Corneal Fluorescein Staining Scores Research Articles

Evaluation of Clinical Efficacy and Safety of a Novel Cyclosporin A Nanoemulsion in the Treatment of Dry Eye Syndrome.

Topical administration of the anti-inflammatory agent cyclosporin A (CsA) is recommended for long-term management of dry eye syndrome (DES), yet standard ophthalmic CsA preparations have been reported to be unstable. In this trial, the efficacy and safety of Clacier™ (based on a phase 3 study developed by Huons Co. Ltd.), a novel 0.05% CsA nanoemulsion formulation, are compared with those of the conventional Restasis® emulsion. Patients with moderate-to-severe DES were randomly assigned to receive topical 0.05% CsA in the form of Clacier or Restasis, to be administered twice daily for 12 weeks. The primary efficacy outcome was the change from baseline in corneal fluorescein staining scores at week 12; changes at weeks 4 and 8 were secondary endpoints. Additional endpoints included score changes from baseline in nonanesthetic Schirmer's test I, tear breakup time, ocular surface disease index, and conjunctival staining. At week 12, corneal staining scores were improved in patients treated with Clacier and Restasis, with no significant difference between treatments (P = 0.41). Temporal conjunctival surface damage was significantly more ameliorated with Clacier treatment than with Restasis treatment (P = 0.034). Notably, tear film stability was improved more rapidly in Clacier patients at week 4 (P = 0.005) than in Restasis patients (P = 0.36). Improvements in tear production were comparable with both Clacier and Restasis treatments. Clacier did not increase the risk of adverse events as compared with Restasis. Treatment with Clacier alleviated clinical signs and symptoms of DES comparably to the commercially available Restasis, resulting in improved quality of life for patients. Clacier is an effective and safe therapeutic agent for DES.

Evaluating Corneal Fluorescein Staining Using a Novel Automated Method.

To evaluate interobserver concordance in measured corneal fluorescein staining (CFS) using the National Eye Institute/Industry (NEI) grading scale and the Corneal Fluorescein Staining Index (CFSi), a computer-assisted, objective, centesimal scoring system. We conducted a study to evaluate CFS in clinical photographs of patients with corneal epitheliopathy. One group of clinicians graded CFS in the images using the NEI while a second group applied the CFSi. We evaluated the level of interobserver agreement and differences among CFS scores with each method, level of correlation between the two methods, and distribution of cases based on the CFS severity assigned by each method. The level of interobserver agreement was 0.65 (P < 0.001) with the NEI, and 0.99 (P < 0.001) with the CFSi. There were statistically significant differences among clinicians' measurements obtained with the NEI (P < 0.001), but not with the CFSi (P = 0.78). There was a statistically significant correlation between the CFS scores obtained with the two methods (R = 0.72; P < 0.001). The NEI scale allocated the majority of cases (65%) within the higher quartile in the scale's severity (12-15/15). In contrast, the CFSi allocated the majority of cases (61%) within the lower quartile in the scale's severity (0-25/100). The CFSi is easy to implement, provides higher interobserver consistency, and due to its continuous score can discriminate smaller differences in CFS. Reproducibility of the computer-based system is higher and, interestingly, the system allocates cases of epitheliopathy in different severity categories than clinicians do. The CFSi can be an alternative for objective CFS evaluation in the clinic and in clinical trials.

Determinants of Ocular Pain Severity in Patients With Dry Eye Disease

To quantify the severity of ocular pain in patients with dry eye disease (DED) and evaluate factors associated with pain severity. Cross-sectional study. Eighty-four patients with DED were asked to score their severity level of ocular pain using a 10-point scale, with 10 indicating the most severe pain. All patients also had a comprehensive ophthalmic assessment including a detailed history, Ocular Surface Disease Index (OSDI) questionnaire, and ocular surface examination. Regression analysis was used to determine the factors associated with ocular pain severity. The mean OSDI score was 45.6 ± 23.1. At least some degree of ocular pain (score >1) was reported by 88.1% of patients, including mild pain (scores 2-4) in 46.4%, moderate pain (scores 5-7) in 34.5%, and severe pain (scores 8-10) in 7.1% of patients. Ocular pain levels significantly correlated with the OSDI score (rs= 0.49, P < .001). Regression analysis showed that the severity of ocular pain had a significant association with use of antidepressant medications (P= .045) but not with tear breakup time, corneal fluorescein staining, or ocular medications used by patients. In patients without pain, a significant correlation was seen between OSDI and corneal fluorescein staining scores (rs= 0.67, P=.01). However, such a correlation was not observed in those with ocular pain. A majority of patients with DED report some degree of ocular pain, which correlates only moderately with the OSDI score. Severity of ocular pain correlates with nonocular comorbidities such as use of antidepressant medications rather than with clinical signs of DED.

