Ophthalmic Emulsion Research Articles

Application of Ultra-Centrifugation and Bench-Top 19F NMR for Measuring Drug Phase Partitioning for the Ophthalmic Oil-in-Water Emulsion Products.

Generic drug products are expected to have the same active pharmaceutical ingredient (API) (Q1) with the same content (Q2) and microstructure arrangement (Q3) as the innovator product. In complex oil-in-water emulsion drugs, the hydrophobic API is mainly formulated in oil droplets stabilized by surfactant and micelles composed of extra surfactant molecules. The API phase partition in oil and water (mainly micelle) is a critical quality attribute (CQA) of emulsion product in demonstrating physicochemical equivalence using difluprednate (DFPN) emulsion product Durezol® as a model, we developed a novel low-field benchtop NMR method to demonstrate its applicability in measuring DFPN phase partition for ophthalmic oil-in-water emulsion products. Low-field 19F spectra were collected for DFPN in formulation, in water phase and oil phase after separation from ultra-centrifugation. The NMR data showed the mass balance of DFPN before and after phase separation. The average water phase content of different Durezol® lots was 32 ± 3% with 1% variation from method reproducibility test. The partition results were 52 ± 2% for the in-house control products prepared in Q1/Q2 equivalence to Durezol® but by a different process. The significant difference in DFPN-phase partition between Durezol® and the in-house formulation demonstrated manufacture difference readily changed the API partition. The newly developed ultra-centrifugation and 19F NMR by benchtop instrument is a simple, robust, and sensitive analytical method for ophthalmic emulsion drug product development and control.

Patient and physician perspectives on the use of cyclosporine ophthalmic emulsion 0.05% for the management of chronic dry eye.

Dry eye disease (DED) is a multifactorial disease of the ocular surface and is one of the most common reasons for patients to visit an eye care provider. Cyclosporine A (CsA) is an immune modulating drug that was approved in the US for topical use in the treatment of DED in 2003, which led to a paradigm change in our understanding and treatment of DED, turning attention to control of inflammation for treatment. This review summarizes the literature to date regarding the impact of CsA on the treatment of DED. A special focus is given to the patient and physician perspectives of CsA, including dry eye symptom improvement, medication side effects, and overall patient satisfaction. Studies evaluating CsA in DED have considerable heterogeneity making generalized conclusions about the effect of CsA difficult. However, most studies have demonstrated improvement in at least some symptoms of dry eye in CsA-treated patients. Side effects, most commonly ocular burning on administration of CsA, are common. The literature is sparse regarding long-term follow-up of patients treated with CsA, optimal duration of treatment, and identifying which patients may receive the most benefit from CsA.

Effectiveness of a Preservative-Free Eye Drop, Cyclosporine 0.05% Emulsion, and Omega-3 Supplementation as a Fixed Combination in Dry Eye Disease – a Pilot Study

Purpose: We aim to evaluate the impact of combining a preservative-free drop, cyclosporine 0.05% emulsion, and omega-3 oral supplementation on the signs and symptoms of dry eye in a typical ophthalmic practice.Design: A retrospective case series conducted on patients with dry eye disease.Methods: Patients diagnosed with dry eye in a typical ophthalmology practice were initiated on a fixed combination regimen which included a preservative-free eye drop (I-DROP ® PUR GEL, I-MED pharma), cyclosporine 0.05% ophthalmic emulsion, and oral omega-3 supplement(Dry Eye Omega Benefits®, PRN)for 3 monthsconsecutively. The primary outcome measured was a symptom score using the Canadian Dry Eye Assessment Tool (CDEA). Secondary outcome measure was Non-invasive Keratograph Break-up Time (NIKBUT). Primary and secondary outcomes measured at baseline and 3 months following intervention were compared.Results: Thirty-six patients were included with a female male ratio of 2.6:1 and average age of 64.Patient symptoms improved significantly following the intervention as demonstrated by a lower CDEA score during the second visit compared to the first visit (16.11 vs. 19.50, respectively) (p< .05). NIKBUT scores were also significantly improved as demonstrated by a higher score during the second visit compared to the first in both the right (13.18 vs. 11.44) (p< .05) and left (14.62 vs. 12.78) (p< .01) eyes, respectively.Conclusion: A fixed combination of preservative-free eye drops, cyclosporine 0.05% and omega-3 supplementation may be an effective first line treatment option in alleviating symptoms and improving signs of patients suffering from dry eye.

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.

