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Retinal damage produced by intraocular fiber optic light
RETINAL
DAMAGE PRODUCED BY INTRAOCULAR FIBER OPTIC LIGHT*+
DWAIS FIILLER:. ROBERTMAC‘HEMEK and ROR~RT W. KNI(;HTO~ Bnscom Palmer
Eye Institute.
University
of Miami
I%TRODUCTIOIV During the last IOyr excellent studies have demonstrated the susceptibility of the retina to damage from visible light of relatively low intensity (Noel] et al.. 1966: Gorn and Kuwnbara. 1967; Kuwabara and Gorn. 196X: Kuwabara. 1970: O’Steen et (II., 1974; Zigman and Vaughan. 1974: Kuwabara and Funashi. 1976). Of particular clinical interest is the work of Friedman and Kuwabara (196X) and Tso rf crl.. 1972. lY73. showing retinal damage in rhesus monkeys exposed to the light of an indirect ophthalmoscope. The recent successes of human pars plana vitrectom! have been greatly facilitated by the development of intraocular fiber optic light sources (Pare1 e’t ul.. 1974). Intense intraocular light is desirable to improve surgical visibility and to enhance surgical cinematography. We have been concerned about the possibility of retina1 damage from the fiber optic intraocular light used for pars plana vitrectomy. The purpose of this study is to determine whether intraocular fiber optic light is indeed a potential source of retinal injury. and. if so. to establish threshold levels of exposure for clinical and histological damage.
\lATERIAL .ARD METHODS The maculas of healthy adult owl monkeys were exposed to light from an intraocular fiber optic light source for specific intervals of time. The light-treated retinas were observed by ophthalmoscopy. fundus photography. and Huorescein angiography. Animals were killed at various posttreatment times. and the ocular tissues were examined by light and electron microscopy. Each eye in the study was examined by indirect ophthalmoscopy. fundus photography, and Buoresccm angiography several days before light-treatment to assure that only normal eyes were included in the
*This inwstlgation was supported in part by Public Health Science Research Grant EY-00841 and EY-01432 from the NatIonal Eye Institute. National Institutes of Health. and b) the Veterans Administration Hospital. Miami. FL. t (‘opyrigh~ 197X. Ophthalmic Publishing Company. Reprinted b) permission from 4twri~u~~ Jourwl of Ophrllulrllillf~~g~~. : Rcprlnt requests to Dwain Fuller, Texas Retina Assoaates. 5421 La Sierra. Dallas. TX 75231, U.S.A.
School of Medicine.
Miami.
FL 33152. U S A
experiment. Pupils were dilated with IO”,, phenylephrine and topically applied I’,, cyclopentolatc. At the time of light exposure. each animal was sedated with intramuscular phencyclidinc hydrochloride and each eye was given a retrobulbar block with I?< lidocaine hydrochloride. The anesthctired animal was positioned with the head secured in a fixed position. A thermal blanket was used to maintain normal owl monkey body temperature at between 36.5 c‘ and 37.5 C. Body temperature was monitored by ;I rectkll thermocouple. A lateral orbitotomy was performed to give adcquate exposure for 3 superotemporal pars plana sclerotomy site. Using an operating microscope. ;I limbalbased conjunctival flap was prepared in tht: superotemporal quadrant. A razor-blade knife was used to make a 2-mm stab opening 2.5 mm behind the corneoscleral limbus through sclera. u~eal tissue. and vitreous base. The blade was passed cleanly into the central midvitreous cavity and then withdrawn. .4 mattress suture of 8-O white silk was placed with each limb at oposite ends of the sclerotomy opening. The tip of the illuminator was introduced into the sclerotomy site. By use of the operating mIcroscope and a fundus contact lens it was possible 10 place the illuminator tip accurately Zmm above the macula (Figs I-2) accurately. The fiber optic shaft U;IS kept m this position by a flexible arm with ;I lever to permit position freezing. The maintenance of proper tip position during each light treatment was assured b! constant visual monitoring. Lactated Ringer’s solution w,ith a level 25 cm above the eye was slowly perfused through the hollow tip of the illuminator to maintain normal intraocular pressure during the light exposure. Gentle tightening of the mattress suture of the hclerotomy site still permitted slow egress of fluid from the eye to simulate the fluid turnover of human pars plans vitrectomy. which might have a cooling effect on the retina. At the conclusion of each light treatment. the intraocular illuminator was withdrawn from the eye and the sclerotom> site was closed b) tightening the mattress suture. A small amount of lactated Ringer‘s solution was introduced into the midvitrcal cavity with a JO-gauge needle via the sclerotomq site to return the globe to normal intraocular pressure. The conjunctiva was closed with 7-O plain catgut suture and the eye was loosely patched without the use of antibiotic eyedrops or ointment. Animals not desip-
1055
10%
DWAIN FULLER r~ ui.
nated for immediate killing were returned to their cages to recover from the anesthesia. At the time of killing. each animal was reanesthetized with intramuscular phencyclidine hydrochloride, and fundus photography and fluorescein angiography were performed. Just before actual killing, O.?ml of fresh glutaraldehyde was injected into the midvitreal cavity of each eye via the pars plana. The eyes were then enucleated and fixed as whole specimens in cold glutaraldehyde for 4X hr. The anterior segment of each globe was removed and the light-exposed areas of retina were excised. The specimens were postfixed in 27; phosphate-buffered osmium tetroxide, dehydrated via a graded series of alcohol. and embedded in Epon. Sections 1.5 pm thick were stained with paraphenylenediamine for light microscopy. Thin sections 0.05 pm thick were made of areas of particular interest and were stained with uranyl acetate and lead citrate for examination with an electron microscope. Eyes were exposed to 30. 20, IS. 10 and 5 min of intraocular light and were then evaluated ophthalmoscopically, photographically. angiographicahy, and histologically at times ranging between 1 hr and 4 wk after light exposure. Animals were killed I hr, 74 hr. I wk. and 4 wks after treatment. Sham eyes were prepared by following identically the protocol of the experimental eyes with the exception that no light was emitted by the intraocular illuminator. These eyes were subjected to ophthalmoscopy, fundus photography and fluorescein angiography before the treatment session and also at the time of killing. In an effort to determine whether the infrared spectrum of fiber optic light plays a potentiating role in retinal light damage. a series of eyes were exposed to light for 30 min and 20 min under identical original experimental conditions with the exception that an infrared reflector was used to attenuate retinal infrared irradiance. Two eyes were exposed to intermittent light with 1 min and 5 set interruptions respectively, for 30 min of cumulative light exposure to learn if intermittency of exposure may be protective to the retina. Table I shows in detail the number of eyes studied in each category and the times of killing.
Table 1. Light exposure. min 30 20 15 10 5 30 20 30 30 30
TreaIment
I
The intraocular illuminator consrsted of flexible fiber optic filaments with a numerical aperture of 0.63 placed within a metal tube 1.65 mm in outside diameter. (The numerical aperture is the smc of the maximum angle at which light entering the fibers will be propagated along it.) A central opening was present to permit infusion of fluid (Fig. 3). Careful end-finishing was achieved with Epoxy cement and diamond wheel polishing. Approximately Sot) fibers were present in the finished cable. which was five feet long, The transmission spectrum of the fibers (as provided by the manufacturer) is significant only above 400 nm with a relatively flat transmission from 540 to 1300 nm. Above 1300 nm transmission falls off rapidly with essentially no transmission above 1700 nm. The light source was a commercially available light box with a standard 150 W halogenated tungsten projector bulb with a dichroic reflector to limit infrared output. Emission characteristics of the filament approximated those of 3300% black body. Bulbs were discarded after only three cumulative hours of an expected lifetime of 15 hr to maintain a mom stable emission spectrum. The intensity of the light from the fiber optic cable was measured with a calibrated radiometer. Total power in the spectral range of the radiometer (4%950nm) was 21 mW. We are aware that 21 mW is an underestimate of the power emitted from the fiber optic cable since shorter wave lengths, especially in the range of 4oo-450 nm were not considered. At a 2-mm distance from the retina. our light source covered an approximately circular area 3.5 mm in diam. The total area illuminated was 9.6 mm”. giving a retinal irradiance of 0.22 W,cm’ Comparison testing revealed that the intensity of light output of our fiber optic cable is comparable to that provided by the best commercially available fiber optic cables being used for human pars plana vitrcctomy. Before exposure of each eye to light, the intraocular illuminator tip was introduced into an integrating sphere in a reproducible fashion and radiometric measurements were obtained to assure identical light
protocol
with time of killing
hr killing
24 hr killing
1 wk killing
4 wks killing
4
2
2
2 2 2
2 1
2 3 4
reduced infrared
:!
reduced infrared with 1 min interruptions with 5 set interruptions sham
3
2
2
I I 1
Fig. 1. Close-up view of intraocular contact lens is necessary to facilitate
illuminator entering accurate placement microscope.
Fig. 2. Typical circular pattern illuminator correctly positioned
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eye via a pars plana sclerotomy. Fundus of illuminator tip by use of an operating
of light on macula with 2 mm above the retina.
Fig. 3. Fiber optic light tip pattern as projected through an objective onto a screen. Note that relatively few of the fibers are not functionat. Central black area is the infusion tube around which the fiber optic filaments are packed.
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Fig. 4. Top left: Normal owl monkey fundus before intraocular light exposure. Top right: Same fundus with severe lesion 24 hr after 30min of light exposure. Note central oval of outer retinal pigment epithelium damage with surrounding halos of hyperpigmentation and hypopigmentation. Bottom left: By 1 wk a bull’s eye pattern has evolved with central mottled hyperpigmentation surrounded by rings of alternating density. Bottom right: At 4 wk prominent central pigment changes are seen with persistence of the surrounding zones of pigment alteration.
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Fig. 5. Fundus change seen in one animal 24 hr after 15 min of light exposure. Note the small but definite area of whitening of the outer retina and retinal pigment epithelium.
Fig. 6. Left: Typical ophthalmoscopic findings at 24 hr in an eye treated with 30 min of normal fiber optic light showing the fundus appearance of altered outer retina and retinal pigment epithelium. Right: Fluorescein angiogram in the arteriovenous phase dearly showing significant earli staining of the retinal pigment epithelium and outer retina. Note that the retinal vessels in the area of light damage do not leak.
