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Fluorophotometric Study of Anterior Segment Barrier Functions After Extracapsular Cataract Extraction and Posterior Chamber Intraocular Lens Implantation
FLUOROPHOTOMETRIC STUDY OF ANTERIOR SEGMENT BARRIER FUNCTIONS AFTER EXTRACAPSULAR CATARACT EXTRACTION AND POSTERIOR CHAMBER INTRAOCULAR LENS IMPLANTATION MITSURU SAWA, M.D., YOSHIHIKO SAKANISHI, AND HIROYUKI SHIMIZU, M.D.
M.D.,
Tochigi, Japan
We used fluorophotometry and pachymetry to examine the longerterm (more than three months) postoperative effects in the anterior segment of extracapsular lens extraction with and without posterior chamber intraocular lens implantation. Fluorophotometry was performed after oral administration of fluorescein solution (5 mg/kg of body weight under fasting condition). We calculated the corneal endothelial transfer coefficient, fluorescein distribution ratio, aqueous transfer coefficient in reference to chamber volume, and loss coefficient and measured corneal thickness with a modified pachymeter. There were no significant differences between the values for corneal endothelial transfer coefficient and corneal thickness in the two groups of surgically treated eyes combined vs the intact fellow eyes. The aqueous transfer coefficient and loss coefficient values were not significantly different between the two surgically treated groups. Anterior chamber depth did not differ significantly between the two surgical groups, but the value for the two groups combined (3.79 mm) did differ significantly from that of the fellow eyes (2.87 mm) (P<.OO5). We concluded that endothelial function recovers three months after extracapsular lens extraction with or without posterior chamber intraocular lens implantation, and that the effects of intraocular lens implantation on anterior segment barrier functions are not significantly different from those of extracapsular lens extraction alone. Although extracapsular cataract extraction and posterior chamber lens implantation have reduced the postoperative complications of intraocular surgery, 1-4 the clinical effects of these surgical manipulations on the intraocular tissues have not been evaluated quantitatively. Several methods are available for in-
Accepted for publication Nov. 22, 1983. From the Department of Ophthalmology, Jichi Medical College, Tochigi, Japan. Reprint requests to Mitsuru Sawa, M.D., Eye Research Institute, 20 Staniford St., Boston, MA 02114.
vestigating intraocular tissue function. Fluorophotometric studies.Y useful in the evaluation of barrier functions in the anterior segment," have disclosed that the deterioration of corneal endothelial barrier function occurs in the early postoperative period after cataracts" or corneal transplant" surgery. Sawa and TanIshima!' reported transient increases in corneal thickness. Overall corneal endothelial functions 12,13 can be estimated by measuring corneal thickness. 14 We studied the longer-term effects of extracapsular cataract extraction alone and combined with posterior chamber
©AMERICAN JOURNAL OF OPHTHALMOLOGY 97:197-204, 1984
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AMERICAN JOURNAL OF OPHTHALMOLOGY
lens implantation on anterior segment functions. SUBJECTS AND METHODS
Subjects-Except for their cataracts, the subjects were generally healthy, although a few had slight hypertension. The minimum follow-up period after cataract extraction was three months. The subjects were divided into two groups. Group 1, who underwent extracapsular cataract extraction alone, included 19 eyes of 17 patients ranging in age from 24 to 84 years (mean age, 62 years). The mean (±S.D.) follow-up period was 15 ± 10 months. Group 2 underwent both extracapsular cataract extraction and posterior chamber intraocular lens implantation. It included 16 eyes of 14 patients ranging in age from 48 to 75 years (mean age, 60 years). The mean (±S.D.) followup period was 17 ± 4.8 months. The following protocol was used for the eyes in Group 1: 0.5% indomethacin oil eyedrops, 1% atropine eyedrops, and phenylephrine eyedrops were instilled three hours, two hours, one hour, and 30 minutes before surgery. Postoperatively the patients received 0.2% dexamethasone four times a day, antibiotic eyedrops four times a day, 1% atropine once a day for two weeks, and topical indomethacin twice a day for one week. Procedure-With the patient under local anesthesia, the surgeon, using an operating microscope, placed a traction suture at the superior rectus muscle. After forming a limbal-based conjunctival flap, he made a two-plane scleral groove along the surgical corneoscleral limbus from the 9 o'clock to the 3 o'clock positions. An anterior capsulotomy was performed with an irrigating cystotome. SMA-2 solution was used for irrigation. The incision was made along the base of the scleral groove. After capsulectomy, a peripheral iridectomy was done at the 12 o'clock position. The lens nucleus was
FEBRUARY, 1984
extracted with a cryotip. After the stay suture at the 12 o'clock position was tied, the cortex was removed with the IIA tip of a phacoemulsifier. The surgeon closed the limbal wound with four other interrupted sutures and the conjunctival wound with a silk suture. The procedure varied in Group 2 in that the cortex was removed without closing the stay suture at the 12 o'clock position. The anterior chamber was filled with air and the intraocular lens was inserted through the incision and fixed in position with a hook. The surgeon then closed the wound with the same method used for Group 1. The surgical and postoperative courses were uneventful in all cases, and slitlamp examinations showed no postsurgical intraocular inflammation. Fluorophotometry-We used fluorophotometry to determine the permeability of the blood-aqueous barrier" and of the corneal endothelium." The subjects were asked to drink 10% sodium fluorescein solution at a dose of 5 mg/kg of body weight while fasting. Using a slit-lamp fluorophotometer, we determined the fluorescein concentration at the center of the cornea and in the anterior chamber at intervals during a period of six hours. We took blood samples from the cubital vein at one, two, four, and six hours after dye ingestion. Blood plasma was prepared and diluted 101 times with 0.1 M phosphate buffer at pH 7.4, and the fluorescein concentration was then determined. We termed these values apparent fluorescein concentrations, because they included both fluorescein and its metabolites. Two examples of the time-course values are shown in the Figure. Data analysis-PERMEABILITY OF THE CORNEAL ENDOTHELIUM-We calculated the transfer coefficient for fluorescein exchange across the corneal endothelium in reference to the corneal volume (k...c) from the time courses of the fluorescein
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FLUOROPHOTOMETRY AFTER INTRAOCULAR LENS
8
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(hours)
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(hours)
Figure (Sawa, Sakanishi, and Shimizu). Time course of apparent fluorescein concentration in whole plasma (squares), aqueous (circles), and cornea (triangles). Left, A patient undergoing extracapsular cataract extraction only (Table 1, Case 15). Right, A patient undergoing extracapsular cataract extraction and posterior chamber implantation (Table 3, Case 31).
concentration in the cornea and the anterior chamber.P''" The following equation was fitted to the data, because slit-lamp microscopy showed no pathologic aqueous protein increase: dCc/dt = keoac (Ca - raeCc)
(1)
where Cc and Ca are apparent fluorescein concentrations in the cornea and anterior chamber respectively, rae is the distribution ratio of the dye between the two structures, and t is time. The equation was fitted to the data by a weighted least-square method." The values of kC'8C and rae were calculated for each individual. PERMEABILITY OF THE BLOOD-AQUEOUS
BARRIER-In eyes that have undergone extracapsular lens extraction, we may
consider the anterior and posterior chambers to be a single chamber, because iridectomy creates an artificial communication between them and because lens material is absent.! The volume of any implanted posterior chamber lens is much less than that of the original lens. We used the following transfer equation'? to analyze the data: dCaidt = k'inCp - k' outCa
(2)
where Ca and Cp are apparent fluorescein concentrations in the anterior chamber and plasma ultrafiltrate respectively, k'in is the apparent transfer coefficient in reference to the chamber volume, k' out is the apparent loss coefficient, and t is time. The equation was fitted to the data by a least-square method.
