Glaucoma surgery: toward a new global vision

Little doubt exists that glaucoma represents a major public health problem in all parts of the world. Glaucoma is becoming an increasingly important cause of blindness as the world’s population ages. It is now the second leading cause of blindness globally, after cataract; however, it presents an even greater public health challenge than cataract because the blindness it causes is irreversible.

The first estimates of global blindness in 1978 reported 28 million blind people. In 1984, the number rose to 31 million and in 1990, to 38 million, with glaucoma being the third major cause of blindnesss [1]. The WHO has recently undertaken a systematic review of all population-based surveys of blindness (defined as visual acuity of less than 3/60 in the better eye with best correction or visual field in each eye restricted to less than 10° from fixation) and low vision and showed that, for the year 2002, approximately 37 million people were blind and 161 million people had visual impairment, without considering uncorrected refractive errors [2,3]. The prevalence of blindness varies from 0.2% in western Europe and North America to 1% in Africa. The major causes of blindness are cataract, glaucoma, corneal scarring, including trachoma, age-related macular degeneration, diabetic retinopathy, childhood blindness and onchocerciasis. Glaucoma is now the second leading cause worldwide, accounting for 13% of the total burden of world blindness [2].

The prevalence of glaucoma is estimated to increase in the near future and its distribution will change [4]. There will be 60.5 million people with open-angle glaucoma (OAG) and angle-closure glaucoma (ACG) in 2010, increasing by 20 million over the next decade. By 2020, India will become second overall in number with glaucoma, surpassing Europe. There will be 6 million more people with glaucoma in China. In 2020, the European region will still contain the greatest number of people with OAG, and the proportion of those with ACG who live in Asian regions will further increase. The total number of people with OAG will be 58.6 million, while the number with ACG will rise to 21 million. Over 8.4 million people will be bilaterally blind from primary glaucoma in 2010, rising to 11.1 million by 2020.

This increase in glaucoma blindness will challenge our resources and ingenuity. We have to consider numerous factors in order to understand the need to find therapeutic approaches that can be applied worldwide. People living in developing countries have the highest risk of developing blindness from glaucoma, with more than 95% of those blind from glaucoma originating from these countries, mostly from Asia and sub-Saharan Africa [1,5]. In East Asia, ACG predominates, whereas in Africa, the Indian subcontinent and in Hispanic populations OAG is more common [5]. In addition, the management of glaucoma is different when considering developed and developing countries. In developed countries, it is current practice to initiate treatment with topical medication or laser trabeculoplasty or a combination of both. Surgery in the form of a drainage procedure is usually reserved for those for whom the initial treatments are inadequate. From a developing world perspective, where we may have only ‘one shot’ at the patient, primary surgery is the treatment of choice.

The importance of glaucoma surgery cannot be overstated. Trabeculoplasty is often unavailable as an option and poor compliance is an even greater barrier to successful medical management of glaucoma than it is in the developed world. Patients have to travel long distances to access eye care facilities; people in rural areas present later in the course of the disease, with more advanced disease and more blindness than those from urban areas [6]. Staffing and equipment are limited. In Europe, there is one ophthalmologist for every 10,000 people; in India, one for every 400,000 and in Africa, one or less for every million. Besides which, the daily patient cost of medical therapy is high [7]; half of the world’s population lives on an income that is less than US$2/day, and the available ocular hypotensive medications cost approximately US$1/day, making them a nonviable option for a considerable percentage of patients. There is also the problem of convincing patients of the need for continuation of treatment for life in spite of the lack of improvement in their vision and the eventual associated side effects. Without this understanding, many patients become discouraged and stop using their medication. One study in Ghana showed that only 19% of patients undergoing treatment were attending follow-up at 6 months [8]. Of those patients treated medically who returned for follow-up at 6 months, only 17% had an intraocular pressure (IOP) less than 22 mmHg, while, of the patients treated surgically, 84% of those seen at 6 months had an IOP below 22 mmHg. Other advantages of glaucoma surgery are the elimination of the compliance factor [9], minimal IOP diurnal fluctuations [10], long-term sufficient IOP reduction [11] and almost no associated systemic complications. Moreover, African people with glaucoma are affected at a younger age and by a more aggressive disease than Caucasians [12]. In the developing world, one out of ten, or even fewer, glaucoma patients are diagnosed and a significant proportion of them are already severely affected. Clearly, the greatest risk factor for development of blindness from glaucoma is being an average citizen of a developing country.

