Congenital ocular abnormalities of
Rocky Mountain horses
David
T. Ramsey, DVM1; Susan L. Ewart, DVM, PhD2; James A.
Render, DVM, PhD3; Cynthia S. Cook, DVM, PhD4; Claire A.
Latimer, DVM, MS5.
1Department
of Small Animal Clinical Sciences, 2Large Animal Clinical Sciences, and 3Pathology
and Animal Health Diagnostic Laboratory, College of Veterinary Medicine,
Michigan State University, East Lansing, MI 48824-1314; 4Veterinary
Vision, 219 North Amphlett Blvd, San Mateo, CA 94401; and 5Rood
& Riddle Equine Hospital, P. O. Box 12070, Lexington, KY
40513-1126.
Supported in part by a competitive grant from the
Harvey Fiege Genetic Research Fund, College of Veterinary Medicine, Michigan
State University.
The
authors thank Drs. Carrie Begin, Kristi Patterson, Joe Hauptman, Hal Schott,
and Mr. Ralph Common for assistance.
Running
title: Congenital eye anomalies of Rocky Mountain horses
Correspondence
to:
David
T. Ramsey, DVM
Department
of Small Animal Clinical Sciences
D-208
Veterinary Medical Center
Michigan
State University
East
Lansing, MI 48824-1314
(517)
353-3792 (office)
(517)
355-5164 (fax)
(e-mail:
ramseyd@cvm.msu.edu).
Structured Abstract:
Objective—To determine the incidence and describe ocular abnormalities in a
cross section of the population of Rocky Mountain Horses.
Design—Prospective
study.
Animals—Five hundred fourteen Rocky Mountain Horses.
Procedure—Ophthalmic examinations were performed using a slit lamp
biomicroscope and an indirect ophthalmoscope.
Intraocular pressures were measured by applanation tonometry.
Eyes from six horses were obtained for histologic examination.
Results— Cysts of the posterior iris, ciliary body, and peripheral retina
were detected most frequently (249 horses) and were always located temporally.
Curvilinear streaks of retinal pigmented epithelium extending from the
peripheral temporal retina marked the boundary of previous retinal separation
in 189 horses. Retinal dysplasia
was detected in 125 horses. Multiple ocular anomalies were evident in 71 horses and were
always bilateral and symmetrical. Affected
eyes had a large, clear, globular contour of the cornea with an apparent short
radius of curvature, a deep anterior chamber, miotic and dyscoric pupil, and
iris hypoplasia. Pupillary light
responses were decreased or absent and pupils failed to dilate after repeated
instillation of mydriatic drugs. Less
frequently encountered abnormalities included peripheral iridocorneal
adhesions and goniosynechiae. Congenital
cataract was always present in eyes with multiple abnormalities.
Intraocular pressures did not differ among horses with normal eyes and
horses with multiple ocular abnormalities.
Histologic examination of eyes corroborated the clinical appearance.
Conclusions—The
clinical and histologic findings in eyes of Rocky Mountain Horses appear
similar to congenital miosis with anterior megalophthalmos and megalocornea in
humans. We propose that the Rocky
Mountain Horse is a novel animal model for comparative study of this disease
in human beings.
Key Words:
Horse, congenital, eye, miosis, macrocornea, anterior megalophthalmos,
partial albinism.
Introduction—Congenital ocular
defects constitute 0.5 to 5.3 percent of the collective congenital defects
reported in horses (1-3). Congenital
ocular abnormalities of horses occur sporadically (4-16) and the cause is
seldom determined. Few studies
have reported results of ophthalmic examination of large numbers of horses of
a specific breed (17-18). In
1986, the Rocky Mountain Horse was recognized as a distinct breed, and an
association and breed registry were established.
Limited foundation stock has been used to intensively breed individual
animals with desirable traits and conformational characteristics, thereby also
favoring expression of undesirable traits.
Recently, we compared data obtained from independent ophthalmic
examinations and medical records of 19 Rocky Mountain Horses examined by two
of us (DTR, CAL). Results of data
review showed similar ophthalmic lesions at a rate considered greater than
sporadic. Ophthalmic lesions
appeared to be more prevalent in horses with a chocolate coat color and a
white mane and tail color. Detection
of high prevalence of similar ophthalmic lesions among related Rocky Mountain
Horses was the catalyst for the current study.
