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Purpose: To determine the effect of sex as a risk factor regarding presbyopia. Methods: Maximum accommodation was pharmacologically induced (40% cabachol corneal iontophoresis) in 97 rhesus monkeys (49 males and 48 females) ranging in age from 8 to 36 years old. Accommodation was measured by Hartinger coincidence refractometry. Results: Accommodative amplitude measured refractometrically decreased with age, and the rate of change was not different between males and females (p = 0.827). Conclusions: Presbyopia is essentially sex neutral, and no one is spared. There may be modest variations between different populations for various reasons, but essentially it is monotonously predictable. At present there is no biological therapeutic. [ABSTRACT FROM AUTHOR]

Objectives: To determine the accuracy, precision, and clinical applicability of the ICare® TONOVET Plus (TVP) in cats. Animals and Procedures: IOP readings obtained with the TVP were compared to values obtained concurrently with the original TONOVET (TV01) and Tono‐Pen Vet™ (TP) in 12 normal cats (24 eyes) and 8 glaucomatous LTBP2‐mutant cats (13 eyes) in vivo. Reproducibility of TVP readings was also assessed for three observers in the above cats. The anterior chambers of five different normal cat eyes were cannulated ex vivo. IOP was measured with the TVP, TV01, and TP at manometric IOPs ranging from 5 to 70 mmHg. Data were analyzed by linear regression, ANOVA and Bland–Altman plots. ANOVA was used to assess reproducibility of TVP readings obtained by different observers and an ANCOVA model controlled for variation of individual cats. p <.05 was considered significant. Results: TVP values strongly correlated with TV01 values (y = 1.045x + 1.443, R2 =.9667). The TP significantly underestimated IOP relative to the TVP and TV01, particularly at high IOP. IOP values obtained by 1 observer were significantly higher (~1 mmHg average) compared to the other 2 observers via ANCOVA analysis (p =.0006479 and p =.0203). Relative to manometry, the TVP and TV01 were significantly more accurate (p <.0001) and precise (p <.0070) than the TP in ex vivo eyes. Conclusions: IOP readings obtained with the TVP and TV01 are broadly interchangeable between models and between observers, but subtle differences may be important in a research context. TP readings vastly underestimate high IOP in feline glaucoma. [ABSTRACT FROM AUTHOR]

Purpose: Angle closure glaucoma (PACG) is highly prevalent in dogs and is often refractory to medical therapy. We hypothesized that pathology affecting the post‐trabecular conventional aqueous outflow pathway contributes to persistent intraocular pressure (IOP) elevation in dogs with PACG. The goal of this study was to determine the potential for aqueous angiography (AA) and optical coherence tomography (OCT) to identify abnormalities in post‐trabecular aqueous outflow pathways in canine PACG. Methods: AA and anterior segment OCT (Spectralis HRA + OCT) were performed ex vivo in 19 enucleated canine eyes (10 normal eyes and 9 irreversibly blind eyes from canine patients enucleated for management of refractory PACG). Eyes were cannulated and maintained at physiologic IOP (10–20 mmHg) prior to intracameral infusion of fluorescent tracer. OCT scleral line scans were acquired in regions of high and low perilimbal AA signal. Eyes were then perfusion fixed and cryosections prepared from 10/10 normal and 7/9 PACG eyes and immunolabeled for a vascular endothelial marker. Results: Normal canine eyes showed segmental, circumferential limbal AA signal, whereas PACG eyes showed minimal or no AA signal. AA signal correlated with scleral lumens on OCT in normal dogs, but lumens were generally absent or flattened in PACG eyes. Collapsed vascular profiles were identified in tissue sections from PACG eyes, including those in which no lumens were identified on AA and OCT. Conclusions: In canine eyes with PACG, distal aqueous outflow channels are not identifiable by AA, despite normalization of their IOP, and intra‐scleral vascular profiles are collapsed on OCT and histopathology. [ABSTRACT FROM AUTHOR]

