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Intravenous Urea and Angle-Closure Glaucoma*
INTRAVENOUS UREA AND ANGLE-CLOSURE GLAUCOMA* AUSTIN I. F I N K , M.D.,
R I C H LRD D . B I N K H O R S T ,
M.D.,
AND
4.HASHI, M.D. Brooklyn, New York
TOMOYA F U N
INTRODUCTION
The treatment of patients with acute angleclosure glaucoma has always presented a problem. Diamox in combination with miotics was introduced in 19541 but, although this drug was a significant aid, a number of patients were refractory to it. Other carbonic anhydrase inhibitors offered no improvement over Diamox. Trying to break a hypertensive crisis by increasing aqueous outflow (miotics) and/or by decreasing inflow (car bonic anhydrase inhibitors) was not com pletely successful. Osmotic therapy with intravenous sucrose has also been utilized2 but its risks (renal toxicity3) and ineffectiveness left much to be desired. The high molecular weight made it necessary to administer huge doses of the drug in order to achieve a satisfactory os motic gradient. The recent reintroduction of urea into clinical ophthalmology seems to have lessened significantly the problems of treating in tractable angle-closure glaucoma. Detailed studies of this osmotic agent have been carried out and its mode of action well de fined.4 Several clinical reports have com mented on its use. 5-7 It is the purpose of this communication to report on the limitations and range of usefulness of intravenous urea in four patients with acute angle-closure glaucoma. MATERIAL AND METHODS
Four patients with intractable angleclosure glaucoma were treated with intra venous urea on the Eye Service of the Long Island College Hospital. One patient required * From the Department of Ophthalmology of the Long Island College Hospital and the Division of Ophthalmology of the State University of New York, Downstate Medical Center.
the drug for control of ocular tension in each eye and so five eyes are included in this study. None of the patients had responded to intensive miotic and Diamox therapy. Intravenous urea was administered, as had been suggested,5 in a dose of one gm. per kg. of weight as a 30-percent lyophilized so lution in 10-percent invert sugar. The rate of flow was usually three to five cc. per minute, but was increased in those patients who demonstrated damage to the blood aque ous barrier (see comment). CASE REPORTS CASE 1
Mrs. R. McN., a 75-year-old white woman, was admitted to the Long Island Hospital with severe pain in the right eye and right-sided headache of 13 hours' duration. This was accompanied by per sistent vomiting and rapid loss of vision in the right eye. On admission, the right eye had a visual acuity of hand movements at two feet, and demonstrated marked congestion of the bulbar conjunctiva. The cornea was edematous, the anterior chamber ex tremely shallow and the pupil oval, fixed, and al most fully dilated. The intraocular pressure was 80 mm. Hg. The left eye was normal except for a shallow anterior chamber and a corrected visual acuity of 20/40 due to nuclear lens changes. Ocu lar tension was normal. Past history revealed treat ment for hypertensive cardiovascular disease of 12 years' duration. In addition, three different attacks of myocardial infarction had occurred four, eight, and 12 years previously. Medical therapy was instituted immediately con sisting of 500 mg. of Diamox intravenously with Prostigmine (five percent) and Mecholyl (20 per cent) solution, administered every 10 minutes in the right eye. Pilocarpine (two percent) was given prophylactically every two hours in the left eye. Demerol and Thorazine were injected intramuscu larly for the control of pain and vomiting. After two hours of such therapy the ocular tension in the right eye was still 70 mm. Hg and the pupil had failed to constrict. At the end of the third hour on this same regime the tension in the right eye was 60 mm. Hg. At this point urea was administered intrave nously. The dosage was one gm. per kg. of weight in a solution of 10-percent invert sugar. Forty-five minutes later the ocular tension in the right eye
UREA AND ANGLE-CLOSURE GLAUCOMA was 8.0 mm. Hg. The patient was taken to the op erating room where a single pillar iridencleisis was performed with excellent results. A successful prophylactic peripheral iridectomy was carried out one week later on the left eye. At this time the corrected visual acuity in the right eye had improved to 20/70. CASE 2
