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Purpose: Activation of the classical complement pathway is thought to contribute to the development and progression of glaucoma. The role of alternative complement or amplification pathways in glaucoma is not well understood. We evaluated complement factor B (FB) expression in postmortem human ocular tissues with or without glaucoma and the effect of FB inhibition and deletion in a mouse ocular hypertensive model of glaucoma induced by photopolymerized hyaluronic acid glycidyl methacrylate (HAGM). Methods: Human CFB mRNA in human eyes was assessed by RNAscope and TaqMan. HAGM model was performed on C57BL6/J mice. The effect of FB in HAGM model was evaluated with an oral FB inhibitor and Cfb -/- mice. Complement mRNA and proteins in mouse eyes were assessed by TaqMan and western blot, respectively. Results: CFB mRNA in human glaucomatous macular neural retina and optic nerve head was upregulated. Cfb mRNA is also upregulated in the HAGM model. Oral FB inhibitor, ED-79-GX17, dosed daily at 200 mg/kg for 3 days after intraocular pressure (IOP) induction in wild-type mice showed complement inhibition in ocular tissues and significantly inhibited systemic complement levels. Daily dosing of ED-79-GX17 for 30 days or Cfb deletion was also unable to prevent retinal ganglion cell or axon loss 30 days after IOP induction in mice. Conclusion: The alternative complement component FB may not substantially contribute to RGC loss in the HAGM mouse glaucoma model despite upregulation of Cfb expression and activation of the alternative pathway. The relevance of these findings to human glaucoma remains to be determined.

Background: To investigate the effect of perioperative intraocular pressure (IOP) lowering medications on controlling postoperative IOP following uncomplicated phacoemulsification., Methods: Ovid MEDLINE, EMBASE, and Cochrane CENTRAL databases were searched up until November 2022. Randomised controlled trials (RCTs) that assessed IOP change via applanation tonometry in medicated and control arms following uncomplicated cataract surgery in healthy eyes were included. The primary outcome was the weighted mean difference (WMD) of IOP at 2-8 h, 12-24 h, and 1-7 days postoperatively within each medication class or common fixed-combination formulations. Risk of bias was assessed using the revised risk of bias in randomised trials (RoB-2). Level of evidence was rated using the Grading of Recommendation, Assessment, Development and Evaluation (GRADE) RESULTS: From 702 screened articles, 30 RCTs involving 2986 eyes were included. There was a statistically significant reduction in IOP favouring treatment arms at 2-8 h (WMD = -3.87 mmHg; 95% CI [-4.75, -3.00]; p < 0.001) and 12-24 h (WMD = -2.69 mmHg; 95% CI [-3.36, -2.02]; p < 0.001), with the effect wearing off beyond 1 day (p = 0.18). Between medication classes, the largest effect at both 2-8 h and 12-24 h was observed with intracameral cholinergics or fixed-combination carbonic anhydrase inhibitor-beta-blocker (FCCB) formulations. Conversely, the smallest effect was observed with prostaglandin analogues, alpha-agonists, and topical carbonic anhydrase inhibitors (CAIs)., Conclusion: Prophylaxis against acute IOP elevations following uncomplicated cataract surgery is effective. FCCB and intracameral cholinergics are the most effective ocular antihypertensive agents, while alpha-agonists, prostaglandin analogues, and topical CAIs were found to be the least effective. These findings may inform future surgical guidelines., (© 2024. The Author(s), under exclusive licence to The Royal College of Ophthalmologists.)

Scope: Our laboratory has previously described the antioxidant and anti-inflammatory potential of a wild olive (acebuche, ACE) oil against hypertension-associated vascular retinopathies. The current study aims to analyze the antifibrotic effect of ACE oil on the retina of hypertensive mice., Methods and Results: Mice are rendered hypertensive by administration of NG-nitro-L-arginine-methyl-ester (L-NAME) and simultaneously subjected to dietary supplementation with ACE oil or a reference extra virgin olive oil (EVOO). Intraocular pressure (IOP) is measured by rebound tonometry, and retinal vasculature/layers are analyzed by fundus fluorescein angiography and optical coherence tomography. Different fibrosis-related parameters are analyzed in the retina and choroid of normotensive and hypertensive mice with or without oil supplementation. Besides preventing the alterations found in hypertensive animals, including increased IOP, reduced fluorescein signal, and altered retinal layer thickness, the ACE oil-enriched diet improves collagen metabolism by regulating the expression of major fibrotic process modulators (matrix metalloproteinases, tissue inhibitors of metalloproteinases, connective tissue growth factor, and transforming growth factor beta family)., Conclusion: Regular consumption of EVOO and ACE oil (with better outcomes in the latter) might help reduce abnormally high IOP values in the context of hypertension-related retinal damage, with significant reduction in the surrounding fibrotic process., (© 2023 The Authors. Molecular Nutrition & Food Research published by Wiley-VCH GmbH.)

