Efficacy and safety of loteprednol etabonate versus fluorometholone in the treatment of patients after corneal refractive surgery: a meta-analysis.

PURPOSE: To perform a systematic evaluation of the efficacy and safety of loteprednol etabonate (LE) 0.5% versus fluorometholone (FML) 0.1% for treating patients after corneal refractive surgery with the aim of providing an evidence-based rationale for clinical drug selection. METHODS: Electronic databases (PubMed, EMBASE, Cochrane Library, Web of Science, WanFang, and CNKI) were searched (from inception to December 2021) for comparative clinical studies that evaluated LE versus FML treatment for post-corneal refractive surgery patients. Meta-analysis was performed using the RevMan 5.3 software. The pooled risk ratio (RR) and weighted mean difference (WMD) with corresponding 95% confidence interval (CI) were calculated. RESULTS: Nine studies with a total sample size of 2677 eyes were included in this analysis. FML 0.1% and LE 0.5% produced a similar incidence of corneal haze within 6 months after surgery (P = 0.13 at 1 month, P = 0.66 at 3 months, and P = 0.12 at 6 months). There was no statistically significant difference between the two groups in terms of the mean logMAR postoperative uncorrected distance visual acuity (WMD: - 0.00; 95% CI: - 0.01 to 0.00; P = 0.29) and spherical equivalent (WMD: 0.01; 95% CI: - 0.01 to 0.03; P = 0.35). LE 0.5% appears to have a higher tendency to reduce the incidence of ocular hypertension compared FML 0.1%, but there was no statistical significance (RR: 0.63; 95% CI: 0.27 to 1.50; P = 0.30). CONCLUSION: This meta-analysis demonstrated that LE 0.5% and FML 0.1% had comparable efficacy in preventing corneal haze and corticosteroid-induced ocular hypertension, with no difference in visual acuity in patients after corneal refractive surgery.

Safety of KPI-121 Ophthalmic Suspension 0.25% in Patients With Dry Eye Disease: A Pooled Analysis of 4 Multicenter, Randomized, Vehicle-Controlled Studies.

PURPOSE: The safety of KPI-121 0.25%, an ophthalmic nanoparticle suspension of loteprednol etabonate, was evaluated in subjects with dry eye disease (DED) in one phase 2 and three phase 3 randomized trials of similar design. METHODS: Adults with DED received KPI-121 0.25% or vehicle drops 4 times daily (QID) for ≥2 weeks; 1430 subjects received KPI-121 0.25% and 1438 subjects received vehicle drops. Main safety assessments were adverse events (AEs) and intraocular pressure (IOP). As a common side effect associated with the use of ocular corticosteroids is elevated IOP, subjects with a history of or current diagnosis of glaucoma were excluded. RESULTS: Instillation site pain was the most common AE, reported by 5.2% of subjects in the KPI-121 0.25% group and 4.4% of subjects in the vehicle group; other AEs were reported by ≤0.8% of subjects in the KPI-121 group. IOP elevations, a side effect associated with the use of ophthalmic corticosteroids, were observed with low incidence: 0.6% and 0.2% of subjects in the KPI-121 and vehicle groups, respectively. An IOP elevation was defined as an increase from baseline of >5 mm Hg that resulted in an IOP of ≥21 mm Hg in either eye during use of the study product. CONCLUSIONS: KPI-121 ophthalmic suspension 0.25% seemed to be safe and well tolerated when dosed QID for 2 to 4 weeks in those DED subjects included in the 4 trials.

Loteprednol Etabonate for the Treatment of Dry Eye Disease.

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.

Gonioscopy-assisted Transluminal Trabeculotomy in a Pediatric Patient With Steroid-induced Glaucoma.

PURPOSE: To report a case of successful intraocular pressure (IOP) reduction after a 360-degree gonioscopy-assisted transluminal trabeculotomy (GATT) using the iTrack catheter in a patient with steroid-induced glaucoma as a result of treatment of vernal keratoconjunctivitis (VKC). MATERIALS AND METHODS: Case report. RESULTS: An 8-year-old male individual with a long-standing history of VKC, treated with topical steroids, developed elevated IOP and glaucoma in the right eye despite maximum topical glaucoma therapy. Reducing the steroid was not a viable option given the severity of VKC. A 360-degree GATT was successfully performed and IOP has been maintained off all glaucoma drops. CONCLUSIONS: GATT is a viable option for steroid-induced glaucoma in the pediatric population. This obviates the need for riskier, more invasive conjunctival-based procedures.

