Clinical utility of cyclosporine (CsA) ophthalmic emulsion 0.05% for symptomatic relief in people with chronic dry eye: a review of the literature.
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ABSTRACT:
SUBMITTER: Rhee MK
PROVIDER: S-EPMC5488761 | biostudies-other | 2017
REPOSITORIES: biostudies-other
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Project description:PurposeWe compare outcomes in eyes with dry eye disease (DED) treated with TearCare (TC) or topical cyclosporine 0.05% (RESTASIS; CsA).SettingNineteen ophthalmic and optometric practices in 11 US states.DesignMulticenter, randomized, assessor-masked, controlled IRB-approved trial. Eligible subjects: ≥22 years of age, dry eye symptoms within 3-6 months, Tear Break-up Time (TBUT) ≥1 to ≤7 s, Meibomian Gland Secretion Score (MGSS) ≤12, Ocular Surface Disease Index (OSDI) of 23-79. Randomized (1:1) to TC or CsA. TC subjects treated at baseline and month 5; CsA was twice daily for 6 months.MethodsFollow-up visits were scheduled for Day 1, Week 1, Months 1, 3, and 6 with primary inference at Month 6. Primary outcomes: TBUT and OSDI; secondary outcomes: MGSS, conjunctival and corneal staining, eye dryness score (EDS), symptoms assessment in dry eye (SANDE) score, and Schirmer tear score (STS). Safety assessments included adverse events, best corrected visual acuity, intraocular pressure, and slit-lamp findings.ResultsOverall, 345 subjects, 172 TC and 173 CsA. TBUT improved at all time points in both groups (p<0.0001), with statistically greater improvement for TC versus CsA (p=0.0006). OSDI improved significantly at all time points in both groups (p<0.0001) with no significant differences between treatments. MGSS and other measures of meibomian gland function improved significantly more with TC eyes versus CsA; other secondary outcomes showed significant improvements in both groups with no difference between groups. Treatment-related adverse events were uncommon (10 total, 8 in the CsA group consistent with prior CsA studies); most (9/10) mild.ConclusionTC provides statistically superior and sustained improvement in TBUT and multiple measures of meibomian gland secretion, and non-inferior improvement in OSDI, corneal and conjunctival staining, SANDE, EDS, and STS versus CsA. TC should be a preferred treatment for DED associated with MGD.
| S-EPMC10741761 | biostudies-literature
Project description:BACKGROUND:Chronic dry eye disease often requires long-term therapy. Tear film alterations in the setting of dry eye may include reduced tear volume as well as an increase in inflammatory cytokines and osmolarity. Topical cyclosporine ophthalmic emulsion 0.05% (Restasis(®); Allergan Inc, Irvine, CA) is indicated to increase tear production in patients with dry eye and reduced tear production presumed to be due to ocular inflammation. This study was designed to evaluate the efficacy of a second trial of topical cyclosporine in patients with dry eye who were previously considered treatment failures. MATERIALS AND METHODS:This multicenter (three cornea practices) retrospective chart review evaluated clinical outcomes in patients with dry eye who received a second trial of cyclosporine after a prior treatment failure, defined as prior discontinuation of topical cyclosporine after less than 12 weeks. RESULTS:Thirty-five patients, most of whom were female (71.4%) and Caucasian (62.9%), were identified. Prior discontinuation was most commonly due to burning/stinging (60%). The median duration of second treatment was 10 months (range 1 week to 45 months). Physician education was provided in the second trial in 97.1% of cases. At initiation of the second trial of cyclosporine, 10 (28.6%) patients received courses of topical corticosteroids. Physicians reported on a questionnaire that 80% of patients achieved clinical benefit with a second trial of cyclosporine. CONCLUSION:A repeat trial with topical cyclosporine can achieve clinical success. Direct patient education via the physician and staff may be key to success. Proper patient education may overcome adherence issues, particularly with respect to the need for long-term treatment of chronic dry eye. This study has the usual limitations associated with a retrospective chart review, and future prospective studies are warranted.