The impact of glaucoma in worldwide blindness and the role of glaucoma surgery in the developing world are more than apparent. Nevertheless, it is interesting to see that glaucoma does not appear among the conditions identified as immediate priorities within the framework of the ‘VISION 2020 – the Right to Sight’ initiative of the WHO and the International Agency for the Prevention of Blindness. The choice of priority conditions – cataract, trachoma, onchocerciasis, childhood blindness, refractive errors and low vision – is based on the burden of blindness they represent and the feasibility and affordability of interventions to prevent and treat them. Glaucoma certainly achieves the first of these and, if the VISION 2020 initiative is successful in its aims, then glaucoma risks gaining the gold medal of global blindness. This is terrifying rather than encouraging. It is only as VISION 2020 is entering its second 5-year phase that it takes glaucoma into consideration but this still remains backstage, while we once again find the same principal characters in the forefront.

A number of features of glaucoma make fulfilling the other criteria difficult to achieve; loss of vision is irreversible, the disease is usually asymptomatic in its early stages and difficult to detect and therapeutic options are less attractive than, for example, cataract surgery. As a result, glaucoma attracts little publicity or funding in the developing world. This cannot but reinforce the need for innovative surgical modalities towards a rapid, inexpensive glaucoma surgery with minimal complications and postoperative care.

Indeed, there have been some (although minor) advances in glaucoma surgery over the last 40 years since the advent of trabeculectomy by Cairns in 1968 [13]. This is in contrast to cataract surgery, where technological leaps in the last 20 years have permitted us to achieve the desired surgical ‘endpoint’ in 95–100% of cases.

Trabeculectomy is an effective operation for lowering IOP; however, success is limited by complications, such as infection, hypotony and scarring leading to bleb encapsulation and fibrosis. Black patients also have higher failure rates with conventional trabeculectomy than white patients [14]. Results from the Advanced Glaucoma Intervention Study (AGIS) support this finding [15]. Advances in trabeculectomy technique – careful choice of the surgical site, anterior chamber maintenance using an infusion, fashioning of the scleral flap to produce diffuse aqueous flow, optimal methods of antimetabolites application, adjustable/releasable sutures – can reduce its complication rate [16]. Over the last few years, the use of antimetabolites, 5-fluorouracil and mitomycin C, to modify the wound-healing response following filtration surgery has increased success rates, but their benefits need to be balanced with their potential complications; there is an increased risk of wound leaks and late bleb leaks from thin-walled cystic blebs that predispose to hypotony and endophthalmitis. We thus have to consider regular follow-up of operated patients and prolonged postoperative care, with postoperative management becoming of equal importance to the surgery itself, but we must also assume that the patient may present only once in a developing country.

We are only going to make an impact on the number of people going blind from glaucoma if we can provide a treatment that is not only effective but also acceptable to those at risk. Patients often delay or refuse surgery until they have severe vision loss. A study in East Africa found that only 46% of patients accepted trabeculectomy, even though they were offered free surgery, hospitalization and food [17].

Trabeculectomy is also associated with a high risk of cataract formation [18]. Trabeculectomy with β-radiation reduces the risk of surgical failure but is associated with a higher incidence of cataract surgery [19]. In the developing world, patients may not present for surgery a second time when they develop cataract, especially if they perceive that the first operation has contributed to their loss of vision. Many ophthalmologists are reluctant to perform trabeculectomies because of poor patient acceptance, the difficulty of postoperative care and uncertain results. One builds a successful practice by cataract extraction and intraocular lens implantation surgery, not by trabeculectomies. These facts once again support the dire need for a more effective and safe means of treating glaucoma in the developing world.

Nonpenetrating glaucoma surgery (NPGS) is another viable option for glaucoma patients requiring surgery. Its principal common concept is to create filtration through a naturally occurring membrane that acts as an outflow resistance site, the trabeculo-descemetic membrane, allowing a progressive decrease in IOP and avoiding postoperative ocular hypotony, without penetration into the anterior chamber. The main advantage of NPGS is the prevention of the complications of trabeculectomy, such as flat anterior chamber, hyphema and choroidal detachment. In 1999, Stegmann and colleagues reported an 83% viscocanalostomy success rate (IOP ≤ 22 mmHg without medical therapy) in a black African population with an average follow-up of 35 months [20]. More recently, Shaarawy and colleagues reported a 90% viscocanalostomy success rate (IOP < 21 mmHg with or without medication) for a longer average follow-up of 60 months [21]. Prospective studies of deep sclerectomy with collagen implant report complete success rates of 45–69% [22–26] with qualified success rates (IOP < 21 mmHg with or without medication) being significantly higher. In addition, the use of a collagen implant enhances the success rates and lowers the need for postoperative medications [25–27].

