throbber
Fr
`
`MICROSURGERY OF SCHLEMM'S CANAL AND THE HUMAN
`AQUEOUS OUTFLOW SYSTEM
`MURRAY A. JOHNSTONE, M.D., AND W. MORTON GRANT, M.D.
`Boston, Massachusetts
`One basis for some of the present ap-
`internal cystotome trabeculotomy, by .ab'ex-
`proaches to microsurgery of Schlemm's ca-
`tern° probing of Schlemm's canal with nidon
`nal is the finding by Grant1-3 that approxi-
`and metal probes, and by causing the.probes
`mately 75% of the resistance of the aqueous
`to rupture from the canal into the anterior
`outflow system could be eliminated in per-
`chamber as in current clinical practice,
`fused enucleated human eyes by providing
`an opening from the anterior chamber into
`PROCEDURES AND METHODS
`Schlemm's canal by internal trabeculotomy
`Quantitative
`aqueous
`perfusion—We
`with a cystotome, and that in open-angle
`made measurements before and after experi-
`glaucomatous eyes, abnormal
`resistance
`mental dissections as follows. We..Storol
`could be eliminated in the same way. Much
`enucleated normal eyes obtained at autopsy
`earlier, Barkan4,5 showed that open-angle
`at 4°C in a moist environment until 30-Min-
`glaucoma could be relieved in adults by an
`utes prior to perfusion, which was started 4
`internal trabeculotomy with a goniotomy
`to 48 hours post mortem. After removal
`knife. The effect of the Barkan trabeculot-
`from refrigeration, we placed the eyes ip a
`omy procedure appears generally not to
`silicone rubber mold that enveloped the pos
`have been long lasting. The cystotome labo-
`terior segment to the equator. We covered
`ratory procedure has not been readily adapt-
`the anterior segment with absorbent',.paper
`able to clinical use, but recently Bietti and
`saturated in perfusion fluid. An opening
`Quaranta° have reported clinical successes
`mm in diameter was trephined in the, cerit,-,
`by internal trabeculotomy with another type
`of the cornea to give access to the anterior
`of cutting instrument.
`chamber and the inner angle. Except: in one
`Other procedures have been devised and
`special group of eyes, we regularly, per-
`applied clinically with the aim of reducing
`formed a radial iridotomy through' the tre-
`resistance to aqueous outflow by surgery on
`phine opening to prevent artificial deepening
`Schlemm's canal, in particular ab externo
`of the chamber. For quantitative : aqueoth
`trabeculotomy procedures, but their effects
`perfusion, we trisect Baritny's7 constant pres-
`have not been evaluated in the same experi-
`sure technique, with a commercial, sterile fil-
`mental manner as those of internal cysto-
`tered, phosphate-buffered balanced salt solu-
`tome trabeculotomy.
`tion containing glucose. We infused' the so
`The present study was carried out to com-
`lution into the anterior chamber through 2
`pare in postmortem enucleated human eyes
`stainless steel fitting (previously described
`the changes induced in the structure and
`which sealed the opening in the cornea. 1,\I-
`function of the trabecular meshwork and
`generally measured steady state flow while
`Schlemm's canal aqueous outflow system by
`maintaining intraocular pressure at:1 S nun
`Hg, but in certain instances at 5, 30, or 511
`From the Howe Laboratory of Ophthalmology
`mm Hg. The measurements made befpi e rach
`of Harvard Medical School, at Massachusetts Eye
`and Ear Infirmary, Boston, Massachusetts. This
`experimental procedure required al ,p1 0%-
`study was supported by Public Health Service cen-
`imately ten minutes of perfusion to Atli"
`ter grant 5-PO1-EY000292, training grant 5-T01-
`what appeared to be a steady state. A it'll'
`EY-00018, and research grant 5-RO1-EY-00002
`from the National Eye Institute.
`manipulation or dissection, we carried out
`Reprint requests to W. Morton Grant, M.D.,
`similar perfusion and monitored floWrik for
`Howe Laboratory of Ophthalmology, 243 Charles
`120 minutes. If the same eye underwent a sec-
`St., Boston, MA 02114.
`906
`
`,j1,. 76, NO. 6
`
`IvIIC
`
`rd experimental piocedure,
`,IfuSion measurement sul
`roue :of eyes was perfused
`‘olsfor the same length of
`..erimental, omitting the diss
`-ng prOcedures.
`:Microscopic ntorphologico
`:1stologic examination, tis:
`rased with 4% glutaraldel
`e,eridional sections contait
`tructUres were excised. IA
`oith :1% osmium tetroxide,
`ehydrated in ethyl alcohol
`non.. For light microscopy,
`1 v.:and stained them wi
`
`For scanning electron mi.(
`e wa'S fixed for 24 to 48 he
`ntaining equal parts of 11
`ilirrlaiid
`glutaraldehy
`15M phosphate buffer (p
`en rinsed in distilled wat(
`'-ozeii in isopentane, and chi
`iuid 'nitrogen. The frozen -
`sated for three hours undi
`'e coated the freeze-dried
`ild and 40% palladium: 'A
`frdm stored enucleated
`c quality generally prepare
`:r exainination. of fine deta
`value in demonstrating th
`:iDlogic features in control :
`e gross alterations resulti
`' seetilon procedures.
`Dissiktions and surgical
`Internal cystotome trabecu
`-irined.:in 180 degrees of th
`the 'same manner as by
`lingsen and Grants T
`ihrougll the 5-mm corneal t
`Ilder direct visualization w-
`111-roscope at 25 to 40X
`cystotome with th,
`right angles to the shaft.
`nt from within the ar
`"'tough
`trabecular
`the
``rjllemn-l's canal, and passe(
`1'141 circumferentially, wits
`Petitioner - New World Medical
`Ex. 1005, p. 1 of 12
`
`

