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Cures for Retinitis Pigmentosa
AMERICAN JOURNAL OF OPHrrHALMOLOGY Published Monthly by the Ophthalmic Publishing Company EDITORIAL STAFF LAWRENCE T. POST, Editor PARK LEWIS 640 S. Kingshighway, Saint Louis 454 Franklin Building, Buffalo WILLIAM H. CRISP, Consulting Editor 530 Metropolitan Building, Denver C. S. O'BRIEN EDWARD JACKSON, Consulting Editor The State University of Iowa, College of Republic Building, Denver Medicine, Iowa City M. URIBE TRONCOSO HANS BARKAN Stanford University Hospital, San Francisco 350 West 85th Street, New York HARRY S. GRADLE 58 East Washington Street, Chicago JOHN M. WHEELER H. ROMMEL HILDRETH 635 West One Hundred Sixty-fifth Street, New York 824 Metropolitan Building, Saint Louis EMMA S. Buss, Manuscript Editor 4907 Maryland Avenue, Saint Louis
Directors: EDWARD JACKSON, President, LAWRENCE T. POST, Vice-President, DR. F. E. WOODRUFF, Secretary and Treasurer, WILLIAM L. BENEDICT, WILLIAM H. CRISP, CHARLES P. SMALL. Address original papers, other scientific communications including correspondence, also books for review and reports of society proceedings to Dr. Lawrence T. Post, 640 S. Kingsltighway,
Saint Louis.
Exchange copies of medical journals should be sent to Dr. William H. Crisp, 530 Metropolitan Building, Denver. Subscriptions, applications for single copies, notices of change of address, and communications with reference to advertising should be addressed to the Manager of Subscriptions and Advertising, 640 S. Kingshighway, Saint Louis. Copy of advertisements must be sent to the manager by
the fifteenth of the month preceding its appearance. Author's proofs should be corrected and returned within forty-eight hours to the manuscript editor. Twenty-five reprints of each article will be supplied to the author without charge. Additional reprints may be obtained from the printer, the George Banta Publishing Company, 450-458 Ahnaip Street, Menasha, Wisconsin, if ordered at the time proofs are returned. But reprints to contain colored plates must be ordered when the article is accepted.
CURES FOR RETINITIS PIGMENTOSA What is the status of cervical sympathectomy as a treatment for retinitis pigmentosa? Whenever, in the course of one or two generations, a great number of remedies have been proposed, tried, and abandoned one after the other as cures for a disease which has therefore come to be regarded as incurable, there is ample justification for skepticism as to the chances of success of any new therapeutic proposal. Above all is such skepticism justified with regard to a disorder which has been included in the group of defects to which Treacher Collins and others have applied the name "abiotrophy"; that is, defects whose development was predetermined
by some failure in the hereditary genes. Karsch has recently prepared a critical review of attempts at therapeutic control of retinitis pigmentosa, as disclosed in the literature of ophthalmology between 1877 and 1935 (Zeitschrift fur Augenheilkunde, 1936, volume 90, page 157). It is of interest to note that preparation of the review was apparently stimulated to some extent by the German Nationalist law providing for sterilization, in order to prevent transmission of hereditary diseases to future generations. The long list of remedies which have been resorted to for this purpose is classified by Karsch under the headings of (1) general treatment, vascular measures; (2) special applications to the eye; (3) surgical treatment; (4) radiotherapy; 311
312
EDITORIALS
(5) hormone and vitamin treatments. Since narrowing of the retinal blood vessels is a striking feature of the disease, vasodilators have been widely employed. Thus, Mellinger reported improvement from sweating. Especially before the Wassermann era antisyphilitic measures were credited with successful results. Strychnine, amyl nitrite, subconjunctival injections of sodium chloride, and retrobulbar injections of atropine may all be reckoned in the class of treatments aimed at improvement in retinal circulation. Mayou and Wheeler are mentioned among those who used the Elliot trephine operation for the same purpose. Sgrosso's claims of material improvement of visual acuity after Roentgen radiation have been supported by a number of Japanese writers, especially Suganuma, who thought he obtained improvement in eight out of fifteen cases which were systematically subjected to this treatment. In view of the unquestionable influence of vitamins upon other conditions in which the dark adaptation of the retina is