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To determine the relationships among tear meniscus parameters, noninvasive tear break-up time (NITBUT), and the Schirmer test.Experimental study.Thirty-six subjects were tested on one randomly selected eye. Real-time corneal optical coherence tomography (OCT) was used to image the upper and lower tear menisci during normal and delayed blinking followed by measurement of NITBUT and the Schirmer test. Digital images of the eye were taken for measuring the lid lengths to estimate tear volume in the menisci.Compared with normal blinking, significant increases of tear menisci occurred during delayed blinking (post hoc, P.01). NITBUT was weakly but significantly correlated with the height (r = 0.36; P = .03) and area (r = 0.37; P = .03) of the lower tear meniscus during normal blinks. NITBUT was also correlated with the lower tear meniscus volume (r = 0.45; P.05) and total tear meniscus volume (r = 0.43; P.05) during normal blinking. The Schirmer test was not significantly related to any parameters of the tear menisci, volumes, or NITBUT; however, it was negatively correlated with the age of the subjects (r = -0.47; P = .004). The age was negatively correlated with the upper tear meniscus (r ranged from 0.36 to 0.37 for the radius, height, and area, P.05) measured during delayed blinking.NITBUT appears correlated with the lower tear meniscus during normal blinking, and the Schirmer test appears not correlated with the noninvasively measured tear meniscus.

Purpose To investigate the effects of preoperative Lipiflow (Johnson & Johnson, Jacksonville, FL, USA) treatment before cataract surgery on meibomian gland dysfunction (MGD) and dry eye induced by surgery. Design Prospective, randomized controlled study. Methods This study comprised 124 eyes of 124 patients with planned surgery for senile cataract. Participants were randomly allocated into control and Lipiflow groups based on administration of Lipiflow treatment 3 weeks before cataract surgery. For meibomian gland (MG) evaluation, MG atrophy, degree of gland expressibility, and quality of gland secretions were examined at the baseline visit and 1 and 3 months postoperatively. Ocular surface parameters of tear film break-up time, Oxford corneal staining score, and tear film lipid layer thickness were measured at each visit. Ocular Surface Disease Index and Dry Eye Questionnaire were also assessed. Results The control group exhibited a significant decrease in MG expressibility, worsened meibum quality, decreased lipid layer thickness, and worsened corneal staining after cataract surgery. Also, dry eye symptom showed significant worsening. Conversely, the Lipiflow group showed significantly improved MG patency and meibum quality, increased tear film break-up time, and reduced corneal staining, and presented improved subjective outcomes reported on both Ocular Surface Disease Index and Dry Eye Questionnaire. The improvement of each parameter in the Lipiflow group showed a linear correlation with baseline MGD grade. In addition, patients without baseline MGD showed less worsening or improvement of MGD and dry eye induced by surgery, with preoperative Lipiflow treatment. Conclusions Preoperative Lipiflow treatment conducted before cataract surgery may be a safe and effective intervention for relieving MGD and dry eye induced by surgery. It might be recommended not only for the patients with preoperative MGD but also for those without baseline MGD, to prevent the development of MGD and dry eye induced by ocular surgeries.

Purpose To compare retention rates of Super Flex (Eagle Vision, Memphis, Tennessee, USA; Softplug-Oasis Medical Inc, Glendora, California, USA) vs Parasol (Odyssey Medical, Memphis, Tennessee, USA; Beaver Visitec International, Waltham, Massachusetts, USA) punctal plugs. Design Randomized, double-masked, interventional controlled clinical trial. Methods Institutional study at Hotel Dieu Hospital (Queen's University) of 50 eyes, from patients with moderate to severe dry eye. Each eye from eligible patients was separately randomized to receive Super Flex or Parasol punctal plugs. The main outcome measure was plug retention at 6 months. Secondary outcome measures included objective tests of Schirmer I (mm), tear meniscus height (mm), tear break-up time (s), inferior fluorescein corneal staining (National Eye Institute [NEI] scale), and average lissamine green conjunctival staining (NEI scale). Results Punctal plug retention was significantly different at 6 months ( P = .011). Sixty-eight percent of Parasol plugs were retained compared to 32% of Super Flex plugs. Parasol plugs required less frequent artificial tear use at 6 months ( P = .024). There was a statistically significant improvement in all secondary outcome measures (Schirmer, tear meniscus height, tear break-up time, fluorescein corneal staining) at 6 months within plug groups except conjunctival staining. There were no additional significant differences between groups and no plug complications reported. Conclusions Punctal plugs improve symptoms of moderate to severe dry eye; however, retention rates differ significantly. These data will allow us to guide patient decision making for the safe and effective treatment of punctal plugs for moderate to severe dry eye.

To investigate the dynamic changes of tear fluid after cosmetic transcutaneous lower blepharoplasty.Prospective, observational case series study.A total of 60 eyes of 30 patients with transcutaneous lower blepharoplasty were involved in the study. All subjects completed the Ocular Surface Disease Index questionnaire and underwent tear film break-up time measurements and the Schirmer test before surgery and 1 week, 1 month, and 3 months after surgery. Tear meniscus parameters measured by optical coherence tomography were recorded. Lower lid margin reflex distance was also measured. At each time point after surgery, these parameters were compared with the baseline parameters. The incidence of dry eye and chemosis after surgery was assessed.The Ocular Surface Disease Index score increased significantly 1 week after surgery (P.01). The Schirmer test values were significantly decreased 1 week postoperatively (P.01), and they returned to baseline by 3 months. There was no significant change in tear film break-up time before and after surgery. The tear meniscus height, depth, and cross section area values were significantly increased at 1 week postoperatively, decreased at 1 month (P.01), and returned to baseline at 3 months (P.05). The cornea-lower eyelid angle significantly decreased at 1 week postoperatively (P.01), increased at 1 month (P.01), and returned to baseline by 3 months (P.05). The lower lid margin reflex distance was increased 1 week after surgery (P.01), and gradually recovered but had not returned to the baseline 3 months after surgery (P.01). The increased tear meniscus height had a positive correlation with lower lid margin reflex distance. The incidence of dry eye and chemosis at 1 week postoperatively was 16.7% and 15%, respectively.Cosmetic transcutaneous lower blepharoplasty affects ocular surface and tear fluid, which leads to dryness, tearful eyes, and chemosis. However, this influence is temporary after surgery, and the symptoms resolve within 3 months. A positive correlation between tear meniscus height and lower lid margin reflex distance was observed. Assessment of the tear meniscus with optical coherence tomography provided a quick, noninvasive, and quantitative method to investigate the dynamic changes of the tear fluid after blepharoplasty.

Purpose To determine if controlled environmental conditions can induce acute exacerbations of signs and symptoms in dry eye and asymptomatic subjects. Design Prospective cross-sectional study. Methods Nineteen patients with dry eye and 20 asymptomatic controls were exposed to controlled low humidity (5% relative humidity, desiccating environment) for 2 hours in our Controlled Environmental Research Laboratory at the University of Valladolid. The patients completed the Single-Item Score Dry Eye Questionnaire and the following diagnostic tests were performed before and after exposure: tear osmolarity, phenol red thread test, conjunctival hyperemia, fluorescein tear film break-up time, Schirmer test, and ocular surface vital staining. Sixteen molecules in the tears samples were analyzed by multiplex bead analysis. Results After exposure, the patients and controls had a significant ( P ≤ .003) increase in corneal staining (from 0.68 ± 0.15 to 1.16 ± 0.14 and from 0.50 ± 0.15 to 1.30 ± 0.19, respectively), significantly decreased ( P ≤ .01) fluorescein tear film break-up time values (from 2.78 ± 0.56 seconds to 1.94 ± 0.24 seconds and from 2.81 ± 0.24 seconds to 2.13 ± 0.19 seconds, respectively), and significantly increased ( P ≤ .03) matrix metalproteinase 9 tear levels (from 10 054.4 ± 7326.6 pg/mL to 25 744.5 ± 13 212.4 pg/mL and from 10 620.5 ± 4494.3 pg/mL to 16 398.7 ± 5538.3 pg/mL, respectively). In the control group, the epidermal growth factor tear levels decreased significantly ( P = .007; from 1872.1 ± 340.7 pg/mL to 1107.1 ± 173.6 pg/mL), and interleukin 6 levels increased significantly ( P Conclusions Adult patients with mild-to-moderate dry eye and asymptomatic subjects of similar ages can experience acute exacerbation in an environmental chamber that resembles the sudden worsening that patients with dry eye experience daily.

