A total of 85
214 individuals with type 2 diabetes mellitus underwent screening for diabetic retinopathy between January 2005 and November 2009; 57
199 (67.1%) had no evidence of retinopathy and were therefore eligible for inclusion in this study. At the initial screening event, 22
501 (26.4%) had evidence of background retinopathy and 3723 (4.4%) had referable retinopathy. Those with referable retinopathy consisted of: 1169 (1.4%) with maculopathy, 1279 (1.5%) preproliferative retinopathy, and 262 (0.3%) proliferative retinopathy (817 (1.0%) preproliferative retinopathy and maculopathy, 196 (0.2%) proliferative retinopathy and maculopathy). We excluded 1791 (2.1%) participants who had images that could not be graded, as well as those with evidence of existing retinopathy.
199 people without evidence of diabetic retinopathy at the first screening event, 7436 (13.0%) did not attend another screening during the study period, 449 (6.0%) of whom were not eligible for a second screen (which would have occurred within 12 months). We do not know why the remaining 6987 (94.0%) people did not attend a second screening event, because anonymisation of the records prevented further investigation; however, this group was older and had a longer known duration of diabetes than the group attending at least one additional screening event (table 1). We did not observe a significant difference in the proportions of male participants between these two groups.
Table 1 Baseline characteristics of study participants
We found that 49
763 participants had a second screening event, 31
924 (64.2%) a third, 10
615 (21.3%) a fourth, and 767 (1.5%) a fifth (total of 93
069 events). Although screening was intended to occur annually, the screening intervals were generally longer than one year, with a mean (standard deviation) interval of 17.8 (6.3) months between the first and second screening events, 15.3 (4.4) months between the second and third, 13.2 (2.7) months between the third and fourth, and 12.0 (1.9) months between the fourth and fifth. Only 4479 (9%) participants had an interval of 12 (1) months between screening events.
During the study, 12
922 (26.0%) participants with type 2 diabetes mellitus developed diabetic retinopathy, of whom the vast majority (12
574 (97.3%)) developed background retinopathy. Of 348 (0.7%) people who developed referable retinopathy, 197 (56.6%) had evidence of maculopathy, 107 (30.7%) had preproliferative retinopathy, and 25 (7.2%) proliferative retinopathy. Sixteen (4.6%) people had preproliferative retinopathy and maculopathy, and three (0.9%) had proliferative retinopathy and maculopathy.
Of 28 participants who developed proliferative diabetic retinopathy (with or without maculopathy), 14 (50.0%) did so between 12 and 24 months after the first screening event, three (10.7%) after 24-36 months, 10 (35.7%) after 36-48 months, and one (3.6%) after 48 months. Duration of diabetes was less than five years in 19 (68%) participants, and 27 (96%) received diet and oral treatment, with only one receiving insulin. Of participants who developed proliferative retinopathy within 12 to 24 months, none were on insulin treatment and only two (14%) had had diabetes longer than 10 years.
In the survival analysis, we selected the Weibull distribution as best fitting the data. Tables 2 and 3 show the estimated annual and cumulative incidence of any and referable diabetic retinopathy. The annual incidence of any retinopathy at one year was 124.94 per 1000 people, decreasing to 66.59 per 1000 at four years, with a cumulative incidence of 360.27 per 1000 people at four years. By contrast, the annual incidence of referable retinopathy increased from 2.02 to 3.54 per 1000 people, with a cumulative incidence of 11.64 at four years. The cumulative incidence of each retinopathy group was about twice as high in participants who received insulin treatment (tables 2 and 3).
Table 2 Yearly incidence of any and referable diabetic retinopathy in participants without retinopathy at baseline
Table 3 Yearly incidence of any and referable diabetic retinopathy in participants using insulin treatment and without retinopathy at baseline
Table 4 summarises the baseline characteristics of the three groups according to outcome—that is, participants who did not develop diabetic retinopathy and those who developed any or referable retinopathy. The mean known duration of diabetes mellitus and the proportion of participants requiring insulin treatment were significantly greater in those who developed referable retinopathy than in those who remained free of retinopathy. Mean ages at diagnosis of diabetes and at first screening were lowest in the group that developed referable retinopathy and highest in the group that did not develop any retinopathy. Sex distribution did not differ between the groups.
Table 4 Baseline characteristics of participants according to outcome
Table 5 shows the effects of putative risk factors on the risk of participants developing diabetic retinopathy. A significantly raised risk of referable retinopathy was associated with an increased duration of diabetes mellitus. Risk was highest in participants diagnosed at age 30-49 years, with significantly reduced risks in those aged up to 70 years at diagnosis. The risk of any or referable retinopathy varied greatly between different types of diabetes treatment. Age, duration of diabetes, and treatment had similar effects on the risk of developing background retinopathy, although age at diagnosis of more than 70 years was associated with a significantly increased risk.
Table 5 Parametric survival analysis with covariates in participants who developed diabetic retinopathy, according to grading category
The incidence of referable retinopathy varied considerably between subgroups. For example, for participants given diet treatment only with a known duration of diabetes of less than five years, the cumulative incidence of retinopathy at one, two, and three years from the first negative screen was 1.83, 3.66, and 5.45 per 1000 people, respectively. Corresponding values for participants receiving insulin treatment with a duration of diabetes of less than 10 years were 0.71, 3.80, and 10.10 per 1000 people, respectively. For participants with a duration of diabetes of 10 years or more, the use of insulin treatment increased cumulative incidence greatly (with insulin treatment 2.24, 5.86, and 10.33 per 1000 people; without insulin treatment 9.61, 17.10, and 24.26 per 1000 people).