Fluorescein Tear Breakup Time Research Articles

Correlation Between Optical Coherence Tomography–Derived Assessments of Lower Tear Meniscus Parameters and Clinical Features of Dry Eye Disease

To measure the correlation between subjective symptom score, conventional clinical tests, and Fourier-domain optical coherence tomography (FD-OCT) of lower tear meniscus parameters in patients with dry eye disease. Eighteen patients with dry eye disease requiring medical therapy and/or punctal occlusion were recruited for this prospective, nonrandomized, observational case series. Severity of symptoms of dry eye disease was assessed using the Indiana University Dry Eye Questionnaire 2002. Clinical assessments were completed using slit-lamp biomicroscopy, rose bengal dye staining, fluorescein tear breakup time (TBUT), and a 5-minute Schirmer test with topical anesthesia. The lower tear meniscus was imaged using an FD-OCT system with 5-μm axial resolution and measured manually by a masked grader using computer calipers. Correlation was assessed using Spearman correlation coefficient (ρ). The mean (±SD) scaled symptom score was 58 ± 21, with a range of 0 to 100. Vital staining test averaged 1.7 ± 3.4, TBUT averaged 4.4 ± 1.8 seconds, and Schirmer tests averaged 10.2 ± 8.1 mm. As determined by optical coherence tomography, the meniscus height was 228 ± 153 μm, depth was 127 ± 79 μm, and cross-sectional area was 0.018 ± 0.021 mm. Optical coherence tomography meniscus area was negatively correlated with the symptom questionnaire score (P < 0.01) and positively correlated with Schirmer test results (P < 0.01). There was no significant correlation between symptom score and rose bengal staining, TBUT, or Schirmer test results (P > 0.01). Lower tear meniscus measurement with FD-OCT is an objective noninvasive test that correlates well with symptoms of dry eye disease and the Schirmer test.

Tolerability and acceptability of Blephagel: a novel eyelid hygiene aqueous gel

Commonly associated with dry eye, blepharitis is the most commonly encountered disorder in general ophthalmologic practice. Although anti-infective and anti-inflammatory therapies are available, eyelid hygiene is the cornerstone of effective management. A variety of products have been used to assist and encourage eyelid cleansing and massage. The present study examines the ocular and periocular tolerability and acceptability of Blephagel, a cosmetic, poloxamer-containing gel designed specifically for cleansing the eyelid in subjects with sensitive skin or eyes or contact lens users. Subjects with blepharitis and sensitive skin or eyes, a history of atopy, or who use contact lenses applied Blephagel twice daily at home. Clinical ophthalmologic examinations were conducted before and 21 days after aqueous gel application, and subjects completed a questionnaire on the acceptability of the preparation. Thirty-three predominantly female subjects entered and completed the study. A total of 36% of the subjects had used similar products in the past, 21% regularly. Upon questioning by the ophthalmologist, 85% of the subjects reported acceptability of the preparation as good to very good, and 73% rated the efficacy as good to very good. There were minor but statistically non-significant changes in fluorescein tear breakup time and visual acuity before and after 21 days of aqueous gel application. The questionnaire results indicated that the subjects found the product to be effective for cleansing the eyelids of mucus and squama around eyelash roots. Moreover, cosmetic qualities, sensation in use, and acceptability were also appreciated. No subject reported any adverse event considered to be related to the aqueous gel. Although the safety of Blephagel has already been established in standard tests, the current results suggest that it is also pleasant to use and acceptable to blepharitis patients with sensitive skin as an aid to an eyelid hygiene regime.

