• Users Online: 140
  • Home
  • Print this page
  • Email this page
Home About us Editorial board Ahead of print Current issue Search Archives Submit article Instructions Subscribe Contacts Login 


 
 Table of Contents  
ORIGINAL ARTICLE
Year : 2016  |  Volume : 17  |  Issue : 3  |  Page : 157-161

Effect of intravitreal bevacizumab on subfoveal choroidal thickness in eyes with diabetic macular edema


Department of Ophthalmology, Faculty of Medicine, Zagazig University, Zagazig, Egypt

Date of Submission26-May-2016
Date of Acceptance14-Jul-2016
Date of Web Publication6-Dec-2016

Correspondence Address:
Haitham Y Al-Nashar
Department of Ophthalmology, Faculty of Medicine, Zagazig University, Zagazig 44519
Egypt
Login to access the Email id

Source of Support: None, Conflict of Interest: None


DOI: 10.4103/1110-9173.195248

Rights and Permissions
  Abstract 

Purpose
The purpose of this study was to evaluate the changes in subfoveal choroidal thickness (SFCT) in eyes with diabetic macular edema (DME) after intravitreal bevacizumab (IVB) injection.
Patients and methods
Thirty eyes diagnosed as nonproliferative diabetic retinopathy with DME were included in this prospective study. All eyes received an intravitreal injection of 1.25 mg/0.05 ml bevacizumab. Best-corrected visual acuity, SFCT, and central macular thickness were measured and recorded before the IVB injection and 1 month after the injection. The choroidal thickness was measured using enhanced depth imaging technique of Heidelberg Spectralis-optical coherence tomography.
Results
The mean age of the patients was 55.63±4.6 years, with a mean duration of diabetes of 8.26±1.96 years. The mean preinjection SFCT was 214.3±7.9 μm. The mean SFCT after 1 month of IVB injection was 215.5±6.8 μm, with no significant difference from the preinjection value (P=0.56). The mean change in the SFCT 1 month after intravitreal injection was 1.1±9.5 μm, with 0.5% change ratio. The correlation between change in SFCT and changes in central macular thickness and best-corrected visual acuity were 0.24 and −0.3, respectively, which were insignificant (P=0.2 and 0.09, respectively).
Conclusion
The IVB injection has no effect on the SFCT in eyes with DME.

Keywords: bevacizumab, choroidal thickness, diabetic macular edema


How to cite this article:
Al-Nashar HY. Effect of intravitreal bevacizumab on subfoveal choroidal thickness in eyes with diabetic macular edema. Delta J Ophthalmol 2016;17:157-61

How to cite this URL:
Al-Nashar HY. Effect of intravitreal bevacizumab on subfoveal choroidal thickness in eyes with diabetic macular edema. Delta J Ophthalmol [serial online] 2016 [cited 2021 Nov 27];17:157-61. Available from: http://www.djo.eg.net/text.asp?2016/17/3/157/195248


  Introduction Top


Diabetic macular edema (DME) is a serious condition that may affect vision in eyes with diabetic retinopathy [1]. Disturbance of the outer and inner blood–retinal barriers plays an important role in the pathogenesis and development of DME, with subsequent accumulation of fluid in the subretinal space and intraretinal tissue [2],[3]. One of the main factors that cause disruption to the inner blood–retinal barrier is the vascular endothelial growth factor (VEGF) [4],[5].

Many pathological changes are present in the choroid of eyes with diabetic retinopathy. These changes include dilatation of choroidal vessels with increased tortuosity, formation of microaneurysms, and the presence of areas of choroidal nonperfusion [6],[7]. Many studies demonstrated that the choroid has an important role in the pathogenesis of diabetic retinopathy. Different types of inflammatory cells and choroidal microvasculature dropout were found in the early stage of diabetic retinopathy [8].

Treatment with intravitreal corticosteroid or anti-VEGF drugs was recommended in eyes with DME [9].

Many studies found that in eyes with DME there is a decrease in the choroidal thickness, and these studies concluded that tissue hypoxia will result from decreased choroidal thickness and volume with subsequent increase in the level of VEGF, resulting in disturbance of the blood–retinal barrier active transport and development of DME [10],[11].

Recently, enhanced depth imaging technique of spectral-domain optical coherence tomography (EDI SD-OCT) was used frequently in choroidal examination and analysis [12],[13].

The aim of this study was to evaluate whether the treatment with anti-VEGF agents is associated with changes in choroidal thickness in eyes with DME.


