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The Cochrane Database of Systematic... Oct 2022Dry eye disease (DED), arising from various etiologic factors, leads to tear film instability, ocular surface damage, and neurosensory changes. DED causes symptoms such... (Review)
Review
BACKGROUND
Dry eye disease (DED), arising from various etiologic factors, leads to tear film instability, ocular surface damage, and neurosensory changes. DED causes symptoms such as ocular dryness, burning, itching, pain, and visual impairment. Given their well-established anti-inflammatory effects, topical steroid preparations have been widely used as a short-term treatment option for DED. Because of potential risks of ocular hypertension, cataracts, and infections associated with the long-term use of topical steroids, published trials comparing the efficacy and safety of topical steroids (versus placebo) have mostly been of short duration (three to eight weeks).
OBJECTIVES
To evaluate the effectiveness and safety of topical corticosteroids compared with no treatment, placebo, other steroidal or non-steroidal therapies, or a combination of therapies for DED.
SEARCH METHODS
We searched the Cochrane Central Register of Controlled Trials (CENTRAL, which contains the Cochrane Eyes and Vision Trials Register; 2021, Issue 8); Ovid MEDLINE; Ovid Embase; Latin American and Caribbean Health Sciences database (LILACS); ClinicalTrials.gov; and the World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP), without restriction on language or year of publication. The date of the last search was 20 August 2021.
SELECTION CRITERIA
We included randomized controlled trials (RCTs) in which topical corticosteroids, alone or in combination with tobramycin, were compared with no treatment, artificial tears (AT), vehicles, AT plus tobramycin, or cyclosporine A (CsA).
DATA COLLECTION AND ANALYSIS
We applied standard Cochrane methodology.
MAIN RESULTS
We identified 22 RCTs conducted in the USA, Italy, Spain, China, South Korea, and India. These RCTs reported outcome data from a total of 4169 participants with DED. Study characteristics and risk of bias All trials recruited adults aged 18 years or older, except one trial that enrolled children and adolescents aged between 3 and 14 years. Half of these trials involved predominantly female participants (median 79%, interquartile range [IQR] 76% to 80%). On average, each trial enrolled 86 participants (IQR 40 to 158). The treatment duration of topical steroids ranged between one week and three months; trial duration lasted between one week and six months. Eight trials were sponsored exclusively by industry, and four trials were co-sponsored by industry and institutional or governmental funds. We assessed the risk of bias of both subjective and objective outcomes using RoB 2, finding nearly half of the trials to be at high risk of bias associated with selective outcome reporting. Findings Of the 22 trials, 16 evaluated effects of topical steroids, alone or in combination with tobramycin, as compared with lubricants (AT, vehicle), AT plus tobramycin, or no treatment. Corticosteroids probably have a small to moderate effect on improving patient-reported symptoms by 0.29 standardized mean difference (SMD) (95% confidence interval [CI] 0.16 to 0.42) as compared with lubricants (moderate certainty evidence). Topical steroids also likely have a small to moderate effect on lowering corneal staining scores by 0.4 SMDs (95% CI 0.18 to 0.62) (moderate certainty evidence). However, steroids may increase tear film break-up time (TBUT) slightly (mean difference [MD] 0.70 s, 95% CI 0.06 to 1.34; low certainty evidence) but not tear osmolarity (MD 1.60 mOsm/kg, 95% CI -10.47 to 13.67; very low certainty evidence). Six trials examined topical steroids, either alone or in combination with CsA, against CsA alone. Low certainty evidence indicates that steroid-based interventions may have a small to moderate effect on improving participants' symptoms (SMD -0.33, 95% CI -0.51 to -0.15), but little to no effect on corneal staining scores (SMD 0.05, 95% CI -0.25 to 0.35) as compared with CsA. The effect of topical steroids compared to CsA alone on TBUT (MD 0.37 s, 95% CI -0.13 to 0.87) or tear osmolarity (MD 5.80 mOsm/kg, 95% CI -0.94 to 12.54; loteprednol etabonate alone) is uncertain because the certainty of the evidence is low or very low. None of the included trials reported on quality of life scores. Adverse effects The evidence for adverse ocular effects of topical corticosteroids is very uncertain. Topical corticosteroids may increase participants' risk of intraocular pressure (IOP) elevation (risk ratio [RR] 5.96, 95% CI 1.30 to 27.38) as compared with lubricants. However, when compared with CsA, steroids alone or combined with CsA may decrease or increase IOP elevation (RR 1.45, 95% CI 0.25 to 8.33). It is also uncertain whether topical steroids may increase risk of cataract formation when compared with lubricants (RR 0.34, 95% CI 0.01 to 8.22), given the short-term use and study duration (four weeks or less) to observe longer-term adverse effects. AUTHORS' CONCLUSIONS: Overall, the evidence for the specified review outcomes was of moderate to very low certainty, mostly due to high risk of bias associated with selective results reporting. For dry eye patients whose symptoms require anti-inflammatory control, topical corticosteroids probably provide small to moderate degrees of symptom relief beyond lubricants, and may provide small to moderate degrees of symptom relief beyond CsA. However, the current evidence is less certain about the effects of steroids on improved tear film quality or quantity. The available evidence is also very uncertain regarding the adverse effects of topical corticosteroids on IOP elevation or cataract formation or progression. Future trials should generate high certainty evidence to inform physicians and patients of the optimal treatment strategies with topical corticosteroids in terms of regimen (types, formulations, dosages), duration, and its time-dependent adverse profile.
