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42  Management of Ocular Hypertension and Primary Open-Angle GlaucomaROGER A HITCHINGS and MARK B SHERWOOD

these three viewpoints and discuss each in turn (see also Chapter 45, Target Intraocular Pressure and Chapter 51, Benefit versus Risk). The same principles will apply for the management of glaucoma secondary to other (chronic) ocular conditions (especially pigment dispersion and pseu-doexfoliation) and, apart from specific indications for the primary condition, the principles of management would be the same.

Ocular Hypertension

The case for treating ocular hypertension needs to be bal-anced against the cost and the patient’s perceived benefits. Although ocular hypertension is an established risk factor for developing POAG, it is not the only one, and does not inevitably lead to ‘conversion’ to POAG.

The cost of treating OHT may become a societal one, with pharmaceutical costs being a significant restricting factor in the widespread use of topical hypotensives.

BACKGROUND

The Ocular Hypertension Treatment Study (OHTS) demon-strated that sustained IOP reduction halved the conversion rate to POAG in a selected group of subjects.1 A number of baseline factors were good predictors of ‘conversion.’2 The European Glaucoma Prevention Study (EGPS) did not dem-onstrate such protection, a fact attributable at least in part to differences in study design and a lower mean IOP differ-ence between the two arms of the study.3 However, a com-parison of the untreated arms from the two studies showed that data from EGPS confirmed the predictive factors for ‘conversion’ shown in the OHTS.4 These were baseline age, intraocular pressure, central corneal thickness, vertical cup-to-disc ratio, and Humphrey VF pattern standard deviation.

Treatment by reducing (elevated) IOP offers protection from developing POAG within 5 years in higher-risk patients. Further long-term data, this time from the Early Manifest Glaucoma Trial (EMGT) identified lower systolic perfusion pressure, lower systolic BP, and cardiovascular disease history as additional predictors, suggesting a vascu-lar role in glaucoma progression.5

Who should receive treatment? Kymes looked at the out-comes from the OHTS and concluded that the treatment of those patients with IOP of ≥24 mmHg and a ≥2% annual risk of the development of glaucoma is likely to be

Introduction

This chapter sets out the principles of management of ocular hypertension and primary open-angle glaucoma. For the purpose of this chapter ocular hypertension (OHT) is defined as an eye having an intraocular pressure (IOP) lying two standard deviations or more above the mean IOP for the population, in the absence of any visible acquired change in the topography of the optic nerve head, or visual field defect characteristic for glaucoma (see Chapter 28, Ocular Hypertension). Usually this means an IOP consist-ently exceeding 21 mmHg, but for some populations this might be higher or (as in the case of native Japanese) lower than 21 mmHg.

Primary open-angle glaucoma (POAG) is said to be present when there is a characteristic deformity of the optic nerve head, characterized as glaucomatous cupping, usually with a demonstrable reduction in visual function, shown as reduced retinal sensitivity in spatial location cor-responding with the anatomic change (see Chapter 29, Primary Open-Angle Glaucoma). The ‘angle’ of the ante-rior chamber is said to be ‘open’ and there is often an ele-vated IOP without visible cause. Some eyes may have an appearance of the optic nerve head or defects in visual func-tion that could be misconstrued as glaucoma and in some cases the diagnosis of glaucoma may only be confirmed by disease progression.

Treatment for OHT and POAG is restricted to reducing intraocular pressure. Currently there is no proven ‘non-IOP’ antiglaucoma therapy available.

Management is based on the assessment of risk, the response to therapy, rate of progression, and the patient’s needs. It requires initial assessment, target setting, and monitoring. This chapter will look at management from

Summary

This chapter discusses the relationship between an elevated intraocular pressure (IOP) and primary open-angle glaucoma (POAG). It points out that not all patients with the former need necessarily develop POAG and that not all patients with POAG need have an elevated IOP. These subjects are dealt with in greater detail in Chapters 28 (OHT) and 43 (Management of Normal-Tension Glaucoma). Management of subjects with OHT and POAG depends on the assessment of risk at diagnosis, the response to initial treatment (if any) and then on long-term monitoring.