Upper and Lower Tear Menisci in Sjögren's Syndrome Dry Eye

To measure the tear menisci in Sjögren's syndrome dry eye (SSDE) by optical coherence tomography (OCT) and to determine its relationships with the clinical tests. Twenty-six SSDE, 26 non-SSDE, and 26 control subjects completed the Ocular Surface Disease Index (OSDI) before OCT determination of upper tear meniscus volume (UTMV), lower tear meniscus volume (LTMV), and total tear meniscus volume (TTMV). These were followed by measurements of noninvasive tear breakup time (NITBUT), fluorescein tear breakup time (FTBUT), fluorescein staining, Schirmer test, and corneal confocal microscopy. UTMV, LTMV, and TTMV were the lowest in SSDE among the three groups (P < 0.05). High sensitivity and specificity of UTMV (1.0; 0.96), LTMV (0.92; 0.92), and TTMV (0.96; 0.96) were found in the diagnosis of SSDE. For SSDE, the areas under the UTMV, LTMV, and TTMV receiver operating characteristic curves were larger than those in NITBUT, FTBUT, and Schirmer test (P < 0.005). In the SSDE group, NITBUT was correlated with UTMV (R = 0.41) and TTMV (R = 0.39) (P < 0.05). Fluorescein staining score was significantly correlated with UTMV (R = -0.46), LTMV (R = -0.41), and TTMV (R = -0.53) (P < 0.05). Superficial epithelial cell density was correlated with UTMV (R = 0.18), LTMV (R = 0.51), and TTMV (R = 0.44) (P < 0.05). Tear menisci volumes estimated by OCT may have great potential in the diagnosis and monitoring of SSDE. They can also reflect ocular surface damage and tear film stability.

The Effect of Decreasing the Dosage of Cyclosporine A 0.05% on Dry Eye Disease After 1 Year of Twice-Daily Therapy

To evaluate the effect of decreasing topical cyclosporine 0.05% (tCSA) (Restasis; Allergan, Irvine, CA) from twice-daily dosing to once-daily dosing in patients who have already completed 12 months of twice-daily therapy for dry eye disease. Prospective, randomized, single-masked, parallel group comparison. One hundred patients who had already been treated with tCSA twice daily for more than 1 year were randomized either to continue tCSA twice daily (n = 50) or to decrease tCSA once daily (n = 50). Clinical measurement of dry eye variables was performed for all patients at baseline, 3 months, and 6 months. Mean data were used for within-group (longitudinal analysis) and between-group comparisons (once daily vs. twice daily). Fluorescein tear break-up time, corneal fluorescein staining score, lissamine green staining score, Schirmer tear test, and ocular surface disease index. At the end of the study, patients whose treatment dose was decreased to once daily demonstrated statistically significant improvement in tear break-up time [4.13 seconds (n = 37) vs. 3.11 seconds at baseline (n = 50); P = 0.0003] and lissamine green staining score [4.42 (n = 37) vs. 6.51 at baseline (n = 50); P = 0.024]; fluorescein staining score, Schirmer test results, and ocular surface disease index did not change significantly (P > 0.05). Furthermore, the once-daily group demonstrated significantly superior ocular surface disease index compared with the twice daily group [15.91 (n = 37) vs. 22.62 (n = 48); P = 0.0496]. The remaining outcome measures between once daily and twice daily were not significantly different (P > 0.05). Seven of 50 patients (14%) in the once-daily group (vs. 0% in the twice-daily group) ended the study early because of worsening dry eye symptoms (P < 0.05) and went back to twice-daily dosing. For patients with dry eye that has been controlled with tCSA twice daily for at least 1 year, decreasing to tCSA once daily may still allow suppression of the dry eye disease.

An NGF mimetic, MIM-D3, stimulates conjunctival cell glycoconjugate secretion and demonstrates therapeutic efficacy in a rat model of dry eye

