TABLE CONTENTS 緑内障 GLAUCOMA 眼房水の産生

緑内障part 2
2013/12/17
TABLE CONTENTS
緑内障総論のまとめ
小動物眼科学セミナーシリーズ⑥ 緑内障の治療（前半）；点眼薬
緑内障を極めるPart 2
緑内障の治療休憩
辻田裕規, DVM, DACVO l  松山ほうじょう動物クリニック l  米国獣医眼科専門医眼房水 -‐ 産生と排泄
緑内障の治療（後半）
内服薬
外科的治療
緑内障 GLAUCOMA 水晶体
前眼房
虹彩
毛様体上皮から後房に分泌
水
房
眼
水晶体前面を通り瞳孔縁
で前房に
櫛状靭帯
虹彩根部と角膜周辺部に
挟まれる前房隅角から流出
緑内障による眼組織への影響
1. 眼表面 Outer Layer=
線維膜 Fibrous Tunic　•  角膜 / 強膜
2. 中間層 Middle Layer =
血管膜 Vascular Tunic
•  虹彩, 毛様体, 脈絡膜
3. 内層Inner Layer =
神経膜 Neural Tunic
•  神経網膜 / 色素上皮
眼房水の産生毛様体突起から
–  毛様体無色素上皮
1. 能動輸送
•  Na-K ポンプ(ATPase)
•  炭酸脱水酵素
2. 受動輸送
•  濾過/拡散
3. 自律神経支配
•  房水産生促進 – 
• 
交感神経 α1受容体・β受容体産生抑制 – 
α2受容体松山ほうじょうクリニック眼科
1
緑内障part 2
2013/12/17
13/02/28
●uveal meshwork scleral spur scleral meshwork
Schwalbe
uveal meshwork scleral meshwork S
■眼房水の排出
S
chlemm
↓
scleral meshwork 500 mℓ ？
000 mℓ Schlemm
①線維柱
帯流出路Ⅳ
chlemm
Ⅳ
0.04
Schlemm
anterior ciliary vein 眼角
endothelial meshwork 櫛状靭帯
■眼房水の排出
↑
毛様体裂
房水叢
deep scleral plexus → 眼房水の流出路 •  眼房水の排泄
episcleral vein
→ ②ぶどう膜
強膜流出路
←
® 
排泄：虹彩角膜角(隅角) drainage
毛様体裂の線維柱帯 r outflow eoscleral outflow r chamber angle
e
毛様体筋
強膜静脈叢
上脈絡膜腔
全身循環
強膜を通過
線維柱帯
流出路 h>p://www.med.teikyo-‐u.ac.jp/より
ciliary Schlemm
scleral spur 房水静脈叢
ＰＧＦ２α誘導体；ラタノプロスト 1. 炭酸脱脂酵素
formation
；トラバプロスト阻害剤；ドルゾラミド 2. Β-‐ブロッカー；チモロール
ぶどう膜強膜
全身循環
流出路 iris process Schlemm
r meshwork trabecular conventional outflow 10 mmHg 8 mmHg ▣ Fontana ' s space (i) spatia anguli iridocornealis
‘
’
Schlemm
uveoscleral outflow space of Fontana trabecular connective tissue meshwork
canal of Schlemm
sinus venosus sclerae
(ii) 緑内障の分類
Duke-Elder
●
gonioprism goniomirror •  急性 or 慢性？ •  目的が・・・ MEDICAL
IOVS, April 2012, Vol. 53, No. 4
緑内障の治療
1. Retinal
ぶどう膜炎
Intrisic Optical Signals in PCG
ü  前房フレア, 角膜後面沈着物, ü  虹彩色素, 水晶体表面への色素
ü  膨隆虹彩 1.  急性 ü  視覚の維持・回復？ ü  アグレッシブに ü  痛みの緩和？？ ü  QOL＞アグレッシブ
goniolens 3.  眼内腫瘍
ü  眼科所見 ü  全身検査
ü  超音波検査 gonio：
●
slit lamp microscope
www.med.teikyo-u.ac.jp/~ortho/med/ana/ana106.htm
1973
2.  原発性水晶体脱臼
ü  前房深度,　硝子体の脱出
ü  犬種, コーヌスの有無 2.  慢性 SURGICAL
Koeppe
u 原発性 or 続発性？？ u 基礎疾患の見極め 6/7
0.8
光断層映像法（OCT） p OpQcal Coherence Tomography 5/7
神経網膜縁
生理的陥凹
慢性緑内障
牛眼（発症後>10-‐14日）
急性or慢性？ v 網膜の断層化 v 10μmから v 非侵襲的 v 定量化可能 v 経過観察◎
水晶体の脱臼
角膜浮腫/瘢痕
FIGURE 1. PERG and OCT data. (A) OCT peripapillary B-scans (Stratus; Carl Zeiss Meditec, Inc., Dublin, CA) show optical reflectance of specific
デスメ膜の条痕
生理的陥凹の消失＝”カッピング”
retinal layers in vivo. Scans of normal cat retinas show strong reflectance arising from the RNFL (red arrow). A representative scan from glaucoma
視神経萎縮
subject 1 (G1)
is shown at right. Pronounced thinning of the RNFL was observed in both the left eye (LE, top) and especially the right eyes (RE,
bottom). Retinal scans are magnified and aligned to RPE Retina
density in (B). RNFL showed reduced density despite relatively normal retinal thickness and
網膜変性
reflectance of middle
and inner layers (regions between
RNFLIntrinsic
and RPE).
(C) PERG
amplitude.
N95ofcomponent
Retinal
Optical
Signals
in a CatThe
Model
Primary of the PERG response was
plotted as a function盲目
of spatial frequency for four data sets.
Normal feline
PERG amplitudes (open black symbols) are significantly greater than either
Congenital
Glaucoma
Schallek respectively).
ら. InvesCgaCve OThe
phthalmology & Visual Science 2012 of a normal
of the recordings of LE or RE recordings of subject G1 (closed gray and black symbols,
average N95
PERG
responses
Jesse B. Schallek,1 Gillian J. McLellan,2 Suresh Viswanathan,3 and Daniel Y. Ts’o4
cat subject to an optic nerve crush experiment are shown
in blue for comparison. The error bars represent the standard error from the mean.
PURPOSE. To examine the impact of reduced inner retinal
function and breed on intrinsic optical signals in cats.
visual stimuli to the eye evokes changes in near infrared (NIR)
reflectance of the retina.1–10 The patterned NIR reflectance
shows tight colocalization with the stimulated region of retina.
. Retinal intrinsic optical signals were recorded from
reports have focused on identifying the biophysical
recovery. Four acquisitions from the same stimulus Manesthetized
condition
cats with were
a modified fundus camera. Near infrared
RESULTS Recent
origins leading to these functional activations.
light (NIR, 700–900 nm) was used to illuminate the retina
Investigations using a variety of techniques, including in
a charge-coupled
device (CCD) camera captured the NIR
averaged together to produce one data file stored for while
offline
analysis.
vitro analysis in the flatmount preparation,
in vivo depthreflectance of the retina. Visible stimuli (540 nm) evoked
resolved analysis in the human retina, comparison to laser
patterned changes in NIR retinal reflectance. NIR intrinsic
Doppler flowmetry recordings, and pharmacologic blockade
Imaging protocols and recording conditions were kept
consistent
PERG
signals were
compared across three subject
groups: twoand OCT
to selectively suppress specific retinal laminae, have revealed
Siamese cats with primary congenital glaucoma (PCG), a
several contributing components to the optical reflectance
control Siameseno
cat without
glaucoma, and a control group of
between recording sessions and for all cats. Cats were imaged
more
signals. However, debate has arisen regarding the contributions
seven normally pigmented cats. Intraocular pressure (IOP),
of ganglion
cells to eye
these intrinsic
Previous work from
Thetomography
left and
right
of signals.
glaucoma
subject G1 showed reduced
pattern electroretinogram,
and optical coherence
than once per week to allow sufficient recovery between
imaging
our group has shown that signals persist after intravitreal
measurements were evaluated to confirm the inner retinal
injections of agents that block inner retinal function, including
deficit in PCG cats.
density and
thickness
ofglutamate
the receptor
RNFL
tetrodotoxin
(TTX), metabotropic
agonist,related to loss of ganglion
sessions
. Stimulus-evoked, NIR retinal reflectance signals were
R
2-amino-4-phosphonobutyric acid (APB), and the ionotropic
ETHODS
3,4,9
10
11
6
松山ほうじょうクリニック眼科
ESULTS
glutamate
receptor antagonist,
cell axonsacid
(Figure
1A). cis-2,3-piperidinedicarboxylic
Decreased reflectance from the RNFL
(PDA). Given that the functional signals remain after
suppression of inner retinal activity, it was
was mostpharmacologic
pronounced
right eye of this cat. A
concluded
that signals arise primarily in
from thethe
outer retinal
layers. Data from another study, however, has shown that
intravitreal
injections
of
TTX
produces
a measurable
reduction
magnification
of
OCT
data
from
the right eye of a normal
C
. Despite increased IOP, reduced nerve fiber layer
in intrinsic signal response. This result from Hanazono et
thickness and ganglion cell function, intrinsic optical signals
al. suggests that
inner retinal
function is a major
contributor
and
a
glaucoma
cat
is
shown
in
Figure
1B. The thickness and
in
cats affected with PCG. The mechanisms
giving
rise
The reflectance changes are small when compared persist
to
background
to these signals. To further tease apart the discrepancies in
to intrinsic signals remain despite inner retinal damage. Signal
these conflicting results, this study examined intrinsic optical
strength was reduced in all Siamese cats compared
to controls, of the neural retina was comparable between normal
density
signals in a naturally occurring cat model of glaucoma. In this
illumination. To reveal the optical changes, a baseline reflectance
frame
suggesting that reduced
intrinsic signals in PCG cats represent
study, two Siamese cats with a form of primary congenital
a difference between breeds rather than loss of ganglion cells.
glaucoma (PCG)
were imaged.
andthatglaucoma
cats,
with the exception of decreased reflection
results corroborated
retinal
(R) was subtracted from all subsequent frames in aThese
given
imagingprevious findings
These animals show chronic elevation in intraocular
ganglion cells are not the dominant source of intrinsic optical
pressure (IOP) and consequent loss of inner retinal function,
signals of the retina. (Invest Ophthalmol
Sci.
fromVis the
RNFL
glaucoma
The average RNFL thickness
acquisition (change in reflectance reported as dR). 2012;53:1971–1981)
The difference
hallmarks thatin
are characteristic
of many cats.
forms of human
DOI:10.1167/iovs.11.8299
glaucoma. Here, spatially-evoked intrinsic signal properties in
these
cats
were
compared
the response
measured
in a
of normalcontrol
cats
was 40to lm;
the
average
RNFL thickness of the
frames (dR) were divided by the baseline reflectance frame to provide
group of healthy, normally pigmented cats and a third
n emerging field in functional retinal imaging has been the
Siamese cat with normal IOP. In this report, data were
A
investigation
of
intrinsic
optical
reflectance
signals
in
the
right
eye
of
G1
was
20
lm,
whereas
the fractional change in reflectance (dR/R). Images presented in this
compared regarding the spectral, spatial, and temporalthe left eye was 8 lm. This
Intrinsic Optical Signal Analysis
2
observed in PCG cats despite severe degeneration of the nerve
fiber layer and inner retinal function. The time course, spectral
dependence, and spatial profile of signals imaged in PCG cats
were similar to signals measured from normal and Siamese
control cats.
