Macular Edema in Diabetes
- Author: Emmanouil Mavrikakis, MD, PhD; Chief Editor: Hampton Roy, Sr, MD more...
Macular edema in diabetes, defined as retinal thickening within 2 disc diameters of the center of the macula, results from retinal microvascular changes that compromise the blood-retinal barrier, causing leakage of plasma constituents into the surrounding retina and, consequently, retinal edema.
Focal edema is associated with hard exudate rings caused by leakage from microaneurysms. Diffuse edema is caused by leakage from microaneurysms, retinal capillaries, and arterioles.
Diabetes is the leading cause of new blindness in the United States, with clinically significant macular edema (CSME) contributing greatly to this vision loss.
Signs and symptoms
The following findings indicate the presence of clinically significant macular edema (CSME), as defined by the Early Treatment Diabetic Retinopathy Study (ETDRS):
Retinal thickening within 500 µm of the center of the fovea
Hard, yellow exudates within 500 µm of the center of the fovea with adjacent retinal thickening
At least 1 disc area of retinal thickening, any part of which is within 1 disc diameter of the center of the fovea
See Clinical Presentation for more detail.
Diabetic macular edema (DME) is diagnosed by funduscopic examination. The following studies can also be performed, to provide information for treatment and follow-up:
Optical coherence tomography (OCT): Captures reflected light from retinal structures to create a cross-sectional image of the retina, which is comparable to histologic sections as seen with a light microscope; it can demonstrate 3 basic structural changes of the retina from diabetic macular edema: retinal swelling, cystoid edema, and serous retinal detachment
Fluorescein angiography: Distinguishes and localizes areas of focal versus diffuse leakage, thereby guiding the placement of laser photocoagulation
Color stereo fundus photographs: Can be used to evaluate long-term changes in the retina
Visual acuity should also be measured. Although it does not aid in the diagnosis of CSME—initially, at least, patients may have a visual acuity of 20/20—it is an important parameter in following the progression of macular edema.
Protein levels: Proteinuria is a good marker for the development of diabetic retinopathy; thus, patients with diabetic nephropathy should be observed more closely
Lipid and triglyceride levels: Elevated triglyceride and lipid levels increase the risk of retinopathy, while normalization of lipid levels reduces retinal leakage and deposition of exudates
See Workup for more detail.
Intravitreal treatments for macular edema include the following:
Triamcinolone acetonide: Significantly reduces macular edema and improves visual acuity, particularly when the macular edema is pronounced [2, 3, 4]
Ranibizumab: Recombinant humanized antibody fragment that is active against all isoforms of vascular endothelial growth factor (VEGF) ̶ A (a protein that causes breakdown of the blood-retina barrier)
Fluocinolone intravitreal implant: Significant improvement in visual acuity maintained for 36 months
Laser photocoagulation is a well-proven therapy to reduce the risk of vision loss from diabetic macular edema. Treatments include the following:
Focal treatment: Addresses leaking microaneurysms
Grid pattern photocoagulation: Used for diffuse leakage
The Early Treatment Diabetic Retinopathy Study (ETDRS) set the guidelines for the treatment of diabetic macular edema (DME). Since that time, the standard of treatment for diabetic macular edema has been glycemic control as demonstrated by the Diabetes Control and Complications Trial (DCCT), optimal blood pressure control as demonstrated by the United Kingdom Prospective Diabetes Study (UKPDS), and macular focal/grid laser photocoagulation.
In ETDRS, laser photocoagulation reduced the risk of moderate visual loss from diabetic macular edema by 50% (from 24% to 12% 3 years after initiation of treatment). Nevertheless, some patients suffer permanent visual loss even after intensive treatment.
Over the past few years, research has started to focus on the use of anti-vascular endothelial growth factor (VEGF) therapy to treat DME. As new and promising treatment options emerge, these treatments will need to be reevaluated.
It is imperative for patients with diabetes to understand that a healthy lifestyle and compliance with medical care can greatly reduce the development and progression of complications of their disease, in the eyes as well as other organs.