affected, it is by no means surprising that vitamin treatment should have been suggested for retinitis pigmentosa. In a series of cases Doyne administered raw retina of oxen and sheep. Clegg tried a glycerin emulsion of sheep retina, without result. Seggel combined injections of strychnine with the use of cod-liver oil and liver. Starting from the observation that retinitis pigmentosa is more frequent in men than in women, whereas the published genealogies of retinitis pigmentosa do not suggest that the disease is sexlinked, Wibaut believes that the female organism is particularly rich in hormones which have a favorable influence upon the degenerative process. He, and others with him, have therefore employed a hormonic preparation (menformon). But this line of treatment has led to very few
claims of success. The assumption that retrmtrs pigmentosa depends upon degeneration of the retinal vessels induced Royle to propose resection of the sympathetic nerve trunk, in order to produce permanent dilatation of the vessels. 'In five cases, in which he divided the sympathetic above the second thoracic ganglion, he reported improvement of visual acuity and of the visual field. In the six years which have elapsed since Royle's preliminary report in the Medical Journal of Australia, this treatment has been extensively tried in various countries. There has been some argument as to which part of the sympathetic trunk is best adapted to the purpose. Campbell and Meighen removed the superior cervical ganglion. Magitot stripped the carotid artery of its periarterial plexus. Others have done a cervicodorsal sympathectomy. Takats and Gifford (Archives of Ophthalmology, 1935, volume 14, page 441) take exception to Royle's method on the grounds that mere section of the sympathetic trunk is rapidly followed by regeneration, that it denervates the upper extremity, and that the preganglionic fibers to the eye may escape division unless the stellate ganglion is removed. In their eleven operations on six patients, they used cervicodorsal sympathectomy four times and superior cervical sympathectomy seven times. These authors point out that there has been a good deal of discussion as to the permanency of vasodilatation following sympathectomy; and that vascular tonus is regained within a few weeks, although the possibility of a permanently increased supply of blood to the part cannot be ruled out. They evidently feel considerable doubt as to the success of this line of treatment. Several authors feel that there is little prospect of success from sympathectomy
EDITORIALS
in the late stages of retinitis pigmentosa. In the early stages of the disease, on the other hand, its development is usualy very slow, and yet the visual condition fluctuates appreciably from time to time. Young patients who still possess fairly good vision, and who are honestly advised as to the extreme uncertainty of beneficial results and also as to the unpleasant disturbances which commonly follow sympathectomy, are hardly likely to show enthusiasm for the experiment. Conscientious surgeons, too, may properly feel a good deal of reluctance to expose patients to these inconveniences in the earlier stages. It seems at least possible that some of the favorable results reported have depended partly upon an excess of credulity in the patient or even in the surgeon, and partly upon natural fluctuations in the patient's condition. It is a suggestive fact that after unilateral sympathectomy improvement has been reported as to both eyes. One patient showed no increase in visual field or acuity, but "believed" her night blindness had improved. Walsh and Sloan (Archives of Ophthalmology, 1935, volume 14, page 699) conclude that the merit of the operation is not yet proved, although they would not discard the procedure until further cases have been thoroughly studied. Karsch's review satisfies him that, in view of the unpleasant disturbances produced, the method has not been sufficiently successful to encourage its continuance or further development. As a general principle, it would be unscientific to argue that failure of previous experiments condemned trial of new measures. To what extent the hazards associated with further experimentation are justifiable is a problem for the surgical conscience. In the presence of substantial risks, it may be questioned whether operations should be urged for the mere purpose of adding to the sur-
313
geon's statistical material, especially when the evidence previously accumulated affords no significant prospect of success. W. H. Crisp.
