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H. A. Jaffee; Measuring Circadian Rhythms. Invest. Ophthalmol. Vis. Sci. 2007;48(13):1238.
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Diurnal variation (DV) of intraocular pressure (IOP) is felt to play a major role in the progression of open-angle glaucoma (OAG), but the diurnal range (DR) at best captures overall daily fluctuation. The time development of diurnal IOP prompts a new model of DV that is more aware of fluctuation.
The DV of diurnal data should only be assessed in terms of the associated 24-hour c-data (for "circadian"), as in the table below. Compute the differences d of successive c-data values [e.g., pt. D: -6, +3, -2, +5]. The sum of the c-increases, SUMd>0 d [pt. D: 3+5], reflects all c-fluctuation and is a range with multiplicity, or m-range (MR). It distinguishes pt. B from pt. A, and pts. C and D from both, so is a strong DR. In order now to distinguish, e.g., pt. D from pt. C, compute the time differences s in hrs between c-data points, and the ratios q = d/s in mmHg/hr [pt. D: -6/5, +3/4, -2/5, +5/10]. Both amount and rate of c-increase are incorporated in an x-range (XR) given by SUMq>0 (eq - 1)*s [pt. D: (e3/4-1)*4+(e5/10-1)*10]. XR may be viewed as MR + higher-order terms and is a strong MR. Both MR and XR (but not DR) are instances of Feynman's action paradigm, q being the average IOP velocity. In order to demonstrate the behavior of MR and XR on real diurnal IOP, i.e. to exercise the calculation of DV and the effect of a treatment on it, they were applied along with DR to 24-hour trial data (Stewart et al., previously reported). IOP was measured every 4 hours starting at 8am for 24 hours, at baseline and after treatment. For each measure, study eye, and treatment, the DV of that eye's baseline and treatment IOP curves were computed via associated c-data (requiring minor alterations).
DR, MR, and XR rank diurnal IOP somewhat differently. MR (resp. XR) can separate IOP rhythms with like DR (resp. MR). In the respective measures (DR, MR, XR), treatment "1" reduced DV relative to baseline on average by (1.3, 1.2, 4.3), treatment "2" by (0.2, 0.2, 0.5). With "1", these effects were all positive with 95% confidence; with "2", none was.
Two alternatives to the diurnal range were developed. They may be better clinical biomarkers and more useful in glaucoma research depending on their correlation with progression and visual field loss, which are yet to be determined.
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