Veterinary Ophthalmology (2008) 11, 2, 91–98

Blackwell Publishing Inc

Congenital orbital cysts of neural tissue in two dogs

Alain Regnier,* Isabelle Raymond-Letron* and Robert L. Peiffer†
*Department of Clinical Sciences, National Veterinary School, 23 chemin des Capelles, B.P. 87614, 31076 Toulouse Cedex 3, France; †Merck Research
Laboratories, Merck & Co. WP45-226, PO Box 4, West Point, PA 19486, USA

Address communications to: Abstract

Alain Regnier
Tel.: +33 561 193832
Fax: +33 561 193203
e-mail: a.regnier@envt.fr
Presented as an abstract at the
Annual Meeting of the
European College of Veterinary
Ophthalmologists and European
Society of Veterinary
Ophthalmology, Porto,
June 2005.
A 3-month-old English Cocker Spaniel and a 6-month-old miniature poodle
presented with clinical signs related to an abnormal right eye since birth. In both dogs,
the right globe could not be identified and was replaced by a fluctuant intraorbital mass
covered by a vascularized mucous membrane. Ultrasonography demonstrated that both
masses were cystic structures markedly larger in size than the normal contralateral
globes. In both cases, surgical excision revealed a multilobular cyst filling the whole
orbital cavity. Histopathologic examination and immunostaining for glial fibrillary acid
protein and S100 protein supported a diagnosis of neural cysts associated with ocular
dysplasia. The definitive diagnosis was congenital cystic eye and microphthalmos with
cyst for the Cocker Spaniel and miniature poodle, respectively. Karyotype was normal in
both dogs. Congenital cystic eye and microphthalmos with cyst result from defects in
early embryonic life that arise following formation of the optic vesicle and prior to
closure of the optic fissure. To the authors’ knowledge neither has been reported in the
canine species. They should be considered in the differential diagnosis of orbital cysts in
dogs.
Key Words: colobomatous cyst, cyst, cystic eye, dog, microphthalmos, orbit

INT RO DUC T IO N C A S E R E P O RT S

Orbital cystic lesions of children encompass a broad range of Case 1

conditions which vary in etiology, presentation, and patho-
logic appearance.1,2 They can be divided into four major
groups: (i) cysts of the surface epithelium, such as dermoid
cysts; (ii) teratomatous cysts; (iii) neural cysts; and (iv)
secondary cysts from adjacent structures, such as mucocele
and dentigerous cysts.1,3 Neural cysts include those associated
with developmental abnormalities of the globe and those
associated with brain and meningeal tissue.1 Those related
to abnormal ocular development are further divided into
congenital cystic eye and microphthalmos with cyst.1,4 The
latter represents a subset in the spectrum of ocular colobomas
and is also termed colobomatous cyst.1,4 These two ocular
abnormalities are evident at birth in most cases, and they are
considered sufficiently uncommon in pediatric ophthalmology
that individual case reports are usually published in the
literature.5–12 In a recent paper on congenital cystic eye in
children, the authors only cited 14 cases, including their two
cases, reported in the medical literature since 1964.3 This
report describes two cases of congenital orbital cysts in the
dog resembling neural cysts associated with ocular maldevelop-
ment in children.
A 3-month-old, male, English Cocker Spaniel presented for
examination with an abnormal right eye, which had slowly
enlarged since the eyelids opened. The other puppies in the
litter were described as normal but were not available for
examination. The dam was primiparturient and had not
received any medical treatment nor had she had access to
chemicals prior to or during pregnancy. The sire had been
used before and had not produced offspring with congenital
defects. The puppy was alert, and the only abnormalities
seen were those limited to the right eye. Ophthalmic exami-
nation revealed that on the right side the palpebral fissure
length was normal, but the interpalpebral space was narrow
and associated with bulging of both eyelids (Fig. 1). Palpa-
tion of the eyelids and periorbital region did not elicit pain,
and did not exhibit any thrill or pulsation. Eyelid retraction
was limited to 4–5 mm by a pink, vascular mucous mem-
brane that extended from the palpebral conjunctiva of the
upper eyelid to that of the lower eyelid and covered an
intraorbital mass. There was no visible globe, and palpation
through the upper eyelid revealed a soft intraorbital mass.
Schirmer tear test value was 7 mm/min. The left eye was normal.