The protection of hydrogen-rich saline on a rat dry eye model induced by scopolamine hydrobromide

Objective: To evaluate the effect of hydrogen-rich saline (HRS) on dry eye rats induced by subcutaneous injection of scopolamine hydrobromide. Methods: Experiment research. Thirty female Wistar rats at about six weeks old were randomly divided into the normal group, dry eye group, HRS eyedrops group, normal saline eyedrops group (NS), HRS intraperitoneal injection group and NS intraperitoneal injection group, with 5 rats in each group. The dry eye was induced by subcutaneous injection of scopolamine hydrobromide in the latter five groups. The clinical signs of dry eye such as tear volume (SⅠt), tear break-up time (BUT) and corneal epithelial fluorescein staining scores were evaluated on day 7, 14, 21 and 28. On the 28th day, ten eyes in each group were enucleated and processed for paraffin sections for HE, PAS and immunohistochemistry stainings. Analysis of variance was used to test the data, and independent samples t-test was used for comparison between the two groups. Two-way repeated measure ANOVA was used to compare the difference among groups at different time points, one-way ANOVA was used to test the comparisons of the clinical signs at one time, and LSD was used to for comparison between two groups. Results: Before and after the experiment of the day 7, 14, 21, 28, the values of SIt in HRS eyedrops group and HRS intraperitoneal injection group were respectively:(3.625±1.157),(3.313±0.704),(3.250±0.535),(3.313±0.372), (3.375±0.582)mm and (3.500±1.019), (2.893±0.656), (3.321±0.668), (3.179±0.575), (3.214±0.871)mm. The values of BUT were respectively: (2.750±0.707), (2.688±0.594), (2.813±0.753), (3.000±0.756), (2.750±0.707)s and (3.000±0.679), (2.321±0.464), (2.750±0.753), (3.214±0.699), (2.679±0.608)s. The values of fluorescein staining score were respectively: (6.250±0.707), (8.875±0.641), (8.750±0.707), (9.250±0.463), (8.250±1.282) and (6.000±0.679), (9.143±1.027), (8.857±0.770), (9.143±0.949), (8.500±0.760). The difference of SIt, BUT and fluorescein staining score between the groups was statistically significant on the 14th day(F=5.194, 3.894, 16.487, P<0.05), the values of SⅠt, BUT and fluorescein staining score of HRS eyedrops group showed significantly better than NS eyedrops group(P<0.05), HRS intraperitoneal injection group showed significantly better than NS intraperitoneal injection group(P<0.05), and there was no significant difference between HRS eyedrops group and HRS intraperitoneal injection group(P>0.05), which remained stable until the day 28. On the 28(th) day, HE, PAS and immunohistochemistry stainings showed the corneal and conjunctival epithelia became smooth and regular, the cell layer number decreased, the tissue hyperplasia and edema were lightened, and the size of goblet cells tended to be normal, and the squamous metaplasia and inflammation were relieved. In HRS eyedrops group and HRS intraperitoneal injection group. Conclusions: HRS eyedrops group and HRS intraperitoneal injection group can relieve the signs of dry eye, improve the pathological damage of cornea and conjunctiva, and protect the ocular surface of a rat dry eye model, which is better than NS groups from the 14(th) day. (Chin J Ophthalmol, 2017, 53: 363-372).

Comparison of 0.3% Hypotonic and Isotonic Sodium Hyaluronate Eye Drops in the Treatment of Experimental Dry Eye

