Description of the condition
Glaucoma is an optic neuropathy that leads to vision loss and blindness (Foster 2002). Among the many known and unknown factors that contribute to the damage to the optic nerve, elevated intraocular pressure (IOP) is the only modifiable risk factor (Coleman 2012). Normally, the IOP is maintained in balance when the rate of aqueous production by the ciliary body is equal to the rate of its outflow from the posterior to the anterior chamber through the trabecular meshwork and the canal of Schlemm in the anterior chamber angle (Small 1986). When excess aqueous humor is produced or when part or all of the drainage system of aqueous humor is blocked, the result is an increase in IOP, which has been shown to be associated with progressive glaucomatous optic nerve damage (Pan 2011; Turkoski 2012).
There are several types of glaucoma, of which open angle glaucoma (OAG) and angle closure glaucoma (ACG) are the two major types.
The World Health Organization (WHO) has estimated that glaucoma is the second leading cause of blindness worldwide (Quigley 2011). It has been estimated that there were 60.5 million people with OAG and ACG in 2010, and the number will increase globally to 79.6 million by 2020. The most common type of glaucoma is OAG, accounting for 74% of glaucoma cases worldwide. ACG is less common and its cause is often genetic. Women comprise 55% of OAG, 70% of ACG, and 59% of all glaucoma cases. Asians represent 47% of those with glaucoma and 87% of those with ACG (Quigley 2006).
Symptoms and diagnosis
OAG is often asymptomatic initially. There is no pain and affected patients tend not to notice loss of visual field until the central vision area is affected in the later stage of the disease; by then optic nerve damage is often already severe (Boland 2008; Quigley 2011; Small 1986). The symptoms for ACG vary. It may occur without warning or with gradual deterioration; patients may have signs including severe pain and red eye, decreased or cloudy vision, nausea, vomiting, and bradycardia (Boland 2008; Douglas 1975; Small 1986). Clinical examinations for diagnosing glaucoma include, but are not limited to, tonometry, gonioscopy, optic nerve imaging, visual acuity, and visual field assessment.
Description of the intervention
Trabeculectomy, first introduced by John Cairns in 1968 and then modified by Watson in 1972, remains the gold standard and the most common incisional surgical procedure for the treatment of glaucoma (Cairns 1968; Watson 1972; Watson 1981). It includes lifting the conjunctiva and dissecting a partial thickness scleral flap and then a perforating scleral entrance into the anterior chamber to allow aqueous drainage, and it may also include removing part of the eye's trabecular meshwork and adjacent structures. This can lower IOP effectively by allowing aqueous fluid to percolate through the scleral hole or the cut ends of the trabecular meshwork into the subconjunctival space. Over the years trabeculectomy has been modified in various ways, including the use of 5-fluorouracil (5-FU) (Wormald 2001) and mitomycin C (MMC) (Wilkins 2005), and a fornix-based rather than a traditional limbus-based conjunctival flap. Most recently, the modifications have included devices in a standard trabeculectomy. They either use a tube without a reservoir (for example, Ex-PRESS) or a space-holder or reservoir (for example, OloGen) to enhance outflow or modify healing and promote continued drainage from the anterior chamber through a standard partial thickness scleral flap used in a standard trabeculectomy.
How the intervention might work
Antimetabolites and biodegradable implant (OloGen)
Wound healing and scar formation are the main problems of a standard trabeculectomy. They may lead to fibrosis of the bleb (bubble-like blister of the conjunctiva) and obstruction of the drainage fistula, and finally cause bleb failure (Skuta 1987). Antifibrotic agents, such as 5-FU and MMC, have been demonstrated to be effective in delaying wound healing and thus improving the success rate of trabeculectomy (Azuara-Blanco 1998; Fraser 2004). Therefore, 5-FU and MMC have become widely utilized as adjuncts with glaucoma filtering surgery. However, although 5-FU and MMC improve the success of trabeculectomy, there has been increased concern about the complications associated with antimetabolites, for example bleb-related infections, bleb leaks, and bleb dysesthesia (defined as burning, foreign body sensation, tearing, pain, or ocular discomfort in an eye with a filtering bleb) (Bell 1997; Jampel 1992; Lama 2003).