The management protocol for patients with neovascular age-related macular degeneration (nAMD) involves multiple intravitreal injections (IVI) of anti-VEGF drugs. The ability to reduce the peak intraocular pressure (IOP) rise is greatly important in clinical practice., Purpose: This study evaluates the effect of topical hypotensive drugs on the short-term IOP rise after IVI of anti-VEGF drugs in patients with nAMD., Material and Methods: The prospective study included 80 patients with newly diagnosed nAMD. Before the start of treatment, the patients were divided into 4 groups of 20 people each: 1st - controls, who received no prophylactic drugs, in the 2nd, 3rd and 4th groups local instillations of one drop of hypotensive drugs brinzolamide 1%, brinzolamide-timolol, brimonidine-timolol were performed in the conjunctival sac twice: 1 day before the injection (at 20:00) and on the day of the injection 2 hours before the manipulation (at 08:00), respectively. IOP was measured in each patient using ICare Pro non-contact tonometer before injection, as well as 1 min, 30 and 60 min after injection., Results: Prophylactic use of hypotensive drugs was associated with a significant decrease in IOP immediately after IVI compared to the same parameter in the 1st group ( p <0.001), the maximum decrease in IOP values was observed when using a fixed combination of brimonidine-timolol by 12.1 mm Hg compared to the controls ( p <0.001), the combination of brinzolamide-timolol reduced IOP by 8.5 mm Hg ( p <0.001), brinzolamide 1% led to the smallest decrease in IOP - by 5.1 mm Hg ( p <0.001)., Conclusion: Study patients that received instillations of brimonidine-timolol combination of one drop into the conjunctival sac 1 day before the injection and on the day of the injection showed the maximum decrease in IOP compared to patients of the other groups.

Acute intraocular pressure (IOP) elevation following repeat intravitreal anti-vascular endothelial growth factor (VEGF) injections (IVI) may pose a risk to the integrity of the retinal nerve fiber (RNFL). This meta-analysis investigates the role of IOP-lowering interventions such as an anterior chamber paracentesis (ACP) and IOP-lowering medications on the IOP in patients undergoing IVIs. MEDLINE, EMBASE, and the Cochrane Library were searched up to February, 2021. Studies investigating IOP-lowering interventions in patients undergoing IVI versus controls were included. The primary outcome was the IOP in the short- and long-term post-IVI. Secondary outcomes were changes in the RNFL thickness and best corrected visual acuity (BCVA). ACP at time of anti-VEGF injection significantly lowered IOP immediately post anti-VEGF (WMD: -27.98 mm Hg, P < 0.001). Patients in the ACP group also had significantly thicker RNFL compared to control (WMD: 2.07 um, P < 0.00001) at median follow-up of 16.5 months. IOP-lowering medications (on the day of injection or in the long-term) significantly reduced IOP up to 30 minutes after injection (WMD: -3.31 mm Hg, P = 0.003). This effect was statistically significant between the 2 arms up to 1 month follow-up. There was no difference in BCVA in intervention versus controls. ACP reduces immediate IOP spikes post-IVI and preserves the RNFL in the short- and longterms IOP-lowering medications also reduce IOP spike, with limited data on RNFL thickness., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Introduction: Postoperative steroid/antibiotic drop regimens are known to effectively suppress inflammation and infection following pars plana vitrectomy (PPV), but the steroid frequently induces ocular hypertension (OHT). The aim of this contemporaneous cohort-control study was to assess safety and efficacy of a novel post-PPV drop regimen conceived to address this problem., Methods: Electronic case notes of consecutive eyes undergoing PPV between December 2020 and April 2021 at St. Thomas' Hospital, London, UK, were reviewed retrospectively. Postoperative drops in the intervention cohort consisted of 1-week g. dexamethasone 0.1%/antibiotic QDS and 1-month g. ketorolac TDS. Standard care controls received 1-month g. dexamethasone 0.1%/antibiotic QDS., Results: Fifty-eight patients were in the intervention cohort, and 151 received standard care. The primary outcome measure was IOP ≥30 mm Hg 2 weeks postoperatively. This occurred in none of the intervention group but in 14% of controls (p = 0.01). Secondary outcomes of rates of anterior uveitis and cystoid macular edema did not differ significantly between the groups, but those in the intervention cohort had fewer hospital visits (p = 0.0004)., Conclusion: A post-PPV drop regimen of 1-week dexamethasone 0.1%/antibiotic and 1-month ketorolac may be as effective as an anti-inflammatory but safer in terms of OHT incidence than standard care 1-month dexamethasone 0.1%., (© 2022 S. Karger AG, Basel.)