ABSTRACTPurpose: To compare the efficacy of 0.3% hypotonic and isotonic sodium hyaluronate (SH) eye drops in the treatment of experimental dry eye.Methods: Experimental dry eye was established in female C57BL/6 mice by subcutaneous scopolamine injection and an air draft. The mice were divided into three groups (n = 15): control, preservative-free 0.3% isotonic SH, and preservative-free 0.3% hypotonic SH. The tear volume, tear film break-up time, and corneal fluorescein staining scores were measured 5 and 10 days after treatment. After conjunctival tissues were excised at 10 days, the levels of interleukin (IL)-6, IL-17, interferon (IFN)-γ, and IFN-γ inducible protein-10 were determined using the multiplex immunobead assay. In addition, PAS staining and flow cytometry were performed to evaluate the counts of conjunctival goblet cells and CD4+ IFN-γ+ T cells.Results: Mice treated with 0.3% hypotonic SH showed a significant decrease in corneal staining scores (P = 0.04) and the levels of IL-6 (16.7 ± 1.4 pg/mL, P = 0.02) and IFN-γ (46.5 ± 11.5 pg/mL, P = 0.02) compared to mice treated with 0.3% isotonic SH (IL-6; 32.5 ± 8.8 pg/mL, IFN-γ; 92.0 ± 16.0 pg/mL) at day 10. Although no significant difference in CD4+ IFN-γ+ T cell numbers was observed, goblet cell counts were higher in the hyopotonic SH group than in the isotonic SH group (P = 0.02).Conclusions: When compared to 0.3% isotonic SH eye drops, 0.3% hypotonic SH eye drops can be more effective by improving corneal staining scores, decreasing inflammatory molecules, and increasing goblet cell counts for experimental dry eye. These data suggest that hypotonic artificial tears may be useful as an adjunctive treatment for inflammatory dry eye.

Evaluation of the Safety and Tolerability of Conjunctival Ring for Posterior Segment of the Eye

ABSTRACTPurpose: To evaluate the safety and tolerability of conjunctival rings (CRs), a novel device for drug delivery to the posterior segment of the eye.Methods: In animal studies, CRs containing 5% dexamethasone sodium phosphate (DSP) or vehicle solution were placed on the right and left eyes of C57BL/6J mice, respectively. Contact lenses (CLs) containing vehicle solution were used as a control. Twenty-four hours after placement of the CRs, corneal fluorescein staining was graded based on the McDonald-Shadduck scoring system, ranging from 0 to 4. In humans, CRs containing vehicle solution were placed on the right eye of healthy volunteers for 9 hours. The corneal curvature, corneal thickness, intraocular pressure, visual acuity, tear production (Schirmer I test), tear film break-up time and fluorescein staining scores of the cornea (scores ranging from 0 to 3) and conjunctiva (scores ranging from 0 to 6) were assessed before and after wearing the CRs. The release characteristics of DSP from CRs were also evaluated.Results: In animal experiments, corneal fluorescein staining scores were 1 or less in all the groups, and there was no significant difference between the CR group and the CL group. In the preclinical safety evaluation of CR for humans, ophthalmic examination revealed that CR caused no significant changes in all the parameters investigated including corneal curvature (p = 0.77), corneal thickness (p = 0.96), intraocular pressure (p = 0.59), visual acuity (p = 0.14), Schirmer I test results (p = 0.76), tear film break-up time (p = 0.68), corneal fluorescein staining scores (p = 0.64), and conjunctival fluorescein staining scores (p = 0.52). The DSP release from CRs occurs within a few hours, which is similar to the drug-release property of medicated CL, as reported previously.Conclusions: The current data showed the safety and tolerability of CR as a drug delivery device for the treatment of posterior segment diseases.

Predictive factors for the placebo effect in clinical trials for dry eye: a pooled analysis of three clinical trials

BackgroundPlacebo effect is one of the methodological difficulties in dry eye clinical trials. If we could elucidate the tendencies of the placebo response and find predictors, we could reduce the...

Influence on ocular surface after cataract surgery and effect of topical diquafosol on postoperative dry eye: a multicenter prospective randomized study.

PurposeTo investigate influences of 3% diquafosol sodium ophthalmic solution (DQS) on ocular surface after cataract surgery and effects on postoperative dry eye.DesignThis study had two consecutive prospective study phases. The former was an observational study from before cataract surgery to 4 weeks after surgery and the latter was a randomized open-label study from 4 to 8 weeks after surgery.MethodsSubjects were 433 eyes of 433 patients undergoing cataract surgery with intraocular lens implantation. Dry eye examination of tear breakup time (BUT), corneal and conjunctival fluorescein staining scores, total subjective symptom score (12 symptoms), and Schirmer I test were conducted before surgery and 4 weeks after surgery. Patient demographics and these examination results were used to analyze risk factors to predict postoperative dry eye. In a randomized study, 154 eyes diagnosed with dry eye postoperatively were applied either DQS or artificial tears (AT) six times daily for 4 weeks. The data of the examinations were compared.ResultsAt 4 weeks after surgery, BUT was shortened significantly (P=0.036), fluorescein staining score increased significantly (P=0.012), but total subjective symptom score was significantly improved (P<0.001). The majority of postoperative dry eye was shortened BUT type (53.1%). The dry eye prevalence after surgery decreased (55.7%) compared with before surgery (69.7%). Females and the patient with dry eye symptoms before surgery had significant risk factors for postoperative dry eye. In a randomized study, BUT was significantly prolonged in the DQS group (P=0.015), but not in the AT group. Fluorescein staining score was significantly improved in both groups (P<0.001). Total subjective symptom score was significantly decreased in the AT group (P<0.001), but not in the DQS group.ConclusionOur study suggests that cataract surgery has harmful effects on tear film stability and ocular surface, and DQS has a capability to improve them.

