Takashi Hasegawa1, Manabu Kawata, Mitsuharu Ota. 1. Laboratory of Advanced Diagnosis and Treatment, Department of Advanced Clinical Medicine, Course of Veterinary Sciences, Graduate School of Life and Environmental Sciences, Osaka Prefecture University, North 1-58, Rinku-orai, Izumisano, Osaka 598-8531, Japan.
Abstract
By using ultrasound biomicroscopy (UBM), the cross-sectional structures of the entire iridocorneal angle (ICA) which are unable to assess with gonioscopic examination were evaluated objectively and quantitatively in live healthy and glaucomatous dogs. The ICAs of normotensive eyes in healthy dogs with normal open angle (NOR), a predisposition to primary closed angle glaucoma (PCAG) (PREDIS) and suffering from unilateral PCAG (UNI), as well as the ICAs of hypertensive eyes with acute and chronic PCAG (ACG and CRG), were assessed. The opening of the ciliary cleft in PREDIS was smaller than that in NOR. In UNI, the opening and area of the ciliary cleft were significantly decreased compared with those of NOR and PREDIS. ACG had widespread structural abnormalities including marked decrease in the ciliary cleft and scleral venous plexus, and a thinner sclera than those in normotensive eyes, whereas the ICA collapsed in CRG with the thinnest sclera. Medical therapy-responsive glaucomatous cases had wider ciliary cleft and scleral venous plexus than unresponsive ones. These findings suggest that the ciliary cleft and scleral venous plexus of the ICA are key structures contributing to not only the pathophysiology of canine glaucoma but also the responsiveness to medical therapy in glaucomatous eyes, and cross-sectional entire structures of the ICA should be evaluated quantitatively with UBM when diagnosing and managing canine glaucoma.
By using ultrasound biomicroscopy (UBM), the cross-sectional structures of the entire iridocorneal angle (ICA) which are unable to assess with gonioscopic examination were evaluated objectively and quantitatively in live healthy and glaucomatousdogs. The ICAs of normotensive eyes in healthy dogs with normal open angle (NOR), a predisposition to primary closed angle glaucoma (PCAG) (PREDIS) and suffering from unilateral PCAG (UNI), as well as the ICAs of hypertensive eyes with acute and chronic PCAG (ACG and CRG), were assessed. The opening of the ciliary cleft in PREDIS was smaller than that in NOR. In UNI, the opening and area of the ciliary cleft were significantly decreased compared with those of NOR and PREDIS. ACG had widespread structural abnormalities including marked decrease in the ciliary cleft and scleral venous plexus, and a thinner sclera than those in normotensive eyes, whereas the ICA collapsed in CRG with the thinnest sclera. Medical therapy-responsive glaucomatous cases had wider ciliary cleft and scleral venous plexus than unresponsive ones. These findings suggest that the ciliary cleft and scleral venous plexus of the ICA are key structures contributing to not only the pathophysiology of canineglaucoma but also the responsiveness to medical therapy in glaucomatous eyes, and cross-sectional entire structures of the ICA should be evaluated quantitatively with UBM when diagnosing and managing canineglaucoma.
Canineglaucoma is associated with structural abnormalities of the iridocorneal angle (ICA)
including pectinate ligament dysplasia and narrow/closed angles; these abnormalities are
evaluated using a gonioscope and slitlamp biomicroscopy in clinical practice [4, 8, 16, 18, 21]. A gonioscopic examination has some problems: for
instance, it is a subjective test, and cannot evaluate abnormalities in the deep ICA and
quantify its structural abnormalities [2, 11, 15, 18, 20, 23, 24]. Veterinary
ophthalmologists use a grading system that was proposed by Ekesten et al.
[7] to classify the angle as open, narrow or closed,
although the system is still defective, such as an imperfect quantitative system, that is,
semi-quantitative evaluation of the ICA. Hence, a simpler procedure is needed to evaluate
abnormalities of the entire ICA objectively and quantitatively for the diagnosis and
management of canineglaucoma.Ultrasound biomicroscopy (UBM), which can provide cross-sectional images of ocular tissues at
low-power microscopic resolution by using high-frequency ultrasound probes, has been
introduced into veterinary ophthalmology and applied to basic and clinical research for
evaluation of the ocular anterior segment including the ICA [1,2,3,
5, 6, 8, 10, 13, 14, 18]. This advanced imaging technique is expected to be
clinically useful for clarifying unknown pathophysiology, selecting accurate management
approaches and improving the prognosis in ocular disorders [1,2,3,
5, 6, 8, 10, 18]. However, there have been few reports dealing with
comparison of microstructures of the ICA between live healthy and glaucomatousdogs [18]. In addition, antemortem structural and quantitative
information on the abnormalities of canineICA is still obscure. The aim of this study is to
evaluate cross-sectional structures of the entire ICA and quantify its microstructures of live
healthy and glaucomatousdogs via UBM examination.
