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Raymond Fong,1 Megan E Cavet,2 Heleen H DeCory,2 Jason L Vittitow31Manhattan Eye, Ear and Throat Hospital and Lenox Hill Hospital, New York, NY, USA; 2Medical Affairs, Bausch + Lomb, Rochester, NY, USA; 3Clinical Affairs, Bausch + Lomb, Bridgewater, NJ, USAPurpose: To evaluate the efficacy and safety of a submicron formulation of loteprednol etabonate (LE) gel 0.38% instilled three times daily (TID) compared with vehicle for the treatment of inflammation and pain following cataract surgery with intraocular lens implantation, integrated across two multicenter, double-masked, randomized, parallel-group, Phase III studies.Patients and methods: Subjects ≥18 years of age with anterior chamber (AC) cells ≥grade 2 (6–15 cells) on day 1 after cataract surgery were randomized to receive 1 drop of LE gel 0.38% TID, twice daily (not reported/analyzed herein), or vehicle instilled in the study eye for 14 days. Primary endpoints were the proportion of subjects with resolution of AC cells and grade 0 (no) pain at postoperative day 8. Safety outcomes included adverse events (AEs), ocular signs, fundoscopy results, visual acuity, intraocular pressure (IOP), and tolerability (drop comfort and ocular symptoms).Results: The integrated intent-to-treat population included 742 subjects (LE gel 0.38% TID, n=371; vehicle, n=371). Significantly more subjects in the LE gel 0.38% TID group compared with the vehicle group had complete resolution of AC cells (29.6% vs 15.1%) and grade 0 pain (74.4% vs 48.8%) at day 8 (P75%) of subjects in each treatment group reported no drop discomfort. There were no reports of blurred vision with LE gel.Conclusion: The results of this integrated analysis indicate that LE (submicron) gel 0.38% administered TID is safe and effective for the treatment of ocular inflammation and pain following cataract surgery, with minimal risk of IOP elevation.Keywords: cataract surgery, postoperative pain, postoperative inflammation, loteprednol etabonate, submicron, integrated analysis

JD Sheppard,1 IP Singh21Department of Ophthalmology, Eastern Virginia Medical School, Norfolk, VA, USA; 2Department of Glaucoma, The Eye Centers of Racine & Kenosha, Racine, WI, USAPurpose: With the increasing use of minimally invasive surgical techniques for intraocular pressure (IOP) lowering in glaucoma patients, there is a need to examine best practices regarding the postoperative management of these patients. Corticosteroids, though effective in controlling postoperative ocular pain and inflammation, present distinct challenges in glaucoma surgery patients, as their use can be associated with IOP elevation. Loteprednol etabonate (LE) is an ocular corticosteroid designed to have an improved safety profile relative to other corticosteroids.Methods: We report here a representative selection of cases in which patients were successfully treated with LE ophthalmic gel 0.5% (LE gel) following a variety of minimally invasive glaucoma surgery (MIGS) procedures. Cases included patients undergoing various procedures including a Trabectome combined with cataract surgery; micro-stent surgery (iStent) combined with cataract surgery; supraciliary CyPass Micro-Stent placement combined with cataract surgery; Kahook Dual Blade goniotomy; and ab interno canaloplasty using the iTrack catheter.Observations: In all cases, use of LE gel during the postoperative period appeared effective and safe in reducing inflammation and controlling pain. No adverse events or IOP elevations were noted, even in those patients continuing use of LE gel past the postoperative period for longer than six months with documented follow-up. In two cases, patients with elevated IOP using either prednisolone or difluprednate postoperatively were switched to LE gel, with a subsequent reduction in IOP.Conclusions: This selection of cases involving patients undergoing MIGS suggests that LE gel may be an effective and safe option for treating postoperative inflammation and pain following such procedures with minimal to no effect on IOP or other negative sequalae.Keywords: loteprednol etabonate, minimally invasive glaucoma surgery, intraocular pressure, postoperative pain and inflammation, safety

