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Author(s): Sutphin, John E; Ying, Gui-Shuang; Bunya, Vatinee Y; Yu, Yinxi; Lin, Meng C; McWilliams, Kathleen; Schmucker, Elizabeth; Kuklinski, Eric J; Asbell, Penny A; Maguire, Maureen G; Dry Eye Assessment and Management (DREAM) Study Research Group | Abstract: PurposeThe purpose of this study was to compare objective, noninvasive assessments of tear function using the OCULUS Keratograph with the corresponding clinical assessments [tear break-up time (TBUT), Schirmer test, and bulbar erythema] among patients with moderate-to-severe dry eye disease.MethodsParticipants in the Dry Eye Assessment and Management study at centers having an OCULUS Keratograph were assessed using standardized procedures. Associations between the assessments from the Keratograph [noninvasive keratograph break-up time (NIKBUT), tear meniscus height (TMH), and bulbar redness (BR)] and clinical examination (TBUT, Schirmer test, and bulbar erythema) and between these test results and Ocular Surface Disease Index (OSDI) scores were summarized with Spearman correlation coefficients (rs); 95% confidence intervals (95% CI) accounted for intereye correlation.ResultsAmong 288 patients (576 eyes), the mean (standard deviation) age was 56.6 (13.8) years, 78.1% were female, and the mean baseline OSDI score was 44.3 (14.0). The mean was 2.9 (1.5) seconds for TBUT and 8.2 (5.7) seconds for NIKBUT (their correlation rs = 0.18, 95% CI = 0.09-0.28). The mean was 10.6 (7.6) mm for the Schirmer test and 0.3 (0.2) mm for TMH (rs = 0.15, 95% CI = 0.04-0.25). The median clinical grade redness was mild, and the mean BR score was 1.1 (0.5) (rs = 0.25, 95% CI = 0.15-0.35). Correlation between results of each of the 6 tests and OSDI scores was low (rs from -0.07 to 0.05).ConclusionsIn the Dry Eye Assessment and Management study, NIKBUT, TMH, and BR were weakly correlated with their clinical counterparts. No measurements were correlated with the OSDI score.

PURPOSE The aim of this study was to quantitatively evaluate dry eye test parameters of pediatric patients with and without vitamin D deficiency (VDD) in type 1 diabetes mellitus. METHODS In this prospective cross-sectional study, the Ocular Surface Disease Index, Schirmer test, tear film breakup time, corneal staining score, and anterior segment optical coherence tomography were used to determine the dry eye test parameters of pediatric patients with type 1 diabetes mellitus (T1-DMPs) (group 1) and a healthy pediatric control group (group 2). Group 1 was divided into 2 subgroups based on their vitamin D status: group 1a, who had a VDD, and group 1b, who had vitamin D levels that were within the normal range. RESULTS This study compared 90 eyes of 90 pediatric T1-DMPs with 80 eyes of 80 healthy controls. The demographic characteristics of the groups were similar (P > 0.05). The tear film breakup time, Schirmer test, corneal staining score, and values of the tear meniscus height and area were observed to have been lower in the patients in group 1a than the healthy pediatric control group, at P < 0.001. The same parameters were statistically significantly lower in the patients in group 1a when compared with group 1b (P < 0.05 for both). CONCLUSIONS The tear measurements of the pediatric T1-DMPs were lower than those in the healthy pediatric control group. The accompanying VDD made this situation more pronounced.

This is a cohort study to evaluate the presence of objective signs and subjective symptoms of dry eye disease in postcoronavirus disease 2019 (COVID-19) patients compared with the control.Prospective, observational, single-ctenter, cohort study. Sixty-four post-COVID-19 patients and 50 control were recruited. All participants underwent a complete ophthalmological examination including Ocular Surface Disease Index Questionnaire (OSDI), best-corrected visual acuity, slit-lamp biomicroscopy, fundus examination, Schirmer test type 1, tear break-up time test (tBUT), evaluation of conjunctival hyperemia, corneal staining, and tear film osmolarity test.The OSDI score was higher in the post-COVID-19 group in the quantitative and qualitative analysis (P0.001 and P =0.012, respectively). The mean tBUT in post-COVID-19 patients was 6.95 ± 4.07 seconds compared with a mean tBUT of 10.12 ± 3.90 seconds in the control group. The post-COVID-19 group showed a higher number of patients with a simultaneous impairment of the OSDI score and tBUT (P = 0.019). The Schirmer test results were strikingly significant both in the quantitative analysis and qualitative analysis (P0.001 and P = 0.0014, respectively). Both quantitative analysis and qualitative analysis revealed a significant difference in tear osmolarity in the 2 groups.Comparing the ocular surface assessment of post-COVID-19 patients with heathy control, a statistically significant increase of dry eye disease has emerged both in subjective and objective evaluations. Our clinical results support the findings that suggested a susceptibility of the ocular surface to the virus, and it underlines the importance of the ocular surface assessment in post-COVID-19 patients for a correct diagnosis and therapy.

PURPOSE Meibomian glands are subject to regulation by sex hormones. We have now investigated the possible relation between benign prostate hyperplasia (BPH) and meibomian gland dysfunction (MGD). METHODS Men diagnosed with BPH and receiving treatment with tamsulosin and age-matched male control subjects who attended Itoh Clinic, Saitama, Japan, were enrolled. An ocular symptom score, lid margin abnormality score, and superficial punctate keratopathy score as well as the meiboscore (0-6), meibum grade, breakup time of the tear film, and Schirmer test values were evaluated. Male pattern baldness was also graded according to the Hamilton-Norwood scale. RESULTS Forty-four eyes of 44 men with BPH (mean age ± SD, 76.1 ± 2.2 years) and 46 eyes of 46 control subjects (mean age ± SD, 75.3 ± 6.2 years) were enrolled. The meiboscore in the BPH group (4.5 ± 1.4) was significantly higher than that in the control group (1.8 ± 1.5, P < 0.0001). Breakup time of the tear film was significantly shorter (3.6 ± 1.7 vs. 5.6 ± 2.5 seconds, P < 0.0001), and Schirmer test value was significantly smaller (9.8 ± 4.8 vs. 13.3 ± 8.0 mm, P = 0.048) in the BPH group than that in the control group. Other ocular parameters did not differ significantly between the 2 groups. The proportion of men with androgenic alopecia was also higher in the BPH group than that in the control group. CONCLUSIONS BPH was associated with meibomian gland loss and instability of the tear film as well as with the presence of androgenic alopecia.

Purpose This systematic review examines the specific effects of pingueculum and pterygium on the ocular surface and evaluates the efficacy of surgical excision in reversing those effects. Methods A systematic review was performed according to the Preferred Reporting Items for the Systematic Review and Meta-Analyses statement and included 59 articles studying the effects of pterygium and pingueculum on the ocular surface as measured by tear break-up time (TBUT), Schirmer testing, tear osmolarity, Ocular Surface Disease Index (OSDI), and the effects of surgical removal on these ocular surface parameters. Results In most studies, eyes with pterygium or pingueculum when compared with control eyes had a statistically significantly lower TBUT (average 3.72 s), lower Schirmer I without anesthesia (average 3.01 mm), lower Schirmer II (average 4.10 mm), higher tear osmolarity (average 12.33 mOsm/L), and higher OSDI (average 6.82 points). Moreover, excision of pterygium and pingueculum led to a statistically significantly higher TBUT (average 3.15 s higher at 1 mo postexcision), lower tear osmolarity (average 3.10 mOsm/L lower at 3 mo postexcision), and lower OSDI score (average 2.86 points lower 1 mo postexcision) in most of the studies. The effect of excision on Schirmer test scores was equivocal because most studies did not reach significance. Conclusions Our data confirm the relationship between pterygium and pingueculum and abnormal tear function and symptoms of dry eye disease. Furthermore, the data suggest that tear film parameters might improve after surgical removal of pterygium or pingueculum. Future studies would be helpful in exploring the potential role of pterygium and pingueculum excision in the management of dry eye disease.

