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Background To evaluate the efficacy and safety of a thermal massager for the treatment of dry eye syndrome. Methods Ninety-five patients with dry eye syndrome were randomly assigned to receive either the thermal massager or artificial tears treatment. Thermal massage consisted of vibration, massage and thermotherapy and was carried out twice daily. Patients in the artificial tears group received 0.1% sodium hyaluronate solution five times daily. The Ocular Surface Disease Index (OSDI) score, break-up time (BUT), Schirmer test, fluorescein staining of the cornea, tear osmolarity test and adverse events were evaluated after 4 weeks. Results OSDI showed a significant improvement in both groups and improvement was significantly greater in thermal massager group (p=0.032). BUT and fluorescein staining also indicated significant improvement. No differences were found between the two groups in measures other than the OSDI. Adverse events were mild and transient. Conclusions Thermal massage was effective in improving dry eye syndrome both subjectively and objectively. It was safe and seems to be a useful treatment option. [ABSTRACT FROM AUTHOR]

Objective To evaluate the feasibility of microvascular autologous transplantation of partial submandibular gland (SMG) to prevent or reduce epiphora in severe keratoconjunctivitis sicca (KCS). Methods A total of 39 patients with KCS, covering 42 eyes, were randomised to undergo transplantation of partial or total SMG from January 2006 to December 2009. Clinical data of survival rate of transplanted SMG, ophthalmologic features of best-corrected visual acuity, Schirmer test results, break-up time (BUT) of tear film, fluorescence staining, incidence of postoperative epiphora and frequency of subsequent surgery were compared between two groups. Results Total SMG transplantation was performed in 22 eyes, and partial SMG transplantation was performed in the other 20 eyes. All transplanted SMGs survived. Microvascular crisis occurred in one case of partial SMG transplantation, but the gland survived after exploration to remove the venous thrombus. Obstruction of the ductal orifice in one case of partial SMG transplantation was resolved by reconstruction of the ductal orifice. Symptoms of dry eyes disappeared, and patients were able to discontinue use of artificial tears. Severe epiphora occurred in 6 eyes undergoing partial SMG transplantation and in 19 eyes undergoing total SMG transplantation ( p<0.01). Surgical reduction was performed in 6 eyes undergoing partial SMG transplantation and 18 eyes undergoing total SMG transplantation ( p<0.01). Conclusions Microvascular transplantation of partial SMG is feasible and effective for severe KCS and does not decrease the survival rate of transplanted SMG. For ample SMGs with normal function, transplantation of partial SMG alleviates the symptoms of dry eye and significantly reduces the incidence of severe postoperative epiphora. [ABSTRACT FROM AUTHOR]

Aims To evaluate the effect of topical diquafosol in patients with meibomian gland dysfunction (MGD) using tear film parameters and quantitatively analyse the meibomian gland morphology. Subjects and Methods The subjects were 19 eyes of 10 patients diagnosed with obstructive MGD. All subjects were given 3% diquafosol ophthalmic solution with instructions to use one drop four times a day. Ocular symptoms were scored from 0 to 14. Lid margin abnormalities were scored from 0 to 4. Changes in the meibomian glands were scored using non-contact meibography (meiboscore). Superficial punctate keratopathy (SPK) was scored from 0 to 3. Meibum was graded from 0 to 3. Tear film production was evaluated by Schirmer's test. Quantitative image analysis of the meibomian glands was performed using the original software. Results 10 patients completed more than 4 months of therapy. Ocular symptoms, lid margin abnormalities, SPK score and meibum grade were decreased. Break-up time and tear film meniscus were increased. Mean ratio of the meibomian gland area was significantly increased after treatment ( p<0.0001). Conclusions Quantitative image analysis was useful for evaluating the morphological changes of the meibomian glands. Topical diquafosol therapy was effective for patients with obstructive MGD. [ABSTRACT FROM AUTHOR]

Aim To investigate, using laser scanning confocal microscopy (LSCM), the morphological changes of meibomian glands (MGs) in patients with glaucoma. Methods A total of 80 patients who were glaucomatous were enrolled, and 20 healthy subjects were used as controls. After completing an Ocular Surface Disease Index (OSDI) questionnaire, all subjects underwent tear film break-up time (BUT), fluorescein staining, Schirmer test I (STI) and LSCM examination of the MGs. The main outcome measures were: eyelid margin epithelial cell density, mean acinar density (MAD) and area (MAA), glandular orifice area, secretion reflectivity and inhomogeneous appearance of interstice and acinar wall. Results According to the number of anti-glaucoma medications they were taking, patients were divided into three groups: group 1 (30 eyes), one drug; group 2 (23 eyes), two drugs; group 3 (27 eyes), three or more drugs. LSCM showed lower MAD and MAA, greater secretion reflectivity and glandular orifice area in groups 2 and 3 than in controls (p<0.05). The inhomogeneity of the interstice and acinar wall was significantly greater in all groups compared to controls (p<0.05). Preserved prostaglandin analogues (PGAs) induced more pronounced modifications of all parameters than preservative free (PF)-PGAs (p<0.05). No significant differences were found between preserved and PF-ß-blockers. Significant relations were found among MAD, MAA, secretion reflectivity and OSDI score, BUT and ST (p<0.05) and between secretion reflectivity and orifice area (p<0.001). Conclusions In vivo LSCM is an effective tool in revealing morphological changes of MGs induced by anti-glaucoma medications. Given the key role in the ocular surface health, the evaluation of MG status in patients who are glaucomatous is worthwhile. [ABSTRACT FROM AUTHOR]

Aims: To assess the changes in ocular surface abnormalities and meibomian fatty acid composition in patients suffering from meibomian gland dysfunction (MGD) after treatment with oral minocycline associated with lid hygiene versus lid hygiene only. Methods: We evaluated the break-up time, corneal staining and quality of meibomian excreta, and collected meibomian oil in 20 individuals suffering from MGD before and after 8 weeks of minocycline associated with lid hygiene (n = 10) or lid hygiene only (n = 10). Meibomian fatty acids were directly transmethylated and analysed by gas chromatography (GC) and GC mass spectrometry. Results: The meibomian fatty acid composition was slightly modified after 8 weeks in both groups. The decrease in a branched-chain fatty acid (isoC20) was greater after minocycline treatment than after lid hygiene only (-65% and -25%, respectively; p<0.05(. Other fatty acids were unchanged. A significant improvement in the BUT was observed after minocycline treatment (p = 0.03). Conclusion: This study showed better tear film stability after minocycline treatment and a biological effect on meibomian fatty acid composition in MGD patients. Minocycline was more effective than lid hygiene alone. Both interventions partly corrected fatty acid composition abnormalities. Among the fatty acids, isoC20 could be a biological marker of MGD. [ABSTRACT FROM AUTHOR]

