Corneal Fluorescein Staining Scores Research Articles

Leptin's concentration in tears and dry eye: a clinical observational study.

To investigate the concentration of leptin in tears and its correlation with dry eye symptoms and signs. The study enrolled individuals (n=39) responding to an advertising or dry eye patients (n=58) from the Ophthalmology Department. Tear samples were collected for leptin concentration measuring. Ocular Surface Disease Index (OSDI), tear meniscus height (TMH), tear break up time (TBUT), cornea fluorescein staining, Schirmer test (ST) and impression cytology (IC) were assessed. Leptin concentration in tears of dry eye patients and healthy controls, and its correlation with clinical features of dry eye disease (DED) were analyzed. Age, body mass index (BMI), OSDI scores and cornea fluorescein staining scores showed a negative correlation with leptin concentration in tears (r=-0.340, P=0.001; r=-0.332, P=0.001; r=-0.258, P=0.011; r=-0.424, P<0.001, respectively). ST showed positive correlation with leptin concentration in tears (r=0.206, P=0.045). No significant difference was observed in leptin concentration between dry eye patients and controls (P=0.682). Multivariate linear regression analysis revealed that dry eye, OSDI, corneal fluorescein staining scores and ST correlated with leptin concentration in tears. This is the first study measuring leptin concentration in tears. The correlation between leptin concentration and DED symptoms and signs reveal that leptin level correlated with the dry eye, potentially contributing to repair of ocular damage and dry eye improvement.

Effect of Proparacaine Hydrochloride Eye Drops on the Ocular Surface

<i>Background: </i>Proparacaine hydrochloride (PH), as a a local anesthetic, is used regularly in ophthalmic surgery and optometry. However, few pieces of research on the ocular surface toxicity<i> </i>of PH eye drops have so far been reported. <i>Purpuse: </i>To evaluate the effect of PH on the ocular surface of mice.<i> Methods: </i>Male C57/BL6 mice were divided into four groups: normal, vehicle-treated, 0.05% PH-treated and 0.5% PH treated 7 days. The clinical indications were tear production, corneal sensitivity, and fluorescein staining. The structure and morphology of the cornea were examined by confocal microscopy; the thickness of the corneal center was examined by anterior segment optical coherence tomography (AS-OCT); and the corneal epithelial microvilli morphology was examined using scanning electron microscopy. Hematoxylin-eosin staining was used to characterize the central corneal morphology. Immunofluorescence staining for cytokeratin 10 (K10) was employed to evaluate squamous metaplasia in the corneal epithelium. <i>Results: </i>The results show that topical PH treatment diminished tear production and corneal sensitivity, and increased corneal fluorescein staining scores. Moreover, PH altered the corneal epithelial microvilli morphology, disrupted the epithelial barrier of the cornea, and promoted apoptosis of ocular surface cells. Furthermore, the expression of K10 in the corneal epithelium was found to be increased. <i>Conclusion: </i>Treatment with 0.5% PH caused instability of the tear film, and changes in corneal sensitivity and ocular surface homeostasis.

Lactobacillus plantarum and Bifidobacterium bifidum alleviate dry eye in mice with exorbital lacrimal gland excision by modulating gut inflammation and microbiota.

In order to understand the efficacy of probiotics against dry eye syndrome, we selected anti-inflammatory probiotics Lactobacillus plantarum NK151 and Bifidobacterium bifidum NK175, which increased the ratio of IL-10 to TNF-α expression, from the human gut bacteria collection and examined their effects on tear secretion and cornea/conjunctiva inflammation in mice with excision of the unilateral exorbital lacrimal gland and 1% atropine and 0.1% benzalkonium chloride solution (ELA)-induced dry eye. Exposure to ELA significantly reduced tear secretion in mice, assessed by the phenol red thread tear test. However, oral gavage of NK151 and/or NK175 significantly increased ELA-suppressed tear secretion, IL-10 expression, and goblet cell population and decreased the ELA-induced corneal fluorescein-staining score, IL-1β and TNF-α expression in the conjunctiva. They also suppressed ELA-induced myeloperoxidase, IL-1β, and TNF-α expression. In particular, they increased the ratio of IL-10 to TNF-α expression in the colon. Their treatments increased ELA-induced α-diversity reduction to that of the control group and partially restored ELA-shifted β-diversity to that of the control group. Oral gavage of NK151 and/or NK175 reduced ELA-induced Verrucomicrobia and Actinobacteria populations at the phylum level. Furthermore, they reduced ELA-induced Bacteroidaceae, Akkemansiaceae, and AC160630_f populations and increased ELA-suppressed Lactobacillaceae and Muribaculaceae populations at the family level. These gut bacteria populations exhibited significant correlation with the tear secretion volume. In conclusion, NK151 and/or NK175 alleviated dry eye by modulating the expression ratio of pro-inflammatory cytokines such as TNF-α and anti-inflammatory cytokines such as IL-10 and gut microbiota composition.