Mrs. D. G., a known hypertensive for 25 years and suffering from angina pectoris for eight years, was admitted to the Long Island College Hospital with an acute myocardial infarction. She had ex perienced intermittent attacks of pain in both eyes during the previous six months, with blurring of vision and redness of the right eye. One day after admission, she developed such an attack in the right eye with decrease in vision. The visual acuity could not be quantitated since the patient was con fined to bed. On examination she appeared to have shallow anterior chambers in each eye with an oval semidilated pupil in the right eye. The tension was 35 mm. Hg in the right eye and 22 mm. Hg in the left eye. With miotic therapy the tension dropped to normal limits and surgery was deferred because of the recent myocardial infarction. The patient was discharged from the hospital five weeks fol lowing the attack of angle-closure glaucoma. She had not been faithful in using her eye medi cation and so was readmitted to the hospital one month later with pain in her right eye accompanied by severe chest pain. Examination revealed marked congestion of the globe, edema of the cornea, a very shallow anterior chamber and moderate dilatation of the pupil. The tension measured 60 mm. Hg in the right eye. The visual acuity of the left eye was 20/70, anterior chamber shallow, and the pupil miotic. The eye was not congested but the tension was 31 mm. Hg. The intraocular pressure was con trolled, using a combination of 500 mg. of Diamox given intravenously and topical Carcholin (1.5 per cent) . Two days later, although on combined oral Dia mox and local miotic therapy, the patient experi enced pain in her left eye. The cornea appeared somewhat steamy with congestion of the globe. The pupil, however, was still miotic. The intraocular pressure, in spite of therapy, was 9.0 mm. Hg in the right eye and 60 mm. Hg in the left eye. Urea, 1.0 gm./kg. was given intravenously in 10-percent invert sugar and the pressure dropped within 45 minutes in both eyes to 4.0 mm. Hg. The patient was scheduled for surgery, but this had to be deferred because of a recurrence of an ginal chest pain. Profuse perspiration, a result of Carcholin toxicity, necessitated changing to Pilocarpine for continued miosis. When, in spite of medication, the pressure the next day was found to be 47 mm. Hg in the left eye, the same dosage of urea was repeated with a drop once again to 4.0 mm. in each eye. A one-pillar iridencleisis was per formed immediately and five days later a similar procedure was carried out on the right eye. The patient made an uneventful recovery and ocular
873
tension was controlled in both eyes thereafter with out medication. CASE 3
Miss K. B., a 43-year-old white woman, was admitted to the Long Island College Hospital be cause of a severe left-sided headache with pain in the left side of her face of three days' duration. These symptoms were accompanied by nausea, vom iting and marked diminution in vision of the left eye. No previous history of ocular symptoms was elicited except for poor vision in the right eye since childhood. Visual acuity on admission was corrected to 20/ 300 in the right eye with a —5.0D. sph. The an terior chamber was moderately deep. The right eye was esotropic (15 degrees) and ocular tension was 22 mm. Hg. No other abnormalities in this eye were observed. The vision of the left eye was found correctible to 20/80 with a +3.5D. sph. and dem onstrated deep perilimbal injection, a steamy cor nea, a shallow anterior chamber and a dilated pupil refractory to light. The tension was 70 mm. Hg. and the f undus appeared to be normal. Medical therapy was started immediately, con sisting of Diamox, 500 mg. intravenously with Carcholin (1.5 percent) every 15 minutes in the left eye and prophylactically every four hours in the right eye. Demerol was given intramuscularly for pain and Compazine for the control of nausea and vomiting. Two hours later the tension was found to be unchanged and so urea (1.0 gm./kg.) was administered in a solution of 10-percent invert sugar. The pressure was still unchanged one and a half hours later