Lifitegrast Ophthalmic Solution 5%: A Review in Dry Eye Disease.

Lifitegrast is a novel small molecule integrin antagonist that blocks the binding of intercellular adhesion molecule 1 (ICAM-1) to lymphocyte function-associated antigen 1 (LFA-1). Lifitegrast ophthalmic solution 5% (Xiidra™) was recently approved in the USA for the treatment of dry eye disease. The efficacy of lifitegrast ophthalmic solution 5% was compared with vehicle in a 12-week phase 2 study and three 12-week phase 3 studies (OPUS-1, OPUS-2 and OPUS-3) in patients with dry eye disease. Taken as a whole, results of these trials support the treatment effect of lifitegrast ophthalmic solution 5% in improving a symptom of dry eye disease (i.e. the change from baseline to day 84 in the eye dryness visual analogue scale score) and a sign of dry eye disease (i.e. the change from baseline to day 84 in the inferior corneal fluorescein staining score). Lifitegrast ophthalmic solution 5% was generally well tolerated. In conclusion, lifitegrast ophthalmic solution 5% provides a new option for the treatment of dry eye disease.

Effects of Exposure to Ozone on the Ocular Surface in an Experimental Model of Allergic Conjunctivitis.

Based on previous findings that ozone can induce an inflammatory response in the ocular surface of an animal model and in cultured human conjunctival epithelial cells, we investigated whether exposure to ozone exacerbates symptoms of allergic conjunctivitis. We evaluated the effects of exposure to ozone on conjunctival chemosis, conjunctival injection, corneal and conjunctival fluorescein staining scores, production of inflammatory cytokines in tears, and aqueous tear production in a mouse model of allergic conjunctivitis. To validate our in vivo results, we used interleukin (IL)-1α-pretreated conjunctival epithelial cells as an in vitro substitute for the mouse model. We evaluated whether exposure to ozone increased the inflammatory response and altered oxidative status and mitochondrial function in IL-1α-pretreated conjunctival epithelial cells. In the in vivo study, ozone induced increases in conjunctival chemosis, conjunctival injection, corneal and conjunctival fluorescein staining scores, and production of inflammatory cytokines, accompanied by a decrease in tear volume. In the in vitro study, exposure to ozone led to additional increases in IL-6 and tumor necrosis factor-α mRNA levels, which were already induced by treatment with IL-1α. Ozone did not induce any changes in cell viability. Pretreatment with IL-1α increased the expression of manganese superoxide dismutase, and exposure to ozone led to additional increments in the expression of this antioxidant enzyme. Ozone did not induce any changes in mitochondrial activity or expression of mitochondrial enzymes and proteins related to mitochondrial function, with the exception of phosphor-mammalian target of rapamycin. Treatment with butylated hydroxyanisole, a free radical scavenger, attenuated the ozone-induced increases in IL-6 expression in IL-1α-pretreated conjunctival epithelial cells. Therefore, we conclude that exposure to ozone exacerbates the detrimental effects on the integrity of the ocular surface caused by conjunctival allergic reactions, and further increases the inflammatory response in IL-1α-pretreated conjunctival epithelial cells.

Short- and long-term effects of zinc treatment on lacrimal gland histopathology and tear functions tests in radioiodine-administered rats.

To investigate the short-term (1 week) and long-term (8 weeks) protective effects of zinc administration on radioiodine (RAI)-induced lacrimal gland damage of rats. A total of 40 rats were divided into two groups: an RAI group (n=20), which was administrated a single dose of 3 mCi of 131I and 1 mL physiologic saline for 7 days by gastric gavage, and a zinc group (n=20), which received a single dose of 3 mCi of 131I and 1 mL of physiologic saline containing zinc sulfate at a concentration of 10 mg/kg concentration for 7 days by gastric gavage. All rats underwent tear function tests before and 1 week after RAI administration. About 1 week after irradiation, half of the animals in each group were sacrificed and the extraorbital lacrimal glands were removed for histopathological examination. The remaining animals of the groups underwent the same procedures at 8 weeks after irradiation. In the RAI and zinc groups, the mean tear production was 3.75 ± 1.55 and 3.65 ± 1.53 mm at baseline, 2.10 ± 1.07 and 3.30 ± 1.34 mm at week 1 (p=0.004), and 3.22 ± 1.48 and 3.50 ± 1.78 mm at week 8, respectively; further, the mean corneal fluorescein staining scores were 4.65 ± 2.16 and 4.80 ± 2.21 points at baseline, 7.85 ± 1.90 and 5.45 ± 2.06 points at week 1 (p=0.001), and 5.44 ± 2.13 and 4.90 ± 2.08 at week 8, respectively. The histopathological changes in rat lacrimal glands at weeks 1 and 8 were consistent with the tear function test results. Zinc treatment seems to be protective against RAI-induced lacrimal gland damage of rats, particularly in the acute period.

