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 Table of Contents  
ORIGINAL ARTICLE
Year : 2016  |  Volume : 17  |  Issue : 2  |  Page : 97-101

Intravitreal bevacizumab plus macular laser photocoagulation for treatment of diabetic macular edema


Department of Ophthalmology, Qena Faculty of Medicine, South Valley University, Qena Governorate, Egypt

Date of Submission25-Nov-2015
Date of Acceptance15-Jan-2016
Date of Web Publication30-Aug-2016

Correspondence Address:
Ahmed H Mohamed
Department of Ophthalmology, Qena Faculty of Medicine, South Valley University, 85111 Qena Governorate
Egypt
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/1110-9173.189073

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  Abstract 

Purpose
The aim of the study was to evaluate the visual outcome and central macular thickness (CMT) after intravitreal injection of bevacizumab in conjunction with macular laser photocoagulation (MLP) for the treatment of diabetic macular edema (DME).
Patients and methods
This is a prospective, interventional, case study. A total of 32 eyes were included in this study. The following data were recorded at baseline and during the follow-up periods (≤6 months): best-corrected visual acuity (BCVA), CMT, fluorescein angiography, slit-lamp biomicroscopy, and intraocular pressure measurement by applanation tonometry. All eyes received intravitreal bevacizumab at a dose of 1.25 mg in 0.05 ml 2 weeks before MLP, which was applied in a focal or grid pattern according to the treatment map.
Results
This study included 32 eyes of 27 patients, 16 of whom were men and 11 were women. The mean baseline BCVA was 0.29 ± 0.11 decimal Snellen’s equivalent, and the final mean BCVA was 0.38 ± 0.13. Analysis of the final BCVA revealed that 15 (47%) eyes improved by two or more lines of BCVA, 16 (50%) eyes remained stable, and one (3%) eye lost one line of BCVA. Mean CMT at baseline was 625.18 ± 82.88 μm, which decreased to a mean of 283.46 ± 22.47 μm at the end of the follow-up period covering 6 months.
Conclusion
Primary treatment for DME with intravitreal bevacizumab in conjunction with MLP results in improvement or stabilization of BCVA and reduces CMT. Combined therapy seems to be an effective modality for treatment of DME.

Keywords: antivascular endothelial growth factor, bevacizumab, diabetic macular edema, intravitreal injection


How to cite this article:
Mohamed AH. Intravitreal bevacizumab plus macular laser photocoagulation for treatment of diabetic macular edema. Delta J Ophthalmol 2016;17:97-101

How to cite this URL:
Mohamed AH. Intravitreal bevacizumab plus macular laser photocoagulation for treatment of diabetic macular edema. Delta J Ophthalmol [serial online] 2016 [cited 2022 May 22];17:97-101. Available from: http://www.djo.eg.net/text.asp?2016/17/2/97/189073


  Introduction Top


Diabetic macular edema (DME) is one of the manifestations of diabetic retinopathy [1]. DME is manifested as retinal thickening primarily due to exudation from incompetent macular retinal capillaries [2], and it remains the most common cause of vision loss among diabetic patients [2].

The current treatment options for DME include macular laser photocoagulation (MLP), intensive glycemic control, and blood pressure control [3]. Other treatment modalities include use of intravitreal triamcinolone acetonide, pars plana vitrectomy, oral protein kinase C inhibitors, and, more recently, antivascular endothelial growth factor (anti-VEGF) therapy [4]. The Early Treatment Diabetic Retinopathy Study (ETDRS) demonstrated that focal (direct/grid) laser photocoagulation reduces moderate vision loss from DME by 50% or more [5].

The effectiveness of focal laser treatment may be partly due to closure of leaky microaneurysms; or with reduced retinal tissue following photocoagulation, autoregulation results in decreased retinal edema [6],[7]. Others have suggested that the reduced retinal blood flow is due to improved oxygenation following photocoagulation [7]. It was also suggested that resolution of the edema may result from changes in biochemical processes within the retinal pigment epithelium (RPE) [8],[9],[10],[11].

