Dear Editor,

The recent report on “Intravitreal Bevacizumab in Vitreous Hemorrhage and DM” is very interesting.1 Alagöz et al.1 noted that “intravitreal bevacizumab was found effective in cases with vitreous hemorrhage secondary to proliferative diabetic retinopathy in terms of reducing the need for surgery and increasing the rate of subjects to whom panretinal photocoagulation could be applied in the early period, although there was no impact on final visual acuity”.1 There is no doubt that intravitreal bevacizumab can be a good alternative management. However, there are many concerns. First, the cost of intravitreal bevacizumab is high and it is an issue for further assessment of cost effectiveness. Second, although there is no serious complication due to intravitreal bevacizumab administration, subconjunctival hemorrhage is common and becomes an issue for consideration in diabetes mellitus cases.2,3 Also, in cases with underlying severe diabetes mellitus, possible unwanted gastrointestinal side effects have been reported.4 Onoda et al.4 suggested that “ophthalmologists should apply alternative therapies instead of intravitreal bevacizumab to patients with severe diabetes mellitus”.

Ethics

Peer-review: Internally peer-reviewed.

Authorship Contributions

Surgical and Medical Practices: Beuy Joob, Viroj Wiwanitkit, Concept: Beuy Joob, Viroj Wiwanitkit, Design: Beuy Joob, Viroj Wiwanitkit, Data Collection or Processing: Beuy Joob, Viroj Wiwanitkit, Analysis or Interpretation: Beuy Joob, Viroj Wiwanitkit, Literature Search: Beuy Joob, Viroj Wiwanitkit, Writing: Beuy Joob, Viroj Wiwanitkit.

Conflict of Interest: No conflict of interest was declared by the authors.

Financial Disclosure: The authors declared that this study received no financial support.

1. Alagöz C, Yıldırım Y, Kocamaz M, Baz Ö, Çiçek U, Çelik B, Demirkale Hİ, Yazıcı AT, Taşkapılı M. The Efficacy of Intravitreal Bevacizumab in Vitreous Hemorrhage of Diabetic Subjects. Turk J Ophthalmol. 2016;46:221–225. [PMC free article] [PubMed]
2. Okoye O, Okonkwo O, Oderinlo O, Hassan K, Ijasan A. Bilateral concomitant intravitreal anti-vascular endothelial growth factor injection: Experience in a Nigerian tertiary private eye care facility. Niger J Clin Pract. 2016;19:544–548. [PubMed]
3. Smith JM, Steel DH. Anti-vascular endothelial growth factor for prevention of postoperative vitreous cavity haemorrhage after vitrectomy for proliferative diabetic retinopathy. Cochrane Database Syst Rev. 2015:CD008214. [PubMed]
4. Onoda Y, Shiba T, Hori Y, Maeno T, Takahashi M. Two cases of acute abdomen after an intravitreal injection of bevacizumab. Case Rep Ophthalmol. 2015;6:110–114. [PMC free article] [PubMed]

Response from the Authors

We thank Drs. Beuy Joob and Viroj Wiwanitkit for their commentary on our article “The Efficacy of Intravitreal Bevacizumab in Vitreous Hemorrhage of Diabetic Subjects”. In our study, we found that intravitreal bevacizumab was effective in vitreous hemorrhage secondary to diabetic retinopathy in terms of reducing the need for surgery and increasing the rate of panretinal photocoagulation (PRP) completion in the early period.1 It has been demonstrated that treatment with only intravitreal anti-vascular endothelial growth factor (anti-VEGF) in proliferative diabetic retinopathy (PDR) patients did not result in worse results compared to PRP treatment alone in 2 years follow-up; that is, PRP was not found superior to intravitreal anti-VEGF treatment.2 Therefore, intravitreal anti-VEGF treatment might be considered as an alternative treatment option for PDR patients, though long-term results are needed. Drs. Beuy Joob and Viroj Wiwanitkit rightly pointed out that intravitreal anti-VEGF treatment is an expensive treatment; however, compared to a vitrectomy surgery, intravitreal bevacizumab is still more cost effective. Like all other intravitreal injection applications, intravitreal bevacizumab may also result in various complications. Subconjunctival hemorrhage is among the most common, but it does not have any impact on visual acuity or the course of the disease. It is well-known that a reduction occurs in serum and plasma-free VEGF levels after intravitreal anti- VEGF injections,3 and that there is an increased risk of artherothrombotic events after systemic use of anti-VEGF agents. Fortunately, meta-analysis could not demonstrate any increased risk in clinical practice.4 This is mostly because high-risk patients such as subjects with a history of recent myocardial infarction or cerebrovascular event were not involved in the studies. In our clinical practice, we also do not administer any kind of intravitreal anti-VEGF treatment to those high-risk patients.

Best Regards

Cengiz Alagöz, Yusuf Yıldırım, Murat Kocamaz, Ökkeş Baz, Uğur Çiçek, Burcu Çelik, Halil İbrahim Demirkale, Ahmet Taylan Yazıcı, Muhittin Taşkapılı

Beyoğlu Eye Traning and Research Hospital, İstanbul, Turkey

1. Alagöz C, Yıldırım Y, Kocamaz M, Baz Ö, Çiçek U, Çelik B, Demirkale Hİ, Yazıcı AT, Taşkapılı M. The Efficacy of Intravitreal Bevacizumab in Vitreous Hemorrhage of Diabetic Subjects. Turk J Ophthalmol. 2016;46:221–225. [PMC free article] [PubMed]
2. Gross JG, Glassman AR, Jampol LM, Inusah S, Aiello LP, Antoszyk AN, Baker CW, Berger BB, Bressler NM, Browning D, Elman MJ, Ferris FL, Friedman SM, Marcus DM, Melia M, Stockdale CR, Sun JK, Beck RW; Writing Committee for the Diabetic Retinopathy Clinical Research Network. Panretinal Photocoagulation vs Intravitreous Ranibizumab for Proliferative Diabetic Retinopathy: A Randomized Clinical Trial. JAMA. 2015;314:2137–2146.[PubMed]
3. Zehetner C, Kirchmair R, Huber S, Kralinger MT, Kieselbach GF. Plasma levels of vascular endothelial growth factor before and after intravitreal injection of bevacizumab, ranibizumab and pegaptanib in patients with agerelated macular degeneration, and in patients with diabetic macular oedema. Br J Ophthalmol. 2013;97:454–459. [PubMed]
4. Virgili G, Parravano M, Menchini F, Brunetti M. Antiangiogenic therapy with anti-vascular endothelial growth factor modalities for diabetic macular oedema. Cochrane Database Syst Rev. 2012;12:CD007419. [PubMed]