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Clinical Sciences |

Relationship Between Tear Volume and Tear Meniscus Curvature FREE

Norihiko Yokoi, MD, PhD; Anthony J. Bron, FRCOphth; John M. Tiffany, PhD; Kunio Maruyama, BS; Aoi Komuro, MD, PhD; Shigeru Kinoshita, MD, PhD
[+] Author Affiliations

From the Department of Ophthalmology, Kyoto Prefectural Universityof Medicine, Kyoto, Japan (Drs Yokoi, Komuro, and Kinoshita and Mr Maruyama);and Nuffield Laboratory of Ophthalmology, University of Oxford, Oxford, England(Drs Bron and Tiffany). The authors have no relevant financial interest inthis article.


Arch Ophthalmol. 2004;122(9):1265-1269. doi:10.1001/archopht.122.9.1265.
Text Size: A A A
Published online

Objective  To investigate the relationship between tear volume and tear meniscuscurvature by means of the video meniscometer.

Methods  Eleven eyes of 11 patients with severe dry eye were studied (all female;mean ± SD age, 66.2 ± 7.7 years; 7 left eyes and 4 right eyes),each of whose puncta had been therapeutically occluded. Four instillationsof balanced salt solution were given at intervals of 1 minute in each studiedeye, with the concentration increasing in 5-µL steps from 5 to 20 µL.Before and after the instillation of balanced salt solution, tear meniscuschanges were recorded by video meniscometer and radius of the meniscus wascalculated from the printed images by means of the concave mirror formula.

Results  The mean radius of the meniscus increased linearly with increased dropvolume (r2 = 0.65, P<.001), with mean ± SD radius values of 0.24 ± 0.08mm at baseline and 0.48 ± 0.13, 0.62 ± 0.13, 0.84 ± 0.26,and 1.00 ± 0.32 mm after separate instillations of 5, 10, 15, and 20µL of balanced salt solution, respectively. For each subject, a significantlydifferent slope defining the relationship between instilled volume and meniscusradius was seen (0.016-0.063 mm/µL; mean ± SD, 0.039 ±0.015 mm/µL), which was thought to depend on the difference in capacityof the fluid reservoir over the ocular surface.

Conclusions  This study confirmed that the volume of instilled eyedrops is linearlyrelated to the resulting radius of the tear meniscus, suggesting that thisradius is a useful measure in monitoring the tear volume. This is likely tohave implications both for dry eye diagnosis and for confirming the efficacyof punctal occlusion in this condition.

Figures in this Article

In human eyes, the total tear volume is distributed among 3 continuouscompartments: the culs-de-sac, menisci, and preocular film.1 Themenisci act as a reservoir supplying fluid from which the preocular film isre-formed at each blink. They also accommodate the excess tears that accumulatewith reflex tearing, from lacrimal drainage obstruction, or after drop instillation.The menisci and tear film are held in place by interfacial forces.2 Tear volume is positively correlated with lacrimalsecretory rate,3 and meniscus volume is reducedin tear-deficient dry eye.4,5 Hence,knowledge of meniscus volume may be useful in the diagnosis of dry eye. Also,in dry eye, meniscus radius can be informative about the efficacy of punctalocclusion, either directly or by demonstrating impaired clearance of an instilleddrop.

Reflective meniscometry57 isa noninvasive technique for the measurement of tear meniscus curvature. Themethod, which uses a specular reflection technique, projects a target ontothe concave, mirrorlike surface of the meniscus, and the size of the reflectedimage is used to calculate its radius of curvature. With certain assumptionsas to the sagittal profile of the meniscus, radius of curvature can be usedto estimate meniscus volume.4,5

Recently, a video-based system (the video meniscometer)5,7 hasbeen developed and used to demonstrate a significant relationship betweenthe meniscus radius and height.7 Both measureshave been used in the diagnosis of dry eye.4,5,810 Thepresent study aims to assess the relationship between radius of tear meniscusand total tear volume.

