Ординатура / Офтальмология / Английские материалы / Mechanisms of the Glaucomas_Shields, Tombran-Tink, Barnstable_2008

44.Eibschitz-Tsimhoni M, Schertzer RM, Musch DC, Moroi SE. Incidence and management of encapsulated cysts following Ahmed glaucoma valve insertion. J Glaucoma 2005;14: 276–279.

45.Lloyd MA, Baerveldt G, Fellenbaum PS, Sidoti PA, Minckler DS, Martone FJ, LaBree L, Heuer DK. Intermediate-term results of a randomized clinical trial of the 350 versus the 500-mm2 Baerveldt implant. Ophthalmology 1994;101:1456–1464.

46.Britt MT, LaBree LD, Lloyd MA, Minckler DS, Heuer DK, Baerveldt G, Varma R. Randomized clinical trial of the 350versus the 500-mm2 Baerveldt Implant. Ophthalmology 1999;106:2312–2318.

47.Minckler DS, Vedula SS, Li TJ, Mathew MC, Ayyala RS, Francis BA. Aqueous shunts for glaucoma (Cochrane review). In: The Cochrane Database of Systematic Reviews. April 2006;(2).

48.Tsai JC, Johnson CC, Dietrich MS. The Ahmed shunt versus the Baerveldt shunt for refractory glaucoma: a single-surgeon comparison of outcome. Ophthalmology 2003;110: 1814–1821.

49.Taglia DP, Perkins TW, Gangnon R, Heatley GA, Kaufman PL. Comparison of the Ahmed glaucoma valve, the Krupin eye valve with disk, and the double-plate Molteno implant. J Glaucoma 2002;11:347–353.

50.Syed HM, Law SK, Nam SH, Li G, Caprioli J, Coleman A. Baerveldt-350 implant versus Ahmed valve for refractory glaucoma: a case-controlled comparison. J Glaucoma 2004;13:38–45.

51.Francis BA, Cores A, Chen J, Alvarado JA. Characteristics of glaucoma drainage implants during dynamic and steady state flow conditions. Ophthalmology 1998;105:1707–1714.

52.Stay MS, Pan T, Brown JD, Ziaie B, Barocas VH. Thin-film coupled fluid-solid analysis of flow through the Ahmed glaucoma drainage device. J Biomech Eng 2005;127:776–781.

53.Eisenberg DL, Koo EY, Hafner G, Schuman JS. In vitro flow properties of glaucoma implant devices. Ophthalmic Surg Lasers 1999;30;662–667.

54.Lloyd MA, Minckler DS, Heuer DK, Baerveldt G, Green RL. Echographic evaluation of glaucoma shunts. Ophthalmology 1993;100:919–927.

55.McDonnell PJ, Robin JB, Schanzlin DJ, Minckler DS, Baerveldt G, Smith RE, Heuer D. Molteno implant for control of glaucoma in eyes after penetrating keratoplasty. Ophthalmology 1988;95:364–369.

56.Sidoti PA, Mosny AY, Ritterband DC, Seedor JA. Pars plana tube insertion of glaucoma drainage implants and penetrating keratoplasty in patients with coexisting glaucoma and corneal disease. Ophthalmology 2001;108:1050–1058.

57.Molteno AC, Sayawat N, Herbison P. Otago glaucoma surgery outcome study: long-term results of uveitis with secondary glaucoma drained by Molteno implants. Ophthalmology 2001;108:603–613.

58.Hoffman KB, Feldman RM, Budenz Dl, Gedde SJ, Chacra GA, Schiffman JC. Combined cataract extraction and Baerveldt glaucoma drainage implant: indications and outcomes. Ophthalmology 2002;1089:1916–1920.

59.Sivak-Callcott JA, O’Day DM, Gass JD, Tsai JC. Evidence-based recommendations for the diagnosis and treatment of neovascular glaucoma. Ophthalmology 2001;108:1767–1776.

60.Every SG, Molteno AC, Bevin TH, Herbison P. Long-term results of Molteno implant insertion in cases of neovascular glaucoma. Arch Ophthalmol 2006;124:355–360.

61.Yalvac IS, Eksioglu U, Satana B, Duman S. Long-term results of Ahmed glaucoma valve and Molteno implant in neovascular glaucoma. Eye 2005 [Epub ahead of print].