MATERIALS AND METHODS
Animals: Two hundred and eighty-seven dogs that were presented at Osaka
Prefecture University Veterinary Medical Center (OPUVMC), Animal Eye Center and Izumi Animal
Hospital for examination and treatment of ophthalmic, medical and surgical diseases were
used in this study. All the dogs underwent a general ophthalmologic examination including
gonioscopy with a Goldmann two-mirror lens and slitlamp biomicroscopy to confirm ocular
conditions. Laboratory examinations including blood works, urinalysis and diagnostic
imagings were also carried out to exclude systemic disorders, if necessary. Animals
suspected of having secondary glaucoma, which was indicated by their history and ophthalmic
conditions, such as the presence of uveitis, cataract, lens luxation, ocular neoplasia and
infections including systemic diseases, were excluded from the study.The examined eyes were divided into 5 groups as follows:(i) normal ocular group (NOR) including 336 normotensive eyes of 168 dogs (57 Beagle, 18
Miniature Dachshund, 15 Shih Tzu, 12 Pembroke Welsh Corgi, 11 Chihuahua, 9 mongrel and
Labrador Retriever, 8 Yorkshire Terrier, 6 Papillon, 5 Pomeranian, 4 Shetland Sheepdog, 3
Cavalier King Charles Spaniel and Miniature Schnauzer, 2 Bernese Mountain Dog, Doberman
Pinscher and Pug, and 1 Afghan Hound and French Bulldog) with normal open angle (Fig. 1A), normal intraocular pressure (IOP) of 10–25 mmHg and no ocular disorders up to the
date of UBM examination;
Fig. 1.
Typical canine iridocorneal angles in the five ocular groups examined in this study:
(A) wide open angle in a normal normotensive eye; (B1) open angle with goniodysgenesis
in a primary closed angle glaucoma (PCAG)-predisposed normotensive eye; (B2) narrow
angle with severe goniodysgenesis in a PCAG-predisposed normotensive eye; (C) very
narrow angle in a normotensive fellow eye of unilateral PCAG; (D) closed angle in an
acute glaucomatous eye; and (E) closed angle in a chronic glaucomatous eye.
Typical canine iridocorneal angles in the five ocular groups examined in this study:
(A) wide open angle in a normal normotensive eye; (B1) open angle with goniodysgenesis
in a primary closed angle glaucoma (PCAG)-predisposed normotensive eye; (B2) narrow
angle with severe goniodysgenesis in a PCAG-predisposed normotensive eye; (C) very
narrow angle in a normotensive fellow eye of unilateral PCAG; (D) closed angle in an
acute glaucomatous eye; and (E) closed angle in a chronic glaucomatous eye.(ii) primary closed angle glaucoma (PCAG)-predisposed ocular group (PREDIS) including 116
normotensive eyes of 58 dogs (18 Shiba, 14 American Cocker Spaniel, 13 Toy Poodle, 7 Golden
Retriever, 2 Maltese Terrier, and 1 Akita, English Springer Spaniel, Flat-Coated Retriever
and Newfoundland, which were recognized as breeds with PCAG [9, 18, 19]) with some kind of ICA abnormalities containing goniodysgenesis and open to
narrow angles (Figs. 1-B1 and B2), normal IOP of
10–25 mmHg and no ocular disorders up to the date of UBM examination;(iii) normotensive fellow ocular group in unilateral PCAG (UNI) including 22 normotensive
eyes of 22 dogs suffering from unilateral PCAG (6 Shiba, 5 Shih Tzu, 3 American Cocker
Spaniel, 2 Flat-Coated Retriever, Miniature Dachshund and mongrel, and 1 Chihuahua and Welsh
Terrier), which had narrow angle with moderate to severe ICA abnormalities (Fig. 1C), normal IOP of 10–25 mmHg and no clinical
signs of glaucoma up to the date of UBM examination;(iv) acute glaucomatous eye group (ACG) including 19 hypertensive non-buphthalmic eyes of
19 dogs (6 Shiba, 3 Miniature Dachshund and Shih Tzu, 2 American Cocker Spaniel, and 1
Chihuahua, English Setter, Flat-Coated Retriever, mongrel and Welsh Terrier) with closed
angle (Fig. 1D), IOP of over 25 mmHg (31–58 mmHg)
and signs of acute glaucoma, such as tenderness about the head and eyes, ocular pain
(blepharospasm), serous discharge, episcleral congestion (red eye), corneal edema, dilated
pupil and mild depression of optic nerve head [21],
in which their clinical signs were observed less than 24 hr after the onset of symptoms on
the date of UBM examination;(v) chronic glaucomatous eye group (CRG) including 20 hypertensive buphthalmic eyes of 20
dogs (6 Miniature Dachshund, 5 American Cocker Spaniel, 3 Shiba, 2 mongrel and Shih Tzu, and
