Maximum Intraocular Pressure Reduction Research Articles

Effects of alfaxalone, medetomidine, and xylazine on intraocular pressure in domestic pigeons (Columba livia domestica).

To evaluate the effects of alfaxalone, medetomidine, and xylazine on intraocular pressure (IOP) in domestic pigeons (Columba livia domestica). Eight 12-month-old pigeons (16 eyes). The pigeons were randomly assigned to three treatment groups (10 mg/kg of alfaxalone, 0.2 mg/kg of medetomidine, or 10 mg/kg of xylazine) with a 7-day washout period. The IOP was measured using a rebound tonometer and calibrated using the formula y = 0.439x + 2.059, where y is the tonometric IOP and x is the actual IOP. All three drugs significantly reduced IOP. Alfaxalone led to the least reduction at 5.2 mm Hg, medetomidine reduced IOP to 12.5 mm Hg, whereas xylazine resulted in the greatest reduction at 15.3 mm Hg. Alfaxalone achieved its maximum IOP reduction in 6 min, whereas medetomidine and xylazine required 95 and 115 min, respectively. Both alpha-2 agonists, medetomidine, and xylazine, showed a prolonged duration of effect and a greater reduction in IOP than those of alfaxalone. All three medications provided adequate sedation without any discernible adverse effects. The findings revealed the varied effects of these drugs on IOP in pigeons, potentially providing valuable insights that could be useful for broader applications in veterinary medicine.

Comparative efficacy of fixed dose combination of brinzolamide 1% and timolol 0.5% without versus with benzalkonium chloride following single ocular instillation in New Zealand white rabbits

Background: Benzalkonium chloride (BAK) is the most used preservative in topical ophthalmic formulations. BAK causes dry eye and trabecular meshwork degeneration. Hence, BAK-free formulations are desirable for chronic conditions like glaucoma. The objective of this study was to compare the efficacy of BAK-free versus BAK-containing ophthalmic suspension of fixed dose combination (FDC) of brinzolamide and timolol on their intraocular pressure (IOP) lowering effect following a single ocular instillation in New Zealand White (NZW) rabbits. Methods: Twelve normotensive NZW rabbits (male) between 9-12 months of age (3.4-4.4 kg) received a single ocular instillation (35 ml) in left eye of either ophthalmic suspension containing FDC of brinzolamide (1% w/v)/timolol (0.5% w/v) without BAK (n=6, test) or with BAK 0.01% w/v (n=6, reference). IOP was measured before ocular instillation (baseline) and at 2, 4, 6, 8 and 24 hours after instillation using a pneumatonometer. Change in IOP from baseline were calculated and analysed using repeated measures analysis of variance (ANOVA) followed by Bonferroni post-test for pairwise comparisons. Results: Significant IOP reduction (p<0.05) from baseline was seen in both test and reference groups, up to 6 hours after instillation. Maximum IOP reduction was 25.5% and 22.6% at 2 hours in the test and reference group respectively. No significant differences (p>0.05) were observed between the test and reference group for the change in IOP at all time points. Conclusions: BAK-free and BAK-containing ophthalmic suspension of FDC of brinzolamide 1% and timolol 0.5% after a single ocular instillation in normotensive NZW rabbits produces similar reductions in IOP.

The Influence of Near Vision Tasks on Intraocular Pressure in Normal Subjects and Glaucoma Patients.

To investigate the effect of static accommodative tasks on intraocular pressure (IOP) of glaucomatous and normal eyes. Four groups of subjects categorized as primary open-angle glaucoma (POAG), primary angle-closure suspects (PACS), normal age-matched controls, and normal young adults (NYA; age 40 years) were enrolled. The baseline IOPs were measured after the subjects were looking at a distant target for 15 min. Static accommodation was obtained by execution of near vision tasks (reading at 33 cm in daylight [300 lux] for 60 min). IOPs were measured at 15, 30, 45, and 60 min intervals while accommodating and then measured again after 15 min of relaxing accommodation while looking at a distant target. One-hundred and eighteen eyes of 98 subjects were recruited. The study groups consisted of the following categories: 25 POAG (46 eyes), 24 PACS (47 eyes), 25 matched controls (50 eyes), and 24 NYA (48 eyes). Within all groups, the mean IOP decreased throughout the accommodation period at all time points. Maximum IOP reduction after accommodation was detected at the 30-min time among the POAG subjects, at the 45-min time in the PACS and matched control groups, and at 15 min after the relaxation of accommodation in the NYA group. IOP reduction levels showed no statistically significant difference among POAG, PACS, and the normal matched groups in their response to accommodation. However, NYA had significantly lower IOP and greater IOP reduction after the resting period (relaxation of accommodation). Static accommodative tasks can significantly reduce IOP in normal, POAG, and PACS individuals. Encouraging glaucoma patients to practice periodical near vision tasks could be viewed as an adjunctive measure for glaucoma management.

