loteprednol-etabonate and Eye-Diseases

Topical corticosteroids are an important pharmacotherapy for the management of various inflammatory conditions affecting the anterior segment of the eye. However, medications in this class are associated with well-known risks including increased intraocular pressure (IOP) and development of cataracts. The topical corticosteroid loteprednol etabonate (LE) was developed with the specific intention of minimizing these side effects.. The focus of this review is to examine published efficacy and safety data for LE, a drug engineered to undergo rapid metabolism to inactive metabolites with the goal of improved safety. Two decades of clinical research focused on LE formulations are reviewed, including the use of LE in combination with tobramycin. The cumulative body of experience affirms the concept that the molecular design of LE confers certain safety benefits without compromising the desired anti-inflammatory efficacy of a topical corticosteroid.. Loteprednol etabonate is a mainstay for topical therapy of a wide variety of commonplace and niche conditions of the ocular surface and the anterior segment, including in the healing post-operative patient. Its versatility and safety allow eye care providers to recommend both acute induction as well as chronic maintenance therapy with appropriate follow-up.

Topics: Clinical Trials as Topic; Conjunctivitis, Allergic; Dry Eye Syndromes; Eye Diseases; Glucocorticoids; Humans; Loteprednol Etabonate; Ointments; Ophthalmic Solutions; Uveitis, Anterior

Corticosteroids are a mainstay therapeutic option for the treatment of ocular inflammation. However, safety remains a concern for clinicians, particularly with long-term use. Though highly effective at suppressing inflammatory and allergic responses, topical ophthalmic corticosteroids carry an inherent risk of side effects, including elevated intraocular pressure (IOP), a risk factor for the development of glaucoma. The corticosteroid loteprednol etabonate (LE) contains an ester rather than a ketone at the C-20 position, minimizing the potential for side effects, including IOP elevation. In early pivotal clinical trials of LE ophthalmic suspension for conjunctivitis (allergic, giant papillary), anterior uveitis, and post-operative inflammation, LE had minimal impact on IOP over short-term (<28 days) and long-term (≥28 days) use. Since then, new LE formulations-including a gel, an ointment, and a suspension of LE in combination with tobramycin-have become commercially available. Multiple studies evaluating the safety and efficacy of LE for inflammatory conditions have been reported, including those requiring longer-term treatment such as photorefractive keratectomy, corneal transplantation, and dry eye disease. We review the available published data on the effect of LE on IOP and report on the cumulative incidence of clinically significant IOP elevations (≥10 mm Hg from baseline) with short-term and long-term LE use. In all studies, LE consistently demonstrated a low propensity to elevate IOP, regardless of formulation, dosage regimen, or treatment duration, including in known steroid responders. The cumulative proportion of patients exhibiting clinically significant IOP increases was 0.8% (14/1725 subjects) in studies evaluating short-term LE treatment and 1.5% (21/1386 subjects) in long-term studies. Furthermore, use of LE was associated with significantly lower rates of IOP elevation ≥10 mm Hg as compared to prednisolone acetate or dexamethasone (when used in combination with tobramycin). The cumulative data to date substantiates a favorable IOP-safety profile for LE with both short-term and long-term use.

Topics: Eye Diseases; Glucocorticoids; Humans; Inflammation; Intraocular Pressure; Long Term Adverse Effects; Loteprednol Etabonate; Ocular Hypertension; Ophthalmic Solutions; Tonometry, Ocular

The treatment of ocular inflammation continues to be a challenge. Topical corticosteroids are effective in reducing ocular inflammation but are limited by adverse events including elevation of intraocular pressure, development of cataracts, glaucoma and inhibition of wound healing with associated risk of infection. Loteprednol etabonate (LE) is a unique C-20 ester corticosteroid designed to produce a predictable therapeutic effect with a low incidence of side effects. Zylet (LE/T) a combination of LE and tobramycin (T) is indicated for the treatment of steroid-responsive ocular inflammatory conditions in which there exists either superficial bacterial ocular infection or a potential risk of bacterial infection.. The current review of the literature (Medline and the Cochrane Library, 1996 - 2009) examines the safety and efficacy of LE/T in the treatment of ocular inflammation.. Studies with either LE or LE/T indicate that LE has a lower risk of IOP elevation compared with C-20 ketone corticosteroids owing to its rapid de-esterification to inactive metabolites. LE also lacks the ability to form Schiff base intermediates with lens proteins, a common first step in cataractogenesis. LE/T was noninferior to dexamethasone 0.1%/tobramycin 0.3% in the treatment of blepharokeratoconjunctivitis.. LE/T may be a safer treatment option for ocular inflammation in which there is risk of superficial bacterial infections.