Fig. 7. Fluorescein angiogram of an eye 1 month after 30 min of light treatment (Fig. 4, bottom right, shows the ophthalmoscopic appearance). Transmission and blockage of choroidal fiuorescein corresponds to the circles of hypopigmentation and hyperpigmentation seen ophthalmoscopically. No staining occurred. I060
Retinal
damage produced by intraocular
output for each experiment. At the conclusion of each experiment, this value was rechecked. For studying the contribution of infrared radiation. a heat reflecting mirror was interposed between the projector bulb and the receiving end of the fiber optic cable. This mirror significantly eliminated light between 700 and 1100nm. Radiometric measurements revealed that greater than 504,: of the infrared light emitted from the fiber optic cable was removed by this measure. The interrupted light exposure experiments were conducted by fashioning a manually operated metal shutter. This shutter, when in position, totally prevented light from reaching the fiber optic cable. RKSI’LTS
Ten eyes were treated with 30 min of light exposure each and followed clinically for from I hr to I month. Four eyes were obtained at I hr. 2 at 24 hr, 2 at 1 wk. and 2 at 4 wks. The earliest retinal changes were noted 5 hr after treatment when whitening of the outer retina and retinal pigment epithelium was noted in the central macular area of some of the eyes. By 24 hr all eyes had prominent ophthalmoscopic changes. Striking circular lesions approximately two disk diameters in size were typically seen (compare Fig. 4. top left and right). The center of each lesion was pale and ringed by a halo of increased pigmentation surrounded by a second halo of decreased pigmentation. By I wk. sufficient evolution of the lesions had occurred to give a bull’s eye pattern with a central focus of mottled hyperpigmentation (Fig. 4. bottom left). In the two eyes observed for 3 wks. further central pigmentation was present and the lesions remained ophtholmoscopically stable until the time of killing at 4 wks (Fig. 4, bottom right). Three eyes were exposed to 20min of intraocular fiber optic light treatment and observed clinically for 7 days. Lesions only moderately less prominent than those produced by 30 min of treatment were noted. At 24 hr a distinct cncle of whitening surrounded by a halo of hyperpigmentation MS present in the macula of each eye. By I wk ;I circular mottled lesion without distinct zones was apparent. Eight eyes were given IS min of light exposure. Two eyes were obtained at I hr. 2 eyes at 24 hrs. and 4 eyes at 1 wk. Only one of the 6 eyes observed 24 hr or longer had an ophthalmoscopically visible lesion by 24 hr. In this eye a small area of whitening of the outer retina was present in the area of the light treatment I Fig. 5). Two of the 4 eyes observed for 7 days had dennite but mild pigment epithelium mottling at the time of killing. Three eyes were given IOmin of light exposure. Two of the eyes were obtained at I hr and one eye was observed 24 hr. No ophthalmoscopic change was noted in any of the 3 eyes,
fiber
optic
light
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Two eyes were treated for 5 min each and the animals were killed after I hr. Ophthalmoscopic changes were not present. Five eyes were exposed to light with the infrared mirror in use. Two of the eyes were treated for 30 min and three eyes were treated for 20 min. All 5 eyes were observed for one week. Each eye showed ophthalmoscopic lesions no less prominent than those seen in eyes treated for similar periods of time v+ith the standard fiber optic light spectrum. Two eyes were subjected to interrupted light for 30min each of cumulative exposure. In one eye the light was alternately on for 1min and off for I min for a period of 60 min. giving 30 min of total cxposuro. In the second eye a 5 set on and off cycle was used. Both eyes showed ophthalmoscopic changes 24 hr after exposure that were as severe as eyes treated with 30 min of uninterrupted exposure. Five eyes were treated in sham fashion. Two eyes were obtained at one hour. two eyes at 24 hr. and one eye at one week. None of the five eyes had ophthalmoscopic changes.
All eyes treated with light for 30 min and examined immediately had completely normal angiography. except for 1 eye in which faint staining in the treated area was noted one hour after Huorescein injection. Eyes given 30min of light exposure (including eyes with infrared light reduction and eyes with interrupted light exposure) and examined angiographically at one day or seven days gave evidence of early staining of the retinal pigment epithelium and outer retina in the treated areas with intense staining as the studies progressed (Fig. 6). No leakage of fluorescein from retinal vessels occurred. In eyes treated for 30 min and studied angiographitally at one month, prominent transmission of choroidal fluorescence in the area of light damage was seen. but no staining was present (Fig. 7). Eyes given 20min of light exposure with or wlthout infrared light reduction behaved angiographically like eyes with 30 min of exposure with significant staining still demonstrable at seven days. Except one, all eyes treated for IS min had normal fluorescein angiograms whether studied immediately. at 24 hr. or at I vvk. The exception U;IS an rye that showed a definite ophthalmoscopic lesion at 23 hr (Fig. 5). Fluorescein angiography of this eye showed definite staining. All ryes treated for IOmm or less had normal angiograms. The sham eyes vvcrc normal angiographically.
(I). Ow hr. The pigment epithelial cells appeared flattened: their pigment granules remained apical in location. Fragmentation of distal outer segments with
I Oh2
DWAIN FULLER c~‘tcd
irregular empty spaces and minute vacuoles in the inner segments were noted. Significant edema of the outer part of the outer nuclear layer was evident with separation of photoreceptor nuclei from each other. Pyknosis of some distal nuclei was present. The inner retina was normal (Fig. 8, top left). (2). T~vurlf~+lrr Ilr. Flattening of pigment epithelial cells with loss of melanin granules from villous processes v~as seen. In areas of major damage. proteinaceous material could bk identified between abnormal pigment epithelial cells and outer segments. The outer segments showed marked fragmentation with prominent irregular empty spaces. Inner segments had significant vacuolization. giving them a ground-glass appearance. Marked pyknosis of nuclei in the outer nuclear layer \\as evident with prominent distal edema. The inner retina was normal (Fig. 8. top right). (3). 0~ \\.I\: In regions of severe damage. the pigment epithelial cells were grossly abnormal with granule dispersion and loss of cell borders. Giant pigmentladen macrophages overlay the altered pigment epithelial cells. Prominent fragmentation of outer and inner photoreceptor segments was seen. There was moderate edema of the outer nuclear layer. The inner retina remained normal. Areas away from the center of light treatment had regained near-normal architecture. Eyes examined histologically I wk after 30min of light exposure with reduction of the infrared spectrum showed changes just as severe as the eyes exposed to the normal fiber optic light (Fig. 8, bottom left). (4). Four dc. The pigment epithelial cells were markedly flattened and nonpigmented. In the center of lesions. the outer and inner segments, as *ell as the outer nuclear layer. were nearly entirely missing and had been replaced by a carpet of large, pigment-bearing round macrophages interposed between flattened pigment epithelial cells and a thin outer plexiform layer. Away from the epicenter of light damage. outer and inner segments were somewhat irregular but appeared viable. The photoreceptor nuclei in these areas showed mild depletion in number but were once more tightly packed (Fig. 8. bottom right).
These specimens. compared to the specimens exposed to 30min of light. showed similar but less extensive changes of the retinal pigment epithelium and outer retina. Reducing rhe infrared component of the fiber optic light caused no reduction in the severity of histologic changes.
(I ), OJW Iv. The pigment epithelium was normal. Mild fragmentation of distal outer segments was present. but no inner segment changes were identified. Some specimens showed edema of the distal outer nuclear layer (Fig. 9, top left). (2). T\cer~ty+ur hr. No definite changes were present in the pigment epithelium. There was marked
edema of the outer segment layer and mild mner segment edema. The outer nuclear layer demonstrated definite edema in its outer part and limited pyknosls (Fig. 10. top left).
(I). One hr. The pigment epitheiium and retina were normal. The pigment epithelium and retina u-ere completely normal in all specimens of sham QL’S (Fig. IO. top right). There was no light microscopic evtdence of abnormality of the choriocdpilaris or choroid m any of the specimens.
31 min of exposure (I ). One hr. The pigment epithelial cells were intact. Mitochondria and endoplasmic reticulum were visible but not as distinct as normal. The cytoplasm was dense and filled with many large inclusion bodies containing lamellar outer segment material. Severe changes were seen in the outer segment layer. Proximally, the outer segments appeared normal, but distally they were heavily swollen by granular material distending the cell membrane sac. The granular material was evenly distributed within a given distal outer segment but of varying density in different cells. These unlike concentrations probably related to the amount of distention of a specific distal outer segment. The disk lamellar material was pushed (usually en bloc) to one side of the distal outer segments. Some lamellae retained an orderly stacked arrangement despite their dislocation, but there were many areas of complete disruption of the disk pattern with fingerprint whorls and overt fragmentation, The inner segments had ballooned mitochondria with short or missing cristae. Often the distal end ol the ellipsoid was slightly distended with granular homogenous material. In the outer half of the outer nuclear layer. the nuclei of photoreceptors were sepstrated by spaces filled with sparse granular material that was more densely packed in some places. usually in proximity to the cell membrane. Occasional whorls of lipoid fixation artifacts and perhaps nuclear envelopes were seen. These spaces represented intracellular edema since they were surrounded with a membrane. Mitochondrial swelling was visible in the cytoplasm of the photoreceptor cells in the outer part of the plexiform layer. The chromdtin of some nuclei was densely packed. indicating pyknosis. SmaH intercelluiar empty spaces were seen as well, identifying extracellular edema. The inner retina was normal (Fig. 11). (2). Twetlty$our hr. The pigment epithelium showed signs of cell death. Cell borders could not be dearly outlined and basal infoldings became indistinct. The cytoplasm had a fine granular appearance of varYi% density with prominent condensation of the end@=-
Fig. 8. Histology of retina following 30 min of light exposure. Top left. after 1hr: top right, after 24 hr; bottom left. after one week; bottom right, after 4 wk.
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Fig. 9. Histology and electron micrograph of retina 1 hr after a 10 min light exposure. Top left, histology of outer retina; top center, outer nuclear layer; top right, inner segments. Bottom left, outer segments: bottom right, pigment epithelium. Bar gauge equals 1 m.
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Fig. 10. Histology and electron micrograph of retina 24 hr after a 10 min light exposure. Top left. histology of outer retina. Bottom left, outer nuclear layer; bottom right, inner segment; top right, histology of outer retina of a sham eye. Bar gauge equals 1 pm.
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Fig. 11. Electron micrograph of retina 1 hr after a 30 min light exposure (see also Fig. 8, top left). Top left, outer nuclear layer; top right, inner segments; bottom, pigment epithelium. Bar gauge equals 1 pm.