Objectives: To determine the accuracy and precision of the Icare® TONOVET Plus rebound tonometer and the Tono‐Pen AVIA Vet™ applanation tonometer for intraocular pressure (IOP) measurement in normal ex vivo canine eyes and comparison to earlier models of these tonometers. Animals & procedures: The anterior chambers of six normal dog eyes were cannulated ex vivo. IOP was measured with the TONOVET (TV01), TONOVET Plus, Tono‐Pen Vet™, and Tono‐Pen AVIA Vet™ at manometric IOPs ranging from 5 to 70 mm Hg. Data were analyzed by linear regression, ANOVA and Bland‐Altman plots. A P value ≤.05 was considered significant. Results: Intraocular pressure values obtained using the TONOVET Plus and TV01 were significantly more accurate than with the Tono‐Pen VET and Tono‐Pen AVIA Vet, particularly at higher IOPs (30‐70 mm Hg). Accuracy was not significantly different between any of the devices in the low to normal physiologic IOP range (5‐25 mm Hg). Level of precision was high for all devices, though the TONOVET Plus was more precise than the Tono‐Pen Vet in the 5‐25 mmHg range and the TV01 was more precise than the Tono‐Pen AVIA Vet over the whole IOP range. Conclusions: All devices underestimated IOP, particularly at higher pressures. Rebound tonometers were more accurate over the full range of IOP tested and in the high IOP range; however, there were no significant differences in accuracy among devices in the physiologic IOP range. All tonometers can provide clinically useful IOP readings in dogs, but rebound and applanation tonometers should not be used interchangeably. [ABSTRACT FROM AUTHOR]

Objective: To determine the effect of feline congenital glaucoma (FCG) on corneal sensitivity, and relationships between corneal sensitivity, central corneal thickness (CT), and corneal diameter (CD). Animals and Procedures: Corneal sensitivity (estimated by corneal touch threshold [CTT] using Cochet‐Bonnet esthesiometry); CT using ultrasonic pachymetry; intraocular pressure (IOP) using rebound tonometry; and maximal horizontal CD were measured in 16 normal and 14 FCG cats, both males and females, aged 7 months‐3.5 years. All procedures complied with an Institutional Animal Care and Use Committee‐approved protocol. Data were analyzed by linear regression: paired Student's t tests for between‐eye comparisons, and unpaired Student's t tests for comparisons between groups. Relationships between parameters were evaluated by Pearson correlation coefficients and linear mixed effects modeling. For statistical tests, with the exception of values that were Benjamini‐Hochberg adjusted for multiple comparisons, P‐values < 0.05 were considered significant. Results: Mean CTT and CT values were lower in FCG eyes relative to normal eyes, but differences were not statistically significant. Mean CD was significantly larger in FCG eyes relative to normal eyes, and there was a significant negative correlation between CD and CTT in FCG (r = −0.8564, corrected P = 0.005). These associations were confirmed in linear mixed effects models. Conclusions: Eyes with FCG have significantly larger CDs when compared with normal eyes, and larger CDs correlated with decreased corneal sensitivity in this group. Further studies are warranted to explore the effect of buphthalmos and corneal enlargement on corneal sensitivity and innervation in feline subjects with chronic glaucoma. [ABSTRACT FROM AUTHOR]

Objective To determine the effects of latanoprost on intraocular pressure ( IOP) and pupil diameter ( PD) in cats with inherited primary congenital glaucoma ( PCG) and normal cats. Animals studied and procedures IOP and PD were measured in both eyes ( OU) of 12 adult cats (six normal, six PCG), three times per week for 3 weeks prior to, for 3 weeks during, and for 2 weeks following twice-daily treatment with 0.005% latanoprost to the right eye ( OD) and vehicle to the left (control) eye ( OS). IOP and PD were measured hourly, for 8 h, 1 day prior to, and on the first and last days of treatment. Aqueous humor flow rate ( AHF) was determined at baseline and at the end of the treatment phase in six normal cats. Results Mean IOP was significantly lower in treated vs. control eyes of PCG cats, for up to 8 h following a single latanoprost treatment, and a maximal IOP reduction of 63% occurred in treated eyes at 3 h. Latanoprost acutely lowered IOP in cats with PCG, but this effect appeared to diminish over 3 weeks of treatment. AHF was modestly increased in the treated eyes of normal cats after 3 weeks of latanoprost treatment, although IOP was not significantly affected. Latanoprost caused miosis, with rebound mydriasis at 24 h posttreatment, in the treated eyes of all cats. Conclusions Further research is needed to determine the suitability and efficacy of latanoprost treatment for long-term IOP-lowering in cats with PCG or other forms of glaucoma. [ABSTRACT FROM AUTHOR]