PURPOSE To investigate the corneal endothelium damage in Graves ophthalmopathy (GO) and its role as a promising quantitative index to evaluate GO activity. DESIGN Cross-sectional study. METHODS This study included 128 eyes of 64 patients with GO. All subjects underwent ophthalmologic examinations, including proptosis, tear break-up time (BUT), corneal fluorescein staining, and Schirmer test. Corneal endothelium was measured by noncontact specular microscope and ocular biometric parameters were measured by IOLMaster 700. Each eye was assigned a specific clinical activity score (CAS), then grouped as active (CAS ≥3 points) or inactive (CAS

To investigate ocular anomalies in joint hypermobility syndrome/Ehlers-Danlos syndrome, hypermobility type (JHS/EDS-HT).Prospective, cross-sectional study.Forty-four eyes of 22 consecutive patients with an established diagnosis of JHS/EDS-HT and 44 eyes of 22 age- and gender-matched control subjects. Administration of a standardized questionnaire (Ocular Surface Disease Index) and a complete ophthalmologic examination, including assessment of best-corrected visual acuity, slit-lamp biomicroscopy, intraocular pressure measurement, indirect ophthalmoscopy, tear-film break-up time, Schirmer I testing, axial length and anterior chamber depth measurement, corneal topography, corneal pachymetry, and confocal microscopy. Main outcome measures included comparing ocular anomalies in JHS/EDS-HT and control eyes.JHS/EDS-HT patients reported dry eye symptoms more commonly than controls (P.0001). Scores of tear-film break-up time and Schirmer I test were significantly lower in JHS/EDS-HT eyes (P.0001). Minor lens opacities were significantly more common in the JHS/EDS-HT group (13.6%; P.05). Pathologic myopia with abnormal vitreous was found in 7 JHS/EDS-HT eyes (15.9%) and 0 controls (P = .01). Corneas were significantly steeper and the best-fit sphere index was significantly higher in JHS/EDS-HT group (P.01). By confocal microscopy, the JHS/EDS-HT group showed lower density of cells in the superficial epithelium (P.001) and higher density of stromal keratocytes in anterior and posterior stroma (P.0001).The most consistent association of eye anomalies in the JHS/EDS-HT group included xerophthalmia, steeper corneas, pathologic myopia, and vitreous abnormalities, as well as a higher rate of minor lens opacities. These findings indicate the need for ophthalmologic survey in the assessment and management of patients with JHS/EDS-HT.

To evaluate the effect of contact lens (CL) wear and visual display terminal (VDT) work on the ocular surface and tear functions.Prospective case-control study.Sixty-nine CL wearers (45 women and 24 men; mean age, 35.2 ± 7.3 years), and 102 age- and sex-matched non-CL wearers were enrolled in the study (66 women and 36 men; mean age, 36.7 ± 7.3 years). Ocular surface and tear function tests, including vital stainings (fluorescein and rose bengal), Schirmer test, tear meniscus height measurement, and tear film break-up time were performed. The subjective symptoms of dry eyes were evaluated using a dry eye symptom questionnaire. The participants were divided into 4 subgroups according to the total time of VDT work in 1 day (VDT work time in 1 day ≥ 4 hours or4 hours) and presence of CL wear. Main outcome measures included ocular surface vital staining scores, Schirmer test results, tear film break-up time, tear meniscus height measurement, and symptom questionnaire score.CL users and long-term VDT workers showed significantly worse tear meniscus height values than non-CL users and short-term VDT workers (P.001). The mean visual symptom scores in CL wearers and long-term VDT workers were significantly higher than the other groups (P.001).Office workers who wore CLs and spent more than 4 hours engaged in VDT work had a lower tear meniscus volume with significant dry eye and visual symptoms triggered by environmental factors.

Purpose To measure the sparkle of the human eye evaluated by the intensity of corneal light reflection in normal subjects and dry eye patients to investigate whether ocular surface wetness has an impact on the sparkle of the eye. Design Prospective case-control study. Methods We examined a consecutive series of eight dry eye patients with Sjogren syndrome (SS, 15 eyes), as well as eight normal subjects (16 eyes). The specular corneal surface light reflection was quantitatively measured with an ophthalmic slit-lamp microscope and image capturing system under fixed conditions of light source, incident angle, and detector sensitivity. The intensity of images from subjects' corneal light reflection was quantified with image analysis software along with the measurement of grade of self-reported brilliancy of the eye, corneal fluorescein staining score, tear film break-up time, and Schirmer test value. The intensity of corneal light reflection was also compared before and after dry eye treatment. Results The mean intensity of corneal light reflection was significantly lower in dry eye patients (125.0 ± 40.1) than normal subjects (167.6 ± 36.6, P = .004). Grade of self-reported brilliancy of the eye, corneal fluorescein staining scores, tear film break-up time, and Schirmer test values showed good correlation to the intensity of corneal light reflection. After punctal plug treatment, the intensity of corneal light reflection significantly increased from 125.0 ± 40.1 to 167.2 ± 45.0 (P Conclusions The intensity of corneal light reflection representing the sparkle of the eye was significantly more intense in normal subjects compared to dry eye patients, and was increased after punctal plug treatment. The intensity of corneal light reflection appeared to correlate well with tear film stability, volume, and ocular surface desiccation. We showed that tears contributed not only to ocular surface wetness but also to the extent of the light reflection from the eye.

Purpose To evaluate the use of tear osmolarity in the diagnosis of dry eye disease. Design A prospective, observational case series to determine the clinical usefulness of tear osmolarity and commonly used objective tests to diagnose dry eye disease. Methods A multicenter, 10-site study consisting of 314 consecutive subjects between 18 and 82 years of age. Bilateral tear osmolarity, tear film break-up time (TBUT), corneal staining, conjunctival staining, Schirmer test, and meibomian gland grading were performed. Diagnostic performance was measured against a composite index of objective measurements that classified subjects as having normal, mild or moderate, or severe dry eye. The main outcome measures were sensitivity, specificity, area under the receiver operating characteristic curve, and intereye variability. Results Of the 6 tests, tear osmolarity was found to have superior diagnostic performance. The most sensitive threshold between normal and mild or moderate subjects was found to be 308 mOsms/L, whereas the most specific was found at 315 mOsms/L. At a cutoff of 312 mOsms/L, tear hyperosmolarity exhibited 73% sensitivity and 92% specificity. By contrast, the other common tests exhibited either poor sensitivity (corneal staining, 54%; conjunctival staining, 60%; meibomian gland grading, 61%) or poor specificity (tear film break-up time, 45%; Schirmer test, 51%). Tear osmolarity also had the highest area under the receiver operating characteristic curve (0.89). Intereye differences in osmolarity were found to correlate with increasing disease severity ( r 2 = 0.32). Conclusions Tear osmolarity is the best single metric both to diagnose and classify dry eye disease. Intereye variability is a characteristic of dry eye not seen in normal subjects.

To compare tear film thickness between normal subjects and aqueous tear deficiency dry eye patients by tear interferometry.Prospective case-control study.Central precorneal tear film thickness was measured noninvasively using an interference thin-film thickness measurement device (Quore MSPA1100; Mamiya-OP). Tear film thickness of 14 eyes from 14 normal subjects and of 28 eyes from 28 aqueous tear deficiency dry eye patients were compared along with noninvasively measured tear meniscus height, DR-1 (Kowa) dry eye severity grading, fluorescein and rose bengal staining scores, tear film break-up time, and Schirmer test results. Among dry eye patients, 13 eyes underwent punctal occlusion, and tear film thickness was compared before and after the surgery.Tear film was significantly thinner in dry eye patients (2.0 ± 1.5 μm) than normal subjects (6.0 ± 2.4 μm; P.0001). Tear film thickness showed good correlation with other dry eye examinations. After punctal occlusion, tear film thickness increased significantly from 1.7 ± 1.5 μm to 4.9 ± 2.8 μm (P = .001) with the improvement of tear meniscus height, fluorescein and rose bengal staining scores, tear film break-up time, and Schirmer test values.Interferometric tear film thickness measurement revealed impaired precorneal tear film formation in aqueous tear deficiency dry eyes and was useful for showing the reconstruction of tear film after punctal occlusion surgery. Interferometry of precorneal tear film may be helpful for the evaluation of aqueous tear deficiency in conjunction with other dry eye examinations.

Purpose 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. Design Prospective observational case series. Methods 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. Results 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. Conclusions The high prevalence of blepharitis and dry eye highlights the importance of ophthalmologic evaluation of patients with Darier disease.

