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Nervous Mechanisms for the Control of Intraocular Pressure*
GLAUCOMA AND MYOPIA
985
REFERENCES
Cori: Cited by Weinstein. D'Ermo, R, and Salvi, G. L.: Boll. Ocul., 34:98 (Feb.) 1955. Gala, A.: Zentrlbl. f. ges. Ophth., 25:30, 1931. Hruby, K.: Arch. f. Ophth., 143:187, 1941. Kraupa, E.: Klin. Monatsbl. f. Augenh., 87:837, 1931. Löhlein: Cited by Weinstein. Weinstein, P.: A glaukoma kor- es gyogytana. Budapest, 1943.
NERVOUS MECHANISMS FOR T H E CONTROL O F INTRAOCULAR P R E S S U R E * MILES A. GALIN,
M.D.
New York That the intraocular pressure in any given normal eye varies within well-defined bound aries is well known. However, the mechanism of this rather rigid homeostatis is not well understood. Perkins 1 has outlined the theo retic factors that might be applicable. These include capillary pressure, rate of aqueous secretion, nature (osmolality) of aqueous, and outflow resistance, including episcleral venous pressure. Of the mechanisms that might be available to inter-relate these factors, nervous control has received the most attention. Vascular and humoral factors, which have been studied,2 · 3 may also reflect changes in innervation. To investigate the effect of sensory path ways on the intact human eye, therefore, is desirable. One factor that readily lends itself to study is the ocular consensual response. Tonography, for example, performed on one eye leads to a reduction in intraocular pres sure in the contralateral eye, apparently with out alteration in outflow facility.4·5 Tonog raphy performed on patients without fifthnerve function would permit assessment of that nerve's function on the ocular consensual response. The nature of "intraocular pressure read justment" after Diamox administration * From the Department of Surgery (Ophthalmol ogy), of The New York Hospital-Cornell Medical Center. Aided in part by a grant from The Na tional Council to Combat Blindness.
would also be of interest in this special group of patients. It has been reported6 that the facility of aqueous outflow is reduced, pre sumably as a compensatory measure, after the intraocular pressure has been lowered by Diamox administration. It was thought that some insight into the mechanism of this phenomenon might be gleaned from studies of the Diamox effect on fifth-nerve denervated eyes. MATERIALS AND METHODS
Six patients who had undergone retrogasserian neurectomy for idiopathic tic doleureux were studied. All patients had total corneal anesthesia and operative evidence of complete section. No ocular or neurologic deficit, except for sensory loss, was present. Tonography was performed on several oc casions until the patients became used to the procedure. Results, after acclimatization, were quite uniform. Tensions were recorded in both eyes and tonography performed on one eye. Immediately after completion of tonography (four minutes), tensions were taken in the contralateral eye. Both eyes were studied in this manner on a minimum of two occasions. The Mueller electronic tonometer was used for all readings and the 1955 tables employed. It is believed that this tonometer can be read to 0.25 scale units with a fair degree of accuracy in the ranges studied. Control patients were handled similarly.
