Duration of corneal anesthesia following topical administration of 0.5% proparacaine hydrochloride solution in clinically normal cats

Daniel R. Binder Department of Small Animal Clinical Sciences, Virginia-Maryland Regional College of Veterinary Medicine, Virginia Polytechnic Institute and State University, Blacksburg, VA 24061-0442.

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Ian P. Herring Department of Small Animal Clinical Sciences, Virginia-Maryland Regional College of Veterinary Medicine, Virginia Polytechnic Institute and State University, Blacksburg, VA 24061-0442.

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Abstract

Objective—To determine duration of corneal anesthesia following topical administration of 0.5% proparacaine hydrochloride solution in domestic shorthair (DSH) cats.

Animals—20 clinically normal DSH cats.

Procedures—Baseline corneal touch threshold (CCT) was established by use of a Cochet-Bonnet aesthesiometer. Treatment consisted of a single 50-μL topical application of an ophthalmic preparation of 0.5% proparacaine solution to a randomly selected eye of each cat. The corneal touch threshold was assessed 1 and 5 minutes after application to the cornea and at 5- minute intervals thereafter for 60 minutes.

Results—Corneal sensitivity, as determined by Cochet-Bonnet aesthesiometry, was significantly reduced from baseline for 25 minutes following topical administration of ophthalmic proparacaine. Maximal anesthetic effect lasted 5 minutes.

Conclusions and Clinical Relevance—As determined by Cochet-Bonnet aesthesiometry, duration of anesthetic effects on the cornea induced by a single topical application of an ophthalmic preparation of 0.5% proparacaine solution in DSH cats is considerably shorter than the reported duration of corneal anesthesia in dogs.

Abstract

Objective—To determine duration of corneal anesthesia following topical administration of 0.5% proparacaine hydrochloride solution in domestic shorthair (DSH) cats.

Animals—20 clinically normal DSH cats.

Procedures—Baseline corneal touch threshold (CCT) was established by use of a Cochet-Bonnet aesthesiometer. Treatment consisted of a single 50-μL topical application of an ophthalmic preparation of 0.5% proparacaine solution to a randomly selected eye of each cat. The corneal touch threshold was assessed 1 and 5 minutes after application to the cornea and at 5- minute intervals thereafter for 60 minutes.

Results—Corneal sensitivity, as determined by Cochet-Bonnet aesthesiometry, was significantly reduced from baseline for 25 minutes following topical administration of ophthalmic proparacaine. Maximal anesthetic effect lasted 5 minutes.

Conclusions and Clinical Relevance—As determined by Cochet-Bonnet aesthesiometry, duration of anesthetic effects on the cornea induced by a single topical application of an ophthalmic preparation of 0.5% proparacaine solution in DSH cats is considerably shorter than the reported duration of corneal anesthesia in dogs.

Topical administration of ophthalmic anesthetic agents, such as 0.5% proparacaine solution, is regularly used to facilitate diagnostic and therapeutic procedures such as tonometry, corneal and conjunctival scraping, corneal suture and foreign body removal, and intracameral injection. Proparacaine is commonly used because of its predictability and minimal adverse effects following topical administration.1

Although widely used in veterinary medicine, duration of corneal anesthesia induced by topical administration of proparacaine has only recently been quantified in a study2 on dogs. Results of that study revealed a significant anesthetic effect from a single drop of ophthalmic proparacaine for up to 45 minutes after topical administration, with a maximal effect lasting 15 minutes. Duration of anesthesia was prolonged with multiple-drop administration. Previous to that study, knowledge on the efficacy and duration of this drug in companion animals was solely based on clinical experience,3 rather than objectively determined data. A similar lack of objective data currently exists on the duration of corneal anesthesia induced by topical administration of proparacaine in cats.

In a limited number of other studies,4–6 duration of corneal anesthesia induced by topical administration of proparacaine in other species, including rabbits and humans, has been investigated. Considering the variation in corneal innervation and sensitivity found among species,7 the duration of corneal anesthesia for this drug in cats should not be assumed on the basis of data obtained from other species. The purpose of the study reported here was to establish the duration of the anesthetic effect following topical administration of an ophthalmic preparation of 0.5% proparacaine solution in clinically normal DSH cats by use of Cochet-Bonnet aesthesiometry.

