New Testing Paradigms

Glaucoma neuroprotection clinical trials achievable with reasonable numbers and cost. Roibeárd Ó hÉineacháin reports from the 9th World Glaucoma E-Congress

Despite glaucoma’s slow rate of progression, clinical trials of neuroprotection do not require large study populations or lengthy follow-up to detect clinically relevant and IOP-independent improvements in the survival and function of the neurons of the visual system, according to Professor Robert Weinreb MD.

“With an appropriate drug and new testing paradigms, a trial of neuroprotection now has a high likelihood of achieving clinical endpoints within a reasonable time period and at a reasonable cost,” said Dr Weinreb.

CLUSTERED TESTING The key endpoint in neuroprotection trials, and the regulatory gold standard, is the improvement or stabilisation of the visual field. One way to optimise the sensitivity of visual field testing in a trial setting is to cluster the testing at baseline and the end of the trial, he explained.

The clustering approach to visual field testing can help overcome the insensitivity of testing in the early stages of glaucoma and its variability at the later stages of the disease. In addition, it allows for a shorter trial duration and a lower number of participants to show a result.

He cited the UKGTS trial as an example of the effective use of clustered testing in assessing visual function changes. The trial involved 516 open-angle glaucoma patients. With the time to visual field progression within two years as the clinical endpoint, visual field testing performed on a clustered basis showed patients who received latanoprost had significantly better visual field preservation than those who received a placebo.

He added the findings of the cohort study he and his associates conducted indicate that by using rate of progression and frequent testing, glaucoma therapy clinical trials could be completed within 18 months of follow-up and with fewer than 300 participants. The study’s authors have named this approach to testing the Short-Term Assessment of Glaucoma progrEssion (STAGE) model.

STRUCTURAL ENDPOINTS Changes in the optic disc and the retinal nerve fibre layer could also be of great value as clinical endpoints, as the changes can occur before detectable changes in visual function. The measurements are also easy to perform, allowing rapid acquisition of a large number of tests, reducing the sample size, trial duration, and expense required to reach a clinical endpoint. The challenge for the future is to determine the features of glaucomatous degeneration of the optic nerve that predict visual field loss, he stressed.

“The FDA is open to using structural endpoints in clinical trials of new glaucoma drugs provided, the structural measures predict clinically meaningful functional change,” he added.

Robert N Weinreb MD is Chair and Distinguished Professor of Ophthalmology at the University of California, San Diego, USA; Director of the Shiley Eye Institute; and Director of the Hamilton Glaucoma Center rweinreb@ucsd.edu SLO/OCT model ・ SLO model

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