The tear film, which includes mucins that adhere to foreign particles, rapidly clears allergens and pathogens from the ocular surface, protecting the underlying tissues. However, the tear film's ability to efficiently remove foreign particles during blinking can also pose challenges for topical drug delivery, as traditional eye drops (solutions and suspensions) are cleared from the ocular surface before the drug can penetrate into the conjunctival and corneal epithelium. In the past 15 years, there has been an increase in the development of nanoparticles with specialized coatings that have reduced affinity to mucins and are small enough in size to pass through the mucus barrier. These mucus-penetrating particles (MPPs) have been shown to efficiently penetrate the mucus barrier and reach the ocular surface tissues. Dry eye disease (DED) is a common inflammatory ocular surface disorder that often presents with periodic flares (exacerbations). However, currently approved immunomodulatory treatments for DED are intended for long-term use. Thus, there is a need for effective short-term treatments that can address intermittent flares of DED. Loteprednol etabonate, an ocular corticosteroid, was engineered to break down rapidly after administration to the ocular surface tissues and thereby reduce risks associated with other topical steroids. KPI-121 is an ophthalmic suspension that uses the MPP technology to deliver loteprednol etabonate more efficiently to the ocular tissues, achieving in animal models a 3.6-fold greater penetration of loteprednol etabonate to the cornea than traditional loteprednol etabonate ophthalmic suspensions. In clinical trials, short-term treatment with KPI-121 0.25% significantly reduced signs and symptoms of DED compared with its vehicle (placebo). Recently approved KPI-121 0.25%, with its novel drug delivery design and ease of use, has the potential to effectively treat periodic flares of DED experienced by many patients. [ABSTRACT FROM AUTHOR]

We report two patients who developed toxic keratopathy following high-dose cytarabine chemotherapy and whose symptoms resolved following topical loteprednol etabonate 0.5% treatment. A 25-year-old woman and a 26-year-old man with acute myeloid leukemia were referred to our department with symptoms of ocular discomfort, photophobia, and blurred vision after consolidation chemotherapy. Central corneal epithelial microcysts were observed bilaterally in both patients, and in vivo confocal microscopy showed highly reflective disseminated granular and irregular intraepithelial opacities, mainly in the basal epithelial layers. Loteprednol etabonate 0.5% relieved both patients' symptoms in less than a week, and the microcysts disappeared in 2 to 3 weeks of treatment. Although there is no standardized treatment protocol for cytarabine-induced corneal toxicity, dexamethasone 0.1% and prednisolone phosphate 1.0% were reported to be effective in the resolution of discomfort and symptoms. In the two patients we report herein, loteprednol etabonate 0.5% four times daily was also effective in suppressing the symptoms. [ABSTRACT FROM AUTHOR]

The crystal structure of loteprednol etabonate Form II has been solved and refined using synchrotron X-ray powder diffraction data, and optimized using density functional techniques. Loteprednol etabonate Form II crystallizes in the space group P21 (#4) with a = 11.96312(6), b = 14.91862(5), c = 6.75715(3) Å, β = 94.1584(3)°, V = 1202.796(6) Å3, and Z = 2. The crystal structure is characterized by herringbone layers in the ab-plane. The anisotropic displacement ellipsoid of the Cl atom is not oriented in a way which corresponds to a chemically sensible motion of this atom. The sample suffered damage in the X-ray beam, probably involving photolysis of the C–Cl bond. The most prominent hydrogen bond is the O–H⋯O hydrogen bond between the hydroxyl group and the carbonyl group of the steroid A ring. This hydrogen bond links the molecules into C1,1(9) chains along the b-axis. The powder pattern is included in the Powder Diffraction File™ (PDF®) as entry 00-066-1602; this study will allow inclusion of the atomic coordinates to the PDF entry. [ABSTRACT FROM AUTHOR]

Terry Kim,1 Kenneth Sall,2 Edward J Holland,3 R Kim Brazzell,4 Susan Coultas,4 Preeya K Gupta1 1Department of Ophthalmology, Duke University Eye Center, Durham, NC, USA; 2Sall Research Medical Center, Inc, Artesia, CA, USA; 3Department of Ophthalmology, Cincinnati Eye Institute, University of Cincinnati, Cincinnati, OH, USA; 4Kala Pharmaceuticals, Inc, Waltham, MA, USA Purpose: KPI-121 is a nanoparticle suspension of loteprednol etabonate with improved ocular pharmacokinetics compared with marketed formulations. The efficacy and safety of KPI-121 1% ophthalmic suspension (INVELTYS™) dosed twice daily (BID) were evaluated in participants who had undergone cataract surgery. Materials and methods: In two multicenter, randomized, double-masked, parallel-group, vehicle-controlled clinical trials, 386 participants with ≥ grade 2 anterior chamber cells (≥6 cells) on the day following routine cataract surgery were treated with KPI-121 1% and 325 participants were treated with placebo (vehicle); each group was dosed BID for 2 weeks. Primary efficacy endpoints were complete resolution of ocular inflammation by slit-lamp biomicroscopy and complete resolution of subject-rated ocular pain at Days 8 and 15 with no rescue medication before Day 15. Safety assessments included adverse events (AEs), visual acuity, intraocular pressure measurements, and evaluation of ocular AEs by slit-lamp biomicroscopy and dilated ophthalmoscopy. Results: Both trials achieved statistical significance favoring KPI-121 1% BID for both primary efficacy endpoints. Combined data analysis showed that significantly more participants treated with KPI-121 vs vehicle achieved complete resolution of anterior chamber cells at Days 8 and 15 (P≤0.0001) and complete clearing of ocular pain at Days 4, 8, and 15 (P

