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Investigative Ophthalmology & Visual... Nov 2023The incidence of myopia has rapidly increased in recent decades, making it a growing public health concern worldwide. Interventions to suppress the progression of myopia...
PURPOSE
The incidence of myopia has rapidly increased in recent decades, making it a growing public health concern worldwide. Interventions to suppress the progression of myopia are needed; one suggested strategy is the prevention of choroidal thinning, which can improve choroidal blood perfusion (ChBP). Bunazosin hydrochloride (BH) is an alpha1-adrenergic blocker and commercialized glaucoma eye drop that increases in blood circulation in the eye. In this study, we evaluated the efficacy of BH in suppressing the progression of myopia in a lens-induced murine model.
METHODS
Lens-induced myopia was induced in 3-week-old C57BL/6 J mice with -30 diopter (D) lenses for three weeks. Refractive error, axial length, and choroidal thickness were evaluated at three and six weeks of age using an infrared photorefractor and a spectral domain optical coherence tomography (OCT) system. Moreover, ChBP and scleral thickness were evaluated using swept-source OCT and histological analysis.
RESULTS
Compared with the controls, the administration of BH eye drops suppressed the myopic shift of refractive error (mean difference ± standard error in the eye with -30 D lens, -13.65 ± 5.69 D vs. 2.55 ± 4.30 D; P < 0.001), axial elongation (0.226 ± 0.013 mm vs. 0.183 ± 0.023 mm; P < 0.05), choroidal thinning (-2.01 ± 1.80 µm vs. 1.88 ± 1.27 µm; P < 0.001), and scleral thinning (11.41 ± 3.91 µm vs. 19.72 ± 4.01 µm; P < 0.01) with myopia progression and increased ChBP (52.0% ± 4.1% vs. 59.5% ± 6.3%; P < 0.05). The suppressive effect of BH eye drops was dose-dependent and higher than that of other glaucoma eye drops and alpha1 blockers.
CONCLUSIONS
These results demonstrate the potential of BH eye drops in the treatment of myopia and support further investigation of their efficacy in humans. Further studies are needed to determine the mechanism of action and long-term safety of this treatment.
Topics: Humans; Animals; Mice; Mice, Inbred C57BL; Myopia; Refractive Errors; Glaucoma; Ophthalmic Solutions; Perfusion
PubMed: 37955611
DOI: 10.1167/iovs.64.14.15 -
BMC Ophthalmology Oct 2023To investigate the efficacy and safety of 0.1% and 0.01% low-dose atropine eye drops in reducing myopia progression in Danish children. (Randomized Controlled Trial)
Randomized Controlled Trial
Safety and efficacy of 0.01% and 0.1% low-dose atropine eye drop regimens for reduction of myopia progression in Danish children: a randomized clinical trial examining one-year effect and safety.
BACKGROUND
To investigate the efficacy and safety of 0.1% and 0.01% low-dose atropine eye drops in reducing myopia progression in Danish children.
METHODS
Investigator-initiated, placebo-controlled, double-masked, randomized clinical trial. Ninety-seven six- to twelve-year old myopic participants were randomized to 0.1% loading dose for six months followed by 0.01% for six months (loading dose group, Number (N) = 33), 0.01% for twelve months (0.01% group, N = 32) or vehicle for twelve months (placebo, N = 32). Primary outcomes were axial length and spherical equivalent refraction. Secondary outcomes included adverse events and reactions, choroidal thickness and ocular biometry. Outcomes were measured at baseline and three-month intervals. Data was analyzed with linear-mixed model analysis according to intention-to-treat.
RESULTS
Mean axial elongation was 0.10 mm less (95% confidence interval (CI): 0.17; 0.02, adjusted-p = 0.06) in the 0.1% loading dose and 0.07 mm less (95% CI: 0.15; 0.00, adjusted-p = 0.16) in the 0.01% group at twelve months compared to placebo. Mean spherical equivalent refraction progression was 0.24 D (95% CI: 0.05; 0.42) less in the loading dose and 0.19 D (95% CI: 0.00; 0.38) less in the 0.01% groups at twelve months, compared to placebo (adjusted-p = 0.06 and 0.14, respectively). A total of 108 adverse events were reported during the initial six-month loading dose period, primarily in the loading dose group, and 14 were reported in the six months following dose switching, all deemed mild except two serious adverse events, unrelated to the intervention.