Clinical Relevance: Posterior capsule opacification is a common late complication of cataract surgery. Posterior capsule opening with Nd:YAG laser, which is the standard treatment, may cause transient elevation of intraocular pressure (IOP)., Background: To evaluate the efficacy of betaxolol 0.‌5% compared to brimonidine 0.2%, in prevention of intraocular pressure increase after Nd:YAG Laser posterior capsulotomy., Methods: In a double masked randomised clinical trial, 38 eyes from 38 pseudophakic patients over 21 years of age who had significant posterior capsule opacification after phacoemulsification were randomly assigned to receive either betaxolol 0.‌5% (18 eyes) or brimonidine 0.‌2% (20 eyes) one hour before Nd:YAG Laser posterior capsulotomy.‌ Exclusion criteria were: glaucoma or history of glaucoma surgery, active uveitis, active ocular infection, pregnancy, unstable cardiovascular condition and severe asthma and lung diseases. Intraocular pressure was measured by Goldmann applanation tonometry, 1 hour before applying the laser and 4 hours after the laser application., Results: There was no statistically significant difference between the two groups regarding the baseline mean IOP and the 4-hour post-laser mean IOP. There was a statistically significant decrease in the 4-hour post-laser mean IOP as compared to the baseline mean IOP in each group. The mean IOP change in the betaxolol group, was -2.39 ± 1.79 mm Hg and in the brimonidine group was -4.25 ± 2.20 mm Hg. The difference was statistically significant (P = 0.007). None of the patients experienced clinically significant IOP increase (≥5 mm Hg) in either group., Conclusion: Use of a single topical dose of betaxolol 0.5% and brimonidine 0.2%, 1 hour before laser treatment, can prevent significant acute IOP increase after Nd:YAG laser posterior capsulotomy, and betaxolol may provide a new alternative for prophylactic use.

Purpose: To determine whether intravenous administration of paracetamol can prevent postoperative ocular hypertension (POH) in dogs following routine phacoemulsification., Methods: Diabetic and non-diabetic patients (total 54 dogs) undergoing unilateral or bilateral phacoemulsification were recruited to this placebo-controlled, prospective study. The control group received 1 ml/kg saline via intravenous infusion while the treatment group received 10 mg/kg paracetamol via intravenous infusion. Infusions were administered 30 min prior to surgery and repeated 12 h following initial administration. All patients received topical latanoprost at the conclusion of surgery. Intraocular pressure (IOP) was measured before premedication (baseline), and at 1 h, 3 h, 5 h and 18 h following extubation. POH was defined as an IOP above 25 mmHg (POH25). In addition, the number of patients with an IOP exceeding 20 mmHg was analyzed (POH20)., Results: POH20 occurred in 33 of 54 animals (61.1%), including 19 of 25 animals (76.0%) in the control group and 14 of 29 animals (55.2%) in the treatment group. POH25 occurred in 23 of 44 animals (52.3%), including 13 of 25 animals (52.0%) in the control group and 10 of 29 animals (34.5%) in the treatment group. Paracetamol administration showed a significant positive effect on reducing the incidence of POH20 (p = .048), but not POH25 (p = .221)., Conclusions: When comparing groups, treatment with paracetamol showed a statistically significant reduction in the incidence of POH20, although no differences were observed in the incidence of POH25 between groups. Further studies are warranted to explore whether alternative drug regimes or routes of administration can provide enhanced efficacy in the prevention of POH25., (© 2022 American College of Veterinary Ophthalmologists.)

