Ueda2016 diabetic retinopathy - sehnaz karadeniz

1. DIABETIC
RETINOPATHY:
an overview
Prof. Dr. Şehnaz Karadeniz
Istanbul Science University
Istanbul Florence Nightingale Hospital

2. …is a common complication of diabetes
…reflects widespread microcirculatory disease
…has been associated with
- Stroke
- Coronary heart disease
- Heart failure
- Nephropathy
- Others
Diabetic retinopathy

3. Nonproliferative diabetic retinopathy
Proliferative diabetic retinopathy

4. Diabetic macular edema

5.  A microvascular disease ??
 Neurovascular disorder ??
 Inflammatory disorder ??
Diabetic retinopathy

6. Wisconsin Epidemiologic Study of Diabetic Retinopathy, Ophthalmology 1995
Wisconsin Epidemiologic Study of Diabetic Retinopathy, Ophthalmology 2008
Wisconsin Epidemiologic Study of Diabetic Retinopathy, Ophthalmology 2009
10-year incidence of DR 74%
In patients with DR at baseline
64% developed more severe DR
17% progressed to PDR
In patients with younger-onset diabetes
25-year incidence of DR 97%
43% developed PDR
29% developed DME (17% CSME)
Incidence of diabetic retinopathy

7. Saaddine JB et al. Arch Ophthalmol 2008
Years/DR Presence of DR Presence of VTDR
2006 5.518.000
1.215.000
2020 9.690.900 2.187.000
2030 12.271.000
2.606.300
2040 14.301.100 3.013.300
2050 15.973.800
3.364.100
Projections for diabetic retinopathy

8. Screening for diabetic retinopathy

9. Boucher MC et al. Can J Ophthalmol 2008
 Teleophthalmology screening
 N:3505, mean duration of DM 8 yrs
 30.1% had not been examined for over 2 years
Compliance with screening recommendations

10. Boucher MC et al, Can J Ophthalmol 2005
 Population based study carried out in Canada
 Time since last eye examination
• Less than 1 yr 49.4 %
• 1-2 yrs 30.7 %
• More than 2 yrs 9.7 %
• Never 10.1 %
Compliance with screening recommendations

11.  Reason for last eye exam more than 2 years ago
Negligence
28.3 %
Difficulty getting an appointment 11.2 %
Examination not important 4.0 %
Examination unpleasant 2.0 %
 Noncompliant due to negligence
T2DM 93.0 %
Aware of DM threat to vision 100.0 %
Acquainted with a person 47.0 %
having a visual handicap from DM
Boucher MC et al, Can J Ophthalmol 2005
Factors of non compliance with screening
recommendations

12. Patient
group
Recommended
time of first
examination
Minimum routine
follow-up
Type 1 DM
Type 2DM
Yearly
Shortly after the
diagnosis
Yearly
ADA Recommendations, Diabetes Care 2015
Within 5 yrs of diagnosis
in adults or older patients
Timetable for ophthalmological examination

13. Patient
group
Recommended
time of first
examination
Minimum
routine follow-
up
Pregnant women
with preexisting
DM
Close follow-up
throughout pregnancy
and for 1 yr
postpartum
In the first
trimester
ADA Recommendations, Diabetes Care 2015
Timetable for ophthalmological examination

14. Nathan DM et al. Arcgh Intern Med 2009
Estimated cumulative incidence of PDR or worse over time
Management of diabetic retinopathy

15. • Are favourable outcomes of clinical research successfully
translated into the real lives of people with diabetes?
Favourable effect of intensified risk factor
control on diabetic retinopathy

16. The extent to which modern intensified risk factor control has
lessened the duration-specific prevalence of retinopathy
 1997-1998 results in Kaiser Permanente Northwest were
compared to the 1980-1982 results from the WESDR
 Mean HbA1c in KPNW was 7.8% vs 10.4% in WESDR
 KPNW BP averaged 138.6/79.5 mmHg compared with
147.0/79.0 in WESDR
Brown JB et al, Diabetes Care 2003
Prevalence of diabetic retinopathy in a well-
controlled population with T2DM

