Effect of Blinking on Tear Dynamics Jayachandra R. Palakuru,1,2 Jianhua Wang,1,2 and James V. Aquavella1 PURPOSE. Optical coherence tomography (OCT) was used to study the impact of blinking on tear dynamics. METHODS. One eye of 21 subjects was imaged at the same time of day on two consecutive days. Dimensional information of the tear film and of the upper and lower tear menisci during normal and delayed blinking were obtained from OCT images using custom software. Digital camera images were used to measure eyelid length and ocular surface area for tear volume estimation. RESULTS. No significant changes in any measured variable occurred between the two repeat visits. During normal and delayed blinking sessions, the tear film thickness increased significantly after each blink (P ⬍ 0.05) and then decreased (P ⬍ 0.05) during the open-eye period. For normal blinks, the tear meniscus did not change significantly during blinking or during the open-eye period. Except for upper tear meniscus curvature, all other parameters of tear menisci during delayed blinks were higher than those measured during normal blinks (P ⬍ 0.05). For delayed blinks, the lower tear meniscus height decreased after the blink (P ⬍ 0.05). Also for delayed blinks, the height and area of both upper and lower tear menisci significantly increased during the open-eye period. The total estimated tear volume on the ocular surface was greater during the delayed blinks (P ⬍ 0.01), and most of the volume was located in the lower tear meniscus (P ⬍ 0.01). CONCLUSIONS. OCT is a promising tool for studying the impact of blinking on tear dynamics. Tear distribution is dynamically balanced and consistent during normal blinking, but it becomes altered during delayed blinking. (Invest Ophthalmol Vis Sci. 2007;48:3032–3037) DOI:10.1167/iovs.06-1507
T
he tear system is highly dynamic, maintaining balance between tear secretion and tear loss so that the ocular surface is protected while the eye is open. Each blink initiates a cycle of tear secretion, spreading, evaporation, and drainage of tears.1–3 Not much is known about the effect of blinking on the dynamically balanced tear system, mainly due to the extreme difficulty in real-time quantification of each tear compartment on the ocular surface. Many studies provide either snapshot information4 – 6 or averaged performance5 about the tear system. Real-time videography4 and video meniscometry7 imaging have been used to study the lower tear meniscus, and
From the 1Department of Ophthalmology, University of Rochester, Rochester, New York; and the 2Department of Ophthalmology, Bascom Palmer Eye Institute, University of Miami, Miami, Florida. Supported by Grant R03 EY016420 from the National Eye Institute (JW), Allergan, Inc. (JW), and a challenge grant from Research to Prevent Blindness to the University of Rochester Eye Institute. Submitted for publication December 19, 2006; revised February 16, 2007; accepted April 5, 2007. Disclosure: J.R. Palakuru, None; J. Wang, Allergan, Inc. (F); J.V. Aquavella, None The publication costs of this article were defrayed in part by page charge payment. This article must therefore be marked “advertisement” in accordance with 18 U.S.C. §1734 solely to indicate this fact. Corresponding author: Jianhua Wang, Bascom Palmer Eye Institute, University of Miami, Miller School of Medicine, 1638 NW 10th Avenue, McKnight Building, Room 202, Miami, FL, 33136;
[email protected].
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video recorded spectrum analysis8 has been used to study tear film thickness. However, only one aspect at a time can be studied using these methods so that the interactions among the different components of the tear system cannot be captured. Using newly developed optical coherence tomography (OCT) for capturing tear film and tear meniscus images simultaneously, the goal of this study was to determine the effect of blinking on tear dynamics.