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Retinal damage produced by intraocular fiber optic light mic reticulum. Pigment granules were no longer restricted to the apical parts of the cell but were also found basally. The cell was tilled with lamellar inclusion bodies. Nearly all outer segments showed at least some irregularities in the Iamellar arrangement of their disks. Many outer segments had complete disruption of inmellae with prominent distention of the membr;mc sac by granular material. This distention was much more extensive than that notrd at i hi-. ‘The inner segments had large intracellular empty spaces and extremely distended mitochondria with loss of cristae. The outer nuclear layer continued to show intraand some extracellular edema in its distal cells. and condensation of nuclear material indicated cell death. (31. @I~, $c!,. The findings varied. with changes in some specimens less severe than those noted at 34 hr. Other specimens showed continued evidence of severe change. Necrotic cells were found in the vicinity of living cells in the pigment epithelial layer. Two layers of cells were often seen. making it difficult to differentl;ltr between original pigment epithelial cells and overlying macrophages. Most of the basal infoldings of the pigment cpithelial cells were lost, and pigment granules were irregularly dispersed in the cytoptasm. Sometimes pigment granules were seen a~cumuiating in phagosomes in various stages of degradation. The cytoplasm was densely packed with lamellar inclusion bodies. In other cells the cytoplasm appeared loose with large vesicles and irregularly dispersed granular material. Mitochondri~~ looked normal but were not frequent. Viable adjoining pigment epithelial cells were linked by junctional complexes. The outer segments in less damaged areas were much less edematous than at 24 hr. but the disk remained irregular and contained tiny interlamellar vacuoles. Between the outer segments debris was noted. possibly remnants of cell membranes of necrotic outer segments. This debris caused separation hctvcecn the distal outer segments and the pigment epithelium in man) areas. and villous processes of pigment epithelial cells were absent. In areas of severe damige. the outer segment space was occupied by giam pigment-London macroph~lges surrounded by cellular debris with no intact outer segments remaining. Inner segments in less damaged areas showed most mitochondria lo be normal. but some swelling was Still
visible.
In regions
of
major
damage.
the
inner
segments were disrupted with rupture of cell membranes. The outer nuclear layer was densely packed in areas of less damage with only slight indication of iI’ItrXellular or extracellular edema. Where the photoreqXor cell bodies of outer and inner segments were completely destroyed. ihe nuclei exhibited pyknosis and loss of cefl ~a!{ integrity. (4). F~~olrrwX. The pigment cpithelium ~‘21s;i mono-
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layer of flattened. nonpigmented cellc with rare basal unfolding and rare cytoplasmic processes. The cells showed junctions between each other in the form of incomplete junctional complexes. The cytoplasm of these cells contained no phagocytosed material. Ocerlying these cells were heavily ballooned macrophages. Their cytoplasm was filled with Iamellar inclusion bodies and secondary lysosomes. Some celIs contained elliptical pigment granules. Cell organelles puch as mitochondria and rough endoplasmic reticulum were intact. In the central area of lesions. photoreceptors and their nuclei (outer nuclear layer) were completely missing. Instead, Miiller cells interdigitated with matrophages and underlying flattened pigment epitheli~ii cells. Multiple cell junctions between Miillcr cells formed an external limiting membrane. The inner retinal layers were normal. In areas away from the epicenter of light damage. the pigment epithelial cells were hypopigmented and fiattened. Overlying outer and inner segments were not completety regular, but were close to normal. and the outer nuclear layer showed little change (Fig. 121.
(1). One hr. The pigment epithelial cells appeared normal. Basal infoldings, cell junctions. and cytoplasmic processes were unremarkable. The qroplasm contained normal mitochondria. Lamellar inclusions did not appear to have increased in number. Pigment granules were in the apical parts of the cells and in the cytoplasmic processes. The outer segments looked essentially normal except for cleft formation between lamellae in close proximity to distal endings. These clefts were not thought to be artifacts since they were filled with granular material. Most inner segments had normal appearance: however, some showed distended mitochondria. The distal ceils of the outer nuclear layer clearly demonstrated severe edema (Fig. 9). (2). Twewr,v7Jixu hr. The pigment epithelium remained normal. The outer segments showed srparation of lamellae and fragmentation of disks in some areas. Distention of the distal outer segment cell membrane with granular material was seen. and many segments showed detachment of the plasma membrane from the lamellae. Fragmentation of \ornc detached plasma membranes was also noted. Some inner segments showed severe ballooning distally with granular material di&scly dispersed in this area. The plasma membrane was disrupted in these areas as well. Many mitochondria appeared normal. but others were moderately swollen. Definite intracellular edema was present II) the outer nuclear layer. and some nuclei showed condensation of ~hronl~itin. ~ndi~~~ting eelI death iFig. 10. hottom ). The inner parts of the retina appeared normal.
DWAIN FULLERt’f 4
106X
o~hth~~lmoscopic changes had the) been observed for (11. ~11~8/IV. Electron
micrographs
longer periods of time. Only two of four eyes showed
exposed 10 light for I5 min and observed clinically for seven
normal
pigment cpithclium and retina.
days had any detectable ophthalmoscopic changes bti seven days, and these changes were subtle.
prkle
epithelium and retina were normal
pigment
in
Threshold
for histologic
and electron microscopic
change was ten minutes
ntl specimens of sham eyes.
There was no electron microscopic evidence of ah-
of exposure
with
modest
~~~ter~~tions noted at one hour hollowing trealment
and
significant changes being present at 7-I hr. With
this
short exposure time. damage was found
11~3rm~~lityof the choriocap~ll~~ris or choroid in any of
outer retina:
the specimens.
mal. Conceivably. exposure
the pigment epitheliiIm
in the
oni?
remained nor-
of less than
ten minutes
resell in minimal microsoopic retina! alterations if such ryes were ttbservcd litr ;I longer period
might
of time. These experiments
clearly demonstrate
tial of intr~~~3c~ll~lrtiber optic light Thirty
&m:lpc. simil;tr
min of exposure
to
the poten-
C~LIS~
to :t light
Eyes exposed to five minutes
retinal
showed
source
croscopy. All previous
to that used for human pars pl:ina vitrectomy
01‘ light
no changes by hist~3lo~~ or studies
of retinal
exposure
electron
damage by visible
GILIX~ ~3phtll~~lm~3s~~3pic changes detectable as early
iight have used extraocular light sources. This
as f\hr after light exposure. By 24 hr the whitening of
ment
the outer retin;il
rotin;!
md
alteration
pigment ~pitheliLIrn
~3f the surrounding
were intense enough to
anpiography typically
alteration
of the light
showed no ab-
experi-
spectrum
by
of the
ocuix
media since only a thin layer of clear vitreous
separ-
absorption.
scattering.
or
reflection
ated the light source from
rumind one of ph~,tocongul~~tion lesions. Fluoresccin
avoids
mi-
vitreous
has been shown
the retina. Additionall>. not
to ahsorh
radiation
normalit> until 76 hr after light exposure when signifi-
appreciably in the visible and near infrared spectrum
cant staining
(Boettner and Walter.
oi’ tho pigment epithelium
and outer
1963). More important
rctin:) U;IS seen without evidence of leakage from reti-
with the advent of vitreous
n;ii vessels. This
tion of the retina has become ;I re;~lit\.
.cuggests that retinal pigment epithe-
litrm cells scre d;unaged and that their cell junctions were incompetent. thereby permitting enter pigment epithelium
Huorescein to
cells and to pss
between
them to stain edematous outer retina. Electron microscopic findings transmission
confirmed this.
By one month. onl?
of choroidal fluorescein through window
TfIe
surger).
histolo_eio changes noted
intraocular
is that
direct illuminam this
study
of
fiber optic light damage to owl monkq
retinas are similar
to changes pre\ iousl!
in rhesus
eyes
monkey
moscope light (Friedman and Fine.
1972: Tso.
documented
exposed to indirect ~3phth~~~and Kuuabara.
1971). But
1%5X: Tso
unlike
these other
defects in the pigment epithelium was present with no
studies, we find that the e&iest
retinal staining. Electron microscopy shelved that pig-
in the outer retina rather than in the pigment cpithe-
ment epitholium
hum.
plasma membrane competence and
.j~1?~1~(311~il complexes had been reest~ib~ished~
Friedman
Light and electron microscopy of JO-minute lesions
exposure
and Kuwabara
of I5 -20 min
for
~~bn~3rm~lliticsoccur
{1%X) found a tilresh(3ld retinal
damage in rhesus
showed major damage to the photoreceptor layers of
monkeys by using an indirect ophthalmoscope. Their
the retina with evidence of impending cell death as
de~nition of threshold exposure wa\ an exposure that
cari) its loss
of
severe
I hr after light eaposurc. By I month total ws
photoreceptors damage. The
abnormal within
noted in areas of most
pigment epith~iium
I hr after 30min
uith increased inclusion
aiso
was
of light exposure
bodies containing outer seg-
ment l~~rnel~~~e. Evidence of pigment e~ith~~iurn cell death US four
not present until
L\CC~S. honeker.
damage. tluttened.
14 hr after exposure, At
even in areas of severe light
h~po~igm~nted
pigment epithe-
lium cells had reformed an intact cell layer. Twent)
minutes and IS minutes of light exposure
caused :i lesser degree of clinical histologjc.
and eiec-
resulted in “definite irreversible
changes in the retinal
pigment cpithelium ophthalmoscopically tally
within
48 hrs.”
Retinal
or histolo_ei-
irradiance in their ex-
periment was cafcufated at 0.2? W cm’. The irradiance in our
experiment
us
rctioal
11.2 W cm’. Our
n~in~rnurn exposure time re~uircd tv produce ;tn ophthalmoscopicall?
visible
lesion
within
I5 min. Ten minutes was the shortust
74 hrs
LIZ
esposure found
to product: definite irreversihk hi\tologlc changes. and these changes were in tht outer retina. not in the pigment epithelium. There
has been conslderahic
discussion
regarding
tron microscopic damage. Fifteen minutes of exposure
the mechanism of retinal damage by vrsihle
h&t
probed to be the threshold for ophthaimoscopically visrble lesions in this study. No animal with less than
re[ativel)
Zigman
and Kuwabara.
15min of light exposure showed ;3phth~ilmoscopic
son.
1971:
low
intensity
Tso
(Noel1 (31 ,r/.. 1966:
1968: Vos. 1967: L;twwill. and La
Pianna.
1975:
chaugcs. although it is possible that some of the eyes
1976: Kuwabaru
with lesser exposure
1976: Geeraets P? rtl.. 19761. Whether
might have dcl’eloped minimal
and Okisaka.
