Carbonic Anhydrase and the Maintenance of Intraocular JensionGREEN, HARRY;BOCHER, CAROL A.;CALNAN, ARTHUR F.;LEOPOLD, IRVING H.;Rosenberg, Allen P.
1955 A M A Archives of Ophthalmology
doi: 10.1001/archopht.1955.00930010465001pmid: 14360875
Abstract It had previously been reported1 that the intravenous administration of acetazoleamide (Diamox; 2-acetylamino-1,3,4-thiadiazole-5sulfonamide) inhibited * the carbonic anhydrase activity of the ciliary body-iris tissue within 30 minutes. This observation, together with a knowledge of the fundamental role of the enzyme in other tissues and cells, suggested the possibility that carbonic anhydrase may be the controlling mediator in the secretion of bicarbonate ions into the aqueous humor. In such a system the inhibition of the carbonic anhydrase activity in the anterior uvea should be reflected in a lowering of the bicarbonate ion concentration in the aqueous humor. Furthermore, according to Kinsey's postulate,2 namely, that the bicarbonate ion plays a pivotal role in the formation of aqueous humor, there should also occur a drop in the intraocular pressure of the rabbit eye. In order to test the possibility that the carbonic anhydrase activity of the ciliary body controlled the secretion of References 1. The inhibition was complete, instead of 93%, as previously reported. 2. Supplied by Dr. James D. Gallagher, Lederle Laboratories Division, American Cyanamid Company, Pearl River, N. Y. 3. Dirnate, supplied by Dr. Gilbert Bayne, Sharp & Dohme Laboratories, West Point, Pa. 4. Technique recommended by Dr. E. J. Ballintine. 5. Measurements made by Dr. Enrique Wudka. The animals in the latter experiments were anesthetized with intravenous pentobarbital (Nembutal). 6. Askovitz.5 Dr. Askovitz assisted in the statistical evaluation of the data. 7. Lederle investigators,6 working with the enzyme obtained from beef erythrocytes, reported a value of 7.8X10-7 M as the minimum concentration of acetazoleamide for complete inhibition. 8. Measurable amounts of the drug were found in the aqueous humor.7 9. Experiments similar to the ones reported herein were performed with rabbits obtained from the Haskins Rabbitry in St. Louis, the same rabbitry which supplied the "responsive" animals used by Becker.10 In our hands these animals showed no appreciable lowering of the intraocular tension after systemic administration of acetazoleamide (Tables 8 and 9). The same animals after bilateral nephrectomy, when given the drug intravenously 18 to 20 hours later, showed a significant fall in the intraocular tension (Table 10), in agreement with Becker. Similar experiments with our usual rabbits showed no lowering in intraocular tension (Tables 11 and 12). In all cases the carbonic anhydrase activity of the anterior uvea was inhibited. It is significant, moreover, to note that we have experimentally found that after intravenous administration the concentration of acetazoleamide in the blood plasma of the nephrectomized rabbit was considerably in excess of that required to inhibit completely the carbonic anhydrase activity in the erythrocytes. Under these conditions interference with the respiratory mechanism of gas exchange may very well account for the local ocular effects observed by Becker with nephrectomized rabbits. 10. Ballintine, E. J.: Personal communication to the authors. 11. Harris, J. L., in discussion on Becker.10 12. Green, H.; Capper. S. A.; Bocher, C. A., and Leopold, I. H.: Effect of Acetazoleamide (Diamox) on Carbonic Anhydrase Activity of Anterior Uvea of the Rabbit Eye , A. M. A. Arch. Ophth. 52:758, 1954.Crossref 13. Kinsey, V. E.: Unified Concept of Aqueous Humor Dynamics and the Maintenance of Intraocular Pressure: An Elaboration of the Secretion-Diffusion Theory , A. M. A. Arch. Ophth. 44:215, 1950.Crossref 14. Lindsay, A. E., and Brown, H.: Clinical Experience with p-Sulfonamido-Benzoic Acid, a Carbonic Anhydrase Inhibitor, as a Diuretic Agent , J. Lab. & Clin. Med. 43:839, 1954. 15. Green, H.; Bocher, C. A., and Leopold, I. H.; Carbonic Anhydrase and Elaboration of Bicarbonate Ion in Aqueous Humor of the Rabbit Eye , A. M. A. Arch. Ophth. , this issue, p. 472. 16. Askovitz, S. I.: Mean Rates of Change and Least Squares—Interpretations and Rapid Graphic Methods, paper in preparation. 17. Miller, W. H.; Dessert, A. M., and Roblin, R. O.: Heterocyclic Sulfonamides as Carbonic Anhydrase Inhibitors , J. Am. Chem. Soc. 72:4893, 1950. 18. Green, H.; Sawyer, J. L., and Leopold, I. H.: Determination of Acetazoleamide (Diamox) in Aqueous Humor of Rabbit Eye , A. M. A. Arch. Ophth. , this issue, p. 478. 19. Friedenwald, J. S.; Herrmann, H., and Moses, R.: Distribution of Certain Oxidative Enzymes in the Ciliary Body , Bull. Johns Hopkins Hosp. 73:421, 1943. 20. Grant, W. M., and Trotter, R. R.: Diamox (Acetazoleamide) in Treatment of Glaucoma , A.M. A. Arch. Ophth. 51:735, 1954. 21. Becker, B.: Mechanism of the Fall in Intraocular Pressure Induced by the Carbonic Anhydrase Inhibitor, Diamox, Am. J. Ophth., to be published.
