Cyclosporine Emulsion Research Articles

Efficacy and safety of 0.05% micellar nano-particulate (MNP) cyclosporine ophthalmic emulsion in the treatment of moderate-to-severe keratoconjunctivitis sicca: a 12-week, multicenter, randomized, active-controlled trial

BackgroundKeratoconjunctivitis sicca or dry eye disease (DED) is a multifactorial disorder underpinned by a complex inflammatory cycle. Introduction of topical cyclosporine has been a significant advance in the management of DED. In recent years advancements in formulation technology have led to development of micellar nano-particulate (MNP) cyclosporine formulations that promise better penetration into ocular target tissues and potential for reduced ocular surface irritation.MethodsWe compared two dosing regimes of a proprietary MNP cyclosporine emulsion with the widely marketed topical cyclosporine formulation Restasis™ in a multicenter parallel-group randomised trial in patients with DED. Patients were randomised to one of 3 treatment groups with 90 patients eligible for the per protocol analysis: 30 in the higher dose test arm A; 32 in the lower dose test arm B; and 28 in the Restasis™ control arm C. All scored efficacy endpoints were tested for significance by comparing the mean change in scores from baseline in the test groups with that in the control group at 12 weeks, using the Student’s t test. Wilcoxon’s rank sum test was used to test individual symptom scores and clinician’s global evaluation of treatment grades.ResultsCorneal fluorescein staining score, the primary efficacy endpoint, decreased by 6.8 ± 4.0, 5.7 ± 3.9, and 4.6 ± 3.6 points in the 3 groups respectively, indicating superior efficacy in test arm A in comparison to control arm C (p = 0.0026). Schirmer’s tear test, conjunctival lissamine staining score, ocular surface disease index, and individual dry eye symptom scores also favoured higher dose MNP cyclosporine over Restasis™. The study failed to differentiate the treatment arms in terms of clinician’s global evaluation of treatment, use of tear substitutes, best corrected visual acuity or safety and toleration.ConclusionThe results indicate that the dose of 1 drop of a 0.05% w/v ophthalmic emulsion of MNP cyclosporine administered topically twice daily yields better outcomes at 12 weeks than the lower dose tested in the study, and is more efficacious than an equivalent dose of Restasis™, the active control used in the study.Trial registrationThis trial was registered in the Clinical Trials Registry of India on 29/03/2019, and was assigned registration number CTRI/2019/03/018319.

Коррекция состояния глазной поверхности у пациентов с синдромом «сухого глаза» на этапе подготовки к кераторефракционной операции

Aim: to analyze the prevalence of dry eye disease (DED) among adult patients with ametropias and the efficacy of its complex treatment when preparing the ocular surface for corneal refractive surgery.Patients and Methods: 1,762 patients with ametropias were examined. In addition to all of the standard eye checks, vital conjunctival and corneal staining, Scheimpflug corneal topography, and anterior segment OCT as well as patient survey were performed. Standard preservative-free tear substitutes with or without a short course of steroids, lubricants, 0.05% anionic cyclosporine emulsion (twice daily), and long-term punctal plugs were prescribed for DED.Results: mild DED was diagnosed in 1,021 patients (57.9%). Of them, corneal lesion was reported in 362 patients (35.4%) and asymptomatic DED in 250 patients (25.5%). Corneal topographic indices of one or both eyes were abnormal (as a result of DED) in 147 patients (14.4%). Significant (p≤0.05) increase in corneal epithelial thickness of one or both eyes was reported in 564 patients (55.2%). Ocular surface treatment in DED patients allowed for uncomplicated corneal refractive procedures while target refraction was achieved in 1,006 patients (98.5%). Conclusion: a complex diagnostic approach to DED involving specific tests, patient survey, corneal topography, and OCT provides the diagnosis of both manifest and latent DED. Combined treatment for conjunctival and corneal xerosis that includes tear substitutes, topical cyclosporine, and punctal plugs, improves ocular surface health in DED thus enlarging the list of indications and the safety of laser eye surgery in these patients.Keywords: dry eye disease, laser eye surgery, corneal refractive procedures, anionic cyclosporine emulsion, punctal plugs, corneal epithelium.For citation: Klokova O.A., Damashauskas R.O., Geidenrich M.S. Ocular surface treatment in dry eye patients before corneal refractive surgery. Russian Journal of Clinical Ophthalmology. 2020;20(4):180–186. DOI: 10.32364/2311-7729-2020-20-4-180-186.

