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Journal of Ocular Pharmacology and... Apr 2022Topical, local anesthetic eye drops in conjunction with antibiotics are commonly used to reduce ocular pain and treat patients in emergency clinics; however, their...
Topical, local anesthetic eye drops in conjunction with antibiotics are commonly used to reduce ocular pain and treat patients in emergency clinics; however, their effects on corneal healing are poorly understood. This study examined whether regular or diluted proparacaine eye drops given in combination with common ophthalmic antibiotics affect corneal wound healing parameters using and models. Primary human corneal fibroblasts generated from donor corneas and New Zealand white rabbits were used. Regular (0.5%) and diluted (0.05%) proparacaine eye drops, twice daily for 3 days, were applied to cultures and rabbit eyes, with or without ophthalmic antibiotics (polymyxin B sulfate and trimethoprim). Trypan blue, 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide (MTT), and scratch wound assays measured cellular viability, proliferation, and migration, respectively, Slit lamp biomicroscopy, tonometry, fluorescein eye test, hematoxylin and eosin (H&E) staining, and 4',6-diamidino-2-phenylindole (DAPI) immunofluorescence were used for studies. Both regular and diluted proparacaine affected wound healing response in the cornea and in a time-dependent manner. Adjunct antibiotic treatments had additive effects characterized by reduced corneal fibroblast viability, proliferation, and migration and corneal epithelial recovery . Regular proparacaine with antibiotics showed most pronounced effects on corneal wound healing parameters, and diluted proparacaine without antibiotics had minimal negative effects and . Both methods of regular (0.5%) and diluted (0.05%) proparacaine topical application to the cornea are safe, but impede corneal wound healing and . Adjunct antibiotic treatments had additive negative effects on corneal wound repair.
Topics: Anesthetics, Local; Animals; Anti-Bacterial Agents; Cornea; Corneal Injuries; Humans; Ophthalmic Solutions; Propoxycaine; Rabbits; Wound Healing
PubMed: 35275738
DOI: 10.1089/jop.2021.0116 -
Journal of Ocular Pharmacology and... Jun 2021To evaluate whether the standard dilating drop regimen consisting of phenylephrine, tropicamide, and proparacaine produces clinically significant improvement in pupil... (Comparative Study)
Comparative Study Randomized Controlled Trial
To evaluate whether the standard dilating drop regimen consisting of phenylephrine, tropicamide, and proparacaine produces clinically significant improvement in pupil size compared to tropicamide and proparacaine during diagnostic eye examination. Sixty-three adult patients at Washington University School of Medicine Eye Clinic were enrolled in this prospective, randomized trial. Each patient received one of two dilating drop regimens: phenylephrine + tropicamide + proparacaine (PE+T+PP), which is considered the standard therapy, or tropicamide + proparacaine (T+PP). Main outcome measures were the proportion of pupils able to achieve successful clinical examination without need for additional dilating drops and change in predilation to postdilation pupil size. Comparisons were made using McNemar's test, repeated measures analysis of variance, and Fisher's test to determine whether PE is a necessary component of the standard eye examination. There were no statistically significant differences between the PE+T+PP and T+PE treatment groups in predilation to postdilation changes in average resting pupil size (1.58 ± 0.66 and 2.61 ± 0.79; = 0.57) or constricted pupil size (2.52 ± 0.93 and 3.56 ± 0.96; = 0.15). There was no statistically significant difference between patients who obtained a successful dilated pupil examination between those receiving PE+T+PP and those receiving T+PP as determined by the examining physicians (Fisher's, = 0.67). The addition of phenylephrine to tropicamide and proparacaine did not improve pupillary dilation size or ability to conduct a clinical examination. A single dilating agent using tropicamide should be considered in clinical practice.
Topics: Adult; Aged; Anesthetics, Local; Diagnostic Techniques, Ophthalmological; Drug Interactions; Drug Therapy, Combination; Female; Humans; Male; Middle Aged; Mydriatics; Ophthalmic Solutions; Outcome Assessment, Health Care; Phenylephrine; Propoxycaine; Prospective Studies; Pupil; Tropicamide
PubMed: 33685234
DOI: 10.1089/jop.2020.0111 -
Anaesthesia Sep 2013
Topics: Anesthetics, Local; Female; Humans; Lidocaine; Male; Ophthalmologic Surgical Procedures; Propoxycaine; Strabismus
PubMed: 24047369
DOI: 10.1111/anae.12406 -
The Journal of Toxicological Sciences Aug 2015Proparacaine is a widely used topical anesthetic in ophthalmic optometry and surgery, and has been reported to have cytotoxic effects on rabbit corneal endothelial cells...
