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DIABETIC RETINOPATHY: an overview Prof. Dr. Şehnaz Karadeniz Istanbul Science University Istanbul Florence Nightingale Hospital
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Transcript of Ueda2016 diabetic retinopathy - sehnaz karadeniz
DIABETIC
RETINOPATHY:
an overview
Prof. Dr. Şehnaz Karadeniz
Istanbul Science University
Istanbul Florence Nightingale Hospital
…is a common complication of diabetes
…reflects widespread microcirculatory disease
…has been associated with
- Stroke
- Coronary heart disease
- Heart failure
- Nephropathy
- Others
Diabetic retinopathy
Nonproliferative diabetic retinopathy
Proliferative diabetic retinopathy
Diabetic macular edema
A microvascular disease ??
Neurovascular disorder ??
Inflammatory disorder ??
Diabetic retinopathy
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
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
Screening for diabetic retinopathy
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
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
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
Patient
group
Recommended
time of first
examination
Minimum routine
follow-up
Type 1 DM
Type 2DM
Yearly
Shortly after thediagnosis
Yearly
ADA Recommendations, Diabetes Care 2015
Within 5 yrs of diagnosis
in adults or older patients
Timetable for ophthalmological examination
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
Nathan DM et al. Arcgh Intern Med 2009
Estimated cumulative incidence of PDR or worse over time
Management of diabetic retinopathy
• 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
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
Brown JB et al, Diabetes Care 2003
Background diabetic retinopathy Proliferative diabetic retinopathy
Prevalence of diabetic retinopathy in a well-
controlled population with T2DM
Klein R, et al. Ophthalmology 2009
Visual impairment by duration and year of
diagnosis in type 1 diabetes
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
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
“ 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
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
o newer term for pharmacogenetics
o the branch of genetics concerned with determining the
likely response of an individual to therapetic drugs
Pharmacogenomics
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
o Candidate gene studies
o Linkage studies
o Genome-wide association studies
Diabetic retinopathy: Genetic factors
Genom-wide association studies
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
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
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
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
Thank you ….