Carbonic Anhydrase and the Elaboration of Bicarbonate Ion in the Rabbit EyeGREEN, HARRY;BOCHER, CAROL A.;LEOPOLD, IRVING H.;Sawyer, John L.;Rosenberg, Allen P.;Waters, Leila P.
1955 A.M.A. Archives of Ophthalmology
doi: 10.1001/archopht.1955.00930010474002pmid: 14360876
Abstract In the preceding paper2 evidence was presented that the maintenance of intraocular tension of a normal rabbit eye was not dependent upon the carbonic anhydrase activity of the anterior uvea. The present study was undertaken to determine whether the inhibition of carbonic anhydrase activity of the anterior uvea by the intravenous and subconjunctival administration of acetazoleamide ( Diamox; 2-acetylamino-1,3,4-thiadiazole-5sulfonamide) affected the concentration of bicarbonate ions in the aqueous humor. Our results show that the elaboration and active transfer of bicarbonate ions into the aqueous humor are not mediated by the carbonic anhydrase of the anterior uvea of the normal rabbit eye. EXPERIMENTAL STUDY The recent observations of Kinsey3 that the concentration of bicarbonate ions in the posterior chamber of the rabbit eye is not only greater than that in the plasma but also greater than that in the anterior chamber were offered in support of Friedenwald's postulate4 that References 1. Nomenclature suggested by Kinsey.3 2. Acetazoleamide was supplied by Dr. James D. Gallagher, Lederle Laboratories Division, American Cyanamid Company, Pearl River, N. Y. 3. Green, H., in discussion on Becker.1 4. Time, 30 minues; values expressed as millimoles per liter. 5. Time, 60 minutes; values expressed as millimoles per liter. 6. Doses up to 10 mg./kg. of body weight are generally used clinically. 7. This may be the reason why the subconjunctival administration of acetazoleamide is not clinically effective in reducing the intraocular pressure of glaucomatous eyes. 8. The accumulated determinations of bicarbonate ion concentration (mM/liter) in blood plasma and anterior aqueous humor of 95 animals gave the following data: blood: 19.4, S.D. 5.3; aqueous humor: 30.1, S.D. 3.6; ratio: 1.55, S.D. 0.37. 9. Becker, B.: Mechanism of the Fall in Intraocular Pressure Induced by the Carbonic Anhydrase Inhibitor, Diamox. Am. J. Ophth., to be published. 10. Green, H.; Bocher, C. A.; Calnan, A. F., and Leopold, I. H.: Carbonic Anhydrase and the Maintenance of Intraocular Tension in the Rabbit Eye , A. M. A. Arch. Ophth. , this issue, p. 463. 11. Kinsey, V. E.: Comparative Chemistry of Aqueous Humor in Posterior and Anterior Chambers of Rabbit Eye: Its Physiologic Significance , A.M. A. Arch. Ophth. 50:401, 1953.Crossref 12. Friedenwald, J. S.: Formation of the Intraocular Fluid , Am. J. Ophth. 32:9 (June, (Pt. II) ) 1949.
Determination of Acetazoleamide in Aqueous Humor of the Rabbit EyeGREEN, HARRY;SAWYER, JOHN L.;LEOPOLD, IRVING H.;Bocher, Carol A.;Rosenberg, Allen P.