6
ONCLUSIONS
11
11
緑内障part 2
2013/12/17
緑内障治療
•  目標　Goals 1. 
2. 
3. 
4. 
眼圧減少；<20 mmHg 予防視覚維持・回復不快症状の軽減方法　Methods 1.  眼房水産生を抑える 2.  流出量を増加させる内科＋外科 Where and how… CAIs 緑内障薬眼房水産生の抑制 •  Beta blockers •  CAI点眼眼房水排泄の増加
•  PG類似薬
•  副交感神経（コリン）作
動薬
緊急眼圧降下治療
•  急性原発性緑内障
•  マンニトール
•  前房穿刺
•  外科的介入
点眼薬(炭酸脱水酵素阻害剤-‐CAI)
炭酸脱水酵素 : 7種類存在
房水産生；毛様体上皮-‐Ⅱ型↑
内服CAI；全てのCAを阻害
点眼CAI；Ⅱ型CAを選択阻害
毛様体のCAが完全抑制
•  房水産生は40％抑制される
効果；犬＞猫
•  色素の親和性
•  猫での分布は不明
炭酸脱水酵素阻害剤；眼房水産生抑制点眼
•  ドルゾラミド 1%（日本）, 2%（米国）
•  ブリンゾラミド1% 経口
•  アセタゾラミド •  dogs: 4-‐10 mg/kg BID-‐TID •  メタゾラミド
•  dogs: 2.2 -‐ 4.4 mg/kg PO q8-‐12 h •  cats: 1-‐2 mg/kg PO q8-‐12h 点眼+経口のコンボ治療；効果の相乗なし
松山ほうじょうクリニック眼科
点眼薬(炭酸脱水酵素阻害剤-‐CAI)
•  ドルゾラミド
–  トルソプト
–  刺激性あり –  日本；1.0％と0.5％の2種類
–  米国; 2%あり
•  ブリンゾラミド
–  エイゾプト:
–  刺激性↓　（PH7.4）
–  1日2回点眼
–  懸濁液なので霞む
3
緑内障part 2
炭酸脱水酵素阻害薬；副作用
2013/12/17
Where and how… β-‐blockers 経口
• 代謝性アシドーシス
• 肝障害
• Blood dyscrasiis • 胃腸障害
点眼
• 刺激性
• 羞明
β-‐ブロッカー点眼薬
•  Beta-‐blockers – 眼房水産生の抑制 •  マレイン酸チモロール
0.25%, 0.5% •  ベタキソロール 0.5% •  1 drop BID〜TID β-‐ブロッカー点眼薬
毛様体無色素上皮に作用
•  アドレナリン作動性β受容体に作用
•  NonselecQve β-‐adrenergic receptor antagonist 縮瞳効果
•  瞳孔括約筋に抑制的に働くβアドレナリン作動線維を
抑制
•  点眼30分後に31.4%の縮瞳率 (Wilkie DA et al , 1991) 副作用
•  徐脈
•  縮瞳
CAI + β-‐ブロッカー点眼薬
CAI + β-‐ブロッカー点眼薬
•  Cosopt –  0.5％チモロール
+ドルゾラミド (米国 2%, 日本 1%) –  点眼本数・回数の減少 –  刺激性あり ⇔0.5％チモプトール単独治療
；さらに20％（5mmHg）眼圧降下(米)
松山ほうじょうクリニック眼科
眼圧・心拍数・瞳孔径への影響
点眼薬
0.5%チモロール 2%ドルゾラミド 0.5%チモロール + 2%ドルゾラミド
眼圧 Day 1
2.83mmHg
6.47mmHg
6.56mmHg
眼圧 Day 4
3.75mmHg
7.50mmHg
8.42mmHg
心拍数
-‐11.9 bpm コントロール群と
-‐8.6 bpm
瞳孔径 -‐1.42 mm
-‐1.3 mm
有意差なし
コントロール群と
有意差なし
4
      77
緑内障part 2
2013/12/17
4. Yablonski ME, Novack GD, Burke PJ et al. The effect of levoA potential limitation of this study was that the effects of
bunolol on aqueous humor dynamics. Experimental Eye Research
general anesthesia on EVP were not specifically evaluated.
1987; 44: 49–54.
      77
Others have previously reported that there are no significant
5. Kanno M, Araie M, Koibuchi H et al. Effects of topical nipradidifferences in EVP recordings using a variety of general
lol, a betaME,
blocking
agent
with
alphaPJblocking
andeffect
nitroglycerin4. Yablonski
Novack
GD,
Burke
et al. The
of levoA potential limitation of this study was that the
2 effects of
anesthesia regimens in normotensive beagles. However,
bunolol
on aqueous
humor dynamics.
Experimental
Research
like activities,
on intraocular
pressure and
aqueous Eye
dynamics
in
general anesthesia on EVP were not specifically evaluated.
1987;
44:
49–54.
there
have
been
no
studies
directly
comparing
EVP
humans. British Journal of Ophthalmology 2000; 84: 293–299.
Others have previously reported that there are no significant
5. Kanno M, Araie M, Koibuchi H et al. Effects of topical nipradimeasurements
with recordings
and withoutusing
general
anesthesia
as EVP
6. Sponsel WE, Mensah J, Kiel JW et al. Effects of latanoprost and
differences
in EVP
a variety
of general
lol, a beta blocking agent with alpha blocking and nitroglycerin2
However,
anesthesia
regimens
in normotensive
timolol-XE
onon
hydrodynamics
in the normal
eye. American
Jourmeasurements
in animals
require a beagles.
general anesthesia.
like
activities,
intraocular pressure
and aqueous
dynamics
in
there have been no studies directly comparing EVP
nal of Ophthalmology
2000;
130: 151–159.2000; 84: 293–299.
humans.
British Journal
of Ophthalmology
Nevertheless, if general anesthesia has an effect on EVP, it
measurements with and without general anesthesia as EVP
6.
Sponsel
WE,
Mensah
J,
Kiel
JW
et
al.
Effects
of
latanoprost
and
7. Blondeau P, Tetrault JP, Papamarkakis C. Diurnal variation of
would have theinsame
effectsrequire
on the absolute
EVP
values in
timolol-XE on hydrodynamics in the normal eye. American Jourmeasurements
animals
a general
anesthesia.
episcleral venous pressure in healthy patients: a pilot study. Journal of Ophthalmology 2000; 130: 151–159.
both the dosed
and nondosed
eyes
with
latanoprost.
Asita
Nevertheless,
if general
anesthesia
has
an effect
on EVP,
nal of Glaucoma
2001; 10:
7.
Blondeau
P, Tetrault
JP, 18–24.
Papamarkakis C. Diurnal variation of
would
samedifferences
effects on in
theEVP
absolute
EVP the
values
in
result,have
the the
relative
between
dosed
8. episcleral
Crowstonvenous
JG, Aihara
M, in
Lindsey
JDpatients:
et al. Effect
of study.
latanoprost
pressure
healthy
a pilot
Jourboth
dosed eyes
and nondosed
As a
and the
nondosed
should beeyes
the with
samelatanoprost.
with or without
nal
Glaucoma
2001;in10:
on ofoutflow
facility
the18–24.
mouse. Investigative Ophthalmology and
result, the relative differences in EVP between the dosed
8. Crowston
JG,2004;
Aihara
Lindsey JD et al. Effect of latanoprost
general
anesthesia,
and
the
conclusions
of
the
paper
would
Visual Science
45:M,
2240–2245.
and nondosed eyes should be the same with or without
on outflow facility in the mouse. Investigative Ophthalmology and
9. Visual
GabeltScience
BT, 2004;
Kaufman
PL. Aqueous humor hydrodynamics. In:
remain anesthesia,
unchanged.and the conclusions of the paper would
general
45: 2240–2245.
■線維柱帯流出路　Adler’s Physiology
of the PL.
Eye, Aqueous
10th edn.humor
(eds Kaufman
PL, Alm In:
A)
9. Gabelt
BT, Kaufman
hydrodynamics.
To conclude,
remain
unchanged.unlike what has been previously demonAdler’s
Physiology
of
the
Eye,
10th edn. (eds Kaufman PL, Alm A)
Mosby,
St.
Louis,
2003;
237–289.
To conclude,
unlike
what
has been
previously
demonstrated
in humans
and the
mouse,
the topical
ana• PGF2a
(主流出路)
St. Louis,
2003; 237–289.
10. Mosby,
Sit AJ, Nau
CB, McLaren
JW et al. Circadian variation of aquestrated in humans and the mouse, the topical PGF2a analogue 0.005% latanoprost increases EVP in dogs. This
10. Sit AJ, Nau CB, McLaren JW et al. Circadian variation of aquelogue 0.005% latanoprost increases EVP in dogs.
This dogs ous dynamics in young healthy adults. Investigative Ophthalmology
–  85% ous dynamics in young healthy adults. Investigative Ophthalmology
responsemay
maybe
beunique
uniqueto
todogs
dogsand
andsuggests
suggeststhat
thatdogs
dogs
may
response
may
and Visual
Visual Science
Science 2008;
2008; 49:
49: 1473–1479.
