Received: 18 March 2019 

|
  Revised: 6 October 2019 
|  Accepted: 18 October 2019

DOI: 10.1111/vop.12719

ORIGINAL ARTICLE

A retrospective analysis of lipid‐laden aqueous humor in dogs:

Thirty cases

Simone A. Schechtmann1,2,3   | Jessica M. Stine1  | Thomas R. Miller4  |

Anja Welihozkiy   2
| Tammy M. Michau 3

1
BluePearl Veterinary Partners, Clearwater,
FL, USA
Abstract
2
BluePearl Veterinary Partners, Sarasota, Objective: To describe the clinical presentation and outcome of canine patients that
FL, USA present with lipid‐laden aqueous humor (LLA) and to evaluate its association with
3
BluePearl Veterinary Partners, Tampa, FL, other ocular and systemic disorders.
USA
4
Methods: Medical records were identified and reviewed of 30 dogs presenting with
Tampa Bay Veterinary Specialists and
Emergency Care Center, Largo, FL, USA
clinical signs of LLA between 2013 and 2017 and compared to the canine referral
population during the same time period. The percentage of dogs affected by LLA and
Correspondence potential risk factors were compared between groups.
Dr. Tammy Miller Michau, BluePearl
Veterinary Partners, 3000 Busch Lake Blvd, Results: There were 40 eyes in 30 dogs with LLA out of 8011 (0.4%) referrals.
Tampa, FL 33614, USA. The mean age of dogs with LLA was significantly younger than dogs without LLA
Email: tammy.miller.michau@effem.com
(P  =  .0334). Sex was not associated with LLA. Miniature Schnauzers were more
likely to have LLA than mixed breeds (P < .0001). Incidence of LLA was significantly
higher in eyes also affected by corneal ulceration (P = .0018) or phacoemulsification
(P = .0001). Sixty‐two percent and 51% of dogs with LLA had concurrent diabetes
mellitus and hypertriglyceridemia, respectively. Average triglyceride level of dogs
with LLA was 1087 mg/dL (±544) (reference 50‐150 mg/dL) and average choles-
terol level was 575 mg/dL (±232) (reference 125‐300 mg/dL). Complete resolution
of LLA was achieved in all dogs re‐examined with an average of 20.2 days (range
4‐175 days) after diagnosis. There were 6/30 dogs lost to follow‐up. Recurrence of
LLA occurred at least once in 4/24 dogs (16.7%) after resolution.
Conclusions: Lipid‐laden aqueous humor occurs more frequently in Miniature
Schnauzers. Corneal ulceration and phacoemulsification are risk factors. Complete
resolution was seen in all cases with a low incidence of recurrence.

KEYWORDS
aqueous humor, canine, hyperlipidemia, lipid‐laden, uveitis

1  |   IN T RO D U C T ION as endocrine disorders, pancreatitis, cholestasis, protein‐losing

Lipid‐laden aqueous humor (LLA) is a condition likely associ-
ated with disorders resulting in hyperlipidemia. Hyperlipidemia
is an increased concentration of lipids (ie, triglycerides, choles-
terol, or both) in the blood.1-3 Hyperlipidemia may be postpran-
dial, primary idiopathic, or secondary to other diseases such
nephropathy, obesity, and the use of certain drugs.1-4 Secondary
hyperlipidemia as a result of endocrine disease such as diabe-
tes mellitus, hyperadrenocorticism, or hypothyroidism is the
more common form in dogs,2,5,6 whereas primary hyperlipid-
emia is less common within the general canine population.1
Primary hyperlipidemia is a familial or hereditary disorder

Veterinary Ophthalmology. 2019;00:1–9. wileyonlinelibrary.com/journal/vop © 2019 American College of Veterinary     1 |

