The prevalence of diabetes mellitus across the world is increasing, paralleled by an evident increase in the incidence of macrovascular and microvascular complications.1 One common microvascular complication is diabetic retinopathy (DR).2,3 DR, a general term for damage to the retinal blood vessels and cells due to prolonged diabetes, is ubiquitous in both type 1 and type 2 diabetes. Within the first two decades after diagnosis of diabetes, nearly all patients with type 1 diabetes and more than 60% of patients with type 2 diabetes have DR.4 DR is also highly specific to diabetes.5 Over time and with a lack of glucose control, neovascularization (new blood vessel formation) can occur and threaten vision. This type of DR is classified as proliferative diabetic retinopathy (PDR). Moreover, the permeable and damaged capillaries and the breakdown of the blood-retina barrier can cause diabetic macular edema (DME), which is a frequent cause of blindness in patients with type 2 diabetes.
DR is the leading cause of blindness in adults under 65 in the US and worldwide, and its prevalence is projected to double by 2030.6,7 Of concern to both diabetic patients and providers, DR and DME may present with few or no symptoms, evading detection until irreversible blindness ultimately occurs.8 Over a third of adults in the US who are diagnosed with diabetes have diabetic retinopathy, and up to 20% of these adults will have the more severe diagnoses of PDR and DME.1,2,9
Natural History of Diabetic Retinopathy
DR is a progressive disease. It is first evident on fundoscopic exam as “dot and blot” intraretinal hemorrhages due to rupture of capillary microaneurysms, hard exudates suggesting chronic edema, and “cotton-wool” spots of retinal microinfarction.2 The early stage of the disease is due to increased blood vessel permeability, while the more severe stages are due to the clotting and death of these vessels. This progression can be seen on retinal exam by an ophthalmologist, but usually is not correlated with any noticeable symptoms. On retinal exam, severe nonproliferative DR is defined by 20 or more intraretinal hemorrhages (“dot and blot” hemorrhages) in all four quadrants, venous beading, and prominent intraretinal microvascular abnormalities on retinal exam.5 Venous beading is what happens when the walls of the retinal veins start to lose their integrity, causing small portions of the vein’s wall to expand. This leads to the appearance of “beads” on the veins. These beads are actually parts of dysfunctional venous walls. Venous beading is a predictor of progression to PDR, in which new blood vessels grow on the retina and posterior vitreous surface. DME, characterized by edema and retinal thickening from these leaky new blood vessels, can develop at all stages of retinopathy. Pregnancy, puberty, poor blood glucose control, hypertension, and cataract surgery can accelerate these changes towards more severe disease.2
DR is typically asymptomatic for years before displaying symptoms.10 Thus, many patients are not aware that they have DR for many years. Floaters are among the earliest symptoms and indicate bleeding within the eye due to rupture of the small retinal vessels. This occurs because the vessel walls are damaged and form microaneurysms, which are easily damaged. Another symptom is the appearance of blind spots, known as visual field defects. These blind spots are indicative of the retina being pulled off of the back of the eye in focal areas, a phenomenon called focal retinal detachment. Because the retina is vital for sight, the loss of the normal retinal connections leads to blind spots. Focal retinal detachment occurs because of the long-term bleeding and healing of the vessels. Over time, these vessels will form scars, and this tough scar tissue increases traction on the retina.
DME is characterized by blurry vision, particularly in the central visual field, in addition to decreased color vision.10,11 Night blindness may occur in either DME or PDR. These symptoms, especially blurry vision, may be intermittent and fluctuate over time, and typically affect both eyes. The appearance of any of these symptoms requires urgent attention to avoid further progression. Unfortunately, the majority of these symptoms cannot be reversed.
The development of symptoms, such as floaters, blind spots, and blurry vision, means that the eye disease is already fairly advanced.10,11 The onset of noticeable vision problems is associated with later stages of the disease, as retinal beading and small hemorrhages occur. The earlier signs of damage, including the appearance of “dot and blot” hemorrhages, hard exudates, and “cotton-wool” spots, can only be noticed by an ophthalmologist’s retinal exam. So, regularly seeing an ophthalmologist or eye doctor is very important in order to determine the extent of disease before irreversible vision loss occurs.