1473–1479.
and
notfully
fullymimic
mimichuman
humanaqueous
aqueoushumor
humordynamics
dynamicswith
with
topinot
topiStuder ME,
ME, Martin
Martin CL,
CL, Stiles
Stiles J.
J. Effects
Effects of
of 0.005%
0.005% latanoprost
latanoprost
–  92~97% c11.ats 11.
Studer
cal
solution
cal0.005%
0.005%latanoprost.
latanoprost.Shunting
Shuntingof
ofblood
bloodfrom
fromthe
thearterioarteriosolution on
on intraocular
intraocular pressure
pressure in
in healthy
healthy dogs
dogs and
and cats.
cats. AmeriAmerican
Journal
of
Veterinary
Research
2000;
61:
1220–1224.
lar
present
■ぶどう膜強膜流出路　can Journal of Veterinary Research 2000; 61: 1220–1224.
lartotovenule
venuleside,
side,regulated
regulated through
through the
the AVA’s
AVA’s
present in
in
12. Woodward DF, Krauss AH, Chen J et al. The pharmacology of bithe episcleral outflow system, may be occurring so as to
12. matoprost
Woodward(Lumigan).
DF, KraussSurvey
AH, Chen
J et al. The pharmacology
of bithe episcleral outflow system, may be occurring
so asthe
to
of Ophthalmology
2001; 45(Suppl
4):
•  (副流出路)
compensate for a lowering of IOP that occurs following
matoprost (Lumigan). Survey of Ophthalmology 2001; 45(Suppl 4):
S337–S345.
compensate of
for atopical
lowering0.005%
of IOP that
occurs following
the
instillation
latanoprost.
Although
13. Chen
J, Dinh T, Woodward DF et al. Bimatoprost: mechanism
S337–S345.
– not
15% frequently
in human
studies,
EVP should
be dogs of ocular surface hyperemia associated with topical therapy.
instillationperformed
of topical
0.005%
latanoprost.
Although
13. Chen J, Dinh T, Woodward DF et al. Bimatoprost: mechanism
regarded
to performed
be a constant
value in
aqueous
humor
dynamic
Drug Reviews 2005; 23: 231–246.
frequently
in human
studies,
EVP
should
not be cats Cardiovascular
of ocular surface hyperemia associated with topical therapy.
–  3~8% studies in the normal beagle dog.
14. Johnstone McLean NS, Ward DA, Hendrix DV. The effect of a
regarded to be a constant value in aqueous humor dynamic
Cardiovascular
Reviews
2005;
23: 眼房水の流体力学 231–246.
single
dose of Drug
topical
0.005%
latanoprost
and 2% dorzolamide/
studies in the normal beagle dog.
14. 0.5%
Johnstone
McLean
NS, Ward
DA,blood-aqueous
Hendrix DV. barrier
The effect
of a
timolol
combination
on the
in dogs:
Where and how… プロスタグランジン製剤プロスタグランジン製剤
眼房水の排泄 FINANCIAL DISCLOSURES
The following co-authors were full-time employees of
F I N A N CInc.
I A Lat
D the
I S C time
LOSU
R Estudy
S
Allergan,
this
was conducted: Susan
プロスタグランジン製剤
•  Prostaglandin analogues Tsai, Alexandra Almazan, James A. Burke, Patrick M.
The following
co-authors
were full-time
of
Hughes,
Huajiang
Li, Paul Conforti,
Susan employees
S. Lee, and
Allergan,
at the time
this study
was conducted:
Susan
Michael
R.Inc.
Robinson.
The study
was performed
at Covance
Laboratories
Inc. Almazan,
with funding
from
Inc., and
Tsai, Alexandra
James
A. Allergan,
Burke, Patrick
M.
Craig
Struble
and Susan
Howard
are full-time
Hughes,
Huajiang
Li, Paul
Conforti,
Susan S.employees
Lee, and
of Covance. Paul E. Miller is a member of the University of
Michael R. Robinson. The study was performed at Covance
Wisconsin Comparative Ophthalmic Research Laboratory
Laboratories
Inc. with
funding
Allergan,
Inc.,
and
and
received funding
for this
studyfrom
through
Covance.
Susan
Tsai
is now
at Colorado
State
University
and is a consultant
Craig
Struble
and Susan
Howard
are full-time
employees
for
of Allergan,
Covance. Inc.
Paul E. Miller is a member of the University of
asingle
pilotdose
study.
Veterinary
11: 158–
of topical
0.005% Ophthalmology
latanoprost and2008;
2% dorzolamide/
161.
0.5% timolol combination on the blood-aqueous barrier in dogs:
15. Smith LN, Miller PE, Felchle LM. Effects of topical administraa
pilot
study.
Veterinary
Ophthalmology
2008;
11: 158–
tion of latanoprost, timolol, or a combination of latanoprost
and
161.
timolol
on intraocular pressure, pupil size, and heart rate in
normal
American
Research
15. clinically
Smith LN,
Miller dogs.
PE, Felchle
LM.Journal
Effects ofof Veterinary
topical administra2010;
71:
1055–1061.timolol, or a combination of latanoprost and
tion of
latanoprost,
16. Zeimer RC, Gieser DK, Wilensky JT et al. A practical venomatimolol on intraocular pressure, pupil size, and heart rate in
nometer. Measurement of episcleral venous pressure and assessclinically
normal
dogs.
American
of Veterinary
Research
ment
of the
normal
range.
ArchivesJournal
of Ophthalmology
1983;
101:
1447–1449.
2010; 71: 1055–1061.
17.
Littell
RC,
Milliken
GA,
Stroup
WW
et
al.
SAS
for
Mixed
Models.
16. Zeimer RC, Gieser DK, Wilensky JT et al. A practical venomaSAS Institute Inc, Cary, NC, USA, 2006.
nometer. Measurement of episcleral venous pressure and assess18. Bito LZ, Camras CB, Gum GG et al. The ocular hypotensive
ment of
theside
normal
range.
Archives of Ophthalmology
101:
effects
and
effects
of prostaglandins
on the eyes 1983;
of experi1447–1449.
mental
animals. In: The Ocular Effects of Prostaglandins and Other
Eichosanoids.
(eds
Bito
LZ,
Stjernschantz
J)
Alan
R.
Liss,
Inc,
New
17. Littell RC, Milliken GA, Stroup WW et al. SAS for Mixed Models.
York, 1989; 349–368.
SAS Institute Inc, Cary, NC, USA, 2006.
19. Gum GG, Kingsbury S, Whitley RD et al. Effect of topical prosta18. glandin
Bito LZ,
Camras
CB,isopropyl
Gum GG
et al.
ocular
hypotensive
PGA2,
PGA2
ester,
andThe
PGF2
alpha
isopropyl
effectsonand
side effects
of prostaglandins
on the
of experiester
intraocular
pressure
in normotensive
andeyes
glaucomatous
canine
eyes.
Journal
of
Ocular
Pharmacology
1991;
7:
107–116.
mental animals. In: The Ocular Effects of Prostaglandins and Other
20. Toris
CB, Gabelt
BT,LZ,
Kaufman
PL. Update
Eichosanoids.
(eds Bito
Stjernschantz
J) Alanon
R.the
Liss,mechanism
Inc, New
of action of topical prostaglandins for intraocular pressure reducYork, 1989; 349–368.
tion. Survey of Ophthalmology 2008;
53(Suppl
1): S107–S120.
図２
ラタノプロストの受容体親和性
(概略図)
19. Ward
Gum GG,
Kingsbury
S, Whitley RD
et al. Effect
of topical
prosta21.
D. Effects
of latanoprost
on aqueous
humor
flow 115,
rate
野村俊治
他：日薬理誌,
280,in
2000より作成
normal
Proceedings,
36th Annual
of thealpha
American
Colglandindogs.
PGA2,
PGA2
isopropyl
ester,Meeting
and PGF2
isopropyl
Pizziraniら(2001)
lege
Veterinary
Ophthalmologists,
Nashville, TN,and
2005.
esterof on
intraocular
pressure in normotensive
glaucomatous
タフルプロストの特徴
プロスタグランジン製剤
ラタノプロスト
FP 受容体作動薬
Wisconsin Comparative Ophthalmic Research Laboratory
–  ぶどう膜強膜流出路, 線維柱帯流出路か
Rand
EFE
RENCE
S
received
funding
for this study through Covance.毛様体筋束と筋間の間を緩める
Susan
らの流出増加 1.
Kaufman
Crawford State
K. Aqueous
humor
dynamics:
how
Tsai
is now PL,
at Colorado
University
and is
a consultant
–  犬 3)
PGF2a lowers intraocular pressure. In: The Ocular Effects• of細胞外マトリックスの変化(↑MMP1, Profor Allergan, Inc.
staglandins and Other Eichosanoids. (eds Bito LZ, Stjernschantz J)
•  0.12%イソプロピルウノプロストン(レス
•  ぶどう膜強膜路からの房水の流出アップ
Alan R. Liss, Inc., New York, 1989; 387–416.
キュラ);1994 2. Gelatt KN, Gum GG, Merideth RE et al. Episcleral venous presR Esure
FER
NCES
inEnormotensive
and glaucomatous beagles. Investigative
Oph縮瞳
•  0.005% ラタノプロスト (Xalatan)；1999 thalmology and Visual Science 1982; 23: 131–135.
Kaufman
Crawford
K. Aqueous
humor effects
dynamics:
how
•  8.6mm→3.6
mm；24時間
3.1.Berson
FG, PL,
Epstein
DL. Separate
and combined
of
timo•  0.004% トラバプロスト (トラバタンズ);
lol
maleate
and intraocular
acetazolamide
in open-angle
glaucoma.
American
PGF2a
lowers
pressure.
In: The Ocular
Effects
Pro- 投与後3時間
•  of最高;
2007 Journal of Ophthalmology 1981; 92: 788–791.
staglandins and Other Eichosanoids. (eds Bito LZ, Stjernschantz J)
canine eyes. Journal of Ocular Pharmacology 1991; 7: 107–116.
•  0.0015%タフルプロスト（タプロス）;2008
タフルプロストは PG の作用発現に必須と考
Alan R. Liss, Inc., New York, 1989; 387–416.