SUBJECTS

In this study, 11 women with severe dry eyes were enrolled (mean ±SD age, 66.2 ± 7.7 years; range, 58-85 years). For each patient, oneeye was randomly selected for study (7 left eyes and 4 right eyes). The 11patients included 8 with Sjögren syndrome, diagnosed on the basis ofthe Fox criteria,11 and 3 patients with non-Sjögrentear-deficient dry eye. All patients either had had upper and lower punctalplugs successfully inserted (8 eyes; Ready-Set M-size Punctum Plug; FCI Ophthalmics,Issy-les-Moulineaux, France), or had undergone upper and lower surgical punctalocclusion by cauterization or suture closure (3 eyes). All eyes showed theseverest form of dry eye, with a diminished Schirmer I test12 value(mean ± SD, 1.5 ± 2.5 mm in 5 minutes) and, before occlusion,severe corneal fluorescein staining scores13,14 (A3D3in 8 eyes, A3D2 in 2 eyes, and A2D3 in 1 eye, where A represents area andD, density, scored from 0 to 3 depending on the severity) and a total rosebengal staining score15 of 7.1 ± 2.2(mean ± SD) for the cornea and nasal and temporal bulbar conjunctiva.Before punctal occlusion, the patients had been treated with a combinationof preservative-free artificial tears containing 0.1% potassium chloride and0.4% sodium chloride (Softsantear; Santen Pharmaceutical Co, Ltd, Osaka, Japan)and hyaluronate sodium ophthalmic solution (HyaleinMini 0.1; Santen PharmaceuticalCo, Ltd) with little improvement. However, after occlusion therapy, fluoresceinstaining scores improved to A0D0 in all cases, and all subjects continuedtreatment with preservative-free artificial tears alone, 4 to 6 times daily.

This group of patients with severe dry eye was selected to provide amodel system in which the effects of instilled eyedrops on the radius of thetear meniscus could be isolated from the influence of reflex tearing and lacrimaldrainage. It was assumed that secretion was close to zero and that the artificialtears provided the major proportion of the tear reservoir in the conjunctivalsac, meniscus, and preocular film. On the day of the study, subjects wererequested not to use their artificial tear preparation until after the examination.

This research conformed to the tenets of the Declaration of Helsinkion the use of human subjects. Before the start of the study, procedures werefully explained to all subjects and informed consent was obtained.

In this study, we used video meniscometry as a noninvasive method toobserve and quantify tear meniscus curvature at the center of the lower eyelidmargin.5,7 The system comprisesan illuminated target, CCD camera, video recorder, and video printer. Thehorizontally striped target is projected onto the center of the lower meniscus,which behaves like a cylindrical, concave mirror.

The line separation in the reflected image is used to calculate meniscuscurvature by means of the concave mirror formula.57

The target consists of a series of black metal bars, 4 mm wide and 4mm apart, set in front of the objective lens and illuminated from behind.A half-silvered mirror, introduced into the optical pathway, permits coaxialviewing and image capture as well as back illumination of the target. Thereflected image appears as a series of black and white stripes (Figure 1). For the purpose of calculating the radius of the tearmeniscus, selected meniscus images were printed (print magnification, ×70). In normal subjects, in the absence of drop instillation and with thesubject blinking spontaneously, the reflective images of the target are highlystable over time.

Place holder to copy figure label and caption
Figure 1.

Schema for meniscometry in a representativeeye. In this case, the eye had successfully received punctal plugs in bothupper and lower puncta. The profile of the tear meniscus at the center ofthe lower eyelid margin was investigated with the meniscometer. The effectof instilled eyedrops on the radius of the tear meniscus could be isolatedfrom the influence of reflex tearing and lacrimal drainage. L indicates damagedlacrimal gland; TM, tear meniscus; P, punctal plug; T, target; and I, image.

Graphic Jump Location

To evaluate the relationship between radius of tear meniscus and instilledfluid volume, 4 instillations of balanced salt solution (BSS) were given atintervals of 1 minute into the selected eye of each subject in 5-µLsteps, increasing from 5 to 20 µL (ie, 5, 10, 15, and 20 µL).After each instillation, patients were allowed to blink spontaneously for30 seconds, after which tear meniscus behavior was recorded with the videomeniscometer. After the meniscus appearance was recorded, the radius was calculatedfrom the video printed images. The procedure for monitoring tear meniscusbehavior at the center of the lower eyelid margin in a typical subject's eyeis shown schematically in Figure 1.

STATISTICAL ANALYSIS

The results were expressed as mean ± SD. Regression analysiswas used to estimate the straight-line relationship between the radius oftear meniscus and the accumulated volume of instilled eyedrops in each patient.Differences in slopes of the regression line between patients were analyzedby analysis of covariance with volume of eyedrops as a covariate. P≤.05 was considered to be significant.