Mahmoud A Khaimi Dean McGee Eye Institute, Oklahoma City, OK, USA Background: While loteprednol etabonate (LE) suspension 0.5% is approved for the treatment of postoperative ocular inflammation, there have been no reported studies of its use in glaucoma patients undergoing canaloplasty.Methods: This was a retrospective medical chart review conducted at a single US center. Data were collected on patients with glaucoma who underwent canaloplasty with or without cataract surgery, and were prescribed LE suspension 0.5% postoperatively. Outcomes evaluated included postsurgical inflammation (anterior chamber [AC] cells and flare), intraocular pressure (IOP), number of IOP-lowering medications, and postsurgical complications.Results: Data were collected on 204 patients (262 eyes) with a mean (SD) age of 71.6 (11.3) years. The most frequent LE dosing regimens at day 1, week 1, and month 1 postsurgery were QID (92.3%; 241/261), TID (52.6%; 133/253), and QD (65.5%; 78/119), respectively. Inflammation (AC flare and cells), mostly mild, was noted in 33.2% (86/259) of eyes on postoperative day 1 and 8.6% (21/244) of eyes at month 1. Mean IOP and mean number of IOP-lowering medications were significantly reduced from baseline (P

Dry eye disease (DED) is a common ocular condition that can impair vision and may adversely impact quality of life. Due to the inflammatory nature of this disorder, topical corticosteroids are an effective treatment option, particularly for moderate-to-severe DED when first-line treatments, such as ocular lubricants, are insufficient. Loteprednol etabonate (LE) is a retrometabolically designed corticosteroid with a low propensity to cause corticosteroid-related adverse effects, such as elevated intraocular pressure (IOP). This review was conducted to provide an assessment of published studies on the use of LE for treatment of inflammation associated with DED. Twelve prospective and 2 retrospective studies evaluating LE ophthalmic suspension 0.5% and 2 prospective studies evaluating LE ophthalmic gel 0.5% were identified. LE given as monotherapy or with artificial tears (AT) improved signs of DED, especially among patients with a more pronounced inflammatory component, and also improved DED symptoms compared to baseline and/or control. Treatment with LE before cyclosporine A (CsA) therapy reduced stinging upon CsA initiation and provided more rapid relief of DED signs and symptoms than CsA plus AT alone. In patients with meibomian gland dysfunction, LE alone, or in addition to eyelid scrubs/warm compresses, reduced clinical signs and symptoms, and tear proinflammatory cytokine levels. Overall, LE was safe and well tolerated, with minimal effects on IOP. While larger and longer-term studies are warranted, these data support the use of LE as a safe and effective treatment option for DED. [ABSTRACT FROM AUTHOR]

Purpose: To evaluate the effects of loteprednol etabonate on cornea and tear film in patients with seasonal allergic conjunctivitis by anterior segment optical coherence tomography (OCT). Methods: The right eyes of 52 subjects with seasonal allergic conjunctivitis were evaluated in the study. Central corneal thickness (CCT), the thicknesses of central corneal epithelium (CET) and central non-epithelial cornea (CnET), and lower and upper tear meniscus areas were measured by spectral-domain OCT and ocular surface disease index (OSDI) were obtained at baseline. After topical use of loteprednol etabonate 0.5% eye drop three times a day for 1 week, the measurements were repeated. Paired T test was used for analysis. Results: Mean CCT and mean thicknesses of CET and CnET at baseline were 528.19 ± 34.47 µm, 64.10 ± 5.30 µm and 462.84 ± 33.43 µm, respectively, and these were 526.31 ± 33.37 µm, 64.65 ± 4.84 µm and 459.84 ± 32.11 µm after the treatment, respectively. OSDI score was 21.55 ± 4.40 at baseline and 13.13 ± 2.39 after 1 week. The lower and upper tear meniscus areas at baseline were 0.026 ± 0.017 mm2 and 0.017 ± 0.007 mm2, respectively, and they were 0.017 ± 0.009 mm2 and 0.016 ± 0.007 mm2, respectively, after the treatment. There is statistically significant difference between before and after values of CCT, CnET, lower tear meniscus area and OSDI score (p < 0.05). Conclusion: There is no change in corneal epithelial thickness and upper tear meniscus area after 1-week treatment with loteprednol etabonate in patients with seasonal allergic conjunctivitis, but it may cause decrease in non-epithelial corneal thickness and lower tear meniscus area. [ABSTRACT FROM AUTHOR]