1976:
]967;
of Ber-
V~~~~siIi~i~is. Ham
rf
{il.,
the damage is
Fig. 12. Electron m~~rograph of retina four weeks after a 30 min light exposure (see also Fig. g, bottom right). Top, outer retina; bottom, pigment epithelium. Bar gauge equals 1 pm.
Retinal damage produced by intraocular fiber optic light primarily thermal or photic has not been entirely resolved. In our experiment the earliest retinal changes in threshold lesions of ten minutes of exposure occurred in the outer retina rather than in the pigment epithelium. This finding suggests to us that absorption of visible light by photopigments in the outer segments is the initial event in the light injury cycle. We speculate that the primary mechanism of retinal damage in this study is photochemical damage. Perhaps injury to the pigment epithelium in this experiment is caused directly by light. but the absence of pigment epithelium changes with threshold exposures despite definite outer retinal damage suggests another mechanism. one which may be secondary to the retinal injury itself. Many studies have shown that increasing animal body temperature by only a few degrees Celsius greatly increases retinal damage caused by visible light (Noel1 1’1rrl.. 1966: Kuwabara. 1968; Kuwabara. 1970: Friedman and Kuwabara, 1968; Tso or (II.. 1972). The question arises whether retinal pigment epithelium and chornidal absorption of infrared energy from a broad spectrum light source such as the one used in this experiment could conceivably raise the temperature of the outer retina and thereby accelerate photic retinal damage. Reducing the infrared component of the light reaching the retina by approximately 50”,, with an infrared reflector. however. gave no significant protection from retinal damage. This finding causes us to speculate that the infrared component of intraocular fiber optic light does not play a major role in the mechanism of retinal damage. but prudence suggests that the visually useless infrared spectrum should be excluded as much as possible from fiber optic light used in human intraocular surgery. Of more importance for retinal damage may be the region of the spectrum below 5OOnm. Although our fiber optic source had only 2.5?,, of its output power below 500 nm (based on manufacturers’ specifications for the fiber optics and the light bulb), the retina is some IO 100 times more susceptible to damage b> light in that region than by light in the infrared. Exclusion of this part of the fiber optic emission spectrum may bc much more important than reducing the infrared component. However, filtering below 500 nm will add coloration to the light, which may prove obJectionable. but such filtering may be necessary if brighter light is required. We plan further investigations in this area. This experiment looked only briefly at the comparison of Intermittent light to constant light. In their classic study of retinal damage by fluorescent light in rats (Noel (‘f trl.. 1968) found that dose fractionation of light actually seemed to produce a more severe effect than when uninterrupted illumination was given for the same total duration. Thus light appeared to have a cumulative action. The 2 animals in our study treated with intermittent light developed severe retinal lesions. This finding suggests that in human pars \ R ‘0 I.
1071
plana vitrectomy intermittent exposure of the macula. as might occur during a lengthy meticulous mcmbrane stripping procedure. would be as potentially retinotoxic as a similar total exposure of the macula to constant illumination. Pars plana vitrectomy is der;ndent on good mtraocular illumination for maximal surgical safety and success. The majority of vitrectomies arc performed in eyes with opaque vitreous. Certainly the opacity of the vitreous protects the retina from significant Ilght exposure during much of the surgical procedure. Our studies suggest. however. that present clinical fiber optic light sources might cause retinal damage in situations where lengthy preretinal membrane stripping procedures are done. We speculate that dlrcct macular exposure of no more than 5 min should he relatively safe to human retinas. It should be kept in mind that the experimental animal used in this stud! is afoveate and nocturnal
and that its retina might have
a different threshold for light damage
than the human retina. However. exposure of rhesus monkc) maculas to indirect ophthalmoscopic light has previousI> shown retinal damage in this diurnal. fovcatc mammalian retina. a retina similar to the human retina (Friedman and Kuwabara, 1968; Tso cl (I/.. 1972; Tso 1973). We conclude that present levels of intraocular light used in human pars plans vitrectomy arc likeI) to be safe in most situations. The retinal irradiancc in our experiment was developed by a source 2 mm above the macula. Such proximity does not occur 111human surgery. At the closest. fiber optics arc placed 5 to 7 mm from the retina, a distance that reduces retinal irradiance significantly. A dangerous cumulative exposure from this distance could conceivabl! occur in protracted retinal membrane stripping procedures. We think the evidence is clear that intraocular fiber optic light has the potential for significant damage to the retina. This evidence must be considcrcd ;I\ efforts are made to develop ever brighter sources of introocular light for human pars plana vitrectomy. St M%IAR\
We exposed the maculas of owl monke! eyes to light from an intraocular fiber optic light source simllar to that used for human pars plana vitrcctom!. Retinal irradiance was calculated at 0.72 W cm’. E!cs were exposed for time intervals ranging from 10 min to 5 min and were observed after light trcatmcnt h> fundus photography and fluorescein angiograph!. Tissue was obtained for light and electron micrc)scopJ by animal killing at I hr. 23 hr. I wk. and 1 Mk Fundus lesions were seen ophth~rlm~)sc~~plc,111\ ;I\ early as five hours following 30 min of light cxposurc. Significant damage lo the photoreceptor Iaycr and less damage to the pigment epithclium was prcscnt bl light and electron microscopy as early ;IS I hr- ;tftcr 30min of light exposure. By one month complctc lo\> of photoreceptors with Miiller cell junction hct\\ccn
DWAIY FULLER
1077
inner retina and flattened abnormal epithelium
retinal
pigment
cells was observed.
Fluorescein
angiography
revealed significant
ing of the pigment epithelium
stam-
and outer retina 24 hr
after ?Omin of light chpnsurc. No leakage from
ret+
nal vessels occurred.
light
treatment, through
At one month
transmission
window
of
following
choroidal
fluorescein
defects in the pigment
epithelium
was present with no retinal staining. The
threshold
fundus
for
g ophthalmoscopically
posure. Ten min of light treatment for
visible
lesions in this study was I5 min of light ex-
microscopic
changes.
damaged the outer
retina
was the threshold
Short
light
exposures
and spared the pigment
ceithelium. Removing
;I substantial
amount
of
the infrared
light from our light source did not protect the retina from damage. Removal of light between 40@ So0 nm is probably
more
Intermittent
light exposure of the retina
harmful
helpful
as uninterrupted
in protecting illumination
the retina. seemed as
for
the same
cumulative period of time. We speculate that intraocular mechanism. lium
the retinal
fiber optic light D:tmagc
to
mny be secondnrq
The
present
human
the
damage caused hy
has primarily retinal
to outer
retinal
levels of intraocular
pars plana vitrectomy
preretinal
ping
vitrectomy.
pose ;I threat
during
of light
epithe-
damage. light
used for
are probably
most instances. Lengthy procedures
a photic
pigment
safe in
membrane however.
damage to the retina.
stripmay This
damage must be appreciated as continued eFforts are made to produce brighter sources of intraocular
light
for human pars plana vitrectomy.
REFEREYCES Bcrson E. (1973) Eiperimrntal and therapeutic Ltspects of photic damage to thr rctinit. /rrr~*sr. Op/~t/~c~l.12. 35. Boettner E. A. and Wolter J. R. (1961) Transmission of the ocul:tr mcdiu. //IIYYI. Oplrtl~rl. 1. 776. Friedman F. and Kuu;lham T. 11968) The retlnal pigment
er d
epithelium 4. The damaging Archs Ophrhcll. 73, 686.
effects of radiant
energy.
Geeraets W. J.. Geeraets R. and Goldman A. I. (1976) Elektromagretische Bostrahlungsverletzungen der Netzhaut. Ahrrchr r. Grccrfrs ,4rc,hs ODhthol. 260, 263 Gorn R. and Kuwabara T.. (1967) R∈ti damage bb visible light. A physiologic stud!. 4rc/1\ O/&r/m/. 77. I 15. Ham W. T. Jr. Mveller H. A. and Slincy D. H. (1976) Retinal sensitivity to damage from \)iort w:i\elenpth light. Nutuw 260. IS?. Kuwabara T. (1970) Retinal recobcrj from exposure to light. 4m. J. Ophthtrl. 70, 187. Kuwlrbara T. and Gorn R. (1968) Retin,ll damage by visible light. .ilrch.s Ophthol. 76, 69. Kuwabarn T. ;md Funahashi M. (1976) Light damage in the developing rut retina. 4rcl1.s Ophr/~r~l. 94, 1369. Kuw;tbera T. and Okisaka S. (1976) Effect of the electronic strobe tlash light on the monkey retin:{ .Itry. .f Op/~t/~u/ 20. 9. Lanum I. C. J. The damaging effects of IIght on the retma. Empirical findings. theoretical and practical implicatlons. Sur. Ophthol. 22, 221. Lawwill T. The ERG and its correlation with damage caused by chronic exposure to light. DII~. Ophthd. Proc. Series. Xth I.S.C.E.R.G. Symposium (1.0s Angeles) Vol ‘. p 65. Noel1 W.. Walker V.. Kand B. S. and Berman S. (I9661 Retinal damage by light in rats. /rlrr.st Ophthul. 5. 450. O’Steen W. K.. Anderson K. V. and Shear C R. (19741 Photoreceptor degeneration in albin-r;tts. Dependenq on upc. f,lrYvt Op/1r/1u/. 13. 334. Parr1 J. M.. Machemer R. and Aumayl W. (19731 A new concept for vitreous surgery. 4. Improvements in instrumrntation and illumination. .4m. J. Ophrhctl. 77. 6. Tso M. (197.3) Photic maculopath) in rhesus monkey. A light and electron microscope stud!. /III r’$~. Opht/d. 12. 1: Tw M. and La Plana F. G. (1975) The human fovea after sungazing. Tr~ns. Am. 4ctrd. Ophrhd. Oto-lcrr. 79, 78X Tso M.. Fine R. and Zimmerman L. (1972) Photic m;lsculop;lth! produced bj the indirect ophthalmoscope. I. (‘linic‘ll ~md histopathologtc study. IIII J. Ophrhul. 73. f>Sh V:losilladls A. (1976) Illumrn.ition threshoids. I%(~. Ophth~ll. Prc)c. Series. Fluorescan Anpiogmphy Symposium Ghent Vol. 9. p. XI. \‘os J. J. (1962) A theory of retinal hulns. &r/i Mtrrh. BIC~p/t\‘\. 24. I 15. Zigmcln S. and Vaughnn T. (1974) Near-ultraviolet hph! effects on the lenses and retinas of mice. ftlrrsr. Opllthtrl. 13. -Ifi?.