As VEGF has been implicated as an important factor in the breakdown of the blood retinal barrier and it is present in significantly high levels in eyes with DME, anti-VEGF drugs have been used in the management of DME [12],[13],[14].

There are different anti-VEGF drugs that have been used in the management of DME, including pegaptanib, bevacizumab, and ranibizumab [15].

Bevacizumab is a humanized monoclonal antibody that competitively inhibits all isoforms of the VEGF-A family in the extracellular space [16].

Bevacizumab was approved for the treatment of metastatic colon cancer but was used widely as off-label treatment for neovascular age-related macular degeneration and retinal vascular disorders including retinal vein occlusion and DME [3],[4],[5].

The use of bevacizumab for the treatment of DME was studied and improvement of best-corrected visual acuity (BCVA) and reduction in central macular thickness (CMT) were observed, but the effect was not sustained [17],[18].

This study aimed to evaluate the visual outcome and CMT after intravitreal injection of bevacizumab in combination with MLP for the treatment of DME.


  Patients and methods Top


This is a prospective noncomparative interventional case study. It included 32 eyes of 27 patients and was conducted from February 2009 to April 2010. Follow-up extended to 6 months for all patients.

Type 2 diabetic patients having DME were included in the study. DME was diagnosed when fluorescein angiography (FA) showed microvascular leakage in the macular area and optical coherence tomography (OCT) showed a CMT of 250 μm or more. Only eyes with a BCVA of 0.5 decimal equivalent or worse were included in this study.

Exclusion criteria were proliferative diabetic retinopathy, cataract that does not allow detailed fundus examination, glaucoma, previous retinal laser treatment, previous cataract surgery within 1 year before initiation of the study, or any previous surgery other than cataract surgery.

All patients were examined at baseline, 1, 3, and 6 months after the first treatment. At each visit, examination included BCVA, slit-lamp biomicroscopy, intraocular pressure measurement, fundus examination, FA (VISUCAM-500; Carl Zeiss Meditec AG, Jena, Germany), and OCT RTVue OCT (SD-OCT) (Optovue Inc., Fremont, California, USA). All patients gave written informed consent to participate in the study. The study was approved by the Ethical Committee of Qena Faculty of Medicine at South Valley University.

Study interventions

(1) Intravitreal bevacizumab injection:

The eye was anesthetized with topical drops of benoxinate hydrochloride 4%, sterilized with povidone–iodine solution 5% for the conjunctival sac and 10% for the lids, and then bevacizumab (Avastin; Roche Genentech Inc., South San Francisco, California, USA) at a dose of 1.25 mg in 0.05 ml was injected using a 27-G needle into the vitreous 3.5–4 mm behind the limbus through the inferotemporal quadrant of the globe.

(2) Macular laser treatment:

Two weeks after bevacizumab injection, macular laser treatment was started. The laser treatment was carried out under the following settings:

Spot size of 50–200 μm, duration of 0.1 s, and power adjusted to obtain a light gray-white (just visible) burn. It was applied in a focal or grid pattern according to the treatment map based on FA.


  Results Top


A total of 32 eyes from 27 consecutive patients with DME who fulfilled the inclusion and exclusion criteria were enrolled in this study. Of the 27 patients, 16 were men and 11 were women. The mean age of the patients was 56.62 ± 6.2 years (range: 43–68 years).

The type of DME was diffuse, focal, or both. The evolution of BCVA data is summarized in [Figure 1] and [Table 1] and [Table 2]. The mean initial BCVA was 0.28 decimal Snellen’s equivalent, which changed to 0.35 after the first month of treatment, then to 0.37 after 3 months of treatment, and finally reached 0.38 at the 6-month follow-up.
Figure 1 Mean best-corrected visual acuity (BCVA) evolution related to time and mean central macular thickness (CMT) improvement with time.

