|Year : 2015 | Volume
| Issue : 1 | Page : 27-31
Evaluation of intravitreal corticosteroids as an adjuvant to bevacizumab for diabetic macular edema using electroretinogram
Hesham A Enany
Department of Ophthalmology, Faculty of Medicine, Zagazig University, Zagazig, Egypt
|Date of Submission||09-Jul-2014|
|Date of Acceptance||08-Nov-2014|
|Date of Web Publication||29-May-2015|
MD Hesham A Enany
Department of Ophthalmology, Faculty of Medicine, Zagazig University, Zagazig
Source of Support: None, Conflict of Interest: None
The aim of this study was to investigate electroretinogram changes after intravitreal injection of bevacizumab with or without adjuvant intravitreal corticosteroids for diabetic macular edema.
Patients and methods
This prospective randomized study evaluated multifocal electroretinogram (MFERG) changes in 60 eyes of 45 diabetic patients who had clinically significant macular edema after treatment with intravitreal bevacizumab (IVB) with or without corticosteroids. Preoperative and postoperative clinical examination, fluorescein angiography, optical coherence tomography, and MFERG were carried out for all cases. The patients were divided into three groups and each group included 20 eyes. The first group was treated with IVB injection alone, the second group was treated with IVB and triamcinolon injection, and the third group was treated with IVB and dexamathosone. The follow-up was carried out up to 3 months.
The mean visual acuity improved in the three groups, and the mean foveal thickness was reduced in the three groups. As regards MFERG-C, P1 amplitudes increased and P1 peak time (ms) was shortened in the three groups. Intraocular pressure rise occurred in 10% of cases in the second group and in 5% of cases of the third group.
Diabetic macular edema can be treated with bevacizumab alone, as the use of adjuvant corticosteroids has many complications.
Keywords: bevacizumb, diabetic macular edema, electroretinogram, intravitreal corticosteroids
|How to cite this article:|
Enany HA. Evaluation of intravitreal corticosteroids as an adjuvant to bevacizumab for diabetic macular edema using electroretinogram. Delta J Ophthalmol 2015;16:27-31
|How to cite this URL:|
Enany HA. Evaluation of intravitreal corticosteroids as an adjuvant to bevacizumab for diabetic macular edema using electroretinogram. Delta J Ophthalmol [serial online] 2015 [cited 2017 Dec 11];16:27-31. Available from: http://www.djo.eg.net/text.asp?2015/16/1/27/157786
| Introduction|| |
Diabetic macular edema (DME) is a major cause of visual impairment. The pathogenesis of macular edema appears to be multifactorial, and several therapeutic options have been proposed for treatment of this condition. It seems that the combined pharmacologic and surgical therapy may be the best approach for the management of macular edema in diabetic patients  .
Available therapies include macular laser photocoagulation, corticosteroids, and antivascular endothelial growth factor (VEGF) drugs. However, single treatments are often not effective enough to control DME during the entire course of the disease, which can be very long. The multifactorial complex pathogenetic mechanisms require a comprehensive approach  .
Intravitreal steroids have played an increasing role in the treatment of macular edema. The corticosteroids have antiangiogenic, antifibrotic, and antipermeability properties  .
Bevacizumab has been used for intravitreal injection in patients with DME. Bevacizumab is a full-length humanized mononclonal antibody against VEGF, which binds and inhibits all the biologically active forms of VEGF  .
Intravitreal injections play a critical role in daily ophthalmic practice. The overall risk for endophthalmitis and retinal detachment appears to be low, and most of the commonly used drugs are well tolerated, even with repeated injection  .
The most common adverse effects associated with intravitreal steroid injection are elevation of intraocular pressure (IOP), progression of cataract, endophthalmitis, psudoendophthalmitis, and retinal detachment  .
The corticosteroids used for treating vitreoretinal diseases include dexamethasone, fluocinolone acetonide, intravitreal implants, and triamcinolone acetonide  .
Eyes with DME that were treated with intravitreal bevacizumab (IVB) showed improvement in visual acuity, which was accompanied by improvement in pattern electroretinogram (ERG) amplitudes. Further randomized trials are needed to investigate the role of pattern ERG measurements in the evaluation of the efficacy of IVB injection  .
Multifocal electroretinogram (MFERG) may provide objective criteria for the functional evaluation of DME before and after surgery  .
Yamamoto et al.  showed that MFERG from the macular area was a good objective indicator of macular function in patients with DME and was strongly correlated with morphologic changes in the macula. Using MFERG as an objective method of assessing retinal function may therefore be a useful tool in documenting the functional changes after treatment of patients with DME.