DAMAGE PRODUCED BY INTRAOCULAR FIBER OPTIC LIGHT*+
DWAIS FIILLER:. ROBERTMAC‘HEMEK and ROR~RT W. KNI(;HTO~ Bnscom Palmer
Eye Institute.
University
of Miami
I%TRODUCTIOIV During the last IOyr excellent studies have demonstrated the susceptibility of the retina to damage from visible light of relatively low intensity (Noel] et al.. 1966: Gorn and Kuwnbara. 1967; Kuwabara and Gorn. 196X: Kuwabara. 1970: O’Steen et (II., 1974; Zigman and Vaughan. 1974: Kuwabara and Funashi. 1976). Of particular clinical interest is the work of Friedman and Kuwabara (196X) and Tso rf crl.. 1972. lY73. showing retinal damage in rhesus monkeys exposed to the light of an indirect ophthalmoscope. The recent successes of human pars plana vitrectom! have been greatly facilitated by the development of intraocular fiber optic light sources (Pare1 e’t ul.. 1974). Intense intraocular light is desirable to improve surgical visibility and to enhance surgical cinematography. We have been concerned about the possibility of retina1 damage from the fiber optic intraocular light used for pars plana vitrectomy. The purpose of this study is to determine whether intraocular fiber optic light is indeed a potential source of retinal injury. and. if so. to establish threshold levels of exposure for clinical and histological damage.
\lATERIAL .ARD METHODS The maculas of healthy adult owl monkeys were exposed to light from an intraocular fiber optic light source for specific intervals of time. The light-treated retinas were observed by ophthalmoscopy. fundus photography. and Huorescein angiography. Animals were killed at various posttreatment times. and the ocular tissues were examined by light and electron microscopy. Each eye in the study was examined by indirect ophthalmoscopy. fundus photography, and Buoresccm angiography several days before light-treatment to assure that only normal eyes were included in the
*This inwstlgation was supported in part by Public Health Science Research Grant EY-00841 and EY-01432 from the NatIonal Eye Institute. National Institutes of Health. and b) the Veterans Administration Hospital. Miami. FL. t (‘opyrigh~ 197X. Ophthalmic Publishing Company. Reprinted b) permission from 4twri~u~~ Jourwl of Ophrllulrllillf~~g~~. : Rcprlnt requests to Dwain Fuller, Texas Retina Assoaates. 5421 La Sierra. Dallas. TX 75231, U.S.A.
School of Medicine.
Miami.
FL 33152. U S A
experiment. Pupils were dilated with IO”,, phenylephrine and topically applied I’,, cyclopentolatc. At the time of light exposure. each animal was sedated with intramuscular phencyclidinc hydrochloride and each eye was given a retrobulbar block with I?< lidocaine hydrochloride. The anesthctired animal was positioned with the head secured in a fixed position. A thermal blanket was used to maintain normal owl monkey body temperature at between 36.5 c‘ and 37.5 C. Body temperature was monitored by ;I rectkll thermocouple. A lateral orbitotomy was performed to give adcquate exposure for 3 superotemporal pars plana sclerotomy site. Using an operating microscope. ;I limbalbased conjunctival flap was prepared in tht: superotemporal quadrant. A razor-blade knife was used to make a 2-mm stab opening 2.5 mm behind the corneoscleral limbus through sclera. u~eal tissue. and vitreous base. The blade was passed cleanly into the central midvitreous cavity and then withdrawn. .4 mattress suture of 8-O white silk was placed with each limb at oposite ends of the sclerotomy opening. The tip of the illuminator was introduced into the sclerotomy site. By use of the operating mIcroscope and a fundus contact lens it was possible 10 place the illuminator tip accurately Zmm above the macula (Figs I-2) accurately. The fiber optic shaft U;IS kept m this position by a flexible arm with ;I lever to permit position freezing. The maintenance of proper tip position during each light treatment was assured b! constant visual monitoring. Lactated Ringer’s solution w,ith a level 25 cm above the eye was slowly perfused through the hollow tip of the illuminator to maintain normal intraocular pressure during the light exposure. Gentle tightening of the mattress suture of the hclerotomy site still permitted slow egress of fluid from the eye to simulate the fluid turnover of human pars plans vitrectomy. which might have a cooling effect on the retina. At the conclusion of each light treatment. the intraocular illuminator was withdrawn from the eye and the sclerotom> site was closed b) tightening the mattress suture. A small amount of lactated Ringer‘s solution was introduced into the midvitrcal cavity with a JO-gauge needle via the sclerotomq site to return the globe to normal intraocular pressure. The conjunctiva was closed with 7-O plain catgut suture and the eye was loosely patched without the use of antibiotic eyedrops or ointment. Animals not desip-
1055
10%
DWAIN FULLER r~ ui.
nated for immediate killing were returned to their cages to recover from the anesthesia. At the time of killing. each animal was reanesthetized with intramuscular phencyclidine hydrochloride, and fundus photography and fluorescein angiography were performed. Just before actual killing, O.?ml of fresh glutaraldehyde was injected into the midvitreal cavity of each eye via the pars plana. The eyes were then enucleated and fixed as whole specimens in cold glutaraldehyde for 4X hr. The anterior segment of each globe was removed and the light-exposed areas of retina were excised. The specimens were postfixed in 27; phosphate-buffered osmium tetroxide, dehydrated via a graded series of alcohol. and embedded in Epon. Sections 1.5 pm thick were stained with paraphenylenediamine for light microscopy. Thin sections 0.05 pm thick were made of areas of particular interest and were stained with uranyl acetate and lead citrate for examination with an electron microscope. Eyes were exposed to 30. 20, IS. 10 and 5 min of intraocular light and were then evaluated ophthalmoscopically, photographically. angiographicahy, and histologically at times ranging between 1 hr and 4 wk after light exposure. Animals were killed I hr, 74 hr. I wk. and 4 wks after treatment. Sham eyes were prepared by following identically the protocol of the experimental eyes with the exception that no light was emitted by the intraocular illuminator. These eyes were subjected to ophthalmoscopy, fundus photography and fluorescein angiography before the treatment session and also at the time of killing. In an effort to determine whether the infrared spectrum of fiber optic light plays a potentiating role in retinal light damage. a series of eyes were exposed to light for 30 min and 20 min under identical original experimental conditions with the exception that an infrared reflector was used to attenuate retinal infrared irradiance. Two eyes were exposed to intermittent light with 1 min and 5 set interruptions respectively, for 30 min of cumulative light exposure to learn if intermittency of exposure may be protective to the retina. Table I shows in detail the number of eyes studied in each category and the times of killing.
Table 1. Light exposure. min 30 20 15 10 5 30 20 30 30 30
TreaIment
I
The intraocular illuminator consrsted of flexible fiber optic filaments with a numerical aperture of 0.63 placed within a metal tube 1.65 mm in outside diameter. (The numerical aperture is the smc of the maximum angle at which light entering the fibers will be propagated along it.) A central opening was present to permit infusion of fluid (Fig. 3). Careful end-finishing was achieved with Epoxy cement and diamond wheel polishing. Approximately Sot) fibers were present in the finished cable. which was five feet long, The transmission spectrum of the fibers (as provided by the manufacturer) is significant only above 400 nm with a relatively flat transmission from 540 to 1300 nm. Above 1300 nm transmission falls off rapidly with essentially no transmission above 1700 nm. The light source was a commercially available light box with a standard 150 W halogenated tungsten projector bulb with a dichroic reflector to limit infrared output. Emission characteristics of the filament approximated those of 3300% black body. Bulbs were discarded after only three cumulative hours of an expected lifetime of 15 hr to maintain a mom stable emission spectrum. The intensity of the light from the fiber optic cable was measured with a calibrated radiometer. Total power in the spectral range of the radiometer (4%950nm) was 21 mW. We are aware that 21 mW is an underestimate of the power emitted from the fiber optic cable since shorter wave lengths, especially in the range of 4oo-450 nm were not considered. At a 2-mm distance from the retina. our light source covered an approximately circular area 3.5 mm in diam. The total area illuminated was 9.6 mm”. giving a retinal irradiance of 0.22 W,cm’ Comparison testing revealed that the intensity of light output of our fiber optic cable is comparable to that provided by the best commercially available fiber optic cables being used for human pars plana vitrcctomy. Before exposure of each eye to light, the intraocular illuminator tip was introduced into an integrating sphere in a reproducible fashion and radiometric measurements were obtained to assure identical light
protocol
with time of killing
hr killing
24 hr killing
1 wk killing
4 wks killing
4
2
2
2 2 2
2 1
2 3 4
reduced infrared
:!
reduced infrared with 1 min interruptions with 5 set interruptions sham
3
2
2
I I 1
Fig. 1. Close-up view of intraocular contact lens is necessary to facilitate
illuminator entering accurate placement microscope.
Fig. 2. Typical circular pattern illuminator correctly positioned
1057
eye via a pars plana sclerotomy. Fundus of illuminator tip by use of an operating
of light on macula with 2 mm above the retina.
Fig. 3. Fiber optic light tip pattern as projected through an objective onto a screen. Note that relatively few of the fibers are not functionat. Central black area is the infusion tube around which the fiber optic filaments are packed.
1058
Fig. 4. Top left: Normal owl monkey fundus before intraocular light exposure. Top right: Same fundus with severe lesion 24 hr after 30min of light exposure. Note central oval of outer retinal pigment epithelium damage with surrounding halos of hyperpigmentation and hypopigmentation. Bottom left: By 1 wk a bull’s eye pattern has evolved with central mottled hyperpigmentation surrounded by rings of alternating density. Bottom right: At 4 wk prominent central pigment changes are seen with persistence of the surrounding zones of pigment alteration.
1059
Fig. 5. Fundus change seen in one animal 24 hr after 15 min of light exposure. Note the small but definite area of whitening of the outer retina and retinal pigment epithelium.
Fig. 6. Left: Typical ophthalmoscopic findings at 24 hr in an eye treated with 30 min of normal fiber optic light showing the fundus appearance of altered outer retina and retinal pigment epithelium. Right: Fluorescein angiogram in the arteriovenous phase dearly showing significant earli staining of the retinal pigment epithelium and outer retina. Note that the retinal vessels in the area of light damage do not leak.
