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Injection of Hyaluronidase into the Anterior Chamber of the Rabbit Eye*
INJECTION O F HYALURONIDASE INTO T H E A N T E R I O R CHAMBER O F T H E RABBIT EYE* JOSEPH E. ALFANO, M.D.,
A ND JAMES CLAMPIT, P H . D .
Chicago, Illinois PART I
Since the isolation of hyaluronidase from bovine vitreous in 1934, various ophthalmologic uses for this preparation have been sug gested. Akinesia1 as produced by either the O'Brien or Van Lint method has been found to be more rapid, certain, and profound when hyaluronidase is added to the procaineepinephrine combination. In surgical proced ures in which retrobulbar anesthesia2 is to be used, particularly in cases where a lowering of the intraocular pressure is desired, the ad dition of hyaluronidase has been helpful. It has also been incorporated2 in retrobulbar injection to reduce the ocular pressure in acute glaucoma. Retrobulbar injection of hyaluronidase has been recommended to re duce the edema of the orbital tissues associ ated with thyrotropic exophthalmos.3 Hyaluronidase has been used subconjunctivally2 to reduce hypopyon associated with corneal ulcers and to increase the penetration and absorption of antibiotics administered subconjunctivally. It also has been of value2 when added to the subconjunctival injection of cocaine-epinephrine and atropine for the releasing of posterior synechias. It has been suggested2 that following in adequate filtering operations for glaucoma subconjunctival injections of five-150 turbid ity-reducing units may increase the efficiency of drainage. Transient and variable improve ment has been reported2 from subconjuncti val administration of hyaluronidase in at tempts to clear corneal edema, scars, opaci ties, and blood vessels. Tassman 4 found that 150 turbidity units of hyaluronidase instilled into the conjunctival sac produces almost immediate improvement
in patients with postoperative chemosis and edema of the conjunctiva persisting after cataract extraction. He further observed that in cases of postoperative chemosis and orbital edema which occasionally occur after enucleation, an injection of 150 turbidity reducing units reduces the chemosis and edema almost immediately. Tassman reported that in five patients with orbital hemorrhage due to traumatism, a retrobulbar injection of procaineepinephrine containing 100 turbidity-reduc ing units of hyaluronidase administered on two successive days produced rapid absorp tion and disappearance of the hemorrhage. In a series of 28 patients with early pterygia, Carriker 5 found that injection of hyaluronidase caused resolution of the growth if the apex of the pterygium had not progressed more than one mm. over the cornea. Instillation of hyaluronidase into the an terior chamber of the eye has been reported by Linn and Ozment.6 According to these workers, this procedure produced iritis, clouding of the cornea, and keratectasia in the rabbit eye. A review of their work in this capacity is as follows: Hyaluronidase was injected into the anterior chamber of 16 normal rabbits in order to determine its effect on the intraocular pressure of the normal eye. The fellow eye of each rabbit was injected with physiologic saline. Observation for a period of 72 hours failed to reveal any significant effect on the intraocular pressure of these rabbits. Concurrently, clinical studies were made by these authors of the effect of instillation of hyaluronidase into the anterior chamber of two patients with secondary glaucoma: The first patient, a 49-yearold woman, had acute nongranulomatous uveitis and secondary glaucoma with an intraocular pressure of 66 mm. Hg (Schijftz). An original anterior chamber paracentesis was reopened daily for six days. Within 24 hours after each reopening the tension would return to 62 to 66 mm. Hg. On the seventh day the anterior chamber was irrigated with a freshly prepared solution of hyaluronidase con taining one turbidity reducing unit per cc. On the Ifollowing day the tension had risen again to 49
* From the Department of Ophthalmology, Northwestern University School of Medicine, and the Department of Biologic Research, G. D. Searle and Company. 198
HYALURONIDASE IN THE ANTERIOR CHAMBER mm. Hg. Irrigation with hyaluronidase was again performed after allowing the aqueous to escape. The tension after the second instillation of the enzyme was 36 mm. Hg (Schijzltz). A subsequent irrigation witfl hyaluronidase three days later failed to produce the same reduction of tension and no further ir rigations were performed. The uveitis subsided a few days thereafter. An anterior chamber paracentesis was performed in a second patient with a similar condition. The paracentesis was reopened daily for four days but tension returned to a high level after each opening. An ocular tension of 77 mm. Hg (Schijftz) was present on the fourth day. On the fifth day reopen ing of the paracentesis was accompanied by irriga tion of the anterior chamber with a freshly prepared solution of hyaluronidase containing one turbidity unit per cc. The tension was normal 24 hours later, but rose again to 72 mm. Hg in 48 hours. Aqueous was again allowed to escape and irrigation with hyaluronidase was repeated. This time the tension remained normal for six days without subsequent opening of the corneal incision.
