Relevance of Lipid-Based Products in the Management of Dry Eye Disease

Components of the ocular surface synergistically contribute to maintaining and protecting a smooth refractive layer to facilitate the optimal transmission of light. At the air-water interface, the tear film lipid layer (TFLL), a mixture of lipids and proteins, plays a key role in tear surface tension and is important for the physiological hydration of the ocular surface and for ocular homeostasis. Alterations in tear fluid rheology, differences in lipid composition, or downregulation of specific tear proteins are found in most types of ocular surface disease, including dry eye disease (DED). Artificial tears have long been a first line of treatment in DED and aim to replace or supplement tears. More recently, lipid-containing eye drops have been developed to more closely mimic the combination of aqueous and lipid layers of the TFLL. Over the last 2 decades, our understanding of the nature and importance of lipids in the tear film in health and disease has increased substantially. The aim of this article is to provide a brief overview of our current understanding of tear film properties and review the effectiveness of lipid-based products in the treatment of DED. Liposome lid sprays, emulsion eye drops, and other lipid-containing formulations are discussed.Peer reviewe

Efficacy and Safety of 0.1% Cyclosporine a Cationic Emulsion in the Treatment of Severe Dry Eye Disease: A Multicenter Randomized Trial:

PurposeThe SANSIKA study was conducted to assess the treatment effect of 0.1% cyclosporine A cationic emulsion (CsA CE) eye drops on signs and symptoms of patients with severe dry eye disease (DED)..

12-Month Results of Cyclosporine A Cationic Emulsion in a Randomized, Study in Patients With Pediatric Vernal Keratoconjunctivitis

Abstract Purpose To assess the safety and efficacy of cyclosporine A cationic emulsion (CsA CE) 0.1% eye drops in pediatric patients with severe active vernal keratoconjunctivitis (VKC). Design Multicenter, double-masked, randomized control trial 8-month safety analysis Methods Of 169 patients (age range, 4-17 years) initially randomized in the 4-month VEKTIS study, 142 entered the 8-month follow-up period during which CsA CE patients remained on their original regimen (CsA CE four times daily [QID, high-dose] or CsA CE twice daily [BID, low-dose] + vehicle BID) and vehicle patients were allocated to one of these 2 active regimens. Main outcome measures were safety, including treatment-emergent adverse events, and efficacy, including corneal fluorescein staining (CFS) score. Results Improvements in CFS score, rescue medication use, key VKC symptoms (photophobia, tearing, itching, and mucous discharge), and quality of life (QoL) assessed by QUICK questionnaire observed with CsA CE compared with vehicle during the 4-month evaluation period remained stable during the 8-month follow-up period, with the high-dose regimen continuing to provide greater benefits in most efficacy measures. CsA CE was well tolerated. Treatment-related treatment-emergent adverse events during the 12-month study were reported in 15 (20.8%) and 11 (15.7%) of the CsA CE high-dose and low-dose patients, respectively, most commonly instillation site pain (13.9% and 7.1%), respectively). Laboratory data, vital signs, slit lamp examination, best-corrected distance visual acuity, and intraocular pressure raised no safety concerns. Conclusions Improvements in keratitis, symptoms, and QoL achieved after CsA CE treatment for 4 months remained stable over the 8-month follow-up period. CsA continued to maintain a favorable safety profile

A Randomized, Controlled Trial of Cyclosporine A Cationic Emulsion in Pediatric Vernal Keratoconjunctivitis: The VEKTIS Study

Purpose Vernal keratoconjunctivitis (VKC) is a chronic, allergic, and potentially severe ocular disease affecting children and adolescents that can lead to impaired quality of life (QoL) and loss of vision. This study evaluated the efficacy and safety of an investigational therapy for severe VKC, cyclosporine A (CsA) cationic emulsion (CE), an oil-in-water emulsion with increased bioavailability versus conventional CsA formulations. Design The VErnal KeratoconjunctiviTIs Study (VEKTIS) is a phase 3, multicenter, double-masked, vehicle-controlled trial. Participants Pediatric patients (4 to younger than 18 years) with active severe VKC (grade of 3 or 4 on the Bonini severity scale) and severe keratitis (corneal fluorescein staining [CFS] score of 4 or 5 on the modified Oxford scale). Methods One hundred sixty-nine patients were randomized to CsA CE 0.1% (1 mg/ml) eye drops 4 times daily (high dose), CsA CE twice daily (low dose) plus vehicle twice daily, or vehicle 4 times daily for 4 months. Main Outcome Measures The primary end point was a mean composite score that reflected CFS, rescue medication use (dexamethasone 0.1% 4 times daily), and corneal ulceration over the 4 months. Results Differences in least-squares means versus vehicle for the primary end point were statistically significant for both the high-dose (0.76; P = 0.007) and the low-dose (0.67; P = 0.010) groups, with treatment effect mainly driven by CFS score. Significant differences were found between both active treatment groups and vehicle for use of rescue medication. Vernal keratoconjunctivitis symptoms and patient QoL (assessed by visual analog scale and the Quality of Life in Children with Vernal Keratoconjunctivitis questionnaire) improved in all 3 groups, with significant improvements for high-dose CsA CE versus vehicle. Conclusions The efficacy of high-dose CsA CE in improving keratitis, symptoms, and QoL for those with severe VKC was demonstrated in these study patients. In addition, in this study cohort, CsA CE was well tolerated

