The effects of subconjunctival bupivacaine, lidocaine, and mepivacaine on corneal sensitivity in healthy horses

Jinks, Maggie R.; Fontenot, Robin L.; Wills, Robert W.; Betbeze, Caroline M.

doi:10.1111/vop.12537

Cited by 7 publications

(11 citation statements)

References 42 publications

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“…The SCo injection of voriconazole-thermogel was easily injected in the SCo space and was well tolerated by all the horses, with no evidence of ocular pain observed for up to 23 days. Safety of the technique and behavior of the thermogel were consistent with previous reports of SCo injections in horses and the use of copolymers in ophthalmology [10,24,[38][39][40][41]. Even though there was a significant increase in conjunctival swelling following SCo injection, a score of 2 is considered to be mild [29,30].…”

Section: Discussionsupporting

confidence: 83%

Sustained-release voriconazole-thermogel for subconjunctival injection in horses: ocular toxicity and in-vivo studies

et al. 2020

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Background: Keratomycosis is a relatively common, sight threatening condition in horses, where treatment is often prolonged and costly. Subconjunctival (SCo) injections offer less resistance to drug diffusion than the topical route, resulting in better penetration to the ocular anterior segment. Voriconazole, a second generation triazole antifungal, is effective against common fungal organisms causing keratomycosis. If combined with a thermogel biomaterial, voriconazole can be easily injected in the SCo space to provide sustained drug release. The purpose of this study was to evaluate the drug concentrations in the anterior segment and clinical effects after SCo injections of voriconazole-containing thermogel: poly (DL-lactide-co-glycolide-b-ethylene glycol-b-DL-lactide-co-glycolide) (PLGA-PEG-PLGA) in healthy equine eyes. Results: Voriconazole aqueous humor (AH) and tear concentrations were compared between 6 horses, receiving 1% voriconazole applied topically (0.2 mL, q4h) (Vori-Top) or 1.7% voriconazole-thermogel (0.3 mL) injected SCo (Vori-Gel). For the Vori-Gel group, voriconazole concentrations were measured in AH and tears at day 2 and then weekly for 23 days, and at day 2 only for the Vori-Top group. Ocular inflammation was assessed weekly (Vori-Gel) using the modified Hackett-McDonald scoring system. Ocular tissue concentrations of voriconazole following SCo 1.7% voriconazole-thermogel (0.3 mL) injections were evaluated post euthanasia in 6 additional horses at 3 different time points. Three horses received bilateral injections at 2 h (n = 3, right eye (OD)) and 48 h (n = 3, left eye (OS)) prior to euthanasia, and 3 horses were injected unilaterally (OS), 7 days prior to euthanasia. Voriconazole-thermogel was easily injected and well tolerated in all cases, with no major adverse effects. On day 2, drug concentrations in tears were higher in the Vori-Top, but not statistically different from Vori-Gel groups. For the Vori-Gel group, voriconazole was non-quantifiable in the AH at any time point. Total voriconazole concentrations in the cornea were above 0.5 μg/g (the target minimum inhibitory concentration (MIC) for Aspergillus sp.) for up to 48 h; however, concentrations were below this MIC at 7 days post treatment. Conclusions: Voriconazole-thermogel was easily and safely administered to horses, and provided 48 h of sustained release of voriconazole into the cornea. This drug delivery system warrants further clinical evaluation.

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Section: Discussionsupporting

confidence: 83%

Sustained-release voriconazole-thermogel for subconjunctival injection in horses: ocular toxicity and in-vivo studies

et al. 2020

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“…To suppress neuronal activation in the cornea, 0.5% bupivacaine solution 62,63 was injected (5 µl) subconjuntivally in anesthetized mice with a Hamilton small volume syringe and small hub 33 gauge needle. Then, 5 µl was topically applied onto the cornea.…”

Section: Corneal Nerve Blockmentioning

confidence: 99%

Nerve‐associated transient receptor potential ion channels can contribute to intrinsic resistance to bacterial adhesion in vivo

