LEAKING F I L T E R I N G BLEBS Z. S I N N R E I C H , M.D.,
R. BARISHAK, M.D., Tel-Hashomer,
After successful filtering operations, aqueous humor escapes either by a sub conjunctival or a transconjunctival route. The subconjunctival route involves resorption of the aqueous by the conjunctival vessels or by the deep venous plexus of the sclera. 1 The transconjunctival route implies the oozing of aqueous through the bleb 2 ; permitting the aqueous to seep to the conjunctival surface and to mix with the tears. Spontaneous filtering blebs that occur after cataract extraction behave the same as filtering blebs. In some cases in the early postoperative period aqueous leaks temporarily because of incomplete closure of the conjunctival wound or an inadvertently buttonholed conjunctiva. In others the leakage be comes permanent and is accompanied by hypotony and eventually a shallow ante rior chamber. Clinically, as may be seen with Seidel's fluorescein test, the aqueous pours, spontaneously or after some pres sure on the eyeball, from a definite site in the bleb. In these cases of permanent leakage, we assumed that some kind of a mechanism prevents the closure of the transconjunctival leak. To study this mechanism, we examined ten excised leaking blebs sent to the Mitrani Foundation Laboratory of Ophthal mic Pathology between 1965 and 1972. M A T E R I A L AND M E T H O D S
The examined specimens included seven blebs that had a permanent leakage From the Mitrani Foundation Eye Pathology Lab oratory, Maurice and Gabriela Goldschleger Eye Institute, the Chaim Sheba Medical Center TelHashomer and the Tel-Aviv University Sackler School of Medicine, Israel. Reprint requests to Z. Sinnreich, M.D., Depart ment of Ophthalmology, Meir Hospital, Kfar-Saba, Israel.
AND R. S T E I N ,
M.D.
Israel
after filtering operations; one bleb after a filtering operation with intermittent leak age; and two leaking spontaneous blebs after cataract extraction. The tissues were paraffin-embedded and serial sections were made. The slides were stained with hematoxylin and eosin, PAS, and Masson's trichrome stains. The histologic findings in the above material were compared with those of two autopsy eyes that had active filtering blebs after Elliot trephining. Four of the ten cases (Table) are presented in detail. CASE REPORTS Case 1—A 60-year-old woman had a flapsclerotomy with a basal iridectomy in her right eye in 1961. Five years later she complained of blurred vision in the operated eye. A hypotony of 8 mm Hg caused by a leak in the filtering bleb was found. The bleb was excised and the defect covered with a free conjunctival graft. A new filtering bleb developed and no further complications occurred during a three-year follow-up. Histology (Fig. 1) revealed a thinned conjunctival epithelium, subepithelial edema, and a tract lined by multilayered conjunctival epithelium extending down to the inner surface of the specimen. Case 2—A 65-year-old man underwent a right ocular Elliot trepanation in 1965 for open-angle glaucoma. Two years later a leaking bleb with marked hypotony (6 mm Hg) was diagnosed. The histologic examination of the excised bleb revealed a moderate subconjunctival inflammation with homogenization of the collagen in some areas. An epithelial tract extended through the whole thickness of the conjunctiva (Fig. 2). Case 3—A 60-year-old woman underwent an intracapsular cataract extraction in her right eye in March 1970. Two months later she had a spontane ous leaking bleb. The Seidel test was positive and the intraocular pressure was 10 mm Hg. A small dehiscence of the wound at the base of the bleb could be seen. The bleb was excised and the wound resutured. T h e conjunctival defect was covered by adjacent conjunctiva. No complications were seen during a two-year follow-up. T h e histologic examination of the bleb (Fig. 3) showed the presence of an epithelial tract through the whole thickness of the specimen, a thickened epithelium with invaginations, and subepithelial inflammation. Case 4—A 70-year-old woman had a cataract ex-
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TABLE SUMMARY O F C L I N I C A L AND H I S T O L O G I C F I N D I N G S
Histologic Findings*
Clinical Findings Case No.
