Clinical manifestations of inherited glaucoma in the beagle - IOVS
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Clinical manifestations of inherited
glaucoma in the beagle
Kirk N. Gelatt, Robert L. Peiffer, Jr., Robert M. Gwin, Glenwood G. Gum,
and Leslie W. Williams
Inherited glaucoma was exhibited in 55 beagles. The glaucomatous process was divided into
early (6 to 12 months of age), moderate (13 to 30 months of age), and advanced (31 months
of age). In early glaucoma the iridocomeal angles, as judged by gonioscopy, were open and
without anomalies, intraocular pressure was elevated, and the tonographic facility of aqueous
outflow was decreased. With moderate glaucoma, the iridocomeal angles were typically open;
intraocular pressure was elevated; facility of aqueous outflow was decreased; and variable
optic disc cupping and focal disinsertion of the zonules from the lens were seen. Advanced
glaucoma exhibited narrow to closed iridocomeal angles, decreased facility of aqueous outflow,
elevated intraocular pressure, lens dislocation, optic disc atrophy, and finally phthisis bulbi.
The beagle in the early and moderate stages of glaucoma, before angle closure and lens dis-
location, is an animal model for studies in open-angle glaucoma.
Key words: glaucoma, canine model, open angle, tonography, tonometry, gonioscopy.
-L he scientific community for several dec- Hereditary buphthalmia in the rabbit to
ades has utilized animal models to study date has been the only source of a spon-
glaucoma.1 In most investigations glau- taneous glaucoma model.10"12 Unfortu-
coma had to be induced by injections of nately, inheritance of congenital glaucoma
substances into the anterior chamber, al- in the rabbit is also linked to a semilethal
terations of the blood flow to the eye or trait and about 30% systemic malforma-
about the limbus, trauma, and recently the tions.13
injection of alpha-chymotrypsin into the The glaucomas in the dog in the United
eye.2"9 States occur primarily in the American
cocker spaniel, basset hound, wirehaired
fox terrier, Sealyham terrier, and the
From the College of Veterinary Medicine, Uni- beagle.1422 The glaucomas in the dog are
versity of Florida, Gainesville. usually classified into (1) primary (no
This work was supported in part by United States antecedent disease), (2) secondary (de-
Public Health Service Research Grant EYO monstrable cause), and (3) congenital
1932-02 and Special Research National Eye (with iridocomeal anomalies).
Institute Fellowships 7F22 EYO 1977-03
(Peiffer), and 7F32 EYO 05100-02 (Gwin). Glaucoma in the dog results from a large
Submitted for publication Aug. 15, 1977. number of causes, similar to man. Glau-
Reprint requests: Dr. K. N. Gelatt, College of
coma in the American cocker spaniel, on
Veterinary Medicine, Box J-125 JHMHC, Uni- the basis of gonioscopy, is the narrow-angle
versity of Florida, Gainesville, Fla. 32610. type, with the iridocomeal angle eventu-
1135
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December 1977
40-
IOP-
mm Hg
Fig. 1. Mean tonometric recordings (Mackay-Marg tonometry) of (A) control, (B) carrier, and
(C) glaucomatous beagles. Bars indicate standard error.
ally closing.15-1G-23 Glaucoma in the basset The purpose of this report is to describe
hound is associated with goniodysgenesis the clinical signs of glaucoma in the beagle
and persistence of large mesodermal bands at the early, moderate, and advanced
across the iridocorneal angle rather than stages of the disease.
the normal branching pectinate liga-
ments.19"21 Although these iridocorneal an- Materials and methods
gle anomalies have been demonstrated in The colony over a period of 5 years consisted of
the basset hound by gonioscopy, histology, 55 glaucomatous beagles, 15 carrier beagles (from
and scanning electron microscopy, their affected x normal matings), and 12 laboratory
quality control beagles. All dogs were examined
exact role in the alteration of aqueous hu- at monthly to bimonthly intervals by slit-lamp
mor outflow and onset of the glaucoma is biomicroscopy, gonioscopy, and direct and indirect
not known. Basset hound glaucoma is fre- ophthalmoscopy. Observations on each dog were
quently exhibited clinically with a concur- recorded by external, iridocorneal angle (gonio-
rent iridocyclitis.14 scopic), and fundus photographs.
