DECREASED TEAR OSMOLARITY AND ABSENCE OF THE INFERIOR MARGINAL TEAR STRIP FOLLOWING SLEEP* BY Jeffrey P.
Gilbard, MD (BY INVITATION), G. Richard Cohen, MD (BY INVITATION), AND Jules Baum, MD INTRODUCTION
THERE
ARE TWO WELL-KNOWN SYNDROMES THAT OCCUR UPON EYELID
opening after sleep. The first is the loosening of corneal epithelium associated with recurrent erosion syndrome, and the second is the tight lens syndrome that can occur with contact lenses. Chandlerl attributed the timing of recurrent erosions to the development of "suction between lid and cornea" overnight, and it seems likely that a similar suction may be responsible for the timing of tight lens syndrome. The mechanism of the putative suction between lid and cornea or contact lens and cornea has yet to be elucidated. We believe that changes in the tear film during sleep could be responsible for this suction. The induction of general anesthesia is associated with a decrease in tear secretion,2 and it has been postulated that such a decrease may also occur with natural sleep and play a role in the development of recurrent erosions and contact lens adhesion.3 In addition, changes in tear film osmolarity also could play a role in the development of suction and the occurrence of these syndromes after sleep. To better understand what happens to the tear film during sleep, we examined four patients clinically and measured tear film osmolarity immediately upon their awakening in the early morning. PATIENTS AND METHODS
Four normal subjects, aged 27 to 38, were hospitalized for two nights. *From the Cornea Unit, Eye Research Institute, and Department of
Ophthalmology,
Harvard Medical School (Dr Gilbard), and the Department of Ophthalmology, Tufts-New England Medical Center (Drs Cohen and Baum), Boston. Dr Cohen is currently in private practice in Lake Worth, Florida. This study was supported in part by research grant RO1 EY03373 from the National Eye Institute, Bethesda. TR. AM. OPHTH. Soc. vol. LXXXIX, 1991
210
Gilbard et al
Subjects slept with their eyes patched shut to prevent lid opening upon awakening in the morning. Patients were awakened at 6 AM and taken to a slit lamp microscope, at which time the patches were removed. Each patient's head was placed in position in the slit lamp, and the patient then was asked to open his or her eyes. One of us immediately examined the tear film and simultaneously watched for an inferior marginal tear strip, from which tear samples were collected as soon as it was present. Additional samples were collected that day at 9 AM and 9 PM and the following day at 6 AM (upon eyelid opening) and at 9 PM. At certain times, tear samples were taken from the inferior fornix after sampling had been performed from the inferior marginal tear strip. For this study, approximately 0.2-,ul tear samples were collected with fine-tipped, L-shaped micropipettes developed specifically to collect tear microvolumes without stimulating reflex tearing. Osmolarity was measured by freezing-point depression.4-6 RESULTS
Immediately upon lid opening, the inferior marginal tear strip was not seen in any patient, and it was not possible to collect a tear sample from this location before the first blink. With the first blink, an inferior marginal tear strip appeared, and a sample was taken for the 6 AM osmolarity measurement, which was significantly lower than the osmolarity at 9 AM and at 9 PM (P < 0. 005 and P < 0. 005, respectively). Tear osmolarity in the inferior marginal tear strip at 6 AM did not differ significantly from osmolarity in the inferior fornix at 6 AM. At 9 AM and 9 PM, tear osmolarity was higher in the inferior marginal tear strip than in the inferior fornix (P < 0.0005 and P < 0.0005, respectively) (Fig 1). DISCUSSION
Mishima and co-workers7 estimated that 38% of the total tear volume resides in the marginal tear strips. The absence of the inferior marginal tear strip upon eyelid opening after sleep suggests decreased tear volume at that moment. Tear film osmolarity is clearly at its nadir upon eyelid opening, and these data are consistent with earlier studies that demonstrated lower tear osmolarity upon eyelid opening8 and in the morning compared with the afternoon.9 One might question whether the 6 AM tear sample accurately reflects the osmolarity of the tear film in the closed-eye condition, or whether it represents the osmolarity of freshly secreted tear fluid. It also may be a
Tear Volume
211
310Interior Marginal Tear Strip
o E 0
0
3050 P~~~~~~~~~~~~~~~~~~~~~~~
0(I ('3~~~~~~o
-
Inerior Fornix
I 9PM
295 6 AM (upon eye
.'
