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American Journal of Ophthalmology Feb 2024To report the heterogeneity in methodology of clinical trials submitted to the US Food and Drug Administration (FDA) for approval of topical dry eye treatments. (Review)
Review
PURPOSE
To report the heterogeneity in methodology of clinical trials submitted to the US Food and Drug Administration (FDA) for approval of topical dry eye treatments.
DESIGN
Comparative analysis of clinical trials' methods.
METHODS
We reviewed the online, publicly available FDA database, application review files, ClinicalTrials.gov registry records, and journal articles for each FDA-approved topical dry eye treatment. For each trial, we extracted information about the study, patient demographics, treatment names and doses, sample size in each arm, and the measurement instrument in a systematic fashion.
RESULTS
Fourteen trials were included that assessed 5 topical treatments for dry eye (cyclosporine 0.05%, cyclosporine 0.09%, lifitegrast 5%, and loteprednol 0.25% eye drops and varenicline 0.03-mg nasal spray). Median treatment duration was 12 weeks (range, 2-24 weeks). In all trials, treatments, including varying concentrations of the same treatment, were compared with vehicle. Twelve trials (85.7%) evaluated a primary clinician-measured clinical sign, and 10 trials (71.4%) evaluated a primary patient-reported symptom. Corneal staining was the most frequently evaluated clinical sign primary outcome, reported in half (6 of 12) of the trials, and was graded using 4 different scoring systems. Conjunctival staining, conjunctival hyperemia, and tear production were each measured using 2 different scoring systems. Ocular discomfort, the only patient-reported symptom primary outcome, was measured using 5 different instruments.
CONCLUSION
A variety of outcome measures were used in these clinical trials. Clinically meaningful dry eye outcome measures and standardized measurements can optimize the assessment of and comparison of therapeutic benefits.
Topics: Humans; Dry Eye Syndromes; Cyclosporine; Ophthalmic Solutions; Administration, Topical; Conjunctiva
PubMed: 37793479
DOI: 10.1016/j.ajo.2023.09.024 -
Translational Vision Science &... Nov 2023Trabecular meshwork (TM) fibrosis is a crucial pathophysiological process in the development of primary open-angle glaucoma. Pirfenidone (PFD) is a new, broad-spectrum...
PURPOSE
Trabecular meshwork (TM) fibrosis is a crucial pathophysiological process in the development of primary open-angle glaucoma. Pirfenidone (PFD) is a new, broad-spectrum antifibrotic agent approved for the treatment of idiopathic pulmonary fibrosis. This study investigated the inhibitory effect of PFD on TM fibrosis and evaluated its efficacy in lowering intraocular pressure (IOP).
METHODS
Human TM cells were isolated, cultured, and characterized. Cell Counting Kit-8 was used to evaluate the proliferation and toxicity of different concentrations of PFD on normal or fibrotic TM cells. TM cells were treated with transforming growth factor beta-2 (TGF-β2) in the absence or presence of PFD. Western blotting and immunofluorescence analyses were used to analyze changes in the TM cell cytoskeleton and extracellular matrix (ECM) proteins, including alpha-smooth muscle actin (α-SMA), F-actin, collagen IV (COL IV), and fibronectin (FN). An ocular hypertension (OHT) mouse model was induced with Ad-TGF-β2C226/228S and then treated with PFD or latanoprost (LT) eye drops to confirm the efficacy of PFD in lowering IOP.
RESULTS
PFD inhibited the proliferation of fibrotic TM cells in a dose-dependent manner and inhibited TGF-β2-induced overexpression of α-SMA, COL IV, and FN in TM cells. PFD stabilized F-actin. In vivo, PFD eye drops reduced the IOP of the OHT models and showed no significant difference compared with LT eye drops.
CONCLUSIONS
PFD inhibited TGF-β2-induced TM cell fibrosis by rearranging the disordered cytoskeleton and decreasing ECM deposition, thereby enhancing the aqueous outflow from the TM outflow pathway and lowering IOP, which provides a potential new approach to treating glaucoma.
TRANSLATIONAL RELEVANCE
Our work with pirfenidone provides a new approach to treat glaucoma.