Comparison of United States and International Ophthalmic Drug Pricing

To compare United States and international drug pricing for commonly prescribed intravitreal and topical ophthalmic medications. Cross-sectional observational study. For 25 commonly used ophthalmic medications (3 intravitreal, 22 topical), we obtained 2017 third quarter United States average wholesale price (AWP), drug acquisition cost, or consumer pricing through United States government health insurance plans (Veterans Affairs [VA], Medicaid, Medicare Part B, and Medicare Part D) and commercial drug plans (CVS Caremark and Navitus Health Solutions), online pricing without insurance through a large United States warehouse retailer (Costco), and international drug pricing through government-sponsored health plans in Italy, Spain, Turkey, Canada, and Japan. Drug acquisition costs and consumer pricing of ophthalmic drugs through various payment systems. All prices were converted to United States dollars. For intravitreal medications in the United States, aflibercept and ranibizumab were priced similarly to each other and were more expensive than dexamethasone implants. Pricing of aflibercept and ranibizumab through government health insurance plans in Italy, Spain, Turkey, Canada, and Japan were less expensive by as much as 84.3% compared with the United States. For topical medications in the United States, pricing varied significantly both across different classes of medications and also between nonbranded and branded medications. Drug acquisition costs through the VA and Medicaid were inexpensive on average, but pricing through a hospital-employee drug insurance plan offered the smallest range (between $2.35 and $60.00). In all 5 non-United States countries studied, each topical medication with the exceptions of cyclosporine emulsion and difluprednate was less than $100, and 94.4% of topical medications in these countries had a nonbranded or branded option that was less than $50. In the United States, for topical more than intravitreal medications, significant price variation exists across both different drug pricing systems and different medications. Price differentials between nonbranded and branded medications can be significant. Internationally, topical medications exhibited a more limited and lower price range compared with drug pricing in the United States.

Manganese(III) tetrakis(1-methyl-4-pyridyl) porphyrin, a superoxide dismutase mimetic, reduces disease severity in in vitro and in vivo models for dry-eye disease

PurposeTo determine the efficacy of the superoxide dismutase mimetic, manganese(III) tetrakis(1-methyl-4-pyridyl) porphyrin (Mn-TM-2-PyP), in vitro in human corneal epithelial (HCE-T) cells and in vivo in a preclinical mouse model for dry-eye disease (DED). MethodsIn vitro, HCE-T cultures were exposed either to tert-butylhydroperoxide (tBHP) to generate oxidative stress or to hyperosmolar conditions modeling cellular stress during DED. Cells were pre-treated with Mn-TM-2-PyP or vehicle. Mn-TM-2-PyP permeability across stratified HCE-T cells was assayed. In vivo, Mn-TM-2-PyP (0.1% w/v in saline) was delivered topically as eye drops in a desiccating stress/scopolamine model for DED. Preclinical efficacy was compared to untreated, vehicle- and ophthalmic cyclosporine emulsion-treated mice. ResultsMn-TM-2-PyP protected HCE-T cells in a dose-dependent manner against tBHP-induced oxidative stress as determined by calculating the IC50 for tBHP in the resazurin, MTT and lactate dehydrogenase release cell viability assays. Mn-TM-2-PyP did not protect HCE-T cells from hyperosmolar insult. Its permeability coefficient across a barrier of HCE-T cells was 1.1 ± 0.05 × 10−6 cm/s and the mass balance was 62 ± 0.6%. In vivo, topical dosing with Mn-TM-2-PyP resulted in a statistically significant reduction of corneal fluorescein staining, similar to ophthalmic cyclosporine emulsion. Furthermore, Mn-TM-2-PyP significantly reduced leukocyte infiltration into lacrimal glands and prevented degeneration of parenchymal tissue. No protective effect against loss of conjunctival goblet cells was observed. Notably, Mn-TM-2-PyP did not produce ocular toxicity when administered topically. DiscussionOur data suggest that Mn-TM-2-PyP, a prototypic synthetic metalloporphyrin compound with potent catalytic antioxidant activity, can improve signs of DED in vivo by reducing oxidative stress in corneal epithelial cells.