The aim of this study was to evaluate the efficacy of MIM-D3, a small molecule nerve growth factor (NGF) peptidomimetic, as a therapeutic agent in rats with scopolamine induced dry eye. NGF plays an important role in ocular surface maintenance and corneal wound healing and was recently shown to have mucin secretagogue activity in conjunctival cells. We investigated whether MIM-D3 increased glycoconjugate secretion in conjunctival cells in vitro and in rat tear fluids in vivo. Primary rat conjunctival cell cultures were treated with increasing concentrations of MIM-D3 and evaluated for glycoconjugate secretion, proliferation and MAPK1/2 activation. Glycoconjugates were quantitated in tear fluids from normal rats treated topically with increasing doses of MIM-D3 (0.4%, 1% and 2.5%). Dry eye was induced in rats by subcutaneous scopolamine treatment, administered by surgically implanted osmotic pumps for 14 or 28 days. Aqueous tear production, tear clearance, fluorescein corneal staining and tear break-up time (tBUT) were evaluated. Glycoconjugates and NGF were quantitated in the tear fluids by enzyme-linked lectin assay (ELLA) and enzyme-linked immunosorbant assay (ELISA), respectively. We found that 50 μM MIM-D3 statistically significantly induced a 1.3-fold increase in glycoconjugate secretion and a 2.3-fold increase in MAPK1/2 activation without increasing proliferation from conjunctival cell cultures. Application of 2.5% MIM-D3 in normal rat eyes statistically significantly increased tear glycoconjugate concentration by 2.3-fold. In the experimental dry eye model, application of 1% MIM-D3 to rat eyes for either 1 or 17 consecutive days, followed by 1 week of no dosing produced a statistically significant decrease in corneal staining ( p < 0.001), a slight increase in tBUT, and increases in tear glycoconjugates ( p < 0.05) compared to vehicle. Scopolamine treatment also caused a statistically significant increase of endogenous NGF in tears ( p < 0.005). We concluded that the increase in glycoconjugate concentration by the 1% MIM-D3 dose may have improved the quality and stability of the tear film, and thereby improved healing on the ocular surface in dry eye. Therefore, MIM-D3 may have therapeutic potential as a topical agent for the treatment of dry eye.

Tear Dynamics and Corneal Confocal Microscopy of Subjects with Mild Self-Reported Office Dry Eye

To investigate changes in tear dynamics and corneal microstructure in mild self-reported office dry eye. Prospective laboratory investigation. Twenty healthy office workers, 20 office workers with mild self-reported dry eye, and 20 office workers with moderate to severe dry eye as determined by the Ocular Surface Disease Index (OSDI). Real-time anterior segment optical coherence tomography was used to obtain upper (UTMV), lower (LTMV), tear meniscus volumes. The total tear meniscus volume (TTMV) was the sum of the UTMV and LTMV. This was followed by measurement of noninvasive tear breakup time (NITBUT), fluorescein tear breakup time (FTBUT), fluorescein staining, Schirmer I test, and in vivo confocal microscopy of cornea. Upper tear meniscus volume, LTMV, TTMV, NITBUT, fluorescein tear FTBUT, fluorescein staining, Schirmer I test, and in vivo confocal microscopy of cornea. There were no significant differences in UTMV and LTMV between the control and mild self-reported dry eye groups (P>0.05). These values in the moderate to severe dry eye group were significantly lower than those in the control and mild dry eye groups (P<0.01). Both mild and moderate to severe office dry eye groups had decreased NITBUT (P<0.05 each) and FTBUT (P<0.01 each) compared with controls. On the basis of receiver operating characteristic curves, the cutoff value for abnormal FTBUT was 3.3 seconds, yielding good diagnostic accuracy with a sensitivity of 0.75 and specificity of 0.80. For NITBUT, when the cutoff time was 9.7 seconds, the sensitivity was 0.90 and specificity was 0.50. The moderate to severe office dry eye group had decreased Schirmer I test values and increased subbasal nerve tortuosity compared with the mild office dry eye and control groups (P<0.05 each). Both the mild dry eye and moderate to severe dry eye groups had decreased cell densities in superficial, intermediate, and basal epithelial layers compared with the controls (P<0.05 each). Although the quantity of tears in patients with mild self-reported office dry eye was not decreased, ocular surface damage was present.