Before drop instillation, the mean baseline meniscus radius was 0.24± 0.08 mm. After the cumulative instillation of 5, 10, 15, and 20 µLof BSS, the mean meniscus radius was calculated to be 0.48 ± 0.13,0.62 ± 0.13, 0.84 ± 0.26, and 1.00 ± 0.32 mm, respectively.A representative example of the change in meniscus image after successiveinstillation of BSS is shown in Figure 2.

Place holder to copy figure label and caption
Figure 2.

A representative example of thechange in the meniscus image after instillation of balanced salt solution.A, Baseline. B-E, Changes after instillation of approximately 5, 10, 15, and20 µL of balanced salt solution, respectively.

Graphic Jump Location

The mean radius increased linearly with total volume instilled (r2 = 0.65, P<.001; y = 0.038x + 0.256, where y = radius [in millimeters] and x =total volume of instilled BSS [in microliters]; Figure 3). The significant regression between radius and total volumeinstilled was found for each subject individually (0.039 ± 0.015 mm/µL[0.016-0.063 mm/µL]; Table 1 and Figure 4). Also, analysis of covariance showedthat there was a significant interaction between volume of eyedrops and patients(F = 12.33, P<.001; Table 2), implying that slopes of regression line between patientswere significantly different.

Place holder to copy figure label and caption
Figure 3.

Relationship between radius oftear meniscus and total volume of instilled balanced salt solution (BSS).The mean radius value increased linearly with total instilled volume of BSS(y= 0.038x + 0.256, where y = radius [in millimeters] and x =total volume of instilled BSS [in microliters]; r2 = 0.65, P<.001).

Graphic Jump Location
Table Graphic Jump LocationTable 1. Regression Between Radius of Meniscus and Total Volume ofInstilled BSS
Place holder to copy figure label and caption
Figure 4.

Relationship between radius oftear meniscus and total volume of instilled balanced salt solution (BSS) foreach subject. The slope of the regression line differed in each case (0.016-0.063mm/µL; mean ± SD, 0.039 ± 0.015 mm/µL). Patientnumbers in the box identify individual eyes and correspond to those in Table 1.

Graphic Jump Location

One view of tear-deficient dry eye is that it is the result of an autoimmuneinflammatory process that destroys lacrimal tissue or function and resultsin reduced tear secretion.16 The autoimmuneprocess can result, directly or indirectly, in inflammatory events at theocular surface, particularly the conjunctiva, and lead to tear hyperosmolaritydue to evaporation from a reduced aqueous pool. Hyperosmolarity itself leadsto surface inflammation.1619 Intear-deficient dry eye, a reduced tear flow leads to a reduced tear volume.It has been suggested that this in turn leads to a thinning of the preoculartear film2,20 and that this isthe major factor leading to hyperosmolarity.1719,21 Amathematical relationship between meniscus curvature and tear film thicknesshas been proposed,20,22 and forthis reason alone, we would expect meniscus curvature to be of diagnosticvalue in dry eye. In this study, we attempted to show in addition that meniscuscurvature, which relates to its volume, is an index of total tear volume.This again would support its potential value in diagnosis of dry eye.

For the purposes of discussion, the term total tearvolume will be used to mean the aggregate volume of tears distributedbetween the culs-de-sac, menisci, and preocular tear film.1 Meniscusvolume is chiefly regulated by the balance between lacrimal secretion andtear drainage, with evaporation playing a minor role. Evaporation is, however,of increasing importance in dry eye and becomes the dominant feature of evaporativedry eye.2326

The present study aimed to assess the relationship between tear meniscusradius and total tear volume under conditions in which total tear volume couldbe increased incrementally. This was achieved by studying a group of aqueous-deficientpatients with severe dry eye, whose tear secretion was minimal (as indicatedby the Schirmer I values before the punctal occlusion), and lacrimal drainagewas completely obstructed by punctal occlusion. In this situation it was reasonablyassumed that the total volume of fluid bathing the ocular surface was determinedchiefly by the experimental instillation of BSS. Evaporation was assumed tohave a negligible effect on tear volume during the short time course of thestudy. Relative to the total volume of BSS instilled, the evaporative lossduring the course of the study, calculated according to a previous study27 for a dry eye population, would be about 0.23 µLper eye, which would be unlikely to have a major effect on the outcome ofthe study. Since all patients exhibited a visible meniscus at baseline, itmust be assumed that an amount of fluid was present at the start of the experiments,reflecting the persistence of residual secretions or of tear substitutes instilledpreviously.