Optimization of Contact Lenses for Corneal Protection During Vitreoretinal Surgery.

To optimize parameters of contact lenses (CLs) and evaluate their ability to protect the cornea during vitreoretinal surgery. We compared the protective effects of balanced saline solution, viscoelastic agent, and CLs on rabbit corneas under conditions simulating vitreoretinal surgery. We evaluated CLs of different thicknesses and compared the protective effects of polymethyl methacrylate (PMMA) and gas-permeable fluorosilicone acrylate (XO) lenses on the corneas of rabbits and patients with severe proliferative diabetic retinopathy (PDR). The corneal fluorescein staining score (FSS) was measured to compare the protective effects of CLs. The FSS was significantly lower in the PMMA group than in the balanced saline solution and viscoelastic agent groups. The thickness of the PMMA lenses had no significant effect on the FSS. The FSS was significantly higher in the PMMA group than in the XO group. In patients with PDR, on day 1 after vitreoretinal surgery, the FSS was significantly higher in the PMMA group than in the XO group, although no significant difference was observed on postoperative day 7. The XO lens offers better corneal protection during noncontact wide-angle vitreoretinal surgery and protects the corneal epithelium more efficiently during vitrectomy in patients with PDR, irrespective of its thickness.

Therapeutic effect of acupoint injection as adjuvant treatment on dry eyes of convalescent herpes simplex keratitis

To evaluate the clinical effect of acupoint injection of houttuynia cordata as the accessory treatment on dry eyes of convalescent herpes simplex keratitis (HSK). A total of 60 patients with dry eyes of convalescent HSK were randomized into an observation group and a control group, 30 cases in each one. In the control group, the artificial tears and anti-inflammatory drugs were combined in treatment. In the observation group, on the base of the treatment as the control group, the acupoint injection of houttuynia cordata at Neiqiuhou (Extra) was combined, 3 mL each time, once a day. After consecutive 3 injections, the injection was adjusted to be once every two days, consecutively for 3 times. The treatment for 6 times was as one course and one course of treatment was required. Separately, before treatment and in 7, 15 and 30 days after treatment, the changes of the scores of visual analogue scale (VAS), theresults of SchirmerⅠtest (SⅠT), the tear break-up time (BUT) and the score of corneal fluorescein staining (CFS) were observed and analyzed in the patients of the two groups. In 7, 15 and 30 days after treatment, VAS scores and CFS scores were all reduced as compared with those before treatment in the patients of the two groups (P<0.05), and the scores of VAS and CFS in the observation group were lower than those in the control group (P<0.05). In 7, 15 and 30 days after treatment, the values of SⅠT and BUT were all increased as compared with those before treatment in the patients of the two groups (P<0.05), and the values in the observation group were higher than the control group in 15 and 30 days after treatment (P<0.05). Acupoint injection of houttuynia cordata promotes corneal epithelial recovery, reduces the discomfort symptoms as well as increases tear secretion and the stability of tear film in dry eyes of convalescent herpes simplex keratitis.

Assessment of tear film lipid layer thickness in patients with Meibomian gland dysfunction at different ages

BackgroundTo evaluate the correlations between lipid layer thickness (LLT) and morphology and function of the meibomian glands in patients who were diagnosed as meibomian gland dysfunction (MGD) in different age groups.MethodsPatients who have diagnosed as obstructive MGD were included in this prospective, cross-sectional study. Patients were divided into three groups: young (ages 20–39 years), middle-aged (ages 40–59 years), and older (aged ≥60 years). All patients completed an Ocular Surface Disease Index (OSDI) questionnaire and were evaluated for LLT, tear meniscus height (TMH), noninvasive tear film break-up time (NI-BUT) measurement, invasive TBUT (ITBUT), corneal fluoresceinstaining (CFS) score, eyelid margin abnormalities, Schirmer I test, and MG function and morphology, by using the Keratograph 5 and LipiView interferometer.ResultsTwo hundred and nine patients (209 eyes) were included. The median LLT of all patient was 57 nm (IQR, 36.5 nm), and the LLT values were significantly different among the young group (median, 51 nm; IQR, 23.5 nm), middle-aged group (median, 59.5 nm; IQR 46.5 nm) and older group (median, 62 nm; IQR, 42.5 nm) (P = 0.033, Kruskal-Wallis test). In regression analyses controlling for confounder factors sex and MG loss, the LLT was positively correlated with age (β = 5.539, P = 0.001). There was a negative correlation between LLT and MG dropout in the all (r = − 0.527, P < 0.001), young (r = − 0.536, P < 0.001), middle-aged (r = − 0.576, P < 0.001), and older (r = − 0.501, P < 0.001) groups. LLT was positively correlated with the MG expressibility in the all (r = 0.202, P = 0.003), middle-aged (r = 0.280, P = 0.044) and older (r = 0.452, p < 0.001) groups, but it was no statistical significance in the young group (r = 0.007, P = 0.949).ConclusionsThe thickness of LLT was increased with age and significantly correlated with both MG secretion and morphology in middle-aged and older patients with obstructive MGD. LLT measurement is a useful screening tool for detecting obstructive MGD and age as an influential factor should be accounted for when interpreting the meaning of the LLT value.Trial registrationNCT02481167; Registered 25 June, 2015.