62.Luttrull JK, Avery RL. Pars plana implant and vitrectomy for treatment of neovascular glaucoma. Retina 1995;15:379–387.

63.Susanna R Jr, Nicolela MT, Takahashi WY. Mitomycin C as adjunctive therapy with glaucoma implant surgery. Ophthalmic Surg 1994;25:458–462.

64.Prata JA Jr, Minckler DS, Mermoud A, Baerveldt G. Effects of mitomycin-C on the function of Baerveldt glaucoma drainage implants in rabbits. Glaucoma 1996;5:29–38.

65.Azuara-Blanco A, Moster MR, Wilson RP, Schmidt CM. Simultaneous use of mitomycin-C with Baerveldt implantation. Ophthalmic Surg Lasers 1997;12:992–997.

66.Cantor L, Burgoyne J, Sanders S, Bhavnani V, Hoop J, Brizendine E. The effect of mitomycin C on Molteno implant surgery: a 1-year randomized, masked, prospective study. J Glaucoma 1998;7(4):240–246.

67.Susanna R Jr and the Latin American Glaucoma Society (SLAG) Investigators. Partial Tenon’s capsule resection with adjunctive mitomycin C in Ahmed glaucoma valve implant surgery. Br J Ophthalmol 2003;87:994–998.

68.Duan X, Jiang Y, Qing G. Long-term follow-up study on Hunan aqueous drainage implantation combined with mitomycin-C for refractory glaucoma. Yan Ke Xue Bao Bian Ji Bu 2003;19(2):81–85.

69.Costa VP, Azuara-Blanco A, Netland PA, Lesk MR, Arcieri ES. Efficacy and safety of adjunctive mitomycin-C during Ahmed glaucoma valve implantation: a prospective randomized clinical trial. Ophthalmology 2004;111:1071–1076.

70.Prata JA Jr, Minckler DS, Mermoud A, Baerveldt G. Effects of mitomycin-C on the function of Baerveldt glaucoma drainage implants in rabbits. J Glaucoma 1996;5:29–38.

71.Rodrigues AM, Corpa MV, Mello PA, de Moura CR. Results of the Susanna implant in patients with refractory primary congenital glaucoma. JAAPOS 2004;8:576–579.

72.Fellenbaum PS, Sidoti PA, Heuer DK, Minckler DS, Baerveldt G, Lee PP. Experience with the Baerveldt implant in young patients with complicated glaucomas. Glaucoma 1995;4:91–97.

73.Djodeyre MR, Peralta CJ, Abelairas GJ. Clinical evaluation and risk factors of time to failure of Ahmed glaucoma valve implant in pediatric patients. Ophthalmology 2001;108:614–620.

74.Shah AA, WuDunn D, Cantor LB. Shunt revision versus additional tube shunt implantation after failed tube shunt surgery in refractory glaucoma. Am J Ophthalmol 2000;129:455–460.

75.Smith MF, Sherwood MB, McGorray SP. Comparison of the double-plate Molteno drainage implant with the Schocket procedure. Arch Ophthalmol 1992;110:1246–1250.

76.Wilson RP, Cantor L, Katz J, Schmidt CM, Steinmann WC, Allee S. Aqueous shunts: Molteno versus Schocket. Ophthalmology 1992;99:672–678.

77.Gerber SL, Cantor LB, Sponsel WE. A comparison of postoperative complications from pressure-ridge Molteno implants versus Molteno implants with suture ligation. Ophthalmic Surg Lasers 1997;28:905–910.

78.Valimaki J, Airaksinen PJ, Tuulonen A, Risteli J. Postoperative systemic corticosteroid treatment and Molteno implant surgery: A randomized clinical trial. Acta Ophthalmol Scand 1999;77:50–56.

79.Wilson MR, Mendis U, Smith SD, Paliwal A. Ahmed glaucoma valve implant vs trabeculectomy in the surgical treatment of glaucoma: a randomized clinical trial. Am J Ophthalmol 2000;130:267–273.

80.Kee C. Prevention of early postoperative hypotony by partial ligation of silicone tube in Ahmed glaucoma valve implantation. J Glaucoma 2001;10:466–469.