`

`D THE HUMAN
`
`GRANT, M.D.
`
`e trabeculonjmy, by ab ex_
`Schlemm's canal with •to,lati
`, and by causing- th4-01,es
`the canal into the "anterior
`-rent clinical practite:
`
`TRES AND METHODS
`aqueous
`perfusion--We
`nts before and a f teiex p ri _
`ls as follows. We, stc,red
`tl eyes obtained at .:atttons\-
`t environment until30
`fusion, which was .started
`st mortem. After removal
`m, we placed the eyes in a
`mid that enveloped 'the pos-
`) the equator. We.Co\-cre,1
`nent with absorbent paper
`fusion fluid. An opening
`was trephined in the.c( liter
`give access to the":anterier
`inner angle. Except in oar
`f eyes, we regularly., per
`iridotomy through the tre-
`prevent artificial deepening
`For quantitative aqueou-
`ed Barany's7 constant pres-
`rith a commercial, sterile fil
`-buffered balanced salt solo
`;lucose. We infused the so-
`tnterior chamber through
`ing (previously described'),
`opening in the cornea. W..
`red steady state floW';..-vhili
`aocular pressure at 45 inn,
`in instances at 5, 30, or 5'•
`tsurements made befOre cad
`-ocedure required approx-
`utes of perfusion to attair
`:o be a steady state.A fter
`dissection, we carried or
`and monitored flow rate fo
`he same eye underwent_ sec
`
`76, NO. 6
`
`MICROSURGERY OF SCHLEMM'S CANAL
`
`907
`
`experimental procedure, we made a third
`Li fusion measurement subsequently. One
`4 „p of eyes was perfused as normal con-
`. k for. the same length of time as the ex-
`„5irnental, omitting the dissection and prob-'
`procedures.
`jlicroscopic morphological methods—For
`sklogic examination, tissues were per-
`.with
`glutaraldehyde, and small
`1-idional sections containing the angle
`4o tures were excised. 'We treated these
`1% osmium tetroxide, then they were
`'Jo drated in ethyl alcohol and embedded in
`fiolt.'.For light microscopy, we cut sections
`1 it and stained them with 1% toluidine
`
`-
`
`For :Scanning electron microscopy the tis-
`c was fixed for 24 to 48 hours in a solution
`staining equal parts of 10% neutral for-
`and 4% glutaraldehyde in Sorensen
`15A phosphate buffer (pH 7.2). It was
`rinsed in distilled water for one hour,
`isopentane, and chilled in a bath of
`Lftil-Mitrogen. The frozen tissue waf5dehy-
`three hours under high vacuum.
`"e coated the freeze-dried tissue with 60%
`l(I and 40%i palladium: Although this tis-
`:e from stored enucleated eyes was not of
`:. quality generally prepared by anatomists
`r (-)drilination • o f fine detail, we felt it was
`utile in dembnstrating the principal mor-
`dugic features in control normal eyes and
`At gross alterations resulting from micro-
`lsectibil procedures.
`Dissections and surgical manipulations—
`[sternal cystotome trabeculotorriy was per-
`-r,q(!ci in 180 degrees of the circumference
`th(!.. ame manner as by Grant" and by
`lifigseii and Grant.8 This was done
`, *rough the 5-mm corneal trephine opening
`,-;:der direct visualization with an operating
`escope at 25 to 40 X magnification, em-
`Yln.g a cystotome with the point oriented
`right. angles to the shaft. We inserted the
`from within the anterior chamber
`'!ugh
`the
`trabecular meshwork
`to
`sdlh-uitu's canal, and passed it along in the
`%1 :eircumferentially, with the blunt sur-
`
`face of the cystotome facing the external
`wall of Schlemm's canal. In this position it
`presented a triangular shape with its base
`facing the external wall of Schlemrn's canal,
`and a sharp slanting edge engaging the tra-
`becular meshwork. This was intended to cut
`the inner wall of the canal and the trabecular
`sheets from within the canal while limiting
`damage to the 'external wall of the canal.
`Usually the cystotome pushed a strip of
`meshwork ahead of itself in the manner of a
`plow.
`2. We performed ab externo trabeculot-
`omy and other ab externo surgical manipu-
`lations on excised human eyes in a manner
`similar to that employed by Dannheim and
`Harms in patients. A 4 X 4-mm lamellar
`scleral flap hinged at the cornea was dis-
`sected to include approximately two thirds
`of the thickness of the sclera. With this flap
`reflected, we localized Schlemm's canal un-
`der the operating microscope, guided by the
`anatomic landmarks of gray corneoscleral
`transition zone and by use of a transillurni-
`nator to demonstrate the position of the
`scleral spur. The transilluminator was most
`helpful when applied to the outer surface of
`the globe just anterior to the limbus, diamet-
`rically opposite the site of dissection. This
`caused the structures anterior to the inser-
`tion of the ciliary body into the sclera to ap-
`pear brightly illuminated, while those poste-
`rior were dark. A bright distinct line of de-
`marcation, which was characteristically seen
`in the posterior part of the gray transition
`zone, provided a particularly reliable guide
`to localization of Schlemm's canal. We then
`made an opening in the outer wall of the ca-
`nal to permit insertion of probes circumfer-
`entially in the canal. The ab externo dissec-
`tions involved either three or six hours of
`the superior circumference, with no attempt
`at selection of quadrants. During the whole
`procedure, we maintained the intraocular
`pressure in the eyes at 15 min Hg through
`connection with a reservoir of perfusion
`fluid. After we completed the experimental
`manipulations, we sutured the scleral flap
`
`Petitioner - New World Medical
`Ex. 1005, p. 2 of 12
`
`55
`pp
`
`

