`Histologic Evidence for the Mechanism of Pressure Reduction
`Jonathan Herschler, MD, E. Barry Davis
`
`\s=b\A modified goniotomy (trabeculodial-
`ysis) was performed on both eyes of a
`33-year-old woman who had glaucoma
`secondary to sarcoid uveitis. One month
`after trabeculodialysis, a cataract extrac-
`tion was performed on one eye and a
`histologic specimen was obtained from
`the area of the filtration angle that was
`previously incised. Successful control of
`intraocular pressure has been maintained
`in both eyes for 18 months following tra-
`beculodialysis. By
`light and electron
`microscopic examination,
`there was a
`nonhealed incision between the anterior
`chamber and Schlemm's canal. Trabecu-
`lodialysis, it is concluded, works by pro-
`viding direct communication between the
`anterior chamber and Schlemm's canal,
`and might be effective in all
`trabecular
`obstructive glaucoma of short duration
`before secondary changes occur in the
`outer drainage channels.
`(Arch Ophthalmol 98:684-687, 1980)
`
`glaucoma secondary to uveitis has
`remained a frustrating and diffi¬
`cult problem. If medical control is not
`adequate, filtering operations have a
`low rate of success. Poor results with
`filtering operations are most
`likely
`due to the young age of patients who
`have uveitis and the increase in
`inflammation caused by the operative
`insult. Haas1 first suggested, several
`years ago, that goniotomy (trabecu-
`
`Accepted for publication May 23, 1979.
`From the Department of Ophthalmology, Bas-
`com Palmer Eye Institute, University of Miami
`School of Medicine.
`Reprint requests to Department of Ophthal-
`mology, Bascom Palmer Eye Institute, Universi-
`ty of Miami School of Medicine, PO Box 016880,
`Miami, FL 33101 (Dr Herschler).
`
`lodialysis) be applied to inflammatory
`glaucoma. He reported an encourag¬
`ing but small series of modified goni-
`otomies performed on patients with
`uveitis who were aphakic. Because of
`its simplicity, easy repeatability, and
`inflammatory re¬
`seeming lack of
`sponse, the procedure was thought to
`be well suited for treating inflamma¬
`In a recent article,
`tory glaucoma.
`Hoskins et al4 reviewed their experi¬
`ence with the surgical
`treatment of
`inflammatory glaucoma and also rec¬
`ommended trabeculodialysis as a use¬
`technique, especially in
`ful surgical
`glaucoma secondary to Still's disease
`(juvenile rheumatoid arthritis).
`Trabeculodialysis is performed in a
`manner very similar to the classical
`Barkan goniotomy.4 However, rather
`than being incised,
`the trabecular
`meshwork is scraped from the scierai
`sulcus with the flat side of a gonioto¬
`my blade. This scraping maneuver is
`performed because elasticity of
`the
`limbic tissue in adults is less than in
`infants, and a simple incision tends to
`close up. The trabecular sheets are
`quite friable in inflammatory glauco¬
`ma and may be easily scraped away.
`trabeculodialysis low¬
`Presumably,
`ers intraocular pressure by increasing
`outflow facility, but
`the mechanism
`by which this occurs has never been
`documented histologically. The mech¬
`anism of successful goniotomy in pri¬
`mary infantile glaucoma has not been
`established either, even though it has
`been the preferred procedure for
`many years.4
`This case report describes a 33-year-
`old woman who had sarcoid uveitis,
`secondary glaucoma, and cataracts.
`Over a two-year period, the secondary
`
`glaucoma became medically uncon¬
`trollable, and trabeculodialysis was
`performed on both eyes. One month
`later, a cataract extraction was per¬
`formed on one eye, and a histologie
`specimen was obtained from the tra¬
`becular meshwork incised by the tra¬
`beculodialysis (Fig 1).
`REPORT OF A CASE
`facial numbness, pain
`In July 1974,
`around the mouth, red eyes, lymphadenop¬
`athy, and night sweats developed in a
`33-year-old woman. A chest
`roentgeno-
`gram showed hilar adenopathy and a liver
`biopsy specimen indicated noncaseating
`granulomas. Both findings supported the
`diagnosis of systemic sarcoidosis. The
`patient was treated with oral prednisone
`for one month. Although her condition
`improved systemically, her ocular symp¬
`toms continued, and she received injections
`of prednisolone acetate in the sub-Tenon's
`space four times in the right eye and three
`times in the left eye.