Changes in the expression of matrix metalloproteinase-9 after intense pulsed light therapy combined with meibomian gland expression in moderate and severe meibomian gland dysfunction

PurposeTo evaluate the combined effect of intense pulsed light (IPL) therapy and meibomian gland expression on extracellular matrix metalloproteinase-9 (MMP-9) levels and clinical outcomes of moderate and severe meibomian gland dysfunction (MGD) treatment. MethodsThis retrospective study was conducted on 45 eyes of 23 patients with moderate and severe MGD. Each eye underwent three IPL sessions and meibomian gland expression at 2-week intervals. In this study the evaluated parameters included tear film break-up time (TBUT), corneal and conjunctival fluorescein staining scores, biomicroscopic examination of lid margins and meibomian glands, ocular surface disease index (OSDI) questionnaire score, and extracellular MMP-9 levels using the immunoassay device before and two weeks after the last treatment session. Linear mixed model and generalized estimating equations model were used to evaluate possible differences. ResultsThere were significant improvements in TBUT (P < 0.001), SICCA ocular staining score (P = 0.008), Oxford staining score (P = 0.023), lid margin irregularity (P < 0.001 for upper and lower eyelids), lid thickness (P < 0.001 for upper and lower eyelids), meibomian gland plugging (P = 0.010 and P = 0.012 for upper and lower eyelids), meibum color (P = 0.044 and P < 0.001 for upper and lower eyelids), meibum consistency (P < 0.001 for upper and lower eyelids), MGD grade (P < 0.001), and OSDI questionnaire score (P < 0.001). Incidence of positive results for MMP-9 immunoassay significantly decreased from 84.0% to 56.0% (P = 0.031) after treatment. ConclusionIn patients with moderate to severe MGD, three sessions of IPL combined with meibomian gland expression improved objective findings, subjective symptoms, meibomian gland function, and MMP-9 immunoassay results. The results support the combination of IPL and meibomian gland expression for treating moderate to severe MGD.

Efficacy and retention of silicone punctal plugs for treatment of dry eye in patients with and without ocular graft-versus-host-disease

PurposeTo examine the retention rates and efficacy of silicone punctal plugs for the treatment of dry eye disease (DED) in patients with ocular graft-versus-host-disease (oGVHD) in comparison to dry eye disease due to non-oGVHD etiologies. MethodsWe reviewed the case-records of 864 consecutive patients with DED who were symptomatic despite topical therapy and had silicone punctal plugs placed over an eight-year- period at a single academic center. We compared plug retention rates in oGVHD and non-oGVHD DED patients using Kaplan–Meier analyses. Furthermore, we analyzed changes in objective ocular surface parameters including tear breakup time (TBUT), Schirmer's test, and corneal fluorescein staining (CFS) score in plug-retaining patients at two-, six- and twelve-month follow-up. ResultsMedian age of dry eye patients was 58 years, and 606 (70%) of patients were women. In the cohort, 264 (31%) patients were diagnosed with oGVHD. Plug retention was significantly lower in oGVHD-DED patients compared to non-oGVHD-DED patients (p < 0.0001). We observed significant improvement in CFS scores in plug retaining-oGVHD and non-oGVHD DED patients at all time points. Tear break-up time was significantly prolonged at six- and twelve-months follow-up in non-oGVHD patients, whereas significant change in TBUT in oGVHD patients was recorded only at twelve months post plug placement. Schirmer's score improved significantly in plug retaining-non-oGVHD DED patients at six- and twelve-months follow-up, however no significant change was observed in Schirmer's score in oGVHD DED patients. ConclusionsAn improvement in ocular surface disease parameters was observed in both plug-retaining oGVHD and non-oGVHD DED patients. However, a majority of oGVHD DED patients spontaneously lost their punctal plugs within 90 days of placement. Therefore, regular follow-up after plug placement is recommended to detect plug loss and ensure adequate disease control.

Impact of Full-Incision Double-Eyelid Blepharoplasty on Tear Film Dynamics and Dry Eye Symptoms in Young Asian Females.

