Novel area-modulation perimetry for identifying changes in visual field sensitivity over time: The REVAMP+ Study

Glaucoma, a chronic, progressive, age-related degeneration of retinal ganglion cells, is characterised by a slow, irreversible loss of the visual field. It is the world's leading cause of irreversible blindness, affecting approximately 500,000 people in England and Wales, and 80million people worldwide. With an ageing population, prevalence of glaucoma is rising. The peripheral visual field is slowly lost first, often going unnoticed by patients until advanced. Perimetry, the clinical method for identifying visual field loss involves presenting stimuli (spots of light) of fixed area, varying in luminance, to the retina and measuring the lowest luminance that can be detected at multiple locations in the visual field. However, the current standard perimetry test was designed >45 years ago, before the pathophysiology of glaucoma was understood. Arbitrarily designed stimuli, imported out of convenience from its predecessor, Goldmann kinetic perimetry, by engineers when tests became more automated, do not target functional biomarkers for glaucoma. Together with high measurement variability, this makes it difficult to identify glaucomatous loss in the first instance and detect signs of progression. In fact, it can take many years of repeated measures to identify even moderate rates of deterioration. There is, therefore, a timely need to redesign perimetry with 45 years of knowledge and understanding from basic science (physiological, psychophysical) and clinical studies, as well as with more accessible and affordable technology, in order to increase accessibility to testing, detect visual loss sooner, treat sooner, and improve prognosis for vision.
We are currently undertaking the REVAMP Study, a major UK-wide, multi-site, academic-led, multi-disciplinary programme of research initiating the path to translation of novel Area-Modulated Perimetry (AMP) from laboratory to the clinical setting (funded by MRC DPFS: MR/V038516/1). Translation is driven by our discovery of two functional biomarkers for glaucoma and our finding of a higher signal/noise ratio (SNR) with stimuli varying in area during the visual field examination (area-modulated stimuli, AMS) than with conventional stimuli varying in luminance. In REVAMP, we optimised various test parameters, further improving SNR, in addition to improving test precision and speed/efficiency for identifying visual loss. It is also essential for commercialisation to determine rates of visual change and precision of estimates over time with optimised AMP parameters (longitudinal SNR), i.e. performance in identifying visual field loss over time in glaucoma.
Building on the strong foundation of REVAMP (including characterisation of the 'noise' component of longitudinal SNR), we now propose Stage 2 of our programme for translation: the REVAMP+ Study. We will determine longitudinal SNR for optimised AMP, and compare with that for conventional stimuli, in a prospective, longitudinal study.
Specific aims and objectives are to:

Characterise rates of glaucomatous visual change (and measurement precision) with AMP over time.
Optimise the spatial arrangement of stimuli for clinical investigations.
Deploy AMP on different screen technology to compare applicability.
Characterise baseline sensitivity, rates of change over time in eyes identified as potentially having ‘dysfunction’.

The primary application of AMP will be identification of visual field loss and progression in patients worldwide. Significant benefits outside the clinic include:

Investigators and pharmaceutical companies in need of more accurate and precise endpoints in clinical trials
Researchers and clinicians widening access to healthcare in difficult-to-reach areas
Researchers working in neuro-regeneration requiring more accurate and precise measurements to confirm or refute signs of neuro-regeneration in clinical trials.