Ophthalmologists
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2       SCHECHTMANN et al.
of lipoprotein metabolism and reported most frequently in
Miniature Schnauzers.1,2,5-8.
The endothelium of iridal vessels and nonpigmented cili-
ary epithelium prevents the passage of large lipid‐laden mol-
ecules into the aqueous humor.9 When the integrity of the
blood‐aqueous barrier (BAB) is compromised and there is
coexisting hyperlipidemia, the likelihood of lipid leakage into
the aqueous humor may be increased.10 Thus, LLA may be
seen when anterior uveitis is present.11,12 However, it has also
been reported in dogs with no obvious ocular disease, thereby
suggesting that the lipids themselves stimulate inflamma-
tion.11-14 A specific cause and effect relationship between
hyperlipidemia and anterior uveitis is not entirely understood.
Ocular lipid pathologies have been described most in hu-
mans, dogs, rabbits, frogs, and cats.15-22 Specific ocular mani-
festations of hyperlipidemia in dogs include lipemia of ocular
blood vessels (lipemia retinalis), corneal opacities (corneal lip-
idosis, crystalline stromal dystrophy, lipid keratopathy, arcus
lipoides corneae, and corneal arcus), and lipemic aqueous
humor.10,11,15 The most common ocular findings of hyperlip-
idemia in small animals include lipemia retinalis and LLA.15,23
There are several case reports of ocular manifestations
of hyperlipidemia (primary or secondary) in dogs, specifi-
cally.9,11,15,24-27 The initial report of canine LLA in veterinary
literature compared serum and aqueous humor profiles in two
dogs with concurrent hyperlipidemia and anterior uveitis il-
lustrating the presence of lipoproteins.9 Neither of these dogs
had concurrent ocular or systemic diseases at the time of di-
agnosis. Other reports have identified LLA associated with
hypothyroidism25 and diabetes mellitus.26
A previous study describing canine LLA etiologies
showed a previous intraocular surgical procedure as the
most common ocular predisposing cause.11 Since intraocu-
lar intervention disrupts the blood‐aqueous barrier,28 more
information about canine patients with a predisposition for
hyperlipidemia can be valuable in the discussion of man-
agement and complications of clinical cataract surgery pa-
tients. Disruption to the BAB following cataract surgery can
be further exacerbated in a hyperlipidemic state, which may
intensify inflammation13,14 resulting in decreased vision and
discomfort to the eye.23
The objective of this study is to describe the clinical pre-
sentation and outcome of canine patients that present with
LLA and to evaluate its association with other ocular and
systemic disorders.
2  |  M AT E R IA L A N D ME T H O DS
Medical records of dogs that were diagnosed with LLA by
a board‐certified ophthalmologist between 2013 and 2017
were evaluated. The diagnosis was based on ophthalmic ex-
amination including pearlescent to creamy appearance of the
aqueous humor and decreased visualization of the iris and
pupil. Data were collected from four referral hospitals in
Florida. Patient information collected included sex, breed,
age, date of presentation, presenting owner complaint, eye(s)
affected, ophthalmic examination findings including tonom-
etry and biomicroscopy, ophthalmic surgical history, con-
current ocular disease, concurrent systemic disease, current
ophthalmic medications, current systemic medications, diag-
nostic tests performed, treatment, outcome, and recurrence.
Follow‐up examination was performed through re‐examina-
tion with a board‐certified ophthalmologist. Resolution of
LLA was determined when no lipemic aqueous was present
in the anterior chamber. Assessment of vision was based on
presence of complete or inconsistent menace response.
2.1  |  Statistical analysis
Collected data were summarized with descriptive statistics.
Signalment data (sex, breed, and age) from the LLA popu-
lation were compared with the BluePearl Florida ophthal-
mology service referral canine population over the same
time period. Logistic regression analysis was used to test for
association of breed or sex with presence of LLA by dog.
Log‐likelihood ratio test P‐values were used. Student's t tests
were used to compare the mean age between dogs with and
without LLA. Generalized linear mixed models (GLMMs)
and Fisher's exact tests were used to test for association of
phacoemulsification and cataracts and LLA presence by eye.