Semifluorinated alkane based systems for enhanced corneal penetration of poorly soluble drugs

Semifluorinated alkanes (SFAs) are amphiphilic liquids that can dissolve hydrophobic drugs to form clear solutions. This study evaluated the potential of two SFAs to act as vehicle for topical ocular drug delivery. After confirming ocular safety, an ex vivo corneal penetration model was developed to determine drug distribution and corneal bioavailability. Hydrophobic dye distribution in the different corneal layers was visualised under a confocal microscope. Corneal bioavailability of cyclosporine A (CsA) dissolved in perfluorobutylpentane (F4H5) or perfluorohexyloctane (F6H8) was compared to commercially available CsA ophthalmic emulsions, Restasis® and Ikervis®. Precorneal residence of the four test vehicles containing the hydrophobic dye was also compared using an ex vivo corneal tissue model. Preferential accumulation of the hydrophobic dye in the corneal epithelium was observed with higher amounts detectable when delivered via the SFAs compared to Restasis or Ikervis. A significant improvement in corneal CsA penetration was observed after application of a single dose of 0.05% CsA in F4H5 and F6H8 when compared to Restasis with the area under curve over 4 h (AUC(0–4h)) being at least 8-fold greater for both SFAs (p < .0001). Moreover, the AUC(0–4h) of 0.1% CsA in F4H5 was almost 5-fold greater than Ikervis (p < .0001). Finally, the precorneal residence time of both SFA solutions was significantly longer than that of the commercial emulsions with the AUC(0–60min) being 2- to 11-fold greater. This study demonstrated that SFAs can significantly improve the local bioavailability of hydrophobic drugs by increasing corneal penetration as well as prolonging precorneal residence. They therefore offer a promising new platform for topical drug delivery to the eye.

Comparison of difluprednate 0.05% versus prednisolone acetate 1% eye drops following uneventful cataract surgery.

Purpose: To compare intraocular pressure (IOP) readings and postoperative inflammation between 2 corticosteroid drops: difluprednate (DP) ophthalmic emulsion 0.05% and prednisolone acetate (PA) 1.0% after uneventful cataract surgery. Patients and methods: randomized, controlled study of 343 patients undergoing uneventful cataract surgery in one eye. Randomization was used to allocate patients to either group: receive prednisolone acetate 1% five times daily or difluprednate 0.05% four times daily for 14 days post-surgery, then tapered over 14 days. Intraocular pressure was measured preoperative, 1st day, 1st week, and one month postoperative. Also, ocular inflammation was monitored in the form of anterior chamber (AC) flare, AC cells, corneal edema and conjunctival congestion. Results: No statistically significant difference in IOP between both groups was detected on postoperative first day and after one month. Yet there was statistically significant difference after first and second week of treatment with higher levels in the difluprednate group. As for ocular inflammation all signs resolved by the end of a month postoperative with no significant difference between both groups. Conclusion: There was significant increased intraocular pressure in the difluprednate group than in the prednisolone acetate group which might be attributed to the increased dosing and duration of use of difluprednate.

Comparasion of efficacy and safety of Difluprednate 0.05% and Nepafenac 0.1% in reducing macular thickness and volume after cataract surgery

Objective- To evaluate and compare efficacy and safety of topical Difluprednate ophthalmic emulsion 0.05% with Nepafenac ophthalmic suspension 0.1% in patients of uneventful cataract surgery with respect to postoperative macular thickness and volume.&#x0D; Design- A prospective, single centric, tertiary care centre based, comparative, interventional study from August 2013 to July 2014&#x0D; Subjects- Total 206 ( Group N=106, Group D=100) patients were followed up who completed their 12 weeks follow up&#x0D; Methodology- Surgery was performed by phacoemulsification technique by clear corneal incision with foldable PCIOL implantation by a single surgeon having 10 years of surgical experience. Post operative patients were divided into 2 groups. Group N were given topical treatment with Nepafenac ophthalmic suspension 0.1% TID starting 24 hours before surgery and continued post-op 4 weeks. Group D were given Difluprednate ophthalmic emulsion 0.05% QID post surgery for 2 weeks followed by BID for 2 weeks. &#x0D; Main outcome measures: Postoperative assessment of patients were done on 1st day and on 1st, 8th and12th weeks after the surgery for best corrected visual acuity (BCVA) by logMAR, intraocular pressure by Applanation tonometry and macular thickness and volume by SD-OCT. Statistical test used was sample Unpaired and paired ‘t’ test and statistical analysis was done with SPSS 20.0 ( IBM, USA).&#x0D; Results- There was increase in the measured mean central subfield thickness( CST) at 8 and 12 weeks as compared to 1 week , in both the study groups (P&lt;0.05). On comparing the volume (in mm3) and average thickness (in µm) at 1 week, it was observed that thickness of group N (266.82±25.06 µm) was statistically higher than that of group D (253.14±22.21µm) (P= 0.03). The comparison of best corrected visual acuity (LogMAR) and the intraocular pressure recordings showed no difference between the patients of two studied groups recorded at 1 week and 8 weeks and 12weeks.&#x0D; Conclusion- Both Nepafenac ophthalmic suspension 0.1% and Difluprednate ophthalmic emulsion 0.05% are equally effective in controlling macular thickness change after uneventful cataract surgery.