Age (yrs)
1 2 3 4 5 6 7 8 9 10
Thick Conjunctival Epithelium
Sex
Seidel Test
IOP (mm Hg)
74 60 71 65 61 29 59 47
F F M M F M M F
Positive Positive Positive Positive Negative Positive Positive Positive
14 8 4 6 6 6 12 0-2
+ + + + + + —
+ + + +
+ + + + + + + +
60 70
F F
Positive Negative
10 6
+ +
+ —
+ +
Epithelial Tract
+ + +
Inflammation
Remarks
Invagination cyst
* +Indicates present; - , absent. showed active blebs (Fig. 5): thin conjunctival epi thelium covering cystic edematous tissue, and the inner opening of the bleb lined by a Descemet-like substance and by endothelial cells.
traction in her left eye in October 1970. A few days later, a spontaneous filtering bleb was observed. Six months later, she was readmitted because of marked hypotony in this eye (4 to 6 mm Hg). The Seidel test was occasionally positive, but always present when pressure was applied to the eyeball. An unsuccessful attempt was made to close the bleb by cryoapplications. Four months later the bleb was excised and the wound resutured. No complications were ob served during a two-year follow-up period. Histologic examination (Fig. 4) showed a surface conjunctival epithelium of variable thickness with moderate subepithelial inflammation and homogenization of the connective tissue. A tortuous epithe lial tract could be followed through the thickness of the conjunctiva and subconjunctiva. The filtering blebs of the two autopsy eyes
The normal filtering bleb appears histologically as a cystic area in an edematous subconjunctival tissue and is connected with the anterior chamber. 2 ' 3 The connec tion between the anterior chamber and the bleb is lined by a Descemet-like sub stance and endothelial cells, pigmented
Fig. 1 (Sinnreich, Barishak, and Stein). Conjuncti val epithelium lines the tract and partly covers the inner face of the bleb (hematoxylin and eosin, x 120).
Fig. 2 (Sinnreich, Barishak, and Stein). Tortuous epithelial tract extending through the whole thick ness of the bleb (hematoxylin and eosin, x50).
DISCUSSION
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Fig. 3 (Sinnreich, Barishak, and Stein). Epithelial tract extending through the whole thickness of the bleb and lining its inner face (hematoxylin and eosin, x l 2 0 ) .
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Fig. 5 (Sinnreich, Barishak, and Stein). Function al filtering bleb, following an Elliot trepanation. A Descemet-like substance and endothelial cells line its inner aperture (hematoxylin and eosin, x l 2 0 ) .
cells, or both. 4 - 7 This arrangement per mits the percolation of aqueous humor into the subconjunctival space. The lytic action of the aqueous on the connective tissue causes the appearance of subcon junctival edema and of cystoid spaces with marked thinning of the overlying conjunctival epithelium. Bleb leakage may be caused by trau matic rupture of the bleb, 8 prolonged use of cortico steroids, 8,9 or extreme thinning of the conjunctiva covering the bleb. 1 0 Duke-Elder 3 stated that the most permanent and efficient factor in keeping a patent channel would appear to be the migration of the pigmentary cells of the iris, which being ectodermal are not engulfed in mesodermal overgrowth.
Fig. 4 (Sinnreich, Barishak, and Stein). Epitheli al tract running through the whole thickness of the conjunctiva and covering part of its inner face (hematoxylin and eosin, x50).
Epithelial cells of the conjunctiva may play a similar role by lining a leaking tract, thus preventing its closure. 6 The tendency of epithelial cells to cover any continuity defect is well documented. 1 1 , 1 2 Conversely, Theobald 1 3 stated that "epi-
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thelial ingrowth has never been reported as occurring in filtering operations." However, the review of our cases shows that the formation of an epithelial tract in leaking blebs is a histologic reality. In eight of our ten cases, we found an in growth of the conjunctival epithelium into the subconjunctival tissue. In one case, an invagination cyst was present, and in the last case we could not identify the site of the leakage. Theobald 1 3 states that on histologic ex amination of 14 cases of epithelization of the anterior chamber, only in five cases was she able to trace the epithelial tract through the wound and that "the condi tion could have been found in the other cases if it had been possible to serial section the entire eye." This method of serial sections enabled us to discover the epithelial tract in the majority of our cases. The epithelial tract was not detect ed in two cases, perhaps because it was at the edge of the specimen and therefore lost during the first sections of the paraf fin block. The material examined by us consisted only of conjunctiva and subconjunctival tissue as it was sliced off by the surgeon. We were, therefore, unable to determine whether the epithelial ingrowth also in volved the corneoscleral limbal opening. Chandler 1 4 described two aphakic eyes with ruptured filtering blebs that were lost because of epithelization of the ante rior chamber. Clinical follow-up did not reveal such an invasion in any of our cases. In some of our cases of leaking blebs, the Seidel test was negative at the time of testing, but with pressure on the globe, the test became positive. A possible ex planation of this finding may be that spontaneous leaking through the wall of the bleb depends on the pressure gradient between the anterior chamber and the conjunctival surface 1,6,15 and also on the