Screening for Meibomian Gland Disease: Its Relation to Dry Eye Subtypes and Symptoms in a Tertiary Referral Clinic in Singapore

PURPOSE. To study screening methods and associated factors of Meibomian gland disease and dry eye subtypes in a specialized eye clinic in Singapore. METHODS. This cross-sectional study involved 200 patients in a dry eye clinic. The outcome measures evaluated were dysfunctional tear syndrome (DTS) level, meibomian gland disease grade, Schirmer test (ST) result, fluorescein tear break-up time (TBUT), corneal fluorescein staining grade, and irritative eye symptoms. RESULTS. The meibomian gland screening grade was associated with TBUT (P = 0.007), especially in the upper eyelid and correlated with reading difficulty (P = 0.007) and reversibility of symptomatic blurring with lubricants (P = 0.006). An abnormal ST result was associated with early morning discomfort (P = 0.001), and reduced TBUT was linked to discomfort in windy conditions (P < 0.001). In all patients examined, evaporative dry eye (58%) was the most common type, followed by the mixed evaporative and aqueous tear deficiency (30.5%) types. Fluorescein staining in the central and inferior cornea was most severe in the mixed type. CONCLUSIONS. In dry eye patients, screening for meibomian gland disease based on anteriorization of Marx's line may predict a decrease in TBUT and difficulty in performing certain visual-function-related activities. These findings facilitate better understanding of the meibomian gland's contribution to multifactorial dry eye syndrome, apart from routine conventional tests performed in clinics.

Production and Activity of Matrix Metalloproteinase-9 on the Ocular Surface Increase in Dysfunctional Tear Syndrome

To evaluate production and activity of metalloproteinase (MMP)-9 on the ocular surface of patients with dysfunctional tear syndrome (DTS) and determine any correlation between MMP-9 activity and clinical parameters. Forty-six patients with newly diagnosed DTS and 18 control subjects were recruited. Complete ocular surface examinations were performed. Tear MMP-9 activity was assessed with an MMP-9 activity assay in 1 microL of unstimulated tear fluid. Using conjunctival epithelial cells from 19 patients with DTS and 16 controls, levels of MMP-9 and its regulating cytokine mRNA transcripts were evaluated by semiquantitative real-time PCR. Each of four DTS severity-based groups had significantly higher mean MMP-9 activities than did the control group, which was 8.39 +/- 4.70 ng/mL. The DTS4 group had the highest MMP-9 activity (381.24 +/- 142.83 ng/mL), for which the mean was significantly higher than that of other DTS groups. In addition, patients with DTS had significantly higher levels of IL-1beta, IL-6, TNF-alpha, and TGF-beta1 mRNA transcripts in their conjunctival epithelia than did the control subjects. Tear MMP-9 activities showed significant correlation with symptom severity scores, decreased low-contrast visual acuity, fluorescein tear break-up time, corneal and conjunctival fluorescein staining, topographic surface regularity index (SRI), and percentage area of abnormal superficial corneal epithelia by confocal microscopy. Tear MMP-9 activity was significantly higher in patients with DTS. This activity was associated with increased mRNA expression of MMP-9 and its regulating genes and correlated strongly with clinical parameters. MMP-9 appears to be a potentially useful biomarker for diagnosing, classifying, and monitoring DTS.

