Development and evaluation of an anatomically designed and 3D printed device to enhance orotracheal intubation success in rabbits by inexperienced veterinarians.

OBJECTIVE: To assess whether the use of a three-dimensional (3D) printed device enhances the success rate of orotracheal intubation in rabbits. STUDY DESIGN: Prospective, crossover randomized controlled trial. ANIMALS: A total of six mixed-breed rabbits. METHODS: A device to guide the endotracheal tube was designed based on computed tomography images and then manufactured using 3D printing. Rabbits were randomly assigned for intubation by two inexperienced veterinarians using the blind (BLI), borescope- (BOR) or device- (DEV) guided techniques. Success rate, number of attempts, time to success, injury scores and propofol dose were recorded and compared. Significance was considered when p < 0.05. RESULTS: Success rate was higher in DEV (58.3%) than in BLI (8.3%) (p < 0.023), but not different from that in BOR (41.6%). Total time until successful intubation was lower in DEV (45 ± 23 seconds) and BOR (85 ± 62 seconds) than in BLI (290 seconds; p < 0.006). Time for the successful attempt was lower for DEV (35 ± 10 seconds) and BOR (74 ± 43 seconds) than in BLI (290 seconds; p < 0.0001). The propofol dose required was lower for DEV (2.3 ± 1.2 mg kg-1) than for BLI (3.4 ± 1.6 mg kg-1) (p < 0.031), but not different from BOR (2.4 ± 0.9 mg kg-1). Number of attempts and oxygen desaturation events were not different among techniques (p < 0.051 and p < 0.326, respectively). Injury scores [median (range)] before and after attempts were different in BLI [0 versus 1 (0-3), p < 0.005] and BOR [0 (0-1) versus 1 (0-3), p < 0.002] but not in DEV [0 (0-2) versus 0 (0-3), p < 0.109]. CONCLUSIONS AND CLINICAL RELEVANCE: The device facilitated orotracheal intubation with a time similar to the borescope-guided technique but faster than the traditional blind technique.

Implementation of a Low-Cost 3D-Printed Feline Larynx Model for Veterinary Students.

Endotracheal intubation (EI) in domestic cats is an important skill that veterinary students learn in order to perform anesthesia safely in this species. Implementing a 3D-printed larynx model (LaryngoCUBE) during the instruction process may improve student's learning of EI in felines. Twenty-two third-year students performed EI in cats with standard training (ST), and 16 students trained with the model (MT) the day before the laboratory. It was evaluated whether training with the model decreases the time and number of EI attempts, students' perceived difficulty performing EI using a visual analog score (VAS; 0 cm = very easy, 10 cm = extremely difficult; median [minimum-maximum]), and the incidence of failure to perform EI. The EI time on ST (58 [18-160] seconds) was longer, but not statistically different from MT (29 [13-120] seconds; p = .101). The number of EI attempts on ST (2 [1-3]) was higher than MT (1 [1-3]; p = .005). The VAS on the ST and MT were 4.5 (0.0-10.0) cm and 3.0 (0.2-10.0) cm, respectively (p = .029). The failure rate was 27% on the ST and 25% on the MT (p = 1.000). Students who practiced with a larynx model took fewer attempts to perform EI, tended to be faster, and found that EI was easier. However, the EI success rate in MT was not improved.

Evaluation of analgesic, sympathetic and motor effects of 1% and 2% lidocaine administered epidurally in dogs undergoing ovariohysterectomy.

