102
VOLUME 11 NUMBER 3 • SEPTEMBER 2014
REVIEW
SA JOURNAL OF DIABETES & VASCULAR DISEASE
Correspondence to: Dr Carl-Heinz Kruse
Department of Opthalmology, University of
KwaZulu-Natal, Durban
e-mail:
S Afr J Diabetes Vasc Dis
2014;
11
: 102–103
The effects of systemic medication on diabetic retinopathy
Carl-Heinz Kruse
The incidence of diabetic retinopathy
Of all the complications of diabetes mellitus, diabetic retinopathy
(DR) is feared most by patients. These fears are well founded since
DR is the third leading cause of irreversible blindness in the world
1
and the leading cause among working-age adults.
2
As a matter
of fact, a diabetic patient is more likely to go blind in the next 14
years
3
than die of a motor vehicle accident in his/her lifetime.
4
The gold standard for the treatment of diabetic retinopathy has
until recently been laser therapy. Thismodality is useful for halting the
progress in both proliferative retinopathy as well as diabetic macular
oedema. Recently the use of intravitreal steroid (Triamcinolone) and
intravitreal anti-VEGF (Bevacizumab) have shown improved results
and have resulted in an overall improvement of vision over laser
therapy alone.
Despite these advances, some patients have relentless disease,
which sometimes inexorably leads to severe visual impairment
despite all treatment. The prevalence of self-rated visual impairment
among US adults with diabetes was almost 25%.
5
The best management for DR remains prevention and the best
way to achieve this in a diabetic patient is meticulous control of
blood glucose levels.
2
In recent studies, it has also been found
that other systemic drugs, often given for the treatment of other
conditions, can have deleterious or beneficial effects on the
initiation and progression of diabetic retinopathy. This article aims
to give a synopsis of the most relevant of these drugs.
Drugs for glucose control
Insulin
It is apparent that glycaemic medication would have the greatest
effect on the initiation and progression of DR. This effect is
particularly pronounced at the early stages of DR where good
glucose control has a stronger protective effect. Although strict
glucose control is almost always beneficial for DR, under certain
circumstances it can actually be harmful.
The Early Treatment Diabetes Retinopathy Study (ETDRS)
6
clearly
showed that improving systemic glucose control reduces the risk of
progression to severe visual loss or vitrectomy at five years. Patients
with HbA
1C
levels above 12% had a 39% greater chance of a poor
outcome than those with HbA
1c
levels less than 8.3%.
6
The exception to this rule is in patients with non-insulin-
dependent diabetes mellitus (NIDDM), who improve their glycaemic
control by changing to aggressive insulin therapy.
7
This effect was
particularly pronounced when the HbA
1c
levels where dropped by
more than 3%; 23% of these patients developed a progression
of retinopathy of three or more levels. This effect is termed ‘early
worsening’ and occurs in the first two years after initiating insulin
therapy.
In most cases, this effect seems to be transient and strict glucose
control eventually gives better retinopathy results, especially after
the first three years.
2,8
Early worsening is therefore not a reason not
to aggressively control glucose levels, but close monitoring of the
DR before and after initiation of insulin therapy is still warranted.
The introduction of antioxidant supplementation might attenuate
this transient insulin-induced worsening of DR.
9
If the DR is severe, the intensive insulin therapy should be delayed
until laser panretinal photocoagulation has been completed. Rapid
development of proliferative DR has been reported in isolated cases
where extremely high doses of insulin were given.
Biguanides
Metformin not only has cardioprotective effects independent of
glucose control but also clinically inhibits inflammation-mediated
angiogenesis. The magnitude of this protective effect on DR is yet
to be elucidated.
Drugs for hypertension management
Controlling blood pressure is in itself a good method of reducing
the progression of DR.
10
Keeping the blood pressure below 150/85
mmHg reduces the chances of deterioration of DR by two levels
in NIDDM by 34% over a nine-year period. A further decrease of
diastolic blood pressure to below 75 mmHg did not give added
benefit with regard to DR progression.
11
Some antihypertensive drugs however seem to have an effect on
diabetic retinopathy independent of the antihypertensive effect.
12
Blockage of the renin–angiotensin system slows progression of
DR in insulin-dependent diabetes. Enalapril and losartan show a
65 and 70% reduction of a two-step progression of DR at five
years.
13
Importantly, this effect is independent of the changes in
blood pressure and is therefore recommended in patients with both
diabetes and hypertension.
Candesartan not only slows progression but has been associated
with an overall regression of DR.
14
This effect was seen in NIDDM
patients with mild to moderate retinopathy.
Drugs for lipid control
Lowering of serum lipid levels in diabetics with hyperlipidaemia
reduces the development of hard exudates and reduces the vision
loss from diabetic macular oedema.
15
Once again, some of these
drugs show an additional advantage on DR independent of the
lipid-lowering effect.
Fenofibrate, a PPAR
α
agonist, has been accepted in a number
of countries as an effective method to modulate and reduce
the progression of DR. Two large trials, the FIELD (Fenofibrate
Intervention and Event Lowering in Diabetes) and ACCORD
(Action to Control Cardiovascular Risk in Diabetes) studies, have