`

`COL 76, NO. 6
`
`MIC
`
`TABLE 1
`
`FER_FUSION FLOW RATE* IN UND
`EyEs, SPONTANEOUS VARIATI
`
`Mint
`
`Eye
`
`3
`4
`
`6 -
`
`0
`
`20
`
`40
`
`2.6
`2.3
`5.3
`3.7
`2.2
`1.8
`
`2.5
`2.4
`5.7
`4.2
`2.2
`1.7
`
`2.5
`2.5
`4.7
`4.3
`2.3
`1.5
`
`Flow in Al/min at 15 mm H
`
`Before
`After
`Dissection Dissecti
`
`10-
`
`o„
`
`A,
`
`0
`
`9-
`
`8-
`
`7-
`
`6-
`
`5-
`
`4-
`
`3-
`
`2—
`
`I-
`
`FLOW NI/min.
`
`o
`
`i0
`
`Fig. 1 (Johnstone and Grant
`ql
`:,;roups of postmortem
`s .:1,(1 manipulations were p
`1,iean in a group of undiss
`Petitioner- New World Medical
`Ex. 1005, p. 3 of 12
`
`908
`
`AMERICAN JOURNAL OF OPHTHALMOLOGY
`
`tightly back in place with six 8-0 silk sutures.
`Testing with fluorescein added to the perfu-
`sion fluid established that we obtained a reli-
`ably leak-free closure in this way. The
`following experimental manipulations were
`performed.
`2A. Ab externo, we made a nylon suture
`of 0.13-mm diameter slide circumferen-
`tially in the canal for 15 mm, and in some
`eyes the suture was pulled taut to rupture the
`trabecular meshwork
`in the manner de-
`scribed by Redmond Smith.9,1°
`2B. We performed ab externo probe tra-
`beculotomy with a curved hairpin probe
`(0.275-mm diameter) of the type described
`by Dannheim and Harms,11 inserting it cir-
`cumferentially within Schlemm's canal and
`then rotating it to rupture through trabecular
`meshwork into the anterior chamber. We at-
`tempted to swing the probe in a plane that
`would cause disruption nearer to scleral spur
`than Schwalbe's line. In certain instances af-
`ter this type of trabeculototny had been com-
`pleted, we performed an additional dissec-
`tion in which we removed persisting flaps of
`trabecular meshwork with jeweler's forceps
`under direct view with the operating micro-
`scope through the corneal trephine opening.
`2C. We performed ab externo diathermy
`probe trabeculotomy with a special probe de-
`vised by Ellingsen. This was made from
`hard stainless steel wire, 0.175-mm diameter,
`conforming to the basic curved hairpin de-
`sign of Dannheim and Harms, but insulated
`with a 0.05-mm coating of TFE Teflon. We
`stripped the insulating Teflon coating from
`along that side of the probe that was to come
`into contact with the trabecular meshwork
`side of Schlemm's canal. The external wire
`handle was left bare. With the probe in the
`canal, a diathermy electrode was touched to
`the handle to carry cutting diathermy cur-
`rent through the probe to the bared portion
`facing the trabecular meshwork. We applied
`two to three bursts of diathermy of 0.5- to 1-
`second duration so the probe could be ro-
`tated into Schlemm's canal with no mechani-
`cal resistance.
`
`DECEMBER; 14,':
`2D. As a control for the trabeculcitom.
`procedures, we carried out an ab extern ch--
`cumferential passage of a standard probe iv.
`Schlemm's canal without actually pedon,,,
`ing a trabeculotomy. We simply inserted
`probe within Schlemm's canal in the: sane
`manner as for probe trabeculotomy, Nit
`stead of application of diathermy or rotaticr
`of the probe into the anterior chamber, the
`probe was merely slid back out again and tr
`scleral flap resutured as after actual trabecu-
`lotomy. We made perfusion measurement,
`in these eyes at pressures of 5, 30, or 50
`Hg, as well as at the standard 15 mm Hg,
`and in another group of eyes that were sub.
`jected to the passage of the probe 41thout
`rupture of the meshwork, we omitted the
`standard iridotomy and determined theinflu-
`ence of artificial deepening of the anteriu-
`chamber.
`
`OBSERVATIONS ON NORMAL CONTROL EYE.
`As a basis for comparison, six eyes Nym
`perfused at 15 mm Hg for 130 minutes
`the same manner as eyes subjected to exper -
`mental dissections or surgical manipulation,-
`but in these six eyes, we performed no ex-
`time the
`perimental procedures. During thi.
`flow changed slightly in individuaUeyes, as
`shown in Table 1, but the meaii:Jor the
`group remained essentially constant,
`shown in Figure 1.
`By light microscopy of 1-11 :section:-
`Schlemm's canal was seen normally to bare
`strikingly plexiform character, witkirregu-
`lar fusiform dilatations of the outer NO'
`Septa were frequently present, diOding the
`canal into two to four channels. The call
`seldom resembled a simple endothelial line,:
`tube. In some normal eyes after perfusion at
`15 mm Hg, the trabecular meshwork almost
`external wall, ,
`touched
`the
`Schlemm's canal to little more than a pPte"'
`tial space in areas without septa, as Prf'\t,
`ously described by Johnstone ariti
`Dissection with fine forceps and rawr blade
`in segments of normal eyes showed that the
`trabecular meshwork could be remcvei
`
`

