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Topic:Clinical Study

Clinical studies in equine research involve the systematic investigation of health and disease in horses through structured scientific methods. These studies aim to evaluate the safety and efficacy of treatments, understand disease mechanisms, and improve veterinary care practices. Clinical studies can include randomized controlled trials, observational studies, and case-control studies. They may focus on various aspects such as pharmacokinetics, therapeutic interventions, and diagnostic techniques. This page compiles peer-reviewed research studies and scholarly articles that explore the design, implementation, and findings of clinical studies in equine medicine, providing insights into their impact on horse health and veterinary practices.
Maternal age and parity influence ultrasonographic measurements of fetal growth in Dutch Warmblood mares.
Animal reproduction science    December 24, 2008   Volume 115, Issue 1-4 110-123 doi: 10.1016/j.anireprosci.2008.12.014
Hendriks WK, Colenbrander B, van der Weijden GC, Stout TA.Ultrasonographic examination of the equine fetus in mid-late gestation is usually performed only if there are concerns about fetal or maternal health. Even then it is difficult to determine whether development is 'normal' for gestational age because the reference values include considerable error margins. This study examined maternal factors that influence fetal growth with the aim of producing more precise late gestation fetal growth curves for Dutch Warmblood horses. Fetal development was monitored at 2-week intervals from day 100 of gestation until term in 32 mares ranging from 4 to 18 year...
Reproductive performance of donor mares subsequent to eFSH treatment in early vernal transition: Comparison between the first, second, and mid-season estrous cycles of the breeding season.
Animal reproduction science    December 24, 2008   Volume 116, Issue 1-2 107-118 doi: 10.1016/j.anireprosci.2008.12.008
Raz T, Hunter B, Carley S, Card C.The objective was to compare the reproductive performances associated with the first (Cycle-1), second (Cycle-2), and mid-season (MS-Cycle) ovulations of the breeding season in donor mares that were treated with equine-FSH (eFSH) in the early vernal transition. Mares (n=15) kept under ambient light were examined ultrasonographically per-rectum starting January 30. When an ovarian follicle > or =25mm in diameter was detected, twice daily eFSH treatments were initiated. The eFSH treatments ceased when a follicle > or =35mm was detected, and 36h later hCG was administered. Thereafter, mares were ...
Histological and biomechanical effects of palatal sclerotherapy in the horse using sodium tetradecyl sulfate.
Veterinary journal (London, England : 1997)    December 23, 2008   Volume 183, Issue 3 316-321 doi: 10.1016/j.tvjl.2008.11.006
Muñoz JA, Marcoux M, Picandet V, Theoret CL, Perron MF, Lepage OM.Palatal sclerotherapy using sodium tetradecyl sulfate has been suggested as a treatment for dorsal displacement of the soft palate in young Standardbred horses. The present study evaluated histological and biomechanical changes in the equine soft palate following trans-endoscopic treatment with a low dose of this compound. Two horses were euthanased and examined at 2 weeks and at 1, 2, 4 and 6 months post-sclerotherapy, while two further horses served as untreated controls. The technique was easily performed in all cases without major complications. On histological examination there was no evi...
Di-tri-octahedral smectite for the prevention of post-operative diarrhea in equids with surgical disease of the large intestine: results of a randomized clinical trial.
Veterinary journal (London, England : 1997)    December 20, 2008   Volume 182, Issue 2 210-214 doi: 10.1016/j.tvjl.2008.06.016
Hassel DM, Smith PA, Nieto JE, Beldomenico P, Spier SJ.The aim of this study was to evaluate the effects of a commercially available di-tri-octahedral (DTO) smectite product on clinical signs and prevalence of post-operative diarrhea in horses with colic associated with disease of the large intestine. Sixty-seven horses with surgical disease of the large intestine were randomly assigned to be treated with DTO smectite (n=37; 0.5 kg via nasogastric intubation every 24 h for 3 days post-operatively) or a placebo (n=30). The effect of treatment on fecal scores and clinical and hematological parameters, including heart rate, mucous membrane color, tem...
Photodynamic therapy for the treatment of periocular squamous cell carcinoma in horses: a pilot study.