To examine the effect of combined blepharoplasty and Müller muscle-conjunctival resection (MMCR) compared to an upper blepharoplasty on dry eye syndrome.Prospective, comparative clinical study.This is prospective, comparative case series. Two groups of patients participated in this study: the blepharoplasty group included adult patients with dermatochalasis and the ptosis group consisted of adult patients with dermatochalasis and ptosis that showed significant improvement after phenylephrine 10% instillation. The following parameters were compared for all patients before the procedure (baseline) and on postoperative day 90: MRD1, Ocular-Surface-Disease-Index (OSDI), Schirmer test 2, tear break-up time (TBUT), fluorescein staining, Lissamine-green staining (LG).Fifty-four patients participated in this study (blepharoplasty group: 23 patients, ptosis group 31 patients). There were significant increases in the postoperative LG scores and in fluorescein staining post ptosis surgery compared with the preoperative values (paired t test, P = .05 and P = .02, respectively). The postoperative OSDI score was significantly higher post ptosis surgery compared with the preoperative score (25.38 vs 17.24, respectively, paired t test, P.01). There were no significant differences, in the blepharoplasty group, between the postoperative and preoperative objective and subjective dry eye tests.MMCR surgery causes an increase in the subjective feeling of dry eye as well as an increase of signs of dry eye. This increase was not noticed after blepharoplasty surgery. Physicians should be aware of the risk of dry eye after ptosis surgery and discuss dry eye as a complication of MMCR surgery with their patients before surgery. Those patients should be examined carefully and treated for dry eye during follow-up.

To evaluate efficacy of topical rebamipide for superior limbic keratoconjunctivitis (SLK) in patients with thyroid eye disease.Retrospective, observational case series.Thirty-three eyes from 20 thyroid eye disease patients with SLK who received topical rebamipide (Mucosta ophthalmic suspension unit dose 2%; Otsuka Pharmaceutical Co, Ltd; chemical name, (2RS)-2-(4-chlorobenzoylamino)-3-(2-oxo-1, 2-dihydroquinolin-4-yl) propanoic acid) were included. The following items were evaluated before and 4 weeks after the start of treatments: presence or absence of SLK, rose bengal staining score, area and density classification of fluorescein staining, Schirmer test I results (without topical anesthesia), tear film break-up time, Hertel exophthalmometry values, and margin reflex distances 1 and 2.Twenty-eight eyes showed complete disappearance of SLK after treatment (84.8%; P.001). The other 5 eyes (15.2%) demonstrated significant improvement, but had residual punctate rose bengal staining and fluorescein staining near the superior corneal limbus. All 5 eyes exhibited at least 1 of the following findings: proptosis of more than 17.7 mm and upper or lower eyelid retractions or both. Incidence of upper eyelid retraction was significantly higher in eyes with SLK than in those without SLK at the 4-week follow-up (P = .021). The severity of rose bengal staining and fluorescein staining improved significantly after treatment (P.001). Although the Schirmer test results remained constant before and after the treatment (P = .212), tear film break-up time increased significantly in the posttherapeutic state (P = .009). No serious adverse events were reported.Topical rebamipide improved SLK in patients with thyroid eye disease, suggesting a first-line treatment in such patients.

PURPOSE: To classify subtypes of meibomian gland dysfunction (MGD) and evaluate the dependency of dry eye signs, symptoms, and parameters on MGD subtype. DESIGN: Cross-sectional study. Study Population: the right eyes of 447 patients with MGD of various subtypes and 20 healthy volunteers. METHODS: Patients were divided into 4 subtypes of MGD based on meibum expression, meibum quality, and MG loss on meibography images (meibograde of 0-6). Subtypes were patients with high meibum delivery (hypersecretory and nonobvious MGD) and those with low meibum delivery (hyposecretory and obstructive MGD). Additional clinical tests included tear film break-up time (TFBUT), ocular staining, osmolarity, Schirmer I, blink interval timing and the Ocular Surface Disease Index (OSDI) questionnaire. RESULTS: A total of 78 eyes had hypersecretory MGD; 49 eyes had nonobvious MGD; 66 eyes had hyposecretory MGD; and 254 eyes had obstructive MGD. Increased tear film osmolarity and lower TFBUT were found in the low-delivery groups; hyposecretory (P = 0.006, P = 0.016) and obstructive MGD (P = 0.008, P = 0.006) relative to high-delivery MGD (hypersecretory and nonobvious groups, respectively). Worse ocular symptoms and ocular staining were also found in low-delivery MGD groups than the high delivery MGD groups (P amp;lt; 0.01 and P amp;lt; 0.006, respectively). " CONCLUSIONS: Patients with low-delivery MGD had worse dry eye parameters and ocular symptoms than those with high meibum delivery, indicating the pivotal role of meibum secretion in ocular surface health that should be targeted in MGD therapy. Furthermore, nonobvious MGD cannot be diagnosed using conventional dry eye tests and requires morphologic assessment of meibography images to confirm MG loss. ((C) 2019 The Author(s). Published by Elsevier Inc. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).)

To evaluate the newly developed Ocular Surface Thermographer (TOMEY Corporation) for dry eye screening.Prospective, controlled study.We studied 30 eyes of 30 patients diagnosed with dry eye (mean age ± standard deviation, 52.9 ± 17.1 years) and 30 eyes of 30 normal subjects (42.7 ± 17.0 years). The ocular surface temperature was measured immediately after eye opening and every second during 10 seconds of eye opening. The reliability of the measurements was determined by calculating intraclass correlation coefficients. Then, the correlations between the change in the ocular surface temperature and tear film break-up time, Schirmer I test values, and fluorescein staining scores were determined.The measurements of the ocular surface temperature had a high degree of reliability. Immediately after eye opening, the temperature in the dry eye did not differ significantly from that in normal eyes in any of the 3 regions tested. The decrease in the ocular surface temperature in dry eyes was significantly greater than that in normal eyes (P.001) at 10 seconds after eye opening. The decrease in the temperature of the cornea was correlated significantly with the tear film break-up time (r = -0.572; P.001). When the changes in ocular surface temperature of the cornea were used as an index for dry eye, the sensitivity was 0.83 and the specificity was 0.80 after 10 seconds.Measurements of the ocular surface temperature obtained with our newly developed Ocular Surface Thermographer after 10 seconds of eye opening may provide a simple, noninvasive screening test for dry eyes.

To enhance the understanding of dry eye (DE) in diabetes by evaluating the ocular surface characteristics and the levels of tear inflammatory cytokines.Cross-sectional study.Subjects were divided into 4 groups: 32 patients in the diabetes with DE group; 24 patients in the diabetes without DE group; 28 patients in the nondiabetes with DE group; and 29 volunteers in the normal group. Ocular surface disease index (OSDI) was self-answered and ocular surface characteristics including tear film break-up time (BUT), Schirmer I test, corneal fluorescein staining (CFS), and corneal sensitivity were evaluated. Concentrations of epidermal growth factor (EGF), IL-17A, IL-1β, and tumor necrosis factor alpha (TNF-α) were measured by mutiplex bead analysis. Spearman correlations between cytokines and ocular surface parameters were calculated.The level of EGF in tears significantly increased in the diabetes with DE group and positively correlated with the CFS and negatively correlated with the Schirmer I test in this group (P.05). No differences were found in the levels of IL-17A, IL-1β, and TNF-α in the diabetes with DE and diabetes without DE groups compared to the normal group (P .05). The nondiabetes with DE group showed increased levels of IL-17A, IL-1β, and TNF-α in tears compared to the normal group and the levels of IL-1β and TNF-α in tears positively correlated with CFS (P .05).Our study showed that levels of EGF in tears have potential to be the diagnostic biomarker of DE in diabetes. No differences of IL-17A, IL-1β, and TNF-α in tears were found between the diabetes with DE and normal group, suggesting different pathogenesis of diabetes DE vs nondiabetes DE.

Purpose To investigate the relationship between meibomian gland (MG) morphology and clinical dry eye tests in patients with meibomian gland dysfunction (MGD). Design Cross-sectional study. Subjects Total 538 MGD patients and 21 healthy controls. Methods MG loss on meibography images of upper (UL) and lower lids (LL) was graded on a scale of 0 (lowest degree of MG loss) to 3. MG length, thickness, and interglandular space in the UL were measured. Clinical tests included meibum expression and quality, tear film break-up time, ocular staining, osmolarity, Schirmer I, blink interval timing, and Ocular Surface Disease Index (OSDI) questionnaire. Results Mean UL and LL meibogrades were significantly higher in MGD patients compared to controls (P < .001 for UL and LL). The sensitivity and specificity of the meibograde as a diagnostic parameter for MGD was 96.7% and 85%, respectively. Schirmer I was significantly increased in MGD patients with meibograde 1 compared to patients with meibograde 0, 2, and 3 in the UL (P < .05). MG thickness increased with higher meibograde (P < .001). MG morphology correlated significantly but weakly with several clinical parameters (P < .05). OSDI did not correlate with any MG morphologic parameter. Conclusions Grading of MG loss using meibograde effectively diagnoses MGD. Compensatory mechanisms such as increased aqueous tear production and dilation of MGs make early detection of MGD difficult by standard clinical measures of dry eye, whereas morphologic analysis of MGs reveals an early stage of MGD, and therefore represents a complementary clinical parameter with diagnostic potential.