1955 A.M.A. Archives of Ophthalmology
doi: 10.1001/archopht.1955.00930010480003pmid: 14360877
Abstract In two previous papers * it had been shown that the intravenous and subconjunctival injection of aceatzoleamide (Diamox) completely inhibited the carbonic anhydrase activity of the anterior uvea of the rabbit eye, without appreciably lowering either the normal intraocular tension or the concentration of bicarbonate ion in the aqueous humor. A better understanding of the mechanism of action of acetazoleamide in the management of glaucoma depends upon a knowledge of the medium through which the drug functions. It was of interest, therefore, to determine whether the drug entered the aqueous humor of the eye after local and systemic administration, and in what concentration. The only method available for the determination of acetazoleamide in biological fluids was that of Maren, Ash, and Bailey.† It is based essentially upon the changing pH method of Philpot and Philpot4 and is dependent on the rate of hydration of CO2 in the presence of References 1. References 1 and 2. 2. Prior to the initiation of this study, Dr. Maren made available to us a preprint of the paper, which at that time did not include his preliminary investigations of a spectrophotometric method. 3. Hexane extraction of the methanol solution of aqueous humor, to remove lipids, had no effect on the absorption spectrum. 4. An average optical density of 0.196/0.15 ml. of aqueous humor was obtained. 5. After this paper had been prepared for publication, we learned of the unpublished observations of Ballintine and Maren3 (cited in reference 3), who found in the aqueous humor of rabbit 0.6γ and 0.5γ per milliliter, respectively, 2 and 0.5 hours after intravenous administration of acetazoleamide (25, and 10 mg/kg., respectively). 6. Green, H.; Bocher, C. A.; Calnan, A. F., and Leopold, I. H.: Carbonic Anhydrase and the Maintenance of Intraocular Tension , A. M. A. Arch. Ophth. , this issue, p. 463. 7. Green, H.; Bocher, C. A., and Leopold, I. H.: Carbonic Anhydrase and the Elaboration of Bicarbonate Ion in the Rabbit Eye , A. M. A. Arch. Ophth. , this issue, p. 472. 8. Maren, T. H.; Ash, V. I., and Bailey, E. M., Jr.: Carbonic Anhydrase Inhibition: II. Method for Determination of Carbonic Anhydrase Inhibitors, Particularly of Diamox , Bull. Johns Hopkins Hosp. 95:244, 1954. 9. Philpot, F. J., and Philpot, J. St. L.: A Modified Colorimetric Estimation of Carbonic Anhydrase , Biochem. J. 30:2191, 1936.
New Method for Fractionation of Lens ProteinsFRANÇOIS, J.;RABAEY, M.;WIEME, R. J.
1955 A.M.A. Archives of Ophthalmology
doi: 10.1001/archopht.1955.00930010483004pmid: 14360878
Abstract In 1894 Mörner demonstrated that there exist four different holoprotein fractions in the lens. A fraction insoluble at physiological pH was called albuminoid. Three watersoluble fractions were found: two atypical globulins (a and β crystallin) and an albumin-like fraction (γ crystallin). The separation and elimination of the insoluble fraction from the crude extract is simple and made by centrifugation. The separation and fractionation of the watersoluble fractions is a much more complicated problem. Following Mörner, different authors have tried to establish a suitable fractionation device, mostly without any control (Krause, 1932; Woods and Burky, 1927; Burky and Woods, 1928; Bonot and Nordmann, 1946; Nordmann, 1949). On the other hand, the proteins by these methods of fractionation are often profoundly modified and even largely denaturated by the different manipulations. The aim of this work is to obtain well-defined and homogeneous protein fractions from the point of view of electrophoretic control. Ox References 1. Professor Sadron, Director of the Centre for the studies of macromolecular physics at Strasbourg, cooperated in this study, and MM. C. Wippler and A. J. Hyde collaborated. 