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.

Heritability of lenticular myopia in English Springer spaniels.

PURPOSE: We determined whether naturally-occurring lenticular myopia in English Springer spaniels (ESS) has a genetic component. METHODS: Streak retinoscopy was performed on 226 related ESS 30 minutes after the onset of pharmacologic mydriasis and cycloplegia. A pedigree was constructed to determine relationships between affected offspring and parents. Estimation of heritability was done in a Bayesian analysis (facilitated by the MCMCglmm package of R) of refractive error in a model, including terms for sex and coat color. Myopia was defined as ≤-0.5 diopters (D) spherical equivalent. RESULTS: The median refractive error for ESS was 0.25 D (range, -3.5 to +4.5 D). Median age was 0.2 years (range, 0.1-15 years). The prevalence of myopia in related ESS was 19% (42/226). The ESS had a strong correlation (r = 0.95) for refractive error between the two eyes. Moderate heritability was present for refractive error with a mean value of 0.29 (95% highest probability density, 0.07-0.50). CONCLUSIONS: The distribution of refractive error, and subsequently lenticular myopia, has a moderate genetic component in ESS. Further investigation of genes responsible for regulation of the development of refractive ocular components in canines is warranted.

Ocular components in three breeds of dogs with high prevalence of myopia.

PURPOSE: Experimental models of human myopia have been developed using animals of various species. However, most of these are an induced rather than a spontaneous, naturally occurring myopia. This study was conducted to evaluate whether the spontaneous myopia found in three canine breeds was axial in nature and therefore similar to humans. METHODS: Refractive error was measured by cycloplegic retinoscopy and ocular components by A-scan ultrasound (ocular axial dimensions) and videophakometry (corneal and lens radii and powers) in 83 dogs of three breeds [English Springer Spaniels (n = 33), Toy Poodles (n = 36), and Collies (n = 14)]. Dogs with refractive errors equal to or more myopic than -0.5 diopters spherical equivalent were considered myopic. RESULTS: Myopia was most common in Toy Poodles (63.9%), followed by English Springer Spaniels (36.4%) and Collies (35.7%). Axial lengths and vitreous chamber depths were not different between myopic and non-myopic dogs (p = 0.84 and 0.63, respectively). The anterior crystalline lens radius was steeper and the lens power was greater in myopic compared with non-myopic dogs (p = 0.048 for each). CONCLUSIONS: Spontaneous myopia was very common in all three breeds in this sample of dogs, with Toy Poodles being most affected. However, the cause of the myopia appeared to be refractive, that is from a steeper, more powerful crystalline lens, rather than from excess axial elongation. These breeds do not appear to be promising models for human axial myopia.

Refractive states of eyes and association between ametropia and breed in dogs.

OBJECTIVE: To assess the refractive state of eyes in various breeds of dogs to identify breeds susceptible to ametropias. ANIMALS: 1,440 dogs representing 90 breeds. PROCEDURES: In each dog, 1 drop of 1% cyclopentolate or 1% tropicamide was applied to each eye, and a Canine Eye Registration Foundation examination was performed. Approximately 30 minutes after drops were administered, the refractive state of each eye was assessed via streak retinoscopy. Dogs were considered ametropic (myopic or hyperopic) when the mean refractive state (the resting focus of the eye at rest relative to visual infinity) exceeded +/- 0.5 diopter (D). Anisometropia was diagnosed when the refractive error of each eye in a pair differed by > 1 D. RESULTS: Mean +/- SD refractive state of all eyes examined was -0.05 +/- 1.36 D (emmetropia). Breeds in which the mean refractive state was myopic (< or = -0.5 D) included Rottweiler, Collie, Miniature Schnauzer, and Toy Poodle. Degree of myopia increased with increasing age across all breeds. Breeds in which the mean refractive state was hyperopic (> or = +0.5 D) included Australian Shepherd, Alaskan Malamute, and Bouvier des Flandres. Astigmatism was detected in 1% (14/1,440) of adult (> or = 1 year of age) dogs; prevalence of astigmatism among German Shepherd Dogs was 3.3% (3/90). Anisometropia was detected in 6% (87/1,440) of all dogs and in 8.9% (8/90) of German Shepherd Dogs. CONCLUSIONS AND CLINICAL RELEVANCE: Refractive states of canine eyes varied widely and were influenced by breed and age. In dogs expected to have high visual function (eg, performance dogs), determination of refractive state is recommended prior to intensive training.