Veterinary ophthalmology    December 17, 2008   Volume 11 Suppl 1 27-34 doi: 10.1111/j.1463-5224.2008.00643.x
Giuliano EA, MacDonald I, McCaw DL, Dougherty TJ, Klauss G, Ota J, Pearce JW, Johnson PJ.Local photodynamic therapy (PDT) is a novel cancer therapy in veterinary ophthalmology. A prospective pilot study seeking to demonstrate proof of principle and safety for the treatment of equine periocular squamous cell carcinoma (PSCC) was therefore conducted. We hypothesized that surgical excision with adjunctive local PDT is an effective and safe treatment for equine PSCC. Methods: Nine horses (10 eyes) with PSCC were treated with surgical resection, local infiltration of resulting wound beds with 2-[1-hexyloxyethyl]-2-devinylpyropheophorbide-a (HPPH) and irradiation with 665-nm wavelength ...
An overview of recent developments in corneal immunobiology: potential relevance in the etiogenesis of corneal disease in the horse.
Veterinary ophthalmology    December 17, 2008   Volume 11 Suppl 1 66-76 doi: 10.1111/j.1463-5224.2008.00635.x
Matthews AG.This paper overviews some recent developments in mammalian corneal immunobiology, and discusses how these may act as pointers towards understanding the immunology underlying some common corneal diseases in the horse, including infectious ulceration and presumptively immune-mediated non-ulcerative disease. Specifically, three aspects of corneal immunobiology are examined: the role of Toll-like receptors in surface immunity and in the etiogenesis of microbial ulceration, the relationship between conjunctiva associated lymphoid tissue (CALT) and immunoprotection of the corneal surface, and the me...
Daily rhythm of tear production in normal horse.
Veterinary ophthalmology    December 17, 2008   Volume 11 Suppl 1 57-60 doi: 10.1111/j.1463-5224.2008.00647.x
Piccione G, Giannetto C, Fazio F, Giudice E.This study was designed to assess the daily rhythm of tear production in clinically healthy horses, to compare left eye and right eye, and to evaluate the influence of time and gender. Methods: For our study 18 horses (nine female and nine male) were subjected to three different light/dark (L/D) schedules: 12/12 L/D cycles, constant light (24/0 L/D) and constant darkness (0/24 L/D). Methods: In all subjects Schirmer tear tests were performed at 4-h intervals over a 24-h period. Results: A circadian rhythm of tear production was found during the 12/12 L/D period and during constant darkness. Al...
Expression of cyclooxygenase-2 by equine ocular and adnexal squamous cell carcinomas.
Veterinary ophthalmology    December 17, 2008   Volume 11 Suppl 1 8-14 doi: 10.1111/j.1463-5224.2008.00623.x
Smith KM, Scase TJ, Miller JL, Donaldson D, Sansom J.To investigate whether cyclooxygenase-2 (COX-2) is expressed by equine ocular and adnexal squamous cell carcinomas (SCC). Methods: Forty-three samples of histologically confirmed cases of ocular SCC or carcinoma in situ (CIS) from 34 horses presented to the Animal Health Trust between 1992 and 2004 were subjected to a standard, two-layered, indirect immunohistochemical method using a rabbit polyclonal antihuman COX-2 antibody. Ten formalin-fixed, paraffin-embedded tissue samples taken from recognized predilection sites for SCC, from the grossly normal eyes of 10 horses euthanized for reasons u...
Deep lamellar endothelial keratoplasty in 10 horses.
Veterinary ophthalmology    December 17, 2008   Volume 11 Suppl 1 35-43 doi: 10.1111/j.1463-5224.2008.00654.x
Plummer CE, Kallberg ME, Ollivier FJ, Barrie KP, Brooks DE.To describe and evaluate a surgical technique utilized for the therapy of deep corneal stromal abscesses (DSA) in horses. The DSA is excised and replaced with a partial thickness corneal lamellar allograft. Methods: A retrospective clinical study describing the indications for the surgical technique utilized and the outcomes of this procedure in 10 eyes of 10 horses. Results: Each affected eye had a discrete DSA within the posterior stroma. An initial partial thickness semicircular corneal incision was made at the limbus, followed by anterior stromal lamellar dissection over the lesion. After ...
Fluorangiographic study of the ocular fundus in normal horses.
