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. 2026 Aug 4;29(5):e70239. doi: 10.1111/vop.70239

Effects of Topical Omidenepag Isopropyl on Intraocular Pressure and Pupil Diameter in Normal Dogs

Hikaru Tsujimura 1, Tomoaki Kameda 1, Kazuya Oikawa 2, Hiroki Takahashi 1,✉
PMCID: PMC13435335  PMID: 42549739

ABSTRACT

Purpose

To determine the effects of 0.002% omidenepag isopropyl (OMDI) ophthalmic solution on intraocular pressure (IOP) and pupil diameter (PD) in clinically normal dogs.

Methods

Five healthy dogs (10 eyes) were included in this prospective randomized, observer‐masked, placebo‐controlled study. An initial pilot study was conducted to evaluate IOP and ocular irritation up to 48 h after a single instillation of OMDI. For the subsequent main study, each dog received one drop of 0.002% OMDI in one randomly selected eye and placebo in the contralateral eye once daily. IOP, PD, and conjunctival hyperemia scores were measured five times daily during the baseline (3 days), treatment (5 days), and recovery (3 days) periods.

Results

A single instillation of topical OMDI significantly lowered IOP by a maximal IOP reduction of 7.2 mmHg (60%). In the repeated‐dose study, once‐daily administration of topical OMDI significantly reduced average daily IOP ± SD by 4.8 ± 0.68 mmHg (38.6%) and 6.1 ± 0.75 mmHg (44.3%), relative to baseline and contralateral controls, respectively. No clinically relevant miosis was observed in OMDI‐treated eyes. Adverse events were limited to mild‐to‐moderate conjunctival hyperemia in OMDI‐treated eyes.

Conclusions

Once‐daily administration of 0.002% OMDI resulted in a robust reduction in IOP without inducing miosis and was well‐tolerated in normal dogs. Further studies are warranted to assess its therapeutic potential and long‐term safety in dogs with glaucoma.

Keywords: anti‐glaucoma medication, canine, EP2 receptor agonists, glaucoma, IOP, OMDI

1. Introduction

Glaucoma is a common optic neuropathy in dogs, which leads to irreversible blindness, with the prevalence estimated between 1% and 2% in the general canine population and even higher in some predisposed breeds [1, 2, 3]. Elevated intraocular pressure (IOP) plays a critical role in the development and progression of canine glaucoma. As IOP remains the only modifiable risk factor, the current therapeutic strategies target lowering IOP either by suppressing aqueous humor production in the ciliary body or by enhancing aqueous humor outflow via the unconventional (uveoscleral) and/or conventional (trabecular meshwork) outflow pathways [4].

Topical anti‐glaucoma drugs commonly used in dogs include prostaglandin analogs [5, 6, 7, 8, 9, 10, 11, 12], carbonic anhydrase inhibitors [13, 14], and β‐adrenergic antagonists [15, 16, 17, 18]. Among these, prostaglandin F2‐alpha (PGF2α) analogs such as latanoprost have a potent IOP‐lowering effect and thus are commonly used for the management of canine glaucoma in clinical settings [8, 12, 19]. The prostaglandin F (FP) receptor is expressed in the ciliary body in canine eyes [20], and PGF2α analogs have been shown to promote aqueous outflow via the uveoscleral pathway in dogs, similar to other species [7, 10, 21, 22]. Ocular adverse effects have been reported with topical PGF2α analogs in dogs, including conjunctival hyperemia and marked miosis [12, 22, 23]. In particular, marked miosis by PGF2α analogs in dogs precludes the assessment of the retina and the optic nerve head by funduscopy and advanced imaging such as optical coherence tomography (OCT) [24, 25, 26]. Despite intensive pharmacological treatments, dogs with glaucoma may still lose vision within months due to uncontrolled IOP, underscoring the need for more effective therapeutic options [27].