20. Toris CB, Gabelt BT, Kaufman PL. Update on the mechanism
血液房水関門の破壊
えられてきた !
"位の水酸基を変換し, !
"位に
2. Gelatt KN, Gum GG, Merideth RE et al. Episcleral venous pres•  0.03% ビマトプロスト　(ルミガン);2009
of action
of topical prostaglandins for intraocular pressure reduc! 2012 American College of Veterinary Ophthalmologists, Veterinary
Ophthalmology,
15,
71–78
•  房水の産生自体も減少
#つのフッ素を含有する新規な PGF 誘導体で
sure in normotensive and glaucomatous beagles. Investigative
Ophtion. Survey of Ophthalmology 2008; 53(Suppl 1): S107–S120.
–  禁忌;ContraindicaQon ある
(図
$
)｡
thalmology and Visual Science 1982; 23: 131–135.
•  炎症 21. Ward D. Effects of latanoprost on aqueous humor flow rate in
•  ぶどう膜炎 3. Berson FG, Epstein DL. Separate and combined effects of timonormal dogs. Proceedings, 36th Annual Meeting of the American Collol maleate and acetazolamide in open-angle glaucoma. American
•  瞳孔ブロック　(水晶体, 硝子体) lege of Veterinary Ophthalmologists, Nashville, TN, 2005.
#
α
Journal of Ophthalmology 1981; 92: 788–791.
! 2012 American College of Veterinary Ophthalmologists, Veterinary Ophthalmology, 15, 71–78
また, 正常眼圧サ
ルプロストは濃度依
し, タフルプロスト
ト&
.&
&
"
％と同程度の
(図 ")｡
図５
単回点眼による
Taka
正常眼圧サルに !
時, タフルプロスト
同様 $日目および "日
効果の減弱はなかっ
の眼圧は, ラタノプ
スラインに戻ったが
目および "日目の点
間後に相当) および
図３タフルプロストの構造
剤に比べ有意な眼圧
+
ロストンの眼圧下降作用に関しては、主経路からの流
■ウノプロストンの作用点はMaxi-K チャネル
復点眼により持続性
進の報告があるなど、プロスト系とは異なる面があると
相原プロストン系薬剤のウノプロストンは、細胞膜表面に
タフルプロストは,
ラタノプロストに比べて
れた (図 ')｡
+
+
られます。ですから、PG関連薬の中でもプロストン系
存在するカリウムイオン
（K ）チャネルの1種であるMaxi-K
約!
#倍高い FP 受容体親和性を示した
(図 %)｡
剤とプロスト系の薬剤を分けて考えるとわかりやすい
（BK）チャネルに作用することが報告されています（図3）
。
プロスタグランジン製剤
このMaxi-K+チャネルは大容量カルシウム
（Ca2+）依存性の
ラタノプロスト
その他のPGF2α誘導体点眼薬
います。
K+チャネルで、細胞内Ca2+濃度の上昇を感知して開口し、
細胞外へK+を流出させます。Maxi-K+チャネル開口薬には
血管平滑筋細胞の弛緩作用、神経細胞保護作用、
さらに線
維柱帯細胞の弛緩作用などがあるといわれています。
血液房水関門の破壊
•  房水の産生自体も減少
•  炎症
•  血液房水関門の破壊 in Normal canine eye
•  フルオレ造影剤の眼内浸透；
•  49％；ラタノプロスト　•  10%; 無治療眼 Veterinary Ophthalmology (2008) 11, 3, 158–161
Blackwell Publishing Inc
The effect of a single dose of topical 0.005% latanoprost and 2%
dorzolamide/0.5% timolol combination on the blood-aqueous barrier
in dogs: a pilot study
Nancy S. Johnstone McLean, Daniel A. Ward and Diane V. H. Hendrix
Department of Small Animal Clinical Sciences, University of Tennessee College of Veterinary Medicine, Knoxville, TN 37996, USA
トラバプロスト (®トラバタンズ)
プロスト系の薬剤は、主にぶどう膜強膜流出路の流出促
進によって眼圧を下げると考えられています。一方、ウノプ
•  イソプロピルエステル; PGF2α前駆物質（ラタノプロストと同じ）
図2 PG
•  EP1 (ラタノプロスト) + EP3（ウサギでも◎？） / 関連薬のプロスタノイド受容体親和性
防腐剤なし
Latanoprost acid
タフルプロスト (®タプロス)
TP
•  ⇔ラタノプロスト(®キサラタン)
•  FP受容体への親和性・選択性が高い
•  エチルアミド；17-‐phenyl-‐PGF2αの前駆物質
•  室温保存が可能
•  より網膜の血流を増加
ビマトプロスト:(®ルミガン)
• 
Travoprost acid
FP
図４
プロスタノイド10FPFP
受容体に対する親和性(in vitro)
10-10
EP1
10-7
TP
10-4
10-1
IP
EP2
!
"
DP
-10
10-1
大阪府薬雑誌
EP3
EP1
10-7
Daniel Ward
Tel.: +865 974 8387
Fax: +865 974 5554
e-mail: [email protected]
Abstract
Objective To determine the effects of 0.005% latanoprost and 2% dorzolamide/0.5%
timolol on the blood-aqueous barrier (BAB) in normal dogs.
Animals studied Eight mixed-breed and pure-breed dogs.
Procedures Baseline anterior chamber fluorophotometry was performed on eight normal
dogs. Sodium fluorescein was injected and the dogs were scanned 60–90 min
post-injection. Seventy-two hours following the baseline scan, one eye received one drop
of latanoprost. Fluorophotometry was repeated 4 h after drug administration. Following
a washout period, the identical procedure was performed 4 h after the administration of
dorzolamide/timolol. The degree of BAB breakdown was determined by comparing the
concentrations of fluorescein within the anterior chamber before and after drug
administration. BAB breakdown was expressed as a percentage increase in the
post-treatment fluorescein concentration over the baseline concentration: %INC
[Fl] = {([Fl]post – [Fl]baseline)/[Fl]baseline} × 100. The percentage increase in fluorescein
concentration in the treated eye was compared to that in the nontreated eye using a
paired t-test with significance set at P ≤ 0.05.
Results Following administration of latanoprost, the fluorescein in the treated eyes
increased 49% (± 58%) from baseline compared to 10% (± 31%) in the untreated eyes
(P = 0.016). Following administration of dorzolamide/timolol, the fluorescein
concentration increased 38% (± 54%) compared to baseline vs. 24% (± 38%) in the
untreated eyes (P = 0.22).
Conclusions The results of this study show that topical latanoprost may cause BAB
disruption in normal dogs while topical dorzolamide/timolol may have no effect on the
BAB in normal dogs.
松山ほうじょうクリニック眼科
Taka
EP2
!"#
$
!
"
%&"$
#
"($
"
"
%
)
DP
EP3
EP4
EP4
Unoprostone acid
TP
FP
10-10
10-7
EP1
プロストン系
10-4
10-1
IP
DP
EP2
Hellberg. M.R. et al.: J. Ocul. Pharmacol. Ther. 17(5): 433, 2001.
Sharif. N.A. et al.: J. Ocul. Pharmacol. Ther. 19(6): 501, 2003.
Nomura. S. et al.: Nippon Yakurigaku Zasshi 115(5): 280, 2000.
EP3
EP4
昼間の眼圧下降効果:他剤と比べてやや強い h>p://rescula.jp/glaucoma/symposium/
upload_docs/pamp_05.pdfより引用
図3 ウノプロストンの作用機序
イソプロピルウノプロストン(®レスキュラ)
（眼外からのルート）
眼底血管平滑筋
ウノプロストン
（眼外からのルート）
網膜神経節
線維柱帯
Ca2+依存性Maxi-K+チャネルの開口
Address communications to:
図６１日１回反復点眼に
Takagi10-4Y et al, Expプロス
Eye ト系
Res 78: 768(2004)
IP
Thieme. H. et al.: IOVS 42(13), 2001.
Cuppoletti. J. et al.: BBA 1768(5), 2007.
血管平滑筋細胞内
神経節細胞内
線維柱帯細胞内
Ca の上昇抑制
Ca の上昇抑制
Ca の上昇抑制
2+
血管拡張
2+
神経細胞の
アポトーシスを抑制
Marcheselli. V. et al.: IOVS 42(S750), 2001.
Lafuente. M.P. et al.: IOVS 41(S15), 2000.
血流増加
杉山、吉冨、木村、
その他多数
視神経保護
Melamed. S.: Drugs. Exptl. Clin. Res. 63, 2002.
2+
房水流出抵抗の減少
主経路からの房水流出の促進
眼圧下降
Thieme. H. et al.: IOVS 42(13), 2001.
志村ほか: 第108回日本眼科学会総会, 2004.
視野維持
5
緑内障part 2
2013/12/17
■ウノプロストンの作用点はMaxi-K+チャネル
ロストンの眼圧下降作用に関しては、主経路からの流
進の報告があるなど、プロスト系とは異なる面があると
相原プロストン系薬剤のウノプロストンは、細胞膜表面に
Veterinary Ophthalmology (2012) 15, Supplement 1, 31–35
犬 VS PG製剤
DOI:10.1111/j.1463-5224.2011.00934.x
Dose response for travoprost! in the glaucomatous beagle
Edward O. MacKay,* Marsha McLaughlin,† Caryn E. Plummer,* Anna Ben-Shlomo* and Kirk N. Gelatt*
*
Department of Small Animal Clinical Sciences and Gwathmey-Adams Laboratory for Vision Research, College of Veterinary Medicine, University of Florida,
Veterinary Ophthalmology (2006) 9, 2, 121–125
PO Box 100126, Gainesville, FL 32610-0126, USA; and †In Vivo Pharmacology, Alcon Research Ltd, Ft Worth, TX, USA
Blackwell Publishing, Ltd.
Abstract0.004% compared with latanoprost 0.005% on
Effects of travoprost
Objective To evaluate the changes in intraocular pressure (IOP) and pupil size in 12
the intraocular pressure
of normal dogs
Beagles with inherited glaucoma after instillations of 0.033, 0.0033, 0.001, 0.00033,
Morning
Evening
1日2回
dogs. After 7 days, the vehicle or concentration was repeated in the contralateral eye
of the same animals.
