3 Epidemiology of Diabetic Retinopathy |
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61 |
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Table 3.5 Demographic risk factors for doubling of visual angle from diabetic retinopathy in WESDR |
|||
|
|
|
|
Association with doubling of visual angle |
Younger onset |
Older onset, taking insulin |
Older onset, not taking insulin |
Increasing age |
X |
X |
X |
Increasing duration of diabetes |
X |
X |
|
Women |
|
X |
X |
All data from Moss et al.22 Data for visual impairment are similar to data for doubling of visual angle for each group. Empty cells mean no association was found on univariate analysis. A black X means that an association was found on univariate analysis. A red X means that the association persisted in a multivariate analysis. The analyses at 10 and 14 years were similar in results, but in the few cases where they differed, the 14 year results are shown.
3.7 By Diabetes Type
At the time of diagnosis of diabetes, the prevalence of retinopathy is lower in type I than in type 2 diabetes. Prevalence rates of 0–3% and 6.7–38% have been
reported at diagnosis in types 1 and 2 diabetes, respectively.19,58 The same is true at other times after diag-
nosis of diabetes. When prevalence is recorded without regard for duration of diabetes, prevalence ranges
from 38.3 to 82% and from 16.4 to 39% for types 1 and 2 diabetes, respectively.23,32,45,46,58 In the
WESDR scheme of diabetes categorization, prevalence rates of any retinopathy were 71, 70, and 39% for the younger onset, older onset taking insulin, and
older onset not taking insulin groups, respectively.45,46After adjusting for duration of diabetes, the
differences in prevalence rates were no longer statistically significant between types 1 and 2 DM.8
In WESDR, for the older onset diabetics, 10-year follow-up data were available, but not 25-year followup data, because too many of the patients had died over a 25-year period of follow-up. On the other hand, 25-year follow-up data were available for the younger onset diabetics. Data on 10-year incidence rates of any DR, two-step progression of DR, and two-step improvement of DR are shown in Table 3.6. The incidence rates are higher in the younger onset group for any DR and two-step progression and lower for two-step improvement. In the younger onset group,
the prevalence and incidence of DR had decreased in those with more recently diagnosed diabetes, suggesting that change in diabetic management over the years is having a beneficial effect with respect to retinopathy.59 Studies that use less sensitive methods of retinopathy detection (such as ophthalmoscopic examination) than seven-field fundus photography report lower 10-year incidence rates of any DR than WESDR. For example, a Spanish study reported 10year incidence rates of any retinopathy in a mixed type diabetic population of 13.8%.29
The reported 25-year cumulative risk of DR in
persons with type 1 diabetes ranges from 89.1 to 97% in different series.11,59 In WESDR in persons
with younger onset diabetes, the 25-year cumulative rate of two-step progression of DR was 83% (95% CI 80–86%). Multivariate analyses showed that male sex and greater body mass index (BMI) were associated with two-step progression of DR severity.59
3.8 By Insulin Use
Among older onset diabetics, both prevalence and incidence of retinopathy depend on use of insulin or not. In WESDR at baseline, the prevalence of any DR at baseline was 70 and 39% in those patients taking and not taking insulin, respectively.46 WESDR
Table 3.6 Ten-year incidence of any retinopathy, progression of retinopathy, and improvement of retinopathy
|
10-year incidence of any |
10-year two-step |
10-year two-step |
Study |
retinopathy (%) |
progression (%) |
improvement (%) |
|
|
|
|
Younger onset diabetes |
89.3 |
75.8 |
9.8 |
Older onset, insulin using diabetes |
79.2 |
68.7 |
21.1 |
Older onset, non-insulin using diabetes |
66.9 |
52.9 |
26.0 |
|
|
|
|
Data from Klein et al.10 |
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|
62 |
A.R. Bhavsar et al. |
|
|
reported higher 4- and 10-year cumulative incidences of retinopathy in older diabetics taking insulin compared to older diabetics not taking insulin.10
Some studies do not classify patients as older onset or younger onset diabetes mellitus or type 1 or 2 DM, but do classify patients as insulin using and non-insulin using. The prevalence of DR is higher in patients using insulin with a 5.79 times
higher risk of having retinopathy compared to patients not using insulin.31,26 This association is
considered to arise from the greater severity of dia-
betes and poorer glycemic control in those individuals taking insulin.26,46
3.9 By Age
The prevalence of DR generally increases with age, although nonlinearly, but in some populations decreases in late life, presumably because many
patients with diabetes die early, the survivor effect.8,26,20,25,31,46,58,60 However, among Barbados
blacks and mixed race persons, prevalence of DR does not depend on age (Table 3.7). In younger onset diabetics, the 10-year incidences of any DR, improvement of retinopathy, and progression of retinopathy are roughly constant over the range of age at baseline examination from puberty to age 34 and shows a slight decline for age 35.10 Among older onset diabetics, an inverse relationship exists between age and 10-year incidence of any DR and progression of DR in adults.10 The 10-year incidences are 1.5–2.0 times greater in those aged 30–44 compared to those older than 75.10 A direct relationship, however, is found between age and 10-year incidence of improvement
of DR.63 As with the prevalence relationships, the incidence relationships probably manifest the effects of selective survival. The oldest persons at risk of progression are less likely to survive to have their retinopathy progression detected.