The purposes of the study reported here were to document ocular
abnormalities in Rocky Mountain Horses and to determine the incidence of
congenital ocular abnormalities within the breed by examining a large cross
section of the Rocky Mountain Horse population.
Material and
Methods—Inclusion
criteria for this study were Rocky Mountain Horses certified by the breed
registry and their progeny that were deemed certifiable by the breed registry
based on gait, temperament, conformation, and parentage.
Ophthalmic examinations were performed in a darkened stall before and
after topical administration of miotic drugs.
Pupillary dilation was induced by instilling 0.2 ml of tropicamide 1% (Mydriacyl,
Alcon Inc, Humacao, Puerto Rico) into the conjunctival fornix.
When pupils failed to dilate, 10% phenylephrine (Schein Pharmaceutical,
Inc, Florham Park, New Jersey) or 1% atropine (Alcon Inc, Humacao, Puerto
Rico) was administered topically. The
anterior ocular segment was examined by diffuse and focal illumination using a
portable hand-held slit lamp biomicroscope (SL 14, Kowa, Tokyo, Japan). Fundoscopy was performed using a portable binocular indirect
ophthalmoscope (Carl Zeiss, West Germany) and a condensing lens (Volk, Mentor,
Ohio). Corneal anesthesia was
achieved by topical instillation of 0.2 ml of proparacaine 0.5% (Alcaine,
Alcon Inc, Humacao, Puerto Rico). Intraocular
pressure (IOP) was measured by use of an applanation tonometer (TonoPen XL,
Mentor, Norwell, Massachusetts) in 30 horses with grossly globular appearing
corneas and in 40 horses with clinically normal eyes. Measurements of IOP were done in horses that ranged in age
between 6 weeks and 12.5 years. Coat
color, mane and tail color, gender, and date of birth were recorded for each
horse. Eyes were photographed and
results of ophthalmic examinations were recorded.
Registration papers and pedigrees of all horses examined were obtained
for future segregation analysis. Whole
blood samples were collected by venapuncture and desquamated epithelial cells
of the oral mucosa were collected on cytology brushes. Cellular DNA was isolated, purified, and stored for future
molecular genetic studies. Results
of segregation analyses are presented in a companion paper (19).
After euthanasia, globes from five horses with multiple ocular
anomalies (3 juvenile horses, two mature horses) and from one mature horse
with clinically normal appearing eyes were available for histologic
examination. Eyes were
enucleated, fixed in neutral-buffered 10% formalin, sectioned along the
midsagittal plane, and calottes were photographed.
Calottes were then processed by routine histologic methods, embedded in
paraffin, and sectioned at seven microns.
Sections were mounted onto glass slides and stained with hematoxylin
and eosin stains for light microscopic examination.
Data
Analysis—Prevalence
of congenital ophthalmic abnormalities and normal eyes was compared with color
of the mane and tail (white, flaxen, chestnut, black) among horses by a Chi
square test. Differences were
considered significant if P <
0.001. The IOP was compared between horses with globular appearing
corneas and horses with normal eyes by a student’s t-test. Differences
were considered significant if P
< 0.01. Ocular abnormalities
were reported in order of highest to lowest prevalence.
Results
Demographic Data—Five
hundred fourteen Rocky Mountain Horses residing on 30 different farms in six
midwest states (Michigan, Illinois, Indiana, Kentucky, Missouri, and Ohio)
were examined. The range in age
of horses was 10 hours to 29.15 years (median 2.92 years, mean 4.53 years). One hundred seventy three horses were male (4 were geldings)
and 341 were female.
Ophthalmic Examination—Large, translucent, cystic structures arising from
the posterior surface of the iris, ciliary body, or peripheral retina were
detected most frequently (Figure ????). Cysts
were detected in eyes of 249 horses (48%), were bilateral in 227 horses, and
unilateral in 22 horses (11 OD, 11 OS). Cysts were only present in the temporal part of the eye and
extended into the vitreous cavity.
Size of cysts varied in approximate diameter of 2 mm to 20 mm but did
not correlate with the age of the horse.
Single
to multiple (up to 13/eye) well-delineated, darkly pigmented curvilinear
streaks of retinal pigmented epithelium in the peripheral tapetal fundus were
present in eyes of 189 horses (37%) ranging in age from 10 hours to 29.15
years. Curvilinear streaks
originated and terminated near the temporal part of the peripheral retina and
always extended toward the optic papilla (Figure ????).