Fisher's exact tests were used to test for the association of
systemic diseases with recurrence. Logistic regression analy-
sis and Fisher's exact tests were used to test for association of
ocular diseases and LLA in eyes from dogs that had LLA in at
least one eye (nonaffected eyes of unilaterally affected dogs
were used as controls for both logistic regression and Fisher's
exact analyses). GLMMs and Fisher's exact tests were used
to test for association of ocular disease and recurrence in eyes
that had LLA. A significance threshold of P < .05 was set.
3  |  RESULTS
From 2013 to 2017, there were a total of 8011 dogs pre-
sented to the ophthalmology service. Medical records of
30 dogs (0.4%) diagnosed with LLA in 40 eyes were iden-
tified and reviewed. The mean age (± standard deviation)
of dogs diagnosed with LLA was significantly (P = .0334)
lower at 9.6 years (±2.5) than dogs not diagnosed with LLA
at 10.6  years (±4.2). Miniature Schnauzers diagnosed with
LLA had a mean age of 8.4 years (±2.4) and ranged from 4
to 11 years old. All other breeds diagnosed had a mean age of
10.2 years (±2.4), ranging from 6 to 15 years old.
In dogs with LLA, there were 15 neutered males (50%),
11 spayed females (36.6%), and four intact males (13.3%). No
SCHECHTMANN et al.   
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intact females were identified with LLA. In the dogs not di- T A B L E 1   Concurrent ocular findings with diagnosis of LLA
agnosed with LLA, there were 3615 (45.2%) spayed females,
Number of
3418 (42.7%) neutered males, 579 (7.2%) intact males, and Concurrent ocular findings eyes (n = 40)
379 (4.7%) intact females. Sex was not associated with the
Conjunctival hyperemia 17 (42.5%)
occurrence of LLA.
Pseudophakia 14 (35%)
There were 17 breeds of dogs that were represented in the
population with LLA, including Miniature Schnauzer (n = 7 Cataracts 10 (25%)
dogs), Yorkshire Terrier (n  =  4 dogs), Miniature Pinscher Superficial corneal ulceration 9 (22.5%)
(n = 3 dogs), mixed breed (n = 2 dogs), Boston Terrier (n = 2 Lens‐induced uveitis 6 (15%)
dogs), and single dogs each of the following breeds: Maltese, Aphakia 5 (12.5%)
Chihuahua, West Highland Terrier, Cairn Terrier, Toy Stromal corneal ulceration 4 (10%)
Poodle, Jack Russell Terrier, Silky Terrier, Beagle, Vizsla, Superficial keratitis 3 (7.5%)
Havanese, Havanese mix, and Pug mix. The prevalence of
Calcific keratopathy 3 (7.5%)
the eight most common breeds in the LLA population was
Keratoconjunctivitis sicca 3 (7.5%)
compared with the overall referral population (n  =  8011
Corneal lipidosis 3 (7.5%)
dogs). The analysis of the frequency of each breed revealed
Miniature Schnauzers were more likely to have LLA than Melting corneal ulceration 1 (2.5%)
mixed breeds (P < .0001). Ectopic cilia 1 (2.5%)
LLA affected the left eye (OS) only in 12/30 dogs (40%), Lagophthalmos 1 (2.5%)
both eyes (OU) in 10/30 dogs (33.3%), and the right eye Distichia 1 (2.5%)
(OD) only in 8/30 dogs (26.6%). The most common present- Posterior lens subluxation 1 (2.5%)
ing clinical signs for LLA were cloudiness in the eye or eyes Glaucoma 1 (2.5%)
in 9/30 dogs (30%) (Figure 1) and squinting in 5/30 dogs Iris bombe 1 (2.5%)
(16.7%), There were 2/30 dogs (6.7%), which presented with
Posterior capsule tear 1 (2.5%)
LLA 24  hours post‐phacoemulsification, 2/30 dogs (6.7%)
one week post‐phacoemulsification, and 1/30 dogs (3.3%)
(P = .5776). There were 15/673 dogs (2.2%) of all dogs in
three weeks postoperatively. There were 2/30 dogs (6.7%)
the reference population that had cataract surgery and were
presented after a recent fatty meal ingestion.
affected with LLA.
There were 38/40 eyes (95%) that had tonometry (Tono‐
Pen XL®; Medtronic Solan) performed at the time of diag-
nosis of LLA. The mean intraocular pressure (IOP) at the
time of diagnosis was 12.7 mm Hg (±4.6). There were 19/40
eyes (47.5%) that had tonometry recorded at the resolution of
LLA. The mean IOP at resolution was 13.8 mm Hg (±6.3).
Concurrent ocular examination abnormalities were iden-
tified in 36/40 eyes (90%) diagnosed with LLA (Table 1).
Lens‐induced uveitis was diagnosed in dogs that had under-
lying mature cataracts at the time of LLA diagnosis (Figure
2). Corneal ulceration of any form was significantly associ-
ated with a diagnosis of LLA (P  =  .0018) (Figure 3). The
likelihood of LLA was also significantly higher in dogs with
phacoemulsification (P = .0001) (Figure 3), but not cataracts