Topics: Adolescent; Adult; Child; Child, Preschool; Female; Humans; Male; Adrenal Cortex Hormones; Cataract; Cyclosporine; Dry Eye Syndromes; Glucocorticoids; Loteprednol Etabonate; Lubricant Eye Drops; Randomized Controlled Trials as Topic; Tobramycin
PubMed: 36269562
DOI: 10.1002/14651858.CD015070.pub2 -
Clinical Drug Investigation Apr 2020Loteprednol etabonate ophthalmic gel 0.38% (Lotemax SM; hereafter referred to as loteprednol etabonate gel 0.38%) is a topical ophthalmic corticosteroid approved in the... (Review)
Review
Loteprednol etabonate ophthalmic gel 0.38% (Lotemax SM; hereafter referred to as loteprednol etabonate gel 0.38%) is a topical ophthalmic corticosteroid approved in the USA for the treatment of post-operative inflammation and pain following ocular surgery. This formulation provides improved drug delivery compared with loteprednol etabonate micronized gel 0.5%, with a smaller drug particle size (in the submicron range) to improve dissolution and penetration into ocular tissues, meaning less loteprednol etabonate is required to exert therapeutic effect. In two multicentre, randomized phase III trials, significantly more loteprednol etabonate gel 0.38% than vehicle recipients displayed complete resolution of ocular inflammation and ocular pain at day 8 post cataract surgery. Complete resolution of pain was seen as early as post-operative day 3. Treatment-related ocular adverse events in the loteprednol etabonate gel 0.38% group occurred in < 1% of subjects and included one incidence each of photophobia, cystoid macular oedema, eyelid oedema and instillation site pain. Treatment with loteprednol etabonate gel 0.38% had no meaningful impact on intraocular pressure (IOP) or visual acuity. Thus, loteprednol etabonate gel 0.38% extends the treatment options available in resolving post-operative inflammation and pain in patients who have undergone ocular surgery.
Topics: Anti-Allergic Agents; Cataract Extraction; Gels; Humans; Inflammation; Intraocular Pressure; Loteprednol Etabonate; Pain, Postoperative; Postoperative Complications; Randomized Controlled Trials as Topic; Visual Acuity
PubMed: 32172521
DOI: 10.1007/s40261-020-00899-2 -
International Ophthalmology Oct 2012Topical corticosteroids are routinely used as postoperative ocular anti-inflammatory drugs; however, adverse effects such as increased intraocular pressure (IOP) are... (Review)
Review
Topical corticosteroids are routinely used as postoperative ocular anti-inflammatory drugs; however, adverse effects such as increased intraocular pressure (IOP) are observed with their use. While older corticosteroids such as dexamethasone and prednisolone acetate offer good anti-inflammatory efficacy, clinically significant increases in IOP (≥10 mmHg) are often associated with their use. Loteprednol etabonate, a novel C-20 ester-based corticosteroid, was retrometabolically designed to offer potent anti-inflammatory efficacy but with decreased impact on IOP. After exerting its therapeutic effects on the site of action, loteprednol etabonate is rapidly converted to inactive metabolites, resulting in fewer adverse effects. Randomized controlled studies have demonstrated the clinical efficacy and safety of loteprednol etabonate ophthalmic suspension 0.5 % for the treatment of postoperative inflammation in post-cataract patients with few patients, if any, exhibiting clinically significant increases (≥10 mmHg) in IOP. Furthermore, safety studies demonstrated a minimal effect of loteprednol etabonate on IOP with long-term use or in steroid responders with a much lower propensity to increase IOP relative to prednisolone acetate or dexamethasone. The anti-inflammatory treatment effect of loteprednol etabonate appears to be similar to that of rimexolone and difluprednate with less impact on IOP compared to difluprednate, although confirmatory comparative studies are needed. The available clinical data suggest that loteprednol etabonate is an efficacious and safe corticosteroid for the treatment of postoperative inflammation.