Fig. 7. Fluorescein angiogram of an eye 1 month after 30 min of light treatment (Fig. 4, bottom right, shows the ophthalmoscopic appearance). Transmission and blockage of choroidal fiuorescein corresponds to the circles of hypopigmentation and hyperpigmentation seen ophthalmoscopically. No staining occurred. I060
Retinal
damage produced by intraocular
output for each experiment. At the conclusion of each experiment, this value was rechecked. For studying the contribution of infrared radiation. a heat reflecting mirror was interposed between the projector bulb and the receiving end of the fiber optic cable. This mirror significantly eliminated light between 700 and 1100nm. Radiometric measurements revealed that greater than 504,: of the infrared light emitted from the fiber optic cable was removed by this measure. The interrupted light exposure experiments were conducted by fashioning a manually operated metal shutter. This shutter, when in position, totally prevented light from reaching the fiber optic cable. RKSI’LTS
Ten eyes were treated with 30 min of light exposure each and followed clinically for from I hr to I month. Four eyes were obtained at I hr. 2 at 24 hr, 2 at 1 wk. and 2 at 4 wks. The earliest retinal changes were noted 5 hr after treatment when whitening of the outer retina and retinal pigment epithelium was noted in the central macular area of some of the eyes. By 24 hr all eyes had prominent ophthalmoscopic changes. Striking circular lesions approximately two disk diameters in size were typically seen (compare Fig. 4. top left and right). The center of each lesion was pale and ringed by a halo of increased pigmentation surrounded by a second halo of decreased pigmentation. By I wk. sufficient evolution of the lesions had occurred to give a bull’s eye pattern with a central focus of mottled hyperpigmentation (Fig. 4. bottom left). In the two eyes observed for 3 wks. further central pigmentation was present and the lesions remained ophtholmoscopically stable until the time of killing at 4 wks (Fig. 4, bottom right). Three eyes were exposed to 20min of intraocular fiber optic light treatment and observed clinically for 7 days. Lesions only moderately less prominent than those produced by 30 min of treatment were noted. At 24 hr a distinct cncle of whitening surrounded by a halo of hyperpigmentation MS present in the macula of each eye. By I wk ;I circular mottled lesion without distinct zones was apparent. Eight eyes were given IS min of light exposure. Two eyes were obtained at I hr. 2 eyes at 24 hrs. and 4 eyes at 1 wk. Only one of the 6 eyes observed 24 hr or longer had an ophthalmoscopically visible lesion by 24 hr. In this eye a small area of whitening of the outer retina was present in the area of the light treatment I Fig. 5). Two of the 4 eyes observed for 7 days had dennite but mild pigment epithelium mottling at the time of killing. Three eyes were given IOmin of light exposure. Two of the eyes were obtained at I hr and one eye was observed 24 hr. No ophthalmoscopic change was noted in any of the 3 eyes,
fiber
optic
light
1061
Two eyes were treated for 5 min each and the animals were killed after I hr. Ophthalmoscopic changes were not present. Five eyes were exposed to light with the infrared mirror in use. Two of the eyes were treated for 30 min and three eyes were treated for 20 min. All 5 eyes were observed for one week. Each eye showed ophthalmoscopic lesions no less prominent than those seen in eyes treated for similar periods of time v+ith the standard fiber optic light spectrum. Two eyes were subjected to interrupted light for 30min each of cumulative exposure. In one eye the light was alternately on for 1min and off for I min for a period of 60 min. giving 30 min of total cxposuro. In the second eye a 5 set on and off cycle was used. Both eyes showed ophthalmoscopic changes 24 hr after exposure that were as severe as eyes treated with 30 min of uninterrupted exposure. Five eyes were treated in sham fashion. Two eyes were obtained at one hour. two eyes at 24 hr. and one eye at one week. None of the five eyes had ophthalmoscopic changes.
All eyes treated with light for 30 min and examined immediately had completely normal angiography. except for 1 eye in which faint staining in the treated area was noted one hour after Huorescein injection. Eyes given 30min of light exposure (including eyes with infrared light reduction and eyes with interrupted light exposure) and examined angiographically at one day or seven days gave evidence of early staining of the retinal pigment epithelium and outer retina in the treated areas with intense staining as the studies progressed (Fig. 6). No leakage of fluorescein from retinal vessels occurred. In eyes treated for 30 min and studied angiographitally at one month, prominent transmission of choroidal fluorescence in the area of light damage was seen. but no staining was present (Fig. 7). Eyes given 20min of light exposure with or wlthout infrared light reduction behaved angiographically like eyes with 30 min of exposure with significant staining still demonstrable at seven days. Except one, all eyes treated for IS min had normal fluorescein angiograms whether studied immediately. at 24 hr. or at I vvk. The exception U;IS an rye that showed a definite ophthalmoscopic lesion at 23 hr (Fig. 5). Fluorescein angiography of this eye showed definite staining. All ryes treated for IOmm or less had normal angiograms. The sham eyes vvcrc normal angiographically.
(I). Ow hr. The pigment epithelial cells appeared flattened: their pigment granules remained apical in location. Fragmentation of distal outer segments with
I Oh2
DWAIN FULLER c~‘tcd
irregular empty spaces and minute vacuoles in the inner segments were noted. Significant edema of the outer part of the outer nuclear layer was evident with separation of photoreceptor nuclei from each other. Pyknosis of some distal nuclei was present. The inner retina was normal (Fig. 8, top left). (2). T~vurlf~+lrr Ilr. Flattening of pigment epithelial cells with loss of melanin granules from villous processes v~as seen. In areas of major damage. proteinaceous material could bk identified between abnormal pigment epithelial cells and outer segments. The outer segments showed marked fragmentation with prominent irregular empty spaces. Inner segments had significant vacuolization. giving them a ground-glass appearance. Marked pyknosis of nuclei in the outer nuclear layer \\as evident with prominent distal edema. The inner retina was normal (Fig. 8. top right). (3). 0~ \\.I\: In regions of severe damage. the pigment epithelial cells were grossly abnormal with granule dispersion and loss of cell borders. Giant pigmentladen macrophages overlay the altered pigment epithelial cells. Prominent fragmentation of outer and inner photoreceptor segments was seen. There was moderate edema of the outer nuclear layer. The inner retina remained normal. Areas away from the center of light treatment had regained near-normal architecture. Eyes examined histologically I wk after 30min of light exposure with reduction of the infrared spectrum showed changes just as severe as the eyes exposed to the normal fiber optic light (Fig. 8, bottom left). (4). Four dc. The pigment epithelial cells were markedly flattened and nonpigmented. In the center of lesions. the outer and inner segments, as *ell as the outer nuclear layer. were nearly entirely missing and had been replaced by a carpet of large, pigment-bearing round macrophages interposed between flattened pigment epithelial cells and a thin outer plexiform layer. Away from the epicenter of light damage. outer and inner segments were somewhat irregular but appeared viable. The photoreceptor nuclei in these areas showed mild depletion in number but were once more tightly packed (Fig. 8. bottom right).
These specimens. compared to the specimens exposed to 30min of light. showed similar but less extensive changes of the retinal pigment epithelium and outer retina. Reducing rhe infrared component of the fiber optic light caused no reduction in the severity of histologic changes.
(I ), OJW Iv. The pigment epithelium was normal. Mild fragmentation of distal outer segments was present. but no inner segment changes were identified. Some specimens showed edema of the distal outer nuclear layer (Fig. 9, top left). (2). T\cer~ty+ur hr. No definite changes were present in the pigment epithelium. There was marked
edema of the outer segment layer and mild mner segment edema. The outer nuclear layer demonstrated definite edema in its outer part and limited pyknosls (Fig. 10. top left).
(I). One hr. The pigment epitheiium and retina were normal. The pigment epithelium and retina u-ere completely normal in all specimens of sham QL’S (Fig. IO. top right). There was no light microscopic evtdence of abnormality of the choriocdpilaris or choroid m any of the specimens.
31 min of exposure (I ). One hr. The pigment epithelial cells were intact. Mitochondria and endoplasmic reticulum were visible but not as distinct as normal. The cytoplasm was dense and filled with many large inclusion bodies containing lamellar outer segment material. Severe changes were seen in the outer segment layer. Proximally, the outer segments appeared normal, but distally they were heavily swollen by granular material distending the cell membrane sac. The granular material was evenly distributed within a given distal outer segment but of varying density in different cells. These unlike concentrations probably related to the amount of distention of a specific distal outer segment. The disk lamellar material was pushed (usually en bloc) to one side of the distal outer segments. Some lamellae retained an orderly stacked arrangement despite their dislocation, but there were many areas of complete disruption of the disk pattern with fingerprint whorls and overt fragmentation, The inner segments had ballooned mitochondria with short or missing cristae. Often the distal end ol the ellipsoid was slightly distended with granular homogenous material. In the outer half of the outer nuclear layer. the nuclei of photoreceptors were sepstrated by spaces filled with sparse granular material that was more densely packed in some places. usually in proximity to the cell membrane. Occasional whorls of lipoid fixation artifacts and perhaps nuclear envelopes were seen. These spaces represented intracellular edema since they were surrounded with a membrane. Mitochondrial swelling was visible in the cytoplasm of the photoreceptor cells in the outer part of the plexiform layer. The chromdtin of some nuclei was densely packed. indicating pyknosis. SmaH intercelluiar empty spaces were seen as well, identifying extracellular edema. The inner retina was normal (Fig. 11). (2). Twetlty$our hr. The pigment epithelium showed signs of cell death. Cell borders could not be dearly outlined and basal infoldings became indistinct. The cytoplasm had a fine granular appearance of varYi% density with prominent condensation of the end@=-
Fig. 8. Histology of retina following 30 min of light exposure. Top left. after 1hr: top right, after 24 hr; bottom left. after one week; bottom right, after 4 wk.
1063
Fig. 9. Histology and electron micrograph of retina 1 hr after a 10 min light exposure. Top left, histology of outer retina; top center, outer nuclear layer; top right, inner segments. Bottom left, outer segments: bottom right, pigment epithelium. Bar gauge equals 1 m.
1064
Fig. 10. Histology and electron micrograph of retina 24 hr after a 10 min light exposure. Top left. histology of outer retina. Bottom left, outer nuclear layer; bottom right, inner segment; top right, histology of outer retina of a sham eye. Bar gauge equals 1 pm.
1065
Fig. 11. Electron micrograph of retina 1 hr after a 30 min light exposure (see also Fig. 8, top left). Top left, outer nuclear layer; top right, inner segments; bottom, pigment epithelium. Bar gauge equals 1 pm.