9AM
opening)
Time FIGURE 1
Diurnal variation in tear film
osmolarity.
composite of the two. Inferior marginal tear strip osmolarity upon eyelid opening does not differ significantly from inferior fornix tear osmolarity. The tear fluid in the fornix is continuously covered by the lids and, in the closed-eye condition, the precorneal tear film, reflected by the inferior marginal tear strip, is covered by the lids as well. Even though a portion of the 6 AM sample from the inferior marginal tear strip may represent fresh tear fluid, its similarity to inferior fornix osmolarity suggests that it has equilibrated osmotically with the tear fluid residual from the closedeye condition. In any case, the osmolarity of the tear fluid in the inferior fornix at 6 AM upon eyelid opening probably most accurately reflects the osmolarity of the tear film in the closed-eye condition. When the eye is open, fluid transport normally occurs from the aqueous humor across the cornea and into the tear film. This transport is to some extent a function of the hydraulic pressure inside the eye, but to a much greater extent a function of the osmotic gradient that normally exists between the aqueous humor and the tear film.'0 Mishima and Maurice" have shown that continuous eyelid closure is associated with thickening of the cornea secondary to reduced evaporation.
212
Gilbard et al
We postulate that the decrease in tear osmolarity with eye closure reduces or reverses water movement out of the cornea (as tear film osmolarity approaches aqueous humor osmolarity) and contributes to the tendency for lid-corneal adhesion during sleep. Capillary action from low tear volume also may contribute to this adhesion.3 It is well known that soft contact lenses may adhere to the cornea if left in the eye overnight, and that this adherence may resolve spontaneously and relatively rapidly upon eye opening. The mechanism for this lenscorneal adhesion may be the same as the mechanism we have proposed for lid-corneal adhesion after eye closure with sleep. Rigid gas-permeable contact lenses have been reported to adhere to the cornea after overnight wear in some patients.'2 Since this adhesion can last for several hours after eye opening, we suspect that osmotic changes do not play a major role in this phenomenon. Our hypothesis may help explain the characteristic development of recurrent erosions upon awakening. Ever since Chandler's classic paper was published in 1945,1 ophthalmologists have prescribed hypertonic ointments for use at bedtime to prevent recurrent erosive episodes. This treatment originally was based on the belief that recurrent erosions were due to "persistent edema" of the corneal epithelium that resulted in loosening of epithelial attachment. More recently, it has become clear that the disorder is due not to a persistent epithelial edema but to abnormalities in the corneal epithelial adhesion complex. 13-15 If volume changes alone account for the adhesion at night, then plain, oil-based ointments would be as effective as hypertonic ointments. If in fact, the decrease in tear film osmolarity that occurs with lid closure contributes to lid-corneal adhesion, this mechanism would provide a rationale for the use of a hypertonic ointment at bedtime in these patients. REFERENCES 1. Chandler PA: Recurrent erosion of the cornea. Am J Ophthalmol 1945; 28:355-363. 2. Krupin T, Cross DA, Becker B: Decreased basal tear production with general anesthesia. Arch Ophthalmol 1977; 95:107-108. 3. Baum JL: Clinical implications of basal tear flow, in FJ Holly (ed): The Pre-Ocular Tear Film in Health, Disease, and Contact Lens Wear. Lubbock, TX, Dry Eye Institute, 1986, pp 646-651. 4. Gilbard JP, Farris RL, Santamaria J: Osmolarity of tear microvolumes in keratoconjunctivitis sicca. Arch Ophthalmol 1978; 96:677-681. 5. Gilbard JP, Farris RL: Ocular surface drying and tear film osmolarity in thyroid eye disease. Acta Ophthalmol 1983; 61:108-116. 6. Gilbard JP, Gray KL, Rossi SR: Improved technique for storage of tear microvolumes. Invest Ophthalmol Vis Sci 1987; 28:401-403. 7. Mishima S, Gasset A, Klyce SD Jr, et al: Determination of tear volume and tear flow. Invest Ophthalmol 1966; 5:264-276.