Aim: To evaluate the effect of oral pilocarpine treatment on conjunctival epithelium of patients with Sjögren's syndrome (SS). Methods: 15 primary SS patients were included in this prospective, single masked, comparative study. Patients underwent oral pilocarpine treatment for 2 months and were studied before (T0) and after 1 month (T1), 2 months (T2), and 15 days after treatment suspension (T3). Systemic and ocular symptoms, tear film break up time (BUT), corneal fluorescein vital staining, Schirmer 1 test, tear basal secretion test, and conjunctival imprinting were performed. Student's t test and Mann-Whitney U test were used for statistics. Results: The conjunctival imprinting showed an increase of goblet cells number at T1 (1.6 (1.2) v 0.6 (0.7) at T0, p=0.025) improving at T2 (5.1 (1.7); p<0.001 v T0 and T1 ). At T3 the number of goblet cells significantly decreased (1.9 (1.1); p<0.001 v T2). An improvement of dry mouth started at T1 and returned towards baseline values at T3. For ocular symptoms, burning and foreign body sensation were improved at T1 while ocular dryness improved at T2. BUT showed a statistically significant improvement at T2. Conclusions: Oral pilocarpine induced an increase in goblet cells number and an amelioration of conjunctival epithelium not dependent on tear secretion. [ABSTRACT FROM AUTHOR]

Aim: To show characteristic ocular surface findings caused by conjunctivochalasis (CCh) in dry eye patients with or without aqueous tear deficiency (ATD). DESIGN: Comparative non-interventional cases. PATIENTS AND METHODS: Clinical data of five ATD patients without CCh (group A), eight CCh patients with ATD (group B), and eight CCh patients without ATD (group C) were retrospectively reviewed. Presence or absence of CCh was determined by fluorescein staining to outline tear meniscus and conjunctival folds with an enhancing filter. Dry eye symptoms, history of subconjunctival haemorrhage, meibum expression, tear break up time, fluorescein and rose bengal staining, and fluorescein clearance test, and other abnormal ocular surface findings were measured. RESULTS: CCh patients were significantly older (p = 0.001). In pure ATD, the principal symptom of dryness became worse as the day progressed. In contrast, blurry vision, burning sensation, and dryness became worse during reading in all CCh patients (p = 0.0008) or worse in the morning upon awakening in the majority patients with CCh only (p = 0.02). Besides the interpalpebral exposure, which was noted in ATD, positive fluorescein or rose bengal staining was noted in the redundant conjunctival folds and the non-exposure zone in CCh (p = 0.0008). Redundant conjunctival folds were present in both lower and upper bulbar conjunctiva, obliterating both lower and upper tear meniscuses, and spatially correlated with anterior migration of the mucocutaneous junction in CCh. Delayed tear clearance was significantly more prevalent in CCh than ATD (p = 0.0008). Vigorous blinking worsened in CCh but not in ATD (p = 0.0008). Lacrimal puncta were swollen in groups B and C, but not in group A (p = 0.04). CONCLUSIONS: CCh is not restricted to the lower bulbar conjunctiva, and contributes to pathogenesis of dry eye by obliterating both lower and upper tear meniscus, causing unstable tear film and by creating delayed tear clearance. Dry eye symptoms were worsened by downgaze during reading and by vigorous blinking. Other characteristic signs including subconjunctival haemorrhage, swollen puncta, anterior migration of the mucocutaneous junction, and patterns of dye staining also help distinguish dry eye associated with CCh from that caused by ATD alone. [ABSTRACT FROM AUTHOR]

PURPOSE: To investigate the presence of anti-Ro/SSA and anti-La/SSB antibodies in the tear fluid and serum of patients with Sj''gren''s syndrome and to evaluate the association of these autoantibodies with the severity of keratoconjunctivitis sicca. METHODS: Tear fluid and serum were obtained from 28 patients with Sj''gren''s syndrome and 17 age matched normal control subjects. Evaluation of tear fluid and sera anti-Ro/SSA and anti-La/SSB levels was done by using a quantitative enzyme linked immunosorbent assay kit designed for the quantitative measurement of IgG class autoantibodies directed against highly purified SSA and SSB antigens. Tear function and ocular surface were evaluated by Schirmer I test, tear break up time, and rose bengal staining. Dry eye symptom scores were recorded. RESULTS: Increased levels of anti-Ro/SSA and anti-La/SSB antibodies were detected in sera of 57.1% and 50% of SS patients, respectively. Six patients had increased levels of anti-Ro/SSA in the tear fluid, in one case anti-Ro/SSA being detected in tear fluid when it was negative in serum. Ten patients had positive anti-La/SSB titres in tear fluid and in four of these patients, anti-La/SSB titres were not elevated in serum. A positive correlation was observed between serum and tear fluid titres of anti-Ro/SSA (r = 0.43, p = 0.02), but not of anti-La/SSB. Serum anti-Ro/SSA and anti-La/SSB concentrations correlated positively with dry eye symptom scores (r = 0.42, p = 0.02 and r = 0.48, p = 0.01, respectively) and negatively correlated with Schirmer I test scores (r = -0.39, p = 0.04 and r = -0.40, p = 0.03, respectively). Significant correlations were found between tear anti-La/SSB concentrations and dry eye symptom score (r = 0.56, p = 0.02) and also rose bengal staining scores of the ocular surface (r = 0.44, p = 0.02). CONCLUSION: This study shows that autoantibodies against Ro/SSA and La/SSB antigens are present in the tear fluid of some patients with SS and their presence in serum or tear fluid is associated with the severity of keratoconjunctivitis sicca. Additional measurement of tear fluid levels of anti-Ro/SSA and anti-La/SSB may serve as a valuable diagnostic indicator of SS. [ABSTRACT FROM AUTHOR]