Purpose: To assess the neuroprotective effects of methylene blue (MB) in a rat model of acute ocular hypertension (AOH) and explore its possible mechanisms., Methods: Our AOH rat model was obtained with anterior chamber perfusion for 60 min. After that, 100 μM MB was injected into the vitreous cavity immediately after injury. Electroretinogram, fundus photography, optical coherence tomography (OCT) and retina morphology examination were utilized to quantify retinal damage before surgery, as well as 7, 14 and 28 days after. The average number of surviving retinal ganglion cells (RGCs) was counted after fluorescent retrograde labelling with 4% DiI. And TUNEL assay was used to investigate retinal cell apoptosis at 24 hours after AOH. Nrf2 and BACE1 in the retina were determined by RT-qPCR analysis., Results: AOH did produce a severe degeneration effect on the whole retinal layer. Intravitreally injected MB maintained certain retinal thickness after AOH, reduced the destruction of electroretinograms, and enhanced RGCs survival. The average number of TUNEL-labelled cells statistically reduced in the MB-treated retina tissue compared with retina treated with normal saline. The relative mRNA level of Nrf2 was also much higher in the MB-treated retinas after AOH, and the expression of BACE1 had a decline in the AOH + MB group., Conclusions: MB can protect the retina from AOH injury and the possible mechanism might involve the inhibition of BACE1 expression and the activation of Nrf2 antioxidant pathway.

Determining the role of vascular endothelial growth factor (VEGF) in the pathogenesis of intraocular neovascularization prompted the development of anti-VEGF therapy. In general, these intravitreal injections (IVI) are considered relatively safe. One of the side effects that can occur after IVI of anti-VEGF agents is ocular hypertension, it can be acute or persistent. Numerous studies investigating the prevention of ophthalmic hypertension have been carried out in connection with the proven risk of short-term intraocular pressure (IOP) elevation after anti-VEGF injections. Scientific literature describes several methods of preventing intraocular pressure spikes after IVI: prophylactic medications, anterior chamber paracentesis, scleral decompression. Despite the significant number of publications, there is no universal consensus on the necessity of prevention measures for IVI of anti-VEGF drugs since the clinical benefits of slightly reducing the short-term IOP spikes remain unclear. This literature review analyzes the prospects of preventing ocular hypertension after IVI of anti-VEGF agents.

Purpose: To assess whether prophylactic use of netarsudil 0.02% ophthalmic solution reduces the risk of intraocular pressure (IOP) elevation associated with prolonged use of topical corticosteroids to prevent cornea transplantation rejection., Design: Prospective, randomized clinical trial., Methods: In this study, 120 subjects were randomized to use netarsudil (off-label) or placebo once daily for 9 months after Descemet membrane endothelial keratoplasty, and 71 fellow eyes were enrolled and assigned to the opposite treatment arm. Participants concurrently used topical prednisolone acetate 1% 4× daily for 3 months, 3× daily for a month, twice daily for a month, and once daily for 4 months. The main outcome was IOP elevation (defined as IOP ≥24 mm Hg or an increase of ≥10 mm Hg over baseline) assessed by Kaplan-Meier and proportional hazards analyses, taking loss to follow-up into consideration., Results: Overall, 95 eyes were assigned to netarsudil and 96 to placebo; 15 eyes (16%) were withdrawn early from the netarsudil arm because of ocular irritation. The rate of IOP elevation was 14% with netarsudil and 21% with placebo (relative risk: 0.6; 95% confidence interval: 0.3-1.3; P = .23). IOP was >30 mm Hg in 7.8% assigned to netarsudil versus 7.4% assigned to placebo (P = .84). Median 6-month central endothelial cell loss was 31% versus 29% with netarsudil versus placebo, respectively (P = .49)., Conclusions: Netarsudil did not produce a statistically significant reduction in the risk of steroid-induced IOP elevation after corneal transplantation relative to placebo., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Aim: To evaluate the effectiveness of brinzolamide-brimonidine fixed combination to control the intraocular pressure elevation throughout the first 24 h following uncomplicated phacoemulsification cataract surgery., Patients and Methods: A total of 62 patients who underwent phacoemulsification cataract surgery were included in this prospective randomized comparative case series. The brinzolamide-brimonidine fixed combination group (34 eyes) was administered a single dose of brinzolamide-brimonidine fixed combination immediately after phacoemulsification. No treatment was administered in the control group (28 eyes). Intraocular pressure was measured 1 day before surgery (baseline) and at 6, 12 and 24 h postoperatively., Results: The brinzolamide-brimonidine fixed combination group had significantly lower intraocular pressure at 6, 12 and 24 h after phacoemulsification compared to baseline (p < 0.0001 for all comparisons), while in control group, intraocular pressure was significantly higher at 6 and 12 h after surgery compared to baseline (p < 0.001 and p < 0.0001, respectively). In control group, an intraocular pressure elevation ⩾ 5 mm Hg was noted in 32.4% of the eyes at 6 and 12 h and in 5.9% of eyes at 24 h after surgery, while in brinzolamide-brimonidine fixed combination group, only 8.8% of the eyes at 6 h postoperatively had such an intraocular pressure elevation., Conclusion: The administration of a single drop of brinzolamide-brimonidine fixed combination effectively prevented intraocular pressure elevations and intraocular pressure spikes during the first 24 h after uneventful phacoemulsification.