`

`76, NO. 6
`
`MICROSURGERY OF SCHLEMM'S CANAL
`
`909
`
`TABLE 1
`FUSION FLOW RATE* IN UNDISSECTED CONTROL
`3SiES, SPONTANEOUS VARIATIONS WITH TIME
`
`Eye
`
`Minutes
`
`0
`
`20
`
`40
`
`70
`
`100
`
`130
`
`2.6 2.5 2.5 2.5 2.7 2.2
`2.3 2.4 2.5 2.7 3.0 2.9
`5.3 5.7 4.7 4.3 4.3 4.3
`3.7 4.2 4.3 4.2 4.5 4.8
`2.2
`2.2 2.3 2.3 2.4 2.5
`1.8 1.7 1.5 1.5 1.5 1.6
`
`Flow in µl/min at 15 mm Hg.
`
`reveal
`undisturbed
`structures within
`Schlemm's canal and along the external wall,
`but this required careful cutting, because
`some of the tissues within the canal were
`firmly adherent to the trabecular meshwork.
`Scanning electron micorscopy of the opened
`canal in normal eyes revealed thick struc-
`tures consisting of nonfibrillar homogeneous
`tissue extending at a slightly oblique angle
`along the canal, joining a ridge of tissue
`along the external wall, as shown in Figure
`2. These structures seemed to represent
`septa previously firmly adherent to trabecu-
`
`Before
`After
`Dissection Dissection
`
`EFFECT OF DISSECTION ON OUTFLOW
`
`•
`
`•
`
`9,
`
`Probe Trabeculotomy
`90"-child-(2 eyes)
`
`A Cystotome Trabeculotomy
`180° (5 eyes)
`
`•
`
`•
`
`Diathermy Trabeculotomy
`180' (1 eye)
`
`Diathermy Trabeculotomy
`0'1' 90" (6 eyes)
`
`• ^ Probe Trabeculotomy
`90' (5 eyes)
`
`Undissected Normal Controls
`(6 eyes)
`
`Probe Trabeculotomy
`180' (5 eyes)
`
`O
`
`o Probe Insertion and Removal
`• 180' (3 eyes)
`
`o ®
`
`(0-
`
`9-
`
`s-
`
`6-
`
`0 5-
`
`FL1
`
`4-
`
`3-
`
`2-
`
`0
`
`to
`
`36
`
`60
`TIME
`(Johnstone and Grant). Aqueous perfusion steady-state flow rate mean values at 15 mm Hg pres-
`:,„ in
`groups of postmortem human eyes before and at intervals during 120 minutes after various dissec-
`and manipulations were performed on Schlemm's canal, in comparison with the spontaneous variation
`t the mean in a group of undissected control eyes.
`
`90
`
`120
`
`..OGY
`
`DECEMBER, 197,
`• •
`:rol for the trahgculotoan
`rried out an ab Orterno cir-
`age of a standard probe in
`without actually. perforai-
`ny. We simply inserted the
`Ilemm's canal in the sThle.
`-obe trabeculotomY; but in_
`)n of diathermy or rotation
`the anterior chamber, the
`slid back out again and the
`fired as after actual trabecti-
`e perfusion meaSuretants
`ressures of 5, 30,..Or 50 nini
`t the standard 151.nm Hg,
`i.oup of eyes that.Were sub-
`;sage of the probe without
`neshwork, we omitted the
`ly and determined the influ-
`deepening of the anterior
`
`)N NORMAL CONTROL EYES
`comparison, six eyes were'
`mn Hg for 130 minutes in
`as eyes subjected to experi-
`s or surgical maniPnlations,
`eyes, we perfornied no ex-
`dures. During this lime th,
`ghtly in individual .eyes,
`1, but the mean for thi
`essentially constant, a
`
`1.
`:roscopy of 1-p. . sections_
`was seen normally .to have 2
`Drm character, with' irregui
`atations of the miter wall.
`uently present, dividing Ot!
`o four channels. Tlie cant'
`3 a simple endothelial liner
`rmal eyes after perftision ;it
`trabecular meshwork alrno,t
`ireducin;
`external wall,
`to little more thad4otel:
`!as without septa, as prevl-
`by Johnstone and 6rant.-
`fine forceps and razor b
`iormal eyes showedlhat th.
`work could be removed
`t5
`
`NIA
`
`4, •
`
`S
`
`w.
`
`N
`
`.f*
`
`tai
`
`Petitiqner- New World Medical
`Ex. 1005, p. 4 of 12
`
``1(
`
`

