`
`Ab-interno trabeculo-canalectomy: surgical
`approach and histological examination
`
`E. FERRARI1, F. BANDELLO1, F. ORTOLA NI2, L. PETRELLI2, M. MARCHINI2, D. PONZIN3
`
`1 Department of Ophthalmology, University of Udine
`2 Department of Medical and Morphological Research, University of Udine
`3 Veneto Eye Bank Foundation, Venezia-Mestre - Italy
`
`PURPOSE. To evaluate, on eye bank eyes, a new surgical approach aimed at removing a quadrant of
`the trabecular meshwork (TM), with an ab interno approach.
`METHODS. Gonioscopically controlled ab interno removal of the TM was done with a sub-
`retinal forcep on six human bank eyes. Serial histological sections were obtained from the
`treated and untreated part of each globe to assess the effect of the technique on intraoc-
`ular tissues.
`RESULTS. Under the gonioscope, the TM was easily removed in strings of varying length.
`Histological examination showed, unexpectedly, that this resulted in a well-defined deep
`furrow in the middle of the trabecular region involving both the TM and the inner wall of
`Schlemm’s canal. The operation created a direct communication between the anterior cham-
`ber and Schlemm ’s canal lumen without any evident damage to the outer canal wall and
`adjacent ocular structures such as the iris base and corneal endothelium.
`CONCLUSIONS. Our small series on human bank eyes showed that the procedure involves
`both the TM and the inner wall of Schlemm’s canal and is therefore called ab interno tra-
`beculocanalectomy (AITC). The intraoperative findings and the histological evidence are
`encouraging, and suggest that the procecedure could have potential clinical application.
`(Eur J Ophthalmol 2002; 12: 401-5)
`KEY WORDS. Ab-interno trabecular surgery, Irido-corneal angle surgery, Glaucoma surgery
`Accepted: October 16, 2001
`
`INTRODUCTION
`
`Trabecular meshwork surgery aims to increase the
`outflow of aqueous humor through its normal pathway
`and lower intraocular pressure (IOP) (1-3). The basis
`of
`this approach
`is
`to relieve
`the resistance
`to
`aqueous humor outflow within the TM, in juxtacana-
`licular tissue and the inner wall of Schlemm’s canal (4-
`7). Many surgical and laser techniques have been
`
`proposed to boost aqueous humor outflow through
`the anterior chamber angle (1-3, 8-13). However, the
`choice remains controversial because of the lack of
`convincing evidence of the superiority of any one ap-
`proach over the others. Theoretically, a therapeutic
`option that removes the resistance to aqueous out-
`flow as far as possible, without damaging the outer
`outflow pathways and the surrounding ocular struc-
`tures, such as the base of the iris and the corneal en-
`
`© Wichtig Editore, 2002
`
`1120-6721/401-06$03.00/0
`
`Petitioner - New World Medical
`Ex. 1018, p. 1 of 5
`
`
`
`Ab-in terno trabeculo-canalectomy: surgical approach and histological examination
`
`dothelium, offers better chances of success.
`The present study was designed to evaluate, on eye
`bank eyes, the histological effect of a new surgical
`technique designed to remove TM mechanically. This
`procedure, uses a peeling-like approach, to remove
`the TM rather than cutting, disrupting or scraping the
`trabeculum as already described (1-3, 13).