2. Boehm, G.: Über die Form der Lensenalbuminoidteilchen , Klin. Monatsbl. Augenh. 92:347-349, 1934. 3. Bonot, A., and Nordmann, J.: Étude du fractionnement des protéines du cristallin , Bull. Soc. chim. biol. 28:850-852, 1946. 4. Burky, E. L., and Woods, A. C.: Lens Protein: Isolation of a Third (Gamma) Crystallin , Arch. Ophth. 57:464-466, 1928. 5. François, J.; Rabaey, M.; Wieme, R. J., and Neetens, A.: Contribution à l'étude des protéines cristalliniennes par l'électrophorèse , Bull. Soc. belge opht. 104:322-331, 1953. 6. François, J.; Rabaey, M.; Wieme, R. J., and Neetens, A.: L'électrophorèse sur papier des protéines hydrosolubles du cristallin , Experientia 10:79-83, 1954.Crossref 7. François, J.; Rabaey, M.; Wieme, R. J., and Neetens, A.: Étude des protéines cristalliniennes hydrosolubles par l'électrophorèse dans la cataracte expérimentale , Ann. ocul. 187:593-610, 1954. 8. Krause, A. C.: Chemistry of the Lens: Composition of Albuminoid and Alpha Crystallin , Arch. Ophth. 8:166-172, 1932.Crossref 9. Mörner, C. T.: Untersuchungen der Proteinsubstanz in den lichtbrechenden Medien des Auges , Ztschr. physiol. Chem. 18:61-106, 213-222, 233-256, 1894. 10. Nordmann, J.: Le durcissement du cristallin , Ophthalmologica 118:369-377, 1949.Crossref 11. Nordmann, J.: Biologie du cristallin , Paris, Masson & Cie, 1954. 12. Woods, A. C., and Burky, E. L.: Lens Protein and Its Fraction: Preparation and Immunologic and Chemical Properties , J. A. M. A. 89:102-109, 1927.Crossref 13. Zimm, B. H.: J. Chem. Physiol. 16:1093-1107, 1948.Crossref
Studies on experimental GlaucomaWUDKA, ENRIQUE;LEOPOLD, IRVING H.
1955 A.M.A. Archives of Ophthalmology
doi: 10.1001/archopht.1955.00930010489005pmid: 14360879
Abstract The aim of the present investigation is the study of experimentally induced glaucoma in the rabbit and the influence of iridectomy on its course. The normal intraocular pressure can be raised (a) by decreasing the aqueous drainage or (b) by increasing the rate of fluid production. Diminished aqueous outflow has been achieved by mechanical blockage of the filtration angle. This can be accomplished in the following ways: (a) by injecting oils and colloids that hinder the outflow of aqueous at the angle of the anterior chamber1; (b) by producing an inflammatory response at the angle, with ultimate development of synechiae1; (c) by developing a proliferative endothelial reaction at the angle by means of electrolytic products,1 and (d) by occlusion of the pupil, which also leads to mechanical blockage of the angle of the anterior chamber. Interruption of the aqueous circulation at the pupil has been produced by obstructing References 1. References 6 and 7. 2. Pentobarbital sodium, supplied as a sterile solution containing 60 mg. per milliliter. 3. Mechlorethamine hydrochloride, also known as methyl-bis(β-chloroethyl) amine hydrochloride, in vials containing 10 mg. of the drug in dry form triturated with 90 mg. of anhydrous sodium chloride. 4. References 20 and 21. 5. Heparin sodium, 1000 U. S. P. units per milliliter in istonic sodium chloride solution. 6. References 6 and 7. 7. Duke-Elder, W. S.: Text-Book of Ophthalmology , Vol. III, St. Louis, C. V. Mosby Company, 1941. 