This study was designed to investigate the ERG changes after intravitreal injection of bevacizumab with or without adjuvant intravitreal corticosteroids for DME.
| Patients and methods|| |
Sixty eyes of 45 patients who had clinically significant DME were included in this study. These patients attended the Ophthalmic Outpatient Clinic of Zagazig University Hospital during the period from March 2008 to March 2010. History was taken, including the approximate date of onset of diabetes, the use of insulin or oral antihyperglycemic agents, and the quality of metabolic control. Any associated medical problems such as hypertension or hypercholesterolemia were identified.
All patients were subjected to a detailed biomicroscopic examination using a slit lamp, as well as an indirect ophthalmoscopy using detailed biomicroscopic contact lens examination of the macula. DME was diagnosed stereoscopically as retinal thickening or hard exudates within one disc diameter of the center of the macula. Clinically significant macular edema (CSME) was clinically diagnosed with retinal thickening within 500 μm of the macular center, hard exudates within 500 μm of the macular center with adjacent retinal thickening, and one or more disc diameters of retinal thickening, part of which is within one disc diameter of the macular center. Treatment was recommended only for CSME.
Optical coherence tomography (OCT) was used for the calculation of standardized macular thickness and to exclude vitreomacular traction.
Fluorescein angiography was performed to identify leaking microaneurysms or capillaries and areas of retinal ischemia. Focal CSME was diagnosed by focal leakage from microaneurysms or capillaries, whereas diffuse DME was diagnosed when poorly demarcated areas of leakage were present on fluorescein angiography.
Patients with retinal vein occlusion, ruptured macroaneurysm, Irvine-Gass syndrome, radiation retinopathy, hypertensive retinopathy, and choroidal neovascularization were excluded from the study.
The patients in this study were divided into three groups, and each group included 20 eyes.
- The first group was treated with IVB injection alone.
- The second group was treated with IVB, triamcinolone injection.
- The third group was treated with IVB, dexamethasone injection.
ERG was performed before and after treatment for each case, and all changes were recorded for every case.
Intravitreal injections were performed under complete aseptic conditions.
In the first group each eye was injected intravitrealy with 1.25 mg in 0.05 ml of bevacizumab.
In the second group each eye was injected intravitrealy with 1.25 mg in 0.05 ml of bevacizumab plus 2 mg in 0.05 ml of triamcinolone acetonide.
In the third group each eye was injected intravitrealy with 1.25 mg in 0.05 ml of bevacizumab plus 2 mg in 0.05 ml of dexamethasone.
The patients were followed up for 3 months. Visual acuity, IOP lens changes, fluorescein angiography, OCT, and MFERG were carried out.
All ERG changes were recorded for each case. Follow-up extended for 3 months.
| Results|| |
Sixty eyes of 45 diabetic patients who had clinically significant DME were included in this study.
All patients had type II diabetes mellitus. The mean duration of diabetes was 8.6 ± 4.7 years (range 1-15 years), 27 patients (59.4%) were female and 18 patients (39.6%) were male. The mean age of the patients was 58 ± 7.1 years (range 45-65 years) [Figure 1] and [Figure 2] and [Table 1], [Table 2] and [Table 3].
|Figure 1: Multifocal electroretinogram (a) before injection of bevacizumab and triamcinolone (b) improvement after injection 3 months later.|
Click here to view
|Figure 2: Multifocal electroretinogram (a) before injection of bevacizumab and dexamethazone (b) improvement after injection 3 months later.|
Click here to view
| Discussion|| |
In this study, 60 eyes of 45 patients had significant DME. The patients in this study were divided into three groups, each one included 20 eyes. The first group was treated with IVB injection alone, the second group was treated with IVB, triamcinolone injection, and the third group was treated with IVB, dexamethasone injection.
In this study we investigated changes in ERG after IVB injection, bevacizumab triamcinolone injection versus combined bevacizumab dexamethasone for DME. MFERG is a technique developed by Sutter and Tran that allows mapping of retinal function in the posterior pole through simultaneous stimulation of different areas of the retina. MFERG utilizes an array of alternating flickers of hexagonal stimuli to stimulate individual retinal areas, and MFERG responses are obtained using cross correction between the raw recording and a pseudorandom m-sequence. The MFERG recording can provide an objective assessment of retinal function. Its sensitivity in detecting functional abnormalities has been demonstrated in various macular disorders  .
After pars plana vitrectomy in patients with DME, limited improvement in MFERG (limited to the implicit times) was noticed. Although both implicit times and the amplitudes of MFERGs are changed after laser photocoagulation for DME, the results of psychophysical tests suggested little or no changes in visual function  .