  Patients and methods Top


Thirty eyes of 19 patients were included in this prospective study.

Inclusion criteria

Eyes with nonproliferative diabetic retinopathy associated with DME diagnosed clinically and with fluorescein angiography were included in this study.

Exclusion criteria

Patients who had a history of previous panretinal or macular laser photocoagulation, or use of intraocular or periocular steroids or anti-VEGF drug injection, were excluded from the study. In addition, exclusion criteria included macular diseases other than DME, proliferative diabetic retinopathy, ocular inflammation, vitreoretinal, and ocular surgeries.

Methods

All patients underwent ocular examination, including best-corrected visual acuity (BCVA), slit-lamp biomicroscopic examination, measurement of intraocular pressure, dilated fundus examination, and fluorescein angiography.

All eyes received an injection of 1.25 mg/0.05 ml bevacizumab [intravitreal bevacizumab (IVB), Avastin; Genentech Inc., USA]. Topical anesthesia was induced by 0.4% benoxinate eye drops before the injection. After disinfection and draping, 0.05 ml containing 1.25 mg of bevacizumab was injected into the vitreous cavity. A 27-G needle was used in intravitreal injection, which was administered 4 mm from the limbus. Paracentesis with aqueous humor removal was performed after the injection to avoid an increase of the intraocular pressure.

Choroidal thickness measurement

All SD-OCT examinations were performed using Heidelberg Spectralis-OCT (Heidelberg Engineering, Heidelberg, Germany) using line scan (30°) centered on the fovea. The choroidal thickness was measured using EDI-OCT technique, by positioning the SD-OCT equipment closer to the eye than the ordinary; with this practice, the sensitivity of imaging in the deeper layers of tissue is increased.

The choroidal thickness was measured manually using the cursor in the software of the instrument. The measure extends from the hyper-reflective layer of the retinal pigment epithelium to the hyporeflective line corresponding to the choroidal scleral junction.

Follow-up software in OCT machine was used to measure the same line that passes through the fovea before and after injection.

All patients gave an informed consent according to the tenets of the Declaration of Helsinki.

Outcome measures

These included BCVA, subfoveal choroidal thickness (SFCT), and central macular thickness (CMT) measured with the same OCT instrument. All these data were collected and recorded before the IVB injection and after 1 month of the injection.

Statistical analysis

Statistical analysis of the collected data was performed using SPSS (IBM SPSS statistics 14.0; IBM, Chicago, Illinois, USA). A P-value less than 0.05 was considered statistically significant.


  Results Top


A total of 30 eyes of 19 patients were included in this study. The mean age of patients was 55.63±4.6 years, and 11 patients were male and eight were female. The mean duration of diabetes was 8.26±1.96 years. No history of ocular disease other than diabetic retinopathy was reported in any patient ([Table 1]).
Table 1 Patients' demographic data

Click here to view


The preinjection baseline value of the mean SFCT was 214.3±7.9 μm (range: 201–225 μm). The mean SFCT after 1 month of IVB injection was 215.5±6.8 μm (range: 205–228 μm), with no significant difference from the preinjection value (P=0.56) ([Table 2] and [Figure 1]).
Table 2 Changes in subfoveal choroidal thickness, central macular thickness and best-corrected visual acuity

Click here to view
Figure 1 Subfoveal choroidal thickness (SFCT) measurement before and 1 month after intravitreal bevacizumab injection.

Click here to view


The mean change in the SFCT after 1 month of intravitreal injection was 1.1±9.5 μm (range: −15 to +22 μm), and it was expressed as the ratio to baseline. After 1 month of IVB injection, the ratio of the SFCT was insignificantly decreased to 0.5% of the baseline value ([Figure 2]).
Figure 2 Changes in subfoveal choroidal thickness (SFCT) 1 month after intravitreal bevacizumab injection

Click here to view


Before IVB injection, the mean CMT was 486.5±27.3 μm (range: 452–558 μm) and mean BCVA was 0.12±0.04 (range: 0.05–0.2), and 1 month after IVB injection they were 337.03±14.5 μm (range: 315–365 μm) and 0.5±0.14 (range: 0.16–0.7), respectively, with significant statistical difference (P≤0.001) ([Figure 3]).
Figure 3 Enhanced depth imaging-optical coherence tomography measurement of subfoveal choroidal thickness: (a) before injection and (b) 1 month after injection.