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92 r e g n i e r , r ay m o n d - l e t r o n a n d p e i f f e r
On B-scan images (10-MHz transducer), the intraorbital
mass appeared as an anechoic and irregularly shaped struc-
ture when scanned in a vertical plane. Patterns of echogenicity
within the cystic cavity resembled curvilinear septations. The
horizontal scan plane disclosed a round echogenic lesion
with an anechoic central area, located near the center of the
anechoic cavity, and compatible with an ectopic lens (Fig. 1).
© 2008 American College of Veterinary Ophthalmologists, Veterinary Ophthalmology, 11, 91–98
Figure 1. External photograph (a) and horizontal
B-scan image (b) of congenital cystic eye in an
English Cocker Spaniel. A narrow vertical
palpebral fissure and bulging of eyelids were
observed on right side (a). No definite intraocular
structures could be identified on the ultrasound
image (b) except for a round echogenic structure
(arrowhead), and an echogenic clump of tissue at
the posterior pole of the hollow structure (arrow).
Figure 2. Photomicrographs of the cyst wall of a
congenital cystic eye in an English Cocker Spaniel.
On this portion of the irregularly shaped
formaldehyde-fixed specimen (a), the neuroglial
tissue (arrows) is surrounded by a variably thick
layer of connective tissue externally (arrowheads).
Adipose tissue (*) is present external to the outer
wall, and a malformed lens (L) lies within the
cavity. H&E, ×10. Section illustrating that various
degrees of differentiation exist in the
neuroepithelial lining (b). H&E, ×200. This area
(c) shows the immature inverted retina with
ganglion cells externally located (arrow) and a
unique internal granular cell layer. H&E, ×200.
A multilayered rosette formation is present in this
area of immature inverted retina (d). H&E, ×200.
The anteroposterior length of the cystic cavity was 20.4 mm
compared to a length of 14.8 mm for the fellow eye. A develop-
mental anomaly of the globe was suspected but a definite
diagnosis was not made. As slow enlargement of the mass was
reported by the owner, surgical excision was recommended
and performed using the lateral enucleation technique.
Intraoperatively, a multilobular, thin-walled, cystic mass was
 o r b i ta l n e u r a l c y s t s i n d o g s 93

found to fill the entire right orbit. The mass was extensively
adherent to the medial orbital wall and during the final
phase of the dissection it ruptured, releasing a clear, yellow,
serous fluid. The third eyelid was identified and removed.
No evidence of communication between the cystic mass and
the frontal sinus or cranial cavity was noted. Gross examination
of the specimen disclosed a ruptured cystic mass characterized
by a smooth but irregular outer surface due to fibrous con-
strictions, and covered by scant orbital fat and extraocular muscle.
All excised tissue was fixed in buffered 10% formalin, rou-
tinely processed for histologic examination, and stained with
H&E. Tissue sections were also submitted for immuno-
histochemical assessment for glial fibrillary acid protein (GFAP
M0761) and S100 protein (Polyclonal rabbit anticow S100
protein, Z0311). The antibodies were from a single commercial
source (Dakocytomation, Trappes, France), and reactivity was
assessed with appropriate positive and negative controls.
Microscopically, the cystic structure was surrounded by
islands of epithelial tissue including scattered lobules of
atrophic lacrimal tissue. The outer layer of the cyst wall con-
sisted of a thin layer of more or less compact, vascularized
connective tissue, resembling sclera, to which adipose tissue
and some extraocular muscles were attached (Fig. 2). This layer
was penetrated at its posterior pole by an optic nerve-like
structure. The inner surface of the cyst wall was lined with a thin
basophilic layer of poorly differentiated neuroepithelial tissue,
in which areas of inverted immature retina with a single granular
layer and occasional foci of photoreceptor differentiation
and rosette formation were seen (Fig. 2). This inner layer
demonstrated GFAP and S100 positive immunohistochemical
staining which attested its neural origin (Fig. 3). The cyst
contained a rudimentary lens covered by a single cuboidal
Figure 3. Areas of the cyst wall lining of a congenital cystic eye in an
layer of epithelial cells surrounded by a thin and regular basal English Cocker Spaniel immunostained for GFAP (a) and S100 protein
lamina to which remnants of the tunica vasculosa lentis were (b) The strong brown reactivity of the immature retina with anti-GFAP
attached (Fig. 2). Retinal pigment epithelium, cornea and antibodies is seen in this area of rosette formation (a). The primitive
uveal tissue could not be identified. Serial 5-μm sections of photoreceptors are stained brown with immunolabeling for S100
the specimen failed to disclose the presence of an associated protein (b). Anti-GFAP and anti-S100 immunoperoxidase,
microphthalmic eye. The pathologic diagnosis for this dog was diaminobenzidine chromogen, hematoxylin counterstain; ×200.

