it is rare that substantive anatomic or functional improvement occurs after satisfactory pressure lowering.295 Medications that may stabilize or slow the progression of glaucomatous damage independent of pressure lowering are currently being developed but are not yet available for clinical use. Some medications may have neuroprotective properties in the laboratory but none has been absolutely proven clinically. Perhaps, by the time the next edition of this book is published, neuroprotective agents will have been shown effective and will be available for clinical use.

It is impossible to determine a priori what level of IOP is necessary to stabilize the patient’s disease. Some patients suffer progressive damage at 16 mmHg, whereas others tolerate IOPs of 40 mmHg for long periods. A general rule is, however, that the higher the IOP, the greater the likelihood of progressive damage. The Advanced Glaucoma Intervention Study (AGIS) strongly suggested that patients with open-angle glaucoma need pressure lowering both in amount and consistently over time. Progressive damage is an indication that more aggressive therapy is needed to lower IOP.The decision to pursue more aggressive therapy is complicated because it must reflect not only the rate of progression and the state of the disease but also the patient’s beliefs, preferences, age, general health, and life expectancy. Costs also need to be considered in many cases.

Target pressure

The current practice is to estimate the pressure level (range) below which further damage to the optic nerve is unlikely to occur (target pressure) and then aim to keep the IOPs consistently below this level or, at least, within the estimated range. The target pressure is estimated by noting the untreated level of IOP; the degree of optic nerve cupping and visual field loss; the family history of glaucoma;

the presence of any other aggravating conditions such as diabetes mellitus or arteriosclerotic vascular disease, and the rate of progression if known. In the average patient, the clinician should aim for a pressure 20–30% below the initial untreated pressure. With greater optic nerve damage (e.g., 0.8 disc diameter cupping or more), increasing age, and more risk factors, the target pressure should be lowered. The target pressure should be reassessed periodically and lowered if progression, optic nerve hemorrhage, or increase in risk factors occurs (see Chapter 22). One should also keep in mind that in the AGIS, not only was lack of progression associated with a low average IOP but also with no IOPs exceeding 18 mmHg during the entire 6 years of the study.296 So, maintaining the IOP consistently below 18 mmHg in the average glaucoma patient and lower yet in the patient with advanced disease seems like a reasonable goal. While lowering pressure definitely slows or stops progression in most patients, it does not do so in all patients and it is difficult to identify those who will progress or reliably determine target pressure from any baseline characteristics.297

Types of treatment

The usual progression of treatment in POAG is medical therapy, followed by laser trabeculoplasty, then filtering surgery. Several large, prospective controlled trials of glaucoma treatment have been completed (Table 17-3). In general, the studies show that lower IOPs tend to preserve vision better, and filtering surgery seems to achieve that best of the three modalities. Laser trabeculoplasty seems to be as effective as timolol for initial treatment of glaucoma. A few studies have been done comparing medical therapy and filtering surgery. Generally these trials have shown that filtering surgery is more

effective than medical therapy in preserving visual field but is associated

with a greater loss of visual acuity and a higher incidence of cataract,303,304although glaucoma itself as well as topical medical

treatment are risk factors for cataract formation.305

Despite the findings of these controlled clinical trials, most experts, at least in the United States, continue to use medical therapy as the first-line approach in POAG (see Chs 21 through 28). The reasons for this approach include the relatively short effectiveness of laser treatment and even surgery as measured against the lifetime needs of the glaucoma patient and the relative safety of medical treatment. Trabeculectomy has the risk of profound visual loss or other significant complications. Although the side effects of medical therapy can be protean, they are rarely permanent and usually disappear after cessation of the particular offending treatment. In Europe, with the advent of the more potent antiglaucoma drugs, glaucoma surgery as primary treatment has declined.306 In general, the clinician should prescribe the safest drug or drugs for the patient in the lowest doses necessary to control the IOP at the desired level. It is important to measure IOP at different times of the day and at different intervals after drug administration to determine the response to therapy. The failure of medical treatment is usually judged by inadequate control of IOP, progressive visual field loss or optic nerve cupping, the appearance of an optic nerve hemorrhage, intolerable side effects of medication, or demonstrated (or admitted) poor compliance with therapy.

