Ординатура / Офтальмология / Английские материалы / Glaucoma Surgery_Trope_2005

Peng Tee Khaw, Ph.D., F.R.C.P., F.R.C.S., F.R.C.Ophth., F.R.C.Path., F.I.Biol., FMed.Sci. Professor of Glaucoma and Ocular Healing & Consultant Ophthalmic Surgeon, Director, Department of Glaucoma and Ocular Healing, ORB Ocular Repair and Regeneration Biology, Glaucoma, Pathology and Cell Biology, Moorfields Eye Hospital and Institute of Ophthalmology, London, UK

Dimitrios Kourkoutas, M.D. Consultant in Ophthalmology, Department of Opthalmology, 401 Hellenic Army General Hospital, Athens, Greece

Wai-Ching Lam, M.D., F.R.C.S.(C.) Associate Professor, University of Toronto, Toronto Western Hospital, Toronto, Ontario, Canada

Ruth Lapid-Gortzak, M.D. Cornea Fellow, Department of Ophthalmology, University of Toronto, Toronto Western Hospital, Toronto, Ontario, Canada and Lecturer in Ophthalmology, Ben Gurion University of the Negev, Israel

Ridia Lim, M.B.B.S., F.R.A.N.Z.C.O., M.P.H. Ophthalmologist, Eye Associates and Prince of Wales and Westmead Hospitals, Sydney, Australia

Roland Ling, B.A., B.M., B.Ch., F.R.C.Ophth. Consultant Opthalmologist & Vitreoretinal Surgeon, The Royal Devon & Exeter Hospital, Exeter, UK

Maurice H. Luntz, M.D., F.A.C.S., F.R.C.S. (E.D.), F.R.C.Ophth., D.O. (R.C.P.&S.), D.O.M.S. (R.C.S.I.), Diplomate A.B.O., Hon. F.C.S. (S.A.) Ophth. Attending and Director Emeritus, Glaucoma Services, Manhattan Eye, Ear and Throat Hospital, New York; Attending, New York Eye, Ear Infirmary, New York; Director Emeritus Department of Ophthalmology, Beth Israel Medical Center, New York; Clinical Professor of Ophthalmology, Mount Sinai School of Medicine, New York; Clinical Professor of Ophthalmology, New York University School of Medicine, New York, New York, USA

Shlomo Melamed, M.D. The Sam Rothberg Glaucoma Center, Sheba Medical Center, Tel Hashomer, Israel

Andre´ Mermoud Professor and Head, Glaucoma Unit, Jules Gonin Eye Hospital, University of Lausanne, Lausanne, Switzerland

Clive Migdal, M.D., F.R.C.S., F.R.C.Ophth. Western Eye Hospital, London, UK

J. E. Morgan, M.A., D.Phil., F.R.C.Ophth. Reader, Department of Ophthalmology, School of Medicine, Cardiff University, Cardiff, UK

Marcelo T. Nicolela, M.D. Associate Professor in Ophthalmology, Dalhousie University, Halifax, Nova Scotia, Canada

Ravikrishna Nrusimhadevara, M.B.B.S., D.N.B. (India) Retina Fellow, Department of Ophthalmology, University of Toronto, Toronto Western Hospital, Toronto, Ontario, Canada

Charles J. Pavlin, M.D., F.R.C.S. Professor, Department of Ophthalmology and Visual Science, University of Toronto, Toronto Western Hospital, Toronto, Ontario, Canada

Paul E. Rafuse, M.D., Ph.D. Assistant Professor in Ophthalmology, Dalhousie University, Halifax, Nova Scotia, Canada

University of Toronto, Toronto Western Hospital, Toronto, Ontario, Canada

Fani Segev, M.D. Department of Ophthalmology, University Health Network and University of Toronto, Toronto, Ontario, Canada

Arthur J. Sit, M.D., P.Eng., F.R.C.S.(C.) Glaucoma Fellow, University of Toronto, Toronto Western Hospital, Toronto, Ontario, Canada

Allan R. Slomovic, M.A., M.D., F.R.C.S.(C.) Associate Professor of Ophthalmology, Department of Ophthalmology, University of Toronto, Toronto Western Hospital, Toronto, Ontario, Canada

Tarek Shaarawy, M.D. Head, Glaucoma Sector, Ophthalmology Service, University of Geneva, Geneva, Switzerland

Adael S. Soares, M.D. Clinical Fellow in Glaucoma, Dalhousie University, Halifax, Nova Scotia, Canada

Graham E. Trope, M.B., B.Ch., Ph.D., F.R.C.S.(C.), F.R.C.Ophth., F.R.C.S. (E.D.), D.O. (R.C.P.&S.) Professor of Ophthalmology, Department of Ophthalmology, University of Toronto, Toronto Western Hospital, Toronto, Ontario, Canada

Section I: Surgical Techniques

estimates can only be determined in a retrospective manner after many years of treatment. Recent multi-center, randomized controlled trials have demonstrated the efficacy of lowering intraocular pressure (IOP) in reducing both the risk of developing glaucoma and progression of the disease, and provide some help in choosing the initial target pressure.

