VARIOUS COURSES OF THE OPEN ANGLE GLAUCOMAS: RELATIONSHIP TO INTRAOCULAR PRESSURE

R A Hitchings
Moorfields Eye Hospital, London

Introduction

By definition, glaucoma is a progressive disease. It can be expected the Glaucoma’s will show diversity in the nature and speed of their progression. Clinicians are all familiar with the ocular hypertensive patient whose optic nerve is seemingly impervious to decades of raised intraocular pressure (IOP), as well as the rapid descent into blindness of the patient with Normal Pressure Glaucoma.

It is the purpose of this presentation to briefly review the natural history of visual loss in the glaucoma’s, relating this to the IOP. The presentation will look at information form surveys and clinical trials as well as studies that typify the type of visual loss that occurs.

Cross sectional surveys

For many years cross sectional surveys have been used as a proxy for natural history studies when estimating rate of change in eyes with glaucoma. Leydhecker (1) noted the age difference between OHT and glaucoma patients at the time of his large scale survey and suggested that a significant time interval needed to elapse before OHT became glaucoma. Jay (2) clearly related time to visual loss with presenting IOP. Poinoosawmy noted the time for unilateral Normal Pressure Glaucoma to become bilateral (3). All these papers are open to the criticism that their surveys may not correctly identify the true natural history of the condition.

Longitudinal studies
Survey data

There have been a number of studies that have looked at the incidence of visual field defects in defined populations. Bengtsson in Sweden(4) and Roy Wilson in St Lucia(5) found no clear association between elevated IOP ad the subsequent development of glaucoma, Leske in Barbados found that although increased IOP increased the risk of developing POAG half those who did so had normal IOP’s (6). Similar findings were reported by Mukesh et al in the Melbourne visual impairment project (7). Analysis of the subjects in Barbados found a closer relation between the incidence of visual field loss and IOP only when systemic blood pressure was taken into account, relating the development of field loss more closely to perfusion pressure

Randomised Controlled Trials

Two recent ‘Treatment no-Treatment’ trials (the Ocular Hypertension Treatment Study –OHTS, and the Early Manifest Glaucoma Trial-EMGT) have looked at the incidence of glaucoma progression over time. These have not been in defined populations, but have been in collected groups, each meeting predefined criteria for entry into these studies. Risk factors for the development of visual field loss in OHTS (central corneal thickness and C/D ratio) were included with elevation of IOP. In EMGT risk factors included with elevated IOP for the development of progressive visual field loss included severity of visual loss (MD), PXF and age.

Both the ‘incidence studies’ and the Treatment /No Treatment studies have shown that the relationship of elevated IOP and the development of (further) visual field loss is complex, with many additional factors contributing.

The nature of visual loss in untreated glaucoma

It is worth noting the difference between ‘time to progression’ and ‘rate of change’. The former provides a useful end point in clinical trials, and has been used in the Treatment/No Treatment trials noted above. Although the definition of ‘change’ may vary between studies the process relies on event analysis, being the comparison between levels of visual function at different time points. Unfortunately ‘time to (detected) progression can give no indication of ‘rate of change’. This is because rate of change requires a measure of change in function over time, whereas studies that measure time to detected change do not include a measure of the amount of function that has been lost. The exception has been in the use of Global indices such as ‘MD’. ‘MD’ however provides a poor measure of visual decline in glaucoma, because of confounders such as media opacities and pupil size, and the focal nature of glaucomatous visual loss. Individual location assessment of visual function does provide such an assessment of area loss of function, and such an approach has been used in Pointwise linear progression with Trend Analysis.

Pointwise linear progression analysis has been shown to take a similar length of time to identify change in the visual field as event analysis shown with HFA (8;9). It requires a sequence of 5 or more visual fields to produce enough points on the graph. This compares with the need for baseline fields, followed by repeated visual field defects as required by event analysis(10). Computer simulations of the different types of visual field change that could occur in glaucoma suggest that a linear model fits best whether the change is linear, exponential or stepwise (11;12).

Linear regression and the rate of change

For a number of years the normal pressure glaucoma clinic at MEH followed a policy of following untreated NPG patients until such time as a change in visual function has been identified. This policy has been given substance by the demonstration that 1/3 of patients with NTG will not show signs for visual field progression for 5 or more years (13-15). The linear regression analysis performed on the patients attending Moorfields NTG clinic allowed the measurement of the rate of change in the untreated patient. Rates of decline in individual point sensitivity exceeding 1 db/year for peripheral points and 2 db/year for the central 20 degrees were considered significant. A measure of the rate of decline could be seen before and after glaucoma surgery in patients with glaucoma progression defined in this way (16).

Using linear progression and knowing the rate of decline allows the prediction visual sensitivity for a single location in the future. Using this process for each tested location allows the prediction the visual sensitivity of the whole of the visual field. Merging the two fields in one individual allows an assessment of the functional deficit now and how it would change over time in the untreated state. Knowing how the treated eye responds allows an assessment of the alteration of the functional change that can occur with treatment with time. This information can be used to guide the patient in the management of their disease.

Reference List

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