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Ophthalmology and Therapy Apr 2023The aim of this case series was to examine the association between unaided binocular visual acuity for near vision and pupil change after the instillation of a special...
INTRODUCTION
The aim of this case series was to examine the association between unaided binocular visual acuity for near vision and pupil change after the instillation of a special topical formulation for presbyopia treatment.
METHODS
This was a case series consisting of consecutive participants with presbyopia aged 40-70 years who were tested for visual acuity and pupil diameter before and 2 h after instillation of a formulation of pilocarpine and phenylephrine drops (FOV Tears) for presbyopia. Participants underwent subjective refraction, photopic and scotopic pupil diameter measurement and unaided monocular and binocular visual acuity testing by logMAR for distance and near vision both pre- and post-instillation of eye drops.
RESULTS
The study enrolled 363 subjects (n = 176 women, 48%) with a mean (± standard deviation) age of 50.4 ± 5.8 years. Mean spherical equivalent (SE) changed significantly (- 0.17 Diopters) after instillation of the FOV Tears formulation (p < 0.001). Post-instillation of eye drops, the scotopic pupil diameter decreased by 0.97 ± 0.98 mm, and the near visual acuity by logMAR improved significantly by nearly two lines (p < 0.01). In the linear regression analyses, age (p < 0.001) and SE pre-drop instillation (p < 0.001) were associated with unaided binocular visual acuity. The changes in photopic pupil diameter and the scotopic pupil diameter were not associated with unaided binocular visual acuity.
CONCLUSIONS
The use of the pilocarpine and phenylephrine formulation (FOV Tears) improved binocular visual acuity for near vision in presbyopic patients, and the effect was independent of pupil change.
PubMed: 36637658
DOI: 10.1007/s40123-023-00648-6 -
Diagnostics (Basel, Switzerland) Dec 2023In this study, we evaluated the effectiveness of a single-dose oral pilocarpine administration on tear film (TF), as well as dry eye and dry mouth symptoms, in 53 eyes...
In this study, we evaluated the effectiveness of a single-dose oral pilocarpine administration on tear film (TF), as well as dry eye and dry mouth symptoms, in 53 eyes of 27 Sjögren syndrome (SS) patients who were experiencing dry mouth. To evaluate the changes in tear volume, a digital video-meniscometer was used to measure the radius of the lower central tear meniscus curvature (R, mm) of each eye at prior to the administration of 5 mg oral pilocarpine, and at 15 (R:(15)), 30 (R:(30)), and 60 (R:(60)) minutes after administration. The fluorescein breakup time (FBUT, seconds) and ocular and oral dryness symptoms were evaluated before and at 60 min after administration using a visual analogue scale (VAS, mm). A significant increase in R was observed at 15 and 30 min after administration compared to that at prior to administration. FBUT showed significant improvement at 60 min after administration, and the VAS score for ocular and oral dryness symptoms was found to have decreased significantly at 60 min after administration. A single-dose administration of 5 mg oral pilocarpine had a beneficial effect on TF, as well as on ocular and oral dryness symptoms, in patients with SS.
PubMed: 38201400
DOI: 10.3390/diagnostics14010091 -
Journal of Ophthalmology 2022To compare the clinical outcomes of the different treatments for acute primary angle closure (APAC).
PURPOSE
To compare the clinical outcomes of the different treatments for acute primary angle closure (APAC).
METHODS
We retrospectively reviewed the clinical charts of 87 eyes of 87 patients undergoing treatment for APAC. We investigated the best spectacle-corrected visual acuity (BSCVA), intraocular pressure (IOP), corneal endothelial cell density (ECD), and secondary interventions after each treatment.
RESULTS
The pretreated IOP was 56.4 ± 9.0 mmHg. As the first treatment for APAC, all eyes underwent topical 2% pilocarpine and systemic mannitol administration. Subsequent laser iridotomy (LI) and lensectomy were necessary in 29 eyes (33%) and 35 eyes (40%), respectively. Bullous keratopathy developed in 1 eye (1%), and following glaucoma surgery was required in 7 eyes (8%). The BSCVA at the final follow-up was 0.16 ± 0.53 and 0.01 ± 0.20 logMAR (Mann-Whitney test, =0.149), the IOP was 12.8 ± 2.6, and 12.6 ± 2.9 mmHg (=0.860), and the ECD was 2295.9 ± 658.2 and 2244.1 ± 622.0 cells/mm (=0.735) in the LI and lensectomy groups, respectively.
CONCLUSIONS
Approximately 26% of eyes with APAC were resolved after the initial medical treatment, and subsequent surgical treatments, such as LI and lensectomy, were required in 33% and 40% of eyes, respectively. We found no significant differences in the BSCVA, the IOP, or the ECD among LI and lensectomy treatment groups.
