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ROENTGEN THERAPY OF OCULAR VACCINIA*
ORAM R. KL Philadelphia,
Ocular vaccinia has existed as a disease entity since the introduction of vaccination by Jenner in 1796. In all the succeeding time, many remedies have been advocated for the treatment of this condition—which is indication enough that none have been entirely satisfactory.
Among the many therapeutic agents suggested have been potassium-permanganate flushes (1:100,000), ascorbic acid locally and generally, immune serum, estrogens, ultraviolet light, repeated vaccinations, and the antibiotics. All of these measures have received varying amounts of support, but still no one has been able to prevent the disabling deep keratitis which develops in about 20 percent of the cases.
It is true, of course, that the condition is not a common one. In 1940,1 slightly more than 200 cases had been reported. The number is indeed quite small when one considers the large number of vaccinations performed every year.
In 1947 Pitman, Holt, and Harrell2 reported a case which they treated with X-ray therapy. They subjected their patient to 22 r per minute for four minutes the first day, and for three minutes the second, third, and fourth days—a total of 286 r. They noted a marked reduction in the swelling within 48 hours after the initial treatment, and the patient quickly recovered with no corneal complications.
Their success with this case led them to carry out, with Reid, Little, Mankin, and Morris,3 a series of experiments on the roentgen therapy of induced ocular vaccinia in rabbits. Their results were quite impressive and well warranted their conclusion that "roentgen therapy for primary or second-
* From the service of Dr. Louis Lehrfeld, The Wills Eye Hospital.
INE, JR., M.D. Pennsylvania
ary vaccinial infection of the eye hastens regression of the acute lesion and probably diminishes the residual corneal opacities."
These writers did not indicate that their idea was original, but it was found on surveying the literature that X-ray therapy has been little used in the treatment of vaccinia. No other references could be found in the American literature, and the foreign literature on the subject is also meager. In 1927, Le Fevre* reported that roentgen rays were effective in the reduction of the extent of vaccinial lesions in the skin of rabbits; and, in 1946, Maury and Frilley5 reported on the effect of roentgen rays on the vaccine virus.
Apparently, roentgen therapy has not been used to any great extent in the treatment of clinical ocular vaccinia. The literature, though scant, is optimistic, and indicates that X rays are worthy of further trial.
It was with this thought in mind that we decided to include X-ray therapy in the treatment of a case of ocular vaccinia admitted to The Wills Eye Hospital this year.
CASE REPORT
History. On October 11, 1949, G. T., a four-year-old colored girl, was admitted to The Wills Eye Hospital with the chief complaint of a painful swollen right upper eyelid of four days' duration.
The patient's mother stated that, four days before, the patient had apparently developed a stye on the right upper eyelid. This had increased in size, and on the day of admission the lid had become so swollen that it was impossible for the patient to raise it.
General physical examination revealed that the patient was apparently quite toxic. Rectal temperature was 103°C. Examination showed the nose, throat, heart, lungs, and abdomen to be normal.
Eye examination. The right upper eyelid
ROENTGEN THERAPY OF OCULAR VACCINIA 343
was swollen to several times its normal size (fig. 1). Along its lower border were noted seven circular lesions—all about 3.0 mm. in diameter. These lesions had raised edges and were definitely depressed in the center. One similar lesion was noted on the border of the lower lid. A scant seromucinous discharge was present, and a large submaxillary node was palpable on that side.
The lids were carefully separated with retractors but the cornea could not be seen. The conjunctiva was quite chemotic and completely hid the cornea from view.
Fig. 1 (Kline). Appearance of eye on admission.
Later in the day the eye was examined again, and this time the cornea was reported as being seen and appearing grossly normal. Further examination of this eye was impossible, however, because of the extensive swelling of the lids and the marked chemosis of the conjunctiva.
Examination showed the left eye to be normal in all respects.
A relatively fresh vaccination scab, about one cm. in diameter, was noted on the left upper arm. The mother stated that the child had been vaccinated on September 30th (seven days before she began to have trouble with her eye, and 11 days before her admission to the hospital).
In view of the history and physical findings, the diagnosis of vaccinia of the right eyelids, secondary to a primary inoculation of the left arm, was made.
Culture revealed Staphylococcus albus and pneumococcus.
Fig. 2 (Kline). Appearance of eye 48 hours after therapeutic regime was instigated.
Treatment. The patient was isolated and the following therapeutic regime instituted: (1) Crystacillin (300,000 units daily); (2) penicillin collyrium (2,500 units per cc.) every hour; (3) aureomycin drops (0.5-percent) four times daily; (4) boric acid flush, twice daily; (5) hot compresses, four times daily; (6) roentgen therapy—consisting of three treatments on successive days of 50 r each (total of 150 r ) .
Course. Forty-eight hours later the swelling had largely subsided. The lesions had crusted and the clear cornea was seen without difficulty (fig. 2) . The child's temperature fell almost to normal by nine o'clock the night of admission and remained so until her discharge three days later.
The child was seen again on October 23rd (nine days after her discharge from the hos-
Fig. 3 (Kline). Appearance of eye nine days after discharge from hospital.
344 ORAM R. KLINE, JR.
pital and 16 days after the onset of the condition). The lesions were completely healed, leaving small definite white scars (fig. 3). An absence of cilia was noted in the involved regions.
One month after the onset the child again returned for examination. At that time no trace of the previous scars could be found
Fig. 4 (Kline). Appearance of the eye one month after onset of ocular vaccinia.
(fig. 4) . The cilia were beginning to grow in the formerly affected areas. The cornea, as on admission, was clear.
COMMENT
This patient was treated successfully, but now the familiar situation arises—to which of our therapeutic agents should go the credit: penicillin, aureomycin, or X-rays.