neural cyst associated with clinical anophthalmia, an abnormal

ocular development in the spectrum of the congenital cystic eye.
Case 2
A female miniature poodle rehomed from a humane shelter
and aged approximately 6 months was presented for exami-
nation of the right eye. Information concerning the dam, sire,
other puppies in litter and the history of the problem was not
available. The right palpebral fissure appeared wider than
that of the fellow eye with a pink mass distending the eyelids.
There was no blepharospasm and only a slight epiphora.
Closer inspection revealed a highly vascular, slightly dark
pigmented mucous membrane protruding through the right
palpebral fissure (Fig. 4), and adherent to a soft intraorbital
mass. No visible cornea and limbus could be identified but
the nictitating membrane and lacrimal puncta were present.
Schirmer tear test value was 15 mm/min. Examination of the
left eye was unremarkable.
B-scan ultrasonography demonstrated a septated cystic
lesion in the right orbit, markedly larger in size (maximum
axial length: 29.1 mm) than the normal left eye (axial length:
17.2 mm). On vertical and horizontal views, the pattern of
echogenicity within the mass appeared as curvilinear septa-
tions manifesting as abnormal echogenic material in conti-
nuity with its wall, and protruding into its lumen (Fig. 5).
Surgical excision of the intraorbital mass was performed
similar to the previous case; intraoperatively, a cystic lesion
was found to fill the whole orbit, extending to the orbital
apex. Although adherent to the orbital wall, the mass was
dissected in toto. Macroscopically, the cystic lesion resembled
that of the previous case, with thin and transparent walls
that allowed visualization of the clear yellow fluid filling the
cavity. Extraocular muscle tissue was present. When cut in
half along the sagittal plane, the formaldehyde-fixed cyst

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94 r e g n i e r , r ay m o n d - l e t r o n a n d p e i f f e r

Figure 4. External photograph of microphthalmos with cyst in a

miniature poodle showing the vascularized and pigmented wall of the
orbital mass that protrudes through the right palpebral fissure.