Tear Volume
213
8. Terry JE, Hill RM: Human tear osmotic pressure: Diurnal variations and the closed eye. Arch Ophthalmol 1978; 96:120-122. 9. Farris RL, Stuchell RN, Mandel ID: Tear osmolarity variation in the dry eye. Trans Am Ophthalmol Soc 1986; 84:250-268. 10. Mishima S: Corneal thickness. Surv Ophthalmol 1968; 13:57-96. 11. Mishima S, Maurice DM: Effect of normal evaporation on the eye. Exp Eye Res 1961; 1:46-52. 12. Swarerick HA, Holden BA: RGP lens binding: A patient dependent phenomenon? Invest Ophthalmol Vis Sci (Suppl) 1988; 29:279. 13. Goldman JN, Benedek GB, Dohlman CH, et al: Structural alterations affecting transparency in swollen human cornea. Invest Ophthalmol 1968; 7:501-519. 14. Khodadoust AA, Silverstein AM, Kenyon KR, et al: Adhesion of regenerating epithelium: The role of basement membrane. Am J Ophthalmol 1968; 65:339-348. 15. Gipson IK, Spurr-Michaud SJ, Tisdale AS: Anchoring fibrils form a complex network in human and rabbit cornea. Invest Ophthalmol Vis Sci 1987; 28:212-220.
DISCUSSION
DR MITCHELL H. FRIEDLAENDER. In 1941, von Bahr predicted that in keratoconjunctivitis sicca, tear film osmolarity would increase as tear secretion decreased. This was later confirmed by Mastmann in 1961 and by Mishima in 1971. Methods for sampling the precorneal tear film and measuring its osmolarity have been refined in recent years by Farris, who has presented his meticulous studies at this meeting, and by Gilbard, who is a co-author of this paper. Tear secretion is known to diminish during general anesthesia, and presumably during sleep. When the eyelids are closed, tear osmolarity also decreases. This appears to be caused by decreased evaporation of aqueous tears in the closed-lid state compared with increased evaporation when the lids are opened. Doctor Gilbard and co-authors have shown that when the eyelids of normal subjects are first opened, the tear meniscus is diminished or absent. When the first blink takes place, the tears sampled do, in fact, have a low osmolarity. Tear samples taken later in the day have a higher osmolarity, as expected. The authors suggest that decreased tear volume and low tear osmolarity may play a role in recurrent corneal erosion and contact lens adherence, two conditions that are accentuated when the eyelids are first opened in the morning. Tear volume and tear osmolarity are difficult to measure, and the authors are to be commended for undertaking this task, especially at 6 o'clock in the morning on two consecutive days. Nelson has called the depression of freezing point technique "tedious and difficult," and has estimated the error in measuring tear film osmolarity at 11%. The significance of tear film osmolarity is difficult to assess. The freezing point depression is not in widespread use, and normal values of tear film osmolarity are sometimes debated. Measurements are affected by reflex tearing and by evaporation of samples. While tear osmolarity may tell us something about the physiology of the cornea and the precorneal tear film, the relationship of this measurement to clinical problems like recurrent erosion and tight lens syndrome remains unclear. The authors postulate that the decrease in tear osmolarity with eye closure reduces and/or reverses water transport out of the
214
Gilbard et al
cornea and contributes to lid-corneal adhesion during sleep. Arguments have been made for hyperosmotic tears adversely affecting the cornea in dry-eye patients, and perhaps equally convincing arguments could be made for hypotonic tears exacerbating recurrent erosion or contact lens adherence. Tear volume appears to be a much more difficult factor to analyze. Few studies of tear volume are available, and we are relegated to assessing the tear volume by observing the presence or absence of the tear meniscus, as in this study. Clinicians are bound to ascribe considerable importance to tear volume, since tear replacement clearly benefits many ocular-surface conditions, such as recurrent erosion, dry eye, and contact lens adherence. On the other hand, therapies