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