and the miotics were changed to Prostigmine (five percent) and Mecholyl (20 per cent) alternating every five minutes "in the left eye. These drugs, too, failed to alter the pressure. It was assumed that urea failed to lower the intraocular pressure because of damage to the blood aqueous barrier as a result of a three-day history of symptoms prior to medication. A satis factory osmotic gradient, essential to lower the pressure, had not been obtained. Eight hours later, a second dose of intravenous urea (1.0 gm./kg. in 10-percent invert sugar) was administered in five minutes (instead of half an hour) with the patient outside the operating room. With this very rapid administration, a satisfactory osmotic gradient was obtained and the pressure dropped to 18 mm. Hg in the left eye one-half hour later. The patient was moved immediately into the operating room where a complete iridectomy was performed. Postoperatively, the tension in the left eye, as measured with the Goldmann applanation tonometer, remained in the 30's and could only be controlled with Diamox. Tonography showed a diminished fa cility of outflow. Three weeks after the initial iri dectomy, a single pillar iridencleisis was performed, resulting in excellent control of the intraocular pressure for the past three months. CASE 4
Mrs. I. P., a 51-year-old white woman with
874
A. I. FINK, R. D. BINKHORST AND T. FUNAHASHI
known diabetes for 17 years and poorly controlled because of irregular diet habits and insulin adminis tration, entered the Long Island College Hospital with severe pain in the left eye of three days' dura tion. The pain was accompanied by a left frontal headache and persistent vomiting. She had noticed a decrease in vision since the onset of symptoms. There had been no such episodes previously. Visual acuity was 20/50 in the right eye and hand movements at one foot in the left eye. Exami nation revealed 4 + injection of the left globe with moderate edema of the cornea. The anterior cham ber was deep in each eye with moderate rubeosis of the iris in the right eye and marked rubeosis in the left eye. Gonioscopic study demonstrated wide anterior chamber angles in each eye with neovascularization of the entire circumference of the trabecular meshwork in the left eye. The ocular tension was 23 mm. Hg in the right eye and 64 mm. Hg in the left eye. Medical therapy, consisting of Diamox, Pilocarpine and Demerol, was instituted. The tension in the left eye dropped to 35 mm. Hg in several hours but failed to respond further. Humorsol (0.25 percent b.i.d.) and Epitrate (two percent) also failed to reduce the tension and two days later the pressure rose to 46 mm. Hg in the left eye. Urea was then given intravenously (1.0 gm./kg. in 10-percent invert sugar) at a rate of four cc. per minute. The pressure dropped to 27 mm. Hg 45 minutes later but failed to respond further. With continued Diamox and miotic therapy the tension was maintained at this level for several days, fluc tuating in the low 30's. Two weeks later, a modi fied Scheie procedure was performed. An eight-mm. scleral incision was made into the anterior cham ber with the Hildreth coagulator and a hole burned into the iris with the coagulator to effect an iridectomy. Postoperatively, a good filtering bleb formed and the tension was controlled. OBSERVATIONS AND C O M M E N T
A review of the cases just presented in dicates that urea was an effective therapeutic agent for lowering the intraocular pressure in patients with acute angle-closure glaucoma who had not responded to a combination of miotic and Diamox therapy. It was most efficacious in the first three cases but not in the fourth. T h e first three were primary and the last a secondary angle-closure variety of glaucoma. This drug satisfies the prerequi sites for an ideal osmotic agent. It has low molecular weight, is nontoxic, with poor ocular penetration, thus permitting the de velopment of a high and sustained osmotic gradient. W i t h this therapy the glaucomatous crisis can be broken and the patient prepared