CONCLUSIONS
Low-dose atropine eye drops are safe over twelve months in otherwise healthy children. There may be a modest but clinically relevant reduction in myopia progression in Danish children after twelve months treatment, but the effect was statistically non-significant after multiple comparisons adjustment. After dose-switching at six months the loading dose group approached the 0.01% group, potentially indicating an early "rebound-effect".
TRIAL REGISTRATION
this study was registered in the European Clinical Trials Database (EudraCT, number: 2018-001286-16) 05/11/2018 and first posted at www.
CLINICALTRIALS
gov (NCT03911271) 11/04/2019, prior to initiation.
Topics: Child; Humans; Atropine; Ophthalmic Solutions; Myopia; Refraction, Ocular; Denmark; Disease Progression; Axial Length, Eye
PubMed: 37904082
DOI: 10.1186/s12886-023-03177-9 -
Clinical Nutrition (Edinburgh, Scotland) Apr 2024Albumin is a relatively small molecule with a radius of 7.5 nm and a molecular weight of 65 kDa. It is the most abundant protein in plasma, accounting for 60-75% of...
Albumin is a relatively small molecule with a radius of 7.5 nm and a molecular weight of 65 kDa. It is the most abundant protein in plasma, accounting for 60-75% of its oncotic pressure. Its concentration in plasma is merely one static measurement reflecting a dynamic and complex system of albumin physiology, and is the net result of several different processes, one or more of which may become deranged by disease or its treatment. It is also unsurprising that hypoalbuminaemia has proved to be an indicator of morbidity and mortality risk since the underlying conditions which cause it, including protein energy malnutrition, crystalloid overload, inflammation, and liver dysfunction are themselves risk factors. In some cases, its underlying cause may require treatment but mostly it is just a parameter to be monitored and used as one measure of clinical progress or deterioration. While malnutrition, associated with a low protein intake, may be a contributory cause of hypoalbuminaemia, in the absence of inflammation and/or dilution with crystalloid its development in response to malnutrition alone is slow compared with the rapid change caused by inflammatory redistribution or dilution with crystalloids. Other significant causes include liver dysfunction and serous losses. These causal factors may occur singly or in combination in any particular case. Treatment is that of the underlying causes and associated conditions such as a low plasma volume, not of hypoalbuminaemia per se.
Topics: Humans; Hypoalbuminemia; Clinical Relevance; Albumins; Inflammation; Malnutrition; Crystalloid Solutions; Liver Diseases
PubMed: 38394971
DOI: 10.1016/j.clnu.2024.02.018 -
Survey of Ophthalmology 2024Vernal keratoconjunctivitis (VKC) is a chronic, progressive, and potentially sight-threatening form of ocular inflammatory disease that primarily affects children and... (Review)
Review
Vernal keratoconjunctivitis (VKC) is a chronic, progressive, and potentially sight-threatening form of ocular inflammatory disease that primarily affects children and young adults. Prevalence varies by region, ranging from <2 per 10,000 in the United States to as high as 1,100 per 10,000 in parts of Africa. The rarity of VKC in developed countries can make differential diagnosis challenging, and treatment is often delayed until the disease is advanced, and symptoms are significantly impacting patients' quality of life. Although once viewed primarily as an immunoglobulin E-mediated condition, approximately 50% of patients with VKC do not exhibit allergic sensitization. It is now recognized that the immunopathology of VKC involves multiple inflammatory pathways that lead to the signs, symptoms, and conjunctival eosinophilic and fibroproliferative lesions that are a hallmark of the disease. We examine the evolution of our understanding of the immunopathology of VKC, the expanding VKC treatment armamentarium, the clinical implications of emerging treatment approaches, and future directions for VKC research and practice.