Curvilinear streaks were frequently bilateral but not symmetrical, and
were only detected in eyes of horses with cysts of the iris, ciliary body, or
peripheral part of the temporal retina.
Retinal
dysplasia was detected in eyes of 125 horses (24%).
Dysplasia of the temporal part of the peripheral retina was detected
most frequently and was characterized clinically as linear folds or vermiform
streaks. Seventeen horses had
retinal dysplasia (folds) affecting the superior peripapillary retina of one
or both eyes (Figure ?????). Retinal
dysplasia was bilateral in 79 horses (63%) and unilateral in 46 horses (33,
[26%] OD, 13, [10%] OS), and was detected only in eyes of horses with ciliary
body or peripheral temporal retinal cysts.
Separation
of the peripheral temporal retina was detected 84 horses (17 bilateral; 40 OD;
27 OS). Retinal separations
appeared to be an extension of ciliary cysts.
Retinal separations extended from the ciliary body and peripheral
retina toward the optic papilla and had a distinct curvilinear border marking
the separated retina from normal appearing retina (Figure ?????).
A dense proliferation of retinal pigment epithelium was observed at the
leading edge of most retinal separations.
Rhegmatogenous detachments restricted to the temporal retina (Figure
??????) were observed in eyes of nine horses and were usually bilateral.
A syndrome of multiple ocular abnormalities involving the cornea, nasal
and temporal iridocorneal drainage angle, iris, lens, ciliary body, and
peripheral retina were observed in 71 horses (14% of the population studied)
and were always bilateral (Table 1). Forty
four horses were female and 27 horses were male, representing 12.9 % of all
female horses and 15.6% of all male horses studied, respectively.
All horses with multiple ocular abnormalities also had cysts of the
iris, ciliary body, or peripheral retina, retinal dysplasia, retinal
separation, and curvilinear streaks of retinal pigmented epithelium.
Abnormalities of the iris included miosis, dyscoria, stromal hypoplasia
of the anterior and peripheral iris with occasional transillumination defects,
absence of a discernible collarette, and a visible sphincter pupillae.
Radially-oriented deep stromal strands of iris tissue extended from the
pupillary ruff toward the ciliary zone of the iris.
The granula iridica was flattened and circumferentially oriented at the
pupillary ruff compared with a normal iris of a Rocky Mountain Horse (Figure
????a and b). Full-thickness holes in the peripheral iris (12 o’clock
position) were detected in eyes of five horses (Figure???) and were always
bilateral. Pupillary light
responses were decreased or absent in eyes of horses with iris abnormalities.
Repeated topical administration of 1% tropicamide, 10% phenylephrine,
or 1% atropine did not induce mydriasis or had minimal to no effect on the
diameter of the pupils.
Macrocornea was evident in 43 of 71 horses with multiple ocular
abnormalities and was always bilateral. Diagnostic
criteria for macrocornea included a clear cornea with unremarkable central
corneal topography, grossly observable excessively large optical diameter of
the cornea with a short radius of curvature, and notably globular contour of
the cornea with atypical protrusion, compared with eyes of horses with normal
appearing corneas (Figure ?????). Horses
with macrocornea had excessively deep anterior chambers but the plane of the
lens-iris diaphragm appeared normal (Figure ????). Most horses that had macrocornea had concurrent
macropalpebral fissures (Figure ?????).
Different
degrees of anatomical abnormality of the iridocorneal drainage angle were
detected in eyes of 65 horses with multiple ocular abnormalities and were
always bilateral. Excessive
mesenchymal tissue in the iridocorneal angle was detected most frequently. The primary pectinate ligament was poorly developed or absent
in eyes of eleven horses. Multiple
goniosynechiae were evident in eyes of six horses and varied from small, thin
strands of pigmented tissue that extended from the temporal peripheral iris to
peripheral cornea, to areas of focal peripheral iridocorneal adhesion (Figure
????). Complete absence of the
temporal and nasal iridocorneal angle was evident in eyes of one horse.
Lenticular cataract was always present in horses with multiple ocular
abnormalities, and was characterized by an immature, spherical, nuclear
opacity that was most dense at the anterior nuclear-cortical junction of the
temporal part of the lens. Anterior
lenticonus internum was evident in many eyes with multiple ocular anomalies,
but the lens nucleus infrequently extended to contact the anterior lens
capsule. Iridodonesis and
phacodonesis attributable to posterior ventral subluxation of the temporal
part of the lens was detected in 11 horses with macrocornea and was always
bilateral (Figure????).
