Topics in Compan An Med 33 (2018) 29–34
Review Article
Canine Diabetes Mellitus Associated Ocular Disease
Eric J. Miller, DVM, MS, DACVOn, Courtenay M. Brines, DVM, MS
Keywords: Diabetes mellitus (DM) is a commonly encountered disease in companion animal veterinary practice.
diabetes mellitus
Ocular complications in dogs with DM are thought to be common but there are no reports of the overall
diabetic cataract
incidence of DM-associated ocular disease. Some complications, such as cataracts and ocular surface
retinopathy
ocular surface disease disease, can lead to vision loss and significant morbidity among DM patients, therefore early recognition
keratoconjunctivitis sicca and intervention are essential for successful outcomes. The purpose of this article is to provide a review
of several currently known or suspected ocular diseases associated with DM.
Department of Clinical Sciences, College of
Veterinary Medicine, The Ohio State University,
Columbus, OH, USA
n
Address reprint requests to Eric J. Miller,
DVM, MS, DACVO, Department of Clinical,
College of Veterinary Medicine, The Ohio
State University, Columbus, OH 43210, USA.
E-mail: miller.5218@osu.edu (E.J. Miller)
Introduction
Diabetes mellitus (DM) is a commonly encountered disease in
companion animal practice with an estimated prevalence of 0.4%-
1.2% in dogs and cats.1 According to the Veterinary Medical Data
Base the prevalence of this disease in dogs appears to be increas-
ing and several breeds have been identified with an increased risk
of development of DM.2 Many different possible etiologies have
been associated with DM in dogs including obesity, immune-
mediated insulitis, drugs, pancreatitis, and other concurrent ill-
nesses1. Diagnosis of DM has a significant negative affect on both
the pet and their owners. One study found that 1 in 10 pets were
euthanized at diagnosis and another 1 in 10 were euthanized
within 1 year with the most frequent motivating factor being the
presence of concurrent disease.3 Ocular disease represents one
area of complications associated with DM. The frequency of ocular
complications in dogs affected with DM is thought to be high,
however, there are no reports of the overall incidence of DM-
associated eye disease in this species. Ocular manifestations of DM
have been associated with the eyelids, conjunctiva, cornea, uvea,
lens, and retina.4-10 Some of these complications can lead to vision
loss and patient discomfort, therefore timely recognition and
treatment are important. A thorough eye examination including
Schirmer tear test (STT), intraocular pressure measurement,
dilated anterior segment evaluation, and dilated fundic examina-
tion should be performed on all diabetic patients as part of patient
management. The purpose of this article is to provide an overview
of several currently known ocular diseases associated with DM.
Diabetes-Related Cataracts
Cataracts in dogs likely represent one of the most frequently
encountered and earliest onset complications associated with DM.
Beam et al reported that approximately 80% of dogs with diabetes
will develop DM-related cataracts within 16 months of diagnosis.
Sixty percent of dogs in this study developed cataracts within
https://doi.org/10.1053/j.tcam.2018.03.001
1527-3369/ & 2018 Topics in Companion Animal Medicine. Published by Elsevier Inc.
& 2018 Elsevier Inc. All rights reserved.