To evaluate the efficacy, safety, and quality of life (QOL) of transdermal androgen in treatment of dry eye patients associated with androgen deficiency.Randomized controlled trial.Fifty patients with dry eye from a tertiary eye center in northern Thailand were randomized to receive transdermal androgen (AndroGel; Besins Healthcare, Brussels, Belgium) or placebo for 4 weeks. Main outcome measures were symptoms and signs of dry eye. Serum level of sex hormone and QOL questionnaires were also evaluated at the baseline and after treatment.After 4 weeks, the Ocular Surface Disease Index decreased significantly in the AndroGel group compared to the placebo (-14.36 ± 7.76 vs 0.14 ± 14.60, P.001). Significant improvements of tear break-up time (7.40 ± 3.37 vs -1.14 ± 1.68 seconds, P.001), corneal fluorescein staining (-0.62 ± 0.30 vs 0.19 ± 0.37, P.001), and Schirmer test (6.84 ± 5.10 vs -0.48 ± 2.14 mm, P.001) were observed in the AndroGel group compared to the placebo. Serum testosterone in female patients significantly increased in the AndroGel group compared to the placebo (P.001), while no different change was observed in serum testosterone in male subjects and the sex hormone-binding globulin in both groups. In the AndroGel group, 20% of patients had oily skin and 4% had acne. No serious adverse effects were reported. The menopause rating score improved significantly in the AndroGel group compared to the placebo (P.001), while the aging male symptoms were not different in both groups (P = .589).Transdermal androgen was effective in relieving symptoms and signs of dry eye as well as improving QOL in aging patients. There were no serious side effects during a short-term treatment.

Purpose Previous studies have suggested an association between dyslipidemia and meibomian gland dysfunction (MGD). The aim of this prospective, nonrandomized clinical study is to evaluate the possible association of dyslipidemia and its treatment with meibomian gland (MG) morphologic changes by standardized meibography. Design Prospective, nonrandomized clinical study. Methods Two groups of participants were enrolled: group 1, comprised of patients under regular 3-hydroxy-3-methyl-glutaryl-coenzyme A (HMG-CoA) reductase inhibitor (statin) treatment for dyslipidemia, and group 2, those with newly diagnosed dyslipidemia who were under lifestyle interventions. Meibography was performed at baseline and at both the 6- and 12-month visits and were graded by meiboscores. Participants underwent slit lamp examination for signs of changes in meibum quality and MG lid morphologic features. The Ocular Surface Disease Index questionnaire was given to measure subjective symptoms of ocular surface disease. Dry eye parameters including tear meniscus height, noninvasive first and average tear film break-up time, and Schirmer test results were also recorded. Results Ninety-eight participants completed this longitudinal study over 12 months. There were statistically significant changes in total meiboscores (P = .01) and upper eyelid meiboscores (P = .012), lid margin abnormality scores (P = .0059), and meibum quality (P = .0002) in the statin group during follow-up visits. Similar changes of upper eyelid meiboscores (P = .046) and meibum quality (P = .046) were noted in the nonstatin group. Conclusion Meibomian gland atrophy and deterioration of meibum quality continued in the long term among participants with dyslipidemia even under statin usage.

To evaluate the relationship between subjective symptoms and clinical signs in dry eye disease (DED) in office workers using visual display terminals (VDTs).Cross-sectional study.This study involved 672 Japanese young and middle-aged office workers who use VDTs. The subjects completed questionnaires designed to detect subjective symptoms and risk factors for DED. Dry eye tests, including tear film break-up time (TBUT), corneal-conjunctival staining with fluorescein and lissamine green, and the Schirmer test, were performed. Based on the Japanese diagnostic criteria for DED, the subjects were classified into 3 groups: definite DED, probable DED, and non-DED. Between each group, subjective symptoms and clinical signs were compared.Of the 672 subjects, 561 (374 male, 187 female) completed the questionnaire (response rate: 83.5%). Definite DED was diagnosed in 65 subjects (11.6%), probable DED in 303 subjects (54.0%), and non-DED in 193 subjects (34.4%). The mean subjective symptom score was significantly less in subjects with probable DED (2.05 ± 0.42) and non-DED (1.63 ± 0.38) than in those with definite DED (2.19 ± 0.40) (P.05 and P.01, respectively). In the subjects with probable DED, a subgroup with positive subjective symptoms and abnormal TBUT (≤5 seconds) was categorized as short TBUT-type DED, and it was found that they had a higher subjective symptom score (2.09 ± 0.40), equivalent to that of those with definite DED (P = .269).Despite no or minor epithelial damage, the severity of subjective symptoms was greater in short TBUT-type DED, most likely attributable to tear film instability. Thus, it might prove important to evaluate TBUT to successfully treat those patients.

To investigate relationships between local tear osmolarity and tear film characteristics and dry eye disease (DED) symptoms.Prospective, cross-sectional, observational study.Nasal and temporal tear osmolarity were measured in subjects with DED. The difference between nasal and temporal tears (OSM difference) was then calculated. Ocular symptoms were evaluated and tear break-up time (TBUT), corneal fluorescein staining score (CFSS), eyelid hyperemia, and tear production were measured. Correlations between DED symptoms and nasal tear osmolarity, temporal tear osmolarity, OSM difference, and tear film characteristics were evaluated using Pearson correlation analyses. Subjects were divided into 3 groups based on OSM difference: the temporal group had a temporal osmolaritynasal osmolarity, the nasal group had a temporal osmolaritynasal osmolarity, and the equal group had an OSM difference10 mOsm/L.Forty-eight eyes of 48 subjects were included. Eleven eyes were in the temporal group, 17 eyes were in the equal group, and 20 eyes were in the nasal group. Temporal osmolarity, nasal osmolarity, and OSM difference were not correlated with TBUT, CFSS, lid hyperemia, or tear production. Nasal tear osmolarity was correlated with cold sensitivity frequency (r = 0.298, P = .040), foreign body sensation severity (r = 0.293, P = .043), and light sensitivity severity (r = 0.293, P = .043). Additionally, OSM difference was correlated with daily symptom frequency (r = 0.339, P = .019).Nasal tear osmolarity and OSM difference play an important role in DED symptoms. Lid hyperemia, TBUT, CFSS, and tear secretion volume are not significantly affected by tear osmolarity. It is important to measure both nasal and temporal tear osmolarity when evaluating patients with DED.

To evaluate occurrence of subtarsal fibrosis in patients with graft-vs-host disease (GVHD) and to determine its association with ocular surface epitheliopathy.Cross-sectional study.We enrolled 40 patients with moderate or severe dry eye disease, including 20 patients with chronic ocular GVHD and 20 patients without (as the control group). All patients had a comprehensive ophthalmic assessment including evaluation for subtarsal fibrosis, corneal and conjunctival staining, tear break-up time (TBUT), and Schirmer test. Furthermore, meibomian gland drop-out area and densities of epithelial and stromal immune cells were measured using meibography and in vivo confocal microscopy, respectively.Subtarsal fibrosis was not seen in any eye of the non-GVHD group. However, 16 eyes (40%) of 10 patients (50%) in the GVHD group had subtarsal fibrosis (P.001) with an average involvement of 28.9% ± 13.7% of the tarsal area. Fibrosis was more frequent in the upper lids (35%) than in the lower lids (5%). Regression analyses showed that corneal fluorescein staining was significantly associated with the extent of fibrosis (P.001, β = 0.14) and TBUT (P.001, β = -0.53) but not with other clinical or imaging parameters. Conjunctival lissamine green staining also had a statistically significant association with the extent of fibrosis (P = .04, β = 0.12) but not other clinical or imaging parameters. Eyes with subtarsal fibrosis had a more severe ocular surface epitheliopathy compared with eyes without fibrosis.Subtarsal fibrosis is present in a significant percentage of patients with chronic ocular GVHD, likely contributing to the ocular surface damage in these patients.

