Short Tear Film Break-up Time Research Articles

Effects of Carbomer Eye Gels on the Ocular Surface in Dry Eye Patients

Purpose: We investigated the clinical effects of Siccafluid carbomer eye gel on the symptoms, tear film, and ocular surface in dry eye patients.Methods: Fifty-five patients with dry eye syndrome were also treated with carbomer eye gel for 6 months. The Dry Eye Questionnaire (DEQ-5), tear film breakup time (TBUT), Schirmer’s test, and ocular surface staining score were assessed during follow-up. Patients were classified into Sjögren’s syndrome and non-Sjögren’s syndrome groups and the effects of the carbomer eye drops in each group were analyzed.Results: Overall, the dry eye patients showed significant improvement in the total DEQ-5 score, frequency and intensity of dryness, and TBUT 6 months after treatment. In the non-Sjögren’s group, the total DEQ-5 score, intensity of dryness, and TBUT improved, while in the Sjögren’s group, the total DEQ-5 score, frequency and intensity of dryness, and TBUT improved. In both groups, patients with a shorter TBUT showed a significant improvement in the total DEQ-5 score.Conclusions: After 6 months of carbomer eye gel use in patients with dry eye syndrome, the symptoms of ocular dryness and tear film breakup time improved. In patients with dry eye syndrome who have a short TBUT, this can be an effective treatment for alleviating dry eye symptoms.

A Comprehensive Assessment of Tear-Film-Oriented Diagnosis (TFOD) in a Dacryoadenectomy Dry Eye Model.

Tear film instability is a major cause of dry eye disease. In order to treat patients with short tear film breakup time (TBUT)-type dry eye, the development of tear film stabilizing agents is essential. However, the lack of an appropriate animal model of tear film instability has made drug development difficult. Although rabbit dry eye models have been reported in the past, there are only a few reports that focus on tear film instability. Herein, we assessed the tear film stability of a rabbit dry eye model induced by dacryoadenectomy. A clinical evaluation of the ocular surface, interferometry, and histological assessments of the cornea and conjunctiva were performed. Following the removal of the lacrimal glands, TBUT was shortened significantly, with dimple and random breakup patterns prominently observed. Furthermore, the blink rate in this model increased after dacryoadenectomy, suggesting that this model partially captured the phenotypes of human short TBUT-type dry eye and may be useful as an animal model for investigating potential drug candidates.

Short tear film breakup time-type of dry eye in India.

Purpose:The aim of this study was to describe the clinical characteristics and risk factors of short tear film break-up time (TBUT) type of dry eye disease and compare it with other types of dry eye diseases.Methods:This cross-sectional study included 570 patients (≥ 20 years) from the outpatient department using systematic random sampling.Results:The age-adjusted prevalence of short TBUT type of dry eye disease was 5.4% (95% confidence interval: 3.2–6.8%). There was no difference (P > 0.05) between the total and subscale scores of the Ocular Surface Disease Index® questionnaire between patients with short TBUT and those with aqueous tear deficiency. Both these groups differed significantly (P < 0.05) in the findings of TBUT, Schirmer I test, and Lissamine green staining score. The common symptoms in patients with short TBUT type of dry eye disease were eye fatigue (25.4%), heaviness in the eye (19.7%), and an uncomfortable sensation (14.1%). The symptoms in the aqueous tear deficiency group were light sensitivity (28.2%), dryness (19.2%), burning (13.0%), foreign body sensation (12.8%), and blurring of vision (14.1%). The risk factors associated with short TBUT type of dry eye disease were the presence of meibomian gland dysfunction (odds ratio: 3.759 [95% confidence interval: 2.135–6.618], P < 0.0001) and female sex [odds ratio: 1.954 (95% confidence interval: 1.042–3.667), P = 0.037].Conclusion:Patients with short TBUT type of dry eye disease have symptom severity similar to aqueous tear-deficient dry eyes, but the pattern is different. The finding of this type of dry eye disease in India indicates its global presence, and ophthalmologists should consider it in their differential diagnoses.