Objective To validate intraocular pressure (IOP) readings obtained in cats with the TonoVet® tonometer. Animals studied IOP readings obtained with the TonoVet® were compared to IOP readings determined by manometry and by the Tono-Pen XL™ in 1 normal cat and two glaucomatous cats. TonoVet® and Tono-Pen XL™ readings were also compared in a further six normal and nine glaucomatous cats. Procedures The anterior chambers of both eyes of three anesthetized cats were cannulated and IOP was varied manometrically, first increasing from 5 to 70 mmHg in 5 mmHg increments, then decreasing from 70 to 10 mmHg in 10 mmHg decrements. At each point, two observers obtained three readings each from both eyes, with both the TonoVet® and Tono-Pen XL™. IOP was measured weekly for 8 weeks with both tonometers in six normal and nine glaucomatous unsedated cats. Data were analyzed by linear regression. Comparisons between tonometers and observers were made by paired student t-test. Results The TonoVet® was significantly more accurate than the Tono-Pen XL™ ( P = 0.001), correlating much more strongly with manometric IOP. In the clinical setting, the Tono-Pen XL™ underestimated IOP when compared with the TonoVet®. Conclusions Both the TonoVet® and Tono-Pen XL™ provide reproducible IOP measurements in cats; however, the TonoVet® provides readings much closer to the true IOP than the Tono-Pen XL™. The TonoVet® is superior in accuracy to the Tono-Pen XL™ for the detection of ocular hypertension and/or glaucoma in cats in a clinical setting. [ABSTRACT FROM AUTHOR]

Objective: To determine if adenovirus-mediated p21[sup WAF-1/Cip-1] (p21) gene therapy can prevent fibroproliferation and wound healing in a rabbit model of glaucoma filtration surgery. Methods: In vitro studies were performed using rabbit Tenon fibroblasts harvested from fresh tissue. In vivo studies were conducted in New Zealand white rabbits. A full-thickness sclerotomy was performed under a limbal-based conjunctival flap. Reagents tested included a replication-deficient recombinant adenovirus containing the human p21 gene (rAd.p21); the nonspecific marker gene for green fluorescent protein or β-galactosidase; mitomycin, 0.5 mg/mL; and balanced saline solution. Each treatment was applied episclerally for 5 minutes before the sclerotomy using a soaked cellulose sponge placed under the surgically created conjunctival flap. Independent experiments were conducted to (1) monitor changes in intraocular pressure during a 30-day period after treatment and examine surgical site histological features, (2) examine changes in bleb morphologic features over 30 days, (3) determine outflow facility 14 days after treatment, and (4) examine the localization and persistence of rAd.p21 expression between 3 and 60 days after treatment. Results: Treatment of Tenon fibroblasts with rAd.p21 resulted in a dose-dependent inhibition of DNA synthesis and cell growth in vitro. In vivo, rAd.p21 inhibited wound healing and fibroproliferation after filtration surgery, comparably to mitomycin. Mitomycin caused notable thinning of the bleb wall. In addition, 2 of the 5 mitomycin-treated eyes exhibited an abscess with hypopyon and hyalitis 30 days after surgery, which was not observed in any of the rAd.p21-treated eyes. None of the treatments resulted in a significantly sustained decrease in intraocular pressure during the 30-day period, although mitomycin treatment resulted in a significant (P=.02) increase in outflow facility 2 weeks after surgery in separate animals. Mitomycin- and... [ABSTRACT FROM AUTHOR]

Abstract: Ocular hypertension is the greatest known risk factor for glaucoma that affects an estimated 70million people worldwide. Lowering intraocular pressure (IOP) remains the mainstay of therapy in the management of glaucoma. By means of microarray analysis, we have discovered that 1α,25-dihydroxyvitamin D3 (1α,25-(OH)2D3) regulates genes that are known to be involved in the determination of intraocular pressure (IOP). Topical administration of 1α,25-(OH)2D3 or its analog, 2-methylene-19-nor-(20S)-1α,25-dihydroxyvitamin D3 (2MD), markedly reduces IOP in non-human primates. The reduction in IOP is not the result of reduced aqueous humor formation, while a 35% increase in aqueous humor drainage by 1α,25-(OH)2D3 was found but this increase did not achieve significance. Nevertheless, our results suggest that 1α,25-(OH)2D3, or an analog thereof, may present a new approach to the treatment of glaucoma. [Copyright &y& Elsevier]

