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Consenual Reactions to Anterior Chamber Paracentesis
286
AMERICAN JOURNAL O F OPHTHALMOLOGY
Additionally, in the third paragraph, the second through fourth sentences should be as follows: "They kept one person with an increased temperature of 1.6° F (0.9° C) in a bath for over two hours; the subject showed no neurologic signs. When the temperature was in creased another 0.1° F (0.06° C) signs appeared. When the temperature was de creased 0.1° F (0.06° C) signs appeared. D O N A L D D. B O D E ,
Denver,
M.D.
Colorado
Consenual Reactions to Anterior Chamber Paracentesis Editor: In the recent article, "Consensual reac tions to anterior chamber paracentesis in the rabbit" (Am. J. Ophthalmol. 85:392, 1978), by Michael H. Kottow and Larry J. Seligman, the authors write that "in creased synthesis and release of prostaglandins from the iris . . . . can be trig gered with topical nitroge.n mustard" and quote an article of mine 1 to support this statement. Much evidence exists that the responses of the rabbit eye to nitrogen mustard (and also the responses to intracameral formaldehyde and antidromic fifth nerve stimulation) are not mediated by prostaglandins. 1 - 4 No prostaglandins are found in the aqueous humor after these stimuli, and the responses are not influenced by prostaglandin synthesis in hibitors. The authors quote an article by Davson and Matchett 5 about a contralateral re sponse to topical nitrogen mustard, as showing "a consensual increase in intraocular pressure (IOP), which is occa sionally more severe than the elevation produced in the directly stimulated eye." In this paper, the contralateral response was always smaller than the ipsilateral response, and many of the animals show ed virtually no contralateral response.
AUGUST, 1978
Further studies in our laboratory have shown a small variable contralateral re sponse to nitrogen mustard with most animals showing no contralateral re sponse at all, even when we have used fluorophotometry to assess this. The authors state that in the normal rabbit eye, no fluorescein dye extravasates into the aqueous. After intravenous injec tion, fluorescein in the aqueous humor is easily visible with the slit lamp or even with the unaided eye. The presence of fluorescein in the aqueous humor can be documented by fluorophotometry,6 al though in most cases, it cannot be seen by means of a less sensitive technique, such as anterior segment fluorescein angiography. Finally, the authors imply that the sympathetics play a key role in the contralat eral response to paracentesis because phenoxybenzamine eliminated the con tralateral response. Because blood pres sure was not monitored (and because the dosage used did kill one rabbit), the di minished contralateral response may have been only a manifestation of systemic hypotension and shock. Until this is ruled out, any speculation about sympathetic mediation is premature. A more sophisti cated way to assess sympathetic media tion would be superior cervical ganglionectomy, a procedure easily performed in the rabbit. L E E M. J A M P O L ,
Chicago,
M.D.
Illinois
REFERENCES 1. Jampol, L. M., Axelrod, A., and Tessler, H.: Pathways of the eye's response to topical nitrogen mustard. Invest. Ophthalmol. 15:486, 1976. 2. Jampol, L. M., Neufeld, A. H., and Sears, M. L.: Pathways for the response of the eye to injury. Invest. Ophthalmol. 14:184, 1975. 3. Cole, D. F., and Unger, W. G.: Prostaglandins as mediators for the responses of the eye to trauma. Exp. Eye Res. 17:357, 1973. 4. Eakins, K. E.: Prostaglandin and nonprostaglandin mediated breakdown of the bloodaqueous barrier. Exp. Eye Res. Suppl. 483, 1977.
VOL. 86, NO. 2
CORRESPONDENCE
5. Davson, H., and Matchett, P. A.: The control of the intraocular pressure in the rabbit. J. Physiol. 113:387, 1951. 6. Cunha-Vaz, J., and Maurice, D.: Fluorescein dynamics in the eye. Doc. Ophthalmol. 26:61,1969.