200
CORNEAL THICKNESS-We determined corneal thickness at the time of fluorophotometry with a modified Haag-Streit pachymeter.P Five measurements were taken at the center of the cornea and the values were averaged. ANTERIOR CHAMBER DEPTH-We measured anterior chamber depth optically and defined it as the distance between the posterior corneal layer and the posterior lens capsule in the eyes in Group 1 and as the distance between the posterior corneal layer and the surface of the posterior chamber lens in the eyes in Group 2. The measurement was made in the center of the anterior chamber. INTRAOCULAR PRESsuRE-We determined intraocular pressure by applanation tonometry at the end of the fluorophotometry.
RESULTS Although our extracapsular cataract extraction procedure did not produce a classic after-cataract, a subtle lens remnant was left at the lens equator under the iris in some cases. Slit-lamp microscopy disclosed seven eyes with lens remnants and five eyes with iris-lens remnant synechiae (Table 1). When we investigated the effects of the lens remnants and iris synechiae on the permeability of corneal endothelium and the function of the blood-aqueous barrier, we found that they made no significant difference (Table 2). The kc..c and corneal thickness values for Group 1 were not significantly different from those for Group 2 (Tables 1 and 3) and were within the same range as
TABLE
1
CLINICAL COURSE AND RESULTS IN GROUP
Patient Intraocular Corneal Anterior No., Sex, Pressure Thickness Chamber kc-ac (mm) Depth (mm) (hr- 1)* Age (yr) (mm Hg) 1, F, 66 2, M, 34 3, F. 52 4, F. 52 5. F, 73 6. F. 77 7, F. 77 8, F. 76 9. F, 66 10. F. 68 11. M, 67 12. F, 66 13. F. 76 14, F, 61 15, M, 57 16. F. 53 17. F. 63 18. M, 84 19. M, 24 Mean 63 S.D. 15
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AMERICAN JOURNAL OF OPHTHALMOLOGY
12 13 10 10 12 16 16 9 10 12 16 15 13 16 16 12 13 10 11 13 2.4
0.51 0.51 0.52 0.51 0.50 0.50 0.50 0.50 0.49 0.50 0.50 0.51 0.51 0.58 0.50 0.53 0.50 0.50 0.49 0.51 0.020
3.85 3.50 3.30 4.00 4.50 4.20 3.30 4.10 4.50 4.30 3.85 4.00 3.95 0.414
0.44 0.75 0.37 0.49 0.59 0.35 0.53 0.59 0.80 0.47 0.79 0.34 0.44 0.53 0.53 0.29
k'in k' oqt (hr- 1)* (hr- 1)* 0.77 0.68 0.50 0.92 0.97 0.42 0.77 0.34 0.75 0.57 0.98 0.34 0.59 0.57 0.84 0.16
0.15 0.058 0.26 0.39 0.21 0.92 0.99 0.24 0.36 0.097 0.16 0.23 0.19 0.08 0.31 0.27 0.14
0.39 0.50 0.28 0.51 0.63 0.30 0.15 0.24 0.26
0.60 0.50 1.7 1.6 0.94 3.1 2.8 0.79 0.91 0.61 0.68 1.4 0.77 0.48 1.4 2.5 1.1 3.00 1.4 0.89
1
Postoperative AfterPeriod (mos) cataract Synechiae 6 4 3 18 15 7 3 5 6 13 30 20 20 14 23 3 32 27 29 15 10
+ +
+
+
+
+
+ +
+ +
+
+
*Values: kc-ac. transfer coefficient for fluorescein exchange across the corneal endothelium; rae. distribution ratio of dye between anterior chamber and cornea; k'in. apparent aqueous transfer coefficient in reference to the anterior chamber volume; k' out, apparent aqueous loss coefficient.
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FLUOROPHOTOMETRY AFfER INTRAOCULAR LENS
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TABLE 2 EFFECT OF LENS REMNANTS AND IRIS SYNECHIAE
Mean (± S.D.) Values (hr-I). Eyes
k'in
With lens remnants Without lens remnants With iris synechiae Without iris synechiae
0.56 0.48 0.53 0.50
± 0.17 ± 0.14
0.25 0.53 0.26 0.31
± 0.16 ± 0.16
± ± ± ±
k'out 0.10 0.32 0.13 0.30
1.1 1.5 1.2 1.4
± ± ± ±
0.90 0.94 1.10 0.89
·Values: ke..c, transfer coefficient for fluorescein exchange across the corneal endothelium; k'in, apparent aqueous transfer coefficient in reference to the anterior chamber volume; k' out, apparent aqueous loss coefficient.
those for the intact fellow eyes (Table 4).9 Mean (±S.D.) anterior chamber depth was 3.79 ± 0.44 mm for 25 of the eyes in Groups 1 and 2 combined and 2.87 ± 0.37 mm for 15 of the intact fellow eyes; this difference was statistically significant (P<.005 by r-test). However, anterior
chamber depth averaged 3.95 ± 0.41 mm for Group 1 and 3.64 ± 0.43 mm for Group 2; this difference was not statistically significant. Because the anterior chamber volume was estimated to be similar in both surgical groups, we compared their values for k'« and k' out and
TABLE 3 CLINICAL COURSE AND RESULTS Patient No., Sex, Age (yr) 20, F, 48 21, F, 75 22, M, 61 23, M, 73 24, F, 61 25, F, 47 26, F, 54 27, F, 49 28, F, 49 29, F, 60 30, F, 66 31, F, 66 32, M, 61 33,M,64 34,M,64 35, F, 66 Mean 60 S.D. 8.7
IN
GROUP 2
Anterior Intraocular Corneal Pressure Thickness Chamber Depth Ic.,... (hr- I). (mm) (mm) (rom Hg) 9 16 12 11 14 9 12 8 10 12 16 15 17 14 16 11 13 2.9
0.50 0.50 0.50 0.52 0.52 0.48 0.49 0.52 0.52 0.50 0.51 0.51 0.51 0.51 0.50 0.50 0.51 0.012
3.10
4.30 2.90 3.85 4.05 3.75 4.30 3.50 3.80 3.40 3.60 3.50 3.30 3.64 0.426
k'in r",,· (hr- I).
0.38 0.35 0.52 0.62
0.96 0.31 0.37 0.61
0.45 0.67
0.53 0.91
0.67
0.74
0.32
0.67
0.40
0.87
0.49 0.14
0.66 0.23
0.31 0.64 0.35 0.53 0.10 0.35 0.58 0.088 0.060 0.14 0.21 0.26 0.60 0.49 0.85 0.31 0.37 0.23
k'
(h/~.