Ciclosporin Ophthalmic Emulsion 0.1%: A Review in Severe Dry Eye Disease.

Ciclosporin ophthalmic emulsion 0.1% (hereafter referred to as ciclosporin 0.1%) [Ikervis®] is an unpreserved cationic emulsion formulation containing an 0.1% concentration of ciclosporin. It has been approved in various countries worldwide, including those of the EU, for the treatment of severe keratitis in adults with dry eye disease, which has not improved despite treatment with tear substitutes. In a multinational, phase III study in this patient population, once-daily ciclosporin 0.1% was associated with statistically significant and clinically relevant improvements in the signs (corneal surface damage and ocular surface inflammation) of dry eye disease relative to vehicle during the first 6-month treatment period. These beneficial effects were maintained or improved in a subsequent 6-month period, with data suggesting sustainability following treatment discontinuation in a 24-month, phase III extension study. Ciclosporin 0.1% was well tolerated in these studies, with instillation-site pain (which was mostly mild in severity) being the most frequently reported ocular treatment-related adverse event. There were no findings to suggest the systemic absorption of ciclosporin. Thus, once-daily ciclosporin 0.1% is an effective and well tolerated option for the treatment of severe keratitis in adults with dry eye disease.

Primary Sjogren Syndrome: Clinical Features and Management

Primary Sjögren syndrome (SS) is a chronic inflammatory disease affecting the lacrimal and salivary glands, resulting in dry eyes and dry mouth. It may also lead to systemic manifestations, including fatigue, arthritis, lung involvement, kidney disease, neuropathy, and vasculitis, and predisposes to B cell lymphoma. The diagnosis of primary SS is based on a composite of clinical, serologic, and pathologic features, namely, objective evidence of dry eyes and dry mouth and either a positive test for anti-SSA (Ro) antibodies or a positive labial salivary gland biopsy. Primary SS may be confused with other conditions affecting the lacrimal and salivary glands, such as chronic hepatitis C virus infection, sarcoidosis, and a new entity, IgG4-related disease. The management of patients with primary SS is largely symptomatic and consists of tear supplementation, regular dental hygiene, and liberal use of moisturizers. Cyclosporine 0.05% ophthalmic emulsion and lifitegrast 5% ophthalmic solution are approved agents for the treatment of dry eyes. Two oral secretagogues, pilocarpine and cevimeline, have been shown in trials to significantly reduce the symptoms of dry eyes and dry mouth. Although hydroxychloroquine may reduce fatigue and joint pain, the results of a randomized controlled trial failed to confirm its efficacy in this clinical setting. More serious organ system involvement may be managed with corticosteroids and other immunomodulatory drugs. Although no disease-modifying drugs are currently approved for the treatment of primary SS, a robust pipeline of promising therapies for this disease is currently in development. This review contains 3 figures, 5 tables, and 69 references. Key words: anti-Ro/SSA antibodies, B cell lymphoma, classification criteria, EULAR Sjögren’s syndrome Patient Reported Index (ESSPRI), EULAR Sjögren’s Syndrome Disease Activity Index (ESSDAI), hydroxychloroquine, keratoconjunctivitis sicca, rituximab, Sjögren syndrome

Brand Medications and Medicare Part D: How Eye Care Providers' Prescribing Patterns Influence Costs