Materials and Methods

Animals—Twenty adult DSH cats were used in the study. Cats were included if they had no history of corneoconjunctival disease or evidence of corneal or adnexal disease, as determined by slit-lamp biomicroscopic examination. Cats with abnormal Schirmer tear test values were excluded from the study. Cats with Schirmer tear test values of > 5 mm/min were considered to have Schirmer tear test values within reference range. The study group comprised 13 spayed females and 7 neutered males. Mean ± SD age was 5.5 ± 3.1 years. The Animal Care and Use Committee of Virginia Tech approved the protocol for all procedures in the study.

Treatment—One randomly selected eye was tested in each cat (10 right eyes, 10 left eyes). A commercially available anesthetic ophthalmic solution was used, containing 0.5% proparacaine hydrochloridea and inactive ingredients (0.01% benzalkonium chloride preservative, glycerin, purified water, sodium chloride, and hydrochloric acid or sodium hydroxide to adjust the pH to between 5.0 and 6.0). Treatment consisted of topical administration of 50 μL of the ophthalmic anesthetic agent, and time of treatment was designated as time 0. Corneal sensitivity measurements began 1 minute after time 0. The same investigator (DRB) performed all treatments and measurements. To maintain consistent efficacy, the proparacaine solution was stored in a refrigerator during the study and anesthetic from the same bottle was used throughout the study.8

Measurement of corneal sensitivity—A Cochet-Bonnet aesthesiometerb with a 0.12–mm cross-sectional diameter nylon monofilament was used to measure sensitivity of the central portion of the cornea. To minimize environmental influences, examinations of all cats were conducted in the same facility in which temperature and humidity were monitored and recorded. To determine corneal sensitivity, the filament of the aesthesiometer was advanced slowly toward the globe and applied perpendicular to the central portion of the cornea. Pressure was increased only until a slight deflection of the filament was evident. Corneal sensitivity, defined as the CTT, was recorded as the length of the aesthesiometer filament in centimeters that induced a blink reflex on at least 3 of 5 stimulations for a specific filament length. After statistical analysis, data were converted to pressure measurements (g/mm2) by use of the manufacturer's conversion table to allow comparisons to previous study results.

Each cat's baseline CTT was established before treatment by the use of an initial length of 5.0 cm for the aesthesiometer filament.9 If a blink reflex was not detected, the filament length was decreased in 0.5-cm increments and testing was repeated until a blink reflex was evident on at least 3 of 5 stimulations at a specific filament length. The CTT was assessed 1 and 5 minutes after topical application of the proparacaine solution and then at 5-minute intervals thereafter until 60 minutes after application. For the measurement obtained 1 minute after treatment, the initial length of the nylon filament was matched to the individual cat's baseline CTT and then decreased in the same manner as for pretreatment measurements. For subsequent measurements, the initial length of the nylon filament was the shortest length that did not result in a positive blink reflex for at least 3 of 5 attempts during the preceding time point.6,10 When a blink reflex was detected for at least 3 of 5 stimulations, the length of the filament was increased by 0.5 cm and testing was repeated. The CTT after treatment was recorded as the longest filament length that elicited a blink reflex on 3 of 5 stimulations. The CTT was recorded as 0 when no blink reflex to stimulation was observed.

Statistical analysis—Filament length was modeled by use of a software programc to perform a mixed-effects repeated-measures ANOVA. Comparisons of the means from each posttreatment time to the time 0 mean were performed by use of the Bonferroni correction to hold the familywise error rate to 0.05. A repeated-measures ANOVA was also used to evaluate for differences in response between eyes receiving treatment (ie, left eyes vs right eyes). Values of P< 0.05 were considered significant.