PURPOSE To evaluate the efficacy of autologous blood eye drops in patients diagnosed with severe ocular surface disease and dry eye who were unresponsive to conventional therapy and who would otherwise be considered for autologous serum eye drops. METHODS A total of 38 eyes of 19 patients (15 women and 4 men) with ocular surface disease and severe dry eye refractory to conventional treatment were treated with fingerprick autologous blood 4 times daily for 6 months. Follow-up visits occurred at 1-, 3-, and 6-month intervals. At each visit, visual acuity, Oxford Grading Scheme score, tear film break-up time, Schirmer test, and ocular surface disease index were measured. RESULTS There was a significant improvement in the ocular surface staining score at all time gates. The mean score at presentation was 2.13, and this improved to 1.50 at 1 month (P < 0.001), 1.29 at 3 months (P < 0.01), and 1.42 at 6 months (P < 0.01). There was an improvement in tear film break-up time from 4.75 seconds at baseline to 6.79 seconds at 3 months (P < 0.01) and 7.0 seconds at 6 months (P < 0.001). An improvement in the Schirmer test was only found at 6 months with an improvement from 3.67 mm to 13.33 mm (P < 0.05). There was no statistical change in visual acuity at any time gate or ocular surface disease index score, although 83% of patients reported an improvement in their symptoms at 6 months. There were no adverse events reported. CONCLUSIONS Fingerprick autologous blood is an effective, readily accessible, and safe therapy for the treatment of recalcitrant cases of severe ocular surface disease and dry eye unresponsive to conventional therapy.

Purpose To compare efficiency and tolerance between topical 0.5% cyclosporine A (CSA) and fluorometholone (FML) for subepithelial infiltrates (SEI) complicating epidemic keratoconjunctivitis. Methods We conducted a prospective double-blind randomized study involving 72 eyes with SEI. Thirty-eight eyes were treated with topical FML (FML group) and 34 eyes with CSA 0.5% eye drops (CSA group). Treatment was considered successful in case of SEI reduction and visual acuity improvement. Tolerance was evaluated by Schirmer test value, burning on eye drops instillation, and conjunctival injection. Results Baseline characteristics of both groups were similar (P > 0.05). After 3 months of the regimen, resolution of SEI was 3 times more observed in the FML group than that in the CSA group (P = 0.026). After 6 months, resolution of SEI was observed in 70% of the FML group and in 47% of the CSA group (P = 0.068). The recurrence of SEI was almost twice higher in the FML group than that in the CSA group (16% vs. 9%). FML was better tolerated during the first 3 months: a higher Schirmer test value (P = 0.0003), less burning on instillation (P = 0.242), and less conjunctival injection (P = 0.003). For the rest of the follow-up period, the 2 groups were comparable in tolerance. No ocular hypertension was noted. Conclusions Epidemic keratoconjunctivitis can evolve favorably under both FML and CSA. The effect of FML is faster and CSA is more durable with fewer recurrences. Both are safe therapeutic options for long-term control of SEI.

PURPOSE To evaluate the effects of different contact lens (CL) replacement schedules and different CL materials on the ocular surface and tear function. METHODS Daily disposable hydrogel CLs were given to group 1 (n = 22), daily disposable silicone hydrogel CLs were given to group 2 (n = 25), and reusable silicone hydrogel CLs were given to group 3 (n = 24). Tear function tests and inflammatory cytokine [interleukin (IL)-6, IL-8, IL-17A, and matrix metalloproteinase (MMP)-9] levels were evaluated before and at 1 and 3 months after CL usage. Impression cytology was evaluated before and at 3 months after CL usage. RESULTS At the first and third months of CL usage, a statistically significant difference was determined between the groups in the levels of IL-6, IL-8, and IL-17A in tears, with the lowest levels in group 1 and the highest levels in group 3 (all P < 0.05). At the third month of CL usage, the levels of these cytokines (in picograms/milliliter) were 6.06 ± 0.83, 78.18 ± 12.42, 61.69 ± 13.95, and 37.71 ± 5.95 in group 1 and 8.04 ± 0.89, 107.34 ± 14.40, 68.63 ± 13.72, and 46.26 ± 6.50 in group 3, respectively. A statistically significant decrease was determined over time in the Schirmer test in group 1, in only the tear breakup time in group 2, and in the tear breakup time and Schirmer test in group 3 (all P < 0.05). A statistically significant increase was determined over time in the levels of IL-6, IL-8, IL-17A, and MMP-9 in all groups. In the third month, a significant progression was observed in the Nelson grade (P < 0.05) in all groups. CONCLUSIONS The wear of daily disposable CLs can be considered to cause less damage to the ocular surface and less increase in proinflammatory cytokine levels.

PURPOSE To evaluate lower tear meniscus and corneal sub-basal nerve plexus in primary Sjogren's syndrome (pSS) and Sicca syndrome patients. METHODS Cross-sectional study of 116 patients with Sicca syndrome associated with pSS and not associated with Sjogren's syndrome (non-SS Sicca) and 20 normal control subjects. Tear meniscus height and area were measured using anterior segment optical coherence tomography; corneal sub-basal nerve plexus density, length, and tortuosity were evaluated using in vivo confocal microscopy. Data analysis was performed using IBM-SPSS Statistics 24.0. RESULTS Corneal sub-basal nerve plexus density and length were significantly lower, and tortuosity was significantly higher in pSS and non-SS Sicca groups than in normal control subjects (P < 0.001; P = 0.018, respectively). Corneal sub-basal nerve plexus presented a strong association with Schirmer test I and tear breakup time. Cutoff values of sub-basal nerve plexus density (36.5 nerve/mm) and length (12.5 mm/mm) presented 80.2% to 81.9% sensitivity and 85% specificity for detecting Sicca syndrome patients. No significant differences were found between the 3 groups regarding tear meniscus height and area. CONCLUSIONS Corneal sub-basal nerve plexus in vivo confocal microscopy may be a useful tool in the assessment of dry eye disease in Sicca syndrome, complementing the information provided by the conventional modalities used in dry eye disease evaluation.

PURPOSE To summarize the results of a cross-sectional epidemiologic study of Japanese office workers who use visual display terminals (VDTs). METHODS Workers in a pharmaceutical company head office were recruited. Participants were requested to complete a questionnaire on symptoms of dry eye disease (DED) and evaluations using the Work Limitations Questionnaire, International Physical Activity Questionnaire, Subjective Happiness Scale, and Pittsburgh Sleep Quality Index. Evaluations of ocular status, including conjunctival and corneal vital staining with lissamine green and fluorescein, measurement of tear film breakup time, and the Schirmer test, were performed. The Japanese 2007 diagnostic criteria for DED were implemented. RESULTS The prevalence of DED among VDT workers was high. Definite DED was present in 11.6% (18.7% women and 8.0% men) of participants, and probable DED was present in 54.0% (57.8% women and 52.1% men). Total loss of workplace productivity was significantly greater in the definite DED group (4.82%) than in the probable DED group (4.06%) and the non-DED group (3.56%, P < 0.014, trend test). Participants with definite DED had significantly lower physical activity scores than those without DED (P = 0.025). Subjective happiness correlated with the dry eye symptom score (r = -0.188; P < 0.001). Participants with DED reported poor sleep quality at a higher rate compared with those without DED (45% vs. 34%), with a significant difference in the global score (P = 0.002). CONCLUSIONS Dry eye is prevalent among VDT workers. Its impacts on work productivity, physical activity, and sleep quality warrant further study.