81.Wilson MR, Mendis U, Paliwal A, Haynatzka V. Long-term follow-up of primary glaucoma surgery with Ahmed glaucoma valve implant versus trabeculectomy. Am J Ophthalmol 2003;136:464–470.

82.Hwang JM, Kee C. The effect of surface area expansion with pericardial membrane (Preclude) in Ahmed glaucoma valve implant surgery. J Glaucoma 2004;13:335–339.

83.Lima FE, Magacho L, Carvalho DM, Susanna R Jr, Avila MP. A prospective, comparative study between endoscopic cyclophotocoagulation and the Ahmed drainage implant in refractory glaucoma. J Glaucoma 2004;13:233–237.

84.Gedde S, Schiffman JC, Feuer WJ, Parrish RK 2nd, Heuer DK, Brandt JD. Tube versus trabeculectomy study group. Am J Ophthalmol 2005;140:275–287.

85.Gedde SJ, Herndon LW, Brandt JD, Budenz DL, Feuer WJ, Schiffman JC and the Tube vs Trabeculectomy Study Group. Surgical complications in the Tube Versus Trabeculectomy (TVT) Study during the first year of follow-up. Am J Ophthalmol 2007;143:23–31.

86.Gedde SJ, Schiffman JC, Feuer WJ, Herndon LW, Brandt JD, Budenz DL and the Tube vs Trabeculectomy Study Group. Treatment outcomes in the Tube Versus Trabeculectomy (TVT) Study after one year of follow-up. Am J Ophthalmol 2007;143:9–22.

87.Rubin PA, Chang E, Bernardino CR, Hatton MP, Dohlman, Claes H. Oculoplastic technique of connecting a glaucoma valve shunt to extraorbital locations in cases of severe glaucoma.

Ophthal Plast Reconstr Surg 2004;5:362–367.

Fig. 1. Currently used procedures for glaucoma drain aqueous humor from the anterior chamber to the subconjunctival space. For standard filtering procedures, including trabeculectomies, drainage leads to the formation of a conjunctival bleb in the perilimbal area (procedure depicted on upper right). For commercially available glaucoma drainage devices, drainage leads to an episcleral plate (with various configurations and surface areas) surrounded by a fibrous capsule located in the equatorial region of the eye (procedure depicted on upper left).

include drainage of aqueous humor directly into Schlemm’s canal, the suprachoroidal space, the external ocular surface, or other spaces or tissues (see Fig. 2). These better efforts will be the focus of this chapter. Newer procedures that currently are being evaluated with innovative approaches to subconjunctival drainage are discussed in chapters 37 and 38.

SHORTCOMINGS OF CURRENT GLAUCOMA SURGERY

Filtering Surgery

Compared with surgical procedures in other areas of ophthalmology, especially cataract, cornea and retinal surgery, as well as in other areas of medicine in general, glaucoma surgical procedures are relatively primitive, with unpredictable results. In addition to unpredictability, safety and efficacy are suboptimal. Identically performed glaucoma filtering procedures in three different eyes may result in three vastly different outcomes. For example, in one eye, an intraocular pressure (IOP) of 10 mmHg with maintenance of 20/20 visual acuity and stable visual fields for a lifetime might be achieved. In a second eye, hypotony, hypotensive maculopathy, choroidal effusions, and/or choroidal hemorrhage with permanent visual loss might occur. In a third eye, scarring might occur within weeks leading to a return to the preoperative IOP of

Fig. 2. New investigational procedures for glaucoma drain aqueous humor to locations other than the subconjunctival space. Some of these new devices have been designed to drain aqueous humor to Schlemm’s canal (A and B), the suprachoroidal space (C–E), or the external ocular surface (F).