Results

Mean filament length before treatment with 1 drop of proparacaine was 1.58 cm (95% confidence limits, 1.43 and 1.72 cm). No cat responded to the maximal stimulation (filament length of 0.5 cm) 1 minute after the application of the corneal anesthetic. The CTT before treatment differed significantly from the CTT after treatment up to and including the 25-minute posttreatment measurement (Figure 1). Maximum effect was observed through 5 minutes, as only 1 cat responded to maximal stimulation at that time point. No significant difference was found in CTT measurements between treated left and right eyes at any time.

Figure 1—
Figure 1—

Mean (95% confidence limits) aesthesiometer filament length for determination of corneal sensitivity in 20 cats before and after topical administration of 1 drop of an ophthalmic preparation of 0.5% proparacaine hydrochloride solution in 1 eye. Baseline filament length is designated as time 0. A lack of elicited blink reflex in response to corneal stimulation by use of a 0.5-cm length of filament is designated as a filament length of 0. Subsequent times are minutes after administration. *Significantly (P < 0.05) different filament length from baseline.

Citation: American Journal of Veterinary Research 67, 10; 10.2460/ajvr.67.10.1780

Discussion

Results of our study indicate that topical administration of an ophthalmic preparation of 0.5% proparacaine solution induces demonstrable corneal anesthesia in cats for up to 25 minutes, as determined by use of Cochet-Bonnet aesthesiometry. Maximum effect was only observed for a 5-minute duration. Onset of topical anesthesia was rapid, as no blink reflex could be elicited at 1 minute after treatment. Similarly, a rapid corneal sensitivity recovery rate was seen in each cat.

Mean baseline central CTT in our study differs from that of a previous report,11 in which mean ± SD central CTT in DSH cats was reported as 1.79 ± 2.33 g/mm2 and 1.74 ± 1.65 g/mm2 for right and left eyes, respectively. After conversion of filament length measurements to force measurements, the mean baseline CTT measurements in our study were 4.64 g/mm2 (right eyes) and 5.16 g/mm2 (left eyes), which are appreciably higher than the previously reported values for DSH cats.11 It should be noted that the range of central CTT values for DSH cats in the previous report was quite wide,11 as evidenced by the large SD, and the mean baseline CTT values in our study fall within this range. Possible reasons for the differences in corneal sensitivity values between these studies include investigator variability in application of the aesthesiometer filament to the cornea; differences in investigator interpretation of the blink response; and variation in the testing environment between the 2 studies, as temperature and humidity differences affect filament stiffness. Because of these variables, it is difficult to directly compare values between the 2 studies, but the differences do highlight the importance of controlling these variables when a Cochet-Bonnet aesthesiometer is used. Because these variables were controlled within our study and baseline corneal sensitivity was not significantly different from corneal sensitivity at the end of the posttreatment evaluation period, results of our study remain valid.

Duration of corneal anesthesia following topical administration of proparacaine in DSH cats differs somewhat from results previously reported for dogs,2 in which maximal anesthetic effect was observed for 15 minutes and a significant decrease in corneal sensitivity was observed up to 45 minutes following application of 1 drop of proparacaine to the eye. The difference in results of these 2 studies may be related to unique physiologic characteristics of corneal innervation or pharmacodynamics of topically applied medications in each species. The amount of proparacaine used in our study was exactly 50 μL, whereas the study conducted in dogs was reported as a single drop from the commercial container. The volume of a single drop from the commercial solutiona container used in both studies measures approximately 25 μL, suggesting that the applied dose in cats of our study does not account for the decreased duration of anesthetic effect relative to that of dogs.

Corneal sensitivity in cats has been shown to vary between DSH cats and brachycephalic breeds, with brachycephalic breeds demonstrating a significantly higher CTT relative to DSH cats.11 Our study involved evaluation of only DSH cats; thus, these results cannot be extrapolated to other breeds. In addition, all cats in our study were deemed healthy at the beginning of the study. It remains to be determined whether disease states that affect corneal sensitivity would have an effect on the efficacy of topical administration of ophthalmic proparacaine, as has been demonstrated for humans.5

The Cochet-Bonnet aesthesiometer has been widely applied in the investigation of corneal sensitivity in veterinary ophthalmology.9,11–14 Limitations of this instrument include subjective interpretation of filament deflection and variability in filament stiffness with temperature and humidity. We attempted to minimize these problems by having a single investigator perform all tests and by performing all tests in the same physical environment. We also recorded the daily temperature and humidity in the testing room during each session to ensure that environmental conditions were nearly identical across testing days.

