Download Focal Chorioretinitis Produced by Ultrasound

Focal chorioretinitis produced by ultrasound
E. W. Purnell,* A. Sokollu, R. Torchia, and N. Taner
Two hundred and forty rabbit eyes toere exposed to focused ultrasonic radiation at either
3.5 me. or 7 me. Circumscribed chorioretinal lesion and localized destruction of the ciliary:
body could, be obtained without evidence of injury to other ocular tissues. The sound beam
retrodisplaces detached retinas. These observations suggest possible uses of ultrasound in
retinal detachment repair, ctjclodiathermy, and destruction of intraocular tumor.
A
sues along the path of the beam. The beam
may be focused through the cornea and
lens, whether these be clear or opaque, or
through the conjunctiva and sclera, or
through a combination of these routes. In
addition, the sound beam may be focused
at some point at the opposite side of the
globe, or at an area within the eye directly
under the point of application. The destructive effects of ultrasound are not dependent upon absorption by pigmented
structures.
method for producing chorioretinal
lesions in rabbit eyes with focused 3 me.
ultrasonic radiation has been reported.1'2
The purpose of this paper is to report additional observations on the effects of ultrasonic radiation at both 3.5 me. and 7 me,
describing the events and histologic
changes occurring both during and after
radiation. The ultimate aim of these investigations is to establish methods for the
therapeutic use of ultrasonic radiation in
the treatment of ocular diseases.
In some respects the therapeutic possibilities of focused ultrasonic radiation may
be compared to those of the light coagulator. However, there are major differences
in the two modalities: A sound beam may
be focused at any point in the eye independently of the optical properties of tis-
Methods and materials
All eyes were exposed in vivo under a combination of light general anesthesia and retrobulbar block. A description of the 3.0 me. ultrasonic
transducer and power source has been reported
elsewhere.1 A comparative summary of the 3.5
me. and 7 me. system components is given in
Table I.
Exposures were made in such a way that the
beam passed through the cornea and lens in some
cases, and through the conjunctiva and sclera in
others. The eyes were proptosed in the latter
cases in order to avoid exposure through the lens.
The focal point of the transducer was set at 17
mm., the approximate length of the rabbit eye, for
the production of chorioretinal lesions. For exposures of the ciliary body the focal point was
set 1 mm. beyond the coupling membrane. The
sound was applied either as a continuous radiation, or as pulsed radiation with a variety of pulse
durations and pulse intervals with different total
From the Department of Surgery (Ophthalmology), Western Reserve University School of
Medicine, Cleveland, Ohio.
This work was supported by grants from the
National Institute of Health (NB 03413-03
and ISO 1 FR-054101-61), by the Howard M.
Hanna Memorial Fund, and by the Ohio Lions
Eye Research Foundation.
"Present address: Department of Surgery (Ophthalmology), Western Reserve University School
of Medicine, Cleveland, Ohio.
657
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Inoe.itigative Ophtiialmologij
December 1964
658 Purnell et al.
A future publication will report experiments designed to elucidate the effects of change in pulse
duration, repetition rates, and total focal point
power as they relate to cataract production.
Observations of the events occurring at the
focal point during exposure were made with the
aid of a binocular ophthalmoscope with a magnification of 16. The eyes were then examined daily
by direct ophthalmoscopy for as long as three
months. After enucleation the eyes were fixed in
formalin, sectioned, and photographed before subjecting them to histologic procedures.
Retinal detachments were produce in a small
number of rabbits by prolonged exposures to 3.0
me. ultrasound, and these eyes were subsequently
re-exposed to determine the effects of the sound
beam on the detached retina.
energies at the focal point. The time required to
produce a given efFect in the retina or ciliary
body with these various dosage programs was
compared to the time required to produce an
immediate cataract with the same program of
exposure. The length of exposure necessary to
cause a grossly observable cataract was arbitrarily
termed a cataract-producing unit (CPU). The
amount of energy required to produce injury to
the retina or ciliary body was then expressed as a
fraction of this unit.
The advantages of using this cataractogenic
unit as an index of ultrasonic power were shown
early in the experimental series. Minor technical
refinements during the period of experimentation
increased the efficiency of converting electrical
energy to ultrasonic power, thus decreasing the
exposure times required for any given effect.
Since the relationship between the amount of
energy required to produce microscopic uveal
tract lesions and the amount required to produce
a grossly discernible cataract appears to be constant, the CPU serves as an excellent biologic
assay of ultrasonic destructive potential in the eye.
Results
The destructive effects of focused ultrasound at the retina are dependent upon the
total amount of sonic energy supplied and
the route of exposure. A one millimeter cir-
Table I. Characteristics of 3.5 and 7 me. systems
Frequency
System characteristics
1. Ultrasonic source
3.5 me.
