Detection and measurement of clinically meaningful visual field progression in clinical trials for glaucoma

Abstract

Glaucomatous visual field progression has both personal and societal costs and therefore has a serious impact on quality of life. At the present time, intraocular pressure (IOP) is considered to be the most important modifiable risk factor for glaucoma onset and progression. Reduction of IOP has been repeatedly demonstrated to be an effective intervention across the spectrum of glaucoma, regardless of subtype or disease stage. In the setting of approval of IOP-lowering therapies, it is expected that effects on IOP will translate into benefits in long-term patient-reported outcomes. Nonetheless, the effect of these medications on IOP and their associated risks can be consistently and objectively measured. This helps to explain why regulatory approval of new therapies in glaucoma has historically used IOP as the outcome variable. Although all approved treatments for glaucoma involve IOP reduction, patients frequently continue to progress despite treatment. It would therefore be beneficial to develop treatments that preserve visual function through mechanisms other than lowering IOP. The United States Food and Drug Administration (FDA) has stated that they will accept a clinically meaningful definition of visual field progression using Glaucoma Change Probability criteria. Nonetheless, these criteria do not take into account the time (and hence, the speed) needed to reach significant change. In this paper we provide an analysis based on the existing literature to support the hypothesis that decreasing the rate of visual field progression by 30% in a trial lasting 12–18 months is clinically meaningful. We demonstrate that a 30% decrease in rate of visual field progression can be reliably projected to have a significant effect on health-related quality of life, as defined by validated instruments designed to measure that endpoint.

Neuroprotection in Glaucoma: Towards Clinical Trials and Precision Medicine

“…De Moraes et al proposed that decreasing the rate of visual field progression by 30% in a clinical trial of 12 to 18-month duration would yield clinically meaningful results and showed that a 30% decrease in rate of visual field progression had a significant effect on health-related quality of life. 76 It has also been suggested that the 10-2 visual field may be a more appropriate outcome measure as the 24-2 field can underestimate the degree of damage at the macular region involved in glaucomatous optic neuropathy. 77 The 10-2 visual field has also been shown to correlate with quality of life outcome measures 78 and may reduce the time required to detect glaucomatous progression.…”

Contribution at the Study of Neuroprotective Properties of Neuroglobin during Severe Chronic Glaucoma

“…This situation makes that, all current pharmacological and surgical treatments aim to reduce IOP [19] [20] [21]. However, although this approach is effective for many patients with glaucoma, a significant proportion of their visual function deteriorates inexorably.…”

“…However, although this approach is effective for many patients with glaucoma, a significant proportion of their visual function deteriorates inexorably. In fact, about one in eight patients with glaucoma become blind in at least one eye despite this treatment [6] [21]. In animals, experimental therapies targeting and protecting retinal ganglion cells against phenomena related to hypoperfusion of the optic nerve (ischemia, hypoxia, oxidative stress, apoptosis) have been evoked and grouped under the term neuroprotection [6] [22]- [27].…”

Complement C3-targeted gene therapy restricts onset and progression of neurodegeneration in chronic mouse glaucoma

“…The pathobiology of this neurodegenerative disease remains unclear due to manifold processes and risk factors, including age, ethnic group and elevated intraocular pressure (IOP) 2 . Current therapies can successfully lower IOP and decelerate but not halt the progression of neurodegeneration 3 . Thus, developing neuroprotective approaches to interrupt progression is a primary goal 4 .…”