1.1 3.9 0.79 1.4 0.47 1.8 1.7 0.41 0.37 0.91 0.82 0.84 2.2 2.2 3.5 2.2 1.5 1.1
Postoperative Period (mos) 15 13 12 13 21 20 19 28 13 17 16 14 22
20 8 18 17 4.8
·Values: Ic.,..." transfer coefficient for fluorescein exchange across the corneal endothelium; r"", distribution ratio of dye between anterior chamber and cornea; k'in, apparent aqueous transfer coefficient in reference to the anterior chamber volume; k' out, apparent aqueous loss coefficient.
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AMERICAN JOURNAL OF OPHTHALMOLOGY TABLE 4 RESULTS IN INTACT FELLOW EYES
Patient No., Sex, Age (yr)
Intraocular Pressure (mm Hg)
Corneal Thickness
I, F, 66 2, M, 34 5, F, 73 8, F, 76 10, F, 68 13, F, 76 15, M, 57 16, F, 53 17, F, 63 19, M, 24 21, F, 75 22, M, 61 23, M, 73 24, F, 61 25, F, 47 26, F, 54 29, F, 60 32, M, 61 33,M,64 34,M,64 35, F, 66 Mean 61 S.D. 13
12 10 10 9 15 13 16 12 12 14 18 8 11 16 10 12 12 16 14 14 11 13 2.6
0.51 0.50 0.50 0.50 0.50 0.51 0.50 0.50 0.50 0.49 0.50 0.50 0.51 0.52 0.48 0.49 0.50 0.51 0.51 0.50 0.50 0.50 0.01
(mm)
Anterior Chamber Depth (mm)
2.10 2.50 2.60 2.60 2.50 3.00 3.10
3.10 2.65 2.50 3.50 2.70 2.90 2.80 2.90 2.76 0.34
I<..ae (hr- 1) .
rae•
0.67 0.49 0.74 0.67 0.55 0.70 0.63 0.40 0.60 0.48 0.40 0.70 0.59
0.62 0.62 0.83 0.70 0.65 0.92 0.90 0.48 0.89 0.70 0.19 0.95 0.79
0.46 0.38 0.43 0.72 0.37 0.26 0.51 0.54 0.14
0.58 0.53 0.91 0.15 0.62 0.21 0.51 0.64 0.24
k'in (hr- 1) .
(hr- ).
0.18 0.040 0.13 0.22 0.063 0.098 0.34 0.082 0.098 0.34 0.26 0.25 0.25 0.066 0.35 0.31 0.13 0.33 0.24 0.24 0.29 0.21 0.10
0.98 0.24 0.52 0.81 0.48 0.48 1.2 0.73 0.47 3.3 1.9 0.75 0.81 0.34 1.8 1.8 0.70 1.3 1.1 1.0 1.5 1.1 0.71
k'o~t
·Values: I<..ae, transfer coefficient for fluorescein exchange across the corneal endothelium; rae, distribution ratio of dye between anterior chamber and cornea; k'in, apparent aqueous transfer coefficient in reference to the anterior chamber volume; k'out, apparent aqueous loss coefficient.
found no significant differences. The intraocular pressures in both groups were within the normal range. DISCUSSION
Fluorophotometry is a useful clinical tool for investigating pathophysiologic changes, especially in the barrier functions of the anterior segment. 7,8,10,19 Each of the several techniques has advantages and disadvantages. 5,6,19-22 The oral method, which we used, is safe and permits the determination of the corneal endothelial transfer coefficient, an index of endothelial permeability, by a simple data reduction. This coefficient can be calculated by measuring the fluorescein concentrations at the center of the cornea and in the anterior chamber Indepen-
dently of the anterior chamber volume, which varies with cataract surgery and aging. 23 Orally administered fluorescein undergoes metabolism, and part of it is converted to the glucuronide." The measured fluorescein concentration, comprising both free fluorescein and its glucuronide, is determined in reference to a standard fluorescein solution. Therefore, we termed the measured value the apparent fluorescein concentration.Y In the early postoperative period the presence of protein-bound fluorescein in the anterior chamber, as a result of breakdown of the blood-aqueous barrier, should be taken into account. 9,10,24,25 Both corneal thickness and endothelial permeability are increased one week after intracapsular cataract extraction''; we have ob-
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FLUOROPHOTOMETRY AFTER INTRAOCULAR LENS
served similar changes in a small number of cases after extracapsular cataract extraction (unpublished data). Pretreatment with indomethacin does not suppress the increase in the transfer coefficient of the corneal endothelium. 9 After the blood-aqueous barrier function recovers, Equation 1 can be applied in eyes that have undergone cataract surgery just as in normal eyes. In our study the kc..c and corneal thickness values in Groups 1 and 2 were not significantly different; further, these values did not differ significantly from those of intact fellow eyes. Thus, we concluded that endothelial functions that deteriorate in the early postoperative period can recover after three months or more. The presence of a posterior chamber intraocular lens does not affect endothelial function. The oral method is also clinically useful for estimating the blood-aqueous barrier function. 7,26 Because of the artificial communication created between the anterior and posterior chambers by peripheral iridectomy and the absence of a lens acting as a septum with the iris, the two chambers should be considered to be a single compartment.P Therefore, we applied the single-compartment model of Davson'? between the anterior chamber and the blood. The value of k' in is the transfer coefficient in reference to the anterior chamber volume. Estimation of the blood-aqueous barrier function using this method takes into account the anterior chamber volume. Comparing the values of k'in among groups that underwent different surgical procedures is of limited value. We found previously-" that the value of k' in increased in the early postoperative period and that indomethacin pretreatment reduced this increase, findings in agreement with other reports on the clinical application of indomethacin to anterior segment surgery. 8,11,20,27 We measured the fluorescein concentration in the plasma ultrafiltrate in the present
203
study because the recovery of the bloodaqueous barrier function does not permit the passage of protein28; slit-lamp examinations did not show the presence of aqueous flare. The value of k'in in the surgically treated eyes was not significantly different from that in the intact fellow eyes but the anterior chamber depth of the fellow eyes was significantly shallower than that of the surgically treated eyes. This indicated that the permeability of the blood-aqueous barrier in surgically treated eyes may increase more than three months postoperatively. Ophthalmologists generally prefer a posterior chamber intraocular lens to other intraocular lenses because it minimizes corneal endothelial damage,I,29-32 but its presence in the posterior chamber may irritate the blood-aqueous barrier or damage tissue.P The breakdown of the blood-aqueous barrier releases prostaglandins.Y" causing increases in intraocular pressure, aqueous protein levels, and miosis. We concluded that posterior chamber intraocular lenses do not affect the blood-aqueous barrier after extracapsular cataract extraction alone. 37,38 The interpretation of the value of k' out is more complicated after surgery because of anatomic changes. Although the individual variations of k' out were large, implantation of a posterior chamber intraocular lens after extracapsular cataract extraction apparently has no grossly observable effect on aqueous outflow. REFERENCES 1. Bourne, W. M., Brubaker, R. F., and O'Fallon, W. M.: Use of air to decrease endothelial cell loss during intraocular lens implantation. Arch. Ophthalmol. 97:1473, 1979. 2. Stark, W. J., Worthen, D. M., Holladay, J. T., Bath, P. E., Jacobs, M. E., Murray, G. C., McGhee, E. T., Talbott, M. W., Shipp, M. D., Thomas, N. E., Barnes, R. W., Brown, D. W. C., Buxton, J. N., Reinecke, R. D., Lao, C.-S., and Fisher, S.: The FDA report on intraocular lenses. Ophthalmology 90:311, 1983. 3. Stark, W. J., Maumenee, A. E., Dangel, M. E., Martin, N. F., and Hirst, L. W.: Intraocular