The Collaborative Normal-Tension Glaucoma Study (CNTGS) evaluated the efficacy of a 30% reduction of IOP on the rate of progression of open-angle glaucoma with normal IOP (,24 mmHg). Over a 5-year follow-up period, 35% of untreated eyes had evidence of progression of disease compared with 12% of treated eyes. The investigators concluded that IOP is related to the pathogenesis of normal-tension glaucoma, and lowering IOP by 30% decreases the risk of progression (1). On the basis of this study, we recommend trying to achieve an initial target reduction of IOP of 30% in all normal-tension glaucoma cases. Surgery may be indicated in cases when this target level is not reached.

The Advanced Glaucoma Intervention Study (AGIS) was originally designed to compare the efficacy and prognosis of two different surgical treatment protocols in white and black patients. Although the original objective of the study has become somewhat irrelevant due to changes in surgical techniques, the data collected has provided important insights into the selection of target pressures. After 7 years of follow-up, the investigators reported a “dose response” between IOP and visual field loss, in which the amount of visual field progression increased with IOP (2). In the “predictive” analysis, the patients were stratified into three groups based on average pressure. The group with average IOP ,14 mmHg had significantly less visual field deterioration than the group with average IOP .17.5 mmHg. In the “associative” analysis, the patients were stratified into four groups based on the proportion of IOP measurements that were ,18 mmHg. The group that was ,18 mmHg for all visits had an average IOP of 12.3 mmHg and demonstrated no visual field progression. The three groups that were ,18 mmHg for ,100% of visits demonstrated visual field progression. It is noteworthy that even in the first group, 14.4% of patients demonstrated visual field progression, which was balanced on average by 18.0% of patients who demonstrated improvement in their visual fields. On the basis of this evidence, we set initial target pressures in the low teens for all patients with advanced glaucomatous optic neuropathy. Clearly, if this is not achieved with medical and laser therapies, surgery may be indicated in such cases.

The Ocular Hypertension Treatment Study (OHTS) compared the rates of progression for treatment vs. no treatment in patients with ocular hypertension, but no clinical evidence of glaucoma as indicated by normal optic discs and visual fields. In this study, 1636 patients with a mean IOP of 24 32 mmHg were randomized to medical treatment with a target of 20% reduction, or observation. At 5 years, the mean reduction in IOP for the treatment arm was 22.5%. In this study, the probability of developing primary openangle glaucoma (POAG), as demonstrated by progression in visual fields or optic discs, was 4.4% for treated patients when compared with 9.5% of controls (3). This study supports lowering IOP in ocular hypotensives especially those at risk for progression, but clearly surgery is not indicated in these cases unless there are very unusual circumstances present.

These studies clearly show the benefit of IOP reduction in the management of glaucoma and selected patients with ocular hypertension, and help us to set initial target pressures. Lower pressures 12 15 mmHg clearly result in a lower risk of progression, but even reducing IOP by 20% has a protective effect. Advanced disease requires lower pressure when compared with early disease in order to halt or minimize the risk of progression. It is for this latter group that surgery should be considered sooner than later.

The risk of progression posed by IOP must always be balanced with the risks of treatment. This is especially true when surgery is being considered. There is even some

discussion as to whether patients are being over-treated in the zeal to reach the target pressure, particularly with early glaucoma. It is instructive to consider that the OHTS found that 90% of untreated ocular hypertensives did not progress over 5 years. Clearly, however, patients with advanced disease require aggressive therapy. However, not all glaucoma patients require an IOP of 12 14 mmHg. For example, an 85-year-old with a 0.75 cup-to-disc ratio and an IOP of 18 mmHg will likely not go blind from progressive optic neuropathy despite this IOP level. However a 55-year-old with a 0.9 cup-to-disc ratio and the same IOP level with a life expectancy of at least another 20 years is at greater risk of blindness if IOP is not dropped into the low teens. Spaeth has suggested that the goal of treatment is not to prevent disease progression, but to prevent patients from becoming symptomatic or from becoming more symptomatic (4).

1.2.Risk Factors for Progression

The decision to proceed with glaucoma surgery must include an evaluation of risk factors other than IOP alone. Table 1.1 lists the risk factors for glaucoma progression other than IOP that were found in the major recent randomized controlled trials of glaucoma treatment. In addition, factors that were assessed and found to be noncontributory, and factors that were found to be protective are listed. All of these factors should be considered prior to proceeding to surgery.