that attempt to restore a normal tear osmolarity, such as hypotonic artificial tears for dry eye and hypertonic saline for recurrent erosion, appear to be no better than conventional nonosmotic preparations. Tears are extremely complex substances, and the role of tear constituents such as lysozyme, lactoferrin, ascorbate, immunoglobulins, interleukins, and prostaglandins have yet to be elucidated. The authors are to be congratulated for helping to advance our understanding of the tear film and its relationship to ocular surface disease. DR GEORGE 0. WARING. Doctor Baum, tear film osmolarity has been available for clinical use for a few years, but it has not become very practical for the clinician. No company has made a tear osmometer available. I wonder if you could comment on that. Should we be trying to encourage some manufacturer to make a freezing point measuring instrument that we could use? If the accuracy really is on the order of 10% and we are measuring 300 mOsm, that is a range of 30 mOsm and your slide is showing variability on the order of about 10 mOsm. So is the accuracy of the measurement of tear film osmolarity good enough that we can really use it clinically? DR JULES BAUM. First, I would like to respond to Doctor Waring's question. Doctor Waring, I do not know how long it takes to measure osmolarity by freezing point depression on a very small volume. If it takes more than a few seconds then the osmolarity may be significantly altered by new tear flow. I just do not know. Perhaps someone in the audience does. I would like to thank Doctor Friedlaender for his kind comments. Doctor Friedlaender, I do not know how to measure early morning tear flow. We have to do it, at least, by the techniques I know, over a fairly extended period of time. Once again, while you are performing the measurements, the tear flow is changing and you are measuring other than the tear flow at the time of eyelid opening after sleep. You brought up a very interesting question about hypertonic tear replacement. If one has a relatively hypotonic condition upon opening the eye in the morning, here may be a case for giving hypertonic ointment before going to sleep. I don't know the effect of 6 to 8 hours of sleep on the toxicity of the ointment. Thank you.
Gilbard, MD (BY INVITATION), G. Richard Cohen, MD (BY INVITATION), AND Jules Baum, MD INTRODUCTION
THERE
ARE TWO WELL-KNOWN SYNDROMES THAT OCCUR UPON EYELID
opening after sleep. The first is the loosening of corneal epithelium associated with recurrent erosion syndrome, and the second is the tight lens syndrome that can occur with contact lenses. Chandlerl attributed the timing of recurrent erosions to the development of "suction between lid and cornea" overnight, and it seems likely that a similar suction may be responsible for the timing of tight lens syndrome. The mechanism of the putative suction between lid and cornea or contact lens and cornea has yet to be elucidated. We believe that changes in the tear film during sleep could be responsible for this suction. The induction of general anesthesia is associated with a decrease in tear secretion,2 and it has been postulated that such a decrease may also occur with natural sleep and play a role in the development of recurrent erosions and contact lens adhesion.3 In addition, changes in tear film osmolarity also could play a role in the development of suction and the occurrence of these syndromes after sleep. To better understand what happens to the tear film during sleep, we examined four patients clinically and measured tear film osmolarity immediately upon their awakening in the early morning. PATIENTS AND METHODS
Four normal subjects, aged 27 to 38, were hospitalized for two nights. *From the Cornea Unit, Eye Research Institute, and Department of
Ophthalmology,
Harvard Medical School (Dr Gilbard), and the Department of Ophthalmology, Tufts-New England Medical Center (Drs Cohen and Baum), Boston. Dr Cohen is currently in private practice in Lake Worth, Florida. This study was supported in part by research grant RO1 EY03373 from the National Eye Institute, Bethesda. TR. AM. OPHTH. Soc. vol. LXXXIX, 1991
