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Effect of Blinking on Tear Elimination as Evaluated by Dacryoscintigraphy
Effect of Blinking on Tear Elimination as Evaluated by Dacryoscintigrap hy WILLIAM L. WHITE, MD, 1 A. TYRONE GLOVER, MD, 2 ARTHUR B. BUCKNER, MD3
Abstract: To document the change in drainage of tears that occurs with blinking, the authors evaluated 17 lacrimal systems of 12 individuals with dacryoscintig raphy. A significant difference in tear drainage was found by keeping the eyelids closed during the first 2 minutes after drop placement (P < 0.03), but not from 2 to 5 minutes (P > 0.4). Retardation of tear drainage after droplet placement can be achieved by simple eyelid closure for 2 minutes.
Ophthalmology 1991; 98:367-369
When topical ophthalmic medications are instilled into the conjunctival fornix, they enter the tear film and the lacrimal outflow system. Absorption ofthese medications through the nasal, conjunctival, and oropharyngeal mu cosa can produce adverse systemic effects. Digital naso lacrimal system occlusion and eyelid closure have been recommended to reduce systemic absorption and adverse effects, while increasing the anterior chamber concentra tion of topical ocular drugs. 1 Since the elimination of tears is affected by the blink-driven "lacrimal pump," simple eyelid closure should decrease systemic absorption and enhance ocular drug penetration. The purpose of this study is to quantitate the effects oflid closure and blinking on tear elimination using dacryoscintigraphy. Dacryoscintigraphy, also referred to as lacrimal scin tillography or nuclear dacryocystography, is an investi gative technique that involves the placement of a dilute radionucleide on the eye or in the inferior fornix. The Originally received: March 27, 1990. Revision accepted: December 3, 1990. 1
Major, Medical Corps. Former Lieutenant Colonel, Medical Corps; Ophthalmology Service, Brooke Army Medical Center, Fort Sam Houston. 3 Lieutenant Colonel, Medical Corps, Department of Nuclear Medicine, Tripier Army Medical Center, Honolulu. 2
Dr. White is currently at the Ireland Army Community Hospital, Ft. Knox. Dr. Glover is currently with Kaiser Permanente, Sacramento. The opinions or assertions contained herein are the private views of the authors and are not to be construed as reflecting the views of the De partment of the Army or the Department of Defense. Reprint requests to Dr. White: USA MEDDAC, Attention: HSXM-DOS-G102, Ft. Knox, KY 40121-5520.
ocular area is then imaged with a pinhole collimator on a gamma camera, which yields a dot matrix image of the lacrimal outflow system. A region ofinterest is then drawn that includes the surface area of the eye but excludes the canaliculi and nasolacrimal system. Computerized anal ysis of the rate of disappearance of the tracer from the region of interest will produce a time versus counts plot from which the tear half-life can be determined. 2•3
MATERIALS AND METHODS The study was approved by the hospital human use review board. Volunteers were accepted who had no his tory of lacrimal drainage problems or lid malposition. Informed consent was obtained and data were collected on 17 lacrimal systems of 12 individuals (three women, nine men; average age, 29 years). Dacryoscintigraphy was performed using a micropipette instilled 10-J,tl aliquot of technetium pertechnetate into the lateral inferior fornix followed by computer imaging for 5 to 7 minutes, in a fashion similar to that described by Rabinovitch et al. 4 A slit-lamp stand, adapted for this purpose, was used to stabilize the subject's head. Each examination was performed with the same equipment in the same physical location so as to idealize environmental factors such as temperature, light, air movement, or other possible stimuli present. The subjects were randomized initially to either a blink normally or an eyelid-closed dacryoscintigram, with the complementary study being performed after the radiotracer had cleared the lacrimal system. (Some examinations were completed the same day, others were completed on separate days.) Imaging
367
OPHTHALMOLOGY
•
MARCH 1991
•
VOLUME 98
Phase
1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17
Mean SEM P*
2-5 Minutes
0-2 Minutes Blink
Nonblink
Blink
Non blink
40 61 97 73 76 224 57 66 65 103 67 115 98 71 104 117 163 93 10
62 348 8390 945 143 930 2110 94 693 103 396 1070 134 343 8190 187 152 1290 578
295 3094 268 236 441 886 398 1397 502 3269 897 1780 811 577 592 666 525 1080 223
328 1136 499 1960 211 673 2320 608 1612 852 1066 1490 377 1220 1240 559 1160 1040 151
<0.03
>0.4
SEM = standard error of the mean. * By Student's t test.