A comparative study on efficacy and safety of Loteprednol Etabonate 0.5% w/v versus Dexamethasone 0.1% w/v in the treatment of pain and inflammation after cataract surgery in a tertiary care hospital, Salem district, Tamilnadu, India. This prospective study was carried out for a period of 6 months from November 2018-April 2019 in which 160 patients who underwent cataract surgery were selected for the study by considering the inclusion and exclusion criteria. The study mainly describes the prevalence of the use of corticosteroids with the mechanism of fluctuation in Intraocular pressure effect in postoperative cataract surgery which is Loteprednol Etabonate or Dexamethasone. The maximum number of patients affected with the cataract is in the age group of 51-60. Among the cataract patients, half of the patients were found with associated diseases, particularly Diabetes Mellitus (15%), Hypertension (18%) and both (15%) are the most seen comorbid condition in this study. Patients of both genders were included in the study. Out of 160 cases, 55 % were found to be female and 45 % were found to be male. From the data of 160 consecutive cataract cases, 80 patients were administered with Loteprednol Etabonate 0.5 % w/v, and the other 80 patients were administered with Dexamethasone 0.1 % w/v. The data were collected based on IOP, Visual acuity, and Slit Lamp Examination which were analyzed in this study individually for both Loteprednol etabonate and Dexamethasone. Since both of the drugs provides anti-inflammatory action in the management of pain and inflammation in postoperative cataract surgery. [ABSTRACT FROM AUTHOR]

Loteprednol etabonate (LE) is a soft corticosteroid with two labile ester bonds at 17α- and 17β-positions. Its corticosteroidal activity disappears upon hydrolysis of either ester bond. Hydrolysis of both ester bonds produces the inactive metabolite, Δ1-cortienic acid (Δ1-CA). The simple high-performance liquid chromatography method using acetic acid gradient was developed for the simultaneous determination of LE and its acidic metabolites. LE was hydrolyzed in rat plasma with a half-life of 9 min. However, LE hydrolysis was undetectable in rat liver and intestine. LE hydrolysis in rat plasma was completely inhibited by paraoxon and bis(p-nitrophenyl) phosphate, thus identifying carboxylesterase as the LE hydrolase. Rat plasma carboxylesterase had a Km of 6.7μM for LE. In contrast to the disappearance rate of LE in rat plasma, the formation rate of 17α-monoester and Δ1-CA was markedly low, and a main hydrolysate of LE was not detected in rat plasma. The metabolism of LE proceeded via different pathways in human and rat plasma. LE was slowly hydrolyzed by paraoxonase in human plasma to 17α-monoester with a half-life of 12h, but by carboxylesterase in rat plasma to yield undetectable products, presumed to include the unstable 17β-monoester. [ABSTRACT FROM AUTHOR]

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To compare the mean rise in intraocular pressure and post-operative inflammation between loteprednol etabonate 0.5% and prednisolone acetatae1%. Out Patient Department of Ophthalmology Department, Government Medical College, Jammu. Comparative case series. Patients aged 18 years and older undergoing cataract surgery were divided into two groups: Group A (n=100) was prescribed loteprednol etabonate 0.5% (LE) four times a day; Group B (n=100) was prescribed prednisolone acetate 1% (PA) four times a day. Patients with pre-existing medical conditions like raised intraocular pressure, maculopathy, uveitis, retinopathy were excluded. Intraocular pressure and post-operative inflammation were assessed over 42 days after cataract surgery. Loteprednol etabonate 0.5% (LE) and prednisolone acetate 1% (PA) were equally efficacious in decreasing Anterior Chamber cells (0.08±0.27 vs 0.05±0.22 respectively; p=0.39) and Anterior Chamber flare (0.06±0.24 vs 0.05±0.22 respectively; p=0.76) at 42 days. There was statistically significant difference in intraocular pressure at 42nd days with LE as compare to PA(16.21±3.34 vs 18.62±2.36 respectively; p<0.001). The equivalent control of inflammation can be obtained through treatment with LE and PA after cataract surgery but the mean rise in intraocular pressure in patients treated with loteprednol etabonate is less than in patients treated with prednisolone acetate. [ABSTRACT FROM AUTHOR]