INTRODUCTION — The development of diabetic retinopathy (DR) occurs in nearly all persons with diabetes and remains a leading cause of blindness worldwide [1]. Despite the availability of highly effective treatment for the sight-threatening complications of diabetes, many persons with diabetes do not receive regular eye care examinations and sight-preserving treatments [2]. Moreover, not all patients achieve the levels of glycemic control demonstrated to reduce the risk of retinopathy in both type 1 and type 2 diabetes [3,4].
Early detection through screening programs and appropriate referral for therapy are important to preserve vision in individuals with diabetes. Issues related to screening for DR will be reviewed here. The pathogenesis, clinical findings, natural history, and treatment of this disorder are discussed separately. (See "Diabetic retinopathy: Pathogenesis" and "Diabetic retinopathy: Classification and clinical features" and "Diabetic retinopathy: Prevention and treatment".)
RATIONALE FOR SCREENING — The onset of diabetic retinal complications is typically insidious, and patients remain generally asymptomatic and unaware of the disease during the early stages when treatment and medical management are most effective. The asymptomatic presentation of DR emphasizes the importance of retinal examinations to detect and evaluate disease severity and identify patients at risk for vision loss. The rate of DR progression may be rapid, and therapy can be beneficial for both symptom amelioration and reduction in the rate of disease progression.
The efficacy of laser photocoagulation and/or vascular endothelial growth factor (VEGF) inhibitors in preventing visual loss from proliferative diabetic retinopathy (PDR) and macular edema (ME) is well established in randomized trials. However, these therapies are more beneficial in preventing visual loss than reversing diminished visual acuity. Therefore, it is important to screen patients with diabetes regularly for the development of retinal disease and, when detected, to refer for sight-preserving therapy. (See "Diabetic retinopathy: Prevention and treatment".)
METHOD OF SCREENING — Initial screening can be accomplished with dilated fundus examination or retinal photography. Screening must be performed by those with expertise in the chosen modality (eg, ophthalmologist/optometrist experienced with diagnosing diabetic retinopathy [DR] or trained photographer and reader for retinal photography).
When previous examinations have been normal, subsequent examinations can be done with retinal photographs. A comprehensive examination is required for follow-up of abnormalities detected on retinal photographs. These recommendations are largely consistent with American Diabetes Association (ADA) guidelines [5].
●Dilated fundus examination – Ophthalmoscopy by well-trained personnel on dilated fundi has been the standard screening method for DR. (The accuracy of ophthalmoscopy is substantially lower when performed by primary care physicians [6].) The availability of digital stereoscopic retinal imaging read by experts via telemedicine may improve retinopathy screening in areas with a shortage of eye care specialists [7-9].
●Retinal photography – Digital stereoscopic retinal imaging takes 15 to 20 minutes, and some devices (nonmydriatic) may not require dilation of the pupil. The images can be interpreted remotely by an ophthalmologist or onsite using a validated automated computer algorithm to identify the presence of referable or vision-threatening disease. When compared with dilated ophthalmoscopic examination or the gold standard seven-field stereoscopic fundus photography for retinopathy screening, digital imaging (three fields) has good sensitivity and specificity for detecting DR [10-13]. As an example, in one study comparing digital imaging with dilated ophthalmoscopic examination, there was agreement in 86 percent of cases [10]. The majority of discordant diagnoses (35 of 46 eyes) were related to a greater frequency of finding mild to moderate nonproliferative diabetic retinopathy (NPDR) with digital images compared with ophthalmoscopic examination. Although there were few cases of macular edema (ME; six eyes), there was 100 percent concordance between the two modalities.
There has been broader adoption of telemedicine programs for DR screening, which range from integration in primary care settings, prison or penal populations, remote areas with limited health care facilities, underserved populations, as well as in hospital-based or tertiary care facilities (picture 1). The use of telemedicine has been shown to overcome patient resistance to eye examinations through the use of nonmydriatic imaging and by locating imaging services at the point of diabetes care [14].
●Automated evaluation of retinal photographs – Automated evaluation of digital retinal images using a computer algorithm with the ability to continually learn and update parameters for detecting referable DR shows promise for use in the clinical setting [15-17]. The automated evaluation should not be used in pregnant women, in whom retinopathy can progress rapidly, as the available device was not intended for evaluation of rapidly changing retinopathy [17]. It should also not be used in patients with previously diagnosed severe NPDR, proliferative diabetic retinopathy (PDR), ME, radiation retinopathy, retinal vein occlusion, or in patients with a history of laser treatment, surgery, injections in the eye, or with persistent vision loss, blurred vision, or floaters [17].
SCREENING INITIATION AND FREQUENCY
When should screening begin?
●Adults – In patients with type 2 diabetes, we suggest an initial comprehensive examination by an ophthalmologist or optometrist shortly after the diagnosis of diabetes is made (table 1) [5]. In patients with type 1 diabetes, we suggest an initial comprehensive examination by an ophthalmologist or optometrist within five years after diagnosis.