OBJECTIVE: To compare, versus a control, the sensory, sympathetic and motor blockade of lidocaine 1% and 2% administered epidurally in bitches undergoing ovariohysterectomy. STUDY DESIGN: Randomized, blinded, controlled clinical trial. ANIMALS: A total of 24 mixed-breed intact female dogs. METHODS: All dogs were administered dexmedetomidine, tramadol and meloxicam prior to general anesthesia with midazolam-propofol and isoflurane. Animals were randomly assigned for an epidural injection of lidocaine 1% (0.4 mL kg-1; group L1), lidocaine 2% (0.4 mL kg-1; group L2) or no injection (group CONTROL). Heart rate (HR), respiratory rate (fR), end-tidal partial pressure of carbon dioxide (Pe'CO2), and invasive systolic (SAP), mean (MAP) and diastolic (DAP) arterial pressures were recorded every 5 minutes. Increases in physiological variables were treated with fentanyl (3 µg kg-1) intravenously (IV). Phenylephrine (1 µg kg-1) was administered IV when MAP was <60 mmHg. Postoperative pain [Glasgow Composite Pain Score - Short Form (GCPS-SF)] and return of normal ambulation were recorded at 1, 2, 3, 4 and 6 hours after extubation. RESULTS: There were no differences over time or among groups for HR, fR, Pe'CO2 and SAP. MAP and DAP were lower in epidural groups than in CONTROL (p = 0.0146 and 0.0047, respectively). There was no difference in the use of phenylephrine boluses. More fentanyl was administered in CONTROL than in L1 and L2 (p = 0.011). GCPS-SF was lower for L2 than for CONTROL, and lower in L1 than in both other groups (p = 0.001). Time to ambulation was 2 (1-2) hours in L1 and 3 (2-4) hours in L2 (p = 0.004). CONCLUSIONS AND CLINICAL RELEVANCE: Epidural administration of lidocaine (0.4 mL kg-1) reduced fentanyl requirements and lowered MAP and DAP. Time to ambulation decreased and postoperative pain scores were improved by use of 1% lidocaine compared with 2% lidocaine.

A low-cost portable simulator of a domestic cat larynx for teaching endotracheal intubation.

OBJECTIVE: To design and construct an affordable simulator of the cat larynx for training intubation maneuvers and to share the designs for its fabrication. STUDY DESIGN: Research and development study. ANIMALS: A domestic cat. METHODS: The cadaver of a cat, dead by natural causes, was frozen in sternal recumbency with the neck extended and the mouth wide open. A computed tomography image was acquired and used to construct a digital three-dimensional (3D) model of the pharynx and trachea. A digitally adapted model was 3D-printed and used to generate a silicone model of these structures, which was placed within a wooden container. The quality of the simulator was assessed by 46 veterinary anesthesiologists and veterinarians with experience in tracheal intubation maneuvers, and their opinions were obtained through an anonymous questionnaire. RESULTS: Several preliminary prototypes were assessed regarding stability, texture and cost. Finally, a silicone model of a cat larynx (LaryngoCUBE) was produced and encased in a wooden container. Results from the questionnaire showed high scores regarding anatomy, tissue texture and intubation maneuver realism, compared with the real procedure. CONCLUSIONS: and clinical relevance Use of LaryngoCUBE as a training tool may improve the skills of students and reduce the use of animals for teaching endotracheal intubation. Blueprints and computational models are provided online so that the simulator can be fully reproduced.

Sedative and physiologic effects of tiletamine-zolazepam following buccal administration in cats.

OBJECTIVES: The aim of this study was to describe the sedative and some physiological effects of tiletamine-zolazepam following buccal administration (BA) in cats. METHODS: Seven healthy spayed European shorthair cats (three males, four females) were studied twice in this randomized, blinded, crossover study. Each cat received two doses of tiletamine-zolazepam by BA: the low-dose (LD) group consisted of 5 mg/kg of each drug, and the high-dose (HD) group consisted of 7.5 mg/kg of each. Baseline systolic blood pressure (SAP), heart rate (HR), respiratory rate (RR) and a sedation score were recorded prior to administration of each treatment. The same variables plus the percentage of hemoglobin saturated with oxygen as measured by pulse oximetry (SpO2) were recorded at predefined intervals for the next 2 h. RESULTS: All cats completed the study. No retching or vomiting were observed. Hypersalivation was observed in 0/7 and 3/7 for LD and HD groups, respectively (P = 0.2). There were significant changes in scores over time for posture, response to clippers and response to manual restraint for both groups, without differences between groups. RR, HR and SAP changed significantly over time. SAP and RR were significantly lower for the HD than for the LD group. No values for hemoglobin saturation <95% were observed. CONCLUSIONS AND RELEVANCE: BA of tiletamine-zolazepam at the doses studied here is a simple and effective method for chemical restraint in cats, where the LD group had a lower impact on SAP and RR than the HD group.