Ophthalmic Assessment in Patients With Darier Disease

To assess the prevalence of ophthalmic findings in patients with Darier disease, an autosomal dominant genetic skin disorder, in an effort to evaluate the need for eye examinations in the management of the disease. Prospective observational case series. Thirty-six individuals with Darier disease were evaluated by both ocular assessment questionnaire and a comprehensive ophthalmic examination (visual acuity, refraction, external examination, and slit-lamp examination) with emphasis on the eyelids, conjunctiva, and cornea. In addition, questionnaire-based medical interview and skin examination were conducted. According to the medical questionnaire, 39% of patients reported eye problems, 36% dry eye, and 42% eye fatigue after prolonged reading. Ocular examination revealed Darier disease lesions on the eyelids in 55% of the patients, blepharitis in 44%, conjunctival hyperemia in 28%, and short tear film break-up time in 83%. There was no significant relationship between any of these ophthalmic findings and systemic retinoid therapy, sex, or age. The high prevalence of blepharitis and dry eye highlights the importance of ophthalmologic evaluation of patients with Darier disease.

Meibum Expressibility Improvement as a Therapeutic Target of Intense Pulsed Light Treatment in Meibomian Gland Dysfunction and Its Association with Tear Inflammatory Cytokines

Many recent studies have demonstrated the efficacy of intense pulsed light (IPL) for the treatment of meibomian gland dysfunction (MGD); however, its effective treatment targets have not yet been elucidated. This study aimed to investigate the baseline characteristics associated with an improvement in symptoms after IPL treatment; to examine the course of change in inflammatory tear cytokines, meibomian gland function, and tear stability; and to investigate the correlation between cytokines and ocular surface parameters. Thirty participants underwent three sessions of IPL treatment. During each examination, tear film lipid layer interferometry, meibography, tear meniscus height measurement, tear sampling, and slit-lamp examination were performed, and the Ocular Surface Disease Index (OSDI) questionnaire was administered. Meibum quality, meibum expressibility, lid margin abnormality, tear film break-up time (TBUT), ocular surface staining, and the OSDI significantly improved after treatment. Poor meibum expressibility and short TBUT were associated with greater recovery in the OSDI after IPL. Tear levels of IL-4, IL-6, IL-10, IL-17A, and TNF-α decreased after IPL, and IL-6, and TNF-α were correlated with the improvement in meibum expressibility. Therefore, IPL treatment improved meibomian gland function, stabilized the tear film, and decreased ocular surface inflammation. Patients with obstructive MGD and tear instability were more likely to experience an improvement in ocular discomfort after IPL treatment.

Short Tear Film Breakup Time-Type Dry Eye.

Measurement of tear film breakup time (TBUT) has become a standard diagnostic procedure in the dry eye clinic. Short TBUT-type dry eye is characterized by TBUT of less than 5 seconds and dry eye symptoms such as ocular fatigue or dryness; the importance of this type has recently been gaining prominence. Patients with this condition show no reduction in tear production and no staining of the ocular surface. The severity of symptoms is almost the same as in dry eye in which the ocular surface is stained with rose bengal or fluorescein. In addition to discomfort, patients suffer from decreased vision due to the unstable tear film, which can be attributed to the relative abnormality of the lipid layer, aqueous layer, and/or mucin layer. The diagnosis should be performed carefully on the basis of the patient's symptoms and the TBUT test, because the ocular surface appears normal and remains unstained.

