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Evaluation of the Water Provocative Test*
EVALUATION O F T H E W A T E R PROVOCATIVE TEST* MILES A.
GALIN, M.D.,
FUTABA AIZAW, L, M.D.,
AND J O H N M. MCLEAN,
M.D.
New York While the water provocative test is fre quently used as a tool for the diagnosis of early open-angle glaucoma, its mechanism of action is not universally agreed upon. Com binations of this test with other methods such as the water and pressor-congestion test1 and water drinking and tonography,2 have in no way clarified the picture. As a possible explanation, Leydhecker,3 Kronfeld,4 Heegaard and Larsen, 5 Argawal and Sharma,6 and others have related the rise in intraocular pressure in glaucomatous eyes to initial hemodilution following water consumption. In this regard, studies by Hertel,7 Duke-Elder, 8 and Davson and Thomassen,9 as well as clinical studies by Poos,10 Dyar and Matthew,11 Galin et al.,12 and others have established that the eye, and particularly the glaucomatous eye, is a sensi tive osmometer. However, Schmidt,13 Yonebayashi,14 and others have reported that the response fol lowing water drinking is not initiated by in duced hypo-osmolality. Becker and Christienson,2 Friedenwald,15 Roberts,1* and others have indicated that the ultimate path for the elevation of intraocular pressure after water may be through re duced facility of aqueous outflow. This latter consideration has been commented upon by Bârâny," and Roberts. 18 They have postu lated that swelling of the trabecular area could increase the resistance to outflow. DeRoetth,19 as well as Scheie et al.,20 how ever, have been unable to confirm the re duction in outflow facility in glaucomatous eyes following water ingestion, and have ex plained pressure increases as due to incre ments in flow. Furthermore, Becker and *From the Department of Surgery (Ophthal mology) of the New York Hospital-Cornell Medi cal Center. This study was aided in part by grants from The National Society for the Prevention of Blindness and The National Council to Combat Blindness.
Gay21 have noted that some cases of appar ent decrease in outflow facility following water may be due to alterations in scierai rigidity. Earlier studies attempting to evaluate hemodilution following water consumption in the human being have been relatively crude in light of presently available techniques. These have included serum conductivity measurements,3 reductions in hemoglobin concentration,6,22 determinations of hematocrit response,· and studies of blood water content.1* Though detailed clinical studies12 relating increased blood osmolality and intra ocular pressure have recently appeared, few investigations using these techniques for the study of reduced blood osmolality and intra ocular pressure have been carried out. It is the purpose of this communication to report the blood osmolality changes, intra ocular pressure variations, and tonographic alterations following water consumption by patients in the glaucomatous age group with no evidence of open-angle glaucoma. MATERIALS AND METHODS
Patients were obtained from the eye clinic of the New York Hospital-Cornell Medical Center. All were past 55 years of age, and had no systemic diseases. These patients had been followed in the eye clinic for at least 10 years, and at no time were tensions greater than 20 mm. Hg recorded. Detailed ophthalmologic studies were carried out, and only those with entirely normal examinations were included in the control group. The knowledge of intraocular pressures for a long period, the presence of completely normal fields, and the absence of any ocular disorder on re peated examinations tend to validate the as sumption that this group is free of openangle glaucoma. The patients were kept in a fasting state following their evening meal the day prior to
M. A. G A L I N , F . A I Z A W A A N D J. M. M c L E A N
452
TABLE 1 BLOOD OSMOLALITY IN MIIXIOSMOLES BEFORE AND AT 15-MINUTE INTERVALS FOLLOWING THE RAPID INGESTION O FO N E LITER O F WATER IN 2 5 NORMAL PATIENTS
Sub jects
Milliosmoles before Water
Reduction in Blood Osmolality (after min.) 15
30
45
60
1 2 3 4 S
286.2 294.3 289.0 281.0 289.5
-4.6 -3.9 -7.4 +3.0 -5.0
-7.5 -8.8 -8.4 -5.0 -12.2
-9.8 -13.5 -5.2 -4.5 -12.0
-5.4 -11.6 -16.2 -8.0 -11.9
6 7 8 9 10
284.0 288.2 284.0 295.0 286.2
-3.5 -6.7 -4.0 -5.3 -7.0
-3.0 -9.7 -3.8 -9.8 -7.5
-5.5 -10.5 -3.3 -11.6 -3.4
-8.0 -6.7 -β.7 -14.2 -14.0
11 12 13 14 IS
291.0 290.2 292.2 287.0 289.8
-8.0 -9.7 -1.5 -12.2 -0.1
-5.5 -12.4 -8.7 -11.4 -5.1
-11.3 -12.6 -16.8 -16.8 -5.7
-9.3 -15.7 -4.7 -15.7 -10.3
16 17 18 19 20
288.0 284.6 296.0 296.0 293.7
-4.2 -7.3 -4.0 -4.0 -2.2
-6.7 -6.7 -8.3 -8.3 -4.2
-6.3 -6.4 -11.0 -11.0 -7.7
-9.7 -6.8 -7.0 -7.0 -5.7
21 22 23 24 25
292.2 295.3 283.5 282.0 292.0
-2.7 -2.3 -3.5 -2.8 -4.0
-2.7 -8.0 -5.2 -4.5 -8.0
-5.7 -8.1 -7.1 -5.5 -11.0
-4.5 -7.2 -3.5 -5.3 -11.5
the examination. In 25 cases, blood samples for subsequent analysis of freezing point de pression utilizing a Fiske osmometer were obtained prior to rapid consumption of one liter of water, and at 15-minute intervals for one hour, thereafter. In a group of 45 patients, tonography was performed on multiple occasions so that they became acclimated to the procedure. Applanation and multiple weight recordings with the Mueller electronic tonometer were recorded at all stages of the study, and cal culations of ocular rigidity obtained. On the days of testing, blood samples were ob tained for subsequent analysis of freezing point depression, tonography was performed, and one liter of water rapidly consumed. Sub sequent blood samples were obtained and to nography was again performed approxi
mately 40 minutes following water consump tion. Outflow facility was calculated utilizing Moses' and Becker's tables23 based on Friedenwald's data.24 When any change of ocular rigidity was noted, the data were recalculated to be comparable to those of average rigidity. Flow in cubic milliliters per minute was cal culated by the equation F = C(Po-Pv). No direct measurements of Pv (episcleral ven ous pressure) were obtained, and this value was assumed to be 11.7 mm. RESULTS
Table 1 lists the results of blood osmolality determined in the group subjected to water drinking only. In only one of 100 samples was there a reading of increased milliosmoles following water drinking and in this case all subsequent samples indicated hemodilution. In virtually all cases, then, reduction of blood osmolality is obtained, and no evidence of hemocencentration or atypical hemodilution patterns obtained. This is contrary to data published by Schmidt22 and Yonebayashi.14 Table 2 illustrates the frequency distribu tion of blood osmolality reduction with re spect to time. Eighty-four percent of cases reached maximum hypo-osmolality at 45 minutes to one hour, with the greatest num ber (44 percent) achieving that level at the 45-minute sample. In only one case was a maximum change noted at the 15-minute sampling. The data on alteration in blood osmolality in the group of 45 patients subjected to water drinking and tonography were essentially TABLE 2 F R E Q U E N C Y DISTRIBUTION O F MAXIMUM BLOOD OS M O L A L I T Y CHANGE IN MILLIOSMOLES WITH RE SPECT TO TIME FOLLOWING THE RAPID INGESTION OF ONE LITER OF WATER IN 25 NORMAL PATIENTS
Time Following Water Ingestion 15 min. 30 min. Frequency Percentage
1/25 4.0
3/25 12
45 min.