Formulation and administration of ramipril prodrug for improving bioactivity significantly: In vitro and in vivo correlation

Ramipril (RAM), a prodrug is converted to the active metabolite, ramiprilat (RAT) after de-esterification in the liver for pharmacologic activity. RAM is advisable for the control of ocular hypertension after oral administration. The absolute oral bioavailability of RAM is 15% as its unchanged form and 44% as ramiprilat (RAT) in plasma. Film formulations have been prepared for the delivery of RAM transdermally for sustained activity using ethyl cellulose (EC) and hydroxypropyl methylcellulose (HPMC) at different ratios by casting and solvent evaporation method, and compared with conventional oral and intravenous administration. Bioavailability has been assessed by measuring intraocular pressure (IOP) on normotensive rabbit eye model. The study revealed a sustained diffusion-controlled release of RAM exceeding 24 h. Ocular hypotensive action was continued for more than 30 h and the maximum reduction of IOP was found to be 33% after transdermal application of the formulation. Bioactivity has been increased about 9 times and 18 times compared to conventional oral and intravenous administration respectively. The elimination rate was found to be very much lower in the films compared to iv and oral administration. Formulation and transdermal administration of ramipril could improve bioactivity significantly.

Formulation and evaluation of brinzolamide encapsulated niosomal in-situ gel for sustained reduction of IOP in rabbits

Glaucoma, the multifactorial disease of the eye, is characterized by many biological risk factors as well as genetic factors which lead to degeneration of optic nerves. The major factor which is associated with glaucoma is increase in intraocular pressure (IOP). Treatment for glaucoma should be such that to reduce the IOP either by decreasing the production of aqueous humor or by enhancing its drainage. Currently, the most commonly used approach is the use of conventional ophthalmic eye drops, which accounts for approximately more than 90% of the available marketed ophthalmic dosage forms. Brinzolamide, the carbonic anhydrase inhibitor, in the present study has been formulated as niosomes to provide a sustained action and compared with niosomal in-situ gel loading Brinzolamide. Brinzolamide loaded niosomes had vesicle size of 236.2 ± 3.1 nm and a high zeta potential of −46.2 ± 3.1 mV. A high Encapsulation efficiency of 79.99 ± 2.2% and a sustained release profile in vitro for 24 h. The Niosomal in-situ gel system showed good gelation capacity and adequate spreadability. In-vivo studies conducted on healthy New Zealand white rabbits showed maximum IOP reduction at 8 h and maintained IOP reduction effect till 24 h. The study showed a sustained release of Brinzolamide from the niosomal in-situ gel and a sustained reduction in IOP in rabbits for 24 h with a single administration.

Factors Associated with Increased Neuroretinal Rim Thickness Measured Based on Bruch's Membrane Opening-Minimum Rim Width after Trabeculectomy.

Purpose: To investigate the factors associated with an increase in the neuroretinal rim (NRR) thickness measured based on Bruch’s membrane opening-minimum rim width (BMO-MRW) after trabeculectomy in patients with primary open-angle glaucoma (POAG). Methods: We analyzed the BMO-MRW using spectral-domain optical coherence tomography (SD-OCT) of patients with POAG who underwent a trabeculectomy for uncontrolled intraocular pressure (IOP) despite maximal IOP reduction treatment. The BMO-MRW was measured before and after trabeculectomy in patients with POAG. Demographic and systemic factors, ocular factors, pre- and post-operative IOP, and visual field parameters were collected, together with SD-OCT measurements. A regression analysis was performed to investigate the factors that affected the change in the BMO-MRW after the trabeculectomy. Results: Forty-four eyes of 44 patients were included in the analysis. The IOP significantly decreased from a preoperative 27.0 mmHg to a postoperative 10.5 mmHg. The mean interval between the trabeculectomy and the date of post-operative SD-OCT measurement was 3.3 months. The global and sectoral BMO-MRW significantly increased after trabeculectomy, whereas the peripapillary retinal nerve fiber layer thickness did not show a difference between before and after the trabeculectomy. Younger age and a greater reduction in the IOP after the trabeculectomy were significantly associated with the increase in the BMO-MRW after trabeculectomy. Conclusions: The NRR thickness measured based on the BMO-MRW increased with decreasing IOP after trabeculectomy, and the increase in the BMO-MRW was associated with the young age of the patients and greater reduction in the IOP after trabeculectomy. Biomechanically, these suggest that the NRR comprises cells and substances that sensitively respond to changes in the IOP and age.