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lenses. Experience at the Wilmer Institute. Ophthalmology 89:104, 1982. 4. Bourne, W.M., Waller, R R, Liesegang, T. J., and Brubaker, R F.: Corneal trauma in intracapsular and extracapsular cataract extraction with lens implantation. Arch. Ophthalmol. 99:1375, 1981. 5. Araie, M., Sawa, M., Nagataki, S., and Mishima, S.: Aqueous humor dynamics in man as studied by oral fluorescein. Jpn. J. Ophthalmol. 24:346, 1980. 6. Sawa, M., Araie, M., and Nagataki, S.: Permeability of the human corneal endothelium to fluorescein. [pn. J. OphthalmoI. 25:60, 1981. 7. Araie, M., Sawa, M., and Takase, M.: Effect of topical indomethacin on the blood-aqueous barrier after intracapsular extraction of senile cataract. A f1uorophotometric study. Jpn. J. OphthalmoI. 25:237, 1981. 8. Sanders, D. R, Kraff, M. C., Lieberman, H. L., Peyman, G. A., and Tarabishy, S.: Breakdown and reestablishment of blood-aqueous barrier with implant surgery. Arch. Ophthalmol. 100:588, 1982. 9. Sawa, M., Araie, M., and Tanishima, T.: A f1uorophotometric study of the barrier functions in the anterior segment of the eye after intracapsular cataract extraction. Jpn. J. Ophthalmol. 27:404, 1983. 10. - - : Permeability of the corneal endothelium to fluorescein. A follow-up of keratoplasty cases. Jpn. J. Ophthalmol. 26:326, 1982. 11. Sawa, M., and Tanishima, T.: The morphometry of the human corneal endothelium and follow-up of postoperative changes. Jpn. J. OphthalmoI. 23:337, 1979. 12. Kaye, G. I., Mishima, S., Cole, J. D., and Kaye, N. W.: Studies on the cornea. VII. Effect of perfusion with a Ca + + -free medium on the corneal endothelium. Invest. OphthalmoI. 7:53, 1968. . 13. Maurice, D. M.: The location of the fluid pump in the cornea. J. Physiol. 221:43, 1972. 14. Mishima, S.: Corneal thickness. Surv. OphthalmoI. 13:57, 1968. 15. Mishima, S., and Maurice, D. M.: In vivo determination of the endothelial permeability to fluorescein. Acta Soc. Ophthalmol. Jpn. 75:236, 1971. 16. Ota, Y: Endothelial permeability to fluorescein in corneal grafts and bullous keratopathy. Jpn. J. OphthalmoI. 19:286, 1975. 17. Davson, H.: Rate of flowof aqueous humor. In Davson, H. (ed.). The Eye, 2nd ed. New York, Academic Press, 1969, vol. 1, pp. 117-141. 18. Mishima, S., and Hedbys, B. 0.: Measurement of corneal thickness with the Haag-Streit pachometer. Arch. Ophthalmol. 80:710, 1968. 19. Ota, Y., Mishima, S., and Maurice, D. M.: Endothelial permeability of the living cornea to fluorescein. Invest. Ophthalmol. 13:945, 1974. 20. Jones, R F., and Maurice, D. M.: New methods of measuring the rate ofaqueous flowin man with fluorescein. Exp. Eye Res. 5:208, 1966.
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21. Kraff, M. C., Sanders, D. R, Peyman, G. A., Lieberman, H. L., and Tarabishy, S.: Slit-lamp f1uorophotometry in intraocular lens patients. Ophthalmology 87:877, 1980. 22. Mishima, S.: Clinical investigations on the corneal endothelium. XXXVIII Edward Jackson Memorial Lecture. Am. J. Ophthalmol. 93:1, 1982. 23. Fontana, S. T., and Brubaker, R F.: Volume and depth of the anterior chamber in the normal aging human eye. Arch. Ophthalmol. 98:1803, 1980. 24. Bengtsson, E.: Studies on the mechanism of the breakdown of the blood-aqueous barrier in the rabbit eye. Acta Ophthalmol. 130(suppl.):1, 1977. 25. Mochizuki, M., Sawa, M., and Masuda, K.: Topical indomethacin in intracapsular extraction of senile cataract. Jpn. J. Ophthalmol. 21:215, 1977. 26. Kinsey, V. E., and Palm, E.: Posterior and anterior chamber aqueous humor formation. Arch. Ophthalmol. 53:330, 1955. 27. Huang, K., Peyman, G. A., McGetrick, J., and Janevicius, R: Indomethacin inhibition of prostaglandin-mediated inflammation following intraocular surgery. Invest. Ophthalmol. Vis. Sci. 16:760, 1977. 28. Sanders, D. R, Spigelman, A., Kraff, C., Lagouros, P., Goldstick, B., and Peyman, G. A.: Quantitative assessment of postsurgical breakdown of the blood-aqueous barrier. Arch. OphthalmoI. 101:131, 1983. 29. Bourne, W. M., and Kaufman, H. E.: Endothelial damage associated with intraocular lenses., Am. J. Ophthalmol. 81:482, 1976. 30. Mauriello, J. A., [r., McLean, 1. W., and Wright, J. D., Jr.: Loss of eyes after intraocular lens implantation. A clinicopathologic study. Ophthalmology 90:378, 1983. 31. Olson, R J., Sevel, D., and Stevenson, D.: A histopathologic study of the Choyce VlII intraocular lens. Am. J. Ophthalmol. 92:781, 1981. 32. Polack, F. M.: Management of anterior segment complications of intraocular lenses. Ophthalmology 87:881, 1980. 33. McDonnell, P. J., Green, W. R., Maumenee, A. E., and Iliff, W. J.: Pathologyof intraocular lenses in 33 eyes examined postmortem. Ophthalmology 90:386, 1983. 34. Bhattacherjee, P., and Hammond, B. R: Inhibition of increased permeability of the bloodaqueous barrier by non-steroidal anti-inflammatory compounds as demonstrated by fluorescein angiography. Exp. Eye Res. 21:499, 1975. 35. Cole, D. F., and Unger, W. G.: Prostaglandins as mediators for the responses of the eye to trauma. Exp. Eye Res. 17:357, 1973. 36. Sawa, M., and Masuda, K.: Topical indomethacin in soft cataract aspiration. Jpn. J. OphthalmoI. 20:514, 1976. 37. Crawford, J. B.: A histopathologic study of the position of the Shearing intraocular lens in the posterior chamber. Am. J. OphthalmoI. 91:458, 1981. 38. Hoffer,K. J.: Pathologic examination of a J-loop posterior chamber intraocular lens in the ciliary sulcus. Am. J. Ophthalmol. 92:268, 1981.