Purpose: We measured tear film parameters, including the morphology and function of meibomian glands, in junior high school students at 15 years of age. Methods: A total of 111 eyes of 111 students (56 males and 55 females) were enrolled in the study. The ocular symptom score (0–14), after-school study time, lipid layer thickness (LLT) of the tear film, partial blink rate, lid margin abnormalities (0–4), tear film breakup time, corneal and conjunctival epithelial damage (fluorescein staining score, 0–9), meiboscore as determined by noncontact meibography (0–6), Schirmer test value, and meibum grade (0–3) were determined. The relationships between parameters were evaluated with the Spearman correlation coefficient (ρ). Results: The meiboscore was 2.8 ± 1.2, and the meibum grade was 1.8 ± 1.2. The meiboscore significantly correlated with the meibum grade (ρ = 0.272, P = 0.004), Schirmer test value (ρ = −0.220, P = 0.021), and LLT (ρ = −0.264, P = 0.005). The breakup time significantly correlated with LLT (ρ = 0.261, P = 0.006), meibum grade (ρ = −0.338, P < 0.001), and fluorescein staining score (ρ = −0.214, P = 0.025). The partial blink rate significantly correlated with the Schirmer test value (ρ = −0.240, P = 0.011). The meiboscore (P < 0.001) and meibum grade (P = 0.032) were significantly greater in males than in females. Conclusions: The morphology and function of meibomian glands are altered even at 15 years of age, with the changes being more prominent in males than in females.

Purpose To evaluate the effect of obstructive sleep apnea-hypopnea syndrome (OSAHS) on the meibomian glands, ocular surface, and tear parameters. Methods The study included 59 individuals (32 subjects with OSAHS, 27 control subjects) who underwent polysomnography in the Chest Diseases Clinic. The right eyes of all individuals were evaluated in the Ophthalmology Clinic. The first noninvasive tear break-up time (f-NTBUT) and the average noninvasive tear break-up time were measured, and Schirmer test was applied. Meibography was taken (Sirius; CSO, Florence, Italy), and meiboscore was used for indexing meibography. Finally, a sample was taken for conjunctival impression cytology. Results In the study and control groups, the median of f-NTBUT was 2.1 seconds [interquartile range (IQR); 1.5-5.0] and 5.7 seconds (IQR; 2.9-8.8) and the median of average noninvasive tear break-up time was 5.6 seconds (IQR; 3.6-9.5) and 7.2 seconds (IQR; 4.2-10.7), respectively (P = 0.007 and P = 0.487, respectively). The mean Schirmer value was 16.3 ± 5.9 mm (range; 5-25) and 17.3 ± 6.6 mm (range; 5-30) in the study and control groups (P = 0.604). In upper eyelid meibography, the median of loss in the meibomian glands was 20.10% (IQR; 11.60%-40.80%) in the study group and 14.70% (IQR; 10.40%-21.30%) in the control group (P = 0.043). In lower eyelid meibography, the median of loss in the meibomian glands was 19.00% (IQR; 13.60%-35.30%) in the study group and 12.40% (IQR; 9.10%-16.40%) in the control group (P = 0.002). The median of the Nelson grade in conjunctival impression cytology was 1 (IQR; 0-1) in the study group and 1 (IQR; 0-1) in the control group (P = 0.445). Conclusions The loss in the meibomian glands together with the shortened f-NTBUT shows that there could be a predisposition in OSAHS for evaporative dry eye originating from meibomian gland damage.

Purpose: To establish determining factors for fast corneal sensitivity (CS) recovery after pterygium excision. Methods: Thirty-two eyes of 14 males and 18 females with primary nasal pterygium were recruited. Differences in CS (in the 4 quadrants and the center using a Cochet–Bonnet esthesiometer), pterygium corneal area (PCA), tear osmolarity, tear break-up time, Schirmer test, and ocular symptoms were analyzed before and 1 month after lesion excision. The relationship between CS recovery (difference between the 2 time points; CS1 – CS0) and the other features was assessed. Results: All the studied locations exhibited normal (6 cm) or near-normal mean CS at the 2 time points, except a tendency for moderate hypoesthesia in nasal CS0 (median 4.5; range: 1.5–6.0 cm). Point by point comparison revealed significant postoperative improvements in nasal location (P = 0.008; Wilcoxon signed-rank test) with normal values in 17 eyes (53%) and a median CS1 = 5.0 cm (2.5–5.5 cm) in 15 eyes with no complete recovery. No significant correlation was found between CS0 and the studied variables, and CS1 was only significantly correlated with PCA (rho: -0.441; P < 0.05). CS recovery also showed significant correlation with PCA (rho = -0.516; P < 0.01). Conclusions: CS recovery after pterygium excision showed important variability, and the only studied factor that seems to be determinant could be PCA. It would be advisable to operate when the lesion is relatively small, with lower surgical injury and faster and complete recovery, thus protecting ocular surface homeostasis.

PURPOSE: (1) To qualify complaints of quality of vision in patients with (severe) keratoconjunctivitis sicca by examining straylight values and (2) to check for an effect of scleral lens wear on straylight. METHODS: Straylight was measured in 16 patients with severe keratoconjunctivitis sicca using the Oculus C-Quant. In 9 of these patients, scleral lenses were used, and straylight was measured with and without scleral lenses. Other tests included the Schirmer test, visual acuity, the van Bijsterveld score, and a straylight questionnaire. RESULTS: Patients with keratoconjunctivitis sicca had a mean straylight OD of log(s) = 1.36 ± 0.19 SD and OS of log(s) = 1.45 ± 0.17 SD. Mean age was 56 ± 9.3 SD. This was significantly higher than the mean age-matched normal value of log(s) = 1.10 (P < 0.001). Such a straylight increase is functionally significant. The difference in straylight with and without scleral lenses was 0.06 log units ± 0.02 SD, but this was not statistically significant for OD (P = 0.134) and OS (P = 0.293). No correlation was found between straylight and the van Bijsterveld score on the corneal section for OD (P = 0.326) and OS (P = 0.433). CONCLUSIONS: Keratoconjunctivitis sicca leads to increased straylight. However, this increase was not correlated to the amount of surface damage graded with the van Bijsterveld score. Further study on the cornea is necessary to determine the source of the increased straylight. Scleral lenses do not have a noteworthy influence on straylight in these patients.

PURPOSE To evaluate the efficacy and safety of autologous serum (AS) eye drops combined with punctal plugs (PPs) in patients with Sjogren syndrome (SS)-related dry eye. METHODS A retrospective clinical study was performed in patients with dry eye caused by SS. We evaluated the Schirmer test value, tear breakup time (tBUT), and fluorescein and Rose Bengal (RB) staining scores at baseline, 3 months, 6 months, 1 year, and >1 year after treatment. The dry eye indexes were also evaluated in 2 subgroups, which determined by the using of PPs, including the AS + PP group and AS only group. RESULTS A total of 56 eyes of 28 patients were investigated with a mean follow-up of 42.3 ± 26.1 months. After the application of AS eye drops, the Schirmer test showed no significant changes. The tBUT (2.7 ± 1.9 seconds) was significantly improved at each time point (3.9 ± 3.1, 4.5 ± 3.1, 3.7 ± 2.5, and 5.1 ± 4.0; P < 0.01), fluorescein staining (4.3 ± 2.8) was significantly improved at each time point (2.2 ± 2.2, 1.9 ± 1.9, 1.8 ± 1.6, and 1.8 ± 1.8; P < 0.01), and RB (2.6 ± 3.0) staining was significantly improved from 6-month treatment (1.5 ± 1.9, 1.9 ± 1.9, and 1.4 ± 1.8; P < 0.05, 0.01, and 0.01, respectively). When combined with PPs, the tBUT and RB staining scores were found to be significantly improved in the AS + PP group compared with those of the AS only group. CONCLUSIONS Long-term application of AS eye drops was found to be an effective and apparently safe treatment for SS dry eye. Furthermore, PPs in combination with AS eye drops were considered to have an additive effect on SS dry eye.