8. Scheie, H. G., and Frayer, W.: Ocular Hypertension Induced by Air in the Anterior Chamber , Arch. Ophth. 44:691, 1950.Crossref 9. Barkan, O.: Glaucoma Induced by Air Blockade: Clinical Observations and Experimental Studies , Am. J. Ophth. 34:567, 1951. 10. Wortham, E.: Experimental Pupil-Block Glaucoma , Am. J. Ophth. 35:477, 1952. 11. Friedenwald, J. S., and Pierce, H. F.: Pathogenesis of Acute Glaucoma , Arch. Ophth. 3:574, 1930.Crossref 12. Davson, H., and Huber, A.: Experimental Hypertensive Uveitis in the Rabbits , Ophthalmologica 120:118, 1950.Crossref 13. Davson, H., and Matchett, P. A.: Control of the Intraocular Pressure in the Rabbit , J. Physiol. 113:388, 1951. 14. von Sallmann, L., and Dillon, B.: Effect of Di-Isopropyl Fluorophosphate on the Capillaries of the Anterior Segment of the Eye in Rabbits , Am. J. Ophth. 30:1244, 1947. 15. Knies, M.: Über das Glaucom , von Graefes Arch. Ophth. 22:163, 1876.Crossref 16. Weber, A.: Die Ursache des Glaucoms , von Graefes Arch. Ophth. 23:1, 1877.Crossref 17. Smith, Priestley: On the Pathology and Treatment of Glaucoma , London, J. & A. Churchill, 1891. 18. Raeder, J. G.: Untersuchungen über die Lage und Dicke der Linse im menschlichen Auge bei physiologischen und pathologischen Zuständen, nach einer Methode gemessen: II. Die Lage der Linse bei glaukomatösen Zuständen , von Graefes Arch. Ophth. 112:29, 1923.Crossref 19. Barkan, O.: Glaucoma: Classification, Causes, and Surgical Control , Am. J. Ophth. 21:1099, 1938. 20. Sugar, H. S.: The Glaucomas , St. Louis, C. V. Mosby Company, 1951. 21. Chandler, P. A.: Narrow-Angle Glaucoma , A. M. A. Arch. Ophth. 47:695, 1952.Crossref 22. Uribe Troncoso, M., and Castroviejo, R.: Microanatomy of the Eye with the Slit Lamp Microscope: I. Comparative Anatomy of the Angle of the Anterior Chamber in Living and Sectioned Eyes of Mammalia , Am. J. Ophth. 19:371, 1936. 23. Hughes, W. L., and Cole, J. G.: Technical Uses of Air in Ophthalmology , Arch. Ophth. 35: 525, 1946.Crossref 24. Friedenwald, J. S., and Pierce, H. F.: Circulation of the Aqueous , Bull. Johns Hopkins Hosp. 49:259, 1931. 25. von Graefe, A.: Über die Iridectomie bei Glaucoma und über den glaucomatösen Prozess , von Graefes Arch. Ophth. 3:456, 1857Crossref 26. Iridectomy in Glaucoma: A Study of the Glaucomatous Process , translation by Francis H. Adler, Arch. Ophth. 1:71, 1929.Crossref 27. Curran, E. J.: New Operation for Glaucoma Involving a New Principle in the Etiology and Treatment of Chronic Primary Glaucoma , Arch. Ophth. 49:131, 1920. 28. Curran, E. J.: Peripheral Iridotomy in Acute and Chronic Glaucoma: Some Results After 10 Years' Duration , Tr. Ophth. Soc. U. Kingdom 51:520, 1931. 29. Elschnig, A.: Currans Iridotomie gegen Glaukom , Klin. Monatsbl. Augenh. 70:667, 1923. 30. Haas, J. S., and Scheie, H. G.: Peripheral Iridectomy in Narrow Angle Glaucoma , Tr. Am. Acad. Ophth. 56:589, 1952. 31. von Hippel, A., and Grünhagen, A.: Über den Einfluss der Nerven auf die Höhe des intraocularen Druckes , von Graefes Arch. Ophth. 16:27, 1870.Crossref
Stereopsis and Vertical DisparityOGLE, KENNETH N.
1955 A.M.A. Archives of Ophthalmology
doi: 10.1001/archopht.1955.00930010497006pmid: 14360880