To quantify costs of eye care providers' Medicare Part D prescribing patterns for ophthalmic medications and to estimate the potential savings of generic or therapeutic drug substitutions and price negotiation. Retrospective cross-sectional study. Eye care providers prescribing medications through Medicare Part D in2013. Medicare Part D 2013 prescriber public use file and summary file were used to calculate medication costs by physician specialty and drug. Savings from generic or therapeutic drug substitutions were estimated for brand drugs. The potential savings from price negotiation was estimated using drug prices negotiated by the United States Veterans Administration (USVA). Total cost of brand and generic medications prescribed by eye care providers. Eye care providers accounted for $2.4 billion in total Medicare part D prescription drug costs and generated the highest percentage of brand name medication claims compared with all other providers. Brand medications accounted for a significantly higher proportion of monthly supplies by volume, and therefore, also by total cost for eye care providers compared with all other providers (38% vs. 23% by volume, P < 0.001; 79% vs. 56% by total cost, P < 0.001). The total cost attributable to eye care providers is driven by glaucoma medications, accounting for $1.2 billion (54% of total cost; 72% of total volume). The second costliest category, dry eye medications, was attributable mostly to a single medication, cyclosporine ophthalmic emulsion (Restasis, Allergan, Irvine, CA), which has no generic alternative, accounting for $371 million (17% of total cost; 4% of total volume). If generic medications were substituted for brand medications when available, $148 million would be saved (7% savings); if generic and therapeutic substitutions were made, $882 million would be saved (42% savings). If Medicare negotiated the prices for ophthalmic medications at USVA rates, $1.09 billion would be saved (53% savings). Eye care providers prescribe more brand medications by volume than any other provider group. Efforts to reduce prescription expenditures by eye care providers should focus on increasing the use of generic medications, primarily through therapeutic substitutions. Policy changes enabling Medicare to negotiate prescription drug prices could decrease costs to Medicare.

Clinical utility of cyclosporine (CsA) ophthalmic emulsion 0.05% for symptomatic relief in people with chronic dry eye: a review of the literature.

To review the literature on the efficacy of cyclosporine (CsA) ophthalmic emulsion 0.05% on symptomatic relief in chronic dry eye disease. There is consistent evidence of objective improvements in chronic dry eye disease (Schirmer score, corneal and interpalpebral dye staining, and tear breakup time) with CsA, but variable results with symptomatic improvement, possibly due to patient tolerance of CsA, similar comforting effect with artificial tears and CsA vehicle, and the inherent subjective nature of symptom monitoring and analysis. This review explores the literature on CsA with special attention to symptomatic relief.

Comparison of prednisolone acetate 1.0% and difluprednate ophthalmic emulsion 0.05% after cataract surgery: Incidence of postoperative steroid-induced ocular hypertension

To compare intraocular pressure (IOP) outcomes between 2 common, commercially available corticosteroid drops: difluprednate ophthalmic emulsion 0.05% and prednisolone acetate 1.0%. TLC Eyecare and Laser Centers, Jackson, Michigan, USA. Retrospective chart review. The outcomes of consecutive patients who had uneventful cataract surgery from April 2013 to September 2013 and used prednisolone acetate postoperatively were compared with the outcomes of consecutive patients who had uneventful cataract surgery from June 2014 to October 2014 and used difluprednate postoperatively. The study included 224 eyes treated with prednisolone acetate 4 times daily for 30days and 225 eyes treated with difluprednate 2 times daily for 30days. There was no significant difference between the 2 groups in age, sex, or race. In addition, the mean IOP did not differ significantly between the prednisolone acetate group and the difluprednate group at the preoperative measurement or 1month after surgery, nor was there a difference in the 1-month change in IOP between groups. No association was found between the incidence of a 6mm Hg or higher increase in IOP 1month after surgery and steroid treatment. One month postoperatively, 4 eyes in the prednisolone acetate group and 5 eyes in the difluprednate group had an IOP higher than 21mm Hg. There was no significant difference in the mean IOP or percentages showing IOP elevation between eyes treated with difluprednate and eyes treated with prednisolone acetate after cataract surgery. This was likely the result of low-frequency dosing and short duration of steroid use.