Aim: To determine the efficacy of using albumin tear supplements in the treatment of ocular surface disorders as a substitute for serum eye drops. METHODS: The effects of albumin on the viability of serum deprived conjunctival cell were observed in vitro. The ability for albumin to compensate for serum was demonstrated by measuring the activity of the apoptosis related enzyme, caspase-3. In an animal study, corneal erosions were inflicted in 40 Japanese white rabbits. Rabbits were treated with 5% or 10% solutions of human albumin, and the decrease in epithelial defect size was compared with saline control and 0.3% sodium hyaluronate. A clinical case series trial of 5% albumin drops was conducted in nine patients with Sj''gren's syndrome with severe dry eye. RESULTS: The addition of albumin to serum deprived conjunctival cells inhibited caspase activity and increased cell viability, showing that albumin can compensate for some of the physiological properties of serum. Corneal erosions in rabbits healed significantly faster (p<0.05) in eyes treated with 10% albumin compared with control and sodium hyaluronate. Patients with Sj''gren's syndrome used albumin drops showed statistically significant improvement in fluorescein and rose bengal scores, but not in tear break up time and subjective symptoms. No adverse effects of albumin were observed during the study. CONCLUSIONS: The use of albumin as a protein supplement in artificial tear solutions is a viable approach in the treatment of ocular surface disorders associated with tear deficiency. [ABSTRACT FROM AUTHOR]

Aim: To test the short term efficacy and safety of an infrared warm compression device (IWCD, Eye Hot, Cept Co, Tokyo, Japan) as treatment for non-inflamed meibomian gland dysfunction (MGD). Methods: 37 subjects with non-inflamed obstructive MGD, with and without aqueous tear deficiency (ATD) dry eye, participated in a prospective non-comparative interventional case series. Symptom scores, face scores, tear evaporation rates, fluorescein and rose bengal vital staining, tear break up time (BUT), Schirmer test, meibomian gland obstruction, and meibography were compared before and after 2 weeks of therapy. Results: In a total of 37 cases, total subjective symptom scores and subjective face scores improved significantly, from 12.3 (SD 5.9) to 8.4 (6.1), and from 7.0 (1.7) to 5.3 (2.0) (both p <0.0001). The results for tear evaporation rates during forced blinking (p = 0.002), fluorescein staining (p = 0.03), rose bengal staining (p = 0.03), BUT (p <0.0001), and meibomian gland orifice obstruction score (p <0.0001) had also improved significantly at the end of the 2 week period of infrared thermotherapy. No complaints and/or complications of the IWCD were reported. Conclusion: The IWCD was effective and safe for the treatment of MGD. Improved tear stability associated with release of meibum is a possible mechanism of this treatment. [ABSTRACT FROM AUTHOR]

Aim: To study the effect of the treatment of dry eye in Sjögren's syndrome patients with hypotonic or isotonic hyaluronate eye drops. Methods: 40 Sjögren's syndrome patients were divided in two groups and treated as follows: group 1 with hypotonic (150 mOsm/l) 0.4% hyaluronate eye drops; group 2 with isotonic 0.4% hyaluronate eye drops. The eye drops were instilled six times a day for 90 days. Grading of subjective symptoms, break up time (BUT), corneal fluorescein staining, conjunctival rose bengal staining, Schirmer's I test, and conjunctival impression cytology were carried out at 0 and 15, 30, 90 days from the beginning of the study. Patients were examined in a blind fashion. For the statistical analysis the Student's t test, Mann-Whitney U test, and χ² test were performed. Results: Symptoms were statistically significantly improved at day 15 in both groups but group 1 patients had a global score statistically significantly better group 2 (p = 0.02). At day 15 group 1 patients had an improvement from baseline values of BUT (p = 0.003), fluorescein, and rose bengal score (p = 0.000001 and p = 0.0004 respectively). Group 2 patients had, at day 15, an improvement of BUT and fluorescein score compared to baseline values (p = 0.05 and p = 0.0001 respectively). A comparison between the two groups showed better results for group 1 patients at day 15 for rose bengal stain (p = 0.01) and for BUT (p = 0.05) and fluorescein score (p = 0.0003) at day 90. The conjunctival impression cytology showed that group 1 had a statistically significant better total score than group 2 starting from day 15 and lasting throughout the study (p < 0.02). Also group 2 patients showed an improvement from baseline values starting from day 30 (p = 0.000005). Conclusion: Hyaluronate eye drops are useful for treating severe dry eye in Sjögren's syndrome patients. The use of a formulation with pronounced hypotonicity showed better effects on corneoconjunctival... [ABSTRACT FROM AUTHOR]

Aim: While the mechanism in the pathogenesis of diabetic corneal disease is unclear, aldose reductase has been implicated in corneal disease. The effects of an oral aldose reductase inhibitor (ARI) on the ocular surface of diabetic patients after cataract surgery were studied. Methods: This clinical trial was designed to be randomised, double blinded, and placebo controlled. Pseudophakic patients with diabetes were randomly assigned to treatment with either oral ARI (ONO-2235) (n = 12) or placebo (n = 9) for 12 weeks. The vital staining of the ocular surface, tear production and clearance, break up time in tears (BUT), corneal and conjunctival sensation, and symptom score before treatments were examined as well as 4, 8, 12 weeks after the administration. Specular microscopic evaluation was also performed. Results: After a 12 week period of oral ARI administration, fluorescein staining scores (from 2.04 (SD 1.12) to 1.46 (1.18); p = 0.016), conjunctival sensation (from 1.15 (0.37) to 1.36 (0.31); p = 0.0006), and symptom scores (from 5.38 (1.932) to 4.00 (2.07); p = 0.0002) recovered significantly. Fluorescein staining of oral ARI administration also decreased compared with placebo (p = 0.017). Rose bengal staining, tear clearance, and corneal sensation were improved although this increase was minor. Tear production, BUT, and specular microscopic evaluation of the corneal epithelium and endothelium did not demonstrate a significant change. Conclusion: Oral ARI opposes the ocular surface changes caused by diabetes, by recovery of ocular surface sensitivity as demonstrated through an improvement in vital staining. [ABSTRACT FROM AUTHOR]