Abnormal prominence of the anterior orbital rim and apparent
hypertelorism was detected occasionally in horses with multiple ocular
abnormalities. Microphthalmos was
detected in fourteen horses, was bilateral in thirteen horses, and was always
associated with multiple ocular abnormalties.
The clinical appearance of ophthalmic lesions did not differ among
foals, mature horses, and aged horses, with the exception of horses that had
subluxation of the lens. In
mature and aged horses with lens subluxation, cataracts were immature but were
more diffuse and involved a greater portion of the nucleus and cortex.
Intraocular Pressure—There
was no significant difference in mean + SD IOP of eyes with normal
corneas (20.4 + 2.8 mm of Hg) and globular appearing corneas (20.0 +
2.8 mm of Hg). Intraocular
pressures of eyes with normal and globular appearing corneas were within the
normal reference range (20).
Histologic Findings—Remarkable histologic findings included hypoplasia of the iridal
stroma, a flattened and hypoplastic granula iridica, ciliary epithelium
located along the posterior iris surface (Figure ?????), hypoplasia of
posterior iris epithelium and iris dilator muscle, and large cysts arising
from the nonpigmented ciliary epithelium of the pars plicata and pars plana
(Figure ????). Focal areas of
glial tissue resembling neural retina and rosettes in primitive sensory
retinal tissue was evident overlying the inner ciliary body epithelium and
posterior iris epithelium. In
some regions with retinal rosettes, concurrent degeneration of the
neurosensory retina was evident but adjacent retinal pigment epithelium was
present. Anterior and posterior,
axial, and equatorial cataract was present at the nuclear-cortical junction.
Curvilinear streaks of retinal pigmented epithelium in the peripheral
temporal retina that were observed clinically (Figure ?????) were focal areas
of retinal pigmented epithelium proliferation (Figure ????).
Areas of retinal dysplasia and hypoplasia, characterized by lack of
normal sensory retinal architecture and occasional rosette formation, were
also detected. Degeneration of
the neurosensory retina was also detected in areas of containing retinal
rosette structures. Lesions
appeared similar in juvenile and mature horses.
No histologic lesions were observed in the globes from a mature horse
with clinically normal eyes.
Analysis by Coat Color—High prevalence of multiple ocular abnormalities
was evident in horses with a chocolate coat color compared to horses of other
colors (Table 2). Seventy-seven
horses examined had a chocolate colored coat and a white mane and tail.
Of these horses, 35 (45%) had multiple ocular abnormalities.
Two hundred eight horses had a chocolate colored coat and a flaxen
colored mane and tail. Of these
horses, 24 (12%) had multiple ocular abnormalities and four had concurrent
macrocornea. Five of 86 horses
(6%) with a chestnut colored coat had multiple ocular abnormalities. Multiple ocular abnormalities were limited to two of 57
horses (4%) with either a palomino, roan, champagne, dunn, bay, gray, or
buckskin coat color. Both of
these horses had a mane and tail color other than black.
None of the 70 horses with a black coat, mane, and tail color had
multiple ocular abnormalities. Only
1 of 129 horses with a black mane and tail had multiple ocular abnormalities.
There was a significant association (P<0.001) between mane and tail
color and multiple ocular abnormalities.
Horses with a white mane and tail color had a significantly higher
incidence of multiple ocular abnormalities compared with horses that had a
mane and tail color other than white (p<0.001).
Discussion—Based
on results of the ophthalmic examination, horses were generally grouped into
three categories: 1) horses with normal eyes, 2) horses with cysts of the
iris, ciliary body, or peripheral retina, with or without proliferation of the
retinal pigmented epithelium, retinal dysplasia, and retinal separation, and
3) horses with multiple ocular abnormalities.
Cysts
of the temporal part of the ciliary body in horses have been described
previously and were attributed to ocular malformation and senile degeneration
of the retina (21, 22). The
clinical and histologic appearance of ciliary body and peripheral retinal
cysts in eyes of horses of this report differs substantially from cysts of the
ora ciliaris retinae (peripheral cystoid retinal degeneration) in horses. Results of histologic examination showed cysts composed of
inner nonpigmented ciliary epithelium and primitive neuroretinal tissue.