Reply Editor: Lee M. Jampol presents four objections to our paper: (1) We state that nitrogen mustard triggers prostaglandin release in the rabbit's eye. I believe this assertion was poorly worded, because we wished to state that similar anterior segment reac tions could be triggered by many stimuli, including nitrogen mustard. That we are aware the mechanisms involved vary ac cording to the stimulus used, is apparent from the discussion following that state ment in the paper. I agree, and apologize for Dr. Jampol's having been quoted in adequately on this point. (2) Dr. Jampol asserts that we incorrect ly quote Davson and Matchett as having stated that contralateral responses may exceed the ipsilateral ones. We stand cor rected. Nevertheless, the quoted paper does state: "Among 21 experiments car ried out to determine the frequency of occurrence of the contralateral effect, a rise of more than 20 cm H 2 0 was obtained in four cases, and a rise of less than 20 but greater than 10 cm H 2 0 in six cases." I consider this as adequate support of our thesis that consensual responses to nitro gen mustard are significant in frequency and magnitude. I am surprised that Dr. Jampol finds consensual responses to nitrogen mustard to be exceptional because he and I worked together on this subject and saw consistent fluorescein angiographic evi dence of contralateral responses to nitro gen mustard. This "consensual response is not always of a permeability breakdown type because in some instances, ischemic manifestations may predominate. Prelim
287
inary evidence shows that ischemic con sensual responses occur after a variety of uniocular injuries. This point further em phasizes certain advantages of fluoresce in angiography over photofluorometry, which only measures fluorescein leakage into the aqueous. (3) We are quoted as having stated that in the normal rabbit eye, no fluorescein extravasates into the aqueous, whereas what we wrote was: "The normal rabbit iris shows no fluorescein leakage." There is ample experimental, clinical, and histologic evidence to support the assertion that the normal iris vessels in rabbit, monkey, and man are impermeable to fluorescein. Dye, of course, passes into the aqueous through the ciliary processes, but this is irrelevant to fluorescein angi ography because it occurs late, slowly, and in small quantities. I therefore cannot share Dr. Jampol's experience of seeing fluorescein with the unaided eye in the aqueous humor of normal rabbits. (4) In animals preheated with the alpha adrenergic antagonist phenoxybenzamine, no consensual response was ob served. We concluded this finding sup ported the concept that consensual re sponses, at least partially, were mediated by adrenergic pathways. Dr. Jampol con siders systemic hypotension as a possible alternative explanation for the lack of consensual responses. Neither am I aware that hypotension decreases endothelial permeability, nor do I believe that sys temic hypotension could inhibit a con sensual response even in those cases in which the ipsilateral response was in tense. Our animals pretreated with phenoxybenzamirie did not show abnor m a l l y l o n g e a n i r i s times. F i n a l l y , phenoxybenzamine is known to cause a slight intraocular pressure increase, which is hardly consistent with simulta neous systemic hypotension or shock. I agree that sympathetic pathways for con-
AMERICAN JOURNAL O F OPHTHALMOLOGY
Additionally, in the third paragraph, the second through fourth sentences should be as follows: "They kept one person with an increased temperature of 1.6° F (0.9° C) in a bath for over two hours; the subject showed no neurologic signs. When the temperature was in creased another 0.1° F (0.06° C) signs appeared. When the temperature was de creased 0.1° F (0.06° C) signs appeared. D O N A L D D. B O D E ,
Denver,
M.D.
Colorado
Consenual Reactions to Anterior Chamber Paracentesis Editor: In the recent article, "Consensual reac tions to anterior chamber paracentesis in the rabbit" (Am. J. Ophthalmol. 85:392, 1978), by Michael H. Kottow and Larry J. Seligman, the authors write that "in creased synthesis and release of prostaglandins from the iris . . . . can be trig gered with topical nitroge.n mustard" and quote an article of mine 1 to support this statement. Much evidence exists that the responses of the rabbit eye to nitrogen mustard (and also the responses to intracameral formaldehyde and antidromic fifth nerve stimulation) are not mediated by prostaglandins. 1 - 4 No prostaglandins are found in the aqueous humor after these stimuli, and the responses are not influenced by prostaglandin synthesis in hibitors. The authors quote an article by Davson and Matchett 5 about a contralateral re sponse to topical nitrogen mustard, as showing "a consensual increase in intraocular pressure (IOP), which is occa sionally more severe than the elevation produced in the directly stimulated eye." In this paper, the contralateral response was always smaller than the ipsilateral response, and many of the animals show ed virtually no contralateral response.
AUGUST, 1978
Further studies in our laboratory have shown a small variable contralateral re sponse to nitrogen mustard with most animals showing no contralateral re sponse at all, even when we have used fluorophotometry to assess this. The authors state that in the normal rabbit eye, no fluorescein dye extravasates into the aqueous. After intravenous injec tion, fluorescein in the aqueous humor is easily visible with the slit lamp or even with the unaided eye. The presence of fluorescein in the aqueous humor can be documented by fluorophotometry,6 al though in most cases, it cannot be seen by means of a less sensitive technique, such as anterior segment fluorescein angiography. Finally, the authors imply that the sympathetics play a key role in the contralat eral response to paracentesis because phenoxybenzamine eliminated the con tralateral response. Because blood pres sure was not monitored (and because the dosage used did kill one rabbit), the di minished contralateral response may have been only a manifestation of systemic hypotension and shock. Until this is ruled out, any speculation about sympathetic mediation is premature. A more sophisti cated way to assess sympathetic media tion would be superior cervical ganglionectomy, a procedure easily performed in the rabbit. L E E M. J A M P O L ,
Chicago,
M.D.