Dry eye symptoms as a complication of double-eyelid blepharoplasty are controversial. This article evaluates tear film dynamics and changes in dry eye symptoms after cosmetic double-eyelid blepharoplasty in young Asian female. One hundred and twenty patients underwent full-incisional double-eyelid blepharoplasty. Subjective and objective parameters were documented before surgery, at 1week, 1month and 3months post-surgery, which included Ocular Surface Disease Index questionnaire (OSDI), tear meniscus height (TMH), noninvasive breakup time (NIBUT), Schirmer I test, corneal and conjunctival fluorescein staining scores, and palpebral fissure height. Dry eyes were defined based on the DEWS II criteria: OSDI ≥ 13 points and NIBUT < 10s. Patients were divided into two groups, group A included patients with redundant skin, while group B included patients with absence of redundant skin. The incident rate of dry eyes preoperatively, and at 1week, 1month and 3months were 12.5%, 12.5%, 32.5%, and 16.67%. OSDI scores were significantly increased at 1 week (9.71 ± 10.07, P < 0.001) and 1 month (11.35 ± 12.28, P < 0.001) postoperatively. A significant increase in TMH, NIBUT and Schirmer's test I values were observed at 1 week post-surgery (P < 0.001). Patients in group A showed higher OSDI scores compared to group B at 1 week and 1 month (P = 0.051) post-surgery, and the other variables showed no difference between the groups. Cosmetic double-eyelid blepharoplasty may temporarily affect tear film dynamics and aggravate dry eye symptoms in young females. However, these changes generally recover 3 months postoperatively. This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

Effect of natural extract eye drops in dry eye disease rats.

To investigate the therapeutic effect of natural extract eye drops containing bee venom, musk, and deer antlers in dry eye disease (DED) animal models. Scopolamine-injected DED rats and lacrimal gland-excised rats were allocated into control, saline, and natural extract groups respectively and a normal group (lacrimal gland excision was not performed) in lacrimal gland-excised rats. After eye drop instillation 4 times a day for 5d, corneal fluorescein staining (CFS) scores, tear MUC5AC levels, and tear lactic dehydrogenase (LDH) levels were measured. In scopolamine-injected rats, the natural extract-treated group had significantly lower CFS scores (1.7±0.5, 4.7±1.4, 3.8±1.9, P=0.006) and tear LDH levels (0.10±0.01, 0.19±0.01, 0.16±0.08 OD, P=0.014) but higher tear MUC5AC levels (12.9±3.7, 7.9±2.0, 9.7±3.6 ng/mL, P=0.041) compared with the control and saline-treated groups. There were no significant differences between the control and saline-treated groups. In lacrimal gland-excised rats, the natural extract-treated group also had lower CFS scores (4.3±1.2, 11.5±2.3, 9.0±1.9, P<0.001, P=0.001) and tear LDH levels (0.30±0.08, 0.48±0.12, 0.39±0.05 OD, P<0.05) but higher tear volume (4.3±0.9, 1.9±0.7, 2.8±1.1 mm, P=0.005, P=0.124) and tear MUC5AC levels (8.2±2.0, 2.9±1.2, 5.4±2.2 ng/mL, P<0.001, P=0.047) compared with the control and saline-treated groups. There were no significant differences in the CFS scores, tear MUC5AC level, and tear LDH level between the normal and natural extract-treated groups. The natural extract consisting of bee venom, musk, and deer antlers may have effectiveness in DED treatment by restoring the damaged ocular surface, increasing tear volume, and recovering the tear mucin layer in DED rats.

Conjunctival microvascular responses to anti-inflammatory treatment in patients with dry eye

PurposeThis study characterized conjunctival microvascular morphological and haemodynamic responses after anti-inflammatory treatment in dry eye (DE). Materials and methodsTwenty-five patients with moderate DE (17 females and 8 males aged 48 ± 16 years) who underwent anti-inflammatory therapy (0.1% fluorometholone) and 25 healthy subjects (20 females and 5 males aged 48 ± 17 years) recruited as controls were enrolled. The conjunctival blood flow rate (BFR), blood flow velocity (BFV) and vessel diameter were measured by functional slit-lamp biomicroscopy (FSLB). DE symptoms and signs were assessed. All measurements were performed at baseline and at 30 and 60 days after commencement of treatment. ResultsAt baseline, the conjunctival BFR, BFV, and vessel diameter were higher in the DE group than in the control group (p < 0.05). The BFR, BFV and corneal fluorescein staining (CFS) scores decreased at 60 days after therapy compared to at baseline and 30 days (all pcorrected < 0.05); Ocular surface diseases index (OSDI), the hyperaemia index (HI) and vessel diameters only showed significant decreases at 30 days. Moreover, significant increases in the noninvasive tear film break-up time (NI-BUT) and Schirmer I test score (ST) were observed. The CFS score correlated positively with BFV (r = 0.46), BFR (r = 0.58) and vessel diameter (r = 0.47). ConclusionThis study characterized conjunctival microvascular responses to anti-inflammatory treatment in DE patients. The results suggest that conjunctival BFV and BFR can be used as dynamic markers for treatment efficacy in DE.