`She first came to the Bascom Palmer
`Eye Institute, Miami, in February 1975 for
`evaluation of her uveitis and secondary
`glaucoma. Her medications at
`the time
`included topical 1% prednisolone acetate
`four times a day in both eyes, topical 1%
`atropine sulfate twice a day in both eyes,
`and 500 mg of oral acetazolamide twice a
`day. Visual acuity was 20/25 in both eyes.
`The IOP determined by Goldmann appla¬
`nation tonometer was 20 mm Hg in both
`eyes. She had irregular posterior syne¬
`chiae, early posterior subcapsular cata¬
`racts, mild cell and flare in the anterior
`chamber, and some cells in the vitreous.
`Scattered peripheral anterior synechiae
`were seen gonioscopically in the nitration
`angles. The optic discs showed early glau¬
`comatous cupping, but no rim loss was
`noted. There was no evidence of periphlebi¬
`tis. Visual fields showed a shallow paracen-
`tral defect superiorly in the right eye. The
`visual field of the left eve was full.
`
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`Petitioner - New World Medical
`Ex. 1037, p. 1 of 4
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`
`
`Right Eye
`Left Eye
`
`.
`
`·
`
`Trabeculodialysis
`
`'-''
`
`r_~-,' Trabeculectomy and'*
`Cataract Extraction
`(Right Eye)
`
`1974
`
`Feb 1975
`
`Jan 1976
`
`Nov 1976
`
`Dec 7,1976
`
`Dec 13,1976
`
`Dec 20, 1976
`
`Jan 6,1977
`
`50
`
`40
`
`-
`
`-
`
`1%A,
`
`l%Pa
`
`4%R 1%E, l%Pa
`
`Right Eye
`-Left Eye-
`
`4%R 1%E. l%Pa
`4%R 1%E,
`l%Pa
`
`^ .-·-*7 7 - —-^^*> None.
`/v0„-^is-
`^ 4%P, 1%E-^ 4%P —^
`1%
`
`March 7,1977 March 28.1977 May 1977
`Nov 1978
`Jan 17,1977 Jan 24,1977
`Dec 1977
`Feb 1977
`Fig 1 .—Clinical course of patient. Distance between adjacent points is not
`time elapsed. = pilocarpine once a day; 1% , 1%
`to actual
`proportional
`pilocarpine four times a day; 4% P, 4% pilocarpine four times a day; 1% E, 1%
`epinephrylborate twice a day; Ac, 500 mg of acetazolamide twice a day; 1 % A, 1 %
`atropine twice a day; 1 % Pa, 1 % prednisolone acetate four times a day; and None,
`no medication.
`
`trabeculectomy specimen from area of
`Fig 2.—Phase contrast photomicrograph of
`filtration angle incised by trabeculodialysis one month previously. Trabecular meshwork
`(TM) has been disrupted and shows no signs of healing. Schlemm's canal (SC) is bared
`to anterior chamber (paraphenylenediamine, 275).
`
`Over the next year and a half, she contin¬
`ued to suffer from chronic uveitis with
`moderate cell and flare in the anterior
`chamber of both eyes. The treatment for
`this consisted of 1% prednisolone four
`times a day, 1% atropine twice a day, 1%
`epinephrylborate twice a day (all topically
`applied to both eyes), and 500 mg of oral
`acetazolamide twice a day. By January
`1976, the IOP was 29 mm Hg in the right
`eye and 14 mm Hg in the left eye on this
`regimen. Visual acuity was
`treatment
`reduced to 20/70 in the right eye and
`20/200 in the left eye.
`By November 1976, the peripheral ante¬
`rior synechiae had become more extensive
`in both eyes, associated with IOPs consis¬
`tently above 40 mm Hg in the right eye and
`around 30 mm Hg in the left eye. Visual
`acuity had decreased to finger counting at
`30 cm in the right eye and finger counting
`at 240 cm in the left eye due to advanced
`cataracts. The discs were difficult to evalu¬
`ate but the right cup appeared to be enlarg¬
`ing.
`A trabeculodialysis procedure, stripping
`away the nasal trabecular sheets, was per¬
`formed through a temporal approach on
`the right eye on Dec 7, 1976.
`Postoperatively, because the acetazolam¬
`ide therapy was stopped, the IOP rose in
`the left eye to 48 mm Hg and corneal
`edema developed. One week following the
`surgery on the right eye, a trabeculodialy¬
`sis was performed on the left eye. Postop¬
`eratively,
`the patient was treated with
`intensive topical and oral prednisone and
`1% pilocarpine hydrochloride medication.