either for immediate surgery or controlled by miotics for surgery at a later date. T h e sur gery is then performed under ideal condi tions. Limitations in the use of Diamox are apparent in Case 2, where an acute attack ensued in a patient under intensive Diamox and miotic therapy. T h e conscientious ad ministration of miotics merely served to drain further an already shallow anterior chamber in an eye where Diamox had failed to break the crisis. I n addition, flooding the conjunctival cul-de-sac with miotics produced symptoms of parasympathetic toxicity. All these factors served to cause a precipitous rise in pressure that was broken only by urea, thus effectively utilizing the osmotic principle. Surgery could then take place un der ideal conditions. The rate of flow of the intravenous urea, as has been mentioned, was three to five cc. per minute. At this rate the entire dosage (1.0 g m . / k g . in 10-percent invert sugar) was delivered in 30 to 60 minutes. However, in one case it was necessary to administer a second dose in five minutes, when earlier urea had failed to produce hypotony of the globe. T h e patient had experienced symptoms of acute glaucoma for three days. Increased turbidity of the aqueous and damage to the blood aqueous barrier, a result of neglect, altered the osmotic reqirements. Rapid ad ministration of urea, however, served sud denly and effectively to increase the osmotic gradient to a point where the drug could exert its effect in the presence of a turbid aqueous and a severely damaged blood aqueour barrier. T h e limitations of urea's usefulness are most apparent in Case 4. Secondary glaucoma was present as a result of the proliferation of new blood vessels on the iris surface and in the anterior chamber angle. This neovascularization was due to diabetes mellitus of long duration. Intravenous urea, administered at a rapid rate, produced a moderate and short lived fall in intraocular pressure. A turbid aqueous, the result of neovascularization,
UREA AND ANGLE-CLOSURE GLAUCOMA coupled with a broken aqueous barrier, made it impossible for urea to produce a high and sustained osmotic gradient. I n this instance, therefore, urea was of limited value. T h e one side-effect noted was occasional headache. This was attributed to a fall in the cerebrospinal fluid pressure of short dura tion. 4 SUMMARY
Intravenous administration of urea pro duced a rapid fall in the intraocular pres-
875
sure in three out of four patients with acute angle-closure glaucoma, who had been re fractory to a combination of Diamox and miotic therapy. T h e drug has only limited usefulness in patients with secondary glaucoma who dem onstrate a turbid aqueous and damage to the blood aqueous barrier. Establishing a satisfactory osmotic gradient is thus pre vented. 450 Clarkson Avenue
(3).
REFERENCES
1. Becker, B.: Decrease in intraocular pressure in man by carbonic anhydrase inhibitor, Diamox: Preliminary report. Am. J. Ophth., 37:13-15 (Jan.) 1954. 2. Dyar, E. W., and Matthew, W. B.: Use of sucrose preparatory in surgical treatment of glaucoma: Preliminary Report. Arch. Oph., 18:57, 1937. 3. Anderson, W. A. D.. and Bethea, W. R.: Renal lesion following administration of hypertonic solution of Sucrose. J.A.M.A., 114:1983-1987,1940. 4. Javid, M.: New use of an old drug. Surg. Clin. N. Am., 1958, p. 907. 5. Galin, M. A., Aizawa, F., and McLean, J. M.: Urea as an osmotic ocular hypotensive agent in glau coma. AM A Arch. Ophth., 62:347, 1959. 6. : Intravenous urea in the treatment of acute angle closure glaucoma. Am. J. Ophth., 50:379 (Sept.) 1960. 7. Kloti, R.: Harnstoff—Infusion in der Glaucomtherapie. Ophthalmologica, 140:135-146, 1960.
THE ACTION OF UREA IN ACUTE GLAUCOMA* A L B E R T L.
ACKERMAN,
M.D.
New York There are few events in ophthalmology as dramatic as the precipitous drop in intra ocular pressure which follows the use of urea in acute glaucoma. This occurs within 45 minutes, regardless of etiology, and despite the failure of previous therapy. T h e measur able effect of intravenous urea lasts five to 12 hours. Although initially it was suggested only in the management of acute glaucoma in preparation for surgery, it has become apparent that the boundaries of its usefulness reach beyond this limitation. In angle-closure glaucoma, urea, by its rapid lowering of in traocular pressure, enables miotics to become effective and terminates the acute attack. Operative management then becomes elective, with iridectomy the procedure of choice. * From the Ophthalmology Service of Montefiore Hospital.