Semi‐fluorinated alkanes for topical delivery of Cyclosporine

PurposeCyclosporine A (CsA) is an anti‐inflammatory agent that has been frequently used to treat ocular inflammatory conditions, such as dry eye syndrome. However, the poor water solubility of CsA makes it difficult to formulate into an acceptable ocular dosage form. Semi‐fluorinated alkanes (SFAs) are a novel class of inert, non‐toxic and amphiphilic liquids that form clear solutions with CsA and have been suggested as efficient carriers for topical administration of CsA. The aim of this study was to assess the corneal bioavailability of CsA from SFAs compared to currently marketed formulations.MethodsAn ex vivo porcine eye model was used to study the penetration of a) Restasis® (0.05% CsA ophthalmic emulsion), b) Ikervis® (0.1% CsA ophthalmic emulsion), and c) 0.05% or 0.1% CsA in SFAs. The amount of drug penetrated per gram of cornea between 0.5 and 4 h after application was assayed by HPLC and statistically compared using a two‐way ANOVA. Drug distribution in different layers of the cornea was also visualized by substituting CsA with a lipophilic fluorescent dye and viewing corneal sections under a fluorescent microscope.ResultsSignificant improvement in corneal penetration of CsA could be observed for 0.05% CsA in SFAs (C1 h = 5.844 ± 2.408 ng/g) over Restasis (C1 h = 761 ± 221 ng/g), with the area under curve (AUC) being more than 8‐folds greater. The AUC of 0.1% CsA in SFAs (C1 h = 12.556 ± 4.017 ng/g) was 3.6 folds greater than Ikervis (C1 h = 2.900 ± 341 ng/g). Microscopic examinations revealed that the dye incorporated into SFAs tended to accumulate mainly in the corneal epithelium.ConclusionsOverall, this study showed that SFAs can significantly improve the corneal absorption of lipophilic drugs, such as CsA, and could therefore be a promising platform for drug delivery to the eye.

The IMPACT study: a prospective evaluation of the effects of cyclosporine ophthalmic emulsion 0.05% on ocular surface staining and visual performance in patients with dry eye.

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%.

Frequent Dosing of Topical Cyclosporine A for Severe Ocular Surface Disease

To study the systemic safety and patient tolerability of frequent dosing of cyclosporine A (CsA) 0.05% eyedrops in the treatment of ocular surface disease. This is a retrospective case series. Patients with significant ocular surface diseases who were treated using topical CsA higher than the usual twice daily dosing (3-8 times daily and over a treatment period of 1-70 months). The main outcome measures are plasma levels of CsA and local tolerability. Symptom assessment, corneal staining using fluorescein, conjunctival staining using lissamine green, tear film breakup time, and other signs according to the disease process were monitored. Discontinuation of treatment due to intolerability was recorded. CsA levels were measured in the plasma at a clinical laboratory. Plasma levels of CsA were below the level of detection (7 ng/mL) in all the 41 patients included. All patients tolerated the treatment well with none discontinuing due to any treatment-related local adverse effects. This study demonstrates that CsA 0.05% ophthalmic emulsion applied more frequently than the usual twice daily dosing was safe and well tolerated in patients with significant ocular surface diseases.

Comparisons for Evaluation of Efficacy and Safety of Cyclosporin A 0.05% Ophthalmic Emulsion Treatment Groups

Comparisons for Evaluation of Efficacy and Safety of Cyclosporin A 0.05% Ophthalmic Emulsion Treatment Groups

To Study the Efficacy of Difluprednate Ophthalmic Emulsion and Prednisolone Acetate Ophthalmic Suspension on Post-operative Inflammation in Cataract Surgery.

Senile cataract is the most common cause of visual impairment. Removal of cataract and implantation of intraocular lens implantation (IOL) is the main surgical approach for cataract. The major block in quick visual rehabilitation of the patient is post-operative inflammation. To limit post-operative inflammation corticosteroids drugs are used in routine prophylactically. Topical prednisolone acetate 1% and betamethasone 0.1% remain gold standard to control post-operative inflammation but newer drugs like difluprednate, loteprednol are also effective in controlling inflammation. To study the efficacy of difluprednate ophthalmic emulsion and prednisolone acetate ophthalmic suspension on Post-operative inflammation in cataract surgery (clear corneal phacoemulsification with foldable IOL). This study was carried out on 100 patients having visually significant cataract requiring surgery, clear corneal phacoemulsification with foldable intraocular lens implantation was done in all patients. Patients were randomly divided into two groups. In group A topical 1% prednisolone acetate ophthalmic suspension was administered six times a day Post-operatively. In group B 0.05% difluprednate ophthalmic emulsion was administered six times a day post-operatively. Efficacy of drug was evaluated in terms of decrease in ocular pain, anterior chamber reaction in the form of aqueous cells and flare and final visual acuity at 4 weeks. In this study, 92% of patients in group A and 90% of patients in group B had BCVA 6/6. None of the patients in group A had ocular pain. In group B, 96% patients had no ocular pain. Remaining 4% had mild discomfort but required no medication. 98% of patients in group A and 100% of patients in group B presented with clearance of aqueous cells at the end of study. Only 2% of patients in group A had showed cell score (±). Though prednisolone acetate has been the gold standard anti inflammatory agent, 0.05% Difluprednate ophthalmic emulsion is equally effective in treatment of post-operative inflammation. Difluprednate have added an advantage of uniform drug dosage and absence of harmful preservative.