M.D.,
Tochigi, Japan
We used fluorophotometry and pachymetry to examine the longerterm (more than three months) postoperative effects in the anterior segment of extracapsular lens extraction with and without posterior chamber intraocular lens implantation. Fluorophotometry was performed after oral administration of fluorescein solution (5 mg/kg of body weight under fasting condition). We calculated the corneal endothelial transfer coefficient, fluorescein distribution ratio, aqueous transfer coefficient in reference to chamber volume, and loss coefficient and measured corneal thickness with a modified pachymeter. There were no significant differences between the values for corneal endothelial transfer coefficient and corneal thickness in the two groups of surgically treated eyes combined vs the intact fellow eyes. The aqueous transfer coefficient and loss coefficient values were not significantly different between the two surgically treated groups. Anterior chamber depth did not differ significantly between the two surgical groups, but the value for the two groups combined (3.79 mm) did differ significantly from that of the fellow eyes (2.87 mm) (P<.OO5). We concluded that endothelial function recovers three months after extracapsular lens extraction with or without posterior chamber intraocular lens implantation, and that the effects of intraocular lens implantation on anterior segment barrier functions are not significantly different from those of extracapsular lens extraction alone. Although extracapsular cataract extraction and posterior chamber lens implantation have reduced the postoperative complications of intraocular surgery, 1-4 the clinical effects of these surgical manipulations on the intraocular tissues have not been evaluated quantitatively. Several methods are available for in-
Accepted for publication Nov. 22, 1983. From the Department of Ophthalmology, Jichi Medical College, Tochigi, Japan. Reprint requests to Mitsuru Sawa, M.D., Eye Research Institute, 20 Staniford St., Boston, MA 02114.
vestigating intraocular tissue function. Fluorophotometric studies.Y useful in the evaluation of barrier functions in the anterior segment," have disclosed that the deterioration of corneal endothelial barrier function occurs in the early postoperative period after cataracts" or corneal transplant" surgery. Sawa and TanIshima!' reported transient increases in corneal thickness. Overall corneal endothelial functions 12,13 can be estimated by measuring corneal thickness. 14 We studied the longer-term effects of extracapsular cataract extraction alone and combined with posterior chamber
©AMERICAN JOURNAL OF OPHTHALMOLOGY 97:197-204, 1984
197
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AMERICAN JOURNAL OF OPHTHALMOLOGY
lens implantation on anterior segment functions. SUBJECTS AND METHODS
Subjects-Except for their cataracts, the subjects were generally healthy, although a few had slight hypertension. The minimum follow-up period after cataract extraction was three months. The subjects were divided into two groups. Group 1, who underwent extracapsular cataract extraction alone, included 19 eyes of 17 patients ranging in age from 24 to 84 years (mean age, 62 years). The mean (±S.D.) follow-up period was 15 ± 10 months. Group 2 underwent both extracapsular cataract extraction and posterior chamber intraocular lens implantation. It included 16 eyes of 14 patients ranging in age from 48 to 75 years (mean age, 60 years). The mean (±S.D.) followup period was 17 ± 4.8 months. The following protocol was used for the eyes in Group 1: 0.5% indomethacin oil eyedrops, 1% atropine eyedrops, and phenylephrine eyedrops were instilled three hours, two hours, one hour, and 30 minutes before surgery. Postoperatively the patients received 0.2% dexamethasone four times a day, antibiotic eyedrops four times a day, 1% atropine once a day for two weeks, and topical indomethacin twice a day for one week. Procedure-With the patient under local anesthesia, the surgeon, using an operating microscope, placed a traction suture at the superior rectus muscle. After forming a limbal-based conjunctival flap, he made a two-plane scleral groove along the surgical corneoscleral limbus from the 9 o'clock to the 3 o'clock positions. An anterior capsulotomy was performed with an irrigating cystotome. SMA-2 solution was used for irrigation. The incision was made along the base of the scleral groove. After capsulectomy, a peripheral iridectomy was done at the 12 o'clock position. The lens nucleus was
FEBRUARY, 1984
extracted with a cryotip. After the stay suture at the 12 o'clock position was tied, the cortex was removed with the IIA tip of a phacoemulsifier. The surgeon closed the limbal wound with four other interrupted sutures and the conjunctival wound with a silk suture. The procedure varied in Group 2 in that the cortex was removed without closing the stay suture at the 12 o'clock position. The anterior chamber was filled with air and the intraocular lens was inserted through the incision and fixed in position with a hook. The surgeon then closed the wound with the same method used for Group 1. The surgical and postoperative courses were uneventful in all cases, and slitlamp examinations showed no postsurgical intraocular inflammation. Fluorophotometry-We used fluorophotometry to determine the permeability of the blood-aqueous barrier" and of the corneal endothelium." The subjects were asked to drink 10% sodium fluorescein solution at a dose of 5 mg/kg of body weight while fasting. Using a slit-lamp fluorophotometer, we determined the fluorescein concentration at the center of the cornea and in the anterior chamber at intervals during a period of six hours. We took blood samples from the cubital vein at one, two, four, and six hours after dye ingestion. Blood plasma was prepared and diluted 101 times with 0.1 M phosphate buffer at pH 7.4, and the fluorescein concentration was then determined. We termed these values apparent fluorescein concentrations, because they included both fluorescein and its metabolites. Two examples of the time-course values are shown in the Figure. Data analysis-PERMEABILITY OF THE CORNEAL ENDOTHELIUM-We calculated the transfer coefficient for fluorescein exchange across the corneal endothelium in reference to the corneal volume (k...c) from the time courses of the fluorescein
VOL. 97, NO.2
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FLUOROPHOTOMETRY AFTER INTRAOCULAR LENS
8
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(hours)
Tim e
(hours)
Figure (Sawa, Sakanishi, and Shimizu). Time course of apparent fluorescein concentration in whole plasma (squares), aqueous (circles), and cornea (triangles). Left, A patient undergoing extracapsular cataract extraction only (Table 1, Case 15). Right, A patient undergoing extracapsular cataract extraction and posterior chamber implantation (Table 3, Case 31).
concentration in the cornea and the anterior chamber.P''" The following equation was fitted to the data, because slit-lamp microscopy showed no pathologic aqueous protein increase: dCc/dt = keoac (Ca - raeCc)
(1)
where Cc and Ca are apparent fluorescein concentrations in the cornea and anterior chamber respectively, rae is the distribution ratio of the dye between the two structures, and t is time. The equation was fitted to the data by a weighted least-square method." The values of kC'8C and rae were calculated for each individual. PERMEABILITY OF THE BLOOD-AQUEOUS
BARRIER-In eyes that have undergone extracapsular lens extraction, we may
consider the anterior and posterior chambers to be a single chamber, because iridectomy creates an artificial communication between them and because lens material is absent.! The volume of any implanted posterior chamber lens is much less than that of the original lens. We used the following transfer equation'? to analyze the data: dCaidt = k'inCp - k' outCa
(2)
where Ca and Cp are apparent fluorescein concentrations in the anterior chamber and plasma ultrafiltrate respectively, k'in is the apparent transfer coefficient in reference to the chamber volume, k' out is the apparent loss coefficient, and t is time. The equation was fitted to the data by a least-square method.