Results
Concentrations of 0.00033, 0.001, and 0.0033% travoprost significantly
Abstract
lowered
IOP
PD, but
0.0001%
concentration
limited IOP
changes,
Purpose
Toand
compare
thethe
effects
of travoprost
0.004%provided
and latanoprost
0.005%
on the
although
PD changes
still
This suggests travoprost is effective in the
intraocular
pressurewere
(IOP)
of significant.
normal dogs.
Tel.: 0055 16 32092626
dogMethods
to lowerTwenty
IOP and
reduce
pupil
at randomized
concentrations
starting
between
0.0001was
andused
mixed
breed
dogssize
were
to two
groups:
latanoprost
Fax: 0055 16 32024275
0.00033%.
e-mail: [email protected]
in group A and travoprost in group B. The drugs were instilled in the right eye of the
Conclusions
The
dose
response
for
travoprost
in
the
glaucomatous
Beagle
indicates
this
dogs,
whereas
the
left
eye
received
placebo.
Both
drugs
were
instilled
once
a
day
at 8 
Faculdade de Ciências Agrárias e
is highly
to this groupwere
of drugs,
at, concentrations
as
Veterinárias – FCAV/UNESP,model
during
5 days.sensitive
IOP measurements
made even
at 8 
10 , 2  andas8low
 during
the
Departamento de Clínica e Cirurgia0.00033% (1/12 the commercially available concentration).
5 days of treatment, the 3 days that preceded treatment, and 3 days following treatment.
Veterinárias, Via de Acesso Prof.
Presence
blepharospasm,
miosis,
anterior chamber
flare, and conjunctival
hyperemia
Paulo Donato Castellane, s/n°,Key
Words:ofanalogue,
glaucoma,
ophthalmology,
pharmacology,
prostaglandin,
CEP: 14884-900, Jaboticabal, São
were evaluated during the study.
travoprost
Paulo, Brazil
Results Mean IOP was significantly reduced in the eyes treated with both latanoprost and
travoprost, when compared with the eyes treated with placebo (P < 0.05). There was no
statistically significant difference between the mean IOPs of eyes treated with latanoprost
and travoprost at all time intervals during baseline, treatment, and recovery (P > 0.05).
On the fifth day of treatment and on the first day of the recovery period, a severe ocular
!
hypotension was noted with both
drugs, resulting
imprecise readings
Latanoprost
(0.005%inXALATAN
; Pfizer,with
Newthe
York,
INTRODUCTION
tonometer. Miosis and conjunctival
hyperemia
were
observed
the evaluated
treated eyes
of both
NY, USA)
ophthalmic
solution
hasin
been
in norgroups,
whereas
flare in
was noticed
in one
Topical prostaglandin-analogs, which
produce
changes
mal cats
and latanoprost-treated
dogs (once daily foreye.
8 days),2 or dogs only
intraocular pressure (IOP) and pupil
diameterTravoprost
(PD) in the0.004%
(twice
daily for reduces
5 days)3 the
as well
Conclusion
significantly
IOPas
in glaucomatous
normal dogs. Beagles
The
4
dog, have been reported for 20 years.
Topical
prostaglandins
(multiple
dose
for
5
days).
IOP
and
PD
decreased
in nor-with
hypotensive effect obtained with travoprost 0.004% is comparable to that obtained
mal dogs; IOP was reduced about 3–4 mmHg. In cats,
can produce considerable reductions
in IOP as well
as intense
latanoprost
0.005%.
miosis, which have made these agents front-line therapeutic
latanoprost did not significantly lower IOP but did cause
2
Key
Words: dogs, intraocular
pressure,
prostaglandin,
travoprost
agents for the treatment of the canine
glaucomas.
miosis.
Withlatanoprost,
5-day dosing
schedules of
once in the
Gum, et al.1 first reported the evaluation of selected promorning or once in the evening, or twice daily, 0.005%
staglandins, i.e., prostaglandin PGA2, prostaglandin PGA2
latanoprost lowered IOP significantly in glaucomatous
isopropyl ester, and prostaglandin PGF2" isopropyl ester in
Beagles.4 The reductions in IOP after only evening instilnormal and glaucomatous Beagles. All concentrations of
lations resulted in less daily fluctuations than when the
PGA2 (1.0, 10, and 20 lg/50 lL) failed to lower IOP in nordrug was instilled only in the morning. Twice daily
4–6
Latanoprost
a prostaother prostaglandin
mal and glaucomatous Beagles. PGA2 isopropyl ester lowinstillations
of 0.005% receptors.
latanoprost
produced
the islargest
INTRODUCTION
glandin
analog
FP daily
receptor
agonist but
thatlonger
acts as an
ered IOP in normal and glaucomatous Beagles; the declines
decline
in IOP
withand
thean
least
fluctuations
Elevated
intraocular
the major
risk
factor duration
ocularmiosis.
hypotensive agent. Latanoprost increases uveoscleral
were
significant
at 30–60pressure
min and(IOP)
lastedisabout
5 h. All
confor the development
ofand
glaucoma.
Although
outflow,
without prostaglandin-analogs
affecting aqueous production
oravailable
conventional
centrations
(0.5, 1.0, 5.0,
10.0 lg/50
lL) ofimprovement
prostaglan- on Later,
additional
became
7–9
dincyclodestructive
PGF2" isopropyl
esterand
significantly
loweredenhancement
IOP in
anddrainage.
their effects
evaluated in the
eyes an
of domestic
animals.
Latanoprost
is also
ester prodrug
and is
surgery
aqueous outflow
!
normal
and glaucomatous
Beagles.
IOP was significantly
; cornea,
Allergan,when
Irvine,
CA,
(0.03%
LUMIGAN
hydrolyzed
by esterases
in the
it becomes
procedures
has given veterinary
ophthalmologists
better results Bimatoprost
decreased
within 1 h of drug
instillation
and persisted
was also evaluated
at different
schedules
latanoprost
biologically
active dosing
acid. The
acid (once
is more
on the treatment
this disease,
medical
therapyalong
remains USA)
with
longerstrategy
than 24toh. glaucoma control.1 Prostaglandin in the
morning,and
or once
in thereleased
evening,
or twice
daily) in
hydrophilic
is slowly
from
the cornea
to the
anmiosis
important
analogs represent a class of ocular hypotensive agents that
aqueous humor for approximately 24 h.8,10,11 Human and
# 2012
American
of effectively
Veterinary Ophthalmologists
canine ocular tissues have been shown to hydrolyze PGF2α
reduce
IOP atCollege
least as
as nonselective β-adrenergic
antagonists, and act by increasing uveoscleral outflow.2,3
prodrugs in a similar manner.12 It has been suggested that
Travoprost is an isopropyl ester prodrug that is rapidly
latanoprost can modify the extracellular matrix in the cillary
hydrolyzed by esterases in the cornea, resulting in travoprost
body by stimulating the activity of metalloproteinases.13
Netland et al. (2001) compared the effects of travoprost and
free acid, its biologic active form. In the nanomolar range,
latanoprost on the IOP of patients with open-angle glaucoma
the acid has demonstrated preferential affinity and full agonist
or ocular hypertension. Eight hundred one patients were
activity for the FP receptor, with no meaningful affinity for
↓↓
↓
Address communications to:
J. L. Laus
↓↓↓ 61%
2.75-‐7.45mmHg (40.3%)
ラタノプロスト（正常犬）
ビモプロスト 0.03% （緑内障犬）
25-‐39%
25-‐39%
25-‐39%
トラバプロスト 0.004% （緑内障犬） 59% 58% 75% (27-‐28mmHg↓)
2.95-‐7.85mmHg (44.6%)
トラバプロスト（正常犬） 50% ウノプロスト（緑内障犬）
25％　（20→15mmHg）
ウノプロスト（正常犬）
剤とプロスト系の薬剤を分けて考えるとわかりやすい
います。
PG製剤の組み合わせ
K+チャネルで、細胞内Ca2+濃度の上昇を感知して開口し、
細胞外へK+を流出させます。Maxi-K+チャネル開口薬には
血管平滑筋細胞の弛緩作用、神経細胞保護作用、
さらに線
Address communications to:
ラタノプロスト0.005% （緑内障犬）
られます。ですから、PG関連薬の中でもプロストン系
（BK）チャネルに作用することが報告されています（図3）
。
このMaxi-K+チャネルは大容量カルシウム
（Ca2+）依存性の
維柱帯細胞の弛緩作用などがあるといわれています。
Edward O. MacKay
Tel.: 352-294-4089
and 0.0001% travoprost (Travatan!-Alcon Laboratories, Inc., Ft Worth, TX, USA)
Fax:Alex
352-392-6125
B. Carvalho,* José L.
Laus,† Vital P. Costa,‡ Paulo S. M. Barros* and Patrícia R. Silveira§
e-mail: [email protected]
in multiple single-dose studies.
*Department of Surgery, University of São Paulo, College of Veterinary Medicine, Brazil; †São Paulo State University, Campus of Jaboticabal, College of
Procedures Intraocular pressure and pupil diameter (PD) measurements were obtained
Agricultural and Veterinarian Sciences, Department of Veterinary Medicine and Surgery, Brazil; ‡Department of Ophthalmology, University of São Paulo Medical
9 AM, 12 PM
, 3 PM,ofand
9 AMMedical
the following
day
(24 h) in
two University
groups of
six glaucoma
School, Brazil; and the Department ofatOphthalmology,
University
Campinas
School, Brazil;
§Veterinary
Hospital,
of Marília,
Brazil
存在するカリウムイオン
（K+）チャネルの1種であるMaxi-K+
ト系の薬剤は、
主にぶどう膜強膜流出路の流出促
JOURNAL OF OCULAR PHARMACOLOGY プロス
AND THERAPEUTICS　2009 進によって眼圧を下げると考えられています。一方、ウノプ
Sudharshan Hariharan et al.
•  ラタノプロスト＋ビマトプロスト図2
–  トラバプロスト単独より眼圧
降下作用強い •  ビマトプロスト VS ラタノプロスト –  ラタノプロストに無反応な犬
の緑内障にビマトプロストが
反応 •  結合するレセプター(FP vs EP) •  またはFPレセプターへの結合力
の違いによる図3
PG関連薬のプロスタノイド受容体親和性
Latanoprost acid
Travoprost acid
FP
10-10
TP
EP1
10-7
TP
FP
10-10
EP1
10-7
10-4
IP
DP
プロスト系
10-4
10-1
EP2
10-1
IP
EP3
DP
EP2
EP3
EP4
EP4
Unoprostone acid
TP
FP
10-10
10-7
EP1
プロストン系
10-4
10-1
IP
DP
EP2
Hellberg. M.R. et al.: J. Ocul. Pharmacol. Ther. 17(5): 433, 2001.