6 months of diagnosis suggesting that this complication occurs
rapidly in the majority of patients.11 Briefly, excess glucose in the
lens is metabolized to the sugar alcohol sorbitol in a process
mediated by the enzyme aldose reductase. Sorbitol accumulation
in the lens results in osmotic imbibition of water from the aqueous
humor leading to lens architectural changes and cataract forma-
tion.9 Dogs appear to be uniquely susceptible to DM-related
cataract formation likely due to high concentrations of lenticular
aldose reductase persisting later in life.12 Other biochemical
alterations and changes in cell membrane permeability may also
be a factor in diabetic cataract formation.13 Based on this patho-
physiology one would assume that cataract formation would be
related to glucose control but one study could not identify a
correlation between cataract development and glucose levels.14
Clinical findings of DM cataract formation in dogs generally
start with vacuole formation in the equatorial region of the lens
followed by anterior and posterior cortical streaks with eventual
and generally rapid progression to fully mature cataracts with
suture clefts (Figs 1 and 2). If the pupils are not dilated and the
lens evaluated thoroughly the early equatorial vacuole formation
can go unrecognized.9 Because of the imbibition of water, swelling
of the lens occurs and causes the cleft formation along the suture
lines noted as the cataract reaches the mature stage. Williams
found that lenses with DM cataracts had significantly increased
axial thickness compared to nondiabetic cataracts as demon-
strated by B-mode ultrasound.15 Due to this intumescence or
swelling the anterior chamber may also be shallow, which may
be a risk factor for elevated intraocular pressure by narrowing of
the iridocorneal angle.15 Uveitis may also be noted in patients with
DM-related cataracts. Lens proteins will elicit an inflammatory
response when leakage from the lens capsule occurs, known as
lens induced uveitis (LIU), and occurs in up 71% of patients with
cataracts.16 LIU can be divided into 2 catagories: phacolytic (when
the lens capsule remains intact) or phacoclastic (when the lens
capsule ruptures) with the later being more severe.17 The swelling
associated with DM cataracts may result in spontaneous lens
capsule rupture and occurrence of the more severe phacoclastic
30 E.J. Miller, C.M. Brines / Topics in Companion An Med 33 (2018) 29–34
Fig. 1. Oblique view of the left eye of a diabetic dog demonstrating equatorial
vacuoles often the earliest evidence of diabetic cataract formation.
LIU.18 LIU can also lead to posterior synechia, retinal detachment,
and secondary glaucoma.17,19 Periodically patients will present for
vision loss due to rapid cataract formation before a diagnosis of
DM has been made.9 If the characteristic suture clefting and rapid
progression are present in these patients, DM should be consid-
ered in differential diagnoses.
Treatment of DM-associated cataracts depends on the stage of
cataract at presentation and the owner’s desire to potentially
pursue cataract surgery. The owner’s perceived effect on quality of
life, financial status, and concurrent health issues that prohibit
general anesthesia are all factors that may determine if a dog
undergoes cataract surgery. Although surgery for cataracts in dogs
is not without complication it is generally considered successful
with good long-term vision outcomes and owner satisfaction.20-22
Cataract surgery in dogs is often not recommended until cataracts
reach an immature to mature stage.23 When vision compromise
due to cataract occurs or is inevitable cataract removal via
phacoemulsification is the surgery of choice among veterinary
ophthalmologists.24 Due to the high prevalence of LIU associated
with cataracts16,25 topical or systemic anti-inflammatory therapy
should be considered regardless of desired approach. Lim et al
investigated the outcomes of dogs with cataracts receiving no
treatment, medical therapy alone, or phacoemulsification, and
found that patients receiving phacoemulsification were most
likely to have a favorable outcome. A favorable outcome was
defined as comfortable eyes without inflammation or glaucoma in
patients not receiving surgery and the same but also including
vision in patients who were surgically treated. In nontreated eyes
the failure rate was 65 and 255 times higher than that of medically
and surgically treated eyes, respectively. The failure rate was just
Fig. 2. Right eye of a diabetic dog with a mature diabetic cataract demonstrating
intumescence and suture clefts.
4 times higher in dogs receiving medical therapy when compared
with surgically treated eyes.26 These findings underscore the
importance of anti-inflammatory therapy in dogs with cataracts
and highlight problems associated with cataracts other than vision
loss. Some early studies suggested decreased cataract surgery
success with the presence of LIU16 while more recent reports
show no difference in outcomes when LIU was present.20,21
Furthermore, the latter reports also found no difference in surgical
outcomes of DM-related cataracts compared to cataracts of other
etiologies.20,21 Recently, medical therapy for DM-related cataracts
before onset or in early stages using an aldose reductase inhibitor
has shown success in prevention or slowed progression.27 An
aldose reductase inhibitor applied topically 3 times daily for 1 year
produced cataract scores that were not significantly different from
the initial scores while cataract scores increased in the placebo
control group.27 Food and Drug Administration approval for use of
this drug to treat DM-related cataracts is anticipated.28 Some
preliminary evidence shows that supplements such as alpha lipoic
acid may also be useful in the prevention or delay of DM-
associated cataracts.29 Recognition of the earliest stages of cataract
formation in patients with DM will likely be an important factor
when considering nonsurgical treatment options.