Omidenepag isopropyl (OMDI) is a prodrug of omidenepag (OMD) that is a non‐prostaglandin, highly selective prostaglandin E2 receptor EP2 subtype (EP2 receptor) agonist. Following topical administration, OMDI is hydrolyzed into its active free acid form, OMD, by endogenous corneal esterases [28]. Its EP2 agonism facilitates aqueous outflow via both the trabecular and uveoscleral pathways, thereby lowering IOP [29]. Topical 0.002% OMDI ophthalmic solution has been available in Japan since 2018 (Eybelis) and was FDA‐approved in the USA in 2022 (Omlonti) for the treatment of glaucoma and ocular hypertension in humans with once‐daily administration. Importantly, the EP2 receptor is expressed in many ocular tissues including the ciliary body and trabecular meshwork, across different species, including dogs [30].

In human clinical trials, once‐daily instillation of 0.002% OMDI ophthalmic solution demonstrated a significant IOP‐lowering effect, comparable to that of latanoprost, in patients with glaucoma or ocular hypertension [31]. While common side effects such as conjunctival hyperemia are observed in these studies, topical OMDI is considered to have high safety profiles and tolerability in human patients [31]. Additionally, previous studies have demonstrated that topical OMDI has effectively reduced IOP without significant adverse ocular effects in multiple species including cats [32, 33], rabbits, and cynomolgus monkeys [28, 29]. These findings support topical OMDI ophthalmic solution as a safe and effective anti‐glaucoma agent across multiple species. Furthermore, previous preclinical studies demonstrated that other topical EP2 agonists including PF‐04217329 (taprenepag isopropyl) and JV‐GL1 (PGN 9856‐isopropyl ester) lower IOP in normal canine eyes [34, 35, 36], although these EP2 agonists are not currently commercially available.

Published data regarding IOP‐lowering effects of topical OMDI in dogs are currently limited to a lower concentration. An earlier preclinical study has demonstrated that once‐daily administration of 0.0006% OMDI ophthalmic solution produced a sustained IOP reduction of approximately 2–6 mmHg over a 4‐week period in ocular normotensive dogs [28]. Despite this, there is a current lack of data on the effects of the commercially available 0.002% OMDI ophthalmic solution on IOP in dogs. Additionally, the effect of topical OMDI on pupil diameter (PD) remains unclear in canine eyes. The primary objective of the study was to assess the effects of 0.002% OMDI ophthalmic solution on IOP and PD in normal dogs. As an ancillary objective, local ocular adverse effects associated with this drug were evaluated.

2. Materials and Methods

2.1. Animals

Five healthy, intact female adult Beagle dogs were used for the study. The mean age of the animals was 26.4 months (range: 26–27 months). The animals were housed in a research laboratory under controlled environmental conditions with a 13‐h light/11‐h dark cycle (room lights on at 7 AM and off at 8 PM) and were fed the same commercial diet. The dogs had been housed in the research laboratory for more than a year and were routinely handled and restrained as part of daily husbandry and care. In addition, rebound tonometry, topical ocular administration, and ophthalmic examinations had been performed repeatedly on multiple occasions before the study. During the several weeks preceding study initiation, all dogs were further acclimated to restraint, rebound tonometry, and slit‐lamp biomicroscopy to minimize effects related to situational stress on IOP and PD measurements [37].

2.2. Ophthalmic Examination and Experimental Design

Prior to study enrollment, an ophthalmic examination was performed on all dogs by a faculty clinician in the ophthalmology service to confirm normal ocular phenotypes. The examination included tonometry using a rebound tonometer (TonoVet TV‐01, Icare Finland Oy) with at least three readings per eye, recording only values displayed (dog mode reading; “d” or “d_”) as well as indirect ophthalmoscopy and slit‐lamp biomicroscopy (SL‐17, Kowa Co. Ltd.). Gonioscopy was not performed for this canine cohort studied because all dogs were purpose‐bred young adult Beagles with no history or clinical signs suggestive of glaucoma. Topical eye drops were administered by trained personnel from the Laboratory of Veterinary Ophthalmology. Each drug administration was confirmed by both the administering personnel and a restraining assistant to ensure accuracy. PD was measured using a universal pupillometer (U‐Med Trading Co.). To ensure measurement consistency, the same veterinarian, who was masked to the treatment status of each eye, performed all IOP and PD measurements at each time point throughout the study.