PubMed: 35677621
DOI: 10.1155/2022/6959479 -
The Journal of Neuroscience : the... Oct 2023A significant proportion of temporal lobe epilepsy (TLE) patients experience drug-resistant seizures associated with mesial temporal sclerosis, in which there is...
A significant proportion of temporal lobe epilepsy (TLE) patients experience drug-resistant seizures associated with mesial temporal sclerosis, in which there is extensive cell loss in the hippocampal CA1 and CA3 subfields, with a relative sparing of dentate gyrus granule cells and CA2 pyramidal neurons (PNs). A role for CA2 in seizure generation was suggested based on findings of a reduction in CA2 synaptic inhibition (Williamson and Spencer, 1994) and the presence of interictal-like spike activity in CA2 in resected hippocampal tissue from TLE patients (Wittner et al., 2009). We recently found that in the pilocarpine-induced status epilepticus (PILO-SE) mouse model of TLE there was an increase in CA2 intrinsic excitability associated with a loss of CA2 synaptic inhibition. Furthermore, chemogenetic silencing of CA2 significantly reduced seizure frequency, consistent with a role of CA2 in promoting seizure generation and/or propagation (Whitebirch et al., 2022). In the present study, we explored the cellular basis of this inhibitory deficit using immunohistochemical and electrophysiological approaches in PILO-SE male and female mice. We report a widespread decrease in the density of pro-cholecystokinin-immunopositive (CCK) interneurons and a functional impairment of CCK interneuron-mediated inhibition of CA2 PNs. We also found a disruption in the perisomatic perineuronal net in the CA2 stratum pyramidale. Such pathologic alterations may contribute to an enhanced excitation of CA2 PNs and CA2-dependent seizure activity in the PILO-SE mouse model. Impaired synaptic inhibition in hippocampal circuits has been identified as a key feature that contributes to the emergence and propagation of seizure activity in human patients and animal models of temporal lobe epilepsy (TLE). Among the hippocampal subfields, the CA2 region is particularly resilient to seizure-associated neurodegeneration and has been suggested to play a key role in seizure activity in TLE. Here we report that perisomatic inhibition of CA2 pyramidal neurons mediated by cholecystokinin-expressing interneurons is selectively reduced in acute hippocampal slices from epileptic mice. Parvalbumin-expressing interneurons, in contrast, appear relatively conserved in epileptic mice. These findings advance our understanding of the cellular mechanisms underlying inhibitory disruption in hippocampal circuits in a mouse model of spontaneous recurring seizures.
Topics: Humans; Male; Female; Mice; Animals; CA2 Region, Hippocampal; Epilepsy, Temporal Lobe; Cholecystokinin; Hippocampus; Interneurons; Seizures; Pilocarpine; Status Epilepticus; Disease Models, Animal
PubMed: 37643861
DOI: 10.1523/JNEUROSCI.2091-22.2023 -
International Journal of Molecular... May 2023Epilepsy is a challenging brain disorder that is often difficult to treat with conventional therapies. The gut microbiota has been shown to play an important role in the...
Epilepsy is a challenging brain disorder that is often difficult to treat with conventional therapies. The gut microbiota has been shown to play an important role in the development of neuropsychiatric disorders, including epilepsy. In this study, the effects of , a probiotic, on inflammation, neuronal degeneration, and behavior are evaluated in a lithium-pilocarpine model of temporal lobe epilepsy (TLE) induced in young adult rats. was administered orally at a dose of 10 CFU/rat for 30 days after pilocarpine injection. The results show that treatment has beneficial effects on the TLE-induced changes in anxiety levels, neuronal death in the amygdala, and body weight recovery. In addition, increased the expression of anti-inflammatory and neuroprotective genes, such as and . However, the probiotic had little effect on TLE-induced astrogliosis and microgliosis and did not reduce neuronal death in the hippocampus and temporal cortex. The study suggests that may have a beneficial effect on TLE and may provide valuable insights into the role of gut bacteria in epileptogenesis. In addition, the results show that may be a promising drug for the comprehensive treatment of epilepsy.
Topics: Rats; Animals; Epilepsy, Temporal Lobe; Pilocarpine; Lithium; Bifidobacterium longum; Hippocampus; Epilepsy; Probiotics; Disease Models, Animal
PubMed: 37176158
DOI: 10.3390/ijms24098451 -
International Journal of Molecular... Apr 2020Epilepsy is a devastating neurological condition exhibited by repeated spontaneous and unpredictable seizures afflicting around 70 million people globally. The basic...
