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Hiroki Nomoto, Katsuyoshi Suzuki, David F Garway-Heath, UKGTS investigators; Measurement of optic nerve head and retinal nerve fibre layer (RNFL) structure can distinguish between treatment groups in a clinical trial: the United Kingdom Glaucoma Treatment Study (UKGTS).. Invest. Ophthalmol. Vis. Sci. 2014;55(13):4776.
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In glaucoma clinical trials, IOP and functional measurements have been the primary endpoints for evaluating drug treatment. However, there is a significant body of evidence supporting the usefulness of imaging devices to assess glaucomatous structural changes. In spite of the findings, structural measurements have not yet been accepted as clinical trial endpoints. The UKGTS, a randomized placebo-controlled treatment trial (latanoprost vs placebo drops), was designed to evaluate the ability of imaging outcomes to distinguish between treatment groups.
516 newly-diagnosed patients were enrolled in the UKGTS. Patients underwent standard automated perimetry (SAP), scanning laser tomography (HRT), optical coherence tomography (Stratus-OCT) and scanning laser polarimetry (GDx) on 11 occasions over 24 months. SAP deterioration was the trial endpoint. A priori (according to the statistical analysis plan), the eye with the worse SAP mean deviation (MD) was selected for analysis of imaging outcomes. Patients with > 6 months follow-up were included: HRT (n=407 eyes), OCT (n=274 eyes), GDx (n=252 eyes). Linear regression analysis was used to evaluate rates of change in global neuroretinal rim area (RA:HRT), average RNFL thickness (OCT, GDx) and MD (SAP).
Baseline mean RA, RNFL and MD were similar between the placebo and latanoprost groups (RA, p=0.24; OCT RNFL, p=0.29; GDx RNFL, p=0.15; MD, p=0.76). Mean MD slopes (dB/year) of the placebo group were significantly steeper (-0.38 [SD 1.30]) than those of the latanoprost group (0.02 [SD 1.01]), p<0.01. Mean HRT RA loss (mm2/year) was significantly faster in the placebo (-0.021 [SD 0.034]), compared to the latanoprost (-0.01 [SD 0.035]), group (p=0.016). Mean OCT RNFL loss (μm/year) was significantly faster in the placebo, compared to the latanoprost, group (-2.12 [SD 4.51] vs -1.14 [SD 3.47], p=0.046). There was no statistically significant difference between treatment groups for mean GDx RNFL loss (μm/year): placebo -0.80 [SD 1.77] and latanoprost -0.87 [SD 1.31] (p=0.72).
HRT and OCT measurements of RA and RNFL can distinguish between treatments groups, and the difference is in the same direction as the functional (SAP) loss. The findings provide strong support for the use of structural measurements as clinical trial endpoints.
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