Diabetes-Related Retinopathy
Retinopathy associated with DM in dogs represents a compli-
cation which appears to occur less frequently than in humans.30
Human diabetic retinopathy is a microvascular disease with initial
retinal hemorrhages and microaneurysms and eventual progres-
sion to proliferative neovascularization resulting in vision com-
promise or loss.31 Diabetic retinopathy is a major cause of
blindness in humans.31 Canine diabetic retinopathy is character-
ized by microvascular changes including capillary microaneur-
ysms and hemorrhages.32 Fundus examination may reveal
multifocal retinal hemorrhages in the tapetal region (Fig 3). These
initial changes are referred to as background retinopathy in
humans31 and appear to be the extent of the disease in dogs.32
Further proliferative changes seen in humans are not reported
with naturally occurring DM in dogs. The pathogenesis of diabetic
retinopathy has been hypothesized to be the same as for cataract
formation with aldose reductase mediated accumulation of sorbi-
tol or by nonenzymatic glycosylation of proteins with subsequent
cell damage.10 In one retrospective study, retinal hemorrhages
following cataract surgery in dogs occurred in 21% of diabetic
patients with only 0.6% of nondiabetics having these lesions.
Median time to onset of retinopathy from original diagnosis of
diabetes was 1.4 years.33 In another longitudinal study carried out
over 2 years no association between time since diagnosis or
Fig. 3. Fundic image of a diabetic dog showing multifocal punctate hemorrhages or
microaneurysms in the tapetal region.
 E.J. Miller, C.M. Brines / Topics in Companion An Med 33 (2018) 29–34
glycemic control and retinopathy could be identified.30 The major
risk factor for development of diabetic retinopathy in humans is
thought to be the duration of DM.34 The lower incidence in dogs
may be explained by age of onset of DM and shorter life span in
dogs yielding a shorter duration of disease in their lifetime. In
humans, an association with elevated aqueous humor vascular
endothelial growth factor (VEGF) and diabetic retinopathy has
been established.35 A study measuring VEGF in the aqueous
humor of diabetic and nondiabetic dogs found no difference. It
was hypothesized that this may also protect the dog from develop-
ment of retinopathy.36 No treatment for diabetic retinopathy is
currently recommended.
Diabetes-Related Ocular Surface Disease
Early identification and appropriate treatment intervention of
ocular surface diseases in the diabetic canine patient can be
achieved by first appreciating the spectrum of diabetic complica-
tions that can arise. Quality of life in the diabetic dog can be
compromised if the ocular surface is affected with conditions like
tear film disorders, ulcers, infections, and polyneuropathies. Such
circumstances can result in pain and compromised vision. Serially
monitoring the diabetic canine patient for ocular surface abnor-
malities is necessary and can be performed with common diag-
nostic tests readily available in a clinic setting.
The tear film has been classically described as being comprised
of 3 layers, which amalgamate on the ocular surface: aqueous
(secreted by the lacrimal and third eyelid gland), mucin (secreted
by the conjunctival goblet cells), and lipid (secreted by the
meibomian glands). The tear film contains enzymes, signaling
molecules, and metabolites that are essential to maintaining
physiological function of the ocular surface.37,38 Concurrent DM
and keratoconjunctivitis sicca (KCS) or “dry eye” has been docu-
mented in dogs5,39-41 as well as in humans.42-44 A diagnosis of KCS
in the dog can be based upon a STT o15 mm/min combined with
the presence of clinical signs such as blepharospasm, conjunctival
hyperemia, mucoid discharge, corneal vascularization, pigmenta-
tion and ulceration, or a dull lackluster appearance of the
cornea.45-47 Commonly performed in the general practice setting,
the STT measures basal tear production plus reflex tearing.48
Human studies have demonstrated that while basal rates of
aqueous tear secretion as measured by fluorophotometry42,49
were equivocal between diabetic and nondiabetic human patients,
STT values were found to be lower in diabetics.42 This indicates
that reflex tearing is affected.