F I G U R E 1   A 12‐year‐old Miniature Pinscher presenting for

cloudiness in both eyes. The white LLA can be seen obscuring the F I G U R E 2   A superficial corneal ulcer concurrent with LLA.
pupil in both eyes Fluorescein stain retention can be seen in the ventral/temporal quadrant
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4       SCHECHTMANN et al.

Lipid‐laden aqueous humor was present in 13/18 dogs

(72.2%) historically diagnosed with diabetes and that had
previously undergone phacoemulsification. There were 5/18
diabetic dogs (27.8%) that did not have phacoemulsification
but developed LLA. There was only one nondiabetic dog that
underwent phacoemulsification and developed LLA. There
were two pseudophakic diabetic dogs, 2/24 eyes, (8.3%) that
presented 24  hours postsurgery. There were two diabetic
dogs, 3/24 eyes (12.5%), one eye that was pseudophakic
and two eyes that were aphakic, which presented one week
postoperatively. One pseudophakic diabetic dog, 2/24 eyes
(8.3%), presented after a recent fatty meal ingestion (lamb
and rotisserie chicken). Of the 13 diabetic dogs that under-
went cataract surgery, 6/13 dogs (46%) developed corneal
ulceration and all six of those dogs exhibited LLA.
At least one ocular medication was already being admin-
istered in 16/30 dogs when diagnosed with LLA. These in-
cluded diclofenac 0.1% (n  =  9 dogs), neomycin‐polymyxin
b sulphates‐dexamethasone (n  =  3 dogs), dorzolamide 2%
F I G U R E 3   LLA with keratic precipitates (n = 3 dogs), cyclosporine 0.2% (Optimmune®) (n = 3 dogs),
lubricant gel (Optixcare®) (n  =  3 dogs), tacrolimus 0.03%
(n = 2 dogs), ketorolac 0.5% (n = 1 dog), demecarium bro-
There were 2/7 Miniature Schnauzers (28.6%) that had mide 0.125% (n = 1 dog), flurbiprofen 0.03% (n = 1 dog),
mature cataracts concurrent with a diagnosis of LLA. There
was 1/7 Miniature Schnauzers (14.3%) that did not have cat-
T A B L E 3   Topical ophthalmic medications prescribed at
aracts, ulceration, or recent phacoemulsification concurrent diagnosis of LLA
with LLA. There were 4/7 Miniature Schnauzers (57.1%) that
exhibited corneal ulceration and/or recent phacoemulsifica- Topical ophthalmic medications at Number of eyes
diagnosis of LLA (n = 40)
tion concurrent with LLA. Regarding systemic disorders, 6/7
Miniature Schnauzers (85.7%) were diabetic, 3/7 (42.9%) had Diclofenac 0.1% 11 (27.5%)
hypertriglyceridemia, and 4/7 Miniature Schnauzers (57%) Atropine 1% 11 (27.5%)
had both diabetes and hypertriglyceridemia. Neomycin‐polymyxin b 10 (25%)
Concurrent systemic disease in dogs with LLA was iden- sulphates‐dexamethasone
tified based on historical records or newly diagnosed at the Ofloxacin 0.03% 5 (12.5%)
time of initial diagnosis of LLA in 22/29 dogs (75.9%) (Table Dorzolamide 2% 5 (12.5%)
2). For one dog, no information was available regarding con- Oxytetracycline/polymyxin B 5 (12.5%)
current systemic disease.
Nonautologous serum 5 (12.5%)
Cefazolin 5.5% 4 (10%)
T A B L E 2   Concurrent systemic diseases with diagnosis of LLA Cyclosporine 0.2% 3 (7.5%)
Number of Tacrolimus 0.03% 3 (7.5%)
Concurrent systemic diseases dogs (n = 29) Prednisolone acetate 1% 3 (7.5%)
Diabetes mellitus 18 (62%) Neomycin‐polymyxin b sulphates‐bacitracin 2 (7.5%)
Hypertriglyceridemia 15 (51.8%) Artificial tears 2 (5%)
Seizures 3 (10.3%) Latanoprost 0.005% 1 (2.5%)
Hyperadrenocorticism 2 (6.9%) Ciprofloxacin 0.3% 1 (2.5%)
Hepatopathy 2 (6.9%) Timolol 0.5% 1 (2.5%)
Hypoadrenocorticism 1 (3.4%) Tropicamide 1 (2.5%)
Chronic kidney disease 1 (3.4%) Edetate disodium (EDTA) 2% 1 (2.5%)
Pancreatitis 1 (3.4%) Moxifloxacin 0.5% 1 (2.5%)
Gastroenteritis 1 (3.4%) Flurbiprofen 0.03% 1 (2.5%)
Recurrent pyoderma 1 (3.4%) Tobramycin 0.3% 1 (2.5%)
SCHECHTMANN et al.   
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   5