Tear ferning in contact lens wearers

Tear ferning (TF) has shown good sensitivity and specificity in the diagnosis of dry eye, but is a relatively uncommon test, especially in contact lens wearers. The aim of this study was to investigate the relationship between TF, ocular comfort and tear film stability amongst contact lens (CL) wearers and non-contact lens (NCL) wearers. Subjects (36 NCL, 24 CL; mean age 23.2 +/- 4.8 years) underwent assessment of non-invasive tear break up time (NIBUT), fluorescein tear break up time (FBUT) and completed the Ocular Comfort Index (OCI) questionnaire. Non-stimulated tears were collected from the inferior tear meniscus with a glass capillary. Samples of 1.5 microL were air dried, observed by light microscopy and the TF pattern quantified according to Rolando's grading scale. Significantly higher grades of TF pattern and discomfort (higher OCI scores) were observed in CL wearers compared to NCL wearers (Mann-Whitney U-test; p < 0.005 and p < 0.05 respectively). Differences in tear film stability were not significant between groups. Even when asymptomatic (low OCI scores) CL and NCL subjects were compared, TF remained significantly different (p < 0.005). In both CL and NCL subjects, TF displayed poor correlation with tear film stability tests and OCI scores. Higher TF grades in CL wearers, even if asymptomatic, indicate an unfavourable ratio of salt to macromolecule concentration within the tear film of such subjects. The lack of significant difference in TF between symptomatic CL and NCL wearers could suggest similar aetiology (tear film hyperosmolarity) in each cohort. The TF technique demonstrates limited sensitivity and specificity for the prediction of ocular surface comfort in both CL and NCL wearers.

Conjunctival Cytokine Expression in Symptomatic Moderate Dry Eye Subjects

To compare ocular surface cytokine expression in healthy controls and subjects with moderate dry eye and to study the ability of interleukin (IL)-1beta to modulate cytokine expression in cultured human conjunctival epithelial cells (CECs). Subjective (symptom questionnaire) and objective (tear osmolality, fluorescein tear break-up time [TBUT]) measures of dry eye were determined in five healthy controls and five subjects with moderate dry eye. Tear clearance rates were measured with a fluorophotometer. Enzyme immunoassay and a cytokine bead assay were used to quantify IL-1beta in tear fluid. RT-PCR was performed to detect expression of IL-1beta, IL-6, IL-8, growth-related oncogene (GRO)-beta, intercellular adhesion molecule (ICAM)-1, tumor necrosis factor-related apoptosis-inducing ligand (TRAIL), and ephrin A5 in conjunctival impression cytology (CIC) samples and in CECs (IOBA-NHC cell line, n=3; primary cultured CEC, n=3) exposed to 10 ng/mL IL-1beta for 6 hours. Subjects with moderate dry eye had significantly higher symptom scores, higher tear osmolality, and shorter TBUT than healthy controls. Subjects with dry eye demonstrated slightly slower tear clearance (13.1% per minute) than healthy controls (15.4% per minute). Very low levels of IL-1beta protein were detected in the tear fluid of both groups. TRAIL was constitutively expressed in CIC samples, whereas IL-1beta, IL-6, and GRO-beta were absent. Weak expression of IL-8 (two healthy, four dry eye), ICAM-1 (four healthy, four dry eye), and ephrin A5 (one healthy, two dry eye) was observed. IL-1beta upregulated its own expression and that of IL-6, IL-8, GRO-beta, and ICAM-1 in cultured CECs but not that of ephrin A5 or TRAIL. The lack of major differences in ocular surface cytokine expression between the two groups of subjects implies other inflammatory pathways or etiologies are involved in moderate dry eye. Although IL-1beta modulated the expression of various cytokines in cultured CECs, its absence in tear fluid and CIC samples suggests that IL-1beta does not play a modulatory role in moderate dry eye.

Reflex Epiphora in Patients with Dry Eye Symptoms: Role of Variable Time Schirmer-1 Test

