Best timing for eye meds

Hello, Summarians!

Welcome to the first eye issue. Here are some useful studies to help with common issues.

Please give me feedback on ways I can make it more useful to you.

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Best way to medicate eyes in dogs (and other species…)

The use of ophthalmic solutions, or eye drops, is a common method for treating ocular conditions in both veterinary and human patients. However, the effectiveness of eye drops is limited by factors such as rapid loss of the solution from the eye due to blinking and drainage through the nasolacrimal duct. This results in poor bioavailability of the drugs in the eye. To address this issue, the present study investigated two strategies to improve ocular drug delivery in dogs. First, the study examined the impact of increasing the drug concentration in the ophthalmic formulation. Previous research in humans has shown that higher drug concentrations in eye drops lead to greater drug levels in the cornea and aqueous humor. Similarly, in dogs, increasing the drug concentration in the formulation resulted in higher tear film concentrations and longer drug retention on the ocular surface. This suggests that using higher drug concentrations in ophthalmic formulations can improve the therapeutic effects of eye drops in dogs. Second, the study investigated the effects of repeated administration of eye drops at different time intervals. It was hypothesized that administering a second eye drop after a certain lag period would be beneficial. The results showed that repeating eye drop administration after a 2- to 5-minute interval significantly increased tear film concentrations and extended drug retention on the ocular surface. In contrast, repeating administration 30 seconds or 1 minute after the first eye drop did not provide significant benefits, possibly due to excessive drainage or spillage. Similarly, administering a second eye drop 10 minutes after the first drop had little effect, as the first drop was mostly cleared from the tear film by that time. The study suggests that by increasing the drug concentration in ophthalmic formulations and repeating eye drop administration at the optimal time interval, the efficacy of topical drug delivery in canine eyes can be improved. These strategies could be particularly useful in the treatment of conditions such as bacterial keratitis, where intensive therapy with frequent administration of antibiotics is required. By increasing tear film concentrations and prolonging drug exposure, these strategies could enhance the pharmacokinetic and pharmacodynamic properties of antibiotics, improving their effectiveness in treating ocular infections. It should be noted that the study focused on fluorescein quantification in the tear film and did not assess drug levels in ocular tissues, intra-ocular fluids, or plasma. Therefore, the potential systemic toxicity of the proposed strategies was not evaluated. Additionally, the study used only two different drug concentrations and did not account for other physicochemical properties of ophthalmic formulations. Further research is needed to validate these findings with different drug classes and concentrations. In conclusion, the present study suggests that optimizing drug concentration in ophthalmic formulations and repeating eye drop administration at the appropriate time interval can enhance ocular drug delivery in dogs. These strategies have the potential to improve treatment outcomes and reduce the frequency of administration, leading to better owner and patient compliance. However, further research is necessary to validate these findings and explore their applicability to different drug formulations and ocular conditions. 

Page, LE, Kubai, MA, Allbaugh, RA, et al. Increased drug concentration and repeated eye drop administration as strategies to optimize topical drug delivery: A fluorophotometric study in healthy dogs. Vet Ophthalmol. 2023; 26: 331- 338. doi:10.1111/vop.13125 