Linn and Ozment felt that hyaluronidase had exerted a definite beneficial action on intraocular pressure in both of these pa tients. To determine the possibility of dam age to the tissue of the iris, additional rabbit experimentation was performed by these investigators : A freshly prepared solution of hyaluronidase con taining 10 turbidity units per cc. was used. Following application of topical pontocaine anesthesia, 0.1 cc. of this solution was injected with a 27-gauge needle into the anterior chamber of the right eye of 12 albino rabbits once daily for five consecutive days. The left eye of the same rabbits was in jected with 0.1 cc. of physiologic saline. Gross find ings were as follows: 1. At the time of the fourth or fifth intraocular injection, the conjunctiva of several eyes receiving hyaluronidase was friable. 2. Gross changes in the hyaluronidase-treated eyes appeared early and were severe. Corneal clouding appeared in all cases after the fifth injection. The corneal opacity varied in density but obscured the details of the iris in the overwhelming majority. Keratectasia appeared in seven of 12 eyes. Iritis was present in 10 eyes after the second injection and in most instances persisted throughout the injec tion. Only one eye had no apparent iritis on the final day. Histologie studies of the enucleated eyes revealed destruction of the corneal stroma with massive corneal edema, iritis, and congestion of the ciliary processes.
A further study of the injection of hyalu ronidase into the anterior chamber of the eye has been reported by Moor and Shahan 7 who
199
administered the drug to 11 patients with glaucoma and who gave a more favorable re port. Their most striking case was a patient with chronic, noncongestive, absolute glau coma with an intraocular pressure of 65 mm. Hg (Schi^tz) before injection. One injec tion of hyaluronidase into the anterior chamber was followed by a very rapid fall of tension to below 20 mm. Hg with a slow return to 30 mm. Hg. The tension remained stable at this point during the 26 days in which the patient was under observation. It has been suggested8 that a difference in preparation of the hyaluronidase may have accounted for the differing results reported by Linn and Ozment6 and Moor and Shahan.7 The latter authors prepared the drug them selves from testicular tissues obtained from the packing plant. The possibility that the reaction produced by the injection of hyalu ronidase into the anterior chamber by Linn and Ozment could have been related to the degree of purification or sterility of the preparation 9 has also been discussed. In this connection it is pointed out that of the 12 eyes used as controls, two showed an iritis on the second day, one showed a probable ir-itis on the first, and another on the second day. On the fifth day three of the control eyes showed a clouding of the cornea and two of these showed a keratectasia. PART II
This report is concerned with a series of 10 rabbit eyes, eight of which received hyalu ronidase (Alidase-Searle) in the anterior chamber and two control eyes which received anterior-chamber injections of physiologic saline. Of the eight Alidase-treated eyes, Eyes 1 through 7 received 0.05 cc. of Alidase (500 viscosity-reducing units* per cc. or 25 vis* While there is no direct clinical measurement correlating viscosity-reducing units with turbidity reducing units, it has been assumed by various authors that 500 viscosity units equals the clinical activity of approximately ISO turbidity-reducing units.
200
JOSEPH E. ALFANO AND JAMES CLAMPIT
cosity reducing units in 0.05 ce.) daily into the anterior chamber for five consecutive days; Eye 8 received 0.1 cc. of Alidase (50 viscosity-reducing units in 0.1 cc.) daily into the anterior chamber for five consecutive days. The control eyes, Eyes 9 and 10, received 0.1 cc. of physiologic saline in the anterior chamber for the same period of time. The in jections were made in the usual fashion, using a 27-gauge needle and topical pontocaine for anesthesia. Beginning 24 hours after the initial injection, the eyes were examined daily for five days and again on the seventh day and in some cases on the 14th day after the initial injection. Table 1 records the observa tions. A mild ciliary flush was graded 1-plus ; moderate, 2-plus ; moderately severe 3-plus ; very severe 4-plus. A mild iris hyperemia was graded 1-plus ; moderate, 2-plus ; moderately severe 3-plus ; very severe 4-plus. Of the seven eyes receiving 0.05 cc. of Alidase, the first showed a mild hyperemia of the iris from the third to the fifth day. The second showed a mild iris hyperemia on the