210
Gilbard et al
Subjects slept with their eyes patched shut to prevent lid opening upon awakening in the morning. Patients were awakened at 6 AM and taken to a slit lamp microscope, at which time the patches were removed. Each patient's head was placed in position in the slit lamp, and the patient then was asked to open his or her eyes. One of us immediately examined the tear film and simultaneously watched for an inferior marginal tear strip, from which tear samples were collected as soon as it was present. Additional samples were collected that day at 9 AM and 9 PM and the following day at 6 AM (upon eyelid opening) and at 9 PM. At certain times, tear samples were taken from the inferior fornix after sampling had been performed from the inferior marginal tear strip. For this study, approximately 0.2-,ul tear samples were collected with fine-tipped, L-shaped micropipettes developed specifically to collect tear microvolumes without stimulating reflex tearing. Osmolarity was measured by freezing-point depression.4-6 RESULTS
Immediately upon lid opening, the inferior marginal tear strip was not seen in any patient, and it was not possible to collect a tear sample from this location before the first blink. With the first blink, an inferior marginal tear strip appeared, and a sample was taken for the 6 AM osmolarity measurement, which was significantly lower than the osmolarity at 9 AM and at 9 PM (P < 0. 005 and P < 0. 005, respectively). Tear osmolarity in the inferior marginal tear strip at 6 AM did not differ significantly from osmolarity in the inferior fornix at 6 AM. At 9 AM and 9 PM, tear osmolarity was higher in the inferior marginal tear strip than in the inferior fornix (P < 0.0005 and P < 0.0005, respectively) (Fig 1). DISCUSSION
Mishima and co-workers7 estimated that 38% of the total tear volume resides in the marginal tear strips. The absence of the inferior marginal tear strip upon eyelid opening after sleep suggests decreased tear volume at that moment. Tear film osmolarity is clearly at its nadir upon eyelid opening, and these data are consistent with earlier studies that demonstrated lower tear osmolarity upon eyelid opening8 and in the morning compared with the afternoon.9 One might question whether the 6 AM tear sample accurately reflects the osmolarity of the tear film in the closed-eye condition, or whether it represents the osmolarity of freshly secreted tear fluid. It also may be a
Tear Volume
211
310Interior Marginal Tear Strip
o E 0
0
3050 P~~~~~~~~~~~~~~~~~~~~~~~
0(I ('3~~~~~~o
-
Inerior Fornix
I 9PM
295 6 AM (upon eye
.'
9AM
opening)
Time FIGURE 1
Diurnal variation in tear film
osmolarity.
composite of the two. Inferior marginal tear strip osmolarity upon eyelid opening does not differ significantly from inferior fornix tear osmolarity. The tear fluid in the fornix is continuously covered by the lids and, in the closed-eye condition, the precorneal tear film, reflected by the inferior marginal tear strip, is covered by the lids as well. Even though a portion of the 6 AM sample from the inferior marginal tear strip may represent fresh tear fluid, its similarity to inferior fornix osmolarity suggests that it has equilibrated osmotically with the tear fluid residual from the closedeye condition. In any case, the osmolarity of the tear fluid in the inferior fornix at 6 AM upon eyelid opening probably most accurately reflects the osmolarity of the tear film in the closed-eye condition. When the eye is open, fluid transport normally occurs from the aqueous humor across the cornea and into the tear film. This transport is to some extent a function of the hydraulic pressure inside the eye, but to a much greater extent a function of the osmotic gradient that normally exists between the aqueous humor and the tear film.'0 Mishima and Maurice" have shown that continuous eyelid closure is associated with thickening of the cornea secondary to reduced evaporation.