`
`METHODS
`
`The procedures were carried out on six human eye
`bank eyes unsuitable for keratoplasty (cadaver time
`less than 24 hours). Surgery was done under direct
`observation of the anterior chamber angle with an
`operating microscope and a surgical gonioprism. After
`an 8.5 mm
`trephination
`the central cornea was
`removed as during a conventional keratoplasty; the
`anterior chamber was filled with viscoelastics and the
`globe was tilted so as to be able to observe the
`anterior chamber angle structures. The central cornea
`was removed because of its poor transparency; the
`goniopri-sm was necessary to properly visualize the
`fine details of the anterior chamber angle. A subretinal
`vi-trectomy forceps (Thomas horizontal subretinal for-
`ceps, Synergetics Inc. MO, USA) was introduced into
`the anterior chamber through a limbal paracente-sis
`and directed towards the irido-corneal angle. The
`trabecular membrane was then pinched and removed
`with a peeling-like approach. The goal of the operation
`was to remove one quadrant of TM (three clock
`hours). The part of the globe subjected to the proce-
`dure was marked so as to be able to recognize the
`treated area afterwards. Great care was taken while
`removing the trabecular membrane to avoid damaging
`adjacent ocular structures such as the base of the iris
`or corneal endothelium. At the end of the surgery the
`viscoelastics was
`removed with an automated
`irrigation-aspiration unit.
`
`Histology
`
`All the samples were (a) fixed with 2.5% formaldehy-
`de + 2.5% glutaraldehyde in 0.1 M phosphate buffer,
`pH 7.4, for 24h at room temperature; (b) dehydrated
`in graded ethanols and (c) embedded in paraffin. Pa-
`raffin blocks were embedded and mounted in such a
`way that microtome cuts were made along meridio-
`
`nal planes. Serial 5 µm thick sections were stained
`with hematoxylin and eosin. Serial sections were ob-
`tained from the treated and the untreated parts of ea-
`ch globe. Samples excised from untreated areas ser-
`ved as controls.
`
`RESULTS
`
`During the procedures the TM was apparently removed
`in strings longer than one clock hour (1-3 hours) in four
`eye globes. In two eyes the membrane was friable,
`resulting
`in strings shorter
`than one clock hour.
`Gonioscopically a membrane that apparently corre-
`sponded to the TM was easily pinched and removed
`from all the eyes. During the procedures no damage
`was detected to the structures adjacent to the TM such
`as the corneal endothelium and the iris base. The
`gonioscopically detectable effect of treatment at the
`end of the surgery was an apparent TM depigmenta-
`tion in the treated area and some trabecular debris
`floating in the viscoelastics in the angular recess. On
`histological section of the control specimens, all the
`structures of the anterior chamber angle were fairly
`well preserved (Fig. 1). The TM appeared to be formed
`of intact thin sheets and the walls of Schlemm’s canal
`were well-preserved. As usual for samples that had
`undergone standard processing for light microscopy,
`topical deformations or even sporadic detachments of
`the endothelium lining the canal walls were observed.
`Another minor artifact was some degree of corneal
`and/or scleral swelling due to slight separation of the
`collagen lamellae. The iris structure was intact but it
`lost its linear course causing a different angular width
`of the recess.
`In histological sections corresponding to the regions
`subjected to peeling, tissue conditions were similar to
`the control specimens, except
`for
`the
`trabecular
`region. Here, in the middle portion of the trabeculum,
`there was a full-thickness lack of trabeculum involving
`both the trabecular meshwork and the inner wall of
`Schlemm’s canal (Fig. 2). This deep cleft caused an
`evident opening of the lumen of Schlemm’s canal into
`the anterior chamber. However, the remaining canal
`wall was intact and was lined by an undamaged
`endothelium (Fig. 2). These histological findings were
`evident for the whole of the trabeculum that had
`undergone the “procedure”. In addition, the sizes of
`
`4 0 2
`
`Petitioner - New World Medical
`Ex. 1018, p. 2 of 5
`
`
`
`Ferrari et al
`
`Fig. 1 - Histological section of human irido-corneal angle (con-
`trol sample). All the anterior chamber angle structures are fairly
`well preserved: the trabecular meshwork is formed of intact thin
`sheets and Schlemm ’s canal (asterisk) has well-preserved
`walls. Staining with hematoxylin and eosin (x 170).
`
`the clefts were comparable to those of the membra-
`nes removed. Extremely fine trabecular debris was
`detectable along the peeled area but none of the spe-
`cimens contained any flaps of uveal tissue capable of
`returning to its pre-treatment position.