2.2.1. Pilot Single‐Drug Administration Study

An initial pilot study was designed as a prospective, masked, placebo‐controlled study to evaluate IOP‐lowering effects of a single topical OMDI administration in normal dogs. All five dogs were included in the pilot study. A coin toss was used to randomly assign one eye of each dog to receive one drop of 0.002% OMDI ophthalmic solution (Eybelis, Santen Pharmaceutical Co. Ltd.), while the contralateral eye received one drop of artificial tears (Mytear Eye Drops, Senju Pharmaceutical Co. Ltd.). IOP and PD were measured for both eyes immediately prior to a single drop treatment at 8 AM and every 2 h for the first 12 h and then at 24, 36, and 48 h posttreatment.

2.2.2. Repeated Drug Administration Study

The second study was a prospective, randomized, masked, placebo‐controlled study, conducted 7 weeks after the initial pilot study to ensure no residual drug effects from the initial pilot study. A coin toss was used to randomly assign one eye of each dog to receive 0.002% OMDI ophthalmic solution, while the contralateral eye was designated as the control, receiving artificial tears. The study duration was 11 consecutive days, which consisted of a 3‐day pretreatment baseline phase, a 5‐day treatment phase, and a 3‐day recovery phase. During the treatment phase, eye drops were administered once daily (at 9 AM following the first IOP and PD measurements of the day). During the study period, ophthalmic examinations were performed daily at 9 AM, 11 AM, 1 PM, 5 PM, and 9 PM by a single veterinarian in the same environment. These examinations included rebound tonometry, PD measurement, and thorough assessments of the anterior segment using a slit‐lamp biomicroscope. Ocular adverse events including conjunctival hyperemia, corneal opacity, and aqueous flare were scored if present using the semiquantitative preclinical ocular toxicology scoring (SPOTS) grading system [38]. Ocular signs consistent with ocular irritation including blepharospasm were recorded if present.

2.3. Statistical Analysis

Statistical analyses were performed using R (ver. 4.5.2) and GraphPad Prism 10 (ver. 10.6.1; GraphPad Software Inc.). Data normality was assessed by the Shapiro–Wilk test and Kolmogorov–Smirnov test. For the pilot single‐dose study, values between OMDI‐treated eyes and contralateral control eyes at each time point were compared using a two‐way repeated‐measures ANOVA followed by the Bonferroni correction. For the repeated dosing study, longitudinal data were analyzed using a linear mixed‐effects model (LMM) to account for the correlation between repeated measurements on the same animals and the paired nature of the study design with treatment and time as fixed effects along with their interaction term. To account for variation between animals and inter‐eye correlation within the same animal, individual dog ID was included as a random intercept. Post hoc comparisons were performed using the Bonferroni correction. For all analyses, p value ≤ 0.05 was considered statistically significant. A post hoc power analysis was performed to determine the sensitivity of the study in comparing mean values between OMDI‐treated and contralateral control eyes. Based on IOP data from this cohort of animals, a sample size of 5 eyes per group was sufficient to detect a 20% reduction in IOP with 80% power at α = 0.05.

3. Results

3.1. A Single Administration of 0.002% OMDI Ophthalmic Solution Significantly Lowered IOP in Normotensive Canine Eyes

The initial pilot study demonstrated that a single topical instillation of 0.002% OMDI ophthalmic solution resulted in a significant reduction in IOP compared to the contralateral control eyes treated with artificial tears (Figure 1A). IOP values in OMDI‐treated eyes were significantly lower from 2 to 24 h post‐instillation compared with contralateral control eye values at the same time point (p < 0.05). At 6 h post‐treatment, OMDI‐treated eyes had a maximal IOP reduction of 7.2 ± 1.9 (SD) mmHg (60% reduction; 95% CI, 45.2%–75.2%) relative to contralateral control eyes (Figure 1B). No ocular irritation including blepharospasm was observed at any time points. Overall, this initial study confirmed that a single instillation of 0.002% OMDI ophthalmic solution provides a significant IOP‐lowering effect in normal canine eyes for at least up to 24 h. Although an upward drift in IOP from the nadir was noted toward the end of the 24‐h post‐instillation interval, the overall IOP in the OMDI‐treated eyes remained significantly lower than the contralateral controls. These findings suggested that once‐daily dosing was an appropriate frequency to evaluate in the subsequent repeated‐dose study.