Intraocular Pressure Reduction Effect of 0.005% Latanoprost Eye Drops in a Hyaluronic Acid-Chitosan Nanoparticle Drug Delivery System in Albino Rabbits.

PurposeThe purpose of this study was to evaluate the intraocular pressure (IOP) reduction efficiency of hyaluronic acid-chitosan-latanoprost link nanoparticle (HA-CS-latanoprost link NP) formulated eye drops.MethodsThe IOP reduction study was performed in 24 normotensive albino rabbits. The test animals were randomized and grouped accordingly to treatment namely, HA-CS-latanoprost link NP, plain latanoprost, and the commercially available Xalatan eye drop, all were formulated with 0.005% latanoprost. The 9 days of the experiment were divided into baseline period (days 1–2), treatment period (days 3–6), and recovery period (days 7–9). A wireless noncontact tonometer was used to measure IOP at a time interval of 2 hours for 12 hours per day with 5 readings each.ResultsThe highest mean daily IOP reduction during the treatment period was 24% for plain latanoprost, 23% for Xalatan, and 29% for HA-CS-latanoprost link NP. The maximum reduction in IOP for plain latanoprost and Xalatan all occurred at the sixth hour with the peak effects of 4.85 mm Hg (37%) and 4.8 mm Hg (36%), respectively. Although HA-CS-latanoprost link NP had peak effects of 5.75 mm Hg (43%) at the sixth hour and 5.22 mm Hg (39%) at the eighth hour. Daily mean IOP measurements of each treatment group showed that HA-CS-latanoprost link NP has a greater IOP reduction effect compared with the other two treatments (P < 0.001).ConclusionsThe results showed that the formulation of latanoprost with CS and HA is more effective in reducing the IOP than by drug alone.Translational RelevanceThe results provide evidence from animal experiment that HA-CS-latanoprost link NP formulation could improve and sustain drug concentration in the anterior segment of the eye. The improved reduction in IOP with that HA-CS-latanoprost link NP formulation can serve as a basis that latanoprost eye drops can be formulated with decreased concentration of benzalkonium HCl, an irritant preservative and penetration enhancer.

Evaluation of efficacy of Aloe vera (L.) Burm. f. gel solution in methylcellulose-induced ocular hypertension in New Zealand white rabbits.

Objectives The present study aimed to evaluate the efficacy of Aloe vera in the methylcellulose-induced ocular hypertension model. Methods Fifty-six rabbits were randomly divided into seven groups. Intraocular pressure (IOP) was raised by anterior chamber injection of 2% methylcellulose in all the groups except the normal control group. Disease control animals were treated with sterile water and active control with topical 0.5% timolol 12 hourly; 6 and 12% A. vera gel topical solutions 8 hourly were given in group IV and V, respectively; 6 and 12% A. vera gel solutions along with timolol were given in group VI and VII animals, respectively. Mean IOP values and percentage of reduction in IOP were compared at 15min, 30min, 1h, 2h, 4h, 8h, 12h, 24h, 36h, and 48h. Results A. vera gel solutions (6 and 12%) showed a significant reduction in mean IOP from 4 to 2h time points, respectively, whereas, A. vera gel solutions (6 and 12%)+timolol showed significant less mean IOP from a 30min time point as compared with disease control. A. vera gel solutions (6 and 12%) showed 8.6 and 10.4% more reduction in IOP, respectively (66.8±4.9% and 68.6±5.4% vs. 58.2±2.3%; p>0.05), whereas 6 and 12% A. vera gel solutions along with timolol showed 14.5 and 16.2% more reduction in IOP, respectively (72.7±4.7% and 74.4±4.1% vs. 58.2±2.3%; p<0.05), than disease control group at 48h. Conclusions Six and twelve percent A. vera gel solutions reduced the IOP effectively. Concurrent treatment with 12% A. vera gel and timolol produced the maximum reduction in IOP.

Intraocular pressure following four different intravenous sedation protocols in normal horses.