3.10 By Duration of Diabetes Mellitus
Prevalence of retinopathy is associated with duration of diabetes mellitus.25,14,20,26,36,60 Longer duration of
diabetes has been associated with increased prevalence of DR and PDR (Tables 3.8 and 3.14).8,20,31,46,60,33
The prevalence of DR in newly diagnosed diabetics ranges from 6 to 33.5%.8,20,26 The proportion of
persons with DR having more severe forms of retino-
pathy increases with increasing duration of diabetes.20,26,31 The relationship of incidence of various
aspects of diabetic retinopathy to duration is more complicated, as there are interactions with diabetes type. For younger onset diabetics, longer duration of diabetes is associated with an increasing 10-year incidence of any DR over durations up to 10 years.10 Likewise, longer duration of diabetes is associated with increasing 10-year incidence of improvement in retinopathy severity.10 However, the 10-year incidence of progression of retinopathy declined once duration of diabetes reached 20 years.10 In the older onset diabetics taking insulin, longer duration of diabetes was associated with decreased risk of incidence of any DR and of progression of retinopathy and had no effect on incidence of improvement of retinopathy.10 In older onset diabetics not taking insulin, duration of diabetes had no effect on incidence of any DR, improvement of DR, or incidence of progression of DR.10
Table 3.7 Relationship of prevalence of diabetic retinopathy and age
|
|
Age (years) |
|
|
|
|
|
|
Population |
<40 |
40–49 |
50–59 |
60–69 |
>70 |
References |
||
South Asian |
|
|
13.4 |
20.9 |
20.5 |
14.8 |
|
Raman et al.26 |
US Latinos |
|
|
40.7 |
46.8 |
48.7 |
53 |
|
Varma et al.8 |
Chinese |
29.4 |
40.0 |
45.6 |
48.7 |
42.1 |
|
Wang et al.20 |
|
Barbados blacks/mixed race |
|
|
30.3 |
27.3 |
26.6 |
31.7 |
|
Leske et al.21 |
United Arab Emirates |
15.8 |
26.8 |
30.1 |
27.3 |
|
|
Al-Maskari and El-Sadig58 |
|
US whites older, taking insulin |
36.2 |
64.6 |
|
67.4 |
51.5 |
|
Klein et al.46 |
|
US whites older, not taking insulin |
28.8 |
30.5 |
|
36.5 |
39.5 |
|
Klein et al.46 |
|
Selected studies providing prevalence rates for DR by age group. Not all studies divide age ranges the same way. When cutpoints for studies differ, the data are placed into the nearest category of this table.
