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Patrick Shorter, Deniz Eren, Shelly G Jain, Andrew T E Hartwick; The Flashing Light-Induced Pupil Response (FLIPR) Glaucoma Study. Invest. Ophthalmol. Vis. Sci. 2014;55(13):5608.
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Rods, cones and intrinsically photosensitive retinal ganglion cells (ipRGCs) contribute to the pupillary light reflex (PLR). ipRGCs exhibit unique temporal properties that enable their contribution to the PLR to be isolated using flickering light stimuli. Our aim was to quantify the pupil response to flashing red and blue lights in individuals with glaucoma to determine whether a flicker-based pupil test can detect altered ipRGC function.
Pupil responses to flashing (0.1 Hz) red and blue lights (2.6 x 1012 and 2.7 x 1012 phots/s/cm2 @ 608 and 448 nm, respectively) were recorded in 11 subjects with moderate to severe glaucoma and 9 healthy controls using the RAPDx pupillometer. The study consisted of 3 tests: 1) alternating red and blue lights, applied OU for 2 min (ALT OU); 2) red light only, applied OU for 1 min (RED OU); and 3) blue light only, applied OU for 1 min (BLUE OU). Changes in normalized pupil size were measured 4 times per sec. Amplitudes of light-evoked pupil fluctuation were determined using Fourier transforms.
In comparing pupil responses to the RED OU and BLUE OU stimuli, we calculated the average difference (blue minus red) of normalized pupil size per time point. This difference was 7.2% ± 2.7 SEM in the glaucoma subjects and 10.4 ± 1.9% in the controls, with no significant difference between the two groups (p=0.40). The amplitudes of pupil fluctuation evoked by the two monochromatic stimuli (RED OU vs. BLUE OU) were also not significantly different (P>0.05) in either subject group. However, in the glaucoma subjects, the pupil fluctuation evoked by the red light was significantly (P=0.01) larger when presented in the ALT OU stimulus, relative to RED OU. In contrast, there was no difference (P=0.43) between these red light-elicited amplitudes in the controls. The difference in pupil size between the two colored lights (blue minus red) in the ALT OU stimulus was significantly (P=0.02) altered in the glaucoma subjects (-0.04 ± 0.02%), compared to controls (+0.01 ± 0.01%).
Using a commercial pupillometer, we detected no change in the pupil responses to flickering monochromatic red versus blue lights in subjects with glaucoma. However, the pupil responses to an alternating blue and red flashing stimulus were significantly different in subjects with glaucoma, relative to controls. We propose that the altered responses elicited by this novel pupil test reflect changed ipRGC function.
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