Intravenous sedation is frequently necessary for ophthalmic examination in horses. Common sedation protocols have not been directly compared in terms of relative intraocular pressure (IOP) reduction, duration of IOP reduction and time to maximum IOP reduction. To compare the effects of standing sedation protocols on IOP. Randomised cross-over experiment. Twelve healthy horses received four intravenous sedation protocols with a 48hours washout: 0.5mg/kg xylazine and 0.01mg/kg butorphanol (SED1); 10µg/kg detomidine and 0.01mg/kg of butorphanol (SED2); 10µg/kg detomidine (SED3); 0.5mg/kg xylazine (SED4). IOP was measured with rebound tonometry before sedation (Tpre) and 5, 10, 15, 30, 45 and 60minutes post-sedation (Tpost). Post-sedation readings were taken with the head elevated to the Tpre position. Separately, IOP readings were also obtained following sedation with the head not elevated (TpostHeadDown). IOP values were compared using mixed ANOVA and ANCOVA models respectively with significance at P<.05. All protocols decreased IOP compared with baseline with greatest reduction at Tpost5. IOP at Tpre (mean±SD) was 21.8±4.4mmHg. At Tpost5, IOP was 16.3±3.8mmHg (SED1), 14.5±2.9mmHg (SED2), 17.1±3.8mmHg (SED3) and 16.9±4.2mmHg (SED4). SED2 Tpost5 IOP was lower than other treatments. Considering all time points following sedation, SED3 IOP readings were higher than other treatments. TpostHeadDown IOPs were higher than readings taken with the head elevated (P<.001). Animals with ocular disease were not studied. No animals received mock sedation or equivalent. A combination of detomidine and butorphanol causes greater IOP reduction 5minutes following sedation than other commonly used sedation protocols. IOP reduction is less pronounced when detomidine is used alone. Consideration of head height is important when performing IOP measurements in horses.

Effects of topical administration of tafluprost and combination of tafluprost and timolol or tafluprost and betaxolol on Schirmer tear test, intraocular pressure, and pupil size in clinically healthy dogs.

The aim of this study was to evaluate the effects of 0.0015% preservative-free (PF) tafluprost alone and in combination with 0.5% timolol maleate or0.5% betaxolol HCl on Schirmer tear test (STT), intraocular pressure (IOP), and pupil diameter (PD) in clinically normal dogs. Twenty-one healthy adult castrated male cross-bred dogs were used in this study. Dogs were randomly divided into three groups. The first group received one drop of (PF) tafluprost (Taf), in a randomly selected eye. The second group received one drop of (PF) tafluprost plus one drop of timolol maleate (Taf-Tim), and the last group received one drop of (PF) tafluprost plus one drop of betaxolol HCl, (Taf-Bet). In all groups, the fellow eyes were served as control and received one drop of saline as a placebo. IOP, STT, and PD measurements were performed at the baseline and every 30min for the first 2h, every 2 h for the next 10 h, and at 24h and 36h post-instillation (PI). In all groups, significant differences in IOP values were observed between treated and untreated eyes (Taf: p < 0.001, Taf-Tim: p = 0.014, Taf-Bet: p = 0.008). The maximum reduction in mean IOP after unilateral administration of Taf, Taf-Tim, and Taf-Bet was 8.3mmHg, 10.7mmHg, and 13mmHg, respectively. No significant differences in STT values were observed between treated and untreated eyes at any time points. In all groups, significant differences in PD values were observed between treated and untreated eyes in all time points except the baseline and 36h post-drug instillation (p < 0.001). Tafluprost alone or in combination with timolol and betaxolol was able to reduce intraocular pressure. The greatest effect of the drugs occurred 6 and 8h PI. The present study revealed that the combination of tafluprost/betaxolol is more potent in decreasing IOP than tafluprost alone or a combination of tafluprost/timolol in healthy dogs.

Pharmacokinetics and intraocular pressure–lowering activity of TAK-639, a novel C-type natriuretic peptide analog, in rabbit, dog, and monkey