FIGURE 1.

FIGURE 1

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A single administration of 0.002% OMDI ophthalmic solution lowers IOP in normotensive canine eyes. (A) Mean intraocular pressure (IOP) values of normal canine eyes immediately prior to (0 h) and following a single instillation of either 0.002% omidenepag isopropyl (OMDI) ophthalmic solution or placebo‐control (artificial tears) are plotted. Error bars represent standard deviation. n = 5 per group. ✱ p < 0.05, ✱✱ p < 0.01, ✱✱✱✱ p < 0.0001 relative to contralateral placebo‐control. (B) Mean percentage difference of IOP in OMDI‐treated eyes relative to contralateral control in normal dogs. Error bars represent 95% confidence interval.

3.2. Once‐Daily Dosing of Topical 0.002% OMDI Provides Sustained IOP Reduction in Normotensive Canine Eyes

Figure 2 illustrates the mean (±SD) IOP values for OMDI‐treated and contralateral control eyes throughout the pretreatment baseline, treatment, and recovery phases. During the pretreatment baseline period and immediately prior to initial administration (at 9 AM on Day 4), there was no significant difference in IOP between the OMDI treated (12.6 ± 1.2 mmHg) and contralateral control eyes (12.7 ± 1.4 mmHg). During the 5‐day treatment phase following the first drug instillation, IOP values in OMDI‐treated eyes were significantly lower compared with pretreatment baseline values in the same eyes (p < 0.001) and with the contralateral control eye values at the same time point (p < 0.001). During the treatment phase, OMDI‐treated eyes exhibited an average IOP reduction of 4.8 ± 0.68 mmHg (38.6% reduction; 95% CI, 36.1–41.1) and 6.1 ± 0.75 mmHg (44.3% reduction; 95% CI, 42.4–46.3), relative to pretreatment baseline and contralateral controls, respectively. In contrast, the contralateral control eyes did not exhibit significant alterations in IOP during the treatment phase relative to pretreatment baseline phase. While the daily minimum IOP values remained consistent throughout the treatment phase, the pre‐dose IOP values (measured 24 h post‐instillation, just prior to the next dose) progressively decreased from Day 5. Consequently, daily IOP fluctuation gradually diminished toward the end of the treatment period on Day 8. In the recovery phase, IOP in OMDI‐treated eyes remained significantly lower than baseline and contralateral control, which persisted up to 60 h after the final instillation (p < 0.05). When comparing OMDI‐treated and control eyes, a significant difference in IOP persisted until 56 h after the final instillation (p < 0.05), but this difference was no longer evident from the Day 3 of the recovery period onwards.

FIGURE 2.

FIGURE 2

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Effects of repeated administration of topical 0.002% OMDI on IOP in normotensive canine eyes. Mean IOP data of normal canine eyes treated either with topical 0.002% OMDI (orange line) or control (blue line) are presented. During the study period, measurements were performed daily at 9 AM, 11 AM, 1 PM, 5 PM, and 9 PM. Arrows indicate the timing of once‐daily topical drug administration (at 9 AM following the first IOP and PD measurements of the day). ✱ p < 0.05, ✱✱✱ p < 0.001 relative to the pretreatment baseline values; # p < 0.05, ### p < 0.001 relative to contralateral control values. Error bars represent SD. n = 5 per group.