SUBJECTS
AND
METHODS
The Research Review Boards of the University of Rochester and University of Miami approved the study. Twenty-one subjects (10 women and 11 men, mean age: 32.1 ⫾ 8.7 years) in good health and with no history of contact lens wear or any current ocular or systemic diseases were recruited in Rochester for a prospective study. Informed consent was obtained from each subject, and all were treated in accordance with the tenets of the Declaration of Helsinki. The temperature (15– 25°C) and humidity (30%–50%) in the small consulting room where the study was conducted were controlled by central air conditioning and two humidifiers. OCT imaging was performed on one randomly selected eye of each subject at the same time of day on two consecutive days. A real-time corneal OCT, developed as described previously,9 was used to perform vertical 12-mm scans across the central cornea (apex) including the upper and lower tear menisci simultaneously. During imaging, the subjects were exposed only to ambient room light and were asked to look at an external target. OCT images were recorded continuously when the subjects blinked normally for three to five blinks. After the normal blinks, the subjects were asked to delay each blink for as long as possible for another set of three to five blinks. After that, the study eye was given a drop of artificial tears (Refresh Liquigel; Allergan, Irvine, CA) followed by OCT scanning to obtain true corneal thickness for the calculation of the tear film thickness, as described in detail previously.9 The selected eye of each subject was also photographed using a digital camera mounted on a slit lamp with a reference scale to measure the length of both upper and lower eyelids and the exposed ocular surface. Image processing and data analysis were performed at the University of Miami by two of the authors (JW, JRP). Eight OCT images corresponding to a 1-second interval immediately before and after each blink were analyzed for measuring the total corneal thickness. One of these eight images showing upper and lower tear menisci (Fig. 1) was processed with custom software to yield tear meniscus variables. Tear film thickness was estimated indirectly by subtracting the true corneal thickness imaged after the instillation of the artificial tears from total corneal thickness obtained at each check point.9 Results immediately before and after two consecutive blinks during normal and delayed blinking sessions were obtained. Results from one interblink interval were obtained since two consecutive blinks formed one interblink interval. Seven variables were obtained including central tear film thickness (TFT), upper tear meniscus curvature (UTMC), height (UTMH), and cross-sectional area (UTMA), and lower tear meniscus curvature (LTMC), height (LTMH), and cross-sectional area (LTMA). Lengths of upper and lower lids and exposed ocular surface area were measured from the two-dimensional digital images of eyes using custom software after calibration. To use the two-dimensional image to estimate the area of the ocular surface that is curved in the third dimension, a multiplication factor of 1.294 was used, as suggested by Tiffany et al.10 As upper and lower lids are also curved in the third dimension, the same factor was used for conversion of the twoInvestigative Ophthalmology & Visual Science, July 2007, Vol. 48, No. 7 Copyright © Association for Research in Vision and Ophthalmology
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FIGURE 1. OCT images obtained during normal and delayed blinks. A vertical, 12-mm OCT scan was performed across the corneal apex during normal (A–C) and delayed (D–F) blinks. Images were obtained (A, D) immediately before and (B, E) immediately after blinks, at the beginning of the interblink period. Images (C) and (F) were obtained immediately before eye closure, at the end of the interblink period. Note the decrease in the lower tear meniscus after blink (E compared with D), and the increase at the end of eye opening (F) compared with the beginning of eye opening (E). Also note less prominent changes in the upper tear meniscus compared with the lower tear meniscus (D–F). (E, asterisk) Tear film. CO, cornea; UL, upper eyelid; LL, lower eyelid; TF, tear film; UTM, upper tear meniscus; LTM, lower tear meniscus. dimensional values of upper and lower lid lengths to three-dimensional values. Preocular tear film volume (TFV) was calculated using the equation in Table 1, as suggested by Johnson and Murphy.11 The lower tear meniscus volume (LTMV) was calculated as the same equation used by Mainstone et al.6 The upper tear meniscus volume (UTMV) was calculated in the same way as the LTMV. Total tear volume on the ocular surface was the sum of these volumes. All formulas are listed in Table 1. The repeatability of the measurements of all variables during both normal and delayed-blinking sessions was estimated as the SD of the differences between repeated measurements between 2 days. Data analysis was conducted on computer (Statistica; StatSoft, Inc., Tulsa, OK). Two- or three-way repeated-measures analysis of variance (Re-ANOVA) was used for overall effects, and post hoc paired t-tests were used to determine whether there were pair-wise differences (P ⬍ 0.05).