Topics: Androstadienes; Animals; Anti-Allergic Agents; Dose-Response Relationship, Drug; Humans; Loteprednol Etabonate; Postoperative Complications; Suspensions; Uveitis, Anterior; Wound Healing
PubMed: 22707339
DOI: 10.1007/s10792-012-9589-2 -
Journal of Ocular Pharmacology and... Sep 2020Dry 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,... (Review)
Review
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.
Topics: Animals; Anti-Allergic Agents; Cyclosporine; Dry Eye Syndromes; Humans; Inflammation; Loteprednol Etabonate; Lubricant Eye Drops; Quality of Life
PubMed: 32391735
DOI: 10.1089/jop.2020.0014 -
Ophthalmology and Therapy Dec 2021Use of a combination corticosteroid and antibiotic in a single formulation is common in the treatment of ocular inflammatory conditions for which corticosteroid therapy... (Review)
Review
Use of a combination corticosteroid and antibiotic in a single formulation is common in the treatment of ocular inflammatory conditions for which corticosteroid therapy is indicated and there exists a risk of superficial bacterial infection. Loteprednol etabonate (LE) is a corticosteroid engineered to maintain potent anti-inflammatory activity while minimizing the risk of undesirable class effects of corticosteroids, such as elevated intraocular pressure and cataract. Tobramycin is a broad-spectrum aminoglycoside antibiotic that is considered generally safe and well tolerated. An ophthalmic suspension combining LE 0.5% and tobramycin 0.3% (LE/T) is approved in the US and several other countries. Use of a combination therapy increases convenience, which may promote patient adherence. A systematic literature review was conducted to examine the efficacy and safety of LE/T for ocular inflammatory conditions within the scope of its labeled indications. Results of published studies indicate that LE/T is effective in the treatment of blepharokeratoconjunctivitis in adults, with similar efficacy as dexamethasone 0.1%/tobramycin 0.3%, but is associated with a lower risk of clinically significant increases in intraocular pressure as demonstrated in both efficacy and safety studies and studies with healthy volunteers. Furthermore, studies in children with blepharitis or blepharoconjunctivitis indicate LE/T was well tolerated in this population, although efficacy vs vehicle was not demonstrated, potentially due to improvements in all groups overall and/or limited sample size. Separately, tobramycin demonstrated potent in vitro activity against most bacterial species associated with blepharitis. In conclusion, published data demonstrate the utility of LE/T for the treatment of the various clinical manifestations of blepharokeratoconjunctivitis in adults.
PubMed: 34708391
DOI: 10.1007/s40123-021-00401-x -
Clinical Ophthalmology (Auckland, N.Z.) 2022Dry eye disease (DED) is a prevalent ocular surface disease. Like with any chronic disease, patients with DED can experience episodic flares. There are many existing and... (Review)
Review
Dry eye disease (DED) is a prevalent ocular surface disease. Like with any chronic disease, patients with DED can experience episodic flares. There are many existing and upcoming treatments for the chronic treatment of DED, yet treatments for DED flares are limited. Loteprednol etabonate 0.25% is an FDA approved treatment modality for the short-term treatment of the signs and symptoms of DED. This medication is formulated with the customized mucus-penetrating particle (MPP) technology, which has a greater ability to penetrate the ocular surface and more effectively deliver the active steroid to the ocular surface tissues as compared with conventional steroid preparations. There is also increasing utility of loteprednol etabonate 0.25% in the treatment of DED before and/or after cataract or refractive surgery or as induction therapy prior to starting chronic immunomodulatory medication for DED.
PubMed: 35173413
DOI: 10.2147/OPTH.S323301 -
Journal of Current Ophthalmology Jun 2018The aim of this study was to compare the ocular hypertensive effect of the commercially available Betamethasone, Fluorometholone in Iran and Loteprednol Etabonate in...