fourth day which had almost disappeared by the fifth day and was completely gone by the next examination on the seventh day. The third eye showed a moderate iris hyperemia on the first day after injection and a mild iris hyperemia from the second to the fifth day. The eye was perfectly normal at the time of the next examination on the seventh day. Eye 4 showed a mild iris hyper emia from the first to the seventh day and was completely normal on the 14th day. The fifth eye was completely normal with the exception of a mild ciliary flush from the second to the fifth day. The sixth eye showed a moderate iris hyperemia 24 hours after the first injection which had almost disappeared in 72 hours and which was completely gone in 96 hours. The seventh eye showed a mild hyperemia of the iris on the first day, a mild local iris hyperemia on the second day, and a moderate hyperemia on the third day. On the fifth day a mild hyperemia was present ; how
ever, hyperemia was gone by the seventh day. The eighth eye, which had received 0.1 cc. of Alidase, showed a moderate iris hyperemia on the first day and mild local iris hyperemia on the second, fourth and fifth days. The eye was completely normal on the seventh day. Eye 9, the first control, appeared es sentially normal. The second control, Eye 10, showed a moderate iris hyperemia on the fourth day which had disappeared on the fifth day. On the fifth day after the initial injection, 24 hours after the last instillation, two of the eyes, Eyes 2 and 5, were considered normal, one of them, Eye 1, was normal except for a mild iris hyperemia, and three of them, Eyes 3, 6, and 8, showed only a mild ciliary flush with a mild hyperemia of the iris. Eye 4 showed, a mild ciliary flush with mild local haze at the site of injection of Alidase, some of which had gone into the cornea. Significantly, by the seventh day after the initial injection none of the Alidase-treated eyes showed anything of significance with the exception of Eye 4 which showed a mild ciliary flush with a mild iris hyperemia, both of which had disappeared at the time of the next examination one week later. At no time did any of the eyes which re ceived anterior chamber injections of Alidase display an alarming reaction such as edema of the lid, conjunctiva, or cornea. Corneal ulcérations, perforation, or hypopyon did not occur. No changes in the clarity of the vitre ous were noted. In none of the eyes was friability of the conjunctiva noted as was re ported by Linn and Ozment.6 In another series of rabbits which had received subconjunctival Alidase, no friability of the con junctiva was observed grossly. In one of these, microscopic examination of the con junctiva revealed no abnormality. If it is possible to consider one turbidityreducing unit as being approximately three viscosity-reducing units, these results are in sharp contrast with those obtained by Linn and Ozment6 in spite of the fact that in Eyes 1 to 7 approximately 7.5 times as much hyal-
HYALURONIDASE IN THE ANTERIOR CHAMBER
201
TABLE 1 OBSERVATIONS AFTER INJECTION OF HYALURONIDASE INTO T H E ANTERIOR CHAMBERS OF RABBIT EYES Before Injection
Findings EYEI
Conjunctival hyperemia Ciliary Flush Corneal Haze Pupil Size Iris Hyperemia Lens haze or opacity EYE 2 Conjunctival hyperemia Ciliary Flush Corneal haze Pupil Size Iris hyperemia Lens haze or opacity EYE 3 Conjunctival hyperemia Ciliary flush Corneal haze Pupil size Iris hyperemia Lens haze or opacity EYE 4 Conjunctival hyperemia Ciliary flush Corneal haze Pupil size Iris hyperemia Lens haze or opacity EYE 5 Conjunctival hyperemia CUiary flush Corneal haze Pupil size Iris hyperemia Lens haze or opacity EYE 6 Conjunctival hyperemia Ciliary flush Corneal haze Pupil size Iris hyperemia Lens haze or opacity EYE 7 Conjunctival hyperemia Ciliary flush Corneal haze Pupil size Iris hyperemia Lens haze or opacity EYE 8 Conjunctival hyperemia CUiary flush Corneal haze Pupil size Iris hyperemia Lens haze or opacity EYE 9 Conjunctival hyperemia Ciliary flush Corneal haze Pupil size Iris hyperemia Lens haze or opacity EYE 10 Conjunctival hyperemia Ciliary flush Corneal haze Pupil size Iris hyperemia Lens haze or opacity
Hours After Initial Injection 24
48
0 0 0 6 0 0
+(Local)
± (Local)
0 0 0 7 0 0 0 0 0 8 0 0 0 0 0 7 0 0 0 0 0 9 0 0 0 0 0 8 0 0 0 0 0 9 0 0 0 0 0 8 0 0 0 0 0 4.5 0 0 0 0 0 S 0 0
72
96
+
+
7th Day
14th
0 0 0 8
0 0 0 7 0 0
0 0 0 8 0 0
0 0 0 6 0 0
0 0 8 0 0
+0 +0
+0
+0
0 0 0 8 0 0
0 0 0 8 0 0
0 0 0 8 0 0
0 0
0 0 0 7
0
0
0 0 8 0 0
8
+0
Sth Day
8
+(Local) 7
+0
± (Local)
± (Local)
± ±0
± (Local)
+0 +
+0
+0
+0
±
+
± 7
0
+
± 7
0
6
+ +(Local)
± +(Local)
+ +(Local)
+0