RESULTS The TFT and tear menisci variables obtained during blinks and interblink periods are listed in Table 2 and repeatability results of these measurements are listed in Table 3. The mean interblink period (mean ⫾ SD) was 5.5 ⫾ 4.0 seconds during normal blinking and 19.1 ⫾ 17.0 seconds during delayed blinking. No significant change of any measured variable was found between the two repeated visits (ANOVA, P ⬎ 0.05). For both the normal and delayed blinking, TFT increased significantly TABLE 1. Estimation of Tear Volumes Variable TFV UTMV LTMV
Calculation mm of tear film thickness ⫻ mm of exposed ocular surface area ⫻ 1.294 mm of upper lid length ⫻ mm2 of upper meniscus area ⫻ 1.294 mm of lower lid length ⫻ mm2 of lower meniscus area ⫻ 1.294
after blinking and decreased during the open-eye period (post hoc, P ⬍ 0.05; Fig. 2). There were no significant differences of TFT between normal and delayed blinks. However, there was a trend toward higher TFTs during the delayed blinks (Fig. 2). The averaged thinning rate of TFT was 4.0 m/min for both blink patterns with no differences between the two blinking sessions. No significant differences in UTMC were found before and after blinks and during the open-eye period for both normal and delayed blinks (Fig. 3A). UTMH and UTMA were greater during delayed blinks than during normal blinks (P ⬍ 0.05; Figs. 3B, 3C, respectively). The UTMH and UTMA were significantly smaller immediately after eye opening than before the next eye closure (P ⬍ 0.005, Figs. 3B, 3C). During delayed blinking, LTMH after blinking decreased compared with that before blinking (P ⬍ 0.05, Fig. 3E). During the open-eye period of delayed blinking, LTMH and LTMA increased (P ⬍ 0.01, Figs. 3E, 3F). The total estimated tear volume on the ocular surface was smaller during normal blinks than during delayed blinks (P ⬍ 0.01, Figs. 4A, 4B, respectively). Similarly, the increase in the total volume during the open-eye period was smaller during the normal blinks than during the delayed blinks (P ⬍ 0.05). TFV did not change during the normal blinks; however, a significant decrease from 1.28 to 1.00 L occurred in the open-eye period during delayed blinking (P ⬍ 0.05, Fig. 4B). The UTMV was higher during delayed blinks (⬃0.8 L; Fig. 4B) compared with normal blinks (⬃0.6 L; P ⬍ 0.001, Fig. 4A). Similarly, the UTMV was greater at the end of the open-eye period than at the beginning of the delayed blinks (P ⬍ 0.01). The LTMV was also greater during the delayed blinks (⬃3 L) than during normal blinks (⬃0.9 L; P ⬍ 0.01), and it increased significantly at the end of the open-eye period of the delayed blinks (P ⬍ 0.05). No significant differences in TFV, UTMV, or LTMV occurred after the blinks (P ⬎ 0.05) compared with that before for either blink pattern, normal or delayed.