M I L E S A. G A L I N
986
In the Diamox study, 500 mg. of Diamox were administered intravenously two hours after tonography had been performed on the involved eye. Thirty to 45 minutes after Dia mox administration, tonography was re peated. Control patients, as well as the nor mal eye, were handled similarly. RESULTS
Table 1, which summarizes the results of the ocular consensual study, shows that all patients exhibited a consistent consensual response regardless of which eye was stimu lated. Though the magnitudes of pressure changes were small, they were essentially similar and quite reproducible. No consistent results could be obtained in the Diamox study in either control or ex perimental patients. Though Diamox reduced intraocular pressure in all patients, altera tions in the facility of aqueous outflow were either negligible or not reproducible. Conse quently, the data from the experimental group have little meaning and have not been included. DISCUSSION
The effect of the fifth nerve on ocular homeostasis has been studied in great de tail. Hartmann 7 investigated the effects of retrogasserian neurectomy in man and con
cluded that no fibers regulating ocular ten sion were carried with the fifth nerve. Perkins, in detailed rabbit studies, demon strated immediate effects on the ipsilateral and contralateral eyes when the intact fifth nerve was stimulated mechanically. On the ipsilateral side, pupillary contraction, a rise in temperature of the ciliary region, increase in intraocular pressure, and increased aque ous protein resulted. In 15 percent of the animals, consensual increase in intraocular pressure occurred. In 50 percent of experi ments increased aqueous protein was noted in the contralateral eye. Perkins further re ported that in rabbits, the fifth cranial nerve can mediate impulses for raising the intra ocular pressure, though perhaps this might not occur in the normal control of intraocular pressure. Somewhat similar conclusions were reached by von Sallmann in his study of cats and monkeys.8 The results of the present study would tend to indicate that whatever the mechanism governing the ophthalmic consensual re sponse may be, it does not depend upon the integrity of the fifth nerve. Furthermore, no abnormalities in the regulation of intraocular pressure have been noted in these patients. All patients in the group were also subjected to detailed provocative testing,9 and demon-
TABLE 1 OCULAR CONSENSUAL RESPONSE TO TONOGRAPHY IN NORMAL AND FIFTH-NERVE DENERVATED EYES
Patient
Controls (average of all patients) E. B. (average of 5 runs) M. M. (average of 4 runs) B. C. (average of 6 runs) M. L. (average of 3 runs) S. H. (average of 2 runs) J. M. (average of 4 runs)
Immediate Immediate Intraocular Intraocular Intraocular Intraocular Facility of Pressure in Facility of Pressure in Pressure in Pressure in Aqueous Normal Aqueous Anesthetic Undisturbed Undisturbed Eye after Outflow in Tonography Outflow in Eye after Anesthetic Normal Anesthetic Normal Tonography Eye Eye in in Normal Eye Eye Anesthetic (mm.Hg) (mm.Hg) Eye Eye (mm.Hg) (mm.Hg) 13.0 12.0 16.0 13.0 15.0 11.0 17.0
12.75 12.0 17.0 14.0 16.0 12.0 18.5
0.31 0.25 0.30 0.25 0.25 0.22 0.34
11.4 10.4 15.0 12.5 14.3 10.1 16.8
0.33 0.30 0.30 0.20 0.32 0.28 0.36
12.0 10.8 14.4 11.8 13.2 10.0 15.4
NERVOUS CONTROL OF INTRAOCULAR PRESSURE strated no abnormalities. This would not be the case if the fifth nerve had a major regu latory function. It would be convenient to explain the maintenance of intraocular pressure by rele gating it to a system in which the afferent arc responds to alterations in pressure and initiates the response that ultimately leads to alteration in outflow facility, aqueous inflow, blood flow, and so forth, until normalcy is restored. No real evidence that the fifth nerve serves such a function has yet ap-
987
peared in the literature, and this study would, in part, tend to controvert such a supposi tion. SUMMARY
The ophthalmic consensual response is in tact in patients who have undergone retrogasserian neurectomy. It is suggested that the fifth nerve does not play a major role in the homeostatic mechanism for the maintenance of intraocular pressure. 525 East 68th Street (21)
REFERENCES
1. Perkins, E. A.: Influence of the fifth cranial nerve on the intraocular pressure of the rabbit eye. Brit. J. Ophth., 41:257, 1957. 2. Becker, B.: Glaucoma: Annual review. A.M.A. Arch. Ophth., 60:1112, 1958. 3. Bock, J., Hellauer, H., and Umrath, K.: Ueber das Vorkommen des Erregungsstoffes der sensiblen Nerven in Kammerwasser bei Glaukon. Arch. f. Ophth., 159:81, 1957. 4. Stocker, F. W.: On changes in intraocular pressure of the other Eye while tonography is done on one Eye. Tr. Am. Ophth. Soc., 54:63, 1956. 5. Waki, T.: Studies on tonography: III. Observations on normal rabbits. Acta Soc. Ophth. Japon., 62:542, 1958. 6. Becker, B., and Constant, M. A.: Experimental tonography: The effect of the carbonic anhydrase inhibitor acetazolamide on aqueous flow. A.M.A. Arch. Ophth., 54:321, 1955. 7. Hartmann, E.: La Neurotomie Retro-gasserienne. Paris, Doin, 1924. 8. von Sallman, L., Fuortes, M. G. F., Macri, F. J., and Grimes, P.: Study of afferent electric im pulses induced by intraocular pressure changes. Am. J. Ophth., 45:211 (Apr. Pt. II) 1958. 9. Galin, M. A., Aizawa, F., and McLean, J. M.: The effects of altered blood osmolality on intra ocular pressure. To be published.