Purpose Baseline ocular surface characteristics in children require investigation. This study characterised blinking and relationships with ocular symptoms, tear film and digital device use. Methods 45 children aged 6–15 years (56% female) participated in a cross-sectional study. Ocular surface symptoms (Instant Ocular Symptoms Survey, Dry Eye Questionnaire 5, Symptoms Assessment in Dry Eye, Ocular Surface Disease Index, Ocular Comfort Index and Numerical Rating Scale) and clinical indices (lipid layer thickness, tear secretion and stability, meibomian gland) were assessed. Blink rate and interblink interval were measured in situ using a wearable eye-tracking headset (Pupil Labs GmbH, Germany). Associations between blinking, ocular surface, age, and digital device use (bivariate and partial correlations) and between automated and manually counted blink rate (Bland & Altman) were examined. Results Mean blink rate and interblink interval were 20.5±10.5 blinks/min and 2.9±1.9 s during conversation. There was no difference between automated and manual blink rate (p=0.78) and no relationship between blinking and digital device use, age or sex. Mean group symptoms were within normal range and not associated with clinical measurements including blinking. Greater tear volume was associated with a faster blink rate (r=0.46, p=0.001) and shorter interblink interval (r=−0.36, p=0.02). Older age was associated with improved tear volume (r=0.37, p=0.01) and stability (r=0.38, p=0.01). Conclusions Blinking characterised in situ was not impacted by age or habitual digital device use. A faster blink rate was associated with greater tear volume but not symptoms. Improved tear function was found with age suggesting that the ocular surface continues to develop through childhood. [ABSTRACT FROM AUTHOR]

Purpose (1) To determine the independent association of dry eye symptoms with health-related quality of life (HRQoL) in the Singapore population and (2) to further investigate which factors mediate this association. Methods In this cross-sectional study, 7707 participants were included. The presence of dry eye symptoms was defined as experiencing at least one out of the six symptoms either ’often’ or ’all the time’. The EuroQoL-5 dimensions (EQ-5D) utility instrument (raw scores converted to UK time trade-off (TTO) values) was used to assess generic HRQoL and the overall score from the Visual Functioning Questionnaire for visual functioning. The association between dry eye symptoms and EQ-5D was investigated using multivariable linear regression, adjusting for demographic and socioeconomic information, comorbidities, systemic and ocular examinations results. Mediation analysis was used to determine whether certain factors mediated this association. Results After adjusting for relevant factors, those with dry eye symptoms had significantly lower HRQoL (difference in EQ-5D TTO: −0.062 (95% CI −0.073 to –0.050)), with the inability to open eyes affected the most (−0.101 (95% CI −0.161 to –0.042)), followed by a sandy sensation (−0.089 (95% CI −0.121 to –0.058)), a burning sensation (−0.070 (95% CI −0.105 to –0.036)), red eyes (−0.059 (95% CI −0.082 to –0.036)), a dry sensation (−0.058 (95% CI −0.072 to –0.044)) and crusting of eyelids (−0.040 (95% CI −0.071 to –0.008)). Visual functioning and the presence of recent falls accounted for 8.63% (4.98%–14.5%) and 2.93% (0.04%–5.68%) of the indirect relationship between dry eye and HRQoL, respectively. Conclusion Dry eye symptoms were independently associated with poor HRQoL. Moreover, this was partly mediated by reduced visual functioning and experiencing recent falls. Our results suggest that efforts to reduce severity of dry eye symptoms are essential to optimise patients’ overall functioning and well-being. [ABSTRACT FROM AUTHOR]

AIMS--The purpose of this study was to assess whether the preservative benzalkonium chloride (BAC 0.01%) present in timolol induced a decrease in basal tear turnover and a deterioration of precorneal tear film in patients with glaucoma and ocular hypertension using topical timolol. METHODS--The basal tear turnover of 20 patients with open angle glaucoma or ocular hypertension was measured by computerised objective fluorophotometry when using topical timolol preserved with BAC and 2 weeks after changing to topical timolol containing no preservative. Evaluation of the precorneal tear film was done by measuring the break up time (BUT) before and 2 weeks after changing medication. RESULTS--The tear turnover of the patients before the change was 32% lower than that of healthy controls (mean tear turnover values (SD) (%/min): 10.7 (3.0) and 15.6 (5.4), respectively, p < 0.0001). A mean increase of 28% (47%) in the individual tear turnover values was found after the change to the preservative-free timolol (p = 0.04). The BUT values before the change of medication did not differ significantly from those after the change (p = 0.5) but both values were significantly lower than the values of healthy controls (p = 0.009 and p = 0.003, respectively). CONCLUSION--Preservative-free timolol solution has a favourable effect on the tear turnover of patients with glaucoma and ocular hypertension in comparison with timolol containing BAC. The integrity of the precorneal tear film persisted to be affected when using timolol without BAC. Timolol without preservative can be recommended in those patients who have keratoconjunctivitis sicca or a borderline tear production since BAC may exacerbate a dry eye state. [ABSTRACT FROM PUBLISHER]

Background/aim: Recent studies have demonstrated that tear lipocalin (TL) and phospholipids have a crucial role in maintaining tear film stability. The level of TL in patients with meibomain gland dysfunction (MGD) was examined and these data were correlated with the severity of their clinical disorder. Methods: 12 patients with obstructive MGD, 12 patients with seborrhoeic MGD, and 12 age matched normal control subjects participated in this study. 3 μl of unstimulated tears were collected with a micropipelte from the inferior tear meniscus in the right eye of all subjects. Tear samples were fractionated by high performance liquid chromatography, and TL concentrations were assayed with a bicinchoninic acid technique. Results: The mean concentration of TL in patients with obstructive and seborrhoeic MGD was significantly lower than in normal controls. TL concentration correlated positively with tear film break up time and negatively with fluorescein staining scores. Conclusion: These results suggest that TL deficiency may be a predisposing factor for the manifestation of symptoms in MGD. [ABSTRACT FROM AUTHOR]

