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ORIGINAL ARTICLE
Year : 2013  |  Volume : 1  |  Issue : 3  |  Page : 45-49

Intravitreal bevacizumab injection for management of macular edema in branch retinal vein occlusion


Department of Ophthalmology, Kasr El Aini Hospital, Cairo University, Giza, Egypt

Date of Web Publication1-Nov-2014

Correspondence Address:
Malak Ismail Elshazly
5 Ibn El Nabih Street, Zamalek, Cairo
Egypt
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/2347-5617.143817

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  Abstract 

Purpose: The aim was to evaluate visual and anatomical outcome of intravitreal bevacizumab (IVB) in eyes with macular edema (ME) due to branch retinal vein occlusion (BRVO). Methods: Retrospective, consecutive case series. Study was done on 26 eyes of 26 patients. Outcome measures include: Best corrected visual acuity (BCVA), central macular thickness (CMT) by spectral domain optical coherence tomography, and complications. Results: BCVA improved by a mean of 3.2 lines from an initial mean BCVA: 0.1 (counting fingers: 1 m-0.3) to a mean BCVA 0.4 (0.05-0.8) over the follow-up period of 6.9 months (4-12 months). CMT was reduced from an initial mean of 613 (401-959 μ) to the mean of 400 μ (274-623 μ) at the end of the follow-up period. No complications were recorded. This was achieved through a mean number of injections: Four with a range (3-6 injections). Conclusion: IVB is an effective treatment for ME secondary to BRVO. There was a significant improvement of VA and significant reduction in macular thickness in many cases, but not in all cases.

Keywords: Branch retinal vein occlusion, inferior temporal, intravitreal bevacizumab, macular edema, retinal vein occlusion, superior temporal


How to cite this article:
Ewais WA, Elshazly MI, Nossair AA. Intravitreal bevacizumab injection for management of macular edema in branch retinal vein occlusion . Egypt Retina J 2013;1:45-9

How to cite this URL:
Ewais WA, Elshazly MI, Nossair AA. Intravitreal bevacizumab injection for management of macular edema in branch retinal vein occlusion . Egypt Retina J [serial online] 2013 [cited 2020 Mar 30];1:45-9. Available from: http://www.egyptretinaj.com/text.asp?2013/1/3/45/143817


  Introduction Top


Retinal vein occlusion is the second most common sight-threatening retinal vascular disorder after diabetic retinopathy. Retinal vein occlusion-whether central or branch-is associated with increased intravitreal levels of vascular endothelial growth factor (VEGF). Intraocular levels of VEGF cause retinal vascular abnormalities and retinal ischemia. Thus, inhibition of VEGF may be a good therapeutic option for retinal vein occlusion. [1],[2],[3],[4],[5]

The standard treatment of macular edema (ME) secondary to branch retinal vein occlusion (BRVO) used to be macular grid laser photocoagulation (according to BRVO study). [1] This resulted in significant improvement of visual acuity (VA) and reduction of ME. Intravitreal steroids (triamcinolone acetonide) were used and showed marked reduction in central macular thickness (CMT), but the incidence of glaucoma was up to 40% of cases, limiting their use. [4],[5],[6],[7],[8],[25],[26],[30]

In recent times, intravitreal injections of anti-VEGF agents replaced the standard laser treatment, and proved to be the most efficient, most commonly used and safest of all measures. [13],[14],[15],[16],[17],[18],[19],[20],[21],[22],[23],[24],[25],[26],[27],[28],[29],[30],[31] Bevacizumab and ranibizumab are the most commonly used anti-VEGF agents nowadays. [2],[3],[4],[5]

Bevacizumab (Avastin; Genentech) is a full-length monoclonal humanized antibody to all active isoforms of VEGF. It has been widely used off-label intravitreally for treatment of: Neovascular age-related macular degeneration, [3],[9],[10] Diabetic ME, and ME secondary to central and BRVO. [13],[14],[19],[21],[22]

The aim of this study is to evaluate the visual and anatomical outcome of intravitreal bevacizumab (IVB) for treatment of ME secondary to retinal vein occlusion based on a Prager protocol.


  Methods Top


Our study was a retrospective consecutive interventional case series performed for eyes receiving IVB for ME due to BRVO. Institutional Review Board approval was obtained. Informed consent was obtained for all patients.

Inclusion criteria included: BRVO whether ischemic or nonischemic according to fluorescein angiography imaging without previous treatments in the form of intravitreal triamcinolone (IVTA) or anti-VEGF injections, macular grid photocoagulation, or vitrectomy. BRVO was identified whether it is superior temporal (ST), or inferior temporal (IT).