Comparison of two sedation protocols for short electroretinography in cats.

Objectives The objectives were to compare two different sedative combinations, xylazine-ketamine and dexmedetomidine-ketamine, for the short electroretinography (ERG) protocol and their impact on sedative effect, reversal times and physiological variables in cats. Methods Six healthy spayed female domestic cats were sedated using one of two ketamine-containing protocols: intramuscular xylazine hydrochloride (1 mg/kg) plus ketamine hydrochloride (3 mg/kg) (XK), and dexmedetomidine hydrochloride (5 µg/kg) plus ketamine hydrochloride (3 mg/kg) (DK). A short ERG protocol was recorded from the left eye of each cat under XK and DK sedation. Thirty minutes later, the effects were reversed with yohimbine or atipamezole for the XK and DK treatment, respectively. The cats were evaluated for time to recumbency, time to head elevation, and time to standing position after reversal treatments. Other variables recorded were: systolic blood pressure, cardiac rhythm, heart rate, pulse oximetry and respiratory rate. Recorded ERG variables included a- and b-wave amplitudes and implicit times under photopic, scotopic and scotopic mixed ERG conditions. Results Time to lateral recumbency with XK was shorter than for DK ( P <0.05). After reversal, head elevation and standing position times were significantly longer for the XK than the DK group ( P <0.05). Heart rate increased and systolic blood pressure decreased from baseline in both groups ( P <0.05), but there were no significant differences between treatment groups. The b-wave amplitude recorded in the photopic study of cats treated with XK was lower than in animals treated with DK ( P <0.05). No other significant differences in ERG variables were observed between treatment groups ( P >0.05). Conclusions and relevance The present study shows that XK and DK treatments are chemical restraint alternatives for ERG recording in cats, with significant differences only in the photopic b-wave amplitude.

Ocular topotecan pharmacokinetics following topical administration to rabbits for diffused anterior retinoblastoma.

OBJECTIVES: We characterized and compared the in-vivo absorption of topotecan into the aqueous humor after instillation of aqueous and ointment formulations. METHODS: A lanolin/petrolatum ointment was used. New Zealand rabbits were instilled with topotecan solution (6 µg, group A), a single 10 µg dose of topotecan ointment (group B) or with five 10 µg doses of topotecan ointment (group C). Aqueous humor samples were collected at different times. Corneal samples were collected only for group A. Topotecan was quantified using HPLC, and pharmacokinetic parameters were calculated. Acute corneal epithelial toxicity was assessed after multiple instillations of topotecan ointment. KEY FINDINGS: Total topotecan maximum aqueous humor concentration (Cmax ) was 16.1, 69.9 and 287 ng/ml in group A, B and C, respectively. A single dose of topotecan ointment increased threefold and sevenfold the aqueous humor Cmax , and exposure compared to the aqueous formulation. Aqueous humor concentrations from group C eyes were substantially above the cytotoxic concentration for retinoblastoma cells. No corneal toxicity was evident after ointment instillation. CONCLUSIONS: Topotecan penetrated into the aqueous humor of the rabbit eye after multiple doses of an ointment in concentrations pharmacologically active against retinoblastoma cells without eliciting acute toxicity. Topotecan ointment may translate to the clinical treatment of anterior segment disseminated retinoblastoma.

Sustained-release hydrogels of topotecan for retinoblastoma.