SECTION 5 PRINCIPLES OF MANAGEMENT

42  • Management of Ocular Hypertension and Primary Open-Angle Glaucoma 473

The Early Manifest Glaucoma Trial (EMGT)9) have demon-strated long-term IOP reduction with treatment. However significant visual field preservation benefit related to this was less easy to demonstrate. Although many factors could account for this, the development of cataract after filtering surgery in both trials may be a major explanation. More-over, in both studies it was noted that for a significant subset of patients, visual field progression in the untreated group might not be detected for 5 years or more. Risk factors for progression in CNTGS included disc hemorrhages, female gender, and migraine, but not age or baseline IOP.10 The EMGT noted that risk factors for progression were a higher baseline IOP, exfoliation, bilateral disease, worse mean devi-ation, and older age, as well as frequent disc hemorrhages during follow-up.11

IOP reduction in POAG will probably slow, if not halt progression. In ‘developing countries’ where medical treat-ment and long-term follow-up care are unavailable and/or too expensive primary surgery should be considered a viable option. However hypotensive treatment can be considered justifiable with a population-attributable risk (PAR) of 16%.8

In ‘developed’ countries there are a range of alternatives. These are: medical treatment; surgical treatment that is considered unlikely to produce cataract or combined glau-coma and cataract surgery where these conditions coexist.

DIAGNOSIS

As for OHT, management for POAG starts with initial assess-ment, the defining of treatment (IOP reduction) goals, and then long-term monitoring. Successful management will be to prevent visual disability during the patient’s lifetime, even if that means that some disease progression may have occurred. Clearly, the sooner the patient is diagnosed the better, even if the decision is made to defer treatment.

Management of glaucoma in any defined population has to be organized in such a way that early cases of glaucoma-tous cupping with visual field defects can be identified. This means the recognition that elevated IOP is not needed for the diagnosis of POAG. For presymptomatic glaucoma this means diagnosis in primary care, whether by other health-care professionals, physicians, ophthalmologists, or glau-coma specialists. Two studies have demonstrated a cost increase for treating glaucoma in the later stages of disease.12,13 Additionally, the response to hypotensive treat-ment would appear less marked with later stages of disease14 while the risk of going blind despite good IOP control is increased.15 Glaucoma management then can be summa-rized as the diagnosis of glaucoma at an early and certainly presymptomatic stage, followed by assessment, the setting of IOP targets, and adequate long-term monitoring.

Compliance and Adherence

A major issue for long-term management of chronic glau-coma is compliance and adherence with treatment.16 It has been demonstrated that adherence may be improved by simplification of drop regimens, education, and self-reporting. All measures depend on patient cooperation and understanding, as well as a realization that failure to

cost-effective, identifying US$42430 per quality-adjusted life year for this group6 (see also Chapter 3, Economics of Glaucoma Care).

In contrast, Thomas and colleagues expressed concern that as ocular hypertension has an ‘effective’ PAR of 8.5%, this is a value not considered high enough to warrant public health intervention (at least in ‘developing countries’) (see also Chapter 51, Benefit versus Risk).7

Public perception and national health budgets will inevi-tably play a role in the allocation of resources for the man-agement of OHT.

ASSESSMENT

Identification of a patient with elevated IOP will lead to assessment, a decision on whether hypotensive therapy was needed from the outset and then formulation of plans for long-term monitoring.

Recognition of patients with elevated IOP needs to be followed by an assessment of primary or secondary cause, consistent together with mean IOP level. Baseline risk factors as identified by OHTS/EGPS need to be looked for.

Identification of risk factors allows a prediction of 5-year risk; this will help the advice given to the patient.

In consultation with the patient about risk, an informed decision is taken on whether to initiate therapy. Influencing factors will include the absolute IOP level, the presence of a positive family history (particularly in siblings), cost, patient concern, and likely compliance.

MONITORING

Following initial assessment and therapeutic management decisions, a course for monitoring needs to be set. To do this, baseline values for visual function, optic nerve head and retinal nerve fiber layer imaging, and response to initial therapy need to be obtained.

