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Barriers to effective medical therapy are numerous and include difficulties with effective and sustained control of intraocular pressure (IOP) and adherence to prescribed anti‐glaucoma drop regimens. In an effort to circumvent these challenges, a number of new anti‐glaucoma therapies with sustained effects have emerged. Methods for sustained delivery of prostaglandin analogs are being intensely investigated and many are in human clinical trials. Intracameral devices include the following: Allergan's Durysta™ Bimatoprost SR, Envisia Therapeutics' ENV515 travoprost implant, Glaukos' iDose™, Ocular Therapeutix's OTX‐TIC travoprost implant, and Santen's polycaprolactone implant with PGE2‐derivative DE‐117. Other prostaglandin‐based technologies include Allergan's bimatoprost ring (placed in the conjunctival fornix), Ocular Therapeutics' OTX‐TP intracanalicular travoprost implant, subconjunctival latanoprost in a liposomal formulation, and the PGE2 derivative PGN 9856‐isopropyl ester that is applied to the periorbital skin. Exciting breakthroughs in gene therapy include using viral vectors to correct defective genes such as MYOC or to modulate gonioimplant fibrosis, CRISPR technology to edit MYOC or to alter aquaporin to reduce aqueous humor production, and siRNA technology to silence specific genes. Stem cell technology can repopulate depleted tissues or, in the case of Neurotech's Renexus® NT‐501 intravitreal implant, serve as a living drug delivery device that continuously secretes neurotrophic factors. Other unique approaches involve nanotechnology, nasal sprays that deliver drug directly to the optic nerve and noninvasive alternating current stimulation of surviving cells in the optic nerve. Over time these modalities are likely to challenge the preeminent role that drops currently play in the medical treatment of glaucoma in animals. [ABSTRACT FROM AUTHOR]

Objectives: To evaluate the effect of QD or BID 0.02% netarsudil ophthalmic solution (Aerie Pharmaceuticals) on intraocular pressure (IOP) in normotensive dogs and to describe any adverse effects. Animals studied: Normotensive Labrador retriever dogs were included in this study: 10 received netarsudil in one eye and artificial tears in the contralateral eye QD, and 10 received netarsudil in one eye and artificial tears in the contralateral eye BID. Procedures: Intraocular pressure curves were acquired over a 3‐day acclimation period, 5‐day dosing period (QD or BID—10 dogs/group), and 3‐day recovery period. Toxicity was assessed daily using slit‐lamp biomicroscopy and the semiquantitative preclinical ocular toxicology scoring system. Results: Once‐daily dosing did not lower IOP over the entire 5‐day dosing period (95% CI 0.1 to −0.9 mm Hg, P =.20) or on the last day of dosing (95% CI 0.4 to −0.9 mm Hg, P =.65). Twice‐daily dosing resulted in a statistically significant, but clinically unimportant, IOP reduction over the entire 5‐day dosing period (−0.6 mm Hg; 95% CI 0.05 to −1.1 mm Hg, P =.02) and on the last day of dosing (−0.9 mm Hg; 95% CI 0.2 to −1.5 mm Hg, P =.003). Adverse events were limited to transient mild‐to‐moderate conjunctival hyperemia during the dosing phase in eyes receiving netarsudil vs control (P <.0001). Conclusions: Netarsudil 0.02% ophthalmic solution twice daily resulted in a small, statistically significant, but clinically unimportant, IOP reduction in normotensive dogs. Future studies should investigate efficacy in glaucomatous dogs. [ABSTRACT FROM AUTHOR]

Objective: The purpose of this study was to compare the leakage rates of perilimbal uniplanar and biplanar clear corneal incisions in dogs when subjected to increased intraocular pressure (IOP) both from within the eye and via external pressure. Procedure: Uniplanar clear corneal incisions were created in eight freshly enucleated canine eyes using a 3.2 mm straight slit knife while 8 fellow eyes received a biplanar clear corneal incision consisting of an approximately 300 μm deep groove followed by a 3.2 mm straight slit knife entry into the anterior chamber. Both wounds were reapposed using three simple interrupted 8‐0 polyglactin 910 sutures. Eyes were cannulated with two 25 g needles: One connected to a pressure transducer, and the other connected to a reservoir of isotonic saline. The IOP at which the wound leaked was recorded when the intraocular pressure was increased internally by raising the height of the fluid bag, and again when the cornea was externally compressed. Kaplan‐Meier survival curves compared incision types for each method of increasing IOP and were evaluated using Mantel‐Cox log‐rank analysis. Results: Both wound types resisted leakage at IOP in the physiologically achievable range and no significant differences were observed between clear corneal incisions when pressure was applied externally (P =.353) or was increased from within the globe (P =.615). Conclusion: Ex vivo uniplanar and biplanar clear corneal incisions in dogs are equally strong, with no significant differences in leakage rates when IOP is increased internally or externally. [ABSTRACT FROM AUTHOR]