was done with a 3-mm pinhole collimator, and data were acquired for the 0- to 2-minute stimulated phase and the 2- to 5-minute initial phase of tear drainage as described by Sorensen. 5 The tear T'12 in the lacrimal lake was esti mated by finding the slope ofthe curve plotting the natural logarithm of counts per second from the region of interest against time. 4 •6 The T'12 in seconds is related to the slope by the following equation: T 112 = 0.693/m
where m =slope in seconds-
1 •
RESULTS The values obtained during the 0- to 2-minute interval of tear elimination showed a statistically significant pro longation tear T'12 in the eyelids closed examinations; the 2- to 5-minute intervals were quite similar with no sta tistical difference observed (Table 1).
DISCUSSION The concept of the lacrimal drainage apparatus as a tear pump is well accepted. One theory states that the pump depends on the muscular action ofthe eyelids (blink mechanism), which involves the superficial and deep in sertions of the preseptal and pretarsal orbicularis ofboth 368
NUMBER 3
llliiiT E1E (1.1.) TIIE-IETIVIn
Table 1. Tear Half-life during Blinking and Eyelids Closed Oacryoscintigrams
Lacrimal System
•
100. 1).0
0 -2 IIIII • 71.4 SEt T I 112 2 - 5 IIIII • 577 SEt
.·
fiO.O
4).0
0.0
... ~.....
...... ·.
20.0
.·
__,...-.....-----r-~~;:==;::::::::.,
.l-j
0.0
100.
•• ••
200. TilE (SEC)
Fig I. Dacryoscintigram with radiotracer applied at time 0. Notice sharp decline in activity count (ordinate) immediately after drop placement.
LEFT E1E TIIE-IlTIVIn C. UfEID E1ES
111'
3W SEt)
110.
too.
1),0
fiO.O 4).0
Tt/2:
20.0 0.0
0.0
too.
2 - 5 IIIII
= 1240
6 112 - 7 IIIII
••
200. TltE (SEC)
SEC
= 131
t
SEC
(:f.IO)
550.
Fig 2. Dacryoscintigram where an eyelids-closed exmination was per formed until 390 seconds, at which time the patient was instructed to start blinking. Notice steepening in slope when blinking begins (and thereby a shorter tear Tl).
the upper and lower eyelids. 7 These portions of the or bicularis envelop the lacrimal system and transmit pres sure through the tear outflow tract. When the eyelids are closed, the ampulla is compressed and a negative pressure is generated in the lacrimal sac; when the lids are opened, the pressure in the ampulla decreases and the pressure in the lacrimal sac increases. 8 Regardless ofthe actual mech anism, numerous studies show that there are dynamic
WHITE et a!