Sharif. N.A. et al.: J. Ocul. Pharmacol. Ther. 19(6): 501, 2003.
Nomura. S. et al.: Nippon Yakurigaku Zasshi 115(5): 280, 2000.
EP3
EP4
h>p://rescula.jp/glaucoma/symposium/
upload_docs/pamp_05.pdf　より引用
ウノプロストンの作用機序
ウノプロストン
（眼外からのルート）
眼底血管平滑筋
（眼外からのルート）
網膜神経節
線維柱帯
Ca2+依存性Maxi-K+チャネルの開口
血管平滑筋細胞内
神経節細胞内
Ca2+の上昇抑制
Ca2+の上昇抑制
血管拡張
神経細胞の
アポトーシスを抑制
Thieme. H. et al.: IOVS 42(13), 2001.
Cuppoletti. J. et al.: BBA 1768(5), 2007.
線維柱帯細胞内
Ca2+の上昇抑制
© 2006 American College of Veterinary Ophthalmologists
Marcheselli. V. et al.: IOVS 42(S750), 2001.
Lafuente. M.P. et al.: IOVS 41(S15), 2000.
血流増加
杉山、吉冨、木村、
その他多数
視神経保護
Melamed. S.: Drugs. Exptl. Clin. Res. 63, 2002.
房水流出抵抗の減少
主経路からの房水流出の促進
眼圧下降
Thieme. H. et al.: IOVS 42(13), 2001.
志村ほか: 第108回日本眼科学会総会, 2004.
その他の点眼薬；自律神経系視野維持
チモロール+ラタノプロスト
アドレナリン受容体関連薬
0.5%チモプトール＋ラタノプロスト配合点眼液 •  眼圧降下作用 –  配合剤とラタノプロスト単独で有意差なし –  配合剤/ラタノプロスト＞＞チモロール(0.5%) •  心拍数 –  💀配合剤とチモロール単独で減少。程度に有意差なし配合剤とチモロール単独で減少。程度に有意差なし •  縮瞳 –  配合剤とラタノプロスト単独で減少。程度に有意差なし Effects of topical administration of latanoprost,
timolol, or a combination of latanoprost
and timolol on intraocular pressure, pupil size,
and heart rate in clinically normal dogs
•  α2-‐ 作動薬
•  アプラクロニジン0.5-‐1%
•  ブリモニジン0.1%
•  選択的β1-‐ 遮断薬
•  塩酸ベタキソロール
•  猫では効き目弱い
Smithら。AJVR (2010)
Lynsey N. Smith, DVM; Paul E. Miller, DVM; Lisa M. Felchle, DVM
Objective—To determine effects after topical administration of latanoprost, timolol, or a
commercially available latanoprost-timolol combination twice daily on intraocular pressure
(IOP), pupil size (PS), and heart rate (HR) in clinically normal dogs.
Animals—17 clinically normal dogs.
Procedures—A randomized controlled clinical trial was performed with a treatment (n =
9) and saline (0.9% NaCl) solution group (8). Each dog in the treatment group received 3
treatments (latanoprost, timolol, and the latanoprost-timolol combination), with a 14-day
washout period between treatments. Baseline values were established on day 1 of each
treatment period. On days 2 through 5, drugs were administered topically every 12 hours to
1 eye of each dog in the treatment group. In both groups, IOP, PS, and HR were measured
at 0, 2, 4, 6, 8, and 9 hours on days 2 and 5.
Results—Eyes treated with latanoprost or the latanoprost-timolol combination had a significant decrease in IOP and a significantly smaller PS, compared with results for dogs receiving only timolol or dogs in the saline solution group. Timolol and the latanoprost-timolol
combination both significantly lowered HR, compared with HR following administration of
latanoprost and the saline solution.
Conclusions and Clinical Relevance—Topical administration of latanoprost alone was
as effective at lowering IOP as was administration of the latanoprost-timolol combination
when both were given every 12 hours to clinically normal dogs. Timolol, either alone or in
combination with latanoprost, appeared to have little or no effect on IOP in clinically normal
dogs but was associated with a reduction in HR. (Am J Vet Res 2010;71:1055–1061)
その他の点眼薬；自律神経系 0.25%ニプラジロール；α1β遮断薬
G
•  β受容体遮断作用による房水の産生抑制
•  α１受容体遮断作用による房水の流出促進
laucoma comprises a group of diseases that are
unified by the common theme of progressive
death of the retinal ganglion cells and their axons,
which results in vision loss.1 An increase in IOP is the
principal risk factor for glaucoma, and the primary
goal of treatment is to reduce the IOP to values that
will halt the death of retinal ganglion cells.1,2 Although
clinicians have numerous medical and surgical options
at their disposal, vision loss and decreased quality of
life are frequent sequelae to glaucoma in domestic
animals. Ideally, topical application of a single ocular
hypotensive agent is the preferred treatment for patients
HR
IOP
PS
ABBREVIATIONS
Heart rate
Intraocular pressure
Pupil size
3
Received July 20, 2009.
Accepted July 29, 2009.
From Eye Care for Animals, 17395 Tomball Pkwy, Ste 3-H, Houston, TX 77064 (Smith); Department of Surgical Sciences, School of
Veterinary Medicine, University of Wisconsin, Madison, WI 53706
(Miller); and Eye Care for Animals, 86 W Juniper Ave, Gilbert, AZ
85233 (Felchle).
Presented in part as an oral presentation at the American College of
Veterinary Ophthalmology Conference, Chicago, November 2009.
The authors thank Dr. Richard Madsen for assistance with the statistical analyses.
Address correspondence to Dr. Smith (lsmith@eyecareforanimals.
com).
副交感神経作動薬
with glaucoma; however, treatment with a single agent
alone often does not achieve the desired degree of IOP
Eﬀects of topical nipradilol and Cmolol maleate on intraocular pressure, facility of reduction,
and treatment
with a combination
of 2 or
more antiglaucoma drugs is required. However, topical
treatment
withpmultiple
or >in 2 dosing
intervals/
ou^low, arterial blood pressure and ulse drugs
rate dogs d is associated with significantly reduced compliance
in human patients with glaucoma. This reduced
S. Maeharaら。Veterinary Ophthalmology (2004) compliance is not a trivial
issue because 1 large study
4
in humans with glaucoma revealed that approximately
45% of patients using an electronic monitoring device
who knew they were being monitored and were
provided free medication used the medications < 75% of
the time.4 Products that combine 2 antiglaucoma drugs
in the same bottle have been introduced. Examples of
such combination treatments include dorzolamidetimolol and brimonidine-timolol.
Timolol maleate is a B-adrenergic receptor antagonist that reduces IOP by decreasing production of
⇔0.5%チモロール単独との比較
•  眼圧降下作用；両剤で有意に減少＋両剤間で有意差なし
→α１受容体遮断作用による房水の流出促進が眼圧↓補助 AJVR, Vol 71, No. 9, September 2010
1055
•  血圧・心拍数の減少；ニプラジロールでは認められず v  演者；チモロールで徐脈が顕著な症例に使用
09-07-0264r.indd 1055
松山ほうじょうクリニック眼科