Normal-tension glaucoma appears to have different risk factors than other types of glaucoma (5). Among the studies of elevated-pressure glaucoma, age is the only factor identified universally. Note that none of the studies found family history to be a significant factor for progression, and only the Collaborative Initial Glaucoma Treatment Study (CIGTS) identified race as a factor (6). This is likely a result of the high prevalence of the disease, but seems to contradict population surveys that clearly show race and family history to be associated with the presence of glaucoma. Race is clearly an important

Table 1.1 Factors for Progression Other than IOP

factor in glaucoma, because blacks have four to five times the prevalence of disease as whites (7). Race may simply be an indicator for other risk factors. Family history as a risk factor may be more useful in glaucoma that occurs at a younger age. Central corneal thickness may also be an important independent risk factor for progression (8).

Advanced disease is generally considered to be more susceptible to further glaucomatous damage than early disease. This is supported by the EMGT (9), CIGTS (6), and OHTS (10), which examined early glaucoma and ocular hypertension. However, the opposite result was found with AGIS (11) which examined advanced glaucoma and found that patients with better baseline visual fields were more likely to demonstrate progression. The investigators suggested that this might be due to greater difficulty in detecting visual field changes in advanced disease when compared with early disease.

1.3.Compliance

Compliance with glaucoma medications, as with medications for any type of chronic diseases, is a major risk factor for progression. In the study by Kass et al. (12) using an eyedrop medication monitor, compliance with pilocarpine was found to be very poor. Fifteen percent of patients administered less than one-half of the prescribed doses. Twenty-five percent of patients missed at least 1 day per month. When interviewed, however, patients reported taking an average of 97% of prescribed doses.

In general, compliance with medications decreases with the frequency of dosing and the number of medications. However, even with newer medical therapies with less frequent dosing, compliance continues to be very poor (13). This is further exacerbated by the fact that glaucoma is an asymptomatic disease until the very late stages, and therapy does not result in any subjective improvement in their condition. Other major reasons for noncompliance include medication side effects (both local and systemic) and difficulty administering the medication.

In a patient where target IOP cannot be achieved consistently due to noncompliance, surgery must be seriously considered but only after patient education has been tried. The majority of the reasons sited by patients for noncompliance is not related to social or environmental factors and may be amenable to patient education or modification of medications (13). These include regimen factors (e.g., cost, complexity and side effects), patient factors (lack of knowledge/skill, forgetfulness, lack of motivation, and complexities created by co-morbidities), and medical provider factors (e.g., dissatisfaction with care and lack of communication).

Some situational compliance factors may be difficult to remedy. Patients who live in parts of the world where drops are not available or are prohibitively expensive, or live alone and have difficulty in administering the drops for physical reasons require earlier glaucoma surgery in order to achieve target pressures (14,15). However, caution must be exercised since good compliance with medications is required postoperatively in order to reduce potential surgical complications and enhance the chance of successful surgery.

1.4.Quality of Life and Lifestyle Factors

Both medical and surgical therapies have an impact on patient quality of life. Multiple medical therapy presents problems for elderly patients who often have difficulty in instilling drops, whereas, younger, active patients often have difficulty in maintaining a schedule for their medications. Surgical therapy often results in fewer medications in

the long-term, but requires intense patient participation in the postoperative period. Complications of surgery can also affect patient quality of life.

In the CIGTS, quality of life factors was evaluated between initial medical and initial surgical therapies (16). Symptoms and vision specific factors were evaluated at baseline, 2 months and 6 months postrandomization, and then at 6 month intervals. Visual function symptoms included evaluation of glare disability, light/dark adaptation, acuity/spatial vision, visual search, visual processing speed, depth perception, color discrimination, and peripheral vision. The results indicated lower IOP in the surgical group (14 15 mmHg) vs. the medical group (17 18 mmHg) but visual field progression was not statistically different between the two groups. Patients in the surgical group reported being bothered by more visual function symptoms than the medical group. Systemic and local eye symptoms were also evaluated. No consistent differences were found in systemic symptoms. The most persistent differences were in the local eye symptoms, which were reported more frequently in the surgical group. However, differences in symptoms between the treatment groups did not result in differences in broader measures of quality of life. Therefore, unless further information to the contrary arises, quality of life should not be used as a major factor in the decision to postpone or proceed with glaucoma surgery.