Therapeutic effects of 3% diquafosol ophthalmic solution in patients with short tear film break-up time-type dry eye disease

BackgroundTo investigate therapeutic effects of topical diquafosol tetrasodium 3% ophthalmic solution in patients with short tear film break-up time (TFBUT)-type dry eye (DE).MethodsThe prospective study was performed in 70 eyes of 70 patients with short TFBUT-type DE. Diagnosis of short TFBUT-type DE was made based on the presence of DE symptoms, TFBUT value ≤5 s, corneoconjunctival staining score ≤ 2 (on a scale of 0 to 4), and Schirmer I value > 5 mm. Patients with systemic immunologic disorders or ocular graft-versus-host disease were excluded. Before and after instillation of 3% diquafosol ophthalmic solution six times per day for 4 weeks, subjective DE symptoms, TFBUT, corneoconjunctival staining score, and Schirmer I value were examined and compared. Also, demographic factors were compared between patients who showed improvement in each DE parameter by treatment and those who did not.ResultsFour-week treatment with 3% diquafosol ophthalmic solution significantly improved DE symptoms (p < 0.0001), increased TFBUT (p < 0.0001), and reduced corneoconjunctival staining scores (p < 0.0001). Schirmer I values were not changed by treatment. The age of patients who showed improvement in subjective DE symptoms after treatment was significantly lower than that of patients who did not (53.4 ± 27.5 vs. 63.3 ± 13.9 years, p = 0.012). Ocular side effects developed in 3 patients (4.3%), including conjunctival chemosis (n = 1) and persistent stinging sensation (n = 2).ConclusionsDiquafosol tetrasodium 3% ophthalmic solution is effective in improving subjective symptoms and tear film stability in short TFBUT-type DE patients.Trial registrationThe study was retrospectively registered on Clinical Research Information Service (CRiS), Republic of Korea.Trial registration number: KCT0003134.Date of registration: 2018-08-15.

Quality of life measures and health utility values among dry eye subgroups

BackgroundTo determine whether quality of life (QOL) and health utility are affected to the same extent among dry eye (DE) patients with short tear film break-up time dry eye (TBUT-DE) with minimal clinical signs were as severe as aqueous-deficient dry eye (ADDE).MethodsA multicenter cross-sectional study was conducted among DE patients who visited one of 10 eye clinics in Japan. Among the 463 registered patients, this study involved 449 patients with DE who were aged 20 years or older. Ophthalmic examination findings were assessed, including tear film break-up time (TBUT), Schirmer I value, and keratoconjunctival staining score. QOL was evaluated with the Dry Eye-Related Quality-of-Life Score (DEQS; 0 [best], 100 [worst]) and health utility (1 [total health], 0 [worst]) with the Health Utilities Index Mark 3 (HUI-3); scores were stratified by DE subgroup.ResultsMedian (interquartile range) of DEQS and HUI-3 scores across all participants were 21.7 (10.0–40.0) and 0.82 (0.69–0.91), respectively. Median (interquartile range) DEQS and HUI-3 scores in the ADDE group were 23.3 (10.0–40.0) and 0.79 (0.69–0.88), respectively; those in the short TBUT-DE group were 23.3 (13.3–38.3) and 0.82 (0.74–0.92), respectively. There were no significant between-group differences in questionnaire scores. Among the ophthalmic examination findings, a weak significant correlation between TBUT, corneal staining score and keratoconjunctival staining score to DEQS; TBUT and Schirmer test values to HUI-3, were seen.ConclusionsThe burden of short TBUT-DE on QOL as assessed by the DEQS and HUI-3 was as severe as that in ADDE. Our findings suggest that clinicians should be aware of the impact of short TBUT-DE on patients QOL and utility values.Trial registrationUniversity Hospital Medical Information Network (registration no. UMIN 000015890). Registered 10th December 2014, retrospectively registered.

Corneal hyperalgesia in patients with short tear film break-up time dry eye

PurposeTo evaluate corneal tactile and pain sensations in patients with short tear film break-up time dry eye (sBUT DE). MethodsThis study enrolled 60 patients with sBUT DE and 46 healthy volunteers from Japan. We evaluated corneal tactile and pain sensations using a modified method with the Cochet-Bonnet corneal esthesiometer. ResultsPatients with sBUT DE had higher corneal pain sensitivity (26.3 ± 23.1 mm) than healthy subjects (6.9 ± 16.4 mm), but similar corneal tactile sensation (52.0 ± 15.5 mm and 52.9 ± 14.9 mm, respectively). In patients with sBUT DE and corneal hyperalgesia (n = 22, 36.7%), defined as a pain sensitivity ≥40 mm (i.e., the cutoff value at the 95th percentile of corneal pain sensitivity in healthy subjects), a strong significant correlation was found between the subjective pain score and objective corneal pain sensation (R = 0.79). However, for the entire cohort, we found a weak positive correlation between the subjective pain score and objective corneal pain sensation. ConclusionsPatients with sBUT DE were hypersensitive to corneal pain, which suggested that corneal hyperalgesia partly accounted for subjective symptoms in patients with sBUT DE.