Purpose The aim of this study was to observe corneal sensitivity (CoS) longitudinally in patients with dry eye and to evaluate the correlation between CoS, severity, and the etiology of dry eye syndrome (DES). Methods In this prospective study, 46 patients with DES were examined on 4 occasions within 3 months. CoS was measured by the Cochet-Bonnet esthesiometer. Tear films were evaluated for lipid layer thickness, breakup time, fluorescein and lissamine green staining, and Schirmer test. Patients were classified into etiologic subgroups: hormonal, immunologic, toxic, neural, and environmental. For statistical statistics, Mann-Whitney and Kruskal-Wallis tests were used. Results Serial data curves of CoS demonstrated pronounced variability of values. CoS and SICCA scores were negatively correlated (r = -0.454, P = 0.007). The Schirmer test and CoS were positively correlated (r = 0.363, P = 0.013). The environmental group had the highest CoS values (5.5). There was no significant difference in CoS neither between nerve-induced and nonnerve-induced DES groups (P = 0.858) nor within the subgroups (P = 0.118). During 3 months, CoS increased in all patients (4.8-5.1). The DES severity was negatively correlated with CoS, indicating a reduction of neural function in severe DES. Conclusions Our results showed diminished CoS in severe dry eye although there was a high variability of CoS. This supports the hypothesis of different states of compensation as the disease continues and an association of CoS with different causes of dry eye. However, no statistical differences were found between etiological subgroups.

Purpose To evaluate the effect of lipid- versus sodium hyaluronate-based eye drops on optical quality and ocular surface parameters. Methods Sixty eyes of 30 patients with mild-to-moderate dry eye disease were included in a prospective randomized study. Each patient received either lipid- or sodium hyaluronate-based eye drops. Ocular symptom scores, breakup time, Schirmer test, fluorescein staining, noncontact meibography, and aberrometry were evaluated before and after 3 months of therapy. Results At the 3-month visit, a statistically significant improvement (P ≤ 0.05) was noted in both groups on the Schirmer test, breakup time, ocular surface staining, and symptom score. In the lipid group, patients with progressive meibomian gland (MG) loss (>50%) showed a significantly greater increase in their corneal higher-order (HO) Strehl ratio (0.25 ± 0.26 vs. -0.01 ± 0.25, P = 0.02) and modulation transfer function (MTF) (0.12 ± 0.17 vs. -0.02 ± 0.06, P = 0.03) than patients with less advanced MG disease. In the lipid group, a significant positive correlation was noted between the MG dropout rate and improvement in Schirmer values [Spearman correlation coefficient (CC): 0.79], corneal HO Strehl (CC: 0.75), and HO modulation transfer function (CC: 0.6), but a significant negative correlation was noted between the MG dropout rate and the HO root mean square (CC: -0.73). Conclusions Lipid-containing artificial tears seem to be superior to sodium hyaluronate-containing drops in terms of improving HO aberrations and optical quality in patients with significant MG dysfunction.

Purpose To evaluate changes in functional visual acuity (FVA) measurements before and after treatment with 0.1% cyclosporine ophthalmic solution for 3 months in patients with severe atopic keratoconjunctivitis (AKC). Methods Pairs of eyes were analyzed from 3 boys (mean age 9 ± 3.6 years) who complained of having severe AKC and were recruited for the study. Conventional Landolt visual acuity, FVA, and visual maintenance ratio (VMR) measurements were conducted before and after 3 months of 0.1% cyclosporine eye drop treatment. Tear film lipid layer interferometry, tear film break-up time, fluorescein and rose bengal vital stainings, and the Schirmer test were also performed before and after treatment. Results Eye drop treatment was associated not only with improvement of tear function and ocular surface status but also with better quality of visual function. The mean logarithm of the minimum angle of resolution FVA and Landolt visual acuity values improved from 0.45 ± 0.26 and 0.13 ± 0.17 before treatment to 0.16 ± 0.03 and -0.06 ± 0.05 after treatment, respectively. Similarly, the mean VMR values were markedly improved from 0.88 ± 0.06 to 0.95 ± 0.03 after treatment. Conclusions FVA and VMR are promising parameters in the assessment of dynamic visual acuity changes in AKC-affected patients and evaluation of treatment outcome.

PURPOSE The aim was to evaluate the effect of autologous platelet-rich plasma on lacrimal function in patients with severe dry eye. METHODS A prospective interventional case series design was adopted. Four patients with severe lacrimal dysfunction and severe dry eye were treated. Platelet rich-activated plasma (1 mL) was injected adjacent to the lacrimal gland on day 0 and at 4, 8, and 12 weeks. The objective parameters included a Schirmer test, ocular surface staining, and tear break-up time (TBUT). The patients were followed up for 12 weeks after the first injection. RESULTS All cases showed a significant improvement in lacrimal volume (from 3.3 ± 0.8 mm to 11.1 ± 2.3 mm). In all the patients, an increase in tear break-up time values and a decrease in ocular staining (basal 8.0 ± 0.61-2.8 ± 0.5) with subjective improvement occurred. None of the patients presented any adverse effect, and none reported pain or discomfort. Additionally, no complications were observed. CONCLUSIONS Injected platelet-enriched plasma was found to be safe and effective in increasing lacrimal production and in improving ocular staining secondary to severe dry eye. This approach could be an alternative for the management of these patients, although additional studies are required to perfect the technique.

PURPOSE To study the ocular surface changes in eyes after Descemet stripping automated endothelial keratoplasty (DSAEK) compared with those after penetrating keratoplasty (PKP). METHODS This prospective study compared the changes in 31 eyes of 28 patients who underwent DSAEK (DSAEK group) with those in 15 disease-matched eyes of 15 patients who underwent PKP (PKP group). Corneal epithelial integrity was evaluated using a fluorescein staining score. Corneal sensation was measured with a Cochet-Bonnet esthesiometer. Tear function was evaluated using the Schirmer test, tear clearance test, tear function index, and tear break-up time. RESULTS The postoperative fluorescein staining score was significantly higher in the PKP group than in the DSAEK group (P = 0.02). Postoperative corneal sensation was significantly better in the DSAEK group than in the PKP group (P < 0.01). Corneal sensation after DSAEK was significantly better than the preoperative value (P = 0.02). There were no statistically significant changes in the Schirmer test, tear clearance test, tear function index, or break-up time before and after the surgery in both the DSAEK and PKP groups. No significant differences were observed between the DSAEK and PKP groups after the surgery. CONCLUSIONS Corneal sensation was preserved, and epithelial damage was less severe after DSAEK compared with PKP. Preservation of corneal sensation may contribute to the early recovery of visual function and long-term maintenance of ocular surface health after DSAEK.

PURPOSE To evaluate the effect of topical cyclosporine A 0.05% after laser epithelial keratomileusis (LASEK). METHODS This retrospective nonrandomized comparative analysis was performed in 40 patients (80 eyes) with myopia who underwent flap-off LASEK. Twenty patients (group A) were treated with topical cyclosporine A 0.05% in combination with conventional treatment, and 20 patients (group B) received conventional treatment only. In each group, 10 patients had preoperative dry eye. Uncorrected visual acuity, refractive error, corneal haze grade, symptom score, and ocular surface parameters were measured in both groups before LASEK and at 1, 2, 4, and 8 weeks postoperatively. RESULTS There were no significant differences between the groups in postoperative uncorrected visual acuity, spherical equivalent, corneal haze grade, Schirmer test values, and keratoepitheliopathy scores. Group A had lower symptom scores (0.80 ± 0.52 vs.1.35 ± 0.49; P < 0.01) and higher tear film break-up time (BUT) (8.05 ± 1.39 vs. 6.55 ± 1.39 seconds; P < 0.01) compared with group B at 4 weeks after LASEK. In addition, in preoperative dry eye patients, symptom scores and tear film BUT returned to preoperative level at 4 weeks postoperatively in group A, whereas they returned to preoperative level at 8 weeks in group B. CONCLUSIONS Treatment with topical cyclosporine A 0.05% can improve ocular discomfort and increase tear film BUT during the early postoperative period, especially in patients with preoperative dry eye.