persistence of efficacy of 0 1 cyclosporin a cationic emulsion in subjects with severe keratitis due to dry eye disease a nonrandomized open label extension of the sansika study

Abstract Purpose Results from a 6-month double-masked and a 6-month open-label study (SANSIKA) established the efficacy and safety of once-daily 0.1% cyclosporin A cationic emulsion (CsA CE) in severe keratitis due to dry eye disease (DED). This article presents results from the Post-SANSIKA study, a 24-month extension of SANSIKA assessing the sustained efficacy of CsA CE after treatment discontinuation. Methods Time to relapse (corneal fluorescein staining [CFS] score ≥4 [modified Oxford scale]) was assessed after treatment discontinuation in patients from the SANSIKA study who had CFS improvement from a score of 4 to ≤2 after 6 or 12 months of treatment with CsA CE. Findings Of 62 patients who achieved a CFS score ≤2 at the end of the SANSIKA study, 38 did not relapse and 24 (39%) relapsed during the 24-month period after CsA CE discontinuation; the latter (relapse) group comprised 35% of patients initially treated with CsA CE for 12 months in SANSIKA versus 47% of those treated for 6 months only. Patients spent the most time during the extension study at CFS scores of 1 or 2 (median duration of 8.5 weeks and 14.7 weeks per year, respectively), indicating marked improvement, and less time at scores of 3, 4, or 5 (median time, 2.0 weeks, 0 weeks, and 0 weeks per year). Of 23 patients eligible for safety analysis (ie, patients who received the study treatment at least once), 12 (52.2%) reported a total of 26 ocular adverse events (AEs). Among these, 5 ocular AEs, reported in 5 patients (21.7%), were considered related to study treatment: 3 events of mild instillation site pain in 3 patients (13.0%) and eye discharge and foreign body sensation, each reported in 1 patient (4.3%). Only 1 systemic AE (nasal congestion), reported in 1 patient (4.3%), was considered related to study treatment. None of the AEs led to treatment discontinuation. Implications The majority of patients who discontinued CsA CE after experiencing DED improvement in the SANSIKA study did not experience a relapse in this 24-month follow-up study; these patients spent the most time at CFS scores consistent with marked improvement. CsA CE had a favorable safety/tolerability profile over 2 years. Treatment for up to 12 months with CsA CE provides sustained improvements in patients with severe keratitis due to DED. EudraCT registration no. 2012-002066-12

Efficacy and safety of 0.1% ciclosporin A cationic emulsion in dry eye disease: a pooled analysis of two double-masked, randomised, vehicle-controlled phase III clinical studies

Background/aim To assess the treatment effect of 0.1% ciclosporin A cationic emulsion (CsA CE) versus vehicle on signs/symptoms of dry eye disease (DED) in various subgroups (moderate-to-severe DED/severe DED/ Sjogren's syndrome (SS)/SS with severe DED). Methods Pooled data were analysed from two similar phase III studies: SICCANOVE (moderate-to-severe DED) and SANSIKA (severe DED with severe keratitis). In both studies, patients aged >= 18 years received CsA CE 0.1% (n=395) or vehicle (n=339) once daily for 6 months. A composite responder efficacy endpoint (corneal fluorescein staining-Ocular Surface Disease Index (CFSOSDI) at month 6) was used to evaluate the efficacy of CsA CE in alleviating signs/symptoms of DED (response defined as improvement of >= 2 grades in CFS and >= 30% in OSDI (baseline to month 6)). Human leucocyte antigen-DR (HLA-DR) conjunctival expression was used as a biomarker of ocular surface inflammation. Results CsA CE-treated patients were significantly more likely to be CFS-OSDI responders than vehicletreated patients in the overall (OR 1.66, 95% CI 1.11 to 2.50;P=0.015), severe DED (1.80, 1.04 to 3.19;P=0.038) and SS with severe DED (3.37, 1.20 to 11.19;P=0.030) populations. The difference was not significant for CsA CE versus vehicle for the overall Sjogren's population (OR 1.77, CI 0.89 to 3.66;P=0.109). CsA CE also significantly reduced median HLA-DR expression versus vehicle at 6 months (P=0.002). Conclusion Pooled phase III data indicate CsA CE produced significant improvement in signs/symptoms versus vehicle in patients with moderate-to-severe DED (especially in those with severe keratitis), including patients with SS with severe DED