3 Epidemiology of Diabetic Retinopathy |
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63 |
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Table 3.8 Prevalence of any diabetic retinopathy (%) by duration of diabetes (years) in selected studies |
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|
|
|
|
|
|
||
|
|
Duration of diabetes mellitus |
|
|
|
|
||
Population |
|
<5 years |
6–10 years |
11–15 years |
>15 years |
References |
|
|
|
|
|
|
|
|
|
|
|
South Asian |
15.5 |
30 |
37.3 |
40.4 |
Raman et al.26 |
|
|
|
Asian Indian |
11.7 |
27.5 |
37.6 |
29.1 |
Rema et al.60 |
|
|
|
US Latino |
27.5 |
56.1 |
59.8 |
79.6 |
Varma et al.8 |
|
|
|
African American |
9.1 |
30.4 |
|
42.2 |
Varma et al.8 |
|
|
|
African Barbados |
11.9 |
39.9 |
|
59.9 |
Varma et al.8 |
|
|
|
US whites (NHANES III) |
12.6 |
15.6 |
|
32.8 |
Varma et al.8 |
|
|
|
US whites (San Antonio, TX) |
29.6 |
NA |
|
46.7 |
Varma et al.8 |
|
|
|
US whites, San Luis Valley, CO |
34.1 |
55.1 |
|
88.2 |
Varma et al.8 |
|
|
|
US whites, Beaver Dam, WI |
22.9 |
37.0 |
|
49.9 |
Varma et al.8 |
|
|
|
US mixed race, type 1 |
6.7 |
40 |
85 |
95 |
Orchard et al.61 |
|
58 |
|
United Arab Emirates |
16.5 |
52.2 |
|
Al-Maskari and El-Sadig |
|
|||
|
48 |
65 |
72 |
82 |
46 |
|
|
|
US whites older, taking insulin |
Klein et al.46 |
|
|
|||||
US whites older, not taking insulin |
25 |
47 |
52 |
55 |
Klein et al.45 |
|
|
|
US whites younger |
27 |
67 |
90 |
100 |
Klein et al. |
|
|
|
= The numbers are estimated from a published graph in the reference. NA = not available. The wide variation may reflect different ratios of types 1 and 2 diabetes, methods of detecting retinopathy, levels of glycemic control, blood pressure, levels of other systemic variables, and differences based on ethnicity. Some studies break the interval 6–15 years into 5-year subintervals as indicated in the table by separate cells for the subintervals.
3.11 By Ethnicity
There is evidence across different studies that the prevalence of diabetic retinopathy among persons with diabetes mellitus varies by ethnicity, although
conclusions are tentative because study designs differ (Table 3.9).26,60 In general terms, South Asian
Indians and Singapore Malay populations have had lower reported prevalences than Caucasian populations.60 Hispanic Caucasian populations have the highest reported prevalences.8 Prevalence rates of DR at diagnosis of DM seem to vary by ethnicity as well. Reported rates are lower in South Asian Indians (5.1%) and higher in Hispanic whites (20–35%).8,60
Prevalence rates for Hispanic whites are inconsistent.8 The San Luis Valley Diabetes Study showed a lower prevalence of diabetic retinopathy of 42% in Hispanics compared to 54% in nonHispanic whites.62 The NHANES III showed a higher prevalence of diabetic retinopathy in Mexican Americans of 33.4% compared to 18.2% in non-Hispanic whites.63 Reports that Hispanic diabetics have more severe retinopathy than nonHispanic whites after adjusting for duration of diabetes, age, glycemic control, and blood pressure are balanced by other studies showing no difference in
severity by ethnic group after adjusting for tightness of control.64,65
Multiple, but not all, studies report that crude
prevalence of DR is higher in blacks than in whites.14,23,45,68,66 In the NHANES III, the preva-
lence of diabetic retinopathy was higher in non-Hispanic blacks (26.5%) compared with non-Hispanic whites (18.2%).63 Likewise in the Barbados Eye Study and the ARIC study, the
rates of retinopathy were higher in blacks than in whites.14,21 In NHANES III and the ARIC
study, the differences vanished after controlling for other variables suggesting that it is differences in glycemic or blood pressure control and not ethnicity that is responsible for the prevalence differences.14 The differences did not go away after adjusting for confounders in the Veterans Affairs Diabetes Trial.64
