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Diabetic Retinopathy/
Maculopathy
Risk Factors and Treatment
Samantha Mann
Consultant Opthalmologist
Purpose of a Screening Programme
To identify those
individuals at risk of
progression/ sight loss
to allow adequate
monitoring
To identify those in
need of treatment to
reduce risk of visual
loss
To identify those with
poor systemic control
to improve glucose/
lipid and BP levels.
DNA
DNA
Risk of Sight
Loss
Failsafe to
reduce risk
American ETDRS
Classification
English National
Screening
Programme
Progression to
Proliferative DR in
1 yr
Mild Non Proliferative DR R1 6%
Moderate Non Proliferative DR R2 11-20%
Severe Non Proliferative DR R2 50%
Very Severe NPDR R2 75%
Proliferative Diabetic
Retinopathy (Disc) NVD
R3
Proliferative DR (Elsewhere)
NVE
R3
Referrable Diabetic
Maculopathy/ Referrable
Macular Oedema
M1
Classification of Diabetes
Risk Factors
Risk Factors for Retinopathy
• Glycaemic control
• Blood Pressure control
• Lipid control
• Renal disease
• Pregnancy
Increased risk of Sight Threatening
Retinopathy
• Some ethnic populations
• Longer duration of
diabetes
Non-modifiable Modifiable
Gulliford et al (2010) Diabetic Medicine. 27(2):283.
Non-modifiable Factors
Duration of Diabetes and DR
• Type 1
• Type 2
Years after
diagnosis
NPDR
0-5 0%
10-15 25-50%
>15 75-95%
>30 <100%
Years after
diagnosis
NPDR
11-13 23%
14-16 41%
>16 60%
Ethnic variation
5.5
10.1
11.5
0
2
4
6
8
10
12
Caucasian South Asian Afro-Caribbean
3.7
7.1
10.1
0
2
4
6
8
10
12
Caucasian South Asian Afro-Caribbean
Sight Threatening Retinopathy Maculopathy Requiring Laser
% %
Gulliford et al (2010) Diabetic Medicine. 27(2):283.
Modifiable Risk Factors
Glycaemic Control (DCCT & UKPDS)
Haemoglobin A1c DCCT Group, NEJM, 993;329(14):977-86
14 13 12 11 10 9 8 7 6 5
0
2
4
6
8
10
12
14
16
Reti
no
path
y p
er
100 p
ati
en
t years
Retinopathy
= Relative benefit (almost ¼ risk)
DCCT
Tight blood glucose control
(HbA1c <7%) was associated with
• 76% reduction in developing
retinopathy.
• 54% slowing of progression in
those with established
retinopathy.
Risks of Intense Glycaemic
Control
• Greater risk of hypoglycaemia
• In type 2 patients- ACCORD study terminated early due
to excess rate of fatal myocardial infarction. (1.4v 1.14%)
• Risk of early worsening of retinopathy (≥3steps on
ETDRS retinopathy scale) with tighter control
(magnitude of HbA1c rather than rate of change)
Recommendations for glycaemic
control (type 1 & 2)
• A personalised HbA1c target should be set,
usually between 48-58 mmol/mol (6.5-7.5%).
• Less strict targets should be set in patients with
type 2/ established cardiovascular disease/older
subjects.
• On-going review of treatment to minimise
hypoglycaemia.
• Glitazones should be avoided in the presence of
macula oedema.
Hypertension Control UKPDS
Years from randomisation
% p
atients
with
retinopath
y
Tight control group Mean BP 144/82 mm Hg
Less tight control group Mean BP 154/87 mm Hg
UKPDS 38. Br Med J. 1998;317:703–713
243 461 207 411 152 300 0
20
40
60
23 20
37
28
51
34
3 years 6 years 9 years
p=0.38
p=0.019
p=0.004 = 34% reduced risk of retinopathy progression 47% reduced risk of VA
NICE
recommends BP
<130/80mmHg
in those with
target organ
damage
Guidelines for hypertension in diabetes
• NICE recommends a target blood pressure of:
– <130/80 mmHg for those with IHD,
nephropathy, CVA, TIA, LVH and DR
• Encourage regular monitoring of BP
• May need multiple therapies
• ACE inhibitors (candesartan) may have
additional benefits, but should be
discontinued during pregnancy.