PURPOSE: To evaluate dry eye in patients with fibromyalgia (FM). METHODS: Fifty-three FM patients and 53 age and sex well-matched controls were included in this study. Visual analog scale (VAS), number of tender points, FM impact questionnaire (FIQ), Beck depression scale (BDS), Ocular Surface Disease Index (OSDI), the tear break-up time (TBUT), Schirmer test, and tear osmolarity (TO) were assessed. RESULTS: The OSDI, TBUT, Schirmer test, and TO scores of the FM and control groups were significantly different (P < 0.05). The OSDI, TBUT, Schirmer test, and TO were higher in FM with high FIQ, and TBUT and TO were higher in FM with high BDS. In FM patients, Schirmer test was correlated with the VAS (r = -0.429, P = 0.001), BDS (r = -0.277, P = 0.044), and FIQ (r = -0.382, P = 0.005), and the TBUT was correlated with the VAS (r = -0.537, P < 0.001), BDS (r = -0.350, P = 0.010), and FIQ (r = -0.456, P = 0.001). In addition, TO was significantly correlated with the VAS (r = 0.681, P < 0.001), BDS (r = 0.661, P < 0.001), and FIQ (r = 0.842, P < 0.001). However, no significant correlation existed between the OSDI and the VAS, BDS, or FIQ. CONCLUSIONS: We have revealed an association between FM disease activity and dry eye severity. The consideration of this relation will be useful in the treatment of FM with deteriorated clinical status.

PURPOSE We aimed to compare the tear meniscus measurements using strip meniscometry (SM) and Keratograph5M (K5M) between 3 subtypes of dry eye disease patient groups, classified according to the presence of meibomian gland dysfunction (MGD), and normal subjects. METHODS We enrolled 145 eyes from 145 subjects and measured the tear meniscus using SM and K5M, tear film breakup time, ocular surface staining, and ocular surface disease index; the Schirmer test; and examined lid margins and meibomian glands. Correlation of tear meniscus parameters with other parameters and efficacy of the 2 measurements were evaluated. RESULTS The SM and K5M results were significantly lower in the non-Sjogren syndrome aqueous-deficient dry eye (non-SS ADDE) with and without MGD groups than in the MGD-only group and normal subjects. The SM or K5M results correlated with each other and with other ocular surface parameters. The area under the curve (AUC) of the SM and K5M results was 0.637 (P = 0.012) and 0.610 (P = 0.042), respectively. Except for the MGD group, the AUC of the SM and K5M results were 0.721 (P < 0.001) and 0.694 (P = 0.001), respectively. The AUC of SM and K5M were 0.947 (P < 0.001) and 0.784 (P = 0.002), differentiating non-SS ADDE-only patients from those with normal eyes. CONCLUSIONS Tear meniscus measurements using SM and K5M can compensate for detection of aqueous-deficient components of dry eye. These results should be interpreted according to the presence or absence of MGD.

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

Purpose To determine the utility of the tear function index (Liverpool modification TFI) in assessing tear turnover rate (TTR), evaluate association of tear clearance rate (TCR) and TFI with measurements of TTR by fluorophotometry, and determine effectivity of these test measures in dry eye (DE) diagnosis. Methods Forty-one subjects with DE and 15 control subjects participated. Tests included symptoms, fluorophotometry (by automated scanning fluorophotometry), and TCR and TFI from a prepared Liverpool modification TFI strip. Results Significant differences between subjects with DE and control subjects were found for all tests. Although wetting length values gave highest sensitivity (SS) and specificity (SP) (71% and 73%, respectively), this resulted from a high degree of selection bias because the Schirmer test was one of the inclusion criteria for patients entering the study. Therefore, the best tear production test was found to be TTR (SS 71% and SP 60%). The TTR test is not readily available in clinical settings; therefore, associations between the TTR test and other tests were determined. Significant correlations were found between TTR and wetting length/TCR/TFI, indicating these latter clinical tests useful as surrogates. The strongest correlations, TTR/TCR at 0.69 (P = 0.000) and TTR/TFI at 0.65 (P = 0.000), indicate TCR/TFI with the Liverpool test can be used as an alternative to TTR by fluorophotometry. The diagnostic effectiveness between these tests was compared, with both TCR and TFI found to have equal effectivity of 78% SS and 40% SP (TCR) and 83% SS and 40% SP (TFI). Conclusions TCR measured by the commercially available Liverpool modification TFI strip is an acceptable alternative to TTR by fluorophotometry as a measure of tear production. It is effective as a single test for the discrimination of those with DE from those without the condition.

To compare the 2- and 5-minute Schirmer test I (test without anesthesia) in healthy individuals so as to exploit the possibility of using the 2-minute instead of the 5-minute test.162 healthy (81 males and 81 females) individuals (without dry eye symptoms and free of pathology affecting tear secretion and tear drainage), aged between 20 and 85 years, were recruited in the study (3 age-groups: 20-45, 46-65, and 66-85 years). Schirmer test I (test without topical anesthesia) was performed in both eyes simultaneously. The values of tear secretion were recorded in 2 and 5 minutes and compared in relation to age and gender. The patients were asked to comment on the duration and the discomfort they felt.In 2 minutes, the average tear secretion was 12.71 +/- 2.47 mm (mean +/- SD) for the right eyes and 12.62 +/- 2.09 mm for the left eyes and in 5 minutes, 16.74 +/- 3.59 and 16.831 +/- 3.38 mm, respectively. For confidence interval of 99%, the mean values of tear secretion, in individuals who were expected to have normal secretion, were higher than 10 mm in 2 minutes and higher than 13 mm in 5 minutes (significance level 1% or a = 0.01). Only 5.55% of the eyes presented values10 mm (7-9.5 mm) in the 2-minute test and values13 mm (8.5-12.5 mm) in the 5-minute test. There was no significant difference in tear secretion between males and females, between the different age-groups, and between right and left eyes. All the examined individuals expressed their negative comments and considered the test as an unpleasant procedure and consequently preferred the shorter possible duration.The 2-minute test is more acceptable by both the examiners and the examined individuals and may be used, in respect to the above results, as an alternative of the 5-minute test. Normal individuals tend to have Schirmer test I valuesor = 10 mm in 2 minutes, irrespective of age and gender.

Purpose To describe a method of quantifying the tear meniscus height (TMH) and using these values to diagnose patients with dry eye. Methods Thirty-eight eyes of 19 healthy subjects and 14 patients diagnosed with dry eye were studied. Each eye received 2 microL of 1% fluorescein-sodium solution in the conjunctival sac, and digital photographs were taken of the external surface of the eye with a fundus camera. The tear meniscus was extracted from the digitalized image and used to measure the TMH with NIH image software. The correlation between the mean TMH and Schirmer test values or cotton-thread test values was evaluated. Results The means of the upper and lower TMH in healthy subjects were 0.22 +/- 0.06 and 0.24 +/- 0.08 mm, respectively. The comparable values in patients with dry eye were 0.17 +/- 0.04 and 0.17 +/- 0.07 mm (upper TMS, P = 0.01; lower TMH, P = 0.04; unpaired t test). A significant correlation was found between the TMH and Schirmer test values (r = 0.72, P = 0.01) but not with cotton-thread test values. Conclusions Fluorescein photographs of the eye can be used to quantify the upper and lower TMH separately and simultaneously without specialized equipment. This technique can be used for the diagnosis of dry eye.