17. Brown JB et al, Diabetes Care 2003
Background diabetic retinopathy Proliferative diabetic retinopathy
Prevalence of diabetic retinopathy in a well-
controlled population with T2DM

18. Klein R, et al. Ophthalmology 2009
Visual impairment by duration and year of
diagnosis in type 1 diabetes

19. Diabetic Retinopathy Study Research Group. Ophthalmology 1981;88(7):583-600
Early Treatment Diabetic Retinopathy Study Research Group. Arch Ophthalmol. 1985;103(12): 1796-1806
Early Treatment Diabetic Retinopathy Study Research Group. Ophthalmology 1991;98(5)(suppl):766-785
Early Treatment Diabetic Retinopathy Study Research Group. Ophthalmology 1992;99(9):1351-1357
Laser treatment
 Panretinal photocoagulation for PDR
 Focal/grid photocoagulation for DME
Management of diabetic retinopathy

20. o An angiogenic factor “Factor X” produced by the retina
Michaelson IC. Trans Ophthalmol Soc UK 1948
o Anti VEGF treatment
o Ranibizumab
o Aflibercept
Intravitreal anti-VEGF treatment

21. “ 8 out of 100 participants with DME, may gain 3 or more lines of
visual acuity using photocoagulation, whereas 28 would do so
with antiangiogenic therapy, meaning that 100 participants
need to be treated with antiangiogenic therapy to allow 20
more people to markedly improve their vision after one year “
Virgili G et al. Cochrane Database Syst Rev 2014
Beyond vascular endothelial growth factor

22. o Factors involved in angiogenesis and downstream signaling
o PKC (PKC-β, Atypical PKC
o Angiopoietins (Ang1, Ang2, receptor Tie2)
o Platelet-derived growth factor
o Wnt signaling axis
o Other proangiogenic growth factors (GH, IGF-1)
o Inflamatory cytokines
o IL-1β
o TNF
o Others
o ......
Other target molecules

23. o newer term for pharmacogenetics
o the branch of genetics concerned with determining the
likely response of an individual to therapetic drugs
Pharmacogenomics

24. o The prevalence and features of diabetic retinopathy in 95
pairs of identical twins
o In the NIDD twins, 35 of the 37 pairs were in the same
retinopathy category including all but one of the 15 pairs with
the same duration of diabetes
o In the IDD twins, 21 of the 31 pairs were in the same
category including 5 pairs of the 10 co-twins with the same
duration of diabetes showed a stiriking difference of
retinopathy
Leslie RD & Pyke DA, Diabetes 1982
Diabetic retinopathy: Genetic factors

25. o Candidate gene studies
o Linkage studies
o Genome-wide association studies
Diabetic retinopathy: Genetic factors

26. Genom-wide association studies

27. o No significant associations at a genome–wide level
o Several novel genetic loci that may be associated with
severe diabetic retinopathy
o Replication and extension in additional cohort will be
necessary
Grassi MA et al.Human Molecular Genetics 2011
Grassi MA et al. Invest Ophthalmol Vis Sci 2012
Diabetic retinopathy : Genom-wide association
studies

28. o Gene therapy
o Enhancing the protective ACE2/Ang(1-7) axis of RAS
Verma A et al. Mol Ther 2012
o Inhibiting the membrane attack complex
Adhi M et al. PLoS ONE 2013
Diabetic retinopathy : Pharmacogenomics

29. Huang S et al. Diabetes Care 2007
Complication
Mild stroke
Diabetic neuropathy
Angina
Diabetic nephropathy
Amputation
Diabetic retinopathy
Blindness
End-stage renal disease
Major stroke
Health related quality of life
Mean
0.70
0.66
0.64
0.64
0.55
0.53
0.38
0.35
0.31

30. As a summary...
o Screening and timely intervention are critical
o Main challenges for screening
o Patients may have no symptoms until very late stages
o Low compliance with existing recommendations
o Major challenge for treatment
o The complex nature of the disease

31. Thank you ….