60 min.
11/25 44
10/25 40
WATER PROVOCATIVE TEST similar to the information presented in Table 1, and will not be repeated. Figure 1 repre sents the intraocular pressure changes, meas ured at approximately 40 minutes, in this normal group following water ingestion. It should be noted that the distribution of val ues corresponds approximately to a normal curve. The range of pressure variation is from a decrease of 4.0 mm. to an increase of 5.0 mm., though the predominant effect is an increase in pressure. This increase is statis tically significant at the one-percent level. Figure 2 depicts the range of facility of aqueous outflow in the normal group before and after water consumption. Table 3 lists the specific data concerning intraocular pres sure, outflow facility, aqueous flow, and Po/C before and after water drinking. It should be noted that approximately 60 per cent of patients had a reduction in outflow facility, the remainder exhibiting either no change or an increase. No correlation be tween initial pressure and facility and ulti mate pressure and facility could be statis tically established. This degree of variability in a normal group is similar to that pub lished by Swanljung and Biodi,25 but varies from the data of Becker and Christienson.2 Analysis of this data with respect to aque ous flow tonographically computed, however, reveals that an increase in flow accounts for the predominant, though small, increase in intraocular pressure. Figure 3 relates the
453
0.05 O.IO 0,15 0.20 0.25 0.30 0.35 0.40 C volt-
Fig. 2 (Galin, Aizawa and McLean). Facilities of aqueous outflow before and 40 minutes after the rapid ingestion of one liter of water in a group of 45 normal patients. change in flow to the change in intraocular pressure, and the apparent correlation is ob vious. Calculations reveal this correlation to be significant at the one-percent level. Calculations of ocular rigidity were made in all cases. However, though data with al tered rigidity have been mathematically changed to be comparable to data with nor mal rigidity, no significant reproducible change in ocular rigidity was ascertainable. Evaluation of the data with respect to Po/C is included in Table 3. Approximately five percent of this normal group had values greater than 100 before water, and 11 per cent greater than 100 following water con sumption. This data, too, is at variance with Becker and Christienson.2 DISCUSSION
Fig. 1 (Galin, Aizawa and McLean). Percentage of patients exhibiting intraocular pressure changes 40 minutes following the rapid ingestion of one liter of water in a group of 45 normals.
Water absorption from the gastro-intes tinal tract is a rather complex process, and subject to a considerable amount of varia tion even in the same patient.26-29 The data herein reported clearly indicate that hypoosmolality occurs following the ingestion of one liter of water. Kinsey30 has indicated, extrapolating rab bit data to man, that the reduction in blood
M. A. GALIN, F. AIZAWA AND J. M. McLEAN
4S4
TABLE 3 INTRAOCULAR PRESSURE ( P O ) ,, FACILITY OF AQUEOUS OUTFLOW ( C )!, AQUEOUS FLOW ( F ) , AND P o / C BEFORE AND AFTER THE RAPID INGESTION OF ONE LITER OF WATER IN 4 5 NORMAL PATIENTS* Right Eye
Left Eye
Po
Po'
ΛΡ
C
C
F
F'
2 3 4 S
14.6 18.1 11.2 12.2 10.2
18.9 20.6 12.2 13.4 10.2
+4.3 +2.1 +1.0 +1.2
.31 .23 .34 .24 .29
.42 .24 .27 .20 .19
0.90 1.47
3.02 2.14
0.12
0.34
6 7 g 9 10
14.0 20.6 10.2 18.1
-0.6
.25 .26 .15 .12 .15
0.43 2,31
+3.4
.23 .30 ,19 .15 .19
0.53 2.67
9.4
13.4 20.6 11.7 18.1 12.8
1.11
0.89
11 12 13 14 15
10.7 15.9 13.4 17.3 14.6
11.7 18.1 15.2 16.6 18.1
+ 1.0 +2.2 + 1.8 +0.7 +3.5
.27 .35 .25 .36 .25
.27 .20 .19 .33 .28
1.47 0.43 2.02 0.73
1.28 0.67 1.76 1.79
16 17 18 19 20
17.3 12.8 14.6 18.9
18.1 15.9 14.6 20.6
9.8
+1.3 +0.8 +3.1 + 1.7
.23 .27 .18 .13 .20
.19 .23 .16 .13 .16
1.51 0.20 0.38 1.44
1.47 0.67 0.38 1.42
2t 22 23 24 25
11.7 14.6 13.4 14.6 15.9
15.2 18.0 15.9 17.3 16.6
+3.5 +3.4 +2.5 +2.7 +0.7
.20 .24 .25 .31 .29
.29 .27 .26 .25 .25
0.70 0.43 0.90 1.22
1.70 1.09 1.40 1.23
26 27 28 29 30
18.9 14.0 11.2 16.6 12.8
15.9 14.6 13.4 15.9 14.0
-3.0 +0.6 +2.2 -0.7 +1.2
.32 .23 .32 .49 .22
.21 .23 .30 .35 .28
2.30 0.53
0.88 0.67
2.40 0.24
1.47 0.64
31 32 33 34 35
17.3 15.9 13.4 12.2 15.9
18.9 17.3 18.9 12.2 18.9
+ 1.6 + 1.4 +5.5 +3.0
.22 .21 .42 .32 .26
.20 .22 .42 .32 .32
1.23 0.88 0.71 0.16 1.09
1.44 1.23 3.02 0.16 2.30
7.5
+5.3 +0.5 -1.2 +S.6 +0.8
.17 .24 .42 .16 .28
.09 .18 .27 .16 .17
+4.9 +2.4 +2.6
.24 .23 .23 .24 .24
.25 .15 .19 .21 .30
J
8.5
36 37 38 39 40
11.7 13.4 15.9 9.4
12.8 12.2 12.2 21.5 10.2
41 42 43 44 45
20.6 14.6 18.9 20,6 15.9
25.5 12.2 21.5 20.6 18.9
0 0
+1.5 0
0
0.0
0.0
+3.0
0.71 0.69