•
EFFECT OF BLINKING
pressure changes in the nasolacrimal system. 8- 11 High speed photography has been used to demonstrate the suc tion effect exerted at the punctum on the lacrimal secre tions and has shown the lids actually sticking together during blinking. 12 Transit times of radioisotope to the lacrimal sac during lid closure have been previously reported. Chavis et al 3 studied the effect of blinking in 14 eyes of 7 volunteers. After instilling tracer, their subjects clQsed their eyelids immediately and kept them closed for the duration of the study. Transit times were grossly prolonged in five vol unteers who did not blink and who had normal findings on previous dacryoscintigraphy. It was not surprising that two systems filled normally since orbicularis contractions were often observed after eyelid closure. 3 Fraunfelder 13 also found increased lacrimal outflow during eyelids closed examinations in individuals in whom "quivering lid movements" were observed. Indeed, in our investigation, some subjects had little or no prolongation with eyelid closure during the first 2 minutes of testing (i.e., subject 10). This could be due to orbicularis contractions occur ring while the lids were closed activating the lacrimal pump. We found a very rapid appearance ofthe isotope drain ing into the lacrimal sac. The greatest decay of tracer oc curred during the first few blinks (Fig 1). During one ex amination, the subject was asked to blink after a 5-minute nonblinking study with continuous data acquisition. A dramatic change in the slope ofthe curve is seen coinciding with the dynamic (blinking) phase of the study (Fig 2). Fraunfelder 13 found that during eyelids closed dac ryoscintigraphy, percent retention of radiotracer at 5 minutes varied from 4.8 to 63.8, depending on where the drop was applied and whether the cornea or the entire ocular surface was used at the region of interest. We in stilled the radiotracer in the lateral inferior cul-de-sac be cause it is an easy area for patients to place topical med ication and the area recommended by Fraunfelder. 13 The large difference (more than 10-fold) in tear half-life we observed in the 0- to 2-minute examinations could be due to the relative filling of the lacrimal lake that occurs when a drop is instilled in the fornix and the eyelids are closed. This leaves a greater quantity of fluid for the tear pump to discharge from the eye than is present under basal con ditions. By 2 minutes, most of the fluid could be drained from the eye by passive means (with little or no input from the lacrimal pump), leaving a situation more closely resembling basal conditions. Thus, a lesser quantity of fluid could remain to be pumped through the lacrimal apparatus and, therefore, account for the minimal differ ence seen in the 2- to 5-minute period. Our data indicate that a significant decrease in tear
elimination can be observed using eyelid closure during the first 2 minutes after instillation of an eye drop. Pro longed contact of topical medications with ocular tissue should be achieved with 2 minutes of lid closure after drop instillation. Zimmerman et al 1 have shown decreased systemic absorption of timolol with 5 minutes of either eyelid closure or nasolacrimal occlusion with eyelid clo sure. It might be expected that the systemic effects of such topical drugs as timolol, phenylephrine, epinephrine, phospholine iodide, scopolamine, and atropine may be decreased with 2 minutes of eyelid closure, but our study did not address this aspect of lacrimal drainage. We only found our data to be statistically significant for the first 2 minutes after drop instillation. Because of the apparent rapid removal of fluid during the first few blinks after drop placement, it might be anticipated that the best re sults would be achieved if the eyelids are immediately closed and kept closed for a minimum of 2 minutes after instillation of an eye drop.
REFERENCES 1. Zimmerman TJ, Kooner KS, Kandarakis AS, Ziegler LP. Improving the therapeutic index of topically applied ocular drugs. Arch Ophthalmol 1984; 102:551-3. 2. Brown B, El Grammal TAM, Luxenberg MN, Eubig C. The value, lim itations, and applications of nuclear dacryocystography. Semin Nucl Med 1981; 11:250-7. 3. Chavis RM, Walham RAN, Maisey MN. Quantitative lacrimal scintil lography. Arch Ophthalmol 1978; 96:2066-8. 4. Rabinovitch J, Hurwitz JJ, Chin-Sang H. Quantitative evaluation of canalicular flow using lacrimal scintillography. Orbit 1984; 3:263-6. 5. Sorensen TB. Studies on tear physiology, pathophysiology, and contact lenses by means of dynamic gamma camera and technetium. Acta Ophthalmol Suppl 1984; 167:1-37. 6. White WL, Glover AT, Buckner AB, Hartshorne MF. Relative canalicular tear flow as assessed by dacryoscintigraphy. Ophthalmology 1989; 96:167-9. 7. Jones LT. An anatomical approach to problems of the eyelids and lacrimal apparatus. Arch Ophthalmo\1961; 66:111-24. 8. Hill JC, Bethell W, Smirmaul HJ. Lacrimal drainage- a dynamic eval uation. Part 1- Mechanics of tear transport. Canad J Ophthalmo\197 4; 9:411-6. 9. Hill JC, Apt R, Smirmaul HJ. Lacrimal pump pressure patterns. Can J Ophthalmol 1975; 10:25-31. 10. Wilson G, Merrill R. The lacrimal drainage system: pressure changes in the canaliculus. Am J Optom Physiol Optics 1976;53:55-9. 11. Maurice OM. The dynamics and drainage of tears. In! Ophthalmol Clin 1973; 13(1):103-16. 12. Doane MG. Blinking and tear drainage. Adv Ophthalmic Plast Reconstr Surg 1984; 3:39-52. 13. Fraunfelder FT. Extraocular fluid dynamics: how best to apply topical ocular medication. Trans Am Ophthalmol Soc 1976; 74:457-87.