Planoquartz crystal
7 vie.
Planoquartz crystal
2. Crystal diameter (mm.)
55
55
3. Quartz driver
Power oscillator
Power amplifier
4. Lens material
Polystyrene
Polystyrene
5. Focal length from crystal (mm.)
102
85
6. Focal point from tip of transducer (mm.),
variable
1-28
1-17
7. Beam width, 17 mm. anterior to focal point
(mm.)
13
13
8. Measured total thrust of sound beam (Gm.)
12
3
9. Estimated average ultrasonic driving power
(watts)
30
2.0
10. Estimated maximum ultrasonic power at
focal point (watts/cm. 2 )
900
60.0
11. Range of pulse interval available (msec.)
40 or greater
40 or greater
12. Range of pulse lengths available (msec.)
40 to continuous
40 to continuous
13. Transducer body
Round bottomed cylinder
Truncated cone
14. Transmitting window, coupling transducer
to eye
Polyethelene membrane
Vinylidene chloride membrane
15. Value of 1 CPU at 100% output, continuous
0.6
pulse (sec.) (see text)
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Volume 3
Number 6
Focal chorioretinitis
The large lesion shown in Fig. 1 measures 2 by 3 mm. It was produced by exposure at 7 me through the sclera with an
exposure equivalent to 0.2 CPU's.
The series of events taking place during
the exposure period was observed with unpigmented rabbits and long exposures of 7
or more seconds at reduced power (0.01
CPU's, 7 m e ) . Coincident with the start
of the sound pulse there was a blanching
of the choroidal circulation at the focal
point. With continuation of the pulse,
blood flow resumed in a few of the larger
choroidal vessels. Within seconds thereafter, a clear view of the choroidal vascular
bed was lost due to the development of a
gray-white haze in the overlying retina.
The area of retinal haze became more
opaque, and at the end of the exposure
presented an appearance similar to that
cumscribed chorioretinal lesion was produced with 0.5 CPU's at 3.5 me. and with
0.65 CPU's at 7 me, when the beam was
directed through the cornea and lens.
When the lens was avoided by passing the
sound beam through the conjunctivalscleral route, an identical lesion could be
produced with 0.3 CPU's at 3.5 me. and
0.07 CPU's at 7 me. Perforation of the
globe at the focal point occurred if an exposure equivalent to 1 CPU was exceeded
via the conjunctival-scleral route at either
frequency. Table II lists examples of lesions produced through the conjunctivalscleral route with variation in the exposure
program. No variation in the exposure program significantly altered the relationship
between the amount of energy required to
produce a chorioretinal lesion and the
cataractogenic dose.
Table II. Examples of lesions produced with selected exposure programs
via the conjunctival route
Exposure used
Equivalent in
CPU's
Lesion produced at
focal point
3 me.
Energy 25% maximum
Pulse duration 1.2 sec.
Pulse interval 1.2 sec.
Total exposure 10.8 sec.
0.6
Chorioretinitis 2 disc diameters in size
Energy 50% maximum
Pulse duration 1.2 sec.
Pulse interval 1.2 sec.
Total exposure 3.6 sec.
0.6
Chorioretinitis 2 disc diameters in size
Energy 35% maximum
Pulse duration 1.2 sec.
Pulse interval 1.2 sec.
Total exposure 2.4 sec.
0.5
Chorioretinitis 1.5 mm.
Total exposure 7.2 sec.
1.2
Perforation of globe
Energy 100% maximum
Pulse duration 40 msec.
Pulse interval 40 msec.
Total exposure 0.68 sec.
0.75
Chorioretinitis 4 mm. lesion
Energy 100% maximum, continuous
Total exposure 6 sec.
0.07
1 by 0.85 chorioretinal lesion
Energy 100% maximum, continuous
Total exposure 102 sec.
0.85
Perforation of globe
7 me.
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659
seen immediately following partial penetrating scleral diathermy. Twenty-four
hours after exposure, the ophthalmoscopic
examination revealed a small, circumscribed area of thickened gray retina surrounded by a larger zone of retinal edema.
The pigmentary changes characteristic of
chorioretinal scarring began after the
fourth day, and were usually completed in
three weeks.
Direct observations of the effect of the
sound beam on animals with retinal detachments could be made in three eyes in
which the media were sufficiently clear for
observation with the indirect ophthalmoscope. In all cases the detached retinal tissue was pushed in the direction of the
sound beam, that is, toward the focal
point.
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Fibrin strands and cellular debris in the
vitreous were similarly displaced.
The most striking finding on microscopic
examination of the chorioretinal lesions is
the sharpness of demarcation between the
area of injury and the surrounding tissue
(Fig. 2). Exposures of 1 CPU or more at
7 me. caused a 2 mm. perforation of the
globe with no microscopic evidence of injury beyond 1.5 mm. of the perforation.
