Editorial Commentary New Insights Into the Management of Diabetic Retinopathy Ahmed M Abu El‑Asrar

D

iabetic retinopathy (DR) is the most common microvascular complication of diabetes and remains one of the leading causes of blindness worldwide among adults aged 20-74 years. DR is characterized by gradual progressive retinal vasculopathy leading to endothelial cell dysfunction, breakdown of the blood–retinal barrier, ischemia‑induced retinal neovascularization, and expansion of extracellular matrix resulting in the outgrowth of fibrovascular tissue at vitreoretinal interface. Strong evidence indicates that chronic low‑grade inflammation is implicated in the pathogenesis of DR. In addition, recent studies proved that neurodegeneration and impaired visual function are initiated early after the onset of diabetes and progress independently of the vascular lesions. The two most important visual complications of DR are diabetic macular edema (DME) and proliferative diabetic retinopathy (PDR). Strict metabolic control and tight blood pressure control represent the cornerstone of medical management of DR and significantly decrease the risk of development as well as the progression of retinopathy. Long‑term lipid‑lowering therapy with fenofibrate reduces the progression of DR and the need for laser treatment in patients with type 2 diabetes, although the mechanism of this effect does not seem to be related to plasma concentration of lipids.1 Several studies suggested that renin‑angiotensin system blockers might reduce the burden of DR.2 The peroxisome proliferator‑activated receptor gamma agonists such as rosiglitazone are used to improve glycemic control in patients with diabetes mellitus. These medications have potential antiangiogenic therapy and may delay the onset of PDR in patients with severe nonproliferative DR at baseline.3 Oral administration of the selective protein kinase C β inhibitor roboxistaurin reduced DME progression.4 Recent studies demonstrated that islet transplantation improved HbA1c and reduced progression of DR. Panretinal photocoagulation is the standard treatment for PDR. Clinically meaningful differences are unlikely in optical coherence tomography thickness or visual acuity following application in one sitting compared with four sittings.5 Modified Early Treatment diabetic Retinopathy Study focal/grid laser photocoagulation

remains the standard management for DME and is a better treatment than intravitreal triamcinolone acetonide (IVTA). The fact that 4‑mg IVTA treatment had a greater positive treatment response on visual acuity and retinal thickening after 4 months of treatment, whereas the photocoagulation treatment had a greater positive response later, raises the possibility that combining focal/ grid photocoagulation with IVTA may produce greater benefit for DME than either focal/grid photocoagulation or IVTA alone. However, IVTA is associated with the risks of elevated intraocular pressure and cataract.6 Currently, there are four anti‑vascular endothelial growth factor (anti‑VEGF) agents, which have been used in the management of DR, including pegaptanib (Macugen), ranibizumab (Lucentis), bevacizumab (Avastin), and VEGF Trap‑Eye (Aflibercept). Anti‑VEGF therapy has been shown to be effective at improving vision in patients with DME. Review of the available literature indicates that anti‑VEGF pharmacotherapy, delivered by intravitreal injection, is safe and effective treatment over 2-3 years for DME. Further evidence is required to support long‑term safety of these agents and their comparative efficacy. Number of injections required for long‑term improvement as well as long‑term efficacy is unknown. The available data suggest no difference in effectiveness between bevacizumab and ranibizumab. Blocking VEGF at least in theory could be detrimental to vascular integrity. Therefore, the decision to offer prolonged anti‑VEGF treatment in cases of significant coexisting macular ischemia should not be based only on measurements of macular thickness; instead repeat fluorescein angiograms should be performed. Currently, most experts consider combination focal/grid laser therapy and pharmacotherapy with intravitreal anti‑VEGF agents in patients with center‑involving DME. Combination therapy was shown to reduce the frequency of injections needed to control edema.7,8 Vitrectomy with removal of the posterior hyaloid seems to be effective in eyes with persistent diffuse DME, particularly in eyes with associated vitreomacular traction. Preliminary data suggest that pharmacologic vitreolysis without the performance of vitrectomy is effective in eyes with refractory diffuse DME.

Department of Ophthalmology, College of Medicine, King Saud University, Riyadh, Saudi Arabia Corresponding Author: Dr. Ahmed M Abu El‑Asrar, Department of Ophthalmology, King Abdulaziz University Hospital, Old Airport Road, P.O. Box 245, Riyadh ‑ 11411, Saudi Arabia. E‑mail: [email protected]

Middle East African Journal of Ophthalmology, Volume 20, Number 4, October - December 2013

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El-Asrar: Management of Diabetic Retinopathy

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Chew EY, Ambrosius WT, Davis MD, Danis RP, Gangaputra S, Greven CM, et al.; ACCORD Study Group; ACCORD Eye Study Group. Effects of medical therapies on retinopathy progression in type 2 diabetes. N Engl J Med 2010;363:233‑44. Sjølie AK, Klein R, Porta M, Orchard T, Fuller J, Parving HH, et al. Effect of candesartan on progression and regression of retinopathy in type 2 diabetes (DIRECT‑Protect 2): A randomised placebo‑controlled trial. Lancet 2008;372:1385‑93. Shen LQ, Child A, Weber GM, Folkman J, Aiello LP. Rosiglitazone and delayed onset of proliferative diabetic retinopathy. Arch Ophthalmol 2008;126:793‑9. Sheetz MJ, Aiello LP, Davis MD, Danis R, Bek T, Cunha‑Vaz J, et al. The effect of the oral PKC β inhibitor ruboxistaurin on vision loss in two phase 3 studies. Invest Ophthalmol Vis Sci 2013;54:1750‑7. Brucker AJ, Qin H, Antoszyk AN, Beck RW, Bressler NM, Browning DJ, et al.; Diabetic Retinopathy Clinical Research Network. Observational study of the development of diabetic macular edema following panretinal (scatter) photocoagulation given in 1 or 4 sittings. Arch Ophthalmol 2009;127:132‑40. Beck RW, Edwards AR, Aiello LP, Bressler NM, Ferris F,

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Glassman AR, et al.; Diabetic Retinopathy Clinical Research Network (DRCR.net). Three‑year follow‑up of a randomized trial comparing focal/grid photocoagulation and intravitreal triamcinolone for diabetic macular edema. Arch Ophthalmol 2009;127:245‑51. Ho AC, Scott IU, Kim SJ, Brown GC, Brown MM, Ip MS, et al. Anti‑vascular endothelial growth factor pharmacotherapy for diabetic macular edema: A report by the American Academy of Ophthalmology. Ophthalmology 2012;119:2179‑88. Ford JA, Elders A, Shyangdan D, Royle P, Waugh N. The relative clinical effectiveness of ranibizumab and bavacizumab in diabetic macular oedema: An indirect comparison in a systematic review. BMJ 2012;345:e5182. Access this article online Quick Response Code: Website: www.meajo.org DOI: 10.4103/0974-9233.119991

Middle East African Journal of Ophthalmology, Volume 20, Number 4, October - December 2013

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