RNA Collection From Human Conjunctival Epithelial Cells Obtained With a New Device for Impression Cytology.

To assess the ability of a new device (Eyeprim; Opia Technologies) designed for impression cytology (IC) to harvest RNA from conjunctival cells as compared with the conventional technique. Cell collection was performed in both eyes using both techniques (conventional and Eyeprim) in different eyes randomized to each technique to avoid bias. The collection order was also randomized. Subjective discomfort assessment was performed using the Symptom Assessment in Dry Eye questionnaire. RNA was quantified in a spectrophotometer. RNA yield and discomfort using each technique were evaluated. A P value ≤0.05 was considered significant. Twenty healthy subjects (8 men and 12 women) aged 24.7 ± 5.8 years were recruited. The mean corneal fluorescein staining scores were 0.10 ± 0.30 for both eyes (P = 1.0), and the mean phenol red thread tear scores were 28.6 ± 1.9 mm for the Eyeprim and 28.7 ± 2.5 mm for the conventional IC eye group (P = 0.64). No significant (P ≥ 0.45) differences were observed in the mean RNA yield between the Eyeprim and the conventional IC, neither in the total amount (0.32 ± 0.28 μg and 0.26 ± 0.28 μg, respectively) nor in the amount normalized to the membrane area (0.0046 ± 0.0040 μg/mm and 0.0040 ± 0.0043 μg/mm, respectively). No significant differences were observed during (P ≥ 0.17) and after sample collection (P ≥ 0.36) in the frequency or intensity of discomfort (Symptom Assessment in Dry Eye scores). This pilot study shows that the Eyeprim provides similar RNA yield as the conventional harvesting conjunctival IC technique. It provides enough quantities of material useful for molecular analysis producing comparable levels of discomfort without using anesthesia.

Effects of 3% diquafosol sodium ophthalmic solution on higher-order aberrations in patients diagnosed with dry eye after cataract surgery.

PurposeTo evaluate the effects of diquafosol sodium ophthalmic solution 3% (DQS) and artificial tears (AT) on higher-order aberrations (HOAs) in patients with dry eye after cataract surgery.DesignThis was a post hoc analysis of a previously conducted randomized clinical study.MethodsFifty-nine eyes from 42 patients (17 males and 25 females, aged 72.6±8.0 years) with verified or suspected dry eye at 4 weeks after cataract surgery were evaluated. The dry eye patients were randomly assigned to receive DQS or AT for 4 weeks. Tear breakup time (BUT), corneal and conjunctival fluorescein staining scores, and HOAs were analyzed before and after instillation. HOAs were measured consecutively for 10 seconds with a wavefront analyzer. Average HOAs, HOA fluctuations (fluctuation index [FI]) and changes in HOAs (stability index [SI]) were compared within and between the two groups.ResultsAfter 4 weeks of instillation, BUT significantly increased (P=0.001) compared with preinstillation values in the DQS group, but not in the AT group. This increase in BUT in the DQS group was significantly greater than in the AT group (P=0.014). Corneal and conjunctival fluorescein staining scores after instillation significantly improved compared with preinstillation values in the DQS group (P=0.018). In HOAs, the cornea aberration changed from an upward curve (a sawtooth pattern) to an almost constant value (a stable pattern) in the DQS group, but not in the AT group. In FI and SI, there were no significant changes in either group; however, FI and SI were significantly lower in the DQS group than in the AT group (both, P=0.004).ConclusionThe dry eye patients after cataract surgery had a visual dysfunction in HOAs. DQS is effective to treat dry eye disease after cataract surgery with improvement of visual function.