GRADUATE STUDY The need for a physician to continue to study so long as he continues in practice, is being more widely recognized every year. The Research Study Club of Los Angeles met for its Sixth Annual Mid-Winter Course on Ophthalmology and Otolaryngology, January 18th to 29th; and the American Board of Ophthalmology held an examination in the Los Angeles County Hospital, on Saturday, January 23d. The registration for the Course was over two hundred, and about thirty took the examination for the Certificate of the Board. This year the foreign guest-teacher was Felix R. Nager, Professor of Otolaryngology in the Medical School of the University of Zurich, Switzerland. He proved to be a good teacher, with a broad view of his subject, of general pathology, and of the public responsibility of a medical man, whatever branch of medicine he may practice. In ophthalmology the principal course was given by Dr. Meyer Wiener, of St. Louis. He gave about twenty lectures on "The surgery of the eye." Beginning with the preparation of the patient, he discussed the details of operations, from those for cataract to those on the lids and lacrimal passages. He amply sustained his reputation as a skillful teacher. These courses were well iIIustrated, largely by lantern slides and drawings on an illuminated background. There were also valuable lectures by Dr. Frederick C. Cordes, Professor of Ophthalmology in the Medical School of the University of California, San Francisco, on the "Histopathology of the eye"
Directors: EDWARD JACKSON, President, LAWRENCE T. POST, Vice-President, DR. F. E. WOODRUFF, Secretary and Treasurer, WILLIAM L. BENEDICT, WILLIAM H. CRISP, CHARLES P. SMALL. Address original papers, other scientific communications including correspondence, also books for review and reports of society proceedings to Dr. Lawrence T. Post, 640 S. Kingsltighway,
Saint Louis.
Exchange copies of medical journals should be sent to Dr. William H. Crisp, 530 Metropolitan Building, Denver. Subscriptions, applications for single copies, notices of change of address, and communications with reference to advertising should be addressed to the Manager of Subscriptions and Advertising, 640 S. Kingshighway, Saint Louis. Copy of advertisements must be sent to the manager by
the fifteenth of the month preceding its appearance. Author's proofs should be corrected and returned within forty-eight hours to the manuscript editor. Twenty-five reprints of each article will be supplied to the author without charge. Additional reprints may be obtained from the printer, the George Banta Publishing Company, 450-458 Ahnaip Street, Menasha, Wisconsin, if ordered at the time proofs are returned. But reprints to contain colored plates must be ordered when the article is accepted.
CURES FOR RETINITIS PIGMENTOSA What is the status of cervical sympathectomy as a treatment for retinitis pigmentosa? Whenever, in the course of one or two generations, a great number of remedies have been proposed, tried, and abandoned one after the other as cures for a disease which has therefore come to be regarded as incurable, there is ample justification for skepticism as to the chances of success of any new therapeutic proposal. Above all is such skepticism justified with regard to a disorder which has been included in the group of defects to which Treacher Collins and others have applied the name "abiotrophy"; that is, defects whose development was predetermined
by some failure in the hereditary genes. Karsch has recently prepared a critical review of attempts at therapeutic control of retinitis pigmentosa, as disclosed in the literature of ophthalmology between 1877 and 1935 (Zeitschrift fur Augenheilkunde, 1936, volume 90, page 157). It is of interest to note that preparation of the review was apparently stimulated to some extent by the German Nationalist law providing for sterilization, in order to prevent transmission of hereditary diseases to future generations. The long list of remedies which have been resorted to for this purpose is classified by Karsch under the headings of (1) general treatment, vascular measures; (2) special applications to the eye; (3) surgical treatment; (4) radiotherapy; 311
312
EDITORIALS
(5) hormone and vitamin treatments. Since narrowing of the retinal blood vessels is a striking feature of the disease, vasodilators have been widely employed. Thus, Mellinger reported improvement from sweating. Especially before the Wassermann era antisyphilitic measures were credited with successful results. Strychnine, amyl nitrite, subconjunctival injections of sodium chloride, and retrobulbar injections of atropine may all be reckoned in the class of treatments aimed at improvement in retinal circulation. Mayou and Wheeler are mentioned among those who used the Elliot trephine operation for the same purpose. Sgrosso's claims of material improvement of visual acuity after Roentgen radiation have been supported by a number of Japanese writers, especially Suganuma, who thought he obtained improvement in eight out of fifteen cases which were systematically subjected to this treatment. In view of the unquestionable influence of vitamins upon other conditions in which the dark adaptation of the retina is affected, it is by no means surprising that vitamin treatment should have been suggested for retinitis pigmentosa. In a series of cases Doyne administered raw retina of oxen and sheep. Clegg tried a glycerin emulsion of sheep retina, without result. Seggel combined injections of strychnine with the use of cod-liver oil and liver. Starting from the observation that retinitis pigmentosa is more frequent in men than in women, whereas the published genealogies of retinitis pigmentosa do not suggest that the disease is sexlinked, Wibaut believes that the female organism is particularly rich in hormones which have a favorable influence upon the degenerative process. He, and others with him, have therefore employed a hormonic preparation (menformon). But this line of treatment has led to very few