Topics: Child; Humans; Conjunctivitis, Allergic; Cyclosporine; Quality of Life; Conjunctiva; Ophthalmic Solutions
PubMed: 37890678
DOI: 10.1016/j.survophthal.2023.10.008 -
Journal of Artificial Organs : the... Jun 2024Excessive albumin losses during HC (haemocatharsis) are considered a potential cause of hypoalbuminemia-a key risk factor for mortality. This review on total albumin... (Review)
Review
Excessive albumin losses during HC (haemocatharsis) are considered a potential cause of hypoalbuminemia-a key risk factor for mortality. This review on total albumin losses considers albumin "leaking" into the dialysate and losses due to protein/membrane interactions (i.e. adsorption, "secondary membrane formation" and denaturation). The former are fairly easy to determine, usually varying at the level of ~ 2 g to ~ 7 g albumin loss per session. Such values, commonly accepted as representative of the total albumin losses, are often quoted as limits/standards of permissible albumin loss per session. On albumin mass lost due to adsorption/deposition, which is the result of complicated interactions and rather difficult to determine, scant in vivo data exist and there is great uncertainty and confusion regarding their magnitude; this is possibly responsible for neglecting their contribution to the total losses at present. Yet, many relevant in vitro studies suggest that losses of albumin due to protein/membrane interactions are likely comparable to (or even greater than) those due to leaking, particularly in the currently favoured high-convection HDF (haemodiafiltration) treatment. Therefore, it is emphasised that top research priority should be given to resolve these issues, primarily by developing appropriate/facile in vivo test-methods and related analytical techniques.
Topics: Humans; Dialysis Solutions; Hemodiafiltration; Hypoalbuminemia; Renal Dialysis; Serum Albumin
PubMed: 38238597
DOI: 10.1007/s10047-023-01430-y -
Journal of Endodontics Aug 2023Laser ablation (LA) therapy is used as an adjunct to endodontic treatment to improve microbial reduction. However, studies evaluating the impact of LA with indocyanine... (Randomized Controlled Trial)
Randomized Controlled Trial
INTRODUCTION
Laser ablation (LA) therapy is used as an adjunct to endodontic treatment to improve microbial reduction. However, studies evaluating the impact of LA with indocyanine green (ICG) are scarce. This study aimed to evaluate the antimicrobial efficacy of LA therapy with ICG in root canal treatment.
METHODS
Sixty patients with periapical lesions in teeth with a single canal and absence of pain, edema, and previous treatment were selected. Patients were randomly allocated into 3 groups according to the apical sizes used (n = 20); 25/04, 30/04, and 35/04 were the final sizes used. In half the patients of each group, 2.5% sodium hypochlorite was used as an irrigating solution, and in the other half, saline solution was used. After instrumentation, all patients received LA therapy with ICG. Root canal sampling was performed before (S1) and after (S2) root canal instrumentation and immediately after LA therapy with ICG (S3). Colony-forming units were counted, and statistical tests were applied (P < .05).
RESULTS
There was a significant reduction in colony-forming units from S1 to S2 in all treatment protocols (P < .05); 2.5% sodium hypochlorite as an irrigating solution showed a greater microbial reduction compared with saline solution (P < .05). LA therapy with ICG further reduced the microbial counts significantly (S2 to S3 and S1 to S3) whether sodium hypochlorite or saline was used (P < .05).
CONCLUSIONS
LA therapy with ICG significantly increased microbial reduction in root canals regardless of instrumentation sizes or the irrigation solution used.
