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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 Downloaded From: http://iovs.arvojournals.org/ on 05/07/2017 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) Downloaded From: http://iovs.arvojournals.org/ on 05/07/2017 120 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. Downloaded From: http://iovs.arvojournals.org/ on 05/07/2017 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. Downloaded From: http://iovs.arvojournals.org/ on 05/07/2017 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 Downloaded From: http://iovs.arvojournals.org/ on 05/07/2017 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 Downloaded From: http://iovs.arvojournals.org/ on 05/07/2017 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 Downloaded From: http://iovs.arvojournals.org/ on 05/07/2017 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 Downloaded From: http://iovs.arvojournals.org/ on 05/07/2017 preliminary report of the production of chorioretinal lesions by ultrasound, Presented at the Association for Research in Ophthalmology Sectional Meeting, Toronto, January, 1964.