Purpose This study describes the histopathological features of different morphological variants of human meibomian glands (MGs) seen on infrared imaging. Methods Tarsal plates dissected from seven cadaveric upper eyelids were imaged using infrared meibography, and then studied histopathologically using H&E, peroxisome proliferator-activated receptor gamma (PPARγ, meibocyte differentiation marker) and Ki-67 (cellular proliferation marker) antibody staining. The different morphological characteristics (varying size and shape) of MGs on meibography were correlated with histopathology findings using image analysis software. Results Of the total 127 glands, the morphological variants observed on meibography based on size were: normal (n=62), short (n=18), severely short (n=6) and dropout (n=12) glands, and on shape were: hooked (n=2), tortuous (n=5), overlapping (n=1), thick (n=15) and fluffy (n=6) glands. Short, hooked, tortuous and overlapping glands had similar acinar and ductal histology as seen in normal glands whereas thick, and fluffy glands had increased acinar diameter. All glands except the severely short type demonstrated normal signs of holocrine secretory activity and normal nuclear and cytoplasmic PPARγ expression. Severely short glands had nil while short glands had reduced Ki-67 proliferation index (3%±1%) as compared with normal and other variants (8%±5.2%). Gland dropout areas showed no evidence of any glandular tissue on histology. Conclusion Hooked, tortuous and overlapping glands had completely normal glandular histology, whereas severely short glands showed atrophic changes with loss of meibocyte differentiation and cellular proliferation. Dropout areas showed total loss of glandular elements. Further studies are needed to validate and to explore the clinical implications of these findings. [ABSTRACT FROM AUTHOR]

Purpose Molecular pathogenesis underlying persistent ocular surface inflammation in chronic Stevens-Johnson syndrome (SJS) still remains largely unexplored. The present study investigates the expression of matrix metalloproteinase 2 (MMP2), MMP3, MMP9, MMP11 and TIMP1 (tissue inhibittor of matrix metalloproteinase 1) in pannus tissues of chronic ocular SJS undergoing cultivated oral mucosal epithelial transplantation (COMET) and their prognostic relevance. Methods In this prospective study, 45 eyes with chronic SJS underwent COMET for visual and anatomical rehabilitation. Preoperative and postoperative clinical parameters were documented. MMP2, MMP3, MMP9, MMP11 and TIMP1 expression were assessed using immunohistochemistry and quantitative real time PCR. Inflammadry MMP9 assay was performed at 1-year follow-up. Kaplan-Meier curves and Cox proportional hazard models were used to correlate protein expression with clinicopathological parameters and COMET graft survival outcomes. Results MMP9 and MMP11 positivity was seen in both pannus epithelia (48% and 55%, respectively) and in stromal layer (57% and 33%, respectively) while MMP2 and MMP3 showed only pannus epithelial positivity in 35% and 51% cases, respectively. High MMP9 stromal expression was significantly associated with preoperative corneal keratinisation (p=0.011), conjunctival hyperaemia (p=0.014), symblepharon (p=0.028). High MMP9 and MMP3 epithelial expression were found to be independent risk factors for poor best-corrected visual acuity (BCVA) outcomes post-COMET (p=0.022 and p=0.048). Multivariate analysis revealed MMP9 to be the best prognostic marker (p=0.050). Conclusion Our findings suggest that differential expression of MMPs and TIMP1 is seen in SJS in chronic stage. Emergence of MMP9 as a poor prognostic predictor of BCVA post COMET and postoperative MMP9 immunoassay positivity could be a useful tool in further studies to understand the unresolved ocular surface inflammation seen in SJS. [ABSTRACT FROM AUTHOR]

Background/aims To evaluate subtypes and characteristics of dry eye (DE) using conventional tests and dynamic tear interferometry, and to investigate determinants of disease severity in each DE subtype. Methods 309 patients diagnosed with DE and 69 healthy controls were prospectively enrolled. All eyes were evaluated using Ocular Surface Disease Index (OSDI), Schirmer's test I (ST1) and Meibomian gland dysfunction (MGD) grade were analysed. The tear interferometric pattern and lipid layer thickness were determined using DR-1a and LipiView II, respectively. Results Dynamic interferometric analysis revealed 56.6% of patients with DE exhibited Jupiter patterns, indicative of aqueous-deficiency, while 43.4% exhibited crystal patterns, indicative of lipid deficiency. These findings were in accordance with classification based on ST1 scores and MGD grade. Conventional assessment indicated 286 patients exhibited evidence of evaporative DE (EDE) due to MGD, while only 11 exhibited signs of pure aqueous-deficient DE (pure ADDE, only ST1 =5 mm). Interestingly, of 286 patients with EDE, 144 were categorised into the mixed-ADDE/EDE group, in which ST1 was identified as a strong negative determinant of OSDI. In contrast, 72.2% of patients with mixed-ADDE/EDE exhibited Jupiter patterns (Jupiter mixed), while 27.8% exhibited crystal patterns (crystal mixed). OSDI values were significantly higher in the crystal-mixed group than in the Jupiter mixed, in which OSDI scores were independently associated with ST1 values only. Conclusions Our findings indicate that majority of EDE patients also exhibit aqueous deficiency, which can aggravate symptoms even in patients with lipid-deficient mixed-ADDE/EDE. Conventional assessments should be combined with interferometric tear analysis to determine the most appropriate treatment for each DE patient. [ABSTRACT FROM AUTHOR]

Purpose To optimise the objective diagnosis of dry eye disease (DED), the capabilities of wide corneal epithelial mapping using optical coherence tomography (OCT) were studied and subsequently integrated into a new scoring method. Methods Fifty-nine patients (118 eyes) with DED and 55 control subjects (110 eyes) were included. All patients underwent a complete ocular surface evaluation. Corneal epithelial thickness was collected using OCT for seven zones. DED and the control group were compared using a t-test, and univariate receiver operating characteristic (ROC) curves were calculated to define the diagnostic ability of OCT epithelial mapping. Multivariate analyses were performed using artificial intelligence (random forest) and logistic regression approaches to define the best way to integrate OCT mapping in the diagnosis of DED. Then, a final multivariable model for diagnosing DED was validated through a bootstrapping method. Results The DED group had significant epithelial thinning compared with the controls, regardless of location. Superior intermediate epithelial thickness was the best marker for diagnosing DED using OCT (binormal estimated area under ROC: 0.87; best cut-off value: 50 pm thickness). The difference between the inferior and superior peripheral zones was the best marker for grading the severity of DED (analysis of variance, p=0.009). A multivariate approach identified other significant covariables which were integrated into a multivariate model to improve the sensitivity (86.4%) and specificity (91.7%) of this innovative diagnostic method. Conclusion Including OCT corneal epithelial mapping in a new diagnostic tool for DED could allow optimisation of the screening and staging of the disease in current practice as well as for clinical research purposes. [ABSTRACT FROM AUTHOR]