All eyes underwent a complete ophthalmological examination at baseline, day 1, week 1, and at monthly intervals during the follow-up period. Examination included: Best corrected VA (BCVA) measured at 3 m, slit-lamp, fundus examination and applanation tonometry for intra-ocular pressure (IOP). Spectral domain optical coherence tomography (SD-OCT) imaging (Cirrhus, Zeiss, Oberkochen, Germany) was done for measuring the CMT and detection of edema. Fluorescein angiography was performed at baseline and during follow-up to evaluate the retinal perfusion status.

Intravitreal bevacizumab injection was given under sterile conditions. Bevacizumab 1.25 mg in 0.05 ml was injected 3.5 mm posterior to the limbus using a 30-gauge needle. Pre-and post-injection povidone iodine 5% was instilled in the conjunctival sac. Topical antibiotic gatifloxacin 0.3% was also instilled twice, separated by 10 min preinjection and postinjection was given 4 times daily for 4 days.

The IVB injection protocol was three loading doses then retreatment on a Pro Re Nata (PRN) style (Prager protocol). [22] Indications of retreatment were: Vision loss of five or more letters or an increase in CMT ≥100 μm as measured by OCT.

The outcome measures included: BCVA with decimal acuity chart at 3 m, ophthalmoscopy, applanation tonometry, SD-OCT (Cirrhus, Zeiss, Oberkochen, Germany). BCVA and OCT were performed at 3 months (1 month after loading), 6 months and at final follow-up visit. Examination was done for complications of both BRVO and IVB including rubeosis and neovascular glaucoma, vitreous hemorrhage, retinal detachment, and endophthalmitis.

Statistical analysis was performed using  Microsoft excel program (Microsoft, Redmond, Washington, USA) including descriptive statistics, sampling, Fisher extract, and Student's t-test, as appropriate.


  Results Top


Baseline characteristics

Twenty-six eyes of 26 patients were treated during the period from January 2013 to February 2014 at Kasr El Aini Hospital, Cairo University, Giza, Egypt. They were 18 males (69.2%) and 8 females (31.8%). The mean age was 52 years, (range: 34-67 years). BRVO was ST in 14 cases (53.9%) and IT in 12 cases (46.1%). Twenty-one cases were hypertensive (80.7%). One case (number 4) had systemic lupus and Reiter syndrome. Fifteen cases had diabetes mellitus (57.7%), 5 of them showed nonproliferative diabetic retinopathy changes and the other 10 cases showed no signs of diabetic retinopathy. Seven cases had glaucoma (26.9%).

The mean initial BCVA was 0.1 (standard deviation [SD]: 0.08) (range: counting fingers [CF] 1 m-0.3). The mean initial CMT was 613 μ (SD: 174) and (range: 401-959 μ) [Table 1].
Table 1: Baseline characteristics for retinal vein occlusion case

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Intravitreal bevacizumab

Intravitreal bevacizumab was given as an initial loading: Three monthly injections. Retreatments were given on an as required PRN protocol. This was done for all cases 100%. The mean number of injections was four injections (range: 3-6 injections). The mean follow-up period was 6.9 months (range: 4-12 months).

Visual outcome

Best corrected visual acuity improved from an initial mean 0.1 (with a range of CF 1 m-0.3) to mean 0.4 (with a range of 0.05-0.8) at the final follow-up visit. The average lines of improvement in VA at final follow-up visit were 3.2 lines (0-6 lines). Four cases had no improvement in BCVA (16%). The lines of improvement in BCVA were inversely proportional to the initial BCVA. The better the initial BCVA, the less final lines of improvement of BCVA. There was no statistically significant difference between lines of improvement of vision in both IT BRVO (mean 3.3, range: 1-6) and ST BRVO cases (mean 3.0, range: 0-6). Three or more lines of improvement of vision were observed in 18 eyes (69% of eyes) [Figure 1] and four cases (16% of eyes) had an improvement of ≤2 lines. The following table illustrates the mean change in lines of BCVA over the follow-up period. The changes in lines of BCVA at 3 and 6 months were compared with baseline BCVA [Table 2].
Table 2: Lines of improvement of vision after IVB

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Figure 1: Lines of improvement of vision after intravitreal bevacizumab treatment

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Anatomical outcome

Mean CMT was reduced from an initial 613 (range: 401-959 μ) to 473 μ (range: 362-719 μ) at 3 months (1 month after the initial IVB loading) (P < 0.001). Mean CMT was further reduced to 400 μ (range: 274-23 μ) at the final follow-up (P < 0.001). The mean CMT reduction was 226 μ (SD: 125, range:

19-443 μ), which is 43.5% at final follow-up [Figure 2] and [Figure 3].
Figure 2: Central macular thickness reduction with intravitreal bevacizumab treatment

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Figure 3: Optical coherence tomography for a case of left branch retinal vein occlusion: (a) Baseline: Cystoid macular edema central macular thickness (CMT): 549 u. (b) After 6 months: Resolved edema CMT: 319 u

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There was no significant correlation between the improvement in vision and a reduction in CMT (r = −0.23).