In the present study, there was improvement in the mean visual acuity among the three groups, but there was no significant difference in the results after injection in the different groups as regards improvement in mean visual acuity after injection [Table 4].
Haritoglou et al.  showed an improvement in the mean visual acuity after IVB injection for DME, with an increase to 0.75 ± 0.37 logMAR of Snellen letters.
Abdallahi et al.  showed a significant visual improvement, which was more significant in the IVB injection group compared with the control group with CSME.
In the present study, the mean foveal thickness (μm) decreased in the first group from 480.33 ± 89.41 to 280.43 ± 71.61 μm after 1 month, and up to 285.40 ± 92.71 μm after 3 months. In the second group, the mean foveal thickness (μm) decreased from 430.56 ± 73.31 to 270.66 ± 53.93 μm after 1 month, and up to 274.56 ± 34.83 μm after 3 months. In the third group, the mean foveal thickness (μm) decreased from 450.93 ± 63 to 290.36 ± 66.91 μm, and up to 299.88 ± 38.86 μm after 3 months. Hence, in the present study, there was no significant difference between the three groups, as illustrated in [Table 5].
Fernado A et al.  showed that after IVB injection for DME, at 1 month, the mean central retinal thickness measurement decreased from 387.0 ± 182.8 to 287.9 ± 102.4 μm. This overall improvement continued throughout the 6-month follow-up.
Mortidis et al.  showed that after intravitreal triamcinolone (IVT) for refractory DME, the central macular thickness (CMT) as measured by OCT decreased by 55, 57.5, and 38% after 1, 3, and 6 months, respectively, from an initial pretreatment mean of 540.3 ± 96.3 μm.
Soheilian et al.  showed that CMT decreased significantly in all groups only at 6 weeks (first group treated with IVB alone, second group IVT treatment, and third group macular photocoagulation treatment). The reduction of CMT was more in the IVB group in relation to the other groups, although their differences did not reach a significant level at any follow-up timepoint.
Zhang et al.  compared the efficacy of the IVT versus IVB alone or IVB combined with IVT in the treatment of DME showed that the reduction was not significant as regards CMT during the earlier follow-up period (1 and 3 months). However, during follow-up at a later visit (6 months), IVT showed significant decrease in CMT when compared with IVB, whereas there was no significant improvement in visual acuity.
In the present study, macular function improvement assessed by MFERG in DME was recorded in the three groups, with significant improvement and increase in P1 response amplitude for both central and peripheral groups at all examinations compared with pretreatment. In addition, there was a shortening of the mean P1 peak latencies for central and peripheral groups, with no significant difference between the three groups.
Karacorlu et al.  stated that there were statistically significant increases in the mean P1 response amplitude for central and peripheral groups at all examinations compared with pretreatment (for each, P < 0.001). The mean P1 peak latencies for both the central and peripheral groups were shortened, but not significantly after IVT acetonide injection in eyes with DME.
Durukan et al.  investigated the changes and the reliability of MFERG after IVT acetonide injection in diffuse DME, and they stated that the positive effect of IVT acetonide in diffuse DME is reversible until the sixth month. Monitoring of the improvement in visual function by MFERG is violated possibly by irreversible macular dysfunction due to the long duration of macular edema and primary neurophysiologic effects of diabetes on the retina.
Abdelghaffar and Ghobasy  stated that the positive effect of IVT acetonide injection in DME is reversible until the sixth month and that MFERG could be used as adjuvant method to evaluate macular functions after IVT acetonide injection.
Abdallahi et al.  stated that IVB for DME showed improvement in the amplitude and the implicit time in MFERG.
Shetty et al.  stated that intravitreal injection of bevacizumab resulted in reduction of the central retinal thickness and mild to moderate improvement in MFERG amplitudes in a short-term study. The visual acuity changes did not directly correlate with the reduced central thickness or improvement in MFERG. The short-term results showed no serious ocular adverse effects.
In the present study many complications were recorded. Sustained IOP rise occurred in 10% of cases in the second group and in 5% of cases in the third group. Complicated cataract was recorded in 15% of cases in the second group and in 5% of cases in the third group, and corneal epitheliopathy occurred in 10% in the three groups.
Abdallahi et al.  stated that the most common complications of intravitreal injection of triamcinolone acetonide were transient elevation of the IOP above 21 mmHg, cataract progression in 6.6% of cases and cataract surgery, endophthalmitis in 0.5%, and pseudoend-ophthalmitis in 0.5%.