appeared multilocular with one large cystic cavity and

several smaller ones. At the approximate center of the cavity,
a small (about 4.0 × 5.2 mm in size), nodular pigmented
mass was connected to the superior and inferior aspects of
the cyst wall by trabeculated strands of white tissue (Fig. 6).
The specimen was processed for histologic and immuno-
histochemical evaluations as described for case 1.
Microscopically, the outer surface of the cyst wall was
composed of dense connective tissue with attached adipose
tissue, muscle, and nerve fibers. The inner surface consisted
of a layer of poorly differentiated neuroepithelial tissue
including areas of immature retina identified by the presence
of small round basophilic nuclei. This layer of neuroepithe-
lium was positive for GFAP and S100 protein. In some areas
the neuroepithelial tissue interdigitated with the overlying
connective tissue layer and in others it formed small projec-
tions into the cyst lumen. On serial sectioning, it was found
that the connective tissue layer of the neural cyst became
continuous with the thicker wall, resembling sclera, of a
small cystic, pigmented mass that was in fact the pigmented Figure 5. Vertical (a) and horizontal (b) plane ultrasonograms
nodular mass macroscopically observed (Fig. 6). The struc- (10 MHz transducer) of microphthalmos with cyst in the right orbit of
tural differentiation seen in this pigmented mass was con- a miniature poodle. The multilobular cystic lesion fills the entire orbital
sidered typical for that of a severely microphthalmic eye. cavity (a). The hyperechoic excrescences of the cyst wall represent the
Internally, the sclera was lined by a layer of pigmented uveal cyst septations protruding into the lumen of the cavity (b).
tissue with areas of choroidal differentiation (Fig. 6). A
segment of normal appearing anterior uveal tissue, including
iris, ciliary body and ciliary processes, was also identified, globe with the cavity of the neural cyst (Fig. 6). The anterior
but the structures of the iridocorneal angle were absent. The part of the microphthalmic globe, in place of the normal
choroid-like tissue was lined by neuroepithelial tissue in an cornea, consisted of a dense thick vascularized collagenous
arrangement which resembled developmentally immature stroma, in continuity with the scleral-like layer, and with an
detached retina (Fig. 6). This immature retina contained irregular multilayered nonkeratinized epithelium with a
areas with dysplastic rosettes. A small, round and dysplastic pigmented basal cell layer. This area of epithelium was
lens was adherent to the ciliary processes. At the posterior circumferentially in continuity with a nonkeratinized bi-
pole of the microphthalmic globe, the presence of a colo- layered cuboïdal epithelium containing numerous goblet cells.
bomatous cleft allowed continuity of the central cavity of the Based on the apposition of a globe with severe microphthalmia

© 2008 American College of Veterinary Ophthalmologists, Veterinary Ophthalmology, 11, 91–98


