`
`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