U r e a is a substance of broad scientific interest which, until recently, has been therapeutically neglected. Historically, urea is im portant as the first organic substance to be synthesized from inorganic compounds (Fredrich Wohler in 1828) thereby initiating the field of organic chemistry. Phylogenetically, it is the chief end-product of protein metabolism in mammals, as dif ferentiated from birds and reptiles, which excrete uric acid, presumably to conserve water. Physiologically, by acting as a carrier, it detoxifies the N H 3 resulting from deamination during metabolism of amino acids. It is formed in the liver from arginine, carried in the blood stream, and excreted by the kidney by glomerular filtration. Fifty percent is reabsorbed by the kidney tubules by an active
R I C H LRD D . B I N K H O R S T ,
M.D.,
AND
4.HASHI, M.D. Brooklyn, New York
TOMOYA F U N
INTRODUCTION
The treatment of patients with acute angleclosure glaucoma has always presented a problem. Diamox in combination with miotics was introduced in 19541 but, although this drug was a significant aid, a number of patients were refractory to it. Other carbonic anhydrase inhibitors offered no improvement over Diamox. Trying to break a hypertensive crisis by increasing aqueous outflow (miotics) and/or by decreasing inflow (car bonic anhydrase inhibitors) was not com pletely successful. Osmotic therapy with intravenous sucrose has also been utilized2 but its risks (renal toxicity3) and ineffectiveness left much to be desired. The high molecular weight made it necessary to administer huge doses of the drug in order to achieve a satisfactory os motic gradient. The recent reintroduction of urea into clinical ophthalmology seems to have lessened significantly the problems of treating in tractable angle-closure glaucoma. Detailed studies of this osmotic agent have been carried out and its mode of action well de fined.4 Several clinical reports have com mented on its use. 5-7 It is the purpose of this communication to report on the limitations and range of usefulness of intravenous urea in four patients with acute angle-closure glaucoma. MATERIAL AND METHODS
Four patients with intractable angleclosure glaucoma were treated with intra venous urea on the Eye Service of the Long Island College Hospital. One patient required * From the Department of Ophthalmology of the Long Island College Hospital and the Division of Ophthalmology of the State University of New York, Downstate Medical Center.
the drug for control of ocular tension in each eye and so five eyes are included in this study. None of the patients had responded to intensive miotic and Diamox therapy. Intravenous urea was administered, as had been suggested,5 in a dose of one gm. per kg. of weight as a 30-percent lyophilized so lution in 10-percent invert sugar. The rate of flow was usually three to five cc. per minute, but was increased in those patients who demonstrated damage to the blood aque ous barrier (see comment). CASE REPORTS CASE 1
Mrs. R. McN., a 75-year-old white woman, was admitted to the Long Island Hospital with severe pain in the right eye and right-sided headache of 13 hours' duration. This was accompanied by per sistent vomiting and rapid loss of vision in the right eye. On admission, the right eye had a visual acuity of hand movements at two feet, and demonstrated marked congestion of the bulbar conjunctiva. The cornea was edematous, the anterior chamber ex tremely shallow and the pupil oval, fixed, and al most fully dilated. The intraocular pressure was 80 mm. Hg. The left eye was normal except for a shallow anterior chamber and a corrected visual acuity of 20/40 due to nuclear lens changes. Ocu lar tension was normal. Past history revealed treat ment for hypertensive cardiovascular disease of 12 years' duration. In addition, three different attacks of myocardial infarction had occurred four, eight, and 12 years previously. Medical therapy was instituted immediately con sisting of 500 mg. of Diamox intravenously with Prostigmine (five percent) and Mecholyl (20 per cent) solution, administered every 10 minutes in the right eye. Pilocarpine (two percent) was given prophylactically every two hours in the left eye. Demerol and Thorazine were injected intramuscu larly for the control of pain and vomiting. After two hours of such therapy the ocular tension in the right eye was still 70 mm. Hg and the pupil had failed to constrict. At the end of the third hour on this same regime the tension in the right eye was 60 mm. Hg. At this point urea was administered intrave nously. The dosage was one gm. per kg. of weight in a solution of 10-percent invert sugar. Forty-five minutes later the ocular tension in the right eye