| S-EPMC3514052 | biostudies-literature
Project description:ObjectiveThe aim of this study was to evaluate the effects of cyclosporine ophthalmic emulsion 0.05% on ocular surface staining and visual performance in patients with dry eye.MethodsThis was a single-center, 6-month, open-label, Phase IV study. Patients with bilateral dry eye disease and a symptom score of ≥2 on the Ocular Discomfort and 4-Symptom Questionnaire, an Ocular Surface Disease Index score of >12, at least one eye with Schirmer's score <10 mm/5 minutes, and central corneal staining graded as ≥2 on the Ora Calibra™ Corneal and Conjunctival Staining Scale were enrolled. Cyclosporine ophthalmic emulsion 0.05% (Restasis(®)) was instilled twice daily in each eye. The primary efficacy endpoints were ocular surface staining and visual function at 6 months. Secondary outcome measures included Schirmer's test, tear film breakup time, symptoms, and adverse events.ResultsA total of 40 patients with the mean age of 59.4 years (range, 40-78 years) were enrolled; 35 (87.5%) were female and 37 (92.5%) completed the study. At 6 months, inferior corneal, central corneal, total corneal, and total ocular surface fluorescein staining were significantly improved from baseline in both eyes (P<0.001). Patient responses on the Ocular Surface Disease Index showed significant improvement in blurred vision and visual function related to reading, driving at night, working with a computer or bank machine, and watching television (P≤0.041). At 6 months, 35.1% of patients achieved ≥5 mm improvement and 18.9% achieved ≥10 mm improvement in the average eye Schirmer score. Mean tear film breakup time improved by >50% in both eyes (P>0.001). Patients reported significant improvement in ocular discomfort and dry eye symptoms (P<0.001). No patients discontinued treatment because of stinging or any other ocular adverse event.ConclusionDry eye patients with difficulties with day-to-day visual function demonstrated improvement in both signs and symptoms of dry eye and reported improved visual function after 6 months of treatment with cyclosporine ophthalmic emulsion 0.05%.
| S-EPMC4874635 | biostudies-literature
Project description:PurposeThe SANSIKA study evaluated the efficacy/safety of 0.1% (1 mg/mL) cyclosporine A cationic emulsion (CsA CE) for treating dry eye disease (DED) with severe keratitis. The double-masked phase demonstrated that CsA CE was effective in reducing corneal damage and ocular surface inflammation, and was well-tolerated over 6 months. Here we report efficacy and safety findings of SANSIKA's open-label extension (OLE).MethodsIn this multicenter, double-masked, phase III study, patients with severe DED (corneal fluorescein staining [CFS] grade 4, modified Oxford scale) were randomized to once-daily CsA CE (Ikervis®) or its vehicle for 6 months, followed by 6-month open-label, once-daily CsA CE (CsA CE/CsA CE and vehicle/CsA CE groups).ResultsA total of 177 patients completed the OLE. Efficacy results reiterated the double-masked phase: CsA CE reduced CFS score and human leukocyte antigen-antigen D related expression, improved corneal clearing, and produced continuous improvements in global symptom scores (ocular surface disease index [OSDI], visual analogue scale). The CFS-OSDI response rates (≥2 CFS points, ≥30% OSDI improvement vs baseline) at 12 vs 6 months were 39.1% vs 28.6%, respectively, for CsA CE/CsA CE and 38.0% vs 23.1% for vehicle/CsA CE. Cyclosporine A CE's safety profile was similar to the initial 6 months. The most common treatment-related treatment-emergent adverse event was instillation site pain (7.8%, CsA CE/CsA CE group; 19.0%, vehicle/CsA CE group). No unexpected safety signals were observed; systemic CsA levels were undetectable/negligible in all patients except 2 previously treated with systemic CsA.ConclusionsIn this 12-month study, once-daily CsA CE was well-tolerated and showed reductions in ocular surface inflammation and improvements in signs/symptoms in DED patients with severe keratitis.