3.3. Effect of Topical 0.002% OMDI on Pupil Diameter in Normal Canine Eyes

The mean (±SD) PD values at each time point during the pretreatment, treatment, and recovery phases are presented in Figure 3. The mean baseline PD was 7.0 ± 0.3 mm for both the OMDI‐treated and contralateral control eyes. No significant differences in PD were observed between OMDI‐treated and contralateral control eyes at any time points examined during the study (p > 0.99). Compared to pretreatment baseline, a statistically significant but clinically negligible degree of pupillary constriction (maximum change < 0.62 mm) was observed in both OMDI‐treated and control eyes during treatment and recovery phases (p < 0.05). Overall, these results indicate that topical 0.002% OMDI did not exert a clinically relevant effect on PD in normal canine eyes.

FIGURE 3.

FIGURE 3

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Effects of topical 0.002% OMDI on pupil diameter in normal canine eyes. Mean pupil diameter values of normal canine eyes treated either with topical 0.002% OMDI (orange dots) and control (blue dots) over the study period were plotted. Arrows indicate the timing of topical drug administration. Error bars represent SD. n = 5 per group.

3.4. Ocular Adverse Events

Conjunctival hyperemia was the only ocular adverse event observed throughout this study (Figure 4). Conjunctival hyperemia was mainly scored as Score 0–1 (normal to mild) and occasionally Score 2 (moderate), with no cases of severe (Score 3) conjunctival hyperemia observed. During the treatment phase, two out of five canine eyes treated with topical OMDI had moderate (Score 2) hyperemia. During the treatment phase, the mean ± SD conjunctival hyperemia score in the OMDI‐treated eyes (1.10 ± 0.46) was higher than in the contralateral control eyes (0.33 ± 0.47; p < 0.01). No aqueous flare or cells in the anterior chamber were observed in any eyes examined at any time points during the study period. No signs of ocular irritation, including blepharospasm, were observed throughout the study.

FIGURE 4.

FIGURE 4

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Effects of topical 0.002% OMDI on conjunctival hyperemia score in normal canine eyes. Mean conjunctival hyperemia scores of normal canine eyes treated either with topical 0.002% OMDI (orange dots) or control (blue dots) over the study period were plotted. Arrows indicate the timing of topical drug administration. ✱✱ p < 0.01 relative to contralateral control values. Error bars represent SD. n = 5 per group.

4. Discussion

This study demonstrates the administration of the commercially available topical 0.002% OMDI resulting in a robust reduction in IOP in normal canine eyes. Additionally, our data suggest that once‐daily administration provides sustained IOP reduction in normal canine eyes. Furthermore, topical 0.002% OMDI appears well‐tolerated in normal dogs, with only mild‐to‐moderate conjunctival hyperemia observed throughout the study. The lack of clinically relevant miosis, ocular irritation or intraocular inflammation during the study further supports the efficacy and safety of topical 0.002% OMDI for use in dogs.

In our pilot study, a single topical instillation of 0.002% OMDI yielded a maximal IOP reduction of 7.2 mmHg (60% reduction) at 6 h following administration. During the treatment phase in the repeated dosing study, once‐daily dosing of 0.002% OMDI ophthalmic solution resulted in average daily IOP reductions of 4.8 mmHg (38.6% reduction) from the pretreatment baseline and 6.1 mmHg (44.3% reduction) compared to contralateral control eyes. Although direct head‐to‐head comparisons were not performed in this study, the magnitude of IOP reduction with topical OMDI appears comparable to, or greater than, that previously reported for latanoprost (3.0–4.5 mmHg from control) [6], and tafluprost (up to 6 mmHg or 39% reduction) [39]. Although repeated daily instillation of topical OMDI did not yield cumulative hypotensive effects, it effectively dampened daily IOP fluctuation and provided a sustained IOP reduction.

Consistent with the use in humans and supported by previous preclinical studies in multiple species [28, 40, 41], our results indicate that once‐daily dosing of topical 0.002% OMDI is sufficient for providing a sustained IOP reduction in normal dogs. Supporting our findings, prior reports on other topical EP2 agonists (taprenepag isopropyl [PF‐04217329] and JV‐GL1 [PGN 9856‐isopropyl ester]) demonstrated that once‐daily administration significantly reduces IOP in normotensive canine eyes [34, 35]. The prolonged duration of IOP lowering with EP2 agonism may offer a clinical advantage over widely used PGF2α analogs such as latanoprost, which often require twice‐ to three‐times daily instillation for sustained IOP control as reported in normal dogs [12].