As mentioned in the "Results" section, a linear relationship was shownbetween the radius of the lower central tear meniscus and the cumulative volumeof instilled fluid, both in the total group (Figure 3) and in individual subjects (Figure 4, Table 1),indicating that the radius of curvature of the meniscus reflects the totalvolume of tears distributed between the tear compartments at any one time.These findings allow the general conclusion to be drawn that meniscus radiusvalues derived from measurements over a small region of the lower centraltear meniscus are probably generalizable to the whole meniscus reservoir,and that the radius is not significantly influenced by any change in surfaceactive properties of the tear fluid28 due todilution.

Extrapolation of the group mean regression line to the x-axis in Figure 3, where the radius is notionallyzero, may be interpreted to reflect the baseline total volume of tear fluiddistributed in sac and film. This value was 6.7 µL for the group. Ifwe take the reported average radius value in normal subjects to be 0.365 mm,using the same video meniscometric technique,5 thenthe relationship plotted for the group in Figure 3 shows that this radius would correspond to an additionalvolume of 2.9 µL above the baseline value for the dry eye group. Ifthe baseline total dry eye volume (6.7 µL) is added to this additionalvolume (2.9 µL), the sum (9.6 µL) is close to the value reportedpreviously1 for the tear volume in the normaleye. We recognize that this is a crude estimate, but we submit it here toshow how such a calculation could be used in the future with more refinedtechniques.

Figure 4 demonstrates importantindividual differences between the patients with dry eye in this study. Itshould be noted that radius values differed between subjects and that forsome subjects these values fell within the reference range. This raises thepossibility that these subjects did not comply with instructions not to instilltear substitutes on the day of study or that artificial tear preparation instilledbefore the day of the experiment remained on the eye because of the completeocclusion of the puncta. Also, not only do basal radius values differ betweenpatients, but the slopes of the regression lines also significantly differ(0.039 ± 0.015 mm/µL [0.016-0.063 mm/µL]; Table 2), implying that the instilled volumes of BSS were accommodatedinto compartments of differing properties. The most likely factor that mightinfluence these slopes would be cul-de-sac size and physical properties, withsurface tension and tear viscosity also playing a small role. Since the tearsacs are not rigid compartments, it might be assumed that elastic factorswould influence the response to added volume and that this might be modifiedby disease.

The differences in individual slopes of the radius-volume curves drawattention to the likelihood that the same meniscus radii in 2 different individualsmay not imply the same total tear volume, probably reflecting differencesin sac capacity. On the other hand, in a given individual, changes in radiuswill directly relate to changes in total tear volume. This is of importancein relation to studies of tear clearance or in clinical trials, particularlyof lacrimal secretogogues.

In summary, the present study indicates that meniscus curvature is anindex of total tear volume, while mathematical considerations suggest thatit predicts tear film thickness.21,22 Theseobservations support the theoretical value of meniscus curvature measurementand of video meniscometry in the diagnosis of dry eye. We will show elsewherethat the same technology can be used to confirm the efficacy of punctal occlusionin this condition.

Correspondence: Norihiko Yokoi, MD, PhD, Department of Ophthalmology,Kyoto Prefectural University of Medicine, 465 Kajii-cho, Hirokoji-agaru, Kawaramachi-dori,Kamigyo-ku, Kyoto 6020841, Japan (nyokoi@ophth.kpu-m.ac.jp).

Submitted for publication July 17, 2003; final revision received November17, 2003; accepted April 6, 2004.

This study was supported in part by grants-in-aid for scientific researchfrom the Japanese Ministry of Health, Labor, and Welfare and the JapaneseMinistry of Education, Culture, Sports, Science, and Technology (Tokyo) andby research grants from the Kyoto Foundation for the Promotion of MedicalScience, the Intramural Research Fund of Kyoto Prefectural University of Medicine(Kyoto, Japan).

This study was presented in part at the annual meeting of the Associationfor Research in Vision and Ophthalmology; April 30, 2000; Ft Lauderdale, Fla.

