Primary Angle-Closure Glaucoma Treatment & Management
- Author: Clement Chee-yung Tham, MA, BM, BCh, FRCS(Glasg); Chief Editor: Hampton Roy, Sr, MD more...
It is important to recognize early stages of appositional angle closure in the absence of peripheral anterior synechiae (PAS) and to recognize deep, circumferential angle closure.
Laser iridotomy is indicated for primary angle closure (PAC) and primary angle-closure glaucoma (PACG). Laser iridotomy involves the creation of a hole in the peripheral iris by laser.[29, 30] The hole provides an alternative pathway for aqueous to flow from the posterior chamber into the anterior chamber, bypassing the pupil. Therefore, iridotomy eliminates pupillary block and prevents forward bowing of the iris as a result of the pressure difference between the two chambers. Iridotomy opens those areas of the angle not involved by PAS and prevents further synechial closure.
Miotic treatment may enhance the development of PACG in the absence of an iridotomy. When miotic-induced angle closure occurs, the approach to treatment should be determined by assessing the medications necessary to control the glaucoma. If a patient is taking dipivefrin, discontinuation may be enough to open the angle and allow the patient to remain on miotics, assuming that intraocular pressure (IOP) remains under control. If the patient has been treated with miotics alone, substitution of aqueous suppressants may suffice. If the patient requires miotics for IOP control, laser iridotomy is warranted.
If the angle remains appositionally closed or spontaneously occludable after laser iridotomy, argon laser peripheral iridoplasty (ALPI) is indicated to prevent progressive damage to the angle or further appositional and/or synechial closure of the angle.[31, 32, 33, 34] If, after iridoplasty, some of the angle still remains appositionally closed, low-dose pilocarpine, such as pilocarpine 2% at bedtime, often suffices to maintain the patency of the angle.
The level of IOP and the extent of glaucomatous damage determine the need for continued medical treatment after iridotomy. Treatment is similar to that of open-angle glaucoma. Repeated gonioscopy is necessary. The need for further surgery cannot be predicted from the level of initial IOP or the gonioscopic changes.
Argon laser trabeculoplasty (ALT) has been reported to be both successful and unsuccessful after iridotomy in combined-mechanism glaucoma; however, overall, it has been found to be reasonably successful.[35, 36] Selective laser trabeculoplasty (SLT) delivers laser energy to pigmented cells in the trabecular meshwork avoiding thermal damage to adjacent cells. In a multicenter prospective study on PACG eyes with high IOP despite iridotomy but with at least 90° of gonioscopically visible pigmented trabecular meshwork, it has shown 20% or more IOP reduction in 54% of eyes at 6 months. The authors suggested selective laser trabeculoplasty to be a safe and effective method of reducing IOP in PACG in which there is a sufficient extent of visible trabecular meshwork. However, long-term therapeutic effectiveness of selective laser trabeculoplasty in PACG eyes will have to be determined. Possible side effects include reduced endothelial cell count, IOP spike, and persistent uveitis.
If the pressure remains uncontrolled and glaucomatous damage develops, filtration surgery is indicated. An increased chance of developing malignant glaucoma is present following filtration surgery in patients who have had angle-closure glaucoma.
The two main challenges in the management of PACG are, firstly, to prevent progression of the angle closure and, secondly, to prevent progression of the glaucomatous optic neuropathy by controlling IOP. Various surgical procedures have different roles in meeting these challenges.
The diminishing role of surgical iridectomy
To prevent progression of the angle closure, all eyes with angle closure or very narrow drainage angles should undergo iridectomy or iridotomy to eliminate pupillary block. Nowadays, laser iridotomy has largely succeeded surgical iridectomy, except in exceptional circumstances.[39, 40]
Laser iridotomy has many advantages over surgical iridectomy. Laser iridotomy is noninvasive, so there is no inherent risk of endophthalmitis and wound complications, such as wound leak. With sequential laser techniques, the wound edge of the iridotomy is well coagulated and the risk of hemorrhage from iris tissue is much reduced. The movement of fluid when the iris is penetrated is a good sign of iris penetration, and the chance of an incomplete iridotomy is minimal. Furthermore, as no ocular incision is required, there is no risk of further shallowing of the anterior chamber and causing iridocorneal adhesion and damage, PAS and permanent closed angle, or precipitating malignant glaucoma. Laser iridotomy can also be conveniently performed on an outpatient basis, and it does not require operating room facilities.