Topics: Administration, Topical; Androstadienes; Anti-Allergic Agents; Anti-Bacterial Agents; Drug Combinations; Eye Diseases; Humans; Inflammation; Intraocular Pressure; Loteprednol Etabonate; Ophthalmic Solutions; Tobramycin

Topics: Androstadienes; Clinical Trials as Topic; Drug Industry; Eye Diseases; Humans; Loteprednol Etabonate

Loteprednol etabonate (LE) is a corticosteroid designed using the "soft drug" concept of Bodor. LE has been extensively evaluated as a treatment for ophthalmic inflammatory conditions. LE is administered as a sterile eye drop suspension and is commercially available as either a 0.5% or a 0.2% suspension. Lotemax (0.5% LE) has been demonstrated as effective in reducing the signs and symptoms of giant papillary conjunctivitis (GPC), acute anterior uveitis and inflammation following cataract extraction with intraocular lens (IOL) implantation. It is also effective for the prophylaxis of seasonal allergic conjunctivitis (SAC) in patients with a history of that condition. Alrex (0.2% LE) is effective for the treatment of the signs and symptoms of SAC. In comparison with other steroids LE has a superior safety profile which has been attributed to its "soft drug" characteristics.

Topics: Androstadienes; Animals; Anti-Inflammatory Agents; Eye Diseases; Humans; Inflammation; Loteprednol Etabonate

This study aimed to compare the anti-inflammatory efficacy and safety of 0.1% Fluorometholone (FML) versus (vs.) 0.5% Loteprednol etabonate (LE) following photorefractive keratectomy (PRK).. A triple-blinded randomized controlled trial was conducted on both eyes of 100 patients with stable refraction who were candidates for PRK. Both eyes in each subject were randomly allocated to the FML or LE groups. The product to be tested was 0.1% FML eye drops packaged in droppers vs. the 0.5% LE sterile ophthalmic suspension (Lotemax®) packaged in identical droppers. The main clinical outcomes were changes in best-corrected distance visual acuity (BCDVA) and corneal optical density. The second clinical outcomes were a change in intraocular pressure (IOP) after the intervention.. There was no significant difference regarding mean corneal optical density changes between the two groups, one (. The results of this clinical trial demonstrate that LE and FML treatment was effective with no clinically meaningful effect on IOP following a short course of treatment.

Topics: Cornea; Eye Diseases; Fluorometholone; Humans; Lasers, Excimer; Loteprednol Etabonate; Ophthalmic Solutions; Photorefractive Keratectomy; Retrospective Studies; Treatment Outcome

Topical ophthalmic corticosteroids are of clinical benefit in the management of pain and inflammation after ocular surgery; however, their use can be associated with class-associated adverse events (AEs) and limited bioavailability. Selection of an appropriate topical corticosteroid depends on drug-specific variables such as AE profile, efficacy, potency, dosing, patient-specific administration needs, and formulation properties aimed at minimizing precorneal drug loss, increasing ocular surface drug residence time, and maximizing drug delivery to the anterior tissues. Recently, strategies for improving ocular penetration of ophthalmic formulations have included use of mucoadhesive formulations (ie, polycarbophil-containing gels) and drug particle size reduction, enabling faster drug dissolution and therefore increased bioavailability and penetration. Loteprednol etabonate (LE) is a carbon-20 ester corticosteroid developed through retrometabolic drug design with potent anti-inflammatory effects and a reduced propensity for eliciting corticosteroid class AEs. This drug has been formulated for topical ophthalmic use after surgery as 0.5% and 1% suspensions, a 0.5% ointment, and a 0.5% gel. Preclinical and clinical data for a new 0.38% LE gel will be reviewed demonstrating that reducing the drug particle size to the nanometer range in diameter provides effective ocular tissue penetration and resolution of pain and inflammation despite a reduced drug concentration (0.38%) and dosing frequency.

Topics: Administration, Topical; Adult; Aged; Aged, 80 and over; Anti-Allergic Agents; Eye Diseases; Eye Pain; Female; Humans; Inflammation; Loteprednol Etabonate; Male; Middle Aged; Ophthalmic Solutions; Postoperative Complications; United States