Click here to view


The mean change in CMT after 1 month of IVB injection was −149.43±31.2 μm, with change ratio of 30.7%. The mean change in BCVA after IVB injection was 0.39±0.1, with a change ratio of 325% ([Table 2]).

The correlation between change in SFCT and changes in both CMT and BCVA was calculated. There was no significant correlation between changes in SFCT and CMT (r=0.24, P=0.2). In addition, there was no statistically significant correlation between the change in SFCT and change in BCVA (r=−0.3, P=0.09), suggesting that changes in CMT and BCVA are not directly related to change in SFCT ([Table 3]).
Table 3 Correlation between the postinjection subfoveal choroidal thickness and both central macular thickness and best-corrected visual acuity

Click here to view



  Discussion Top


Systemic hyperglycemia and increased level of free radicals in the eye are important factors in the pathogenesis of DME, as they cause activation and increased level of VEGF [14].

A normal choroidal function with normal structure of its blood vessels is essential for a normal retinal function. Abnormality of choroidal volume or decreased blood flow may cause dysfunction of photoreceptors with subsequent damage and death. Histological examination of the eye had demonstrated the role of blood vessels of the choroid in the pathological changes that affect the retina in diabetic patients [15],[16].

Histological examination of the choroid in patients with diabetic eye disease revealed the presence of areas of localized dilatation of the blood vessels with increased vascular tortuosity. In addition, areas of localized vascular narrowing are seen with capillary dropout in advanced cases [17],[18].Querques et al. [19] in their study to investigate the changes in macular choroidal thickness in eyes with diabetic retinopathy concluded that there was a generalized thinning of the choroid on EDI examination technique of SD-OCT. Decreased choroidal circulation and thickness results in disturbance of blood–retinal barrier because of increased level of VEGF.

The results of the present study showed that the SFCT of DME eyes was insignificantly changed from the baseline after IVB, as the SFCT baseline level was 214.3±7.9 μm and after 1 month of IVB injection it was 215.5±6.8 μm.

Sonoda et al. [20] in their study compared the effect of intravitreal triamcinolone acetonide (IVTA) and IVB on SFCT in eyes with DME, and they found that there was no significant difference in the SFCT after IVB, whereas the SFCT was reduced significantly after IVTA. They concluded that the decrease in choroidal thickness in eyes with DME after IVTA suggests that the choroidal pathological changes in diabetic maculopathy may be steroid sensitive. They also concluded that VEGF had a lower effect on choroidal pathological changes in DME.

The results of this study showed that changes in CMT did not correlate with SFCT. IVB has a different effect on macula and choroid, and thus it is considered that the macula is more affected by IVB than the choroid. This may be because of the slow and difficult movement of bevacizumab to the choroidal vasculature. However, the exact mechanism is still unclear.


  Conclusion Top


This study demonstrated that IVB injection has no effect on the SFCT in eyes with DME.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.

 
  References Top

1.
Antonetti DA, Klein R, Gardner TW. Diabetic retinopathy. N Engl J Med 2012; 366:1227–1239.  Back to cited text no. 1
    
2.
Yau JW, Rogers SL, Kawasaki R, Lamoureux EL, Kowalski JW, Bek T et al. Global prevalence and major risk factors of diabetic retinopathy. Diabetes Care 2012; 35:556–564.  Back to cited text no. 2
    
3.
Bhagat N, Grigorian RA, Tutela A, Zarbin MA. Diabetic macular edema: pathogenesis and treatment. Surv Ophthalmol 2009; 54:1–32.  Back to cited text no. 3
    
4.
Deissler HL, Deissler H, Lang GK, Lang GE. VEGF but not PlGF disturbs the barrier of retinal endothelial cells. Exp Eye Res 2013; 115:162–171.  Back to cited text no. 4
    
5.
Nguyen QD, Tatlipinar S, Shah SM, Haller JA, Quinlan E, Sung J et al. Vascular endothelial growth factor is a critical stimulus for diabetic macular edema. Am J Ophthalmol 2006; 142:961–969.  Back to cited text no. 5
    
6.
Xu J, Xu L, Du KF, Shao L, Chen CX, Zhou JQ et al. Subfoveal choroidal thickness in diabetes and diabetic retinopathy. Ophthalmology 2013; 120:2023–2028.  Back to cited text no. 6
    
7.
Shiragami C, Shiraga F, Matsuo T, Tsuchida Y, Ohtsuki H. Risk factors for diabetic choroidopathy in patients with diabetic retinopathy. Graefes Arch Clin Exp Ophthalmol 2002; 240:436–442.  Back to cited text no. 7
    