Mechanisms of IOP lowering by topical OMDI appear distinct from that of conventional prostaglandin analogs. In contrast to topical PGF2α analogs, which mainly target the uveoscleral outflow, EP2 receptor agonism modulates aqueous humor dynamics [29]. In addition to enhancing the uveoscleral outflow, topical OMDI stimulates EP2 receptors to promote trabecular meshwork remodeling through repeated administration [42], which leads to a sustained decrease in aqueous outflow resistance. This remodeling process may explain the persistent IOP‐lowering effect observed during the recovery phase of our study even after treatment discontinuation. Additionally, the elevation in cyclic AMP (cAMP) levels associated with EP2 receptor agonism promotes aqueous humor outflow by increasing trabecular and uveoscleral outflow [29, 42], which is suggested to persist for a certain period and potentially contribute to the continued enhancement of aqueous humor outflow. Furthermore, this cAMP elevation may have the potential to reduce aqueous flow resistance in the distal aqueous outflow pathway, which could be compromised in canine glaucoma [43, 44]. Since EP2 receptors are also present in the nonpigmented ciliary epithelial cells, it is possible that OMDI may act on these cells as well, implying that changes in aqueous humor production could also persist [29].

Although specific pharmacokinetic studies were not performed in dogs, these multifactorial mechanisms supported by prior pharmacokinetic data from preclinical studies collectively explain the prolonged IOP‐lowering effects observed in this study.

Contrary to its robust ocular hypotensive effects, topical 0.002% OMDI did not induce overt miosis in normal dogs in this study. The lack of miotic effect by topical 0.002% OMDI has also been reported in other species including cats [32, 33]. Similarly, previous preclinical studies showed that topical instillation of a selective EP2 agonist (JV‐GL1 [PGN 9856‐isopropyl ester]) did not induce detectable miosis in normal dogs [35]. These findings highlight a sharp contrast to topical FP receptor agonists such as latanoprost and tafluprost, which induce profound miosis in dogs [39, 45, 46, 47, 48]. Therefore, the absence of miosis with topical OMDI may represent a key clinical advantage over conventional prostaglandin analogs as it is likely to allow for fundus examinations and advanced imaging such as OCT [24, 25] and potentially reduce the risk of posterior synechiae and pupillary block. Thus, unlike many FP‐receptor agonists, topical OMDI may not be contraindicated in canine glaucoma cases with anterior lens luxation, although further clinical studies are warranted to validate.

Topical 0.002% OMDI was generally well‐tolerated in normal dogs, only with mild‐to‐moderate conjunctival hyperemia observed following administration. Although individual variation existed, all five dogs in this study showed a mild worsening of conjunctival hyperemia scores in the OMDI‐treated eyes during the treatment. This mild ocular adverse effect has also been observed in human clinical trials with topical OMDI [49], and this study confirmed that similar mild adverse events can occur in dogs. Importantly, no other adverse effects such as aqueous flare were observed in the OMDI‐treated eyes throughout the study, suggesting a minimal likelihood of inducing intraocular inflammation in healthy canine eyes. While no severe adverse effects were observed in a cohort of normal dogs in this study, previous human clinical trials reported that topical OMDI may be associated with a higher incidence of cystoid macular edema in pseudophakic and aphakic eyes, possibly due to blood aqueous barrier disruption by cataract surgery [50]. However, in order to thoroughly assess the risk of intraocular inflammation in dogs, long‐term administration studies remain necessary.