•  ピロカルピン, 臭化デメカリウム
•  縮瞳作用
•  線維柱帯からの房水排泄促進
•  副作用＞眼圧降下作用
•  結膜炎, 眼痛（PH4.5-‐5） •  胃腸障害
8/23/2010 12:28:49 PM
6
緑内障part 2
2013/12/17
緑内障内服薬
眼圧降下内服薬（ACVO 2010でのアップデート）イソソルビド：正常犬
•  1.5 g/kg, po •  効果-‐ 90分
•  Na↓；投与２時間後
•  K,Cl；変化なし
グリセリン (Glycerol)：正常犬
Break・・・・
緑内障内服薬
Glaucoma NeuroprotecQon 緑内障＝網膜神経節細胞の障害（機序） ◯細胞内のグルタミンの枯渇⇄細胞外グルタミン↑ →神経内カルシウムの流入↑ / グルタミン酸興奮毒性 ※NMDA, カイニン酸, AMPA, 代謝調節型受容体を介して →フリーラジカル↑, 一酸化窒素合成↑ アムロジピン
•  カルシウムチャンネルBlockers
•  神経保護
塩酸メマンチン MemanQne（Namenda®）
•  NMDA受容体の非競合的拮抗薬
•  Ca2+ 透過性を減弱
•  視神経保護
Where and how… 高浸透圧薬 •  1.4g/kg, po BID~TID •  毒性なし
•  グルコース↑(糖尿病禁忌)
•  効果MAX発現; 60分、効果持続 120 分
両薬剤とも優位な眼圧降下作用なし緑内障内服薬
Glaucoma NeuroprotecQon アムロジピン
•  カルシウムチャンネルBlockers
•  神経保護
•  犬: : 0.1-‐0.4mg/kg SID-‐BID
•  猫: 5 kg以下 -‐ 0.625 mg SID, 5 kg以上;1.25 mg SID 塩酸メマンチン MemanQne（Namenda®）
•  0.15-‐0.30mg/kg SID or 20mg/頭/週に2回
•  NMDA受容体の非競合的拮抗薬
•  Ca2+ 透過性を減弱
•  視神経保護
•  副作用（少ない）
•  ヒト；幻覚､精神障害､昏睡
急性緑内障の緊急治療；静脈注射高浸透圧製剤
マンニトール　◯
•  硝子体の脱水
•  1-‐1.5 g/kg IV over 15 min •  １時間以内に効果
•  ６時間効果持続
•  4-‐6時間の飲水制限
•  ぶどう膜炎では禁忌
Veterinary Ophthalmology (2006) Sabine Volopichら
松山ほうじょうクリニック眼科
ヘタスターチ　△
•  マンニトールとほぼ同様の眼
圧効果作用
•  効果時間短い（〜２時間）
•  リバウンド効果・・２時間後に
コントロール群より眼圧上昇
傾向
7
緑内障part 2
2013/12/17
急性原発性緑内障の緊急治療急性原発性緑内障の緊急治療 GOAL = IOP < 20 mmHg
Emergency Therapy •  ラタノプロスト 0.005% •  前房穿刺　Aqueocentesis/ AC paracentesis ü  点眼後１５分以降で効果 ü  必要により複数回点眼（３０分おき + ステロイド点眼） •  +/-‐ マンニトール Choroid
ü  1 to 1.5 g/kg IV １５分以上かけて •  ドルゾライマイド or ブリンゾラマイド ü  点眼；維持　ＴＩＤ •  チモロール0.5% Iris
ü  点眼；維持　ＢＩＤ～ＴＩＤ Ciliary body
•  前房穿刺急性原発性緑内障の緊急治療 -‐ 前房穿刺 -‐ •  副作用 p  ブドウ膜炎 •  -‐ 25 G >> 30G> 27G ■原発性緑内障の予防 •  反対側眼への発症率・W/ 0.25%チモロール点眼→18.7ヵ月・W/O:抗緑内障点眼→平均7.7ヵ月緑内障の外科的治療経強膜毛様体光凝固術
•  急性緑内障　-‐ 視覚回復が見込まれる眼への
治療 TransScleral CycloPhotocoagulaQon (TSCP) •  1．毛様体光凝固術＝眼房水産生の減少効果 ☠ブドウ膜炎, 前房出血, 白内障, 網膜剥離 •  2．隅角インプラントＧonioimplant ＝眼房水流出の増加 ☠ 低眼圧, 網膜剥離, 線維化, 感染 •  3. 1+2= レーザーとインプラントの併用 -‐ 50%の症例で一年後も視覚の維持松山ほうじょうクリニック眼科
8
緑内障part 2
2013/12/17
■毛様体光凝固術条件 (イヌ) CLITICAL TIPS
角膜輪部より3－4mm後方から
重度の色素部位は避ける
3時ならびに9時部位以外の経強膜
角膜輪部から毛様体突起中央部までの距離
1000mW×5000mS；20~30発の照射
Diode laser 780– 850 nm 術直後に前房穿刺（27G）
Nd:YAG laser: 1064 nm ポップ音
Diode laser •  メラニン含有組織への吸収＞Nd:YAG laser
経強膜；破壊術＞凝固
緑内障の外科的治療 Surgical Therapy •  毛様体は隅角より1.5~2mm後方
•  背側＞外側, 腹側＞内側（背側の約半分の距離）
•  Ichihara ら。J. Vet. Med. Sci 2006 （ビーグル犬） •  急性緑内障　For visual eye: ＝視覚回復が見込まれる眼への治療 u  隅角インプラントＧonioimplant ＝眼房水流出の増加 ☠ 低眼圧, 網膜剥離, 線維化, 感染 TSCPとGIの併用
メリット
•  GI; 即効性かつ短期　⇔　TSCP; 遅効性かつ長期
•  組織が100℃に達した時に聞こえる細胞内外液の蒸発音（ショック
波）
•  20-‐33%で聞こえるのがベスト
■前房シャント/隅角インプラント術 -‐GONIOIMPLANT (GI)-‐ ■前房シャント/隅角インプラント術 -‐GONIOIMPLANT（GI）-‐ 術後合併症 ü  GI周囲の線維化 ü  血餅・フィブリン ü  MMCによる壊死
デメリット
•  より重度のインプラント周囲の線維化・眼内炎症
•  GIの閉塞を起こすリスク↑
•  マイトマイシン / 5 –FU / TPA / ステロイド点眼
松山ほうじょうクリニック眼科
9
緑内障part 2
2013/12/17
エンドレーザー毛様体光凝固術 Endoscopic CyclophotocoagulaQon 目標　Goals 1.  視覚維持・回復 2.  不快症状の軽減 •  急性緑内障 •  ＝視覚回復が見込ま
れる眼への治療 formation
•  急性緑内障 •  ＝視覚回復が見込ま
れる眼への治療エンドレーザー毛様体光凝固術エンドレーザー毛様体光凝固術 ■成績；TSCP/隅角インプラント(GI) •  Bras, Sapienza, Wilkieら。ACO 2013 –  犬257頭/309眼 –  200-‐850mW X 9000ms；原発緑内障:324mW > 続発-‐:293mW •  続発性緑内障；大部分が白内障手術後または水晶体脱臼オペ後 –  4-‐6個の毛様体を画面に可視眼圧維持(%)　１年後　２年後　3年後　4年後
•  原発性緑内障　91 85 81 90
•  続発性緑内障 93 96 91 100
視覚維持(%)　１年後　２年後　3年後　4年後
•  原発性緑内障　68 58 51 48
•  続発性緑内障 67 56 54 53
手術1年後の視覚維持率〜2011年
1. TSCP単独；50-53% 2. TSCP+GI; 約50％
3. GI単独; 3 - 42%
Cookら。 Diode laser transscleral cyclophotocoagulaCon for the treatment of glaucoma in　dogs: results of six and twelve month follow-‐up. Vet Comp Ophthalmol　1997 Hardmanら。Diode laser transscleral cyclophotocoagulaCon　for the treatment of primary glaucoma in 18 dogs: a Vet Ophthalmol 2001.
TSCP　GI　TSCP + GI　眼圧維持(%) 67 - 92 74 – 76 視覚維持（%） <50 22-100 41-58 期間（ヶ月） 1-21ヶ月 9-22ヶ月 12ヶ月術後合併症；%　（続発性緑内障）　①なし; 37 (62)> ②眼内フィブリン析出; 36 (31)> ③角膜潰瘍; 29 (38)> ④前房出血; 10 (9)
緑内障の外科的治療慢性緑内障
目標　Goals 1.  視覚維持・回復 2.  不快症状の軽減 •  盲目眼； p  眼球内容除去術 -‐義眼挿入術 p  ＧＭ硝子体注入術 p  眼球摘出術松山ほうじょうクリニック眼科
緑内障の外科的治療慢性緑内障
目標　Goals 1.  視覚維持・回復 2.  不快症状の軽減ゲンタマイシン硝子体注入術
ü  毛様体破壊術＋全ての眼内組織
ü  一般に15〜25mgのゲンタマイシン投与量
ü  標準全身投与量；6~8 mg/kg/day以下
ü  ＋デキサメタゾン1〜2mg
ü  65-80% 眼圧降下成功率（1回の注入）
ü  短時間麻酔（１０分）
ü  効果発現に2週間〜
合併症
ü  10% で眼球癆
ü  眼内出血
ü  重度のぶどう膜炎
ü  外傷性眼内肉腫（猫）
ü  全身毒性；腎不全,中毒性難聴
10
緑内障part 2
2013/12/17
緑内障の外科的治療慢性緑内障
ゲンタマイシン硝子体注入術
目標　Goals GM硝子体注入の副作用の最新知見
1.  視覚維持・回復 2.  不快症状の軽減 •  硝子体注入後の血清中GM濃度 –  Lanuza et al. Kansan State Univ. ACVO 2011 •  18頭の犬 ; 体重；8〜49 kg •  成功率(眼圧< 25mmHg); 82% •  硝子体注入量； ü GM + Dexamethasone用意 ü 20G針+5mlシリンジ+三方活栓 ü ベノキシールを染込ませた綿棒
を角膜輪部-‐12時方向から8mm
後方に数秒あてる　ü 同部位に挿針 ü まず硝子体を1ml吸引 ü 次にGM+Dexaを側管より注入 ü 挿針部位より出血が見られる場
合は2.5%フエニレフリンもしくは
1/10000エピネフリンを滴下
緑内障の外科的治療慢性緑内障
シドフォビル硝子体注入術
–  25~40mg/GM & 1mg/ Dexa •  血清中のGM濃度; 30min, 1hr, 2hrs, 4 hrs –  2 hrs でMAX; 9.71 μg/ml ⇔ IM inj; 54,5 μg/ml 目標　Goals 緑内障の外科的治療慢性緑内障
1.  視覚維持・回復 2.  不快症状の軽減 MC Low et al. USA. ACVO 2011 ü  202 dogs (222 eyes) ü  525 or 750 μg シドフォビル硝子体注入 ü  シドフォビル; 注射液濃度75mg/ml ü  0.05ml; シドフォビル + 0.95ml注射用水＝3.75 mg/ml ü  角膜輪部より5mm後方 w/ 30 G ü  + 1mgトリアムシノロン　結膜下注射
合併症; Ø  17%の眼球勞のみ Ø  眼圧；投与前; 平均46mmHg　⇔　投与後; 平均10mmHg Ø  >500μgの注入で効果あり Ø  GM注入より眼内炎症, 白内障形成の副作用低い
経強膜義眼挿入術
眼球内容除去＋眼内シリコンボール適応 1.  慢性緑内障 2.  眼疼痛緩和 3.  美観的理由 4.  経済的理由（内科的 VS 義眼）
義眼挿入術で用いる器具
緑内障の外科的治療慢性緑内障
経強膜義眼挿入術
眼球内容除去＋眼内シリコンボール術式 1.  背側リンバスから5-‐8mmの結膜を120-‐150°切開 2.  続いてリンバスから4-‐6mmの強膜を切開 3.  正常眼の角膜横径より1mm大きいシリコンボール 4.  縫合糸は6-‐0Vicryl 5.  義眼のサイズにフィットしてくるのは3～6週間後松山ほうじょうクリニック眼科
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テノトミー剪刀（曲）ドベーキー鑷子ビショップハーモン鑷子毛様体分離スパーテル義眼挿入器義眼シリコンボール 11
緑内障part 2
2013/12/17
義眼後の合併症
1.  視覚維持・回復 2.  不快症状の軽減経強膜義眼挿入術
• 義眼の不適応症例！！
• 眼内腫瘍
• 眼内感染
• 角膜疾患
• 角膜潰瘍
• ＫＣＳ
緑内障の外科的治療
目標　Goals 緑内障の外科的治療慢性緑内障
経強膜義眼挿入術
150       
義眼後の合併症の発生率 NARANJOら, Wisconsin univ, ACVO, 2008 1.  義眼挿入犬全体の9-‐16% 2.  8 %のイヌ；眼球外に転移 3.  義眼後、眼摘になった症例；4.5 -‐ 8 % Linら, J.Vet. Med.sci., 2007 KCS・・・10%（2/20） ET AL.