+0
+0
0
± + +8
+0
7
7
±
+ +(Local) 8 0 0
± ++ ± (Local) 8
0 0
±
± + (Local)
0
6 0 0
+
+0 + 7
± 6
0
0 0 0
0 0 0 6 0 0
+0 9
±0 0
±
+(Local)
+ + ++ +(Local)
± ++
0
±
± +
+ + ±8
± (Local)
± (Local)
+0 +
+(Local)
7
0
+0 5 0 0 0
+0 0s 0
7
0
0 0
7 0 0
0 0 0 8 0 0
0
0
0
±0
+0 7
+ 0
uronidase was injected and in Eye 8 ap proximately 16.32 times as much hyaluroni dase was used. SUMMARY
Various ophthalmologic uses of hyaluroni dase are reviewed. The clinical and experi-
+ 0 8 0 0
0 0 0 5 0 0
+0
+ + +5 0
0
+0
6
0
6
0
0 0 0 7 0 0
+0
9 0 0
+0 +
7
+0
0 0 0 7 0 0
+0
+(Local)
+(Local)
0
+
± (Local)
+0
+0
0
0
+0
+0 + ± ±7 +0
8
0 7
0
+
+(Local) 6 0 0
6
s0 0
0 0 0 7 0 0
0 0 0 7
0 0 0 7 0 0
±0
0
+
+(Local)
+(Local)
+(Local)
+0
0
++ ±0
++ 7 0
+0 6 0 0 0
+0+ s +0+
7
± + +7 0 0
+ S
5 0 0
0
±
+(Local) 7 0 0
Day
0
+ 0 6 0 0
0 0 0 8 0 0
± +0 s 0 0
+ +
+(Local) 7
+ 0
mental work of Linn and Ozmet6 is pre sented; these authors reported that instilla tion of hyaluronidase into the anterior chamber of the rabbit eye produced iritis, clouding of the cornea, and keratectasia. The results are compared with our series in which no adverse effects of consequence were
202
GUÖMUNDUR BJÖRNSSON
noted when hyaluronidase was injected into the anterior chamber of the rabbit eye. It is suggested that the difference in the results obtained may have been due to differences in preparations used or in the degree of purifi-
cation of the earlier hyaluronidase product. On the basis of these studies, further clini cal investigations utilizing anterior-chamber injections of hyaluronidase are planned. 303 East Chicago Avenue (H).
REFERENCES
1. Atkinson, W. S. : Use of hyaluronidase with local anesthesia in ophthalmology; Preliminary report. Arch. Ophth., 42:628 (Nov.) 1949. 2. Lebensohn, J. E. : Hyaluronidase in ocular surgery and therapy. Am. J. Ophth., 33 :86S (June) 1950. 3. Kadin, M. : Hyaluronidase in thyrotropic exophthalmos ; Report of a case. Am. J. Ophth., 33:962 (June) 1950. 4. Tassman, I. S. : The use of hyaluronidase in ophthalmology, Am. J. Ophth., 35:683 (May) 1952. 5. Carriker, R. F . : The use of hyaluronidase in ophthalmology. Am. J. Ophth., 35:1765 (Dec.) 1952. 6. Linn, J. G., Jr., and Ozment, T. L. : Some effects of injection of hyaluronidase into the anterior chamber. Am. J. Ophth., 33:33 (Jan.) 1950. 7. Moor, W. E., and Shahan, P. : Some possible applications of spreading factors in ophthalmology : Preliminary report. Midwest Sect. A. Res. Ophth., St. Louis, 1949. 8. Miles, P. W. : In discussion of Linn, J. G., Jr., and Ozment, T. L. : Some effects of injection of hyaluronidase into the anterior chamber. Am. J. Ophth., 33:33 (Jan.) 1950. 9. von Sallmann, L. : In discussion of Linn, J. G., Jr., and Ozment, T. L. : Some effects of injection of hyaluronidase into the anterior chamber. Am. J. Ophth., 33 :33 (Jan.) 1950.
PREVALENCE AND CAUSES O F BLINDNESS IN ICELAND WITH
SPECIAL REFERENCE TO GLAUCOMA S I M P L E X GUOMUNDUR BJÖRNSSON,
M.D.
Reykjavik, Iceland PREVIOUS
INFORMATION
In the Annual Health Report for Iceland, figures are given showing the number of blind persons reported by the district physi cians. As stated there, however, the report is far from exhaustive. Thus the figure of 295 given for 1948 and referred to in the Epidemiological and Vital Statistics Report ( 6 : No. 1, 1953) is by far too low. The true number of blind persons has undoubtedly been well over 400 as will be seen from this article. More accurate information on the prev alence of blindness is obtained through the census methods. Not only are the blind enu merated and registered at the general de cennial censuses but they are also registered toward the end of each year, when the parish rectors and municipal authorities take the annual census. The census papers include a column in
which is stated whether the enumerated per son suffers from blindness. According to the instructions given "all persons who are totally blind, or cannot find their way in places unknown to them before by means of their sight," shall be registered as blind. Table 1 shows the number of blind persons registered and the rate of blindness according to the census of 1880 and 1890 and the de cennial censuses from 1910 on. SPECIAL SURVEY,
1940
An experienced ophthalmologist in Reyk javik (Sveinsson, 1944) examined critically the blind register for 1940. With the aid of the Iceland Association for the Aid of Blind People, he tried to contact all the registered blind and to obtain information from the doctors about those he had not seen himself. He arrived at the conclusion that the number of blind persons was at least 409 (379 ac-
A ND JAMES CLAMPIT, P H . D .