SYSTEMIC HISTIOCYTOSIS* WITH
INTRAOCULAR I N V O L V E M E N T : R E P O R T OF A CASE H E N R Y J. K I N O S I A N ,
M.D.
Ogdensburg, New York
Buphthalmos due to infiltration of the iris, ciliary body, and trabecular meshwork with histiocytes has been reported in cases of nevoxantho-endothelioma,4-6'8 but no case of systemic histiocytosis with similar ocular in volvement has appeared in the literature. It is the purpose of this report to consider the classification of the histiocytic diseases and to describe such a case. Histiocytes (macrophages) are derived * From the Department of Surgery (Ophthalmol ogy) of The New York Hospital-Cornell Medical Center.
from the monocytes of the blood and from the fixed tissue macrophages of the reticuloendothelial system.1 They appear in response to inflammation, and their function is phagocytjc, for example, if they ingest dead or dy ing cells they have the appearance of a multinucleated cell, and if the ingested material is lipid, they appear as foam cells. Lichtenstein2 suggested the term histiocytosis X to include all cases of generalized histiocytosis which had previously been classified as eosinophilic granuloma of bone, Hand-Schüller-Christian disease, or Letterer-Siwe disease, for he felt
985
REFERENCES
Cori: Cited by Weinstein. D'Ermo, R, and Salvi, G. L.: Boll. Ocul., 34:98 (Feb.) 1955. Gala, A.: Zentrlbl. f. ges. Ophth., 25:30, 1931. Hruby, K.: Arch. f. Ophth., 143:187, 1941. Kraupa, E.: Klin. Monatsbl. f. Augenh., 87:837, 1931. Löhlein: Cited by Weinstein. Weinstein, P.: A glaukoma kor- es gyogytana. Budapest, 1943.
NERVOUS MECHANISMS FOR T H E CONTROL O F INTRAOCULAR P R E S S U R E * MILES A. GALIN,
M.D.
New York That the intraocular pressure in any given normal eye varies within well-defined bound aries is well known. However, the mechanism of this rather rigid homeostatis is not well understood. Perkins 1 has outlined the theo retic factors that might be applicable. These include capillary pressure, rate of aqueous secretion, nature (osmolality) of aqueous, and outflow resistance, including episcleral venous pressure. Of the mechanisms that might be available to inter-relate these factors, nervous control has received the most attention. Vascular and humoral factors, which have been studied,2 · 3 may also reflect changes in innervation. To investigate the effect of sensory path ways on the intact human eye, therefore, is desirable. One factor that readily lends itself to study is the ocular consensual response. Tonography, for example, performed on one eye leads to a reduction in intraocular pres sure in the contralateral eye, apparently with out alteration in outflow facility.4·5 Tonog raphy performed on patients without fifthnerve function would permit assessment of that nerve's function on the ocular consensual response. The nature of "intraocular pressure read justment" after Diamox administration * From the Department of Surgery (Ophthalmol ogy), of The New York Hospital-Cornell Medical Center. Aided in part by a grant from The Na tional Council to Combat Blindness.