Purpose: A controlled uniocular study to evaluate the short-term efficacy of lacrimal punctum occlusion in the treatment of severe dry eye caused by Sjogren syndrome. Methods: Uniocular punctum occlusion by punctum plug in the upper and lower puncta in 1 eye was performed in 20 patients with severe keratoconjunctivitis Sicca caused by Sjogren syndrome. To overcome possible interindividual variability between patients, the other eye, in the same patient, was not occluded and served as a control eye. The eye to be occluded was randomly selected. The patients were instructed to continue using their dry eye medications. Tear function tests (Schirmer test, rose Bengal test, and debris in de cul-de-sac) were performed in both eyes. Subjective complaints (discomfort) were registered for both eyes. All the above-mentioned data were collected before starting the treatment and at least 6 weeks later. The above-mentioned parameters were compared and statistically analyzed in both eyes. Results: Of the 20 patients, 7 patients dropped out. The remaining 13 patients completed the final analysis. In the occluded eye, we found a significant improvement in both the subjective complaints and the rose Bengal score, but the Schirmer test and the tear mucus score did not change. Conclusion: Punctum occlusion therapy in a short-term study improved the rose Bengal score and discomfort score in our patients and thus may be helpful in the treatment of severe dry eye caused by Sjogren syndrome.

PURPOSE Given that early-stage dry eye is difficult to diagnose, the purpose of this study was to evaluate the performance of matrix metalloproteinase 9 (MMP-9) and tear film osmolarity (TFO) in a cohort of elderly patients with potential dry eye disease (DED). METHODS A group of 20 patients, aged 60 years and above, previously undiagnosed with DED were selected. The following DED tests were performed: tear osmolarity, MMP-9 (InflammaDry), Schirmer test, tear film break-up time, Ocular Surface Disease Index (OSDI) questionnaire, corneal fluorescein staining, and conjunctival lissamine green staining. MMP-9 concentrations in tears collected through Schirmer strips were analyzed by an MMP-9 enzyme-linked immunosorbent assay [ELISA]. Subjects were classified by symptoms (classification A: OSDI ≥10, n = 9), based on suspected mild dry eye (classification B: n = 14), TFO difference >8 mOsm/L between both eyes (classification C: n = 13), and TFO cutoff at 308 mOsm/L (classification D: >308 mOsm/L, n = 11). RESULTS Eleven percent (1/9) of the symptomatic and 14% (2/14) of the suspected mild dry eye were positive for MMP-9. InflammaDry MMP-9 tests were confirmed to be accurate through an ELISA. Sixty-seven percent (6/9) of the symptomatic and 64% (9/14) of the suspected mild dry eye were positive for tear osmolarity. None of the evaluated tear film parameters showed a significant correlation, although tear osmolarity and symptoms trended toward significance (r = 0.433, P = 0.06), whereas MMP-9 and corneal staining showed a positive association (r = 0.376, P = 0.10). CONCLUSIONS Similar to corneal staining, the MMP-9 is likely a late-stage sign that is rarely overexpressed in mild subjects, whereas tear osmolarity tends to be a more frequent early indicator of ocular surface disequilibrium within mild subjects.

PURPOSE The aim of this study was to evaluate the efficacy of hypotonic 0.18% sodium hyaluronate (SH) eye drops under the clinical settings of the dry eye workshop treatment guideline for mild dry eye disease (DED). METHODS This analysis included 60 patients with DED. Patients with level 1 DED were treated with either isotonic 0.1% SH (group 1) or with hypotonic 0.18% SH eye drops (group 2). Patients with level 2 DED were treated with 0.1% fluorometholone, 0.05% cyclosporine A, and either isotonic 0.1% SH (group 3) or hypotonic 0.18% SH (group 4) eye drops. Tear film breakup time (TBUT), Schirmer test, corneal staining with fluorescein, and ocular surface disease index score were recorded at baseline, 1 month, and 3 months after treatment. RESULTS In group 2, TBUT at 3 months (P = 0.03) and corneal staining scores at 1 and 3 months (P ≤ 0.03) were significantly improved after the treatment compared with baseline scores, whereas these parameters were not changed during the follow-up period in group 1. In groups 3 and 4, TBUT and corneal staining scores at 1 and 3 months, and ocular surface disease index score and Schirmer test results at 3 months after the treatment showed significant improvements compared with the baseline score (P < 0.05). Group 4 patients showed an extended TBUT and an improved corneal staining score (P ≤ 0.01) at 3 months after treatment, compared with the values of group 3. CONCLUSIONS Hypotonic 0.18% SH eye drops seemed to be effective in improving tear film stability and ocular surface integrity compared with isotonic 0.1% SH eye drops in patients with mild DED.

We examined a group of normal subjects to evaluate the tear film function by measuring reflex tear capacity using the Schirmer test without anesthetic, steady state tear flow using fluorophotometry, meibomian gland function based on gland drop-out, expressible lipid volume and viscosity, tear loss from evaporation, and tear osmolarity. We found the average tear flow to be 0.19 +/- 0.19 microliters/min, lower than previously measured. The average tear volume was also correspondingly less, 2.74 +/- 2.0 microliters. We found there was a decline associated with advancing age for all parameters except the decay constant and lipid volume. The highest correlations with aging were tear volume (-0.64), Schirmer test (-0.63), and tear osmolarity (0.59). Our results indicate that there is a decline in tear film function throughout life and that tear flow is considerably less than previously estimated.

The 5-minute Schirmer test is a commonly described test for dry eye syndrome but is impractical for most ophthalmologists to perform routinely because of the 5-minute time frame. Hence, we decided to evaluate the intraindividual reliability of different wetting times of the Schirmer basal tear secretion test correlated to that of the standard 5-minute Schirmer test.A prospective study was performed using 60 eyes of 30 patients. All patients had symptoms of dry eye syndrome. Patients were excluded if they had anatomic lid abnormalities that could interfere with the conduct of the test. The reliability of the Schirmer test at 30 seconds and 1, 2, 3, and 4 minutes was compared with that of the standard 5-minute test using the intraclass correlation coefficient (ICC).The ICC for each eye was only moderate at 30 seconds but was high to extremely high thereafter. Specifically, at 1 minute, the ICC for right eyes was 0.938 and for left eyes was 0.817. Furthermore, 100% of patients with severe dry eye (defined as a 5-minute Schirmer test of 5.5 mm or less) had a 1-minute Schirmer test less than or equal to 2 mm. Also, 80% of patients with a moderate dry eye (defined as a 5-minute Schirmer test between 5.5 to 10 mm) had a 1-minute test between 3 to 6 mm.Our results support the hypothesis that shorter durations of the 5-minute Schirmer test correlate highly with those of the 5-minute test. Specifically, the 1-minute test correlates highly with the 5-minute test and will make this test much more practical for ophthalmologists.