| S-EPMC6380090 | biostudies-literature
Project description:IntroductionThe PERSPECTIVE study evaluated, in routine clinical practice, the effectiveness, tolerability and safety of cyclosporine A (CsA) 0.1% cationic emulsion (CE) in controlling severe keratitis in adults with dry eye who remained insufficiently controlled despite artificial tear (AT) use.MethodsA prospective, multicenter, observational study was conducted at 44 ophthalmology clinics across Finland, Germany, Norway, Sweden and the UK. Adults treated with ATs for severe keratitis and dry eye received CsA 0.1% CE therapy (1 drop in both eyes at bedtime) and were followed up at weeks 4, 12 and 24 and at month 12. Primary endpoint was mean [standard deviation (SD)] change from baseline in corneal fluorescein staining (CFS; Oxford Grade Scale) at month 12 following CsA 0.1% CE initiation. Secondary endpoints examined ocular sign and symptom severity and adverse events (AEs).ResultsThe full analysis set included 472 adults (75.9% female). Mean (SD) age was 61.9 (15.41) years. Mean (SD) CFS score was significantly reduced from baseline [2.56 (1.10)] at month 12 [1.10 (SD 1.13); P < 0.0001]. CFS score reductions were statistically significant from week 4, with further incremental decreases reported at study visits through month 12 (P < 0.0001). Severity of eyelid and conjunctival erythema was significantly reduced from baseline at week 4 and maintained through month 12 (P < 0.001). Tear film breakup time increased significantly from baseline at all study visits through month 12 (P < 0.001). Ocular symptom severity was significantly reduced from baseline at all study visits through month 12 (P < 0.001). Overall, 101 treatment-related AEs were reported. Most were mild/moderate (83.6%) and resolved by month 12 (73.3%).ConclusionsIn routine clinical practice, CsA 0.1% CE provided statistically significant reductions in dry eye signs and symptoms. Improvements were seen at week 4 and maintained over 12 months. Treatment tolerability was good and consistent with previous CsA 0.1% CE clinical studies.Trial registrationEU PAS register number: EUPAS 22376.
| S-EPMC9114212 | biostudies-literature
Project description: Not available
| S-EPMC6743670 | biostudies-literature
Project description:BackgroundDry eye disease (DED) is a chronic ocular surface disease that affects hundreds of millions of people worldwide. Although 0.05% cyclosporine ophthalmic emulsion (CsA OE) has long been prescribed in the U.S. for the treatment of DED, it is not commercially available in China. Our study aims to compare the efficacy and safety profile of 0.05% CsA OE versus vehicle in Chinese patients with moderate to severe DED.MethodsThis was a multicenter, randomized, double-masked, 2-parallel-arm, 3-month phase III study. Patients with moderate to severe DED were randomized to receive twice-daily 0.05% CsA OE or its vehicle, along with unpreserved hypromellose eye drops 3 times per day. Patients were followed up at day 7, 28, 56, and 84, as well as 2 weeks after the medications were discontinued for safety assessment.ResultsA total of 240 patients were randomized. The overall effective rate (OER) and efficacy index were significantly better in the CsA OE than vehicle group at all follow up times (all P < .05), and the OER of CsA OE and vehicle group at month 3 was 70.6% and 27.8%, respectively (P < .001) (primary endpoint). The patients in CsA OE group displayed a significant improvement in dry eye symptoms from day 28 and ocular surface test results from day 7 (all P < .05). The ocular surface disease index scores of 0.05% CsA OE treated patients were significantly better than those treated with vehicle control at day 56 and 84 (P = .0061 and <.001, respectively). Drug related adverse events (AEs) were recorded in 6(5%) and 3(2.5%) patients in the CsA OE and vehicle groups respectively (P = .4061) with ocular pain as the most frequently reported AEs, and it was mostly mild to moderate. There were no detrimental effects on visual acuity, intraocular pressure, or vital signs.ConclusionsTwice-daily instillation of 0.05% CsA OE was effective and well tolerated for the treatment of moderate to severe DED in Chinese population during the 3 months of the study.
| S-EPMC6709181 | biostudies-literature
Project description:PurposeThe SICCANOVE study aimed to compare the efficacy and safety of 0.1% cyclosporine A cationic emulsion (CsA CE) versus vehicle in patients with moderate to severe dry eye disease (DED).MethodsIn this multicenter, double-masked, parallel-group, controlled study, patients were randomized (1:1) to receive CsA CE (Ikervis®) or vehicle for 6 months. The co-primary efficacy endpoints at month 6 were mean change from baseline in corneal fluorescein staining (CFS; modified Oxford scale) and in global ocular discomfort (visual analogue scale [VAS]).ResultsThe mean change in CFS from baseline to month 6 (CsA CE: n = 241; vehicle: n = 248) was significantly greater with CsA CE than with vehicle (-1.05 ± 0.98 and -0.82 ± 0.94, respectively; p = 0.009). Ocular discomfort improved similarly in both groups; however, the percentage of patients with ≥25% improvement in VAS was significantly higher with CsA CE (50.2%) than with vehicle (41.9%; p = 0.048). In a post hoc analysis of patients with severe ocular surface damage (CFS score 4) at baseline (CsA CE: n = 43; vehicle: n = 42), the percentage of patients with improvements of ≥2 grades in CFS score and ≥30% in Ocular Surface Disease Index score was significantly greater with CsA CE (p = 0.003). Treatment compliance and ocular tolerability were satisfactory and as expected for CsA use.ConclusionCyclosporine A CE was well-tolerated and effectively improved signs and symptoms in patients with moderate to severe DED over 6 months, especially in patients with severe disease, who are at risk of irreversible corneal damage.