PURPOSE
The aim of this study was to compare the ocular hypertensive effect of the commercially available Betamethasone, Fluorometholone in Iran and Loteprednol Etabonate in patients undergoing keratorefractive surgery.
METHODS
In this prospective randomized clinical trial, 300 eyes of 150 patients were included, and patients were randomly assigned to 3 groups and used one of the 3 steroid drops (Betamethasone 0.1%, Fluorometholone 0.1%, and Loteprednol Etabonate 0.5%) after myopic photorefractive keratectomy (PRK). Intraocular pressure (IOP) was measured 2, 4, and 6 weeks post-surgery. Twenty-two mmHg was set as the threshold IOP for starting anti-glaucoma medication and tapering steroid drops.
RESULTS
Of 300 eyes from 150 patients over the first 6 postoperative weeks, 2 eyes in Fluorometholone group (2%), 12 eyes in Betamethasone group (12%), and 16 eyes in Loteprednol group (16%) had IOP equal or more than 22 mmHg. Analysis of variance (ANOVA) test showed that the rise in IOP was significantly different between groups in the 2nd and 4th ( ≤ 0.001) postoperative weeks but not at 6th week ( = 0.230). An IOP rise equal or more than 10 mmHg was detected in 13 and 15 eyes in Betamethasone and Loteprednol groups, respectively. None of the eyes in Fluorometholone group had such an IOP rise.
CONCLUSIONS
Loteprednol and Fluorometholone were associated with the most and least increase in IOP, respectively. The highest pressures were detected 4 weeks after surgery in the Betamethasone and Loteprednol groups and 6 weeks after surgery in the Fluorometholone group. Fluorometholone was the safest among the three examined steroid drops in terms of IOP rise.
PubMed: 29988925
DOI: 10.1016/j.joco.2017.11.008 -
Advances in Therapy Apr 2016Corticosteroids are a mainstay therapeutic option for the treatment of ocular inflammation. However, safety remains a concern for clinicians, particularly with long-term... (Review)
Review
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
PubMed: 26984315
DOI: 10.1007/s12325-016-0315-8 -
Clinical Ophthalmology (Auckland, N.Z.) 2014Pterygium, a sun-related eye disease, presents as wing-shaped ocular surface lesions that extend from the bulbar conjunctiva onto the cornea, most commonly on the nasal... (Review)
Review
Pterygium, a sun-related eye disease, presents as wing-shaped ocular surface lesions that extend from the bulbar conjunctiva onto the cornea, most commonly on the nasal side. Pterygia show characteristic histological features that suggest that inflammation plays a prominent role in their initial pathogenesis and recurrence. Appropriate surgery is the key to successful treatment of pterygia, but there is also a rationale for the use of anti-inflammatory agents to reduce the rate of recurrence following surgery. Multiple surgical techniques have been developed over the last two millennia, but these initially had little success, due to high rates of recurrence. Current management strategies, associated with lower recurrence rates, include bare sclera excision and various types of grafts using tissue glues. Adjunctive therapies include mitomycin C and 5-fluorouracil, as well as the topical ocular steroid loteprednol etabonate, which has been shown to have a lower risk of elevated intraocular pressure than have the other topical ocular steroids. Here, the surgical management of pterygium is presented from a historical perspective, and current management techniques, including the appropriate use of various adjunctive therapies, are reviewed, along with an illustrative case presentation and a discussion of the conjunctival forceps designed to facilitate surgical management. Despite thousands of years of experience with this condition, there remains a need for a more thorough understanding of pterygium and interventions to reduce both its incidence and postsurgical recurrence. Until that time, the immediate goal is to optimize surgical practices to ensure the best possible outcomes. Loteprednol etabonate, especially the ointment formulation, appears to be a safe and effective component of the perioperative regimen for this complex ocular condition, although confirmatory prospective studies are needed.
PubMed: 24966664
DOI: 10.2147/OPTH.S55259 -
Journal of Cataract and Refractive... Oct 2018To 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... (Randomized Controlled Trial)
Randomized Controlled Trial
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.
Topics: Adult; Aged; Aged, 80 and over; Anti-Allergic Agents; Double-Blind Method; Eye Pain; Female; Gels; Humans; Inflammation; Intraocular Pressure; Loteprednol Etabonate; Male; Microscopy, Acoustic; Middle Aged; Ophthalmoscopy; Phacoemulsification; Postoperative Complications; Treatment Outcome; Visual Acuity
PubMed: 30193927
DOI: 10.1016/j.jcrs.2018.06.056