Bottom line — 2-5 minute interval dosing is the best

Distichiasis in dogs

Distichiasis is a condition in dogs where abnormal hairs grow along the eyelid margin, typically emerging from the meibomian gland openings. It can cause ocular discomfort and surface changes in the eye, such as keratitis. The prevalence of distichiasis varies among different dog breeds, and it is considered to be an inherited condition, although the mode of inheritance is unknown. A study conducted in France over a 10-year period found a prevalence of 5.5% in dogs presented to the Ophthalmology Unit. This prevalence was higher compared to a previous study in Scotland, which reported a prevalence of 0.8%. The difference in prevalence could be due to variations in inclusion criteria and diagnostic methods between the studies. Certain dog breeds, including English bulldogs, American cocker spaniels, Cavalier King Charles spaniels, Boxers, and English cocker spaniels, were found to have a higher prevalence of distichiasis. However, the prevalence can vary among different countries, suggesting possible geographic variations. Brachycephalic breeds (those with short noses and flat faces) had a significantly higher prevalence of distichiasis compared to non-brachycephalic breeds. There was no significant difference in prevalence between males and females, although previous studies have reported a higher prevalence in females in some breeds. The age at diagnosis and the bilaterality of the condition were consistent with previous findings. Ectopic cilia, which are abnormal eyelashes growing in an unusual location, were observed in a subset of dogs with distichiasis. These dogs may also develop corneal ulcers. Corneal pigmentation was not found to be associated with distichiasis. In terms of clinical impact, most dogs with distichiasis in the study did not exhibit signs of ocular discomfort or surface lesions. However, brachycephalic breeds were more likely to experience ocular discomfort and surface diseases associated with distichiasis. English bulldogs, Pugs, and French bulldogs had the highest prevalence of ocular discomfort. Surgical treatment options for distichiasis include manual epilation, eyelid eversion, and various methods for removing or destroying the abnormal hair follicles. The specific surgical procedures performed varied in the study, and the outcomes could not be compared due to the small sample size and concurrent ocular surgeries. Overall, this study provides insights into the epidemiology and clinical impact of distichiasis in a large population of dogs. It highlights breed predispositions, geographic variations, and the low clinical impact in most cases. 

Jondeau, C, Gounon, M, Bourguet, A, Chahory, S. Epidemiology and clinical significance of canine distichiasis: A retrospective study of 291 cases. Vet Ophthalmol. 2023; 26: 339- 346. doi:10.1111/vop.13091 

Bottom line — Most dogs don’t have clinical problems — unless you’re a Bulldog ;)

Ocular lubricants

This study investigated the precorneal retention time of different ocular lubricants in dogs. The purpose was to provide information that can guide clinicians in selecting the appropriate lubricant and determining the frequency of administration. The study compared five commonly used lubricants: Artificial Tears Solution, I-Drop Vet Plus, Optixcare Eye Lube Plus, Systane Ultra lubricant eye drops, and Artificial Tears Ointment. The study found that ophthalmic ointments, such as Artificial Tears Ointment, provided longer ocular lubrication and retention compared to standard artificial tears solutions. This can be attributed to the nonpolar properties of mineral oil in the ointment, which prolongs contact time with the ocular surface. The study also showed that Systane Ultra, which contains hydrophilic demulcents and a polysaccharide gelling agent, enhanced precorneal retention time by minimizing tear evaporation and improving adherence to the ocular surface. Hyaluronic acid-based lubricants, such as I-Drop Vet Plus and Optixcare Eye Lube Plus, also prolonged contact time by reducing washout and enhancing water retention on the ocular surface. The study used fluorophotometry to measure tear film concentrations of the lubricants and observed a biphasic fluorescein decay for all formulations. Ointments exhibited a slower initial decline, leading to higher tear film concentrations and longer precorneal retention time compared to other lubricants. The findings of this study are relevant not only for dogs but also for humans, as there are similarities in ocular parameters between the two species. However, it is important to consider species differences in ocular surface anatomy and physiology when applying these findings to companion animals. The study acknowledges certain limitations, such as the use of fluorescein, which may have altered the viscosity and kinetics of the lubricants, as well as the relatively small sample size of the study. Future research could explore alternative techniques to assess precorneal retention time in awake canine subjects. In summary, this study provides valuable information on the precorneal retention time of different ocular lubricants in dogs. This data can assist clinicians in selecting the appropriate lubricant and determining the optimal frequency of administration. Further studies are needed to evaluate the effects of lubricant type and administration frequency on tear film quality and ocular health in various diseased eyes and during anesthesia. 

Bedos, L, Allbaugh, RA, Roy, M, Kubai, MA, Sebbag, L. Precorneal retention time of ocular lubricants measured with fluorophotometry in healthy dogs. Vet Ophthalmol. 2023; 26: 81- 88. doi:10.1111/vop.13065 

Bottom line — Some differences between formulations but nothing really lasts over 60 minutes…

Just putting things in perspective …