Purpose: To determine the effect of topical brimonidine tartrate prophylaxis on intraocular pressure (IOP) spikes following intravitreal injection of antivascular endothelial growth factor (anti-VEGF) agents., Methods: This is a randomised crossover trial of consecutive non-glaucomatous eyes receiving intravitreal anti-VEGF injections between December 2016 and July 2017. All eyes were randomly assigned to no prophylaxis or topical brimonidine tartrate 0.15 % administered 20 min prior to injection in one of two consecutive visits. Measurements of IOP were obtained immediately (T0), 10 min (T10) and 20 min (T20) after injection during the visits with and without prophylaxis., Results: Among the 58 eyes of 55 patients (116 visits), the mean (SD) age was 74.3 (11.6), and 62% were female. The mean baseline IOP was 15.3 (2.3) mm Hg (range: 11-20). On average, the immediate postinjection IOP during the visit without prophylaxis was 41.6 (12) mm Hg (range: 17-81). Compared with no prophylaxis, the visit with preadministered topical brimonidine tartrate had a lower IOP at T0 (p<0.001), T10 (p=0.001) and T20 (p=0.043), and a smaller proportion of eyes with IOP elevation of greater than 20 mm Hg from preinjection (p=0.002) and IOP greater than 50 mm Hg at T0 (p=0.036). Without prophylaxis, two eyes (two patients) had an IOP of greater than 70 mm Hg at T0 and thus underwent anterior chamber paracentesis., Conclusion: Topical brimonidine tartrate prophylaxis for intravitreal injection of anti-VEGF agents effectively reduces IOP spikes in non-glaucomatous eyes and may be easily incorporated into ophthalmologists' current practice., Trial Registration Number: NCT03513172., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2019. No commercial re-use. See rights and permissions. Published by BMJ.)

Purpose: To compare the effects of a topical intraocular pressure (IOP)-lowering medication for preventing an IOP increase after cataract surgery in eyes with glaucoma., Design: Randomized clinical study., Methods: A total of 165 eyes of 165 patients with primary open-angle glaucoma or pseudoexfoliation glaucoma scheduled for phacoemulsification were randomly assigned to 1 of 3 groups to receive each medication immediately postoperatively: 1) prostaglandin F 2α analog (travoprost), 2) β-blocker (timolol maleate), or 3) carbonic anhydrase inhibitor (brinzolamide). Intraocular pressure (IOP) was measured using a rebound tonometer at 1 hour preoperatively, at the end of surgery, and at 2, 4, 6, 8, and 24 hours postoperatively. The incidence of eyes exhibiting a marked IOP increase to greater than 25 mm Hg was compared among the groups., Results: At 1 hour preoperatively and at the end of surgery, mean IOP did not differ significantly among the groups. Mean IOP increased significantly between 4 and 8 hours postoperatively and then decreased at 24 hours postoperatively in all groups (P < .0001). Mean IOP was significantly lower in the brinzolamide group than in the travoprost or timolol group at 4, 6, and 8 hours postoperatively (P ≤ .0374) and did not differ significantly among groups at 2 and 24 hours postoperatively. The incidence of an IOP spike was significantly lower in the brinzolamide group than in the travoprost and timolol groups (P = .0029)., Conclusions: Brinzolamide reduces the short-term IOP increase after cataract surgery more effectively than travoprost or timolol in eyes with glaucoma, suggesting that brinzolamide is preferable for preventing an IOP spike., (Copyright © 2019 The Author(s). Published by Elsevier Inc. All rights reserved.)