Epilepsy is a devastating neurological condition exhibited by repeated spontaneous and unpredictable seizures afflicting around 70 million people globally. The basic pathophysiology of epileptic seizures is still elusive, reflecting an extensive need for further research. Developing a novel animal model is crucial in understanding disease mechanisms as well as in assessing the therapeutic target. Most of the pre-clinical epilepsy research has been focused on rodents. Nevertheless, zebrafish disease models are relevant to human disease pathophysiology hence are gaining increased attention nowadays. The current study for the very first time developed a pilocarpine-induced chronic seizure-like condition in adult zebrafish and investigated the modulation in several neuroinflammatory genes and neurotransmitters after pilocarpine exposures. Seizure score analysis suggests that compared to a single dose, repeated dose pilocarpine produces chronic seizure-like effects maintaining an average seizure score of above 2 each day for a minimum of 10 days. Compared to the single dose pilocarpine treated group, there was increased mRNA expression of HMGB1, TLR4, TNF-α, IL-1, BDNF, CREB-1, and NPY; whereas decreased expression of NF-κB was upon the repeated dose of pilocarpine administration. In addition, the epileptic group demonstrates modulation in neurotransmitters levels such as GABA, Glutamate, and Acetylcholine. Moreover, proteomic profiling of the zebrafish brain from the normal and epileptic groups from LCMS/MS quantification detected 77 and 13 proteins in the normal and epileptic group respectively. Summing up, the current investigation depicted that chemically induced seizures in zebrafish demonstrated behavioral and molecular alterations similar to classical rodent seizure models suggesting the usability of adult zebrafish as a robust model to investigate epileptic seizures.
Topics: Animals; Chromatography, Liquid; Disease Models, Animal; Dose-Response Relationship, Drug; Female; Gene Expression Regulation; Gene Regulatory Networks; Male; NF-kappa B; Neurotransmitter Agents; Pilocarpine; Proteomics; Seizures; Tandem Mass Spectrometry; Zebrafish; Zebrafish Proteins
PubMed: 32260203
DOI: 10.3390/ijms21072492 -
Applied Bionics and Biomechanics 2022The cellular and molecular mechanisms in pathogenesis and development of epilepsy are still unclear. Specific inflammatory mediators and immune cells may play an...
The cellular and molecular mechanisms in pathogenesis and development of epilepsy are still unclear. Specific inflammatory mediators and immune cells may play an important role. The aim of the present study was to investigate the temporal and spatial changes of Th17, Tregs, and related cytokines in epilepsy lesions. LiCl-pilocarpine-induced temporal lobe epilepsy (TLE) rat models were established, sensorimotor function was examined using modified neurological severity score (mNSS), cognitive function was evaluated by Morris water maze (MWM) test, pathological damages were detected by H&E staining and Nissl staining, helper T cells 17 (Th17), regulatory CD4+ T cells (Tregs), and their related cytokines were detected by Western blotting and immune staining. Results showed that Th17 and its related cytokines in epilepsy lesions played a role mainly at acute phase of epilepsy, and they were positively correlated with the pathological changes in the hippocampus and neurological and cognitive dysfunction caused by epilepsy. Conversely, Tregs and their related cytokines mainly played a role at progressive phase and had the opposite effect. Th17 and Tregs restricted each other during the recovery phase to achieve functional balance. Our results suggested that Th17, Tregs, and related cytokines in epilepsy lesions played an important role in the pathogenesis and development of epilepsy and balancing Th17 and Tregs may be efficacious therapeutics for patients with epilepsy.
PubMed: 35528532
DOI: 10.1155/2022/7871302 -
Cellular, molecular, and therapeutic characterization of pilocarpine-induced temporal lobe epilepsy.Scientific Reports Sep 2021Animal models have expanded our understanding of temporal lobe epilepsy (TLE). However, translating these to cell-specific druggable hypotheses is not explored. Herein,...
Animal models have expanded our understanding of temporal lobe epilepsy (TLE). However, translating these to cell-specific druggable hypotheses is not explored. Herein, we conducted an integrative insilico-analysis of an available transcriptomics dataset obtained from animals with pilocarpine-induced-TLE. A set of 119 genes with subtle-to-moderate impact predicted most forms of epilepsy with ~ 97% accuracy and characteristically mapped to upregulated homeostatic and downregulated synaptic pathways. The deconvolution of cellular proportions revealed opposing changes in diverse cell types. The proportion of nonneuronal cells increased whereas that of interneurons, except for those expressing vasoactive intestinal peptide (Vip), decreased, and pyramidal neurons of the cornu-ammonis (CA) subfields showed the highest variation in proportion. A probabilistic Bayesian-network demonstrated an aberrant and oscillating physiological interaction between nonneuronal cells involved in the blood-brain-barrier and Vip interneurons in driving seizures, and their role was evaluated insilico using transcriptomic changes induced by valproic-acid, which showed opposing effects in the two cell-types. Additionally, we revealed novel epileptic and antiepileptic mechanisms and predicted drugs using causal inference, outperforming the present drug repurposing approaches. These well-powered findings not only expand the understanding of TLE and seizure oscillation, but also provide predictive biomarkers of epilepsy, cellular and causal micro-circuitry changes associated with it, and a drug-discovery method focusing on these events.