Type 2 diabetes is typically a disease with insidious onset, and some patients already have retinopathy at the time of diagnosis of hyperglycemia (figure 1). In contrast, it is unusual for patients with type 1 diabetes (under age 30 years) to develop retinopathy that requires specific ophthalmologic therapy earlier than five years after the onset of diabetes (figure 2). As an example, in 1613 patients with type 1 diabetes of less than five years' duration who were screened for enrollment in the Diabetes Control and Complications Trial (DCCT), 874 had evidence of DR either by fundus photography or fluorescein angiography [18]. However, none had proliferative diabetic retinopathy (PDR) requiring laser treatment, and only six (0.4 percent) had preproliferative retinopathy.
●Children and adolescents – In children with type 1 diabetes, it is unusual to develop retinopathy prior to age 10 years. Initial screening in children and adolescents is reviewed separately. (See "Complications and screening in children and adolescents with type 1 diabetes mellitus", section on 'Retinopathy' and "Chronic complications and screening in children and adolescents with type 2 diabetes mellitus", section on 'Retinopathy'.)
Frequency of examinations — The frequency of follow-up examinations should be individualized, with more frequent follow-up in patients who have abnormal findings or if retinopathy is progressing (table 1) [5]. Patients with any level of diabetic retinopathy (DR) should be evaluated annually, with more severe disease requiring more frequent evaluation. Less frequent examinations (every two years) may be considered with the advice of an eye care professional in the setting of a normal examination and the absence of risk factors for progression [19]. An individualized schedule for ophthalmologic evaluation as well as for glycemic and blood pressure management, rather than a uniformly annual or biannual screening intervals, may be preferable and more cost effective [20,21].
Patients with diabetes who do not have DR are still at increased risk for age-associated vision loss related to refractive errors (correctable visual impairment), cataracts, and glaucoma (the latter two are more prevalent in persons with diabetes). Therefore, findings other than DR may dictate frequency of follow-up eye examinations. (See "Overview of general medical care in nonpregnant adults with diabetes mellitus", section on 'Routine eye examination'.)
There are few data evaluating the frequency of follow-up examinations after the initial DR screening examination [22-24].
●Type 2 diabetes – In the Wisconsin Epidemiology Study of Diabetic Retinopathy (WESDR), patients with type 2 diabetes and no retinopathy on baseline examination (standard stereoscopic color fundus photographs) did not progress to PDR over four years [22]. However, patients with a longer duration of diabetes, retinopathy on baseline examination, gross proteinuria, or poor glycemic management were at greater risk of developing PDR.
Similarly, a cohort study from the United Kingdom found that the incidence of sight-threatening DR (moderate preproliferative retinopathy or worse, or clinically significant macular edema [ME]) in patients with type 2 diabetes with no retinopathy on initial screening was 0.3 percent (95% CI 0.1-0.5) in the first year and 1.8 percent (95% CI 1.2-2.5) in the fifth year, suggesting that screening every three or four years may be adequate in those with normal initial examinations [23]. Yearly or more frequent screening was required for those with background or preproliferative retinopathy on initial screening.
Based upon these studies, some health care organizations and auditing groups (such as the National Committee on Quality Assurance) have suggested that those who have no DR may be screened every two years. However, it is not clear if the results of the above studies are applicable to all patients with type 2 diabetes. As an example, the WESDR study individuals were White Americans of northern European extraction, and some studies suggest racial and ethnic variation in DR (see "Diabetic retinopathy: Pathogenesis"). In the Veterans Affairs Diabetes Trial (VADT), the prevalence of moderate to severe DR was higher for Hispanic American (36 percent) and Black American persons (29 percent) than for non-Hispanic White American persons (22 percent) [25]. The greater risk was reportedly independent of any imbalance in risk factors. Furthermore, it is not clear that the standards used in the WESDR study for evaluation of the photographs can be adopted nationwide. Finally, there is greater potential to lose patients to follow-up with less frequent screening intervals and may give the impression to patients that vision loss is unlikely and not a concern. (See "Overview of general medical care in nonpregnant adults with diabetes mellitus", section on 'Routine eye examination'.)
●Type 1 diabetes – The appearance and progression of retinopathy has been assessed regularly with scheduled fundus photography in patients with type 1 diabetes participating in the DCCT and Epidemiology of Diabetes Interventions and Complications (EDIC) study, giving rise to a mean 23.5 years of follow-up data [20]. Among almost 24,000 retinopathy examinations, 14.5 percent showed worsening from the previous visit, 7.8 percent showed improvement, and 77.7 percent showed no change. Higher glycated hemoglobin (A1C) levels were associated with a significantly increased risk of worsening retinopathy.