Following onset of topical anesthesia, the aesthesiometer filament was initially set at the shortest length that did not result in a positive blink during the prior measurement. If a blink reflex was then elicited at that length, the filament was lengthened by 0.5 cm, and testing was repeated, as previously described.6,10 By starting with a shorter filament length (a more noxious stimulus) and then lengthening the filament, it is possible that conditioning to the stimulus could have occurred to some degree, which would confound the results. However, corneal sensitivity returned to values identical to baseline by the end of the study period, suggesting that any such effect was negligible.

Objective studies on the duration of corneal anesthesia following topical administration of proparacaine in other animals are limited. In rabbits, the onset of action reportedly is < 1 minute and duration of anesthesia is 63 minutes.4 In humans with clinically normal eyes, maximal effect of 0.5% proparacaine solution is 11.7 minutes,5 with a complete recovery time of 34.95 to 456 minutes. Comparison of our results with those of studies in other species, including the previously described dog study,2 suggests that corneas of DSH cats recover more rapidly from topical administration of proparacaine than those of other species.

ABBREVIATIONS

DSH

Domestic shorthair

CTT

Corneal touch threshold

a.

Ophthetic, Allergan Inc, Irvine, Calif

b.

Cochet-Bonnet aesthesiometer, Luneau Ophtalmologies, Chartres Cedex, France

c.

MIXED procedure of the SAS System, version 8.02, SAS Institute Inc, Cary, NC.

References

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    Ward DA. Clinical ophthalmic pharmacology and therapeutics. Part 3. In: Gelatt KN, ed. Veterinary ophthalmology. 3rd ed. Baltimore: Lippincott Williams & Wilkins, 1999;336354.

    • Search Google Scholar
    • Export Citation
  • 2.

    Herring IP, Bobofchak MA & Landry MP, et al. Duration of effect and effect of multiple doses of topical ophthalmic 0.5% proparacaine hydrochloride in clinically normal dogs. Am J Vet Res 2005;66:7780.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 3.

    Forstom C. Ophthaine (proparacaine hydrochloride): a local anesthetic for ophthalmic surgery (lett). Vet Rec 1964;76:385.

  • 4.

    Liu JC, Steinemann TL & McDonald MB, et al. Topical bupivacaine and proparacaine: a comparison of toxicity, onset of action, and duration of action. Cornea 1991;12:228232.

    • Search Google Scholar
    • Export Citation
  • 5.

    Weiss JS, Goren MB. The effect of corneal hypesthesia on duration of proparacaine anesthetic eyedrops. Am J Ophthalmol 1991;112:326330.

  • 6.

    Polse KA, Keener RJ, Jauregui MJ. Dose-response effects of corneal anesthetics. Am J Optom Physiol Opt 1978;55:814.

  • 7.

    Chan-Ling T. Sensitivity and neural organization of the cat cornea. Invest Ophthalmol Vis Sci 1989;30:10751082.

  • 8.

    Stiles J, Krohne S & Rankin A, et al. The efficacy of 0.5% proparacaine stored at room temperature. Vet Ophthalmol 2001;4:205207.

  • 9.

    Barrett PM, Scagliotti RH & Meredith RE, et al. Absolute corneal sensitivity and corneal trigeminal nerve anatomy in normal dogs. Prog Vet Comp Ophthalmol 1991;1:245254.

    • Search Google Scholar
    • Export Citation
  • 10.

    Nomura K, Singer DE, Aquavella JV. Corneal sensation after topical anesthesia. Cornea 2001;20:191193.

  • 11.

    Blocker T, van der Woerdt A. A comparison of corneal sensitivity between brachycephalic and domestic short-haired cats. Vet Opthalmol 2001;4:127130.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 12.

    Weigt AK, Herring IP & Marfurt CF, et al. Effects of cyclophotocoagulation with a neodymium:yttrium-aluminum-garnet laser on corneal sensitivity, intraocular pressure, aqueous tear production, and corneal nerve morphology in eyes of dogs. Am J Vet Res 2002;63:906915.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 13.