Proliferation
of retinal pigment epithelium observed histologically corresponded
topographically to well-delineated curvilinear streaks of pigment observed
clinically in the peripheral temporal tapetal fundus.
These curvilinear streaks marked the delineation of previous retinal
separation (“high-water marker”). Detection
of multiple curvilinear streaks in eyes of neonatal and aged horses suggests
that age is not a primary risk factor for development of retinal separation.
Retinal
dysplasia may result from: 1) proliferative outgrowth of the retina beyond its
normal anatomical confines, away from the underlying retinal pigment
epithelium, 2) separation of the neurosensory retina from the retinal pigment
epithelium, with proliferation and dysplasia as a secondary consequence, 3)
over areas that are congenitally devoid of retinal pigment epithelium, or 4)
as an in situ process with normal underlying retinal pigment epithelium
(23). Retinal dysplasia is
frequently associated with different forms of anterior segment dysgenesis, but
may represent a late embryonic form of abnormal organization of the developing
retina. Degeneration of the
neurosensory retina containing rosette structures may be attributable to
antecedent retinal dysplasia (24).
In horses of this report, dysplastic regions of neurosensory retina
were in contact with the retinal pigment epithelium.
Whether retinal dysplasia is attributable to dysfunctional retinal
pigment epithelium is unknown.
Many
of the clinical features described in horses of this report appear similar to
those described in humans with megalocornea, anterior megalophthalmos, and
congenital miosis (25-34). Megalocornea
in humans occurs in three distinct patterns: 1) simple megalocornea
unassociated with other concurrent ocular anomalies; 2) anterior
megalophthalmos with megalocornea; and 3) buphthalmos in infantile glaucoma
(35). Simple megalocornea is
usually bilateral and is defined as a clear cornea of normal thickness,
measuring 12 mm or more in horizontal diameter in neonates up to two years of
age, equal to or larger than 13 mm in horizontal diameter after two years of
age, and absence of intraocular pressure elevation or other concurrent ocular
anomalies (34, 35).
Megalocornea in humans occurs most frequently in combination with
anterior megalophthalmos and is characterized as a bilateral, nonprogressive,
congenital enlargement of the anterior ocular segment with absence of elevated
intraocular pressure (25, 28-30, 33-35).
Concurrent anterior segment abnormalities with megalocornea include
iris stromal hypoplasia which may be manifest as transillumination defects,
and peripheral iridal holes. Deep
stromal tissue appears as radially oriented strings or sheets.
Pupils are usually miotic and the iris responds minimally or not at all
to mydriatic drugs (25, 27, 31, 32). The
iridocorneal drainage angle frequently contains excessive mesenchymal tissue
that appears as strands or sheets that are visible by direct transcorneal
examination. Lens subluxation,
phacodonesis, and iridodonesis occur frequently, and congenital or
developmental cataract is common (27, 30, 33, 35).
Buphthalmos attributable to congenital or infantile glaucoma may appear
clinically similar to simple megalocornea and anterior megalophthalmos, but
congenital glaucoma may be unilateral and is usually associated with elevated
intraocular pressure and its sequelae (ruptures in Descemet’s membrane,
limbal ectasia, atrophy of the ciliary body, iris, and choroid, retinal
degeneration, and cupping and atrophy of the optic papilla, blindness) (36).
Megalocornea and congenital glaucoma are clearly specific and separate
entities. Evidence for this
includes normal posterior segment anatomy on histopathologic examination (37,
38), normal or increased endothelial cell densities and normal endothelial
morphologic characteristics in eyes of human beings with megalocornea compared
with diminished endothelial cell counts in human beings with congenital
glaucoma (28), and characteristic biometric measurements that are
pathognomonic for megalocornea (32). Specular
microscopy and biometric measurements could not be performed on horses of this
report because of the lack of facilities at each farm.
To our knowledge, corneal endothelial cell counts have not reported in
horses. Future studies will be
necessary to determine endothelial cell counts of normal horses and those with
megalocornea, and to calculate the cupula and postlimbal depth of the anterior
chamber to differentiate anterior megalopthalmos from total megalophthalmos
(32). In the horses of this report, none had evidence of glaucoma.
Eyes of horses that had lens subluxation did not exhibit secondary
elevated intraocular pressure. Absence of signs of glaucoma in eyes of horses with apparent
drainage angle malformations may be attributable to the anatomy of the
iridocorneal angle and predominance of uveoscleral outflow of aqueous humor in
horses compared with corneoscleral outflow as the primary drainage pathway in
eyes of humans (36, 39, 40).