Abstract Stereoscopic perception of depth between any two objects in space can be attributed only to the stimuli of the transverse (horizontal) disparity between the images of those objects in the two eyes. Experiment has shown,* however, that for a given retinal region of the two eyes the disparities that give rise to the stereoscopic experience are limited to a definite range; for disparities outside that range there is no patent stereopsis. In the same way that we account for the experimental fact of Panum's areas of fusion, we can also explain the range of disparities for stereopsis by the extent of overlapping of particular arborizations of neurons in the terminal regions of the cortex which arise from disparate retinal elements of the two eyes. This explanation would fit the concept that stereopsis rests on a neuroanatomic and physiologic basis. We would expect these arborizations to overlap not only in a References 1. References 1 and 2. 2. The experiments of Weinhold,12 Kothe,13 and Depène,14 in which no depth effect was found for a vertical disparity introduced between the images of the center of three horizontal lines, provide poor contributing evidence, since disparities of this kind at the fixation point would not exist in ordinary surroundings. 3. Ogle, K. N.: Disparity Limits of Stereopsis , A. M. A. Arch. Ophth. 48:50-60 ( (July) ) 1952.Crossref 4. Ogle, K. N.: On the Limits of Stereoscopic Vision , J. Exper. Psychol. 44:253-259 ( (Oct.) ) 1952.Crossref 5. Loy, A. W.: A Preliminary Report upon a New Instrument for the Determination of Depth Perception , Am. J. Ophth. 18:447-450 ( (May) ) 1935. 6. Ogle, K. N.: Basis of Stereoscopic Vision , A. M. A. Arch. Ophth. 52:197-211 ( (Aug.) ) 1954.Crossref 7. Lothridge, C. D.: Stereoscopic Settings as Functions of Vertical Disparity and Target Declination , J. Gen. Psychol. 49:241-260 ( (Oct.) ) 1953.Crossref 8. Hering, E.: Spatial Sense and Movements of the Eye , translated by C. A. Radde, Baltimore, American Academy of Optometry, 1942, pp. 49-54. 9. Helmholtz, H. L.: The Perceptions of Vision , in Helmholtz's Treatise on Physiological Optics , translated from the third German edition by James P. C. Southall, Rochester, N. Y., The Optical Society of America, 1925, Vol. 3, p. 267. 10. Hillebrand, F.: Die Stabilität der Raumwerte auf der Netzhaut , Ztschr. Psychol. u. Physiol. Sinnesorg. 5:1-60, 1893. 11. Heine, L.: Über die Bedeutung der Längenwerte für des Körperlichsehen , Ber. Versamml. deutsch. ophth. Gesellsch. 31:179-199, 1903. 12. Monjé, M.: Über eine neue Methode zur Untersuchung der Tiefensehschärfe , Ztschr. Sinnesphysiol. 69:73-90, 1940. 13. Walker, R. Y.: Superiority of Binocular over Monocular Vision in Depth Perception in Respect to the Vertical or Horizontal Position of the Object , J. Aviation Med. 11:87-95 ( (June) ) 1940. 14. Weinhold, M.: Über das Sehen mit längsdisparaten Netzhautmeridianen , von Graefes Arch. Ophth. 54:201-210 ( (July) ) 1902.Crossref 15. Kothe, R.: Über Längsdisparationen und über die Überplasticität naher Gegenstände , Arch. Augenh. 49:338-350, 1903. 16. Depène, R.: Über die Abhängigkeit der Tiefenwahrnehmung von der Kopfneigung , Klin. Monatsbl. Augenh. 43:48-54, 1905. 17. Ogle, K. N.: Researches in Binocular Vision , Philadelphia, W. B. Saunders Company, 1950, pp. 173-199. 18. Ogle, K. N.: Precision and Validity of Stereoscopic Depth Perception from Double Images , J. Optic. Soc. America 43:906-913 ( (Oct.) ) 1953.Crossref 19. Brown, K. T.: Factors Affecting Differences in Apparent Size Between Opposite Halves of a Visual Meridian , J. Optic. Soc. America 43:464-472 ( (June) ) 1953.Crossref 20. Burian, H. M.: Stereopsis, Docum. ophth. 5-6:169-183, 1951.Crossref 21. Roelofs, C. O.: Die optische Lokalisation , Arch. Augenh. 109:395-415, 1936.
Treatment of Retinoblastoma by Radiation and TriethylenemelamineREESE, ALGERNON B.;HYMAN, GEORGE A.;MERRIAM, GEORGE R.;FORREST, ARNOLD W.;KLIGERMAN, MORTON M.