Treatment of retinoblastoma, the most common primary ocular malignancy in children, has greatly improved over the last decade. Still, new devices for chemotherapy are needed to achieve better tumor control. The aim of this project was to develop an ocular drug delivery system for topotecan (TPT) loaded in biocompatible hydrogels of poly(ε-caprolactone)-poly(ethyleneglycol)-poly(ε-caprolactone) block copolymers (PCL-PEG-PCL) for sustained TPT release in the vitreous humor. Hydrogels were prepared from TPT and synthesized PCL-PEG-PCL copolymers. Rheological properties and in vitro and in vivo TPT release were studied. Hydrogel cytotoxicity was evaluated in retinoblastoma cells as a surrogate for efficacy and TPT vitreous pharmacokinetics and systemic as well as ocular toxicity were evaluated in rabbits. The pseudoplastic behavior of the hydrogels makes them suitable for intraocular administration. In vitro release profiles showed a sustained release of TPT from PCL-PEG-PCL up to 7days and drug loading did not affect the release pattern. Blank hydrogels did not affect retinoblastoma cell viability but 0.4% (w/w) TPT-loaded hydrogel was highly cytotoxic for at least 7days. After intravitreal injection, TPT vitreous concentrations were sustained above the pharmacologically active concentration. One month after injection, animals with blank or TPT-loaded hydrogels showed no systemic toxicity or retinal impairment on fundus examination, electroretinographic, and histopathological assessments. These novel TPT-hydrogels can deliver sustained concentrations of active drug into the vitreous with excellent biocompatibility in vivo and pronounced cytotoxic activity in retinoblastoma cells and may become an additional strategy for intraocular retinoblastoma treatment.

Pharmacokinetics, Safety, and Efficacy of Intravitreal Digoxin in Preclinical Models for Retinoblastoma.

PURPOSE: To assess in vitro cytotoxic activity and antiangiogenic effect, ocular and systemic disposition, and toxicity of digoxin in rabbits after intravitreal injection as a potential candidate for retinoblastoma treatment. METHODS: A panel of two retinoblastoma and three endothelial cell types were exposed to increasing concentrations of digoxin in a conventional (72-hour exposure) and metronomic (daily exposure) treatment scheme. Cytotoxicity was defined as the digoxin concentration that killed 50% of the cells (IC50) and was assessed with a vital dye in all cell types. Induction of apoptosis and cell-cycle status were evaluated by flow cytometry after both treatment schemes. Ocular and systemic disposition after intravitreal injection as well as toxicity was assessed in rabbits. Electroretinograms (ERGs) were recorded before and after digoxin doses and histopathological examinations were performed after enucleation. RESULTS: Digoxin was cytotoxic to retinoblastoma and endothelial cells under conventional and metronomic treatment. IC50 was comparable between both schedules and induced apoptosis in all cell lines. Calculated vitreous digoxin Cmax was 8.5 µg/mL and the levels remained above the IC50 for at least 24 hours after intravitreal injection. Plasma digoxin concentration was below 0.5 ng/ml. Retinal toxicity was evident after the third intravitreal dose with considerable changes in the ERG and histologic damage to the retina. CONCLUSIONS: Digoxin has antitumor activity for retinoblastoma while exerting antiangiogenic activity in vitro at similar concentrations. Metronomic treatment showed no advantage in terms of dose for cytotoxic effect. Four biweekly injections of digoxin led to local toxicity to the retina but no systemic toxicity in rabbits.

Novel protease inhibitor-loaded Nanoparticle-in-Microparticle Delivery System leads to a dramatic improvement of the oral pharmacokinetics in dogs.

With the advent of the Highly Active Antiretroviral Therapy, the morbidity and the mortality associated to HIV have been considerably reduced. However, 35-40 million people bear the infection worldwide. One of the main causes of therapeutic failure is the frequent administration of several antiretrovirals that results in low patient compliance and treatment cessation. In this work, we have developed an innovative Nanoparticle-in-Microparticle Delivery System (NiMDS) comprised of pure drug nanocrystals of the potent protease inhibitor indinavir free base (used as poorly water-soluble model protease inhibitor) produced by nanoprecipitation that were encapsulated within mucoadhesive polymeric microparticles. Pure drug nanoparticles and microparticles were thoroughly characterized by diverse complementary techniques. NiMDSs displayed an encapsulation efficiency of approximately 100% and a drug loading capacity of up to 43% w/w. In addition, mucoadhesiveness assays ex vivo conducted with bovine gut showed that film-coated microparticles were retained for more than 6 h. Finally, pharmacokinetics studies in mongrel dogs showed a dramatic 47- and 95-fold increase of the drug oral bioavailability and half-life, respectively, with respect to the free unprocessed drug. These results support the outstanding performance of this platform to reduce the dose and the frequency of administration of protease inhibitors, a crucial step to overcome the current patient-incompliant therapy.