claims of success. The assumption that retrmtrs pigmentosa depends upon degeneration of the retinal vessels induced Royle to propose resection of the sympathetic nerve trunk, in order to produce permanent dilatation of the vessels. 'In five cases, in which he divided the sympathetic above the second thoracic ganglion, he reported improvement of visual acuity and of the visual field. In the six years which have elapsed since Royle's preliminary report in the Medical Journal of Australia, this treatment has been extensively tried in various countries. There has been some argument as to which part of the sympathetic trunk is best adapted to the purpose. Campbell and Meighen removed the superior cervical ganglion. Magitot stripped the carotid artery of its periarterial plexus. Others have done a cervicodorsal sympathectomy. Takats and Gifford (Archives of Ophthalmology, 1935, volume 14, page 441) take exception to Royle's method on the grounds that mere section of the sympathetic trunk is rapidly followed by regeneration, that it denervates the upper extremity, and that the preganglionic fibers to the eye may escape division unless the stellate ganglion is removed. In their eleven operations on six patients, they used cervicodorsal sympathectomy four times and superior cervical sympathectomy seven times. These authors point out that there has been a good deal of discussion as to the permanency of vasodilatation following sympathectomy; and that vascular tonus is regained within a few weeks, although the possibility of a permanently increased supply of blood to the part cannot be ruled out. They evidently feel considerable doubt as to the success of this line of treatment. Several authors feel that there is little prospect of success from sympathectomy
EDITORIALS
in the late stages of retinitis pigmentosa. In the early stages of the disease, on the other hand, its development is usualy very slow, and yet the visual condition fluctuates appreciably from time to time. Young patients who still possess fairly good vision, and who are honestly advised as to the extreme uncertainty of beneficial results and also as to the unpleasant disturbances which commonly follow sympathectomy, are hardly likely to show enthusiasm for the experiment. Conscientious surgeons, too, may properly feel a good deal of reluctance to expose patients to these inconveniences in the earlier stages. It seems at least possible that some of the favorable results reported have depended partly upon an excess of credulity in the patient or even in the surgeon, and partly upon natural fluctuations in the patient's condition. It is a suggestive fact that after unilateral sympathectomy improvement has been reported as to both eyes. One patient showed no increase in visual field or acuity, but "believed" her night blindness had improved. Walsh and Sloan (Archives of Ophthalmology, 1935, volume 14, page 699) conclude that the merit of the operation is not yet proved, although they would not discard the procedure until further cases have been thoroughly studied. Karsch's review satisfies him that, in view of the unpleasant disturbances produced, the method has not been sufficiently successful to encourage its continuance or further development. As a general principle, it would be unscientific to argue that failure of previous experiments condemned trial of new measures. To what extent the hazards associated with further experimentation are justifiable is a problem for the surgical conscience. In the presence of substantial risks, it may be questioned whether operations should be urged for the mere purpose of adding to the sur-
313
geon's statistical material, especially when the evidence previously accumulated affords no significant prospect of success. W. H. Crisp.
GRADUATE STUDY The need for a physician to continue to study so long as he continues in practice, is being more widely recognized every year. The Research Study Club of Los Angeles met for its Sixth Annual Mid-Winter Course on Ophthalmology and Otolaryngology, January 18th to 29th; and the American Board of Ophthalmology held an examination in the Los Angeles County Hospital, on Saturday, January 23d. The registration for the Course was over two hundred, and about thirty took the examination for the Certificate of the Board. This year the foreign guest-teacher was Felix R. Nager, Professor of Otolaryngology in the Medical School of the University of Zurich, Switzerland. He proved to be a good teacher, with a broad view of his subject, of general pathology, and of the public responsibility of a medical man, whatever branch of medicine he may practice. In ophthalmology the principal course was given by Dr. Meyer Wiener, of St. Louis. He gave about twenty lectures on "The surgery of the eye." Beginning with the preparation of the patient, he discussed the details of operations, from those for cataract to those on the lids and lacrimal passages. He amply sustained his reputation as a skillful teacher. These courses were well iIIustrated, largely by lantern slides and drawings on an illuminated background. There were also valuable lectures by Dr. Frederick C. Cordes, Professor of Ophthalmology in the Medical School of the University of California, San Francisco, on the "Histopathology of the eye"