1955 A.M.A. Archives of Ophthalmology
doi: 10.1001/archopht.1955.00930010507007pmid: 14360881
Abstract We have been treating retinoblastoma by radiation according to a method described by us first in 1936.1 The technique, which was devised by Dr. Hayes E. Martin, Memorial Center for Cancer and Allied Diseases, includes the employment of special cones at a temporal and a nasal portal in an effort to deliver an adequate dose to the posterior sector of the eye, to the exclusion of the vulnerable anterior sector. Subsequent reports on the use of this technique were made in 1942,2 1945,3 and 1949.4 The treatment is employed for patients with bilateral tumors whose eye with the more advanced disease has been enucleated. The less involved eye has been treated when it was thought that useful vision might be salvaged if the tumor could be arrested. Since the institution of the treatment in 1936,1 a total of 148 patients have been treated. Forty-three patients References 1. Gillette, R., and Bodenstein, D.: J. Exper. Zool. 103:1-32, 1946Crossref 2. This report was made as of Sept. 15, 1954. During the six additional months of follow-up (as of March 15, 1955) with regular examinations under chloroform anesthesia, there has been no growth of the tumor in any of the 22 eyes. 3. In these eyes the tumor was not controlled, and enucleation has either been done or advised. A feature in common to these eyes was tumor seeds floating in the vitreous. This seems to occur only when the tumors are large and extensive. It seems probable that the effect of the TEM does not reach these seeds in the avascular and inert vitreous. 4. References 1 through 4. 5. References 9 and 10. 6. Martin, H. E., and Reese, A. B.: Treatment of Retinal Gliomas by the Fractionated or Divided Dose Principle of Roentgen Radiation: Preliminary Report , Arch. Ophth. 16:733 ( (Nov.) ) 1936.Crossref 7. Martin, H. E., and Reese, A. B.: Treatment of Retinoblastoma (Retinal Glioma) by a Combination of Surgery and Radiation , Arch. Ophth. 27: 40 ( (Jan.) ) 1942.Crossref 8. Martin, H. E., and Reese, A. B.: Treatment of Bilateral Retinoblastoma (Retinal Glioma) by Surgery and Irradiation , Arch. Ophth. 33:429 ( (June) ) 1945.Crossref 9. Reese, A. B.; Merriam, G. R., and Martin, H. E.: Treatment of Bilateral Retinoblastoma by Irradiation and Surgery: Report on 15-Year Results , Am. J. Ophth. 32:175 ( (Feb.) ) 1949. 10. Kupfer, C.: Retinoblastoma Treated with Intravenous Nitrogen Mustard , Am. J. Ophth. 36: 1721, 1953. 11. Gillette, R., and Bodenstein, D.: Specific Developmental Inhibitions Produced in Amphibian Embryos by a Nitrogen Mustard Compound , J. Exper. Zool. 103:1, 1946.Crossref 12. Gilman, A., and Philips, F. S.: Biological Actions and Therapeutic Applications of β-Chloroethyl Amines and Sulfides , Science 103:409, 1946.Crossref 13. Gellhorn, A.; Kligerman, M. M., and Jaffe, I.: Triethylene Melamine in Clinical Cancer Chemotherapy , Am. J. Med. 13:428 ( (Oct.) ) 1952.Crossref 14. Rhoads, C. P.; Karnofsky, D. A.; Burchenal, J. H., and Craver, L. F.: Triethylene Melamine in the Treatment of Hodgkin's Disease and Allied Neoplasms , Tr. A. Am. Physicians 63:136, 1950. 15. Karnofsky, D. A.; Burchenal, J. H.; Armistead, C. G., Jr.; Southam, C. M.; Bernstein, J. L.; Carver, L. F., and Rhoads, C. P.: Triethylene Melamine in Treatment of Neoplastic Disease: Compound with Nitrogen-Mustard-Like Activity Suitable for Oral and Intravenous Use , Arch. Int. Med. 87:477, 1951.Crossref 16. Klopp, C. T.; Alford, T. C.; Bateman, J.; Berry, G. N., and Winship, I.: Fractionated IntraArterial Cancer: Chemotherapy with Methyl bis Amine Hydrochloride; A Preliminary Report , Ann. Surg. 132:811, 1950.Crossref 17. Sullivan, R. D.; Jones, R., Jr.; Schnabel, T. G., Jr., and Shorey, J. McC.: Treatment of Human Cancer with Intra-Arterial Nitrogen Mustard (Methylbis[2-Chloroethyl]Amine Hydrochloride) Utilizing a Simplified Catheter Technique , Cancer 6:121, 1953.Crossref
Effect of Oxygen Weaning in Retrolental FibroplasiaBEDROSSIAN, ROBERT H.;CARMICHAEL, PAUL;RITTER, JOSEPH A.