The clinician should use the patient’s previous course in both eyes as a guide for judging the adequacy of therapy. For example, if an individual has progressive damage in either eye when IOP was in the range of 20 mmHg, and the pressure is at that level again, more aggressive treatment is probably indicated rather than waiting for further damage. Studies have shown that from a societal point of view (as well as the patient’s), treating the disease adequately to prevent progression is more cost effective than trying to manage more advanced disease.307

In developed countries like the US and western Europe, the prostaglandin analogues are the usual first medications to try since their once a day regimen makes compliance easier and their side effects are relatively benign. The non-selective -blockers are also popular because they can be given once or twice a day and have infrequent ocular side effects, although significant systemic side effects often occur after months of treatment. These two classes of medications represent the most effective for monotherapy.308 Wide variations occur in treatment patterns in the US and women are often treated less aggressively than men.309 When one medication lowers the IOP but not enough, a second medication can be added. However, if the first fails to lower the IOP a significant amount, then substitution is preferable. When a second or third medication becomes necessary, the use of combination drops may help compliance. Studies on compliance and persistence suggest that neither are achieved anywhere near the rate that doctors think.310 Nevertheless, over 90% of patients can be expected to be controlled with medications over their lifetime. For the typical glaucoma patient, two or three medications would be the maximum suggested before resorting to laser or incisional surgery. At present, maximum medical therapy consists of a prostaglandin-like agent, a -adrenergic antagonist, a topical carbonic anhydrase inhibitor, and an -agonist. Most ophthalmologists recommend laser trabeculoplasty before resorting to miotics (except in aphakic or pseudophakic eyes), although these agents should not be forgotten as potential therapy. Systemic carbonic anhydrase inhibitors are rarely used unless surgery is not feasible or has failed.

When medical treatment fails or when at least two topical agents have been found wanting, argon or selective laser trabeculoplasty is the next therapeutic option for most individuals with POAG, as well as being the primary treatment for those unable or unlikely to use medical therapy (see Ch. 32). This technique reduces IOP substantially in 70–80% of patients. Most individuals continue to require at least some medical therapy after laser trabeculoplasty, although it is possible to reduce the number of medications in a significant percentage of patients.311 Unfortunately, in many patients, IOP rises again months to years after laser treatment. There seems little difference in the long-term outcome between argon and selective laser trabeculoplasty.312

If medical treatment and laser surgery are inadequate to control POAG, filtering surgery is the next appropriate step. Filtering surgery controls IOP in approximately 80–90% of patients with POAG. Approximately one-third of Caucasian patients with POAG go on to filtration surgery according to one retrospective study in Minnesota.313 Racial differences exist in the response to laser surgery and filtering surgery; for example, the AGIS showed that whites responded better to filtering surgery first compared to blacks who responded better to argon laser trabeculoplasty first.314 Economics and the results of the Collaborative Initial Glaucoma Treatment Study (CIGTS), where surgical and medical therapy in newly diagnosed glaucoma patients were found to be equally effective at long-term pressure control, probably justify filtering surgery as the primary treatment in developing countries.315

If one drainage procedure fails to control IOP or if the risk factors for failure are high (e.g., black African ancestry, youth, secondary glaucoma), many ophthalmologists repeat filtering surgery with an inhibitor of wound healing, such as 5-fluorouracil or mitomycin C. On the other hand, many use topical application or injection of these agents even in primary filtering operations. If two or more filtering surgeries have failed despite antifibrosis agents or there is a high likelihood of failure after a single filtering operation fails, a tube-shunt (glaucoma drainage) device such as a Molteno, Baerveldt, or Ahmed implant can be used. A recently concluded randomized controlled trial suggests that non-valved implants such as the Molteno or Baerveldt are as good if not somewhat better at controlling IOP at 1 year than a trabeculectomy in a previously operated eye. So, some would consider a tube-shunt procedure after the first trabeculectomy (or similar) fails.316 It is also possible to reduce aqueous humor formation by treating the ciliary body with trans-scleral cyclophotocoagulation or endocyclophotocoagulation, although these are usually reserved for end-stage cases.

Prognosis

The prognosis in POAG is determined by (1) the degree of optic nerve damage;317–320 (2) the height of the IOP;317,318,320–325 (3) the

vulnerability of the disc tissue;326 (4) the presence of systemic vascular disease;327 (5) the compliance with treatment,328 and (6) the timeliness and appropriateness of treatment. Age is also a factor, as the older one gets the more likely the disease is to progress.329 Few prospective studies exist on the prognosis of untreated open-angle glaucoma. One such study, done on the island of St Lucia in the Caribbean, noted progression to end-stage disease over a 10-year period in about 35% of untreated eyes, with about 55% of eyes progressing.330 Generally, treated open-angle glaucoma progresses relatively slowly. In one study, approximately one-third of patients with open-angle glaucoma became worse over 9 years.331 In another retrospective study done in Iowa on mostly Caucasian patients, 68%