Comparison of therapeutic effects between a new warm moist air device assisted with eyelid massage and eyedrops with only eyedrops for meibomian gland dysfunction

Background Meibomian gland dysfunction (MGD) is a common eye disease that leads to ocular surface damage.Conventional treating method is hot compress with heating pads or warm towels combined with eyelid massage, but the temprature of heat source is difficult to ensure precisely.A new warm moist air device is used in ophthalmology now, however, its clinical effect for MGD is under evaluation. Objective This study was to evaluate the therapeutic effects of a new warm moist air device assisted with eyelid massage for MGD. Methods A randomized-controlled clinical trail was performed.Sixty MGD patients were recruited in Tonghua Eye Hospital from January to June 2015.The patients were divided into two groups according to random number table with matched age, gender and the findings of ocular surface, and the unilateral eyes of the patients were used to analysis.The eyes in the trail group received topical administration of polyethylene glycol eye drops and new warm moist air device combined with eyelid massage, and the eyes in the control group received only topical administration of polyethylene glycol eye drops.The eye examinations were carried out before treatment and 2, 4 weeks after treatment, including ocular surface disease index questionnaire (OSDI), meibomian gland function under the slit lamp microscope, breakup time of tear film (BUT), corneal fluorescein staining scores and Schirmer Ⅰtest (SⅠt). The treating results over time were intergrouply compared.This study protocol was approved by Ethic Committee of Tonghua Eye Hospital, and written informed consent was obtained from each patient prior to entering the group. Results All the patients finished this therapeutic process.In the trail group, the OSDI scores were 13.29±4.06 and 9.29±3.21 at 2 and 4 weeks after treatment, which were significantly lower than those in the control group (16.82±3.21 and 15.41±4.03) (t=-3.5, -6.12, both at P 0.05). In addition, there were not significant differences in SⅠt and meibomian gland secretory levels over time between two groups (SⅠt: Fgroup=0.10, P>0.05; Ftime=0.72, P>0.05; secretion: Fgroup=1.64, P>0.05; Ftime=0.92, P>0.05). Conclusions This new warm moist air device assisted with eyelid massage and polyethylene glycol eye drops can effectively treat MGD, and this combination therapy appears to have a favorable therapeutic effects in comaprison with only polyethylene glycol eye drops. Key words: Meibomian gland dysfunction/therapy; Ocular surface diseases/therapy; Tear film; Prospective study; Randomized-controlled clinical study; Water vapor heating apparatus, ophthalmology/therapeutic use

Lifitegrast for the Treatment of Dry Eye Disease: Results of a Phase III, Randomized, Double-Masked, Placebo-Controlled Trial (OPUS-3)

Lifitegrast is a lymphocyte function-associated antigen-1 antagonist developed to reduce inflammation in dry eye disease (DED). We report the results of OPUS-3 (NCT02284516), a phase III study evaluating the efficacy and safety of lifitegrast versus placebo in participants with DED. Twelve-week, phase III, randomized, double-masked, multicenter, placebo-controlled study. Adults aged ≥18 years with Schirmer tear test (without anesthesia) ≥1 and ≤10 mm, corneal fluorescein staining score ≥2.0 (0-4 scale), eye dryness score (EDS) ≥40 (0-100 visual analogue scale [VAS]), and history of artificial tear use within 30 days of study entry. After a 14-day placebo run-in, participants were randomized 1:1 to lifitegrast ophthalmic solution 5.0% or placebo twice daily for 84 days. The primary efficacy end point was change from baseline to day 84 in EDS. Key secondary efficacy end points were change from baseline to days 42 and 14 in EDS. Other secondary efficacy end points included additional VAS items (burning/stinging, itching, foreign body sensation, eye discomfort, photophobia, pain), ocular discomfort score (ODS), and safety/tolerability of lifitegrast versus placebo. In the study, 711 participants were randomized: placebo, 356; lifitegrast, 355 (intention-to-treat [ITT] population). At day 84, lifitegrast-treated participants experienced significantly greater improvement from baseline in EDS versus those receiving placebo (treatment effect [TE], 7.16; 95% confidence interval [CI], 3.04-11.28; P= 0.0007). Mean changes from baseline in EDS also significantly favored lifitegrast on days 42 (TE, 9.32; 95%CI, 5.44-13.20; P < 0.0001) and 14 (TE, 7.85; 95% CI, 4.33-11.37; P < 0.0001). No statistically significant differences were observed in ODS between treatment groups at days 84, 42, or 14. A greater improvement was observed in lifitegrast-treated participants at day 42 in itching (nominal P= 0.0318), foreign body sensation (nominal P= 0.0418), and eye discomfort (P= 0.0048) versus participants receiving placebo. Most treatment-emergent adverse events were mild to moderate in severity; no serious ocular adverse events were reported. Lifitegrast significantly improved symptoms of eye dryness, as measured by EDS, versus placebo in participants with DED. Improvement in EDS was observed as early as day 14. Lifitegrast appeared well tolerated.