Ophthalmic abnormalities of Rocky Mountain Horses appear to be
nonprogressive, and therefore, similar clinically and histologically across
all age groups observed in this study. Mature
and aged horses with lens subluxation did exhibit a greater degree of lens
opacification compared with lenses of juvenile horses.
When subluxation occurs, the nutritional microenvironment of the lens
may be altered and may result in more rapid cataractogenesis.
Although cataract is progressive in horses with lens subluxation,
functional vision did not appear to be impaired in any horse of this report.
Complete lens luxation was not detected in any horses.
Megalocornea was reported previously in two foals but was unilateral
and was not associated with other ocular abnormalities (41).
Optical diameter of the cornea was not reported for foals of that
report. Corneal dimensions of the
neonatal foal or mature Rocky Mountain Horse have not been reported.
In a previous study, the range of corneal diameter of Saddlebred,
Standardbred, and Thoroughbred foals that ranged in age between 5 days and
19.5 weeks was reported (18). The range of mean corneal measurements were 25.7 to 26.6 mm
(horizontal plane ) and 19.5 to 20.4 mm (vertical plane) for the three breeds,
respectively. Presumably, the
rate of ocular growth decreases inversely proportional with increasing age
until adult size of the globe is attained.
Documentation of optical diameter of the cornea (vertical and
horizontal corneal measurements) of foals of different ages and breeds would
be beneficial. In the horses of
this report, the age of horses with macrocornea ranged between 10 hours and 14
years. Measurements of the
optical diameter of the cornea, corneal thickness, and keratometry, streak
retinoscopy, and specular microscopic studies of endothelial cell counts will
be necessary to definitively diagnose macrocornea and anterior macrophthalmos
in horses.
The etiopathogenesis of anterior macrophthalmos and macrocornea is
poorly understood and controversial. Abnormal
growth of neurectoderm of the anterior optic cup (day 33-41 in humans) has
been proposed (42, 43). Decreased
growth of the optic cup may result in an excessively large, broad ciliary
girdle over which successive waves of mesenchymal tissue migrate to form an
enlarged corneal diameter (43). While
this hypothesis could explain macrocornea and iris hypoplasia, we believe that
a more generalized, earlier sequence alteration is responsible for the
combination of macrophthalmos and macrocornea.
The optic vesicle contacts the surface ectoderm by day 25 in the human.
At this developmental stage, the fate of the surface ectoderm is
determined with regard to later development of lens, cornea, and palpebral
fissure (44) (Figure 10). Thus,
the combination of macrophthalmos and macrocornea is most directly explained
by earlier events initiated by an enlarged optic vesicle.
Deficiency of the intrinsic pupillary muscles is evidence of a primary
optic cup (neural ectoderm) abnormality.
Iris hypoplasia in Rocky Mountain Horses and in human beings with
macrocornea is most likely attributable to failure of the anterior rim of the
optic cup to migrate axially, and subsequent failure to induce the iris stroma
from neural crest mesenchyme. Migration
of mesenchymal tissue into an optic cup with an enlarged anterior opening may
result in formation of a hypoplastic anterior iridal stroma (Figure 11).
The outer layer of the optic cup is derived from neuroectoderm and is
the anlage of the internal epithelial layer of the iris and ciliary body.
This anterior iris epithelial layer gives rise to the intrinsic
pupillary muscles. Abnormal
development of this layer may lead to dyscoria, miosis, and the clinical
observation that affected irides failed to dilate after administration of
mydriatic drugs (45). This
epithelial layer also induces differentiation of the iris stroma from neural
crest mesenchyme. Therefore, iris
colobomas and iris hypoplasia may result from a primary deficiency in the
anterior optic cup. Other ocular
abnormalities evident in eyes of horses of this report that have not been
described in eyes of humans with megalocornea and congenital miosis include
dyscoria, anterior displacement of ciliary processes on the posterior iris,
cysts of the temporal ciliary body and retina, retinal dysplasia,
macropalpebral fissures, and hypertelorism.
Dyscoria may be attributable to dysplasia or hypoplasia of the iris
stroma and pupillary musculature. Differential
growth rates of the epithelial layers of the optic cup result in folding and
anterior displacement of the ciliary processes. Failure of the ciliary and iridal processes to recede
posteriorly during late gestation may also result in anteriorly positioned
ciliary and iridal processes, and malformation of the iridocorneal angle (46).
