Diabetic Retinopathy Clinical Presentation
- Author: Abdhish R Bhavsar, MD; Chief Editor: Romesh Khardori, MD, PhD, FACP more...
In the initial stages of diabetic retinopathy, patients are generally asymptomatic; in the more advanced stages of the disease, however, patients may experience symptoms that include floaters, blurred vision, distortion, and progressive visual acuity loss.
The mainstay of diagnosing diabetic retinopathy is a complete ophthalmic examination and dilated retinal examination by an ophthalmologist or retina specialist or retina surgeon.
Outreach screening has the potential to increase screening coverage of high-risk patients with diabetic retinopathy in remote and resource-poor settings or in areas in which no ophthalmologist or retina specialist is available, without the risk of missing diabetic retinopathy and the opportunity to prevent vision loss.
Microaneurysms are the earliest clinical sign of diabetic retinopathy and occur secondary to capillary wall outpouching due to pericyte loss. They appear as small red dots in the superficial retinal layers, and there is fibrin and red blood cell accumulation in the microaneurysm lumen. A rupture produces blot/flame hemorrhages. Affected areas may appear yellowish in time, as endothelial cells proliferate and produce basement membrane.
Dot and blot hemorrhages
Dot and blot hemorrhages occur as microaneurysms rupture in the deeper layers of the retina, such as the inner nuclear and outer plexiform layers. These appear similar to microaneurysms if they are small; fluorescein angiography may be needed to distinguish between the two.
Flame-shaped hemorrhages are splinter hemorrhages that occur in the more superficial nerve fiber layer.
Retinal edema and hard exudates
Retinal edema and hard exudates are caused by the breakdown of the blood-retina barrier, allowing leakage of serum proteins, lipids, and protein from the vessels.
Cotton-wool spots are nerve fiber layer infarctions from occlusion of precapillary arterioles. With the use of fluorescein angiography, there is no capillary perfusion. These are frequently bordered by microaneurysms and vascular hyperpermeability.
Venous loops and venous beading
Venous loops and venous beading frequently occur adjacent to areas of nonperfusion and reflect increasing retinal ischemia. Their occurrence is the most significant predictor of progression to proliferative diabetic retinopathy.
Intraretinal microvascular abnormalities
Intraretinal microvascular abnormalities are remodeled capillary beds without proliferative changes. These collateral vessels do not leak on fluorescein angiography and can usually be found on the borders of the nonperfused retina.
Macular edema is the leading cause of visual impairment in patients with diabetes. A reported 75,000 new cases of macular edema are diagnosed annually. This may be due to functional damage and necrosis of retinal capillaries.
Clinically significant macular edema is defined as any of the following:
Retinal thickening located 500 μm or less from the center of the foveal avascular zone (FAZ)
Hard exudates with retinal thickening 500 µm or less from the center of the FAZ
Retinal thickening 1 disc area or larger in size located within 1 disc diameter of the FAZ
Nonproliferative diabetic retinopathy
Mild nonproliferative diabetic retinopathy (NPDR) is indicated by the presence of at least 1 microaneurysm. Mild NPDR reflects structural changes in the retina caused by the physiological and anatomical effects of diabetes.
More advanced stages of NPDR reflect the increasing retinal ischemia, setting the stage for proliferative changes.
Moderate nonproliferative diabetic retinopathy includes the presence of hemorrhages, microaneurysms, and hard exudates. With this condition, soft exudates, venous beading, and intraretinal microvascular abnormalities (IRMA) occur less frequently than with severe NPDR.
Severe NPDR (4-2-1) is characterized by hemorrhages and microaneurysms in 4 quadrants, with venous beading in at least 2 quadrants and IRMA in at least 1 quadrant.
Proliferative diabetic retinopathy
Neovascularization is the hallmark of PDR. It most often occurs near the optic disc (neovascularization of the disc [NVD]) or within 3 disc diameters of the major retinal vessels (neovascularization elsewhere [NVE]). (See the image below.)