Subgroup analysis of two phase III studies of 0.1% cyclosporine A cationic emulsion (CsA CE) in patients with dry eye disease

PurposeDry eye disease (DED) increases the risk of ocular surface damage, severe keratitis, vision loss and impaired quality of life. In two randomized phase III studies (SANSIKA and SICCANOVE), the cationic emulsion formulation containing 0.1% (1 mg/ml) cyclosporine A (CsA CE) improved ocular damage and inflammation in patients with moderate to [AS1] severe DED. This analysis evaluated the efficacy of CsA CE in improving signs of DED in specific patient subgroups.MethodsAnalysis was performed based on efficacy data from the SANSIKA study (n = 215) and pooled efficacy data from the SANSIKA and SICCANOVE studies (n = 629); change from baseline in corneal fluorescein staining (CFS) at Month 6 was analyzed in subgroups of DED patients defined by age, sex, menopausal status, DED duration (ranging from &lt;4 to ≥12 years) and the presence of Sjögren disease.ResultsOf the patients included in the pooled analysis, 65% were &lt;65 years old, 83% were female (72% in menopause) and 38% had Sjögren disease. The overall change in CFS score from baseline to Month 6 favored CsA CE over vehicle (treatment difference −0.303; 95% confidence interval, −0.464 to −0.142). In the SANSIKA study and in the pooled analysis, the effect of CsA CE on CFS score was comparable in patients regardless of age, sex, menopausal status, DED duration and Sjögren disease status. In the subset of patients with severe keratitis, the effect of CsA CE on CFS was also comparable across all subgroups. CsA CE was well tolerated, with a safety profile consistent with ophthalmic CsA use.ConclusionsThese data suggest that CsA CE is well tolerated and comparably efficacious in improving signs of DED across multiple DED patient subpopulations.

Influence of Light Emitting Diode-Derived Blue Light Overexposure on Mouse Ocular Surface.

PurposeTo investigate the influence of overexposure to light emitting diode (LED)-derived light with various wavelengths on mouse ocular surface.MethodsLEDs with various wavelengths were used to irradiate C57BL/6 mice at an energy dose of 50 J/cm2, twice a day, for 10 consecutive days. The red, green, and blue groups represented wavelengths of 630 nm, 525 nm, and 410 nm, respectively. The untouched group (UT) was not exposed to LED light and served as the untreated control. Tear volume, tear film break-up time (TBUT), and corneal fluorescein staining scores were measured on days 1, 3, 5, 7, and 10. Levels of interferon (IFN)-γ, interleukin (IL)-1β, IL-6, and tumor necrosis factor (TNF)-α were measured in the cornea and conjunctiva using a multiplex immunobead assay at day 10. Levels of malondialdehyde (MDA) were measured with an enzyme-linked immunosorbent assay. Flow cytometry, 2’7’-dichlorofluorescein diacetate (DCF-DA) assay, histologic analysis, immunohistochemistry with 4-hydroxynonenal, and terminal deoxynucleotidyl transferase-mediated dUTP-nick end labeling (TUNEL) staining were also performed.ResultsTBUT of the blue group showed significant decreases at days 7 and 10, compared with the UT and red groups. Corneal fluorescein staining scores significantly increased in the blue group when compared with UT, red, and green groups at days 5, 7, and 10. A significant increase in the corneal levels of IL-1β and IL-6 was observed in the blue group, compared with the other groups. The blue group showed significantly increased reactive oxygen species production in the DCF-DA assay and increased inflammatory T cells in the flow cytometry. A significantly increased TUNEL positive cells was identified in the blue group.ConclusionsOverexposure to blue light with short wavelengths can induce oxidative damage and apoptosis to the cornea, which may manifest as increased ocular surface inflammation and resultant dry eye.

Diquafosol for Soft Contact Lens Dryness: Clinical Evaluation and Tear Analysis.