To explore a modified Schirmer test for patients with submandibular gland (SMG) transplant.Thirty-seven patients (39 eyes) with severe keratoconjunctivitis sicca who underwent SMG transplantation in an institutional setting were included. Schirmer test I was performed on each eye under 4 different conditions: (1) Basal condition: a single test at 23°C room temperature after 30 minutes of rest (ST1 results); (2) Physical activity: 6 consecutive tests 0 to 30 minutes after stair climbing (ST2-ST7 results in a time sequence); (3) Glandular massage: 5 consecutive tests 0 to 25 minutes after glandular massage (ST8-ST12 results in a time sequence); and (4) High temperature: a single test at 30°C room temperature (ST13 results). The main outcome measurement was value of Schirmer test.Compared with the basal condition (median ST1 score was 23 mm), physical activity produced increased ST scores within the first 20 minutes (median ST2 to ST5 scores were 73, 69, 39, and 34 mm, respectively, P0.01). At the first 10 minutes after glandular massage, median ST8 and ST9 scores were 72 and 18 mm, respectively (P0.01). At 30°C room temperature, median ST13 score was 59 mm (P0.01), whereas 20 to 30 minutes after physical activity and 10 to 25 minutes after glandular massage, median ST6 to ST7 and ST10 to ST12 scores were 25, 25, 19, 17, and 21 mm, respectively (P0.05).A basal condition without physical activity or glandular stimulation at a comfortable and stable room temperature could be considered a standardized condition for Schirmer test for patients with SMG transplant.

We analyzed patients with dry eye syndrome with regard to autoimmune conditions. A total of 116 patients with dry eye syndrome were divided into three groups: simple dry eye (SDE), i.e., dry eye with no circulating autoantibodies; autoimmune positive dry eye (ADE), dry eye with circulating autoantibodies; and Sjogren's syndrome (SS), dry eye associated with Sjogren's syndrome. Schirmer test showed values of 3.0 +/- 2.2 mm in SDE, 3.1 +/- 2.0 mm in ADE, and 2.4 +/- 2.3 mm in SS reflecting the inadequacy of this test in differentiating among the groups. However, Schirmer test with nasal stimulation showed values of 19.1 +/- 12.4 mm in SDE and 16.4 +/- 10.9 mm in ADE, which were significantly higher than the 7.0 +/- 6.6 mm found in SS (p < 0.01). Moreover, ocular surface alterations evaluated by vital staining and brush cytology were significantly milder in SDE and ADE than in SS. SDE and ADE have less ocular surface abnormalities with good reflex tearing, whereas SS has less reflex tearing and more squamous metaplasia.

Objective To assess the results of 1-minute and 5-minute Schirmer test (ST) when eyes are open (STo) and closed (STc) in normal subjects and patients with dry eye disease. Methods In a comparative, observational case series study, 34 normal volunteers (group 1) and 34 patients with dry eye disease (DED) associated with Sjogren syndrome (group 2) were included in the study. STo and STc for 1 minute and 5 minutes were performed separately for all subjects with an interval of at least 24 hours using Whatman No. 41 (5 × 60 mm) with bended end of the paper inserted into the lateral side of the lower conjunctival fornix. Results In group 1, there were 19 females and 15 males with a mean age of 20.8 years (range 18 to 23 years). In group 2, there were 29 females and 5 males with a mean age of 53.7 years (range 35 to 75 years). Mean value of STc was significantly less than STo in both 1 minute and 5 minutes in both groups. One-minute STo and STc showed significantly less wetting than the 5-minute test in both healthy and patients with DED. Normal distribution was observed for all the values. A significant correlation between 1-minute and 5-minute tests in both STo and STc were found in the two groups. Therefore, two equations were proposed to calculate the 5-minute from 1-minute ST in each group. Statistical analysis did not provide a reliable equation for calculating the standard ST (5-minute STo) from the most comfortable state (1-minute STc). Conclusion Faster and more comfortable ST (1-minute) is a reliable test to calculate the 5-minute ST in both open and closed eyes, using the provided equations. The 1-minute STc is not a reliable test to calculate the 5-minute STo.

We evaluated the meibomian gland function of 11 patients before and during treatment with isotretinoin (Accutane) by assessing tear osmolarity, meibomian gland morphology, tear production, rose bengal staining, and meibomian gland excreta. We found, during Accutane use, that meibomian glands appeared significantly less dense and atrophic by meibography. Excreta thickness increased from 1.7 +/- 0.9 to 3.1 +/- 1.2 (p less than 0.005), and expressible excreta volume decreased from 1.52 +/- 0.68 to 1.10 +/- 0.3 (p less than 0.05) (scale 1-4). We also found a significant increase in tear osmolarity from 304.9 +/- 11 to 316.3 +/- 10 mosmol/L (p less than 0.005). There was no significant change in the Schirmer test during treatment. We suggest that the clinical symptoms of blepharitis during Accutane therapy are related to decreased meibomian gland function and consequent increased tear evaporation and tear osmolarity.

PURPOSE To investigate the changes in tear flow and tear film stability after photorefractive keratectomy (PRK) for myopia. MATERIAL AND METHOD One eye of 32 patients underwent unilateral PRK procedure for the correction of myopia ranging from -1.50 to -6.00 diopters (D) (mean -3.65 +/- 1.55 D). Schirmer test values and break-up time (BUT) scores were measured 6 weeks after the PRK procedure. Unoperated, contralateral eyes were used as control eyes for each patient. The Schirmer test scores and BUT values were statistically analyzed using independent t test. RESULTS The mean Schirmer test value was 14.45 +/- 7.79 mm in the operated eyes. It was 28.83 +/- 5.89 in the control eyes. The decrease in Schirmer test value was statistically significant (t = 8.28, p = 0.0001). The mean BUT scores were 13.19 +/- 5.09 s in the operated eyes and 27.83 +/- 9.31 s in the control eyes. The decrease was statistically significant (t = 7.86, p = 0.0001). CONCLUSION PRK causes a decrease in tear flow and tear film stability that is probably caused by decreased corneal sensation after PRK.

Purpose To describe corneal sensitivity changes caused by different incision methods-manual small-incision cataract surgery (manual SICS) and phacoemulsification-and their influence on tear film quantity and quality. Methods This was a prospective observational study conducted in 30 subjects undergoing manual SICS or phacoemulsification. Corneal sensitivity was assessed before and 1, 7, and 15 days after surgery by Cochet-Bonnet esthesiometer. Tear meniscus, noninvasive breakup time, lipid pattern, and Schirmer test results were evaluated. Patient symptoms were reviewed based on the Ocular Surface Disease Index. Results In the group undergoing phacoemulsification, corneal sensitivity decreased at the incision site and at other sites on days 1, 7, and 15 after surgery, whereas in the group undergoing manual SICS, no change in corneal sensitivity was noted. Between-group difference in corneal sensitivity was significant on days 1, 7, and 15. Aqueous production significantly (P = 0.016) increased on the first day in both groups and returned to presurgery level on day 15. Tear film quality decreased on day 1 only in the group undergoing manual SICS (P = 0.035). Tear meniscus and tear lipid profile showed no change in either group. Patient symptoms significantly increased on day 1 in both groups, and the difference between the 2 groups was significant on day 15 (P = 0.044). Conclusions Compared with manual SICS, temporal-side incision in phacoemulsification decreased corneal sensitivity in the incision site and other sites until day 15 and changes in tear film quantity and patient symptoms only on day 1.

To compare the repeatability of the Schirmer test (ST) administered with the eyes open (STo) with the repeatability of the ST administered with the eyes closed (STc).STo and STc without anesthesia were alternately applied with 1-day intervals for a total of 6 times on 28 eyes of 14 healthy volunteers. The intraclass correlation coefficients (ICCs) and their 95% confidence intervals (CIs) were calculated to assess test-retest reliability of the STo and STc.STc scores were found to be statistically lower than the STo scores in general (right eyes: t = 2.033, P = 0.048; left eyes: t = 3.474, P = 0.004). The ICC was 0.632 (right eyes) and 0.618 (left eyes) for STo and 0.943 (right eyes) and 0.933 (left eyes) for STc.Our study suggests that administering the ST with the patient's eyes closed produces less variable results and more repeatability than STo in normal subjects. Although our results may not extend to dry eye patient populations, we propose that STc without anesthesia can be considered by those ophthalmologists who frequently use the ST as an adjunct to the differential diagnosis of dry eye in patients presenting with ocular discomfort, making ST a more reliable test in everyday practice.