A Markov model was used to calculate the probabilities of transitioning from lower levels of retinopathy with varying screening intervals. The time interval during which patients progressed from lower to higher categories of retinopathy was dependent upon the previous retinal examination and A1C level, with optimal screening intervals ranging from every three months among patients with severe nonproliferative diabetic retinopathy (NPDR) to every four years among those who had no retinopathy. This individualized schedule for retinopathy screening resulted in an overall reduction in the frequency of eye examinations and a substantial reduction in cost. These data support an individualized approach based on DR severity and systemic risk factors to tailor the optimal examination interval for each patient.
Pregnancy — The effect of pregnancy on the natural history of DR has been addressed in several studies; progression has been observed in 16 to 85 percent of patients, and the rate of progression may be accelerated. This topic is reviewed in more detail elsewhere. (See "Diabetic retinopathy: Classification and clinical features", section on 'Worsening during pregnancy'.)
Because pregnancy may exacerbate underlying DR, women with diabetes who are planning pregnancy should have a comprehensive eye examination and be counseled on the risk of development and/or progression of DR (table 1). (See "Pregestational (preexisting) diabetes mellitus: Antenatal glycemic control".)
Women with diabetes who become pregnant should have a comprehensive eye examination in the first trimester and have close follow-up throughout pregnancy and for one year postpartum. This guideline does not apply to women who develop gestational diabetes, as these women are not at increased risk for DR.
SCREENING IMPACT — Two studies have addressed the value of screening for DR in type 1 and type 2 diabetes [26,27]. They concluded that, in patients with type 1 diabetes, annual screening (ophthalmoscopy with dilated pupils) for those without retinopathy and follow-up every six months for those with retinopathy followed by appropriate treatment would result in a saving of 70,000 to 80,000 person-years of sight and 60 to 80 million US dollars annually in the United States [26]. Comparable numbers for type 2 diabetes were over 94,000 person-years of sight and over 250 million US dollars per year [27].
SOCIETY GUIDELINE LINKS — Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Diabetes mellitus in adults" and "Society guideline links: Diabetes mellitus in children".)
INFORMATION FOR PATIENTS — UpToDate offers two types of patient education materials, "The Basics" and "Beyond the Basics." The Basics patient education pieces are written in plain language, at the 5th to 6th grade reading level, and they answer the four or five key questions a patient might have about a given condition. These articles are best for patients who want a general overview and who prefer short, easy-to-read materials. Beyond the Basics patient education pieces are longer, more sophisticated, and more detailed. These articles are written at the 10th to 12th grade reading level and are best for patients who want in-depth information and are comfortable with some medical jargon.
Here are the patient education articles that are relevant to this topic. We encourage you to print or e-mail these topics to your patients. (You can also locate patient education articles on a variety of subjects by searching on "patient info" and the keyword(s) of interest.)
●Basics topics (see "Patient education: Diabetic retinopathy (The Basics)")
SUMMARY AND RECOMMENDATIONS
●Method of screening – In patients with diabetes, we recommend screening for diabetic retinopathy (DR) (Grade 1B). Screening must be performed by those with expertise and can be accomplished with dilated fundus examination or retinal photography. (See 'Method of screening' above.)
●Initiation of screening – In patients with type 1 diabetes, we suggest initiating screening three to five years after diagnosis (Grade 2B). In patients with type 2 diabetes, we suggest initiating screening soon after the time of diagnosis (Grade 2B). (See 'Screening initiation and frequency' above.)
●Frequency of examinations – The frequency of follow-up examinations should be individualized.
•Nonpregnant – In patients who are found to have retinopathy on initial screening examination, we suggest annual follow-up examinations (Grade 2C). More frequent follow-up is necessary if retinopathy is progressing. Patients with macular edema (ME), severe nonproliferative diabetic retinopathy (NPDR), or proliferative diabetic retinopathy (PDR) should be closely followed by an ophthalmologist experienced in the management of DR. If there is no evidence of retinopathy on initial examination, less frequent examinations (every two years) may be adequate. (See 'Screening initiation and frequency' above and "Diabetic retinopathy: Prevention and treatment".)
•Planning a pregnancy – Women with diabetes who are planning pregnancy should have a comprehensive eye examination and be counseled on the risk of development and/or progression of DR during pregnancy. (See "Diabetic retinopathy: Classification and clinical features", section on 'Worsening during pregnancy'.)
•During pregnancy – In pregnant women with preexisting diabetes who would not otherwise be due for screening, we suggest that such screening be performed during the first trimester (Grade 2C). More frequent retinal evaluations are required during pregnancy and for one year postpartum (table 1).
This guideline does not apply to women who develop gestational diabetes, as these women are not at increased risk for DR. (See 'Pregnancy' above.)
ACKNOWLEDGMENT — The UpToDate editorial staff acknowledges David McCulloch, MD, who contributed to an earlier version of this topic review.