Intraocular pressure was estimated in all dogs
Glaucoma occurred in nine related bea- by Mackay-Marg tonometry (Biotronics, Inc.,
gles.24 Both eyes were similarly affected Redding, Calif.) one to four times daily. Tonom-
and in the advanced stages exhibited lens etry was performed with the dog in the sitting
subluxations, posterior and anterior luxa- position and under topical 0.4 percent benoxinate
tions. The iridocorneal angles were open; anesthesia (Dorsey Laboratories, Lincoln, Neb.).
Tonometric recordings were compared with a
two dogs exhibited limited areas of per- three-way analysis for variance and co-variance
sistent mesodermal bands in the angle. between the control and glaucomatous beagles as
Since then, a colony of glaucomatous bea- well as the carrier and glaucomatous groups. Sig-
gles has been developed.22 Affected beagles nificance of F valves was assumed at the p
respond with elevated intraocular pressureVolume 16 Inherited glaucoma in the beagle 1137
Number 12
Table I. Gonioscopic findings in glaucomatous beagles
Age (mo.) Glaucoma group Angle width Other findings
0- 6 Preglaucoma Normal No angle anomalies
7-12 Early glaucoma Normal
13-18 Glaucoma Normal
19-24 Glaucoma Normal to narrow Narrow areas are focal
25-30 Glaucoma to advanced glaucoma Normal to narrow
31-36 Advanced glaucoma Narrow
36+ Advanced glaucoma Narrow to closed Focal peripheral anterior
synechiae
ketamine (Parke, Davis & Co., Detroit, Mich.), eye occurred with elevated intraocular
10 mg./kg. intramuscularly, with a procedure pressures from 60 to 100 mm. Hg. Treat-
previously described.9 The coefficients of aqueous
humor outflow of the three groups were com-
ment with topical miotics and diuretics
pared statistically as previously described. was usually initiated to moderate these at-
All dogs were divided into groups by ages at tacks.
6-month intervals. The affected beagles were The gonioscopic appearance of the irido-
classified into the following groups: (1) pre- corneal angle was a dynamic process, with
glaucoma, consisting of beagles 0 to 6 months
old from affected parents, (2) early glaucoma,
the open iridocorneal angle gradually nar-
consisting of beagles 6 to 12 months old, (3) rowing and eventually closing (Table I). In
moderate glaucoma with dogs from 13 to 30 preglaucomatous and early glaucomatous
months old, and (4) advanced glaucoma with beagles the iridocorneal angle was open
beagles in excess of 31 months old. and without anomalies (Fig. 2). The inner
and outer pigment zones and the trabecu-
Results lar areas were normal. Small, infrequent
The applanation tonometric recordings focal areas of consolidated pectinate liga-
(in millimeters of mercury) of the control, ments spanned the iridocorneal angle; but
carrier, and glaucomatous beagles are de- they usually affected less than 5 to 10 per-
picted in Fig. 1. Intraocular pressure, as cent of the angle circumference and oc-
determined by tonometry, demonstrated curred with equal frequency in the control
significant increases in the later group laboratory quality beagle.
when the affected dogs were about 8 In the moderate stages of the disease,
months of age. The tonometric recordings the iridocorneal angle width was more
of both normal and glaucomatous beagles variable, but usually open. Various quad-
from 2 to 4 months of age may not be rants of the iridocorneal angle were open,
highly reliable, since during this time the narrow, or closed, but the entire circumfer-
animals are being trained and handled for ence was not usually closed. In the ad-
the first time. Of the different families in vanced glaucomatous beagles the irido-
the glaucomatous strain, the offspring from corneal angle was usually narrow and
one bitch exhibited earlier and more infrequently closed. In some narrow irido-
marked elevations in intraocular pressure. corneal angles the bases of the pectinate
After the lens became dislocated from ligaments nearly touched the trabecular
the patella fossa, greater daily variability area, suggesting closure of the sclerociliary
in intraocular pressure resulted. Intermit- cleft (Fig. 3). Eventually the onset of
tent marked elevations in intraocular pres- phthisis bulbi and/or corneal edema pre-
sure occurred, associated with lens and vented further evaluations of the iridocor-
vitreous pupillary blockage and perhaps neal angle.
