Emerging Complications: Diabetic Retinopathy

1. Emerging Complications:Diabetic Retinopathy Irl B. Hirsch, M.D. University of Washington

2. Natural History Pittsburgh Epidemiology of Diabetes Complications Study • 657 type 1 patients diagnosed between 1950 and 1980 with mean duration of 20 years • NPDR universal after 20 years duration • PDR present in 70% after 30 years duration • With shorter durations, PDR more prevalent in females Orchard TJ et al: Diabetes 1990;39:1116-24

3. Natural History Pittsburgh Epidemiology of Diabetes Complications Study • The prevalence of retinopathy and overt nephropathy in 552 White T1 subjects mean DM duration 20.8 yr was significantly greater in subjects diagnosed during puberty compared with those diagnosed before puberty. Kolstraba JN et al: Diabetes Care. 1989;12:686-9

4. Natural History Pittsburgh Epidemiology of Diabetes Complications Study • Results concerning the risk of diabetes-related mortality in a cohort of 1582 subjects (mean duration 12.9 yr) indicated that postpubertal duration of T1DM may be a more accurate determinant of the development of microvascular complications and diabetes-related mortality than total duration, and it is suggested that the contribution of the prepubertal years of diabetes to long-term prognosis may be minimal. Kolstraba JN et al: Diabetes Care. 1989;12:686-9

5. Major Question RE: PDR and T1DM When does the clock start ticking? Does pre-pubertal status protect against DR? How does puberty impact duration of diabetes for teens and young adults?

6. German Registry Study University of Ulm • N=441, median age = 15.5 years, median duration DM 6.3 years • 19% BID NPH/REG; 42% TID injections, 40% QID injections • Shortest duration prior to Dx of NPDR was 2.2 years • Youngest child with NPDR 5.5 years old Holl RW, et al: J Pediatr 1998:132:79--794

7. German Registry Study • Life table analysis revealed a median duration of 16.6 years until the occurrence of early DR Holl RW, et al: J Pediatr 1998:132:79--794

8. German Registry Study Pubertal Duration • Comparing children with onset before to during/after puberty, those with pre-pubertal Dx developed DR a median of 10.9 years after puberty compared to 15.1 years with pubertal onset of DM Holl RW, et al: J Pediatr 1998:132:79--794

9. German Registry Study • “Good” glycemic control (A1C < 7.5%) delayed the onset of DR by about 3 years NOTE: DR was generally not prevented by “good control” Holl RW, et al: J Pediatr 1998:132:79--794

10. German Registry Study • Pre-pubertal glycemic exposure does not protect against DR • Metabolic control should be attempted irrespective of age Holl RW, et al: J Pediatr 1998:132:79--794

11. Ophthalmology 1993;100:1125-31

12. Missouri DR Data • N=420 with onset < 20 years of age enrolled between 1979 and 1988 • Annual stereo fundus photographs • Results: • No DR before 2 years in anyone • 50% by 9 years DM duration • 100% by 20 years duration • DR developed 2 years sooner in females, but no difference when considering pubertal status

14. Missouri PDR Data • PDR developed in 11 patients • Higher A1C with PDR (10.9 vs. 8.6%) • The higher the A1C, the sooner PDR detected

15. Missouri DR Data Conclusions • Long-term glycemic control impacts both the appearance and the progression of DR • Prepubertal duration of diabetes is a significant risk factor for the development of DR

16. What About Screening of DR in Youth • 667 children and adolescents at the Children’s Hospital at Westmead, Sydney Australia • DR in < 11 years old: • 16% baseline; 1-2 years later, regressed in 80%, progressed in none • DR in > 11 year olds • 22% baseline; 1-2 years later, regressed in 36%, progressed in 13%

17. Screening of DR in Diabetic Youth Risk of DR progression in children < 11 years of age Maguire A et al. Diabetes Care 2005;28 509-13

18. Screening of DR in Diabetic Youth Risk of DR progression in children > 11 years of age Maguire A et al. Diabetes Care 2005;28 509-13

19. Screening of DR in Diabetic Youth • In the highest risk group (> 10 years duration DM with A1C at any screening > 10%) DR progressed significantly after 2 years but not until after 3 years in the group whose A1C was always < 10% • Although patients with diabetes > 10 years were < likely to have an improvement of their DR after 1 year, there was no increase in DR at 1 year follow-up Maguire A et al. Diabetes Care 2005;28 509-13

20. Screening of DR in Diabetic Youth • These studies suggest that adolescents in reasonable metabolic control could safely be screened every 2 years instead of the current yearly recommendation • In younger children the next screening could be > 2 years later • Those with poor control (A1C > 10%), duration > 10 years, or significant DR should be screened more frequently Maguire A et al. Diabetes Care 2005;28 509-13

21. Current ADA Recommendations • 1. Adults and children aged 10 years or older with type 1 diabetes should have an initial dilated and comprehensive eye examination by an ophthalmologist or optometrist within 5 years after the onset of diabetes. (B) • 2. Subsequent examinations for type 1 and type 2 diabetic patients should be repeated annually by an ophthalmologist or optometrist. Less frequent exams (every 2–3 years) may be considered following one or more normal eye exams. Examinations will be required more frequently if retinopathy is progressing. (B) Diabetes Care 33 (Suppl 1): S11-61, 2010