To determine the accuracy and precision of the Icare ® TONOVET Plus rebound tonometer for measuring intraocular pressure (IOP) in normal rabbit eyes, as well as compare it to three other commercially available tonometers: the Icare ® TONOVET (TV01), Tono-Pen Vet™, and Tono-Pen AVIA Vet™. The anterior chambers of both eyes of three New Zealand White rabbits were cannulated, post-mortem. IOP was measured using each of the above four tonometers at manometric pressures ranging between 5 mmHg and 70 mmHg. Data were analyzed by linear regression, ANOVA, and Bland-Altman plots. A p-value of ≤0.05 was considered significant for all statistical tests. IOP values obtained with the TONOVET Plus (in 'lapine' mode) were significantly closer to manometric IOP than those obtained with the other tonometers tested. The TV01 (in 'd' dog setting) and Tono-Pen AVIA Vet™ were significantly more accurate compared to the Tono-Pen Vet™. All tonometers had high levels of precision, though the TONOVET Plus and TV01 were significantly more precise compared to the Tono-Pen AVIA Vet™. All tonometers tended to underestimate IOP, particularly at high pressures, however the TONOVET Plus was highly correlated with manometric IOP in the clinically relevant range of 5-50 mmHg. The TONOVET Plus is an appropriate choice of instrument for measuring IOP in rabbit eyes in both research and clinical settings., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Objective  To validate intraocular pressure (IOP) readings obtained in cats with the TonoVet(®) tonometer. Animals studied  IOP readings obtained with the TonoVet(®) were compared to IOP readings determined by manometry and by the Tono-Pen XL(™) in 1 normal cat and two glaucomatous cats. TonoVet(®) and Tono-Pen XL(™) readings were also compared in a further six normal and nine glaucomatous cats. Procedures  The anterior chambers of both eyes of three anesthetized cats were cannulated and IOP was varied manometrically, first increasing from 5 to 70 mmHg in 5 mmHg increments, then decreasing from 70 to 10 mmHg in 10 mmHg decrements. At each point, two observers obtained three readings each from both eyes, with both the TonoVet(®) and Tono-Pen XL(™) . IOP was measured weekly for 8 weeks with both tonometers in six normal and nine glaucomatous unsedated cats. Data were analyzed by linear regression. Comparisons between tonometers and observers were made by paired student t-test. Results  The TonoVet(®) was significantly more accurate than the Tono-Pen XL(™) (P = 0.001), correlating much more strongly with manometric IOP. In the clinical setting, the Tono-Pen XL(™) underestimated IOP when compared with the TonoVet(®) . Conclusions  Both the TonoVet(®) and Tono-Pen XL(™) provide reproducible IOP measurements in cats; however, the TonoVet(®) provides readings much closer to the true IOP than the Tono-Pen XL(™) . The TonoVet(®) is superior in accuracy to the Tono-Pen XL(™) for the detection of ocular hypertension and/or glaucoma in cats in a clinical setting., (© 2012 American College of Veterinary Ophthalmologists.)

Purpose: To determine the effects of the advanced glycation end product (AGE) cross-link breaker alagebrium on intraocular pressure (IOP), accommodation (ACC), outflow facility (OF), anterior segment morphology, and ocular AGE and receptors for AGE (RAGE) in older rhesus monkeys., Methods: Six rhesus monkeys (aged 19 to 20 years) received 3 or 4 intracameral and intravitreal (final concentration, 1 mM) injections of alagebrium to one eye over 2.5 to 3 weeks and vehicle to the opposite eye. ACC and OF responses to intramuscular or intravenous pilocarpine were measured at baseline and at 1 to 2 weeks and 2, 4, and 6 months postinjection. IOP was measured prior to all injections, ACC, and OF measurements. Monkeys were euthanized 3 to 6 months after the last injection, the eyes were enucleated, and anterior and posterior segments were examined by electron microscopy or immunohistochemistry., Results: No significant differences were found in ACC or IOP at any time point after alagebrium treatment. Baseline OF was higher (37.0 +/- 6.0%; P < or = .005) in alagebrium-treated vs control eyes at 6 months postinjection. In 3 monkeys, alagebrium-treated eyes, compared to control eyes, showed greater focal plaque formation, similar to that seen in primary open-angle glaucoma, in the juxtacanalicular meshwork/inner wall of Schlemm's canal. No changes in anterior segment AGE or RAGE were detectable. However, some areas of the retina and optic nerve head exhibited decreased AGE and increased RAGE immunostaining., Conclusions: Intraocular injection of AGE cross-link breakers is an unlikely approach for glaucoma therapy. However, it may generate a model for further study of glaucomatous-like plaque formation. Immunohistochemical changes in the posterior segment in response to alagebrium warrant further functional studies.