tobramycin 0.3% (n = 1 dog), timolol 0.5% (n = 1 dog), pred- dogs), serum biochemistry (n = 15 dogs), minimum 12 hours
nisolone acetate 1% (n = 1 dog), ciprofloxacin 0.3% (n = 1 fasting triglycerides (n = 10 dogs), urinalysis (n = 4 dogs),
dog), cefazolin 5.5% (n  =  1 dog), and lubricant eye drops serum cholesterol (n = 3 dogs), total thyroxine level (n = 4
(Genteal Tears®) (n = 1 dog). dogs), urine culture (n = 2 dogs), fructosamine (n = 2 dogs),
Systemic oral medications were already being adminis- specific canine pancreatic lipase (n  =  1 dog), bile acids
tered in 20/29 dogs at the time of diagnosis. Medications in- (n = 1 dog), thyroid stimulating hormone level (n = 1 dog),
cluded were carprofen (n  =  2 dogs), amoxicillin/clavulanic abdominal ultrasound (n = 1 dog), liver cytology (n = 1 dog),
acid (n  =  2 dogs), phenobarbital (n  =  2 dogs), and aspirin polymerase chain reaction (PCR) canine Leptospirosis pro-
(n  =  2 dogs), and one dog each received prednisone, leve- file (n  =  1 dog), PCR canine tick borne panel for Babesia
tiracetam, clonazepam, enrofloxacin, diphenhydramine, tra- canis, Bartonella henselae, Bartonella vinsonii, Anaplasma
madol, and marbofloxacin. Subcutaneous isophane insulin phagocytophilum, Ehrlichia canis, Rickettsia rickettsii,
suspension was administered in 18/30 dogs (60%). Neorickettsia risticii, Mycoplasma hemocanis (n  =  1 dog),
There were 40/40 eyes (30 dogs) diagnosed with LLA, and adrenocorticotropic hormone stimulation test (n  =  1
which were administered topical ophthalmic medications. dog).
The topical medications were either specifically for LLA Hypertriglyceridemia was present in 15/18 dogs that had
and/or concurrent ocular disease (Table 3). Oral systemic triglyceride levels measured concurrent with LLA diagnosis
medications were also administered at time of diagnosis of with an average of 1,087 mg/dL (±544), with normal serum
LLA (Table 4). triglyceride reference range reported to be 50‐150  mg/dL.6
Topical and oral medications administered differed be- The 18 dogs that had triglyceride levels measured included 10
tween ulcerated and nonulcerated dogs diagnosed with LLA. dogs with fasted triglycerides and eight dogs with nonfasted
There were 14/30 dogs (46.7%) with concurrent corneal serum biochemistry levels. Hypercholesterolemia was pres-
ulcers and LLA. Of these dogs, nine received oral anti‐in- ent in 11/15 dogs that had serum cholesterol levels measured.
flammatories only. No topical anti‐inflammatories were The average was 575 mg/dL (±232), with normal serum cho-
prescribed to any ulcerated patient. There were 16/30 dogs lesterol reference range reported to be 125‐300 mg/dL.6
(53.3%) that were nonulcerated with LLA. Topical anti‐in- Follow‐up examinations after diagnosis were available for
flammatories were prescribed to all nonulcerated patients. 24/30 dogs. The mean number of days until first re‐examina-
There were seven nonulcerated dogs, which received both tion was 8.1 days (±7.2), ranging from 1 to 29 days. Of the
topical and oral anti‐inflammatories. 24 dogs that were re‐examined (31 eyes with LLA), the LLA
Diagnostic testing was performed concurrent with the di- resolved in all eyes. The mean number of days between date
agnosis of LLA in 21/29 dogs. Complete blood count (n = 15 of diagnosis and date of complete resolution was 20.2 days
(±34.0) and ranged from 4 to 175 days.
T A B L E 4   Oral medications prescribed at diagnosis of LLA The mean number of days to LLA resolution in dogs with
Number of dogs corneal ulceration was 13.2 days (±9.5) and ranged from 2
Oral medications at diagnosis of LLA (n = 30) to 29 days. There were 7/14 dogs (50%) that resolved LLA
at the same time the ulcers were healed. LLA did not persist
Meloxicam 6 (20%)
in any patients that had healed ulcers. The mean time to LLA
Carprofen 6 (20%)
resolution in the nonulcerated group was 28.5 days (±47.0)
Aspirin (acetylsalicylic acid) 4 (13.3%)
and ranged from 4 to 175 days.
Tramadol 3 (10%) Lipid‐laden aqueous humor recurred at least once in 4/24
Minocycline 2 (6.7%) dogs (16.6%). One diabetic Maltese with hypertriglyceri-
Omega 3 fish oils 2 (6.7%) demia had two episodes of recurrence, first in OU and sec-
Niacin 1 (3.3%) ondly in only OS. That specific dog had recurrence in OU
Niacinamide 1 (3.3%) due to lens‐induced uveitis and then in OS again caused by
Doxycycline 1 (3.3%) lens‐induced uveitis 33 days apart. Lens‐induced uveitis was
a presumed contributor to LLA due to the presence of ma-
Enrofloxacin 1 (3.3%)
ture cataracts with water clefting. In animals with LLA, the
Metronidazole 1 (3.3%)
chance of a recurrence was not significantly associated with
Cefpodoxime 1 (3.3%)
either phacoemulsification or corneal ulcers specifically or
Famotidine 1 (3.3%) concurrent systemic disease.
Ocu‐GLO™(lutein, grapeseed, extract, and 1 (3.3%) The majority of eyes, 32/40 (80%), with LLA presented
omega 3 fatty acids) with vision and maintained it for the duration of having LLA.
DiaVetin™(astaxanthin, fenugreek, and cin- 1 (3.3%) There were 8/40 eyes (20%) that were nonvisual at the diag-
namon extract) nosis of LLA and regained vision at resolution. There was
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6       SCHECHTMANN et al.