Different adverse effects of air pollutants on dry eye disease: Ozone, PM2.5, and PM10

To date, there have been no well-organized clinical studies evaluating which air pollutants affect dry eye disease (DED). In this study, we investigated changes in the clinical parameters of DED according to exposure to outdoor air pollutants, including PM2.5 (particulate matter with an aerodynamic diameter of less than 2.5 μm), PM10 (less than 10 μm), and ozone. A prospective observational study was conducted on 43 DED patients who had used the same topical eye drop treatment between 2016 and 2018 in South Korea. Ocular surface discomfort index (OSDI) score, tear film break-up time (TBUT), corneal fluorescein staining score (CFSS), and tear secretion were measured during each visit. Air pollution data of ambient PM10, PM2.5, and ozone, based on the patients’ address, were obtained, and mean concentrations were computed for one day, one week, and one month before the examination. The relationships between air pollutants and DED were analyzed in single- and multi-pollutant models adjusted for demographic and clinical factors. In the multi-pollutant model, the OSDI score was positively correlated with ozone and PM2.5 exposure [ozone: β(exposure for 1 day/1 week) = 0.328 (95% CI: 0.161–0.494)/0.494 (0.286–0.702), p < 0.001/<0.001, per 1 ppb increase; PM2.5: β(1 day/1 week) = 0.378 (0.055–0.699)/0.397 (0.092–0.703), p = 0.022/ = 0.011, per 1 μg/m3 increase], and tear secretion decreased with increased ozone exposure [ozone: β(1 week/1 month) = −0.144 (−0.238 to −0.049)/-0.164 (−0.298 to −0.029), p = 0.003/ = 0.017, per 1 ppb increase]. Interestingly, increased PM10 exposure was only associated with decreased TBUT [β(1 day/1 week/1 month) = −0.028(-0.045 to −0.011)/-0.029(-0.046 to −0.012)/-0.023(-0.034 to −0.006), p = 0.001/ = 0.001/ = 0.018, per 1 μg/m3 increase]. Tear secretion and CFSS were not associated with PM10 exposure. Increased ozone and PM2.5 exposure led to aggravated ocular discomfort, and increased PM10 concentration aggravated tear film stability in patients with DED. Thus, each air pollutant may aggravate DED via different mechanisms of action.

The effect of astaxanthin on inflammation in hyperosmolarity of experimental dry eye model in vitro and in vivo

Hyperosmolarity is pro-inflammatory stress to the ocular surface epithelium associated with dry eye disease (DED). Astaxanthin (AST) is a kind of carotene, which exists in seafood and plays important roles in the amelioration of inflammatory diseases like arteriosclerosis, inflammatory bowel disease, sepsis, rheumatoid arthritis, gastric inflammation, brain inflammatory diseases. The aim of this study was to characterize the protective effect and potential mechanism of AST on DED in vitro and in vivo. Mouse models and human corneal epithelial cell (HCEC) cultures were exposed to hyperosmotic saline solution (HOSS) in in vitro and in vivo experiments, respectively. Experimental subjects were first pretreated with AST, and then the effect of the compound was assessed with clinical evaluation, real-time PCR (RT-PCR), western blot and immunofluorescent staining. We further investigated the possible mechanism of AST in DED by pre-treating with phosphoinositide 3-kinase inhibitor (LY294002). The addition of AST significantly reduced the expression of High-mobility group box 1 (HMGB1), as well as significantly inhibited the increases of TNF-α, IL-1β in a dose-dependent manner, but promoted the expression of phospho-Akt (p-Akt). BALB/c mice in DE group pretreated with AST showed significantly decreased corneal fluorescein staining scores. Moreover, pretreatment with LY294002 could eliminate the effects of AST preconditioning on the decrease of HMGB1. Our study provides evidence that AST could ameliorate DED which may be related to the inhibition of HMGB1, TNF-α, IL-1β, while PI3K/Akt signaling pathway may be involved in the expression of HMGB1 and the protective effect of AST preconditioning.

The effect of oral isotretinoin therapy on meibomian gland morphology and dry eye tests

Purpose The aim of study was to evaluate the effects of oral isotretinoin on meibomian gland (MG) morphology detected with non-contact meibography and to investigate its relation with clinical dry eye tests. Methods Forty-five acne patients treated with isotretinoin underwent a full ophthalmological examination at baseline and in the fourth month as follows: ocular surface disease index (OSDI) questionnaire, assessments of tear film break-up time (TFBUT), corneal fluorescein staining, Schirmer test, meibum expression, and lid margin abnormalities. Non-contact meibography imaging and noninvasive tear break up time (NI-BUT) assessments were also performed. The changes in MGs were scored (meibography score) as grade 0, no change; grade 1, mild; grade 2, moderate; and grade 3, marked. Results There was a statistically significant change in OSDI, corneal fluorescein staining, lid margin abnormality, and meibum expression score during the treatment compared to baseline values (p < .001, p = .02, p < .001, and p < .001, respectively). All meibography scores showed a positive correlation with the lid margin abnormality and meibum expression score but did not correlate with the TFBUT, NI-BUT, Schirmer test, or the corneal fluorescein staining score. Conclusion The morphologic analysis using non-contact meibography is a useful method for assessing isotretinoin-related changes in MGs.