Asymmetric flow field flow fractionation for the characterization of globule size distribution in complex formulations: A cyclosporine ophthalmic emulsion case

Commonly used characterization techniques such as cryogenic-transmission electron microscopy (cryo-TEM) and batch-mode dynamic light scattering (DLS) are either time consuming or unable to offer high resolution to discern the poly-dispersity of complex drug products like cyclosporine ophthalmic emulsions. Here, a size-based separation and characterization method for globule size distribution using an asymmetric flow field flow fractionation (AF4) is reported for comparative assessment of cyclosporine ophthalmic emulsion drug products (model formulation) with a wide size span and poly-dispersity. Cyclosporine emulsion formulations that are qualitatively (Q1) and quantitatively (Q2) the same as Restasis® were prepared in house with varying manufacturing processes and analyzed using the optimized AF4 method. Based on our results, the commercially available cyclosporine ophthalmic emulsion has a globule size span from 30 nm to a few hundred nanometers with majority smaller than 100 nm. The results with in-house formulations demonstrated the sensitivity of AF4 in determining the differences in the globule size distribution caused by the changes to the manufacturing process. It is concluded that the optimized AF4 is a potential analytical technique for comprehensive understanding of the microstructure and assessment of complex emulsion drug products with high poly-dispersity.

Effects of combined oral doxycycline and topical cyclosporine treatment on ocular signs, symptoms, and tear film parameters in rosacea patients.

This study reports the effects of combined use of oral doxycycline and topical cyclosporine on ocular signs, symptoms, and tear film parameters in rosacea patients. Fifty-four right eyes of 54 patients were included in this study. All patients underwent full ophthalmologic examination-including best corrected visual acuity measurement, slit-lamp anterior segment and fundus examination, tear film break-up time, and Schirmer test-before treatment and six months post-treatment. Patients were divided into two treatment groups. The first group was treated with oral doxycycline 100 mg twice daily for the first month and once daily for the following two months. The second group received topical 0.05% cyclosporine emulsion drops twice daily for six months in addition to the oral doxycycline treatment regimen. All patients received preservati ve-free artificial tear drops, warm compress, eyelash cleaning, and topical corticosteroid drops three times daily for one month. A significant improvement in ocular signs and symptoms was recorded for all patients in groups 1 and 2 after treatment. There was not a significant difference in terms of itching, burning, meibomian gland inspissation, corneal neovascularization, and conjunctival hyperemia score changes between groups 1 and 2. The increases in Schirmer test and break-up time scores were significantly higher in group 2 than in group 1. Our results support the finding that topical cyclosporine in addition to the standard regimen improves tear function, as shown by Schirmer test and break-up time scores, in ocular rosacea patients.

Allergan seeks tribe’s help in patent case

In a novel arrangement, the pharmaceutical maker Allergan has enlisted the Saint Regis Mohawk Tribe to help protect the dry-eye drug Restasis against patent challenges by would-be competitors. The New York tribe, which could be immune from federal patent challenges, has taken ownership of six patents covering the cyclosporine emulsion eye treatment. Allergan retains exclusive licenses to the patents until they end in 2024. Allergan will make a one-time payment of $14 million plus $15 million in annual royalty payments to the American Indian tribe. If it succeeds, Allergan’s gamble will protect a $1.5 billion revenue stream representing about 10% of the firm’s annual sales. The deal could also be a harbinger of similar agreements by other branded pharmaceutical makers who had previously relied on “pay for delay” drug deals. Those deals pay competitors to delay the introduction of generic versions of drugs with disputed patents. Because the tribe is

Cyclosporine ophthalmic emulsions for the treatment of dry eye: a review of the clinical evidence

Dry eye has gained recognition as a public health problem given its high prevalence, morbidity and cost implications. Although dry eye is common and affects patients' quality of life, only one medication, cyclosporine 0.05% emulsion, has been approved by the US FDA for its treatment. In this review, we summarize the basic science and clinical data regarding the use of cyclosporine in the treatment of dry eye. Randomized controlled trials showed that cyclosporine emulsion outperformed vehicles in the majority of trials, consistently decreasing corneal staining and increasing Schirmer scores. Symptom improvement was more variable, however, with ocular dryness shown to be the most consistently improved symptom over vehicle.