Chicago, Illinois PART I
Since the isolation of hyaluronidase from bovine vitreous in 1934, various ophthalmologic uses for this preparation have been sug gested. Akinesia1 as produced by either the O'Brien or Van Lint method has been found to be more rapid, certain, and profound when hyaluronidase is added to the procaineepinephrine combination. In surgical proced ures in which retrobulbar anesthesia2 is to be used, particularly in cases where a lowering of the intraocular pressure is desired, the ad dition of hyaluronidase has been helpful. It has also been incorporated2 in retrobulbar injection to reduce the ocular pressure in acute glaucoma. Retrobulbar injection of hyaluronidase has been recommended to re duce the edema of the orbital tissues associ ated with thyrotropic exophthalmos.3 Hyaluronidase has been used subconjunctivally2 to reduce hypopyon associated with corneal ulcers and to increase the penetration and absorption of antibiotics administered subconjunctivally. It also has been of value2 when added to the subconjunctival injection of cocaine-epinephrine and atropine for the releasing of posterior synechias. It has been suggested2 that following in adequate filtering operations for glaucoma subconjunctival injections of five-150 turbid ity-reducing units may increase the efficiency of drainage. Transient and variable improve ment has been reported2 from subconjuncti val administration of hyaluronidase in at tempts to clear corneal edema, scars, opaci ties, and blood vessels. Tassman 4 found that 150 turbidity units of hyaluronidase instilled into the conjunctival sac produces almost immediate improvement
in patients with postoperative chemosis and edema of the conjunctiva persisting after cataract extraction. He further observed that in cases of postoperative chemosis and orbital edema which occasionally occur after enucleation, an injection of 150 turbidity reducing units reduces the chemosis and edema almost immediately. Tassman reported that in five patients with orbital hemorrhage due to traumatism, a retrobulbar injection of procaineepinephrine containing 100 turbidity-reduc ing units of hyaluronidase administered on two successive days produced rapid absorp tion and disappearance of the hemorrhage. In a series of 28 patients with early pterygia, Carriker 5 found that injection of hyaluronidase caused resolution of the growth if the apex of the pterygium had not progressed more than one mm. over the cornea. Instillation of hyaluronidase into the an terior chamber of the eye has been reported by Linn and Ozment.6 According to these workers, this procedure produced iritis, clouding of the cornea, and keratectasia in the rabbit eye. A review of their work in this capacity is as follows: Hyaluronidase was injected into the anterior chamber of 16 normal rabbits in order to determine its effect on the intraocular pressure of the normal eye. The fellow eye of each rabbit was injected with physiologic saline. Observation for a period of 72 hours failed to reveal any significant effect on the intraocular pressure of these rabbits. Concurrently, clinical studies were made by these authors of the effect of instillation of hyaluronidase into the anterior chamber of two patients with secondary glaucoma: The first patient, a 49-yearold woman, had acute nongranulomatous uveitis and secondary glaucoma with an intraocular pressure of 66 mm. Hg (Schijftz). An original anterior chamber paracentesis was reopened daily for six days. Within 24 hours after each reopening the tension would return to 62 to 66 mm. Hg. On the seventh day the anterior chamber was irrigated with a freshly prepared solution of hyaluronidase con taining one turbidity reducing unit per cc. On the Ifollowing day the tension had risen again to 49
* From the Department of Ophthalmology, Northwestern University School of Medicine, and the Department of Biologic Research, G. D. Searle and Company. 198
HYALURONIDASE IN THE ANTERIOR CHAMBER mm. Hg. Irrigation with hyaluronidase was again performed after allowing the aqueous to escape. The tension after the second instillation of the enzyme was 36 mm. Hg (Schijzltz). A subsequent irrigation witfl hyaluronidase three days later failed to produce the same reduction of tension and no further ir rigations were performed. The uveitis subsided a few days thereafter. An anterior chamber paracentesis was performed in a second patient with a similar condition. The paracentesis was reopened daily for four days but tension returned to a high level after each opening. An ocular tension of 77 mm. Hg (Schijftz) was present on the fourth day. On the fifth day reopen ing of the paracentesis was accompanied by irriga tion of the anterior chamber with a freshly prepared solution of hyaluronidase containing one turbidity unit per cc. The tension was normal 24 hours later, but rose again to 72 mm. Hg in 48 hours. Aqueous was again allowed to escape and irrigation with hyaluronidase was repeated. This time the tension remained normal for six days without subsequent opening of the corneal incision.
