Laser-Induced Primate Glaucoma
`
`I. Progression of Cupping
`Jonathan E. Pederson, MD, Douglas E. Gaasterland, MD
`
`\s=b\Sustained intraocular pressure ele-
`vations were induced in 15 monkey eyes
`by argon laser photocoagulation of
`the
`trabecular meshwork. Large fluctuations
`of IOP resulted. Posttreatment goniosco-
`py revealed an open angle with scattered
`low peripheral anterior synechiae. Optic
`disc cupping progressed during pressure
`elevations, manifested first as posterior
`bowing of the optic nerve head and peri-
`papillary tissues. Reversal of
`this early
`phase of cupping occurred in eight eyes
`during spontaneous normalization of IOP.
`In most eyes, as cupping evolved from
`saucerization to a deeper cup,
`the cup
`remained round. In four eyes, focal slop-
`ing of the cup to the inferotemporal rim
`occurred with nerve fiber layer defects.
`Total cupping with undermining of the rim
`occurred in five eyes with prolonged IOP
`elevation. Laser-induced primate glauco-
`ma has features in common with juvenile
`human glaucoma and is a useful model for
`the study of cupping of the optic nerve
`head.
`(Arch Ophthalmol
`1692)
`
`1984;102:1689-
`
`Argon laser photocoagulation of the
` ** trabecular meshwork has recent¬
`ly gained favor in the treatment of
`open-angle glaucoma.1 If the entire
`circumference of the trabecular mesh¬
`work is treated, approximately 10
`joules of energy are used. However,
`
`Accepted for publication May 18, 1984.
`From the Department of Ophthalmology, Uni-
`versity of Minnesota, Minneapolis (Dr Pederson);
`and the National Eye Institute, National Insti-
`tutes of Health, Bethesda, Md (Dr Gaaster-
`land).
`Read in part before the Association for
`Research in Vision and Ophthalmology, Saraso-
`ta, Fla, April 28, 1981.
`Reprint requests to Box 493 Mayo Memorial
`Bldg, University of Minnesota, Minneapolis, MN
`55455 (Dr Pederson).
`
`laser photocoagulation can induce
`glaucoma in monkey eyes if more than
`50 joules are applied to the trabecular
`meshwork.2·3 Laser-induced primate
`See also pp 1604, 1626,
`1629, 1693, and 1699.
`glaucoma is typified by large fluctua¬
`tions in intraocular pressure, allowing
`for study of
`the progression and
`reversal of cupping.4 To our knowl¬
`edge, the clinical features of optic disc
`changes have not been described. The
`present report describes the clinical
`features of laser-induced glaucoma in
`the monkey, with special emphasis on
`the
`the development of cupping of
`optic nerve head.
`MATERIALS AND METHODS
`Fourteen monkeys, ten rhesus and four
`initially weighing 2.5 to 7.1
`cynomolgus,
`kg, were used in this study. Pretreatment
`optic disc photographs and IOP measure¬
`ments were made. With the use of pento-
`barbital sodium anesthesia, 15 eyes under¬
`went argon laser photocoagulation of the
`trabecular meshwork with an argon laser
`(Coherent model
`photocoagulator
`900)
`using a small Koeppe lens or single-mirror
`Goldmann goniolens. Laser settings were
`as follows: 50 Mm, 700 to 850 mW, 0.5 to 1.0
`s, and 38 to 115 spots (average, 71 spots).
`Confluent laser burns were made on the
`light-gray trabecular meshwork. The laser
`spot was moved circumferentially,
`in a
`"painting" fashion, during the burn. If no
`IOP elevation occurred within several
`months, the treatment was repeated.
`All eyes were examined weekly, when
`possible, with the use of
`intramuscular
`ketamine hydrochloride anesthesia. Tests
`included slit-lamp examination, IOP mea¬
`surement with a tonometer (Perkins), and
`optic disc photographs with a fundus cam¬
`era (Zeiss). The animals were killed at
`varying intervals to obtain representative
`samples for histopathologic determina¬
`tions.
`
`—
`
`Gonioscopic appearance of angle
`Fig 1.
`structures two months following laser photo-
`coagulation of trabecular meshwork. Irregular
`pigmentation of trabecular meshwork is noted,
`low peripheral anterior syne-
`with several
`chiae.
`
`RESULTS
`to the laser
`Prior
`treatment, no
`animal exhibited appreciable optic
`disc cupping. A small-diameter, shal¬
`low depression was sometimes noted
`in the center of the optic disc, measur¬
`ing less than 0.1 cup-disc ratio. All
`animals
`had
`IOPs
`pretreatment
`between 10 and 20 mm Hg.