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TABLE 2. Tear Film and Menisci Variables Associated with the Blink and Interblink Periods
Normal blinking Blink Before blink Mean ⫾SD After blink Mean ⫾SD Eye opening After opening Mean ⫾SD Before closure Mean ⫾SD Delayed blinking Blink Before blink Mean ⫾SD After blink Mean ⫾SD Eye opening After opening Mean ⫾SD Before closure Mean ⫾SD
TFT (m)
UTMC (m)
UTMH (m)
UTMA (m2)
LTMC (m)
4.9 2.2
258 95
263 46
19,270 6,991
5.8 2.8
249 101
253 38
5.3 2.4
244 93
4.9 2.4
LTMH (m)
LTMA (m2)
392 310
310 88
30,660 19,031
18,134 5,696
363 307
297 79
27,910 15,899
248 44
17,288 6,300
323 274
288 77
26,162 16,085
271 134
266 55
19,924 8,424
395 298
313 93
31,401 21,519
5.4 2.7
299 111
296 52
25,517 8,386
1,774 2,700
591 423
131,556 169,634
6.4 3.5
293 118
295 64
25,015 11,634
1,068 1,544
493 294
92,332 119,231
6.8 4.2
288 128
284 67
23,368 12,101
1,130 1,738
483 307
83,110 103,727
5.5 3.1
299 117
297 61
25,344 9,541
1,527 2,279
617 428
144,573 174,922
DISCUSSION Blinking plays an important role in the distribution and drainage of tears and helps in maintaining equilibrium of the tear volume on the ocular surface and in the conjunctival sac. It also plays a critical role in periodic renewal of the preocular tear film. Any alterations in the blinking pattern may affect tear distribution and drainage, leading to changes in the tear volume and other tear system parameters. McDonald and Brubaker12 observed nonquantitatively that upper and lower menisci draw fluid from the preocular tear film and swell with time after a blink. Slit lamp photography13 and video meniscometry7,14 –16 have also been used to measure the tear meniscus around the lower eyelid. These techniques have the disadvantage of using visible light and/or introduction of fluorescein dye into the eye, which may induce reflex tearing and alter the test results. Savini et al.17 used OCT to image the LTMH and found a good correlation with Schirmer’s test with some modifications. The upper tear meniscus and tear film cannot be imaged with slowly scanning OCT systems or other methods.5,13,14,17 Most of these studies reported static values of various lower tear meniscus parameters some time after blinking. These findings may not reflect the impact of a blink and time course after a blink on the dynamic tear system. Wang et al.9 demonstrated for the first time that the upper tear meniscus can be imaged along with the lower tear meniscus and tear film simultaneously by using real-time OCT. The method was validated in repeated measurements of tear distribution on human eyes.9 In the present study, the same method was used and yielded repeatable results of the tear distribution changes effected by blinking. For this study, we assumed that tear film thickness is uniform over the entire ocular surface. If this assumption is not true, it could introduce some error into our calculations. Un-
fortunately, there is no method available to measure tear film thickness at multiple locations on the ocular surface simultaneously. Another potential source of errors may be associated with the measurement of the curved ocular surface area and lid lengths. For this, we used two-dimensional images and a conversion factor according to a previous study.10 We did not independently verify the factor in our study group. In addition, palpebral aperture height may have varied between blinks, and it was almost impossible to control the aperture height during noninvasive imaging. These variations may have altered our results slightly. Other possible errors induced by the method used in this study have been discussed elsewhere.9 Repeatability of the measurements of all variables was tested on 2 days and compared with results in our previously published study.9 During normal blinking, the results were found to be almost identical between these two studies with different study groups. However, the repeatability decreased during delayed blinks, mainly due to reflex tearing (Tables 1 and 2). Fortunately, the changes in these variables, especially for the lower tear meniscus, were larger during delayed blinks, and the OCT appeared effective in detecting changes caused by blinking during the delayed blinks. To ensure adequate wetting, it appears that during the normal blinking process, a dynamic balance is maintained with minimal changes in tear volume on the ocular surface. During delayed blinking, this balance is altered due to reflex tearing and possibly decreased drainage, which was found dependent on blink frequency.18 With frequent blinks, a full coverage of the ocular surface with tear film is maintained during the open-eye period, and the ocular surface is protected. Tear film thickness varies over time, with thinning during interblink intervals and thickening after blinks. Using a fluorophotometric method, Benedetto et al.19 observed thinning of the tear
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TABLE 3. Repeatability of All Measurements between Two Consecutive Days