one dog historically blind in one eye from chronic glaucoma

when diagnosed with LLA. One dog developed glaucoma at
the resolution of LLA but was still visual. That particular dog
became blind in the eye diagnosed with glaucoma 7 months
after LLA resolution. There was also one dog that was nonvi-
sual at the diagnosis of LLA and remained nonvisual in that
eye despite resolution due to the development of severe lens‐
induced uveitis.

4  |   D IS C U SS ION
Lipid‐laden aqueous humor occurs when there is increased
permeability of the blood‐aqueous barrier (BAB), and there
is either physiological (postprandial) or pathological hy-
perlipidemia (primary or secondary).9,10,23,25,29-31 Systemic
hyperlipidemia refers to increased serum or plasma concen-
trations of cholesterol and/or triglycerides.1-3 Because lipids
are water‐insoluble molecules, they cannot be transported F I G U R E 4   Creamy white lipemic aqueous
in aqueous solutions such as plasma and are therefore trans-
ported in macromolecular complexes called lipoproteins.2 the majority of dogs diagnosed with LLA. Furthermore, both
The four main classes of lipoproteins in dogs each have a studies showed that most dogs had complete resolution of
separate function and differ in their physical characteristics.3 LLA at the first re‐evaluation and there was a low rate of
The largest lipoproteins are the chylomicrons responsible for recurrence after complete resolution.
the transfer of dietary (exogenous) lipids from the small in- Conversely, in the previous study describing canine LLA
testine to the circulatory system. The three other lipoproteins etiologies, there was not a statistically significant difference
transport endogenous lipids: very‐low‐density lipoproteins between the mean age of the study population and the refer-
(VLDL) and low‐density lipoprotein (LDL) carry triglyc- ral population. Additionally, in the previous analysis, male
erides and cholesterol whereas high‐density lipoproteins dogs were statistically overrepresented whereas there was no
(HDL) carry excess cholesterol.3 In dogs, it is the triglyc- significance of sex in the current study. The previous study
eride‐rich lipoproteins, both chylomicrons and VLDL that identified hypothyroidism as one of the most commonly di-
result in visible lipemia in the lumen of blood vessels or in agnosed systemic diseases. Notably, hypothyroidism was not
the anterior chamber.10 The lipid is only visible if triglyceride
levels are abnormally high (>450 mg/dL) because triglycer-
ides are transported by lipoproteins whose size is of the same
order of magnitude as the wavelength of visible light; raised
cholesterol levels do not alter aqueous appearance.15,31 The
appearance of lipemic aqueous may be white (Figure 4) or
creamy if chylomicrons are elevated or pearlescent (Figure
5) if there are excessive triglycerides without the presence of
chylomicrons.15,31
Lipid‐laden aqueous humor and its etiologies have been
previously well described in a retrospective study evaluating
75 dogs.11 The current study shares similar findings with
the previous study, including Miniature Schnauzers being
overrepresented and a parallel in the mean age of diagno-
sis. Moreover, in both studies, previous intraocular surgical
procedure, corneal ulcerations, and cataracts were identified
as the most common predisposing ocular causes of LLA.11
The previous and current study also showed LLA as an idio-