0.14 1.57
2.14 0.67 1.66 2.14 1.01
3.45 0.08 1.86 1.87 2.16
Po
Po'
c C _ _ — _ — _. — _ - ^ _ — _ — _ + +_ _ *, — _~ — _ — __ - _ _ _ — _ — _ + + + — _ _ _ — — _ __ - __ _ _ _ _ _ _ _ — _ _- _ — — _ -, _ — — _ + — _ — _ _ + — __ + — __ + _ — —
Po
Po'
ΔΡ
C
e
15.9 13.4
15.2 17.3 13.4 14.6
-0.7 +3.9 +3.6
8.9
-1.1
.32 .20 .26 .37 .19
.16 .22 .20 .28 .09
11.2 17.3 10.7 13,4
14.0 17.3 10.2 14.6 10.2
+2.8 -0,5 +1.2 +0.4
.29 .22 .19 .15 .19
.23 .30 .17 .11 .11
8.5
10.7 14.6 15.2 15.2 15.9
+2.2 +2.9 -2.1 +0.6 + 1.3
.23 .38 .30 .28 .23
.17 .25 .19 .21 .19
1.68 0.81 0.67
0.67 0.74 0.80
9.8
14.6 7.8
9.8
11.7 17.3 14.6 14.6
0
0
F
F'
1.34 0.34
0.56 1.23
1.07
0.81
1.23
1.68
0.26
0.32
15.9 13.4 13.4 14.0
17.3 15.9 15.9 14.6
9.4
+2.0 +1.4 +2.5 +2.6 +0.6
.19 .21 .18 .15 .20
.15 .17 .14 .12 .15
0.88 0.31 0.26 0.46
1.18 0.59 0.50 0.44
11.7 14.0 15.3 13.4 13.4
12.8 15.3 16.6 15.2 12.1
+ 1.1 +1.3 +1.3 +1.8 +0.6
.32 .23 .26 .23 .18
.20 .19 .30 .21 .11
0.53 0.94 0.39 0.31
0.68 1.47 0.74 0.04
15.2 11.2 11.7 15.2 10.2
14.6 14.0 12.2 13.4 11.7
-0.6 +2.8 +0.5 -1.8 +1.5
.21 .24 .32 .50 .24
,2S .23 .35 .39 .29
0.74
0.73
1.75
0.66
14.6 13.4 18.1
17.3 12.8 14.6 11.2 14.6
+3.3 .18 .15 .15 .13 -0.6 . 34 .48 -3.5 + 1.8 > . 3 9 >.45 . 1 8 .18 +1.2
0.52 0.22 3.07
0.84 0.17 1.39
0.31
0.52
10.2 12.2 11.7
11.7 12.8 13.4 16.6
.15 .24 .32 .15 .28
.15 .20 .28 .17 .19
0,16
0.48
9.8
+3.2 +2.6 + 1.2 +4.7 +0.4
18.1 13,4 18.1 19.7 13.2
20.6 12.2 20.6 18.9 14.4
+2.5 -1.2 +2.5 -0,8 +1.2
.20 .18 .20 .27 .17
.27
1.28 0.31 1.28 0.22
2.40
7.4
9.4
13.4 8.5
9.4
.24 .17
2.14
Po C~
_ — — — _ — — — — _ — — — _ — — — ^ — — — _ — — — _
Po'
c _ — — — — _ — —
+
_ — — — _ + + + _ — — —
+
— — — -
+ + _ — _ — — — — _ — —
— _ — — — — _ — —
* Values of Po/C greater than 100 are indicated as + ; those below 100 as —.
osmolality following ingestion of one liter of water would be about four millimoles. This figure is similar to our observed results and close to those theoretically obtainable if total body water is assumed to be in the range of 60 percent. We may at least infer, therefore, that with respect to intraocular pressure the initiating sequence of events following water ingestion is related to a reduction in blood osmolality. Fluid will then enter the eye on the basis of the induced osmotic gradient. The eye with a significantly elevated pressure would be most sensitive to the slightest alteration in ocular
volume12 with moderate to large pressure changes resulting. In this regard, Bârâny" has commented that the water drinking test could act by fa cilitating inflow. He also has noted that any prolonged elevation of intraocular pressure would be due to a change in resistance or to an increase in resultant venous pressure. The use of tonography, or tonography combined with water drinking, would label quite a few of these normal patients glaucomatous, if Becker and Christienson's cri teria were followed.2 Perhaps the variance of our data with theirs lies in the choice of con-
4SS
WATER PROVOCATIVE TEST trol groups, as all of our patients were in the commonly accepted glaucomatous age range. The progressive decrease in outflow facility accompanying the aging process has been described by Becker.31 Detailed analysis of the data presented here discloses several major shortcomings in the application of "quantitative" tonography. First, we have little accurate data on the ef fect of rapid increase in total body water on the episcleral venous pressure. Duke-Elder 8 has demonstrated a prompt increase in ven ous pressure following the administration of hypotonie and even isosmotic solutions in animals. Second, all calculations of outflow facility assume the eye to be in a steady-state with the assumption that flow remains con stant. It is apparent that after water drink ing the eye is not in a steady-state, and that ocular volume increases. Only the fact that tonography is performed for just four min utes during which time major changes in flow probably do not occur permits a com parison of outflow facility before and after water. However, any comparison is not ab solutely mathematically sound. Last, the term, flow, is rather loosely used in these and other studies. Osmotic alterations may cause changes in aqueous flow, but cer tainly may alter ocular volume through changes in intravascular volume, as well as secretion. It has been noted that intraocular pressure reflects the pressure in several dif ferent vascular beds.32 Until the effect of al tered blood osmolality on these systems is known, there is insufficient basis to relate intraocular pressure change solely to changes in flow, even when outflow facility appears unaltered. It should be apparent, then, that calculât-
mm. Hg.