`This histological evidence indicated that the proce-
`dure resulted in the removal of both the TM and Sch-
`lemm’s canal inner wall. It was therefore called ab-
`interno trabeculocanalectomy (AITC). Like in the con-
`trol specimens, there were artifacts such as corneal-
`scleral swelling or different width of the angular re-
`cess.
`
`DISCUSSION
`
`Ab-interno trabecular surgery comprises many diffe-
`rent procedures with the same purpose: to improve
`aqueous outflow through conventional pathways. The
`rationale for these approaches is to remove the resi-
`stance to outflow within the TM, in juxtacanalicular
`tissue and in the inner wall of Schlemm’s canal (4-7,
`14). Experimental studies have shown that incising
`the TM and Schlemm’s canal can increase outflow
`(15, 16). Clinical studies confirmed that trabecular in-
`cision or trabecular scraping can reduce intraocular
`
`Fig. 2 - Histological section corresponding
`the region
`to
`subjected to AITC. A full thickness trabecular lack involving both
`the tra becular meshwork and the inner wall of Schlemm’s canal
`is evi dent. This creates a direct communication between the
`lumen of the canal (asterisk) and the anterior chamber (curved
`arrows). The outer wall of the canal (double arrows) is intact and
`is
`lined with an undamaged endothelium. Staining with
`hematoxylin and eosin (x 170).
`
`pressure (1-3, 12, 13).
`Microsurgical dissection of the TM was first described
`by Tailor (17) and De Vincentiis (18). The procedure
`has been modified over the years (1-3, 8) and is now
`attracting renewed interest among ophthalmologists
`for the treatment of juvenile glaucoma (19, 20) and for
`chronic open angle glaucoma (12, 21-23). New
`surgical and laser approaches such as goniocuretta-
`ge (13), goniopuncture (24), Erbium:YAG (10) or ex-
`cimer laser trabecular ablation (11) have been pro-
`posed to reduce IOP in glaucomas. This search for
`novel approaches is seeking a technique that can re-
`store a physiological route of aqueous outflow without
`the complications of filtering surgery.
`To date there is no convincing evidence of the supe-
`riority of any one trabecular approach over the other.
`The creation of small holes with the goniopuncture
`approach or the disruption of the TM with the trabe-
`culotomy technique removes little tissue and may be
`followed by filling and scarring with subsequent clo-
`sure of the trabecular opening (9, 25, 26).
`AITC is a new experimental surgical procedure devi-
`sed to mechanically remove the TM, with the func-
`tional purpose of opening an exit route for aqueous
`humor into Schlemm’s canal and out through the nor-
`mal pathway. Histological examination showed that
`
`4 0 3
`
`Petitioner - New World Medical
`Ex. 1018, p. 3 of 5
`
`
`
`Ab-in terno trabeculo-canalectomy: surgical approach and histological examination
`
`our original idea of peeling away the TM alone ac-
`tually removed both the TM and the inner wall of
`Sch-lemm’s canal. This unexpected result might
`possibly achieve a better outflow than TM removal
`alone. Considering that the site of major resistance
`to
`the outflow of aqueous humor
`is at
`the
`juxtacanalicular portion of the TM and the inner wall
`of Schlemm’s canal and that often, during non-
`penetrating
`filtering
`surgery
`better
`aqueous
`percolation is achieved by peeling the inner wall of
`the canal (27, 28), we suggest that removal of both
`the TM and the inner wall of Sch-lemm’s canal would
`ensure better outflow than removal of the TM alone.
`However, with non-penetrating
`filtering surgery
`outflow can also be improved by an ab externo
`approach, leaving the TM intact (27-30).
`We found that the histological effects of AITC were
`different from with the classical goniotomy and tra-
`beculotomy procedures (25). These latter produce a
`deep incision in the trabecular tissue with close edges
`of the wound. The histological picture after AITC also
`differs
`from goniocurettage.
`In
`this procedure
`trabecular removal is associated with damage to the
`posterior wall of Schlemm’s canal and collector ves-
`sels (13).