UREA AND ANGLE-CLOSURE GLAUCOMA was 8.0 mm. Hg. The patient was taken to the op erating room where a single pillar iridencleisis was performed with excellent results. A successful prophylactic peripheral iridectomy was carried out one week later on the left eye. At this time the corrected visual acuity in the right eye had improved to 20/70. CASE 2
Mrs. D. G., a known hypertensive for 25 years and suffering from angina pectoris for eight years, was admitted to the Long Island College Hospital with an acute myocardial infarction. She had ex perienced intermittent attacks of pain in both eyes during the previous six months, with blurring of vision and redness of the right eye. One day after admission, she developed such an attack in the right eye with decrease in vision. The visual acuity could not be quantitated since the patient was con fined to bed. On examination she appeared to have shallow anterior chambers in each eye with an oval semidilated pupil in the right eye. The tension was 35 mm. Hg in the right eye and 22 mm. Hg in the left eye. With miotic therapy the tension dropped to normal limits and surgery was deferred because of the recent myocardial infarction. The patient was discharged from the hospital five weeks fol lowing the attack of angle-closure glaucoma. She had not been faithful in using her eye medi cation and so was readmitted to the hospital one month later with pain in her right eye accompanied by severe chest pain. Examination revealed marked congestion of the globe, edema of the cornea, a very shallow anterior chamber and moderate dilatation of the pupil. The tension measured 60 mm. Hg in the right eye. The visual acuity of the left eye was 20/70, anterior chamber shallow, and the pupil miotic. The eye was not congested but the tension was 31 mm. Hg. The intraocular pressure was con trolled, using a combination of 500 mg. of Diamox given intravenously and topical Carcholin (1.5 per cent) . Two days later, although on combined oral Dia mox and local miotic therapy, the patient experi enced pain in her left eye. The cornea appeared somewhat steamy with congestion of the globe. The pupil, however, was still miotic. The intraocular pressure, in spite of therapy, was 9.0 mm. Hg in the right eye and 60 mm. Hg in the left eye. Urea, 1.0 gm./kg. was given intravenously in 10-percent invert sugar and the pressure dropped within 45 minutes in both eyes to 4.0 mm. Hg. The patient was scheduled for surgery, but this had to be deferred because of a recurrence of an ginal chest pain. Profuse perspiration, a result of Carcholin toxicity, necessitated changing to Pilocarpine for continued miosis. When, in spite of medication, the pressure the next day was found to be 47 mm. Hg in the left eye, the same dosage of urea was repeated with a drop once again to 4.0 mm. in each eye. A one-pillar iridencleisis was per formed immediately and five days later a similar procedure was carried out on the right eye. The patient made an uneventful recovery and ocular
873
tension was controlled in both eyes thereafter with out medication. CASE 3
Miss K. B., a 43-year-old white woman, was admitted to the Long Island College Hospital be cause of a severe left-sided headache with pain in the left side of her face of three days' duration. These symptoms were accompanied by nausea, vom iting and marked diminution in vision of the left eye. No previous history of ocular symptoms was elicited except for poor vision in the right eye since childhood. Visual acuity on admission was corrected to 20/ 300 in the right eye with a —5.0D. sph. The an terior chamber was moderately deep. The right eye was esotropic (15 degrees) and ocular tension was 22 mm. Hg. No other abnormalities in this eye were observed. The vision of the left eye was found correctible to 20/80 with a +3.5D. sph. and dem onstrated deep perilimbal injection, a steamy cor nea, a shallow anterior chamber and a dilated pupil refractory to light. The tension was 70 mm. Hg. and the f undus appeared to be normal. Medical therapy was started immediately, con sisting of Diamox, 500 mg. intravenously with Carcholin (1.5 percent) every 15 minutes in the left eye and prophylactically every four hours in the right eye. Demerol was given intramuscularly for pain and Compazine for the control of nausea and vomiting. Two hours later the tension was found to be unchanged and so urea (1.0 gm./kg.) was administered in a solution of 10-percent invert sugar. The pressure was still unchanged one and a half hours later and the miotics were changed to Prostigmine (five percent) and Mecholyl (20 per