+6
• •
+5 +4
-
*
+S
•
<'·..;
•
+2
•
·
+1 0
..
- 1
■.
-2 -3 -4
1
. 1·„ i
.
·■»
■
■■ i
+ to
Î +20
+M> mmVmm
Fig. 3 (Galin, Aizawa and McLean). Relation ship of inflow, tonographically computed, and intra ocular pressure change following the rapid inges tion of one liter of water in 45 normal patients. ing outflow facility in an eye not in a steadystate, and flow using assumptions that have not been proved, leaves much to be desired. SUMMARY
Following rapid ingestion of one liter of water, blood osmolality is reduced, the great est reduction occurring at the 45- to 60minute sample. In a nonglaucomatous group of patients in the glaucomatous age group, there is a statistically significant increase in aqueous "flow," tonographically calculated, accounting for an increase in intraocular pressure that is statistically significant, though small in magnitude after water drink ing. This data would tend to indicate that the initiating sequence of events following water consumption is related to the osmotic gradient established. It would also tend to indicate theoretical errors in utilizing quantitative to nography following water ingestion. 525 East 68th Street (21).
REFERENCES
1. Sugar, H. S.: The provocative tests in the diagnosis of the glaucomas. Am. J. Ophth., 31:1193, 1948. 2. Becker, B., and Christienson, R. E.: Water drinking and tonography in the diagnosis of glaucoma. AMA Arch. Ophth., 56:321,1956. 3. Leydhecker, W.: The water drinking test. Brit. J. Ophth., 34:457, 1950. 4. Kronfeld, P.: Glaucoma: A Symposium, Springfield, 111., Thomas, 1955, p. 233. 5. Heegaard, S., and Larsen, V.: Einiges über den Wasserstoffwechsel bei Normalen und Glaucomkranken. Acta. Ophth., 9:302,1931.
456
M. A. GALIN, F. AIZAWA AND J. M. McLEAN
6. Argawal, L. P., and Sharma, C K.: Two provocative tests for glaucoma. Brit. J. Ophth., 37:330, 19S3. 7. Hertel, E.: Experimentelle Untersuchungen über die Abhängigkeit des Augendrucks von der Blutbeschaffenheit. Arch. f. Ophth., 88:197, 1914. 8. Duke-Elder, W. S. : The reaction of the intraocular pressure to osmotic variation in the blood. Brit. J. Ophth., 10:1,1926. 9. Davson, H., and Thomassen, T. L. : The effect of intravenous infusion of hypertonic saline on the intraocular pressure. Brit. J, Ophth., 34:355, 1950. 10. Poos, F.: Klinische Untersuchungen über die Beziehungen Zurschen Osmose, Blutdruck und Augendruck. Klin. Monatsbl. f. Augenh., 84:340, 1930. 11. Dyar, E. W., and Matthew, W. B.: Use of sucrose preparatory to surgical treatment of Glaucoma: A preliminary report. Arch. Ophth., 18:57, 1937. 12. Galin, M. A., Aizawa, F., and McLean, J. M. : Urea as an osmotic ocular hypotensive agent in glaucoma. AMA Arch. Ophth., 62:347, 1959. 13. Schmidt, K.: Trinkversuch und Glaukomproblem. Arch, f. Augenh., 104:102, 1931. 14. Yonebayashi, M.: Blood water content and water drinking test. Acta. Ophth. Jap., 62:1454, 1958. 15. Friedenwald, J.: Glaucoma: A Symposium. Springfield, Thomas, 1955, p. 251. 16. Roberts, W.: Tonographic criteria in early glaucoma: Clinical tonography as an aid to the diag nosis and management of early glaucoma. Am. J. Ophth., 48:31 (Nov. Pt. I) 1959. 17. Bârâny, E.: Glaucoma: A Symposium. Springfield, 111., Thomas, 1955, p. 251. 18. Roberts, W.: Glaucoma: Tr. Third Conference. New York, Josiah Macy, Jr., Foundation, 1958, p. 214. 19. de Roetth, A., Jr.: Effect of changes in osmotic pressure of blood on aqueous humor dynamics. AMA Arch. Ophth., 52:571, 1954. 20. Scheie, H. G., Spencer, R. W., and Helmick, E. D.: Tonography in the clinical management of glaucoma. AMA Arch. Ophth., 56:797, 1956. 21. Becker, B., and Gay, A.: Applanation tonometry in the diagnosis and treatment of glaucoma. AMA Arch. Ophth., 62:211, 1959. 22. Schmidt, K.: Untersuchungen über Capillarendothelstorungen bei Glaucoma Simplex. Arch. f. Augenh., 98:569,1928. 23. Moses, R. A., and Becker, B.: Clinical tonography: The scierai rigidity correction. Am. J. Ophth., 45:196, 1958. 24. Friedenwald, J.: Tonometer calibration: An attempt to remove discrepancies found in 1954 calibra tion for Schi^tz tonometers. Tr. Am. Acad. Ophth., 61:108, 1957. 25. Swanljung, H., and Biodi, F.: Tonography in some provocative tests for glaucoma. Am. J. Ophth., 46:187,1956. 26. Benson, J. A., Jr., Lee, P. R., Scholer, J. F., Kim, K. S., and Bollman, J. L.: Water absorption from the intestine via portal and lymphatic pathways. Am. J. Physiol., 41:143, 1957. 27. Curran, P. P., and Solomon, A. K.: Ion and water flumes in the ileum of rats. J. Gen. Physiol., 41:143,1957. 28. Verney, E. B.: Water diuresis. Irish J. M. Se, 8:377, 1954. 29. Smith, M. : Salt and water volume receptors. Am. J. Med., 23:623, 1957. 30. Kinsey, V. E.: Glaucoma: A Symposium. Springfield, 111., Thomas, 1955, p. 251. 31. Becker, B.: The decline in aqueous secretion and outflow facility with age. Am. J. Ophth., 46:731 (Nov. Pt. II) 1958. 32. Newell, F.: Glaucoma: Tr. Third Conference. New York City, Josiah Macy, Jr., Foundation, 1958, p. 38.
T H E R A P Y O F R E T I N A L VEIN OCCLUSION U S E OF FIBRINOLYSIN AND ANTICOAGULANTS H A R O L D I.
LINDERE,
M.D.,
A N D S H E R M A N R.
MASLER,
M.D.