`Although our histological findings on cadaver eyes
`are encouraging problems may be encountered in cli-
`nical application of AITC. The fine details of anterior
`chamber angle structures cannot be clearly visualized
`in every case: corneal opacities, corneal edema
`
`or the presence of blood in the anterior chamber may
`render gonioscopic observation inadequate.
`Like other ab-interno procedures, other pre-requisites
`for AICT are a stable anterior chamber and wide irido-
`corneal angle. Although viscoelastics can be used to
`stabilize the anterior chamber, sufficient widening of
`the irido-corneal angle cannot be achieved in every
`case. Predictable risks with AITC are: lens or corneal
`endothelium contacts, bleeding from the trabecular
`vessels and/or from Schlemm’s canal, early intrao-
`cular pressure rise due to retention of viscoelastics,
`iris root damage, inadvertent cyclodialysis, bulbar hy-
`potony.
`
`ACKNOWLEDGEMENTS
`
`The authors thank the Veneto Eye Bank Foundation for their
`kind co-operation.
`Supported by funds from the Department of Surgical Sciences,
`University of Udine.
`
`Reprint requests to:
`Ettore Ferrari, MD
`Department of Ophthalmology
`University of Udine
`Viale Venezia 410
`33100 Udine
`ettore.ferrari@dsc.uniud.it
`
`REFERENCES
`
`for chronic glaucoma.
`1. Barkan O. A new operation
`function by opening
`Restoration of physiological
`Schlemm’s canal under direct magnified vision. Am J
`Ophthalmol 1936; 19: 951-66.
`2. Burian HM. A case of Marfan’s syndrome with bilater-
`al glaucoma. A description of a new type of operation
`for developmental glaucoma (trabeculotomy ab exter-
`no). Am J Ophthalmol 1960, 50: 1187-95.
`3. Smith R. A new technique for opening the canal of Schlemm.
`Preliminary report. Br J Ophthalmol 1960; 44: 370-5.
`4. Nesterov AP, Batmanov YrE. Study on morphology and
`function of drainage area of the eye of a man. Acta
`Ophthalmol 1972; 50: 337-41.
`5. Nesterov AP, Batmanov YE. Trabecular wall of Schlemm’s
`
`canal in the early stage of primary open-angle glaucoma.
`Am J Ophthalmol 1974; 78: 639-47.
`0. Murphy CG, Johnson M, Alvarado JA. Juxtacanalicu-lar
`tissue in pigmentary and primary open angle glau-
`coma: the hydrodynamic role of pigment and other con-
`stituents. Arch Ophthalmol 1992; 110: 1779-85.
`1. Lütjen-Drecoll E, Shimizu T, Rohrbach M, Rohen JW.
`Quantitative analysis of “plaque material” in the inner
`and outer wall of Sclemm’s canal in normal and glau-
`comatous eyes. Exp Eye Res 1986; 42: 443-455.
`2. Bietti GB, Quaranta CA. Indications for and results of
`iridocorneal
`angle
`incision.
`(Goniotomy,
`goniotra-
`beculotomy or trabeculectomy). Trans Ophthal Soc New
`Zeal 1968; 20 (suppl): S20-42.
`3. Melamed S, Pei J, Puliafito CA, Epstein DL. Q-switched
`neodymium:YAG laser trabeculopuncture in monkeys.
`
`4 0 4
`
`Petitioner - New World Medical
`Ex. 1018, p. 4 of 5
`
`
`
`Ferrari et al
`
`13.
`
`Arch Ophthalmol 1985; 103: 129-33.
`10. Dietlein TS, Jacobi PC, Krieglstein GK. Erbium:YAG laser
`trabecular ablation (LTA) in the surgical treatment of
`glaucoma. Lasers Surg Med 1998; 23: 104-10.
`11. Vogel M, Lauritzen K, Quentin CD. Targeted ablation
`of the trabecular meshwork with excimer laser in
`primary open-angle glaucoma. Opthalmologe 1996;
`93: 5658.