`

`jy.
`
`910
`
`AMERICAN JOURNAL
`
`Fig. 2 (Johnstone and Grant). Scanning electron
`micrograph of Schlemm'S canal (between large
`arrows) after trabecular meshwork has been dis-
`sected away with razorblade knife and forceps, re-
`vealing a large septum (S) left intact within the
`canal anterior to the scleral .spur (SS) (X100).
`
`lar meshwork. The prominent ridges along
`the posterior portion of the external wall,
`which were joined by septa, ran in a circum-
`ferential fashion at a slightly oblique angle.
`An infolding was present along the posterior
`border of the ridges forming a narrow zone
`of discontinuity. Several deep clefts, appar-
`ently representing collector channel en-
`trances, were visible at intervals along this
`line of discontinuity.
`
`RESULTS OF EXPERIMENTAL PROCEDURES
`1. Trabeculotomy performed
`internally
`with a cystotome in half the circumference
`caused a marked increase in outflow in each
`of five eyes, as recorded in. Table 2. During
`120 minutes of perfusion after trabeculot-
`omy, the rate of flow generally remained
`high, with only a slight tendency to decrease
`toward pretrabeculotomy values, as shown in
`Figure 1 where mean values for the group
`are plotted.
`As observed through the operating micro-
`scope, the cystotome generally passed along
`near the scleral ,spur, tending to push trabec-
`tilar tissue ahead of it, but usually leaving
`the anterior portion of the trabecular mesh-
`
`'74
`
`76, NO. 6
`
`-
`
`MICI
`
`;.3 (Johnstone and Grant).
`cular meshwork and also disc
`
`tissue along the posteri
`ided. in Figure 5. Ab ext.
`-.ailotorny ruptured the ti
`
`OF OPHTHALMOLOGY
`
`DECEMBER,-.197;
`work in place. The residual material. ..was
`rather ragged and what was exposed of the
`external wall of the canal had an irregular
`pattern.
`From light microscopy of histologic ..see.
`tions (Fig. 3) it was evident that in addition
`to disruption of the trabecular meshwork:tl
`cystotome trabeculotomy caused damage to
`endothelitim of
`the external wall. .o
`Schlemm's canal, disruption of septa;:iaii4
`splitting along the posterior wall of the ca
`nal. Scanning electron microscopy (Pik;
`showed that a strip of trabecular meshwork
`was pulled from its attachments and Moved
`ahead of the cystotome, leaving struleture:,
`within the canal in a configuration suggest-
`ing that prior to disruption they had been
`drawn away from the external wall.
`Ab externo procedures on Schlernria's ca-
`nal gave the following results.
`2A. Ab extern() insertion of a nylon su-
`ture circumferentially in Schlenarres- canal
`was. accomplished without difficulty, and
`0
`though the suture had a diameter
`0.13 mm compared with the 0.275 mm of
`steel trabeculotomy probe, it stretched ant
`distorted the walls of the canal. Light mi-
`the
`croscopy of sections after insertion'
`suture showed damage to the trabecular mesh
`work, to the endothelium of both the interne''
`and external walls, compression of scleral
`mellae along the external wall, and splitting
`
`TABLE 2
`PERFUSION FLOW RATE* BEFORE AND AFTER
`CYSTOTOME TRABECULOTOMY IN HATS
`THE CIRCUMFERENCE
`
`a
`
`Eye
`
`Before
`
`Minutes
`After Trabeculotorny
`
`10
`
`0
`
`10
`
`30
`
`60
`
`90 12t)
`
`7
`8
`9
`10
`11
`
`4,0
`2.9 -
`4.3
`1.8
`2.4
`
`8.0 7.7 7.7 7.5 6.8
`10.8 10.8 10.3 10.1 9.8
`6.6 6.8 6.7 6.3 6.2
`4,0
`4.0
`5.3
`4.3
`3.7
`6•5
`.6.8
`7.8
`8.3
`9.0
`
`* Flow in µl/min at 15 mm Hg.
`
`Fig. 4 (Johnstone and Grant).
`lirograph demonstrating a st
`'shworIc (arrows) which had "
`. ;` cystotome just anterior tc
``*)• In the sulcus (S) of Sch
`the"cystotone was -remov
`do not appear to be corn'
`
`etitioner - New. World Medical
`Ex. 1005, p. 5 of 12
`
`