to a neural cyst and apparent continuity of globe and cyst
cavities, the diagnosis of microphthalmos with cyst was
established.
To complement the pathological diagnoses, a chromo-
some analysis of both dogs was carried out from cultures of
peripheral blood lymphocytes, as currently performed in the
cytogenetics laboratory of our institution.13 No altered
chromosomes were identified, so the karyotype was inter-
preted as normal for each case.
© 2008 American College of Veterinary Ophthalmologists, Veterinary Ophthalmology, 11, 91–98
o r b i ta l n e u r a l c y s t s i n d o g s 95
Figure 6. Gross photograph (a) of the parasagittal section of a
formaldehyde-fixed microphthalmos with cyst in a miniature poodle
and microscopic sections (b–d) of the microphthalmic eye. Notice the
relationship between the microphthalmic eye (arrows) and the orbital
cyst (a). The communicating cleft between the microphthalmic eye and
the cavity of the orbital cyst is indicated by the bent arrow (b). H&E,
×10. Close-up view of the choroid and partially detached immature
retina (c). H&E, ×100. Ciliary body with muscle fibers and long and fine
ciliary processes (d). H&E, ×100.
D I S C U S S IO N
Neural cysts associated with ocular dysplasia in children are
thought to result from failures of embryologic events that
take place early in ocular development.1,3 In vertebrates the
first morphological sign of eye development is the bilateral
evagination of diencephalon that marks the appearance of
the optic sulci,14,15 identified on day 13 of gestation in the
dog.16 Continued evagination of the optic sulci leads to the
96 r e g n i e r , r ay m o n d - l e t r o n a n d p e i f f e r
formation of the optic vesicles that come into proximity with
the surface ectoderm, giving rise to a focal thickening of the
surface ectoderm, the lens placodes, identified by gestational
days 15–17 in the dog.16 Interaction of the optic vesicle with
the lens placode leads to their coordinated invagination
resulting in the formation of the primitive lens vesicle and a
double-layered optic cup that will give rise to the photo-
receptor and pigment epithelial layers of the retina.14,15 Normally,
the lens vesicle and optic cup are distinct by gestational day
19 in the dog.16 When, for unknown reasons the optic vesicle
does not invaginate, the development of the globe is arrested
and the cavity of the optic vesicle persists. The ectodermal
and neural elements do not differentiate, and the orbit thus
contains, instead of an eye, a congenital cystic eye lined by
neuroglial tissue with no evidence of normal ocular struc-
ture.3,17,18 In children, the arrest in transformation of the
optic vesicle into optic cup most commonly occurs before
the end of the 7 mm stage of the embryonic development.8 If
the insult occurs shortly after this stage, partial invagination
of the optic vesicle may result in rudimentary cornea,3 or
lens and immature retina with rosette formation.8
Under normal circumstances, the process of optic vesicle
invagination progresses from inferior to superior and leads
to the formation of a groove that runs along the inferior side
of the optic cup and stalk.15 This slit-like channel is termed
the optic, embryonic, choroid or fetal fissure.14,15 From the
8-mm stage of gestation in humans9 and after gestational day
25 in the dog,16 the two lips of the optic fissure and stalk will
fuse so that the optic cup will be complete and optic stalk
will become a tube.14,15 Improper fusion of the edges of the
fissure may occur anywhere along the length of the cleft, and
produces a defect in the neuroectodermal tissues manifested
as a typical coloboma, or rarely as microphthalmos with
cyst.5 This latter congenital malformation is defined as a
neuroectoderm-lined mass that protrudes through a colo-
boma in the wall of a microphthalmic eye.1 The probable
mechanism of formation of microphthalmos with cyst is
overgrowth of the inner neuroectodermal layer at the mar-
gin of the persistent optic fissure, resulting in development
of a cyst originally continuous with the space between the
two layers of the optic cup.5,9 If the wall of the cyst separating
the vitreous cavity from the future subretinal space is absent,
the cyst communicates directly with the vitreous cavity.9
Congenital cystic orbital lesions associated with ocular
maldevelopment seem uncommon in domestic animals, even
though they probably occur more frequently than the two
cases of this report suggest. In addition to these cases, anecdotal
reports of congenital cystic eye in a foal,17 and in a rabbit,19 can
be found in the current literature. To the authors’ knowledge,
the unique combination of clinical findings and histopatho-
logical lesions seen in the two patients of this study has not
been previously reported in the canine species. These ocular
malformations were probably congenital as they were appar-
ent in the first few months of life, and they fulfilled many of
the clinical and histological criteria of orbital cysts of neural
tissue associated with ocular maldevelopment in children.1,3–9
© 2008 American College of Veterinary Ophthalmologists, Veterinary Ophthalmology, 11, 91–98
Congenital cystic eye usually presents as a soft mass filling
the orbit and distending the upper or lower eyelid,1,3 as in
the English Cocker Spaniel of the present study (case 1).
Microphthalmos with cyst varies in its presentation, and may
appear as a cyst associated with an obvious microphthalmic
eye, or as a large cyst associated with a small eye that is not
clinically detectable.1,3,9 This clinical manifestation was present
in the miniature poodle of this study (case 2). Congenital
orbital cysts of neural tissue usually occur unilaterally,1,3 but
cases of bilateral congenital cystic eye11 or microphthalmos
with cysts6,20,21 have been reported. Congenital cystic eye
associated with contralateral microphthalmos with cyst has
also been observed in one child.9 Orbital neural cysts can occur
in isolation or with associated malformations including eyelid
abnormalities, such as eyelid coloboma10 contralateral hyper-
plastic primary vitreous,10 and nonocular abnormalities, such as
facial clefting and malformation of the nostril,9,11 which are
more frequent when there is bilateral involvement. No such
abnormalities were observed in the dogs of this study.
Differential diagnoses of orbital cysts in the dog, include
cystic structures of the orbit and periorbital region arising
from the orbital lacrimal gland, gland of the nictitating
membrane, zygomatic salivary gland, or lacrimal system.22,23
Inflammatory cysts, such as abscess or parasitic cyst can also
be considered,23,24 although parasitic cysts are rarely encoun-
tered in the orbit.24 All these ocular lesions are usually dif-
ferentiated by the presence of a globe and their external
appearance which includes periorbital swelling, exophthal-
mos and/or protrusion of the nictitating membrane.22–24
Orbital ultrasonography was useful in the two present cases,
because it demonstrated for each of them the presence of a
large multilobulated cystic structure filling the entire orbital
cavity. In children, ultrasonography,11,12,25 computed tomography
scan3,11,12,20 and magnetic resonance imaging3,11,12,21 have been
used to demonstrate the cystic appearance of the orbital mass,
and help differentiate the two types of neural cysts. Diagnostic
imaging studies can show a uni- or multilocular cyst without
clearly defined structures in patients with congenital cystic
eye,3,11,12 while they can reveal a small globe in apposition to
a cystic cavity and sometimes apparent continuity of vitreous
cavity and cyst contents in cases of microphthalmos with
cyst.20,21,25 In our case of microphthalmos with cyst, ultra-
sonography failed to detect the microphthalmic eye, probably
because it was too small. Fine needle aspiration of the
cystic structure and cytologic examination of the aspirate is
not currently recommended to confirm the diagnosis of
orbital neural cysts in children. In the dog, it might help in
differentiating congenital orbital cysts from inflammatory
cysts.
Definitive diagnosis is supported by pathologic examina-
tion of the orbital mass after its complete surgical excision.
Congenital cystic eye is histopathologically similar to the
cystic portion of microphthalmos with cyst, but the main
differentiating feature between the two malformations is
evidence of an associated microphthalmic eye detected with
serial sectioning of the specimen in case of microphthalmos

