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 Table of Contents  
ORIGINAL ARTICLE
Year : 2013  |  Volume : 106  |  Issue : 3  |  Page : 134-137

Comparison of the effects of multiple intravitreal bevacizumab injections and single triamcinolone acetonide injection in diabetic macular edema


Mansoura Ophthalmic Center, Mansoura University, Mansoura, Egypt

Date of Submission11-Oct-2013
Date of Acceptance11-Oct-2013
Date of Web Publication28-Feb-2014

Correspondence Address:
Mohammed M Elwan
Mansoura Ophthalmic Center, Mansoura University, Mansoura
Egypt
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/2090-0686.127355

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  Abstract 

Purpose
The aim of this study was to compare the effects of a single intravitreal injection of triamcinolone acetonide versus three consecutive monthly intravitreal injections of bevacizumab for the treatment of diabetic macular edema.
Patients and methods
In this prospective, randomized study, patients were divided into two groups: 15 eyes that were treated with three consecutive monthly intravitreal injections of 1.25 mg bevacizumab (bevacizumab group) and 15 eyes treated with single intravitreal injections of 4 mg triamcinolone acetonide (triamcinolone group). Changes in the best-corrected visual acuity (BCVA), intraocular pressure, and optical coherence tomography measurements were evaluated in both groups. Follow-up visits up to 3 months from baseline were reported.
Results
The bevacizumab group showed a significant decrease in the median central foveal thickness from 236 μm ± 91.5 to 221 μm ± 43.5 after 3 months (P < 0.05). The triamcinolone group also showed a significant reduction in central foveal thickness from 339 μm ± 130.5 to 273 μm ± 84.5 (P < 0.05). The bevacizumab group showed an increase in the BCVA from a median of 0.8 ± 0.45 logMAR to a median of 0.48 ± 0.3 logMAR after 3 months (P < 0.05). The triamcinolone group also showed an increase in BCVA from a median of 0.7 ± 0.18 logMAR to a median of 0.3 ± 0.41 logMAR (P < 0.05). Statistical analysis showed no significant difference between both groups at 3 months.
Conclusion
A single intravitreal injection of triamcinolone acetonide is as effective as three consecutive monthly intravitreal injections of bevacizumab for the treatment of diabetic macular edema.

Keywords: Bevacizumab-Triamcinolone


How to cite this article:
Abouelkheir HY, Elwan MM. Comparison of the effects of multiple intravitreal bevacizumab injections and single triamcinolone acetonide injection in diabetic macular edema. J Egypt Ophthalmol Soc 2013;106:134-7

How to cite this URL:
Abouelkheir HY, Elwan MM. Comparison of the effects of multiple intravitreal bevacizumab injections and single triamcinolone acetonide injection in diabetic macular edema. J Egypt Ophthalmol Soc [serial online] 2013 [cited 2019 Aug 19];106:134-7. Available from: http://www.jeos.eg.net/text.asp?2013/106/3/134/127355


  Introduction Top


Diabetic macular edema (DME) is a common ocular complication of diabetes mellitus and remains the most common threat to sight in individuals of working age [1]. It is caused by excessive vascular permeability, which results in the leakage of fluid and plasma constituents into the retina, which causes retinal thickening [2].

Macular laser photocoagulation is widely considered to be the benchmark with which other treatments should be compared in evaluating DME therapies. However, its destructive nature, adverse effects, and suboptimal efficacy have led to investigations of several intravitreal agents, such as steroids (triamcinolone acetonide) and vascular endothelial growth factor (VEGF) inhibitors, to treat DME [3].

Several promising results have been obtained in different studies that compared single or multiple injections of bevacizumab, triamcinolone acetonide, or their combinations [4],[5],[6],[7],[8]. In this study, we aimed to compare the effect of a single intravitreal injection of triamcinolone acetonide versus three consecutive monthly intravitreal injections of bevacizumab for the treatment of DME.


  Patients and methods Top


This study included 30 eyes of 30 patients with DME divided into two groups:

Group I included 15 eyes of 15 patients treated with three consecutive monthly intravitreal injections of 1.25 mg bevacizumab (bevacizumab group).

Group II included 15 eyes of 15 patients treated with single intravitreal injections of 4 mg triamcinolone acetonide (triamcinolone group).