`

`GY
`
`PEC4OR
`
`76,' NO. 6
`
`MICROSURGERY OF SCI4LEMM'S CANAL
`
`911
`
`• • •
`
`".d.%
`
`• ,
`
`IS
`
`S N
`
`'t
`
`1 (Johnstone and Grant). Light micrograph after internal trabeculotomy with a cystotome, showing
`cillar meshwork and also disruption of Schlemm's canal ( X470).
`issue along the posterior wall, as re-
`-in Figure 5. Ab externo suture tra-
`lOmy ruptured the trabecular mesh-
`...
`I
`
`'
`
`S
`
`(Johnstone and Grant). Scanning electron
`li.ajih demonstrating a strip of trabecular
`-pik (arrows) which had been pushed ahead
`Ostotome just anterior to the sclera! spur
`to the sulcus (S) of Schlemm's.canal from
`the cystotome was removed, structural de-
`*, not appear to be compressed (x300).
`— •
`
`kw:
`
`i
`
`I ,
`
`work in its anterior third in three of four
`specimens, and produced only a slit-like rent,
`as shown in Figure 6. In the fourth speci-
`men disruption occurred in the mid-portion
`of the meshwork tissue.
`2B. Ab externo probe trabeculotomy in
`the manner of Dannheim and Harms pro-
`duced varied results. Trabeculotomy in one
`quarter of the circumference produced ini-
`tially a moderate increase in outflow in four
`of fives eyes, and a decrease in one, as re-
`corded in Table 3.
`We obtained an exceptional response in a
`pair of eyes from a child in which we per-
`formed probe trabeculotomy in a quarter of
`the circumference. The means of the results
`in these eyes, as well as for the adult eyes,
`are shown in Figure 1. In the child's eyes,
`flow increased markedly after trabeculot-
`omy, and remained high during the subse-
`quent 120 minutes of perfusion.
`Probe trabeculotomy in half the circum-
`ference in adult eyes produced initially more
`
`•
`Petitioner - New World Medical
`Ex. 1005, p. 6 of 12
`
`e residual tri4eg%
`shat was exposed
`e canal had an iii'
`
`3scopy of histolii
`s evident that in,
`trabecular meshiCii
`)tomy caused dinii
`the external - wal
`fisruption of seb.1-
`posterior wall of
`ron microscopy. (A-
`of trabecular mes
`s attachments arid:'
`)tome, leaving sO,Ii
`a configuration*"
`lisruption they :ha
`he external wall.. .
`edures on Schlerikt
`ing results.
`insertion of a nVo
`ally in Schlemrd
`without difficult
`a,
`had a diameter.df
`with the 0.275 rnifi,
`/ probe, it stretch's'
`of the canal. 1.4.;1
`us after insertion43
`age to the trabecular.,
`ielium of both the riq
`00
`compression of ,s*
`,
`Kternal wall, and
`0
`
`'ABLE 2
`RATE* BEFORE AND
`ABECULOTOMY IN RAVE
`IRCUMFERENCE
`
`Minutes
`
`After Trabecul9tA
`
`10
`
`30
`
`60
`
`8.0 7.7 7.7
`10.8 10.8 10.3 1042
`6.6 6.8 6.7 6.14:
`5.3 4.3 3.7 44!
`9.0 8.3 7.8 683
`
`grit
`
`t 15 mm Hg.
`
`

`

`912
`
`AMERICAN JOURNAL OF OPHTHALMOLOGY
`
`DECEMBE
`
`...3•10"
`
`r,
`
`41-
`
`•
`
`s.
`
`Fig. 5 (Johnstone and Grant). Light micrograph showing a 5-0 nylon suture (crosshatched beca.
`poor staining) within Schlemm's canal producing splitting of the sclera posteriorly, and compression ô
`sclera along the external wall of the canal. The trabecular meshwork (TM) also appears compressed;04
`than do.ubling of outflow in one eye, a minor
`increase in two eyes, and essentially no
`change in another two, as recorded in Table
`4. During 120 minutes of perfusion after
`
`probe trabeculotomy the behavior. . Tv4s
`rather Aried. The facility of outflow
`immediately after trabeculotomy fT41ge
`some eyes but decreased in others. TW
`
`-:;76, NO. 6
`
`•MIC
`
`TABLE 3
`BBOUSION FLOW RATE* BEFOR
`4XTERNO PROBE TRABECULX
`• •• QUARTER OF THE CIRCI.M
`
`Minut
`
`After
`
`10
`
`30
`
`Before
`
`10
`
`0
`
`14
`
`3.4 — 5.0 4.1
`4.7 — 5.1 4.!
`3.3 — 5.0 4.`
`1.6 —
`2 . 2 2 . (
`3.6 —
`2.8 2.4
`
`Flow in µl/min at 15 mm Hg
`
`aiiior is shown in Figure
`Observations of the trabe
`e the dissecting microsa
`ly
`e.opening produced by p
`-)generally was simply a
`1 11
`tissue, leaving a flap tha
`able of returning to its r
`on. At reexamination, aft
`used for 120 minutes
`y,
` the rent it
`14ork was no longer di:
`r,!a gaping of the origin
`0:10r portion of the mes
`
`• •
`
`•
`
`. '
`
`rttir_
`
`1
`
`• ..
`
`%41.!7•61a. . r .,
`,..
`•
`
`•
`
`•
`
`•
`
`41.k
`
`4,..I0 i • , - ...--
`
`1
`
`AN*
`
`.
`
`- „ * 7
`
`1.
`
`•
`
`•
`
`..,
`
`: N.:vs.
`'t".....:
`... „
`.:-.; • ,
`. ..i.;" "•••••
`.
`s.
`
`,,N1,*.‘*, .
`. 2 - •
`..,
`-,- --•'',. '..5- -
`..
`.• "
`.., • •e;„, .... .,-,.- :•-•
`• .. 4
`,,;:i -,%. t C:: ,. ... ...i.,.;..j,. , = 4' 47 '' ,,,„,..,
`-
`.;oe ;01::`•:' ..,..V'',
`.07 ..1-,
`N.. .. . • t
`.,
`i
`
`•••••*.. --s:.
`
`
`r........,.
`.....,...,..
`
`.
`..4 r..
`
`.
`
`.
`
`,
`- *....
`
`.... -NS P...::, •
`
`'-
`
`* ; 5 -.- ....
`
`:. 7-
`
` '
`
`,
`
`'
`
`'''t . -'
`
`vo,....fit?"...: . a ....
`' •• ••••
`
`•
`
`• •
`
`fe.
`
`-
`Fig. 6 (Johnstone and Grant). Light micrograph after suture trabeculotomy demonstratin
`rent in the mid-trabecular meshwork, splitting of the sclera posteriorly, and disruption of endoth.e
`the external wall ( X470).
`
`=47 (Johnstone and Grant)
`,(lie'anterior part of the tr:
`(x470).
`
`titloner - New World Medical
`Ex..1005, p. 7 of 12
`
`