Objective The pig has an increasingly important role in ocular drug delivery models, but the most accurate tonometer in this species is unknown. The purpose of this study was to evaluate the accuracy of TonoVet and Tono-Pen Vet tonometers in the ex vivo porcine eye. Procedure Four freshly enucleated normal porcine eyes were cannulated with two 25-gauge needles; one connected via tubing to a mercury manometer calibrated continuous physiologic recorder and the other connected to a reservoir of lactated Ringer's solution on an adjustable stand. Triplicate IOP readings were taken with the TonoVet and then the Tono-Pen Vet at 5, 10, 15, 20, 25, 30, 35, 40, 50, 60, 70, 80 mmHg. Results Linear regression showed strong linear trends for both the TonoVet ( r2 = 0.969) and Tono-Pen Vet ( r2 = 0.983). The TonoVet slightly underestimated IOP at lower pressures and slightly overestimated IOP at higher pressures ( y = 1.092 x − 4.0, where y = tonometer reading, x = manometer reading, and 4.0 = intercept). The Tono-Pen Vet consistently underestimated IOP ( y = 0.773 x − 2.1). These differences were statistically significant ( P = <0.001, one-way repeated-measures ANOVA). Conclusion As in other species, both the TonoVet and Tono-Pen Vet tonometers do not measure true IOP in the porcine eye; however, the TonoVet more closely approximated true IOP in the normal porcine eye than the Tono-Pen Vet and may be the tonometer of choice for this species. [ABSTRACT FROM AUTHOR]

Objective To evaluate feasibility and accuracy of intraocular pressure ( IOP) measurement by rebound tonometry in adult red-eared slider turtles and determine the effects of manual and chemical restraint on IOP. Animal studied Seventeen adult red-eared slider turtles. Procedures Intraocular pressure was measured with TonoLab® and TonoVet® tonometers in conscious, unrestrained turtles. To evaluate the effects of manual restraint, turtles were restrained by digital pressure on the rostral head or proximal neck. The effect of two chemical restraint protocols (dexmedetomidine, ketamine, midazolam [ DKM] and dexmedetomidine, ketamine [ DK] subcutaneously) on IOP was evaluated. Triplicate TonoLab® and TonoVet® readings were compared with direct manometry in three ex vivo turtle eyes. Results TonoLab® correlated better with manometry at IOPs < 45 mmHg than TonoVet® (linear regression slopes of 0.89 and 0.30, respectively). Mean (± SD) IOP in unrestrained conscious turtles was significantly lower ( P < 0.01) with TonoLab® (10.02 ± 0.66 mmHg) than with TonoVet® (11.32 ± 1.57 mmHg). Manual neck restraint caused a significant increase in IOP (+6.31 ± 5.59 mmHg), while manual rostral head restraint did not. Both chemical restraint protocols significantly reduced IOP ( DKM: −1.0 ± 0.76 mmHg; DK: −1.79 ± 1.17) compared with measurements in conscious unrestrained turtles. Conclusions Chemical and manual neck restraint affected IOP. Rostral head restraint had no significant effect on IOP and is, therefore, recommended as the appropriate restraint technique in red-eared slider turtles. TonoLab® measurements estimated actual IOP more accurately, within physiologic range, than measurements obtained using the TonoVet®. [ABSTRACT FROM AUTHOR]

Objective Topical latanoprost 0.005% is commonly used in dogs with primary angle closure glaucoma ( PACG), and marked miosis has been reported in the literature. To further explore the effect of topical latanoprost on anterior segment anatomy, we performed iridocorneal angle biometrics in normal beagle dogs. Methods Thirty-five normal female beagle dogs were assessed using anterior segment optical coherence tomography ( AS- OCT). One eye of each dog was scanned with the AS- OCT in the superotemporal quadrant. One drop of latanoprost 0.005% was applied topically, and the OCT scan was repeated 30 min later. Images were imported into ImageJ, and pupil diameter, anterior chamber angle, angle opening distance, angle recess area (ARA), anterior chamber hemifield, and anterior chamber depth were measured. Results A single drop of latanoprost resulted in marked miosis, anterior bowing of the peripheral iris, narrowing of the iridocorneal angle, and shallowing of the anterior chamber. The anterior segment parameters demonstrated a significant reduction ( P-value ≤ 0.001) from baseline following latanoprost with the exception of the ARA ( P = 0.07). Conclusions Latanoprost significantly decreases pupil diameter and narrows the iridocorneal angle in normal female beagle dogs. Therefore, the utility of latanoprost as a prophylactic treatment for PACG in fellow eyes may be limited. Studies using quantitative iridocorneal angle measurements in goniodysgenic dogs are warranted to understand the changes in iridocorneal angle morphology that occur in PACG in response to topical application of latanoprost. [ABSTRACT FROM AUTHOR]