Preretinal hemorrhages appear as pockets of blood within the potential space between the retina and the posterior hyaloid face. As blood pools within this space, they may appear boat shaped. (See the image below.)
Hemorrhage into the vitreous may appear as a diffuse haze or as clumps of blood clots within the gel.
Fibrovascular tissue proliferation is usually seen associated with the neovascular complex and also may appear avascular when the vessels have already regressed. (See the images below.)
Traction retinal detachments usually appear tented up, immobile, and concave, as compared to rhegmatogenous retinal detachments, which are bullous, mobile, and convex. A combination of both mechanisms is not an uncommon finding, however.
Macular edema is the leading cause of visual impairment in patients with diabetes. It may result from functional damage and necrosis of retinal capillaries. In cases of PDR, edema also may be caused by retinal traction if the retina is sufficiently elevated away from the retinal pigment epithelium.
Proliferative diabetic retinopathy is classified as early or high risk. In early PDR, new vessels are present, but they do not meet the criteria for high-risk PDR. In high-risk PDR, NVD is one-third to one-half, or greater, of the disc area (DA); there may be any amount of NVD with vitreous or preretinal hemorrhage; and NVE is one-half or greater of the DA, with preretinal or vitreous hemorrhage.
Frank RN. Etiologic mechanisms in diabetic retinopathy. Ryan SJ, ed. Retina. 1994. Vol 2: 1243-76.
Crawford TN, Alfaro DV 3rd, Kerrison JB, Jablon EP. Diabetic retinopathy and angiogenesis. Curr Diabetes Rev. 2009 Feb. 5(1):8-13. [Medline].
Klein R. The Diabetes Control and Complications Trial. Kertes C, ed. Clinical Trials in Ophthalmology: A Summary and Practice Guide. 1998. 49-70.
Rodriguez-Fontal M, Kerrison JB, Alfaro DV, Jablon EP. Metabolic control and diabetic retinopathy. Curr Diabetes Rev. 2009 Feb. 5(1):3-7. [Medline].
Liew G, Mitchell P, Wong TY. Systemic management of diabetic retinopathy. BMJ. 2009 Feb 12. 338:b441. [Medline].
Bhavsar AR. Diabetic retinopathy: the latest in current management. Retina. 2006 Jul-Aug. 26(6 Suppl):S71-9. [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].
Federman JL, Gouras P, Schubert H, et al. Systemic diseases. Podos SM, Yanoff M, eds. Retina and Vitreous: Textbook of Ophthalmology. 1994. Vol 9: 7-24.
Bhavsar AR, Emerson GG, Emerson MV, Browning DJ. Diabetic Retinopathy. Browning DJ. Epidemiology of Diabetic Retinopathy. Springer, New York.: 2010.
Williams R, Airey M, Baxter H, Forrester J, Kennedy-Martin T, Girach A. Epidemiology of diabetic retinopathy and macular oedema: a systematic review. Eye (Lond). 2004 Oct. 18(10):963-83. [Medline].
Gupta R, Kumar P. Global diabetes landscape-type 2 diabetes mellitus in South Asia: epidemiology, risk factors, and control. Insulin; 2008. 3:78-94.
Zhang X, Saaddine JB, Chou CF, Cotch MF, Cheng YJ, Geiss LS, et al. Prevalence of diabetic retinopathy in the United States, 2005-2008. JAMA. 2010 Aug 11. 304(6):649-56. [Medline]. [Full Text].
Aiello LM, Cavallerano JD, Aiello LP, Bursell SE. Diabetic retinopathy. Guyer DR, Yannuzzi LA, Chang S, et al, eds. Retina Vitreous Macula. 1999. Vol 2: 316-44.
Benson WE, Tasman W, Duane TD. Diabetes mellitus and the eye. Duane's Clinical Ophthalmology. 1994. Vol 3:
Barchetta I, Riccieri V, Vasile M, et al. High prevalence of capillary abnormalities in patients with diabetes and association with retinopathy. Diabet Med. 2011 Sep. 28(9):1039-44. [Medline].