Corneal nerves arising from the ophthalmic branches of the
trigeminal nerve comprise the afferent arm of neural pathways
that provide essential sensory input involved in both lacrimation
and blinking. In health, these nerves are vital for corneal protec-
tion, and impairment of corneal sensitivity would leave corneal
epithelium vulnerable to both trauma (e.g., epithelial erosions)
and desiccation. Impairment of corneal sensitivity is suspected to
be a component of diabetic neuropathy. Diabetic neuropathy has
been described to affect peripheral sensorimotor nerves, including
corneal nerves and lacrimal gland secretory function, and is
characterized by segmental demyelination and axonal degenera-
tion.50,51 The cause of nerve injury is suggested to be multi-
factorial, including altered metabolism52-54 and vascular
changes55 that occur secondary to the hyperglycemic state in the
diabetic patient.56 Corneal nerve functionality can be assessed
indirectly by corneal sensitivity tests, such as the Cochet Bonnet
aesthesiometer.57 Lower corneal sensitivity in diabetics compared
to nondiabetics has been found in both dogs 5,6,41 and humans.57-59
Decreased corneal sensitivity therefore is likely responsible for
negatively affecting reflex tearing, thus resulting in lower STT
31
values among patients. Furthermore, decreased corneal sensitivity
leaves the corneal epithelial cells vulnerable and negatively affects
their ability to recover from injury.60,61
A number of clinically relevant risk factors have been identified
that could influence the prevalence of KCS in the diabetic canine
population. Duration of diabetic disease was reported to nega-
tively influence STT values in a small retrospective study of
diabetic dogs, indicating that tear production may gradually
decline over the animal’s life.41 Another study found that diabetics
that underwent phacoemulsification appeared to be almost twice
as likely to develop KCS within the first 2-week postoperative
period compared to nondiabetic dogs.7 The STT values of both
diabetic and nondiabetic dogs trended upward over time post-
phacoemulsification, and the proportion of eyes diagnosed with
KCS between the 2 groups at postoperative examinations did not
significantly differ. This same study also identified that small
diabetic dogs weighing less than 10 kg were reportedly 1.7 times
more likely to be diagnosed with KCS than the nondiabetic small
dog group postoperatively.7
Qualitative changes in tear film composition, such as mucin
deficiency, can arise leading to tear film instability. For example,
tear film break-up times (TFBUT) have been reported to be
significantly shorter in human diabetics compared to healthy
controls43,62 and diabetic cataractous dogs compared to non-
diabetic dogs without cataracts and nondiabetic cataractous dogs.5
The TFBUT is a measurement of precorneal tear film stability, and
faster break-up times indicate that the ocular surface has a
compromised ability to retain a homogenous tear covering.45
Impression cytology of conjunctiva, an indirect measure of mucin
production, revealed loss of goblet cells and epithelial squamous
metaplasia in human diabetic.43 A small DM canine study dem-
onstrated that diabetic cataractous dogs exhibited varying degrees
of conjunctival epithelial dysplasia sometimes with squamous
metaplasia and reduced mean goblet cell density compared to
nondiabetic catractous and nondiabetic noncataractous controls
groups, although the reduction in mean goblet cell density did not
reach statistical power given a low sample size.5 Loss of goblet
cells, secondary to corneal and conjunctival epithelial damage
from diabetic neuropathy has been described as the pathogenesis
of reduced mucin production thereby leading to tear film insta-
bility.62 Furthermore, poor diabetic control and decreased corneal
sensitivity were related to decreased TFBUT, goblet cell loss, and
epithelial squamous metaplasia in humans.43
It is unclear as to whether poor DM control is an important
factor in manifestation of dry eye diseases in diabetic canines as
has been documented in humans.43,63,64 Canine studies have
reported no significant correlation between poor DM control and
low STT.5,6,41 This may be due to difficulties with inherently small
veterinary population sample sizes and accuracy of historical
medical records. Interestingly in humans, longer duration of DM
has been associated with a less severe score of ocular surface
disease index; lack of or less commonly reported symptoms of dry
eye disease may result from a reduction in corneal sensitivity
caused by diabetic peripheral corneal neuropathy.65
Collectively, the clinical implications of these studies suggest
that tear production should be serially monitored in all diabetic
dogs, and examination of the ocular surface and tear function
should become routine in follow-up examinations. Subclinical or
milder forms of KCS may be more prevalent than severe forms of
KCS in our diabetic canine population. Early treatment for dogs