Los Angeles, California INTRODUCTION
Although occlusion of the central retinal vein usually results in some visual loss, it has been brought out by many observers that
any improvement of vision depends upon the type of condition present. Klien and Olwin 1 described three mecha nisms of branch or retinal vein obstruction:
GALIN, M.D.,
FUTABA AIZAW, L, M.D.,
AND J O H N M. MCLEAN,
M.D.
New York While the water provocative test is fre quently used as a tool for the diagnosis of early open-angle glaucoma, its mechanism of action is not universally agreed upon. Com binations of this test with other methods such as the water and pressor-congestion test1 and water drinking and tonography,2 have in no way clarified the picture. As a possible explanation, Leydhecker,3 Kronfeld,4 Heegaard and Larsen, 5 Argawal and Sharma,6 and others have related the rise in intraocular pressure in glaucomatous eyes to initial hemodilution following water consumption. In this regard, studies by Hertel,7 Duke-Elder, 8 and Davson and Thomassen,9 as well as clinical studies by Poos,10 Dyar and Matthew,11 Galin et al.,12 and others have established that the eye, and particularly the glaucomatous eye, is a sensi tive osmometer. However, Schmidt,13 Yonebayashi,14 and others have reported that the response fol lowing water drinking is not initiated by in duced hypo-osmolality. Becker and Christienson,2 Friedenwald,15 Roberts,1* and others have indicated that the ultimate path for the elevation of intraocular pressure after water may be through re duced facility of aqueous outflow. This latter consideration has been commented upon by Bârâny," and Roberts. 18 They have postu lated that swelling of the trabecular area could increase the resistance to outflow. DeRoetth,19 as well as Scheie et al.,20 how ever, have been unable to confirm the re duction in outflow facility in glaucomatous eyes following water ingestion, and have ex plained pressure increases as due to incre ments in flow. Furthermore, Becker and *From the Department of Surgery (Ophthal mology) of the New York Hospital-Cornell Medi cal Center. This study was aided in part by grants from The National Society for the Prevention of Blindness and The National Council to Combat Blindness.
Gay21 have noted that some cases of appar ent decrease in outflow facility following water may be due to alterations in scierai rigidity. Earlier studies attempting to evaluate hemodilution following water consumption in the human being have been relatively crude in light of presently available techniques. These have included serum conductivity measurements,3 reductions in hemoglobin concentration,6,22 determinations of hematocrit response,· and studies of blood water content.1* Though detailed clinical studies12 relating increased blood osmolality and intra ocular pressure have recently appeared, few investigations using these techniques for the study of reduced blood osmolality and intra ocular pressure have been carried out. It is the purpose of this communication to report the blood osmolality changes, intra ocular pressure variations, and tonographic alterations following water consumption by patients in the glaucomatous age group with no evidence of open-angle glaucoma. MATERIALS AND METHODS
Patients were obtained from the eye clinic of the New York Hospital-Cornell Medical Center. All were past 55 years of age, and had no systemic diseases. These patients had been followed in the eye clinic for at least 10 years, and at no time were tensions greater than 20 mm. Hg recorded. Detailed ophthalmologic studies were carried out, and only those with entirely normal examinations were included in the control group. The knowledge of intraocular pressures for a long period, the presence of completely normal fields, and the absence of any ocular disorder on re peated examinations tend to validate the as sumption that this group is free of openangle glaucoma. The patients were kept in a fasting state following their evening meal the day prior to
M. A. G A L I N , F . A I Z A W A A N D J. M. M c L E A N
452
TABLE 1 BLOOD OSMOLALITY IN MIIXIOSMOLES BEFORE AND AT 15-MINUTE INTERVALS FOLLOWING THE RAPID INGESTION O FO N E LITER O F WATER IN 2 5 NORMAL PATIENTS
Sub jects
Milliosmoles before Water
Reduction in Blood Osmolality (after min.) 15
30
45
60
1 2 3 4 S
286.2 294.3 289.0 281.0 289.5
-4.6 -3.9 -7.4 +3.0 -5.0
-7.5 -8.8 -8.4 -5.0 -12.2
-9.8 -13.5 -5.2 -4.5 -12.0
-5.4 -11.6 -16.2 -8.0 -11.9
6 7 8 9 10
284.0 288.2 284.0 295.0 286.2
-3.5 -6.7 -4.0 -5.3 -7.0
-3.0 -9.7 -3.8 -9.8 -7.5
-5.5 -10.5 -3.3 -11.6 -3.4
-8.0 -6.7 -β.7 -14.2 -14.0
11 12 13 14 IS
291.0 290.2 292.2 287.0 289.8
-8.0 -9.7 -1.5 -12.2 -0.1
-5.5 -12.4 -8.7 -11.4 -5.1
-11.3 -12.6 -16.8 -16.8 -5.7
-9.3 -15.7 -4.7 -15.7 -10.3
16 17 18 19 20
288.0 284.6 296.0 296.0 293.7
-4.2 -7.3 -4.0 -4.0 -2.2
-6.7 -6.7 -8.3 -8.3 -4.2
-6.3 -6.4 -11.0 -11.0 -7.7
-9.7 -6.8 -7.0 -7.0 -5.7
21 22 23 24 25
292.2 295.3 283.5 282.0 292.0
-2.7 -2.3 -3.5 -2.8 -4.0
-2.7 -8.0 -5.2 -4.5 -8.0
-5.7 -8.1 -7.1 -5.5 -11.0
-4.5 -7.2 -3.5 -5.3 -11.5
the examination. In 25 cases, blood samples for subsequent analysis of freezing point de pression utilizing a Fiske osmometer were obtained prior to rapid consumption of one liter of water, and at 15-minute intervals for one hour, thereafter. In a group of 45 patients, tonography was performed on multiple occasions so that they became acclimated to the procedure. Applanation and multiple weight recordings with the Mueller electronic tonometer were recorded at all stages of the study, and cal culations of ocular rigidity obtained. On the days of testing, blood samples were ob tained for subsequent analysis of freezing point depression, tonography was performed, and one liter of water rapidly consumed. Sub sequent blood samples were obtained and to nography was again performed approxi
mately 40 minutes following water consump tion. Outflow facility was calculated utilizing Moses' and Becker's tables23 based on Friedenwald's data.24 When any change of ocular rigidity was noted, the data were recalculated to be comparable to those of average rigidity. Flow in cubic milliliters per minute was cal culated by the equation F = C(Po-Pv). No direct measurements of Pv (episcleral ven ous pressure) were obtained, and this value was assumed to be 11.7 mm. RESULTS
Table 1 lists the results of blood osmolality determined in the group subjected to water drinking only. In only one of 100 samples was there a reading of increased milliosmoles following water drinking and in this case all subsequent samples indicated hemodilution. In virtually all cases, then, reduction of blood osmolality is obtained, and no evidence of hemocencentration or atypical hemodilution patterns obtained. This is contrary to data published by Schmidt22 and Yonebayashi.14 Table 2 illustrates the frequency distribu tion of blood osmolality reduction with re spect to time. Eighty-four percent of cases reached maximum hypo-osmolality at 45 minutes to one hour, with the greatest num ber (44 percent) achieving that level at the 45-minute sample. In only one case was a maximum change noted at the 15-minute sampling. The data on alteration in blood osmolality in the group of 45 patients subjected to water drinking and tonography were essentially TABLE 2 F R E Q U E N C Y DISTRIBUTION O F MAXIMUM BLOOD OS M O L A L I T Y CHANGE IN MILLIOSMOLES WITH RE SPECT TO TIME FOLLOWING THE RAPID INGESTION OF ONE LITER OF WATER IN 25 NORMAL PATIENTS
Time Following Water Ingestion 15 min. 30 min. Frequency Percentage
1/25 4.0
3/25 12
45 min.