Influence of Meibomian Gland Dysfunction and Friction-Related Disease on the Severity of Dry Eye

To evaluate the effect of meibomian gland dysfunction (MGD) and friction-related disease (FRD) on the severity of dry eye disease (DED). Cross-sectional observational study. This study enrolled 449 patients with DED (63 men and 386 women; mean age, 62.6±15.7 years [range, 21-90 years]) for analysis. Subjective symptoms, the ocular surface, tear function, and the presence of MGD and FRD (superior limbic keratoconjunctivitis, conjunctivochalasis, and lid wiper epitheliopathy) were investigated. Schirmer value, tear film breakup time (TBUT), and keratoconjunctival score. We classified the participants into aqueous-deficient dry eye (ADDE; n= 231 [51.4%]) and short TBUT dry eye subtype (TBUT-DE; n= 109 [24.3%]) subgroups. The TBUT was shorter in patients with MGD than in those without MGD, whereas other ocular signs showed no difference (TBUT: MGD present, 1.97±1.02 seconds; MGD absent, 2.94±1.63 seconds [P < 0.001]; ADDE/MGD present, 1.94±1.08 seconds; ADDE/MGD absent, 2.77±1.61 seconds [P < 0.001]; short TBUT-DE/MGD present, 2.07±0.97 seconds; short TBUT-DE/MGD absent, 2.94±1.23 seconds [P= 0.01]). The ADDE patients with FRD showed a worse TBUT than ADDE patients without FRD (TBUT: ADDE/FRD present, 2.08±1.39 seconds; ADDE/FRD absent, 2.92±1.54 seconds; P<0.001). This study showed associations between MGD, FRD, or both and ocular signs in DED. In the presence of MGD, FRD, or both, TBUT was significantly shortened regardless of the dry eye status or subtype.

Effectiveness of Combined Tear Film Therapy in Patients with Evaporative Dry Eye with Short Tear Film Breakup Time

The aim of this study was to evaluate the effectiveness of combined tear film therapy targeted to aqueous, mucin, and lipid layers in patients with refractory evaporative dry eye (EDE) with short tear film breakup time (TBUT). The patients who had EDE with short TBUT and severe symptoms refractory to artificial tears were treated with hyaluronic acid (HA) 0.15% and diquafosol tetrasodium (DQS) 3% (Group 1), HA and carbomer-based lipid-containing eyedrops (Liposic EDO Gel, LPO) (Group 2), or HA, DQS, and LPO (Group 3). Ocular Surface Disease Index (OSDI) score, visual analog scale (VAS) symptom score, TBUT, Schirmer score, and corneal and conjunctival staining scores were evaluated, and noninvasive tear film breakup time (NIBUT) and tear meniscus height were measured using Keratograph® 5 M before and 1 and 3 months after treatment. OSDI scores, VAS scores, TBUT, and NIBUT were improved at 1 and 3 months after treatment in all groups (all P < 0.05). At each follow-up visit, the total OSDI, OSDI symptom, and all VAS scores were significantly lower in group 3 compared with groups 1 and 2 (all P < 0.05). In addition, TBUT and NIBUT were significantly higher in group 3 compared with groups 1 and 2 (all P < 0.05). No significant adverse effects were noted in the groups during treatment. Mucin or lipid-targeting agents combined with aqueous supplements in patients with refractory EDE with short TBUT might improve subjective symptoms and TBUT. Of this, targeting whole tear film layers was most effective in improving ocular symptoms and tear film quality.