`During the laser treatment, the tra¬
`becular meshwork would
`blanch
`markedly, with visible swelling and
`bubble formation. Because of the long
`duration of the laser burn, the area of
`blanching would expand onto the cili¬
`ary body band, which was more heavi¬
`ly pigmented than the trabecular
`meshwork. Immediately following the
`laser
`treatment, mild iridocyclitis
`developed in all eyes, with anterior
`chamber flare and cells (+1 on a scale
`of 1 to 4). The anterior chamber reac¬
`tion cleared within three to four
`weeks. Frequently the IOP fell
`for
`about one week. If the IOP subse¬
`quently rose, it occurred one to two
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`Time, wk
`Fig 2.—Intraocular pressure of monkey eye 6, with disc photographs
`shown in Fig 4. Letters A through F correspond to Fig 4, A through F.
`Solid arrows indicate laser treatments.
`
`Time, wk
`Fig 3.—Intraocular pressure of monkey eye 13, with disc photographs
`shown in Fig 5. Letters A through F correspond to Fig 5, A through F.
`Solid arrows indicate laser treatments.
`
`Fig 4.—Disc photographs for monkey 6: A, pretreatment; , following laser treatment,
`reversal of cupping and loss of
`slight saucerization, and peripapillary shadow; C,
`peripapillary shadow; D, minimal increase in cupping; E, more cupping; F, more extensive
`cupping, with nerve fiber layer thinning inferiorly.
`prolonged pressure elevation. This
`weeks following the laser treatment.
`condition was not due to stretching of
`Gonioscopic examination after laser
`the iris by peripheral anterior syne-
`treatment in all eyes revealed an open
`angle, with indistinct angle struc¬
`chiae. Corneal edema developed dur¬
`tures, pigment mottling of the trabec¬
`ing periods of extremely high IOP,
`occasionally interfering with ade¬
`ular meshwork, and scattered,
`low,
`tentlike peripheral anterior synechiae
`quate optic disc photographs. Since
`(to ciliary body or scierai spur) (Fig
`the upper limit of IOP measurement
`1). More than one laser treatment was
`with the tonometer we used is 50 mm
`Hg, IOPs above that level were desig¬
`usually required to produce a perma¬
`nent IOP rise. The IOP rise was rapid,
`nated as greater than 50 mm Hg. The
`followed by alternating periods of
`mean fluctuation in IOP (highest
`normal and elevated IOP (Figs 2
`recorded IOP to lowest) was 41 mm
`and 3).
`Hg.
`Progression of optic disc cupping
`Fixed mydriasis, with absent light
`reflex, occurred in all eyes following
`only occurred following IOP eleva-
`
`tions above 39 mm Hg. One eye
`showed no cupping, but had a maxi¬
`mum IOP of 37 mm Hg, with a total of
`only four weeks of IOP above 30 mm
`Hg. Cupping in the other 14 eyes
`typically began as conical or funnel-
`shaped
`the change
`saucerization,
`being best detected with stereoscopic
`viewing. Posterior bowing of the optic
`nerve head and peripapillary region
`was noted in 11 of 15 eyes. A peripap¬
`illary "shadow," detectable without
`stereoscopic viewing, was observed in
`those eyes; it was due to an increase in
`posterior sloping of the peripapillary
`region (Fig 4, B). With normalization
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`Fig 5.—Disc photographs for monkey 13: A, pretreatment; , following laser treatment, moderate
`saucerization; C, early nerve fiber layer defect inferiorly; D, increased cupping and nerve fiber layer
`defect; E, cup extends to rim inferiorly; F, virtually total cupping, with undermining of rim and
`development of collateral vessel
`in base of cup.
`
`Clinical Features of Monkey Eyes After Sustained Elevation of Intraocular Pressure*
`
`Eye
`
`Saucer¬
`ization
`
`Reversal
`of
`Cupping
`
`Nerve Fiber
`Layer Defect
`
`Peripapillary
`Shadow
`
`Duration of
`Experiment, mo
`
`No. of
`Laser
`Treatments
`
`15
`15
`10
`
`10
`
`10
`
`13
`14
`
`12
`
`Total
`Mean
`'Plus indicates noted; minus, not noted.
`
`IOP Needed
`for Cupping,
`mm Hg
`
`Final Vertical
`Cup-Disc
`Ratio
`0.0
`
`50
`
`39
`43
`
`47
`50
`
`0.5
`
`0.8
`0.8
`0.8
`0.9
`
`1.0
`1.0
`1.0
`
`Total
`Energy,
`Joules
`71
`65
`69
`
`110
`80
`137
`
`90
`
`81
`
`of IOP (which periodically occurred
`spontaneously), reversal of sauceriza¬
`tion was noted in eight of 15 eyes (Fig
`4, C). After the initial phases of cup¬
`ping, a gradual increase in sauceriza¬
`tion of the optic nerve head was noted,
`resulting in a deeper cup with steeper
`walls, and an increase in the area of
`pallor (Fig 4, E). The cup remained
`round during this phase, and definite
`vertical ovalization of the cup was not
`observed. Reversal of cupping did not
`
`occur during this stage of cupping.