    Good KL, Maggs DJ & Hollingsworth SR, et al. Corneal sensitivity in dogs with diabetes mellitus. Am J Vet Res 2003;64:711.

  • 14.

    Brooks DE, Clark CK, Lester GD. Cochet-Bonnet aesthesiometer-determined corneal sensitivity in neonatal foals and adult horses. Vet Ophthalmol 2000;3:133137.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • Figure 1—

    Mean (95% confidence limits) aesthesiometer filament length for determination of corneal sensitivity in 20 cats before and after topical administration of 1 drop of an ophthalmic preparation of 0.5% proparacaine hydrochloride solution in 1 eye. Baseline filament length is designated as time 0. A lack of elicited blink reflex in response to corneal stimulation by use of a 0.5-cm length of filament is designated as a filament length of 0. Subsequent times are minutes after administration. *Significantly (P < 0.05) different filament length from baseline.

  • 1.

    Ward DA. Clinical ophthalmic pharmacology and therapeutics. Part 3. In: Gelatt KN, ed. Veterinary ophthalmology. 3rd ed. Baltimore: Lippincott Williams & Wilkins, 1999;336354.

    • Search Google Scholar
    • Export Citation
  • 2.

    Herring IP, Bobofchak MA & Landry MP, et al. Duration of effect and effect of multiple doses of topical ophthalmic 0.5% proparacaine hydrochloride in clinically normal dogs. Am J Vet Res 2005;66:7780.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 3.

    Forstom C. Ophthaine (proparacaine hydrochloride): a local anesthetic for ophthalmic surgery (lett). Vet Rec 1964;76:385.

  • 4.

    Liu JC, Steinemann TL & McDonald MB, et al. Topical bupivacaine and proparacaine: a comparison of toxicity, onset of action, and duration of action. Cornea 1991;12:228232.

    • Search Google Scholar
    • Export Citation
  • 5.

    Weiss JS, Goren MB. The effect of corneal hypesthesia on duration of proparacaine anesthetic eyedrops. Am J Ophthalmol 1991;112:326330.

  • 6.

    Polse KA, Keener RJ, Jauregui MJ. Dose-response effects of corneal anesthetics. Am J Optom Physiol Opt 1978;55:814.

  • 7.

    Chan-Ling T. Sensitivity and neural organization of the cat cornea. Invest Ophthalmol Vis Sci 1989;30:10751082.

  • 8.

    Stiles J, Krohne S & Rankin A, et al. The efficacy of 0.5% proparacaine stored at room temperature. Vet Ophthalmol 2001;4:205207.

  • 9.

    Barrett PM, Scagliotti RH & Meredith RE, et al. Absolute corneal sensitivity and corneal trigeminal nerve anatomy in normal dogs. Prog Vet Comp Ophthalmol 1991;1:245254.

    • Search Google Scholar
    • Export Citation
  • 10.

    Nomura K, Singer DE, Aquavella JV. Corneal sensation after topical anesthesia. Cornea 2001;20:191193.

  • 11.

    Blocker T, van der Woerdt A. A comparison of corneal sensitivity between brachycephalic and domestic short-haired cats. Vet Opthalmol 2001;4:127130.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 12.

    Weigt AK, Herring IP & Marfurt CF, et al. Effects of cyclophotocoagulation with a neodymium:yttrium-aluminum-garnet laser on corneal sensitivity, intraocular pressure, aqueous tear production, and corneal nerve morphology in eyes of dogs. Am J Vet Res 2002;63:906915.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 13.

    Good KL, Maggs DJ & Hollingsworth SR, et al. Corneal sensitivity in dogs with diabetes mellitus. Am J Vet Res 2003;64:711.

  • 14.

    Brooks DE, Clark CK, Lester GD. Cochet-Bonnet aesthesiometer-determined corneal sensitivity in neonatal foals and adult horses. Vet Ophthalmol 2000;3:133137.

    • Crossref
    • Search Google Scholar
    • Export Citation

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