Retina] detachment could not be produced
with the 7 me. system, nor was tissue destruction at the point of entry (the area of
the globe opposite the focal point area)
obtained with this system. Chorioretinal
lesions at the point of entry, vitreous liquefaction, and retinal detachment were noted
frequently with prolonged exposures at
3.5 me.
Fig. 2. HLstologic appearance of focal chorioretinal lesion. The retina was detached during
preparatioa of the section, except at the area of the lesion.
At sonic power levels used to produce
small, circumscribed chorioretinal lesions,
the sequence of microscopic findings was
similar to that found after nonp erforating
scleral diathermy, with the notable exception that no injury to the sclera was evident. Early, at the focal point, there was
an edematous thickening of the retina and
hyperemia of the underlying choroid. A
serofibrinous exudate covered the innerlimiting membrane in the area of injury.
There was subsequently a marked thinning
of the retina, with compression and disorganization of the nuclear layers, and infiltration of the chorioretinal stroma by
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lymphocytes and plasma cells. The choroid
showed necrosis of stromal cells and melanocytes. Eyes removed between one and
three weeks following exposure showed
various stages of fibroblastic repairs, with
proliferation of the pigment epithelium
and firm adhesion between the choroid and
retina. Fig. 3 shows the atrophy taking
place in the ciliary processes after an exposure equivalent to 0.75 CPU's at 7 me.
The transducer in this case was applied
through the intact conjunctiva directly over
the affected area. Histologic sections revealed almost complete destruction of the
ciliary processes, as shown in Fig. 4. Promi-
Fig. 3. View of the ciliary body, in sectioned eye previously fixed in formalin. A portion of
the ciliary processes (shown between arrows) has been destroyed by ultrasound.
nent microscopic features after radiation
of the ciliary body were the disappearance
of the inner epithelial cellular layer, necrosis of the pigment epithelial layer, and
hyperemia and necrosis of the stroma. Histologic evidence of injury to the ciliary
muscle or zonules was lacking; however,
impairment of function was implied by the
flattening of the lens equator, as shown in
Fig. 3.
Discussion
Most of the investigators concerned with
the destructive effect of ultrasound on tissue believe that the localized thermal effect
is primarily responsible for the production
of injury. There is nothing in our histologic
findings to suggest otherwise. The transitory blanching of the choroidal circulation
during the period of exposure, however, is
probably a direct result of compression of
the vascular
bed by the sound
beam. This
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decrease in blood flow undoubtedly reduces heat transfer from the area and helps
account for the localized nature of the
thermal injury.
A comparison of the 3.5 me. and 7 me.
systems cannot be made at this time. The
data do not indicate that the 7 me. frequency is preferable in producing small
chorioretinal lesions with less chance of
producing cataract, since two different
transducer systems were employed.
Microscopic studies confirm our previous
impression1 that chorioretinal lesions can
be produced by focused ultrasound without
injury to other ocular tissues. The technique certainly should be investigated as
an adjunct to surgery in retinal detachment
repair. The lesions are ideal in size for
retinopexy, and can be made with the area
to be treated under direct observation. In
these animal experiments, proper alignment
of the sound beam was easily obtained by
Fig. 4. Histologic appearance of injury to the ciliary processes. The eye was sectioned 40
hours after exposure.
observing the blanching of the choroidal
circulation, with power levels below that
sufficient to cause tissue damage. The
retrodisplacement of detached retina by
the sound beam is an interesting and potentially important observation from the
standpoint of retinal detachment repair.
The detachments created in the experimental animals were near complete. In
these eyes it was not possible to force the
retina back to its proper position against
the choroid. The effects of this sonic force
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on retinal-vitreous
adhesions
will require
further investigation. Possible uses of ultrasound in the destruction of intraocular tumors are entirely speculative. Judging by
the ease of destruction of normal tissue
with prolonged exposures, the potential
energy for tumor destruction appears to be
available.
At the present time the danger of inadvertent cataract production and the prolonged exposure times required make ultrasonic treatment hazardous. Time constants
for safe (noncataractogenic) exposures in
the human eye have not been determined.
664
Purnell et al.
Investigative Ophthalmology
December 1964
REFERENCES
1. Purnell, E., Sokollu, A., and Holasek, E.: The
production of chorioretinitis by ultrasound,
Am. J. Ophth. (In press.)
2. Purnell, E., Sokollu, A., and Holasek, E.: A
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preliminary report of the production of chorioretinal lesions by ultrasound, Presented at the
Association for Research in Ophthalmology
Sectional Meeting, Toronto, January, 1964.