Download Medical Management of Diabetic Retinopathy

ALGORITHM DESCRIBING
THE MEDICAL MANAGEMENT OF DIABETIC RETINOPATHY 09/01/14
DIABETIC RETINOPATHY (DR) / MACULOPATHY
REQUIRING TREATMENT

Glycaemic control: aim for HBA1c as near 48mmol/mol as possible, taking patient
factors and patient’s own priorities into account

Blood pressure control: aim for systolic BP 130mmHg. This may require up to four
medications

Beware the elderly patient with co-morbidities, who may be vulnerable to illeffects such as falls/confusion with lowered blood sugar levels and/or BP

Control blood cholesterol as far as possible (see below)

Once blood sugar, BP and cholesterol have been optimised, even if targets are not
reached, and there is continuing need for treatment for diabetic maculopathy or
progressive retinopathy (see below) then addition of fenofibrate should be
considered.
Lipid management

Control plasma lipids initially using
simvastatin :40 mg daily for both primary prevention
and secondary prevention, but 20mg if
on amlodipine, diltiazem or verapamil.
Increase to atorvastatin 80mg, if
required, as outlined on page 2 under
Protocol

Consider adding fenofibrate to the
statin for the following groups:
o Proliferative retinopathy and
maculopathy
o Progressive retinopathy
(background to pre-proliferative
and pre-proliferative to
proliferative retinopathy)
Those with stable background
retinopathy should not be prescribed
fenofibrate.






Appropriate patients will usually be
identified by the ophthalmologist
The combination of a statin and
fenofibrate for diabetic retinopathy
indication is not licensed in the UK.
The MHRA has issued a warning on
using the combination, which should
be used with caution, and only
when expected benefits outweigh
potential risks.
Dose of fenofibrate is 160 mg daily if
eGFR is ≥50 ml/min/1.73m²; 67 mg
daily if eGFR is 30–<50
ml/min/1.73m²; do not use if eGFR
is <30 ml/min/1.73m².
Carefully monitor renal function
when prescribing fenofibrate. See
Protocol for details.
Prescribing a statin with a fibrate
carries with it an increased risk of
myopathy, albeit small. See
Protocol for monitoring details
PROTOCOL REGARDING MEDICAL MANAGEMENT OF DIABETIC
RETINOPATHY
Background
In the UK, retinopathy affects about 40% of people with diabetes and nearly 20%
have retinopathy at the time of diagnosis of type 2 diabetes, the incidence being
higher in certain ethnic groups specifically in those of Hispanic, Afro Caribbean,
Indo-Asian origin.
Strict glycaemic control and control of blood pressure in those with hypertension
substantially reduce the progression of diabetic eye disease. Diabetic patients with
dyslipidaemia, but not familial hypercholesterolaemia, have an increased incidence
of retinal abnormalities. This suggests that elevated cholesterol and triglycerides
may be implicated in the development of retinovascular lesions occurring in diabetic
retinopathy.
Important recent data is now available on the use of fenofibrate in the Fenofibrate
Intervention and Event Lowering in Diabetes (FIELD) and The Action to Control
Cardiovascular Risk in Diabetes (ACCORD) Eye studies (see Evidence section).
This protocol provides recommendations for the medical management of diabetic
retinopathy, including where the use of fenofibrate in addition to a statin may be
considered.
PROTOCOL
In diabetic retinopathy, essential management should focus on:



Optimising control of blood glucose, with no target set but to aim for HBA1c as
near 48mmol/mol as possible for the individual patient (beware frail elderly).
Optimising control of blood pressure, aiming for 130mmHg systolic. This may
require up to four medications, but beware the elderly patient with co-morbidities
who may be more likely to fall at lower BP levels
Optimising control of plasma lipids using simvastatin initially in all patients (40 mg
daily for primary and for secondary prevention, reduced to 20mg where drug
interactions).
o Primary prevention:
Consider intensifying statins with atorvastatin (max dose 80mg daily) if
LDL-C remains >2.0 mmol/l and total cholesterol >4.0 mmol/l (in the
presence of HDL<1.4 mmol/l) despite treatment with simvastatin 40mg
o Existing or newly diagnosed cardiovascular disease, or an increased
albumin creatinine ratio (ACR):
Consider intensifying therapy with atorvastatin (max dose 80mg daily)
or ezetimibe to achieve a target LDL-C of <2.0 mmol/l or total
cholesterol <4.0 mmol/l (in the presence of HDL<1.4mmol/l).
For details, including drug interactions, see Sheffield Lipid Modification Guideline


Give patients appropriate advice not only at the time of diagnosis of diabetes,
but also as soon as retinopathy is first diagnosed. Better outcomes follow
good glycaemic control early in the course of the diabetes; it is rarely too late
to show benefit from improved control.
Care should be taken to avoid over-zealous glycaemic and blood pressure
control in older patients and in those with established cardiovascular disease.
Aim to give as much benefit as possible and minimise the risks.