SAT0164 MC2-03 (CICLOSPORIN EYEDROPS) IMPROVES TEAR PRODUCTION IN SJÖGREN’S PATIENTS WITH MODERATE-TO-SEVERE KERATITIS: RESULTS FROM A PHASE 2B RANDOMIZED, CONTROLLED TRIAL

Background:Sjögren Syndrome (SS) is a multifaceted disease with variable symptoms, but the SS associated keratoconjunctivitis is one of the most frequent disease manifestations of the syndrome and the manifestation that has the greatest impact on the quality of life for these patients.Objectives:To report the clinical efficacy of MC2-03 eyedrops in Sjögren’s patients with moderate-to-severe keratitis from a 6-month trial looking at the Schirmer score which assess the tear production by the lacrimal gland. A Schirmer score of ≤5mm/5 min is one of the criteria used in the 2016 final classification of ACR/EULAR to diagnose Sjögren`s syndrome.Methods:The NORTHERN LIGHTS trial is a randomized, double masked, controlled multicentre European trial that assessed MC2-03 eyedrops (ciclosporin 0.03% and 0.06%) for the treatment of moderate-to-severe dry eye disease in 255 patients having corneal fluorescein staining score 3 or 4 at baseline. The Schirmer score (per 5 min) was assessed during this trial. A total of 66 patients (25.9%) with medical history of Sjögren’s syndrome were randomized in the trial.Results:Demographics and baseline disease characteristics were comparable between treatment arms: mean age 60.4 years, 90.9% were females (n=60) and the mean Schirmer score in the worst eye was ~3mm (2.8mm – 3.2mm, except for the vehicle, mean Schirmer score of 5.5mm).The mean Schirmer score improved rapidly from baseline to month 1 for MC2-03 0.03% eye drops (+2.4mm) reaching statistical significance versus vehicle (-0.5mm, p=0.028) and lubricant therapy (-0.6mm, p=0.020). This improvement was maintained at month 6 where the change was +2.5mm for MC2-03 0.03% eye drops compared to -1.1mm for vehicle (p=0.028). Statistical significance was also achieved at Month 6 comparing the higher strength MC2-03 0.06% eye drops (+2.8mm) to vehicle (-1.1mm, p=0.005) and lubricant alone (-0.5mm, p=0.009).Three in eleven (27.3%) Sjögren`s patients treated with MC2-03 0.03% eye drops improved from a diagnostically low Schirmer ≤5mm at baseline (10/12, 83.3% ≤5mm) to Schirmer &gt;5mm at month 3 and month 6 (6/11, 54.5% ≤5mm), while on the other hand 1 in 14 (7.1%) patients worsened in the vehicle group. A similar response was seen for MC2-03 eye drops 0.06%.For Sjögren´s patients with Schirmer ≤5mm at baseline, a greater proportion of patients improved ≥3mm at month 6 when treated with MC2-03 eye drops 0.03% (44.4%, 4/9) and 0.06% (53.8%, 7/13) compared to vehicle (0%, 0/9) and lubricant (7.7%, 1/12). At month 6, a statistically significantly higher proportion of patients achieved clinically meaningful improvements in both corneal staining (≥2 grades improvement) and Schirmer score (≥3mm/5 min) when treated with MC2-03 0.03% eye drops (45.5%, 5/11) compared to both vehicle (0%, 0/14, p=0.009) and lubricant (0%, 0/15, p= 0.007). A higher number of patients treated with MC2-03 0.06% was observed without statistical significance.Conclusion:MC2-03 eye drops once daily rapidly increased tear production and further improved corneal staining in Sjögren´s patients with moderate to severe keratitis, which both are objectives included as diagnostic criteria for Sjögren’s disease. MC2-03 eye drops were well tolerated with no unexpected safety findings.Disclosure of Interests: :Frederic Gomez Consultant of: MC2 Therapeutics, Morten Præstegaard Employee of: MC2 Therapeutics, Johan Selmer Employee of: MC2 Therapeutics, Jutta Horwath-Winter Consultant of: CromaPharma, Omnivision, MC2 Therapeutics, Speakers bureau: Allergan, Bausch&amp;Lomb, Cromapharma, Ursapharma, Thea, TRB-Chemedica, Santen, Maite Sainz de la Maza: None declared, Steffen Heegaard Consultant of: Sanofi, MC2 Therapeutics, Speakers bureau: Santen, Sanofi, Thea, Leo

Climatic and Environmental Correlates of Dry Eye Disease Severity: A Report From the Dry Eye Assessment and Management (DREAM) Study.

