in 18% cases [Figure 3]. History of previous incomplete PRP was positive in 60% cases, and neovascularization of iris was present in 15% cases.{Figure 2}{Figure 3}

Intraoperative data

Group A

As shown in [Table 2]: Intraoperative bleeding was noted in 40%. Iatrogenic break occurred in 12% of cases with extensive TRD. In all cases of intraoperative bleeding, diathermy was used to stop the bleeders.{Table 2}

A total of 35% received silicone oil in the primary vitrectomy, C3F8 was used in only 20 % cases and air was used in 45%. PFCL was used to flatten the retina in 8 cases. The mean surgical time taken from draping to patching was calculated, and it was around 90–120 min.

Group B

After receiving IVB 3 days back, patients noticed mild-to-moderate improvement in their previous BCVA. No injection-related complication was noticed. On the 4th day, patients were taken for the surgery after metabolic control. Intraoperative bleeding occurred in 20% cases, and we noticed easy clearing of the VH and ease in membrane peeling in cases of TRD. The iatrogenic break occurred in six cases. Diathermy was used in all cases with intraoperative bleeding. PFCL was used in 5% cases. Regarding intraoperative tamponade, silicone oil was used in 25% cases with all combined RD, extensive TRD, multiple breaks, and two one patients for early visual recovery. C3F8 was used in 15% cases; air was used in 60%. The mean surgical time was 60–90 min in this group.

Postoperative data

Group A

As shown in [Table 3]: Anatomical attachment was noted in 65% cases; five cases had redetachment due to reproliferation so silicon oil removal + RePPV + ReSOI was done after the second surgery anatomical attachment received in 70% cases.{Table 3}

Early VH noted in 30%, and late VH noted 15%. Dispersed VH (unresolved) 15% were taken for vitreous lavage, and anterior retinal cryotherapy (ARC) and IVB was given. Progression of cataract was noticed in 18%, in these cases cataract surgery with silicone oil removal done as combined procedure. Four cases developed neovascular glaucoma (NVG) were also given IVB where media was not clear but where media allows fill-in PRP was done. Reoperations were done in 40% cases. Final visual acuity showed improvement in 65% cases and approximately 35% of patients achieve vision of 20/80 or better. Four eyes developed NVG. One eye underwent phthisis because of repeated surgeries.

Group B

Anatomical attachment was noted in 85% cases. Early VH noted in ten cases and late VH were noted five cases. Hence, the incidence of postoperative VH was seen in only 15% cases which are half of Group A. In 10 cases, it resolved over a period of month. Dispersed VH (unresolved) only in 5 cases which were taken for vitreous lavage and ARC and repeat intravitreal Avastin was given. In this group, cataract surgery with IOL implantation with silicone oil removal was done in 18 cases after 6 months. NVI which present in 15 cases preinjection of bevacizumab regressed in 13 cases preventing progression to NVG, only two patient developed NVG. Significant visual improvement occurred in IVB with the final visual acuity showing improvement in 78 cases; approximately 48% of patients achieve vision of 20/80 or better. Reoperations were done in 25% cases. One eye landed up in phthisis.

 Discussion



In this retrospective study, IVB plus microincision vitrectomy surgery (MIVS) offered success in visual and anatomic outcome in patients with TRD in advanced PDR. This technique shortened the surgical time minimizing intraoperative complications and gave favorable visual outcome. It has been shown IVB plus MIVS offered a comparable anatomic success compared with conventional 20-gauge PPV in patients with TRD resulting from severe PDR. This technique shortened the surgical time with fewer intraoperative complications and favorable visual recovery.[19]

In Group B, patients had received IVB, bevacizumab injections are given at day 0 and patient is taken for the surgery on the 3rd day is considered to be the optimum time for vascular regression.[20]

In the present study, intraoperative hemorrhage was noted in 40% cases of Group A and in 20% in Group B. In Group B, there was marked reduction in intraoperative bleed thus minimizing the use of endodiathermy and facilitating complete removal of membranes which further increases the visual outcome. It has been reported that the removal of hemorrhage not only extends preexisting retinal break but also may create new retinal breaks; therefore, hemorrhage should be avoided whenever possible.[21]

The mean surgical time was reduced from 90 min to 60 min in patients given IVB which was due to reduced intraoperative bleed, better visualization, easier peeling of membranes, less use of endodiathermy, and MIVS system. In a study, after preoperative injection of bevacizumab, there was reduction in surgical time as well as reduction in frequency of intraoperative use of endodiathermy.[22]

The prevalence of NVG in our study was 2%, which is comparable to previous studies that reported percentages of 2%–17%. Intraocular injection of anti-VEGF drugs induces a rapid regression of retinal and iris neovascularization. Although currently bevacizumab is usually used to treat macular edema in DR patients, it is also widely used to induce the regression of neovascularization in NVG and before PPV.[7],[23],[24],[25]

In our study, the prevalence of postoperative VH was lower than that reported in other studies which could be explained by the use of IVB on 3rd day preoperatively.[10],[12],[26],[27],[28],[29],[30] It usually clears in 50% cases within a month as shown by another study, there is a trend to reduced incidence of early postvitrectomy hemorrhage in patients undergoing vitrectomy for complications of PDR that have been pre-treated with IVB 1 week before surgery.[31] In another study, IVB was found effective in cases with VH secondary to PDR in terms of reducing the need for surgery and increasing the rate of subjects to who PRP could be applied in the early period, although there was no impact on final visual acuity.[32]

Preoperative IVB was helpful in achieving the surgical and anatomical goals by reducing the time of surgery, the intraoperative and postoperative bleeding, and the use of silicone oil with subsequent reduction of second surgery. Significant visual improvement occurred in IVB with the final visual acuity showing improvement in 38 cases, approximately 20% of patients achieve vision of at least 20/40.[33] In DR vitrectomy study, patients with active proliferation and good vision preoperatively attained vision of 20/40 or better in 41% eyes postoperatively.[34] In our study, in Group A, final visual acuity showed improvement in 65% cases and approximately 35% of patients achieve vision of 20/80 or better. Significant visual improvement occurred in IVB with final visual acuity showing improvement in 78 cases; approximately 48% of patients achieve vision of 20/80 or better [Table 3], [Table 4], [Table 5].{Table 4}{Table 5}

A major drawback in this comparative series is its retrospective nature and the fact that the comparison group was nonrandomized which might generate bias and allow confounding factors to mask the true effect of IVB injections in facilitating surgery and limiting postvitrectomy hemorrhage and complications.

 Conclusion



In the era of MIVS, anti-VEGF therapy plays an effective role in minimizing complications and giving the patient better visual and anatomical outcome. In developing countries like India, bevacizumab being cheap can contribute in reducing postoperative complications in advanced PDR.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.

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