Key points with Systemic Risk
Factors
• Glucose
• 1% decrease in HbA1c
– Reduced progression to sight-threatening DR 25%
– Reduced need for laser by 25%
– Reduced risk of blindness 15%
• Hypertension
• 10mmHg decreased systolic BP
– Reduced risk of retinopathy progression 35%
– Reduced need for laser by 35%
– Reduced risk of visual loss 50%
Cholesterol control
Chew et al (1996) Arch Ophthalmol. 114(9):1079-1084
0.5 1 1.5 2 2.5 3
<5.17
5.17-6.2
≥6.21
Cholesterol Mmol/l
Odds Ratio 95% CI
Increased risk of hard exudates = ↑ in sight threatening disease
Cholesterol & hard exudate risk-ETDRS
Cholesterol/ Fenofibrate story
• 2xRCT some benefit in established retinopathy.
– Fenofibrate Intervention and Event Lowering in
Diabetes (FIELD) study- fenofibrate (200
mg/day) fenofibrate group reduced the requirements
for laser therapy 3.4%v 4.9% placebo (both macula
and PRP laser) and reduced disease progression to
DMO. Independent of lipid levels.
– ACCORD Eye study showed a 40% reduction in
progression of DR over 4 years in patients allocated to
fenofibrate (160 mg/day) in combination with a statin,
compared to simvastatin alone with increase in HDL.
Pre and Post fibrates
February 2014 September 2014
Recommendations for lipid
management in diabetes
• Consider statins
• Consider adding fenofibrate to a statin for non-
proliferative retinopathy in type 2 diabetes.
– Risk of muscle toxicity
– Risk of GFR
– GFR at baseline, U&E’s monitoring
Dose in ACCORD-
160 mg daily if GFR was ≥50 ml/min
54 mg daily if GFR 30-50 ml/min
Discontinued if GFR <30 ml/min
Treatments for Diabetic Eye
Disease
Proliferative DR- R3: will bleed/ lead to
Traction Retinal Detachment if untreated
Treatment: Urgent Vitrectomy
+/- PRP laser
Treatment of R3= Pan Retinal
Photocoagulation (PRP laser)
Maculopathy (M1)/ Diabetic
Macula Oedema (DMO)
◦ Treatment
◦Non- Centre-involving
◦Grid/focal laser
photocoagulation
◦Centre-involving
(>400m)
◦ Anti-VEGF treatment
(Lucentis) injections
OCT scan to measure central thickness of
macula (Diabetic Macula Oedema)
Maculopathy
No Maculopathy
> 400µm
< 250µm
PRP Laser Treatment
Benefits Risks
Reduced risk of severe visual loss Reduced peripheral/night vision
Discomfort during treatment
Dazzling (temporary)
Macular Oedema (temporary)
Benefits Risks
Reduced risk of moderate visual loss
in 50% (improvement in Vision in 3%)
Foveal burn/scotoma (rare)
Enlargement of scars over time
Slow response (4-6 months)
Macular Laser Treatment
RESTORE study- RCT
n= 345, Treatment of Diabetic
Macula Oedema (Type 1&2 DM)
Anti-VEGF/ Ranibizumab/
Aflibercept for DMO
Benefits Risks Occurrence
Significant
improvement in
vision compared to
laser alone
(22% v 8% gained 3
lines)
Local
Sub conj haem
Air bubbles
Endophthalmitis
Retinal Detachment
Systemic
MI/CVA
common
rare (0.1%)
negligible
Alternatives/Steroid
Implants
• FAME study- Iluvien implant (3 years)
• Ozurdex- Yet to be NICE Approved.
Benefits Risks Occurrence
Significant
improvement in
vision
Especially in
chronic oedema
>3yrs
Raised IOP –
requiring
treatment &
Requiring surgery
Cataract
(Licensed in
pseudophakes)
40%
5%
80%
Iluvien implant v Control
(FAME study)
Iluvien implant v Control
(FAME study)
Summary: Tx Diabetic Retinopathy
Stage Examination Treatment
Mild Non-Proliferative
(R1)
Microaneurysms (Dot and
blot haem), Exudates
Observe/ Systemic control
Mod/Severe Non-
Proliferative
(R2)
Cotton wool spots, venous
beading, extensive retinal
haemorrhage, IRMA’s
Careful observation/
Systemic control
Proliferative
(R3)
Fine new vessels at disc
(NVD) or elsewhere (NVE)
+/- pre-retinal/ vitreous
haemorrhage
Urgent pan-retinal Laser
Photocoagulation (PRP)
Maculopathy Exudates, microaneurysms
in macula
Macular Laser treatment/
AntiVEGF injections/
Steroid implants
End Stage Fibrosis, vitreous
haemorrhage, Retinal
detachment
Vitreoretinal surgery + PRP
Recommended