Topics: Humans; Dental Pulp Cavity; Sodium Hypochlorite; Indocyanine Green; Saline Solution; Root Canal Preparation; Root Canal Therapy; Anti-Infective Agents; Laser Therapy; Root Canal Irrigants
PubMed: 37355163
DOI: 10.1016/j.joen.2023.06.009 -
Renal Failure Dec 2023Patients with diabetic kidney disease (DKD) are at increased risk to develop post-contrast acute kidney injury (AKI). Diabetic patients under dipeptidyl peptidase 4... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
Patients with diabetic kidney disease (DKD) are at increased risk to develop post-contrast acute kidney injury (AKI). Diabetic patients under dipeptidyl peptidase 4 inhibitors (DPP4Is) experience a lower propensity to develop AKI. We speculated that linagliptin as a single agent or in combination with allopurinol may reduce the incidence of post-contrast AKI in stage 3-5 chronic kidney disease (CKD) patients with underlying DKD.
METHODS
Out of 951 DKD patients eligible for this study, 800 accepted to sign informed consent. They were randomly allocated to 4 equal groups that received their prophylaxis for 2 days before and after radiocontrast. The first control group received N-acetyl cysteine and saline, the 2 received allopurinol, the 3 group received linagliptin, and the 4 received both allopurinol and linagliptin. Post-procedure follow-up for kidney functions was conducted for 2 weeks in all patients.
RESULTS
20, 19, 14, and 8 patients developed post-contrast AKI in groups 1 through 4, respectively. Neither linagliptin nor allopurinol was superior to N-acetyl cysteine and saline alone. However, the combination of the two agents provided statistically significant renal protection: post-contrast AKI in group 4 was significantly lower than in groups 1 and 2 ( < 0.02 and <0.03, respectively). None of the post-contrast AKI cases required dialysis.
CONCLUSION
Linagliptin and allopurinol in combination may offer protection against post-contrast AKI in DKD exposed to radiocontrast. Further studies are needed to support this view.
TRIAL REGISTRATION CLINICALTRIALS.GOV
NCT03470454.
Topics: Humans; Acute Kidney Injury; Allopurinol; Diabetic Nephropathies; Kidney Failure, Chronic; Linagliptin; Prospective Studies; Renal Insufficiency, Chronic; Contrast Media; Chemoprevention; Drug Therapy, Combination; Acetylcysteine; Protective Agents; Saline Solution
PubMed: 36974638
DOI: 10.1080/0886022X.2023.2194434 -
The American Journal of Managed Care Oct 2023Dry eye disease (DED) is a common condition in which tear film abnormalities result in a damaging cycle of tear hyperosmolarity, desiccating stress, inflammation, and...
Dry eye disease (DED) is a common condition in which tear film abnormalities result in a damaging cycle of tear hyperosmolarity, desiccating stress, inflammation, and ocular surface injury. In a healthy tear film, meibum produced by the meibomian glands forms a lipid layer that stabilizes the tear film and protects against aqueous tear evaporation. Excessive tear evaporation due to a deficient lipid layer is believed to be the most common cause of DED, and most evaporative DED is associated with meibomian gland dysfunction (MGD); this highlights the pathophysiologic importance of the dysfunctional tear lipid layer. Current treatments for DED may be used to supplement hyperosmolar aqueous tears, lubricate the ocular surface, increase meibum flow, decrease inflammation, promote tear production, or otherwise decrease clinical signs of ocular surface damage and/or improve symptoms. Until now, no prescription eye drop has directly addressed the excessive evaporation that occurs in most patients with DED. Perfluorohexyloctane (PFHO) ophthalmic solution (MIEBO™; Bausch + Lomb) is a preservative-free eye drop that has demonstrated the ability to form a long-lasting barrier that inhibits evaporation in preclinical studies. FDA approval of PFHO was based on results from 2 pivotal clinical trials (GOBI [NCT04139798] and MOJAVE [NCT04567329]) in patients with DED and clinical signs of MGD which demonstrated consistent improvements in both signs and symptoms of disease, with a safety profile similar to that of saline eye drops. PFHO is the first and only FDA-approved eye drop that directly targets tear evaporation in patients with DED, thereby promoting ocular surface healing and providing symptomatic relief.
Topics: Humans; Dry Eye Syndromes; Inflammation; Lipids; Meibomian Glands; Ophthalmic Solutions; Clinical Trials as Topic
PubMed: 37844320
DOI: 10.37765/ajmc.2023.89448 -
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