Producción Científica, To evaluate the response of the lacrimal function unit in Sjogren syndrome (SS)-associated dry eye patients exposed to 2 simulated daily life environ-mental conditions. Fourteen female SS dry eye patients were exposed for 2 hours to a controlled normal condition (23 C, 45% relative humidity, and air flow 0.10 m/s) and a controlled adverse condition that simulates desic- cating stress (23 C, 5% relative humidity, and air flow 0.10 m/s). The following dry eye tests were performed before and after the exposure: tear osmolarity, phenol red thread test, conjunctival hyperemia, fluorescein tear break-up time, corneal fluorescein staining, conjunctival lissamine green staining, and Schirmer test. Levels of 16 molecules were analyzed in tears by multiplex immu- nobead analysis., Junta de Castilla y León (programa de apoyo a proyectos de investigación – Ref. VA174U14)

Purpose To compare corneal sensitivity in tear dysfunction due to a variety of causes using contact and noncontact esthesiometers and to evaluate correlations between corneal sensitivity, blink rate, and clinical parameters. Design Comparative observational case series. Methods Ten normal and 33 subjects with tear dysfunction (meibomian gland disease [n = 11], aqueous tear deficiency [n = 10]—without (n = 7) and with (n = 3) Sjogren syndrome (SS)—and conjunctivochalasis [n = 12]) were evaluated. Corneal sensitivity was measured with Cochet-Bonnet and air jet esthesiometers and blink rate by electromyography. Eye irritation symptoms, tear meniscus height, tear break-up time (TBUT), and corneal and conjunctival dye staining were measured. Between-group means were compared and correlations calculated. Results Compared with control (Cochet-Bonnet 5.45 mm, air esthesiometer 3.62 mg), mean sensory thresholds were significantly higher in aqueous tear deficiency using either Cochet-Bonnet (3.6 mm; P = .003) or air (11.7 mg; P = .046) esthesiometers, but were not significantly different in the other groups. Reduced corneal sensitivity significantly correlated with more rapid TBUT and blink rate and greater irritation and ocular surface dye staining with 1 or both esthesiometers. Mean blink rates were significantly higher in both aqueous tear deficiency and conjunctivochalasis compared with control. Among all subjects, blink rate positively correlated with ocular surface staining and irritation and inversely correlated with TBUT. Conclusion Among conditions causing tear dysfunction, reduced corneal sensitivity is associated with greater irritation, tear instability, ocular surface disease, and blink rate. Rapid blinking is associated with worse ocular surface disease and tear stability.

To compare the effect of Epi-LASIK or Laser In Situ Keratomileusis (LASIK) on corneal sensitivity and tear function.Prospective, non-randomized comparative clinical trial.Seventy-nine eyes (Group A) underwent Epi-LASIK and 61 eyes underwent LASIK (Group B) for the treatment of myopia. Matching parameters between the groups were age and attempted correction. Corneal sensitivity, tear break-up time (BUT), and Schirmer test II were evaluated before and at one, three, and six months after the procedure.Corneal sensitivity and BUT were decreased at one month in Group A (P.001) to be restored by the third month (P = .71 and P = .58, respectively). In Group B, corneal sensitivity and BUT were reduced postoperatively (P.001). There was a significant difference in corneal sensitivity between the two groups at all postoperative intervals. Schirmer test II was not significantly decreased postoperatively in Group A. In Group B, it was decreased at one and three months and restored by the sixth month.Epi-LASIK-treated eyes had faster rehabilitation of corneal sensitivity and tear function than LASIK-treated eyes.

Purpose To evaluate the possible advantages of combination therapy with diquafosol tetrasodium and sodium hyaluronate for dry eye after laser in situ keratomileusis (LASIK). Design Prospective randomized comparative trial. Methods A total of 206 eyes of 105 patients who underwent LASIK were enrolled in this study. Patients were randomly assigned to 1 of 4 treatment groups according to the postoperative treatment: artificial tears, sodium hyaluronate, diquafosol tetrasodium, and a combination of hyaluronate and diquafosol. Questionnaire responses reflecting subjective dry eye symptoms, uncorrected and corrected visual acuity, functional visual acuity, manifest refraction, tear break-up time, fluorescein corneal staining, Schirmer test, and corneal sensitivity were examined before and 1 week and 1 month after LASIK. Results Distance uncorrected visual acuity was significantly better in the combination group than in the hyaluronate group 1 week and 1 month after LASIK. Near uncorrected visual acuity was significantly better in the combination group than in the artificial tear and diquafosol groups 1 week and 1 month after LASIK. Distance functional visual acuity improved significantly only in the combination group 1 month after LASIK. The Schirmer value in the combination group was significantly higher than that in the hyaluronate group at 1 month after LASIK. Subjective dry eye symptoms in the combination group improved significantly compared with those in the other groups 1 week after surgery. Conclusions Our results suggest that hyaluronate and diquafosol combination therapy is beneficial for early stabilization of visual performance and improvement of subjective dry eye symptoms in patients after LASIK.

Purpose To study the influence of blepharospasm on dry eye disease by analyzing the clinical features, tear cytokine, and treatment response of patients with dry eye disease accompanied by benign essential blepharospasm. Design Prospective case series study. Methods Forty adults with a diagnosis of benign essential blepharospasm (BEB) and dry eye disease (DED) were consecutively recruited. Forty subjects with dry eye disease only and 40 healthy adults were recruited as eligible controls. A tear specimen was collected from all participants for cytokine analysis. The patients with benign essential blepharospasm were treated with botulinum neurotoxin type A. The main outcome measures were the following: (1) Ocular Surface Disease Index (OSDI) questionnaire; (2) clinical features, including tear break-up time (BUT), Schirmer І test, and fluorescein staining; (3) conjunctival impression cytology; and (4) multiplex cytokine immunobead assay. Results The symptoms of DED + BEB patients were significantly different from those of DED controls and healthy controls. Cytokine analysis in tear fluid also showed that tumor necrosis factor-α, interleukin (IL)-1β, IL-6, IL-2, IL-17, and vascular endothelial growth factor levels were significantly increased in DED + BEB patients. In treatment, botulinum neurotoxin type A injection effectively relieved blepharospasm in all of the DED + BEB patients. Moreover, in this group of patients, OSDI decreased significantly after the botulinum neurotoxin type A injection, and BUT was increased as well. Conclusion BEB may participate in the progress of inflammation in DED + BEB patients. Botulinum neurotoxin type A injections could effectively relieve the symptoms of DED + BEB patients and improve their ocular surface condition.

Purpose To investigate the efficacy and safety of 2% rebamipide ophthalmic suspension administered 4 times daily for 52 weeks in patients with dry eye. Design Multicenter (17 sites), open-label, single-arm study. Methods A total of 154 patients with dry eye were enrolled in this study. After a 2-week screening period, patients received 2% rebamipide, instilled as 1 drop in each eye, 4 times daily for 52 weeks. The signs and symptoms measures were assessed at baseline, at weeks 2 and 4, and at every 4 weeks thereafter. The objective signs were fluorescein corneal staining score, lissamine green conjunctival staining score, and tear film break-up time, while subjective symptoms were dry eye–related ocular symptoms (foreign body sensation, dryness, photophobia, eye pain, and blurred vision). The safety variable was the occurrence of adverse events. Results For all objective signs and subjective symptoms, the scores significantly improved at week 2 compared with baseline ( P t test). Interestingly, further improvements of those scores were observed at every visit up to week 52. No deaths were reported, yet serious adverse events that were not thought to be drug related were observed in 6 patients. The incidence of any of the adverse events did not markedly increase throughout the 52-week treatment period. Conclusion The results of this study show that 2% rebamipide is effective in improving both the objective signs and subjective symptoms of dry eye patients for at least 52 weeks. In addition, 2% rebamipide treatment was generally well tolerated.

To evaluate the efficacy of a thermosensitive atelocollagen punctal plug in the treatment of dry eye disease.Prospective observational case series.The thermosensitive atelocollagen punctal plug was warmed at 37 C, 39 C, 41 C, and 43 C to evaluate the appropriate temperature and time for solidification. Dry eye patients were divided into 2 groups according to the preparation method of the atelocollagen punctal plug. In the conventional implantation group, atelocollagen gel was kept at room temperature for 15 minutes before implantation (27 eyes of 14 patients). In the preheating group, atelocollagen was warmed at 41 C for 8 minutes before implantation (23 eyes of 13 dry eye patients). Strip meniscometry, vital stainings, tear film break-up time (BUT), and symptom scores were evaluated before and 1 month after plug implantation.In vitro experiments revealed that heating at 41 C for 8 minutes was sufficient to solidify the gel. The mean fluorescein score in the conventional implantation group significantly improved after treatment (before, 3.5 ± 2.3 points; after, 2.5 ± 0.9 points, P.05). In the preheating group, the mean fluorescein score (before, 3.7 ± 1.7 points; after, 1.5 ± 1.2 points), strip meniscometry (before, 0.6 ± 0.7 mm; after, 1.1 ± 0.3 mm), BUT (before, 3.2 ± 0.7 seconds; after, 4.8 ± 1.0 seconds), and visual analog scale scores (before, 6.6 ± 1.5 points; after, 4.1 ± 0.9 points) significantly improved after treatment (P.05).The thermosensitive atelocollagen punctal plug was effective for dry eye treatment. The preheating method was found to be useful to strengthen the efficacy of the thermosensitive atelocollagen punctal plug.