Effects of Diquafosol Sodium Eye Drops on Tear Film Stability in Short BUT Type of Dry Eye

To investigate the effects of diquafosol sodium (DQS) eye drops, a purinergic P2Y2 receptor agonist, on tear film stability in patients with unstable tear film (UTF). Two prospective studies were conducted. One was an exploratory nonrandomized trial on 39 eyes with dry eye symptoms and short tear film break-up time (BUT), but without epithelial damage. Changes in symptoms, BUT, Schirmer value, and ocular surface fluorescein staining (FS) scores were studied for 3 months. The other was a randomized clinical trial of DQS and artificial tears (AT) in 17 eyes with short BUT. Eyes with decreased Schirmer values (≤ 5 mm) were excluded. Changes in symptoms, BUT, FS scores, and tear film stability using continuous corneal topographic analysis were studied for 4 weeks. In the exploratory study, while Schirmer values were not significantly increased, significant improvements in symptoms and BUT were noted at both 1 and 3 months. In the randomized clinical trial, significant improvements in symptoms were noted in the DQS group, but not in the AT group, at 2 weeks. BUT was significantly prolonged in the DQS group at 4 weeks but not in the AT group. No significant changes were noted in FS scores or tear film stability. DQS improved subjective symptoms and prolonged BUT in eyes with UTF not associated with low tear secretion and ocular surface epithelial damage. Because many patients who have UTF are refractory to conventional treatments, DQS may offer benefits in the treatment of dry eyes.

Simultaneous Measurement of Tear Film Dynamics Using Wavefront Sensor and Optical Coherence Tomography

PURPOSE. To investigate tear film dynamics using simultaneous measurements of ocular aberrations and lower tear meniscus. METHODS. Simultaneous measurements of wavefront aberration and lower tear meniscus were performed for 11 normal eyes and 7 eyes with short tear film break-up time (SBUT) dry eye, with a tear film break-up time shorter than 5 seconds, using a wavefront sensor and an anterior segment optical coherence tomography (OCT). During the measurement, the subjects were instructed to blink every 6 seconds for a total of 30 seconds. From the measured aberration, root mean square (RMS) wavefront error and volume modulation transfer function (vMTF) induced by changes in tear film dynamics were calculated for a 5-mm pupil. Lower tear meniscus height (TMH) and area (TMA) were estimated from the cross-sectional OCT images of lower tear meniscus. RESULTS. There was a positive correlation between RMS and tear meniscus dimensions and a negative correlation between vMTF and tear meniscus in both groups. There were moderate negative correlations between the postblink initial RMS change and baseline TMH (R = -0.61) and TMA (R = -0.54) in SBUT dry eyes that were stronger than in normal eyes (R = -0.37, R = -0.38). CONCLUSIONS. Tear meniscus dimensions increase with RMS over time, and tear quantity before blink has a significant role in maintaining initial optical integrity, especially in SBUT dry eye. Simultaneous measurement of optical quality and tear meniscus has the potential to improve understanding of tear stability in normal eyes and dry eyes.

Effects of Suppression of Blinking on Quality of Vision in Borderline Cases of Evaporative Dry Eye

To study the effects of suppression of blinking on quality of vision in borderline cases of evaporative dry eye. Ocular higher-order aberrations (HOAs) were measured sequentially for 30 seconds in 10 eyes with a short tear film breakup time (TBUT; 3.0 +/- 0.6 seconds) without ocular surface staining or tear deficiency. During measurements, the subjects suppressed blinking to every 10 seconds, which is more than double the TBUT. The aberration data were analyzed for comalike and spherical-like aberrations and total HOAs to the sixth-order Zernike polynomials. Sequential changes in total HOAs in subjects with a short TBUT showed a sawtooth pattern with a marked upward curve that increased after blinking. From 5 to 9 seconds after blinking, the total HOAs were significantly higher than immediately after blinking (P < 0.001). Serial HOA measurements showed that optical quality might deteriorate in subjects with a short TBUT by suppressed blinking, such as when gazing at a video display terminal, even with sufficient tear volume.