The main disadvantage of both deep sclerectomy and viscocanalostomy is the fact that they are associated with a long and demanding learning curve since they are more technically complicated than trabeculectomy, and so they do not meet the requirement of a simple, rapid procedure. Goniopuncture may be necessary in up to 50% of cases to control IOP [23]. Furthermore, as safe as it is, NPGS, as well as its associated manipulations, brings with it a new set of complications that we are called on to resolve. If one positive thing has emerged from NPGS, it is the ripple effect it has created in the stagnant waters of glaucoma surgery.

The use of glaucoma drainage devices (GDDs) is becoming more frequent in the treatment of glaucoma, both as a primary procedure of choice and following failure of other filtering procedures. In 1973, Molteno introduced the concept of draining the aqueous away from the limbus to increase the success rate of the first drainage devices that were sutured to the sclera adjacent to the limbus. All the currently available GDDs are based on this concept of the Molteno implant, which has a long silicone tube attached to a large explant placed 9–10 mm posterior to the limbus. Since then, two major concepts have been introduced. The first was a valve to offer a set resistance to the outflow and thus reduce the incidence of postoperative hypotony, such as the Krupin and the Ahmed valves. The second was the increase in the surface area of the end plate resulting in lower IOPs. Fenestrations have been added to the plate of the Baerveldt glaucoma implant [28]. There are no statistically significant differences among the devices in the overall surgical success rate ranging from 22 to 78% for neovascular glaucoma, 75 to 100% for uveitic glaucoma, 50 to 88% for eyes that have undergone cataract surgery and 44 to 88% for eyes with failed glaucoma filtering surgery [29]. Inflammation around the end plate, resulting in excessive scar tissue formation, is the leading cause of GDD failure, which limits its long-term success. The incidence of bleb encapsulation has been estimated to be between 40 and 80% with the Ahmed valve and between 20 and 30% with the Baerveldt and double-plate Molteno implants [29]. There appears to be no clear advantage in using mitomycin C in patients undergoing GDD implantation [30]. Another potential complication is corneal decompensation, which has been reported in up to 30% patients with long-term follow-up [28]. Moreover, GDDs are expensive and do not offer a favorable option from an economic standpoint in developing countries.

Most GDDs are composed of silicone or polypropylene. Modifying the biomaterial of the end plate, as well as its flexibility and shape, may influence the fibroproliferative response and thus the surgical success rate. The contemporary standing of GDDs is in some ways analogous to that of intraocular lenses in the early 1970s, with frequent complications attributable to design and material inadequacies. Success will depend on a marriage of design and biomaterials improvement with well-controlled pharmacological modulation of wound healing. Just as improved intraocular lenses have revolutionized cataract surgery, new biomaterials, design changes and antifibrotic drug delivery systems are the key to enhance the success rate in the future.

The Ex-Press™ mini glaucoma shunt is a 3-mm stainless steel tube that was originally designed to be inserted at the limbus directly under a conjuctival flap. It was introduced to offer a quick and simple alternative to conventional glaucoma surgery. The procedure is indeed rapid but is also associated with new complications [31]. The modification of the technique by introducing the tube under a scleral flap seems to overcome these complications [32] and it now has similar IOP-lowering efficacy with a lower rate of early hypotony compared with trabeculectomy [33] but more experience and long-term follow-up is needed. Trabecular shunts that drain the aqueous into the Schlemm’s canal, such as the GMP Eye Pass^® and the Glaukos trabecular bypass shunt (iShunt), and implants that drain the fluid into the suprachoroidal space, such as the Deep Light^® Glaucoma Treatment System (SOLX), are under clinical trials.

All of the above remind us of the shortcomings of our current techniques. It also highlights the need for more precise and focused surgical modalities that can only emerge through insightful research on the basic and experimental level of glaucoma surgery. All those interested in the glaucoma field should be encouraged towards this approach and be open to advances in all fields, including less popular areas, such as aqueous flow regulation and wound-healing response, and newer areas, such as innovative surgical techniques, biological materials, nanotechnology and molecular and cell biology. Given enough emphasis along these lines, an acceptable rapid, safe and cost-effective procedure may soon be found. One step forward in glaucoma surgery, a great step forward in global sight.