Both groups of patients were enrolled according to similar clinically based inclusion and exclusion criteria. We chose only one eye of each patient with clinically significant macular edema involving the foveal center with best-corrected visual acuity (BCVA) 6/60 or better. Patients who had other ophthalmological disorders associated with macular edema such as central retinal vein occlusion, branch retinal vein occlusion, uveitis, pseudophakic macular edema, evidence of tractional macular detachment by epiretinal membrane or fibrovascular proliferations, and accompanying severe ocular illness such as advanced glaucoma were excluded.

A complete clinical examination before each injection including measurement of the BCVA using Snellen's chart and the equivalent logMAR visual acuity (VA) was also performed. Slit-lamp biomicroscopy was carried out for examination of the anterior segment; measurement of intraocular pressure (IOP) was performed by Goldmann applanation tonometry. Retinal examination by slit-lamp biomicroscopy using +78 D lens and/or Goldmann three-mirror contact lens were used for a more detailed macular assessment of the presence of clinically significant macular edema, areas of macular thickening, and any cystoid changes. Measurement of the central macular thickness by optical coherence tomography and fluorescein angiography were performed. The examination protocol was repeated 3 months after the injection of triamcinolone acetonide and 1 month after the third injection of bevacizumab.

This study received approval from the Ethics Committee, Faculty of Medicine, Mansoura University, and adhered to the Declaration of Helsinki. Written informed consent was obtained from all patients after a detailed explanation of the nature of the study was provided to them.

Injection method

Before injection, the conjunctiva bulbi, fornices, eyelid margins, and lashes were cleaned repeatedly with povidone-iodine and then topical anesthesia was induced by applying benoxinate hydrochloride (0.4%) at least three times. After the application of a sterile drape, a lid speculum was inserted. Then, an intravitreal injection of either 0.1 ml/4 mg triamcinolone acetonide or 0.05 ml/1.25 mg bevacizumab using a 27-G needle was administered through the pars plana at a distance of 3.5-4.0 mm from the limbus. After the injection, topical antibiotics were administered four times daily for 10 days.

Statistical analysis

Statistical analysis was carried out using SPSS (version 11, 2000). The quantitative data were presented in the form of median and interquartile range. The Mann-Whitney U-test was used to compare two independent samples. The Wilcoxon signed-rank test was used to compare two paired samples. Significance was considered when the P value was less than 0.05. Insignificance was considered when the P value was more than 0.05.


  Results Top


The characteristics of the patients are shown in [Table 1]. The patients in both groups were similar in terms of age, sex, preoperative VA, and central foveal thickness (CFT).
Table 1: Characteristics of the groups (median ± interquartile range)

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The median preoperative logMAR VA in group I (bevacizumab) was 0.8 (range 1.0-0.4). However, the median preoperative logMAR VA in group II (triamcinolone) was 0.7 (range 1.0-0.3). The Mann-Whitney U-test showed no statistically significant difference in the preoperative logMAR VA among the two groups (P > 0.05).

At the third month after surgery, patients in group I showed an improvement in logMAR VA. The median logMAR VA was 0.48 (range 0.3-1.0). Statistical analysis showed a significant improvement in the logMAR VA in the patients in group I 3 months after surgery (Wilcoxon signed-rank test, P < 0.05). Patients in group II showed an improvement in the logMAR VA. The median logMAR VA was 0.3 (range 0.18-1.0). The Wilcoxon signed-rank test showed a significant improvement in the logMAR VA in the patients in group II (P < 0.05). There was no significant difference in the logMAR VA at the third month after surgery between the patients in group I and group II (Mann-Whitney U-test, P > 0.05).

In group I (bevacizumab), the baseline median CFT was 236 mm (range 218-377 mm), whereas the baseline median CFT in group II (triamcinolone) was 339 mm (range 267-501 mm).

At the 3-month control visit, the patients in the bevacizumab group showed a significant decrease in the median CFT to 221 ± 43.5 mm (range 182-257 mm, P < 0.05). The patients in the triamcinolone group also showed a significant reduction in the median CFT to 273 ± 84.5 mm (range 190-395 mm, P < 0.05). Statistical analysis showed no significant difference between the groups with respect to CFT at 3 months.

The mean IOP after 3 months was not significantly different between the two groups. No other adverse events were observed that could be related to the injections, except for only one patient in the triamcinolone group, who showed an IOP elevation to 27 mmHg requiring medical treatment.