The purpose of this systematic review was to evaluate the literature regarding prophylactic treatment of intraocular pressure (IOP) elevation after uncomplicated cataract surgery to provide an evidence-based guideline for cataract surgeons. The relevant literature was identified in EMBASE and PubMed. The risk of bias was assessed according to the 'Cochrane Handbook for Systematic Reviews of Interventions' and the ROBINS-I tool. The Grading of Recommendation, Assessment, Development and Evaluation (GRADE) criteria were used to rate the quality of evidence, and relevant data were systematically extracted to evaluate the pressure-lowering effect of the active substances. The primary outcomes for this systematic review were the absolute and relative pressure-lowering effect of the different drugs after 3-8 hr and 1 day after surgery. In total, 23 randomized controlled trials and one nonrandomized controlled study consisting of 45 treatment arms with 14 different active substances were included in the qualitative synthesis. According to the GRADE criteria, nine trials were graded as 'high' quality of evidence, 12 trials as 'moderate', while three trials were given the grade 'low' quality of evidence. The primary outcomes showed most consistency between the trials, which studied the effect of timolol, and presented a relative effect from 18.6% to 29.6% at 3-8 hr and 9.8% to 23.6% at day 1. This systematic review indicates that timolol, latanoprost and travoprost alone or medications containing timolol as an additive active substance, such as dorzolamide + timolol, brinzolamide + timolol and brimonidine + timolol, are characterized by a good relative IOP-lowering effect, which can be gained by a single dose postoperatively., (© 2019 Acta Ophthalmologica Scandinavica Foundation. Published by John Wiley & Sons Ltd.)

Objective: To evaluate the postoperative effect of intracameral tPA (alteplase; Activase®, Genentech, San Francisco, CA), administered at immediate conclusion of phacoemulsification, on anterior chamber fibrin formation in dogs., Procedures: Forty-one dogs (82 eyes) undergoing bilateral phacoemulsification received 25 μg/0.1 mL intracameral tPA in one eye and 0.1 mL unmedicated aqueous vehicle in the contralateral eye immediately after corneal incision closure. Intraocular pressure (IOP) was measured, and severity of anterior chamber fibrin formation, aqueous flare, pigment precipitates on the intraocular lens (IOL) implant, posterior capsular opacification (PCO), and corneal edema were graded at approximately 1 week, 2-3 weeks, 4-6 weeks, 8-12 weeks, and greater than 3 months postoperatively., Results: Anterior chamber fibrin developed postoperatively in 68.3% of dogs (28/41) and 50% of eyes (41/82). In tPA-treated eyes, 53.7% (22/41) developed fibrin compared to 46.3% of control eyes (19/41). Some degree of postoperative ocular hypertension (POH) occurred in 53.7% of dogs (22/41) and 36.5% of eyes (30/82). In tPA-treated eyes, 34.1% (14/41) experienced POH compared to 39% of control eyes (16/41). Additional intracameral tPA injection was later required in 29.3% of both tPA-treated (12/41) and control eyes (12/41)., Conclusions: Administration of intracameral tPA at immediate conclusion of canine phacoemulsification had no clinically observable effect on anterior chamber fibrin incidence at any time point. tPA-treated eyes showed no prophylaxis against POH or secondary glaucoma compared to control eyes and received late postoperative tPA injections at the same frequency as control eyes., (© 2019 American College of Veterinary Ophthalmologists.)

With the increasing popularity, frequency, and acceptance of the robotic-assisted laparoscopic radical prostatectomy procedure, an awareness of unique intra- and postoperative complications is heightened, including that of increases in intraocular pressure. The steep Trendelenburg positioning required for operative exposure has been shown to increase this value. While the literature is infrequent and undeveloped, certain anesthetic parameters including deep neuromuscular blockade, modified positioning, and the use of dexmedetomidine have been shown to have mild-to-modest decreases in intraocular pressure for baseline. In the four randomized control trials and four observational studies that were found via PubMed/Medline search, the aforementioned techniques demonstrate some preliminary evidence of operative considerations in this unique patient population. These modifications may prove to have even greater significance in patients with pre-existing ophthalmologic pathologies, such as glaucoma, which were excluded from the studies' analyses. This review summarizes the early literature obtained in this subject, with the intent of emphasizing the initial hypotheses and identifying areas for future study.