60 min.
11/25 44
10/25 40
WATER PROVOCATIVE TEST similar to the information presented in Table 1, and will not be repeated. Figure 1 repre sents the intraocular pressure changes, meas ured at approximately 40 minutes, in this normal group following water ingestion. It should be noted that the distribution of val ues corresponds approximately to a normal curve. The range of pressure variation is from a decrease of 4.0 mm. to an increase of 5.0 mm., though the predominant effect is an increase in pressure. This increase is statis tically significant at the one-percent level. Figure 2 depicts the range of facility of aqueous outflow in the normal group before and after water consumption. Table 3 lists the specific data concerning intraocular pres sure, outflow facility, aqueous flow, and Po/C before and after water drinking. It should be noted that approximately 60 per cent of patients had a reduction in outflow facility, the remainder exhibiting either no change or an increase. No correlation be tween initial pressure and facility and ulti mate pressure and facility could be statis tically established. This degree of variability in a normal group is similar to that pub lished by Swanljung and Biodi,25 but varies from the data of Becker and Christienson.2 Analysis of this data with respect to aque ous flow tonographically computed, however, reveals that an increase in flow accounts for the predominant, though small, increase in intraocular pressure. Figure 3 relates the
453
0.05 O.IO 0,15 0.20 0.25 0.30 0.35 0.40 C volt-
Fig. 2 (Galin, Aizawa and McLean). Facilities of aqueous outflow before and 40 minutes after the rapid ingestion of one liter of water in a group of 45 normal patients. change in flow to the change in intraocular pressure, and the apparent correlation is ob vious. Calculations reveal this correlation to be significant at the one-percent level. Calculations of ocular rigidity were made in all cases. However, though data with al tered rigidity have been mathematically changed to be comparable to data with nor mal rigidity, no significant reproducible change in ocular rigidity was ascertainable. Evaluation of the data with respect to Po/C is included in Table 3. Approximately five percent of this normal group had values greater than 100 before water, and 11 per cent greater than 100 following water con sumption. This data, too, is at variance with Becker and Christienson.2 DISCUSSION
Fig. 1 (Galin, Aizawa and McLean). Percentage of patients exhibiting intraocular pressure changes 40 minutes following the rapid ingestion of one liter of water in a group of 45 normals.
Water absorption from the gastro-intes tinal tract is a rather complex process, and subject to a considerable amount of varia tion even in the same patient.26-29 The data herein reported clearly indicate that hypoosmolality occurs following the ingestion of one liter of water. Kinsey30 has indicated, extrapolating rab bit data to man, that the reduction in blood
M. A. GALIN, F. AIZAWA AND J. M. McLEAN
4S4
TABLE 3 INTRAOCULAR PRESSURE ( P O ) ,, FACILITY OF AQUEOUS OUTFLOW ( C )!, AQUEOUS FLOW ( F ) , AND P o / C BEFORE AND AFTER THE RAPID INGESTION OF ONE LITER OF WATER IN 4 5 NORMAL PATIENTS* Right Eye
Left Eye
Po
Po'
ΛΡ
C
C
F
F'
2 3 4 S
14.6 18.1 11.2 12.2 10.2
18.9 20.6 12.2 13.4 10.2
+4.3 +2.1 +1.0 +1.2
.31 .23 .34 .24 .29
.42 .24 .27 .20 .19
0.90 1.47
3.02 2.14
0.12
0.34
6 7 g 9 10
14.0 20.6 10.2 18.1
-0.6
.25 .26 .15 .12 .15
0.43 2,31
+3.4
.23 .30 ,19 .15 .19
0.53 2.67
9.4
13.4 20.6 11.7 18.1 12.8
1.11
0.89
11 12 13 14 15
10.7 15.9 13.4 17.3 14.6
11.7 18.1 15.2 16.6 18.1
+ 1.0 +2.2 + 1.8 +0.7 +3.5
.27 .35 .25 .36 .25
.27 .20 .19 .33 .28
1.47 0.43 2.02 0.73
1.28 0.67 1.76 1.79
16 17 18 19 20
17.3 12.8 14.6 18.9
18.1 15.9 14.6 20.6
9.8
+1.3 +0.8 +3.1 + 1.7
.23 .27 .18 .13 .20
.19 .23 .16 .13 .16
1.51 0.20 0.38 1.44
1.47 0.67 0.38 1.42
2t 22 23 24 25
11.7 14.6 13.4 14.6 15.9
15.2 18.0 15.9 17.3 16.6
+3.5 +3.4 +2.5 +2.7 +0.7
.20 .24 .25 .31 .29
.29 .27 .26 .25 .25
0.70 0.43 0.90 1.22
1.70 1.09 1.40 1.23
26 27 28 29 30
18.9 14.0 11.2 16.6 12.8
15.9 14.6 13.4 15.9 14.0
-3.0 +0.6 +2.2 -0.7 +1.2
.32 .23 .32 .49 .22
.21 .23 .30 .35 .28
2.30 0.53
0.88 0.67
2.40 0.24
1.47 0.64
31 32 33 34 35
17.3 15.9 13.4 12.2 15.9
18.9 17.3 18.9 12.2 18.9
+ 1.6 + 1.4 +5.5 +3.0
.22 .21 .42 .32 .26
.20 .22 .42 .32 .32
1.23 0.88 0.71 0.16 1.09
1.44 1.23 3.02 0.16 2.30
7.5
+5.3 +0.5 -1.2 +S.6 +0.8
.17 .24 .42 .16 .28
.09 .18 .27 .16 .17
+4.9 +2.4 +2.6
.24 .23 .23 .24 .24
.25 .15 .19 .21 .30
J
8.5
36 37 38 39 40
11.7 13.4 15.9 9.4
12.8 12.2 12.2 21.5 10.2
41 42 43 44 45
20.6 14.6 18.9 20,6 15.9
25.5 12.2 21.5 20.6 18.9
0 0
+1.5 0
0
0.0
0.0
+3.0
0.71 0.69
0.14 1.57
2.14 0.67 1.66 2.14 1.01