212
Gilbard et al
We postulate that the decrease in tear osmolarity with eye closure reduces or reverses water movement out of the cornea (as tear film osmolarity approaches aqueous humor osmolarity) and contributes to the tendency for lid-corneal adhesion during sleep. Capillary action from low tear volume also may contribute to this adhesion.3 It is well known that soft contact lenses may adhere to the cornea if left in the eye overnight, and that this adherence may resolve spontaneously and relatively rapidly upon eye opening. The mechanism for this lenscorneal adhesion may be the same as the mechanism we have proposed for lid-corneal adhesion after eye closure with sleep. Rigid gas-permeable contact lenses have been reported to adhere to the cornea after overnight wear in some patients.'2 Since this adhesion can last for several hours after eye opening, we suspect that osmotic changes do not play a major role in this phenomenon. Our hypothesis may help explain the characteristic development of recurrent erosions upon awakening. Ever since Chandler's classic paper was published in 1945,1 ophthalmologists have prescribed hypertonic ointments for use at bedtime to prevent recurrent erosive episodes. This treatment originally was based on the belief that recurrent erosions were due to "persistent edema" of the corneal epithelium that resulted in loosening of epithelial attachment. More recently, it has become clear that the disorder is due not to a persistent epithelial edema but to abnormalities in the corneal epithelial adhesion complex. 13-15 If volume changes alone account for the adhesion at night, then plain, oil-based ointments would be as effective as hypertonic ointments. If in fact, the decrease in tear film osmolarity that occurs with lid closure contributes to lid-corneal adhesion, this mechanism would provide a rationale for the use of a hypertonic ointment at bedtime in these patients. REFERENCES 1. Chandler PA: Recurrent erosion of the cornea. Am J Ophthalmol 1945; 28:355-363. 2. Krupin T, Cross DA, Becker B: Decreased basal tear production with general anesthesia. Arch Ophthalmol 1977; 95:107-108. 3. Baum JL: Clinical implications of basal tear flow, in FJ Holly (ed): The Pre-Ocular Tear Film in Health, Disease, and Contact Lens Wear. Lubbock, TX, Dry Eye Institute, 1986, pp 646-651. 4. Gilbard JP, Farris RL, Santamaria J: Osmolarity of tear microvolumes in keratoconjunctivitis sicca. Arch Ophthalmol 1978; 96:677-681. 5. Gilbard JP, Farris RL: Ocular surface drying and tear film osmolarity in thyroid eye disease. Acta Ophthalmol 1983; 61:108-116. 6. Gilbard JP, Gray KL, Rossi SR: Improved technique for storage of tear microvolumes. Invest Ophthalmol Vis Sci 1987; 28:401-403. 7. Mishima S, Gasset A, Klyce SD Jr, et al: Determination of tear volume and tear flow. Invest Ophthalmol 1966; 5:264-276.
Tear Volume
213
8. Terry JE, Hill RM: Human tear osmotic pressure: Diurnal variations and the closed eye. Arch Ophthalmol 1978; 96:120-122. 9. Farris RL, Stuchell RN, Mandel ID: Tear osmolarity variation in the dry eye. Trans Am Ophthalmol Soc 1986; 84:250-268. 10. Mishima S: Corneal thickness. Surv Ophthalmol 1968; 13:57-96. 11. Mishima S, Maurice DM: Effect of normal evaporation on the eye. Exp Eye Res 1961; 1:46-52. 12. Swarerick HA, Holden BA: RGP lens binding: A patient dependent phenomenon? Invest Ophthalmol Vis Sci (Suppl) 1988; 29:279. 13. Goldman JN, Benedek GB, Dohlman CH, et al: Structural alterations affecting transparency in swollen human cornea. Invest Ophthalmol 1968; 7:501-519. 14. Khodadoust AA, Silverstein AM, Kenyon KR, et al: Adhesion of regenerating epithelium: The role of basement membrane. Am J Ophthalmol 1968; 65:339-348. 15. Gipson IK, Spurr-Michaud SJ, Tisdale AS: Anchoring fibrils form a complex network in human and rabbit cornea. Invest Ophthalmol Vis Sci 1987; 28:212-220.