1.5.Diurnal Variations

IOP has long been known to undergo diurnal variations (17). As well, IOP can undergo short-term fluctuations in response to environmental factors such as food or fluid intake. Consumption of large amounts of water results in an osmotic shift into the aqueous resulting in increased IOP. The opposite effect occurs when hyperosmotic solutions are used in the treatment of glaucoma. Current evidence suggests that IOPs normally peak at the end of the sleep cycle or upon awakening, and decrease through the course of the day (18). The reason for IOP increase at night is unclear, as there are currently no studies of human 24 h IOP measurements that do not require opening the eyes of the patient and/or waking the patient. It is unlikely to be related to aqueous production, since production is actually higher during the day than at night (19,20).

Diurnal IOP variation has been implicated as an independent risk factor for glaucoma progression (21). In a study by Asrani et al., patients used a self-tonometer to measure IOP five times a day for 5 days at home. The diurnal IOP range and the IOP range over multiple days were found to be significant risk factors for progression, even after adjusting baseline factors including for office IOP, age, race, gender, and visual field damage at baseline. Further studies are indicated to confirm these results.

Interestingly, glaucoma patients seem to have larger diurnal/waking IOP variations, but may actually have smaller nocturnal/sleeping IOP variations when compared with normals. Twenty-four-hour IOP measurements on newly diagnosed, untreated glaucoma patients show a peak at night similar to normal patients (22). However, after taking into account the change in positioning of the patient (i.e., upright while awake and supine while asleep), the diurnal-to-nocturnal IOP change was less in glaucoma patients than in normal patients.

Although the role of diurnal and nocturnal IOP variations in the pathogenesis and progression of glaucoma is still not fully elucidated, it is reasonable to target therapy towards reducing diurnal IOP variations, as well as lowering mean IOP. Although any measure to lower the IOP will decrease the pressure variations, therapy that increases outflow facility, instead of decreasing aqueous production, may result in more stable measurements (23). A recent study has suggested that trabeculectomy results in reduced IOP variations compared with medical therapy, likely due to improved outflow facility

(24). In the study by Asrani et al. (21), the risk of progression was 5.76 times higher in patients with a diurnal IOP range of 5.4 mmHg (75th percentile) compared with a range of 3.1 mmHg (25th percentile). Therefore, in a patient with progression of glaucoma on maximally tolerated medical therapy, surgical treatment may be indicated if there is evidence of large diurnal pressure range (.5 mmHg) even if the mean IOP is within the target range.

1.6.The Case for Early Surgery

Early surgical intervention has been advocated by the European glaucoma community. This approach was initially supported by a study from Scotland that compared initial medical therapy with initial surgical therapy for newly diagnosed POAG (25). In this study, 116 patients were randomized to either trabeculectomy at diagnosis or initial medical therapy followed by trabeculectomy in unsuccessful cases. No difference in visual acuity was detected, but greater visual field loss was found in patients with initial medical therapy. The investigators suggested that this was due to delay of surgery, whereas medical therapy was modified in patients with minimal visual field loss at diagnosis.

The Moorfields Primary Treatment Trial also evaluated medical therapy vs. surgical therapy for the primary treatment of glaucoma. This study randomized 48 patients to initial surgery and 40 patients to initial medical therapy. Surgery as primary treatment resulted in a lower mean IOP than medicine as primary treatment, although the visual fields were not statistically different (26). The investigators suggested that initial surgery is a safe and more cost-effective method for treating glaucoma.

CIGTS evaluated initial medical therapy vs. initial surgical therapy for the primary treatment of glaucoma (6,16). In that study, the surgical group achieved a lower average IOP than the medical group, but there was no statistically significant difference in the visual field scores between the two groups. As well, the medical treatment group had a better average visual acuity than the surgical group, and was less likely to have a clinically substantial visual loss (15 letters or more). This was partially due to the surgical group having a cataract extraction rate almost three times higher than the medical group. However, the difference remained even after adjusting for cataracts. The investigators speculated that the differences in the results of this study compared with the European studies might be related to having patients with glaucoma earlier in the disease course, as well as the availability of newer, more effective medical treatments. They did not suggest changing current treatment protocols based on their 5 year results indicating that longer-term studies were required for a chronic diseases such as glaucoma.

These studies suggest that both medical and surgical therapies as initial treatment for glaucoma are effective and safe. In general, surgery results in a slightly lower IOP than medical treatment alone. However, the importance of this additional IOP lowering in early glaucoma must be considered in relation to potential complications and effect on central vision. Since the potential for vision threatening complications is real, we feel surgical treatment should still be reserved for secondor third-line therapy until conclusive evidence becomes available to show that surgical treatment of glaucoma results in better visual function outcomes.

The exception to this rule is in developing countries, where early surgical intervention is often indicated. With limited health care resources, there is often limited access to long-term follow-up care. In addition, life-long medical treatment is commonly prohibitively expensive for the patient. Under these circumstances, primary surgical treatment for glaucoma is a cost-effective solution despite the increased potential for complications (14,15).