would also be of interest in this special group of patients. It has been reported6 that the facility of aqueous outflow is reduced, pre sumably as a compensatory measure, after the intraocular pressure has been lowered by Diamox administration. It was thought that some insight into the mechanism of this phenomenon might be gleaned from studies of the Diamox effect on fifth-nerve denervated eyes. MATERIALS AND METHODS
Six patients who had undergone retrogasserian neurectomy for idiopathic tic doleureux were studied. All patients had total corneal anesthesia and operative evidence of complete section. No ocular or neurologic deficit, except for sensory loss, was present. Tonography was performed on several oc casions until the patients became used to the procedure. Results, after acclimatization, were quite uniform. Tensions were recorded in both eyes and tonography performed on one eye. Immediately after completion of tonography (four minutes), tensions were taken in the contralateral eye. Both eyes were studied in this manner on a minimum of two occasions. The Mueller electronic tonometer was used for all readings and the 1955 tables employed. It is believed that this tonometer can be read to 0.25 scale units with a fair degree of accuracy in the ranges studied. Control patients were handled similarly.
M I L E S A. G A L I N
986
In the Diamox study, 500 mg. of Diamox were administered intravenously two hours after tonography had been performed on the involved eye. Thirty to 45 minutes after Dia mox administration, tonography was re peated. Control patients, as well as the nor mal eye, were handled similarly. RESULTS
Table 1, which summarizes the results of the ocular consensual study, shows that all patients exhibited a consistent consensual response regardless of which eye was stimu lated. Though the magnitudes of pressure changes were small, they were essentially similar and quite reproducible. No consistent results could be obtained in the Diamox study in either control or ex perimental patients. Though Diamox reduced intraocular pressure in all patients, altera tions in the facility of aqueous outflow were either negligible or not reproducible. Conse quently, the data from the experimental group have little meaning and have not been included. DISCUSSION
The effect of the fifth nerve on ocular homeostasis has been studied in great de tail. Hartmann 7 investigated the effects of retrogasserian neurectomy in man and con
cluded that no fibers regulating ocular ten sion were carried with the fifth nerve. Perkins, in detailed rabbit studies, demon strated immediate effects on the ipsilateral and contralateral eyes when the intact fifth nerve was stimulated mechanically. On the ipsilateral side, pupillary contraction, a rise in temperature of the ciliary region, increase in intraocular pressure, and increased aque ous protein resulted. In 15 percent of the animals, consensual increase in intraocular pressure occurred. In 50 percent of experi ments increased aqueous protein was noted in the contralateral eye. Perkins further re ported that in rabbits, the fifth cranial nerve can mediate impulses for raising the intra ocular pressure, though perhaps this might not occur in the normal control of intraocular pressure. Somewhat similar conclusions were reached by von Sallmann in his study of cats and monkeys.8 The results of the present study would tend to indicate that whatever the mechanism governing the ophthalmic consensual re sponse may be, it does not depend upon the integrity of the fifth nerve. Furthermore, no abnormalities in the regulation of intraocular pressure have been noted in these patients. All patients in the group were also subjected to detailed provocative testing,9 and demon-
TABLE 1 OCULAR CONSENSUAL RESPONSE TO TONOGRAPHY IN NORMAL AND FIFTH-NERVE DENERVATED EYES
Patient
Controls (average of all patients) E. B. (average of 5 runs) M. M. (average of 4 runs) B. C. (average of 6 runs) M. L. (average of 3 runs) S. H. (average of 2 runs) J. M. (average of 4 runs)