3.45 0.08 1.86 1.87 2.16
Po
Po'
c C _ _ — _ — _. — _ - ^ _ — _ — _ + +_ _ *, — _~ — _ — __ - _ _ _ — _ — _ + + + — _ _ _ — — _ __ - __ _ _ _ _ _ _ _ — _ _- _ — — _ -, _ — — _ + — _ — _ _ + — __ + — __ + _ — —
Po
Po'
ΔΡ
C
e
15.9 13.4
15.2 17.3 13.4 14.6
-0.7 +3.9 +3.6
8.9
-1.1
.32 .20 .26 .37 .19
.16 .22 .20 .28 .09
11.2 17.3 10.7 13,4
14.0 17.3 10.2 14.6 10.2
+2.8 -0,5 +1.2 +0.4
.29 .22 .19 .15 .19
.23 .30 .17 .11 .11
8.5
10.7 14.6 15.2 15.2 15.9
+2.2 +2.9 -2.1 +0.6 + 1.3
.23 .38 .30 .28 .23
.17 .25 .19 .21 .19
1.68 0.81 0.67
0.67 0.74 0.80
9.8
14.6 7.8
9.8
11.7 17.3 14.6 14.6
0
0
F
F'
1.34 0.34
0.56 1.23
1.07
0.81
1.23
1.68
0.26
0.32
15.9 13.4 13.4 14.0
17.3 15.9 15.9 14.6
9.4
+2.0 +1.4 +2.5 +2.6 +0.6
.19 .21 .18 .15 .20
.15 .17 .14 .12 .15
0.88 0.31 0.26 0.46
1.18 0.59 0.50 0.44
11.7 14.0 15.3 13.4 13.4
12.8 15.3 16.6 15.2 12.1
+ 1.1 +1.3 +1.3 +1.8 +0.6
.32 .23 .26 .23 .18
.20 .19 .30 .21 .11
0.53 0.94 0.39 0.31
0.68 1.47 0.74 0.04
15.2 11.2 11.7 15.2 10.2
14.6 14.0 12.2 13.4 11.7
-0.6 +2.8 +0.5 -1.8 +1.5
.21 .24 .32 .50 .24
,2S .23 .35 .39 .29
0.74
0.73
1.75
0.66
14.6 13.4 18.1
17.3 12.8 14.6 11.2 14.6
+3.3 .18 .15 .15 .13 -0.6 . 34 .48 -3.5 + 1.8 > . 3 9 >.45 . 1 8 .18 +1.2
0.52 0.22 3.07
0.84 0.17 1.39
0.31
0.52
10.2 12.2 11.7
11.7 12.8 13.4 16.6
.15 .24 .32 .15 .28
.15 .20 .28 .17 .19
0,16
0.48
9.8
+3.2 +2.6 + 1.2 +4.7 +0.4
18.1 13,4 18.1 19.7 13.2
20.6 12.2 20.6 18.9 14.4
+2.5 -1.2 +2.5 -0,8 +1.2
.20 .18 .20 .27 .17
.27
1.28 0.31 1.28 0.22
2.40
7.4
9.4
13.4 8.5
9.4
.24 .17
2.14
Po C~
_ — — — _ — — — — _ — — — _ — — — ^ — — — _ — — — _
Po'
c _ — — — — _ — —
+
_ — — — _ + + + _ — — —
+
— — — -
+ + _ — _ — — — — _ — —
— _ — — — — _ — —
* Values of Po/C greater than 100 are indicated as + ; those below 100 as —.
osmolality following ingestion of one liter of water would be about four millimoles. This figure is similar to our observed results and close to those theoretically obtainable if total body water is assumed to be in the range of 60 percent. We may at least infer, therefore, that with respect to intraocular pressure the initiating sequence of events following water ingestion is related to a reduction in blood osmolality. Fluid will then enter the eye on the basis of the induced osmotic gradient. The eye with a significantly elevated pressure would be most sensitive to the slightest alteration in ocular
volume12 with moderate to large pressure changes resulting. In this regard, Bârâny" has commented that the water drinking test could act by fa cilitating inflow. He also has noted that any prolonged elevation of intraocular pressure would be due to a change in resistance or to an increase in resultant venous pressure. The use of tonography, or tonography combined with water drinking, would label quite a few of these normal patients glaucomatous, if Becker and Christienson's cri teria were followed.2 Perhaps the variance of our data with theirs lies in the choice of con-
4SS
WATER PROVOCATIVE TEST trol groups, as all of our patients were in the commonly accepted glaucomatous age range. The progressive decrease in outflow facility accompanying the aging process has been described by Becker.31 Detailed analysis of the data presented here discloses several major shortcomings in the application of "quantitative" tonography. First, we have little accurate data on the ef fect of rapid increase in total body water on the episcleral venous pressure. Duke-Elder 8 has demonstrated a prompt increase in ven ous pressure following the administration of hypotonie and even isosmotic solutions in animals. Second, all calculations of outflow facility assume the eye to be in a steady-state with the assumption that flow remains con stant. It is apparent that after water drink ing the eye is not in a steady-state, and that ocular volume increases. Only the fact that tonography is performed for just four min utes during which time major changes in flow probably do not occur permits a com parison of outflow facility before and after water. However, any comparison is not ab solutely mathematically sound. Last, the term, flow, is rather loosely used in these and other studies. Osmotic alterations may cause changes in aqueous flow, but cer tainly may alter ocular volume through changes in intravascular volume, as well as secretion. It has been noted that intraocular pressure reflects the pressure in several dif ferent vascular beds.32 Until the effect of al tered blood osmolality on these systems is known, there is insufficient basis to relate intraocular pressure change solely to changes in flow, even when outflow facility appears unaltered. It should be apparent, then, that calculât-
mm. Hg.
+6
• •
+5 +4
-
*
+S
•
<'·..;
•
+2
•
·
+1 0
..