`The IOP rose in both eyes over the next
`two weeks, and the patient was restarted
`on a regimen of 500 mg of acetazolamide
`i% pilocarpine four times a
`twice a day,
`day, and 1% epinephrine twice a day in
`both eyes. The patient was scheduled for
`combined cataract extraction and trabecu¬
`lectomy in the right eye. However, on
`admission for surgery one month after the
`trabeculodialysis,
`the IOP was 17
`initial
`mm Hg in the right eye and 16 mm Hg in
`the left eye. There was no corneal edema
`present and, by gonioscopic examination, a
`trabecular cleft could be seen in the area of
`trabeculodialysis in both eyes. Because of
`the patient's need for better vision, a cata¬
`ract extraction was performed on the right
`eye (first eye to have trabeculodialysis).
`Since the future course of the IOP regula¬
`tion was uncertain, a trabeculectomy was
`combined with the cataract extraction.
`Care was taken to excise the trabeculecto¬
`my specimen from the nasal end of the
`cataract section so that the specimen would
`include the trabecular meshwork that had
`previously undergone trabeculodialysis.
`A bleb developed initially following tra¬
`beculectomy, but closed within six weeks.
`Associated with the closure of the bleb, the
`IOP rose to 30 mm Hg in the right eye, and
`1% pilocarpine therapy was restarted. This
`was increased to 4% pilocarpine and epi¬
`nephrine, and has since been gradually
`tapered. The right eye has a visual acuity
`of 20/20, moderate glaucomatous cupping,
`and an early visual field defect. The IOP
`has remained below 20 mm Hg since March
`
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`Fig 3.—Electron micrograph montage. Same area as in Fig 2. Areas outlined indicate fields of view in Fig 4.
`
`Fig 4—Electron micrographs of areas indicated in Fig 3. (a), Trabecular meshwork anterior to goniotomy incision.
`Adjacent collagen (AC) cores (C) are collapsed and adherent, (b), Trabecular meshwork just posterior to goniotomy
`loss and fragmentation of endothelium (E), and absence of
`incision. Note disorganization of trabecular sheets (C),
`intertrabecular spaces, (c), Endothelial cells (E) lying in sulcus exposed to anterior chamber by goniotomy. Fresh
`lined (collector) channels (arrow), (d), Sclera posterior to goniotomy
`RBCs are present. RBC is entering endothelial
`incision. Note loosely packed collagen (C) with interspersed endothelial cells (E) ( 3,300).
`
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`1977 and is kept steady with a regimen of
`4% pilocarpine taken at night.
`The left eye's medication has gradually
`been tapered, and since May 1977 the eye
`has required no further medication. The
`left eye has had no further surgery (only
`the single trabeculodialysis), and continues
`to have IOP between 12 and 15 mm Hg
`with no medication required. Since the left
`eye has only had a trabeculodialysis, no
`possibility of external filtration exists, and
`the lowering of pressure can only be
`ascribed to this procedure. Although the
`situation in the right eye is more compli¬
`cated, due to the subsequent trabeculecto¬
`my operation, the IOP was normal at the
`time the histologie specimen was obtained
`and at that time no possibility of external
`filtration existed for the right eye either.
`HISTOPATHOLOGY
`OF SPECIMEN
`Light microscopic examination of
`the surgical specimen (Fig 2) showed
`superficial,
`nonhealed
`incision
`a
`through scarred trabecular meshwork
`into the area of Schlemm's canal. Elec¬
`tron microscopic examination (Fig 3)
`showed disruption in the scarred, col¬
`lapsed trabecular meshwork.
`In the trabecular meshwork anteri¬
`or to the incision (Fig 4, a), adjacent
`collagen cores were cemented togeth¬
`er with loss of endothelial covering
`and absence of intertrabecular spaces.
`The posteriorly hinged flap of trabec¬
`ular meshwork created by the trabec¬
`ulodialysis incision shows the same
`collapsed structure (Fig 4, b).
`In the cleft created surgically, endo¬
`lined channels communicate
`thelial
`with the anterior chamber (Fig 4, c).