Purpose To report the real-world experience of using topical ciclosporin, Ikervis, in the management of ocular surface inflammatory diseases (OSIDs). Methods This was a retrospective study of patients treated with Ikervis for OSIDs at the Queen's Medical Centre, Nottingham, between 2016 and 2019. Relevant data, including demographics, indications, clinical parameters, outcomes and adverse events, were collected and analysed for patients who had completed at least 6 months follow-up. For analytic purpose, clinical outcome was categorised as 'successful' (resolved or stable disease), 'active disease' and 'drug intolerance'. Results 463 patients were included; mean age was 51.1±21.6 years, with a 59.0% female predominance. Mean follow-up was 14.6±9.2 months. The most common diagnosis was dry eye disease (DED; 322, 69.5%), followed by allergic eye disease (AED; 53, 11.4%) and ocular mucous membrane pemphigoid/Steven-Johnson syndrome (OMMP/SJS; 38, 8.2%). Successful treatment was achieved in 343 (74.1%) patients, with 44 (9.5%) requiring additional treatment and 76 (16.4%) reporting drug intolerance. The efficacy of Ikervis was highest in DED (264, 82.0%), followed by OMMP/SJS (25, 65.8%) and post-keratoplasty (7, 50.0%; p<0.001). Logistic regression analysis demonstrated age <70 years (p=0.007), AED (p=0.002) and OMMP/SJS (p=0.001) as significant predictive factors for Ikervis intolerance. AED and post-keratoplasty were 8.16 times (95% CI, 2.78 to 23.99) and 13.98 times (95% CI, 4.22 to 46.28), respectively, more likely to require additional treatment compared with DED. Conclusions Ikervis is a useful steroid-sparing topical treatment for managing OSIDs in the real-world setting. Preparations with improved tolerability are needed to benefit a larger number of patients. [ABSTRACT FROM AUTHOR]

Background To compare the role of topically applied serum therapy with preservative-free artificial tear (AT) drops in patients with moderate to severe dry eye in Hansen's disease along with change in tear protein profile. Methods 144 consecutive patients were randomly divided into three groups. After a baseline examination of clinical parameters, each of the patients received designated modality of topical therapy six times a day for 6 weeks. Post-treatment documentation of clinical parameters was done at 6 weeks, and then at 12 weeks after discontinuation of topical therapy. Analysis of three tear proteins using gel electrophoresis (sodium dodecyl sulfate polyacrylamide gel electrophoresis) was done at baseline, at the first and second post-treatment visits. Results In the cord blood serum (CBS) group, except for McMonnies score and staining score, all other clinical parameters showed continued improvement in the first and second post-treatment analyses. In the autologous serum (ALS) group, all the clinical parameters except Schirmer's I showed significant improvement in the first post-treatment analysis .This was sustained at a significant level in the second analysis except for tear film break-up time (TBUT) and conjunctival impression cytology grading. In the AT group, all the parameters improved at a non-significant level except for TBUT in the first analysis. In the next analysis, apart from McMonnies score and TBUT, other clinical parameters did not improve. In the ALS and CBS groups, tear lysozyme, lactoferrin levels improved in both posttreatment measurements (statistically insignificant).Total tear protein continued to increase at statistically significant levels in the first and second post-treatment analyses in the CBS group and at a statistically insignificant level in the ALS group. In the AT group, the three tear proteins continued to decrease in both the analyses. Conclusions In moderate to severe dry eye in Hansen's disease, serum therapy in comparison with AT drops, improves clinical parameters and causes betterment in tear protein profile. [ABSTRACT FROM AUTHOR]

Aims: To use minor salivary glands' flow rate (MSGFR) measurement in minor salivary glands (MSGs) autotransplantation for the treatment of severe dry eye disease (DED). Methods: MSGs autotransplantations were performed in 18 eyes (17 patients) with severe DED. MSGFR were measured before operation. The upper or lower lip with higher MSGFR was selected as the donor site. Buccal mucosa was the back-up in cases labial MSGs showing markedly decreased MSGFRs. Two pieces of salivary lobules with the covering mucosa were harvested and transplanted to the recipient beds prepared in both upper and lower lids. Results: The donor sites included lower lip in 12 eyes, upper lip in 5 eyes and buccal mucosa in 1 eye. Postoperative follow-up confirmed viable grafts in all cases. The overall subjective relief rate of DED symptoms was 58.8%, with Schirmer test values increasing from 0 mm to 4 mm (p<0.05). The mean preoperative MSGFR was 1.7 (range: 0.9-3.3) μL/min/cm². ROC analysis indicated an outstanding discrimination power for preoperative MSGFR to predicate postoperative relief of DED symptoms (area under the curve (AUC)=0.948, p<0.01). The maximum sensitivity (100%) and specificity (72.7%) were reached at a cut-off of 1.785 μL/min/cm². Patients with preoperative MSGFR >1.785 µL/min/cm2 showed greater improvement of Schirmer test values after surgery than those with MSGFR =1.785 µL/min/cm2 (p<0.05). Conclusion: MSGs transplantation proved to be useful for treating severe DED. The amount of postoperative lubrication and the treatment effect were positively correlated with preoperative MSGFR. MSGFR measurement and donor-site selection should be critical steps before the operation. [ABSTRACT FROM AUTHOR]