Consider adding fenofibrate to the statin * for the following groups:
o Proliferative retinopathy and maculopathy
o Progressive retinopathy (background to pre-proliferative and preproliferative to proliferative retinopathy)
Those with stable background retinopathy should not be prescribed
fenofibrate. Appropriate patients will usually be identified by the
ophthalmologist.

Dose of fenofibrate is 160 mg daily if eGFR is ≥50 ml/min/1.73m²; 67 mg daily
if eGFR is 30–<50 ml/min/1.73m²; and do not use if eGFR is <30
ml/min/1.73m².

Prescribing a statin with a fibrate carries with it an increased risk of myopathy,
albeit small. CK measurement is recommended at baseline, then again if
there are symptoms of muscle pains on starting combined treatment, or if
symptoms worsen, but monitoring is not required on a regular basis.
Fenofibrate should be stopped if CK has markedly risen i.e. above 5xULN.

Fenofibrate can cause deterioration in renal function, and monitoring of renal
function is required. Many patients with progressive DR will have renal
compromise as well. Monitor U&Es monthly for the first 3 months and 3-4
monthly when stable. Treatment should be interrupted in case of an increase
in creatinine levels > 50% ULN (upper limit of normal)
* Note: the combination of a statin and fenofibrate for diabetic retinopathy indication
is not licensed in the UK. The MHRA has issued a warning on using the
combination, which should be used with caution, and only when expected benefits
outweigh potential risks. (Drug Safety Update November 2007)
Evidence.
Effect of fenofibrate on the need for laser treatment for diabetic retinopathy
(FIELD study): a randomised controlled trial.
Keech AC, Mitchell P, Summanen PA, O'Day J, Davis TM, Moffitt MS, Taskinen MR, Simes RJ, Tse
D, Williamson E, Merrifield A, Laatikainen LT, d'Emden MC, Crimet DC, O'Connell RL, Colman PG;
FIELD study investigators.
Lancet. 2007 Nov 17;370(9600):1687-97. Epub 2007 Nov 7
In the FIELD eye substudy, in patients with proliferative retinopathy and/or macular oedema, there
was a lower rate of first laser treatment for any retinopathy in the fenofibrate group compared with
placebo (3.4% vs 4.9%; HR 0.69, 95% CI 0.56 to 0.84; p=0·0002; NNT=67 over 5 years).
Effects of medical therapies on retinopathy progression in type 2 diabetes.
ACCORD Study Group; ACCORD Eye Study Group, Chew EY, Ambrosius WT, Davis MD, Danis RP,
Gangaputra S, Greven CM, Hubbard L, Esser BA, Lovato JF, Perdue LH, Goff DC Jr, Cushman WC,
Ginsberg HN, Elam MB, Genuth S, Gerstein HC, Schubart U, Fine LJ.
N Engl J Med. 2010 Jul 15;363(3):233-44. doi: 10.1056/NEJMoa1001288. Epub 2010 Jun 29.
The primary outcome for the ACCORD substudy was a composite end point of either progression of
diabetic retinopathy (≥3 steps worsening on a 17 point scale) or development of proliferative
diabetic retinopathy necessitating photocoagulation therapy or vitrectomy. The study excluded
participants who, at baseline, had a history of proliferative diabetic retinopathy that had been
treated with laser photocoagulation or vitrectomy. The analysis found that adding fenofibrate to
simvastatin reduced progression of diabetic retinopathy (by 40% odds ratio) but not worsening of
visual acuity. The absolute risk reduction was 3.7% (NNT of 27 over 4 years).
Guideline written by Dr Jenny Stephenson, GP NHS Sheffield CCG, with
contributions from Ophthalmology and Diabetes consultants, STHFT and Formulary
Subgroup, NHS Sheffield CCG
Date guideline approved by APG: March 2014
Review date: February 2017