| S-EPMC6380092 | biostudies-literature
Project description:Background: The purpose is to perform a cost effectiveness analysis amniotic membrane vs. topical medications in the use of treating dry eye disease. A cost effectiveness analysis comparing amniotic membrane?+?other topical medications to topical cyclosporine A?+?other topical medications was evaluated using accepted decision tree modeling software.Methods: TreeAge Pro 2019 software was used to evaluate the base case costs over a one year timeframe. Sensitivity analysis was performed on those variables which had the greatest effect on choosing one therapy versus the other based on cost. Monte Carlo simulation was run 1,000 times to determine the most effective, least costly alternative. Costs were evaluated from a societal level (direct?+?indirect). Quality of life utility scores were evaluated using known time tradeoffs from prior studies (scale 0-1; with 1 being perfect vision).Results: Over a one year timeframe, the base case demonstrated that amniotic membrane?+?topical medications was the less expensive alternative and provided for incremental utilities versus topical cyclosporine?+?other medications (Cost/utility: $18,275/0.78 vs. $20,740/0.74). If examining direct costs only, topical cyclosporine was the least expensive option over a one year timeframe: $4,112 vs. $10,300. Sensitivity analysis demonstrated that in order for topical cyclosporine to be the less expensive alternative the following variables would need to be:?<?68 days productivity lost;?<?$161 productivity lost/day;?>?79% of amniotic membrane implants would need to be re-implanted at month 4 (for whatever reason);?>?$2677 per amniotic membrane implant procedure (Medicare reimbursement rate);?>?96% positive response to topical cyclosporine A at month 4;?>?58% positive response to topical cyclosporine A at month 6 and;?<?54% probability clinical improvement with amniotic membrane. Monte Carlo simulation demonstrated that amniotic membrane was the less costly, most effective alternative 91.5% of the time.Conclusion: Based on improved outcomes using amniotic membrane, patient productivity was improved resulting in lower societal costs (less days lost from work). When considering the untoward effects of dry eye disease on societal costs, an improvement of the dry eye disease condition was accomplished most often with amniotic membrane.
| S-EPMC7709448 | biostudies-literature
Project description:PurposeTo determine if a Microemulsion Drug Ocular Penetration System (MiDROPS) formulation of cyclosporine A (CsA) delivers more drug and is more efficacious for treatment of dry eye disease (DED) than the current clinical formulation.MethodsTissue distribution of CsA was quantified by liquid chromatography with tandem mass spectrometry (LC-MS/MS). To assess tolerability, CsA-MiDROPS (0.1%) was applied to the eyes of rabbits twice per day for 14 days and assessed using ophthalmoscopic examinations. Mice were exposed to desiccating stress for 10 days and received daily topical instillation of the vehicle or test agent. Cornea staining was done to quantify corneal permeability. Histologic quantification of goblet cell (GC) density and CD4+ T-cell infiltration in the conjunctiva was performed.ResultsOphthalmic distribution studies indicate significantly increased drug concentration with CsA-MiDROPS compared with Restasis. CsA-MiDROPS is well tolerated with little toxicity in a 2-week tolerability study. In the DED model, both 0.05% and 0.1% CsA-MiDROPS conferred a significant effect and were more effective than Restasis for treating experimental DED when dosed twice per day. As compared with Restasis dosed twice per day, 0.1% CsA-MiDROPS dosed once per day demonstrated superiority.ConclusionsCsA-MiDROPS showed superior drug delivery and efficacy compared with other clinical formulations. As this product is simple to produce and needs to be only applied once daily, the clinical development of CsA-MiDROPS will help to reduce societal and patient burdens by lowering drug costs and accelerating/improving the activity of CsA.Translational relevanceMiDROPS has broad application concerning the ophthalmic development of lipophilic small molecule therapeutics.
| S-EPMC6181191 | biostudies-literature