369
Abstract: To document the change in drainage of tears that occurs with blinking, the authors evaluated 17 lacrimal systems of 12 individuals with dacryoscintig raphy. A significant difference in tear drainage was found by keeping the eyelids closed during the first 2 minutes after drop placement (P < 0.03), but not from 2 to 5 minutes (P > 0.4). Retardation of tear drainage after droplet placement can be achieved by simple eyelid closure for 2 minutes.
Ophthalmology 1991; 98:367-369
When topical ophthalmic medications are instilled into the conjunctival fornix, they enter the tear film and the lacrimal outflow system. Absorption ofthese medications through the nasal, conjunctival, and oropharyngeal mu cosa can produce adverse systemic effects. Digital naso lacrimal system occlusion and eyelid closure have been recommended to reduce systemic absorption and adverse effects, while increasing the anterior chamber concentra tion of topical ocular drugs. 1 Since the elimination of tears is affected by the blink-driven "lacrimal pump," simple eyelid closure should decrease systemic absorption and enhance ocular drug penetration. The purpose of this study is to quantitate the effects oflid closure and blinking on tear elimination using dacryoscintigraphy. Dacryoscintigraphy, also referred to as lacrimal scin tillography or nuclear dacryocystography, is an investi gative technique that involves the placement of a dilute radionucleide on the eye or in the inferior fornix. The Originally received: March 27, 1990. Revision accepted: December 3, 1990. 1
Major, Medical Corps. Former Lieutenant Colonel, Medical Corps; Ophthalmology Service, Brooke Army Medical Center, Fort Sam Houston. 3 Lieutenant Colonel, Medical Corps, Department of Nuclear Medicine, Tripier Army Medical Center, Honolulu. 2
Dr. White is currently at the Ireland Army Community Hospital, Ft. Knox. Dr. Glover is currently with Kaiser Permanente, Sacramento. The opinions or assertions contained herein are the private views of the authors and are not to be construed as reflecting the views of the De partment of the Army or the Department of Defense. Reprint requests to Dr. White: USA MEDDAC, Attention: HSXM-DOS-G102, Ft. Knox, KY 40121-5520.
ocular area is then imaged with a pinhole collimator on a gamma camera, which yields a dot matrix image of the lacrimal outflow system. A region ofinterest is then drawn that includes the surface area of the eye but excludes the canaliculi and nasolacrimal system. Computerized anal ysis of the rate of disappearance of the tracer from the region of interest will produce a time versus counts plot from which the tear half-life can be determined. 2•3
MATERIALS AND METHODS The study was approved by the hospital human use review board. Volunteers were accepted who had no his tory of lacrimal drainage problems or lid malposition. Informed consent was obtained and data were collected on 17 lacrimal systems of 12 individuals (three women, nine men; average age, 29 years). Dacryoscintigraphy was performed using a micropipette instilled 10-J,tl aliquot of technetium pertechnetate into the lateral inferior fornix followed by computer imaging for 5 to 7 minutes, in a fashion similar to that described by Rabinovitch et al. 4 A slit-lamp stand, adapted for this purpose, was used to stabilize the subject's head. Each examination was performed with the same equipment in the same physical location so as to idealize environmental factors such as temperature, light, air movement, or other possible stimuli present. The subjects were randomized initially to either a blink normally or an eyelid-closed dacryoscintigram, with the complementary study being performed after the radiotracer had cleared the lacrimal system. (Some examinations were completed the same day, others were completed on separate days.) Imaging
367
OPHTHALMOLOGY
•
MARCH 1991
•
VOLUME 98
Phase
1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17
Mean SEM P*
2-5 Minutes
0-2 Minutes Blink
Nonblink
Blink
Non blink
40 61 97 73 76 224 57 66 65 103 67 115 98 71 104 117 163 93 10
62 348 8390 945 143 930 2110 94 693 103 396 1070 134 343 8190 187 152 1290 578
295 3094 268 236 441 886 398 1397 502 3269 897 1780 811 577 592 666 525 1080 223
328 1136 499 1960 211 673 2320 608 1612 852 1066 1490 377 1220 1240 559 1160 1040 151
<0.03
>0.4
SEM = standard error of the mean. * By Student's t test.