As laser equipment and expertise have become widely available, the role of surgical iridectomy in the management of angle-closure glaucoma is now limited to situations in which laser iridotomy is not possible or effective, for example, in patients with significant corneal opacity. The inability of patients to cooperate may also be a relative indication for surgical iridectomy, which can be performed under sedation or even general anesthesia. Severe anterior chamber inflammation may repeatedly occlude a laser iridotomy, while the relatively larger iridectomy created by surgery is much more likely to remain open under such circumstances.
Trabeculectomy is effective for PACG.[41, 42, 43, 44, 45] Trabeculectomy has been shown to have an overall success rate of 68% in controlling IOP. However, compared to primary open-angle glaucoma (POAG), any aqueous-draining procedure in an eye with a shallow anterior chamber and a chronic closed angle poses the risk of further shallowing the anterior chamber or precipitating malignant glaucoma. Trabeculectomy in PACG is associated with a higher risk of filtration failure, shallow anterior chamber, and malignant glaucoma/aqueous misdirection. As the incidence of PACG increases with age, many patients with PACG have co-existing cataract. Trabeculectomy increases the rate of cataract progression, and a significant proportion of patients will soon need cataract extraction after trabeculectomy.
Furthermore, future cataract extraction may result in loss of the functioning filter. It has been reported that 30-100% of previously functioning blebs required antiglaucoma medications to control IOP after extracapsular cataract extraction (ECCE). Therefore, trabeculectomy alone is not the ideal surgical option in medically uncontrolled PACG.
In theory, adjunctive antimetabolite should be used with trabeculectomy when performed in eyes with a high risk of filtration failure or when a very low target pressure needs to be attained. However, the risk factors for filtration failure specific to angle-closure glaucoma and the target pressure in angle-closure glaucoma have not yet been clearly defined. Trabeculectomy is associated with various complications, both early and late, including bleb leaks and bleb-related infections. These risks are further increased by adjunctive antimetabolite.
Lens extraction—alone or in combination with trabeculectomy
Lens position and thickness both play important roles in the etiology of angle-closure glaucoma. Lens extraction significantly increases anterior chamber depth and width of the drainage angle. Lens extraction has been actively studied and reported in recent years in the treatment of PACG. The lens may narrow the angle by pushing the peripheral iris anteriorly, and this effect will be more marked if the lens is cataractous. Both traditional extracapsular cataract extraction and phacoemulsification have been reported to lower IOP in PACG. Phacoemulsification alone has also been shown to normalize IOP in PACG.
Hayashi has shown that the depth of the anterior chamber and the width of the drainage angle in eyes with angle-closure glaucoma increased significantly after cataract extraction and intraocular lens implantation, which may lead to the decrease in IOP seen in the postoperative period. It has been postulated that removal of a large cataractous lens from an eye with a crowded anterior segment may improve aqueous outflow. It has also been postulated that during phacoemulsification, the irrigating fluid flushes cellular debris from the trabecular meshwork, decreasing resistance to aqueous outflow.
A multicenter, randomized controlled clinical trial comparing lens extraction versus laser iridotomy in patients with newly diagnosed PAC or PACG is being conducted by The Effectiveness in Angle-closure Glaucoma of Lens Extraction (EAGLE) Study Group. This ongoing study is aimed at evaluating the effect of cataract extraction with regards to IOP, quality of life, and cost in angle-closure glaucoma at 3 years.
Randomized controlled surgical trials by Tham et al in Hong Kong directly compared cataract extraction alone by phacoemulsification against combined phaco-trabeculectomy in PACG eyes with coexisting cataract. Their first study focused on PACG eyes that were adequately controlled by glaucoma drugs before surgery, while their second study focused on PACG eyes that were medically uncontrolled. In both clinical scenarios, it was demonstrated that phacoemulsification alone could significantly reduce IOP, as well as the requirement for glaucoma drugs, for at least two years after surgery. Combined phacotrabeculectomy resulted in even greater IOP and drug reductions, but was associated with more complications and additional surgery to manage the complications. Based on these initial results, the authors concluded that in medically controlled PACG with cataract, phacoemulsification alone may be considered as an initial treatment. In PACG eyes with cataract, higher preoperative IOP and increased requirement for glaucoma drugs correlate with failure to control IOP after phacoemulsification or phacotrabeculectomy. In medically uncontrolled PACG with cataract, either phacoemulsification alone or combined phacotrabeculectomy may be considered, depending on patient factors.[48, 49, 50, 51]
In situations where medically uncontrolled PACG coexisted with an optically clear lens, a third randomized controlled trial by Tham et al compared the outcomes of clear lens extraction by phacoemulsification versus trabeculectomy alone. In this study, both phacoemulsification and trabeculectomy reduced IOP by over 30% at 24 months after surgery. Phacoemulsification reduced the requirement for glaucoma drugs by 60% and trabeculectomy by 89% at 24 months after surgery. Trabeculectomy was associated with more complications. Compared to trabeculectomy, clear lens extraction resulted in a significant reduction in synechial angle closure and an increase in anterior chamber angle width and anterior chamber depth in PACG eyes without cataract. The authors concluded that, with available data, either surgery could be considered for medically uncontrolled PACG eyes without cataract, depending on patient factors.