Local and systemic toxicity of intravitreal melphalan for vitreous seeding in retinoblastoma: a preclinical and clinical study.

PURPOSE: Intravitreal melphalan is emerging as an effective treatment for refractory vitreous seeds in retinoblastoma, but there is limited understanding regarding its toxicity. This study evaluates the retinal and systemic toxicity of intravitreal melphalan in retinoblastoma patients, with preclinical validation in a rabbit model. DESIGN: Clinical and preclinical, prospective, cohort study. PARTICIPANTS: In the clinical study, 16 patient eyes received 107 intravitreal injections of 30 µg melphalan given weekly, a median of 6.5 times (range, 5-8). In the animal study, 12 New Zealand/Dutch Belt pigmented rabbits were given 3 weekly injections of 15 µg of intravitreal melphalan or vehicle to the right eye. METHODS: Electroretinogram (ERG) responses were recorded in both humans and rabbits. For the clinical study, ERG responses were recorded at baseline, immediately before each injection, and at each follow-up visit; 82 of these studies were deemed evaluable. Median follow-up time was 5.2 months (range, 1-11). Complete blood counts (CBCs) were obtained on the day of injection at 46 patient visits. In the animal study, ERG responses were obtained along with fluorescein angiography, CBCs, and melphalan plasma concentration. After humane killing, the histopathology of the eyes was evaluated. MAIN OUTCOME MEASURES: For the clinical study, we measured peak-to-peak ERG amplitudes in response to 30-Hz photopic flicker stimulation with comparisons between ERG studies before and after intravitreal melphalan. For the animal study, we collected ERG parameters before and after intravitreal melphalan injections with histopathologic findings. RESULTS: By linear regression analysis, over the course of weekly intravitreal injections in retinoblastoma patients, for every additional injection, the ERG amplitude decreased by approximately 5.8 µV. The ERG remained stable once the treatment course was completed. In retinoblastoma patients, there were no grade 3 or 4 hematologic events. One week after the second injection in rabbits, the a- and b-wave amplitude declined significantly in the melphalan treated eyes compared with vehicle-treated eyes (P<0.05). Histopathology revealed severely atrophic retina. CONCLUSIONS: Weekly injections of 30 µg of melphalan can result in a decreased ERG response, which is indicative of retinal toxicity. These findings are confirmed at an equivalent dose in rabbit eyes by ERG measurements and by histopathologic evidence of severe retinal damage. Systemic toxicity with intravitreal melphalan at these doses in humans or rabbits was not detected.

Plasma and ocular prednisolone disposition after oral treatment in cats.

OBJECTIVE: To evaluate the plasma and aqueous humor disposition of prednisolone after oral administration in cats. METHODS: Six cats were administered with a single oral dose of prednisolone (10 mg). Blood and aqueous humor samples were serially collected after drug administration. Prednisolone concentrations in plasma and aqueous humor were measured at 0.25, 0.5, 1.0, 1.5, 2.0, 3.0, 4.0, and 5.0 h after administration by a high-performance liquid chromatographic analytical method developed and validated for this purpose. RESULTS: Mean ± standard error (SE) of maximum plasma prednisolone concentration (300.8 ± 67.3 ng/mL) was reached at 1 h after administration. Prednisolone was distributed to the aqueous humor reaching a mean peak concentration of 100.9 ± 25.5 ng/mL at 1.25 h after administration. The mean ± SE systemic and aqueous humor exposure (AUC) was 553.3 ± 120.0 ng h/mL and 378.8 ± 64.9 ng h/mL, respectively. A high AUC(aqueous humor)/AUC(plasma) ratio was observed (0.68 ± 0.13). The mean half-life time of elimination in plasma and aqueous humor was 0.87 ± 0.16 h and 2.25 ± 0.44 h, respectively. CLINICAL SIGNIFICANCE: The observed high ratio between aqueous humor and plasma prednisolone concentrations indicates that extensive penetration of prednisolone to the anterior segment of the eye may occur. This is the first step that contributes to the optimization of the pharmacological therapeutics for the clinical treatment of uveitis.

