Intravitreal Bevacizumab (Avastin) for Primary Treatment of Diabetic Macular Oedema

A. Özkirş


Eye. 2009;23(3):616-620. 

In This Article


DME is the most important cause of VA impairment in patients with diabetes mellitus and may be localized or diffused. The prognosis of diffused macular oedema is poorer when compared with focal oedema. Although the exact pathophysiologic mechanism responsible for DME remain uncertain, the disruption of the inner blood-retinal barrier is known to be associated with metabolic alterations affecting the retinal epithelium or retinal vascular endothelium.[1,2,3,4] The ETDRS[7] demonstrated the beneficial effect of laser photocoagulation on preventing visual loss in eyes with diffuse DME. However, macular oedema may persist in some eyes despite laser treatment. IVTA injection appears to be a promising treatment for DME, the treatment is not without risks, and complications can be attributed to the injection procedure or to the corticosteroid suspension. Reported injection-related complications include endophthalmitis, lens injuries, vitreous haemorrhage, and retinal detachment.[23,24] Corticosteroid-associated adverse events include IOP elevation, cataract progression, pseudoendophthalmitis, and pseudohypopyon. Moreover, the efficacy of IVTA is transient and repeated injections are required.

VEGF plays an important role in breakdown of the blood-retina barrier with increased vascular permeability resulting in retinal oedema. Therefore, anti-VEGF therapy may be a promising treatment option for ocular neovascularization and DME. Intravitreal injection of pegaptanib (anti-VEGF aptamer) has recently demonstrated promising results for DME. Cunningham et al[25] reported that patients who had underwent intravitreal injection of pegaptanib had better VA outcomes with reduction in central retinal thickness and less additional therapy with laser photocoagulation. More recently, intravitreal bevacizumab has been used to reduce the breakdown of the inner blood-retinal barrier, extravasation from leaking blood vessels, and inhibition of neovascularization. They inhibit the release of VEGF, contribute to the integrity of the inner blood-retinal barrier, reduce extravasation from leaking blood vessels, and have beneficial effect in the prevention and treatment of macular oedema.[20,26,27] The safety of intravitreal bevacizumab has been confirmed by previous animal studies and human trials,[28,29] and intravitreal injection of bevacizumab has recently been reported to be effective in macular oedema of various etiologies.[20,30,31,32,33]

Results of our study suggest that intravitreal bevacizumab injection appears to be effective in the primary treatment of DME. In our study, 24 eyes showed an improvement in VA with a decrease in fluorescein leakage on FFA (Figure 1a and b). Oedema map values of HRT II showed a reduction in 27 eyes (Figure 2a and b). The results of our study confirm previous reports showing the beneficial effect of intravitreal bevacizumab in the treatment of DME. In a recent study with an intravitreal injection of 1.25 mg bevacizumab, Haritoglou et al[20] reported an improvement in VA from a baseline value of 0.86 logMAR to a value of 0.75 logMAR after 6 weeks of injection in patients with DME who did not respond to other treatments such as photocoagulation, IVTA injection, or vitrectomy. An increase in VA of at least three lines was observed in 15 of 51 eyes at a 6-week follow-up, and in 6 of 23 eyes completing 12 weeks of follow-up. Mean reduction in central macular thickness was 16.9% at 6 weeks, 24.75% at 12 weeks after the injection. In this study, VA increased with a mean of 2.4, 2.7, and 2.8 Snellen lines at 1-, 3-month, and last visit follow-up intervals, respectively. This high success in our study may be explained by performing intravitreal bevacizumab injection as the primary treatment of DME or a short duration of DME in our patients or using of 2.5 mg of bevacizumab.

Figure 1.

Late phase of FFA of a patient. (a) Before injection (b) 6 weeks after intravitreal bevacizumab injection. Note the decrease in fluorescein leakage after treatment.

Figure 2.

Note the decrease in EM values. (a) Before treatment (b) 6 weeks after intravitreal bevacizumab injection.

After intravitreal bevacizumab injection, complications such as anterior chamber inflammation, endophthalmitis, vitreous haemorrhage, subconjunctival haemorrhage, and retinal detachment may occur. In our study, four eyes developed mild anterior segment inflammation, which completely resolved in a week after topical application of corticosteroids. No other complications were observed during the follow-up period.

This study has some differences from previous studies. First, the dosage of bevacizumab injected as the primary treatment of macular oedema. Haritoglou et al[20] used 1.25 mg bevacizumab in the treatment of DME. Second, macular oedema was evaluated by HRT II before and after bevacizumab injection, and reduction in oedema map values was demonstrated as the effectiveness of bevacizumab application. This study has several limitations. First, the follow-up time was relatively short, but visual and anatomical responses were apparent during the follow-up time. Second, there is no control group in this study, but it can be argued that the enrolled eyes serve as their own controls because the pre-and post-treatment VAs and oedema map values of the same patients were compared. Third, VA was measured on a Snellen chart, as opposed to the more standardized and accepted ETDRS chart. However, all eyes were tested with the same correction throughout the follow-up period.

In conclusion, this study demonstrated that intravitreal bevacizumab application is an effective approach with promising results for the primary treatment of DME. Intravitreal bevacizumab provides significant resolution of macular oedema and improvement in VA. However, further studies are needed to obtain the long-term results of such application.