45 mmHg. The final postoperative result of subconjunctival filtering surgery is often more dependent on the process of wound healing of the ocular tissues, especially the conjunctiva, Tenon’s capsule, episclera, and sclera, than on the quality of the surgical procedure itself. The tissues of each individual eye heal differently and cannot be predicted. To modulate wound healing, adjunctive agents, such as 5-fluorouracil or mitomycin C, are being used clinically, and new, experimental anti-scarring agents are being developed. Although these agents undoubtedly are helpful in modulating wound healing, thereby increasing success rate, they do not enhance the predictability of the surgical result. Although increasing overall success rate, these agents also increase the incidence of complications, including flat anterior chambers, hypotony, hypotensive maculopathy, choroidal effusions, choroidal hemorrhages, cataracts, bleb leaks, blebitis, and endophthalmitis. Because wound healing is such a complicated process (5), it currently is not, and perhaps never will be, possible to predict how a particular eye may heal. Even with the advent of newer, more effective anti-scarring agents, it will not be possible to determine the dose, concentration, or method of delivery that will guarantee a desired outcome in a particular eye.

Drainage Devices

Glaucoma drainage devices (GDDs), including the most commonly used Baerveldt, Ahmed, and Molteno devices, in which aqueous is drained through a tube to a subconjunctival plate, surrounded by a fibrous capsule, may increase the success in some eyes in which glaucoma filtering procedures have failed or are felt to have a low

chance of success. Nevertheless, failures still occur with GDDs, and the results remain unpredictable because they are still dependent on wound healing around the episcleral implant. Although complications such as bleb leaks and endophthalmitis appear to be reduced compared with standard filtering surgery, almost all the other complications associated with the latter procedures are seen with GDDs, plus several unique problems, such as malpositioned tubes, corneal decompensation, erosion with exposure, and strabismus.

Therefore, the safety and efficacy of current glaucoma procedures cannot be vastly improved without the development of new methods to improve its predictability and adjustability. A surgical procedure for glaucoma that can predictably, reliably, and reproducibly achieve the desired target IOP is still a goal awaiting future research.

AREAS OF RESEARCH FOR NEW GLAUCOMA SURGERY

Drainage into Schlemm’s Canal

Because the primary site of resistance to aqueous outflow is thought to be the juxtacanalicular area near the inner wall of Schlemm’s canal (6–12), many approaches have been used to remove the tissue in this area using a variety of techniques, including surgery, electrocautery, and/or laser (13–33). Removing tissue in this area of high resistance theoretically would increase drainage into Schlemm’s canal and into the distal channels of physiologic aqueous outflow, avoiding drainage to the subconjunctival space, thereby eliminating the formation of a bleb and the innumerable bleb-related problems.

Procedures that have been used for many years to increase drainage of aqueous directly into Schlemm’s canal include goniotomies and trabeculotomies. These procedures have proven to be useful in infants with congenital glaucoma, especially when diagnosed during the first several months of life (34). Their success rates are somewhat reduced when the glaucoma is diagnosed at birth or beyond 1 year of age, or in secondary childhood glaucomas and primary or secondary juvenile glaucomas (34). In general, they are not thought to be helpful for glaucoma in adults, although a few publications suggest some benefit (35–38). With few exceptions, goniotomies and trabeculotomies are not performed in adults.

The failure of these procedures in adults is thought to be due to scarring in the incised area of Schlemm’s canal and the anterior chamber, although it is not known why this scarring does not occur as frequently in children with congenital glaucoma. On the conversely, the success in children may be more related to circumferential flow in Schlemm’s canal, which is more limited in adults than in infants (39,40).

Many attempts have been made to modify the goniotomy or trabeculotomy procedures to enhance their success rates in the adult glaucomas. Such techniques include the use of a suture, which is inserted 360º in Schlemm’s canal and then pulled tight into the anterior chamber, cutting through trabecular meshwork for 360º. Unfortunately, even this technique has not been proven to be highly successful in adults (41–43). Many other novel techniques have been tried in an attempt to increase the success rate of these procedures in adults (13–33), but none have resulted in long-term success.

A novel device, called the “Trabectome,” has been introduced to perform an ab interno trabeculectomy (see Fig. 2B) (44). The term “trabeculectomy” is used in this circumstance to describe the removal of the trabecular meshwork, although it does not involve subconjunctival drainage into a filtering bleb. The trabectome is introduced into the anterior chamber through a limbal stab incision, and the automated distal end is used to excise and remove the trabecular meshwork, theoretically exposing Schlemm’s canal to the anterior chamber (44). In a preliminary clinical trial, 37 patients with baseline IOPs of 28 ± 4 mmHg were treated with this technique. The 15 patients who were followed for 1 year had a mean IOP of 16 ± 2 mmHg and a reduction in the mean number of glaucoma medications (44). It is unclear whether the tissue in the excised area will eventually scar and lead to failure, similar to the experience with goniotomy and trabeculotomy in adults, and longer-term follow-up in more patients is required.