Proparacaine is a widely used topical anesthetic in ophthalmic optometry and surgery, and has been reported to have cytotoxic effects on rabbit corneal endothelial cells after prolonged and repeated usage. Since rabbit is an exceptive mammal whose corneal endothelial cells still maintaining proliferation abilities even in adulthood, whether proparacaine has cytotoxic effects on human corneal endothelial (HCE) cells need to be further verified. Our objectives in the present study were to investigate the cytotoxicity to HCE cells of proparacaine and its underlying mechanisms in vitro and verify the cytotoxicity using cat corneal endothelial (CCE) cells in an in vivo model of cat corneas. Cytotoxic evaluation results indicated that a dose- and time-dependent toxic response of HCE cells to proparacaine over 0.03125% was rated based on morphology and viability, and a toxic response of CCE cells to 0.5% (clinical applied dosage) proparacaine was also rated based on cell density and histology. Importantly, treatment with proparacaine resulted in significant elevation of plasma membrane permeability, cell cycle arrest at S phase, fragmentation of genomic DNA, formation of apoptotic bodies, and externalization of phosphatidylserine (PS) of HCE cells. Moreover, proparacaine demonstrated disrupting effects on mitochondrial transmembrane potential (MTP) of HCE cells and activating effects on caspase-3, -8 and -9. This study demonstrates that proparacaine has notable cytotoxicity to both HCE cells in vitro and CCE cells in vivo, and its dose- and time-dependent cytotoxicity to HCE cells is achieved by inducing apoptosis via a mitochondrion-mediated caspase-dependent pathway. These findings provide new insights into the cytotoxicity and apoptosis-inducing effect of local anesthetics which should be used with great caution in the eye clinic.
Topics: Anesthetics, Local; Animals; Apoptosis; Caspases; Cats; Cell Cycle; Cell Membrane Permeability; Cells, Cultured; DNA Fragmentation; Dose-Response Relationship, Drug; Endothelial Cells; Endothelium, Corneal; Humans; Membrane Potential, Mitochondrial; Phosphatidylserines; Propoxycaine; Rabbits; S Phase; Time Factors
PubMed: 26165639
DOI: 10.2131/jts.40.427 -
Investigative Ophthalmology & Visual... May 2015Dry eye disease (DED) produces ocular pain and irritation, yet a detailed characterization of ocular sensitivity in a preclinical model of DED is lacking. The aim of the...
PURPOSE
Dry eye disease (DED) produces ocular pain and irritation, yet a detailed characterization of ocular sensitivity in a preclinical model of DED is lacking. The aim of the present study was to assess nociceptive behaviors in an aqueous tear deficiency model of DED in the rat.
METHODS
Spontaneous blinking, corneal mechanical thresholds, and eye wipe behaviors elicited by hypertonic saline (5.0 M) were examined over a period of 8 weeks following the unilateral excision of either the exorbital lacrimal gland or of the exorbital and infraorbital lacrimal glands, and in sham surgery controls. The effect of topical proparacaine on spontaneous blinking and of systemic morphine (0.5-3.0 mg/kg, subcutaneous [SC]) on spontaneous blinking and eye wipe responses were also examined.
RESULTS
Lacrimal gland excision resulted in mechanical hypersensitivity and an increase in spontaneous blinking in the ipsilateral eye over an 8-week period that was more pronounced after infra- and exorbital gland excision. The time spent eye wiping was also enhanced in response to hypertonic saline (5.0 M) at both 1- and 8-week time-points, but only in infra- and exorbital gland excised animals. Morphine attenuated spontaneous blinking, and the response to hypertonic saline in dry eye animals and topical proparacaine application reduced spontaneous blinking down to control levels.
CONCLUSIONS
These results indicate that aqueous tear deficiency produces hypersensitivity in the rat cornea. In addition, the increase in spontaneous blinks and their reduction by morphine and topical anesthesia indicate the presence of persistent irritation elicited by the activation of corneal nociceptors.