One study suggested that the IOP-lowering effect of lens extraction may be less pronounced in PACG cases with PAS covering three fourths or more of the angle. Therefore, lens extraction alone may have a role in improving IOP control in PACG, especially in cases with less extensive PAS and when the IOP is not grossly out of control. Good long-term IOP control has been found following lens extraction for PACG, and lens extraction should be considered in patients with PACG, especially those with hyperopia or a thick and anteriorly vaulted lens.
Goniosynechialysis with/without lens extraction
Goniosynechialysis (GSL) is a surgical technique performed to strip the PAS from the trabecular surface in the angle and provide aqueous renewed access to the trabecular meshwork.[55, 56, 57] In eyes with minimal PAS, trabeculectomy is preferred because trabecular function in these eyes is expected to be poor and a fistula procedure would be more appropriate. On the other hand, there may be spikes of raised IOP during and after the GSL procedure leading to loss of vision. GSL is more suitable for eyes with a minimal to moderate degree of neuronal damage.
In the past, ophthalmologists have tried to sweep open a closed angle without direct visualization. This often failed because accurate instrument placement could not be achieved. In 1984, Campbell and Vela introduced a technique using direct intraoperative visualization of the angle and anterior chamber deepening with viscoelastic agents. Visualization has been further improved with the use of the Swan-Jacob lens. This specially-designed lens has a handle attached to a small diameter prism so that it will not obstruct the spatula from entering the anterior chamber at the limbus. When PAS has been present for less than 1 year, the overall success rate in terms of IOP control is approximately 80%. Irreversible damage to the meshwork may occur in areas of synechial closure, with proliferation of iris or fibrous tissue into the intertrabecular space. This may explain why GSL appeared to be less effective in closed angle of longer duration.
In order for GSL to be effective, it must be performed before there is irreversible histological change in the meshwork. The mechanisms causing the angle closure should also be eliminated by performing peripheral iridotomy, laser peripheral iridoplasty, or lens extraction, either alone or in combination, to minimize the possibility of recurrent closure. Tanihara et al reported success in using GSL followed by argon laser peripheral iridoplasty.
The most common complication of GSL is intraoperative hemorrhage. Other complications include iridodialysis, cyclodialysis, and lens damage.
Teekhasaenee and Ritch have reported success with phacoemulsification combined with GSL, and Lai et al were successful with combined phacoemulsification and limited GSL, followed by diode laser peripheral iridoplasty, for PACG. The authors demonstrated with ultrasound biomicroscopy that lens removal in PACG would only deepen the peripheral anterior chamber, without actually opening up the angle, while GSL opened up the angle and allowed aqueous access to the trabeculum.
Nevertheless, both lens extraction and GSL performed alone have been shown to lower the IOP, although the mechanisms are uncertain and may or may not be common to both procedures. Combining GSL with lens extraction has the advantages of noticeable visual improvement after surgery, and the combined IOP-lowering effect of the two procedures. Furthermore, removal of the lens may decrease the possibility of recurrent angle closure. It has been shown that eyes undergoing combined phacoemulsification with GSL have a greater reduction in circumferential iridotrabecular contact area than eyes undergoing phacoemulsification alone. A 2015 prospective study, however, demonstrated that IOP-lowering effects of phacoemulsification and GSL do not differ significantly from those of phacoemulsification alone in medically well-controlled PACG with cataract.
In 1950, Bietti introduced cyclocryotherapy. A temperature of -80°C was applied with a cryoprobe to destroy the ciliary body epithelium, stroma, and vasculature. The clinical usefulness of cyclocryodestruction is limited by its complications, which include hypotony, phthisis, hyphema, choroidal detachment, and retinal detachment.