200
CORNEAL THICKNESS-We determined corneal thickness at the time of fluorophotometry with a modified Haag-Streit pachymeter.P Five measurements were taken at the center of the cornea and the values were averaged. ANTERIOR CHAMBER DEPTH-We measured anterior chamber depth optically and defined it as the distance between the posterior corneal layer and the posterior lens capsule in the eyes in Group 1 and as the distance between the posterior corneal layer and the surface of the posterior chamber lens in the eyes in Group 2. The measurement was made in the center of the anterior chamber. INTRAOCULAR PRESsuRE-We determined intraocular pressure by applanation tonometry at the end of the fluorophotometry.
RESULTS Although our extracapsular cataract extraction procedure did not produce a classic after-cataract, a subtle lens remnant was left at the lens equator under the iris in some cases. Slit-lamp microscopy disclosed seven eyes with lens remnants and five eyes with iris-lens remnant synechiae (Table 1). When we investigated the effects of the lens remnants and iris synechiae on the permeability of corneal endothelium and the function of the blood-aqueous barrier, we found that they made no significant difference (Table 2). The kc..c and corneal thickness values for Group 1 were not significantly different from those for Group 2 (Tables 1 and 3) and were within the same range as
TABLE
1
CLINICAL COURSE AND RESULTS IN GROUP
Patient Intraocular Corneal Anterior No., Sex, Pressure Thickness Chamber kc-ac (mm) Depth (mm) (hr- 1)* Age (yr) (mm Hg) 1, F, 66 2, M, 34 3, F. 52 4, F. 52 5. F, 73 6. F. 77 7, F. 77 8, F. 76 9. F, 66 10. F. 68 11. M, 67 12. F, 66 13. F. 76 14, F, 61 15, M, 57 16. F. 53 17. F. 63 18. M, 84 19. M, 24 Mean 63 S.D. 15
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AMERICAN JOURNAL OF OPHTHALMOLOGY
12 13 10 10 12 16 16 9 10 12 16 15 13 16 16 12 13 10 11 13 2.4
0.51 0.51 0.52 0.51 0.50 0.50 0.50 0.50 0.49 0.50 0.50 0.51 0.51 0.58 0.50 0.53 0.50 0.50 0.49 0.51 0.020
3.85 3.50 3.30 4.00 4.50 4.20 3.30 4.10 4.50 4.30 3.85 4.00 3.95 0.414
0.44 0.75 0.37 0.49 0.59 0.35 0.53 0.59 0.80 0.47 0.79 0.34 0.44 0.53 0.53 0.29
k'in k' oqt (hr- 1)* (hr- 1)* 0.77 0.68 0.50 0.92 0.97 0.42 0.77 0.34 0.75 0.57 0.98 0.34 0.59 0.57 0.84 0.16
0.15 0.058 0.26 0.39 0.21 0.92 0.99 0.24 0.36 0.097 0.16 0.23 0.19 0.08 0.31 0.27 0.14
0.39 0.50 0.28 0.51 0.63 0.30 0.15 0.24 0.26
0.60 0.50 1.7 1.6 0.94 3.1 2.8 0.79 0.91 0.61 0.68 1.4 0.77 0.48 1.4 2.5 1.1 3.00 1.4 0.89
1
Postoperative AfterPeriod (mos) cataract Synechiae 6 4 3 18 15 7 3 5 6 13 30 20 20 14 23 3 32 27 29 15 10
+ +
+
+
+
+
+ +
+ +
+
+
*Values: kc-ac. transfer coefficient for fluorescein exchange across the corneal endothelium; rae. distribution ratio of dye between anterior chamber and cornea; k'in. apparent aqueous transfer coefficient in reference to the anterior chamber volume; k' out, apparent aqueous loss coefficient.
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FLUOROPHOTOMETRY AFfER INTRAOCULAR LENS
201
TABLE 2 EFFECT OF LENS REMNANTS AND IRIS SYNECHIAE
Mean (± S.D.) Values (hr-I). Eyes
k'in
With lens remnants Without lens remnants With iris synechiae Without iris synechiae
0.56 0.48 0.53 0.50
± 0.17 ± 0.14
0.25 0.53 0.26 0.31
± 0.16 ± 0.16
± ± ± ±
k'out 0.10 0.32 0.13 0.30
1.1 1.5 1.2 1.4
± ± ± ±
0.90 0.94 1.10 0.89
·Values: ke..c, transfer coefficient for fluorescein exchange across the corneal endothelium; k'in, apparent aqueous transfer coefficient in reference to the anterior chamber volume; k' out, apparent aqueous loss coefficient.
those for the intact fellow eyes (Table 4).9 Mean (±S.D.) anterior chamber depth was 3.79 ± 0.44 mm for 25 of the eyes in Groups 1 and 2 combined and 2.87 ± 0.37 mm for 15 of the intact fellow eyes; this difference was statistically significant (P<.005 by r-test). However, anterior
chamber depth averaged 3.95 ± 0.41 mm for Group 1 and 3.64 ± 0.43 mm for Group 2; this difference was not statistically significant. Because the anterior chamber volume was estimated to be similar in both surgical groups, we compared their values for k'« and k' out and
TABLE 3 CLINICAL COURSE AND RESULTS Patient No., Sex, Age (yr) 20, F, 48 21, F, 75 22, M, 61 23, M, 73 24, F, 61 25, F, 47 26, F, 54 27, F, 49 28, F, 49 29, F, 60 30, F, 66 31, F, 66 32, M, 61 33,M,64 34,M,64 35, F, 66 Mean 60 S.D. 8.7
IN
GROUP 2
Anterior Intraocular Corneal Pressure Thickness Chamber Depth Ic.,... (hr- I). (mm) (mm) (rom Hg) 9 16 12 11 14 9 12 8 10 12 16 15 17 14 16 11 13 2.9
0.50 0.50 0.50 0.52 0.52 0.48 0.49 0.52 0.52 0.50 0.51 0.51 0.51 0.51 0.50 0.50 0.51 0.012
3.10
4.30 2.90 3.85 4.05 3.75 4.30 3.50 3.80 3.40 3.60 3.50 3.30 3.64 0.426
k'in r",,· (hr- I).
0.38 0.35 0.52 0.62
0.96 0.31 0.37 0.61
0.45 0.67
0.53 0.91
0.67
0.74
0.32
0.67
0.40
0.87
0.49 0.14
0.66 0.23
0.31 0.64 0.35 0.53 0.10 0.35 0.58 0.088 0.060 0.14 0.21 0.26 0.60 0.49 0.85 0.31 0.37 0.23
k'
(h/~.