Quality by Design Approach for Understanding the Critical Quality Attributes of Cyclosporine Ophthalmic Emulsion

Restasis is an ophthalmic cyclosporine emulsion used for the treatment of dry eye syndrome. There are no generic products for this product, probably because of the limitations on establishing in vivo bioequivalence methods and lack of alternative in vitro bioequivalence testing methods. The present investigation was carried out to understand and identify the appropriate in vitro methods that can discriminate the effect of formulation and process variables on critical quality attributes (CQA) of cyclosporine microemulsion formulations having the same qualitative (Q1) and quantitative (Q2) composition as that of Restasis. Quality by design (QbD) approach was used to understand the effect of formulation and process variables on critical quality attributes (CQA) of cyclosporine microemulsion. The formulation variables chosen were mixing order method, phase volume ratio, and pH adjustment method, while the process variables were temperature of primary and raw emulsion formation, microfluidizer pressure, and number of pressure cycles. The responses selected were particle size, turbidity, zeta potential, viscosity, osmolality, surface tension, contact angle, pH, and drug diffusion. The selected independent variables showed statistically significant (p < 0.05) effect on droplet size, zeta potential, viscosity, turbidity, and osmolality. However, the surface tension, contact angle, pH, and drug diffusion were not significantly affected by independent variables. In summary, in vitro methods can detect formulation and manufacturing changes and would thus be important for quality control or sameness of cyclosporine ophthalmic products.

Dry eye medication use and expenditures: data from the medical expenditure panel survey 2001 to 2006.

To study dry eye medication use and expenditures from 2001 to 2006 using a nationally representative sample of US adults. This study retrospectively analyzed dry eye medication use and expenditures of participants of the 2001 to 2006 Medical Expenditure Panel Survey, a nationally representative subsample of the National Health Interview Survey. After adjusting for survey design and for inflation using the 2009 inflation index, data from 147 unique participants aged 18 years or older using the prescription medications Restasis and Blephamide were analyzed. The main outcome measures were dry eye medication use and expenditures from 2001 to 2006. Dry eye medication use and expenditures increased between the years 2001 and 2006, with the mean expenditure per patient per year being $55 in 2001 to 2002 (n=29), $137 in 2003 to 2004 (n=32), and $299 in 2005 to 2006 (n=86). This finding was strongly driven by the introduction of topical cyclosporine emulsion 0.05% (Restasis; Allergan, Irvine, CA). In analysis pooled over all survey years, demographic factors associated with dry eye medication expenditures included gender (female: $244 vs. male: $122, P<0.0001), ethnicity (non-Hispanic: $228 vs. Hispanic: $106, P<0.0001), and education (greater than high school: $250 vs. less than high school: $100, P<0.0001). We found a pattern of increasing dry eye medication use and expenditures from 2001 to 2006. Predictors of higher dry eye medication expenditures included female gender, non-Hispanic ethnicity, and greater than a high school education.

Study of Utilization Pattern and Compliance with Topical 0.05% Cyclosporine Emulsion in Korean Dry Eye Patients

We investigate the utilization pattern and self-reported compliance with topical 0.05% cyclosporine emulsion in patients with dry eye. In 136 patients with dry eye using 0.05% cyclosporine emulsion, the level of compliance, the symptoms before and after use, the length of time taken before symptoms improved and adverse effects when use were evaluated. Eighty two percent of 136 patients used at least 1 box of 0.05% cyclosporine emulsion. One hundred and sixty patients were divided into three groups. Patients whose compliance level was higher than 50% were assigned to Group I; those with a compliance level between 25 to 50% belonged to Group II and those whose compliance was less than 25% were in Group III. The symptom score of all subjects decreased from 2.96 before cyclosporine use to 1.72 (p=0.011) after cyclosporine use. Patients in Group I experienced an improvement in their symptoms earlier (4.3 months) compared to those in Group II (6.5 months, p=0.030) and Group III (9.6 months, p=0.010). Adverse effects were experienced in 60% of patients, the most common being a sensation of pain (20%) and burning (20%). Patients who had the highest level of compliance noticed an improvement in their symptoms earliest. Patients need to be given detailed explanations about the adverse events of 0.05% cyclosporine emulsion.

Factors Affecting Compliance With 0.05% Cyclosporine Emulsion in Patients With Dry Eye Syndrome

Purpose: To evaluate the factors affecting compliance with the use of 0.05% cyclosporine emulsion in patients with dry eye syndrome. Methods: A total of 148 patients using 0.05% cyclosporine emulsion for dry eye were divided into two groups (compliant vs. non-compliant). The compliant group included the patients who used 0.05% cyclosporine emulsion more than 50% of frequency as they had been prescribed. We analyzed factors affecting compliance, including age, gender, severity of symptoms, side effects, use of topical steroid, socioeconomic status, associated systemic disease, number of eyedrops, visit interval, and detailed instruction about 0.05% cyclosporine emulsion. Results: The compliant group included 124 patients (83.8%), and the non-compliant group included 24 patients (16.2%). Multivariate analysis showed that the factors associated with low compliance were severe symptoms, longer visit interval, side effects, lower socioeconomic status, and poor detailed instruction (P