Topics: Animals; Anticonvulsants; Biomarkers; Datasets as Topic; Disease Models, Animal; Drug Discovery; Epilepsy, Temporal Lobe; Gene Expression Regulation; Hippocampus; Humans; Interneurons; Male; Mice; Pilocarpine; Pyramidal Cells; RNA-Seq; Single-Cell Analysis; Temporal Lobe
PubMed: 34580351
DOI: 10.1038/s41598-021-98534-3 -
Cancers Nov 2021There has been speculation that IOP-lowering medication, which increases aqueous humor outflow, increases the risk of metastatic uveal melanoma (UM). This hypothesis has...
BACKGROUND
There has been speculation that IOP-lowering medication, which increases aqueous humor outflow, increases the risk of metastatic uveal melanoma (UM). This hypothesis has not been studied previously but is relevant for UM patients who use IOP-lowering medication. The aim of the current study is to assess the association between the use of intraocular pressure (IOP)-lowering medication and the risk of metastatic UM, and mortality.
METHODS
A retrospective cohort study, in which patients from the Rotterdam Ocular Melanoma Study were included from 1986 onwards. Medical records were evaluated for use of IOP-lowering medication at baseline (i.e., before diagnosis). For each IOP-lowering medication, we divided patients into two groups for comparison (e.g., patients with alpha2-agonist use and patients without alpha2-agonist use). All patients underwent regular ophthalmic examinations and routine screening for metastasis. Survival analyses were initiated to compare groups in each IOP-lowering medication group. In addition, secondary analyses were performed to examine the association between IOP and the development of metastatic UM, and mortality.
RESULTS
A total of 707 patients were included of whom 13 patients used prostaglandin or pilocarpine at baseline. For alpha2-agonist, beta-blocker, carbonic anhydrase inhibitor, and oral IOP-lowering medication these were 4, 14, 11, and 12 patients, respectively. The risk of metastatic UM (choroid and ciliary body melanoma) among the prostaglandin/pilocarpine users was significantly higher than controls (HR [95% CI]: 4.840 [1.452-16.133]). Mortality did not differ significantly among the IOP-lowering medications groups, except for the prostaglandin or pilocarpine group (HR [95% CI]: 7.528 [1.836-30.867]). If we combined all IOP-lowering medication that increase aqueous humor outflow, the risk (HR [95% CI]) of metastatic UM and mortality was 6.344 (1.615-24.918) and 9.743 (2.475-38.353), respectively. There was an association between IOP and mortality, but not for the onset of metastatic UM.
CONCLUSION
The use of topical prostaglandin or pilocarpine may increase the risk of metastatic UM and mortality compared to patients without prostaglandin or pilocarpine use. Therefore, use of IOP-lowering medication which increases aqueous humor outflow, should be avoided in patients with (presumed) UM.
PubMed: 34830810
DOI: 10.3390/cancers13225657 -
International Journal of Molecular... Apr 2021Temporal lobe epilepsy (TLE) is one of the most common types of focal epilepsy, characterized by recurrent spontaneous seizures originating in the temporal lobe(s), with... (Review)
Review
Temporal lobe epilepsy (TLE) is one of the most common types of focal epilepsy, characterized by recurrent spontaneous seizures originating in the temporal lobe(s), with mesial TLE (mTLE) as the worst form of TLE, often associated with hippocampal sclerosis. Abnormal epileptiform discharges are the result, among others, of altered cell-to-cell communication in both chemical and electrical transmissions. Current knowledge about the neurobiology of TLE in human patients emerges from pathological studies of biopsy specimens isolated from the epileptogenic zone or, in a few more recent investigations, from living subjects using positron emission tomography (PET). To overcome limitations related to the use of human tissue, animal models are of great help as they allow the selection of homogeneous samples still presenting a more various scenario of the epileptic syndrome, the presence of a comparable control group, and the availability of a greater amount of tissue for in vitro/ex vivo investigations. This review provides an overview of the structural and functional alterations of synaptic connections in the brain of TLE/mTLE patients and animal models.
Topics: Animals; Astrocytes; Disease Susceptibility; Epilepsy, Temporal Lobe; Glutamic Acid; Hippocampus; Humans; Neurons; Oligodendroglia; Receptors, GABA; Receptors, Ionotropic Glutamate; Synapses; Synaptic Transmission; gamma-Aminobutyric Acid
PubMed: 33917911
DOI: 10.3390/ijms22083860