To compare the outcomes and complications of topical difluprednate 0.05% and loteprednol gel 0.5% after routine cataract surgery.. Subjects received either difluprednate emulsion 0.05% (n=30 eyes) or loteprednol gel 0.5% (n=30 eyes) after routine cataract surgery. Topical steroid drops were initiated 3 days before cataract surgery and continued for 2 weeks postoperatively. Anterior chamber (AC) cell grade, corneal edema, corneal pachymetry, visual acuity, ocular surface quality (Oxford scale), and intraocular pressure (IOP) were evaluated at 1 day, 1 week, and 1 month postoperatively.. Patients treated with difluprednate or loteprednol had statistically similar resolution of their AC cell grade and corneal edema at 1 day, 1 week, and 1 month postoperatively (P>0.05 at each study visit). Difluprednate-treated and loteprednol-treated eyes achieved a mean best-corrected visual acuity of at least 20/25 by 1 week postoperatively (0.055 and 0.061 logarithm of the minimum angle of resolution, respectively; P=0.82). The nasal ocular surface quality at 1 week had improved in loteprednol-treated eyes compared with difluprednate-treated eyes (1.0 vs. 1.9 Oxford score, respectively; P<0.001), but similar at all other visits. There was no statistical difference between IOP levels between both treatment groups (P>0.05). In the difluprednate-treated group, one patient developed rebound inflammation and two patients developed cystoid macular edema at their 1-month postoperative visit.. The anti-inflammatory effect, visual recovery, and IOP of patients using topical difluprednate or loteprednol gel after cataract surgery are equivalent. There may be an additional short-term benefit of loteprednol gel in protecting the ocular surface after cataract surgery.

Topics: Aged; Aged, 80 and over; Anterior Chamber; Anti-Inflammatory Agents; Cataract Extraction; Cornea; Corneal Edema; Eye Diseases; Female; Fluprednisolone; Gels; Glucocorticoids; Humans; Inflammation; Intraocular Pressure; Loteprednol Etabonate; Male; Middle Aged; Postoperative Complications; Visual Acuity

The purpose of the present study was to develop loteprednol etabonate (LE) loaded poly(d,l-lactide co-glycolide) (PLGA) nanoparticles (NPs) and study their penetration profile into the excised goat cornea. In the present study, LE loaded PLGA NPs were prepared by solvent evaporation with high speed homogenization method and the penetration profile was studied using confocal laser scanning microscopy (CLSM). Rhodamine (Rd) was used as a fluorescent marker to prepare Rd-LE-PLGA-NPs. The NPs were characterized for particle size, X-ray diffraction (XRD), differential scanning calorimetry (DSC), transmission electron microscopy (TEM), drug entrapment, and permeation profile. Intense fluorescence observed across the depths of goat corneal tissue suggested an improved penetration profile of NPs. The entrapment efficiency and mean diameter of the optimized formulation (F5) were found to be 96.31 ± 1.68% and 167.6 ± 0.37 nm, respectively. These findings indicate that LE loaded PLGA NPs may serve as a potential drug carrier for ocular administration in eye disease.

Topics: Administration, Ophthalmic; Animals; Cornea; Drug Delivery Systems; Eye Diseases; Goats; Lactic Acid; Loteprednol Etabonate; Nanoparticles; Permeability; Polyglycolic Acid; Polylactic Acid-Polyglycolic Acid Copolymer

Ocular corticosteroids can cause elevations in intraocular pressure (IOP). The purpose of this study was to characterize the timing and severity of IOP elevations in patients receiving loteprednol etabonate 0.5% or loteprednol etabonate 0.5%/tobramycin 0.3%.. A retrospective chart review was conducted at 5 academic and private practices. Any patient who experienced an elevation in IOP ≥5 mm Hg while using loteprednol etabonate or loteprednol etabonate/tobramycin was eligible for inclusion in the study. Data collected included patient demographics, medical and ophthalmic history, concomitant medications, reason for treatment, IOP, and medical and surgical interventions.. Fifty patients experienced IOP elevations after use of topical loteprednol etabonate and were included in the study. The mean (standard deviation [SD]) patient age was 58.8 (20.3) years and 66% were women. The most common reasons for prescribing loteprednol etabonate were dry eye (30%), postoperative therapy (22%), and allergic conjunctivitis (16%). Before treatment, 28% of patients had a history of open-angle glaucoma or ocular hypertension. Mean (SD) IOP before treatment was 15.5 (3.2) mm Hg and increased to a mean (SD) of 24.7 (6.5) mm Hg, a statistically significant increase of 9.2 (SD: 5.8; range: 5-29) mm Hg (P<0.0001). The median duration of treatment with loteprednol etabonate at the time of observed IOP elevation was 55 days (range: 3 days to 3 years). Twenty-four percent of patients required IOP-lowering medications and 8% required surgery to control the elevated IOP.. Alternatives to corticosteroids should be considered when long-term treatment is required for an ocular surface condition.

Topics: Adult; Aged; Androstadienes; Anti-Inflammatory Agents; Cohort Studies; Drug Combinations; Drug Monitoring; Eye Diseases; Female; Glucocorticoids; Humans; Intraocular Pressure; Loteprednol Etabonate; Male; Medical Records; Middle Aged; Ocular Hypertension; Ophthalmic Solutions; Retrospective Studies; Severity of Illness Index; Time Factors; Tobramycin