Value-Based Medicine, Comparative Effectiveness, and Cost-effectiveness Analysis of Topical Cyclosporine for the Treatment of Dry Eye Syndrome

To assess the comparative effectiveness and cost-effectiveness (cost-utility) of a 0.05% emulsion of topical cyclosporine (Restasis; Allergan Inc, Irvine, California) for the treatment of moderate to severe dry eye syndrome that is unresponsive to conventional therapy. Data from 2 multicenter, randomized, clinical trials and Food and Drug Administration files for topical cyclosporine, 0.05%, emulsion were used in Center for Value-Based Medicine analyses. Analyses included value-based medicine as a comparative effectiveness analysis and average cost-utility analysis using societal and third-party insurer cost perspectives. Outcome measures of comparative effectiveness were quality-adjusted life-year (QALY) gain and percentage of improvement in quality of life, and for cost-effectiveness were cost-utility ratio (CUR) using dollars per QALY. Topical cyclosporine, 0.05%, confers a value gain (comparative effectiveness) of 0.0319 QALY per year compared with topical lubricant therapy, a 4.3% improvement in quality of life for the average patient with moderate to severe dry eye syndrome that is unresponsive to conventional lubricant therapy. The societal perspective incremental CUR for cyclosporine over vehicle therapy is $34,953 per QALY and the societal perspective average CUR is $11,199 per QALY. The third-party-insurer incremental CUR is $37,179 per QALY, while the third-party-insurer perspective average CUR is $34,343 per QALY. Topical cyclosporine emulsion, 0.05%, confers considerable patient value and is a cost-effective therapy for moderate to severe dry eye syndrome that is unresponsive to conventional therapy.

Effects of Sequential Artificial Tear and Cyclosporine Emulsion Therapy on Conjunctival Goblet Cell Density and Transforming Growth Factor-β2 Production

To evaluate the effects of sequential treatment with artificial tears and cyclosporine emulsion on conjunctival goblet cell density and production of transforming growth factor (TGF)-beta2 in patients with dry eye disease. Patients with dry eye disease (N = 6) defined by an Ocular Surface Disease Index symptom score >or=25, Schirmer test 1 <10 mm, and corneal fluorescein and conjunctival lissamine green staining scores >or=3 were treated with artificial tears (Refresh Plus; Allergan, Irvine, CA) 4 times a day for 4 weeks, followed by 0.05% cyclosporine emulsion (Restasis; Allergan) twice a day for 12 weeks. Impression cytology was performed on the bulbar conjunctiva of both eyes at baseline, after artificial tear therapy, and after 6 and 12 weeks of cyclosporine therapy. Goblet cells were counted in 5 representative microscopic fields per membrane in those taken from the temporal and inferior bulbar conjunctiva of the worse eye, and membranes taken from the fellow eye were immunostained for TGF-beta2. There were no differences in mean goblet cell density between baseline and 4 weeks of artificial tears in the temporal and inferior bulbar specimens. After 6 weeks of cyclosporine emulsion, goblet cell density was significantly greater than baseline and artificial tears in the inferior bulbar conjunctiva (P < 0.01). After 12 weeks of cyclosporine emulsion, goblet cell density was significantly greater than baseline and artificial tears in both temporal and inferior bulbar sites (P < 0.01). The number of TGF-beta2-positive goblet cells was also noted to increase after 6 and 12 weeks of cyclosporine therapy (P < 0.001). Cyclosporine emulsion, but not artificial tears, increases goblet cell density and production of the immunoregulatory factor TGF-beta2 in the bulbar conjunctiva in patients with dry eye.

Self-reported compliance with topical cyclosporine emulsion 0.05% and onset of the effects of increased tear production as assessed through patient surveys