Topics: Animals; Humans; Mice; Actins; Cells, Cultured; Fibrosis; Glaucoma; Glaucoma, Open-Angle; Ocular Hypertension; Ophthalmic Solutions; Trabecular Meshwork; Transforming Growth Factor beta2
PubMed: 37975842
DOI: 10.1167/tvst.12.11.21 -
BMC Ophthalmology Nov 2023Dry eye disease (DED) is a disorder characterized by loss of tear film homeostasis that causes ocular surface inflammation and damage. The incidence of DED increases...
Real-world treatment patterns of OTX-101 ophthalmic solution, cyclosporine ophthalmic emulsion, and lifitegrast ophthalmic solution in patients with dry eye disease: a retrospective analysis.
BACKGROUND
Dry eye disease (DED) is a disorder characterized by loss of tear film homeostasis that causes ocular surface inflammation and damage. The incidence of DED increases with age. Cyclosporine ophthalmic solution 0.09% (CEQUA; OTX-101), cyclosporine ophthalmic emulsion 0.05% (Restasis; CsA), and lifitegrast ophthalmic solution 5% (Xiidra; LFT) are anti-inflammatory agents indicated for DED. This analysis compared treatment patterns in patients with DED receiving OTX-101, CsA, or LFT.
METHODS
This real-world, retrospective, longitudinal cohort study utilized Symphony Health Integrated Dataverse claims from July 2019 to June 2021. The dataset included all patients with OTX-101 claims and patients with CsA or LFT claims randomly selected 2:1 to OTX-101. Patients were sorted into 3 cohorts based on index treatment. Index date was that of first treatment claim, and follow-up period was from index date to end of clinical activity or data availability. Time to treatment discontinuation (TTD), probability of discontinuation, and treatment persistence were assessed for OTX-101 vs. CsA, then OTX-101 vs. LFT. Subgroup analysis was performed based on age and prior DED treatment. Kaplan-Meier analysis and log-rank test were used to examine TTD. A logistic model evaluated association between index treatment and discontinuation. Unadjusted and adjusted odds ratios, 95% confidence intervals, and P-values were reported, with statistically significant associations based on P-values < 0.05.
RESULTS
Overall, 7102 patients (OTX-101 n = 1846; CsA n = 2248; LFT n = 3008) were eligible. Median TTD was 354 days for patients receiving OTX-101 vs. 241 days for CsA and 269 days for LFT. Log-rank test indicated TTD was significantly longer for patients on OTX-101 vs. CsA (P = 0.033). Patients on CsA were 35% more likely to discontinue treatment than patients on OTX-101; OTX-101 and LFT groups had similar discontinuation rates. After 360 days, 49.8% of patients receiving OTX-101 remained on treatment vs. 39.4% of patients on CsA (P = 0.036) and 44.0% of patients on LFT (P = 0.854).
CONCLUSIONS
Patients receiving OTX-101 remained on treatment significantly longer and were significantly less likely to discontinue treatment than patients on CsA. Older patients remained on OTX-101 significantly longer than CsA. These findings highlight treatment pattern differences in patients with DED receiving these anti-inflammatory agents.
Topics: Humans; Ophthalmic Solutions; Emulsions; Retrospective Studies; Longitudinal Studies; Dry Eye Syndromes; Cyclosporine; Anti-Inflammatory Agents
PubMed: 37919692
DOI: 10.1186/s12886-023-03174-y -
Therapeutic Apheresis and Dialysis :... Dec 2023Hemodialysis is considered a treatment of choice for patients with renal failure worldwide, allowing the replacement of some kidney functions by diffusion and... (Review)
Review
Hemodialysis is considered a treatment of choice for patients with renal failure worldwide, allowing the replacement of some kidney functions by diffusion and ultrafiltration processes. Over 4 million people require some form of renal replacement therapy, with hemodialysis being the most common. During the procedure, contaminants in the water and the resulting dialysate may pass into the patient's blood and lead to toxicity. Thus, the quality of the associated dialysis solutions is a critical issue. Accordingly, the discussion of the importance of a dialysis water delivery system controlled by current standards and recommendations, with efficient monitoring methods, disinfection systems, and chemical and microbiological analysis, is crucial for improving the health outcomes of these patients. The importance of treatment, monitoring, and regulation is emphasized by presenting several case studies concerning the contamination of hemodialysis water and the adverse effects on the respective patients.