1 Flat-Coated Retriever and Welsh Terrier) with closed angle (Fig. 1E), IOP of over 25 mmHg (42–78 mmHg) and signs of chronic
glaucoma, such as globe enlargement with or without Descemet streaks, mydriasis, tapetal
hyperreflectivity with vascular attenuation, optic nerve cupping and blindness [21] on the date of UBM examination.Examination procedure: Ultrasonographic images of the ICA were obtained
with UBM by using a UD-1000 with 40-MHz probes (Tomey Corp., Nagoya, Japan) with background
room illuminance of 1,200–1,300 lux in a general examination room. Non-anesthetized or
non-sedated dogs were examined using manual restraints in sternal recumbency. When sedation
was required, it was achieved following a protocol described previously [14]; these animals were assessed in a lateral recumbent
position. UBM examination was also performed by a procedure described previously [14], and the following 7 parameters were evaluated with
the measurement software of the UBM: (i) SLD [the distance between Schwalbe’s line (the
borderline between the cornea and sclera) and the anterior lens capsule] (Fig. 2B); (ii) the width of the ciliary cleft (CCW), measured from the superior surface of
the root of the iris to the inner surface of the sclera on a perpendicular line (Fig. 2B); (iii) the area of the ciliary cleft (CCA),
measured as the area surrounded by the width of the ciliary cleft, the line of the inner
scleral side of the ciliary cleft from the inner surface of the sclera to the angle recess
and the line of the superior side of the root of the iris from the angle recess to the
superior surface of the root of the iris (Fig.
2B); (iv) the angle of the ciliary cleft (ACC), the angle of the inner surface of the
sclera to the angle recess and the superior surface of the root of the iris to the angle
recess (Fig. 2C); (v) the scleral thickness at the
position of the width of the ciliary cleft (ST), as measured from the inner surface of the
sclera on a perpendicular line to the outer surface of the sclera (Fig. 2C); (vi) the minimum distance between the angle recess and the
scleral venous plexus (ASD, Fig. 2C); and (vii)
the total area of the scleral venous plexus (SVPA) on the UBM image of the ICA (Fig. 2D). Raw UBM measurements were detected from all
obtained images in the examined dogs. In order to exclude differences of raw UBM values
caused by taking different breeds with varied ocular size, the UBM measurements except for
the angle of the ciliary cleft were corrected by using the ratio with SLD on the
distance/length, that is, CCW/SLD, ST/SLD and ASD/SLD, or SLD2 on the area, that
is, CCA/SLD2 and SVPA/SLD2 [14]. The mean of UBM values was calculated to obtain a UBM measurement of each
parameter of the ICA in an individual eye.
Fig. 2.
Typical canine images of ultrasound biomicroscopy (UBM) on the iridocorneal angle
(ICA, A) and the same images of the ICA with indication of UBM parameters evaluated in
this study (B to D). The following 7 parameters were evaluated with the measurement
software included in the UD-1000: (i) SLD [the distance between Schwalbe’s line (SL,
the borderline between the cornea and sclera) and the anterior lens capsule (ALC)];
(ii) the width of the ciliary cleft (CCW), measured from the superior surface of the
root of the iris (SSRI) to the inner surface of the sclera (ISS) on a perpendicular
line; (iii) the area of the ciliary cleft (CCA), measured as the area surrounded by
the width of the ciliary cleft, the line of the inner scleral side of the ciliary
cleft from the inner surface of the sclera to the angle recess (AR) and the line of
the superior side of the root of the iris from the angle recess to the superior
surface of the root of the iris; (iv) the angle of the ciliary cleft (ACC), the angle
of the inner surface of the sclera to the angle recess and the superior surface of the
root of the iris to the angle recess; (v) the scleral thickness at the position of the
width of the ciliary cleft (ST), as measured from the inner surface of the sclera on a
perpendicular line to the outer surface of the sclera; (vi) the minimum distance
between the angle recess and the scleral venous plexus (SVP) [ASD]; and (vii) the
total area of the scleral venous plexus (SVPA) on the UBM image of the ICA.