We thank Tatsuo Terashima and Kousei Terasaki (Biostatistics Department,Santen Pharmaceutical Co Ltd, Osaka, Japan) for statistical assistance.

Mishima  SGasset  AKlyce  SD  JrBaum  JL Determination of tear volume and tear flow. Invest Ophthalmol. 1966;5264- 276
PubMed
McDonald  JBrubaker  S Meniscus-induced thinning of tear films. Am J Ophthalmol. 1971;72139- 146
PubMed
Mishima  SKubota  ZFarris  RL The tear flow dynamics in normal and keratoconjunctivitis sicca cases. Excerpta Medica Int Congr Ser. 1970;2221801- 1805
Mainstone  JCBruce  AGolding  R Tear meniscus measurement in the diagnosis of dry eye. Curr Eye Res. 1996;15653- 661
PubMed Link to Article
Yokoi  NBron  AJTiffany  JMKinoshita  S Reflective meniscometry: a new field of dry eye assessment. Cornea. 2000;19 (3) supplS37- S43
PubMed Link to Article
Yokoi  NBron  AJTiffany  JMBrown  NAHsuan  JDFowler  CW Reflective meniscometry: a non-invasive method to measure tear meniscuscurvature. Br J Ophthalmol. 1999;8392- 97
PubMed Link to Article
Oguz  HYokoi  NKinoshita  S The height and radius of the tear meniscus and methods for examiningthese parameters. Cornea. 2000;19497- 500
PubMed Link to Article
Scherz  WDoane  MGDohlman  CH Tear volume in normal eyes and keratoconjunctivitis sicca. Albrecht Von Graefes Arch Klin Exp Ophthalmol. 1974;192141- 150
PubMed Link to Article
Taylor  HRLouis  WJ Significance of tear function test abnormalities. Ann Ophthalmol. 1980;12531- 535
Port  MJAAsaria  TS Assessment of human tear volume. J Br Contact Lens Assoc. 1990;1376- 82
Link to Article
Fox  RIRobinson  CCurd  JKozin  FHowell  F Sjögren syndrome: proposed criteria for classification. Arthritis Rheum. 1986;29577- 584
PubMed Link to Article
Schirmer  O Studien zur Physiologie und Pathologie der Träneabsonderung undTränenabfuhr. Albrecht von Graefes Arch Klin Exp Ophthalmol. 1903;56197- 291
Link to Article
Miyata  KSawa  MNishida  TMishima  HMiyamoto  YOtori  T Classification of severity of superficial punctate keratitis. Rinsho Ganka. 1994;48183- 188
Yokoi  NTakehisa  YKinoshita  S Correlation of tear lipid layer interference patterns with the diagnosisand severity of dry eye. Am J Ophthalmol. 1996;122818- 824
PubMed
van Bijstereveld  OP Diagnostic tests in sicca syndrome. Arch Ophthalmol. 1969;8210- 24
PubMed Link to Article
Stern  MEBeuerman  RWFox  RIGao  J-PMircheff  AKPflugfelder  SC The pathology of dry eye: the interaction between the ocular surfaceand lacrimal glands. Cornea. 1998;17584- 589
PubMed Link to Article
Gilbard  JPFarris  RLSantamaria  J  II Osmolarity of tear microvolumes in keratoconjunctivitis sicca. Arch Ophthalmol. 1978;96677- 681
PubMed Link to Article
Gilbard  JPRossi  SRGray  KLHanninen  LAKenyon  KR Tear film osmolarity and ocular surface disease in two rabbit modelsfor keratoconjunctivitis sicca. Invest Ophthalmol Vis Sci. 1988;29374- 378
PubMed
Gilbard  JPCarter  JBSang  DNRefojo  MFHanninen  LAKenyon  KR Morphologic effect of hyperosmolarity on rabbit corneal epithelium. Ophthalmology. 1984;911205- 1212
PubMed Link to Article
Wong  HFatt  IRadke  CJ Deposition and thinning of the human tear film. J Colloid Interface Sci. 1996;18444- 51
PubMed Link to Article
Bron  AJTiffany  JMYokoi  NGouveia  SM Using osmolarity to diagnose dry eye: a compartmental hypothesis anda review of our assumptions. Adv Exp Med Biol. 2002;5061087- 1095
PubMed
Creech  JLDo  LTFatt  IRadke  CJ In vivo tear-film thickness determination and implications for tear-filmstability. Curr Eye Res. 1998;171058- 1066
PubMed Link to Article
Mishima  SMaurice  DM The oily layer of the tear film and evaporation from the corneal surface. Exp Eye Res. 1961;139- 45
PubMed Link to Article
Gilbard  JPRossi  SRHeyda  KG Tear film and ocular surface changes after closure of the meibomiangland orifices in the rabbit. Ophthalmology. 1989;961180- 1186
PubMed Link to Article
Lemp  MA Report of the National Eye Institute/Industry Workshop on clinicaltrials in dry eyes. CLAO J. 1995;21221- 232
PubMed
Mathers  WDDaley  TD Tear flow and investigation in patients with and without dry eye. Ophthalmology. 1996;103664- 669
PubMed Link to Article
Tsubota  KYamada  M Tear evaporation from the ocular surface. Invest Ophthalmol Vis Sci. 1992;332942- 2950
PubMed
Tiffany  JMWinter  NBliss  G Tear film stability and tear surface tension. Curr Eye Res. 1998;8507- 515
PubMed Link to Article