Normal blinking Blink Before blink Mean ⫾SD After blink Mean ⫾SD Eye opening After opening Mean ⫾SD Before closure Mean ⫾SD Delayed blinking Blink Before blink Mean ⫾SD After blink Mean ⫾SD Eye opening After opening Mean ⫾SD Before closure Mean ⫾SD
TFT (m)
UTMC (m)
UTMH (m)
UTMA (m2)
LTMC (m)
LTMH (m)
⫺0.58 3.21
3 146
9 69
753 9,824
7 344
0 85
1,684 15,940
⫺1.12 4.45
18 144
16 77
2,596 9,024
35 346
19 80
4,305 14,957
⫺0.67 4.11
10 117
12 75
2,211 8,062
⫺55 348
10 61
2,131 12,873
⫺0.13 2.44
⫺12 156
7 67
1,035 10,663
79 353
17 72
5,250 16,877
0.04 3.71
12 146
269 194
⫺332 13,231
392 5,367
⫺77 522
⫺42,788 240,428
⫺1.03 5.60
21 168
264 399
2,646 15,283
⫺372 3,290
⫺76 486
⫺49,429 234,588
⫺0.67 6.38
23 193
204 416
2,660 16,195
⫺3 3,172
⫺17 397
⫺12,261 159,904
⫺0.67 3.82
33 149
245 326
2,505 10,716
⫺520 4,713
⫺145 640
⫺89,623 300,244
film after a blink. Using an interferometric method, Nichols et al.8 also reported the thinning rate during the open-eye period. They suggested that the rate of thinning depends on the initial thickness of the tear film. In the present study, thickening of tear film after blinks and thinning during open-eye periods were evident for both normal and delayed blinks. The thinning rates, 4.0 m/min in the present study, were identical during normal and delayed blinks. This is in agreement with the finding of Nichols et al.8 that the thinning rate is 3.8 m/min for precorneal tear film. Changes in the lower tear meniscus over time have been studied previously.4,6,7,11 Using a video camera to assess timedependent changes in LTMH in elderly whites, Doughty et al.4
FIGURE 2. Changes in TFT during normal and delayed blinks in 21 subjects. Data were from two blinks and one interblink interval. TFT increased after blinks (P ⬍ 0.05) and decreased (P ⬍ 0.05) during the open-eye period. There were no significant differences between normal and delayed blinks (P ⬍ 0.05), though there was a trend toward higher values during delayed blinks. Bars, 95% CI.
LTMA (m2)
found that there were no time-related changes over 20 seconds. In the present study, during the delayed blink period, significant variations of the lower tear meniscus occurred. This difference may be due to the elderly group of participants in the study by Doughty et al., who may not have had reflex tearing during the study period. In the young subjects imaged in our study, prolonged eye-opening induced tearing, resulting in significant changes in the tear system. Reflex tearing induced by delayed blinks may be evidence of a tear reserve. Using live digital video recording, Johnson and Murphy11 studied the early postblink temporal changes in the lower and upper tear menisci in young adults and observed that both menisci swelled in the 10 seconds after a blink. This agrees with our findings during delayed blinks. They also noted that both upper and lower tear menisci increased by a similar amount after a blink. They suggested that the influence of gravity, which opposes fluid movement from the preocular tear film to the upper tear meniscus, might be negligible. In contrast, we found that the lower tear meniscus increased significantly more than the upper tear meniscus during delayed blinking. Our different results may be attributed to the duration of the open-eye period, which was 19.1 seconds in our study and 10 seconds in theirs. In addition, both upper and lower tear menisci were recorded separately in their study, whereas simultaneous imaging of both menisci was performed in ours. During normal blinking, the upper meniscus values were lower than that of lower meniscus and neither showed significant changes with relation to blinking. During delayed blinking the upper meniscus increased when compared with normal blinking, but not on par with the lower meniscus, indicating that there is a limitation to the upper tear meniscus beyond which the tears tend to flow down. As the upper meniscus swells and the radius of curvature increases, the capillary pressure that draws fluid toward the upper meniscus
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FIGURE 3. Changes in upper and lower menisci during normal and delayed blinks in 21 subjects. UTMC (A) before blinking was not significantly different from that after blinking during either normal or delayed blinks. Similarly, UTMC did not change after eye opening and before the next closure for delayed or normal blinks. UTMH (B) and UTMA (C) during delayed blinks were greater than comparable values during normal blinking (P ⬍ 0.005). During delayed blinking, the UTMH (B) and UTMA (C) increased during the open-eye period (P ⬍ 0.005). LTMC (D) before blinking was not significantly different from that after blinking during either normal or delayed blinks. Similarly, LTMC (D) did not change significantly during the openeye period. During delayed blinking, LTMH (E) was greater before blinking than after blinking (P ⬍ 0.05). In contrast, during delayed blinking, LTMH (E) and LTMA (F) increased during the open-eye period (P ⬍ 0.01). Note the different scales for the UTM and LTM. Bars, 95% CI.