To report reflex epiphora in patients with dry eye symptoms and describe the role of variable time Schirmer-1 test. The study was conducted in 16 consecutive dry eye patients (32 eyes), nine male and seven female, aged 16 to 73 years (mean 48.56-/+16.68 years), presenting with reflex epiphora. Each eye was subjected to Schirmer-1 test and the time elapsed in total wetting of the 35 mm strip from its placement into the conjunctiva was noted and test was graded. This was compared with symptomatology, closed chamber infrared thermometry, humidity, fluorescein tear break-up time (FTBUT), fluorescein stain test, and Lissamine green stain. Schirmer-1 test differentiated reflex epiphora in dry eye patients into groups 0 to 4 based on time it took to wet the 35 mm strip (Group 0 = <=5 min; Group 1 = <=2 min; Group 2 = <=1.5 min; Group 3= <=1 min; Group 4 = <=1/2 min). The score was -0.04 in 8 eyes, -0.03 in 10 eyes, -0.02 in 2 eyes, -0.01 in 6 eyes, and 0.00 in 6 eyes in Groups 4, 3, 2, 1, and 0, respectively. Reflex epiphora had a statistically significant correlation to the symptomatology (p<0.001), lissamine green staining (p<0.001), closed chamber humidity difference (p<0.001), and FTBUT score (p=0.001). Fluorescein stain test and difference in infrared thermometry did not show any correlation. A statistically significant correlation existed between severe and mild to moderate reflex epiphora (p=0.002). However, the two groups separately failed to show any statistically significant relationship with the symptomatology (p=0.16), Lissamine green (p=0.69), humidity difference from close to open eye position (p=0.17), and FTBUT (p=0.25). Thermometry and fluorescein stain test showed no relationship. Schirmer-1 test with variable time quantifies reflex epiphora in dry eye patients, which was significantly related to the other tear function tests.

Decreased Corneal Sensitivity in Patients with Dry Eye

To explore changes in corneal sensitivity that develop in patients with dry eye and the relationship between sensibility and severity of the dry eye disease. Experiments were performed in 44 patients with dry eye and 42 healthy individuals. Corneal sensitivity was measured with the Belmonte noncontact gas esthesiometer. Mechanical (air jets at flow rates from 0 to 200 mL/min, reaching the corneal surface at 34 degrees C), thermal (cold or warm air at subthreshold flow rates changing corneal basal temperature +/-1 degrees C), and chemical stimuli (air containing 0% to 50% CO2 at subthreshold flow rate and temperature at the cornea of 34 degrees C) were applied to the center of the cornea to determine the sensitivity threshold for each stimulus modality. The clinical state of the ocular surface was also explored, measuring the fluorescein tear break-up time, the degree of corneal staining with fluorescein and Lissamine green, and tear production with the Schirmer test. Both in control subjects and patients with dry eye, the corneal thresholds for mechanical, chemical, and thermal stimulation increased with age. Moreover, the thresholds for the three modalities of stimuli were significantly higher in patients with dry eye than in control subjects. In both groups, individual mechanical, chemical, and thermal thresholds correlated significantly. Also, high thresholds in patients with dry eye correlated with the intensity of fluorescein and Lissamine green corneal staining but not with the results of the Schirmer test. Patients with dry eye exhibit corneal hypoesthesia after mechanical, thermal, and chemical stimulation that appears to be related to damage to the corneal sensory innervation.

Preservation of Tear Film Integrity and Inhibition of Corneal Injury by Dexamethasone in a Rabbit Model of Lacrimal Gland Inflammation–Induced Dry Eye

The aim of this study was to establish a clinically relevant short-term animal model of dry eye with utility in identifying compounds with potential therapeutic efficacy. Rabbit lacrimal glands were injected with the T-cell mitogen Concanavalin A (Con A) and inflammation, tear function, and corneal epithelial cell integrity were subsequently assessed. The inflammatory response was characterized by quantifying biochemical markers of inflammation ex vivo and by confirming inflammatory cell influx by histology. Matrix metalloproteinase-9 (MMP-9) and proinflammatory cytokines IL-1beta, IL-8, and TGF-beta1 were quantified in tissue extracts. Tear function was monitored by measuring tear fluorescein clearance and tear breakup time (TBUT). Corneal epithelial cell integrity was determined by quantifying the uptake of methylene blue dye following the exposure of rabbits to a low-humidity environment. The anti-inflammatory corticosteroid, dexamethasone, was administered topically as indicated for each study. Histopathologic evaluation of lacrimal glands injected with Con A revealed a pronounced inflammatory process characterized by lymphocytic infiltration, multifocal necrosis, and fibroplasia. Elevated levels of MMP-9 and cytokines IL-1beta, IL-8, and TGF-beta1 were detected in the lacrimal gland and cornea. Inflammation of the rabbit lacrimal gland following an injection of Con A significantly reduced tear clearance and TBUT and increased susceptibility to desiccation-induced corneal damage. Dexamethasone was prophylactically and therapeutically effective in this inflammation model of dry eye, restoring tear function and inhibiting corneal injury following topical ocular application. Characteristics of this rabbit lacrimal gland inflammation model of dry eye are consistent with the current understanding of dry eye as a local ocular surface inflammatory response to abnormal tear volume and composition. These results suggest that this rabbit model of dry eye may be employed to assess the therapeutic efficacy of mechanistically diverse agents on clinically relevant signs of ocular surface disease. These methods were strategically developed to be applicable for advancing drug discovery for a broad spectrum of dry eye patients.