Figures

Place holder to copy figure label and caption
Figure 1.

Schema for meniscometry in a representativeeye. In this case, the eye had successfully received punctal plugs in bothupper and lower puncta. The profile of the tear meniscus at the center ofthe lower eyelid margin was investigated with the meniscometer. The effectof instilled eyedrops on the radius of the tear meniscus could be isolatedfrom the influence of reflex tearing and lacrimal drainage. L indicates damagedlacrimal gland; TM, tear meniscus; P, punctal plug; T, target; and I, image.

Graphic Jump Location
Place holder to copy figure label and caption
Figure 2.

A representative example of thechange in the meniscus image after instillation of balanced salt solution.A, Baseline. B-E, Changes after instillation of approximately 5, 10, 15, and20 µL of balanced salt solution, respectively.

Graphic Jump Location
Place holder to copy figure label and caption
Figure 3.

Relationship between radius oftear meniscus and total volume of instilled balanced salt solution (BSS).The mean radius value increased linearly with total instilled volume of BSS(y= 0.038x + 0.256, where y = radius [in millimeters] and x =total volume of instilled BSS [in microliters]; r2 = 0.65, P<.001).

Graphic Jump Location
Place holder to copy figure label and caption
Figure 4.

Relationship between radius oftear meniscus and total volume of instilled balanced salt solution (BSS) foreach subject. The slope of the regression line differed in each case (0.016-0.063mm/µL; mean ± SD, 0.039 ± 0.015 mm/µL). Patientnumbers in the box identify individual eyes and correspond to those in Table 1.

Graphic Jump Location

Tables

Table Graphic Jump LocationTable 1. Regression Between Radius of Meniscus and Total Volume ofInstilled BSS