Evaluation of a cyclosporine A ophthalmic ointment in an experimental mouse model of dry eye

PurposeDry eye syndrome is a common disease with multifactorial causes. Symptoms typically include irritation, dryness, burning and decreased or fluctuating vision. Anti‐inflammatory drugs are widely used for the treatment of the inflammation produced by the disease with corticoid or cyclosporine A (CsA). Restasis® (Allergan), a CsA emulsion, was approved by the FDA but is not available in Europe. Here we propose to show the action of Optimmune® (MSD Animal Health) a marketed veterinary ophthalmic ointment that contains CsA in an experimental mouse model of dry eye induced by scopolamine, a tropane alkaloid drug with muscarinic antagonist effects.MethodsAnimals were divided in three groups of ten pigmented mice: Two groups were exposed to desiccating conditions (relative humidity &lt;25%, air‐flow 15 L/min, temperature 20‐22°C) with transdermal scopolamine administration (0.5 mg/72 h) for 14 days. Animals were treated topically three times a day with 0.2% CsA ointment or vehicle. Controls were saline‐treated animals placed in a normal environment. Tear production was measured with the phenol red thread test, corneal defects were examined by slit‐lamp observation using blue light after 0.5% fluorescein eye drop. These examinations were performed in both eyes before exposure and on days 3, 7 and 14. A histological study was performed at the end of the study.ResultsCyclosporine A eye ointment appeared to show efficacy in this model.ConclusionsCyclosporine A eye ointment significantly reduced clinical signs of dry eye by decreasing corneal defect more than cyclosporine A ophthalmic emulsion (internal studies).

Interventions for rosacea: abridged updated Cochrane systematic review including GRADE assessments.

Rosacea is a common chronic facial dermatosis. This update of our Cochrane review on interventions for rosacea summarizes the evidence, including Grading of Recommendations Assessment, Development and Evaluation (GRADE) Working Group assessments, of the effects of the currently available treatments. Searches included the following: Cochrane Skin Group Specialised Register, CENTRAL in The Cochrane Library, MEDLINE, EMBASE, LILACS and the Science Citation Index, and ongoing trials registries (July 2014). We included 106 randomized controlled trials (RCTs) with 13631 participants, a more than 80% increase since the last update in 2011. Pooling of data was feasible for a few outcomes, for topical metronidazole and azelaic acid and both appeared to be more effective than placebo (moderate and high-quality evidence, respectively). Topical ivermectin was more effective than placebo based on two studies (high-quality evidence), and slightly more effective than metronidazole in one study. Brimonidine was more effective than vehicle in reducing erythema in rosacea (high-quality evidence). Ciclosporin ophthalmic emulsion was effective for ocular rosacea (low-quality evidence). For oral treatments there was moderate-quality evidence for the effectiveness of tetracycline based on two old studies, and high-quality evidence for doxycycline 40mg compared with placebo according to physician assessments. One study at high risk of bias demonstrated equivalent effectiveness for azithromycin and doxycycline 100mg. Minocycline 45mg may be effective for papulopustular rosacea (low-quality evidence). Low-dose isotretinoin appeared to be slightly more effective than doxycycline 50-100mg (high-quality evidence). Laser and light-based therapies for erythema in rosacea were effective (low-quality evidence). Further RCTs are required for ocular rosacea.

Efficacy and safety of topical difluprednate in persistent diabetic macular edema.

To evaluate the efficacy and safety of treatment of diabetic macular edema (persistent type) with difluprednate ophthalmic emulsion 0.05% (off label use). 20 patients with persistent diabetic macular edema were enrolled. In all subjects, more than 4months had passed since prior treatment. All patients were treated with difluprednate ophthalmic emulsion 0.05% three times daily for 3months. At the end of 3months the visual acuity had increased by two lines to a mean value of 0.61±0.18 on logMAR from a baseline value of0.885±0.20 and the central retinal thickness had decreased from423±72.04 microns to 345±68.7 microns. Hence, there was a total of 18.4% decrease in retinal thickness on difluprednate. Major side effects included raised intraocular pressure in 20%. Difluprednate is a potent and strong steroid which causes a rapid decrease in persistent diabetic macular edema. However, the potential side effect of raised intraocular pressure limits its use as an adjuvant therapy in non-steroid responders.