TAK-639 is a topical, 9–amino acid, synthetic, C-type natriuretic peptide analog in development for the treatment of primary open-angle glaucoma and ocular hypertension. This study investigated the impact of TAK-639 on intraocular pressure (IOP), the levels of TAK-639 in aqueous humor, and the pharmacokinetic/pharmacodynamic relationship of TAK-639 following topical ocular administration to normotensive female Dutch belted rabbits, beagle dogs, and cynomolgus monkeys. In the IOP studies, rabbits (n = 6/group) and dogs (n = 8/group) received a single topical ocular dose of TAK-639 0.03%, 0.1%, 0.3%, or 0.6% in the right eye and vehicle in the left eye; monkeys (n = 8/group) received TAK-639 0.1%, 0.3%, 0.6%, 0.9%, or 1.2% in the right eye only. IOP was measured pre dose and at various time points from 0.5 to 24 h post dose for rabbits, and 1–48 h post dose for dogs and monkeys. To assess exposure in aqueous humor, another set of animals received a single ocular dose of TAK-639 0.03%, 0.1%, 0.3%, or 0.6% (rabbits, n = 20/group; dogs, n = 14/group) or TAK-639 0.3%, 0.6%, or 1.2% (monkeys, n = 10/group) in both eyes. Aqueous humor and plasma were collected at the same post dose time points at which IOP was measured. Aqueous humor and plasma TAK-639 concentrations were measured by liquid chromatography–mass spectrometry, and pharmacokinetic parameters were estimated with non-compartmental analysis. Topical ocular administration of TAK-639 resulted in a dose-dependent decrease in IOP, with maximum mean decreases in IOP ranging from −8.90% to −34.4% in the rabbit, from −16.5% to −26.4% in the dog, and from −3.43% to −13.5% in the monkey. The duration of the IOP-lowering effect was 12 h in the rabbit and monkey and 48 h in the dog. TAK-639 exposure in aqueous humor (both maximum concentration and area under the curve) was also dose dependent, with maximum concentration ranging from 0.152 to 93.6 ng/mL (0.03% and 0.6% doses, respectively) in rabbits, 0.490–13.8 ng/mL (0.03% and 0.3% doses, respectively) in dogs, and 1.16–18.1 ng/mL (0.3% and 1.2% doses, respectively) in monkeys. The pharmacokinetic/pharmacodynamic profile, when fitted to an inhibitory sigmoidal model, demonstrated that TAK-639 exposure in aqueous humor correlated well with IOP reduction in these species. The TAK-639 exposure in aqueous humor at half maximal IOP reduction (EC50) was lower in monkey and dog than in rabbit (0.2 and 0.4 vs. 2.0 ng/mL, respectively). In plasma, quantifiable concentrations of TAK-639 were low and detectable predominantly at early time points. In conclusion, in rabbit, dog, and monkey, a single topical ocular drop of TAK-639 had a significant IOP-lowering effect that correlated well with increases in TAK-639 levels in aqueous humor and resulted in minimal systemic exposure of TAK-639.

IOP Lowering Effects of Ocimum basilicum Seed Extract in Two Rabbit Models of Ocular Hypertension

Introduction: Ocimum basilicum (OB), a herb known for its antihypertensive, anticholinesterase and antioxidant properties was investigated for possible intraocular pressure (IOP) lowering effects in rabbits with ocular hypertension (OHT). Methods: The IOP lowering effect of a single drop of OB extract (OBE) was evaluated in oculonormotensive rabbits using three concentrations (0.25, 0.5 and 1% w/v). The concentration showing maximum IOP reduction was further evaluated in rabbits with water-loading and steroid-induced OHT. Results: IOP lowering effect of OBE 0.5% in oculonormotensive rabbit eyes was significantly greater compared to OBE 0.25% (p&lt;0.05) but was comparable (p&gt;0.05) to OBE 1%. Therefore, 0.5% concentration was selected for further evaluation. Pretreatment with OBE (0.5%) caused significantly lower increase in IOP after water loading amounting to 23.39% above baseline as compared to 54.00% in control eye, 15 minutes post water loading. At 60 minutes, post water loading, mean IOP rise was 95.12% and 63.58% in control and test eyes, respectively. Significant difference between the mean IOP of two eyes persisted during the 2nd hr. In rabbits with steroid induced OHT, OBE 0.5% produced a mean IOP reduction of 24.73% at the end of first hr and the mean peak IOP reduction of 31.63% was observed at the end of 2 hr. A significant difference between the IOP of test and control eyes persisted from 1 to 6 hr. Conclusions: Ocimum basilicum seed extract showed significant IOP lowering effect in rabbits with water loading and steroid induced OHT, however, its utility as an effective antiglaucoma medication needs further investigations.

Intraocular pressure-lowering effects of imidazo[1,2-a]- and pyrimido[1,2-a]benzimidazole compounds in rats with dexamethasone-induced ocular hypertension