Ocular and systemic toxicity of intravitreal topotecan in rabbits for potential treatment of retinoblastoma.

Treatment of intraocular retinoblastoma with vitreous seeding is a challenge. Different routes of chemotherapy administration have been explored in order to attaining pharmacological concentrations into the posterior chamber. Intravitreal drug injection is a promissing route for maximum bioavailability to the vitreous but it requires a well defined dose for achieving tumor control while limited toxicity to the retina. Topotecan proved to be a promising agent for retinoblastoma treatment due to its pharmacological activity and limited toxicity. High and prolonged concentrations were achieved in the rabbit vitreous after 5 µg of intravitreal topotecan. However, whether a lower dose could achieve potentially therapeutic levels remained to be determined. Thus, we here study the pharmacokinetics of topotecan after 0.5 µg and the toxicity profile of intravitreal topotecan in the rabbit eye as a potential treatment of retinoblastoma. A cohort of rabbits was used to study topotecan disposition in the vitreous after a single dose of 0.5 µg of intravitreal topotecan. In addition, an independent cohort of non-tumor bearing rabbits was employed to evaluate the clinical and retinal toxicity after four weekly injections of two different doses of intravitreal topotecan (Group A, 5 µg/dose; Group B, 0.5 µg/dose) to the right eye of each animal. The same volume (0.1 ml) of normal saline was administered to the left eye as control. A third group of rabbits (Group C) served as double control (both eyes injected with normal saline). Animals were weekly evaluated for clinical and hematologic values and ocular evaluations were performed with an inverse ophthalmoscope to establish potential topotecan toxicity. Weekly controls included topotecan quantitation in plasma of all rabbits. Electroretinograms (ERGs) were recorded before and after topotecan doses. One week after the last injection, topotecan concentrations were measured in vitreous of all eyes and samples for retinal histology were obtained. Our results indicate that topotecan shows non linear pharmacokinetics after a single intravitreal dose in the range of 0.5-5 µg in the rabbit. Vitreous concentration of lactone topotecan was close to the concentration assumed to be therapeutically active after 5 h of 0.5 µg intravitreal administration. Eyes injected with four weekly doses of topotecan (0.5 or 5 µg/dose) showed no significant differences in their ERG wave amplitudes and implicit times in comparison with control (p > 0.05). Animals showed no weight, hair loss or significant changes in hematologic values during the study period. There were no significant histologic damage of the retinas exposed to topotecan treatments. After intravitreal administration no topotecan could be detected in plasma during the follow-up period nor in the vitreous of treated and control animals after 1 week of the last injection. The present data shows that four weekly intravitreal injection of 5 µg of topotecan is safe for the rabbit eye. Despite multiple injections of 0.5 µg of topotecan are also safe to the rabbit eye, lactone topotecan vitreous concentrations were potentially active only after 5 h of the administration. We postulate promising translation to clinics for retinoblastoma treatment.

Therapeutic benefit of melatonin in experimental feline uveitis.

Uveitis is a frequent ophthalmic disorder which constitutes one of the main causes of blindness in domestic cats. The aim of this report was to analyze the effect of melatonin on experimentally induced uveitis in cats. Bacterial lipopolysaccharide (LPS) was injected intravitreally into one eye from intact cats, while the contralateral eye was injected with vehicle. Melatonin was orally administered every 24 hr to a group of ten cats, from 24 hr before until 45 days after intravitreal injections. Eyes were evaluated by means of clinical evaluation, intraocular pressure (IOP), blood-ocular barrier integrity (via measurement of protein concentration and cell content in samples of aqueous humor [AH]), electroretinogram (ERG), and histological examination of the retinas. In LPS-treated eyes, several clinical signs were observed until day 45 postinjection. The treatment with melatonin significantly decreased clinical signs and prevented the reduction in IOP induced by LPS. In LPS-injected eyes, melatonin significantly preserved the blood-ocular barrier integrity, as shown by a decrease in the number of infiltrating cells and protein concentration in the AH. Mean amplitudes of scotopic ERG a- and b-waves were significantly reduced in eyes injected with LPS, whereas melatonin significantly prevented the effect of LPS. At 45 days after injection, LPS induced alterations in photoreceptors and at the middle portion of the retina, whereas melatonin preserved the retinal structure. These results indicate that melatonin prevented clinical, biochemical, functional, and histological alterations induced by LPS injection. Thus, melatonin might constitute a useful tool for the treatment of feline uveitis.

Characterization of uveitis induced by use of a single intravitreal injection of bacterial lipopolysaccharide in cats.

OBJECTIVE: To investigate the use of a single intravitreal injection of bacterial lipopolysaccharide (LPS) to experimentally induce uveitis in cats. ANIMALS: 7 young male European shorthair cats that were considered physically and ophthalmologically healthy. PROCEDURES: In each cat, LPS was injected intravitreally into 1 eye; the contralateral eye was injected with the preparation vehicle. During a period of 45 days, both eyes were evaluated by means of clinical evaluation; assessment of the integrity of the blood-aqueous humor barrier (determined via measurement of protein concentration and cell content in samples of aqueous humor); functional analysis (via electroretinography); and following euthanasia, histologic examination of the retinas. RESULTS: In LPS-treated eyes, several clinical signs were observed until day 45 after injection. Compared with vehicle-treated eyes, intraocular pressure was significantly lower and protein concentration and the number of infiltrating cells were significantly higher in LPS-treated eyes. Mean amplitudes of scotopic electroretinographic a- and b-waves were significantly reduced in eyes injected with LPS, compared with findings in eyes injected with vehicle. At 45 days after injection, LPS-induced alterations in photoreceptors and the middle portion of the retina were detected histologically. CONCLUSION AND CLINICAL RELEVANCE: Results indicated that a single intravitreal injection of LPS in eyes of cats induced clinical, biochemical, functional, and histologic changes that were consistent with the main features of naturally occurring uveitis. This technique may be a useful tool in the investigation of new treatment strategies for uveitis in cats.

Circadian rhythm of intraocular pressure in cats.

OBJECTIVE: To evaluate the rhythm of intraocular pressure (IOP) in healthy domestic cats with no evidence of ocular disease and to analyze the influence of photoperiod, age, gender and ocular diseases on diurnal-nocturnal variations of cat IOP. ANIMALS: All animals were Domestic Short-haired cats; 30 were without systemic or ocular diseases, classified as follows: 12 male intact adult cats, five intact adult female, five adult spayed female, and eight male cats; the latter were less than 1 year of age. In addition, five adult cats with uveitis and three adult cats with secondary glaucoma were included. PROCEDURE: IOP was assessed with a Tono-Pen XL at 3-h intervals over a 24-h period in 12 healthy adult male cats kept under a photoperiod of 12-h light/12-h darkness for 2 weeks. Eight animals from the same group were then kept under constant darkness for 48 h, and IOP was measured at 3-h intervals for the following 24 h. In addition, IOP was assessed at 3 p.m. and 9 p.m. in five intact females, five spayed females, and in eight young cats, as well as in five adult cats with uveitis and three glaucomatous cats. RESULTS: Consistent, daily variations in IOP were observed in animals exposed to a light-dark cycle, with maximal values during the night. In cats exposed to constant darkness, maximal values of IOP were observed at subjective night. Differences of IOP values between 3 p.m. and 9 p.m. (diurnal-nocturnal variations) persisted in intact females, spayed females, and young animals, as well as in uveitic and glaucomatous eyes. CONCLUSIONS: The present results indicate a daily rhythm of cat IOP, which appears to persist in constant darkness, suggesting some level of endogenous circadian control. In addition, daily variations of cat IOP seem to be independent of gender, age, or ocular diseases (particularly uveitis and glaucoma).