The OloGen implant is a plate-shaped, tissue bioengineered, biodegradable porous collagen-glycosaminoglycan matrix used during trabeculectomy. The device can randomly reorganize the regeneration of myofibroblasts, fibroblasts, and the secreted extracellular matrix, and consequently reduce the postoperative scar formation (Dietlein 2008). Recently, studies in animal models and several randomized clinical trials have reported that OloGen implanted in the subconjunctival space can provide an alternative method for controlling the wound-healing process and to avoid the complications of using antifibrotic agents (Chen 2006; Cillino 2011; Hsu 2008; Papaconstanitinou 2010; Rosentreter 2010).
1. Ex-PRESS mini glaucoma implant
Aiming at promoting continued aqueous drainage, the Ex-PRESS implant is a miniature stainless steel shunt developed recently as an alternative to trabeculectomy. The device is implanted under a partial thickness scleral flap to allow aqueous humor to flow from the anterior chamber to the subconjunctival space and leads to the formation of a thin-walled filtration bleb, similar to the process in a standard trabeculectomy. It has been reported in recent years, in both retrospective studies and randomized clinical trials, that the Ex-PRESS shunt provides better or similar IOP control as a trabeculectomy, and results in a lower rate of complications, fewer postoperative surgical interventions, and less need for glaucoma medications (Dahan 2012; de Jong 2009; de Jong 2011; Francis 2011; Gallego-Pinazo 2009; Maris 2007).
2. Silicon tube implant
Jordan et al reported the use of a silicon tube implant for the suprachoroidal drainage during a standard trabeculectomy approach (Jordan 2006). The tube was inserted as a junction connecting the anterior chamber and the suprachoroidal space, and it proved to be a new effective surgical technique option to treat intractable glaucoma. However, randomized controlled trials on the effectiveness and safety of a silicon tube have not been reported to date.
Other than the most recent widely used OloGen and ExPRESS devices, there are other new devices being developed or being studied, including the SKgel and T-flux for non-penetrating glaucoma surgeries. Below are the devices reported to have been used in a trabeculectomy approach.
1. Expanded polytetrafluoroethylene (E-PTFE) membrane implant
E-PTFE is an expanded polytetrafluoroethylene implant made up of solid nodes inter-connected by a thin fibril matrix. Its use has been reported in several animal studies and human trials in the form of either a membrane patch or implant placed beneath the partial thickness scleral flap (Bae 1988; Cillino 2008; Jacob 2001) or combined with a silicone tube (Choi 2003; Kim 2003) shunt. Similarly, data from randomized controlled trials were scarce.
2. SOLX Gold Shunt
The SOLX Gold Shunt is a new biocompatible device made of pure gold (24-carat) that can reduce IOP utilizing the eye's natural pressure difference (http://www.solx.com/content/solx-gold-shunt). Through a special corneal or scleral incision, the device is inserted into the anterior chamber with the posterior end left in the suprachoroidal space. The device is currently approved for use in Canada and a few countries in Europe, and is under a multi-center clinical trial in the United States. No trial data have been published to date.
Why it is important to do this review
The purpose of this review is to compare the effectiveness and safety of modified trabeculectomy procedures versus standard trabeculectomy in the surgical treatment of glaucoma. We will also consider the use of antifibrotic agents and compare the surgical procedures when 5-FU or MMC is used by patients. Modified trabeculectomy is a relatively new procedure; therefore, individual studies do not report a large sample size or the study designs do not provide enough evidence of the effectiveness and safety of modified trabeculectomy procedures. In addition, there are no known systematic reviews assessing the effectiveness and safety of modified trabeculectomy devices in surgical therapy for glaucoma. Therefore, it becomes important to seek evidence across studies and to analyze effects of different devices in trabeculectomy on IOP control.