Background: Keratoconjunctivitis sicca is a common eye condition characterized by itchiness, redness, and dryness due to a lack of tear production or abnormalities in the tear film. Cyclosporine works to increase the production of natural tears, which contain nutrients and proteins not found in artificial tears. Objective: The purpose of this report was to assess the association between self-reported compliance with topical cyclosporine 0.05% emulsion and the onset of effects of increased tear production in patients with dry eye. Methods: Practicing physicians were asked to identify patients for whom treatment with cyclosporine was appropriate and who were willing to participate in the study. Patients who agreed to participate were given medication samples and study materials. The participants were asked to respond to automated survey questions before they used cyclosporine and 30 and 60 days after initiating cyclosporine. Participants were asked how frequently they used the medication, how rapidly their symptoms were relieved, and whether they intended to continue using cyclosporine. Results: Of the 5367 patients initially enrolled in the study, 3145 (59%) patients completed the baseline and 60-day follow-up surveys. The mean age of the participants was 60 years; 2677 (85%) of them were women, and 468 (15%) were men. Compliance with cyclosporine therapy was reported as follows: 2477 (79%) participants said they used cyclosporine twice daily as prescribed by their physicians, 468 (15%) reported missing some doses of cyclosporine, and 189 (6%) reported missing -50% or ≥50% of the doses. The effects of increased tear production were reported to occur significantly sooner in participants who complied with cyclosporine treatment as prescribed than in those who did not comply with treatment ( P < 0.01). Among those who complied with treatment, 1822 (73 %) participants reported experiencing the effects of increased tear production in <5 weeks compared with 468 (70%) participants who did not comply with treatment. Overall, the mean rate of satisfaction with cyclosporine was 7.5 on a scale from 0 (not at all satisfied) to 10 (very satisfied). Participants who reported using cyclosporine twice daily as prescribed gave satisfaction with cyclosporine a mean rating of 7.7 compared with 7.3 given by those who missed some doses and 5.3 from those who missed ≈50% or ≥50% of the doses ( P < 0.01). An intention to continue using cyclosporine was reported by 2611 (83%) participants. Conclusion: The results of this study in participants using cyclosporine for dry eye in an actual-practice setting suggest an association between patient-reported compliance with medication and more rapid onset of the effects of increased tear production.

Pharmacokinetics of enteric‐coated mycophenolate sodium in stable pediatric renal transplant recipients

This study aims to characterize the pharmacokinetics of mycophenolic acid (MPA) and its glucuronide metabolite (mycophenolic acid 7-O-glucuronide, MPAG) following single oral administration of enteric-coated mycophenolate sodium (EC-MPS, myfortic) at an approximate dose level of 450 mg/m(2) body surface area (BSA) to 25 stable renal transplant recipients (aged 5-16 yr), and to evaluate the safety and tolerability of EC-MPS in this pediatric population. Patients had been maintained on a cyclosporine emulsion, Neoral-based immunosuppressive regimen for at least 3 months and had received their first or second renal transplant more than 6 months prior to entry into the study. After a brief lag phase (t(lag) 0.75 h), MPA was rapidly absorbed (t(max) 2.5 h) and rapidly converted to MPAG (t(max) 3.25 h), with relatively high plasma concentrations of MPAG (C(max) 67.7 microg/mL) compared with MPA (C(max) 36.3 microg/mL). The elimination half-life for MPAG was slightly longer than for MPA (approximately 13 h vs. 8.5 h), and the apparent oral clearance of MPA was approximately 0.2 L/h/kg. The pharmacokinetics of MPA or MPAG were not affected by age, body weight or BSA, within the study population. The pharmacokinetic results for pediatric patients are comparable with those obtained previously in adults, although exposure based on AUC(0-infinity) was approximately 23% higher, and this finding may be a result of dosing on the basis of BSA, rather than body weight. The recommended dose of EC-MPS in pediatric patients is 400-450 mg/m(2) twice daily or, alternatively, approximately 10-14 mg/kg twice daily when used in combination with cyclosporine microemulsion.

Cyclosporine distribution into the conjunctiva, cornea, lacrimal gland, and systemic blood following topical dosing of cyclosporine to rabbit, dog, and human eyes.

Cyclosporine is an immune modulator that inhibits T-lymphocyte-mediated immunoreactivity. Allergan is currently evaluating the clinical efficacy of 0.05%–0.4% cyclosporine emulsion for the treatment of immuno-inflammatory eye diseases, such as keratoconjunctivitis sicca, or dry eye syndrome. Topical ocular application of cyclosporine, formulated as 2% cyclosporine in olive oil, 0.2% cyclosporine in corn oil ointment (Schering-Plough), or 0.2% cyclosporine emulsion (Allergan), was found to reduce ocular surface inflammation and improve lacrimal gland secretion in dogs with KCS.1–3 KeywordsLacrimal GlandCyclosporine ConcentrationKeratoconjunctivitis SiccaBlood Trough ConcentrationOcular Surface InflammationThese keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.