Glaucoma is a common heterogeneous eye disorder that may lead to irreversible blindness. In the present study, we examined whether etidronate, a member of bisphosphonates, may have neuroprotective effects in in vivo and in vitro rat model of glaucoma. In an in vivo setting, chronic ocular hypertension (COH) was induced in adult rat retina. We discovered that systemic injection of etidronate reduced COH-induced retinal oxidative stress, including caspase-3 activity and MDA level, as well as promoted retinal ganglion cell survival. In an in vitro setting, neonatal retinal ganglion cell was incubated with etidronate. We found etidronate incubation promoted neurite growth, upregulated IGF-1 and p-IGF-1R protein expressions in retinal ganglion cell. In addition, application of a selective IGF-1R antagonist effectively blocked the pro-neuronal effect of etidronate on retinal ganglion cell growth, and reduced p-IGF-1R protein expression. Thus, our results demonstrated that etidronate might reduce retinal oxidative stress and promote retinal neuronal growth through IGF-1 signaling pathway. Future work may define its clinical feasibility to treating human patients with glaucoma., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Purpose: To determine if bone marrow-derived stem cell (BMSC) small extracellular vesicles (sEV) promote retinal ganglion cell (RGC) neuroprotection in the genetic DBA/2J mouse model of glaucoma for 12 months., Methods: BMSC sEV and control fibroblast-derived sEV were intravitreally injected into 3-month-old DBA/2J mice once a month for 9 months. IOP and positive scotopic threshold responses were measured from 3 months: IOP was measured monthly and positive scotopic threshold responses were measured every 3 months. RGC neuroprotection was determined in wholemounts stained with RNA binding protein with multiple splicing (RBPMS), whereas axonal damage was assessed using paraphenylenediamine staining., Results: As expected, DBA/2J mice developed chronic ocular hypertension beginning at 6 months. The delivery of BMSC sEV, but not fibroblast sEV, provided significant neuroprotective effects for RBPMS+ RGC while significantly reducing the number of degenerating axons seen in the optic nerve. BMSC sEV significantly preserved RGC function in 6-month-old mice, but provided no benefit at 9 and 12 months., Conclusions: BMSC sEV are an effective neuroprotective treatment in a chronic model of ocular hypertension for 1 year, preserving RGC numbers and protecting against axonal degeneration.

Hypertension is an independent risk factor for diabetic retinopathy, yet anti-hypertensive medications such as blockade of angiotensin II do not completely protect against vision-threatening vascular disease. We hypothesized that the potent vasoactive factor, endothelin (ET), is up-regulated in diabetic retinopathy and antagonism of the ET type A receptor (ETRA) or ET type B receptor (ETRB) ameliorates retinal vascular leakage independently of any blood pressure lowering effects. Spontaneously hypertensive rats (SHR) and their normotensive and genetic controls, Wistar Kyoto rats, were randomized to become diabetic or non-diabetic and studied for 8 weeks. Rats were further randomized to receive by intravitreal injection the ETRA antagonist, BQ123, the ETRB antagonist, BQ788, or vehicle, 5 days after the induction of streptozotocin diabetes and 4 weeks later. The treatments had no effect on systolic blood pressure which remained elevated in SHR. ET-1, ET-2, ETRA and ETRB were expressed in retina and retinal pigment epithelium (RPE)/choroid and increased by hypertension or diabetes. BQ123 reduced ET-1 and ET-2 expression in retina and RPE/choroid, while BQ788 had a similar effect but did not influence the mRNA levels of ET-1 in retina. Retinal vascular leakage and Müller cell stress as well as vascular endothelial growth factor (VEGF) expression in retina and RPE/choroid, were increased by hypertension or diabetes and there was an additive effect of these conditions. Treatment with BQ123 or BQ788 effectively reduced these events as well as the elevated levels of inflammatory factors in the retina. Our findings indicate that local ET systems exist in the retina and RPE/choroid that are up-regulated by hypertension and diabetes. The ability of locally delivered ET receptor antagonists to supress these overactive ET systems and reduce retinal vascular leakage and VEGF in the presence of hypertension indicate the potential of these approaches for the treatment of diabetic retinopathy., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Purpose: This study evaluated the effect of preoperative brimonidine tartrate 0.2% on intraocular pressure (IOP) during robotic-assisted laparoscopic radical prostatectomy in steep Trendelenburg position (sTBURG)., Materials and Methods: In this prospective randomized controlled masked interventional trial, eligible patients scheduled for robotic-assisted laparoscopic radical prostatectomy in sTBURG at the Toronto General Hospital had one eye randomized to placebo (artificial tears) or drug (brimonidine tartrate 0.2%) preoperatively. Visual acuity (VA), tonometry, disc photography, visual field (VF), and retinal nerve fiber layer (RNFL) assessments were performed preoperatively and postoperatively. A standardized anesthetic protocol was followed intraoperatively. IOP was measured using Tono-Pen AVIA (Reichert Inc., New York, NY) as follows: preanesthesia supine, anesthetized supine, hourly in sTBURG and awake supine. The primary outcome was IOP in sTBURG in the drug group compared with the placebo group. Secondary outcomes were changes in VA, VF, RNFL thickness, mean arterial pressure, and ocular perfusion pressure. This study was approved by University Health Network Research Ethics Board., Results: In total, 26 eligible patients, mean age 61.9±5.1 years, were randomized to brimonidine (11 patients) and placebo (15 patients). Baseline IOP was not significantly different between the drug and placebo groups (P=0.42). Significant and sustained IOP elevation of >1.5X baseline in the sTBURG was noted in both groups. The mean IOP 1 hour after sTBURG was 29.4±6.9 and 27.2±3.4 mm Hg in the drug and placebo groups, respectively (P=0.35). No significant changes were noted in VA, VF, or RNFL., Conclusions: Significant and sustained IOP increases occur during sTBURG. Preoperative brimonidine does not prevent IOP spikes in sTBURG.