Purpose To investigate the secretory status of the main lacrimal gland in healthy and dry eye disease (DED) via fluorescein-assisted direct assessment of tear secretion from the palpebral lobes. Methods Included were 25 healthy subjects (50 lobes) and 75 subjects with DED (cicatrising conjunctivitis (CC, n=27), evaporative dry eyes (EDE, n=25) and Sjogren's syndrome (SS, n=23)). Analysed parameters included number and location of ductular openings, tear flow rate per gland and per ductule, and the time lag for the initiation of secretion. Results Ductular openings could be observed in all patients with EDE and healthy subjects whereas only 33% (18/54) glands of CC patients and 67% glands (31/46) patients with SS revealed ductules. The median number of ductules per lobe was 4 in normal (range 3-5), 3 in EDE (3-6), 1 in SS (0-3) and 0 in CC group (0-3) (p<0.000001). The median tear flow rate per lobe in CC (0.00 µL/min) and SS (0.21 µL/min) was significantly lesser than normal lobes (1.05 µL/min, and EDE (0.99 µL/min eyes. The tear flow rate differed significantly between SS and CC group (p<0.0001). The maximum time lag occurred in the CC group (median, 20 s), followed by the SS group (median, 1.5 s) whereas the EDE group had similar time lag (<1 s) as of normal glands (p<0.0001). Conclusion Direct assessment of tear secretion from the palpebral lobe demonstrates significant differences between EDE, aqueous deficient dry eye and dry eye in CC. [ABSTRACT FROM AUTHOR]

Background/aim An objective marker is needed to detect when corneal nerve abnormalities underlie neuropathic corneal pain (NCP), as symptoms often overlap with those of dry eye (DE). This study evaluated microneuroma (MN) frequency in various populations and investigated relationships between MN presence and DE clinical features in individuals with DE symptoms but without a history of refractive surgery, in order to eliminate refractive surgery as a potential confounder of nerve abnormalities. Methods This was a retrospective study that included individuals with and without DE symptoms who underwent a clinical evaluation for DE (symptom surveys and ocular surface evaluation) and in vivo confocal microscopy imaging. DE clinical features (including those suggestive of neuropathic pain) were compared based on MN presence using t-tests, X2 analyses and Pearson's correlation coefficients with 0.05 alpha level. Results MN frequencies did not significantly differ between individuals with DE symptoms (Dry Eye Questionnaire 5 score =6) and a history of refractive surgery (n=1/16, 6%), individuals with DE symptoms without a history of refractive surgery (n=26/119, 22%) and individuals without DE symptoms (n=2/18, 11%, p=0.22). Among individuals with DE symptoms without a history of refractive surgery, DE clinical features, including those indicative of NCP (burning sensation and sensitivity to light, wind and extreme temperatures), did not significantly differ based on MN presence (p>0.05). Conclusion MN frequencies did not significantly differ between individuals with and without DE symptoms. Their presence alone could not distinguish between DE subtypes, including features of NCP in our study population. [ABSTRACT FROM AUTHOR]

OBJECTIVE: To evaluate the efficacy and safety of two different concentrations of cyclosporine A (CsA) in aqueous solution compared to vehicle in patients with dry eye syndrome. DESIGN: Multicentre, randomised, double-masked, vehicle-controlled, clinical trial. METHODS: A total of 183 patients were enrolled and randomised to either CsA 1% (group A), CsA 0.05% (group B) or vehicle only (group C). The main objective was to evaluate the efficacy of CsA aqueous solution in the reduction of signs and symptoms in patients with moderate to severe dry eye disease. RESULTS: An early (day 21) statistically significant improvement (p<0.05) was evident in four symptoms and three ocular signs in group A. An equivalent improvement in three symptoms and three ocular signs was demonstrated in group B. A significant improvement was identified in two symptoms and two ocular signs in group C. Comparing the three groups together, group A performed better in four symptoms than group B did with just one symptom. Group C did not show significant improvement. At day 42, group A showed improvement in four symptoms, while group B showed improvement in one symptom and one ocular sign. CONCLUSIONS: Cyclosporine A reduced complaints and improved major ocular signs in patients with moderate-to-severe dry eye disease. The group treated with the 0.1% cyclosporine A aqueous solution outperformed the other groups. [ABSTRACT FROM AUTHOR]

Background Corneal nerve damage after laser epithelial keratomileusis (LASEK) is thought to be the cause of dry eye and pain. Therefore, we investigated whether taking pregabalin (Lyrica), which reduces peripheral neuropathic pain, alleviates corneal nerve sensitivity after surgery and reduces dry eye and pain. Methods Patients were treated with pregabalin (150 mg two times a day for 15 days) from the day before surgery onward and compared with those who did not receive the medications. Before surgery, the severity of dry eye was assessed. Then, corneal sensitivity was assessed by esthesiometry and pain was assessed according to the Visual Analogue Scale. Images of the sub-basal nerve plexus were analysed using confocal microscopy to evaluate nerve regeneration at 6 months. Results Forty eyes in the pregabalin group and 40 eyes in the control group were included in this study. No significant differences regarding the severity of dry eye, corneal sensitivity test results and nerve fibre density existed between the two groups until 6 months. The pregabalin group showed significantly reduced pain at 1 week. Conclusions Taking pregabalin during LASEK surgery may affect corneal nerve sensitivity and reduce pain. However, for up to 6 months thereafter, corneal sensitivity and nerve fibre density are not significantly different from findings in the control group, so pregabalin does not seem to affect nerve regeneration or structural changes. [ABSTRACT FROM AUTHOR]

Aim To study the morphological features of the palpebral lobe of the main lacrimal gland in normal and dry eyes. Methods This cross-sectional study included 25 healthy subjects and 83 patients with dry eye disease (DED). The aetiological groups of DED were cicatrising conjunctivitis (CC, n=35), evaporative dry eyes (EDE, n=25) and Sjogren's syndrome (SS, n=23). The palpebral lobes in both eyes were evaluated using slit-lamp biomicroscopy and photography for size (exposed area in mm²), shape (convex or flat), presence of cicatrisation (scarring and/or symblepharon) and appearance of the overlying conjunctival vessels. Results The palpebral lobes in the normal and EDE group were similar in terms of size (41.5±15.6 mm² vs 39 ±12.2 mm2, p=0.203), convex shape (100%) and absence of cicatrisation or vascular engorgement (0%). However, as compared to normal controls, the size of the palpebral lobe was markedly reduced in the SS (27.9 ±12.3, p<0.0001) and CC (18.1±13.7, p<0.0001) groups. The size of the lobes was asymmetric in the CC group (p<0.0001) and differed significantly from the SS group (p=0.0003). Flat contour (79% vs 50%, p=0.0028), subepithelial scarring with or without symblepharon (52% vs 13%, p<0.0001) and engorged conjunctival vessels (96% vs 63%, p=0.00011) were seen in a significantly higher proportion of lobes in the CC as compared to the SS group. Conclusion The morphological features of the palpebral lobe of the main lacrimal gland are significantly distorted in aqueous deficient dry eyes due to CC and SS; however, the lobes in patients with EDE are similar to normal eyes. [ABSTRACT FROM AUTHOR]