was done with a 3-mm pinhole collimator, and data were acquired for the 0- to 2-minute stimulated phase and the 2- to 5-minute initial phase of tear drainage as described by Sorensen. 5 The tear T'12 in the lacrimal lake was esti mated by finding the slope ofthe curve plotting the natural logarithm of counts per second from the region of interest against time. 4 •6 The T'12 in seconds is related to the slope by the following equation: T 112 = 0.693/m
where m =slope in seconds-
1 •
RESULTS The values obtained during the 0- to 2-minute interval of tear elimination showed a statistically significant pro longation tear T'12 in the eyelids closed examinations; the 2- to 5-minute intervals were quite similar with no sta tistical difference observed (Table 1).
DISCUSSION The concept of the lacrimal drainage apparatus as a tear pump is well accepted. One theory states that the pump depends on the muscular action ofthe eyelids (blink mechanism), which involves the superficial and deep in sertions of the preseptal and pretarsal orbicularis ofboth 368
NUMBER 3
llliiiT E1E (1.1.) TIIE-IETIVIn
Table 1. Tear Half-life during Blinking and Eyelids Closed Oacryoscintigrams
Lacrimal System
•
100. 1).0
0 -2 IIIII • 71.4 SEt T I 112 2 - 5 IIIII • 577 SEt
.·
fiO.O
4).0
0.0
... ~.....
...... ·.
20.0
.·
__,...-.....-----r-~~;:==;::::::::.,
.l-j
0.0
100.
•• ••
200. TilE (SEC)
Fig I. Dacryoscintigram with radiotracer applied at time 0. Notice sharp decline in activity count (ordinate) immediately after drop placement.
LEFT E1E TIIE-IlTIVIn C. UfEID E1ES
111'
3W SEt)
110.
too.
1),0
fiO.O 4).0
Tt/2:
20.0 0.0
0.0
too.
2 - 5 IIIII
= 1240
6 112 - 7 IIIII
••
200. TltE (SEC)
SEC
= 131
t
SEC
(:f.IO)
550.
Fig 2. Dacryoscintigram where an eyelids-closed exmination was per formed until 390 seconds, at which time the patient was instructed to start blinking. Notice steepening in slope when blinking begins (and thereby a shorter tear Tl).
the upper and lower eyelids. 7 These portions of the or bicularis envelop the lacrimal system and transmit pres sure through the tear outflow tract. When the eyelids are closed, the ampulla is compressed and a negative pressure is generated in the lacrimal sac; when the lids are opened, the pressure in the ampulla decreases and the pressure in the lacrimal sac increases. 8 Regardless ofthe actual mech anism, numerous studies show that there are dynamic
WHITE et a!
•
EFFECT OF BLINKING
pressure changes in the nasolacrimal system. 8- 11 High speed photography has been used to demonstrate the suc tion effect exerted at the punctum on the lacrimal secre tions and has shown the lids actually sticking together during blinking. 12 Transit times of radioisotope to the lacrimal sac during lid closure have been previously reported. Chavis et al 3 studied the effect of blinking in 14 eyes of 7 volunteers. After instilling tracer, their subjects clQsed their eyelids immediately and kept them closed for the duration of the study. Transit times were grossly prolonged in five vol unteers who did not blink and who had normal findings on previous dacryoscintigraphy. It was not surprising that two systems filled normally since orbicularis contractions were often observed after eyelid closure. 3 Fraunfelder 13 also found increased lacrimal outflow during eyelids closed examinations in individuals in whom "quivering lid movements" were observed. Indeed, in our investigation, some subjects had little or no prolongation with eyelid closure during the first 2 minutes of testing (i.e., subject 10). This could be due to orbicularis contractions occur ring while the lids were closed activating the lacrimal pump. We found a very rapid appearance ofthe isotope drain ing into the lacrimal sac. The greatest decay of tracer oc curred during the first few blinks (Fig 1). During one ex amination, the subject was asked to blink after a 5-minute nonblinking study with continuous data acquisition. A dramatic change in the slope ofthe curve is seen coinciding with the dynamic (blinking) phase of the study (Fig 2). Fraunfelder 13 found that during eyelids closed dac ryoscintigraphy, percent retention of radiotracer at 5 minutes varied from 4.8 to 63.8, depending on where the drop was applied and whether the cornea or the entire ocular surface was used at the region of interest. We in stilled the radiotracer in the lateral inferior cul-de-sac be cause it is an easy area for patients to place topical med ication and the area recommended by Fraunfelder. 