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R. Zuckerman; Objective Perimetry: Noninvasive Measurement of Retinal Tissue Mitochondrial Function in Space During Darkness and Flickered Light Stimulation . Invest. Ophthalmol. Vis. Sci. 2006;47(13):3344.
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© ARVO (1962-2015); The Authors (2016-present)
The Biometric Imaging Metabolic Mapper (IOVS 46:4759, 2005) is the first technology that allows non–invasive measurement of mitochondrial function in space, time and depth in retinal tissue. Last year I presented data showing its ability to detect primary open angle glaucoma at its earliest stages (0 to –3 dB MD) and early stage retinal vascular disease. I have now investigated the effects of darkness and flickered light on metabolic maps to determine whether light–dark metabolic maps may be used as a high spatial resolution objective form of perimetry, with high speed acquisition (<1 min).
Measurements were made on healthy human subjects without ocular pathology ranging in age from 25–60 yrs. The Metabolic Mapper measures fluorescence anisotropy of endogenous fluorophores, and spectral and anisotropy bandpass filtering were employed to isolate contributions from flavin adeninedinucleotide (FAD) within mitochondria. For measurement of metabolism in darkness (D) the retina was imaged at 830 nm for orientation and metabolic maps obtained within 100 msec. Under light conditions (L) the retina was imaged at 830 nm followed by 20–30 sec of flickered blue (488 nm), green (514 nm) or red (730 nm) light at flicker rates ranging from 6–13 Hz and fluorescence anisotropy images acquired during flicker. L and D anisotropy images were aligned and subtracted pixel–by–pixel to map visual fields.
With constant light adaptation, mean fluorescence anisotropy values and its spatial distribution remained constant (1 S.E.M = 0.0007) during repeated measurements (>20 min). Variation between sessions was negligible (+/– 2 S.E.M of 10 measurements within each session). Mean L–D measurements of 20 degree fields centered at the disc showed large values of anisotropy increase with flickered light (≈ 0.200 out of a theoretically possible range of 0.400). Measurements at the disk showed an increase of ≈ 0.150. Line profiles in darkness showed lower values in the temporal retina and temporal neuroretinal rim compared to the nasal side, while light stimulation reversed this trend with dominance of the temporal retina.
Objective perimetry revealed data consistent with the known anatomic distribution of retinal nerve fibers and the density of photoreceptors that input these fibers. Metabolic mapping, when combined with dark and flickered light stimulation, provides a sensitive, high spatial resolution, and rapid technique that may supplant subjective perimetry and overcome its deficiencies. As such it may allow for early detection of functional deficits in the glaucomas and retinal vascular diseases.
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