Shahin and El-Lakkany  , in their study on the short-term outcomes in comparison with IVT acetonide versus IVB in DME, indicated that intravitreal injection of bevacizumab was not associated with surgical complications compared with triamcinolone acetonide. Triamcinolone acetonide appears to be a more effective treatment for DME than bevacizumab.
| Acknowledgements|| |
Conflicts of interest
| References|| |
Bhagat N, Grigorian RA, Tutela A, Zarbin MA. Diabetic macular edema: pathogenesis and treatment. Surv Ophthalmol 2009; 54:1010-1018.
Zur D, Loewenstein A. Combination therapy for diabetic macular edema. J Ophthalmol 2012 (2012), p. 6
Cunningham MA, Edelman JL, Kausha LS. Intravitreal steroid injection for macular edema. Surv Ophthalmol 2008; 53:139-149.
Ozkirs A. Intravitreal bevacizumab (avastin) for primary treatment of DME. Eye 2009; 23:616-620.
Sampat KM, Gorg SJ. Complications of intravitreal injections. Curr Opin Ophthalmol 2010; 21:178-183.
Reichle ML. Complications of intravitreal steroid injections. Optometry 2005; 76:450-460.
Kiernan DF, Mieler WF. Intraocular corticosteroids for posterior segment disease. Expert Opin Pharmacother 2012; 13:1679-1694.
Ozkiris A. Multifocal ERG may provide objective criteria for the functional evaluation of DME before and after surgery. Doc Ophthalmol 2010; 83:243-250.
Yaok MAJ, Jiang J, Gaor W, et al.
Assessment of macular function by multifocal electroretinogram in diabetic macular edema. Doc Ophthalmol 2004; 109:131-137.
Yamamoto S, Yamamoto T, Hayashi M, Graefes T. Assessment of macular function by multifocal electroretinogram in diabetic macular edema. Arch Chin Exp Ophthalmol 2001; 239: 96-101.
Sutter EE, Tran D. Macular function by mFERG in diabetic macular edema after IVT. Vision Res 1992; 32:433-446.
Greenstein VC, Chen H, Hood DC, et al.
Macular function by an mFERG. Invest Ophthalmol Vis Sic 2000; 41:3655-3664.
Haritoglou C, Kook D, Neubauer A, Wolf A, Priglinger S, Strauss R, et al.
Intravitreal bevacizumab (avastin) therapy for persistent diffuse diabetic macular edema. Retina 2006; 26:999-1005.
Abdallahi A, Movassat M, Nili M, et al.
Multifocal electroretinogram assisted comparison of macular photocoagulation versus macular. Iranian J Ophthalmol 2010; 22:23-28.
Fernando A, et al.
Primary intravitreal bevacizumab for the treatment of CNV secondary to AMD: results of the Pan-American collaborative retina study group. J Ophthalmol 2006; 12:28-33.
Mortides A, Duker J, Greenberg PB, et al.
Intravitreal triamcinolone for refractory diabetic macular edema. Eur J Ophthalmol 2002; 103:920-927.
Soheilian M, Obudi A, Bijanzadeh B, et al.
Randomized trial of intravitreal bevacizamb alone or combined with rimecinolone versus macular photo-coagulation in diabetic macular edema. Ophthalmology 2009; 116:1-11.
Zhang XL, Chen J, Zhang RJ, et al.
Intravitreal triamcinolone versus intervitrea bevacizumab for diabetic macular edema: a meta-analysis. Int J Ophthalmol 2013; 6:546-552.
Karacorlu M, Ozdemir HG, Senturk F, Arfjaracirkysm Uysal O. Macular function by multifocal electroretinogram in diabetic macular edema after intravitreal a triamcinolone injection. Eur J Ophthalmol 2008; 18:601-608.
Durukun AH, Memisoglu S, Gundogan FC. Is multifocal ERG a reliable index of macular function after triamcinolone acetonide injection in diffuse macular edema. Eur J Ophthalmol 2009; 19:1017-1027.
Abdelghaffar W, Ghobasy W. Changes in multifocal ERG after intra-vitreal injection of triamcinolone acetonide in diffuse diabetic macular edema. Benha M J 2010; 27:115-120.
Shetty R, Pai SA, Vincent A, et al.
Electrophysiological and structural assessment of the central retina following intravitreal injection of bevacizumab of treatment of macular edema. Doc Ophthalmol 2008; 116:129-135.
Shahin MM, El-Lakany RS. A prospective, randomized comparisons of intravitreal triamcinolone acetenoid versus intravitreal bevacizumab in diffuse macular edema. Middle East Afr J Ophthalmol 2010; 17:250-253.
[Figure 1], [Figure 2]
[Table 1], [Table 2], [Table 3], [Table 4], [Table 5]