Veterinary ophthalmology    December 17, 2008   Volume 11 Suppl 1 2-7 doi: 10.1111/j.1463-5224.2008.00621.x
Molleda JM, Cervantes I, Galán A, Tardón R, Gallardo JM, Martín-Suárez EM.To describe the protocol and appearance of fluorescein angiography (FA) in normal horses. Methods: A total of 25 healthy horses aged between 5 and 15 years. Methods: The horses were sedated with 15 microg/kg detomidine and 50 microg/kg butorphanol and dilated with topical tropicamide 1%. All angiograms were recorded after intravenous bolus injection of 10 mg/kg of fluorescein sodium solution. Results: Two successive angiographic phases could be discerned: the choriopapillary phase, starting at 46.95 +/- 9.48 s, and the retinal vascular phase, starting at 47.79 +/- 10.38 s. The retinal vascular...
Incidence rate of musculoskeletal injuries and determinants of time to recovery in young Australian Thoroughbred racehorses.
Australian veterinary journal    December 17, 2008   Volume 86, Issue 12 473-480 doi: 10.1111/j.1751-0813.2008.00359.x
Cogger N, Evans DL, Hodgson DR, Reid SW, Perkins N.To describe the incidence rate of musculoskeletal (MS) injuries and investigate the factors that influence recovery from MS injury in young Thoroughbred horses in Australia. Methods: Training and injury data were collected at fortnightly intervals from 14 trainers in New South Wales. Incidence rates were calculated for initial injuries stratified by age-class and sex. Survival analysis methods were used to investigate the time to recovery after the first MS injury (measured as a start in a race or barrier trial). Results: For the 248 racehorses enrolled, there were 428 injuries recorded; 2-yea...
Management of equine skull fractures using fixation with polydioxanone sutures.
Australian veterinary journal    December 17, 2008   Volume 86, Issue 12 481-485 doi: 10.1111/j.1751-0813.2008.00369.x
Schaaf KL, Kannegieter NJ, Lovell DK.Ten horses presented with severe distortion of the facial contour, crepitus on palpation and mild to moderate epistaxis. Individual horses also showed ocular damage, ptosis, severe dyspnoea and movement of the facial bones concurrent with respiration. The fracture fragments were exposed using a large curvilinear incision and elevated using a retractor, periosteal elevator, chisel or Steinmann pin. The fracture fragments were unstable following reduction and fixation was necessary. Stabilisation was achieved with polydioxanone sutures placed through holes drilled in opposing sides of the fractu...
Effects of competition experience and transportation on the adrenocortical and thyroid responses of horses.
The Veterinary record    December 17, 2008   Volume 163, Issue 24 713-716 doi: 10.1136/vr.163.24.713
Fazio E, Medica P, Cravana C, Ferlazzo A.To evaluate whether the amount of experience of sport horses and the stress of transport affected their adrenocortical and thyroid responses, the plasma concentrations of total cortisol and total and free iodothyronine of 63 horses were studied before and after show jumping competitions. There were 14 trained inexperienced jumpers (group 1), 20 trained experienced jumpers (group 2), 10 trained inexperienced jumpers that had been transported just before the competition (group 3) and 19 trained experienced jumpers that had been transported just before the competition (group 4). The concentration...
Update on veterinary cataract surgery.
Current opinion in ophthalmology    December 17, 2008   Volume 20, Issue 1 61-68 doi: 10.1097/ICU.0b013e32831a98aa
Wilkie DA, Colitz CM.The purpose of this review is not to specifically discuss the techniques of veterinary cataract surgery, but rather to emphasize some of the differences between the veterinary and human cataract patients, procedures and outcomes. Results: In general, veterinary cataract surgery has more similarities than differences when compared to its human counterpart. This is especially true when comparing pediatric cataract patients. Veterinary cataract surgery has changed dramatically in recent years with regards to surgical technique, ocular pharmacology, viscoelastic devices, phacoemulsification, and t...
Evaluation of tramadol and its main metabolites in horse plasma by high-performance liquid chromatography/fluorescence and liquid chromatography/electrospray ionization tandem mass spectrometry techniques.
Rapid communications in mass spectrometry : RCM    December 17, 2008   Volume 23, Issue 2 228-236 doi: 10.1002/rcm.3870
De Leo M, Giorgi M, Saccomanni G, Manera C, Braca A.Tramadol is a centrally acting analgesic drug that has been used clinically for the last two decades to treat pain in humans. The clinical response of tramadol is strictly correlated to its metabolism, because of the different analgesic activity of its metabolites. O-Desmethyltramadol (M1), its major active metabolite, is 200 times more potent at the micro-receptor than the parent drug. In recent years tramadol has been widely introduced in veterinary medicine but its use has been questioned in some species. The aim of the present study was to develop a new sensible method to detect the whole ...
