Abstract
Abstract: :
Purpose: Current models of tear flow assume gravity makes little contribution to the rate of tear drainage. Anecdotal evidence has suggested that gravity may have a role in the residency times of drugs. This study attempts to clarify this issue. If modest increases in residency were to be observed in particular head orientations this would allow topical drugs with systemic toxicity, such as cyclosporine, to attain therapeutic ocular levels at lower administered doses. Methods: Tear turnover rate (TTR) was measured using scanning fluorophotometry on 12 pathology free subjects (5 male, 7 female, age range 20-52 years) in different head orientations. TTR was measured first for 10 min with the subject in an upright position. Subjects were then instructed to lie on their left side for 5 min, so that in the upper (right) eye tear flow was encouraged towards the puncta by gravity. The converse was the case for the lower (left) eye. The subjects were then returned to the upright position and TTR observed for a further 10 min. TTR was not directly observed during the period of lying down due to technical limitations of the fluorophotometer but was calculated by extrapolation from the other data. Results: The TTR data was found to be not normally distributed, so appropriate non-parametric tests were utilised throughout. As expected, initial TTR was found to be the same in the right and left eye (22.3 ± 11.6 %min-1 and 20.6 ± 7.9 %min-1 respectively) (p = 0.388, Wilcoxon signed-ranks test). In subjects lying on their sides the extrapolated TTR was 22.0 ± 6.1 %min-1 for the right (upper eye) and 15.8 ± 11.5 %min-1 for the left (lower eye). The difference was found to be highly variable and was indicative but did not reach significance (p = 0.139). The TTR on sitting up was 12.9 ± 9.6 %min-1 and 14.4 ± 8.0 %min-1 respectively, with no significant difference between the right and left eye (p = 0.347). Interestingly, when the TTR values for the two periods that the subjects were upright were compared, both the right and left eye show significantly lower TTR (p ≤ 0.05) after the period of lying down. Conclusion: The study indicates that head position does play a role in driving tear drainage. The data suggest that TTR in the lower eye is less than the upper eye, when the head is on one side. The effect appeared highly variable between subjects leading to the difference not reaching significance for the whole study population. A more general effect was also seen, in that after lying down TTR was significantly reduced in both eyes, irrespective of head orientation. As TTR is inversely proportional to residency time, both of these effects could offer a means of increasing drug residency and reducing therapeutic dose.
Keywords: 376 cornea: tears/tear film/dry eye • 356 clinical (human) or epidemiologic studies: systems/equipment/techniques • 514 pharmacology