The repeatability of clinical measurements of dry eye.

The repeatability of individual dry eye diagnostic tests has been reported in the literature on normal samples of patients and to a lesser degree in dry eye patients. In this study, the repeatability of a battery of clinical diagnostic tests for dry eye was assessed on mild to moderate dry eye patients. A dry eye examination was performed on 75 patients on two occasions by a single examiner. The battery of dry eye tests included symptom assessment, contact lens and medical history, slit-lamp biomicroscopic evaluation of the eyelids, evaluation of Meibomian glands, assessment of tear film quality, tear meniscus height, assessment of blink quality, fluorescein tear breakup time (TBUT), fluorescein and rose bengal staining of the cornea and conjunctiva, phenol red thread test, and Schirmer test. The repeatability of subjective report of dryness (kappaW = 0.62) and grittiness (kappaW = 0.73) was moderate to high. In contrast, the repeatability of Meibomian gland disease classification (kappaW = 0.20), presence or absence of inferior corneal fluorescein staining (kappa = 0.25), and inferior conjunctival rose bengal staining (kappa = 0.21) was poor. When a summed staining score of corneal and conjunctival regions was evaluated, weighted kappa reliability was fair. The repeatability of tear breakup time was substantial [95% limits of agreement -5.71 to 5.83 seconds; intraclass coefficient coefficient (ICC) 0.65], and improved when the two timed readings were averaged. Repeatability of the Schirmer test is more variable as wetting scores increase. When the average Schirmer scores </= 10 mm were evaluated, moderate repeatability was demonstrated, indicating that the test performs better with more advanced disease. Although patient-reported symptoms are moderately repeatable from visit to visit, many of the procedures clinically used to diagnose and monitor dry eye syndromes are largely unrepeatable.

The relation between tear film tests in patients with dry eye disease.

The purpose of this report was to investigate the relation between dry eye diagnostic tests. Dry eye patients were enrolled to complete a clinical examination, including the following dry eye tests: a meibomian gland evaluation, tear meniscus height, fluorescein tear breakup time, fluorescein staining of the cornea, the Schirmer 1 test, the phenol red thread test, and rose bengal staining of the conjunctiva. Statistical analyses, including correlation coefficients, the Wilcoxon sign rank test, chi-square test, and logistic regression were used to address the relation between these clinical tests of dry eye. There was a strong relation between the Schirmer test and fluorescein staining in all four statistical analyses. Similarly, there was also a strong relation between the phenol red thread test and both fluorescein and rose bengal staining. Finally, the results of the Schirmer test were associated with the tear breakup time test in three of four analyses. The results indicate that tests of aqueous deficiency (volume or production) are associated with ocular surface desiccation. This important relation should be recognized when choosing dry eye tests as outcomes in clinical trials and epidemiological studies.