cent) alternating every five minutes "in the left eye. These drugs, too, failed to alter the pressure. It was assumed that urea failed to lower the intraocular pressure because of damage to the blood aqueous barrier as a result of a three-day history of symptoms prior to medication. A satis factory osmotic gradient, essential to lower the pressure, had not been obtained. Eight hours later, a second dose of intravenous urea (1.0 gm./kg. in 10-percent invert sugar) was administered in five minutes (instead of half an hour) with the patient outside the operating room. With this very rapid administration, a satisfactory osmotic gradient was obtained and the pressure dropped to 18 mm. Hg in the left eye one-half hour later. The patient was moved immediately into the operating room where a complete iridectomy was performed. Postoperatively, the tension in the left eye, as measured with the Goldmann applanation tonometer, remained in the 30's and could only be controlled with Diamox. Tonography showed a diminished fa cility of outflow. Three weeks after the initial iri dectomy, a single pillar iridencleisis was performed, resulting in excellent control of the intraocular pressure for the past three months. CASE 4
Mrs. I. P., a 51-year-old white woman with
874
A. I. FINK, R. D. BINKHORST AND T. FUNAHASHI
known diabetes for 17 years and poorly controlled because of irregular diet habits and insulin adminis tration, entered the Long Island College Hospital with severe pain in the left eye of three days' dura tion. The pain was accompanied by a left frontal headache and persistent vomiting. She had noticed a decrease in vision since the onset of symptoms. There had been no such episodes previously. Visual acuity was 20/50 in the right eye and hand movements at one foot in the left eye. Exami nation revealed 4 + injection of the left globe with moderate edema of the cornea. The anterior cham ber was deep in each eye with moderate rubeosis of the iris in the right eye and marked rubeosis in the left eye. Gonioscopic study demonstrated wide anterior chamber angles in each eye with neovascularization of the entire circumference of the trabecular meshwork in the left eye. The ocular tension was 23 mm. Hg in the right eye and 64 mm. Hg in the left eye. Medical therapy, consisting of Diamox, Pilocarpine and Demerol, was instituted. The tension in the left eye dropped to 35 mm. Hg in several hours but failed to respond further. Humorsol (0.25 percent b.i.d.) and Epitrate (two percent) also failed to reduce the tension and two days later the pressure rose to 46 mm. Hg in the left eye. Urea was then given intravenously (1.0 gm./kg. in 10-percent invert sugar) at a rate of four cc. per minute. The pressure dropped to 27 mm. Hg 45 minutes later but failed to respond further. With continued Diamox and miotic therapy the tension was maintained at this level for several days, fluc tuating in the low 30's. Two weeks later, a modi fied Scheie procedure was performed. An eight-mm. scleral incision was made into the anterior cham ber with the Hildreth coagulator and a hole burned into the iris with the coagulator to effect an iridectomy. Postoperatively, a good filtering bleb formed and the tension was controlled. OBSERVATIONS AND C O M M E N T
A review of the cases just presented in dicates that urea was an effective therapeutic agent for lowering the intraocular pressure in patients with acute angle-closure glaucoma who had not responded to a combination of miotic and Diamox therapy. It was most efficacious in the first three cases but not in the fourth. T h e first three were primary and the last a secondary angle-closure variety of glaucoma. This drug satisfies the prerequi sites for an ideal osmotic agent. It has low molecular weight, is nontoxic, with poor ocular penetration, thus permitting the de velopment of a high and sustained osmotic gradient. W i t h this therapy the glaucomatous crisis can be broken and the patient prepared