decreases,12,13,20 and gravity takes the upper hand. In contrast, the lower tear meniscus can hold a large amount of fluid because of its structure and because of gravity. The quick swelling of the lower tear meniscus due to reflex tearing while the upper tear meniscus remains relatively unchanged indicates that both tear menisci may be connected. Therefore, tears from the upper meniscus may flow to the lower meniscus during eye opening through the connections at the canthi. It is unlikely that the tear flow occurs across the ocular surface, since tear film thickening did not occur.
We estimated the total tear volume over the exposed ocular surface and tear menisci to be 2 to 4 L including the TFV of 1 L. These figures agree with previous studies based on fluorophotometry.21,22 Mishima et al.21 estimated approximately 2.9 and 1.1 L in the tear menisci and preocular tear film respectively, and Mathers et al.22 estimated approximately 2.7 L on the ocular surface. In another study using photography,6 tear volume in the lower tear meniscus was estimated at approximately 0.5 L, which appears to be too low compared with our data and those reported by others.9,23 We
FIGURE 4. Total tear volume during normal and delayed blinks in 21 subjects. The UTMV, TFV, and LTMV were estimated during normal (A) and delayed (B) blinks. The total tear volume was greater during delayed blinking than during normal blinking (P ⬍ 0.01). Most of the change was due to increases in the LTMV (B). Both UTMV and LTMV were higher (P ⬍ 0.001) during delayed blinking (B) compared with normal blinking (A). The UTMV and LTMV increased significantly at the end of the eye-opening period compared with the beginning during delayed blinking (P ⬍ 0.05).
IOVS, July 2007, Vol. 48, No. 7 observed minimal changes in all three compartments during normal blinking. During delayed blinking, increased secretion was associated with reduced drainage due to decreased blink frequency.18 These events increased the total exposed tear volume, with the majority of the increase in the lower tear meniscus. Increased tear volume increases the blink output as evidenced by the decrease after the blink and some fluid loss, presumably due to the drainage and redistribution in such a short time. After a period with the eye opened, tearing supplies some additional volume to the ocular surface, most of which collects in the lower tear meniscus. Surprisingly, during the period with reflex tearing, TFV did not increase. The tear film thickened during the blink itself. This indicates that blinking is essential in spreading tears from the menisci to the ocular surface. Further studies may be needed to compare fluorophotometric estimation of tear volume with the OCT method in the same group. In summary, OCT appears to be a promising tool for the study of tear dynamics impacted by blinking, especially the effect of reflex tearing on tear dynamics. During normal blinking, the tear system maintains a dynamic balance between tear secretion and the loss. This balance becomes altered during delayed blinking. Further studies are needed to evaluate the impact of blinking on the tear system in elderly patients and patients with dry eye.
Acknowledgments The authors thank Britt Bromberg of Xenofile Editing for providing editing services for this manuscript.