`Nerve fiber layer defects were noted
`in four of 15 eyes (Figs 4 and 5). Those
`eyes in which nerve fiber layer defects
`developed had corresponding thinning
`of the rim tissue, resulting in a slight¬
`ly vertically oval cup. If the IOP eleva¬
`tion remained extremely high for a
`considerable time, total cupping with
`undermining of
`the rim ultimately
`occurred (Fig 5, F). No flame-shaped
`hemorrhages or notches of the neural
`
`rim were noted in any eye during the
`features are
`study. Other clinical
`summarized in the Table. The cup-
`disc ratio in the Table is the contour
`stereoscopic
`ratio, determined by
`viewing of optic disc photographs.
`Discernible enlargement of
`the
`globe was often noted following IOP
`elevation.
`Immediately following re¬
`moval of the eyes for histopathologic
`evaluation, the globe dimensions were
`measured. The mean (±SD) antero-
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`posterior dimension of ten globes was
`20.7 ± 1.1 mm and the horizontal
`dimension was 20.2 ± 0.9 mm. Com¬
`parable dimensions of six normal
`monkey eyes were 18.8 ± 1.2 and
`17.8 ± 0.3 mm, respectively.
`COMMENT
`Although several reports have out¬
`creating
`lined the technique for
`laser-induced primate glaucoma,
`to
`our knowledge the clinical
`features
`have not previously been detailed.24
`Primate glaucoma differs from hu¬
`man open-angle glaucoma in several
`respects. Although the angle is open
`in primate glaucoma, scattered,
`low,
`synechiae are
`peripheral anterior
`present. They do not extend over the
`trabecular meshwork and may be due
`to postlaser iridocyclitis from absorp¬
`laser energy by the darkly
`tion of
`pigmented ciliary body. Fixed mydria¬
`sis, noted in all eyes, may also be due
`to laser-induced damage of ciliary
`nerves that pass through the ciliary
`body and innervate the iris sphinc¬
`ter.
`Another difference between human
`and primate glaucoma is the variabil¬
`the IOP. Although a direct
`ity of
`comparison
`statistical
`be
`cannot
`made, the IOP fluctuation in primate
`glaucomas (41 mm Hg) is greater than
`in untreated human primary open-
`
`angle glaucoma, which has an average
`IOP fluctuation of about 15 mm Hg.5
`The IOP fluctuation in untreated
`human secondary open-angle glauco¬
`ma is unknown but would offer a more
`direct comparison.
`In the early phases of cupping in
`laser-induced primate glaucoma, pos¬
`terior bowing of the optic nerve head
`and peripapillary tissues was fre¬
`quently observed. The posterior dis¬
`placement was of sufficient magni¬
`tude to produce a characteristic shad¬
`ow around the optic disc (Fig 4, B).
`Viewed stereoscopically, this feature
`was saucerization of the optic disc and
`surrounding tissues, creating a slop¬
`ing margin, visible as a shadow. Pre¬
`sumably the thin monkey
`sclera
`allows the entire region to stretch
`posteriorly. This characteristic is not
`observed in older patients with open-
`angle
`but
`glaucoma
`been
`has
`described in younger patients.6 In the
`early phases of glaucoma in the mon¬
`reversal of saucerization was
`key,
`observed during periods of lower IOP.
`This change is well described in infan¬
`tile glaucoma7 and has been noted in
`young adults.6 Additional similarities
`between infantile human glaucoma
`and primate glaucoma include en¬
`the globe and corneal
`largement of
`edema with markedly elevated IOP.
`Symmetrical expansion of the cup,
`
`References
`
`localized
`with later development of
`thinning of the disc rim tissue, has
`been noted in a longitudinal study of
`cupping in human adult glaucoma.8
`Similar observations were made in
`the
`the
`IOP
`study.
`If
`present
`remained elevated, a definite round
`cup would develop after the phase of
`saucerization. The rim tissue of the
`optic nerve head remained symmetri¬
`in most eyes, but in four monkey
`cal
`eyes localized thinning of the disc rim
`tissue developed in association with
`nerve fiber
`layer defects (Figs 4
`and 5).
`A follow-up study of patients with
`childhood glaucoma found visual field
`defects similar to those found in adult
`open-angle glaucoma.9 This finding
`suggests a similar mechanism of optic
`nerve damage in infantile and adult
`human glaucoma. Since primate glau¬
`coma resembles infantile human glau¬
`coma, by inference the primate model
`should be useful
`for studying the
`pathogenesis of cupping of both infan¬
`tile and adult human glaucoma.
`
`This study was supported in part by Public
`Health Service grant EY-03277.
`Technical help was provided by Carol Toris.
`Key Words.—Argon laser photocoagula-
`tion; experimental glaucoma;
`intraocular
`pressure; monkey eye; optic disc cupping.
`
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`
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`
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