Hypertelorism, iris strands bridging the iridocorneal angle, and
hypoplasia of the anterior iris stroma evident in horses appears similar to
some of the abnormalities described in human beings with the
Axenfeld-Rieger’s syndrome (47).
Many systemic diseases and syndromes are associated with megalocornea
in humans. Megalocornea has been
reported in humans with Hallermann-Strieff syndrome, Marfan’s syndrome,
Marchesani syndrome, Aarskog syndrome, Down syndrome, icthyosis, poikiloderma
congenitale, mental retardation, dwarfism, cranoistenosis, oxycephaly,
progressive facial hemiatrophy, osteogenesis imperfecta, multiple skeletal
anomalies, nonketotic hyperglycinemia, tuberous sclerosis, and albinism (30,
48, 49). With regard to the
horses of this report, non-ocular abnormalities were limited to hypertelorism,
a prominent orbital rim, macropalpebral fissures, and partial albinism. Experimental studies of teratogen exposure during
gastrulation (day 16-21 in humans) induced an opposite spectrum of
microphthalmos, and micropalpebral fissures and concurrent craniofacial and
ocular abnormalities associated with reduced size of the optic vesicle (46).
Association of albinism and megalocornea have been reported in humans
(49). Effect of coat color and
mane and tail color on likelihood of congenital miosis and macrocornea in
Rocky Mountain Horses may be attributable to partial albinism.
Horses with chocolate coat color and flaxen or white mane and tail are
color dilute. Of 129 horses with
a black mane and tail, <0.1% had congenital miosis and only 8.5% had
ciliary cysts, compared with 42% congenital miosis and 44% cysts of 97 horses
with a white mane and tail. Environmental
influences and ocular teratogens are unlikely contributing factors to this
anomaly based on the fact that horses of different breeds with normal eyes
resided concurrently on the same farm or in the same geographic area as
affected horses. Wide geographic
distribution of affected and normal horses, different husbandry practices, and
different environmental conditions further support this assertion.
The mechanisms by which megalocornea may be inherited in humans include
X-linked, autosomal dominant, autosomal recessive, or as autosomal dominant
with germ-line mosaicism (25, 27, 30, 33, 34).
Segregation analyses performed on the horses in this report indicate
that this disease has a semidominant mode of inheritance (19).
Further genetic studies will be necessary to identify specific
mechanisms that determine anterior macrophthalmos and macrocornea in horses.
Congenital macrocornea with iris hypoplasia and miosis is not
restricted to the Rocky Mountain Horse breed.
We have observed ocular lesions identical to those described here in
many horses of other breeds (Kentucky Mountain Saddle Horse, Mountain Pleasure
Horse, Morgan Horse, and pony and miniature breeds).
Pedigree analysis indicates that the Kentucky Mountain Saddle Horse,
Mountain Pleasure Horse, and Rocky Mountain Horse breeds are derived from the
same founder stallion. Ocular
lesions that appear identical to those described here have only been
documented in the aformentioned breeds that have a chocolate colored coat and
white or chocolate flaxen colored mane and tail.
A dominant gene at the Silver
Dapple locus phenotypically influences only black base color, changing
horses with a black colored coat, mane, and tail to a dark chocolate colored
coat with white/silver or flaxen
colored mane and tail (50). We
hypothesize that the genetic mutation responsible for heritable ocular
abnormalities reported here may be closely linked to the dominant gene at the Silver Dapple locus.
Results of this study support the diagnosis of macrocornea with iris
hypoplasia and congenital miosis in horses, a phenotype that appears similar
to megalocornea and congenital miosis in humans.
Reports of histologic examination of eyes of humans with megalocornea
are rare (37, 38). Since
congenital miosis and anterior megalophthalmos are poorly understood diseases
in human beings, and since ocular lesions in horses with a chocolate coat
color occur frequently, these horses may be valuable animal models for further
comparative histologic, developmental, and genetic studies of the disease.
Addendum: The Equine Eye Registration Foundation (EERF) was recently
established to catalog ocular diseases presumed to be heritable in horses.
The American College of Veterinary Ophthalmologists in collaboration
with EERF collect data based on results of clinical ophthalmic examinations to
determine the frequency with which breed-specific heritable ocular anomalies
occur in horses.
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Abnormality
Number of horses affected
Possible developmental
explanation