other factors such as iridocyclitis and vitre- Changes in the lens and its position in
ous humor in the anterior chamber. During the patella fossa are summarized in Table
these episodes, corneal edema, fixed pupil, II. In the preglaucomatous beagles no
episcleral congestion, and tenderness of the changes in the lens, zonules, or lens posi-
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December 1977
Fig. 2. Iridocorneal angle of normal width, pig- Fig. 3. Iridocorneal angle of a 55-month-old ad-
ment zones, and pectinate ligaments in an 18- vanced-glaucoma beagle bitch exhibiting heavy
month-old affected beagle bitch. pigmentation and closure of the sclerociliary cleft.
Table II. Changes in the lens during kic crescent occurred (Fig. 5), but the lens
glaucoma in the beagle usually remained in the patella fossa.
As the glaucoma advanced, zonules con-
Mean age Standard
Changes in tens (mo.) error tinued to detach from the lens equator.
When more than 180 degrees of the lens*
Position:
"In situ" 17.6 1.6 zonulary attachments were lost, subluxa-
Focal zonulary disin- tion of the lens from the patella fossa oc-
sertion 20.1 1.8 curred and was exhibited as tilting, usually
Zonulary disinsertion
for 1 or more quad- anteriorly, pushing focal areas of the iris
rants 21.7 1.8 forward. Iridodonesis was usually present.
Lens subluxation 29.9 1.8 In the advanced glaucomatous beagles,
Anterior luxation 35.5 3.6
Posterior luxation 45.0 3.8 lens position was variable, with loss of most
Aphakic crescents: to all of its zonular attachments. Disloca-
Medial 27.6 5.5 tion of the lens occurred into the anterior
Lateral 27.3 2.3
Cataract formation 27.6 3.8 chamber most frequently (Fig. 6); occa-
sionally the lens luxated posteriorly into
the vitreous body (Fig. 7). Cataracts
tion were apparent. In the early glauco- formed in most of the luxated lenses.
matous beagles, stretching of the ciliary The ocular fundi, including the optic
processes usually occurred about the lens discs, were normal in the preglaucomatous
periphery, detectable only with the maxi- and early glaucomatous beagles. Changes
mum mydriasis. Eventually focal disinser- in the optic disc were variable but occurred
tion of the zonules from the lens equator earlier in glaucomatous beagles that de-
and even transection of the distal ciliary veloped early and extensive elevations in
processes occurred (Fig. 4). The loss of intraocular pressure. Some glaucomatous
several zonular attachments usually re- beagles demonstrated loss of the lateral op-
quired a period of several months. When tic disc rim. Others exhibited central to
the loss of zonular attachment occurred paracentral cupping of the optic disc (Fig.
primarily in one quadrant, a narrow apha- 8). Retinal blood vessels, especially the
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Number 12
Fig. 4. Focal disinsertions of two focal zonules in a Fig. 6. Anterior lens luxation (arrows) and asso-
23-month-old glaucomatous beagle dog. Note ab- ciated corneal edema in a 54-month-old glaucoma-
sence of a stretched ciliary body process in the tous beagle bitch.
same area (arrows).
Fig. 5. Small aphakic crescent (arrows) in a 49- Fig. 7. Posterior lens luxation and early cataract
month-old glaucomatous beagle dog. Focal equa- formation (arrows) in a 40-month-old advanced-
torial cataract formation is evident at the 7 o'clock glaucoma beagle bitch.
position.
small retinal arterioles about the disc, Consecutive Schi0tz tonographic record-
gradually disappeared. The optic discs ings of control, carrier, and glaucomatous
eventually became quite round, depressed, beagles are summarized in Fig. 10. The
and not infrequently pigmented in ad- carrier and control dogs exhibited similar
vanced glaucomatous beagles. With optic coefficients of aqueous humor outflow that
atrophy, most retinal blood vessels disap- were significantly different from the glau-
peared; however, the primary veins and comatous beagles (p1140 Gelatt et al Invest. Ophthalmol. Visual Set.