with milder or subclinical forms of KCS may be more likely to be
successful than initiating treatment when clinical signs of KCS are
conspicuous.41 Furthermore, diabetic dogs may undergo surgical
treatments to restore vision secondary to diabetic cataracts like
phacoemulsification and intraocular lens implantation. The first
2-week postoperative period may yield a greater risk for KCS for
32 E.J. Miller, C.M. Brines / Topics in Companion An Med 33 (2018) 29–34
all diabetic canine patients. Tear supplementation rather than
institution of a stimulant tear product may be considered to
protect the cornea during the anesthetic and surgery recovery
period as tear values may improve after a 2-week postoperative
period.7 However, in general, use of tear stimulants such as topical
cyclosporine (Optimmune; Schering Plough), or when appropriate,
compounded versions of cyclosporine and tacrolimus should be
considered when faced with low tear production in a diabetic
canine patient. Such drugs not only boost tear production, but
suppress inflammation by inhibition of the expression of inflam-
matory cytokines and chemokines, thereby promoting corneal
epithelial health.66
A compromised ocular surface may be vulnerable to bacterial,
fungal, and viral infections. Established risk factors for atypical
corneal infections in humans include systemic immunodeficiency,
topical ophthalmic corticosteroid use, ocular trauma, previous
ophthalmic surgery, and DM. Tear glucose concentrations have
been reported to be elevated in both dog5 and human diabetic
patients compared to nondiabetic control groups.67 Elevated tear
glucose levels affect tear osmolality and contributes to precorneal
tear film instability.68 Conjunctival flora in dogs has been reported
to be similar between diabetic and nondiabetic controls, unlike
humans in which systemic risk factors like DM result in 2-fold
increase in likelihood to harbor antibiotic-resistant bacteria on
their conjunctiva compared to individuals without systemic risk
factors.69 It has been suggested that ocular and corneal surface
infections and infectious keratitis occur more frequently in people
with DM.70-74 However, some human studies suggest that while
conjunctivitis appears more prevalent in the diabetic population,
diabetics were not at an increased risk for development of other
ocular infections including ulcerative infectious keratitis.75
In veterinary ophthalmology, postoperative ulcerative keratitis
is more likey to develop in diabetic dogs compared to nondiabetic
dogs undergoing cataract surgery.6 Corneal nerves also provide
critical neurotrophic regulation of epithelial cell proliferation,
differentiation, adhesion, and migration.76 There are a few reports
in the literature that tie ulcerative keratitis with DM in the canine.
DM, along with administration of topical ophthalmic corticoste-
roids, and stresses associated with hospitalization were suggested
to have contributed to reactivation of a latent herpes virus
infection in a diabetic dog 3 weeks postphacoemulsification.77
Anaerobic corneal stromal infection with Actinomyces bowdenii
was found in a dog 2 months following phacoemulsification.78 The
authors of this study concluded that both endogenous (i.e., DM)
and exogenous (i.e., topical ophthalmic corticosteroids and cyclo-
sporine) factors likely contributed to establishment of the corneal
abscessation in this case. Another study comprised of dogs, cats,
and horses diagnosed with septic ulcerative keratitis and isolated
obligate anaerobic organisms which included Actinomyces species
found no significant associations between anaerobic bacterial
culture results and immunosuppressive systemic diseases and
other factors such as KCS, corneal foreign bodies, antimicrobial
administration, and corticosteroid administration.79 The preva-
lence of anaeorobic bacteria in ulcerative keratitis in domestic
animals is presumed to be low, and most frequently occurs in
association with other ocular pathogens and previous corneal
abnormalities.
Diabetes-Related Corneal Disease
The corneal endothelium serves to maintain corneal clarity and
normal thickness by prevention of corneal edema. Several reports
of endothelial abnormalities in patients with DM exist in the
human literature. Reported abnormalities include decreased
endothelial cell density with morphologic changes of increased
pleomorphism and polymegethism.80-82 Some variability and
controversy over the findings exists but it seems clear that some
abnormalities involving the corneal endothelium occur.83 One
study evaluating the corneal endothelium in diabetic dogs is
found in the literature. In this study of experimentally induced
DM it was found that dogs exhibited the morphologic changes of
increased pleomorphism and polymegethism but no change in
endothelial density was detected. It was also demonstrated that
the severity of changes appeared to correlate with level of diabetic
control.84 The possibility of corneal endothelial dysfunction may
predispose diabetic dogs to more corneal edema following cata-
ract surgery.