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Table 1 Best-corrected visual acuity and central macular thickness changes with time

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Table 2 Paired sample test for initial best-corrected visual acuity and best-corrected visual acuity at 6 months after treatment

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At the end of follow-up, 97% of the eyes had the same or better vision compared with their initial vision and 47% of the eyes presented a visual gain of two or more lines.

The change in CMT is summarized in [Table 1] and [Table 3]. The mean initial CMT was 625.18 μm and improved to 321.39 μm after the first month of treatment, then to 295.78 μm after 3 months of treatment, and reached 283.46 μm at the 6-month follow-up. At the end of follow-up, all eyes showed a reduction in CMT, as shown in [Figure 2]. The reduction in CMT was marked after the first month of treatment.
Table 3 Paired sample test for initial central macular thickness and central macular thickness at 6 months after treatment

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Figure 2 Optical coherence tomography of a 59-year-old man with diabetic macular edema. (a) Central macular thickness (CMT) at baseline was 760 μm; (b) CMT at 6 months was 217 μm.

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There were no ocular complications such as consistently high intraocular pressure, retinal tear, uveitis, or endophthalmitis.


  Discussion Top


The aim of the treatment of DME is to prevent deterioration of visual acuity and even improve it.

MLP is the standard treatment for DME, with the ETDRS demonstrating that prompt laser treatment of the macula reduces the frequency of vision loss by 50% in diabetic patients with macular edema compared with untreated controls. In addition, almost half of the patients with poor vision initially demonstrated some improvement in vision at 3-year follow-up [19].

MLP improves DME when focal laser spots are applied to the leaking microaneurysms, which stops the leakage of fluid, and grid laser spots are applied lightly to the RPE in areas of diffuse leakage, which consequently enhances the reuptake of edema fluid by the RPE pump [20]. MLP destroys few photoreceptors, and thus reduces the oxygen demand by the retinal tissues and consequently decreases macular edema [21].

MLP alone for the treatment of DME is insufficient to achieve the goals of treatment, which are prevention of deterioration and improvement of visual acuity [3],[4].

In the current study, macular laser (focal/grid) photocoagulation was performed with intravitreal bevacizumab injection 2 weeks earlier. The benefit of bevacizumab may be attributed to its binding to VEGF, thus decreasing the permeability of retinal capillaries and reducing the CMT. In addition, reduction of CMT potentiates the efficiency of laser treatment [22].

An interval of 2 weeks was chosen between intravitreal bevacizumab injection and MLP treatment on the assumption of a half-life of bevacizumab in the vitreous of 4.9 days [23] and a duration of action of about 2 weeks [24].

In the current study, the authors noticed a significant improvement in mean BCVA, where 15 (47%) of the eyes improved by two or more lines at the 6-month follow-up. The mean CMT decreased significantly from 625.18 ± 82.88 to 283.46 ± 22.47 μm at the end of follow-up.

Treatment options for DME are increasing. However, the combined use of intravitreal bevacizumab and MLP has been published in few clinical trials or series. The Diabetic Retinopathy Clinical Research Network (DRCRNET) published results of a phase II randomized clinical trial on the use of intravitreal bevacizumab for DME in 121 eyes of 121 patients followed up for over 6 months. They described 22 cases with DME who received intravitreal injection of 1.25 mg bevacizumab at baseline and 6 weeks with photocoagulation at 3 weeks. They concluded that combining photocoagulation with bevacizumab resulted in no apparent short-term benefit in either improving visual outcome or reducing the CMT. They reported improvement in vision by one line and reduction of CMT by more than 11% from baseline [3].

Lee et al. [22], in a study comparing treatment with bevacizumab only (90 eyes) with treatment with a combination of bevacizumab and macular photocoagulation (38 eyes) for DME, with a follow-up of over 6 months, reported an improvement in visual acuity and reduction in CMT without significant difference between the two groups. However, they demonstrated faster visual acuity improvement that was maintained until the end of the follow-up period in eyes that received combination treatment in comparison with those that received only bevacizumab.