  Discussion Top


Macular edema is the main cause of decreased VA for several diseases. Approximately 10% of all diabetic patients manifest macular edema, with 40% of the patients showing involvement of the center of the macula [9]. It is primarily caused by a breakdown of the blood-retinal barrier, resulting in leakage of retinal vessels. VEGF is a well-known potent angiogenic factor. It is involved in the increased vascular permeability leading to macular edema and induces retinal neovascularization. Recent studies have shown that VEGF plays a major role in increasing vascular permeability in diabetic eyes [2],[10],[11] and that vitreous levels of VEGF, interleukins (IL-6 and IL-8), and monocyte chemotactic protein-1 are related to DME [12],[13]. There is evidence that the pathogenesis of diabetic retinopathy is mediated by inflammatory responses including leukostasis and that DME has some features of chronic inflammation [14],[15]. Inflammatory characteristics of diabetic retinopathy are increased expression of inflammatory mediators, macrophage infiltration, increased leukocyte adhesion, complement activation, and acute-phase response protein expression [16],[17].

Paccola et al. [4] reported that a more favorable BCVA improvement was observed with intravitreal injection of triamcinolone acetonide compared with that of intravitreal bevacizumab as early as 4 weeks after treatment and persisting up to 12 weeks. Similarly, other reports have shown significant VA improvements at the same study points after intravitreal injection of triamcinolone acetonide [18],[19],[20].

The present study showed that a single injection of triamcinolone acetonide and three consecutive monthly injections of bevacizumab had similar effects on CFT and BCVA for the treatment of DME. Both bevacizumab and triamcinolone acetonide significantly improved BCVA and reduced CFT. No side-effect was observed in either group, except for increased IOP in one patient in the triamcinolone group.

Combinations of intravitreal drugs have also been used for the treatment of DME. In a recent study, Wang et al. [21] compared the efficacy and safety of a single intravitreal injection of bevacizumab alone versus bevacizumab combined with triamcinolone acetonide in eyes with DME. Their results showed that there was no significant difference between the treatments. Folgosa et al. [22] showed that 2 mg of intravitreal triamcinolone acetonide plus intravitreal bevacizumab was associated with a similar amount of maximal CFT reduction and BCVA improvement compared with 4 mg of intravitreal triamcinolone acetonide. They suggested that the addition of intravitreal bevacizumab enhanced the effect of intravitreal triamcinolone acetonide at this lower dose without increasing the risk of side-effects. Ahmadieh et al. [7] evaluated the effect of three intravitreal injections of bevacizumab alone or combined with triamcinolone acetonide in the first injection for the treatment of refractory DME. They showed that the addition of triamcinolone acetonide in the first injection seemed to induce earlier visual improvement; however, it did not show any significant additive effect later during follow-up.

Consequently, treatments with intravitreal injections of both triamcinolone acetonide and bevacizumab were effective for the recovery of visual loss caused by DME and in conclusion, the present study showed that a single intravitreal injection of triamcinolone acetonide is as effective as three consecutive monthly intravitreal injections of bevacizumab for the treatment of DME with respect to BCVA and CFT measured by optical coherence tomography. However, the IOP-increasing effect of triamcinolone acetonide must be considered.


  Acknowledgements Top


Conflicts of interest

There are no conflicts of interest.

 
  References Top

1.Harris MI. Diabetes in America: epidemiology and scope of the problem. Diabetes Care 1998; 21 Suppl 3:C11-C14.  Back to cited text no. 1
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3.Diabetic Retinopathy Clinical Research Network Beck RW, Edwards AR, Aiello LP, Bressler NM, Ferris F, Glassman AR, et al. Three-year follow-up of a randomized trial comparing focal/grid photocoagulation and intravitreal triamcinolone for diabetic macular edema. Arch Ophthalmol 2009; 127:245-251.  Back to cited text no. 3
    
4.Paccola L, Costa RA, Folgosa MS, Barbosa JC, Scott IU, Jorge R. Intravitreal triamcinolone versus bevacizumab for treatment of refractory diabetic macular oedema (IBEME study). Br J Ophthalmol 2008; 92 : 76-80.  Back to cited text no. 4
    
5.Faghihi H, Roohipoor R, Mohammadi SF, Hojat-Jalali K, Mirshahi A, Lashay A, et al. Intravitreal bevacizumab versus combined bevacizumab-triamcinolone versus macular laser photocoagulation in diabetic macular edema. Eur J Ophthalmol 2008; 18 : 941-948.  Back to cited text no. 5
    