Screening and Monitoring
There is abundant evidence that early DR detection can prevent severe vision loss and blindness.3,12-14 Consequently, the indolent and asymptomatic course of DR and its progression to PDR or DME highlights the importance of annual eye exams for patients with diabetes. The American Diabetes Association recommends an eye exam at the time of diagnosis for people with Type 2 diabetes and within 5 years of onset for people with type 1 diabetes.3 If there is no evidence of eye disease on one or more exams and glucose is well-controlled, the person should have an eye exam every one to two years. If any eye disease is detected, eye exams should be done annually at a minimum. These exams should include a thorough history of diabetes control and vision symptoms, as well as an assessment of visual acuity (central and peripheral) and intraocular pressure and a dilated retinal exam.3,12-14 Retinal photography and fluorescein angiography may also be done, as needed, to most accurately characterize the status of abnormal blood vessels.
If any level of DR or macular edema is found, the patient should be referred promptly to an ophthalmologist, preferably one who specializes in the management of DR.3 Better glycemic, blood pressure, and lipids control may slow the progression of DR. Panretinal laser photocoagulation therapy may be used to lower the risk of vision loss for people with high-risk PDR or severe non-proliferative DR. Intravitreous injections of endothelial growth factor are also an equivalent treatment to laser therapy for PDR as well as the treatment of choice for people with central-involved DME.
- Zhang X, Saaddine JB, Chou CF, et al. Prevalence of diabetic retinopathy in the United States, 2005-2008. JAMA 2010; 304 (6): 649-656.
- Ciulla TA, Amador AG, Zinman B. Diabetic retinopathy and diabetic macular edema: pathophysiology, screening, and novel therapies. Diabetes Care 2003; 26 (9): 2653-2664.
- 11. Microvascular complications and foot care: standards of medical care in diabetes-2019. Diabetes Care 2019; 42 (Suppl 1): S124-s138.
- Fong DS, Aiello L, Gardner TW, et al. Diabetic retinopathy. Diabetes Care 2003; 26 Suppl 1: S99-S102.
- Morello CM. Etiology and natural history of diabetic retinopathy: an overview. Am J Health Syst Pharm 2007; 64 (17 Suppl 12): S3-7.
- Bennett GH, Tuthill A. Investigating the barriers to the uptake of diabetic RetinaScreen. Ir Med J 2017; 110 (9): 628.
- Ting DS, Cheung GC, Wong TY. Diabetic retinopathy: global prevalence, major risk factors, screening practices and public health challenges: a review. Clin Exp Ophthalmol 2016; 44 (4): 260-277.
- Kashim RM, Newton P, Ojo O. Diabetic retinopathy screening: a systematic review on patients' non-attendance. Int J Environ Res Public Health 2018; 15 (1).
- Yau JW, Rogers SL, Kawasaki R, et al. Global prevalence and major risk factors of diabetic retinopathy. Diabetes Care 2012; 35 (3): 556-564.
- Viswanath K, McGavin DD. Diabetic retinopathy: clinical findings and management. Community Eye Health 2003; 16 (46): 21-24.
- Henricsson M, Heijl A. Visual fields at different stages of diabetic retinopathy. Acta Ophthalmol (Copenh) 1994; 72 (5): 560-569.
- Arden GB, Sivaprasad S. The pathogenesis of early retinal changes of diabetic retinopathy. Doc Ophthalmol 2012; 124 (1): 15-26.
- Early photocoagulation for diabetic retinopathy. ETDRS report number 9. Early Treatment Diabetic Retinopathy Study Research Group. Ophthalmology 1991; 98 (5 Suppl): 766-785.
- Kern TS. Contributions of inflammatory processes to the development of the early stages of diabetic retinopathy. Exp Diabetes Res 2007; 2007: 95103.