Topics: Analgesics, Opioid; Analysis of Variance; Anesthetics, Local; Animals; Blinking; Cornea; Disease Models, Animal; Dry Eye Syndromes; Fluorescein Angiography; Lacrimal Apparatus; Male; Morphine; Propoxycaine; Rats; Rats, Sprague-Dawley; Sensory Thresholds; Tears
PubMed: 26024120
DOI: 10.1167/iovs.15-16717 -
Diabetes Aug 2008Protein kinase C (PKC)-delta, an upstream regulator of the Akt survival pathway, contributes to cellular dysfunction in the pathogenesis of diabetes. Herein, we examined...
OBJECTIVE
Protein kinase C (PKC)-delta, an upstream regulator of the Akt survival pathway, contributes to cellular dysfunction in the pathogenesis of diabetes. Herein, we examined the role of PKC-delta in neuronal apoptosis through Akt in the retinas of diabetic rats.
RESEARCH DESIGN AND METHODS
We used retinas from 24- and 35-week-old male Otsuka Long-Evans Tokushima fatty (OLETF) diabetic and Long-Evans Tokushima Otsuka (LETO) nondiabetic rats. To assess whether PKC-delta affects Akt signaling and cell death in OLETF rat retinas, we examined 1) PKC-delta activity and apoptosis; 2) protein levels of phosphatidylinositol 3-kinase (PI 3-kinase) p85, heat shock protein 90 (HSP90), and protein phosphatase 2A (PP2A); 3) Akt phosphorylation; and 4) Akt binding to HSP90 or PP2A in LETO and OLETF retinas in the presence or absence of rottlerin, a highly specific PKC-delta inhibitor, or small interfering RNAs (siRNAs) for PKC-delta and HSP90.
RESULTS
In OLETF retinas from 35-week-old rats, ganglion cell death, PKC-delta and PP2A activity, and Akt-PP2A binding were significantly increased and Akt phosphorylation and Akt-HSP90 binding were decreased compared with retinas from 24-week-old OLETF and LETO rats. Rottlerin and PKC-delta siRNA abrogated these effects in OLETF retinas from 35-week-old rats. HSP90 siRNA significantly increased ganglion cell death and Akt-PP2A complexes and markedly decreased HSP90-Akt binding and Akt phosphorylation in LETO retinas from 35-week-old rats compared with those from nontreated LETO rats.
CONCLUSIONS
PKC-delta activation contributes to neuro-retinal apoptosis in diabetic rats by inhibiting Akt-mediated signaling pathways.
Topics: Acetophenones; Animals; Apoptosis; Benzopyrans; Body Weight; Diabetes Mellitus, Type 2; HSP90 Heat-Shock Proteins; Immunoblotting; Immunohistochemistry; Immunoprecipitation; In Situ Nick-End Labeling; Male; Neurons; Pentobarbital; Phosphatidylinositol 3-Kinases; Propoxycaine; Protein Binding; Protein Kinase C-delta; Protein Phosphatase 2; Proto-Oncogene Proteins c-akt; RNA, Small Interfering; Rats; Rats, Inbred OLETF; Retina; Retinal Ganglion Cells; Signal Transduction
PubMed: 18443201
DOI: 10.2337/db07-1431 -
Psychiatria Danubina Sep 2019
Review
Topics: Behavior, Addictive; Diagnostic Errors; Eye Pain; Humans; Male; Middle Aged; Ophthalmic Solutions; Patient Satisfaction; Prescription Drug Misuse; Propoxycaine; Self Medication
PubMed: 31596831
DOI: 10.24869/psyd.2019.360 -
New application of an old drug proparacaine in treating epilepsy via liposomal hydrogel formulation.Pharmacological Research Jul 2021Proparacaine (PPC) is a previously discovered topical anesthetic for ophthalmic optometry and surgery by blocking the central Nav1.3. In this study, we found that...