Shiba T, Takahashi M, Hori Y, Saishin Y, Sato Y, Maeno T. Relationship between sleep-disordered breathing and iris and/or angle neovascularization in proliferative diabetic retinopathy cases. Am J Ophthalmol. 2011 Apr. 151(4):604-9. [Medline].
Klein R, Knudtson MD, Lee KE, Gangnon R, Klein BE. The Wisconsin Epidemiologic Study of Diabetic Retinopathy XXIII: the twenty-five-year incidence of macular edema in persons with type 1 diabetes. Ophthalmology. 2009 Mar. 116(3):497-503. [Medline].
Akduman L, Olk RJ. The early treatment for diabetic retinopathy study. Kertes C, ed. Clinical Trials in Ophthalmology: A Summary and Practice Guide. 1998. 15-36.
Quillen DA, Gardner TW, Blankenship GW. Clinical Trials in Ophthalmology: A Summary and Practice Guide. Kertes C, ed. diabetic retinopathy study. 1998. 1-14.
Bragge P, Gruen RL, Chau M, Forbes A, Taylor HR. Screening for Presence or Absence of Diabetic Retinopathy: A Meta-analysis. Arch Ophthalmol. 2011 Apr. 129(4):435-44. [Medline].
Genuth S. The UKPDS and its global impact. Diabet Med. 2008 Aug. 25 Suppl 2:57-62. [Medline].
Massin P, Lange C, Tichet J, Vol S, Erginay A, Cailleau M, et al. Hemoglobin A1c and fasting plasma glucose levels as predictors of retinopathy at 10 years: the French DESIR study. Arch Ophthalmol. 2011 Feb. 129(2):188-95. [Medline].
Elman MJ, Aiello LP, Beck RW, Bressler NM, Bressler SB, Edwards AR, 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].
Bhavsar AR, Grillone LR, McNamara TR, Gow JA, Hochberg AM, Pearson RK. Predicting response of vitreous hemorrhage after intravitreous injection of highly purified ovine hyaluronidase (Vitrase) in patients with diabetes. Invest Ophthalmol Vis Sci. 2008 Oct. 49(10):4219-25. [Medline].
Wells JA, Glassman AR, Ayala AR, et al. Aflibercept, bevacizumab, or ranibizumab for diabetic macular edema. N Engl J Med. 2015 Mar 26. 372(13):1193-203. [Medline].
Brown DM, Nguyen QD, Marcus DM, Boyer DS, Patel S, Feiner L, et al. Long-term outcomes of ranibizumab therapy for diabetic macular edema: the 36-month results from two phase III trials: RISE and RIDE. Ophthalmology. 2013 Oct. 120(10):2013-22. [Medline]. [Full Text].
Korobelnik JF, Do DV, Schmidt-Erfurth U, Boyer DS, Holz FG, Heier JS, et al. Intravitreal aflibercept for diabetic macular edema. Ophthalmology. 2014 Nov. 121(11):2247-54. [Medline].
Arevalo JF, Garcia-Amaris RA. Intravitreal bevacizumab for diabetic retinopathy. Curr Diabetes Rev. 2009 Feb. 5(1):39-46. [Medline].
Rodriguez-Fontal M, Alfaro V, Kerrison JB, Jablon EP. Ranibizumab for diabetic retinopathy. Curr Diabetes Rev. 2009 Feb. 5(1):47-51. [Medline].
FDA Drug and Safety Alerts. FDA Alerts Health Care Professionals of Infection Risk from Repackaged Avastin Intravitreal Injections. August 30, 2011. Available at http://www.fda.gov/drugs/drugsafety/ucm270296.htm.
Meredith TA. Clinical Trials in Ophthalmology-A Summary and Practice Guide. Kertes C, ed. The diabetic vitrectomy study. 1998. 37-48.
Harrison P. Monthly Ranibizumab Improves Diabetic Retinopathy. Medscape Medical News. Sep 5 2013. Available at http://www.medscape.com/viewarticle/810491. Accessed: September 17, 2013.