Purpose To evaluate the long-term results of autologous submandibular gland transplantation in eyes with cicatrizing conjunctivitis and to determine biomechanical and biochemical features of the resulting salivary tear film. Design Prospective, observational case series. Methods Fifteen eyes with cicatrizing conjunctivitis with a viable autologous submandibular gland transplantation were compared with 10 eyes with cicatrizing conjunctivitis and a failed submandibular gland transplantation or no submandibular gland transplantation. Best-corrected visual acuity, frequency of tear substitute instillation, severity of dry eye discomfort, lid margin erythema, conjunctival hyperemia, corneal epithelial edema, tear film break-up time, Schirmer test results, and corneal fluorescein and conjunctival Rose Bengal staining were evaluated. In a subgroup central corneal thickness and sensitivity, corneal epithelial barrier function, conjunctival and lid margin flora, and conjunctival impression cytologic analysis results were evaluated. In 3 patients, preoperative and postoperative tear samples were analyzed for viscosity, surface tension, and presence of mucins. Results Submandibular gland autotransplantation resulted in long-term improvement of subjective, objective, and some ocular surface parameters. Salivary mucins were detectable in salivary tears after submandibular gland transplantation. The viscosity of salivary tears was more similar to normal saliva and the surface tension was intermediate between the 2 original secretions. Conclusions Submandibular gland autotransplantation provides long-term relief from pain and reduces the need for frequent installation of lubricants.

Purpose To describe the clinical presentation, laboratory features, and treatment outcomes in a series of patients with occult thyroid eye disease (TED). Design Retrospective observational case series. Methods Among 539 patients who were referred for dry eye evaluation over 2 years, 21 were diagnosed with occult TED, based on typical findings in orbital echography. Medical records of these patients were reviewed to collect information on demographics, clinical findings, laboratory studies, and treatment response. Results All patients presented with symptoms of dry eye. Median age of patients was 57 years (range, 24 to 78 years), with the majority female (86%). No patients carried prior diagnosis of TED or had typical findings of TED such as proptosis, dysmotility, or diplopia. Suspicion of TED was based on conjunctival hyperemia with or without chemosis localized to extraocular muscles (100%), and subtle widening of interpalpebral fissure (48%). Clinical findings included corneal fluorescein staining (57%), rapid tear break-up time (31%), and abnormal Schirmer test (19%). Nineteen percent of patients had other rheumatologic disorders commonly associated with dry eye: Sjogren syndrome (n = 3), and rheumatoid arthritis (n = 1). Patients were treated topically using cyclosporine 0.05% 2 to 4 times a day, with or without steroid. Other treatments were also employed as necessary including warm compresses, artificial tears, and puntal plugs. Majority of patients (76%) had improvement of their symptoms. Conclusion Occult TED is a potential cause of inflammatory ocular surface disease with dry eye symptomatology and should be considered in the differential diagnosis when evaluating dry eye patients.

Purpose To compare the therapeutic effect between autologous serum and umbilical cord serum eye drops in the treatment of severe dry eye syndrome. Design Prospective case-control study. Methods Ninety-two eyes of 48 patients with severe dry eye syndrome (34 eyes of 17 patients with Sjogren syndrome and 58 eyes of 31 patients with non-Sjogren syndrome) were treated with either 20% autologous serum (41 eyes of 21 patients) or umbilical cord serum eye drops (51 eyes of 27 patients). Symptom scoring, corneal sensitivity test, tear film break-up time (BUT), Schirmer test, tear clearance rate (TCR), corneal fluorescein staining, and conjunctival impression cytologic analysis were performed before and one month and two months after treatment. Results Both autologous serum and umbilical serum treatments led to improvement in the symptom score, tear film BUT, keratoepitheliopathy score, and impression cytologic findings. Symptom and keratoepitheliopathy scores were lower at one month ( P = .03 and P = .12) and two months ( P = .04 and .02) for those treated with umbilical cord serum compared with those treated with autologous serum. In Sjogren syndrome patients, goblet cell density was higher at two months of umbilical cord serum treatment compared with autologous serum treatment ( P = .04). Conclusions Umbilical cord serum eye drops were more effective in decreasing symptoms and keratoepitheliopathy in severe dry eye syndrome and increasing goblet cell density in Sjogren syndrome compared with autologous serum eye drops.

Purpose To evaluate the diagnostic value of tear osmolarity and several ocular surface parameters in screening for ocular surface alterations in ocular graft-vs-host disease (GVHD) patients. Design Case-control study. Methods Sixty-three patients with ocular GVHD and 74 healthy participants were screened for ocular surface changes using the Ocular Surface Disease Index (OSDI), tear osmolarity, Schirmer test, tear break-up time (TBUT), and fluorescein corneal staining. The severity of ocular GVHD was diagnosed according to the National Institutes of Health (NIH) grading system. The diagnostic sensitivity and specificity and cutoff values were determined for each ocular parameter using a receiver operating characteristic (ROC) curve and area under the curve (AUC) analysis. Significance was defined at P Results The tear osmolarity, corneal staining score, and OSDI score gradually increased as the severity of ocular GVHD increased, and Schirmer value gradually decreased as the GVHD grade increased in severity. The Schirmer test showed greatest diagnostic sensitivity and specificity for ocular GVHD (92.1% sensitivity, 85.7% specificity, cutoff = 9 mm), followed by the TBUT (87.3% sensitivity, 75.0% specificity, cutoff = 6 s), tear osmolarity (98.4% sensitivity, 60.7% specificity, cutoff = 311 mOsm/L), corneal staining score (66.7% sensitivity, 82.1% specificity, cutoff = 2), and OSDI score (77.8% sensitivity, 66.1% specificity, cutoff = 20.8). Conclusions Multiple diagnostic modalities should be used to detect ocular surface changes in GVHD patients. The severity of ocular GVHD can be effectively monitored using tear osmolarity; however, additional studies are required.

Purpose To investigate the efficacy and safety of long-term maintenance treatment with tacrolimus ointment in chronic ocular graft-vs-host disease (GVHD) with ocular surface inflammation. Design A retrospective interventional consecutive case series. Method Long-term maintenance treatment (≥6 months) with topical 0.02% tacrolimus ointment was applied to patients with chronic ocular GVHD with ocular surface inflammation (at least grade 2 inflammatory score). We evaluated the inflammatory score, steroid score and steroid use period of total duration, and numbers of inflammatory aggravations before and after tacrolimus treatment. The clinical outcomes were assessed by symptom score, ocular surface staining, Schirmer I test, tear break-up time (TBUT), and classification of chronic GVHD conjunctivitis at the initial and final examinations. Results Thirteen patients (24 eyes) were treated with tacrolimus ointment for up to 20 months (average 12.2 months). The ocular surface inflammatory score decreased from 2.8 to 0.6 ( P = .001) within 2–8 weeks after starting tacrolimus ointment treatment. The numbers of inflammatory aggravation and the need for steroid treatment also decreased after initiating tacrolimus treatment. At the final follow-up, all patients reported improvement in clinical outcomes, compared to initial findings. Except for blurred vision or mild burning sensation, there were no reported side effects. Conclusion Considering the chronic course of GVHD, long-term maintenance treatment with tacrolimus ointment could be useful and safe to locally treat ocular surface inflammation in chronic ocular GVHD.

Purpose To evaluate the incidence of dry eye in rheumatoid arthritis (RA) patients with or without Sjogren syndrome (SS), and to investigate the correlation between dry eye and RA activity. Design Prospective case-control study. Methods In 72 RA patients, the severity of dry eye was assessed by the Schirmer test, tear break-up time, rose bengal staining, and fluorescein staining. The RA activity was evaluated by the Lansbury index (LI), which is based on the duration of morning stiffness, erythrocyte sedimentation rate (ESR), grip strength, and joint score. Results Ten percent of patients met the Japanese criteria for SS. No difference in dry eye tests or LI was observed between SS patients and non-SS patients. Even in the non-SS group, 90% of patients were diagnosed with probable dry eye. In SS patients, positive correlations were observed between LI and Schirmer test ( P = .048), ESR and Schirmer test ( P = .035), ESR and rose bengal staining ( P = .001), and grip strength and rose bengal staining ( P = .047). No such correlations were observed in the non-SS patients. Conclusions Dry eye is common in RA patients, including those without SS. We found that there was a correlation between LI and Schirmer test in RA patients with SS, but no correlation when the entire group was analyzed. Dry eye always should be taken into consideration regardless of the RA activity, because the severity of dry eye is independent of RA activity.