`

`)GY
`
`DECEMBF
`
`a. 76, NO, 6
`
`-MICROSURGERY OF SCHLEMM'S CANAL
`
`913
`
`TABLE 3
`PERFUSION FLOW RATE* BEFORE AND AFTER AB
`STERNO PROBE TRABECULOTOMY IN ONE
`QUARTER OF THE CIRCUMFERENCE
`
`TABLE 4
`PERFUSION FLOW RATE* BEFORE AND AFTER AB
`EXTERN() PROBE TRABECULOTOMY IN
`HALF THE CIRCUMFERENCE
`
`Minutes
`
`E,ye
`
`Before
`
`After Trabeculotomy
`
`Eye
`
`10
`
`0
`
`10
`
`30
`
`60
`
`90 120
`
`12
`13
`14
`15
`16
`
`3.4 -
`4.7 -
`3.3 -
`1.6 -
`3.6 -
`
`5.0 4.7 4.0 3.1 3.8
`5.1 4.5 4.5 4.7 4.7
`5.0 4.5 4.8 4.5 4.3
`2.2 2.0 2.0 1.9 2.0
`2.8 2.4 2.3 2.3 2.1
`
`17
`18'
`19
`20
`21
`
`Minutes
`
`Before
`
`10
`
`0
`
`2.5 -
`2.0 -
`2.8 -
`4.0 -
`3.3 -
`
`After Trabeculotomy
`
`10
`
`30
`
`60
`
`90 120
`
`2.7 2.8 2.3 2.5 2.7
`2.0 1.5 1.6 1.3 1.5
`5.0 4.5 4.5 4.7 4.3
`5.3 4.0 3.7 3.1 2.8
`6.8 5.5 3.8 4.3 3.7
`
`• Flow in Al/min at 15 mm Hg.
`
`* Flow ill µl/ min at 15 mm Hg.
`
`x.'hai.ior is shown in Figure 1.
`Observations of the trabecular meshwork
`-vifh the dissecting microscope showed that
`lie opening produced by probe trabeculot-
`,RI)/ generally was simply a slit-like rent in
`tissue, leaving a flap that appeared to be
`;ipable of returning to its predissection po-
`on.lAt reexamination, after the eyes were
`rffised for 120 minutes after trabeculot-
`y,-:•commonly the rent in the trabecular
`esfiWork was no longer discernable. How-
`gaping of the original wound in the
`ilteribi portion of the meshwork could be
`
`produced by pressing with a fine instrument
`on the scleral spur, and a glistening white
`sulcus corresponding to Schlemm's canal
`could be exposed in this way. We removed
`the residual flap of trabecular meshwork
`with jeweler's forceps in five eyes, which
`caused an increase in 'facility of outflow in
`four of the eyes.
`By light microscopy of sections, such as
`shown in Figure 7, probe trabeculotomy pro-
`duced effects• similar to the insertion of the
`nylon suture, injuring the endothelium and
`disrupting the external and posterior wall of
`
`ture (crosshatched•because
`riorly, and compression of t;,,,
`o appears compressed (X470),
`
`ly the behavior was aIn
`facility of outfldiv
`:rabeculotomy persisted
`eased in others. The
`
`tiw
`
`s•-••••.,.
`•
`
`•
`
`I, •
`
`•
`
`ker
`
`II +t
`
`tomy demonstrating a slit-1
`lisruption of endothelium al,
`
`ig. 7 (Johnstone and Grant). Light micrograph after probe trabeculotomy demonstrating a slit-like
`ni the anterior part of the trabecular meshwork, splitting of the sclera posteriorly and disruption of the
`,,t,mal wall (x470).
`
`Tqf
`
`•
`
`Petitioner- New World Medical
`Ex. 1005, p. 8 of 12
`
`;,•,•
`
`