Typical canine images of ultrasound biomicroscopy (UBM) on the iridocorneal angle
(ICA, A) and the same images of the ICA with indication of UBM parameters evaluated in
this study (B to D). The following 7 parameters were evaluated with the measurement
software included in the UD-1000: (i) SLD [the distance between Schwalbe’s line (SL,
the borderline between the cornea and sclera) and the anterior lens capsule (ALC)];
(ii) the width of the ciliary cleft (CCW), measured from the superior surface of the
root of the iris (SSRI) to the inner surface of the sclera (ISS) on a perpendicular
line; (iii) the area of the ciliary cleft (CCA), measured as the area surrounded by
the width of the ciliary cleft, the line of the inner scleral side of the ciliary
cleft from the inner surface of the sclera to the angle recess (AR) and the line of
the superior side of the root of the iris from the angle recess to the superior
surface of the root of the iris; (iv) the angle of the ciliary cleft (ACC), the angle
of the inner surface of the sclera to the angle recess and the superior surface of the
root of the iris to the angle recess; (v) the scleral thickness at the position of the
width of the ciliary cleft (ST), as measured from the inner surface of the sclera on a
perpendicular line to the outer surface of the sclera; (vi) the minimum distance
between the angle recess and the scleral venous plexus (SVP) [ASD]; and (vii) the
total area of the scleral venous plexus (SVPA) on the UBM image of the ICA.Nineteen ACG cases received first medical therapy including an intravenous injection of 20%
mannitol (Yoshindo, Toyama, Japan) at a dose of 1.5 g/kg on the first admission and
administrations of 0.005% latanoprost (Xalatan®, Pfizer, Tokyo, Japan), 1%
dorzolamide hydrochloride (Trusopt®, Santen Pharmaceutical Co., LTD., Osaka,
Japan) and 0.5% timolol maleate (Timoptol®, Santen Pharmaceutical Co., LTD.,
Osaka, Japan) on OPUVMC. Then, the responsiveness to the therapy, which means keeping
reduction in normal IOP of under 25 mmHg, and the seven parameters of the ICA structures
described above were evaluated simultaneously.Statistical analysis: To exclude unexpected bias effects of pooling UBM
measurements of right and left eyes, the average UBM values calculated from both eyes were
used as UBM measurements in NOR and PREDIS [22].
Comparison between ocular groups was performed using non-repeated measurement one-way
analysis of variance (ANOVA) or Kruskal-Wallis H test followed by Scheffe’s test (Statcel
2nd ed.; OMS Publishing Co., Tokyo, Japan). A P-value less than 0.05 was
considered to be statistically significant.Reference ranges of UBM measurements in NOR and PREDIS were calculated by interative
truncation method with correction (Usui’s method) using STSS/EXCEL Ver. 8.8
(http://www.chiringi.or.jp/soft/soft.html) [25].
RESULTS
As shown in Fig. 3, cross-sectional microstructures of the entire ICA could be observed clearly by UBM
examination in all ocular groups. Abnormal structures of the ICA were not found in NOR. The
width of the ciliary cleft of PREDIS was narrower than that of NOR. It was difficult to
identify the width of the ciliary cleft of UNI, and the area of the ciliary cleft of UNI
would be smaller than those of NOR and PREDIS. The ciliary cleft was almost collapsed, and
it was very difficult to detect the width and area of the ciliary cleft in ACG. The ciliary
cleft was completely collapsed in CRG. The scleral venous plexus could be observed in UBM
images of most ACG, although it was not found in CRG. The basal iris of the anterior part of
the ciliary cleft was slightly inserted into the sclera of ACG, whereas it was inserted into
the sclera in CRG.
Fig. 3.