pathic manifestation. Diabetes mellitus was the most statisti-
cally represented systemic disease in both analyses. In each
study, triglyceride and cholesterol values were increased in F I G U R E 5   Pearlescent lipemic aqueous
SCHECHTMANN et al.
identified as a contributing factor in our study, perhaps be-
cause thyroid testing was performed in only five cases.
In the present study, Miniature Schnauzers were signifi-
cantly more likely to have LLA compared with mixed‐breed
dogs. This was based, however, on a small sample size of
Miniature Schnauzers and mixed‐breed dogs with LLA.
Miniature Schnauzers are likely predisposed to LLA due to
primary idiopathic hyperlipidemia encountered in the breed.6-8
The hyperlipidemia in Miniature Schnauzers is characterized
by primary hypertriglyceridemia, which is caused by increased
amounts of VLDL with or without chylomicronemia.32 The
mechanism of the aberrant lipid metabolism is not entirely
known; however, it is suggested that it is due to delayed clear-
ance of triglyceride‐rich lipoproteins from circulation.8,32
Diabetes mellitus can worsen primary hypertriglycer-
idemia because insulin insufficiency causes decreased
lipoprotein lipase production and subsequent delayed tri-
glyceride‐rich lipoprotein clearance.32 In this study, almost
all Miniature Schnauzers with LLA also had diabetes mel-
litus. Other breeds most commonly identified in this LLA
study included Yorkshire Terriers and Miniature Pinschers.
Previous reports show that Yorkshire Terriers and Miniature
Schnauzers have increased risk of developing diabetes melli-
tus and therefore secondary hyperlipidemia.33,34
The mean age of all dogs diagnosed with LLA in the study
was 9.6 years (±2.5) and significantly younger than the referral
population (P = .0034). The mean age of Miniature Schnauzers
specifically diagnosed with LLA was 8.4 years (±2.4). Dogs
with LLA were on average one year younger than dogs with-
out LLA. Primary hyperlipidemia has been shown to be more
prevalent among older dogs; >75% of healthy Miniature
Schnauzers at least 9 years of age had hypertriglyceridemia.35
Moreover, severity of hypertriglyceridemia has been shown to
increase with age as the majority of Miniature Schnauzers with
moderate to severe hyperlipidemia were 6  years or older.35
Since the majority of dogs affected with LLA were Miniature
Schnauzers either 9 years or slightly younger, this may explain
the significant age difference between the sample size and the
referral population. The small LLA study population may have
skewed the data, however, to show age as a significant risk
factor for LLA and may not be a true clinical finding. Sex was
not associated with LLA in the overall test of association of sex
and LLA. It has been shown that there is no difference between
male and female Miniature Schnauzers with respect to preva-
lence to hypertriglyceridemia.35 It has also been reported that
there are no sex differences in total lipids between entire male
dogs and entire females. 15
LLA was seen most commonly in eyes that had corneal
ulcers, pseudophakia, and cataracts. All three of these ocular
findings cause uveal inflammation.12,29,36-38 Uveitis is caused
by tissue injury, and the clinical signs that follow are due to
the disruption of the BAB and release of chemical media-
tors after damage.11,29 Lipoproteins cannot enter the anterior
  