`

`ix
`
`ty
`
`,Y-#4
`A.4
`
`914
`
`TABLE 5
`PERFUSION FLOW RATE* BEFORE AND AFTER
`DIATHERMY TRABECULOTOMY IN ONE
`QUARTER OF THE CIRCUMFERENCE
`
`Eye
`
`22
`23.
`24
`25
`26
`^ 27
`
`Before
`
`10
`
`0
`
`4.8 -
`3.0 -
`4.4 -
`3.2
`4.0 -
`3.5 -
`
`Minutes
`
`After Trabeculotomy
`
`10
`
`30
`
`60
`
`90 120
`
`6.5 5.5 4.8 4.0 3.8
`3.8 2.8 2.9 2.7 2.8
`4.6 4.1 4.0 4.1 3.8
`6.5 4.8 4.3 4.2 3.5
`4.0 4.0 3.3 3.7 3.0
`7.3 7.2 5.2 5.2 4.7
`
`* Flow in µl/min at 15 mm Hg.
`
`the canal in most instances. In specimens
`from eyes in which we performed only probe
`trabeculotomy, without subsequent excision
`of the residual flap, the probe had passed
`within Schlemm's canal in seven of eight
`quadrants. In three specimens, disrupted
`septa were recognizable, but in other speci-
`mens septa were not recognizable after pas-
`sage of the probe. The opening from rupture
`into the anterior chamber was generally slit-
`like, and involved, about one third the width
`of the meshwork at most. In three instances,
`entry to the anterior chamber occurred ante-
`rior to Schwalbe's line through a tear in
`Descemet's membrane. In the others, entry
`tended to be through the anterior part of the
`trabecular meshwork leaving a flap over
`Schlernm's canal.
`In microscopic examination of sections of
`the angles of the eyes in which we removed a
`residual flap of trabecular meshwork after
`probe trabeculotomy and after the regular
`120 minutes of perfusion,-at least half of the
`trabecular meshwork had been removed, and
`there was increased damage to the external
`wall and splitting of the posterior wall.
`2C. Ab externo trabeculotomy performed
`with the diathermy probe in only one quarter
`of the circumference caused an initial in-
`crease in facility of outflow to at least twice
`the original values in two of six eyes; in
`three there was a smaller increase, and in
`
`AMERICAN JOURNAL OF OPHTHALMOLOGY
`
`DECEMBER, 1973
`one there was no change, as recorded in Ta-
`ble 5. During 120 minutes of perfusion after
`diathermy probe trabeculotomy, the otitfiolv
`in these eyes tended to return to predissec-
`tion values, as shown by the plot of the mean
`in Figure 1. Only one of these eyeSiipre.
`served an increase in its outflow during the
`120-minute perfusion after trabeculotomy.
`We performed ab externo trabeculotomy
`with the diathermy probe in one half tlie cir-
`cumference in one eye. This caused an im-
`mediate increase of flow to fourfold the pre-
`dissection value, and this remained ap-
`proximately twice the initial value after 120
`minutes of perfusion, as shown in Figure 1.
`Under the dissecting microscope, we could
`see that diathermy trabeculotomy pibducied
`an opening in the trabecular meshwork with
`well-defined borders. The whole trabecular
`meshwork appeared obliterated in some eyes,
`but in others a small flap of the posterior
`edge remained. From the appearance, we
`could conceive that the remaining pOsterior
`part of the meshwork in these eyes might oc-
`clude entrances of collector channelgi.during
`prolonged perfusion, and might thereby ac-
`count for the drop in outflow observed in
`most instances during the 120-minute.period
`after performance of the diathermy t:rabecu-
`lotomies.
`Microscopic examination of sections of
`the angles of

This document is available on Docket Alarm but you must sign up to view it.


Or .

Accessing this document will incur an additional charge of $.

After purchase, you can access this document again without charge.

Accept $ Charge
throbber

Still Working On It

This document is taking longer than usual to download. This can happen if we need to contact the court directly to obtain the document and their servers are running slowly.

Give it another minute or two to complete, and then try the refresh button.

throbber

A few More Minutes ... Still Working

It can take up to 5 minutes for us to download a document if the court servers are running slowly.

Thank you for your continued patience.

This document could not be displayed.

We could not find this document within its docket. Please go back to the docket page and check the link. If that does not work, go back to the docket and refresh it to pull the newest information.

Your account does not support viewing this document.

You need a Paid Account to view this document. Click here to change your account type.

Your account does not support viewing this document.

Set your membership status to view this document.

With a Docket Alarm membership, you'll get a whole lot more, including:

  • Up-to-date information for this case.
  • Email alerts whenever there is an update.
  • Full text search for other cases.
  • Get email alerts whenever a new case matches your search.

Become a Member

One Moment Please

The filing “” is large (MB) and is being downloaded.

Please refresh this page in a few minutes to see if the filing has been downloaded. The filing will also be emailed to you when the download completes.

Your document is on its way!

If you do not receive the document in five minutes, contact support at support@docketalarm.com.

Sealed Document

We are unable to display this document, it may be under a court ordered seal.

If you have proper credentials to access the file, you may proceed directly to the court's system using your government issued username and password.


Access Government Site

We are redirecting you
to a mobile optimized page.





Document Unreadable or Corrupt

Refresh this Document
Go to the Docket

We are unable to display this document.

Refresh this Document
Go to the Docket