Typical images of the iridocorneal angle (ICA) detected by ultrasound biomicroscopy
(UBM) in (A) normotensive eyes with no ocular disorders, intraocular pressure (IOP) of
10–25 mmHg and normal open angle (NOR), (B) normotensive eyes of primary closed angle
glaucoma (PCAG)-predisposed dogs with no ocular disorders, IOP of 10–25 mmHg, open to
narrow angle and some kind of abnormalities of the ICA (PREDIS), (C) normotensive
fellow eyes of dogs suffering from unilateral PCAG, which had IOP of 10–25 mmHg,
narrow angle with moderate to severe abnormalities of the ICA and no clinical signs of
glaucoma (UNI), (D) hypertensive non-buphthalmic eyes with acute PCAG having IOP of
over 25 mmHg, closed angle and clinical signs of acute glaucoma (ACG) and (E)
hypertensive buphthalmic eyes with chronic PCAG having IOP of over 25 mmHg, closed
angle and clinical signs of chronic glaucoma (CRG). Abnormal structures of the ICA
were not found in NOR. The width of the ciliary cleft (CCW) of PREDIS was narrower
than that of NOR (an arrow in B). The area of the ciliary cleft (CCA) of UNI was
smaller than those of NOR and PREDIS, and significantly narrow CCW was observed in the
case of UNI (an arrow in C). The ciliary cleft was almost or completely collapsed, and
it was difficult or impossible to detect CCW and CCA in ACG and CRG (arrows in D and
E). Although the scleral venous plexus could be observed in UBM images of ACG
(asterisks in D), it was not found in a dog with CRG. The basal iris of the anterior
part of the ciliary cleft would be slightly inserted into the sclera of ACG (an
arrowhead in D). The sclera became thin, and the basal iris was inserted into the
sclera in CRG (arrowheads in E).
Typical images of the iridocorneal angle (ICA) detected by ultrasound biomicroscopy
(UBM) in (A) normotensive eyes with no ocular disorders, intraocular pressure (IOP) of
10–25 mmHg and normal open angle (NOR), (B) normotensive eyes of primary closed angle
glaucoma (PCAG)-predisposed dogs with no ocular disorders, IOP of 10–25 mmHg, open to
narrow angle and some kind of abnormalities of the ICA (PREDIS), (C) normotensive
fellow eyes of dogs suffering from unilateral PCAG, which had IOP of 10–25 mmHg,
narrow angle with moderate to severe abnormalities of the ICA and no clinical signs of
glaucoma (UNI), (D) hypertensive non-buphthalmic eyes with acute PCAG having IOP of
over 25 mmHg, closed angle and clinical signs of acute glaucoma (ACG) and (E)
hypertensive buphthalmic eyes with chronic PCAG having IOP of over 25 mmHg, closed
angle and clinical signs of chronic glaucoma (CRG). Abnormal structures of the ICA
were not found in NOR. The width of the ciliary cleft (CCW) of PREDIS was narrower
than that of NOR (an arrow in B). The area of the ciliary cleft (CCA) of UNI was
smaller than those of NOR and PREDIS, and significantly narrow CCW was observed in the
case of UNI (an arrow in C). The ciliary cleft was almost or completely collapsed, and
it was difficult or impossible to detect CCW and CCA in ACG and CRG (arrows in D and
E). Although the scleral venous plexus could be observed in UBM images of ACG
(asterisks in D), it was not found in a dog with CRG. The basal iris of the anterior
part of the ciliary cleft would be slightly inserted into the sclera of ACG (an
arrowhead in D). The sclera became thin, and the basal iris was inserted into the
sclera in CRG (arrowheads in E).The data of each UBM parameter are shown in Fig.
4, and Table 1 shows reference ranges of each UBM measurement in NOR and PREDIS. In PREDIS,
UBM measurements of the corrected width of the ciliary cleft and the angle of the ciliary
cleft were significantly lower than those of NOR. In UNI, significantly low values were
found for the corrected width and area of the ciliary cleft, and the angle of the ciliary
cleft, when compared with those in NOR and PREDIS. In ACG, the corrected width and area of
the ciliary cleft, the total area of the scleral venous plexus and the scleral thickness,
and the angle of the ciliary cleft were significantly smaller than those of NOR and PREDIS.
The corrected width and area of the ciliary cleft, the total area of the scleral venous
plexus and the scleral thickness in ACG were also significantly decreased compared with
those of UNI. In CRG, the anatomical structures of the sclerociliary cleft including the
scleral venous plexus completely collapsed, and all UBM values except the corrected scleral
thickness were zero or undetectable. There were significant differences for the corrected
width and area of the ciliary cleft, and the total area of the scleral venous plexus between
CRG and NOR, PREDIS and UNI. The angle of the ciliary cleft in CRG was significantly lower
than those of NOR and PREDIS. The corrected scleral thickness of CRG was significantly
smaller than those of NOR, PREDIS, UNI and ACG, as a result of the buphthalmos.