either for immediate surgery or controlled by miotics for surgery at a later date. T h e sur gery is then performed under ideal condi tions. Limitations in the use of Diamox are apparent in Case 2, where an acute attack ensued in a patient under intensive Diamox and miotic therapy. T h e conscientious ad ministration of miotics merely served to drain further an already shallow anterior chamber in an eye where Diamox had failed to break the crisis. I n addition, flooding the conjunctival cul-de-sac with miotics produced symptoms of parasympathetic toxicity. All these factors served to cause a precipitous rise in pressure that was broken only by urea, thus effectively utilizing the osmotic principle. Surgery could then take place un der ideal conditions. The rate of flow of the intravenous urea, as has been mentioned, was three to five cc. per minute. At this rate the entire dosage (1.0 g m . / k g . in 10-percent invert sugar) was delivered in 30 to 60 minutes. However, in one case it was necessary to administer a second dose in five minutes, when earlier urea had failed to produce hypotony of the globe. T h e patient had experienced symptoms of acute glaucoma for three days. Increased turbidity of the aqueous and damage to the blood aqueous barrier, a result of neglect, altered the osmotic reqirements. Rapid ad ministration of urea, however, served sud denly and effectively to increase the osmotic gradient to a point where the drug could exert its effect in the presence of a turbid aqueous and a severely damaged blood aqueour barrier. T h e limitations of urea's usefulness are most apparent in Case 4. Secondary glaucoma was present as a result of the proliferation of new blood vessels on the iris surface and in the anterior chamber angle. This neovascularization was due to diabetes mellitus of long duration. Intravenous urea, administered at a rapid rate, produced a moderate and short lived fall in intraocular pressure. A turbid aqueous, the result of neovascularization,
UREA AND ANGLE-CLOSURE GLAUCOMA coupled with a broken aqueous barrier, made it impossible for urea to produce a high and sustained osmotic gradient. I n this instance, therefore, urea was of limited value. T h e one side-effect noted was occasional headache. This was attributed to a fall in the cerebrospinal fluid pressure of short dura tion. 4 SUMMARY
Intravenous administration of urea pro duced a rapid fall in the intraocular pres-
875
sure in three out of four patients with acute angle-closure glaucoma, who had been re fractory to a combination of Diamox and miotic therapy. T h e drug has only limited usefulness in patients with secondary glaucoma who dem onstrate a turbid aqueous and damage to the blood aqueous barrier. Establishing a satisfactory osmotic gradient is thus pre vented. 450 Clarkson Avenue
(3).
REFERENCES
1. Becker, B.: Decrease in intraocular pressure in man by carbonic anhydrase inhibitor, Diamox: Preliminary report. Am. J. Ophth., 37:13-15 (Jan.) 1954. 2. Dyar, E. W., and Matthew, W. B.: Use of sucrose preparatory in surgical treatment of glaucoma: Preliminary Report. Arch. Oph., 18:57, 1937. 3. Anderson, W. A. D.. and Bethea, W. R.: Renal lesion following administration of hypertonic solution of Sucrose. J.A.M.A., 114:1983-1987,1940. 4. Javid, M.: New use of an old drug. Surg. Clin. N. Am., 1958, p. 907. 5. Galin, M. A., Aizawa, F., and McLean, J. M.: Urea as an osmotic ocular hypotensive agent in glau coma. AM A Arch. Ophth., 62:347, 1959. 6. : Intravenous urea in the treatment of acute angle closure glaucoma. Am. J. Ophth., 50:379 (Sept.) 1960. 7. Kloti, R.: Harnstoff—Infusion in der Glaucomtherapie. Ophthalmologica, 140:135-146, 1960.
THE ACTION OF UREA IN ACUTE GLAUCOMA* A L B E R T L.
ACKERMAN,
M.D.
New York There are few events in ophthalmology as dramatic as the precipitous drop in intra ocular pressure which follows the use of urea in acute glaucoma. This occurs within 45 minutes, regardless of etiology, and despite the failure of previous therapy. T h e measur able effect of intravenous urea lasts five to 12 hours. Although initially it was suggested only in the management of acute glaucoma in preparation for surgery, it has become apparent that the boundaries of its usefulness reach beyond this limitation. In angle-closure glaucoma, urea, by its rapid lowering of in traocular pressure, enables miotics to become effective and terminates the acute attack. Operative management then becomes elective, with iridectomy the procedure of choice. * From the Ophthalmology Service of Montefiore Hospital.
U r e a is a substance of broad scientific interest which, until recently, has been therapeutically neglected. Historically, urea is im portant as the first organic substance to be synthesized from inorganic compounds (Fredrich Wohler in 1828) thereby initiating the field of organic chemistry. Phylogenetically, it is the chief end-product of protein metabolism in mammals, as dif ferentiated from birds and reptiles, which excrete uric acid, presumably to conserve water. Physiologically, by acting as a carrier, it detoxifies the N H 3 resulting from deamination during metabolism of amino acids. It is formed in the liver from arginine, carried in the blood stream, and excreted by the kidney by glomerular filtration. Fifty percent is reabsorbed by the kidney tubules by an active