Immediate Immediate Intraocular Intraocular Intraocular Intraocular Facility of Pressure in Facility of Pressure in Pressure in Pressure in Aqueous Normal Aqueous Anesthetic Undisturbed Undisturbed Eye after Outflow in Tonography Outflow in Eye after Anesthetic Normal Anesthetic Normal Tonography Eye Eye in in Normal Eye Eye Anesthetic (mm.Hg) (mm.Hg) Eye Eye (mm.Hg) (mm.Hg) 13.0 12.0 16.0 13.0 15.0 11.0 17.0
12.75 12.0 17.0 14.0 16.0 12.0 18.5
0.31 0.25 0.30 0.25 0.25 0.22 0.34
11.4 10.4 15.0 12.5 14.3 10.1 16.8
0.33 0.30 0.30 0.20 0.32 0.28 0.36
12.0 10.8 14.4 11.8 13.2 10.0 15.4
NERVOUS CONTROL OF INTRAOCULAR PRESSURE strated no abnormalities. This would not be the case if the fifth nerve had a major regu latory function. It would be convenient to explain the maintenance of intraocular pressure by rele gating it to a system in which the afferent arc responds to alterations in pressure and initiates the response that ultimately leads to alteration in outflow facility, aqueous inflow, blood flow, and so forth, until normalcy is restored. No real evidence that the fifth nerve serves such a function has yet ap-
987
peared in the literature, and this study would, in part, tend to controvert such a supposi tion. SUMMARY
The ophthalmic consensual response is in tact in patients who have undergone retrogasserian neurectomy. It is suggested that the fifth nerve does not play a major role in the homeostatic mechanism for the maintenance of intraocular pressure. 525 East 68th Street (21)
REFERENCES
1. Perkins, E. A.: Influence of the fifth cranial nerve on the intraocular pressure of the rabbit eye. Brit. J. Ophth., 41:257, 1957. 2. Becker, B.: Glaucoma: Annual review. A.M.A. Arch. Ophth., 60:1112, 1958. 3. Bock, J., Hellauer, H., and Umrath, K.: Ueber das Vorkommen des Erregungsstoffes der sensiblen Nerven in Kammerwasser bei Glaukon. Arch. f. Ophth., 159:81, 1957. 4. Stocker, F. W.: On changes in intraocular pressure of the other Eye while tonography is done on one Eye. Tr. Am. Ophth. Soc., 54:63, 1956. 5. Waki, T.: Studies on tonography: III. Observations on normal rabbits. Acta Soc. Ophth. Japon., 62:542, 1958. 6. Becker, B., and Constant, M. A.: Experimental tonography: The effect of the carbonic anhydrase inhibitor acetazolamide on aqueous flow. A.M.A. Arch. Ophth., 54:321, 1955. 7. Hartmann, E.: La Neurotomie Retro-gasserienne. Paris, Doin, 1924. 8. von Sallman, L., Fuortes, M. G. F., Macri, F. J., and Grimes, P.: Study of afferent electric im pulses induced by intraocular pressure changes. Am. J. Ophth., 45:211 (Apr. Pt. II) 1958. 9. Galin, M. A., Aizawa, F., and McLean, J. M.: The effects of altered blood osmolality on intra ocular pressure. To be published.
SYSTEMIC HISTIOCYTOSIS* WITH
INTRAOCULAR I N V O L V E M E N T : R E P O R T OF A CASE H E N R Y J. K I N O S I A N ,
M.D.
Ogdensburg, New York
Buphthalmos due to infiltration of the iris, ciliary body, and trabecular meshwork with histiocytes has been reported in cases of nevoxantho-endothelioma,4-6'8 but no case of systemic histiocytosis with similar ocular in volvement has appeared in the literature. It is the purpose of this report to consider the classification of the histiocytic diseases and to describe such a case. Histiocytes (macrophages) are derived * From the Department of Surgery (Ophthalmol ogy) of The New York Hospital-Cornell Medical Center.
from the monocytes of the blood and from the fixed tissue macrophages of the reticuloendothelial system.1 They appear in response to inflammation, and their function is phagocytjc, for example, if they ingest dead or dy ing cells they have the appearance of a multinucleated cell, and if the ingested material is lipid, they appear as foam cells. Lichtenstein2 suggested the term histiocytosis X to include all cases of generalized histiocytosis which had previously been classified as eosinophilic granuloma of bone, Hand-Schüller-Christian disease, or Letterer-Siwe disease, for he felt