First-line latanoprost therapy in ocular hypertension or open-angle glaucoma patients: a 3-month efficacy analysis stratified by initial intraocular pressure

<p>Abstract</p> <p>Background</p> <p>Prospective, multicenter, randomized, double-masked trials have shown latanoprost instilled once daily to be at least as effective as and generally superior to timolol administered twice daily and to be as effective as other frequently prescribed prostaglandin analogues. This study prospectively assessed the efficacy of latanoprost monotherapy in a large cohort of treatment-naive patients with a broad range of baseline intraocular pressure (IOP) levels treated in actual clinical practice settings.</p> <p>Methods</p> <p>This prospective, open-label, multicenter, uncontrolled, phase IV study included treatment-naive ocular hypertension or open-angle glaucoma subjects initiating latanoprost once daily (evening). IOP levels were measured at baseline and after 1 and 3 months. The primary efficacy outcome was mean change in IOP from baseline to month 3. Analyses were stratified by baseline IOP: ≥ 20 and <24 mmHg <it>vs </it>≥ 24 mmHg.</p> <p>Results</p> <p>Efficacy analyses (intent to treat) included 572 subjects: 20 to <24 mmHg group, N = 252; ≥ 24 mmHg group, N = 320. Mean baseline IOP levels were 22.2 ± 0.9 mmHg and 26.7 ± 2.8 mmHg, respectively. At month 3, significant IOP reductions were seen in both groups (p < 0.0001, within-group differences); reductions were smaller in the 20 to <24 mmHg group (-6.3 ± 2.4 <it>vs </it>-9.2 ± 3.7 mmHg, respectively; -28.0 ± 10.6% <it>vs </it>-34.1 ± 11.9%, respectively). An IOP reduction of ≥ 30% from baseline to month 3 was noted in 48.4% and 65.6% of subjects, respectively (p < 0.0001). At month 3, targets IOPs of ≤ 18 mmHg were achieved by ≥ 70% of subjects in both groups. Latanoprost was well tolerated with an adverse event profile similar to that reported in the literature.</p> <p>Conclusions</p> <p>This "real world" study found once-daily latanoprost to be effective and safe in treatment-naive ocular hypertension or open-angle glaucoma patients. Patients with baseline IOP levels of 20 to <24 mmHg as well as ≥ 24 mmHg benefitted from initial latanoprost therapy.</p> <p>Trial Registration</p> <p>Trial Registration Number: NCT00647101</p

Correlation Between the Inflammatory Marker HLA-DR and Signs and Symptoms in Moderate to Severe Dry Eye Disease

International audienc

Contribution to characterization of the Zinc retention by marl collected from the aquifer substratum

Two samples (S20 and S6) of marl are collected from aquifer substratum of the watershed of Wadi El-Ghoula in order to make a comparative study to remove Zinc from solution. The DRX analysis indicate five phases Montmorillonite, Illite, Kaolinite, Calcite and Quartz X-Fluorescence shows the predominance of silica, alumina and lime. In FTIR analysis, all bands are identified for S20, S6. The specific surface area for S20 and S6 are equal respectively to 21.6206 m2/g and 24.6445 m2/g and our materials have a meso-porous character. The retention capacity at equilibrium for S20 and S6 are equal respectively to 9.94 (mg/g) and 9.87 (mg/g). Liquid film diffusion and intraparticle diffusion models control simultaneously the process of adsorption of zinc in Marl. Non-linear treatment gives Langmuir and Temkin as best model for S20 and Freundlich for S6. Radlish-Peterson is the best model for S20 but for S6 the best model is given simultaneously by Sips and Radlish-Peterson. The values of AIC and AICc give a good opportunity to separate between used isotherms models