Uterine influences on embryogenesis and early placentation in the horse revealed by transfer of day 10 embryos to day 3 recipient mares.
Reproduction (Cambridge, England)    December 12, 2008   Volume 137, Issue 3 583-593 doi: 10.1530/REP-08-0328
Wilsher S, Allen WR.Eight day 10 horse embryos were transferred non-surgically to recipient mares that had ovulated 7 days after the donors. The embryonic vesicle was seen ultrasonographically in all eight recipients, and three out of eight (38%) of the vesicles developed an embryo proper with a beating heart. Conceptus expansion was initially slower than that in control mares but continued until day 22 (recipient day 15). Time of fixation of the vesicle was related to its diameter, rather than uterine stage. Although the embryo proper first appeared ultrasonographically on day 22, as normal, it grew more slowly ...
2D versus 3D in the kinematic analysis of the horse at the trot.
Veterinary research communications    December 11, 2008   Volume 33, Issue 6 507-513 doi: 10.1007/s11259-008-9196-x
Miró F, Santos R, Garrido-Castro JL, Galisteo AM, Medina-Carnicer R.The handled trot of three Lusitano Purebred stallions was analyzed by using 2D and 3D kinematical analysis methods. Using the same capture and analysis system, 2D and 3D data of some linear (stride length, maximal height of the hoof trajectories) and angular (angular range of motion, inclination of bone segments) variables were obtained. A paired Student T-test was performed in order to detect statistically significant differences between data resulting from the two methodologies With respect to the angular variables, there were significant differences in scapula inclination, shoulder angle, c...
The effect of lidocaine on in vitro adhesion and migration of equine neutrophils.
Veterinary immunology and immunopathology    December 11, 2008   Volume 129, Issue 1-2 137-142 doi: 10.1016/j.vetimm.2008.12.017
Cook VL, Neuder LE, Blikslager AT, Jones SL.The effect of lidocaine on in vitro migration and adhesion of equine neutrophils was evaluated. Neutrophils were isolated from equine whole blood using a Percoll-gradient centrifugation protocol. Purified neutrophils were incubated with lidocaine at concentrations from 0.1 to 1000 microg/ml for 30 min at 37 degrees C, after calcein loading. Neutrophil integrin-mediated adhesion in response to stimulation with 100 nM LTB(4), 100 nM PAF, or 100 ng/ml IL-8, or integrin-mediated migration in response to stimulation with 100 nM LTB(4), 150 nM PAF, or 100 ng/ml IL-8 was assessed. Statistical signifi...
Ultrasonographic and Doppler findings of subclinical clitoral microtraumatisms in mountain bikers and horseback riders.
The journal of sexual medicine    December 9, 2008   Volume 6, Issue 2 464-468 doi: 10.1111/j.1743-6109.2008.01124.x
Battaglia C, Nappi RE, Mancini F, Cianciosi A, Persico N, Busacchi P.Repeated microtraumas in horseback riders and mountain bikers are, in males, associated with perineal and scrotal lesions. No data are reported in the females. Objective: To report five cases of clitoral microcalcifications, diagnosed by ultrasonography, in six healthy, eumenorrheic athletes, and to verify the clinical and sexual impact of the ultrasonographic findings. Methods: Translabial ultrasonographic evaluation of the clitoris, Doppler analysis of dorsal clitoral arteries, and the two-factor Italian McCoy Female Sexuality Questionnaire (MFSQ) METHODS: The patients were assessed with a d...
Evaluation of four topical preparations for the treatment of cannon hyperkeratosis in a horse.
Veterinary dermatology    December 6, 2008   Volume 19, Issue 6 385-390 doi: 10.1111/j.1365-3164.2008.00715.x
Hilton H, Affolter VK, White SD.The response to treatment with four topical preparations was evaluated in an 11-year-old Morgan horse mare with histologically confirmed quadrilateral cannon hyperkeratosis. Each limb was treated for 30 days with 0.1% tacrolimus ointment, 0.1% adapalene gel, 0.2% phytosphingosine spray or a water-based emollient. Response to treatment was evaluated both histologically and visually. A water-based emollient and 0.1% tacrolimus ointment produced encouraging clinical responses. Pre-treatment histopathology identified marked, mostly compact, hyperkeratosis and follicular hyperkeratosis, most promin...