Topics: Humans; Water Quality; Renal Dialysis; Dialysis Solutions; Ultrafiltration; Continuous Renal Replacement Therapy; Hemodialysis Solutions
PubMed: 37381091
DOI: 10.1111/1744-9987.14032 -
BMJ Case Reports Sep 2023A man in his 70s on regular follow-up with an ophthalmologist for 10 years presented with blurry vision in his right eye for 4 days. He was diagnosed with elevated...
A man in his 70s on regular follow-up with an ophthalmologist for 10 years presented with blurry vision in his right eye for 4 days. He was diagnosed with elevated intraocular pressure (IOP) bilaterally 18 months earlier and treated with antiglaucoma eye-drops. On direct questioning, he admitted to using fixed combination tobramycin 0.3%/dexamethasone 0.1% eye-drops frequently to relieve ocular redness and discomfort in both eyes for 3.5 years without his ophthalmologist's knowledge. Examination disclosed markedly elevated IOP, advanced optic disc cupping and tunnel vision due to steroid-induced glaucoma bilaterally. After cessation of the eye-drops and 2 weeks of antiglaucoma therapy, his IOP returned to normal and his visual field remained stable for 4 years.Our case highlights the danger of habitual self-treatment of prescription medications containing corticosteroids and the importance of taking a detailed medication history in the diagnosis and management of steroid-induced glaucoma.
Topics: Glaucoma; Humans; Male; Aged; Blindness; Tobramycin, Dexamethasone Drug Combination; Glucocorticoids; Ophthalmic Solutions; Self Medication; Withholding Treatment
PubMed: 37666571
DOI: 10.1136/bcr-2023-254709 -
Acta Ophthalmologica Feb 2024The morphological changes in the cornea and crystalline lens have not been closely evaluated after the administration of atropine 0.01%. This study aims to evaluate the... (Randomized Controlled Trial)
Randomized Controlled Trial
PURPOSE
The morphological changes in the cornea and crystalline lens have not been closely evaluated after the administration of atropine 0.01%. This study aims to evaluate the radii of curvature and refractive power of the cornea and lens in myopic eyes during atropine 0.01% treatment.
METHODS
Children aged 6-14 years with myopia <-6.0 D were randomized to receive atropine 0.01% once nightly with single vision lenses or simply wear single vision lenses. Ocular biometric parameters were measured using the IOLMaster 700 biometry and the radii of corneal and lenticular curvature were simulated using a customized program.
RESULTS
At the 9-month visit, 69 atropine-treated eyes and 50 control eyes were included in the final analyses. In atropine-treated eyes, the posterior corneal surface steepened (-0.05 ± 0.13 mm) and the anterior lenticular surface flattened (0.20 ± 0.69 mm) significantly within 3-6 months, whereas the posterior corneal surface and anterior lenticular surface gradually flattened (0.07 ± 0.23 and 0.32 ± 0.80 mm respectively) in the control eyes over 9 months. The difference in the change of corneal refractive power was significant between groups (-0.03 ± 0.18 D vs. 0.11 ± 0.24 D, p = 0.001), while that in the change of lenticular refractive power was statistically insignificant (0.01 ± 0.92 D vs. -0.22 ± 0.86 D, p = 0.161).
CONCLUSIONS
The administration of atropine 0.01% exhibited a clinically short and subtle impact on the cornea and lens, which may shed light on new targets of action for atropine in inhibiting myopia.