Fig. 4.
Box-plots of each ultrasound biomicrosopic measurement in the five ocular groups: (A)
corrected width of the ciliary cleft (CCW) [CCW/SLD (the distance/length of Schwalbe’s
line to the anterior lenticular capsule)]; (B) the angle of the ciliary cleft (ACC);
(C) corrected area of the ciliary cleft (CCA) [CCA/SLD2]; (D) corrected
minimum distance/length from the angle recess to the scleral venous plexus (ASD)
[ASD/SLD]; (E) corrected total area of the scleral venous plexus on the ultrasound
biomicrosopic image of the iridocorneal angle (SVPA) [SVPA/SLD2]; (F)
corrected scleral thickness (ST) [ST/SLD]. The boxes define the 25th and 75th
percentiles, with the median value indicated by a horizontal bar. The whiskers
delineate the 5th and 95th percentiles, with outliers indicated as open circles. Not
available means no detectable data due to complete collapse of the ciliary cleft
and/or the scleral venous plexus. Different letters/alphabets indicate statistically
significant differences between groups (P<0.05).
Table 1.
Reference ranges of corrected ultrasound biomicroscopic values in healthy
dogs
Corrected CCW (CCW/SLD)
ACC (°)
Corrected CCA (CCA/SLD2)
Corrected ASD (ASD/SLD)
Corrected SVPA (SVPA/SLD2)
Corrected ST (ST/SLD)
NOR (n=168)
0.064–0.149
8.3–22.2
0.019–0.042
0.110–0.317
0.014–0.058
0.253–0.384
PREDIS (n=58)
0.028–0.131
4.8–19.0
0.006–0.043
0.118–0.302
0.012–0.052
0.224–0.339
NOR; normotensive eyes in normal open angle, PREDIS; normotensive eyes in
predisposition to primary closed angle glaucoma. CCW; the width of the ciliary cleft,
SLD; the distance between Schwalbe’s line (the borderline of the cornea and sclera)
and the anterior lens capsule, ACC; the angle of the ciliary cleft, CCA; the area of
the ciliary cleft, ASD; the minimum distance between the angle recess and the scleral
venous plexus, SVPA; the total area of the scleral venous plexus on the ultrasound
biomicroscopic image of the iridocorneal angle, ST; the scleral thickness at the CCW.
Data are presented as lower and upper limits of reference ranges.
Box-plots of each ultrasound biomicrosopic measurement in the five ocular groups: (A)
corrected width of the ciliary cleft (CCW) [CCW/SLD (the distance/length of Schwalbe’s
line to the anterior lenticular capsule)]; (B) the angle of the ciliary cleft (ACC);
(C) corrected area of the ciliary cleft (CCA) [CCA/SLD2]; (D) corrected
minimum distance/length from the angle recess to the scleral venous plexus (ASD)
[ASD/SLD]; (E) corrected total area of the scleral venous plexus on the ultrasound
biomicrosopic image of the iridocorneal angle (SVPA) [SVPA/SLD2]; (F)
corrected scleral thickness (ST) [ST/SLD]. The boxes define the 25th and 75th
percentiles, with the median value indicated by a horizontal bar. The whiskers
delineate the 5th and 95th percentiles, with outliers indicated as open circles. Not
available means no detectable data due to complete collapse of the ciliary cleft
and/or the scleral venous plexus. Different letters/alphabets indicate statistically
significant differences between groups (P<0.05).NOR; normotensive eyes in normal open angle, PREDIS; normotensive eyes in
predisposition to primary closed angle glaucoma. CCW; the width of the ciliary cleft,
SLD; the distance between Schwalbe’s line (the borderline of the cornea and sclera)
and the anterior lens capsule, ACC; the angle of the ciliary cleft, CCA; the area of
the ciliary cleft, ASD; the minimum distance between the angle recess and the scleral
venous plexus, SVPA; the total area of the scleral venous plexus on the ultrasound
biomicroscopic image of the iridocorneal angle, ST; the scleral thickness at the CCW.
Data are presented as lower and upper limits of reference ranges.Nineteen cases received first medical therapy on OPUVMC, and the responsiveness to the
therapy and the ICA structures were evaluated simultaneously. Twelve dogs showing no
response to the first medical therapy had significant decrease of the corrected width and
area of the ciliary cleft, and the total area of the scleral venous plexus, compared with 7
cases responding to the therapy (Fig. 5).
