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Diabetes: a risk factor for
glaucoma?
Sally Primus,1 Alon Harris,1 Brent A Siesky,1
Giovanna Guidoboni2
Diabetes and glaucoma are two of the
leading causes of blindness worldwide. In
the USA, it is estimated that by the year
2020, 3.3 million patients will have glau-
comatous eye disease. Up to 45% of dia-
betics will develop retinopathy, with an
expected 7.2 million patients with diabetic
eye disease by 2020.1 The relationship
between diabetes and glaucoma is not well
established and currently remains the
subject of much controversy. This contro-
versy poses several important questions.
Do patients with diabetes have a greater
risk of developing glaucoma? Is glaucoma
progression faster and more severe in
patients with diabetic glaucoma? If dia-
betes increases risk for glaucoma, what is
the aetiology of this increased risk?
Elucidation of the possible interaction
of mechanisms of diabetes and glaucoma
and their associated risks, is currently
unclear, as studies over the last several
decades have been contradictory. Several
population-based studies have shown that
patients with diabetes have increased risk
for the development and severity of glau-
coma.2 3 An investigation into the effects
of diabetes on glaucoma visual-field
progression has shown that the presence
of diabetes is a significant risk factor for
a sustained decrease in visual field.4
However, other similar studies have found
no such association between glaucoma
and diabetes, furthering the need for
larger, more in-depth studies.5 6
Both glaucoma and diabetes are diseases
with vascular components, which may be
the common denominator to under-
standing the ocular effects in patients
with both conditions. Elevated intraocular
pressure is the only currently treatable risk
factor for open-angle glaucoma (OAG),
but disease progression despite normal-
isation of intraocular pressure proves that
1
Department of Ophthalmology, Indiana University
School of Medicine, Indianapolis, Indiana, USA;
2
Department of Mathematics, Indiana University School
of Medicine, Indianapolis, Indiana, USA
Correspondence to Professor Alon Harris, Department
of Ophthalmology, 702 Rotary Circle, Room 137,
Indianapolis, IN 46202, USA; alharris@indiana.edu
Br J Ophthalmol December 2011 Vol 95 No 12
other factors are associated with glau-
coma.7 Along with other identified risk
factors, many studies have implicated
vascular dysfunction as a factor in the
progression of glaucoma.8 9 Abnormalities
in blood flow in retrobulbar and retinal
microcirculation have been identified in
both diabetes and glaucoma.10e13 The
shared vascular component of diabetes and
glaucoma presents a possible contributory
pathway, which may explain the increased
risk seen in diabetic OAG patients.
The macrovascular damage in diabetes
suggests a similar pathology to some of
the vascular abnormalities seen in glau-
coma. The macrovascular complications
of diabetes have been well established,
leading to increased risk of cerebrovas-
cular, cardiovascular and peripheral
vascular damage.14 Cerebral blood-flow
abnormalities have been associated with
the development of glaucoma. Visual-field
deficits in glaucoma are associated with
more widespread cerebrovascular abnor-
malities. In an MRI study by Stroman
et al, patients with normal-tension glau-
coma showed increased white-matter
lesions suggestive of decreased cerebral
flow.15 Similar macrovascular effects are
seen in both diabetes and glaucoma but
are merely part of the whole picture of
vascular complications of both diseases.
Microvascular implications of both dia-
betes and glaucoma may also elucidate the
similar aetiology of end-organ damage
seen in these conditions. Diabetic reti-
nopathy progression is dependent on the
level of blood sugar control. However, up
to 10% of diabetics with good glycaemic
control will develop retinopathy,16
suggesting a possible role of vascular
dysregulation.17 Diabetic nephropathy,
which often occurs simultaneously, is
characterised by an initial enlargement of
the kidney with a period of hyper-
filtration, follwed by a progressive decline
of glomerular filtration rate and kidney
function.18 Similar increases in retinal
blood flow have been seen in early diabetic
eyes, suggesting a similar vascular
dysfunction as seen in nephropathy.12 A
similar compensatory response has been
Editorial
described in glaucoma,19 but this response
was significantly stronger in patients with
underlying diabetes. In a unique, large,
longitudinal, prospective study, The Indi-
anapolis Glaucoma Progression Study
(IGPS) has compared ocular haemody-
namics in patients with glaucoma with
and without diabetes. Interestingly, early
diabetics had a higher retinal microcircu-