Proparacaine (PPC) is a previously discovered topical anesthetic for ophthalmic optometry and surgery by blocking the central Nav1.3. In this study, we found that proparacaine hydrochloride (PPC-HCl) exerted an acute robust antiepileptic effect in pilocarpine-induced epilepsy mice. More importantly, chronic treatment with PPC-HCl totally terminated spontaneous recurrent seizure occurrence without significant toxicity. Chronic treatment with PPC-HCl did not cause obvious cytotoxicity, neuropsychiatric adverse effects, hepatotoxicity, cardiotoxicity, and even genotoxicity that evaluated by whole genome-scale transcriptomic analyses. Only when in a high dose (50 mg/kg), the QRS interval measured by electrocardiography was slightly prolonged, which was similar to the impact of levetiracetam. Nevertheless, to overcome this potential issue, we adopt a liposome encapsulation strategy that could alleviate cardiotoxicity and prepared a type of hydrogel containing PPC-HCl for sustained release. Implantation of thermosensitive chitosan-based hydrogel containing liposomal PPC-HCl into the subcutaneous tissue exerted immediate and long-lasting remission from spontaneous recurrent seizure in epileptic mice without affecting QRS interval. Therefore, this new liposomal hydrogel formulation of proparacaine could be developed as a transdermal patch for treating epilepsy, avoiding the severe toxicity after chronic treatment with current antiepileptic drugs in clinic.
Topics: Animals; Anticonvulsants; Drug Delivery Systems; Electroencephalography; Epilepsy; Hindlimb Suspension; Hydrogels; Liposomes; Male; Maze Learning; Mice, Inbred C57BL; Open Field Test; Propoxycaine; Mice
PubMed: 33932606
DOI: 10.1016/j.phrs.2021.105636 -
BMJ Case Reports Apr 2013A 72-year-old man was admitted to our clinic because of pain in the right eye. Corneal oedema, peripheral anterior synechiae formation and intraocular lens were...
A 72-year-old man was admitted to our clinic because of pain in the right eye. Corneal oedema, peripheral anterior synechiae formation and intraocular lens were determined in the right eye. The left eye was normal except for nuclear sclerosis. Intraocular pressure was 35 mm Hg in the right eye and 14 mm Hg in the left eye. The patient was diagnosed as having bullous keratopathy and glaucoma. He was treated with antiglaucoma drugs and artificial tears as an outpatient. Persistent keratopathy was observed at follow-up, despite adequate therapy. In the detailed anamnesis of the patient, we discovered that he had used a topical anaesthetic instead of the prescribed medicine owing to ocular pain. The patient was still using topical anaesthetic eye drops, despite warnings. Finally, evisceration was performed on his right eye because of corneal melting and perforation.
Topics: Administration, Topical; Aged; Anesthetics, Local; Corneal Diseases; Eye Evisceration; Glaucoma; Humans; Male; Ophthalmic Solutions; Propoxycaine
PubMed: 23608875
DOI: 10.1136/bcr-2013-009539 -
Cornea Jul 2013Ocular local anesthetics currently used in routine clinical practice for corneal anesthesia are short acting and their ability to delay corneal healing makes them...
PURPOSE
Ocular local anesthetics currently used in routine clinical practice for corneal anesthesia are short acting and their ability to delay corneal healing makes them unsuitable for long-term use. In this study, we examined the effect of the site 1 sodium channel blocker tetrodotoxin (TTX) on the duration of corneal anesthesia, applied with either proparacaine (PPC) or the chemical permeation enhancer octyl-trimethyl ammonium bromide (OTAB). The effect of test solutions on corneal healing was also studied.
METHODS
Solutions of TTX, PPC, and OTAB, singly or in combination, were applied topically to the rat cornea. The blink response, an indirect measure of corneal sensitivity, was recorded using a Cochet-Bonnet esthesiometer, and the duration of corneal anesthesia was calculated. The effect of test compounds on the rate of corneal epithelialization was studied in vivo after corneal debridement.
RESULTS
Combination of TTX and PPC resulted in corneal anesthesia that was 8 to 10 times longer in duration than that from either drug administered alone, whereas OTAB did not prolong anesthesia. The rate of corneal healing was moderately delayed after coadministration of TTX and PPC.
CONCLUSIONS
Coadministration of TTX and PPC significantly prolonged corneal anesthesia, but in view of delayed corneal reepithelialization, caution is suggested in the use of the drug combination.
Topics: Anesthesia, Local; Anesthetics, Combined; Anesthetics, Local; Animals; Cell Line; Chemistry, Pharmaceutical; Cornea; Corneal Keratocytes; Epithelium, Corneal; Humans; Male; Propoxycaine; Quaternary Ammonium Compounds; Rats; Rats, Sprague-Dawley; Sodium Channel Blockers; Tetrodotoxin; Time Factors; Wound Healing
PubMed: 23615270
DOI: 10.1097/ICO.0b013e31828cbfe6