1.1 3.9 0.79 1.4 0.47 1.8 1.7 0.41 0.37 0.91 0.82 0.84 2.2 2.2 3.5 2.2 1.5 1.1
Postoperative Period (mos) 15 13 12 13 21 20 19 28 13 17 16 14 22
20 8 18 17 4.8
·Values: Ic.,..." transfer coefficient for fluorescein exchange across the corneal endothelium; r"", distribution ratio of dye between anterior chamber and cornea; k'in, apparent aqueous transfer coefficient in reference to the anterior chamber volume; k' out, apparent aqueous loss coefficient.
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AMERICAN JOURNAL OF OPHTHALMOLOGY TABLE 4 RESULTS IN INTACT FELLOW EYES
Patient No., Sex, Age (yr)
Intraocular Pressure (mm Hg)
Corneal Thickness
I, F, 66 2, M, 34 5, F, 73 8, F, 76 10, F, 68 13, F, 76 15, M, 57 16, F, 53 17, F, 63 19, M, 24 21, F, 75 22, M, 61 23, M, 73 24, F, 61 25, F, 47 26, F, 54 29, F, 60 32, M, 61 33,M,64 34,M,64 35, F, 66 Mean 61 S.D. 13
12 10 10 9 15 13 16 12 12 14 18 8 11 16 10 12 12 16 14 14 11 13 2.6
0.51 0.50 0.50 0.50 0.50 0.51 0.50 0.50 0.50 0.49 0.50 0.50 0.51 0.52 0.48 0.49 0.50 0.51 0.51 0.50 0.50 0.50 0.01
(mm)
Anterior Chamber Depth (mm)
2.10 2.50 2.60 2.60 2.50 3.00 3.10
3.10 2.65 2.50 3.50 2.70 2.90 2.80 2.90 2.76 0.34
I<..ae (hr- 1) .
rae•
0.67 0.49 0.74 0.67 0.55 0.70 0.63 0.40 0.60 0.48 0.40 0.70 0.59
0.62 0.62 0.83 0.70 0.65 0.92 0.90 0.48 0.89 0.70 0.19 0.95 0.79
0.46 0.38 0.43 0.72 0.37 0.26 0.51 0.54 0.14
0.58 0.53 0.91 0.15 0.62 0.21 0.51 0.64 0.24
k'in (hr- 1) .
(hr- ).
0.18 0.040 0.13 0.22 0.063 0.098 0.34 0.082 0.098 0.34 0.26 0.25 0.25 0.066 0.35 0.31 0.13 0.33 0.24 0.24 0.29 0.21 0.10
0.98 0.24 0.52 0.81 0.48 0.48 1.2 0.73 0.47 3.3 1.9 0.75 0.81 0.34 1.8 1.8 0.70 1.3 1.1 1.0 1.5 1.1 0.71
k'o~t
·Values: I<..ae, transfer coefficient for fluorescein exchange across the corneal endothelium; rae, distribution ratio of dye between anterior chamber and cornea; k'in, apparent aqueous transfer coefficient in reference to the anterior chamber volume; k'out, apparent aqueous loss coefficient.
found no significant differences. The intraocular pressures in both groups were within the normal range. DISCUSSION
Fluorophotometry is a useful clinical tool for investigating pathophysiologic changes, especially in the barrier functions of the anterior segment. 7,8,10,19 Each of the several techniques has advantages and disadvantages. 5,6,19-22 The oral method, which we used, is safe and permits the determination of the corneal endothelial transfer coefficient, an index of endothelial permeability, by a simple data reduction. This coefficient can be calculated by measuring the fluorescein concentrations at the center of the cornea and in the anterior chamber Indepen-
dently of the anterior chamber volume, which varies with cataract surgery and aging. 23 Orally administered fluorescein undergoes metabolism, and part of it is converted to the glucuronide." The measured fluorescein concentration, comprising both free fluorescein and its glucuronide, is determined in reference to a standard fluorescein solution. Therefore, we termed the measured value the apparent fluorescein concentration.Y In the early postoperative period the presence of protein-bound fluorescein in the anterior chamber, as a result of breakdown of the blood-aqueous barrier, should be taken into account. 9,10,24,25 Both corneal thickness and endothelial permeability are increased one week after intracapsular cataract extraction''; we have ob-
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FLUOROPHOTOMETRY AFTER INTRAOCULAR LENS
served similar changes in a small number of cases after extracapsular cataract extraction (unpublished data). Pretreatment with indomethacin does not suppress the increase in the transfer coefficient of the corneal endothelium. 9 After the blood-aqueous barrier function recovers, Equation 1 can be applied in eyes that have undergone cataract surgery just as in normal eyes. In our study the kc..c and corneal thickness values in Groups 1 and 2 were not significantly different; further, these values did not differ significantly from those of intact fellow eyes. Thus, we concluded that endothelial functions that deteriorate in the early postoperative period can recover after three months or more. The presence of a posterior chamber intraocular lens does not affect endothelial function. The oral method is also clinically useful for estimating the blood-aqueous barrier function. 7,26 Because of the artificial communication created between the anterior and posterior chambers by peripheral iridectomy and the absence of a lens acting as a septum with the iris, the two chambers should be considered to be a single compartment.P Therefore, we applied the single-compartment model of Davson'? between the anterior chamber and the blood. The value of k' in is the transfer coefficient in reference to the anterior chamber volume. Estimation of the blood-aqueous barrier function using this method takes into account the anterior chamber volume. Comparing the values of k'in among groups that underwent different surgical procedures is of limited value. We found previously-" that the value of k' in increased in the early postoperative period and that indomethacin pretreatment reduced this increase, findings in agreement with other reports on the clinical application of indomethacin to anterior segment surgery. 8,11,20,27 We measured the fluorescein concentration in the plasma ultrafiltrate in the present
203
study because the recovery of the bloodaqueous barrier function does not permit the passage of protein28; slit-lamp examinations did not show the presence of aqueous flare. The value of k'in in the surgically treated eyes was not significantly different from that in the intact fellow eyes but the anterior chamber depth of the fellow eyes was significantly shallower than that of the surgically treated eyes. This indicated that the permeability of the blood-aqueous barrier in surgically treated eyes may increase more than three months postoperatively. Ophthalmologists generally prefer a posterior chamber intraocular lens to other intraocular lenses because it minimizes corneal endothelial damage,I,29-32 but its presence in the posterior chamber may irritate the blood-aqueous barrier or damage tissue.P The breakdown of the blood-aqueous barrier releases prostaglandins.Y" causing increases in intraocular pressure, aqueous protein levels, and miosis. We concluded that posterior chamber intraocular lenses do not affect the blood-aqueous barrier after extracapsular cataract extraction alone. 37,38 The interpretation of the value of k' out is more complicated after surgery because of anatomic changes. Although the individual variations of k' out were large, implantation of a posterior chamber intraocular lens after extracapsular cataract extraction apparently has no grossly observable effect on aqueous outflow. REFERENCES 1. Bourne, W. M., Brubaker, R. F., and O'Fallon, W. M.: Use of air to decrease endothelial cell loss during intraocular lens implantation. Arch. Ophthalmol. 97:1473, 1979. 2. Stark, W. J., Worthen, D. M., Holladay, J. T., Bath, P. E., Jacobs, M. E., Murray, G. C., McGhee, E. T., Talbott, M. W., Shipp, M. D., Thomas, N. E., Barnes, R. W., Brown, D. W. C., Buxton, J. N., Reinecke, R. D., Lao, C.-S., and Fisher, S.: The FDA report on intraocular lenses. Ophthalmology 90:311, 1983. 3. Stark, W. J., Maumenee, A. E., Dangel, M. E., Martin, N. F., and Hirst, L. W.: Intraocular