PURPOSE: To evaluate the safety and efficacy of an original warm moist air device on tear functions and ocular surface of patients with simple meibomian gland dysfunction (MGD). METHODS: Fifteen patients with simple MGD and 20 healthy volunteers were recruited in an initial prospective interventional clinical trial to evaluate the safety and short-term effects of the warm moist air device. The device was applied to the eyes of the subjects for 10 minutes. Temperatures of the eye lids and corneas were measured with an infrared thermometer. Symptoms of ocular fatigue were scored using visual analog scales (VASs). Schirmer test, tear film break-up time (BUT), DR-1 tear film lipid layer interferometry, fluorescein staining, and rose bengal staining were also performed before and after the application of the eye steamer. After the initial study, another 2-week prospective clinical trial was carried out in 10 patients with MGD who received the warm moist air treatment. Ten other patients were also recruited and received warm compress treatment with hot towels for 2 weeks to evaluate the long-term effects of the warm moist air device and the warm compresses on tear film lipid layer thickness and ocular surface health. The warm moist air device and the warm compresses were applied for 10 minutes twice a day. The changes in VAS scores for symptoms, BUT values, fluorescein, and rose bengal staining scores were examined before and after each treatment during the second trial. RESULTS: VAS scores of ocular fatigue improved significantly with short- and long-term applications of the warm moist air device in both studies. The mean corneal surface and eye lid temperatures showed significant elevation within safe limits 10 minutes after the moist air application. The mean BUT prolonged significantly in the patients receiving warm moist air applications but did not change significantly in those treated with warm compresses. DR-1 tear film lipid layer interference showed evidence of lipid expression in the patients and controls, with thickening of the tear film lipid layer after 10 minutes of warm moist air device use. In the 2-week trial, tear film lipid layer thickness increased in both warm moist air device and warm compress groups, with a greater extent of increase in the warm moist air device group. CONCLUSION: Warm moist air device use provided symptomatic relief of ocular fatigue and improvement of tear stability in patients with MGD. The new warm moist air device seems to be a safe and promising alternative in the treatment of MGD.

To investigate the efficacy of umbilical cord serum eyedrops for the treatment of severe dry eye syndrome.Fifty-five eyes of 31 patients with severe dry eye syndrome were treated with umbilical cord serum eyedrops. Symptom scoring, tear film break-up time (BUT), Schirmer test, corneal sensitivity test, and corneal fluorescein staining were performed before and 1 and 2 months after treatment, and conjunctival impression cytology was performed before and 2 months after treatment. The concentrations of epidermal growth factor (EGF), vitamin A, and transforming growth factor-beta (TGF-beta) in umbilical cord serum and normal peripheral blood serum were measured.Two months after treatment, significant improvement was observed in symptom score (from 3.07 +/- 0.54 to 0.96 +/- 0. 58), BUT (from 3.96 +/- 1.56 to 5.45 +/- 2.54 seconds), and keratoepitheliopathy score (from 4.87 +/- 3.22 to 1.71 +/- 1.84) (P0.01). There was no statistically significant change in Schirmer and corneal sensitivity tests. In impression cytology, the grade of squamous metaplasia (from 2.35 +/- 0.72 to 1.44 +/- 0.69) and goblet cell density (from 80.91 +/- 31.53 to 154.68 +/- 43.06 cell/mm) improved significantly (P0.01). The mean concentrations of EGF, TGF-beta, and vitamin A were 0.48 +/- 0.09, 57.14 +/- 18.98, and 230.85 +/- 13.39 ng/mL in umbilical cord serum and 0.14 +/- 0.03, 31.30 +/- 12.86, and 372.34 +/- 22.32 ng/mL in peripheral blood serum, respectively.Umbilical cord serum contains essential tear components, and umbilical cord serum eyedrops are effective and safe for the treatment of severe dry eye syndrome.

PURPOSE To assess the alterations of the tear film lipid layer and tear functions in patients with seasonal allergic conjunctivitis (SAC) and to compare the results with healthy control subjects. METHODS Seventy-eight eyes of 39 consecutive patients diagnosed as SAC (mean age 32.6 years; 11 male, 28 female) as well as 20 eyes of 10 healthy control subjects (mean age 32.5 years; 6 male, 4 female) underwent slit-lamp examinations, tear film breakup time measurements (BUT), corneal fluorescein stain scoring, Schirmer test, and tear film lipid layer interferometry. The 2 groups were then compared for the examined parameters. RAST and serum IgE level evaluations were also carried out in the patients to confirm the diagnosis of allergy. RESULTS The mean BUT was 3.4 +/- 1.5 seconds in patients with SAC compared with the mean value of 12.4 +/- 2.4 seconds in the controls (P < 0.05). There were no significant differences in relation to Schirmer test values between the 2 groups; 78% of the patients with SAC had grade 3 or above dry eye change in tear film lipid layer interferometry, whereas none of the controls had an interferometry grade greater than 3 (grade 1-2 normal; grade 3-4 dry eye; grade 5 severe dry eye). Eyes with SAC had significantly higher tear film lipid layer thickness ranges compared with the control eyes (P < 0.05). CONCLUSION SAC was associated with advanced tear instability and thickening of the tear film lipid layer. Evaluation of the tear film lipid layer thickness might be useful in the assessment of the extent of dry eye disease and the treatment outcomes in patients with allergy.

Our purpose was to investigate the relationship between insufficient tear secretion and decreased corneal sensitivity. We studied 59 patients with dry eye, 15 of whom had Sjogren's syndrome (SS), and 26 healthy subjects. Corneal sensitivity was measured by the esthesiometer of Cochet and Bonnet. Schirmer test with or without anesthesia, tear clearance rate, tear function index, and rose bengal and fluorescein staining were also evaluated. The mean corneal sensitivity of either dry-eye group (4.6 +/- 1.2 and 4.5 +/- 1.2 cm for non-SS and SS dry eye, respectively) was significantly lower than that of the control (5.8 +/- 0.4 cm, p < 0.001). Corneal sensitivity correlated significantly with the Schirmer values with anesthesia and the tear function index in the two dry-eye groups and the control (p < 0.05). There were significant relationships between corneal sensitivity and the rose bengal and fluorescein scores in the three groups (p < 0.05). Hyposecretion of tears in dry eye may lead to pathologic changes in corneal epithelium and a decline in corneal sensitivity. Prompt treatment of dry eye is essential to maintain a normal corneal protective mechanism.

Blepharitis patients have a number of disturbances in their tear film associated with meibomian gland dysfunction that affect evaporation and tear osmolarity. We tested a series of 156 consecutive patients, with a presumed diagnosis of blepharitis, dry eye, or allergic disease, and a series of 72 normals. We compared their tear film characteristics using tear osmolarity, tear volume, tear production (fluorophotometric and Schirmer test), tear turnover (decay constant), tear evaporation, and meibomian gland function evaluated by gland drop-out, expressed lipid viscosity, and volume. Of the 156 patients tested, we found 37 had dry eye, 10 had only allergic disease, 73 had meibomian gland dysfunction and dry eye, and 36 had only meibomian gland dysfunction. We created a model of the relative influence some of these factors had on each other using their correlation coefficients. The highest correlations for osmolarity were Schirmer test (-0.44), lipid volume low (-0.44), lipid viscosity high (0.39), gland drop-out (0.39), and tear evaporation (0.36). With regression analysis we accounted for 47% of the total variation in osmolarity, but only 17% of the variation in tear evaporation. We also present our classification system for blepharitis and dry eye patients based on our measurable physiologic parameters.