et al. 2021

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The cornea of the eye differs from other mucosal surfaces in that it lacks a viable bacterial microbiome and by its unusually high density of sensory nerve endings.Here, we explored the role of corneal nerves in preventing bacterial adhesion.Pharmacological and genetic methods were used to inhibit the function of corneal sensory nerves or their associated transient receptor potential cation channels TRPA1 and TRPV1. Impacts on bacterial adhesion, resident immune cells, and epithelial integrity were examined using fluorescent labeling and quantitative confocal imaging. TRPA1/TRPV1 double gene-knockout mice were more susceptible to adhesion of environmental bacteria and to that of deliberatelyinoculated Pseudomonas aeruginosa. Supporting the involvement of TRPA1/ TRPV1-expressing corneal nerves, P. aeruginosa adhesion was also promoted by treatment with bupivacaine, or ablation of TRPA1/TRPV1-expressing nerves using RTX. Moreover, TRPA1/TRPV1-dependent defense was abolished by enucleation which severs corneal nerves. High-resolution imaging showed normal corneal ultrastructure and surface-labeling by wheat-germ agglutinin for TRPA1/ TRPV1 knockout murine corneas, and intact barrier function by absence of fluorescein staining. P. aeruginosa adhering to corneas after perturbation of nerve or TRPA1/TRPV1 function failed to penetrate the surface. Single gene-knockout mice showed roles for both TRPA1 and TRPV1, with TRPA1 −/− more susceptible to P. aeruginosa adhesion while TRPV1 −/− corneas instead accumulated environmental bacteria. Corneal CD45+/CD11c+ cell responses to P. aeruginosa challenge, previously shown to counter bacterial adhesion, also depended on TRPA1/ TRPV1 and sensory nerves. Together, these results demonstrate roles for corneal How to cite this article: Wan SJ, Datta A, Flandrin O, et al. Nerve-associated transient receptor potential ion channels can contribute to intrinsic resistance to bacterial adhesion in vivo.

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“…9 Subconjunctival injection of bupivacaine, lidocaine, and mepivacaine was recently found to provide effective corneal anesthesia in horses. 10 Mepivacaine 2% (0.2 mL) injected subconjunctivally had the fastest onset and longest duration of action (mean 138.8 min) without signs of corneal toxicity. 10 These findings support the use of subconjunctival mepivacaine to provide analgesia for brief standing corneal procedures, therefore it is currently used by some veterinary ophthalmologists.…”

Section: Introductionmentioning

confidence: 94%

“…10 Mepivacaine 2% (0.2 mL) injected subconjunctivally had the fastest onset and longest duration of action (mean 138.8 min) without signs of corneal toxicity. 10 These findings support the use of subconjunctival mepivacaine to provide analgesia for brief standing corneal procedures, therefore it is currently used by some veterinary ophthalmologists. (R. McMullen, personal communication, August 19, 2022).…”

Section: Introductionmentioning

confidence: 94%

Effects of subconjunctival ropivacaine, liposomal bupivacaine, and mepivacaine on corneal sensitivity in healthy horses

et al. 2023

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ObjectiveTo evaluate corneal sensitivity and adverse events following subconjunctival administration of three local anesthetics in horses.Study designRandomized, masked, crossover study.AnimalsTwelve healthy adult mares.MethodsThe subconjunctival space of the treated eye was injected with 0.2 mL of liposomal bupivacaine (1.3%), ropivacaine (0.5%), or mepivacaine (2%). All horses received each medication once and the contralateral eye received saline (control). Corneal touch threshold (CTT) was measured using a Cochet‐Bonnet esthesiometer before sedation, after sedation, and at specified intervals until it returned to baseline. Ocular examinations were performed at 24‐, 72, and 168 h post‐injection to monitor for adverse effects.ResultsThe mean total time of anesthesia (TTA) was 168.3 min for ropivacaine, 169.2 min for liposomal bupivacaine, 103.3 min for mepivacaine and 30.7 min for the control. TTA for liposomal bupivacaine (p < .001) and ropivacaine (p = .001) was longer than the control. TTA for mepivacaine was not different from the control (p = .138), liposomal bupivacaine (p = .075) or ropivacaine (p = .150). Injection site hemorrhage reduced TTA regardless of treatments (p = .047). No adverse effects attributed to injections were noted.ConclusionAll three medications were well tolerated. Subconjunctival administration of ropivacaine and liposomal bupivacaine resulted in longer TTAs compared to the control; however, their TTAs were not different from that of mepivacaine.Clinical significanceSubconjunctivally administered liposomal bupivacaine and ropivacaine are viable options to provide prolonged corneal analgesia in horses. Future studies are needed to assess the efficacy in diseased eyes.

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The effects of subconjunctival bupivacaine, lidocaine, and mepivacaine on corneal sensitivity in healthy horses

Abstract: Subconjunctival injections of lidocaine, bupivacaine, and mepivacaine effectively and safely reduce corneal sensitivity in eyes of healthy horses for 1.5-2 h, and may be useful for providing perioperative analgesia for equine corneal procedures.

Cited by 7 publications

References 42 publications

Sustained-release voriconazole-thermogel for subconjunctival injection in horses: ocular toxicity and in-vivo studies

Sustained-release voriconazole-thermogel for subconjunctival injection in horses: ocular toxicity and in-vivo studies

Nerve‐associated transient receptor potential ion channels can contribute to intrinsic resistance to bacterial adhesion in vivo

Effects of subconjunctival ropivacaine, liposomal bupivacaine, and mepivacaine on corneal sensitivity in healthy horses

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