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lenses. Experience at the Wilmer Institute. Ophthalmology 89:104, 1982. 4. Bourne, W.M., Waller, R R, Liesegang, T. J., and Brubaker, R F.: Corneal trauma in intracapsular and extracapsular cataract extraction with lens implantation. Arch. Ophthalmol. 99:1375, 1981. 5. Araie, M., Sawa, M., Nagataki, S., and Mishima, S.: Aqueous humor dynamics in man as studied by oral fluorescein. Jpn. J. Ophthalmol. 24:346, 1980. 6. Sawa, M., Araie, M., and Nagataki, S.: Permeability of the human corneal endothelium to fluorescein. [pn. J. OphthalmoI. 25:60, 1981. 7. Araie, M., Sawa, M., and Takase, M.: Effect of topical indomethacin on the blood-aqueous barrier after intracapsular extraction of senile cataract. A f1uorophotometric study. Jpn. J. OphthalmoI. 25:237, 1981. 8. Sanders, D. R, Kraff, M. C., Lieberman, H. L., Peyman, G. A., and Tarabishy, S.: Breakdown and reestablishment of blood-aqueous barrier with implant surgery. Arch. Ophthalmol. 100:588, 1982. 9. Sawa, M., Araie, M., and Tanishima, T.: A f1uorophotometric study of the barrier functions in the anterior segment of the eye after intracapsular cataract extraction. Jpn. J. Ophthalmol. 27:404, 1983. 10. - - : Permeability of the corneal endothelium to fluorescein. A follow-up of keratoplasty cases. Jpn. J. Ophthalmol. 26:326, 1982. 11. Sawa, M., and Tanishima, T.: The morphometry of the human corneal endothelium and follow-up of postoperative changes. Jpn. J. OphthalmoI. 23:337, 1979. 12. Kaye, G. I., Mishima, S., Cole, J. D., and Kaye, N. W.: Studies on the cornea. VII. Effect of perfusion with a Ca + + -free medium on the corneal endothelium. Invest. OphthalmoI. 7:53, 1968. . 13. Maurice, D. M.: The location of the fluid pump in the cornea. J. Physiol. 221:43, 1972. 14. Mishima, S.: Corneal thickness. Surv. OphthalmoI. 13:57, 1968. 15. Mishima, S., and Maurice, D. M.: In vivo determination of the endothelial permeability to fluorescein. Acta Soc. Ophthalmol. Jpn. 75:236, 1971. 16. Ota, Y: Endothelial permeability to fluorescein in corneal grafts and bullous keratopathy. Jpn. J. OphthalmoI. 19:286, 1975. 17. Davson, H.: Rate of flowof aqueous humor. In Davson, H. (ed.). The Eye, 2nd ed. New York, Academic Press, 1969, vol. 1, pp. 117-141. 18. Mishima, S., and Hedbys, B. 0.: Measurement of corneal thickness with the Haag-Streit pachometer. Arch. Ophthalmol. 80:710, 1968. 19. Ota, Y., Mishima, S., and Maurice, D. M.: Endothelial permeability of the living cornea to fluorescein. Invest. Ophthalmol. 13:945, 1974. 20. Jones, R F., and Maurice, D. M.: New methods of measuring the rate ofaqueous flowin man with fluorescein. Exp. Eye Res. 5:208, 1966.
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21. Kraff, M. C., Sanders, D. R, Peyman, G. A., Lieberman, H. L., and Tarabishy, S.: Slit-lamp f1uorophotometry in intraocular lens patients. Ophthalmology 87:877, 1980. 22. Mishima, S.: Clinical investigations on the corneal endothelium. XXXVIII Edward Jackson Memorial Lecture. Am. J. Ophthalmol. 93:1, 1982. 23. Fontana, S. T., and Brubaker, R F.: Volume and depth of the anterior chamber in the normal aging human eye. Arch. Ophthalmol. 98:1803, 1980. 24. Bengtsson, E.: Studies on the mechanism of the breakdown of the blood-aqueous barrier in the rabbit eye. Acta Ophthalmol. 130(suppl.):1, 1977. 25. Mochizuki, M., Sawa, M., and Masuda, K.: Topical indomethacin in intracapsular extraction of senile cataract. Jpn. J. Ophthalmol. 21:215, 1977. 26. Kinsey, V. E., and Palm, E.: Posterior and anterior chamber aqueous humor formation. Arch. Ophthalmol. 53:330, 1955. 27. Huang, K., Peyman, G. A., McGetrick, J., and Janevicius, R: Indomethacin inhibition of prostaglandin-mediated inflammation following intraocular surgery. Invest. Ophthalmol. Vis. Sci. 16:760, 1977. 28. Sanders, D. R, Spigelman, A., Kraff, C., Lagouros, P., Goldstick, B., and Peyman, G. A.: Quantitative assessment of postsurgical breakdown of the blood-aqueous barrier. Arch. OphthalmoI. 101:131, 1983. 29. Bourne, W. M., and Kaufman, H. E.: Endothelial damage associated with intraocular lenses., Am. J. Ophthalmol. 81:482, 1976. 30. Mauriello, J. A., [r., McLean, 1. W., and Wright, J. D., Jr.: Loss of eyes after intraocular lens implantation. A clinicopathologic study. Ophthalmology 90:378, 1983. 31. Olson, R J., Sevel, D., and Stevenson, D.: A histopathologic study of the Choyce VlII intraocular lens. Am. J. Ophthalmol. 92:781, 1981. 32. Polack, F. M.: Management of anterior segment complications of intraocular lenses. Ophthalmology 87:881, 1980. 33. McDonnell, P. J., Green, W. R., Maumenee, A. E., and Iliff, W. J.: Pathologyof intraocular lenses in 33 eyes examined postmortem. Ophthalmology 90:386, 1983. 34. Bhattacherjee, P., and Hammond, B. R: Inhibition of increased permeability of the bloodaqueous barrier by non-steroidal anti-inflammatory compounds as demonstrated by fluorescein angiography. Exp. Eye Res. 21:499, 1975. 35. Cole, D. F., and Unger, W. G.: Prostaglandins as mediators for the responses of the eye to trauma. Exp. Eye Res. 17:357, 1973. 36. Sawa, M., and Masuda, K.: Topical indomethacin in soft cataract aspiration. Jpn. J. OphthalmoI. 20:514, 1976. 37. Crawford, J. B.: A histopathologic study of the position of the Shearing intraocular lens in the posterior chamber. Am. J. OphthalmoI. 91:458, 1981. 38. Hoffer,K. J.: Pathologic examination of a J-loop posterior chamber intraocular lens in the ciliary sulcus. Am. J. Ophthalmol. 92:268, 1981.