Diabetic macular edema results from retinal microvascular changes. Thickening of the basement membrane and reduction in the number of pericytes are believed to lead to increased permeability and incompetence of the retinal vasculature. This compromise of the blood-retinal barrier leads to the leakage of plasma constituents into the surrounding retina, with subsequent retinal edema. Hypoxia produced by this mechanism can also stimulate the production of vascular endothelial growth factor (VEGF). There is evidence that VEGF is up-regulated in diabetic macular edema and proliferative diabetic retinopathy.
A study suggests that the pathogenesis of diabetic macular edema is not only related to VEGF dependency but also to other inflammatory and angiogenic cytokine levels that can be suppressed by corticosteroids.
Diabetes is the leading cause of new blindness in the United States, and clinically significant macular edema (CSME) contributes greatly to this vision loss. In the absence of ophthalmologic treatment, persons with diabetes have a 25-30% risk of moderate vision loss. With treatment, the risk drops by 50%. According to 2007 data, 23.6 million people in the United States have diabetes, but only 17.9 million have been diagnosed. . About 50% of those with diagnosed diabetes do not receive appropriate eye care. The World Health Organization estimates that worldwide, more than 150 million people have diabetes.
Although diabetes is more common in Hispanics, African Americans, and Native Americans than in whites, no data describe a greater risk of developing macular edema among diabetic patients of any one racial group. Likewise, no data describe a difference in risk of diabetic macular edema between the sexes.
Diabetic retinopathy, not specifically diabetic macular edema, generally occurs in persons older than 40 years. It rarely occurs before puberty.
Albert DM, Jakobiec FA. Principles and Practice of Ophthalmology. 2nd ed. Philadelphia: WB Saunders Co; 2000.
Bonini-Filho MA, Jorge R, Barbosa JC, Calucci D, Cardillo JA, Costa RA. Intravitreal injection versus sub-Tenon's infusion of triamcinolone acetonide for refractory diabetic macular edema: a randomized clinical trial. Invest Ophthalmol Vis Sci. 2005 Oct. 46(10):3845-9. [Medline].
Jonas JB, Martus P, Degenring RF, Kreissig I, Akkoyun I. Predictive factors for visual acuity after intravitreal triamcinolone treatment for diabetic macular edema. Arch Ophthalmol. 2005 Oct. 123(10):1338-43. [Medline].
Patelli F, Fasolino G, Radice P, Russo S, Zumbo G, DI Tizio FM, et al. Time course of changes in retinal thickness and visual acuity after intravitreal triamcinolone acetonide for diffuse diabetic macular edema with and without previous macular laser treatment. Retina. 2005 Oct-Nov. 25(7):840-5. [Medline].
Aiello LP, Avery RL, Arrigg PG, Keyt BA, Jampel HD, Shah ST, et al. Vascular endothelial growth factor in ocular fluid of patients with diabetic retinopathy and other retinal disorders. N Engl J Med. 1994 Dec 1. 331(22):1480-7. [Medline].
Sohn HJ, Han DH, Kim IT, et al. Changes in aqueous concentrations of various cytokines after intravitreal triamcinolone versus bevacizumab for diabetic macular edema. Am J Ophthalmol. 2011 Oct. 152(4):686-94. [Medline].
National Diabetes Information Clearinghouse. National Diabetes Statistics, 2007. [Full Text].
Otani T, Kishi S, Maruyama Y. Patterns of diabetic macular edema with optical coherence tomography. Am J Ophthalmol. 1999 Jun. 127(6):688-93. [Medline].
Early Treatment Diabetic Retinopathy Study Research Group. Treatment techniques and clinical guidelines for photocoagulation of diabetic macular edema. Early Treatment Diabetic Retinopathy Study Report Number 2. Early Treatment Diabetic Retinopathy Study Research Group. Ophthalmology. 1987 Jul. 94(7):761-74. [Medline].