Fig. 5.
Box-plots of each ultrasound biomicrosopic measurement in 7 dogs responding to first
medical therapy (Effect) and 12 dogs showing no response to the therapy (No Effect):
(A) corrected width of the ciliary cleft (CCW) [CCW/SLD (the distance/length of
Schwalbe’s line to the anterior lenticular capsule)]; (B) the angle of the ciliary
cleft (ACC); (C) corrected area of the ciliary cleft (CCA) [CCA/SLD2]; (D)
corrected minimum distance/length from the angle recess to the scleral venous plexus
(ASD) [ASD/SLD]; (E) corrected total area of the scleral venous plexus on the
ultrasound biomicrosopic image of the iridocorneal angle (SVPA)
[SVPA/SLD2]; (F) corrected scleral thickness (ST) [ST/SLD]. The boxes
define the 25th and 75th percentiles, with the median value indicated by a horizontal
bar. The whiskers delineate the 5th and 95th percentiles. Data of ASD in the group of
no effect were calculated from 3 cases, because it could not be detected in the other
9 cases due to complete collapse of the ciliary cleft and/or the scleral venous
plexus.
Box-plots of each ultrasound biomicrosopic measurement in 7 dogs responding to first
medical therapy (Effect) and 12 dogs showing no response to the therapy (No Effect):
(A) corrected width of the ciliary cleft (CCW) [CCW/SLD (the distance/length of
Schwalbe’s line to the anterior lenticular capsule)]; (B) the angle of the ciliary
cleft (ACC); (C) corrected area of the ciliary cleft (CCA) [CCA/SLD2]; (D)
corrected minimum distance/length from the angle recess to the scleral venous plexus
(ASD) [ASD/SLD]; (E) corrected total area of the scleral venous plexus on the
ultrasound biomicrosopic image of the iridocorneal angle (SVPA)
[SVPA/SLD2]; (F) corrected scleral thickness (ST) [ST/SLD]. The boxes
define the 25th and 75th percentiles, with the median value indicated by a horizontal
bar. The whiskers delineate the 5th and 95th percentiles. Data of ASD in the group of
no effect were calculated from 3 cases, because it could not be detected in the other
9 cases due to complete collapse of the ciliary cleft and/or the scleral venous
plexus.
DISCUSSION
Glaucoma is a leading cause of blindness in dogs, and there are no perfect therapies for
prevention of vision impairment in glaucomatousdogs [16, 26]. This may be attributable to
inadequate assessment of entire structural changes within the ICA and lack of a predictive
system of canineglaucoma. Hence, anatomical structures of the ICA were evaluated by UBM for
comparison of its cross-sectional microstructures in healthy and glaucomatous live dogs. UBM
clearly revealed abnormalities deep within the ICA, especially on the ciliary cleft and the
scleral venous plexus, in not only glaucomatousdogs but also in healthy canines with a
predisposition to PCAG, which were anatomical changes similar to those described in previous
reports [4, 6,
8, 10, 16, 18]. In
PREDIS, UBM values of the width and angle of the ciliary cleft were significantly lower than
those of NOR, although there were no significant differences in terms of the area of the
ciliary cleft, the minimum distance between the angle recess and the scleral venous plexus,
the total area of the scleral venous plexus and the scleral thickness between PREDIS and
NOR, indicating that the pathway of the aqueous humor in the PCAG-predisposed dogs would
function as well as that in dogs with a normal open angle, despite the presence of
structural abnormalities of the angular aperture (the opening of the ciliary cleft).Significant differences were found for UBM measurements related to the ciliary cleft
between non-glaucomatous healthy dogs and animals with unilateral glaucoma (Fig. 4). The width, angle and area of the ciliary
cleft of UNI were decreased significantly compared with those of NOR and PREDIS, and the
75th percentile values of the corrected width (0.041) and angle (6.0°) of the ciliary cleft
in UNI were smaller than the lower limits of their reference ranges in NOR. These
quantitative results suggest unilateral PCAG has decreased capacity of aqueous outflow from
the anterior chamber in the eyes. However, the aqueous outflow might be able to retain a
normal level, because there were no differences in the minimum distance between the angle
recess and the scleral venous plexus, the total area of the scleral venous plexus and the
scleral thickness between UNI and healthy normotensive eye groups (NOR and PREDIS).