DISCUSSION
DR MITCHELL H. FRIEDLAENDER. In 1941, von Bahr predicted that in keratoconjunctivitis sicca, tear film osmolarity would increase as tear secretion decreased. This was later confirmed by Mastmann in 1961 and by Mishima in 1971. Methods for sampling the precorneal tear film and measuring its osmolarity have been refined in recent years by Farris, who has presented his meticulous studies at this meeting, and by Gilbard, who is a co-author of this paper. Tear secretion is known to diminish during general anesthesia, and presumably during sleep. When the eyelids are closed, tear osmolarity also decreases. This appears to be caused by decreased evaporation of aqueous tears in the closed-lid state compared with increased evaporation when the lids are opened. Doctor Gilbard and co-authors have shown that when the eyelids of normal subjects are first opened, the tear meniscus is diminished or absent. When the first blink takes place, the tears sampled do, in fact, have a low osmolarity. Tear samples taken later in the day have a higher osmolarity, as expected. The authors suggest that decreased tear volume and low tear osmolarity may play a role in recurrent corneal erosion and contact lens adherence, two conditions that are accentuated when the eyelids are first opened in the morning. Tear volume and tear osmolarity are difficult to measure, and the authors are to be commended for undertaking this task, especially at 6 o'clock in the morning on two consecutive days. Nelson has called the depression of freezing point technique "tedious and difficult," and has estimated the error in measuring tear film osmolarity at 11%. The significance of tear film osmolarity is difficult to assess. The freezing point depression is not in widespread use, and normal values of tear film osmolarity are sometimes debated. Measurements are affected by reflex tearing and by evaporation of samples. While tear osmolarity may tell us something about the physiology of the cornea and the precorneal tear film, the relationship of this measurement to clinical problems like recurrent erosion and tight lens syndrome remains unclear. The authors postulate that the decrease in tear osmolarity with eye closure reduces and/or reverses water transport out of the
214
Gilbard et al
cornea and contributes to lid-corneal adhesion during sleep. Arguments have been made for hyperosmotic tears adversely affecting the cornea in dry-eye patients, and perhaps equally convincing arguments could be made for hypotonic tears exacerbating recurrent erosion or contact lens adherence. Tear volume appears to be a much more difficult factor to analyze. Few studies of tear volume are available, and we are relegated to assessing the tear volume by observing the presence or absence of the tear meniscus, as in this study. Clinicians are bound to ascribe considerable importance to tear volume, since tear replacement clearly benefits many ocular-surface conditions, such as recurrent erosion, dry eye, and contact lens adherence. On the other hand, therapies that attempt to restore a normal tear osmolarity, such as hypotonic artificial tears for dry eye and hypertonic saline for recurrent erosion, appear to be no better than conventional nonosmotic preparations. Tears are extremely complex substances, and the role of tear constituents such as lysozyme, lactoferrin, ascorbate, immunoglobulins, interleukins, and prostaglandins have yet to be elucidated. The authors are to be congratulated for helping to advance our understanding of the tear film and its relationship to ocular surface disease. DR GEORGE 0. WARING. Doctor Baum, tear film osmolarity has been available for clinical use for a few years, but it has not become very practical for the clinician. No company has made a tear osmometer available. I wonder if you could comment on that. Should we be trying to encourage some manufacturer to make a freezing point measuring instrument that we could use? If the accuracy really is on the order of 10% and we are measuring 300 mOsm, that is a range of 30 mOsm and your slide is showing variability on the order of about 10 mOsm. So is the accuracy of the measurement of tear film osmolarity good enough that we can really use it clinically? DR JULES BAUM. First, I would like to respond to Doctor Waring's question. Doctor Waring, I do not know how long it takes to measure osmolarity by freezing point depression on a very small volume. If it takes more than a few seconds then the osmolarity may be significantly altered by new tear flow. I just do not know. Perhaps someone in the audience does. I would like to thank Doctor Friedlaender for his kind comments. Doctor Friedlaender, I do not know how to measure early morning tear flow. We have to do it, at least, by the techniques I know, over a fairly extended period of time. Once again, while you are performing the measurements, the tear flow is changing and you are measuring other than the tear flow at the time of eyelid opening after sleep. You brought up a very interesting question about hypertonic tear replacement. If one has a relatively hypotonic condition upon opening the eye in the morning, here may be a case for giving hypertonic ointment before going to sleep. I don't know the effect of 6 to 8 hours of sleep on the toxicity of the ointment. Thank you.