To evaluate the efficacy of a new continuous functional visual acuity measurement (FVAM) system for the assessment of dry eye patients.Prospective comparative study.Monocular recognition acuity measured continuously by the FVAM system during a 30-second blink-free period was defined as functional visual acuity (FVA). Examinations using the FVAM system were conducted in 35 eyes of 20 healthy controls and 19 eyes of 13 dry eye patients. Tear function examinations including the Schirmer test, tear film break-up time, and fluorescein and Rose Bengal staining were performed in all subjects. Functional visual acuity and tear functions were also examined before and after insertion of punctum plugs in dry eye patients. Functional visual acuity results at 10, 20, and 30 seconds were compared.Functional visual acuity in dry eyes were significantly lower than control subjects at all time points (P.05). Functional visual acuity after punctum plugs insertion improved significantly at all time points (P.05).FVAM system seemed not only to be an effective tool in the assessment of dynamic visual acuity changes in dry eye and normal subjects but in evaluating the outcome of management of dry eye disease by punctum plugs.

Purpose To assess tear cytokine levels and clinical outcomes in moderate and severe meibomian gland dysfunction (MGD) after 2 months of treatment with topical loteprednol etabonate and eyelid scrubs with warm compresses vs eyelid scrubs with warm compresses alone. Design Randomized controlled trial. Methods Patients with moderate and severe MGD were randomized into 2 groups: topical loteprednol etabonate and eyelid scrubs with warm compresses (Group I, 34 eyes) or eyelid scrubs with warm compresses (Group II, 36 eyes). We evaluated cytokine levels, tear film break-up time (TBUT), corneal and conjunctival fluorescein staining, biomicroscopic examination of lid margins and meibomian glands, and the Ocular Surface Disease Index before initiating treatment and 1 month and 2 months after treatment. Results There were significant decreases in the levels of interleukin (IL)-6, IL-8, and IL-1β in Group I, and IL-6 and IL-8 in Group II. Moreover, the observed decreases of these cytokines in Group I were attributed to a remarkable decrease between treatment and 1 month after treatment. In Group I, there were improvements in all of the clinical outcomes, with prominent improvement in TBUT, corneal and conjunctival fluorescein staining, and meibum quality after 1 month of treatment, compared with Group II. An improvement in meibomian gland expressibility and MGD stage reduction were more remarkable in Group I. Conclusions Topical loteprednol etabonate and eyelid scrubs with warm compresses were tolerated and efficacious for the treatment of moderate and severe MGD. We suggest that such beneficial effects could manifest after 1 month.

To evaluate dry eye and meibomian gland dysfunction after cataract surgery.Prospective observational case series.We studied 58 eyes of 48 patients who underwent phacoemulsification and evaluated them preoperatively and at 1 month and 3 months postoperatively. Ocular symptom scores, lid margin abnormalities, superficial punctate keratopathies (SPKs), tear film break-up time (TBUT), Schirmer test, lower tear meniscus height, depth, and area using Fourier domain optical coherence tomography, meibum expressibility and images of the meibomian glands using meibography were measured.The ocular symptom scores were worse at 1 month and 3 months postoperatively (P0.001 and P0.001, respectively). Lid margin abnormalities were significantly increased (P0.001 and P0.001, respectively) and TBUT decreased postoperatively (P0.001 and P0.001, respectively). Meibum expressibility decreased at 3 months postoperatively (P = 0.016); however, meibography score, SPK, lower tear meniscus height, depth and area and the Schirmer test did not change significantly postoperatively (all P values0.05).Meibomian gland function may be altered without accompanying structural changes after cataract surgery.

The results of this study may be summarized as follow: Dry eye is common in RA patients (92% dry eye and 47% probable dry eye). In patients with RA and SS, there is a correlation between LI and tests of dry eye severity but there is no correlation evident in patients with RA but not SS. In RA patients without SS, increased activity of RA (deterioration) does not seem to lead to aggravation of dry eye disease. The authors suggest that the etiology of dry eye may be different in SS and non-SS patients with RA. To interpret these results, it is useful to consider the criteria used to establish patient categories. In this study, dry eye was diagnosed on the basis of objective signs that is, an abnormality of “tear dynamics” (Schirmer test with anesthetic or tear film break up time [TFBUT]) and an abnormality of the ocular surface (fluorescein staining of the cornea or rose Bengal staining of the conjunctiva). The presence of an abnormality in each category qualified the patient with the diagnosis of dry eye; the presence of only one category of abnormality is considered “probable dry eye.” This formulation differs from that in general use outside of Japan in that symptoms are not included. Roughly, however, those considered “dry eye” in this study would correspond to moderate to severe dry eye and those labeled “probable dry eye” to mild dry eye. This is, admittedly, an oversimplification but it enables us to interpret these findings in a format that is more widely in use.

Purpose To investigate tear function and prevalence of dry eye disease (DED) in visual display terminal (VDT) users. Design Cross-sectional study. Methods Six hundred and seventy-two young and middle-aged Japanese office workers who used VDT completed questionnaires and underwent dry eye testing. We estimated the prevalence of DED using logistic regression analysis to examine associations between DED and possible risk factors. The ocular surface feature, prevalence of DED, and risk factors were evaluated. Results Of the 672 workers, 561 (83.5%, mean age: 43.3 ± 9.1 years) completed the questionnaire. The percentage of women with a composite outcome of definite DED or probable DED was 76.5%, which was higher than that among men (60.2%; odds ratio [OR] = 2.00; 95% confidence interval [CI], 1.29-3.10, P = .002). Workers over 30 years of age had a higher risk of DED (OR = 2.22; 95% CI, 1.06-4.66), as did workers using a VDT >8 hours per day (OR = 1.94; 95% CI, 1.22-3.09). Average Schirmer value was 18.7 ± 11.7 mm and tear break-up time (TBUT) was 4.0 ± 2.5 seconds (78.6% of study participants had TBUT ≤5 seconds). Conclusions DED is prevalent among young to middle-aged Japanese VDT users. Ophthalmic findings revealed short TBUT and corneal staining accompanied by normal Schirmer test values. Increased risk for DED was noted for women aged over 30 years and prolonged VDT use. Measures to modify the adverse impact of VDT use on the ocular surface may provide a positive impact on public health and quality of life for office workers using VDTs.

To discover a relationship between Vogt-Koyanagi-Harada (VKH) syndrome and Sjögren syndrome.Observational case-control study.Sixteen Italian patients with VKH syndrome and 16 controls with diffuse uveitis underwent tear analysis and rheumatologic evaluation. Biopsy specimens of the minor salivary glands were obtained or salivary gland scintigraphy was performed in patients with xerostomia.The Schirmer test (P.0001), break-up time (P.0001), the Ferning test (P.001), and fluorescein and rose bengal staining (P.0001) resulted in changes in VKH. Biopsy was positive in two patients and scintigraphy in four. Human leukocyte antigen DR4 was found in 68.75% of VKH cases and in 83.3% of the cases with Schirmer test less than 3 mm.The incidence of keratoconjunctivitis sicca was higher in VKH syndrome patients than in controls. Two patients satisfied the criteria for Sjögren syndrome, and two others had scintigraphy indicative of salivary gland involvement. The association of these two autoimmune disorders is suggested by the low incidence of VKH syndrome in Italy and might be related to HLA DR4.

Purpose To assess clinical outcomes and tear cytokine levels in patients with moderate and severe meibomian gland dysfunction (MGD) after treatment with oral minocycline and artificial tears versus artificial tears only. Design Prospective, randomized clinical trial. Methods Sixty eyes of 60 patients with stage 3 or 4 meibomian gland dysfunction were enrolled. We evaluated the tear film break-up time, Schirmer test results, corneal and conjunctival fluorescein staining results, biomicroscopic examination results of lid margins and meibomian glands, and tear cytokine levels before and after 1 month and 2 months of oral minocycline and artificial tears (group 1) or artificial tears only (group 2). Tear samples were collected and analyzed using a BD Cytometric Bead Array (BD Bioscience, San Jose, California, USA) for detection of interleukin (IL)-1β, IL-6, IL-7, IL-8, IL-12p70, IL-17α, interferon-γ, tumor necrosis factor-α, and monocyte chemotactic protein-1. The Wilcoxon signed-rank test, Mann–Whitney U test, generalized linear model, and linear mixed model were performed. Results Patients in group 1 showed statistically significant improvement in all clinical signs and symptoms after 1 month and 2 months of treatment. Patients of group 1 showed more significant improvement compared with those in group 2. Patients in group 1 also showed statistically significant reductions in IL-6, IL-1β, IL-17α, tumor necrosis factor-α, and IL-12p70 after 2 months of treatment. Conclusions Oral minocycline can provide clinical benefits in treating moderate and severe meibomian gland dysfunction by reducing inflammatory cytokine levels.