Linn and Ozment felt that hyaluronidase had exerted a definite beneficial action on intraocular pressure in both of these pa tients. To determine the possibility of dam age to the tissue of the iris, additional rabbit experimentation was performed by these investigators : A freshly prepared solution of hyaluronidase con taining 10 turbidity units per cc. was used. Following application of topical pontocaine anesthesia, 0.1 cc. of this solution was injected with a 27-gauge needle into the anterior chamber of the right eye of 12 albino rabbits once daily for five consecutive days. The left eye of the same rabbits was in jected with 0.1 cc. of physiologic saline. Gross find ings were as follows: 1. At the time of the fourth or fifth intraocular injection, the conjunctiva of several eyes receiving hyaluronidase was friable. 2. Gross changes in the hyaluronidase-treated eyes appeared early and were severe. Corneal clouding appeared in all cases after the fifth injection. The corneal opacity varied in density but obscured the details of the iris in the overwhelming majority. Keratectasia appeared in seven of 12 eyes. Iritis was present in 10 eyes after the second injection and in most instances persisted throughout the injec tion. Only one eye had no apparent iritis on the final day. Histologie studies of the enucleated eyes revealed destruction of the corneal stroma with massive corneal edema, iritis, and congestion of the ciliary processes.
A further study of the injection of hyalu ronidase into the anterior chamber of the eye has been reported by Moor and Shahan 7 who
199
administered the drug to 11 patients with glaucoma and who gave a more favorable re port. Their most striking case was a patient with chronic, noncongestive, absolute glau coma with an intraocular pressure of 65 mm. Hg (Schi^tz) before injection. One injec tion of hyaluronidase into the anterior chamber was followed by a very rapid fall of tension to below 20 mm. Hg with a slow return to 30 mm. Hg. The tension remained stable at this point during the 26 days in which the patient was under observation. It has been suggested8 that a difference in preparation of the hyaluronidase may have accounted for the differing results reported by Linn and Ozment6 and Moor and Shahan.7 The latter authors prepared the drug them selves from testicular tissues obtained from the packing plant. The possibility that the reaction produced by the injection of hyalu ronidase into the anterior chamber by Linn and Ozment could have been related to the degree of purification or sterility of the preparation 9 has also been discussed. In this connection it is pointed out that of the 12 eyes used as controls, two showed an iritis on the second day, one showed a probable ir-itis on the first, and another on the second day. On the fifth day three of the control eyes showed a clouding of the cornea and two of these showed a keratectasia. PART II
This report is concerned with a series of 10 rabbit eyes, eight of which received hyalu ronidase (Alidase-Searle) in the anterior chamber and two control eyes which received anterior-chamber injections of physiologic saline. Of the eight Alidase-treated eyes, Eyes 1 through 7 received 0.05 cc. of Alidase (500 viscosity-reducing units* per cc. or 25 vis* While there is no direct clinical measurement correlating viscosity-reducing units with turbidity reducing units, it has been assumed by various authors that 500 viscosity units equals the clinical activity of approximately ISO turbidity-reducing units.
200
JOSEPH E. ALFANO AND JAMES CLAMPIT
cosity reducing units in 0.05 ce.) daily into the anterior chamber for five consecutive days; Eye 8 received 0.1 cc. of Alidase (50 viscosity-reducing units in 0.1 cc.) daily into the anterior chamber for five consecutive days. The control eyes, Eyes 9 and 10, received 0.1 cc. of physiologic saline in the anterior chamber for the same period of time. The in jections were made in the usual fashion, using a 27-gauge needle and topical pontocaine for anesthesia. Beginning 24 hours after the initial injection, the eyes were examined daily for five days and again on the seventh day and in some cases on the 14th day after the initial injection. Table 1 records the observa tions. A mild ciliary flush was graded 1-plus ; moderate, 2-plus ; moderately severe 3-plus ; very severe 4-plus. A mild iris hyperemia was graded 1-plus ; moderate, 2-plus ; moderately severe 3-plus ; very severe 4-plus. Of the seven eyes receiving 0.05 cc. of Alidase, the first showed a mild hyperemia of the iris from the third to the fifth day. The second showed a mild iris hyperemia