Serial gastrointestinal ultrasonography following exploratory celiotomy in normal adult ponies. Epstein K, Short D, Parente E, Reef V, Southwood L.The objective was to characterize ultrasonographic changes in bowel wall thickness, contractility, degree of distension, luminal contents, and peritoneal fluid associated with exploratory celiotomy in normal ponies. Gastrointestinal ultrasonographic examination was performed in 14 ponies on days 1, 3, 5, and 7 after an exploratory celiotomy. Wall thickness, contractility, degree of distension, and luminal contents were recorded for the duodenum and jejunum. Stomach wall thickness and location, cecal wall thickness, and peritoneal fluid location and character were recorded. Peritoneal fluid was...
Is a magic angle effect observed in the collateral ligaments of the distal interphalangeal joint or the oblique sesamoidean ligaments during standing magnetic resonance imaging? Smith MA, Dyson SJ, Murray RC.Collagen fibers oriented at 55 degrees to the static magnetic field (B0) are characterized by an artifactual increase in signal intensity due to the magic angle effect. We hypothesized that there would be increased signal intensity in the collateral ligaments of the distal interphalangeal joint and oblique sesamoidean ligaments when these ligaments were at angles approaching 55 degrees to a horizontal B0 during standing magnetic resonance (MR) imaging. MR imaging was performed on four cadaver forelimbs in a 0.27 T standing system. Transverse and dorsal images were obtained using various sequen...
Magnetic resonance imaging of distal sesamoidean ligament injury. Smith S, Dyson SJ, Murray RC.Distal sesamoidean ligament injury is a recognized cause of lameness but diagnosis using ultrasonography is sometimes difficult. Herein, we describe the normal appearance of the distal sesamoidean ligaments on magnetic resonance (MR) images and the changes that occur when the ligaments are injured. The appearance of the distal sesamoidean ligaments on MR images from 66 control horses and 58 horses with distal sesamoidean desmitis were described and the cross-sectional area and signal intensity of the ligaments measured. In control horses, the ligaments had a characteristic appearance and stron...
Anti-inflammatory and analgesic effects of intra-articular injection of triamcinolone acetonide, mepivacaine hydrochloride, or both on lipopolysaccharide-induced lameness in horses.
American journal of veterinary research    December 3, 2008   Volume 69, Issue 12 1646-1654 doi: 10.2460/ajvr.69.12.1646
Kay AT, Bolt DM, Ishihara A, Rajala-Schultz PJ, Bertone AL.To assess analgesia, inflammation, potency, and duration of action associated with intra-articular injection of triamcinolone acetonide (TA), mepivacaine hydrochloride, or both in metacarpophalangeal (MCP) joints of horses with experimentally induced acute synovitis. Methods: 18 horses. Methods: Both forelimbs of each horse were injected with lipopolysaccharide (LPS) 3 times. After the first LPS injection, 1 forelimb of each horse was treated with intra-articular injection of mepivacaine (80 mg; n=6), TA (9 mg; 6), or mepivacaine with TA (same doses of each; 6) 12 hours after the initial LPS i...
Biomechanical evaluation of the equine masticatory action: calculation of the masticatory forces occurring on the cheek tooth battery.
Journal of biomechanics    December 3, 2008   Volume 42, Issue 1 67-70 doi: 10.1016/j.jbiomech.2008.09.040
Huthmann S, Staszyk C, Jacob HG, Rohn K, Gasse H.The forces generated during equine mastication influence the teeth, as well as the periodontium, the jaw bones, the temporomandibular joints and materials used in dental therapy. Due to the limited accessibility of the cheek teeth located farther caudal in the equine oral cavity the measurement of the masticatory forces on these teeth is virtually impossible. The calculation of such forces is an appropriate, indirect alternative to direct measuring. Hence, a mathematical model, which respects several morphological features of the equine dentition, e.g. the Curve of Spee, is presented. The rele...
Doxycycline levels in preocular tear film of horses following oral administration.