Effect of Topical Periocular Steroid Use on Intraocular Pressure: A Retrospective Analysis.

PURPOSE: To study the effect of periocular steroid use on intraocular pressure (IOP). METHODS: Charts of adult patients with atopic dermatitis or eczema treated with topical periocular steroid creams and ointments from January 1st, 2007 to October 1st, 2017 were reviewed. Patients with the following were excluded: glaucoma, ocular hypertension, known systemic/topical/injectable steroid history, and lack of documented IOP prior to or during treatment with periocular steroid ointment. Patient data were collected regarding gender, treatment regimen, as well as IOP prior to and during treatment. Steroid responders were identified. Statistical analysis was performed using linear mixed effects models adjusting for follow-up time to test the relationship between pre and posttreatment IOP change adjusting for intereye correlations. RESULTS: Thirty-one patients were identified. Twenty-one were treated bilaterally and 10 unilaterally. Five patients were glaucoma suspects. The mean treatment period was 14.2 weeks with a range of 0.1-83.9 weeks. Patients were treated with fluorometholone (42%), loteprednol etabonate (23%), dexamethasone-neomycin-polymyxin B (13%), hydrocortisone 1% or 2.5% (3%), and tobramycin-dexamethasone (19%). In the combined sample, there was no significant IOP change even after adjusting for follow-up time (mean change: +0.44 mm Hg, p = 0.126). However, eyes with baseline IOP ≥ 14 mm Hg had a significant increase (+0.73 mm Hg/year, p = 0.032). Individual steroid responses included the following: 1 intermediate and 30 low responders, of which 19 patients had an IOP change of <1 mm Hg. One patient had a clinically significant intermediate steroid response of 7 mm Hg. CONCLUSIONS: Periocular steroid treatment causes a statistically significant rise in IOP in eyes with higher baseline IOP measurements, the risk of which increases with follow up. While this change is not always correlated with a clinically significant rise in IOP, clinicians should monitor more closely patients at greatest risk of steroid response.

Submicron loteprednol etabonate ophthalmic gel 0.38% for the treatment of inflammation and pain after cataract surgery.

PURPOSE: To assess the safety and efficacy of a 0.38% submicron formulation of loteprednol etabonate (LE) gel for the treatment of postoperative inflammation and pain after cataract surgery. SETTING: Forty-five United States ophthalmology practices. DESIGN: Double-masked vehicle-controlled randomized parallel group study. METHODS: Patients 18 years of age or older with anterior chamber cells grade 2 or higher on day 1 after uncomplicated cataract surgery were randomized to 14 days of treatment with LE gel 2 times a day, LE gel 3 times a day, or vehicle. Hierarchical primary endpoints were the proportion of patients with resolution of anterior chamber cells and grade 0 (no) pain at postoperative day 8. Safety outcomes included adverse events, intraocular pressure (IOP), biomicroscopy, visual acuity, ophthalmoscopy, and tolerability (drop comfort and ocular symptoms). RESULTS: The intent-to-treat population included 514 patients. Significantly more patients in the LE gel 2 times a day and 3 times a day groups compared with the vehicle group had complete resolution of anterior chamber cells (26.9% and 28.7% versus 9.3%) and reported grade 0 pain (73.7% and 73.1% versus 47.7%) on day 8 (P < .001 vs vehicle for all). The safety findings were unremarkable, with 1 patient experiencing an IOP increase of 10 mm Hg or higher while on LE gel. More than 75% of patients in each group reported no drop discomfort. CONCLUSION: In this study, submicron loteprednol etabonate gel 0.38% appeared safe and effective in the treatment of postoperative inflammation and pain whether instilled 2 times or 3 times a day.

Efficacy and Safety of Loteprednol 0.5% and Fluorometholone 0.1% After Strabismus Surgery in Children.