Another method designed to enhance aqueous drainage into Schlemm’s canal through an ab interno approach uses radiofrequency-mediated “sclerothalamotomy,” in which a high-frequency diathermic probe is used to penetrate into the sclera through the trabecular meshwork and Schlemm’s canal at four sites in a quadrant to form four small deep sclerotomies (45). It was performed in 53 consecutive eyes with mean preoperative IOPs of 26 mmHg. After a 2-year follow-up, the mean IOP was reduced to 15 mmHg, with a reduction in the mean number of medications (45).

GDDs designed to drain aqueous humor directly into Schlemm’s canal have been evaluated. Trabecular bypass stents have been shown to reduce IOP in cultured human anterior segments (see Fig. 2A) (46). Trabecular bypass micro stents (iStent) coupled with phacoemulsification were used in 51 patients with uncontrolled openangle glaucoma and cataract (47). With a mean follow-up of 5 months, the mean IOP was reduced by 5 mmHg from a mean baseline of 21 mmHg, with a decrease in mean number of glaucoma medications from 1.5 to 0.5 (47). It is unclear whether the phacoemulsification procedure, independent of the stent insertion, contributed to this IOP reduction.

The implantation of a trabecular bypass tube shunt with micro stents was attempted in 6 eyes of 5 patients with uncontrolled open-angle glaucoma (48,49). The tubes were successfully implanted into 5 of the 6 eyes. Four of these five eyes had follow-up of 5–9 months and demonstrated an IOP reduction from 23 to 16 mmHg along with a reduction of medications from a mean of 3 to 0.5. The tube was explanted in 1 of these 5 eyes because of excessive bleeding. Two of the five eyes demonstrated a diffuse bleb, suggesting subconjunctival filtration. In another study, the micro stents were implanted in 11 eyes with primary open-angle glaucoma that required filtering surgery (50). Target IOPs were successfully achieved in 9 of the 11 eyes, but the range of follow-up was only 2–3 months. IOP was reduced from 17 mmHg preoperatively to 14 mmHg postoperatively in those eyes that achieved success. Obstruction of the implant with iris occurred in 3 eyes (50).

A bi-directional implant that shunts aqueous from the anterior chamber into Schlemm’s canal has also been designed (Eyepass) (51). It has been implanted into 70 eyes. A phase 2/3 study included 62 patients with open-angle glaucoma. The procedure reduced IOP by 24% in those 21 eyes with follow-up data for 1 year. One device that

dislocated into the anterior chamber was removed (51). To our knowledge, this device is no longer being evaluated.

Despite the attempts to drain aqueous directly from the anterior chamber to Schlemm’s canal to bypass the presumed greatest site of resistance in the juxtacanalicular area, the preliminary results with the techniques and devices described above have yet to demonstrate long-term success and safety, compared with conventional glaucoma filtering procedures. Failure may be related to the lack of circumferential flow in Schlemm’s canal of adult eyes, the resistance of which may be further enhanced by the glaucomatous process. Other issues may include scarring and occlusion of the tubes within Schlemm’s canal. Similar to other surgical procedures for glaucoma, predictable results are hampered by the variable tissue healing that occurs in response to implantation of these devices or performance of the procedure.

Drainage into the Suprachoroidal Space

Another direction of research for alternatives to current glaucoma surgery is to shunt aqueous humor into the suprachoroidal space. This essentially enhances the physiologic route of aqueous outflow called the uveoscleral pathway (52). Although this outflow pathway initially was believed to only account for 5–15% of aqueous outflow in the normal human eye (53), more recent studies suggest that it might account for 35–60% of total aqueous outflow (54–64) and that enhancement through surgical techniques, trauma, and especially the remarkably effective prostaglandin analogs can have a profound effect on IOP reduction.