In the past 10 years, transscleral diode laser cyclophotocoagulation (TSCPC) using the G-probe is becoming more popular and is used to treat many different types of glaucoma.[63, 64] The semiconductor diode laser emits light of wavelength 810 nm, near the infrared spectrum. It is transmitted through the sclera and absorbed by melanin. The success rates of cyclodestruction vary among the different procedures and the types of glaucoma. Diode TSCPC was reported effective in controlling IOP to less than 21 mm Hg in 70-81% of pediatric and adult refractory glaucoma. However, there has been no large-scale study on its efficacy in the treatment of PACG. Since it decreases IOP by destroying the ciliary epithelium and reducing aqueous production, it should, theoretically, be effective even in eyes with complete synechial closed angle closure.
In a recent study, adjunctive diode TSCPC was effective in lowering IOP in 4 cases of PACG that were uncontrolled despite a glaucoma aqueous tube shunt and multiple medications. In another study, diode TSCPC appeared to be an effective and safe primary surgical treatment of medically-uncontrolled PACG, with IOP-lowering effect persisting up to two years.
The efficacy and relative safety, the portability of the equipment, the ease of learning, and the short duration required for performing this technique make diode TSCPC a potential primary or secondary surgical procedure in the future treatment of PACG. However, TSCPC is associated with some rare but potentially serious complications, and these should be balanced against its many advantages. Potential complications include uveitis, pupillary distortion, conjunctival burns, hyphema, chronic hypotony, cystoid macular edema, retinal detachment, phthisis bulbi, and scleral perforations.
An alternative to TSCPC is endoscopic cyclophotocoagulation (ECP), which involves laser treatment of the ciliary processes under direct visualization and is most commonly performed in combination with lens extraction in refractory cases. Endoscopic laser allows a more precise application of laser to the targeted ciliary tissue. An animal study has also shown that TSCPC is associated with a more persistent poor perfusion of the ciliary processes and therefore a higher risk of hypotony and phthisis. In an earlier retrospective study, it was reported to be able to achieve an IOP of less than 21 mm Hg in 90% of refractory glaucoma, including PACG eyes. Although hypotony and phthisical change were not reported in this series, reported complications of ECP included uveitis, hyphema, cystoid macular edema, visual loss, choroidal detachment and malignant glaucoma.
A more recent randomized prospective study has tried to compare the safety between combined cataract surgery with ECP and combined cataract surgery with trabeculectomy. With a mean follow up period of 2 years, 30% of ECP eyes achieved an IOP of less than 19 mm Hg without medication and 52% with medication. The authors suggested that combined cataract surgery with ECP to be a reasonably safe and effective alternative surgical option.
Glaucoma implants in primary angle-closure glaucoma
The use of a glaucoma implant for difficult-to-treat glaucoma is not new. There is a wide variety of such glaucoma drainage devices, from the early Molteno implant to the currently popular valve-equipped variety, such as the Ahmed implant. Overall, the success rates for controlling IOP for complicated cases range from 70-90%. However, because it is technically more difficult than trabeculectomy, and potentially serious complications can occur, the use of a glaucoma implant for PACG has been mainly confined to those patients in whom one or more previous filtering procedures have failed.
Among the studies that included PACG, the proportion of patients with PACG ranged from 1.7-9%. Aside from the small number of patients, another major problem with these studies is that only two published the results of the subgroup with PACG. One had only a single non-Asian patient with angle-closure glaucoma, who ended up with no light perception at 6 months, while the other included 10 patients of unspecified race, 7 of whom had successful surgery.
A more recent randomized study evaluated non-valved tube shunt surgery against trabeculectomy in patients with glaucoma who had previously failed trabeculectomy and/or cataract extraction with intraocular lens implantation. In this study, there were 18 eyes with PACG, with 7 randomized to the implant group and 11 to the trabeculectomy group. In the former study, there were 15 eyes (23%) with the diagnosis of PACG, iridocorneal endotheliopathy, and juvenile open-angle glaucoma treated with the 350 mm2 Baerveldt glaucoma implant. The immediate-term failure rate in this subgroup was 47%, compared with 19% in the group with POAG. Although this study did not provide a subgroup analysis for patients with PACG, the 1-year results found a higher success rate in the tube group compared to the trabeculectomy group. These results suggest a possible expanded role for the use of implants in eyes with previous ocular surgery.
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