AIMS: The corneal temperature change following each blink was investigated in patients with dry eye using an infrared radiation thermometer. METHODS: Twenty patients with dry eye and 20 normal controls were enrolled in this study. Subjects kept their eyes open for 10 seconds without blinking and corneal temperature was measured every second with a recently improved infrared radiation thermometer. RESULTS: In the 20 patients with dry eye, corneal temperature change after keeping the eye open for 10 seconds was 0.21 (SD 0.06) degree C while it was 0.61 (0.28) degree C in the 20 normal patients (p = 0.0001). In an exponential equation, the inclination of the slope of a patient with dry eye was smaller than the normal. The correlation coefficient was r = 0.79 (0.16) in patients with dry eye and r = 0.90 (0.07) in normal patients. The mean K value of patients with dry eye was 0.20 (0.13)/second and that of normal subjects was 0.31 (0.19)/second (p = 0.03). CONCLUSION: Findings demonstrate the usefulness of this thermometer for measuring corneal temperature in the evaluation of dry eye. Decrease in corneal temperature with each blink in patients with dry eye was smaller than in normal subjects. [ABSTRACT FROM PUBLISHER]

Dry eye disease (DED) is a growing public health concern affecting quality of life and visual function, with a significant socio-economic impact. It is characterised by the loss of homoeostasis, resulting in tear film instability, hyperosmolarity and inflammation of the ocular surface. If the innate immune response is unable to cope with internal bodily or environmental adverse conditions, the persistent, self-maintaining vicious circle of inflammation leads to the chronic form of the disease. Treatment of DED should be aimed at the restoration of the homoeostasis of the ocular surface system. A proper diagnostic approach is fundamental to define the relevance and importance of each of the DED main pathogenic factors, namely tear film instability, epithelial damage and inflammation. Consideration also needs to be given concerning two other pathogenic elements: lid margin changes and nerve damage. All the factors that maintain the vicious circle of DED in the patient's clinical presentation have to be considered and possibly treated simultaneously. The treatment should be long-lasting and personalised since it has to be adapted to the different clinical conditions observed along the course of the disease. Since DED treatment is frequently unable to provide fast and complete relief from symptoms, empathy with patients and willingness to explain to them the natural history of the disease are mandatory to improve patients' compliance. Furthermore, patients should be instructed about the possible need to increase the frequency and/or change the type of treatment according to the fluctuation of symptoms, following a preplanned rescue regimen. [ABSTRACT FROM AUTHOR]

Purpose To evaluate use of infrared meibography video to visualise meibomian gland probing and correlate probe findings of intraductal space with meibography images. Methods Videos were reviewed and probe findings recorded of 996 probed gland orifices from 38 lower lids. Results 996/997 (99.9%) of gland orifices were successfully probed with 91.8% revealing probe location. There were no false passages. 14% (140/997) of all gland orifices showed whole gland atrophy (WGA) with 99.3% (139/140) probed to 1 mm. Cumulative probe findings for all WGA (not differ significantly from non-WGA) showed 106 (76%), 21 (15%) and 12 (9%) glands with fixed, non-fixed and no resistance (NR), respectively. Lids without WGA showed increased NR/total glands probed while lids with WGAs (=5) showed increased NR/WGA compared with lids with only 1-4 WGAs (p=0.011, p=0.005, respectively, Mann-Whitney U test) suggesting bimodal NR profile. Visualisation of microtube placement was successfully obtained for therapeutic injections and retrieval of meibum specimens. Conclusion Video confirmed intraductal location and safety of devices. For 73% of non-WGA and 76% of WGAs as well as proximal ducts of glands with proximal atrophy, probing released fixed resistance restoring ductal integrity. A bimodal profile of NR suggests it is found with less diseased gland ducts as well as more advanced atrophic gland disease. Gland and ducts appeared flexible but not distendable while periglandular tissue appeared spongy. Visualisation of devices enables whole or localised gland therapy and meibum specimen retrieval, elegantly raising future research, therapeutic and regenerative opportunities. [ABSTRACT FROM AUTHOR]

Purpose To evaluate the effect of one TrueTear session on change in tear volume and symptoms of dryness and ocular pain. Methods Retrospective interventional case series of patients seen in a dry eye clinic. Seventy-five individuals underwent an ocular surface examination and one session of neurostimulation. Outcome measures included objective change in tear volume measured via phenol red test, and subjective change in sensations of dryness and ocular pain measured on a 0-10 Numerical Rating Scale. Results The mean age of the 75 individuals was 59±13 years, and the majority were male (73%). Intranasal neurostimulation increased tear volume (mean 13.40 ±8.00 mm, p<0.0005) and reduced intensities of dryness (mean -2.85±2.79, p<0.0005) and ocular pain (mean -1.48±2.41, p<0.0005 for both). However, these effects were independent of one another as change in symptom report did not correlate with change in tear volume (r=-0.13, p=0.25 for dryness; r=0.07, p=0.56 for pain). In a multivariable model, the strongest predictors for increased tear volume were lower baseline tear volume (standardised beta (β)=-0.50, p<0.0005) and absence of an autoimmune disease (β=-0.36, p=0.001) (R2=0.30). The strongest predictors for reduced dryness and pain scores were lower baseline dryness and ocular pain scores. No complications related to neurostimulation were noted. Conclusion Intranasal neurostimulation increased tear volume and reduced intensities of dryness and ocular pain, independently of one another. [ABSTRACT FROM AUTHOR]