Veterinary ophthalmology    December 3, 2008   Volume 11, Issue 6 381-385 doi: 10.1111/j.1463-5224.2008.00662.x
Baker A, Plummer CE, Szabo NJ, Barrie KP, Brooks DE.To determine the concentration of doxycycline in preocular tear film following oral administration in horses as a possible therapeutic modality for infectious and keratomalacic equine keratitis. Methods: Eight broodmares without ocular disease from a Thoroughbred breeding facility were included in this study. Each mare received 20 mg/kg of doxycycline by mouth once daily in the morning for five consecutive days. Tears were collected 1 h after doxycycline administration starting on day one of administration and continuing for 10 consecutive days. Doxycycline levels in the tears were measured us...
Effects of intravenous administration of caffeine on physiologic variables in exercising horses.
American journal of veterinary research    December 3, 2008   Volume 69, Issue 12 1670-1675 doi: 10.2460/ajvr.69.12.1670
Ferraz GC, Teixeira-Neto AR, Mataqueiro MI, Lacerda-Neto JC, Queiroz-Neto A.To investigate the effect of acute administration of caffeine on the athletic performance of Arabian horses. Methods: 12 healthy adult Arabian horses that were trained for exercise on a treadmill. Methods: By use of a crossover study design, horses received each of the following treatments: IV administration of caffeine (5 mg/kg) and IV administration of approximately the same volume of saline (0.9% NaCl) solution. Order of treatment was randomized, and there was a 10-day interval between treatments. Thirty minutes after treatments, horses underwent an incremental exercise test (IET) on a trea...
Risk factors for development of neurologic disease after experimental exposure to equine herpesvirus-1 in horses.
American journal of veterinary research    December 3, 2008   Volume 69, Issue 12 1595-1600 doi: 10.2460/ajvr.69.12.1595
Allen GP.To identify risk factors associated with development of clinical neurologic signs in horses exposed to equine herpesvirus-1 (EHV-1). Methods: 36 adult horses. Methods: Blood samples collected before and after challenge inoculation with nonneuropathogenic or neuropathogenic EHV-1 were analyzed for leukocyte-associated viremia, serum neutralizing antibody, and EHV-1-specific cytotoxic T-lymphocyte precursors (CTLPs). Associations between variables and neurologic disease and correlations between age category or breed and development of neurologic disease were examined. Results: 9 horses developed...
In vivo effects of intra-articular injection of gelatin hydrogen microspheres containing basic fibroblast growth factor on experimentally induced defects in third metacarpal bones of horses.
American journal of veterinary research    December 3, 2008   Volume 69, Issue 12 1555-1559 doi: 10.2460/ajvr.69.12.1555
Sasaki N, Minami T, Yamada K, Yamada H, Inoue Y, Kobayashi M, Tabata Y.To evaluate the effect of intra-articular injection of gelatin hydrogel microspheres containing basic fibroblast growth factor (bFGF) on experimentally induced defects in third metacarpal bones (MC3s) of horses, in vivo. Methods: 6 healthy adult Thoroughbreds. Methods: Horses were anesthetized, and a hole (diameter, 4.5 mm) was drilled into the medial condyle of both MC3s of each horse. One milliliter (100 microg) of a solution of gelatin hydrogel microspheres (2 mg) containing bFGF was injected into the joint capsule of the right metacarpophalangeal joint of each horse (bFGF joint). One milli...
Evaluation of duration of corneal anesthesia induced with ophthalmic 0.5% proparacaine hydrochloride by use of a Cochet-Bonnet aesthesiometer in clinically normal horses.
American journal of veterinary research    December 3, 2008   Volume 69, Issue 12 1655-1658 doi: 10.2460/ajvr.69.12.1655
Kalf KL, Utter ME, Wotman KL.To measure duration of corneal anesthesia and time and degree of maximal anesthetic effect of 0.5% proparacaine hydrochloride by use of a Cochet-Bonnet aesthesiometer in horses. Methods: 10 clinically normal adult horses. Methods: Baseline corneal touch threshold (CTT) was measured in millimeters for 1 randomly selected eye of each horse by use of the aesthesiometer by applying the filament to the cornea at maximum length (60 mm) and decreasing in 5-mm increments until a consistent blink response was elicited. Following baseline CTT measurement, 0.2 mL of 0.5% proparacaine hydrochloride was in...