|LETTER TO THE EDITOR
|Year : 2013 | Volume
| Issue : 2 | Page : 123
Are anti-vascular endothelial growth factor drugs the panacea for all diabetic retinopathy patients?
Department of Ophthalmology, Christian Medical College, Ludhiana, Punjab, India
|Date of Web Publication||20-May-2013|
Department of Ophthalmology, Christian Medical College, Ludhiana - 141 008, Punjab
Source of Support: None, Conflict of Interest: None
|How to cite this article:|
Koshy J. Are anti-vascular endothelial growth factor drugs the panacea for all diabetic retinopathy patients?. J Clin Ophthalmol Res 2013;1:123
|How to cite this URL:|
Koshy J. Are anti-vascular endothelial growth factor drugs the panacea for all diabetic retinopathy patients?. J Clin Ophthalmol Res [serial online] 2013 [cited 2020 Jul 10];1:123. Available from: http://www.jcor.in/text.asp?2013/1/2/123/112183
I read with enormous interest, the article by Bali and Bali  and congratulate them on the same. This article has beautifully reviewed the current evidence available for the pathological ocular angiogenesis and its treatment in diabetes. However, there is a foremost concern, I would like to highlight here.
Intravitreal anti-vascular endothelial growth factor (VEGF) drugs are being used in the eye for many years now, but not much attention is being paid towards the safety of these drugs. This is of clinical relevance given that most patients have comorbidities and may require serial treatment over many years. There is a need for heightened surveillance for systemic adverse events with intraocular anti-VEGF injections especially in the elderly primarily because they are already at increased risk of cardiovascular and cerebrovascular diseases.
There is clear evidence of greater treatment-related mortality with intravenous bevacizumab in cancer patients.  It is also becoming apparent that intraocular injections of bevacizumab can significantly suppress systemic VEGF levels. Although the dose and volume of delivery with intraocular injections (1.25 mg in 0.05 ml typically) are much lower than the typical dose of 2.5-5 mg/kg/week administered intravenously, there is accumulating evidence that intraocular injections of bevacizumab can still suppress systemic VEGF levels, in some cases by as much as intravenous injections.  Direct assays of plasma levels of VEGF after a single intravitreal injection of bevacizumab have also shown suppression by almost 117-fold 1 day after injection. This suppression persisted with 4-fold reductions at 1-month after injection.  Consistent with these observations, Ranpura reported that the risk of mortality with intravenous use did not differ between high- and low-dose intravenous regimens. 
The RESTORE study, which looked at the use of ranibizumab to treat diabetic macular edema (DME), found non ocular serious adverse events related to the drug/procedure to be intestinal obstruction, hypoglycemia, pulmonary embolism, dyspnea, arterial thrombosis limb, coronary artery occlusion, arthralgia and hypertension.  The RISE and the RIDE studies also looking at ranibizumab for DME found the most frequent systemic adverse events to be myocardial Infarction, pneumonia and congestive heart failure with overall adverse events potentially related to systemic VEGF inhibition occurred in 5.6-11.9% of ranibizumab treatment patients. 
In conclusion, there remains a need for strategies that are effective in preventing diabetic retinopathy or slowing down its progression, which are safe, well tolerated, effective, have a lower risk profile, and with less morbidity than the current regimens. The ocular and systemic adverse events due to intravitreal anti-VEGF medications are probably being underreported as they are often not looked for. A standardized work up protocol for all patients to receive these medications should be devised to monitor these adverse events.
| References|| |
|1.||Bali J, Bali RT. Pathological ocular angiogenesis in diabetes: A perspective of emerging paradigms and current evidence. J Clin Ophthalmol Res 2013;1:3-10. |
|2.||Ranpura V, Hapani S, Wu S. Treatment-related mortality with bevacizumab in cancer patients: A meta-analysis. JAMA 2011;305:487-94. |
|3.||Matsuyama K, Ogata N, Matsuoka M, Wada M, Takahashi K, Nishimura T. Plasma levels of vascular endothelial growth factor and pigment epithelium-derived factor before and after intravitreal injection of bevacizumab. Br J Ophthalmol 2010;94:1215-8. |
|4.||Mitchell P, Bandello F, Schmidt-Erfurth U, Lang GE, Massin P, Schlingemann RO, et al. The RESTORE study: Ranibizumab monotherapy or combined with laser versus laser monotherapy for diabetic macular edema. Ophthalmology 2011;118:615-25. |
|5.||Nguyen QD, Brown DM, Marcus DM, Boyer DS, Patel S, Feiner L, et al. Ranibizumab for diabetic macular edema: Results from 2 phase III randomized trials: RISE and RIDE. Ophthalmology 2012;119:789-801. |