To evaluate the efficacy of topical application of 3% diquafosol tetrasodium solution for the treatment of soft contact lens (SCL) wearers with dryness. In addition to clinical tests and subjective symptoms, we assessed the fluorescence intensity of wheat germ agglutinin conjugate of fluorescein (F-WGA) used as a marker of membrane-associated mucins and sialic acid concentration in tear fluids as a marker of secreted mucins. Twelve SCL wearers with dryness symptoms were treated with diquafosol for 4 weeks. Clinical tests included the tear film break-up time (BUT), corneal and conjunctival fluorescein staining scores, and Schirmer values. Subjective symptoms were evaluated by the Dry Eye-Related Quality-of-Life Score (DEQS). Fluorescence intensities in the central cornea were measured by fluorophotometry at 5 minutes after a 5% F-WGA solution was applied to the eye. The tears collected by the Schirmer test strips were analyzed by high-performance liquid chromatography (HPLC), and the concentrations of sialic acid; total protein; and the four major tear proteins secretory IgA, lactoferrin, lipocalin-1, and lysozyme proteins were measured. Comparing the results before and after diquafosol treatment, BUT (p < 0.01), kerato-conjunctival staining score (p < 0.05), corneal staining score (p < 0.05), and DEQS score (p < 0.01) showed statistically significant improvements. The F-WGA fluorescence intensities (p < 0.0001) significantly increased after treatment, whereas the concentrations of sialic acid and tear proteins remained unchanged. Topical application of diquafosol solution to the SCL wearers with dryness improved biomarker of membrane-associated mucins, BUT, staining of cornea and conjunctiva, and subjective symptoms.

Dry eye disease in an adult population in South-West Nigeria.

To determine the prevalence and factors associated with dry eye disease (DED) in an adult population in south-west Nigeria. A descriptive cross-sectional community-based study was conducted among respondents aged 40 years and above. Questionnaires were administered on symptoms of DED, followed by ocular examination to elicit signs of DED by determining the tear film break-up time, corneal fluorescein staining score, and Schirmer I tests. Dry eye was diagnosed by the simultaneous presence of at least one symptom experienced "often or all of the time" and at least one sign in either eye. The respondents (n=363; females 188) were aged 59.1±13.1years. The prevalence of DED was 32.5% (95% CI=27.7-37.3), and the most commonly reported symptoms were grittiness (53.4%, 95% CI=44.4-62.4) and burning/stinging sensation (48.3%, 95% CI=39.3-57.3). On multivariate analysis, DED was significantly associated with age (OR 2.89, 95% C.I=1.67-4.93, p<0.001) but not use of benzalkonium containing topical medications, previous ocular surgery, household fuel use, menopausal status and presence of pterygium. The outcome of the study shows that the prevalence of DED among adults above 40 years in south-west Nigeria is 32.5% and the associated risks include older age.

In vivo confocal microscopy of meibomian glands in primary blepharospasm

The aim of the study was to evaluate the morphological changes of meibomian glands (MGs) in primary blepharospasm (PBS) by in vivo laser scanning confocal microscopy (LSCM) and to investigate the correlations between clinical data of PBS and LSCM parameters of MGs. This prospective and case–control study recruited 30 consecutive PBS patients and 30 age- and gender-matched healthy controls. After questionnaire assessments of ocular surface disease index (OSDI), Jankovic rating scale, and blepharospasm disability index, all subjects underwent blink rate evaluation, tear film break-up time (TBUT), corneal fluorescein staining (CFS), Schirmer test, MG expressibility, meibum quality, MG dropout, and LSCM examination of the MGs. The main LSCM outcomes included the mean MG acinar area and density, orifice diameter, meibum secretion reflectivity, acinar irregularity, and inhomogeneity of interstice and acinar wall. The PBS patients had significantly higher blink rate, higher OSDI and CFS scores, lower TBUT and Schirmer test value, and worse MG expressibility than the controls (All P < 0.05), whereas meibum quality showed no difference (P > 0.05). The PBS patients showed lower values of MG acinar area, orifice diameter and meibum secretion reflectivity, and higher scores of acinar irregularity and inhomogeneity of interstices than the controls (All P < 0.05). For the PBS patients, the severity of blepharospasm evaluated by JCR scale was strong correlated with MG acinar area (P < 0.001), orifice diameter (P = 0.002), meibum secretion reflectivity (P = 0.002), and MG acinar irregularity (P = 0.013). The MG expressibility was significantly correlated to MG acinar area (P = 0.039), orifice diameter (P < 0.001), and MG acinar irregularity (P = 0.014). The OSDI score was moderate correlated with MG acinar irregularity (P = 0.016), whereas the TBUT value was positively correlated with MG acinar area (P = 0.045) and negatively correlated to MG acinar irregularity (P = 0.016). The CFS score was negatively correlated to MG orifice diameter (P = 0.008). The LSCM provided a noninvasive tool for in vivo histopathologic studies of MGs in PBS patients. The excessive constriction of lid muscles closely related to MG morphological alterations of PBS, which offered a new research approach to interpret the interactional mechanism between dry eye and PBS.