PurposeCorrelate climate, weather parameters, and environmental exposures with the severity of symptoms and signs of dry eye disease (DED) in Dry Eye Assessment and Management (DREAM) study participants.MethodsParticipants from five distinct climates completed the Ocular Surface Disease Index (OSDI) and were examined for corneal and conjunctival staining, tear breakup time (TBUT), and Schirmer's testing at baseline, 3, 6, and 12 months. Climate, weather parameters, and pollutants including ozone (O3), carbon monoxide (CO), nitrous oxides (NO2, NOx, NOy), sulfur dioxide (SO2), particulate matter, and optical depth were obtained from governmental databases. Multivariate analysis and partial correlation coefficients (ρ) were used to assess associations, adjusted for age, sex, and the presence of Sjögren disease.ResultsAmong 535 participants, 81% were female and mean age was 58 years. Participants from the Mediterranean climate demonstrated better corneal fluorescein staining, better TBUT, and higher Schirmer's test scores throughout the calendar year (each P < 0.0001). Greater corneal fluorescein staining was associated with lower humidity (P < 0.0038). TBUT measurements positively correlated with temperature, humidity, and dewpoint and inversely correlated with NO2 levels (P < 0.0038). Paradoxically, some airborne pollutants were associated with less severe signs of dry eye (P < 0.0038). Windspeed was not correlated with signs of DED, and OSDI scores did not correlate with individual environmental exposures.ConclusionsDry eye signs differed between climates and local humidity levels. With the exception of NO2, airborne pollutants were not associated with detrimental dry eye features.Translational RelevanceThese results support limiting dry air exposure for patients with DED.

Aged Mice Exhibit Severe Exacerbations of Dry Eye Disease with an Amplified Memory Th17 Cell Response

The prevalence as well as the severity of dry eye disease increase with age. Memory T helper 17 (Th17) cells(CD4+IL-17A+CD44+) drive the chronic and relapsing course of dry eye disease. Here, we investigated the contribution of memory Th17 cells to age-related dry eye disease, and evaluated memory Th17 cell depletion with anti-IL-15 antibody as a strategy to abrogate the severe exacerbations of dry eyedisease observed in aged mice. After initial exposure to desiccating stress, aged mice maintained higher frequencies of memory Th17 cells in the draining lymph nodes relative to young mice. Upon secondary exposure to desiccating stress, aged mice developed more severe corneal epitheliopathy than young mice, which is associated with increased local frequencies of Th17 cells (CD4+IL-17A+). Treatment with anti-IL-15 antibody decreased the enlarged memory Th17 pool in aged mice to frequencies comparable with young mice. Furthermore, anti-IL-15-treated mice showed significantly reduced conjunctival infiltration of Th17 cells and lower corneal fluorescein staining scores compared with saline-treated control mice. Our data suggest that age-related increases in the memory Th17 compartment predispose aged mice toward the development of severe corneal epithelial disease after exposure to a dry environment. Selectively targeting memory Th17 cells may be a viable therapeutic approach in the treatment of age-related dry eye disease.

A Retrospective Study of Treatment Outcomes and Prognostic Factors of Intense Pulsed Light Therapy Combined With Meibomian Gland Expression in Patients With Meibomian Gland Dysfunction.

Objectives:To evaluate clinical changes after intense pulsed light and meibomian gland expression (IPL/MGX) treatment in meibomian gland dysfunction (MGD) patients, and to identify ideal candidates, and the therapeutic window, for IPL/MGX.Methods:This retrospective study reviewed the medical records of 44 MGD patients (44 eyes). The IPL/MGX treatment was applied on the eyelids three times at intervals of 4 weeks. Age, sex, relevant ocular history, Standard Patient Evaluation of Eye Dryness (SPEED), Ocular Surface Disease Index (OSDI), tear break-up time (TBUT), corneal fluorescein staining score (CFSS), meiboscore, meibomian gland loss score (MGLS), meibomian glands yielding secretion score (MGYSS), meibomian glands yielding clear secretion (MGYCS), and meibomian glands yielding liquid secretion (MGYLS) were analyzed.Results:Standard Patient Evaluation of Eye Dryness, OSDI, TBUT, CFSS, MGYSS, MGYLS, and MGYCS were significantly improved after three IPL/MGX treatments, but the meiboscore and MGLS remained unchanged. In patients who had better treatment outcomes (improvement in MGYSS >7), younger age (36.0, 22.5 vs. 53.0, 25.0 years; P=0.012), a longer TBUT (8.0, 4.5 vs. 6.0, 3.0 sec; P=0.010), better meiboscore (1.0, 0.5 vs. 2.0, 1.0; P=0.012), and less gland loss (19.8%, 20.3% vs. 41.1%, 30.2%; P=0.008) before IPL/MGX were noted. Sex, relevant ocular history, SPEED, OSDI, MGYSS, MGYLS, and MGYCS before IPL/MGX showed no significant differences between patients with an improvement in MGYSS >7 versus those with an improvement of ≤7. Meibomian glands yielding secretion score changes in patients who had a meiboscore of 0 to 1 and MGYSS of 0 before IPL/MGX (12.0, 10.0) were significantly higher than those who had a meiboscore of 2 to 3 and MGYSS of 0 (6.5, 9.3; P=0.031), or a meiboscore of 0 to 1 and MGYSS >0 (5.0, 11.5; P=0.041).Conclusions:Improved dry eye symptoms, TBUT, corneal staining, and meibomian gland secretion were observed in MGD patients after IPL/MGX. Patients in the early stages of MGD maybe benefited most from IPL/MGX treatment.