There are some studies that used bevacizumab as monotherapy to treat DME. Diabetic Retinopathy Clinical Research Network [25] published a prospective noncomparative case series of 51 patients with diffuse DME treated with 1.25 mg bevacizumab. The follow-up period was short (6–12 weeks). There was a significant reduction in macular thickness at 12 weeks after one injection in most cases, and the mean visual acuity improved significantly at 6 weeks, but this was not sustained at 12 weeks, which may reflect the reduction of the drug effect.

Scott et al. [3] conducted a multicenter uncontrolled retrospective study of 78 eyes with DME treated with at least one injection of intravitreal bevacizumab (56/78 eyes) at a dose of 1.25 and 2.5 mg. Follow-up ranged from 6 to 9 months. There was a statistically significant improvement in BCVA; 43 (55%) eyes improved (0 or more ETDRS lines) and CMT decreased significantly from 387 to 276 μm at the end of follow-up.

It was observed in the present study that visual acuity (V/A) improvement and CMT reduction were marked at the first month following treatment (49.6%).

These outcomes are comparable to those in previous reports [3],[22]. It was also observed in the current study that V/A improvement and CMT reduction were maintained or even increased at the 6-month of follow-up. This may be explained by the assumption that MLP continues its effect to improve vision and reduce CMT [3], and help to decrease the recurrence of DME [22].

In the present study the patients were treated with a single injection of intravitreal bevacizumab as good results were obtained after a single injection [3],[17], followed by MLP 2 weeks later without additional treatment being considered as the beneficial effect of laser treatment is deemed to continue for a long period of time [3],[25].


  Conclusion Top


Combined intravitreal bevacizumab and MLP therapy appears to be a helpful option for improving or stabilizing BCVA in DME patients.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.

 
  References Top

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Kasim R, Tang B. Use of antivascular growth factor for diabetic macular edema. Clin Ophthalmol 2010; 4:493-505.  Back to cited text no. 1
    
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Arevalo JF, Fromow-Guerra J, Quiroz-Mercado H, Sanchez JG, Wu L, Maia M, et al. Pan-American collaborative retina study group Primary intravitreal bevacizumab (Avastin) for diabetic macular edema: results from the Pan-American collaborative retina study group at 6 month followup. Ophthalmology 2007; 14:743-750.  Back to cited text no. 18
    
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[No authors listed]. Photocoagulation for diabetic macular edema. Early Treatment Diabetic Retinopathy Study report number 1. Early Treatment Diabetic Retinopathy Study research group. Arch Ophthalmol 1985; 103:1796-1806.  Back to cited text no. 19
    
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Lee HY, Lee SY, Park JS. Comparison of photocoagulation with combined intravitreal triamcinolone for diabetic macular edema. Korean J Ophthalmol 2009; 23:153-158.  Back to cited text no. 21
    
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Lee SJ, Kim ET, Moon YS. Intravitreal bevacizumab alone versus combined with macular photocoagulation in diabetic macular edema. Korean J Ophthalmol 2011; 25:299-304.  Back to cited text no. 22
    
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Bakri SJ, Snyder MR, Reid JM, Pulido JS, Ezzat MK, Singh RJ, et al. Pharmacokinetics of intravitreal ranibizumab (Lucentis). Ophthalmology 2007; 114:2179-2182.  Back to cited text no. 23
    
24.
Shah AR, Delpriore LV. Duration of action of intravitreal ranibizumab and bevacizumab in exudative AMD based on macular volume measurements. Br J Ophthalmol 2009; 93:1027-1032.  Back to cited text no. 24
    
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    Figures

  [Figure 1], [Figure 2]
 
 
    Tables

  [Table 1], [Table 2], [Table 3]



 

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