Ocular hypertension is believed to be involved in the etiology of primary open-angle glaucoma. Although many pharmaceutical agents have been shown to be effective for the reduction of intraocular pressure (IOP), a significant opportunity to improve glaucoma treatments remains. Thus, the aims of the present study were: (1) to evaluate the IOP-lowering effect of four compounds RU-551, RU-555, RU-839 (pyrimido[1,2-a]benzimidazole), and RU-615 (imidazo[1,2-a]benzimidazole) on steroid-induced ocular hypertension in rats after single drop and chronic applications; and (2) to test in silico and in vitro conventional rho-associated kinase (ROCK) inhibitory activity of the selected compound. This study demonstrated that RU-551, RU-555, RU-839, and RU-615 significantly reduced IOP in Sprague Dawley rats with dexamethasone (DEXA) induced ocular hypertension after single drop administration (0.1%), however RU-615 showed the best IOP lowering effect as indicated by maximum IOP reduction of 22.32% from baseline. Repeated dose topical application of RU-615 caused sustained reduction of IOP from baseline throughout the 3 weeks of treatment with maximum IOP reduction of 30.31% on day 15. This study also showed that the steroid-induced increase in IOP is associated with increased retinal oxidative stress and significant retinal ganglion cells (RGCs) loss. Prolonged treatment with RU-615 over 3 weeks results in normalization of IOP in DEXA-treated rats with partial restoration of retinal antioxidant status (catalase, glutathione and superoxide dismutase) and subsequent protective effect against RGC loss. Thus, IOP lowering activity of RU-615 together with antioxidant properties might be the factors that contribute to prevention of further RGC loss. In vitro part of this study explored the ROCK inhibitory activity of RU-615 using dexamethasone-treated human trabecular meshwork cells as a possible mechanism of action of its IOP lowering activity. However, this study didn’t show conventional ROCK inhibition by RU-615 which was later confirmed by in silico consensus prediction. Therefore, in the future studies it is important to identify the upstream target receptors for RU-615 and then delineate the involved intracellular signalling pathways which are likely to be other than ROCK inhibition.

Effects of cataract surgery on short-term and long-term intraocular pressure fluctuations in non-glaucomatous and medically controlled primary open-angle glaucoma patients

Introduction. It has been recognized that cataract surgery leads to a reduction of intraocular pressure, both in healthy and in glaucoma patients. This prospective interventional clinical study aimed to investigate the effects of cataract surgery on intraocular pressure and its short- and long-term fluctuations in medically controlled primary open-angle glaucoma patients and non-glaucomatous patients. Material and Methods. Two groups of 31 patients (31 eyes) were studied. The observed group included patients with glaucoma and cataract, and the control group included patients with senile cataract only. The intraocular pressure was measured three times daily pre- and at 1, 3 and 6 months postoperatively. Results. In both groups, a significant postoperative reduction in both mean and maximum intraocular pressure. Six months after surgery, in the observed group the average and maximum intraocular pressure reduction levels were -2.73 ? 1.91 mmHg and -3.16 ? 2.19 mmHg, and -2.26 ? 1.71 mmHg and -2.53 ? 1.70 mmHg in the control group. In the observed group, at 3 and 6 months after surgery, a significant reduction in short-term fluctuations was observed. Six months after surgery, short-term fluctuations decreased by -1.04 ? 2.20 mmHg compared to preoperative. Postoperatively, in the observed group, long-term fluctuations of average and maximum intraocular pressure were 2.69 ? 2.15 mmHg and 2.88 ? 2.22 mmHg, respectively, and in the controls they were 2.02 ? 1.28 mmHg and 2.42 ? 1.47 mmHg, showing no significant differences between groups. Conclusion. In patients with primary open-angle glaucoma, cataract surgery results in a statistically significant reduction in both average and maximum intraocular pressure as well as of short-term fluctuations.

Efficacy of selective laser trabeculoplasty in primary angle closure disease.

To study the role of selective laser trabeculoplasty (SLT) in intraocular pressure (IOP) reduction in post-laser iridotomy primary angle-closure disease patients with inadequately controlled IOP. In this prospective cross-sectional study, 34 patients with primary angle-closure disease with post-laser iridotomy open angles up to at least 180° were recruited. Following SLT, patients were examined at 1 day, 1 week, 1 and 3 months, 6 months and 1 year post SLT. Data of 34 patients (34 eyes; 8 males and 26 females), with a mean age of 57.80 ± 6.44 years, were analysed. The reduction in IOP at each follow-up visit was significant (p < 0.001). The maximum reduction in IOP was noticed on post-laser day 1 and the least reduction was noticed 1 week post laser. Post-SLT range of IOP reduction varied from 9 to 46% at 1 year, which indicates the variability of a response to SLT. Mean IOP in both primary angle closure (PAC) and primary angle closure glaucoma (PACG) groups was comparable at all visits except at post-SLT week 1 when IOP in the PACG group was significantly higher than that in the PAC group (p = 0.035). None of the patients complained of pain and/or discomfort or had any clinically significant anterior segment inflammation on any of the follow-up visits. None of the patients underwent repeat SLT or surgery. The mean pre-SLT and post-SLT visual field index at 1-year follow-up was 95.47 ± 3.58 and 95.90 ± 4.13, respectively, which was not significant (p = 0.84). High baseline IOP significantly correlated with reduction in IOP. Our results suggest that SLT is a safe, cost-effective modality for reducing IOP in primary angle-closure disease with patent laser iridotomy with a visible trabecular meshwork.

Novel Water-Soluble Mucoadhesive Carbosilane Dendrimers for Ocular Administration.