Objective Gonioscopy provides limited quantitative information to compare the iridocorneal anatomy across different species. In addition, the anatomic relationships by histologic examination are altered during processing. As a result, the comparative anatomy of the iridocorneal angle across several mammalian species was evaluated by Optical Coherence Tomography (OCT). Methods Cats, beagle dogs, minipigs, owl monkeys, cynomolgus monkeys, and rhesus monkeys (n = 6 or 7 per species) were evaluated. Imaging was performed using the OCT. The anterior chamber angle (ACA), angle opening distance (AOD), and the angle recess area (ARA) were evaluated. Results AC angle: cat (63 ± 6°) > owl monkey (54 ± 4°) > beagle dog (42 ± 4°) > minipig (40 ± 3°) > rhesus monkey (36 ± 1°) > cynomolgus monkey (34 ± 2°). AOD: cat (3.3 ± 0.5 mm) > owl monkey (2.05 ± 0.2 mm) > beagle dog (1.08 ± 0.1 mm) > rhesus monkey (0.92 ± 0.06 mm) > minipig (0.64 ± 0.04 mm) > cynomolgus monkey (0.43 ± 0.03 mm). ARA: cat (3.5 ± 0.1 mm2) > owl monkey (1.41 ± 0.2 mm2) > dog (0.88 ± 0.1 mm2) > rhesus monkey (0.62 ± 0.06 mm2) > minipig (0.21 ± 0.05 mm2) > cynomolgus monkey (0.15 ± 0.01 mm2). Conclusions This study benchmarks the normative iridocorneal angle measurements across different mammalian species by OCT. These data can be useful to compare iridocorneal angle measurements in disease states as OCT evolves as a common diagnostic tool in veterinary ophthalmic research and practice. [ABSTRACT FROM AUTHOR]

Introduction Episcleral venous pressure (EVP) has an important role in intraocular pressure (IOP) homeostasis and accounts for more than 70% of the IOP in the normal dog. A frequently used species in glaucoma research is the normotensive dog especially when evaluating the efficacy of prostaglandin analogues and prostamides; however, aqueous humor dynamic studies in normal dogs are lacking, and the effect of 0.005% latanoprost on canine EVP is not known. We sought to determine the effects to the EVP of topically applied 0.005% latanoprost in the normotensive beagle dog. Methods Female beagle dogs ( n = 14) were used and each had a normal ophthalmic examination on study entry. EVP was determined using a standard episcleral venomanometer. Animals were dosed in one eye with 0.005% latanoprost, and the effects on EVP were compared with the averaged baseline EVP's determined in the predosing phase and the fellow nondosed eye. The Mixed Model Repeated Measures method was used to analyze the EVP data. Results During the dosing phase of the study with topical 0.005% latanoprost, the mean EVPs of dosed eyes were significantly higher than that of nondosed eyes ( P < 0.0001). Conclusions The increase in EVP in the dog with exposure to topical 0.005% latanoprost has not been observed in other species that have been studied, such as in the mouse and in humans, where the drug had no significant effect on the EVP. This response may be unique to dogs and suggests that dogs may not fully mimic human aqueous humor dynamics with topical 0.005% latanoprost. Although frequently performed in human studies, EVP should not be regarded to be a constant value in aqueous humor dynamic studies in the normal beagle dog. [ABSTRACT FROM AUTHOR]

Objective Female dogs have approximately twice the risk of males for developing primary angle closure glaucoma (PACG). The cause of this gender difference is unknown, but one theory proposes that the gender differences in iridocorneal angle morphology are involved in this risk differential. Procedures Fifty beagles (25 males, 25 females) were included into this study and had normal baseline ophthalmic examinations. Normal dogs were selected so as to avoid any potentially confounding influence of goniodysgenesis. Standardized 20-MHz high-resolution ultrasound images of the iridocorneal angle were acquired from one eye of each dog with the scan plane perpendicular to the limbus in the superior temporal quadrant. Images were imported into ImageJ, and the angle opening distance (AOD) and angle recess area (ARA) were measured by a masked observer, and the analysis of variance method was used to compare differences. Results The mean (±SD) AOD was significantly smaller for female dogs (0.847 ± 0.241 mm) vs. male dogs (1.058 ± 0.322 mm) P-value = 0.012. The mean (±SD) ARA tended to be smaller for female dogs (0.584 ± 0.278 mm) vs. male dogs (0.748 ± 0.385 mm), but this difference was not significant ( P-value = 0.092). Conclusions Female dogs have a significantly smaller AOD vs. males. This difference may render the female iridocorneal angle more susceptible to closure and may partially explain the 2:1 female/male predisposition to PACG. Further studies using goniodysgenic dogs are warranted. [ABSTRACT FROM AUTHOR]