on the fourth day which had almost disappeared by the fifth day and was completely gone by the next examination on the seventh day. The third eye showed a moderate iris hyperemia on the first day after injection and a mild iris hyperemia from the second to the fifth day. The eye was perfectly normal at the time of the next examination on the seventh day. Eye 4 showed a mild iris hyper emia from the first to the seventh day and was completely normal on the 14th day. The fifth eye was completely normal with the exception of a mild ciliary flush from the second to the fifth day. The sixth eye showed a moderate iris hyperemia 24 hours after the first injection which had almost disappeared in 72 hours and which was completely gone in 96 hours. The seventh eye showed a mild hyperemia of the iris on the first day, a mild local iris hyperemia on the second day, and a moderate hyperemia on the third day. On the fifth day a mild hyperemia was present ; how
ever, hyperemia was gone by the seventh day. The eighth eye, which had received 0.1 cc. of Alidase, showed a moderate iris hyperemia on the first day and mild local iris hyperemia on the second, fourth and fifth days. The eye was completely normal on the seventh day. Eye 9, the first control, appeared es sentially normal. The second control, Eye 10, showed a moderate iris hyperemia on the fourth day which had disappeared on the fifth day. On the fifth day after the initial injection, 24 hours after the last instillation, two of the eyes, Eyes 2 and 5, were considered normal, one of them, Eye 1, was normal except for a mild iris hyperemia, and three of them, Eyes 3, 6, and 8, showed only a mild ciliary flush with a mild hyperemia of the iris. Eye 4 showed, a mild ciliary flush with mild local haze at the site of injection of Alidase, some of which had gone into the cornea. Significantly, by the seventh day after the initial injection none of the Alidase-treated eyes showed anything of significance with the exception of Eye 4 which showed a mild ciliary flush with a mild iris hyperemia, both of which had disappeared at the time of the next examination one week later. At no time did any of the eyes which re ceived anterior chamber injections of Alidase display an alarming reaction such as edema of the lid, conjunctiva, or cornea. Corneal ulcérations, perforation, or hypopyon did not occur. No changes in the clarity of the vitre ous were noted. In none of the eyes was friability of the conjunctiva noted as was re ported by Linn and Ozment.6 In another series of rabbits which had received subconjunctival Alidase, no friability of the con junctiva was observed grossly. In one of these, microscopic examination of the con junctiva revealed no abnormality. If it is possible to consider one turbidityreducing unit as being approximately three viscosity-reducing units, these results are in sharp contrast with those obtained by Linn and Ozment6 in spite of the fact that in Eyes 1 to 7 approximately 7.5 times as much hyal-
HYALURONIDASE IN THE ANTERIOR CHAMBER
201
TABLE 1 OBSERVATIONS AFTER INJECTION OF HYALURONIDASE INTO T H E ANTERIOR CHAMBERS OF RABBIT EYES Before Injection
Findings EYEI
Conjunctival hyperemia Ciliary Flush Corneal Haze Pupil Size Iris Hyperemia Lens haze or opacity EYE 2 Conjunctival hyperemia Ciliary Flush Corneal haze Pupil Size Iris hyperemia Lens haze or opacity EYE 3 Conjunctival hyperemia Ciliary flush Corneal haze Pupil size Iris hyperemia Lens haze or opacity EYE 4 Conjunctival hyperemia Ciliary flush Corneal haze Pupil size Iris hyperemia Lens haze or opacity EYE 5 Conjunctival hyperemia CUiary flush Corneal haze Pupil size Iris hyperemia Lens haze or opacity EYE 6 Conjunctival hyperemia Ciliary flush Corneal haze Pupil size Iris hyperemia Lens haze or opacity EYE 7 Conjunctival hyperemia Ciliary flush Corneal haze Pupil size Iris hyperemia Lens haze or opacity EYE 8 Conjunctival hyperemia CUiary flush Corneal haze Pupil size Iris hyperemia Lens haze or opacity EYE 9 Conjunctival hyperemia Ciliary flush Corneal haze Pupil size Iris hyperemia Lens haze or opacity EYE 10 Conjunctival hyperemia Ciliary flush Corneal haze Pupil size Iris hyperemia Lens haze or opacity
Hours After Initial Injection 24
48
0 0 0 6 0 0
+(Local)
± (Local)
0 0 0 7 0 0 0 0 0 8 0 0 0 0 0 7 0 0 0 0 0 9 0 0 0 0 0 8 0 0 0 0 0 9 0 0 0 0 0 8 0 0 0 0 0 4.5 0 0 0 0 0 S 0 0
72
96
+
+
7th Day
14th
0 0 0 8
0 0 0 7 0 0
0 0 0 8 0 0
0 0 0 6 0 0
0 0 8 0 0
+0 +0
+0
+0
0 0 0 8 0 0
0 0 0 8 0 0
0 0 0 8 0 0
0 0
0 0 0 7
0
0
0 0 8 0 0
8
+0
Sth Day
8
+(Local) 7
+0
± (Local)
± (Local)
± ±0
± (Local)
+0 +
+0
+0
+0
±
+
± 7
0
+
± 7
0
6
+ +(Local)