References 1. Doane MG. Blinking and the mechanics of the lacrimal drainage system. Ophthalmology. 1981;88:844 – 851. 2. Tsubota K, Nakamori K. Effects of ocular surface area and blink rate on tear dynamics. Arch Ophthalmol. 1995;113:155–158. 3. Doane MG. Interactions of eyelids and tears in corneal wetting and the dynamics of the normal human eyeblink. Am J Ophthalmol. 1980;89:507–516. 4. Doughty MJ, Laiquzzaman M, Button NF. Video-assessment of tear meniscus height in elderly Caucasians and its relationship to the exposed ocular surface. Curr Eye Res. 2001;22:420 – 426. 5. Johnson ME, Murphy PJ. The agreement and repeatability of tear meniscus height measurement methods. Optom Vis Sci. 2005;82: 1030 –1037.
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6. Mainstone JC, Bruce AS, Golding TR. Tear meniscus measurement in the diagnosis of dry eye. Curr Eye Res. 1996;15:653– 661. 7. Yokoi N, Komuro A. Non-invasive methods of assessing the tear film. Exp Eye Res. 2004;78:399 – 407. 8. Nichols JJ, Mitchell GL, King-Smith PE. Thinning rate of the precorneal and prelens tear films. Invest Ophthalmol Vis Sci. 2005; 46:2353–2361. 9. Wang J, Aquavella J, Palakuru J, Chung S, Feng C. Relationships between central tear film thickness and tear menisci of the upper and lower eyelids. Invest Ophthalmol Vis Sci. 2006;47:4349 – 4355. 10. Tiffany JM, Todd BS, Baker MR. Computer-assisted calculation of exposed area of the human eye. Adv Exp Med Biol. 1998;438:433– 439. 11. Johnson ME, Murphy PJ. Temporal changes in the tear menisci following a blink. Exp Eye Res. 2006;83:517–525. 12. McDonald JE, Brubaker S. Meniscus-induced thinning of tear films. Am J Ophthalmol. 1971;72:139 –146. 13. Golding TR, Bruce AS, Mainestone JC. Relationship between tearmeniscus parameters and tear-film breakup. Cornea. 1997;16: 649 – 661. 14. Oguz H, Yokoi N, Kinoshita S. The height and radius of the tear meniscus and methods for examining these parameters. Cornea. 2000;19:497–500. 15. Doughty MJ, Laiquzzaman M, Oblak E, Button N. The tear (lacrimal) meniscus height in human eyes: a useful clinical measure or an unusable variable sign? Cont Lens Anterior Eye. 2002;25:57– 65. 16. Yokoi N, Bron AJ, Tiffany JM, Maruyama K, Komuro A, Kinoshita S. Relationship between tear volume and tear meniscus curvature. Arch Ophthalmol. 2004;122:1265–1269. 17. Savini G, Barboni P, Zanini M. Tear meniscus evaluation by optical coherence tomography. Ophthalmic Surg Lasers Imaging. 2006; 37:112–118. 18. Sahlin S, Laurell CG, Chen E, Philipson B. Lacrimal drainage capacity, age and blink rate. Orbit. 1998;17:155–159. 19. Benedetto DA, Clinch TE, Laibson PR. In vivo observation of tear dynamics using fluorophotometry. Arch Ophthalmol. 1984;102: 410 – 412. 20. Miller KL, Polse KA, Radke CJ. Black-line formation and the “perched” human tear film. Curr Eye Res. 2002;25:155–162. 21. Mishima S, Gasset A, Klyce SD Jr, Baum JL. Determination of tear volume and tear flow. Invest Ophthalmol. 1966;5:264 –276. 22. Mathers WD, Lane JA, Zimmerman MB. Tear film changes associated with normal aging. Cornea. 1996;15:229 –234. 23. Wang J, Aquavella J, Palakuru J, Chung S. Repeated measurements of dynamic tear distribution on the ocular surface after instillation of artificial tears. Invest Ophthalmol Vis Sci. 2006;47:3325–3329.