PURPOSE: To compare the effects of topical loteprednol and fluorometholone in children who underwent strabismus surgery. METHODS: This is a retrospective observational case series. A total of 60 Korean children who underwent strabismus surgery between January 2016 and September 2016 were included. Patients were prescribed topical loteprednol etabonate 0.5% or fluorometholone 0.1% until 3 weeks after surgery. Four parameters (intraocular pressure [IOP], conjunctival injection, conjunctival inflammation, and patient discomfort) were assessed every week for up to 4 weeks after surgery. Main outcome measures were comparison of parameters between the 2 groups at each following week after surgery. In addition, factors associated with clinically meaningful IOP elevation were evaluated. RESULTS: IOP was significantly elevated at the second and third postoperative week compared with baseline (P = 0.028 and 0.001) in the loteprednol group but not significantly in the fluorometholone group. The mean IOP of the loteprednol group at 1 and 3 weeks after surgery were significantly higher than that of the fluorometholone group (P = 0.032 and 0.017, respectively). Multivariate analysis revealed that age ≤8 years (odds ratio 14.52, 95% confidence interval 1.16-139.05) was associated with IOP >21 mmHg. There was no significant difference between the 2 groups in patient discomfort, conjunctival inflammation, and conjunctival injection. CONCLUSIONS: Loteprednol and fluorometholone showed similar anti-inflammatory effect after strabismus surgery in children. Loteprednol appeared to have more effect on IOP elevation than fluorometholone, especially in children ≤8 years of age. When treating young patients with loteprednol, clinicians should be aware of IOP elevation.

Loteprednol etabonate for inflammatory conditions of the anterior segment of the eye: twenty years of clinical experience with a retrometabolically designed corticosteroid.

INTRODUCTION: 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. AREAS COVERED: 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. EXPERT OPINION: 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.

Symptomatic Treatment of Subepithelial Infiltrates after Viral Conjunctivitis: Loteprednol or Dexamethasone?

PURPOSE: To compare the efficiency and ocular side-effect profile of topical loteprednol applied to one eye and topical dexamethasone applied to the other eye in the early period on the same patient who has subepithelial infiltrates (SEI). METHODS: The patients who developed bilateral SEI following epidemic keratoconjunctivitis (EKC) were applied topical loteprednol on one eye (group 2) and topical dexamethasone on the other (group 1). RESULTS: Decrease in the symptoms was faster in the dexamethasone group, but this difference between the groups was not statistically significant (p = 0.073). Both groups were found to have substantial recurrence. However, the difference between the groups was not statistically significant (p = 0.131). CONCLUSIONS: The study has found that in the treatment of SEI, which developed after EKC, statistically similar results can be obtained with loteprednol, which is known to have fewer adverse effects.

Impact of the Topical Ophthalmic Corticosteroid Loteprednol Etabonate on Intraocular Pressure.

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.

Loteprednol etabonate in the treatment of allergic conjunctivitis: a meta-analysis.

OBJECTIVE: This meta-analysis was designed to assess the efficacy, as well as the safety of loteprednol etabonate (LE) ophthalmic suspension compared with placebo and other commonly used eye drops for treatment of allergic conjunctivitis. METHODS: Comprehensive searches of randomized controlled trials were carried out in a database of Medline, Embase, and the Cochrane Library. Eight qualified studies were included. This study assessed the reduction from baseline in scores of cardinal signs and symptoms, proportion of patients with improvement of allergic signs and symptoms, and incidence of clinically significant intraocular pressure (IOP) elevation (IOP elevation ≥10 mmHg). RESULTS: The results showed that topical LE was significantly superior to placebo in reduction from baseline in signs scores (standardized mean difference [SMD] = -0.48; 95% confidence interval [CI] = -0.65 to -0.32) and symptoms scores (weighted mean difference [WMD] = -0.51; 95% CI = -0.64 to -0.38) of allergic conjunctivitis, and as effective as olopatadine and fluorometholone acetate. Topical LE was associated with a higher improvement rate of signs (risk ratio [RR] = 1.53; 95% CI = 1.26-1.86; I (2 )= 57%) and symptoms (RR = 1.29; 95% CI = 1.15-1.46; I (2 )= 54%) than placebo and the positive control treatment. Clinically significant IOP elevation was more frequent in the group of LE than the group of control treatment (pooled odds ratio = 3.03; 95% CI = 1.04-8.80), which was affected by the response to corticosteroid of the individual patient and the wearing of contact lenses. CONCLUSIONS: Topical LE is effective in treating allergic conjunctivitis. However, it should be used with caution due to the higher incidence of IOP elevation compared with placebo and olopatadine. A large-scale trial would be required to confirm the effect of different concentrations of LE on IOP.