with cyst.3,11,26 Microscopically, the cyst wall of our two cases
consisted of an outer layer of fibrous connective tissue lined
by neuroepithelial tissue which stained positively for markers
of the primitive retina (i.e. GFAP and S100 protein), as
previously reported in children with neural cysts associated
with ocular maldevelopment.1,3,9,11,12 In the English Cocker
Spaniel (case 1) a dysplastic lens was present but serial
sections failed to disclose the presence of an associated
microphthalmic eye, hence the diagnosis of congenital cystic
eye. It is generally assumed that the lack of surface ectodermal
elements is a common feature of congenital cystic eye,1,17
but as stated before, partial invagination of the optic cup may
result in the presence of ectodermal elements and retinal
differentiation.3 Analysis of the human cystic eyes currently
published shows that malformed cornea or incompletely
developed lens have been identified in three of them.7,8,11
Presence of lens material and rosettes in our dog is consistent
with an embryonic effect that probably occurred after gesta-
tional day 19. An optic nerve-like structure was also identi-
fied in this cystic eye, as previously reported in the human
literature.8 In the miniature poodle (case 2), the malformed
eye associated with the cyst had many features in common
with cases previously described in children.6,9,20,21 The
microphthalmic eye of this dog demonstrated a spectrum of
anterior segment abnormalities, dysplastic lens, immature
retina, and a choroidal and scleral coloboma through which
the vitreous cavity communicated directly with the cyst
cavity. Extraocular muscles were observed in both dogs of
this study, which agrees with the fact that these ocular struc-
tures form independently and seem not to require normal
development of the globe.21
While one case of congenital cystic eye with coincidental
maternal varicella infection has been reported in a child,27
the etiology of orbital cysts of neural tissue in children is
usually unknown. Neither hereditary tendencies nor obvious
abnormalities during pregnancy have been described.1,3 The
etiology in our cases remained undetermined. Prenatal insult
due to drugs, particularly anthelmintics, or to other environ-
mental factors was not identified for the English Cocker
Spaniel with the congenital cystic eye, and no such informa-
tion was available for the miniature poodle with micro-
phthalmos with cyst. No chromosomal abnormality has been
noted in affected children,3,6,10–12 and similarly the results of
karyotype analysis were normal for the two dogs of the present
report.
In conclusion, the congenital cystic eye and micro-
phthalmos with cyst exhibited by these two dogs represent
abnormalities in early embryonic development of the eye.
These ocular malformations have clinical features in common
and their differentiation requires diagnostic imaging and
histopathologic studies.
A CKN O WLEDGMENT
We wish to thank Hélène Berland and Anne Calgaro for
performing the karyotype analyses.
© 2008 American College of Veterinary Ophthalmologists, Veterinary Ophthalmology, 11, 91–98
o r b i ta l n e u r a l c y s t s i n d o g s 97
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© 2008 American College of Veterinary Ophthalmologists, Veterinary Ophthalmology, 11, 91–98