± +(Local)
+ +(Local)
+0
+0
+0
0
± + +8
+0
7
7
±
+ +(Local) 8 0 0
± ++ ± (Local) 8
0 0
±
± + (Local)
0
6 0 0
+
+0 + 7
± 6
0
0 0 0
0 0 0 6 0 0
+0 9
±0 0
±
+(Local)
+ + ++ +(Local)
± ++
0
±
± +
+ + ±8
± (Local)
± (Local)
+0 +
+(Local)
7
0
+0 5 0 0 0
+0 0s 0
7
0
0 0
7 0 0
0 0 0 8 0 0
0
0
0
±0
+0 7
+ 0
uronidase was injected and in Eye 8 ap proximately 16.32 times as much hyaluroni dase was used. SUMMARY
Various ophthalmologic uses of hyaluroni dase are reviewed. The clinical and experi-
+ 0 8 0 0
0 0 0 5 0 0
+0
+ + +5 0
0
+0
6
0
6
0
0 0 0 7 0 0
+0
9 0 0
+0 +
7
+0
0 0 0 7 0 0
+0
+(Local)
+(Local)
0
+
± (Local)
+0
+0
0
0
+0
+0 + ± ±7 +0
8
0 7
0
+
+(Local) 6 0 0
6
s0 0
0 0 0 7 0 0
0 0 0 7
0 0 0 7 0 0
±0
0
+
+(Local)
+(Local)
+(Local)
+0
0
++ ±0
++ 7 0
+0 6 0 0 0
+0+ s +0+
7
± + +7 0 0
+ S
5 0 0
0
±
+(Local) 7 0 0
Day
0
+ 0 6 0 0
0 0 0 8 0 0
± +0 s 0 0
+ +
+(Local) 7
+ 0
mental work of Linn and Ozmet6 is pre sented; these authors reported that instilla tion of hyaluronidase into the anterior chamber of the rabbit eye produced iritis, clouding of the cornea, and keratectasia. The results are compared with our series in which no adverse effects of consequence were
202
GUÖMUNDUR BJÖRNSSON
noted when hyaluronidase was injected into the anterior chamber of the rabbit eye. It is suggested that the difference in the results obtained may have been due to differences in preparations used or in the degree of purifi-
cation of the earlier hyaluronidase product. On the basis of these studies, further clini cal investigations utilizing anterior-chamber injections of hyaluronidase are planned. 303 East Chicago Avenue (H).
REFERENCES
1. Atkinson, W. S. : Use of hyaluronidase with local anesthesia in ophthalmology; Preliminary report. Arch. Ophth., 42:628 (Nov.) 1949. 2. Lebensohn, J. E. : Hyaluronidase in ocular surgery and therapy. Am. J. Ophth., 33 :86S (June) 1950. 3. Kadin, M. : Hyaluronidase in thyrotropic exophthalmos ; Report of a case. Am. J. Ophth., 33:962 (June) 1950. 4. Tassman, I. S. : The use of hyaluronidase in ophthalmology, Am. J. Ophth., 35:683 (May) 1952. 5. Carriker, R. F . : The use of hyaluronidase in ophthalmology. Am. J. Ophth., 35:1765 (Dec.) 1952. 6. Linn, J. G., Jr., and Ozment, T. L. : Some effects of injection of hyaluronidase into the anterior chamber. Am. J. Ophth., 33:33 (Jan.) 1950. 7. Moor, W. E., and Shahan, P. : Some possible applications of spreading factors in ophthalmology : Preliminary report. Midwest Sect. A. Res. Ophth., St. Louis, 1949. 8. Miles, P. W. : In discussion of Linn, J. G., Jr., and Ozment, T. L. : Some effects of injection of hyaluronidase into the anterior chamber. Am. J. Ophth., 33:33 (Jan.) 1950. 9. von Sallmann, L. : In discussion of Linn, J. G., Jr., and Ozment, T. L. : Some effects of injection of hyaluronidase into the anterior chamber. Am. J. Ophth., 33 :33 (Jan.) 1950.
PREVALENCE AND CAUSES O F BLINDNESS IN ICELAND WITH
SPECIAL REFERENCE TO GLAUCOMA S I M P L E X GUOMUNDUR BJÖRNSSON,
M.D.
Reykjavik, Iceland PREVIOUS
INFORMATION
In the Annual Health Report for Iceland, figures are given showing the number of blind persons reported by the district physi cians. As stated there, however, the report is far from exhaustive. Thus the figure of 295 given for 1948 and referred to in the Epidemiological and Vital Statistics Report ( 6 : No. 1, 1953) is by far too low. The true number of blind persons has undoubtedly been well over 400 as will be seen from this article. More accurate information on the prev alence of blindness is obtained through the census methods. Not only are the blind enu merated and registered at the general de cennial censuses but they are also registered toward the end of each year, when the parish rectors and municipal authorities take the annual census. The census papers include a column in
which is stated whether the enumerated per son suffers from blindness. According to the instructions given "all persons who are totally blind, or cannot find their way in places unknown to them before by means of their sight," shall be registered as blind. Table 1 shows the number of blind persons registered and the rate of blindness according to the census of 1880 and 1890 and the de cennial censuses from 1910 on. SPECIAL SURVEY,
1940
An experienced ophthalmologist in Reyk javik (Sveinsson, 1944) examined critically the blind register for 1940. With the aid of the Iceland Association for the Aid of Blind People, he tried to contact all the registered blind and to obtain information from the doctors about those he had not seen himself. He arrived at the conclusion that the number of blind persons was at least 409 (379 ac-