Tracer studies have shown that, in the uveoscleral pathway, aqueous passes from the anterior chamber through the root of the iris and interstitial spaces of the longitudinal ciliary muscle to the supraciliary (between the ciliary body and the sclera) and suprachoroidal (between the choroid and the sclera) spaces (52,65,66). From the latter, much larger space, aqueous is absorbed into the choroidal circulation or passes through scleral pores surrounding ciliary blood vessels and nerves or directly through the collagen substance of the sclera into the orbital tissues. Direct cannulation studies in cynomolgus monkey eyes showed the hydrostatic pressure to be 0.8 ± 0.2 mmHg lower in the supraciliary space and 3.7 ± 0.4 mmHg lower in the suprachoroidal space, compared with the IOP (67). Although uveoscleral outflow is said to be “pressure independent,” because the pressure differential between the IOP and the choroidal pathways is constant at different IOPs (68–70), the cannulation studies showed that, although the pressure differential in the supraciliary space remained constant with a change in IOP, that in the suprachoroidal space increased at higher IOPs, which was felt to be the driving force for uveoscleral outflow (67).

Anatomically, the only separation between the anterior chamber and the supraciliary space is at the insertion of the ciliary body into the scleral spur. Separation of that insertion, therefore, offers a surgical means of enhancing uveoscleral outflow. In fact, this option was exploited over 100 years ago by Heine, who introduced an operation called cyclodialysis in 1905 (69). The procedure consists of passing a spatula through a scleral incision into the supraciliary space and advancing forward into the anterior chamber, thereby separating the ciliary body from the scleral spur. Although it was commonly used during the first half of the twentieth century, it lost popularity because

of complications associated with hypotony, when flow into the suprachoroidal space was excessive, followed by a sudden, profound IOP rise, when the surgical cleft scarred and closed. Today, cyclodialysis is primarily dealt with as a consequence of blunt ocular trauma with associated hypotony.

Because the main problems with cyclodialysis, as an operation for glaucoma, are inability to regulate the flow into the suprachoroidal space and to prevent closure of the surgical cleft, an obvious next step was to place a shunt from the anterior chamber into the suprachoroidal space. Early attempts at this were not uniformly successful, because they used solid materials to keep the cleft open, which did not address the main problems. Subsequently, several investigative teams have reported success with placing tubes across the cleft (see Fig. 2C–E) (70–72), and refinement of this approach offers the best chance for a practical glaucoma operation through enhancement of uveoscleral outflow.

The potential advantages of drainage into the suprachoroidal space, as an operation for glaucoma, are that it enhances a physiologic route of aqueous outflow and avoids the complications associated with subconjunctival drainage. However, it is not without its own set of potential complications, including hypotony, bleeding, and obstruction of the drainage tube. If these complications can be minimized, it is possible that a modification of the old cyclodialysis procedure could become a safe and effective operation for glaucoma.

Drainage to the External Ocular Surface

All the established and experimental procedures described above are at the mercy of the unpredictable ocular wound-healing process. The greatest theoretical advantage of draining aqueous humor to the external ocular surface, therefore, would be to circumvent the process of wound healing, allowing outflow resistance to be controlled by the design of drainage device. The most serious potential limitation, however, is the obvious concern of infection.

A glaucoma drainage tube without a micro-pore filter, which drained aqueous to the external ocular surface through a limbal stab incision, was evaluated in two normotensive rabbits with a 1-week follow-up (73). Because in vitro perfusion studies suggested that incorporation of a Millipore filter with a pore diameter small enough to prevent bacterial ingress would provide too much resistance to maintain a sufficiently low IOP, the device was being considered only for temporary use during emergency situations of excessive IOP, such as those that might occur after surgery or trauma (73).

In 1983, one of us (CBC) proposed an external drainage device, in which a micropore filter is incorporated within the lumen to prevent infection. Despite the previous suggestion to the contrary (73), in vitro flow measurements demonstrated sufficient flow through filters with reasonable surface area and pore size sufficient to block the ingress of the smallest bacteria (74). A prototype of the GDD with a micro-pore filter, which drained to the tear film surface, was implanted into one eye in each of three cynomolgus monkeys with laser-induced glaucoma (75). The contralateral, control eyes underwent standard trabeculectomies. Follow-up ranged from 8 to 17 months. Preoperative IOPs were >25 mmHg in all eyes. Pseudomonas aeruginosa was used to determine whether intraocular infection could be produced. The postoperative IOPs