Illinois
REFERENCES 1. Jampol, L. M., Axelrod, A., and Tessler, H.: Pathways of the eye's response to topical nitrogen mustard. Invest. Ophthalmol. 15:486, 1976. 2. Jampol, L. M., Neufeld, A. H., and Sears, M. L.: Pathways for the response of the eye to injury. Invest. Ophthalmol. 14:184, 1975. 3. Cole, D. F., and Unger, W. G.: Prostaglandins as mediators for the responses of the eye to trauma. Exp. Eye Res. 17:357, 1973. 4. Eakins, K. E.: Prostaglandin and nonprostaglandin mediated breakdown of the bloodaqueous barrier. Exp. Eye Res. Suppl. 483, 1977.
VOL. 86, NO. 2
CORRESPONDENCE
5. Davson, H., and Matchett, P. A.: The control of the intraocular pressure in the rabbit. J. Physiol. 113:387, 1951. 6. Cunha-Vaz, J., and Maurice, D.: Fluorescein dynamics in the eye. Doc. Ophthalmol. 26:61,1969.
Reply Editor: Lee M. Jampol presents four objections to our paper: (1) We state that nitrogen mustard triggers prostaglandin release in the rabbit's eye. I believe this assertion was poorly worded, because we wished to state that similar anterior segment reac tions could be triggered by many stimuli, including nitrogen mustard. That we are aware the mechanisms involved vary ac cording to the stimulus used, is apparent from the discussion following that state ment in the paper. I agree, and apologize for Dr. Jampol's having been quoted in adequately on this point. (2) Dr. Jampol asserts that we incorrect ly quote Davson and Matchett as having stated that contralateral responses may exceed the ipsilateral ones. We stand cor rected. Nevertheless, the quoted paper does state: "Among 21 experiments car ried out to determine the frequency of occurrence of the contralateral effect, a rise of more than 20 cm H 2 0 was obtained in four cases, and a rise of less than 20 but greater than 10 cm H 2 0 in six cases." I consider this as adequate support of our thesis that consensual responses to nitro gen mustard are significant in frequency and magnitude. I am surprised that Dr. Jampol finds consensual responses to nitrogen mustard to be exceptional because he and I worked together on this subject and saw consistent fluorescein angiographic evi dence of contralateral responses to nitro gen mustard. This "consensual response is not always of a permeability breakdown type because in some instances, ischemic manifestations may predominate. Prelim
287
inary evidence shows that ischemic con sensual responses occur after a variety of uniocular injuries. This point further em phasizes certain advantages of fluoresce in angiography over photofluorometry, which only measures fluorescein leakage into the aqueous. (3) We are quoted as having stated that in the normal rabbit eye, no fluorescein extravasates into the aqueous, whereas what we wrote was: "The normal rabbit iris shows no fluorescein leakage." There is ample experimental, clinical, and histologic evidence to support the assertion that the normal iris vessels in rabbit, monkey, and man are impermeable to fluorescein. Dye, of course, passes into the aqueous through the ciliary processes, but this is irrelevant to fluorescein angi ography because it occurs late, slowly, and in small quantities. I therefore cannot share Dr. Jampol's experience of seeing fluorescein with the unaided eye in the aqueous humor of normal rabbits. (4) In animals preheated with the alpha adrenergic antagonist phenoxybenzamine, no consensual response was ob served. We concluded this finding sup ported the concept that consensual re sponses, at least partially, were mediated by adrenergic pathways. Dr. Jampol con siders systemic hypotension as a possible alternative explanation for the lack of consensual responses. Neither am I aware that hypotension decreases endothelial permeability, nor do I believe that sys temic hypotension could inhibit a con sensual response even in those cases in which the ipsilateral response was in tense. Our animals pretreated with phenoxybenzamirie did not show abnor m a l l y l o n g e a n i r i s times. F i n a l l y , phenoxybenzamine is known to cause a slight intraocular pressure increase, which is hardly consistent with simulta neous systemic hypotension or shock. I agree that sympathetic pathways for con-