Evaluation of Tear Protein Markers in Dry Eye Disease with Different Lymphotoxin-Alpha Expression Levels

To compare tear protein markers between normal subjects and patients with dry eye (DE) and high and low lymphotoxin-alpha (LT-α) levels. Prospective cross-sectional study. Patients with DE were divided into low(≤700 pg/mL) and high (>700 pg/mL) LT-α groups. Twelve protein markers were measured by microsphere-based immunoassay and ocular surface parameters were determined in right eyes (33 high LT-α DE, 27 low LT-α DE, and 20 control eyes) and left eyes (21 high LT-α DE, 39 low LT-α DE, and 20 control eyes). In both eyes, tumor necrosis factor-α (TNF-α), interleukin (IL)-10, IL-1β, IL-1 receptor antagonist (IL-1Ra), IL-17A, and IL-12/23 p40 levels in high LT-α DE were significantly higher (P < .01) than in low LT-α DE. Significant correlations identified in high LT-α DE were: Standard Patient Evaluation Eye Dryness with IL-10 (R= 0.43, P= .013), IL-1β (R= 0.48, P= .005), and IL-12/23 p40 (R= 0.50, P= .003), IL-12/23 p40 with ocular surface disease index (R= 0.35, P= .049), and epidermal growth factor with corneal fluorescein staining score (R=-0.36, P= .038). Significant correlations in low LT-α DE were: Standard Patient Evaluation Eye Dryness with IL-10 (R=-0.39, P= .046), TNF-α (R=-0.39, P= .047), and IL-17A (R=-0.48, P= .013), ocular surface disease index with TNF-α (R=-0.47, P= .017) and IL-17A (R=-0.46, P= .018), and IL-6 with tear breakup time (R=-0.40, P= .044). Lastly, IL-1Ra levels significantly increased in DE patients, positively correlated with temporal conjunctival hyperemia index, and negatively correlated with Schirmer I test (P < .05). Our study identified tear IL-1Ra level as a potential biomarker to replace the Schirmer I test. Multiple tear protein marker levels increased in high LT-α DE, indicating that high LT-α DE might have a different pathogenesis.

Evaluation of the efficacy of optimal pulsed technology treatment in patients with cataract and Meibomian gland dysfunction in the perioperative period

BackgroundThe aim of this study was to evaluate the efficacy and safety of M22 Optimal Pulsed Technology (OPT) applied in patients with age-related cataract and Meibomian gland dysfunction (MGD) in perioperative period.MethodsThis prospective observational study was carried out in the Jinan Mingshui Eye Hospital (Zhangqiu, China). We studied 60 patients (30 in the OPT treatment group and 30 in the conventional surgery group) with age-related cataract and MGD who underwent phacoemulsification and evaluated the efficacy of OPT treatment before and 1 month and 3 months after surgery. Ocular Surface Disease Index (OSDI) questionnaire, biomicroscopic examination of lid margins, Meibomian gland yielding secretion score (MGYSS), corneal fluorescein staining scores (CFS), tear film break-up time (TBUT), tear meniscus height (TMH) and the morphology of the MG (meibography) followed by Keratograph 5 M (K5M) were used to assess the patients’ conditions.ResultsThere were significant differences in the scores of OSDI, MGYSS, TBUT, and CFS between the preoperative and postoperative outcomes (p < 0.05). In the OPT treatment group, the postoperative ocular surface condition was obviously better and the patient satisfaction rate was higher than those before surgery. There were significant differences in the scores of OSDI, EMAS, MGYSS and CFS before and 1 month after surgery (p < 0.05). In addition, there were also significant differences in the scores of OSDI, EMAS, MGYSS and MGLS before and 3 months after surgery (p < 0.05). No complications appeared during OPT treatment.ConclusionsCataract surgery can aggravate MGD and is detrimental to ocular surface health. OPT treatment was a safe and effective intervention for patients with MGD and cataract during perioperative period.