It is uncertain whether ethnic differences reflect genetic predisposition to increased or decreased risk of retinopathy or are instead markers of some other important environmental factor. In a multiethnic population in San Francisco, there was no difference in retinopathy prevalence across ethnic groups suggesting that ethnic differences may be eliminated when social factors are eliminated.70
64
Table 3.9 Prevalence of diabetic retinopathy by ethnicity
|
Type I |
Type II |
Mixed cohort |
|
Population |
(%) |
(%) |
(%) |
References |
|
|
|
|
|
USA Caucasian |
0–84 |
7–55 |
37–61.1 |
Varma et al.,8 Williams et al.,19 Raman et al.26 |
USA biracial (blacks, whites) |
|
|
20.5 |
Klein et al.14 |
UK Caucasian |
33.6–36.7 |
21–52 |
16.5–41 |
Williams et al.,19 Raman et al.26 |
Australian Caucasian |
42 |
13–59.7 |
29.1–32.4 |
Williams et al.,19 Raman et al.,26 Mitchell |
|
|
|
|
et al.32 |
European Caucasian |
16.6–76.5 |
32.6–61.8 |
26.2 |
Williams et al.19 |
Scandinavian Caucasian |
10.8–68.3 |
18.8–65.9 |
13.8–75.1 |
Williams et al.19 |
African American |
63.9 |
26.5–31.4 |
28.5 |
Williams et al.19 |
Hispanic American |
|
33.4–46.9 |
48 |
Varma et al.,8 Williams et al.19 |
Mexican |
|
|
50.5 |
Villalpando et al.67 |
American Indian |
19.7–20.9 |
19–49.3 |
|
Williams et al.19 |
West Indies |
|
|
28.5 |
Leske et al.,21 Raman et al.,26 Leske et al.56 |
South Asian |
13.6 |
6.7–34.1 |
18.0 |
Williams et al.,19 Raman et al.,31 Rema et al.60 |
Singapore |
|
|
21.8 |
Raman et al.26 |
Singapore Malays |
|
|
35 |
Williams et al.,19 Wong et al.1 |
Mauritius |
|
|
30 |
Raman et al.26 |
UK South Asian |
|
11.6 |
|
Williams et al.19 |
Indian |
|
|
12–30.1 |
Raman et al.,26 Emanuele et al.64 |
Sri Lanka |
|
|
15% |
Raman et al.26 |
Pakistan |
|
|
15.7% |
Raman et al.26 |
Japanese |
|
31.6–38 |
38 |
Williams et al.,19 Raman et al.26 |
Chinese |
|
19–43.1 |
28–45.2 |
Williams et al.,19 Wang et al.,20 Raman et al.,26 |
|
|
|
|
Xie et al.36 |
African |
26–43 |
30.5–43 |
12.7–42.4 |
Williams et al.19 |
South American |
|
45–51.2 |
|
Williams et al.19 |
Taiwan |
|
35.0 |
|
Chou et al.34 |
United Arab Emirates |
|
|
19 |
Al-Maskari and El-Sadig58 |
Iran |
|
|
36%* |
Amini and Parvaresh68 |
North American Indigenous |
|
|
25%** |
Naqshbandi et al.69 |
People |
|
|
|
|
|
|
|
|
|
*Median prevalence of 11 studies. **Median prevalence of five studies.
Adapted and expanded from Williams et al.19 Wide ranges partially reflect variations in factors of importance among the studies such as criteria for diagnosis of diabetes (e.g., self-reported, oral glucose tolerance test, fasting blood glucose with various cutpoints, random blood glucose with various cutpoints, and hemoglobin A1C), duration of diabetes mellitus among studies (generally longer in developed countries), technical components such as number of photographic fields used for detection and staging of retinopathy, and genetic components inherent in ethnic variation.
3.12 Gender
The effect of gender is inconsistent among popula- tion-based studies. In one study in a population of Singapore Malays, women have been reported to have higher prevalence of diabetic retinopathy, diabetic macular edema, and vision-threatening retinopathy, but after adjusting for metabolic and socioeconomic variables, the gender differences
lose their statistical significance as associations.1 In independent studies of South Asian Indians and
people from the United Arab Emirates, men had a higher prevalence of DR than women.26,31,58,60 In
an Hispanic population from the United States, a predominantly white population from Australia, a white population in the Netherlands, and a rural Chinese population, no gender differences in pre-
valence of DR or incidence of DR were found (Table 3.10).8,20,31,52