New drug improves diabetic retinopathy
Stefanie Petrou-Binder MD
BERLIN - Long-acting somatostatin (SMS) analogues which slow the
angiogenic process appear promising for improved treatment of diabetic
retinopathy, according to reports at the annual Congress of the
German Society of Ophthalmology.
"New drug treatments for diabetic retinopathy either target
the factors that permit angiogenesis or restore the natural production
of regulatory hormones that would normally block neovascular production.
"They will become central to the future of diabetic retinopathy
therapy. Drug therapies will bolster the effects of laser coagulation
treatment to better preserve visual acuity," Bernhard Böhm
Dr Böhm reported the results of a recent randomised controlled
clinical study which implemented octreotide (Sandostatin, Novartis
Pharmaceuticals), a somatostatin analogue, in diabetes mellitus
patients with retinopathy.
The outcome revealed octreotide reduced the neovascularisation associated
with diabetic retinopathy by binding to specific SMS receptors in
the human eye where SMS is naturally produced.
SMS receptors are located on the surface of the retinal vascular
endothelial cells. They become altered in diabetic disease by the
increase in pro-angiogenic signals.
Long-acting SMS analogues, such as octreotide, have been proven
to reduce diabetic retinopathy progression, bleeding, macular oedema
and the need for vitreoretinal surgery, he reported.
A parallel study showed that octreotide could induce weight loss
in diabetic patients, a bonus effect of sorts by reducing one of
the primary risk factors associated with diabetic retinopathy.
Somatostatin is a potent inhibitory molecule. It is normally responsible
for the inhibition of IGF and other growth hormones.
The IGF cascade is critical for the normal vascularisation of the
retina. In diabetes, the serum levels of free IGF-I are lower and
researchers have reported changes in IGF binding proteins in patients
with diabetic retinopathy, he noted.
Previous studies have verified that the absence of anti-angiogenic
factors, such as angiostatin or PEDF, promotes angiogenesis. The
collagen-binding activity of PEDF has been shown to curb angiogenesis
in the vitreous humour and bone where it naturally occurs.
Laser coagulation is a mainstay in diabetic retinopathy therapy
and is effective in obliterating the pathologic microvasculature.
While it has been known to decrease VEGF (Vascular endothelial growth
factor) levels and increase angiostatin levels, laser therapy has
no proven effect on the growth hormone/IGF-1 system.
Dr Böhm reported that octreotide therapy inhibits the IGF system.
Related studies reveal that octreotide not only significantly reduced
the necessity for laser treatments in patients with non-proliferative
type and early phases of proliferative diabetic retinopathy, but
also reduced the loss of vision that might have ensued through retinopathy
progression following laser coagulation.
Dr Böhm noted that in addition to the focus on octreotide therapy,
new studies aim to pinpoint the clinical advantages of pharmacologically
inhibiting the protein kinase-C pathway (PKC).
Research has shown that changes in the signal cascade of the PKC-dependent
pathway result from hyperglycemia and the modified growth factor
milieu. The activation of the PKC pathway is thought to play a direct
role in vascular endothelial growth factor expression.
Both protein kinase C-beta (PKC-beta) inhibitors and antivascular
endothelial growth factor (anti-VEGF) compounds are now being evaluated
for treatment of diabetic retinopathy.
"Retinopathy is the most common microvascular complication
associated with diabetes mellitus. It is still the most common cause
of blindness. The causative agents are numerous and interrelated.
"Treatment programmes must be designed to target the various
causative factors involved in angiogenesis. The successful outcome
of combination drug regimens with laser coagulation treatments have
already substantiated the importance of combined therapy,"
Dr Böhm stressed.