Chew EY, Klein ML, Ferris FL 3rd, Remaley NA, Murphy RP, Chantry K, et al. Association of elevated serum lipid levels with retinal hard exudate in diabetic retinopathy. Early Treatment Diabetic Retinopathy Study (ETDRS) Report 22. Arch Ophthalmol. 1996 Sep. 114(9):1079-84. [Medline].
Avitabile T, Longo A, Reibaldi A. Intravitreal triamcinolone compared with macular laser grid photocoagulation for the treatment of cystoid macular edema. Am J Ophthalmol. 2005 Oct. 140(4):695-702. [Medline].
Tucker M. FDA OKs Implant (Ozurdex) for Some With Diabetic Macular Edema. Medscape Medical News. Available at http://www.medscape.com/viewarticle/827594. Accessed: July 5, 2014.
Ozurdex (dexamethasone intravitreal implant) [package insert]. Irvine, CA: Allergan, Inc. September, 2014. Available at [Full Text].
Boyer DS, Yoon YH, Belfort R Jr, Bandello F, Maturi RK, Augustin AJ, et al. Three-year, randomized, sham-controlled trial of dexamethasone intravitreal implant in patients with diabetic macular edema. Ophthalmology. 2014 Oct. 121(10):1904-14. [Medline].
Reuters. Eye Implant Iluvien for Diabetic Macular Edema Clears FDA. Medscape Medical News. Available at http://www.medscape.com/viewarticle/832439. Accessed: October 6, 2014.
Campochiaro PA, Brown DM, Pearson A, Chen S, Boyer D, Ruiz-Moreno J, et al. Sustained delivery fluocinolone acetonide vitreous inserts provide benefit for at least 3 years in patients with diabetic macular edema. Ophthalmology. 2012 Oct. 119(10):2125-32. [Medline].
Cunningham ET Jr, Adamis AP, Altaweel M, Aiello LP, Bressler NM, D'Amico DJ, et al. A phase II randomized double-masked trial of pegaptanib, an anti-vascular endothelial growth factor aptamer, for diabetic macular edema. Ophthalmology. 2005 Oct. 112(10):1747-57. [Medline].
Massin P, Bandello F, Garweg JG, et al. Safety and efficacy of ranibizumab in diabetic macular edema (RESOLVE Study): a 12-month, randomized, controlled, double-masked, multicenter phase II study. Diabetes Care. 2010 Nov. 33(11):2399-405. [Medline]. [Full Text].
Nguyen QD, Shah SM, Heier JS, et al. Primary End Point (Six Months) Results of the Ranibizumab for Edema of the mAcula in diabetes (READ-2) study. Ophthalmology. 2009 Nov. 116(11):2175-81.e1. [Medline].
Lang G, RESTORE study group. Safety and efficacy of ranibizumab as monotherapy or adjunctive to laser photocoagulation in diabetic macular edema: 12-month results of the RESTORE study. Late-breaker presentation at EASDec Meeting. May 22, 2010.
Elman MJ, Aiello LP, Beck RW, et al. Randomized trial evaluating ranibizumab plus prompt or deferred laser or triamcinolone plus prompt laser for diabetic macular edema. Ophthalmology. 2010 Jun. 117(6):1064-1077.e35. [Medline]. [Full Text].
Elman MJ, Bressler NM, Qin H, et al. Expanded 2-Year Follow-up of Ranibizumab Plus Prompt or Deferred Laser or Triamcinolone Plus Prompt Laser for Diabetic Macular Edema. Ophthalmology. 2011 Apr. 118(4):609-14. [Medline].
Elman MJ, Qin H, Aiello LP, Beck RW, Bressler NM, Ferris FL 3rd, et al. Intravitreal Ranibizumab for Diabetic Macular Edema with Prompt versus Deferred Laser Treatment: Three-Year Randomized Trial Results. Ophthalmology. 2012 Sep 19. [Medline].
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 Apr. 119(4):789-801. [Medline].