Previous pharmacological studies demonstrated that OMD and OMDI selectively interacted with EP2 receptor [28]. Neither OMD nor OMDI binds to α2A, β1, and β2 adrenergic receptors, nor do they interact with carbonic anhydrase enzymes (CA1 and CA2) [28]. Thus, OMD and OMDI do not likely share the mechanism of IOP lowering with other conventional anti‐glaucoma medications. Furthermore, the additive IOP‐lowering effects of topical OMDI when combined with brinzolamide, timolol, and brimonidine have been reported in rabbits and monkeys [51]. Together, these data suggest the potential of OMDI as a viable option for combination therapy in a clinical setting for the management of canine glaucoma.

The reduction of IOP via EP2 agonism may hold significant promise for a subset of the canine glaucoma population refractory to FP agonists. A previous study reported that 11% of dogs with secondary glaucoma are considered nonresponders and 77% have only transient responses to FP receptor agonists like latanoprost [50]. As studies in humans have reported that topical OMDI is effective in reducing IOP in non‐ or poor FP receptor agonist responders [49, 52], OMDI may provide an effective therapeutic alternative for these challenging canine cases by leveraging a different mechanism of action.

The primary limitations of this study include the small sample size and the short treatment duration. While a post hoc power calculation indicated that the study was sufficiently powered to detect a clinically meaningful 20% difference in IOP in normal dogs at 80% power with α = 0.05, the relatively small sample size remains a limitation of this study. A larger sample size would be needed to identify potential nonresponders, as previously documented with prostaglandin analogs. Furthermore, while prior studies demonstrated that once‐daily topical 0.0006% OMDI effectively reduces IOP for 28 days [28], the long‐term treatment effects of topical 0.002% OMDI on IOP remain uninvestigated in dogs, including the potential for tachyphylaxis. As this study was limited to healthy female Beagle dogs with normotensive eyes, further studies are warranted to determine whether sex‐ or breed‐related differences influence the response to topical OMDI. While anti‐glaucoma medications often have greater potency in hypertensive eyes, whether OMDI can effectively lower IOP in glaucomatous or ocular hypertensive dogs warrants further investigation. Finally, although our data support a sustained IOP reduction with once‐daily dosing in normal dogs, further studies in glaucomatous dogs are required to determine if alternative or higher frequency dosing regimens are necessary to maintain sustained IOP lowering and limit IOP fluctuations.

5. Conclusion

Once‐daily administration of 0.002% OMDI ophthalmic solution effectively reduced IOP in normal dogs without inducing profound miosis. Topical 0.002% OMDI was well tolerated in normal dogs with only mild‐to‐moderate conjunctival hyperemia observed. Topical OMDI may represent a promising anti‐glaucoma agent for dogs, warranting further investigation in clinical canine patients with glaucoma.

Author Contributions

Hikaru Tsujimura: writing – original draft, investigation, visualization, formal analysis, software, methodology. Hiroki Takahashi: conceptualization, writing – review and editing, investigation, funding acquisition, supervision, resources, data curation, project administration, software, validation. Tomoaki Kameda: writing – original draft, investigation, formal analysis, visualization, methodology. Kazuya Oikawa: conceptualization, writing – review and editing, visualization, supervision, formal analysis.

Funding

This study was supported by internal research funding from Azabu University.

Ethics Statement

All animal procedures were conducted in accordance with the Association for Research in Vision and Ophthalmology (ARVO) Statement on the Use of Animals in Ophthalmic and Vision Research, and in compliance with protocols approved by the Institutional Animal Care and Use Committee at the School of Veterinary Medicine in Azabu University (approval number: 241209‐3). This study complies with the Guidelines for Ethical Research in Veterinary Ophthalmology (GERVO).

Conflicts of Interest

The authors declare no conflicts of interest.

Acknowledgments

The authors would like to thank the veterinary students of the Laboratory of Small Animal Clinics, Azabu University for their assistance during the study. The authors have not used AI to generate any part of the manuscript.

Data Availability Statement

The data that support the findings of this study are available from the corresponding author upon reasonable request.

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Associated Data

This section collects any data citations, data availability statements, or supplementary materials included in this article.

Data Availability Statement

The data that support the findings of this study are available from the corresponding author upon reasonable request.

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