We do believe that the course of the disease was altered by the therapy. However, these secondary inoculations, as a rule, run a much more rapid course than the primary inoculations, due to the increasing body immunity. . ,
Their usual course is 8 to 10 days, but this varies greatly, as the longer the lapse of time between the primary and secondary inoculation, the more quickly does the secondary infection run its course and heal. In this case, however the healing was so dramatic that we do feel that the clinical course was
altered by one of these three therapeutic agents.
Penicillin has been used in these cases before. It is of great value in combating secondary infection but has little effect against the virus. It has been found experimentally that penicillin, when injected into rabbits within 24 hours after inoculation with a rabbit-passed vaccinia virus, will prevent the typical lesion from developing. However, if it is injected later than this the course of the disease is unaltered.6
One case of eczema vaccinatum treated successfully with oral aureomycin has been recently reported in the literature.7 Perhaps aureomycin will become a valuable aid in the treatment of ocular vaccinia. However, we only used three drops in the conjunctival sac of the right eye, four times daily. This might have been of some aid in preventing corneal complications but we do not feel that it could have caused the dramatic improvement in the lid lesions—with which it did not even come in contact.
X rays were our only other therapeutic agent and it is to them we think credit is due. Our result was very similar to the case reported by Pitman, Holt, and Harrell. We, however, gave a total of only 150 r in contrast to their total of 256 r.
The exact method by which X rays work in this condition is not known. Possibly, as Pitman, Holt, and Harrell suggested, it acts by diminishing the rate of spread of the virus through the tissue. It is known that it does not act by killing the virus. It has been shown experimentally in vitro that roentgen irradiation will reduce the infectivity of vac-cinial lymph, but the dosage required is extremely high and would not be tolerated by the eye.8
SUMMARY AND CONCLUSIONS
1. A case of ocular vaccinia has been discussed.
2. An attempt to evaluate the efficacy of
TOPICAL CORTISONE IN EYE DISEASE 345
roentgen therapy as a therapeutic agent in this condition has been made.
3. The experimental and clinical work on the treatment of vaccinia with X-ray therapy, though meager, is worthy of note.
In a previous paper1 it has been pointed out that the therapeutic benefits derived from fever therapy, which is so commonly used in the treatment of ocular disease, probably result from stimulation of the pituitary-adrenal system. The basic mechanism appears to be the liberation of pituitary adrenocorticotropic hormone (ACTH) with resultant stimulation of the adrenal cortex. On this premise, ACTH has been used in the treatment of a variety of ocular diseases, and excellent results have been obtained, especially in acute inflammatory lesions.
In the reports of several investigators2-5
it was postulated that the 11-oxycortico-steroid group was of basic importance in the response to injury and disease. It seemed possible, then, that the benefits from ACTH
* From the Divisions of Ophthalmology and Metabolism, Henry Ford Hospital.
4. Roentgen therapy should be included more often as an agent in the treatment of ocular vaccinia so that its worth might be better evaluated.
16th and Spring Garden Streets.
in the treatment of ocular inflammatory disease was achieved primarily through liberation of the 11-oxycorticosteroids. To test this hypothesis, one of these steroids, 11-dehydro-17-hydroxycorticosterone (cortisone t), was used in a series similar to the one treated with ACTH. As previously reported,6 the results in the two series were comparable.
It seemed theoretically possible that cortisone might have physiologic activity when applied directly to ocular tissues and might even penetrate the cornea in quantities sufficient to alter inflammations of the anterior
t The ll-dehydro-17-hydroxycorticosterone in the acetate form (Cortone Acetate of Merck) was made available through the courtesy of Dr. J. M. Carlisle, Medical Director, Merck Laboratories, Rahway, N.J. This preparation is a crystallin suspension of cortisone acetate, 25 mg. per cc. in normal saline, with suspending agents and 1.5-percent benzyl alcohol as a preservative.
REFERENCES • 1. Atkinson, W. S., and Scullard, G.: Vaccinia with ocular involvement. Arch. Ophth., 23:584 (Mar.)
1940. 2. Pitman, H. W., Holt, L. B., and Harrell, G. T.: Effect of irradiation, immunity, and other factors
on vaccinial infection. Arch. Int. Med., 80:61-67 (July) 1947. 3. Harrell, G. T., Reid, C. H., Little, J. M., Mankin, J. W., Pitman, H. W., Holt, L. B., and Morris,
L. M.: Effect of roentgen therapy on experimental ocular vaccinia in nonimmune and partially immune rabbits. Arch. Ophth., 39:313-324 (Mar.) 1948.
4. M. Le Fevre de A.: Inhibitory action of X-ray on experimental vaccination in rabbits. Compt. rend. Soc. de biol., 96:208 (Jan.) 1927.
5. P. Bonet-Maury and Frilley, M.: Effect of roentgen rays on vaccine virus. Ann. Inst. Pasteur., 72:432-437 (May-June) 1946.
6. Gohar, M. A., and Bashatli, A.: Effect of penicillin on vaccinia virus. J. Trop. Med., 49:115-116 (Dec.) 1946.
7. Perry, F. G., and Martineau, P. C.: Eczema vaccinatum—rapid recovery following treatment with aureomycin, J.A.M.A., 141:657-658 (Nov.) 1949.
8. Gowen, J. W., and Lucas, A. M.: Reaction of variola vaccine virus to roentgen rays. Science, 90:621 (Dec.) 1939.
TOPICAL. CORTISONE IN T H E TREATMENT OF ANTERIOR-SEGMENT EYE DISEASE*
E. H. STEFFENSEN, M.D., A. J. WISHBOW, M.D., F. O. NAGLE, M.D., R. W. SMITH, M.D., AND E. L. WHITNEY, M.D.
Detroit, Michigan