The purpose of this research was to determine the potential use of water-soluble anionic and cationic carbosilane dendrimers (generations 1-3) as mucoadhesive polymers in eyedrop formulations. Cationic carbosilane dendrimers decorated with ammonium -NH3(+) groups were prepared by hydrosylilation of Boc-protected allylamine and followed by deprotection with HCl. Anionic carbosilane dendrimers with terminal carboxylate groups were also employed in this study. In vitro and in vivo tolerance studies were performed in human ocular epithelial cell lines and rabbit eyes respectively. The interaction of dendrimers with transmembrane ocular mucins was evaluated with a surface biosensor. As proof of concept, the hypotensive effect of a carbosilane dendrimer eyedrop formulation containing acetazolamide (ACZ), a poorly water-soluble drug with limited ocular penetration, was tested after instillation in normotensive rabbits. The methodology used to synthesize cationic dendrimers avoids the difficulty of obtaining neutral -NH2 dendrimers that require harsher reaction conditions and also present high aggregation tendency. Tolerance studies demonstrated that both prototypes of water-soluble anionic and cationic carbosilane dendrimers were well tolerated in a range of concentrations between 5 and 10 μM. Permanent interactions between cationic carbosilane dendrimers and ocular mucins were observed using biosensor assays, predominantly for the generation-three (G3) dendrimer. An eyedrop formulation containing G3 cationic carbosilane dendrimers (5 μM) and ACZ (0.07%) (289.4 mOsm; 5.6 pH; 41.7 mN/m) induced a rapid (onset time 1 h) and extended (up to 7 h) hypotensive effect, and led to a significant increment in the efficacy determined by AUC0(8h) and maximal intraocular pressure reduction. This work takes advantage of the high-affinity interaction between cationic carbosilane dendrimers and ocular transmembrane mucins, as well as the tensioactive behavior observed for these polymers. Our results indicate that low amounts of cationic carbosilane dendrimers are well tolerated and able to improve the hypotensive effect of an acetazolamide solution. Our results suggest that carbosilane dendrimers can be used in a safe range of concentrations to enhance the bioavailability of drugs topically administered in the eye.

EP3/FP dual receptor agonist ONO-9054 administered morning or evening to patients with open-angle glaucoma or ocular hypertension: results of a randomised crossover study

Background/aimsThe novel prostaglandin E (EP) 3 and prostaglandin F (FP) receptor agonist ONO-9054 is effective in lowering intraocular pressure (IOP) in patients with ocular hypertension and open-angle glaucoma when administered...

IStent as a Solo Procedure for Glaucoma Patients: A Systematic Review and Meta-Analysis.

BackgroundGlaucoma is a leading cause of irreversible blindness. It is firmly entrenched in the traditional treatment paradigm to start with pharmacotherapy. However, pharmacotherapy is not benign and has been well documented to have a number of significant challenges. Minimally invasive glaucoma surgery (MIGS) that targets the outflow pathway with minimal to no scleral dissection has resulted in the need to reconsider the glaucoma treatment paradigm.PurposeTo perform a systematic review and meta-analysis to evaluate and quantify the effect on post-operative intraocular pressure (IOP) and number of topical glaucoma medications, in patients receiving the iStent MIGS device as the solo procedure without concurrent cataract surgery.MethodsA systematic review was conducted by searching various databases between January 1, 2000, and June 30, 2014. Studies reporting up to a maximum follow-up period of 24 months were retrieved and screened using the EPPI-Reviewer 4 gateway. Percentage reduction in IOP (IOPR%), and mean reduction in topical glaucoma medications after surgery were computed. Meta-analysis was performed using STATA v. 13.0. The standardized mean difference (SMD) was calculated as the effect size for continuous scale outcomes. Heterogeneity was determined using the I 2 statistics, Z-value, and χ2 statistics. Fixed-effect and random-effect models were developed based on heterogeneity. Sub-group analysis was performed based on the number of iStents implanted and the follow-up period. The outcome measures were changes in the IOP and number of glaucoma medications.ResultsThe search strategy identified 105 records from published literature and 9 records from the grey literature. Five studies with 248 subjects were included for quantitative synthesis. A 22% IOP reduction (IOPR%) from baseline occurred at 18-months after one iStent implant, 30% at 6-months after two iStents implantations, and 40% at 6-months after implantation of three iStents. A mean reduction of 1.2 bottles per patient of topical glaucoma medications occurred at 18-months after one iStent implant, 1.45 bottles per patient at 6-months after two iStents, and one bottle of medication per patient was reduced at 6-months following placement of three iStents implants. Meta-analysis results showed a significant reduction in the IOP after one iStent (SMD = -1.68, 95% CI: [-2.7, -0.61]), two iStents (SMD = -1.88, 95% CI: [-2.2, -1.56]), and three iStents (SMD = -2, 95% CI: [-2.62, -1.38]) implantation. Results showed a significant drop in the topical glaucoma medications after one iStent (SMD = -2.11, CI: [-3.95, -0.27]), two iStent (SMD = -1.88, CI: [-2.20, -1.56]), and three iStents (SMD = -2.00, CI: [-2.62, -1.38]) implantation. The maximum reduction in IOP occurred at 12-months (SMD = -2.21, CI: [-2.53, -1.88]) and a significant reduction in post-operative topical glaucoma medications occurred even after 18-months of iStent implantation (SMD = -0.71, CI: [-1.15, -0.26]).ConclusioniStent implantation as a solo procedure without concurrent cataract extraction does lower IOP, and reduces the dependency on glaucoma medications. This effect seems to last at least 18 months.