References

Mishima  SGasset  AKlyce  SD  JrBaum  JL Determination of tear volume and tear flow. Invest Ophthalmol. 1966;5264- 276
PubMed
McDonald  JBrubaker  S Meniscus-induced thinning of tear films. Am J Ophthalmol. 1971;72139- 146
PubMed
Mishima  SKubota  ZFarris  RL The tear flow dynamics in normal and keratoconjunctivitis sicca cases. Excerpta Medica Int Congr Ser. 1970;2221801- 1805
Mainstone  JCBruce  AGolding  R Tear meniscus measurement in the diagnosis of dry eye. Curr Eye Res. 1996;15653- 661
PubMed Link to Article
Yokoi  NBron  AJTiffany  JMKinoshita  S Reflective meniscometry: a new field of dry eye assessment. Cornea. 2000;19 (3) supplS37- S43
PubMed Link to Article
Yokoi  NBron  AJTiffany  JMBrown  NAHsuan  JDFowler  CW Reflective meniscometry: a non-invasive method to measure tear meniscuscurvature. Br J Ophthalmol. 1999;8392- 97
PubMed Link to Article
Oguz  HYokoi  NKinoshita  S The height and radius of the tear meniscus and methods for examiningthese parameters. Cornea. 2000;19497- 500
PubMed Link to Article
Scherz  WDoane  MGDohlman  CH Tear volume in normal eyes and keratoconjunctivitis sicca. Albrecht Von Graefes Arch Klin Exp Ophthalmol. 1974;192141- 150
PubMed Link to Article
Taylor  HRLouis  WJ Significance of tear function test abnormalities. Ann Ophthalmol. 1980;12531- 535
Port  MJAAsaria  TS Assessment of human tear volume. J Br Contact Lens Assoc. 1990;1376- 82
Link to Article
Fox  RIRobinson  CCurd  JKozin  FHowell  F Sjögren syndrome: proposed criteria for classification. Arthritis Rheum. 1986;29577- 584
PubMed Link to Article
Schirmer  O Studien zur Physiologie und Pathologie der Träneabsonderung undTränenabfuhr. Albrecht von Graefes Arch Klin Exp Ophthalmol. 1903;56197- 291
Link to Article
Miyata  KSawa  MNishida  TMishima  HMiyamoto  YOtori  T Classification of severity of superficial punctate keratitis. Rinsho Ganka. 1994;48183- 188
Yokoi  NTakehisa  YKinoshita  S Correlation of tear lipid layer interference patterns with the diagnosisand severity of dry eye. Am J Ophthalmol. 1996;122818- 824
PubMed
van Bijstereveld  OP Diagnostic tests in sicca syndrome. Arch Ophthalmol. 1969;8210- 24
PubMed Link to Article
Stern  MEBeuerman  RWFox  RIGao  J-PMircheff  AKPflugfelder  SC The pathology of dry eye: the interaction between the ocular surfaceand lacrimal glands. Cornea. 1998;17584- 589
PubMed Link to Article
Gilbard  JPFarris  RLSantamaria  J  II Osmolarity of tear microvolumes in keratoconjunctivitis sicca. Arch Ophthalmol. 1978;96677- 681
PubMed Link to Article
Gilbard  JPRossi  SRGray  KLHanninen  LAKenyon  KR Tear film osmolarity and ocular surface disease in two rabbit modelsfor keratoconjunctivitis sicca. Invest Ophthalmol Vis Sci. 1988;29374- 378
PubMed
Gilbard  JPCarter  JBSang  DNRefojo  MFHanninen  LAKenyon  KR Morphologic effect of hyperosmolarity on rabbit corneal epithelium. Ophthalmology. 1984;911205- 1212
PubMed Link to Article
Wong  HFatt  IRadke  CJ Deposition and thinning of the human tear film. J Colloid Interface Sci. 1996;18444- 51
PubMed Link to Article
Bron  AJTiffany  JMYokoi  NGouveia  SM Using osmolarity to diagnose dry eye: a compartmental hypothesis anda review of our assumptions. Adv Exp Med Biol. 2002;5061087- 1095
PubMed
Creech  JLDo  LTFatt  IRadke  CJ In vivo tear-film thickness determination and implications for tear-filmstability. Curr Eye Res. 1998;171058- 1066
PubMed Link to Article
Mishima  SMaurice  DM The oily layer of the tear film and evaporation from the corneal surface. Exp Eye Res. 1961;139- 45
PubMed Link to Article
Gilbard  JPRossi  SRHeyda  KG Tear film and ocular surface changes after closure of the meibomiangland orifices in the rabbit. Ophthalmology. 1989;961180- 1186
PubMed Link to Article
Lemp  MA Report of the National Eye Institute/Industry Workshop on clinicaltrials in dry eyes. CLAO J. 1995;21221- 232
PubMed
Mathers  WDDaley  TD Tear flow and investigation in patients with and without dry eye. Ophthalmology. 1996;103664- 669
PubMed Link to Article
Tsubota  KYamada  M Tear evaporation from the ocular surface. Invest Ophthalmol Vis Sci. 1992;332942- 2950
PubMed
Tiffany  JMWinter  NBliss  G Tear film stability and tear surface tension. Curr Eye Res. 1998;8507- 515
PubMed Link to Article

Correspondence

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Accreditation Information
The American Medical Association is accredited by the Accreditation Council for Continuing Medical Education to provide continuing medical education for physicians. The AMA designates this journal-based CME activity for a maximum of 1 AMA PRA Category 1 CreditTM per course. Physicians should claim only the credit commensurate with the extent of their participation in the activity. Physicians who complete the CME course and score at least 80% correct on the quiz are eligible for AMA PRA Category 1 CreditTM.
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For CME Course: A Proposed Model for Initial Assessment and Management of Acute Heart Failure Syndromes
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