Stromal intracorneal hemorrhage (ICH) is a relatively uncom-
mon condition closely associated with corneal vascularization,
which can be observed in older canine patients with variable
concurrent ocular surface or intraocular disease.85,86 DM, among
other commonly diagnosed systemic diseases in our canine
population such as hypothyroidism, hyperadrenocorticism, and
hypertension may be a risk factor in the development of stromal
ICH in canines.86 The new vessels created during angiogenesis in
diabetic canines, like diabetic humans, may have certain charac-
teristics that make them more susceptible to bleeding indirectly
by virtue of their underlying systemic disease. DM is a major
cardiovascular risk factor for atherosclerosis in humans due to
promotion of inflammation and vascularization.87 Dogs with DM
have been shown to be at risk for development of atherosclerosis
compared to age and sex-matched controls.88 Elevated serum
cholesterol concentrations along with other endocrinopathies
such as hypothyroidism are commonly reported in the diabetic
canine and are thought to contribute to the development of
atherosclerosis.88-90 Canine stromal ICH, irrespective of topical
ophthalmic treatment or surgery, resolves with time but contin-
ued monitoring for complications is recommended.85,86
Diabetes-Related Ocular Neuropathy
Diabetic neuropathy is histopathologically characterized by
axonal degeneration and segmental demyelination.50,91-93 Distal
symmetric polyneuropathies, sensory polyneuropathies, cranial
nerve palsies, and autonomic neuropathies comprise major cate-
gories of neuropathies reported in the human literature. Overt
clinical signs of diabetic neuropathy in dogs are infrequent.
Definitive testing for a diabetic neuropathy requires electrodiag-
nostic testing or peripheral nerve biopsy. Cases of diabetic dogs
with apparent neuropathies reported involvement of bilateral
lower motor neuron paraparesis with postural deficits, depressed
spinal reflexes, and muscle atrophy.94-97 Severe cases can result in
tetraparesis.98
The cranial nerves reportedly affected in the human diabetic
population include V, VII, VIII, IX, X, and XI, particularly in
unregulated diabetics.4 More specifically, diabetic cranial nerve
palsies in humans reported are facial palsy, trigeminal neuralgia,
optic neuritis, and internal and external ophthalmoplegia.99-101
Diabetic related ocularsympathetic dysfunction, namely Horner
syndrome, has also been reported in the literature.8,97 One case
report concluded that confirmation of Horner syndrome was aided
in a diabetic canine patient with bilateral disease using denerva-
tion hypersensitivity testing using 10% phenylephrine drops.8
Results from this report, which demonstrated significant pupillary
dilation between 30 and 45 minutes after instillation of 10%
phenylephrine, was similar to phenylephrine testing in human
diabetics with oculosympathetic dysfunction.102 Second-order,
preganglionic sympathetic fibers are largely myelinated, and
therefore were suspected to be the target for demyelination injury
described in diabetic neuropathy in the case report. Infrequent
 E.J. Miller, C.M. Brines / Topics in Companion An Med 33 (2018) 29–34
reporting of the prevalence of overt clinical neuropathies in
diabetic dogs and cats may be due to difficulty in recognizing or
definitively testing for subclinical or sensory neuropathies in these
animal patients. Anecdotally, in the authors’ practice it is sus-
pected that Horner syndrome and facial nerve palsies occur more
frequently in diabetic patients than the nondiabetic population.
Conclusions
Ocular disease associated with DM represents a major source of
morbidity among veterinary and human patients. DM-related
ocular complications can affect nearly all parts of the eye and
may result in loss of vision and discomfort. Evidence for the exact
role of DM in several canine ocular diseases is lacking in the
literature but in many areas dogs exhibit similar abnormalities to
human patients, therefore it is likely they suffer the same
complications. Early recognition and treatment of these compli-
cations is essential to good outcomes especially when considering
cataracts and ocular surface disease. Cataract surgery can restore
vision and improve quality of life and the authors believe that dry
eye disease presumed to be related to DM in dogs typically
responds well to therapy when early intervention is achieved.
Client education regarding the nature and timing of DM-associ-
ated ocular disease should improve satisfaction and compliance
when these problems occur.
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