6.Song JH, Lee JJ, Lee SJ. Comparison of the short-term effects of intravitreal triamcinolone acetonide and bevacizumab injection for diabetic macular edema. Korean J Ophthalmol 2011 ; 25:156-160.  Back to cited text no. 6
    
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8.Rensch F, Spandau UH, Wickenha¨user A, Jonas JB. Diffuse diabetic macular oedema treated with intravitreal bevacizumab or triamcinolone acetonide. Acta Ophthalmol 2010; 88:36-37.  Back to cited text no. 8
    
9.Kim HK, Han YB, Laser photocoagulation in diabetic macular edema. J Korean Ophthalmol Soc 1992; 33:759-763.  Back to cited text no. 9
    
10.Adamis AP, Miller JW, Bernal MT, D′Amico DJ, Folkman J, Yeo TK, et al. Increased vascular endothelial growth factor levels in the vitreous of eyes with proliferative diabetic retinopathy. Am J Ophthalmol 1994; 118 : 445-450.  Back to cited text no. 10
    
11.Funatsu H, Yamashita H, Nakamura S, Mimura TEguchi S, Noma H, et al. Vitreous levels of pigment epithelium-derived factor and vascular endothelial growth factor are related to diabetic macular edema. Ophthalmology 2006; 113:294-301.  Back to cited text no. 11
    
12.Funatsu H, Noma H, Mimura T, Eguchi S, Hori S Association of vitreous inflammatory factors with diabetic macular edema. Ophthalmology 2009; 116:73-79.  Back to cited text no. 12
    
13.Roh MI, Kim HS, Song JH, Lim JB, Kwon OW. Effect of intravitreal bevacizumab injection on aqueous humor cytokine levels in clinically significant macular edema. Ophthalmology 2009; 116:80-86.  Back to cited text no. 13
    
14.Meleth AD, Agrón E, Chan CC, Reed GF, Arora K, Byrnes G, et al. Serum inflammatory markers in diabetic retinopathy. Invest Ophthalmol Vis Sci 2005; 46:4295-4301.  Back to cited text no. 14
    
15.Adamis AP, Berman AJ. Immunological mechanisms in the pathogenesis of diabetic retinopathy. Semin Immunopathol 2008; 30:65-84.  Back to cited text no. 15
    
16.Zhang J, Gerhardinger C, Lorenzi M. Early complement activation and decreased levels of glycosylphosphatidylinositol-anchored complement inhibitors in human and experimental diabetic retinopathy. Diabetes 2002; 51:3499-3504.  Back to cited text no. 16
    
17.Joussen AM, Poulaki V, Le ML, Koizumi K, Esser C, Janicki H, et al. A central role for inflammation in the pathogenesis of diabetic retinopathy. FASEB J 2004; 18 : 1450-1452.  Back to cited text no. 17
    
18.Martidis A, Duker JS, Greenberg PB, Rogers AH, Puliafito CA, Reichel E, Baumal C Intravitreal triamcinolone for refractory diabetic macular edema. Ophthalmology 2002; 109:920-927.  Back to cited text no. 18
    
19.Sutter FK, Simpson JM, Gillies MC Intravitreal triamcinolone for diabetic macular edema that persists after laser treatment: three-month efficacy and safety results of a prospective, randomized, double-masked, placebo-controlled clinical trial. Ophthalmology 2004; 111:2044-2049.  Back to cited text no. 19
    
20.Bonini-Filho MA, Jorge R, Barbosa JC, Calucci D, Cardillo JA, Costa RA. Intravitreal injection versus sub-Tenon′s infusion of triamcinolone acetonide for refractory diabetic macular edema: a randomized clinical trial. Invest Ophthalmol Vis Sci 2005; 46:3845-3849.  Back to cited text no. 20
    
21.Wang YS, Li X, Wang HY, Zhang ZF, Li MH, Su XN. Intravitreal bevacizumab combined with/without triamcinolone acetonide in single injection for treatment of diabetic macular edema. Chin Med J (Engl) 2011; 124 : 352-358.  Back to cited text no. 21
    
22.Folgosa MS, Messias A, Takata C, Costa RA, Scott IU, Jorge R. Single intravitreal injection of triamcinolone combined with bevacizumab for the treatment of diffuse diabetic macular oedema refractory to grid photocoagulation. Acta Ophthalmol 2010; 88:297-298.  Back to cited text no. 22
    



 
 
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