The following table illustrates the mean change in CMT over the follow-up period. The changes in CMT at 3 and 6 months were compared to baseline CMT [Table 3].
Table 3: mean change in CMT

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Adverse events

No complications were reported after IVB injections, no intraocular spikes, endophthalmitis or vitreous hemorrhage occurred in any case after injection. One case developed vitreous hemorrhage due to underlying retinal neovascularization, 4 months after IVB loading. Pars plana vitrectomy was performed for this case. One case developed retinal neovascularization, for which scatter laser photocoagulation was performed. Both cases were diabetic, and they presented with concomitant nonproliferative diabetic retinopathy.


  Discussion Top


The results of this study suggest that IVB with a Prager style protocol may be an efficient therapeutic option for ME secondary to BRVO.

Blocking VEGF elicits a significant reduction in ME, and this proves the critical role of VEGF in the development of ME in retinal vein occlusion. [11],[12],[13],[14],[15],[16],[17]

We had 69% of eyes gaining three or more lines of vision as compared to Ehlers et al., [28] who had only 26% of eyes gaining three or more lines and 49% of eyes gaining one or more lines, but 7.5% of eyes gaining six or more lines. The mean lines of improvement in this study were 3.2 and in that of Ehlers was 1.6. In Ehlers's study, the inclusion criteria was BRVO with presence of ME, treatment with at least one IVB injection, with a reduction of VA ≤20/25, and previous treatment with laser or IVTA was allowed ≥4 months before the IVB treatment. It did not follow the Prager protocol, nor had any loading doses. The number of injections, interval between injections, and retreatment criteria was dictated by physician preference, and reasons for retreatment included recurrence of ME on OCT, decreased VA or new intraretinal hemorrhage. However, the follow-up period in this study was shorter than others, 6.9 months compared to 9 months in Ehlers et al.'s study, [28] and 2 years follow-up Hikichi et al.'s study. [18],[19],[20],[21],[22],[23],[24],[25],[26],[27],[28],[31]

The improvement of vision was not necessarily associated with a marked reduction in the CMT. This correlation was there in some other studies. [18],[19],[20],[21],[22],[23],[24],[25],[26],[27],[28],[29],[30],[31] This may be because of the relatively shorter follow-up period in this study. In our study, no cases showed disruption of the outer retinal layers, such as the inner segment/outer segment junction or external limiting membrane destruction, which have a direct impact on the final visual outcome. [32]

There is no consensus for a specific protocol for IVB in ME in retinal vein occlusion. The BRAVO study displays impressive results with monthly ranibizumab injections for 6 months. However, others suggest that there is no need for monthly ranibizumab to get a favorable response. They state that an OCT-guided protocol and PRN approach result in significant improvement of vision with only 2.9 injections over 59 weeks. [4] Gokce et al. found out no difference in the outcome between giving IVTA and bevacizumab at 12 months. [30] Although the number of injections in the IVB group was much higher (2.83 ± 1.9) than in the IVTA group (1.38 ± 0.60), yet the incidence of complications was more in the IVTA group, with an increase in the IOP of ≥30 mmHg in 26.9% of patients and ≥21 mmHg in 53.8% of the patients. The IOP level did not increase to 30 mmHg in any patient in the IVB group, the highest value measured was 28 mmHg. Furthermore, 23.1% of the patients in the IVTA group developed cataract, while this percentage was only 5.6% in the IVB group.

Our study proves the efficacy of Prager style IVB in the treatment of ME secondary to BRVO. During the follow-up duration of 6 months, our mean number of injections was four. This is similar to 3.4 injections which were given over 6 months in the study done by Ahn et al. [29]

However, IVB needs to be compared with other anti-VEGF agents such as ranibizumab and also with the option of vitrectomy and internal limiting membrane peeling.

Limitations of this study were: The relatively small number of cases and the short duration of follow-up. Further studies on IVB and other treatment modalities for retinal vein occlusion are still required till a standardized approach is reached.

 
  References Top

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