To evaluate the long-term effects of preservative-free and preservative-containing antiglaucoma eye drops on the tear secretion and ocular surface.Comparative retrospective study.A total of 84 patients with bilateral primary open-angle glaucoma or ocular hypertension divided into 5 groups according to type of topical hypotensive therapy and 20 healthy age-matched volunteers were studied. Clinical tests (corneal sensitivity, Schirmer I test, and lachrymal film break-up time), and in vivo confocal microscopy were performed in all patients.A significant reduction of the scores was found between groups on topical hypotensive therapy and the control group in all clinical parameters studied (P.05). In particular, the clinical scores were significantly lower in the preservative medication groups than in the preservative-free group (P.05). The density of superficial epithelial cells was reduced in all glaucomatous patients, except for the preservative-free group (P.05), with respect to control subjects (P.001). On the contrary, the density of basal epithelial cells of glaucomatous preservative therapy groups was higher than control and preservative-free groups (P.05). Stromal keratocyte activation and the number of beads were higher in all glaucoma preservative groups (P.05). The number of sub-basal nerves was lower in all glaucoma groups than in the control group (P.05) and tortuosity was significantly higher in glaucoma than control groups (P.05). Reflectivity of fibers did not show any significant difference between the 6 groups (P.05).Glaucomatous patients with chronic treatment show ocular surface alterations. The development of nontoxic antiglaucoma treatment may reduce damage to the ocular surface and improve the compliance and the adherence in the medical therapy.

To compare the efficacy of vitamin A (retinyl palmitate) and cyclosporine A 0.05% eye drops in treating patients with dry eye disease.Prospective, randomized, controlled, parallel group study.A total of 150 patients with defined dry eye disease participated (50 in each treatment group). In 3 identical clinical trials, patients were treated twice daily with cyclosporine A 0.05%, or four times daily with retinyl palmitate 0.05%, or with neither cyclosporine or retinyl palmitate. Adjunctive treatment with preservative-free artificial tears was undertaken four times daily in all 3 groups. Corneal fluorescein staining results, Schirmer tear test (without anesthesia) results, tear film break-up time (BUT), dry eye symptom score, and impression cytologic analysis results were obtained before treatment and at the first, second, and third months after initiation of treatment.Both vitamin A eye drops and topical cyclosporine A 0.05% treatments led to significant improvement in blurred vision, tear film BUT, Schirmer I score results, and impression cytologic findings in patients with dry eye syndrome (P.05) compared to the control group treated with preservative-free artificial tears alone.Both vitamin A eye drops and topical cyclosporine A 0.05% treatments are effective for the treatment of dry eye disorder.

To determine the clinical value and relevance of punctal and proximal canalicular stenoses after punctal plug therapy in moderate to severe dry eye syndrome.Retrospective, observational case series.Seventeen eyes were determined to have punctum or proximal canalicular stenoses after spontaneous loss of a collared silicone punctal plug. After initial diagnosis all patients had 12 months or more of follow-up (mean, 39; range, 12 to 87 months). The clinical data collected included gender and age of patients, localization of the stenosis, plug size, duration of punctal occlusion, subjective symptoms, objective ocular surface disease parameters, and occurrence of complications.A statistically significant correlation between localization of the stenosis and plug size, and localization of the stenosis and duration of punctal occlusion could not be found. At follow-up, subjective symptoms (P.01) and frequency of artificial tear application (P.001) were significantly reduced compared to data before plug insertion. Schirmer I test results (P.001), corneal fluorescein staining (P.01), and rose bengal staining (P.001) improved significantly, whereas tear break-up time (P.2) and impression cytology scores of the conjunctival surface (P = .2) remained almost unchanged. Complications could not be found.Within the observation period of up to seven years, all stenoses remained asymptomatic. Additionally, subjective symptoms and most dry eye parameters in our study population improved.

Purpose To investigate the effect of grade 3 nasal conjunctivochalasis (NCCh) on the tear film inflammation, ocular surface findings, and tear function findings. Design Prospective, observational case series. Methods Eleven eyes with Yokoi grade 3 NCCh in which the chalatic conjunctiva occluded the punctum and 18 eyes without NCCh but with central or temporal conjunctivochalasis, or both, and 16 eyes of healthy controls were recruited prospectively. Enzyme-linked immunosorbent assay for inflammatory tear cytokines, tear film break-up time (BUT), Schirmer I test measurements, and fluorescein and rose bengal vital stainings and impression cytologic and brush cytologic analysis for real-time reverse-transcriptase polymerase chain reaction analysis of MUC5AC messenger ribonucleic acid (mRNA) expression were performed. Results Eyes with grade 3 NCCh had significantly delayed tear clearance. All inflammatory cytokines showed higher values in eyes with grade 3 NCCh compared with the eyes without nasal chalasis with a comparably significant elevation in interleukin-1b and tumor necrosis factor α levels. The mean rose bengal score in eyes with grade 3 NCCh was significantly higher compared with eyes without nasal chalasis and eyes of controls. The mean goblet cell density was significantly lower in eyes with grade 3 NCCh with downregulation of the relative MUC5AC mRNA expression. Conclusions Inflammation plays an important role in the pathogenesis of conjunctivochalasis and is more pronounced in eyes with nasal chalasis. Pooling of inflammatory cytokines in tears of patients with NCCh associated with delayed tear clearance induces distinct adverse effects that affect the ocular surface health.

The authors aimed to define the ocular symptomatology of women with polycystic ovaries and hyperandrogenism.Prospective, observational case series.Of the 62 consecutive patients with an ultrasonographic diagnosis of polycystic ovary (PCO), 16 were identified as having clinical and biochemical signs of hyperandrogenism. All women with a history of ocular symptoms (20/62 total patients [32.3%], 15/16 polycystic ovary syndrome (PCOS) patients [93.7%], and 5/46 PCO patients [10.8%]) underwent a complete eye examination with conjunctival impression cytologic sampling. Clinical measurements of tear function (tear film break-up time [BUT], Schirmer I test) were completed along with analysis of conjunctival goblet cell number, conjunctival immunostaining, and reverse-transcriptase polymerase chain reaction for the mucins MUC1 and MUC5AC. Clinical, histologic, and biochemical data of patients with PCOS were compared statistically with that of patients with PCO and with eight age- and gender-matched healthy controls. Eight of the most severely affected patients received systemic antiandrogen therapy and underwent further ocular evaluation four months after systemic therapy.Women with PCOS had greater conjunctival hyperemia (P.001), dryness (P.001), itching (P.001), mucous discharge (P.001), and contact lens intolerance (P.001) than patients with PCO. Patients with PCOS had a significant reduction of the tear film BUT accompanied by a significant increase in goblet cell number and conjunctival MUC5AC messenger ribonucleic acid expression compared with both PCO patients and healthy subjects.Evaluation of the ocular surface should be considered in patients with PCO or PCOS. Women with PCOS were more likely to have itchy-dry eyes, decreased tear film BUT, and increased goblet cell density.

To investigate the tear and ocular surface findings between controls, children, and adults with atopic keratoconjunctivitis (AKC).Prospective comparative study.Twenty eyes of 10 childhood-onset, 10 eyes of five adult-onset, AKC adult patients, and 12 eyes of six children with infantile-onset AKC, 14 eyes of seven normal adults and seven normal children were recruited. Corneal aesthesiometry, Schirmer test, tear film break-up time (BUT), vital staining, and conjunctival impression cytology were performed.The Schirmer and Rose Bengal scores in childhood-onset adult AKC patients were considerably worse than adult-onset adult AKC patients, pediatric subjects, and the controls (P.05). The same significant relation was observed in impression cytology parameters.Ocular surface disease in childhood-onset adult AKC patients was characterized by greater ocular surface epithelial damage. Prolonged inflammation may be important in the evolution and progression of ocular surface disease in patients with longstanding active AKC.

To compare the short-term efficacy of collagen and silicone plugs for treating dry eye using quantitative lacrimal scintigraphy.Prospective randomized clinical trial.In this institutional study, 24 dry eye patients were evaluated in two groups: group I (n = 22 eyes) received collagen plugs and group II (n = 26 eyes) received silicone plugs. Comparisons were made with normal control subjects (n = 22 eyes). Data for the Schirmer I test, tear break-up time, and ocular surface staining with rose bengal dye were recorded before and after punctal occlusion. Lacrimal scintigraphy was performed at each time point, and the time to half maximum activity on the ocular surface (T(1/2)), and the percentage retention of activity on the ocular surface at the end of the dynamic study (RI) were recorded.In both patient groups, Schirmer I results, tear break-up times, and rose bengal staining scores improved significantly after plug insertion. Mean T(1/2) values and RI values increased significantly in both groups (P.0001 for both). The differences for these values between groups I and II was statistically insignificant (P.05).Collagen and silicone plugs both resulted in significant increases in aqueous tear volume, half-life of nuclear material on the ocular surface, and percentage of nuclear material retention. The groups' post-insertion values for all parameters were similar. These results suggest that these two plug types have similar efficacy as treatments for dry eye in the short term. Further studies evaluating long-term results are required.