Topics: Child; Humans; Atropine; Cornea; Corneal Topography; Lens, Crystalline; Myopia; Ophthalmic Solutions; Radius; Refraction, Ocular; Adolescent
PubMed: 37143398
DOI: 10.1111/aos.15679 -
Journal of Investigational Allergology... Dec 2023Ocular allergy covers a series of immune-allergic inflammatory diseases of the ocular surface, with different degrees of involvement and severity. These pathologies are... (Review)
Review
Ocular allergy covers a series of immune-allergic inflammatory diseases of the ocular surface, with different degrees of involvement and severity. These pathologies are caused by a variety of IgE- and non-IgE-mediated immune mechanisms and may involve all parts of the external eye, including the conjunctiva, cornea, eyelids, tear film, and commensal flora. The most frequent is allergic conjunctivitis, a condition with different clinical forms that are classified according to the degree of involvement and the presence or absence of proliferative changes in the palpebral conjunctiva, associated atopic dermatitis, and mechanical stimuli by foreign bodies, including contact lenses. Treatment guidelines for allergic conjunctivitis propose a stepwise approach that includes medications for both ophthalmic and oral administration depending on symptom severity, allergic comorbidities, and degree of control. In the case of antihistamines, eye drops are the most prescribed ophthalmic formulations. To avoid disrupting the delicate balance of the ocular surface, topical ophthalmic medications must be well tolerated. The primary aim of this article is to review the physicochemical characteristics and other features of excipients (preservative agents, buffers, pH adjusters, viscosity enhancers, wetting agents or cosolvents, antioxidants, tonicity adjusters, and osmo-protectants) and active compounds (ocular antihistamines) that must be considered when developing formulations for ophthalmic administration of antihistamines. We also provide a brief overview of antihistamine eye drops that could be of interest to professionals treating ocular allergy and encourage the use of preservative-free formulations when possible.
Topics: Humans; Conjunctivitis, Allergic; Histamine Antagonists; Histamine H1 Antagonists; Ophthalmic Solutions
PubMed: 38095492
DOI: 10.18176/jiaci.0963 -
Advances in Therapy Sep 2023This multicenter, randomized, comparative, and investigator-masked crossover clinical trial sought to compare the efficacy and tolerability of fixed combinations of 0.1%... (Randomized Controlled Trial)
Randomized Controlled Trial
Randomized Multicenter Clinical Trial Comparing 0.1% Brimonidine/0.5% Timolol Versus 1% Dorzolamide/0.5% Timolol as Adjuncts to Prostaglandin Analogues: Aibeta Crossover Study.
INTRODUCTION
This multicenter, randomized, comparative, and investigator-masked crossover clinical trial sought to compare the efficacy and tolerability of fixed combinations of 0.1% brimonidine/0.5% timolol (BTFC) versus 1% dorzolamide/0.5% timolol (DTFC) as adjunctive therapies to prostaglandin analogues.
METHODS
A total of 110 patients with open-angle glaucoma or ocular hypertension previously treated with prostaglandin analogue monotherapy were randomized to receive either BTFC or DTFC as adjunctive therapy for 8 weeks. These patients were then crossed over to the alternative treatment arm for another 8 weeks. The reduction in intraocular pressure (IOP) (primary outcome), occurrence of adverse events, ocular discomfort after instillation, and patient preference (secondary outcomes) were recorded through patient interviews.
RESULTS
BTFC instillation for 8 weeks reduced IOP by 3.55 mmHg, demonstrating non-inferiority to DTFC instillation (3.60 mmHg; P < 0.0001, mixed-effects model). Although adverse events were rare with both combinations, patients reported greater discomfort with DTFC than with BTFC (P < 0.0001). More patients preferred BTFC (P < 0.0001) over DTFC, as BTFC caused minimal or no eye irritation.
CONCLUSION
As BTFC offered better tolerability than DTFC with comparable reduction in IOP, we recommend it as an alternative for patients who experience ocular discomfort with DTFC-prostaglandin analogue combination therapy.
TRIAL REGISTRATION NUMBER
jRCTs051190125.
Topics: Humans; Timolol; Glaucoma, Open-Angle; Cross-Over Studies; Antihypertensive Agents; Ophthalmic Solutions; Brimonidine Tartrate; Intraocular Pressure; Prostaglandins, Synthetic; Drug Combinations
PubMed: 37452961
DOI: 10.1007/s12325-023-02589-9 -
Journal of Nephrology Sep 2023This systematic review summarises the stability of less commonly prescribed antibiotics in different peritoneal dialysis solutions that could be used for... (Review)
Review
BACKGROUND
This systematic review summarises the stability of less commonly prescribed antibiotics in different peritoneal dialysis solutions that could be used for culture-directed therapy of peritonitis, which would be especially useful in regions with a high prevalence of multidrug antibiotic-resistant strains.