Assessing the severity of keratitis sicca with videokeratoscopic indices

Purpose To determine the correlation between the regularity indices of the Tomey TMS-2N computerized videokeratoscopy (CVK) instrument (Tomey, Waltham, MA) with conventional measures of dry eye symptoms and disease. Design A retrospective, clinic-based, case-control study. Participants A total of 16 eyes of 16 asymptomatic normal subjects and 74 eyes of 74 patients with reports of ocular irritation. Methods Corneal surface regularity and potential visual acuity indices of the Tomey TMS-2N CVK instrument were evaluated in patients with ocular irritation symptoms and in normal subjects. Main outcome measures The surface regularity index (SRI), surface asymmetry index (SAI), potential visual acuity index (PVA), and irregular astigmatism index (IAI) of the Tomey TMS-2N were compared between normal and dry-eye patients. Severity of dry-eye symptoms was assessed with a validated questionnaire. Schirmer 1 test (without anesthesia), biomicroscopic meibomian gland evaluation with a composite severity score (MGD score), fluorescein tear break-up time (TBUT), and corneal fluorescein staining were performed. The correlations between CVK indices of the Tomey TMS-2N and the symptom severity score, Schirmer 1 test, MGD score, TBUT, and corneal fluorescein staining score were studied. Results Dry-eye patients had greater mean symptom severity scores, lower Schirmer 1 test scores, greater MGD scores, more rapid TBUT, and greater total corneal fluorescein staining scores ( P < 0.001 for all parameters). The SRI, SAI, and IAI were all significantly greater in dry-eye patients than normal subjects. These were 0.46 ± 0.36 (normal) versus 1.09 ± 0.76 (dry) for the SRI ( P = 0.0017), 0.30 ± 0.15 (normal) versus 0.90 ± 1.09 (dry) for the SAI ( P = 0.0321), and 0.42 ± 0.28 (normal) versus 0.56 ± 0.24 (dry) for the IAI ( P = 0.0321). The PVA index was significantly lower in the dry-eye patients (0.89 ± 0.13) than normal eyes (0.68 ± 0.23; P = 0.0008). The SRI, SAI, and IAI were positively correlated with total and central corneal fluorescein staining scores ( P < 0.00001 for all indices). An SRI (≥0.80), SAI (≥0.50), and IAI (≥0.50) had sensitivities in predicting total corneal fluorescein staining (score ≥ 3) of 89%, 69%, and 82%, respectively. The specificity of these indices was 80%, 78%, and 82%, respectively. In all 90 eyes, the mean SRI was greater in subjects older than 50 years ( P = 0.012) compared with younger patients, whereas no age effect was noted in the dry-eye patients. The SRI and PVA index showed better correlation with symptoms of blurred vision than the best-corrected visual acuity. Conclusions Patients with ocular irritation have an irregular corneal surface that may contribute to their irritation and visual symptoms. Because of their high sensitivity and specificity, the regularity indices of the Tomey TMS-2N have the potential to be used as objective diagnostic indices for dry eye, as well as a means to evaluate the severity of this disease.

Zidovudine in primary Sjögren's syndrome

To evaluate the efficacy of the administration of zidovudine (AZT), an antiretroviral drug, in patients with primary Sjögren's syndrome (SS). Seven female patients (age 57 +/- 8.6 yr) with primary SS were enrolled in an open, uncontrolled trial of AZT (250 mg b.i.d.) for the treatment of primary SS. The efficacy variables were oral and ocular dryness symptoms, fatigue, tender points, physician's and patient's global assessments (GA), ocular function tests (fluorescein tear break-up time, Schirmer's test, Rose Bengal staining) and laboratory parameters [erythrocyte sedimentation rate (ESR), serum IgG, IgA and IgM]. A significant improvement was observed in all subjective manifestations, as well as the objective parameters of ocular dryness. The treatment was well tolerated, except for mild and transitory gastrointestinal disturbances in 6/7 patients. Laboratory parameters did not change significantly. The clinical benefit persisted in 5/7 patients 1 month after the end of therapy. AZT seems to be effective and well tolerated in patients with primary SS.