Introduction

Intravitreal bevacizumab (IVB) (Avastin®, Genentech, San Francisco, CA, USA) is used off-label for the treatment of VEGF-mediated ocular diseases such as choroidal neovascularization, proliferative diabetic retinopathy, retinal vein occlusions, and pseudophakic macular oedema.1, 2, 3, 4, 5 The purpose of this study is to describe short-term visual and anatomic outcomes following IVB for macular oedema (ME) due to branch retinal vein occlusion (BRVO).

Materials and methods

After institutional review board (IRB) approval, a retrospective review of 12 eyes of 12 consecutive patients with ME due to BRVO, treated with IVB, was performed. Informed consent about the benefits, risks, off-label nature, and alternatives to treatment was obtained from all the patients.

Each patient underwent complete ocular examination and optical coherence tomography (OCT) measurement of central macular thickness (CMT) at baseline and follow-up examinations. Ten of 12 patients had fluorescein angiography immediately prior to the first IVB treatment. After topical anaesthesia, using sterile technique, 0.05 ml (1.25 mg) bevacizumab was given intravitreally, 3.5 mm posterior to the limbus.

The patients were initially followed up at 4-week intervals. IVB was given as needed based on the presence of ME on OCT. The interval of follow-up examinations was increased to longer periods once the ME resolved. The patients were advised to call back sooner as needed.

The Snellen visual acuities (VA) were converted into LogMAR for statistical analysis, then back to Snellen. The differences in visual acuity and CMT were analysed using the Student's paired t-test.

Results

The mean age of the 12 patients was 69.8 years (range: 42–95 years, 10 female, 3 male). Two patients had a prior diagnosis of glaucoma. Systemic associations included hypertension in five patients, hypertension and diabetes mellitus in one patient, hypertension and hypercholesterolemia in one patient, and hypertension and anaemia in one patient. Table 1 depicts the visual acuity and CMT at initial examination, at 1 month, 6 months, and at the final examination, and the follow-up and time interval(s) for IVB injections in 12 eyes with BRVO and ME.

Table 1 Visual acuity and central macular thickness at initial examination, at 1 month, 6 months, and at the final examination for 12 eyes of 12 patients with branch retinal vein occlusion and macular oedema who received intravitreal bevacizumab
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Prior ocular treatment included focal laser treatment and posterior subtenon triamcinolone in four eyes (nos. 2, 7, 8, 11), focal laser treatment and intravitreal triamcinolone in one eye (no. 1), intravitreal triamcinolone in one eye (no. 6), and posterior subtenon triamcinolone in one eye (no. 4). The ME associated with BRVO either did not respond to or recurred after these treatments. These treatments were performed at least 3 months prior to IVB. There was some macular ischaemia in 4 of 10 patients by fluorescein angiography (nos. 3–6).

All patients had at least 6 months of follow-up. The mean number of IVB injections given over the 6-month interval was 2.8 (range: 1–5). At a mean follow-up of 9.8 months (range: 6–17 months), the mean number of IVB injections given was 4 (range: 1–6). Three patients (nos. 5, 6, 9) did well at follow-ups of 8–9 months after the initial one or two injections (Figures 1 and 2). Patient no. 10 required five subsequent injections at 1-month intervals for persistent ME. The other patients had recurrent ME at a mean follow-up of 3.4 months (range: 2–6 months) after the last IVB injection. No ocular or systemic side effects were noted.

Figure 1
figure 1

OCT showing the presence of intraretinal oedema before intravitreal bevacizumab.

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Figure 2
figure 2

OCT showing complete resolution of the intraretinal oedema after a single injection of intravitreal bevacizumab.

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The mean logMAR VA was 0.91 (Snellen equivalent: 20/163) at baseline, 0.66 (Snellen equivalent: 20/91) at 1 month, 0.58 (Snellen equivalent: 20/76) at 6 months, and 0.48 (Snellen equivalent: 20/60) at the final follow-up (Figure 3). The mean CMT was 506.6 μm at baseline, 270.1 μm at 1 month, 321.8 μm at 6 months, and 267.5 μm at the final follow-up (Figure 4). The differences in logMAR VA between baseline and 1 month, between baseline and 6 months, and between baseline and final follow-up were statistically significant (P=0.040, 0.028, and 0.004, respectively). The differences in CMT between baseline and 1 month, baseline and 6 months, and between baseline and final follow-up were also statistically significant (P=0.003, 0.038, and 0.003, respectively).

Figure 3
figure 3

Bar graph showing the Snellen visual acuities at baseline, 1 month, 6 months, and at the final follow-up.

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Figure 4
figure 4

Bar graph showing the CMT at baseline, 1 month, 6 months, and at the final follow-up.

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Discussion

The cause of BRVO is usually a localized thrombus formation in a branch retinal vein due to arteriosclerosis adjacent to a branch retinal arteriole. Complications of BRVO include disc and retinal neovascularization as well as ME. Results of the branch vein occlusion study (BVOS) showed that if ME persists beyond 3 months and visual acuity is reduced below 20/40, the patient may be treated with focal laser photocoagulation.6 Intravitreal triamcinolone acetonide (IVTA) and intravitreal ranbizumab are currently in clinical trials for the treatment of ME due to BRVO. However, intravitreal injections have a short half-life (bevacizumab 4.32 days, ranibizumab 2.88 days, and triamcinolone 18.6 days)7, 8, 9 and require repeated injections. Repeated IVTA injections are associated with cataract and glaucoma in up to 50% of the cases.10, 11 Long-acting steroid implants such as the Posurdex biodegradable dexamethasone implant are also currently in clinical trials for the treatment of ME due to vein occlusions.

Our results point out that with longer follow-up the need for IVB injections may increase due to recurrent ME. The mean time for recurrence of ME was 3.4 months in our series. Other reports also disclosed similar periods ranging from 2 to 3 months from the last IVB to recurrence of ME.11, 12, 13

In conclusion, this short-term study shows that IVB was useful in decreasing ME and improving visual acuity in patients with BRVO with no side effects. Most eyes will require multiple injections for persistent or recurrent ME.