VOLUME 10 NUMBER 4 • NOVEMBER 2013
121
SA JOURNAL OF DIABETES & VASCULAR DISEASE
REVIEW
DMOby at least two-thirds, compared togridphotocoagulation.
10,13,14
This effect was less pronounced at two years compared to laser
therapy.
12,15
The long-term systemic sequelae of inhibiting VEGF in a
vasculopath have not been clearly elucidated. Recent large
trials have not shown an increase in thrombo-embolic events or
mortality rate at one year in anti-VEGF agents over laser or sham
treatments.
10,16
Ranibizumab has shown no new safety signals at
three years of treatment.
17
Aflibercept (VEGF Trap-eye™) was approved by the FDA in
2011 for treating choroidal neovascularisation. This anti-VEGF was
shown to be non-inferior to ranibizumab, but the injections need
only be injected every eight months instead of four.
18
Aflibercept
has also been shown to be effective in treating DMO and reduces
the treatment and follow-up burden.
10
Other treatment modalities
Hypoglycaemic, anti-hypertensive and even hypolipidaemic systemic
drugs have shown significant results in controlling the progression
of diabetic retinopathy and DMO.
19,20
Although invasive, total pars plana vitrectomy surgery has been
shown to be beneficial in reducing DMO, even in cases that are
unresponsive to laser therapy.
21,22
The mechanisms involved are
probably reduced traction on the macula, temporary dramatic
reduction of VEGF as well as increased oxygen saturation to the
retina. This therapy seems to be effective even in eyes with no
vitreo-retinal traction.
23
Medical vitrectomy is an office procedure where enzymatic
vitreolytic agents such as microplasmin are injected into the vitreous
humour without the need for formal surgery. These agents have
shown promise in improving refractory DMO but they have not
been widely accepted due to safety concerns.
24
Emerging drug technologies include, among others, small
interfering RNA, protein kinase C inhibitors and hydroxy-3-methyl-
glutaryl coenzyme A reductase inhibitors.
25
None have been
approved yet for treatment of DMO.
Combination treatment
An approach to capitalise on the positive aspects of the different treat-
ment options would be to give combination therapy. Combining an
anti-VEGF with laser therapy should give us a dramatic improvement
as well as a sustained effect, respectively. Laser combined with ranibi-
zumab, however, has shown no improvement in final vision but it
does reduce the amount of injections needed in the first two years.
26
A combination of triamcinolone and ranibizumab has been
studied in order to minimise the exposure of the eye to steroids.
27
The studies show that after six months, both drugs, used separately,
have equal clinical outcomes but an increase in glaucoma in the
steroid groups. A combination of the two drugs is no better than
single-drug therapy.
27
Conclusion
Despite being the current gold standard, laser treatment alone
seems not to have as good outcomes as intravitreal steroids or
anti-VEGF agents. On the other hand, the major problem of the
injectable drugs is their short duration of action and recurrence
of the oedema. Add to this the propensity of steroids to cause
cataract and glaucoma, and the ideal treatment of DMO seems out
of our grasp.
The best treatment of DMO currently seems to be a multi-
therapeutic approach. The management should also be tailored to
each patient due to the great variation in individual response.
At minimum, this approach should include: (1) strict control
of serum glucose levels, blood pressure and lipids, (2) regular
screening and early referral for treatment of diabetic retinopathy,
(3) focal laser of leaking micro-aneurisms as soon as possible –
preferably before a loss in vision, (4) grid laser if the DMO is diffuse,
(5) resistant cases should get anti-VEGF or steroids to temporarily
flatten the retina to be more receptive to subsequent grid laser, (6)
prolonged intravitreal therapy combined with adequate laser for
chronic, resistant cases.
The choice of intravitreal injection depends on each individual.
Steroids should be reserved for post-cataract surgery eyes at a low
risk for glaucoma. Patients where regular follow up is difficult may
benefit from sustained-release preparations. Anti-VEGF agents are
relatively safe in most patients but regular follow up and sustained
treatment become crucial.
Pars plana vitrectomy or vitreolysis remains a last resort, unless
there is evidence of vitreomacular traction, in which case it becomes
the primary treatment option for DMO.
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