METHODS
A literature search of Medline, Scopus, Embase and Google Scholar for articles published from inception to 25 January, 2023 was conducted. Only antibiotic stability studies conducted in vitro and not recently reviewed by So et al. were included. The main outcomes were chemical, physical, antimicrobial and microbial stability. This protocol was registered in PROSPERO (registration number CRD42023393366).
RESULTS
We screened 1254 abstracts, and 28 articles were included in the study. In addition to those discussed in a recent systematic review (So et al., Clin Kidney J 15(6):1071-1078, 2022), we identified 18 antimicrobial agents. Of these, 9 have intraperitoneal dosing recommendations in the recent International Society for Peritoneal Dialysis (ISPD) peritonitis guidelines, and 7 of the 9 had stability data applicable to clinical practice. They were cefotaxime, ceftriaxone, daptomycin, ofloxacin, and teicoplanin in glucose-based solutions, tobramycin in Extraneal solution only and fosfomycin in Extraneal, Nutrineal, Physioneal 1.36% and 2.27% glucose solutions.
CONCLUSIONS
Physicochemical stability has not been demonstrated for all antibiotics with intraperitoneal dosing recommendations in the ISPD peritonitis guidelines. Further studies are required to determine the stability of antibiotics, especially in icodextrin-based and low-glucose degradation products, pH-neutral solutions.
Topics: Humans; Anti-Bacterial Agents; Dialysis Solutions; Glucose; Icodextrin; Peritoneal Dialysis; Peritonitis
PubMed: 37548827
DOI: 10.1007/s40620-023-01716-7 -
Efficacy and safety of atropine in myopic children: A meta-analysis of randomized controlled trials.Journal Francais D'ophtalmologie Oct 2023To evaluate the safety and efficacy of atropine for childhood myopia and further explore the optimal concentration of atropine, so as to provide more reference for... (Meta-Analysis)
Meta-Analysis
PURPOSE
To evaluate the safety and efficacy of atropine for childhood myopia and further explore the optimal concentration of atropine, so as to provide more reference for clinical application.
METHODS
PubMed, Embase, Cochrane Library and ClinicalTrials.gov were comprehensively searched for randomized controlled trials (RCTs) up to October 14, 2021. The efficacy outcomes were progression of spherical equivalent (SE) and axial length (AL). The safety outcomes included accommodation amplitude, pupil size and adverse effects. The meta-analysis was performed using Review Manager 5.3.
RESULTS
Eighteen RCTs involving 3002 eyes were included. The results showed that at 6-36 months of treatment, atropine was effective in slowing the progression of myopia in children. At 12 months, the WMD of SE and AL of low-dose atropine was 0.25 diopters (D) and 0.1 millimeter (mm), moderate-dose atropine was 0.44 D and 0.16mm, high-dose atropine was 1.21 D and 0.82mm, respectively, compared with the control group. Similarly, at 24 months, low-dose atropine was 0.22 D and 0.14mm, moderate-dose atropine was 0.60 D, high-dose atropine was 0.66 D and 0.24mm, respectively. Interestingly, we also found that there was no significant difference in the effects of low-dose atropine on accommodation amplitude and photopic pupil size compared with the control group, and the rate of photophobia, allergy, blurred vision and other side effects was similar between the low-dose atropine group and the control group. In addition, atropine appears to be more effective in myopic children in China than in other countries.
CONCLUSIONS
Atropine in various concentrations can effectively slow myopia progression in children, and its effect is dose-dependent, while low-dose atropine (0.01% atropine) appears to be safer.
Topics: Child; Humans; Atropine; Ophthalmic Solutions; Randomized Controlled Trials as Topic; Myopia; Refraction, Ocular; Disease Progression
PubMed: 37147148
DOI: 10.1016/j.jfo.2023.01.030