`12. Quaranta L, Hitchings RA, Quaranta CA. Ab-interno go-
`niotrabeculotomy versus mitomycin C trabeculectomy for
`adult open angle glaucoma. Ophthalmology 1999; 106:
`1357-62.
`Jacobi PC, Dietlein TS, Krieglestein GK. Technique of
`goniocurettage: a potential
`treatment
`for advanced
`chronic open angle glaucoma. Br J Ophthalmol 1997;
`81: 302-7.
`14. Grant WM. Further studies on facility of flow through
`the trabecular meshwork. Arch Ophthalmol 1958; 60:
`523-33.
`15. Grant WM. Experimental aqueous perfusion in enucle-ated
`human eyes. Arch Ophthalmol 1963; 69: 783-91.
`16. Grant WM. Laboratory research. Microsurgery of outflow
`channels
`(symposium). Trans Am Acad Ophthal-mol
`Otolaryngol 1972; 76: 398-402.
`17. Tailor U. Sulla incisione dell’angolo irideo (Contribuzione
`alla cura del glaucoma). Ann Oftalmol 1891; 20: 117-27.
`18. De Vincentiis C. Sulla cosiddetta sclerotomia interna. In:
`Lavori della clinica oculistica dell’Università di Napoli.
`Napoli: Pasquale V; 1894-1896: 227-35.
`19. Anderson DR. Trabeculectomy compared to gonioto-
`my for glaucoma in children. Ophthalmology 1983; 90:
`805-6.
`20. McPherson SD Jr, Berry DP. Goniotomy vs external tra-
`
`beculotomy for developmental glaucoma. Am J Oph-thalmol
`1983; 95: 427-31.
`21. Tanihara H, Negi A, Akimoto M, Terauki H, et al. Sur-
`gical effects of trabeculotomy ab externo on adult eyes
`with primary open-glaucoma and pseudoexfoliation
`syndrome. Arch Ophthalmol 1993, 111: 1653-61.
`22. Schwenn O, Grehn F, Olbert D. Cataract extraction com-
`bined with trabeculotomy. Klin Monatsbl Augenheilkd 1993;
`203: 144-52.
`23. Gimbel HV, Meyer D, DeBroff BM, et al. Intraocular
`pressure response to combined phacoemulsification
`and
`trabeculotomy
`versus
`ab
`externo
`phacoemulsification alone
`in primary open-angle
`glaucoma. J Cataract Refract Surg 1995; 14: 650-5.
`24. Epstein DL, Melamed S, Puliafito CA, Steinert RF.
`Neodymi-um:YAG laser trabeculopuncture in open angle
`glaucoma. Ophthalmology 1985; 92: 931-7.
`Ito S, Nishikawa M, Tokura T, et al. Histopathological study
`of trabecular meshwork after trabeculotomy in monkeys.
`Nippon Ganka Gakkai Zasshi 1994; 98: 811-9.
`26. Van der Zypen E, Fankhauser F. The ultrastructural
`features of laser trabeculopuncture and cyclodialysis:
`problems related to successful treatment of chronic
`simple glaucoma. Opthalmologica 1979; 179: 189-200.
`27. Mermoud A, Ravinet E. Aqueous outflow mechanism and
`glaucoma surgery. J Glaucoma 2001; 10: 365-7.
`28. Mermoud A, Schnyder CC. Non-penetrating filtering surgery
`in glaucoma. Curr Opin Ophthalmol 2000; 11: 151-7.
`29. Carassa RG, Bettin P, Fiori M, Brancato R. Viscocanalostomy:
`a pilot study. Eur J Ophthalmol 1998; 8: 57-61.
`30. Stegmann R, Pienaar A, Miller D. Viscocanalostomy for
`open angle glaucoma in black African patients. J Cataract
`Refract Surg 1999; 25: 316-22.
`
`25.
`
`4 0 5
`
`Petitioner - New World Medical
`Ex. 1018, p. 5 of 5
`
`