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chamber without some degree of disturbance to the BAB, but
may themselves disrupt the barrier9,10,12,23,25,39 The intercel-
lular junctions of the endothelium of iridal vessels and the
nonpigmented ciliary epithelium comprising the BAB usu-
ally prevent molecules larger than 40 Angstroms (A) from
passing.9,24 Canine lipoproteins, in particular, may vary in
size from 55 to 5000 A.25
Concurrent systemic disease affected 22/29 dogs (75.9%).
The most prevalent systemic diseases included diabetes mel-
litus and hypertriglyceridemia. Systemic diseases suspected
to have potential impact on the development of LLA have
mechanisms that may contribute to BAB breakdown. Primary
or secondary hyperlipidemia may cause BAB breakdown by
causing endothelial dysfunction via oxidative stress.40,41 In
hyperlipidemic states, the vascular endothelium is exposed to
increased triglyceride‐rich lipoproteins causing endothelial
instability by inducing oxidative stress.40,41 Hyperlipidemia
affects lipoprotein composition with excessive triglyceride
enhancement resulting in prolonged endothelial residence
time and therefore leading to increased predisposition to
endothelial cell injury.41 There is evidence suggesting that
postprandial hyperlipidemia is correlated with triglyceride
enrichment of VLDLs and LDLs inducing oxidative stress.
The oxidative stress may be the result of greater free radi-
cal production, which form reactive nitrogen species causing
blunted flow‐mediated vasodilation and subsequent endothe-
lial dysfunction.40,41
Diabetes mellitus also causes dysfunction of small blood
vessels throughout the body, which manifests in the eye as
BAB breakdown.28 Increased levels of glucose in human di-
abetic patients cause edema of the iris capillary endothelium
contributing to decreased vessel resistance and increased
fragility.42 Diabetes mellitus has also been associated with
increased retinal vessel permeability in canines disrupt-
ing the blood‐retinal barrier.42 Surgical trauma induced by
phacoemulsification could potentially cause disruption to the
BAB more easily in diabetic patients. This may explain why
LLA in patients with both diabetes mellitus and phacoemul-
sification was found in the present study.
There were 5/10 dogs with bilateral LLA with no history
of recent phacoemulsification (>14 months postoperatively),
corneal ulceration, or mature cataracts. It has been proposed
that the leaking of vessel endothelium is a function of the con-
centration and potentially the quality of lipoproteins and not
solely a function induced by inflammatory processes.39 Thus,
elevated circulating lipoproteins, particularly those contain-
ing triglycerides, may have the potential to be delivered to
ocular tissues without pre‐existing vascular damage. This
could explain why there were dogs with bilateral LLA with
no clinical evidence indicating recent BAB disturbance. It can
be suggested that systemic hyperlipidemia incited uveitis.
All dogs diagnosed with LLA had complete resolu-
tion with an average of 20.2 days (range 4‐175 days) from
 |
8       SCHECHTMANN et al.
diagnosis with topical and oral anti‐inflammatory medica-
tions, as is the standard for the treatment of anterior uve-
itis.12,29 These data are skewed, however, as there were
some dogs that did not have an initial follow‐up for up to
three weeks. Moreover, in the study population LLA was
found to resolve more quickly in ulcerated versus nonul-
cerated dogs. This was likely because ulcerated patients
had more frequent recheck examinations and closer mon-
itoring. This suggests LLA resolution was identified ear-
lier than in nonulcerated dogs. It is also possible that with
healed ulceration, there is more immediate resolution of
the reflex uveitis that caused the LLA compared to other
causes such as lens‐induced uveitis in which disruption to
the iridal vasculature may persist.
Recurrence after complete resolution was minimal with
only 4/24 dogs (16.7%) having a single episode of recur-
rence, and 1/24 dog (4.2%) having two episodes of recurrence.
Phacoemulsification and corneal ulcers along with systemic
disease were found to have no significant effect on recurrence of
LLA. However, since the number of recurrences was so small,
conclusions based on the lack of significance cannot be made.
Limitations of the study were associated with its retrospec-
tive nature and the small sample size of dogs identified with
LLA. There was inconsistent and limited data including lack
of comprehensive diagnostics and follow‐up examinations for
some dogs. Additional research is required to further elucidate
the effects of diet for at‐risk patients and systemic diseases such
as pancreatitis with the manifestation of LLA. Future studies to
determine the pathophysiology of the BAB in hyperlipidemic
states are necessary to better understand the causation of LLA,
whether hyperlipidemia alone causes breakdown.
Lipid‐laden aqueous humor resolved in all patients exam-
ined, and only one dog developed an immediate complication
after its resolution. This study suggests a good short‐term
prognosis for LLA. Given the inflammatory nature of lipid,
however, and potential for short or long‐term complications
such as glaucoma, aggressive medical intervention is rec-
ommended in cases with LLA. After initial diagnosis and
commencing treatment of LLA, the first recheck should be at
1 week and then 2 weeks after that considering the resolution
period.
ORCID
Simone A. Schechtmann  https://orcid.
org/0000-0002-1153-6981
Tammy M. Michau  https://orcid.
org/0000-0001-8161-7851
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How to cite this article: Schechtmann SA, Stine JM,
Miller TR, Welihozkiy A, Michau TM. A
retrospective analysis of lipid‐laden aqueous humor in
dogs: Thirty cases. Vet Ophthalmol. 2019;00:1–9.
https​://doi.org/10.1111/vop.12719​