December 1977
mor outflow have not been defined, pre-
cipitating factors are absent in the early
stages of the disease. Dependent on the
stage of the disease, the iridocorneal angle
is open in the early and moderate glauco-
matous stages but eventually narrows as
the lens luxates in advanced glaucoma. As
a result, the canine model has gonioscopic
similarities to both open- and narrow-angle
glaucoma in man, but most importantly to
the primary open-angle type.
The accurate measurement of intraocular
pressure in the glaucomatous dog is essen-
tial in the investigation of the disease. Use
of the Schi0tz tonometer with tables de-
rived from human eyes results in under-
estimation of actual intraocular pressure.28
Fig. 8. Early cupping (arrows) of the optic disc Schi0tz tables specifically for the dog assist
in a 26-month-old glaucomatous beagle bitch. in minimizing this error; however, applana-
(Original fundus magnification x38.) tion tonometry offers additional advan-
tages. The Mackay-Marg tonometer, of
four applanation types evaluated for the
normal eye,29 is superior in the dog. In the
control, carrier, and glaucomatous beagles,
intraocular pressures as measured by Mac-
kay-Marg tonometry were significantly dif-
ferent after the glaucomatous dogs were
8 months old. The greater variance in the
glaucomatous beagles may be related to
poor intraocular pressure-regulating mech-
anisms, the lens luxation, occasional severe
"acute" attacks, and vitreous humor in the
anterior chamber.
The onset of elevated intraocular pres-
sure and decreased facility of aqueous hu-
Fig. 9. Optic atrophy in a 33-month-old glauco- mor outflow precede the subluxation of the
matous beagle dog. Note the reduced retinal vas- lens. Hence in the genesis of the disease,
culature and the depressed optic disc. (Original the lens luxation appears secondarily and
fundus magnification *18.) simply aggravates the disease process. Con-
secutive ultrasonic studies currently in pro-
which became lower as the glaucomatous gress may provide additional information
beagles aged and the glaucoma worsened. about the lens position and size, and axial
length of the globe to the glaucoma.
Discussion
Gonioscopy of affected beagles at differ-
Primary glaucoma in man exists as two ent stages of the disease indicates an open
distinct diseases: (1) primary chronic iridocorneal angle that gradually narrows
open-angle glaucoma and (2) primary nar- and eventually closes. Persistent meso-
row-angle glaucoma.27 Inherited glaucoma dermal bands described in the basset
in the beagle is a primary type; although hound glaucoma have not been detected
the mechanisms of decreased aqueous hu- in the beagle by gonioscopy, light micros-
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Number 12
Coefficient of
Aqueous Outflow
(ul/mm.Hg/min.)
.20"
.10-
Fig. 10. Schi0tz tonographic recordings (/tl/mm. Hg/min.) of carrier (A), control (B), and
glaucomatous beagles (C) from ages of 4 to 36+ months old. Bars indicate standard error.
copy, or preliminary scanning electron mi- are not necessary. This glaucoma model ex-
croscopy. In pharmacologic studies with hibits a reasonably predictable clinical
glaucomatous beagles, pilocarpine, epi- course over a period of at least 2 to 3 years,
nephrine, dipivalyl epinephrine, and the thereby permitting numerous and serial
carbonic anhydrase diuretics have been ef- investigations. Gonioscopic and prelimi-
ficacious.30' 31 Dependent on the iridocor- nary scanning electron microscopic exami-
neal angle morphology and the stage of the nations support an open iridocomeal angle
glaucoma, certain cholinergic and adrener- without congenital anomalies. Intraocular
gic drugs might have certain advantages as pressure of the glaucomatous beagles with
well as contraindications. open iridocomeal angles has been effec-
The effects of elevated intraocular pres- tively lowered by several drugs, which in-
sure on the dog optic disc have been con- clude, in part, topical pilocarpine, epi-
troversial. In our experience detection of nephrine, dipivalyl epinephrine, and the
early and subtle changes in the variable carbonic anhydrase diuretics. The useful-
shape optic disc of the dog necessitates ness of the glaucomatous beagle as a phar-
serial fundus photographs. Eventually, macologic model appears promising.
however, extensive optic atrophy occurs
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