A model-based dose-response meta-analysis of ocular hypotensive agents as a drug development tool to evaluate new therapies in glaucoma.

To characterize dose and response for intraocular pressure (IOP) reduction and incidence of hyperemia using a model-based meta-analysis of IOP-lowering monotherapy studies to evaluate new ocular antihypertensive therapies for glaucoma. Published randomized controlled trials, regulatory documents, and sponsor reports of IOP-lowering monotherapies were used to develop dose-response models to characterize efficacy (IOP change from baseline) and safety (incidence of hyperemia) profiles. The meta-analysis for efficacy included 31 trials with 6,516 patients receiving bimatoprost, latanoprost, travoprost, timolol, or placebo. Estimated IOP reduction with placebo was -2.01 mmHg. Maximal IOP reduction was similar among the prostaglandin analogs (estimate, -6.27 mmHg; baseline, 25 mmHg). Estimated median effective IOP-lowering dose (ED50) was 0.002%, 0.00098%, and 0.00063% daily with bimatoprost, latanoprost, and travoprost, respectively. The hyperemia (safety) analysis included 25 trials with 6,244 patients. Typical maximal estimated difference between drug and placebo was 43%, and estimated ED50 of 0.011%, 0.014%, and 0.0015% daily for bimatoprost, latanoprost, and travoprost, respectively. Latanoprost treatment was predicted to incur the lowest rate of hyperemia of the prostaglandins, for equivalent IOP reduction. Model-based meta-analyses for IOP reduction and incidence of hyperemia among prostaglandin analogs are well described by maximal efficacy models and can provide a useful methodology for evaluating glaucoma therapies.

Eye rubbing-induced changes in intraocular pressure and corneal thickness measured at five locations, in subjects with ocular allergy.

To assess the effects of eye rubbing on corneal thickness (CT) and intraocular pressure (IOP) measurements obtained 0-30min after habitual eye rubbing in symptomatic patients. Measurements of IOP and CT were obtained at five locations (central, temporal, superior, nasal and inferior) before, and every 5min for 30min interval after 30s of eye rubbing, for 25 randomly selected eyes of 14 subjects with ocular allergy and 11 age-matched normals. Differences in measurements were calculated in each group [Baseline measurements minus measurements recorded at each time interval after eye rubbing (for IOP), and for each corneal location (for CT)] and comparison were then made between groups (allergic versus control) for differences in any observed effects. Within groups, baseline mean IOPs in the allergic patient-group (14.2±3.0 mm Hg) and in the control group (13.1±1.9 mm Hg) were similar at all times, after eye rubbing (P >0.05, for all). The maximum reduction in IOP was 0.8 mm Hg in the control subjects and the maximum increase was also 0.8 mm Hg in the allergic subjects. Between groups (allergic versus control), the changes in IOP remained under 1 mm Hg at all times (P=0.2) after 30min of eye rubbing. Between 0 and 30min of CT measurements after eye rubbing, the mean central CT (CCT), inferior CT (ICT), superior CT (SCT), temporal CT (TCT) and nasal CT (NCT) did not vary significantly from baseline values in the control and allergic-subject groups (P>0.05, for both). Between both groups, changes in CT were similar at all locations (P>0.05) except for the TC which was minimally thinner by about 4.4 µm (P=0.001) in the allergic subjects than in the control subjects, 30min following 30s of eye rubbing. IOP measured in allergic subjects after 30s of habitual eye rubbing was comparable with that obtained in normal subjects at all times between 0 and 30min. Although, CT in the allergic subjects were similar to those of the control subjects at all times, it varied between +10 and -7.5 µm following eye rubbing, with the temporal cornea showing consistent reductions in thickness in the subjects with allergy. However, this reduction was minimal and was considered to not be clinically relevant.