- 1
■.
-2 -3 -4
1
. 1·„ i
.
·■»
■
■■ i
+ to
Î +20
+M> mmVmm
Fig. 3 (Galin, Aizawa and McLean). Relation ship of inflow, tonographically computed, and intra ocular pressure change following the rapid inges tion of one liter of water in 45 normal patients. ing outflow facility in an eye not in a steadystate, and flow using assumptions that have not been proved, leaves much to be desired. SUMMARY
Following rapid ingestion of one liter of water, blood osmolality is reduced, the great est reduction occurring at the 45- to 60minute sample. In a nonglaucomatous group of patients in the glaucomatous age group, there is a statistically significant increase in aqueous "flow," tonographically calculated, accounting for an increase in intraocular pressure that is statistically significant, though small in magnitude after water drink ing. This data would tend to indicate that the initiating sequence of events following water consumption is related to the osmotic gradient established. It would also tend to indicate theoretical errors in utilizing quantitative to nography following water ingestion. 525 East 68th Street (21).
REFERENCES
1. Sugar, H. S.: The provocative tests in the diagnosis of the glaucomas. Am. J. Ophth., 31:1193, 1948. 2. Becker, B., and Christienson, R. E.: Water drinking and tonography in the diagnosis of glaucoma. AMA Arch. Ophth., 56:321,1956. 3. Leydhecker, W.: The water drinking test. Brit. J. Ophth., 34:457, 1950. 4. Kronfeld, P.: Glaucoma: A Symposium, Springfield, 111., Thomas, 1955, p. 233. 5. Heegaard, S., and Larsen, V.: Einiges über den Wasserstoffwechsel bei Normalen und Glaucomkranken. Acta. Ophth., 9:302,1931.
456
M. A. GALIN, F. AIZAWA AND J. M. McLEAN
6. Argawal, L. P., and Sharma, C K.: Two provocative tests for glaucoma. Brit. J. Ophth., 37:330, 19S3. 7. Hertel, E.: Experimentelle Untersuchungen über die Abhängigkeit des Augendrucks von der Blutbeschaffenheit. Arch. f. Ophth., 88:197, 1914. 8. Duke-Elder, W. S. : The reaction of the intraocular pressure to osmotic variation in the blood. Brit. J. Ophth., 10:1,1926. 9. Davson, H., and Thomassen, T. L. : The effect of intravenous infusion of hypertonic saline on the intraocular pressure. Brit. J, Ophth., 34:355, 1950. 10. Poos, F.: Klinische Untersuchungen über die Beziehungen Zurschen Osmose, Blutdruck und Augendruck. Klin. Monatsbl. f. Augenh., 84:340, 1930. 11. Dyar, E. W., and Matthew, W. B.: Use of sucrose preparatory to surgical treatment of Glaucoma: A preliminary report. Arch. Ophth., 18:57, 1937. 12. Galin, M. A., Aizawa, F., and McLean, J. M. : Urea as an osmotic ocular hypotensive agent in glaucoma. AMA Arch. Ophth., 62:347, 1959. 13. Schmidt, K.: Trinkversuch und Glaukomproblem. Arch, f. Augenh., 104:102, 1931. 14. Yonebayashi, M.: Blood water content and water drinking test. Acta. Ophth. Jap., 62:1454, 1958. 15. Friedenwald, J.: Glaucoma: A Symposium. Springfield, Thomas, 1955, p. 251. 16. Roberts, W.: Tonographic criteria in early glaucoma: Clinical tonography as an aid to the diag nosis and management of early glaucoma. Am. J. Ophth., 48:31 (Nov. Pt. I) 1959. 17. Bârâny, E.: Glaucoma: A Symposium. Springfield, 111., Thomas, 1955, p. 251. 18. Roberts, W.: Glaucoma: Tr. Third Conference. New York, Josiah Macy, Jr., Foundation, 1958, p. 214. 19. de Roetth, A., Jr.: Effect of changes in osmotic pressure of blood on aqueous humor dynamics. AMA Arch. Ophth., 52:571, 1954. 20. Scheie, H. G., Spencer, R. W., and Helmick, E. D.: Tonography in the clinical management of glaucoma. AMA Arch. Ophth., 56:797, 1956. 21. Becker, B., and Gay, A.: Applanation tonometry in the diagnosis and treatment of glaucoma. AMA Arch. Ophth., 62:211, 1959. 22. Schmidt, K.: Untersuchungen über Capillarendothelstorungen bei Glaucoma Simplex. Arch. f. Augenh., 98:569,1928. 23. Moses, R. A., and Becker, B.: Clinical tonography: The scierai rigidity correction. Am. J. Ophth., 45:196, 1958. 24. Friedenwald, J.: Tonometer calibration: An attempt to remove discrepancies found in 1954 calibra tion for Schi^tz tonometers. Tr. Am. Acad. Ophth., 61:108, 1957. 25. Swanljung, H., and Biodi, F.: Tonography in some provocative tests for glaucoma. Am. J. Ophth., 46:187,1956. 26. Benson, J. A., Jr., Lee, P. R., Scholer, J. F., Kim, K. S., and Bollman, J. L.: Water absorption from the intestine via portal and lymphatic pathways. Am. J. Physiol., 41:143, 1957. 27. Curran, P. P., and Solomon, A. K.: Ion and water flumes in the ileum of rats. J. Gen. Physiol., 41:143,1957. 28. Verney, E. B.: Water diuresis. Irish J. M. Se, 8:377, 1954. 29. Smith, M. : Salt and water volume receptors. Am. J. Med., 23:623, 1957. 30. Kinsey, V. E.: Glaucoma: A Symposium. Springfield, 111., Thomas, 1955, p. 251. 31. Becker, B.: The decline in aqueous secretion and outflow facility with age. Am. J. Ophth., 46:731 (Nov. Pt. II) 1958. 32. Newell, F.: Glaucoma: Tr. Third Conference. New York City, Josiah Macy, Jr., Foundation, 1958, p. 38.
T H E R A P Y O F R E T I N A L VEIN OCCLUSION U S E OF FIBRINOLYSIN AND ANTICOAGULANTS H A R O L D I.
LINDERE,
M.D.,
A N D S H E R M A N R.
MASLER,
M.D.
Los Angeles, California INTRODUCTION
Although occlusion of the central retinal vein usually results in some visual loss, it has been brought out by many observers that
any improvement of vision depends upon the type of condition present. Klien and Olwin 1 described three mecha nisms of branch or retinal vein obstruction: