Increased drug concentration and repeated eye drop administration as strategies to optimize topical drug delivery: A fluorophotometric study in healthy dogs.

OBJECTIVES: Determine tear film kinetics with different fluorescein concentrations and repeated eye drop administration at various time intervals. ANIMALS STUDIED: Six healthy Beagles. PROCEDURES: Six experiments were conducted on separate days: single eye drop administration (control) or two separate eye drops administered at 30 s, 1, 2, 5, and 10 min intervals. For each experiment, one eye received 0.3% fluorescein solution while the other eye received 1% fluorescein solution, and tear fluid was collected with capillary tubes at 0, 1, 5, 10, 20, 30, 40, 50, 60, 90, 120, and 180 min. Fluorescein concentrations were measured using automated fluorophotometry. RESULTS: Compared with 0.3% solution, eyes receiving 1% fluorescein solution had significantly higher tear film concentrations (p ≤ .046) and the area-under-the-fluorescein-time curve was twofold greater (p = .005). Compared with control: (i) Tear film concentrations were significantly higher for up to 20 min when repeating administration 30 s to 5 min after the first drop (p ≤ .006); (ii) The highest increase in area-under-the-curve was obtained with 2 and 5 min intervals for 0.3% (+109%-130%) and 1% solutions (+153%-157%); (iii) The highest increase in median precorneal retention time (defined as tear film concentration < 5% from baseline values) was obtained with 5 min intervals for 0.3% (55 min vs. 15 min in control) and 2-5 min intervals for 1% solutions (50 min vs. 25 min in control). CONCLUSIONS: Drug delivery to the ocular surface can be enhanced by using more concentrated formulations and/or by repeating eye drop administration 2-5 min after the first dose.

Precorneal retention time of ocular lubricants measured with fluorophotometry in healthy dogs.

OBJECTIVE: Determine the precorneal retention time of five different ocular lubricants commonly used in dogs. ANIMALS STUDIED: Six healthy Beagle dogs (n = 12 eyes). PROCEDURES: Five ocular lubricants were studied: Artificial Tears Solution® (1.4% polyvinyl alcohol), I-Drop® Vet Plus (0.25% hyaluronate), Optixcare® Eye Lube Plus (0.25% hyaluronate), Systane® Ultra (0.4% polyethylene glycol 400 and 0.3% propylene glycol), and Artificial Tears Ointment® (mineral oil/white petrolatum). Each lubricant was mixed with 10% sodium fluorescein to achieve 1% fluorescein formulations. Following topical administration of 35 mg in each eye, tear fluid was collected with capillary tubes at selected times (0, 1, 5, 10, 20, 30, 40, 50, 60, 90, 120, 180 min) and fluorescein concentrations were measured with a computerized scanning ocular fluorophotometer. RESULTS: Tear fluorescence was significantly greater with Artificial Tears Ointment® compared with other lubricant formulations from 1 to 20 min post-administration. Median (range) precorneal retention times were significantly different among the 5 lubricants, ranging from 40 minutes (20-90 min) for Artificial Tears Ointment®, 35 min (20-90 min) for Systane® Ultra, 30 min (10-60 min) for I-Drop® Vet Plus, 25 min (10-60 min) for Optixcare® Eye Lube Plus, and 10 min (10-20 min) for Artificial Tears Solution®. Precorneal retention time was significantly lower for Artificial Tears Solution® compared with the other 4 formulations. CONCLUSIONS: This study established normative data for the retention time of common lubricants on the ocular surface of dogs, which may be used to guide clinicians with their choice of lubricant and frequency of administration.

Impact of acute conjunctivitis on ocular surface homeostasis in dogs.

OBJECTIVE: To investigate the effects of acute conjunctivitis on tear film characteristics and corneal sensitivity in dogs. ANIMALS STUDIED: Eight female spayed Beagle dogs (1.5-2 years old, 7.5-10 kg). PROCEDURES: On two consecutive days, one randomly selected eye in each dog received 1 or 375 mg/mL histamine solution to induce mild or severe conjunctivitis, while the contralateral eye served as control. Diagnostic tests were performed in the following order: fluorescein instillation and repeated tear collection over 20 minutes (to determine tear volume [TV] and turnover rate [TTR] by fluorophotometry), Schirmer tear test-1 (STT-1), tear ferning, corneal esthesiometry, and tear film breakup time (TFBUT). RESULTS: Results are presented as median values for severe conjunctivitis, mild conjunctivitis, and control eyes. Eyes with severe conjunctivitis had significantly higher STT-1 (24, 19.5, 17.5 mm/min; P = .002) and significantly lower TFBUT (10.5, 13.5, 15.5 s; P = .002), but no changes were noted in corneal tactile sensation (2, 2.5, 2.5 cm) or tear ferning (grades 2, 2, 2.5). Severe conjunctivitis significantly increased TV by nearly 10-fold (631, 97, 65 µL) initially (reflex tearing), although basal TV returned rapidly (<5 minutes) in all eyes (46, 58, 48 µL). Finally, there was a nonsignificant trend for higher reflex TTR in the conjunctivitis vs control eyes (68, 58, 43%/min). CONCLUSIONS: Experimentally induced conjunctivitis increases tear quantity and decreases tear quality in dogs, but has no impact on corneal sensitivity. Changes in tear film dynamics could affect ocular pharmacology (eg, precorneal retention time), although homeostasis of lacrimal volume and drainage is rapidly restored.

Effect of topical ophthalmic administration of 0.005% latanoprost solution on aqueous humor flow rate and intraocular pressure in ophthalmologically normal adult Beagles.

OBJECTIVE: To determine the effect of topical ophthalmic administration of 0.005% latanoprost solution on aqueous humor flow rate (AHFR) and intraocular pressure (IOP) in ophthalmologically normal dogs. ANIMALS: 12 adult Beagles. PROCEDURES: In a masked crossover design involving two 10-day experimental periods separated by a 7-day washout period, dogs were randomly assigned to first receive latanoprost or artificial tears (control) solution and then the opposite treatment in the later experimental period. Each experimental period was divided into a baseline phase (days 1 to 3), baseline fluorophotometry assessment (day 4), treatment phase (1 drop of latanoprost or artificial tears solution administered twice daily in each eye on days 5 to 9 and once on day 10), and posttreatment fluorophotometry assessment (day 10). Measured fluorescein concentrations were used to calculate baseline and posttreatment AHFRs. The IOP was measured 5 times/d in each eye during baseline and treatment (days 5 to 9) phases. RESULTS: Mean baseline and posttreatment AHFR values did not differ significantly in either experimental period (latanoprost or control). In the latanoprost period, mean IOP was significantly lower during treatment than at baseline; there was no difference in corresponding IOP values during the control period. In the latanoprost period, mean IOP was significantly higher on the first day of treatment than on subsequent treatment days. CONCLUSIONS AND CLINICAL RELEVANCE: In ophthalmologically normal dogs, topical ophthalmic administration of 0.005% latanoprost solution significantly decreased IOP but did not affect AHFR. Thus, the ocular hypotensive effect of latanoprost did not appear to have been caused by a reduction in aqueous humor production. (Am J Vet Res 2019;80:498-504).

Effects of oral administration of anti-inflammatory medications on inhibition of paracentesis-induced blood-aqueous barrier breakdown in clinically normal cats.

OBJECTIVE: To assess inhibitory effects of orally administered anti-inflammatory medications on paracentesis-induced intraocular inflammation in clinically normal cats. ANIMALS: 30 clinically normal domestic shorthair cats. PROCEDURES: Cats were randomly assigned to a control group and 4 treatment groups. Cats in the treatment groups received an anti-inflammatory medication orally once daily at 7 AM (acetylsalicylic acid [40.5 mg/cat], meloxicam [0.1 mg/kg], prednisone [5 mg/cat], or prednisolone [5 mg/cat]) for 5 days beginning 2 days before paracentesis-induced breakdown of the blood-aqueous barrier (BAB) and continuing until 2 days after paracentesis. Paracentesis of the anterior chamber was performed in 1 randomly selected eye of each cat. Fluorophotometry was performed in both eyes of each cat immediately before (time 0) and 6, 24, and 48 hours after paracentesis. RESULTS: At 24 and 48 hours after paracentesis, fluorescein concentration in the eye subjected to paracentesis in the cats receiving prednisolone was decreased, compared with that in the control cats. At 48 hours, a decrease in the fluorescein concentration was also apparent in the eye subjected to paracentesis in the cats receiving meloxicam, compared with that in the control cats. There was no evidence of treatment effects for acetylsalicylic acid or prednisone. There was no evidence of treatment effects in eyes not subjected to paracentesis. CONCLUSIONS AND CLINICAL RELEVANCE: Orally administered prednisolone and meloxicam significantly decreased intraocular inflammation in clinically normal cats with paracentesis-induced BAB breakdown. Oral administration of prednisolone or meloxicam may be an effective treatment for cats with uveitis.

Effects of a topically applied 2% delta-9-tetrahydrocannabinol ophthalmic solution on intraocular pressure and aqueous humor flow rate in clinically normal dogs.

OBJECTIVE: To determine the effects of topically applied 2% delta-9-tetrahydrocannabinol (THC) ophthalmic solution on aqueous humor flow rate (AHFR) and intraocular pressure (IOP) in clinically normal dogs. ANIMALS: 21 clinically normal dogs. PROCEDURES: A randomized longitudinal crossover design was used. Following acquisition of baseline IOP (morning and evening) and AHFR (afternoon only) data, dogs were randomly assigned to 2 treatment groups and received 1 drop of either 2% THC solution or a control treatment (olive oil vehicle) to 1 randomly selected eye every 12 hours for 9 doses. The IOPs and AHFRs were reassessed after the final treatment. Following a washout period of ≥ 7 days, dogs were administered the alternate treatment in the same eye, and measurements were repeated. RESULTS: Mean ± SD IOPs in the morning were 15.86 ± 2.48 mm Hg at baseline, 12.54 ± 3.18 mm Hg after THC treatment, and 13.88 ± 3.28 mm Hg after control treatment. Mean ± SD IOPs in the evening were 13.69 ± 3.36 mm Hg at baseline, 11.69 ± 3.94 mm Hg after THC treatment, and 12.13 ± 2.99 mm Hg after control treatment. Mean IOPs were significantly decreased from baseline after administration of THC solution but not the control treatment. Changes in IOP varied substantially among individual dogs. Mean ± SD AHFRs were not significantly different from baseline for either treatment. CONCLUSIONS AND CLINICAL RELEVANCE: Topical application of 2% THC ophthalmic solution resulted in moderate reduction of mean IOP in clinically normal dogs. Further research is needed to determine efficacy in dogs with glaucoma.

Repeated anterior chamber fluorophotometric evaluation of the eyes of ophthalmologically normal dogs.

OBJECTIVE: To perform repeated anterior chamber fluorophotometry on both eyes of ophthalmologically normal dogs to measure fluorescein concentrations over a 5-day period and identify any change in the degree of anterior chamber fluorescence over time or difference between eyes. ANIMALS: 9 healthy adult dogs (18 eyes). PROCEDURES: Each dog received an IV injection of 10% fluorescein solution, and anterior chamber fluorophotometry was performed 1 hour later on both eyes. This procedure was repeated at the same time each day for 5 consecutive days. RESULTS: A significant increase in fluorescein concentration was evident in the anterior chamber on day 5 in the right eye and days 2, 3, 4, and 5 in the left eye. There was no significant difference in concentration between the left and the right eyes on any day. CONCLUSIONS AND CLINICAL RELEVANCE: The increase in ocular fluorescein concentration in the study dogs was unlikely to be of clinical importance and is only pertinent for subsequent research studies. This is a limitation that should be considered when reporting fluorophotometry data as fluorescein concentration or as change in fluorescein concentration from baseline.

Effects of ocular administration of ophthalmic 2% dorzolamide hydrochloride solution on aqueous humor flow rate and intraocular pressure in clinically normal cats.

OBJECTIVE: To determine the effects of ocular administration of ophthalmic 2% dorzolamide hydrochloride solution on aqueous humor flow rate (AHFR) and intraocular pressure (IOP) in clinically normal cats. ANIMALS: 20 clinically normal domestic shorthair cats. PROCEDURES: Following an acclimation period, IOP was measured in each eye of all cats 5 times daily for 3 days to determine baseline values. Fifteen cats received 1 drop of 2% dorzolamide solution and 5 cats received 1 drop of control solution in each eye every 8 hours for 5 days (treatment phase). The IOP of each eye was measured 5 times during each day of the treatment phase. Prior to and after the treatment phase, AHFR in both eyes of each cat was measured via fluorophotometry. RESULTS: Prior to treatment, AHFR or IOP did not differ between the treatment and control groups. In dorzolamide-treated cats, mean AHFR after the treatment phase (3.47 ± 1.5 µL/min) was significantly lower than the value prior to treatment (5.90 ± 2.2 µL/min) and mean IOP during the treatment phase (11.1 ± 1.0 mm Hg) was significantly lower than the baseline mean IOP (14.9 ± 1.0 mm Hg). In the control group, IOP values did not differ before or during the treatment phase and AHFRs did not differ before and after the treatment phase. CONCLUSIONS AND CLINICAL RELEVANCE: Ocular administration of 2% dorzolamide solution significantly decreased AHFR and IOP in clinically normal cats. Application of 2% dorzolamide solution may be an effective treatment in cats with glaucoma.

Evaluation of the aqueous humor flow rate in the eyes of clinically normal cats by use of fluorophotometry.

OBJECTIVE: To evaluate aqueous humor flow rate in the eyes of clinically normal cats by use of a noninvasive technique successfully used in other species. ANIMALS: 20 domestic shorthair cats. PROCEDURES: 1 drop of 10% fluorescein sodium was instilled into both eyes of 5 cats every 5 minutes until 3 drops had been administered. Fluorophotometry was performed at 2, 4, 5, 6, 7, 8, 9, and 10 hours after fluorescein application to monitor fluorescein removal and determine aqueous humor flow rate. The 3-drop protocol was used for the remaining 15 cats, and fluorophotometry was performed at 5, 6, 7, and 8 hours after fluorescein application. Aqueous humor flow rates were calculated manually by use of established equations with minor adjustments to constant values to reflect feline anatomic features. Correlation coefficients and slope ratios were calculated to assess the legitimacy of the flow rate data. Paired t tests were calculated to assess for differences between the right and left eyes. RESULTS: Mean ± SD calculated aqueous humor flow rate in the right, left, and both eyes of the 20 cats was 5.94 ± 2.30 µL/min, 5.05 ± 2.06 µL/min, and 5.51 ± 2.21 µL/min, respectively. Correlation coefficients and slope ratios revealed that the aqueous humor flow rates were accurate. No significant differences in values for the right and left eyes were detected. CONCLUSIONS AND CLINICAL RELEVANCE: Accurate aqueous humor flow values for cats can be determined by use of the fluorophotometric technique evaluated in this study.

Fluorophotometric determination of aqueous humor flow rates in red-tailed hawks (Buteo jamaicensis).

OBJECTIVE: To determine aqueous humor flow rate (AHFR) in an avian species by use of anterior segment fluorophotometry. ANIMALS: 9 healthy red-tailed hawks (Buteo jamaicensis; 4 males and 5 females) that ranged from 8 months to 8 years of age. PROCEDURES: A protocol was developed for fluorophotometric determination of AHFR. Topical administration of 10% fluorescein was used to load the corneas, and corneal and aqueous humor fluorescein concentrations were measured approximately 5, 6.5, and 8 hours later. Concentration-versus-time plots were generated, and slopes and cornea-to-aqueous humor concentration ratios from these plots were used to manually calculate flow rates. RESULTS: Mean ± SD AHFRs for the right eye, left eye, and both eyes were 3.17 ± 1.36 µL/min (range, 1.67 to 6.21 µL/min), 2.86 ± 0.88 µL/min (range, 2.04 to 4.30 µL/min), and 2.90 ± 0.90 µL/min (range, 1.67 to 4.42 µL/min), respectively. The AHFRs were similar for right and left eyes. These flow rates represented a mean aqueous humor transfer coefficient of 0.0082/min, which is similar to that of mammalian species. CONCLUSIONS AND CLINICAL RELEVANCE: The AHFR in red-tailed hawks was similar to that of most mammalian species, and the fractional egress was almost identical to that of other species. This information will allow a greater understanding of aqueous humor flow in avian eyes, which is crucial when evaluating diseases that affect avian eyes as well as medications that alter aqueous humor flow.

Fluorophotometric and tonometric evaluation of ocular effects following aqueocentesis performed with needles of various sizes in dogs.

OBJECTIVE: To measure ocular effects (blood-aqueous barrier breakdown and intraocular pressure [IOP]) following aqueocentesis performed with needles of various sizes in dogs. ANIMALS: 28 healthy adult dogs. PROCEDURES: 24 dogs underwent unilateral aqueocentesis (24 treated eyes and 24 contra-lateral untreated eyes); 25-, 27-, or 30-gauge needles were used in 3 treatment groups (n = 8/group). Four dogs were untreated controls. Aqueocentesis was performed during sedation and topical anesthesia. Anterior chamber fluorophotometry was performed before and after aqueocentesis on day 1. On days 2 through 5, sedation and fluorophotometry were repeated. Intraocular pressure was measured with a rebound tonometer at multiple time points. RESULTS: Aqueocentesis resulted in blood-aqueous barrier breakdown detected via fluorophotometry in all treated eyes, with barrier reestablishment by day 5. On day 2, the contralateral untreated eyes of all 3 groups also had significantly increased fluorescence. Use of a 25-gauge needle resulted in a significant increase in treated eyes' anterior chamber fluorescence on days 3 and 5 as well as a significant increase in IOP 20 minutes following aqueocentesis, compared with the other treatment groups. CONCLUSIONS AND CLINICAL RELEVANCE: Aqueocentesis performed with a 25-gauge needle resulted in the greatest degree of blood-aqueous barrier breakdown and a brief state of intraocular hypertension. Use of a 27- or 30-gauge needle is recommended for aqueous paracentesis. A consensual ocular reaction appeared to occur in dogs following unilateral traumatic blood-aqueous barrier breakdown and may be of clinical importance.

Tear volume, turnover rate, and flow rate in ophthalmologically normal horses.

OBJECTIVE: To determine tear volume, turnover rate, and flow rate in ophthalmologically normal horses by use of fluorophotometry. ANIMALS: 12 mares free of ophthalmic disease. PROCEDURES: 2 microL of 10% sodium fluorescein was instilled onto 1 eye of each horse, and tear samples were collected via microcapillary tubes from the inferonasal conjunctival culde-sac at 0, 2, 4, 6, 10, 15, and 20 minutes after instillation. Collected tear samples were then measured for fluorescein concentrations with a computerized scanning ocular fluorophotometer. A decay curve plot of concentration changes over time was used to determine tear flow rate and volume through 2 different mathematical treatments of the data (the including method and the excluding method). RESULTS: Fluorescein concentration in tears decreased in a first-order manner. The including method yielded a mean tear volume of 360.09 microL, a turnover rate of 12.22%/min, and a flow rate of 47.77 microL/min. The excluding method yielded values of 233.74 microL, 13.21%/min, and 33.62 microL/min, respectively. Mean +/- SD correlation coefficients for the natural logarithm of the fluorescein concentration versus time were 0.93 +/- 0.12 for the including method and 0.98 +/- 0.03 for the excluding method. CONCLUSIONS AND CLINICAL RELEVANCE: The excluding method yielded more accurate results. A tear flow rate of 33.62 microL/min and a tear volume of 233.74 microL imply a complete recycling of the tear volume in approximately 7 minutes and suggest that increased dosing regimens or constant infusion methods for topical administration of ophthalmic drugs may be indicated when treating horses for corneal disease in which high ocular surface concentrations are needed.

Effect of lacrimal punctal occlusion on tear production and tear fluorescein dilution in normal dogs.

OBJECTIVE: To evaluate effects of lacrimal punctal plugs positioned in either the upper, lower, or combination of upper and lower lacrimal canaliculi on plug retention and tolerance; tear production, as measured by the Schirmer tear test; and the dilution of fluorescein within the tear film in normal dogs. MATERIAL AND METHODS: Lacrimal punctal plugs were positioned in the lower, upper, or combination of lower and upper plugs in six laboratory-quality Beagles under topical anesthesia. Retention of plugs was evaluated daily from 8 to 23 days by visual inspection and slit-lamp biomicroscopy. Schirmer tear tests (STT 1 without topical anesthesia) were performed at 48-h intervals. Dilution of fluorescein was determined at 5- and 45-min post-fluorescein instillations once weekly. RESULTS: Lacrimal punctal plugs of 0.4 and 0.6 mm in diameter were retained for 14 (lower plugs: 100%) and 23 days (75%), and for the upper plugs at 8 days less often (75%), and were infrequently locally nonirritating. Combination of lower and upper plugs seemed to adversely affect retention of either plug. When loss of the plugs occurred, a next larger size plug was necessary suggesting some stretching of the lacrimal canaliculi occurred. Pre- and postplug placement STT results indicated no change with lower and combination lacrimal punctal plugs, but decreased levels following upper lacrimal punctal plugs. Tear fluorescein levels at 5 and 45 min in control eye (no punctum plugs) were 3.39% and 0.14%, respectively. With lower, upper, and the combination of lower and upper lacrimal puncta plugs, tear fluorescein levels at 45 min were higher than the controls (lower: 0.76%; upper: 0.45%, and combination 0.56%). CONCLUSION: Lacrimal punctal silicone plugs are retained for 8-23 days in the lower, upper, and combined lower and upper canaliculi at high rates. Effects on STT levels appear limited. Fluorescein within the tear film persists longer with all different positioned lacrimal punctum plugs than in the control eyes.

Spontaneous chronic corneal epithelial defects (SCCED) in dogs: clinical features, innervation, and effect of topical SP, with or without IGF-1.

PURPOSE: To delineate the clinical features and alterations in innervation and substance P (SP) content in spontaneous chronic corneal epithelial defects (SCCED) in dogs and to conduct a preliminary investigation evaluating the efficacy of topical SP, with or without insulin-like growth factor (IGF)-1, in the treatment of this disorder. METHODS: Complete ophthalmic examinations, including Cochet-Bonnet aesthesiometry, were performed in 45 canine patients that had spontaneous corneal epithelial defects of at least 3 weeks' duration and with no identifiable cause. Eighteen patients had superficial keratectomies performed, and the corneal nerves were labeled immunohistochemically with antibodies against protein gene product (PGP)-9.5, SP, vasoactive intestinal peptide (VIP), and tyrosine hydroxylase (TH). Relative fiber densities were assessed qualitatively and quantitatively. Corneal epithelial cell and tear SP contents were determined in affected and normal dogs by an enzyme immunoassay. A preliminary open-label treatment trial of topical SP, with and without IGF-1, was conducted in 21 dogs. RESULTS: The duration of the erosion before admittance into the study was a mean of 9.22 weeks (range, 3-52). The average patient was middle aged (mean, 9.25 +/- 1.85 years [SD]); no sex predisposition of the disease was identified. Boxers, golden retrievers, and keeshonds were overrepresented when compared with the normal hospital population. Corneal sensation was normal. Marked alterations in corneal innervation were identified in affected dogs with abnormal increased SP and calcitonin gene-related peptide (CGRP)-immunoreactive nerve plexuses identified surrounding the periphery of the epithelial defect. The SP content of epithelial cells surrounding the defect increased, whereas the tear SP content remained unchanged. Of the canine patients treated with SP, with or without IGF-1, 70% to 75% had complete healing of the defect. CONCLUSIONS: This idiopathic spontaneous corneal disease in dogs shares clinical features with chronic epithelial defects in humans. The presence of marked alterations in peptidergic innervation and positive response to topical therapy with SP suggest that SP plays a critical role in corneal wound-healing processes.

Fluorophotometric determination of aqueous humor flow rate in clinically normal dogs.

OBJECTIVE: To determine aqueous humor flow rate in clinically normal dogs, using fluorophotometry. ANIMALS: 20 clinically normal Beagles. PROCEDURE: A study was performed on 5 dogs to establish an optimal protocol for fluorophotometric determination of aqueous humor flow rate. This protocol then was used to measure aqueous humor flow rate in 15 dogs. Corneas were loaded with fluorescein by topical application, and corneal and aqueous humor fluorescein concentrations were measured 5, 6.5, and 8 hours after application. Concentration-versus-time plots were generated, and slopes and ratios of the fluorescein concentration in the cornea and aqueous humor from these graphs were used to calculate flow rates. Calculations were performed by use of automated software provided with the fluorophotometer and by manual computation, and the 2 calculation methods were compared. RESULTS: The protocol established for the 5 dogs resulted in semilogarithmic and parallel decay of corneal and aqueous humor concentrations. Manually calculated mean +/- SD aqueous humor flow rates for left, right, and both eyes were 5.58 +/- 2.42, 4.86 +/- 2.49, and 5.22 +/- 1.87 microl/min, respectively, whereas corresponding flow rates calculated by use of the automated software were 4.54 +/- 3.08, 4.54 +/- 3.10, and 4.54 +/- 2.57 microl/min, respectively. Values for the left eye were significantly different between the 2 computation methods. CONCLUSIONS AND CLINICAL RELEVANCE: Aqueous humor flow rates can be determined in dogs, using fluorophotometry. This technique can be used to assess pathologic states and medical and surgical treatments that alter aqueous humor dynamics.

Effects of topical application of a 2% solution of dorzolamide on intraocular pressure and aqueous humor flow rate in clinically normal dogs.

OBJECTIVE: To evaluate effects of topical application of a 2% solution of dorzolamide on intraocular pressure (IOP) and aqueous humor flow rate in clinically normal dogs. ANIMALS: 15 Beagles. PROCEDURE: The IOP was measured in both eyes of all dogs for 3 days to determine baseline values. In a single-dose study, 50 microl of dorzolamide or control solution was applied in both eyes at 7:00 AM, and IOP was measured 7 times/d. In a multiple-dose study, dorzolamide or control solution was applied to both eyes 3 times/d for 6 days, and IOP was measured 4 times/d during treatment and for 5 days after cessation of treatment. Aqueous humor flow rate was measured for all dogs fluorophotometrically prior to treatment and during the multiple-dose study. RESULTS: In the single-dose study, dorzolamide significantly decreased IOP from 30 minutes to 6 hours after treatment. Mean decrease in IOP during this time span was 3.1 mm Hg (18.2%). Maximal decrease was detected 6 hours after treatment (3.8 mm Hg, 22.5%). In the multiple-dose study, dorzolamide decreased IOP at all time points, and maximal decrease was detected 3 hours after treatment (4.1 mm Hg, 24.3%). Mean aqueous humor flow rate decreased from 5.9 to 3.4 microl/min (43%) after treatment in the dorzolamide group. CONCLUSIONS AND CLINICAL RELEVANCE: Topical application of a 2% solution of dorzolamide significantly decreases IOP and aqueous humor flow rate in clinically normal dogs. Therefore, topical administration of dorzolamide should be considered for the medical management of dogs with glaucoma.

Comparative efficacy of topically applied flurbiprofen, diclofenac, tolmetin, and suprofen for the treatment of experimentally induced blood-aqueous barrier disruption in dogs.

OBJECTIVE: To compare the relative efficacies of 4 topical nonsteroidal anti-inflammatory drugs at preventing blood-aqueous barrier (BAB) disruption in dogs. DESIGN: 1 eye of each dog was treated with 1% suspensions of diclofenac, flurbiprofen, suprofen, or tolmetin, or with control solution. After 4 applications of eyedrops at 10-minute intervals, BAB disruption was induced in the treated eye by anterior chamber paracentesis. The severity of BAB disruption was measured by anterior chamber fluorophotometry. ANIMALS: 40 ocular-normal dogs. PROCEDURE: After pretreatment with eyedrops, rapid 100-microliters nonleaking anterior chamber paracentesis was performed in 1 eye of each dog to induce BAB disruption. 1 day after paracentesis, 1 ml of 10% fluorescein sodium was injected i.v.. The amount of fluorescein entering the anterior chamber of each eye was measured 30 to 60 minutes later by use of a computerized scanning fluorophotometer. The degree of BAB disruption was determined by comparing the amount of fluorescein entering the aqueous humor of the paracentesed eye with that of the nonparacentesed eye. RESULTS: At postparacentesis day 1, the order of statistically significant BAB-stabilizing efficacy among groups was: diclofenac > flurbiprofen > suprofen > tolmetin = control solution. CONCLUSIONS: Topically applied 1% suspensions of diclofenac, flurbiprofen, and suprofen are effective at preventing BAB disruption after paracentesis in dogs, indicating their potential usefulness for treatment of prostaglandin-mediated ocular disease. 1% tolmetin is no more effective than control solution.

Fluorophotometric evaluation of experimental blood-aqueous barrier disruption in dogs.

A protocol for performing slit-lamp fluorophotometry of the anterior chamber in dogs was established. The technique was then used to develop a model of blood-aqueous barrier disruption that can be used for comparative testing of ophthalmic anti-inflammatory drugs. It was determined that barrier disruption induced by a slow, controlled paracentesis of a small volume of aqueous humor may provide the most reliable model for drug testing. Additionally, fluorophotometry proved to be a sensitive and accurate means of detecting breakdown of the blood-aqueous barrier.