lation blood flow than non- diabetes
patients. These preliminary data may
suggest that a compensatory response,
similar to the hyperfiltration seen in early
diabetic nephropathy, is present in OAG
patients with diabetes. While microvas-
cular complications are seen in both
glaucoma and diabetes, the exact aetiology
of the relationship is not completely
understood.
While current thought has divided
vascular disease into distinct macro- and
microvascular categories, it is becoming
increasingly clear that the relationship
between the two is not that simple. In
diabetes, both macro- and microvascular
changes often occur simultaneously, with
several aetiologies of common pathology
suggested. Microvascular complications,
such as retinopathy, have been shown to
be linked to increased macrovascular
disease.20 A study by van Hecke et al
demonstrated that abnormalities in
microvascular disease correlate with
macrovascular complications in diabetes.
Patients with retinal venule dilation had
a significant increase in carotid intimal
thickness, which is a known macro-
vascular change in diabetes.21 Macro- and
microvascular changes also occur in glau-
coma and, like diabetes, may not be indi-
vidual problems but two interlinked
aspects of the same disease process.
One leading theory into the mecha-
nistic aetiology of vascular dysregulation
in both diseases supports the role of nitric
oxide (NO) and endothelin-1 (ET-1). NO
produced by endothelial nitric oxide
synthase leads to vascular smooth-muscle
dilation. While low NO leads to a state of
vasoconstriction, abnormally high NO
leads to retinal neurotoxicity. Hyper-
glycaemia, as seen in diabetes, inhibits the
formation of NO, as well as decreasing
vascular smooth muscle cell sensitivity to
NO, leading to vasoconstriction.22
Patients with OAG have been shown to
have abnormal serum concentrations of
NO.23 Additionally, several haplotypes of
endothelial nitric oxide synthase have
been associated with increased risk of
developing glaucoma, further showing
the potential mechanistic importance of
NO in glaucoma pathology.24 Endothelin-
1621
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Editorial
1 (ET-1) opposes NO, leading to a state of
vasoconstriction, and increased aqueous
humour levels of ET-1 have also been
found in patients with glaucoma.25 The
roles of NO and ET-1 in glaucoma and
diabetes provide a potential mechanism
for vascular dysfunction in both diseases.
The relationship between glaucoma and
diabetes is not well established, and
several important questions remain. While
multiple studies currently seem contro-
versial, could this discrepancy be due to
differing levels of diabetes that are evalu-
ated? For example, the Beaver Dam Eye
Study used treatment of diabetes as an
inclusion factor,2 while the Rotterdam Eye
Study excluded such patients.3 Second,
should patients with diabetes be evaluated
for vascular dysfunction and for the pres-
ence of other vascular diseases, such as
hypertension? Finally, do patients with
diabetes warrant more aggressive preven-
tion and therapy of glaucoma? Better
treatment of both diseases lies in the
answers to these questions.
Competing interests None.
Contributors Conception and design: SP, AH, BS, GG&
Drafting the manuscript: Critical revision: SP, AH, BS,
GG. AH proposed project idea. SP carried out the
relevant literature searches and drafting of manuscript
with the aid of BS and GG, both of whom continually
aided in the reshaping of the project. SP, AH, BS and GG
were involved in the critical revision and approval prior to
publication.
Provenance and peer review Not commissioned;
internally peer reviewed.
Accepted 20 August 2011
Published Online First 6 October 2011
Br J Ophthalmol 2011;95:1621e1622.
doi:10.1136/bjophthalmol-2011-300788
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Br J Ophthalmol December 2011 Vol 95 No 12
 Downloaded from http://bjo.bmj.com/ on March 22, 2015 - Published by group.bmj.com

Diabetes: a risk factor for glaucoma?

Sally Primus, Alon Harris, Brent A Siesky and Giovanna Guidoboni

Br J Ophthalmol 2011 95: 1621-1622 originally published online October

6, 2011
doi: 10.1136/bjophthalmol-2011-300788

Updated information and services can be found at:

http://bjo.bmj.com/content/95/12/1621

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References This article cites 24 articles, 5 of which you can access for free at:
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Topic Articles on similar topics can be found in the following collections

Collections Angle (933)
Glaucoma (918)
Intraocular pressure (930)
Epidemiology (939)
Neurology (1237)
Retina (1454)
Vision (582)

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