Loteprednol Etabonate 0.5% Gel Vs. Prednisolone Acetate 1% Solution After Descemet Membrane Endothelial Keratoplasty: Prospective Randomized Trial.

PURPOSE: To compare intraocular pressure (IOP) elevation and graft rejection with loteprednol etabonate 0.5% gel and prednisolone acetate 1% solution after Descemet membrane endothelial keratoplasty (DMEK). METHODS: In this prospective, evaluator-masked trial, 167 patients were randomized to loteprednol or prednisolone in a 1:1 ratio 1 month after DMEK; 66 fellow eyes were enrolled and assigned to the opposite treatment. Dosing was 4 times daily for 2 months, thrice daily for 1 month, twice daily for 1 month, and once daily for 7 months. The main outcomes were IOP elevation (defined as IOP ≥ 24 mm Hg or an increase of ≥10 mm Hg over the baseline preoperative level) and immunologic rejection episodes, assessed by Kaplan-Meier survival analysis and proportional hazards modeling. RESULTS: A total of 233 eyes were assigned to treatment. Loteprednol etabonate 0.5% gel and prednisolone acetate 1% solution were equally effective in preventing immunologic rejection episodes; none (0%) occurred with either treatment (P = 1). IOP elevation was twice as likely in the prednisolone-treated eyes (relative risk = 2.3, 95% confidence interval: 1.2-4.5, P = 0.016). The proportion with IOP elevation was 25% in prednisolone-treated eyes versus 11% in loteprednol-treated eyes (P = 0.013). In 66 subjects with fellow eyes assigned to opposite treatments, an IOP increase of ≥10 mm Hg was significantly more likely in the prednisolone-treated eye (P = 0.031). CONCLUSIONS: Loteprednol etabonate 0.5% gel was as effective as prednisolone acetate 1% solution in preventing immunologic graft rejection episodes after DMEK and was significantly less likely to cause IOP elevation.Clinical Trial Registration-URL: http://www.clinicaltrials.gov. Unique identifier: NCT01853696.

A randomized controlled trial comparing dexamethasone with loteprednol etabonate on postoperative photorefractive keratectomy.

PURPOSE: To compare loteprednol etabonate 0.5%/tobramycin 0.3% (Zylet(®)) with dexamethasone 0.1%/tobramycin 0.3% (Tobradex(®)) in terms of the epithelial healing time, postoperative visual acuity, corneal haziness score, and intraocular pressure (IOP) in postoperative treatment after photorefractive keratectomy (PRK). METHODS: This prospective, randomized, double-masked (participants and assessors blinded) controlled study included 32 patients who underwent PRK. The patients were allocated equally into 2 groups by block randomization to receive either loteprednol etabonate (Lot) or dexamethasone (Dex) for 1 month after the surgery. The epithelial healing time, uncorrected visual acuity (UCVA), corneal haziness score, and IOP were evaluated at 1 week, 1 month, and 3 months. RESULTS: The corneal epithelium was healed within 3 days in both groups; however, the epithelium was closed on the second day in 3 cases in the Lot group compared with 1 case in the Dex group. No significant differences were found for UCVA at 1 and 3 months (Fisher exact test, P>0.01). Similarly, there was no statistically significant difference in corneal haziness scores between the 2 groups at 1 and 3 months (Mann-Whitney U test, P>0.05). The number of patients experiencing significantly increased IOP (≥5 mmHg) from baseline at any visit for the Lot group (1/16 patients) was fewer than for the Dex group (3/16 patients). CONCLUSIONS: Loteprednol etabonate was effective in postoperative PRK management and was significantly less likely to produce elevations in IOP than was dexamethasone.