1066
Retinal damage produced by intraocular fiber optic light mic reticulum. Pigment granules were no longer restricted to the apical parts of the cell but were also found basally. The cell was tilled with lamellar inclusion bodies. Nearly all outer segments showed at least some irregularities in the Iamellar arrangement of their disks. Many outer segments had complete disruption of inmellae with prominent distention of the membr;mc sac by granular material. This distention was much more extensive than that notrd at i hi-. ‘The inner segments had large intracellular empty spaces and extremely distended mitochondria with loss of cristae. The outer nuclear layer continued to show intraand some extracellular edema in its distal cells. and condensation of nuclear material indicated cell death. (31. @I~, $c!,. The findings varied. with changes in some specimens less severe than those noted at 34 hr. Other specimens showed continued evidence of severe change. Necrotic cells were found in the vicinity of living cells in the pigment epithelial layer. Two layers of cells were often seen. making it difficult to differentl;ltr between original pigment epithelial cells and overlying macrophages. Most of the basal infoldings of the pigment cpithelial cells were lost, and pigment granules were irregularly dispersed in the cytoptasm. Sometimes pigment granules were seen a~cumuiating in phagosomes in various stages of degradation. The cytoplasm was densely packed with lamellar inclusion bodies. In other cells the cytoplasm appeared loose with large vesicles and irregularly dispersed granular material. Mitochondri~~ looked normal but were not frequent. Viable adjoining pigment epithelial cells were linked by junctional complexes. The outer segments in less damaged areas were much less edematous than at 24 hr. but the disk remained irregular and contained tiny interlamellar vacuoles. Between the outer segments debris was noted. possibly remnants of cell membranes of necrotic outer segments. This debris caused separation hctvcecn the distal outer segments and the pigment epithelium in man) areas. and villous processes of pigment epithelial cells were absent. In areas of severe damige. the outer segment space was occupied by giam pigment-London macroph~lges surrounded by cellular debris with no intact outer segments remaining. Inner segments in less damaged areas showed most mitochondria lo be normal. but some swelling was Still
visible.
In regions
of
major
damage.
the
inner
segments were disrupted with rupture of cell membranes. The outer nuclear layer was densely packed in areas of less damage with only slight indication of iI’ItrXellular or extracellular edema. Where the photoreqXor cell bodies of outer and inner segments were completely destroyed. ihe nuclei exhibited pyknosis and loss of cefl ~a!{ integrity. (4). F~~olrrwX. The pigment cpithelium ~‘21s;i mono-
1067
layer of flattened. nonpigmented cellc with rare basal unfolding and rare cytoplasmic processes. The cells showed junctions between each other in the form of incomplete junctional complexes. The cytoplasm of these cells contained no phagocytosed material. Ocerlying these cells were heavily ballooned macrophages. Their cytoplasm was filled with Iamellar inclusion bodies and secondary lysosomes. Some celIs contained elliptical pigment granules. Cell organelles puch as mitochondria and rough endoplasmic reticulum were intact. In the central area of lesions. photoreceptors and their nuclei (outer nuclear layer) were completely missing. Instead, Miiller cells interdigitated with matrophages and underlying flattened pigment epitheli~ii cells. Multiple cell junctions between Miillcr cells formed an external limiting membrane. The inner retinal layers were normal. In areas away from the epicenter of light damage. the pigment epithelial cells were hypopigmented and fiattened. Overlying outer and inner segments were not completety regular, but were close to normal. and the outer nuclear layer showed little change (Fig. 121.
(1). One hr. The pigment epithelial cells appeared normal. Basal infoldings, cell junctions. and cytoplasmic processes were unremarkable. The qroplasm contained normal mitochondria. Lamellar inclusions did not appear to have increased in number. Pigment granules were in the apical parts of the cells and in the cytoplasmic processes. The outer segments looked essentially normal except for cleft formation between lamellae in close proximity to distal endings. These clefts were not thought to be artifacts since they were filled with granular material. Most inner segments had normal appearance: however, some showed distended mitochondria. The distal ceils of the outer nuclear layer clearly demonstrated severe edema (Fig. 9). (2). Twewr,v7Jixu hr. The pigment epithelium remained normal. The outer segments showed srparation of lamellae and fragmentation of disks in some areas. Distention of the distal outer segment cell membrane with granular material was seen. and many segments showed detachment of the plasma membrane from the lamellae. Fragmentation of \ornc detached plasma membranes was also noted. Some inner segments showed severe ballooning distally with granular material di&scly dispersed in this area. The plasma membrane was disrupted in these areas as well. Many mitochondria appeared normal. but others were moderately swollen. Definite intracellular edema was present II) the outer nuclear layer. and some nuclei showed condensation of ~hronl~itin. ~ndi~~~ting eelI death iFig. 10. hottom ). The inner parts of the retina appeared normal.
DWAIN FULLERt’f 4
106X
o~hth~~lmoscopic changes had the) been observed for (11. ~11~8/IV. Electron
micrographs
longer periods of time. Only two of four eyes showed
exposed 10 light for I5 min and observed clinically for seven
normal
pigment cpithclium and retina.
days had any detectable ophthalmoscopic changes bti seven days, and these changes were subtle.
prkle
epithelium and retina were normal
pigment
in
Threshold
for histologic
and electron microscopic
change was ten minutes
ntl specimens of sham eyes.
There was no electron microscopic evidence of ah-
of exposure
with
modest
~~~ter~~tions noted at one hour hollowing trealment
and
significant changes being present at 7-I hr. With
this
short exposure time. damage was found
11~3rm~~lityof the choriocap~ll~~ris or choroid in any of
outer retina:
the specimens.
mal. Conceivably. exposure
the pigment epitheliiIm
in the
oni?
remained nor-
of less than
ten minutes
resell in minimal microsoopic retina! alterations if such ryes were ttbservcd litr ;I longer period
might
of time. These experiments
clearly demonstrate
tial of intr~~~3c~ll~lrtiber optic light Thirty
&m:lpc. simil;tr
min of exposure
to
the poten-
C~LIS~
to :t light
Eyes exposed to five minutes
retinal
showed
source
croscopy. All previous
to that used for human pars pl:ina vitrectomy
01‘ light
no changes by hist~3lo~~ or studies
of retinal
exposure
electron
damage by visible
GILIX~ ~3phtll~~lm~3s~~3pic changes detectable as early
iight have used extraocular light sources. This
as f\hr after light exposure. By 24 hr the whitening of
ment
the outer retin;il
rotin;!
md
alteration
pigment ~pitheliLIrn
~3f the surrounding
were intense enough to
anpiography typically
alteration
of the light
showed no ab-
experi-
spectrum
by
of the
ocuix
media since only a thin layer of clear vitreous
separ-
absorption.
scattering.
or
reflection
ated the light source from
rumind one of ph~,tocongul~~tion lesions. Fluoresccin
avoids
mi-
vitreous
has been shown
the retina. Additionall>. not
to ahsorh
radiation
normalit> until 76 hr after light exposure when signifi-
appreciably in the visible and near infrared spectrum
cant staining
(Boettner and Walter.
oi’ tho pigment epithelium
and outer
1963). More important
rctin:) U;IS seen without evidence of leakage from reti-
with the advent of vitreous
n;ii vessels. This
tion of the retina has become ;I re;~lit\.
.cuggests that retinal pigment epithe-
litrm cells scre d;unaged and that their cell junctions were incompetent. thereby permitting enter pigment epithelium
Huorescein to
cells and to pss
between
them to stain edematous outer retina. Electron microscopic findings transmission
confirmed this.
By one month. onl?
of choroidal fluorescein through window
TfIe
surger).
histolo_eio changes noted
intraocular
is that
direct illuminam this
study
of
fiber optic light damage to owl monkq
retinas are similar
to changes pre\ iousl!
in rhesus
eyes
monkey
moscope light (Friedman and Fine.
1972: Tso.
documented
exposed to indirect ~3phth~~~and Kuuabara.
1971). But
1%5X: Tso
unlike
these other
defects in the pigment epithelium was present with no
studies, we find that the e&iest
retinal staining. Electron microscopy shelved that pig-
in the outer retina rather than in the pigment cpithe-
ment epitholium
hum.
plasma membrane competence and
.j~1?~1~(311~il complexes had been reest~ib~ished~
Friedman
Light and electron microscopy of JO-minute lesions
exposure
and Kuwabara
of I5 -20 min
for
~~bn~3rm~lliticsoccur
{1%X) found a tilresh(3ld retinal
damage in rhesus
showed major damage to the photoreceptor layers of
monkeys by using an indirect ophthalmoscope. Their
the retina with evidence of impending cell death as
de~nition of threshold exposure wa\ an exposure that
cari) its loss
of
severe
I hr after light eaposurc. By I month total ws
photoreceptors damage. The
abnormal within
noted in areas of most
pigment epith~iium
I hr after 30min
uith increased inclusion
aiso
was
of light exposure
bodies containing outer seg-
ment l~~rnel~~~e. Evidence of pigment e~ith~~iurn cell death US four
not present until
L\CC~S. honeker.
damage. tluttened.
14 hr after exposure, At
even in areas of severe light
h~po~igm~nted
pigment epithe-
lium cells had reformed an intact cell layer. Twent)
minutes and IS minutes of light exposure
caused :i lesser degree of clinical histologjc.
and eiec-
resulted in “definite irreversible
changes in the retinal
pigment cpithelium ophthalmoscopically tally
within
48 hrs.”
Retinal
or histolo_ei-
irradiance in their ex-
periment was cafcufated at 0.2? W cm’. The irradiance in our
experiment
us
rctioal
11.2 W cm’. Our
n~in~rnurn exposure time re~uircd tv produce ;tn ophthalmoscopicall?
visible
lesion
within
I5 min. Ten minutes was the shortust
74 hrs
LIZ
esposure found
to product: definite irreversihk hi\tologlc changes. and these changes were in tht outer retina. not in the pigment epithelium. There
has been conslderahic
discussion
regarding
tron microscopic damage. Fifteen minutes of exposure
the mechanism of retinal damage by vrsihle
h&t
probed to be the threshold for ophthaimoscopically visrble lesions in this study. No animal with less than
re[ativel)
Zigman
and Kuwabara.
15min of light exposure showed ;3phth~ilmoscopic
son.
1971:
low
intensity
Tso
(Noel1 (31 ,r/.. 1966:
1968: Vos. 1967: L;twwill. and La
Pianna.
1975:
chaugcs. although it is possible that some of the eyes
1976: Kuwabaru
with lesser exposure
1976: Geeraets P? rtl.. 19761. Whether
might have dcl’eloped minimal
and Okisaka.