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amount of fluid present in the anterior chamber. For this reason leaking blebs may not leak if there is a shallow anterior chamber. 1 6 Because an epithelial tract running from the conjunctival surface down to the sclera was found in eight of the ten cases, we surmise that this formation is responsible for the persistent leakage of filtering blebs. Because this epithelial tract is an established anatomic struc ture, conservative treatment can be of no avail. We believe that the only reasonable treatment in these cases is the surgical removal of the bleb 1 7 and covering of the defect by healthy conjunctiva, thus pre venting epithelial downgrowth into the anterior chamber, diminishing the danger of late infection, 18,19 and eliminating the harmful effects of hypotony. SUMMARY
Histologic examination of ten leaking filtering blebs revealed an epithelial tract running from the surface of the bleb down to the episclera in eight cases. These epithelial tracts were considered the real cause of the persistent leakage. REFERENCES 1. Galin, M. A., Baras, I., and McLean, J. M.: The mechanism of external filtration. Am. J. Ophthalmol. 61:63, 1966. 2. Duke-Elder S. and Perkins, E. S.: Diseases of the Uveal Tract. In Duke-Elder, S. (ed.): System of Ophthalmology, vol. 9. London, H. Kimpton, 1969, p. 541 3. Duke-Elder, S.: Textbook of Ophthalmology, vol. 3. London, H. Kimpton, 1945, p. 3405. 4. Kirk, H. Q.: Cauterization of filtering blebs following cataract extraction. Trans. Am. Acad. Ophthalmol. Otolaryngol. 77:573, 1973. 5. Seidel, E.: Weitere experimentelle Untersuchungen iiber die Quelle und den Verlauf der intraokulaeren Saftstroemung. Albrecht von Graefes Arch. Klin. Ophthalmol. 104:403, 1921. 6. Teng, C. C , Chi, H. H. and Katzin H. M.: Histology and mechanism of filtering operations. Am. J. Ophthalmol. 47.16, 1959. 7. Teng, C. C , Chi, H. H„ and Katzin, H. M.: Aqueous degenerative effect and the protective role of endothelium in eye pathology. Am. J. Ophthal mol. 50:365, 1960.
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8. Sugar, H. S.: Limboscleral trepanation. Arch. Ophthalmol. 85:703, 1971. 9. :Clinical effects of corticosteroids on conjunctival filtering blebs. Am. J. Ophthalmol. 59:854, 1965. 10. Complications, repair and reoperations of antiglaucoma filtering blebs. Am. J. Oph thalmol. 63:825, 1967. 11. Hervougt, F.: Travaux d'anatomie pathologique oculaire. Paris, Masson et Cie., 1964, p. 9. 12. Swan, K. C : Fibroblastic ingrowth following cataract extraction. Arch. Ophthalmol. 89:445,1973. 13. Theobald, G. D., and Haas, J. S.: Epithelial invasion of the anterior chamber following cataract extraction. Trans. Am. Acad. Ophthalmol. Otolaryngol. 52:470, 1948.
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14. Chandler, P. A., and Grant, W. M.: Lectures on glaucoma. Philadelphia, Lea and Febiger, 1968, p. 401. 15. Galin, M. A., Baras, I., and Cavero, R.: Stimu lation of a filtering bleb. Arch. Ophthalmol. 74:777, 1965. 16. Welsh, R. C.: Late flat anterior chambers after cataract surgery. Ann. Ophthalmol. 3:765, 1971. 17. Stallard, W.: Eye Surgery. Bristol, J. Wright and Sons, 1965, p. 694. 18. Sugar, H. S., and Zekman, T.: Late infection of filtering conjunctival scars. Am. J. Ophthalmol. 46:155, 1958. 19. Swan, K. C., and Campbell, L.: Unintentional filtration following cataract surgery. Arch. Ophthal mol. 71:43, 1964.
O P H T H A L M I C MINIATURE
The doctor had moved to the nearest crate and, with stolid competence, was prying off the lid. "The first thing we do is fit you out competently. Oh! I know you two believe in God. And the Lieutenant in Confucius." He bent and .produced rubber boots from the case. "But I believe in prophylaxis." H e completed the unpacking of his supplies, fitting white overalls and goggles upon them, berating their negligence of their own safety. His remarks ran on, matter-of-fact, composed. "Don't you realize, you confounded innocents. . . one cough in your eye and you're done for. . . penetration of the cornea. They knew that even in the fourteenth century. . . they wore vizors of isinglass against this pneumonic plague. . . it was brought down from Siberia by a band of marmoset hunters." A. J. Cronin, The Keys of the Kingdom Victor Gollancz, 1942