13 The large difference (more than 10-fold) in tear half-life we observed in the 0- to 2-minute examinations could be due to the relative filling of the lacrimal lake that occurs when a drop is instilled in the fornix and the eyelids are closed. This leaves a greater quantity of fluid for the tear pump to discharge from the eye than is present under basal con ditions. By 2 minutes, most of the fluid could be drained from the eye by passive means (with little or no input from the lacrimal pump), leaving a situation more closely resembling basal conditions. Thus, a lesser quantity of fluid could remain to be pumped through the lacrimal apparatus and, therefore, account for the minimal differ ence seen in the 2- to 5-minute period. Our data indicate that a significant decrease in tear
elimination can be observed using eyelid closure during the first 2 minutes after instillation of an eye drop. Pro longed contact of topical medications with ocular tissue should be achieved with 2 minutes of lid closure after drop instillation. Zimmerman et al 1 have shown decreased systemic absorption of timolol with 5 minutes of either eyelid closure or nasolacrimal occlusion with eyelid clo sure. It might be expected that the systemic effects of such topical drugs as timolol, phenylephrine, epinephrine, phospholine iodide, scopolamine, and atropine may be decreased with 2 minutes of eyelid closure, but our study did not address this aspect of lacrimal drainage. We only found our data to be statistically significant for the first 2 minutes after drop instillation. Because of the apparent rapid removal of fluid during the first few blinks after drop placement, it might be anticipated that the best re sults would be achieved if the eyelids are immediately closed and kept closed for a minimum of 2 minutes after instillation of an eye drop.
REFERENCES 1. Zimmerman TJ, Kooner KS, Kandarakis AS, Ziegler LP. Improving the therapeutic index of topically applied ocular drugs. Arch Ophthalmol 1984; 102:551-3. 2. Brown B, El Grammal TAM, Luxenberg MN, Eubig C. The value, lim itations, and applications of nuclear dacryocystography. Semin Nucl Med 1981; 11:250-7. 3. Chavis RM, Walham RAN, Maisey MN. Quantitative lacrimal scintil lography. Arch Ophthalmol 1978; 96:2066-8. 4. Rabinovitch J, Hurwitz JJ, Chin-Sang H. Quantitative evaluation of canalicular flow using lacrimal scintillography. Orbit 1984; 3:263-6. 5. Sorensen TB. Studies on tear physiology, pathophysiology, and contact lenses by means of dynamic gamma camera and technetium. Acta Ophthalmol Suppl 1984; 167:1-37. 6. White WL, Glover AT, Buckner AB, Hartshorne MF. Relative canalicular tear flow as assessed by dacryoscintigraphy. Ophthalmology 1989; 96:167-9. 7. Jones LT. An anatomical approach to problems of the eyelids and lacrimal apparatus. Arch Ophthalmo\1961; 66:111-24. 8. Hill JC, Bethell W, Smirmaul HJ. Lacrimal drainage- a dynamic eval uation. Part 1- Mechanics of tear transport. Canad J Ophthalmo\197 4; 9:411-6. 9. Hill JC, Apt R, Smirmaul HJ. Lacrimal pump pressure patterns. Can J Ophthalmol 1975; 10:25-31. 10. Wilson G, Merrill R. The lacrimal drainage system: pressure changes in the canaliculus. Am J Optom Physiol Optics 1976;53:55-9. 11. Maurice OM. The dynamics and drainage of tears. In! Ophthalmol Clin 1973; 13(1):103-16. 12. Doane MG. Blinking and tear drainage. Adv Ophthalmic Plast Reconstr Surg 1984; 3:39-52. 13. Fraunfelder FT. Extraocular fluid dynamics: how best to apply topical ocular medication. Trans Am Ophthalmol Soc 1976; 74:457-87.
369