Long-term follow-up needs to be at a frequency compat-ible with the patient’s wishes and ability to attend, com-bined with the perceived likelihood of demonstrable change (suggesting ‘conversion’) between visits. For OHT without treatment (low risk), an annual visit usually suffices. With treatment, a biannual visit may be required. Image and functional assessment should be undertaken once a year to look for stability or change.

Primary Open-Angle Glaucoma

The expectation is for elevated IOP to coexist with acquired change at the optic disc and in visual function. However, in many populations POAG may occur without elevated IOP. Whereas the management of OHT can be relatively straight-forward, namely, a decision whether or not to lower the IOP. The management in POAG becomes more complicated when the IOP lies in the normal range (see Chapter 33, Normal-Tension Glaucoma).

BACKGROUND

Two randomized treatment/no treatment trials (the Col-laborative Normal-Tension Glaucoma Study (CNTGS),8 and

SECTION 5 • Principles of Management 474

first 2 years. Long-term analysis of visual field testing has suggested that the frequency should be high in the first two years (to identify those patients who are showing signs of ‘rapid progression’). If there is no evidence for this then a reduction in the annual retest rates is permissible.18

Comparison with the baseline assessment of the optic disc should be undertaken. As more sophisticated software becomes available this type of monitoring will assume greater importance.

Progression despite achieving a target IOP offers the phy-sician three choices. First, to ask whether the IOPs meas-ured at a clinic visit accurately reflect levels the rest of the time. Here, an investigation into compliance, adherence, and diurnal IOPs is warranted. Secondly, to further lower the IOP. This may be achieved medically by adding further medications or switching to an alternative. The former may be achieved by the use of combination therapy, although two drugs in combination do not always provide the expected IOP reduction from their actions when given alone. Thirdly, to switch to or add laser trabeculoplasty, or to offer filtration surgery. If the third choice is taken, it is necessary to recall that cataract- and bleb-related infections are a sequel of standard guarded filtration procedures (‘trabeculectomy’) and that the IOP level achieved after nonfiltration procedures may not be as low as that for trabeculectomy.

References1. Kass MA, Heuer DK, Higginbotham EJ, et al. The Ocular Hypertension

Treatment Study: a randomized trial determines that topical ocular hypotensive medication delays or prevents the onset of primary open-angle glaucoma. Arch Ophthalmol 2002;120:701–13.

2. Gordon MO, Beiser JA, Brandt JD, et al. The Ocular Hypertension Treatment Study: baseline factors that predict the onset of primary open-angle glaucoma. Arch Ophthalmol 2002;120:714–20.

3. Miglior S, Zeyen T, Pfeiffer N, et al. Results of the European Glaucoma Prevention Study. Ophthalmology 2005;112:366–75.

4. Ocular Hypertension Treatment Study Group; European Glaucoma Prevention Study Group, Gordon MD, Torri V, Miglior S, et al. Validated prediction model for the development of primary open-angle glau-coma in individuals with ocular hypertension. Ophthalmology 2007;114:10–19.

5. Leske MC, Heijl A, Hyman M, et al. Predictors of long-term progres-sion in the Early Manifest Glaucoma Trial. Ophthalmology 2007;114(11):1965–72.

6. Kymes SM, Kass MA, Anderson DR, et al. Management of ocular hypertension: a cost-effectiveness approach from the Ocular Hypertension Treatment Study. Am J Ophthalmol 2006;141: 997–1008.

7. Thomas R, Kumar RS, Chandrasekhar G, et al. Applying the recent clinical trials on primary open angle glaucoma: the developing world perspective. J Glaucoma 2005;14:324–7.

8. Collaborative Normal-Tension Glaucoma Study Group. The effectiveness of intraocular pressure reduction in the treatment of normal-tension glaucoma. Am J Ophthalmol 1998;126:498– 505.

9. Heijl A, Leske MC, Bengtsson B, et al. Reduction of intraocular pres-sure and glaucoma progression: results from the Early Manifest Glau-coma Trial. Arch Ophthalmol 2002;120:1268–79.

10. Drance S, Anderson DR, Schulzer M, Collaborative Normal-Tension Glaucoma Study Group. Risk factors for progression of visual field abnormalities in normal-tension glaucoma. Am J Ophthalmol 2001;131:699–708.