1955 A.M.A. Archives of Ophthalmology
doi: 10.1001/archopht.1955.00930010520008pmid: 14360882
Abstract The conflicting views on the role of oxygen in the pathogenesis of retrolental fibroplasia have created much confusion. Two studies made at the Philadelphia General Hospital have already been reported.* One study was based on the uncontrolled use of oxygen. The second study utilized controlled oxygen environments for premature infants with birth weights below 1.8 kg. (4 lb.). Both studies showed that the incidence and severity of retrolental fibroplasia are significantly increased by the use of greater oxygen supplements and the rapid reduction in the oxygen concentration of the infant's environment. Additional data were presented to support the hypothesis that the major precipitating factor in the disease was the improper withdrawal of supplemental oxygen. It was, however, clearly stated that the direct effects of oxygen were also of importance. The present study was designed to evaluate the effects of the following factors: Rapid and slow withdrawal of supplemental oxygen References 1. References 1 and 2. 2. References 3 and 4. 3. Bedrossian, R.: Retinopathy of Prematurity (Retrolental Fibroplasia) and Its Relationship to Oxygen , A. M. A. Arch. Ophth. 50:266 ( (Aug.) ) 1953.Crossref 4. Bedrossian, R.; Carmichael, P., and Ritter, J.: Retinopathy of Prematurity (Retrolental Fibroplasia) and Oxygen , Am. J. Ophth. 37:78 ( (Jan.) ) 1954. 5. Ashton, N.; Ward, B., and Serpell, G.: Role of Oxygen in Genesis of Retrolental Fibroplasia , Brit. J. Ophth. 37:513 ( (Sept.) ) 1953.Crossref 6. Patz, A.; Eastham, A.; Higginbottom, D. H., and Kleb, T.: Oxygen Studies in Retrolental Fibroplasia , Am. J. Ophth. 36:1511 ( (Nov.) ) 1953.
Preservation of Cornea by Dehydration: A Preliminary ReportMcNAIR, JOEL N.;KING, J. H.
1955 A.M.A. Archives of Ophthalmology
doi: 10.1001/archopht.1955.00930010525009pmid: 14360883
Abstract The operation of keratoplasty is frequently limited by the unavailability of donor corneal material. This report concerns preliminary experiments on the storage of cornea by dehydration and its successful use in lamellar transplantation in animals. Many attempts have been made to store corneal grafts over long periods, and various methods have been tried in animals, without success. Katzin (1947),1 Leopold and Adler (1947),2 and Smelser and Ozanics (1946)3 all used rapid freezing in liquid nitrogen, with and without isopentane as an intermediate heat-transfer medium. In the method described in the first two papers, the grafts, after freezing, were dried in vacuo over P2O5 at -40 C. They were reconstituted before use, in most cases, by the addition of isotonic sodium chloride solution. Smelser and Ozanics did not dry their materials but stored them at -195 C for periods of from one hour up to References 1. Katzin, H. M.: Preservation of Corneal Tissue by Freezing and Dehydration , Am. J. Ophth. 30:1128, 1947. 2. Leopold, I. H., and Adler, F. H.: Use of Frozen-Dried Cornea as Transplant Material , Arch. Ophth. 37:268, 1947.Crossref 3. Smelser, G. H., and Ozanics, V.: Effect of Quick Freezing at Various Temperatures of Donor Tissues in Corneal Transplants , Proc. Soc. Exper. Biol. & Med. 62:274-277, 1946. 4. Polge, C.; Smith, A. U., and Parkes, A. S.: Revival of Spermatozoa After Vitrification and Dehydration at Low Temperature , Nature, London 164:666, 1949. 5. Smith, A. U., and Parkes, A. S.: Preservation of Ovarian Tissue at Low Temperature , Lancet 2:570, 1951. 6. Eastcott, H. H. G.; Cross, A. G.; Leigh, A. G., and North, D. P.: Preservation of Corneal Grafts by Freezing , Lancet 1:237, 1954.
Effect of Retrolental Fibroplasia in ChildrenKRAUSE, ARLINGTON C.
1955 A.M.A. Archives of Ophthalmology
doi: 10.1001/archopht.1955.00930010528010pmid: 14360884
Abstract Retrolental fibroplasia may be a lifelong disease. The child with retrolental fibroplasia may become a useful, independent adult with a handicap of some degree of ocular damage, or, in the extreme severe form of the disease, may have a futile, passive life as a physically and mentally stunted child in a state institution for retarded children. Infantile blindness is then a minor, and the total deterioration a major, catastrophe of life. Most children range between these two extremes. The progress of these children now can be determined, as sufficient time has elapsed for an investigative study. THE STUDY An evaluation of the effects of retrolental fibroplasia on children was made so that ophthalmologists and pediatricians may know what happens to the child in later years. For this purpose all of the children with retrolental fibroplasia of the University of Chicago Clinics were followed in the clinic, home, and institution and