8.
Kook PE, Maier M, Schuster T, Feucht N, Lohmann CP. Nine-month results of intravitreal bevacizumab versus triamcinolone for the treatment of diffuse diabetic macular oedema: a retrospective analysis. Acta Ophthalmol 2011; 89:769–773.  Back to cited text no. 8
    
9.
Zhang X, Zeng H, Bao S, Wang N, Gillies M. Diabetic macular edema: new concepts in pathophysiology and treatment. Cell Biosci 2014; 4:27–41.  Back to cited text no. 9
    
10.
Mori F, Hikichi T, Takahashi J, Nagaoka T, Yoshida A. Dysfunction of active transport of blood-retinal barrier in patients with clinically significant macular edema in type 2 diabetes. Diabetes Care 2002; 25:1248–1249.  Back to cited text no. 10
    
11.
Adhi M, Brewer E, Waheed NK, Duker JS. Analysis of morphological features and vascular layers of choroid in diabetic retinopathy using spectral-domain optical coherence tomography. JAMA Ophthalmol 2013; 131:1267–1274.  Back to cited text no. 11
    
12.
Spaide RF, Koizumi H, Pozonni MC. Enhanced depth imaging spectral-domain optical coherence tomography. Am J Ophthalmol 2008; 146:496–500.  Back to cited text no. 12
    
13.
Giuseppe Q, Rosangela L, Lea Q, Claudia DT, Raimondo F, Luisa P et al. Enhanced depth ımaging optical coherence tomography in type 2 diabetes. Invest Ophthalmol Vis Sci 2012; 53:6017–6024.  Back to cited text no. 13
    
14.
Esmaeelpour M, Povazay B, Hermann B, Hofer B, Kajic V, Hale SL et al. Mapping choroidal and retinal thickness variation in type 2 diabetes using three-dimensional 1060-nm optical coherence tomography. Invest Ophthalmol Vis Sci 2011; 52:5311–5316.  Back to cited text no. 14
    
15.
Sogawa K, Nagaoka T, Takahashi A, Tanano I, Tani T, Ishibazawa A et al. Relationship between choroidal thickness and choroidal circulation in healthy young subjects. Am J Ophthalmol 2012; 153:1129–1132.  Back to cited text no. 15
    
16.
Nagaoka T, Kitaya N, Sugawara R, Yokota H, Mori F, Hikichi T et al. Alteration of choroidal circulation in the foveal region in patients with type 2 diabetes. Br J Ophthalmol 2004; 88:1060–1063.  Back to cited text no. 16
    
17.
Fryczkowski AW, Sato SE, Hodes BL. Changes in the diabetic choroidal vasculature: scanning electron microscopy findings. Ann Ophthalmol 1988; 20:299–305.  Back to cited text no. 17
    
18.
Hidayat AA, Fine BS. Diabetic choroidopathy. Light and electron microscopic observations of seven cases. Ophthalmology 1985; 92:512–522.  Back to cited text no. 18
    
19.
Querques G, Lattanzio R, Querques L, Turco CD, Forte R, Pierro L et al. Enhanced depth ımaging optical coherence tomography in type 2 diabetes. Invest Ophthalmol Vis Sci 2012; 53:6017–6024.  Back to cited text no. 19
    
20.
Sonoda S, Sakamoto T, Yamashita T, Otsuka H, Shirasawa M, Kakiuchi N et al. Effect of ıntravitreal triamcinolone acetonide or bevacizumab on choroidal thickness in eyes with diabetic macular edema. Invest Ophthalmol Vis Sci 2014; 55:3979–3985.  Back to cited text no. 20
    


    Figures

  [Figure 1], [Figure 2], [Figure 3]
 
 
    Tables

  [Table 1], [Table 2], [Table 3]



 

Top
 
 
  Search
 
Similar in PUBMED
   Search Pubmed for
   Search in Google Scholar for
 Related articles
Access Statistics
Email Alert *
Add to My List *
* Registration required (free)

 
  In this article
Abstract
Introduction
Patients and methods
Results
Discussion
Conclusion
References
Article Figures
Article Tables

 Article Access Statistics
    Viewed1437    
    Printed58    
    Emailed0    
    PDF Downloaded119    
    Comments [Add]    

Recommend this journal


[TAG2]
[TAG3]
[TAG4]