1976:
]967;
of Ber-
V~~~~siIi~i~is. Ham
rf
{il.,
the damage is
Fig. 12. Electron m~~rograph of retina four weeks after a 30 min light exposure (see also Fig. g, bottom right). Top, outer retina; bottom, pigment epithelium. Bar gauge equals 1 pm.
Retinal damage produced by intraocular fiber optic light primarily thermal or photic has not been entirely resolved. In our experiment the earliest retinal changes in threshold lesions of ten minutes of exposure occurred in the outer retina rather than in the pigment epithelium. This finding suggests to us that absorption of visible light by photopigments in the outer segments is the initial event in the light injury cycle. We speculate that the primary mechanism of retinal damage in this study is photochemical damage. Perhaps injury to the pigment epithelium in this experiment is caused directly by light. but the absence of pigment epithelium changes with threshold exposures despite definite outer retinal damage suggests another mechanism. one which may be secondary to the retinal injury itself. Many studies have shown that increasing animal body temperature by only a few degrees Celsius greatly increases retinal damage caused by visible light (Noel1 1’1rrl.. 1966: Kuwabara. 1968; Kuwabara. 1970: Friedman and Kuwabara, 1968; Tso or (II.. 1972). The question arises whether retinal pigment epithelium and chornidal absorption of infrared energy from a broad spectrum light source such as the one used in this experiment could conceivably raise the temperature of the outer retina and thereby accelerate photic retinal damage. Reducing the infrared component of the light reaching the retina by approximately 50”,, with an infrared reflector. however. gave no significant protection from retinal damage. This finding causes us to speculate that the infrared component of intraocular fiber optic light does not play a major role in the mechanism of retinal damage. but prudence suggests that the visually useless infrared spectrum should be excluded as much as possible from fiber optic light used in human intraocular surgery. Of more importance for retinal damage may be the region of the spectrum below 5OOnm. Although our fiber optic source had only 2.5?,, of its output power below 500 nm (based on manufacturers’ specifications for the fiber optics and the light bulb), the retina is some IO 100 times more susceptible to damage b> light in that region than by light in the infrared. Exclusion of this part of the fiber optic emission spectrum may bc much more important than reducing the infrared component. However, filtering below 500 nm will add coloration to the light, which may prove obJectionable. but such filtering may be necessary if brighter light is required. We plan further investigations in this area. This experiment looked only briefly at the comparison of Intermittent light to constant light. In their classic study of retinal damage by fluorescent light in rats (Noel (‘f trl.. 1968) found that dose fractionation of light actually seemed to produce a more severe effect than when uninterrupted illumination was given for the same total duration. Thus light appeared to have a cumulative action. The 2 animals in our study treated with intermittent light developed severe retinal lesions. This finding suggests that in human pars \ R ‘0 I.
1071
plana vitrectomy intermittent exposure of the macula. as might occur during a lengthy meticulous mcmbrane stripping procedure. would be as potentially retinotoxic as a similar total exposure of the macula to constant illumination. Pars plana vitrectomy is der;ndent on good mtraocular illumination for maximal surgical safety and success. The majority of vitrectomies arc performed in eyes with opaque vitreous. Certainly the opacity of the vitreous protects the retina from significant Ilght exposure during much of the surgical procedure. Our studies suggest. however. that present clinical fiber optic light sources might cause retinal damage in situations where lengthy preretinal membrane stripping procedures are done. We speculate that dlrcct macular exposure of no more than 5 min should he relatively safe to human retinas. It should be kept in mind that the experimental animal used in this stud! is afoveate and nocturnal
and that its retina might have
a different threshold for light damage
than the human retina. However. exposure of rhesus monkc) maculas to indirect ophthalmoscopic light has previousI> shown retinal damage in this diurnal. fovcatc mammalian retina. a retina similar to the human retina (Friedman and Kuwabara, 1968; Tso cl (I/.. 1972; Tso 1973). We conclude that present levels of intraocular light used in human pars plans vitrectomy arc likeI) to be safe in most situations. The retinal irradiancc in our experiment was developed by a source 2 mm above the macula. Such proximity does not occur 111human surgery. At the closest. fiber optics arc placed 5 to 7 mm from the retina, a distance that reduces retinal irradiance significantly. A dangerous cumulative exposure from this distance could conceivabl! occur in protracted retinal membrane stripping procedures. We think the evidence is clear that intraocular fiber optic light has the potential for significant damage to the retina. This evidence must be considcrcd ;I\ efforts are made to develop ever brighter sources of introocular light for human pars plana vitrectomy. St M%IAR\
We exposed the maculas of owl monke! eyes to light from an intraocular fiber optic light source simllar to that used for human pars plana vitrcctom!. Retinal irradiance was calculated at 0.72 W cm’. E!cs were exposed for time intervals ranging from 10 min to 5 min and were observed after light trcatmcnt h> fundus photography and fluorescein angiograph!. Tissue was obtained for light and electron micrc)scopJ by animal killing at I hr. 23 hr. I wk. and 1 Mk Fundus lesions were seen ophth~rlm~)sc~~plc,111\ ;I\ early as five hours following 30 min of light cxposurc. Significant damage lo the photoreceptor Iaycr and less damage to the pigment epithclium was prcscnt bl light and electron microscopy as early ;IS I hr- ;tftcr 30min of light exposure. By one month complctc lo\> of photoreceptors with Miiller cell junction hct\\ccn
DWAIY FULLER
1077
inner retina and flattened abnormal epithelium
retinal
pigment
cells was observed.
Fluorescein
angiography
revealed significant
ing of the pigment epithelium
stam-
and outer retina 24 hr
after ?Omin of light chpnsurc. No leakage from
ret+
nal vessels occurred.
light
treatment, through
At one month
transmission
window
of
following
choroidal
fluorescein
defects in the pigment
epithelium
was present with no retinal staining. The
threshold
fundus
for
g ophthalmoscopically
posure. Ten min of light treatment for
visible
lesions in this study was I5 min of light ex-
microscopic
changes.
damaged the outer
retina
was the threshold
Short
light
exposures
and spared the pigment
ceithelium. Removing
;I substantial
amount
of
the infrared
light from our light source did not protect the retina from damage. Removal of light between 40@ So0 nm is probably
more
Intermittent
light exposure of the retina
harmful
helpful
as uninterrupted
in protecting illumination
the retina. seemed as
for
the same
cumulative period of time. We speculate that intraocular mechanism. lium
the retinal
fiber optic light D:tmagc
to
mny be secondnrq
The
present
human
the
damage caused hy
has primarily retinal
to outer
retinal
levels of intraocular
pars plana vitrectomy
preretinal
ping
vitrectomy.
pose ;I threat
during
of light
epithe-
damage. light
used for
are probably
most instances. Lengthy procedures
a photic
pigment
safe in
membrane however.
damage to the retina.
stripmay This
damage must be appreciated as continued eFforts are made to produce brighter sources of intraocular
light
for human pars plana vitrectomy.
REFEREYCES Bcrson E. (1973) Eiperimrntal and therapeutic Ltspects of photic damage to thr rctinit. /rrr~*sr. Op/~t/~c~l.12. 35. Boettner E. A. and Wolter J. R. (1961) Transmission of the ocul:tr mcdiu. //IIYYI. Oplrtl~rl. 1. 776. Friedman F. and Kuu;lham T. 11968) The retlnal pigment
er d
epithelium 4. The damaging Archs Ophrhcll. 73, 686.
effects of radiant
energy.
Geeraets W. J.. Geeraets R. and Goldman A. I. (1976) Elektromagretische Bostrahlungsverletzungen der Netzhaut. Ahrrchr r. Grccrfrs ,4rc,hs ODhthol. 260, 263 Gorn R. and Kuwabara T.. (1967) R∈ti damage bb visible light. A physiologic stud!. 4rc/1\ O/&r/m/. 77. I 15. Ham W. T. Jr. Mveller H. A. and Slincy D. H. (1976) Retinal sensitivity to damage from \)iort w:i\elenpth light. Nutuw 260. IS?. Kuwabara T. (1970) Retinal recobcrj from exposure to light. 4m. J. Ophthtrl. 70, 187. Kuwlrbara T. and Gorn R. (1968) Retin,ll damage by visible light. .ilrch.s Ophthol. 76, 69. Kuwabarn T. ;md Funahashi M. (1976) Light damage in the developing rut retina. 4rcl1.s Ophr/~r~l. 94, 1369. Kuw;tbera T. and Okisaka S. (1976) Effect of the electronic strobe tlash light on the monkey retin:{ .Itry. .f Op/~t/~u/ 20. 9. Lanum I. C. J. The damaging effects of IIght on the retma. Empirical findings. theoretical and practical implicatlons. Sur. Ophthol. 22, 221. Lawwill T. The ERG and its correlation with damage caused by chronic exposure to light. DII~. Ophthd. Proc. Series. Xth I.S.C.E.R.G. Symposium (1.0s Angeles) Vol ‘. p 65. Noel1 W.. Walker V.. Kand B. S. and Berman S. (I9661 Retinal damage by light in rats. /rlrr.st Ophthul. 5. 450. O’Steen W. K.. Anderson K. V. and Shear C R. (19741 Photoreceptor degeneration in albin-r;tts. Dependenq on upc. f,lrYvt Op/1r/1u/. 13. 334. Parr1 J. M.. Machemer R. and Aumayl W. (19731 A new concept for vitreous surgery. 4. Improvements in instrumrntation and illumination. .4m. J. Ophrhctl. 77. 6. Tso M. (197.3) Photic maculopath) in rhesus monkey. A light and electron microscope stud!. /III r’$~. Opht/d. 12. 1: Tw M. and La Plana F. G. (1975) The human fovea after sungazing. Tr~ns. Am. 4ctrd. Ophrhd. Oto-lcrr. 79, 78X Tso M.. Fine R. and Zimmerman L. (1972) Photic m;lsculop;lth! produced bj the indirect ophthalmoscope. I. (‘linic‘ll ~md histopathologtc study. IIII J. Ophrhul. 73. f>Sh V:losilladls A. (1976) Illumrn.ition threshoids. I%(~. Ophth~ll. Prc)c. Series. Fluorescan Anpiogmphy Symposium Ghent Vol. 9. p. XI. \‘os J. J. (1962) A theory of retinal hulns. &r/i Mtrrh. BIC~p/t\‘\. 24. I 15. Zigmcln S. and Vaughnn T. (1974) Near-ultraviolet hph! effects on the lenses and retinas of mice. ftlrrsr. Opllthtrl. 13. -Ifi?.