11. Leske MC, Heijl A, Hussein M, et al. Factors for glaucoma progression and the effect of treatment: the Early Manifest Glaucoma Trial. Arch Ophthalmol 2003;121:48–56.

12. Lee PP, Walt JG, Doyle JJ, et al. A multicenter, retrospective pilot study of resource use and costs associated with severity of disease in glau-coma. Arch Ophthalmol 2006;124:12–19.

maintain IOP control can lead to significant disability. A recent study demonstrated that the main fear was disability such as loss of the driving license and blindness rather than the mode of treatment.17

ASSESSMENT

Initial assessment of the patient recently diagnosed with POAG involves looking at the risk of visual disability devel-oping in the patient’s lifetime. This will involve assessment of binocular function, age, likely compliance, as well as severity of disease in the two eyes, and any comorbidity, whether ocular (such as external eye inflammation, cata-ract or age-related macular degeneration), or systemic (such as diabetes).

It is important to identify the IOP level at which glauco-matous optic nerve damage occurred. This may require phasing over 24 hours if the initial readings are within the normal range.

The patient will require indefinite monitoring. Training is needed to obtain repeatable performances on visual field testing (see Chapter 11, Visual Fields).

TREATMENT

The decision on whether to initiate medical treatment will depend upon the baseline IOP and the presence of other risk factors identified from the no-treatment studies. Addition-ally, the response to acceptable trials of therapy and the availability and affordability of hypotensive medications need to be considered. Many patients with normal-tension glaucoma are elderly and, if they have early visual field loss, may be safely watched as progression will be slow, if at all. Some patients with moderately elevated ‘high tension glau-coma’ respond little to therapy, or prove to be poor compli-ers. Other patients cannot obtain or instill medications (and may not be able to comply with the demands of monitor-ing). For this last group a decision needs be taken whether to offer laser or conventional surgery, or, again, just to monitor them. In conjunction with the patient, a decision to monitor without treatment may be the chosen option.

Any ‘new’ patient with glaucoma needs careful instruc-tion about their condition, the risks of non-compliance and the need for regular follow-up. Those starting on topical treatment should be instructed on methods to correctly instill their drops.

A ‘target pressure’ for the patient needs to be set, and an assessment made, if the ‘target’ is not met, whether to add therapy or switch medications (see Chapter 45, Target Intraocular Pressure).

Baseline imaging of the optic nerve head and retinal nerve fiber layer should be undertaken. Baseline photo-graphs of the optic disc (preferably stereophotographs) form a reasonable alternative at the present time (see Chapter 19, Optic Disc Photography in the Diagnosis of Glaucoma and Chapter 20, Optic Disc Imaging).

MONITORING

Whatever the chosen target pressure, there is no guarantee that progression will be halted. All patients with POAG, whether treated or not, should be closely monitored for the

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16. Tsai JC. Medication adherence in glaucoma: approaches for optimiz-ing patient compliance. Curr Opin Ophthalmol 2006;17:190–5.

17. Bhargava JS, Patel B, Foss AJ, et al. Views of glaucoma patients on aspects of their treatment: an assessment of patient preference by conjoint analysis. Invest Ophthalmol Vis Sci 2006;47:2885–8.

18. Chauhan BC, Garway-Heath DF, Goni FJ, et al. Practical recommenda-tions for measuring rates of visual field change in glaucoma. Br J Ophthalmol 2008;92:569–73.

13. Traverso CE, Walt JG, Kelly SP, et al. Direct costs of glaucoma and severity of the disease: a multinational long term study of resource utilisation in Europe. Br J Ophthalmol 2005;89:1245–9.

14. Oliver JE, Hattenhauer MG, Herman D, et al. Blindness and glaucoma: a comparison of patients progressing to blindness from glaucoma with patients maintaining vision. Am J Ophthalmol 2002;133: 764–72.

15. Forsman E, Kivela T, Vesti E. Lifetime visual disability in open-angle glaucoma and ocular hypertension. J Glaucoma 2007;16:313–19.