Korobelnik JF, Do DV, Schmidt-Erfurth U, Boyer DS, Holz FG, Heier JS, et al. Intravitreal Aflibercept for Diabetic Macular Edema. Ophthalmology. 2014 Jul 8. [Medline].
Michaelides M, Kaines A, Hamilton RD, et al. A prospective randomized trial of intravitreal bevacizumab or laser therapy in the management of diabetic macular edema (BOLT study) 12-month data: report 2. Ophthalmology. 2010 Jun. 117(6):1078-1086.e2. [Medline].
Rajendram R, Fraser-Bell S, Kaines A, Michaelides M, Hamilton RD, Esposti SD, et al. A 2-Year Prospective Randomized Controlled Trial of Intravitreal Bevacizumab or Laser Therapy (BOLT) in the Management of Diabetic Macular Edema: 24-Month Data: Report 3. Arch Ophthalmol. 2012 Apr 9. [Medline].
Diabetic Retinopathy Clinical Research Network, Wells JA, Glassman AR, Ayala AR, Jampol LM, Aiello LP, et al. Aflibercept, bevacizumab, or ranibizumab for diabetic macular edema. N Engl J Med. 2015 Mar 26. 372 (13):1193-203. [Medline].
Diabetic Retinopathy Clinical Research Network. A randomized trial comparing intravitreal triamcinolone acetonide and focal/grid photocoagulation for diabetic macular edema. Ophthalmology. 2008 Sep. 115(9):1447-9, 1449.e1-10. [Medline]. [Full Text].
O'Day R, Barthelmes D, Zhu M, Wong TY, McAllister IL, Arnold JJ, et al. Baseline central macular thickness predicts the need for retreatment with intravitreal triamcinolone plus laser photocoagulation for diabetic macular edema. Clin Ophthalmol. 2013. 7:1565-70. [Medline]. [Full Text].
Hsu J. Drug delivery methods for posterior segment disease. Curr Opin Ophthalmol. 2007 May. 18(3):235-9. [Medline].
Lewis H, Abrams GW, Blumenkranz MS, Campo RV. Vitrectomy for diabetic macular traction and edema associated with posterior hyaloidal traction. Ophthalmology. 1992 May. 99(5):753-9. [Medline].
Tachi N, Ogino N. Vitrectomy for diffuse macular edema in cases of diabetic retinopathy. Am J Ophthalmol. 1996 Aug. 122(2):258-60. [Medline].
Fong DS, Segal PP, Myers F, Ferris FL, Hubbard LD, Davis MD. Subretinal fibrosis in diabetic macular edema. ETDRS report 23. Early Treatment Diabetic Retinopathy Study Research Group. Arch Ophthalmol. 1997 Jul. 115(7):873-7. [Medline].
Takagi H, Otani A, Kiryu J, Ogura Y. New surgical approach for removing massive foveal hard exudates in diabetic macular edema. Ophthalmology. 1999 Feb. 106(2):249-56; discussion 256-7. [Medline].
Barclay L. Patients With Diabetic Macular Edema May Get Care Too Late. Medscape Medical News. Available at http://www.medscape.com/viewarticle/818278. Accessed: January 2, 2014.
Bressler NM, Varma R, Doan QV, Gleeson M, Danese M, Bower JK, et al. Underuse of the Health Care System by Persons With Diabetes Mellitus and Diabetic Macular Edema in the United States. JAMA Ophthalmol. 2013 Dec 19. [Medline].
Lowes R. FDA OKs aflibercept (Eylea) for diabetic macular edema. Medscape Medical News. July 30, 2014. [Full Text].
McNamara D. Laser Reduces Retreatment in Diabetic Macular Edema. Medscape Medical News. Oct 2 2013. [Full Text].
Scott IU, Edwards AR, Beck RW, Bressler NM, Chan CK, Elman MJ, et al. A phase II randomized clinical trial of intravitreal bevacizumab for diabetic macular edema. Ophthalmology. 2007 Oct. 114(10):1860-7. [Medline]. [Full Text].