Therefore, aqueous humor production should be restricted to decrease the aqueous outflow
from the anterior chamber, thereby maintaining the balance of the aqueous inflow and outflow
in the ciliary cleft to prevent onset of glaucoma. This proposal has already been accepted
as prophylactic therapy in the management of canineglaucoma [17, 18, 26]. Prophylactic medical treatment from the time of confirmed or
presumed glaucoma in the first eye is helpful for delaying or preventing the onset of the
disease in the second normotensive eye, although the median delay was about 22 months, less
than 2 years [17]. Greater delay of the onset of
glaucoma may be provided by early start of prophylactic treatment in dogs with a
predisposition to PCAG or unilateral type. UBM evaluation of the ICA is helpful for
providing objective criteria regarding the start of prophylactic treatment in dogs with a
risk of glaucoma onset. Judging from our results presented here, glaucomatous prophylaxis is
suggested for cases in which the UBM value of the corrected width, angle or area of the
ciliary cleft decreases and is less than the lower limit of the reference range in dogs with
normotensive eyes with open angle (NOR).In glaucomatousdogs, UBM also revealed ICA abnormalities that were available for
management of canineglaucoma. There were UBM parameters associated with responsiveness to
medical therapies (Fig. 5), namely, the opening of
the ciliary cleft and the total area of the scleral venous plexus. Both the opening of the
ciliary cleft (width and area of the ciliary cleft) and the total area of the scleral venous
plexus would represent valuable information for prediction of the responsiveness to medical
therapies, because the opening of the ciliary cleft and the scleral venous plexus in cases
that were responsive to the medical therapies were significantly larger than in dogs that
were unresponsive (Fig. 5). These findings suggest
that the presence of observable ciliary cleft and scleral venous plexus is important for
maintaining aqueous outflow from the anterior chamber in the eye. These UBM parameters are
useful for prediction of the effects of medical therapies with ocular hypotensive agents.
The opening of the ciliary cleft and the scleral venous plexus are key structures
contributing to not only the pathophysiology of canineglaucoma [4, 8, 16, 18, 21] but also the responsiveness to medical therapy in glaucomatous
eyes.The minimum distance between the angle recess and the scleral venous plexus was only
measured in 10 of 19 hypertensive eyes in ACG, because it could not be detected in the nine
eyes with loss of the angle recess due to complete collapse of the ciliary cleft. No
significant differences of the corrected minimum distance between the angle recess and the
scleral venous plexus, and the scleral thickness were detected between ACG and the other
ocular groups, such as NOR, PREDIS and UNI (Fig.
4), suggesting that the minimum distance between the angle recess and the scleral
venous plexus may only contribute to the aqueous outflow resistance in canine eyes, but may
not be involved in the causes of increased IOP. Meanwhile, there were statistically
significant differences in the corrected scleral thickness between ACG and CRG (Fig. 4). These abnormalities might be associated with
structural changes, such as scleral stretching or buphthalmos, induced by increased IOP in
the long term [12, 16, 18].Although gonioscopic examination is an essential diagnostic tool as a conventional
procedure for assessing abnormalities of the ICA in the field of veterinary ophthalmology,
objective and quantitative information of the ICA is needed to establish new diagnostic
criteria for improving strategies of glaucomatous managements in animals. Since UBM can
provide objective and quantitative data of entire ICA abnormalities which are unable to
assess with classical gonioscopic examination, UBM examination should be more widely applied
for detecting quantitative abnormalities of the ICA in dogs, especially in
glaucoma-predisposed dogs or cases suffering from unilateral glaucoma. The potential for UBM
examinations to contribute to analysis of glaucomatous mechanisms and provide advanced
diagnosis and management of glaucoma warrants further investigation in caninepatients.
Authors: Mary Rebecca Telle; Kevin C Snyder; Kazuya Oikawa; Jacob P Nilles; Shaile Gehrke; Leandro B C Teixeira; Julie A Kiland; Alex Huang; Gillian J McLellan Journal: Vet Ophthalmol Date: 2021-09-28 Impact factor: 1.444
Authors: András M Komáromy; Dineli Bras; Douglas W Esson; Ronald L Fellman; Sinisa D Grozdanic; Larry Kagemann; Paul E Miller; Sayoko E Moroi; Caryn E Plummer; John S Sapienza; Eric S Storey; Leandro B Teixeira; Carol B Toris; Terah R Webb Journal: Vet Ophthalmol Date: 2019-05-20 Impact factor: 1.644