•  角膜の知覚減少 –  関連因子 •  術前の牛眼の程度 •  術中の強膜切開の長さ –  シルマーティアーの減少 •  STT-‐1, STT-‐2とも減少 •  術後２週間〜 –  術後のドライアイ, 上皮びらん Figure 1. Plot of nylon filament length means and standard errors vs.
time for control and surgery eyes. Corneal sensitivity was significantly
lower in surgery eyes than in control eyes both preoperatively (week 0)
and at all times postoperatively (weeks 2, 7, 14, 28), but there was no
significant difference between preoperative and postoperative corneal
sensitivity when the two groups were evaluated separately.
緑内障の外科的治療慢性緑内障
眼球摘出術
目標　Goals 1.  視覚維持・回復 2.  不快症状の軽減適応； ü 視覚回復の見込みのない慢性緑内障 ü 眼内腫瘍症による続発性緑内障 ü 眼内感染症例 ü 痛みの緩和
SMALL ANIMALS
6/23/2006
9:57 AM
Page 220
2- and 14-week postoperative mean STT II in the control
eye (Fig. 2b). Additionally, there was a significant difference
between preoperative and 28-week postoperative STT IIvalues in the surgery eye (Fig. 2b).
There was a statistically insignificant trend toward decreased
Development of a retrobulbar injection technique
corneal sensitivity with increased degree of buphthalmos
for ocular surgery and analgesia in dogs
(Fig. 3). Likewise, there was a statistically insignificant trend
toward decreased corneal sensitivity with increased scleral
Peter J. Accola, DVM; Ellison Bentley, DVM, DACVO; Lesley J. Smith, DVM, DACVA
; length (Fig. 4).
incision
Lisa J. Forrest, VMD, DACVR; Cheryl A. Baumel; Christopher J. Murphy, DVM, PhD, DACVO
眼球摘出術
Objective—To develop and compare 3 techniques for
retrobulbar injection of local anesthetic agents for
ocular surgery and analgesia in dogs.
Design—Prospective study.
Animals—17 dogs (including 9 cadavers).
Procedure—Inferior-temporal palpebral (ITP), perimandibular, and combined superior-inferior peribulbar
injection techniques were compared by assessing the
distribution of latex after injection into the orbits of 5
canine cadavers; magnetic resonance imaging (MRI)
evaluation of the distribution of contrast agent after
injection in the retrobulbar space of 4 canine cadavers;
and assessment of the efficacy and MRI evaluation of
the anatomic distribution of injections of a lidocainecontrast agent mixture in 4 anesthetized, nonrecovery
dogs. By use of the preferred technique (ITP), the ocular effects of lidocaine anesthesia were evaluated in 4
dogs; during a 2-week period after treatment, dogs
underwent ophthalmic examination, Schirmer tear
testing (STT), intraocular pressure (IOP) measurement, and Cochet–Bonnet esthesiometry.
Results—Of the 3 techniques, the ITP technique was
the preferred method for retrobulbar administration of
anesthetic agent in dogs because it was efficacious
(pupil dilation and central rotation of the globe achieved
in all eyes), easiest to perform, and provided thorough
coverage of the intraconal retrobulbar space without
complication. During the 2-week follow-up period, the
ITP injection did not significantly affect STT, IOP, or
Cochet-Bonnet esthesiometry values in dogs.
Conclusions and Clinical Relevance—In dogs, retrobulbar administration of anesthetic agents via the ITP
technique is a potential alternative to systemic administration of neuromuscular blocking agents for ophthalmic
surgery and provides the additional benefit of local ocular analgesia. (J Am Vet Med Assoc 2006;229:220–225)
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CN III, IV, V, and VI ü  外眼筋の不動化 ü  眼球の位置が中央に毛様体神経節 ü  散瞳局所鎮痛注意すべき合併症 ü  眼球の穿孔 ü  血管・神経内への注入 ü  球後出血松山ほうじょうクリニック眼科
Figure 2. (a) Schirmer tear test I-means and st
control and surgery eyes at preoperative week 0
weeks 2, 7, 14 and 28. A significant reduction fr
was noted in the surgery eye at week 2. A reduc
value was noted in the surgery eye at week 28 b
of statistical significance (P = 0.05) A significan
control and surgery eye was noted at week 28. (
test II-values and standard errors for control an
preoperative week 0 and postoperative weeks 2
significant difference from preoperative value w
eye at postoperative week 28.
capnometry or arterial blood gas measurement to ensure 23
decreases
with
age. Diurnal fluctuations in corneal sensithat adequate ventilation is achieved.
Without the
ability
to appropriately monitor the effects
of NBAs
dogs,24 Numerous pathologic conditions of the
tivity
also in
occur.
which is common in many practice settings, hypoventilaeye have respiratory
been shown to increase the corneal touch threshold
tion will lead to hypercapnia and considerable
acidosis, with potential cardiovascular,
neurologic,
and
in
humans
including
scleritis,25 keratoconjunctivitis sicca,26
metabolic consequences.2 Additionally, respiratory acidoviral
keratitis,27 corneal edema,28,29 and glauOur study revealed a statistically sign
sis induces an increase in choroidalherpes
blood flow,
resulting
30,31
in increased IOP and anterior vitreal
displacement,
both
coma.
Additionally,
systemic diseases that can affect the
preoperative corneal sensitivity betwee
of which can increase the potential for surgical complicaperipheral nerves, such as diabetes mellitus, myasthenia
eyes that undergo an evisceration with
tion.3,4 Therefore, there are considerable advantages in
gravis,
andwithout
leprosy, can also lead to an increase in corneal
sis, which was characterized by a signifi
preferentially paralyzing the extraocular
muscles
impairment of patient ventilation. touch threshold.14,32–36
sensitivity in eyes undergoing surger
Retrobulbar anesthesia provides excellent extraocular muscle akinesis and has the added benefit of providing local analgesia that could reduce the need for peri© 2007 American College of Veterinary Ophthalmologists, Veterinary Oph
operative systemic administration of analgesics such as
opioids or nonsteroidal anti-inflammatory drugs. Also,
without the specific need for a mechanical ventilator
and additional monitoring equipment with associated
personnel, the overall operative cost may be reduced.
A thorough understanding of the relevant canine
ophthalmic and orbital anatomic features as well as consideration of ocular axial length, orbital depth, and
orbital axis is required to accurately administer retrobulbar injections. Targets of retrobulbar anesthesia
include cranial nerves III, IV, V, and VI and the ciliary
ganglion. Options for induction of retrobulbar anesthesia include placing the anesthetic agent internal or external to the retrobulbar muscular cone. In general, injection of an anesthetic agent into the intraconal space will
result in the most rapid and consistent effect with the
least volume required. In comparison, extraconal injection of an anesthetic agent, although perhaps safer
because the needle is not as close to the globe, can have
a longer onset of action and typically requires a higher
drug volume; moreover, multiple injections are often
required, each having its own associated potential complications. Possible complications of retrobulbar anesthesia include retrobulbar hemorrhage, IV injection of
the anesthetic, globe perforation, optic nerve damage or
other neuropathy, extraocular muscle myopathy, and
犬:
リドカイン 8mg　(2%; 0.4ml); <8 mg/kg
ブピバカイン　8mg (0.5%; 1.6ml) <2mg/kg
猫
リドカイン 5mg (2%; 0.25ml)；<2mg/kg
ブピバカイン 5mg (0.5%; 1 ml) <2mg/kg ondepolarizing
neuromuscular-blocking agents0are
+/-‐ エピネフリン(1:1000) .02 ml (0.01mg)
N
commonly used in veterinary ophthalmologic prac-
目標　Goals Scientific Reports: Original Study
JAVMA, Vol 229, No. 2, July 15, 2006
眼球摘出術で用いる器具
1.  視覚維持・回復 2.  不快症状の軽減 21,22
2.  わずかな”ポップ音”; ＝眼窩筋膜を通る音
220
眼球摘出術球後麻酔注射法 muscle paralysis, and thus patients require specific moni20
toring such as train-of-4 peripheral nerve stimulation
to
In another
study, brachycephalic cats were shown
accurately determine the duration of effect. The use of
to have
a higher
intermittent positive-pressure ventilation
is necessary
and corneal touch threshold and thus a lower
1.  約20°に針中央部を曲げる) requires the use of specialized anesthetic
equipment
and than DSH cats.
Corneal sensitivity
corneal
sensitivity
From the Veterinary Emergency Service, 1612 N High Point Rd, Ste 100,
Middleton, WI 53562 (Accola); and the Department of Surgical
Sciences, School of Veterinary Medicine, University of Wisconsin,
Madison, WI 53706-1102 (Bentley, Smith, Forrest, Baumel, Murphy).
The authors thank Drs. Richard Dubielzig and Laura Goodman for
image acquisition.
Address correspondence to Dr. Bentley.
NBA
IOP
ITP
MR
1.  22ゲージスパイナル針-‐ 1.5 inch sensitive.
tice because they are easy to administer systemically in
animals and provide the necessary extraocular muscle
paralysis for intraocular and corneal surgery.
Unfortunately, with NBA administration, it is not possible
to adequately eliminate extraocular muscle activity for
surgery without inducing major respiratory compromise.1
Systemic administrations of NBAs induce respiratory
緑内障の外科的治療慢性緑内障
DISCUSSION
ABBREVIATIONS
Nondepolarizing neuromuscular-blocking agent
Intraocular pressure
Inferior-temporal palpebral
Magnetic resonance
球後麻酔注射法 Normal variations in corneal sensitivity exist among differing species and corneal regions. A study comparing canine
skull types revealed that corneas of dolicocephalic dogs were
most sensitive and those of brachycephalic dogs were least
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テノトミー剪刀ビショップハーモン鑷子滅菌綿棒マッスルフック眼球摘出剪刀血管鉗子/曲モスキート眼球摘出剪刀 12
緑内障part 2
眼球摘出術
2013/12/17
QuesQons??
•  メッシュワーク縫合 –  術後の眼球陥没の防止 •  シリコン挿入 –  眼窩内△ –  合併症 •  犬；4% •  猫；40％松山ほうじょうクリニック眼科
13

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