`These may represent either preexist¬
`ing collector channels or newly formed
`
`the col¬
`aqueous channels. However,
`lagen that
`lies at
`the base of
`the
`incision is loosely packed and disor¬
`ganized with bands of endothelial cells
`interspersed (Fig 4, d). This may
`reflect a change in the collagen pro¬
`duced by exposure to aqueous humor,
`filtering
`as occurs in the lining of
`blebs.4
`
`COMMENT
`In his original study, Haas4 pointed
`that goniotomy is presumed to
`out
`work by reducing the resistance to
`outflow of
`through the
`aqueous
`trabecular meshwork, but
`that
`the
`mechanism by which this occurs had
`not yet been established. The opening
`produced by goniotomy or trabeculo-
`tomy in nonglaucomatous experimen¬
`tal animals (such as the rhesus mon¬
`key) scars within one month after
`surgery.4" Tears in the trabecular
`meshwork in rhesus monkeys also scar
`soon after injury.7 In contrast,
`the
`human eye with glaucoma seems to
`have a different healing tendency, as
`shown by the histologie specimen in
`this case. One possible explanation is
`that in a glaucomatous eye there is a
`generalized
`increased
`trabecular
`resistance, and when the resistance to
`flow is reduced over a small area (eg,
`with goniotomy), the aqueous humor
`is routed through this area, keeping
`the surgical site open. However, in an
`eye with normal outflow facility (such
`as the normal eye of an experimental
`animal),
`there is a continued flow
`through the nonincised trabecular
`the injured area
`meshwork, and
`undergoes healing and scarring.
`
`References
`
`Our observations in this case sug¬
`gest that in glaucomatous eyes with
`filtration channels
`functional outer
`(Schlemm's canal and the outer collec¬
`tor channels), satisfactory control of
`IOP may be achieved through the
`normal drainage pathways by estab¬
`lishing a patent communication be¬
`tween the outer channels and the
`anterior chamber, provided this com¬
`munication remains open.
`This is consistent with the clinical
`experience that goniotomies work
`well in early cases of infantile glauco¬
`ma,48 and in inflammatory glauco¬
`ma.12 On rare occasions, goniotomy
`has been applied successfully to corti¬
`costeroid-induced glaucoma." All three
`types of glaucoma have in common the
`relatively short duration of elevated
`pressure prior to surgery. In contrast,
`goniotomy is less successful late in the
`course of infantile glaucoma,3-8 or in
`chronic
`in
`open-angle
`glaucoma
`adults.10 Perhaps the poor results of
`goniotomy in these two instances are
`due to secondary changes that have
`occurred in Schlemm's canal, the col¬
`lector channels, or both, due to the
`long interval of elevated pressure
`prior
`to surgical
`intervention. An
`alternate, but more unlikely, explana¬
`tion is that chronic open-angle glauco¬
`ma and late infantile glaucoma are
`due to a primary malfunction of
`Schlemm's canal or the collector chan¬
`nels.
`
`This investigation was supported in part by
`Public Health Service research grant EY-00031
`from the National Eye Institute.
`
`1. Haas J: Goniotomy in aphakia, in Welsh R
`(ed): The Second Report on Cataract Surgery.
`Miami, Miami Educational Press, 1971, pp 551\x=req-\
`554.
`2. Hoskins HD, Hetherington J Jr, Shaffer
`RN: Surgical management of the inflammatory
`glaucomas. Perspect Ophthalmol 1:173-181, 1977.
`3. Barkan 0: Present status of goniotomy. Am
`J Ophthalmol 36:445-453, 1953.
`4. Teng CC, Chi HH, Katzin HM: Histology
`filtering operations. Am J
`and mechanism of
`Ophthalmol 47:16-34, 1959.
`5. Dannheim R, van der Zypen E: Klinische,
`
`funktionelle, und elektronenmikroskopische Un-
`tersuchungen ueber die Regenerationsfaehigkeit
`der Kammerwinkelregion des Primatenauges
`nach Trabekulotomie. Albrecht Von Graefes Arch
`Klin Exp Ophthalmol 184:222-247, 1972.
`6. Dannheim R, Barany EM: The effect of
`trabeculotomy in normal eyes of
`rhesus and
`cynomolgus monkeys studied by anterior cham-
`ber perfusion. Doc Ophthalmol 26:90-107, 1969.
`7. Herschler J: Trabecular damage due to blunt
`anterior segment injury and its relationship to
`traumatic glaucoma. Trans Am Acad Ophthal-
`mol Otolaryngol 83:239-248, 1977.
`
`8. Chandler PA, Grant WM: Lectures on Glau-
`coma. Philadelphia, Lea & Febiger, 1965, pp
`325-326, 330.
`Intraocular hypertension in-
`9. Herschler J:
`duced by repository corticosteroids. Am J Oph-
`thalmol 82:90-93, 1976.
`10. Richardson KT: Surgical control of chronic
`open angle glaucoma, in Symposium on Glauco-
`ma. Transactions of the New Orleans Academy of
`Ophthalmology. St Louis, CV Mosby Co, 1975, pp
`275-281.
`
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`New World Medical, Inc. v. MicroSurgical Tech., Inc., IPR2020-01573
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