Phacoemulsification (phaco) for cataract extraction is 1 of the most commonly performed ophthalmic surgeries. With increasing evidence of significant intraocular pressure (IOP) reduction after phaco, the paradigm for glaucoma treatment has been shifting toward more cataract extraction instead of glaucoma surgery; thus, the population of glaucoma patients undergoing phaco is likely to continue to increase in the coming years. Although the safety of surgery has improved over the years with newer technologies and machines, postoperative IOP spike remains an important condition even after an uneventful operation. Glaucoma patients undergoing phacoemulsification are particularly at risk of further glaucomatous optic nerve damage from the transient yet potentially high pressures after phaco. Common treatments include topical, intracameral, oral, and systemic IOP-lowering medications; postoperative anterior chamber paracentesis (ACP); and so on. No single treatment to date can guarantee effective prevention or control IOP rise in the first 24 hours after phaco. Sometimes, the IOP remains high despite all of the above treatments and the risk for further glaucomatous damage may be unavoidable. In this perspective article, we discuss the incidence, causes, and treatments of IOP rise after phaco and introduce a new technique, a non-self-sealing (leaky) ACP that may be of use in regulating postoperative IOP rise, especially for patients with glaucoma., (Copyright 2018 Asia-Pacific Academy of Ophthalmology.)

Study Objective: To study the effects of intraoperative dexmedetomidine on the intraocular pressure (IOP) in patients undergoing robot-assisted laparoscopic radical prostatectomy (RALRP) under propofol-remifentanil anesthesia., Design: Double-blind, randomized controlled trial., Setting: Operating room., Patients: Forty consenting male patients aged ≥20 to <80 years with American Society of Anesthesiologists physical status classes I and II., Interventions: The patients were randomly assigned to either dexmedetomidine (DEX) (n = 20) or control (n = 20) group. Anesthesia was induced and maintained using propofol, remifentanil, and rocuronium. In the dexmedetomidine group, dexmedetomidine was administered at 0.4 μg/kg/h immediately after anesthesia induction until the end of the surgery, whereas normal saline was administered as placebo in the control group., Measurements: IOP was measured using a rebound tonometer. Time points of measuring IOP were as follows: T1: before anesthesia induction, T2: 5 min after intubation, T3: 60 min after placing patient in the Trendelenburg position, T4: 120 min after placing patient in the Trendelenburg position, T5: 180 min after placing patient in the Trendelenburg position, T6: 5 min after placing patient in a horizontal position, T7: 5 min after extubation, and T8: 30 min after extubation., Main Results: A linear mixed model analysis demonstrated a significant intergroup difference in IOP over time and during pneumoperitoneum in the steep Trendelenburg position. IOP at T5 was significantly lower in the dexmedetomidine group than in the control group even after post-hoc analysis in the steep Trendelenburg position periods with Bonferroni correction., Conclusions: Dexmedetomidine combined with propofol decreases IOP in the steep Trendelenburg position during RALRP., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Glaucoma is a vision threatening optic neuropathy that affects millions of people worldwide. In primary open angle, increased intraocular pressure (IOP) is the main risk factor for the development of this disease. Studies investigating the causes and mechanisms of increased IOP show fibrotic changes in the trabecular meshwork (TM) that are different from those of age-matched controls. Tissue transglutaminase (TGM2), an extracellular matrix (ECM) crosslinking enzyme, covalently crosslinks ECM proteins and causes excessive ECM protein deposition in the TM that could cause increased IOP. Previous literature reports increased expression of TGM2 in glaucomatous eyes compared to controls. We recently have shown that overexpression of TGM2 causes increased ECM crosslinking in the TM, increases IOP, and decreases aqueous humor (AH) outflow facility in mouse eyes. Therefore, we wanted to study the effect of TGM2 knockout (KO) on IOP in TGM2 floxed mice. Ad5.Cre transduction caused partial KO of TGM2, which decreased TGM2 expression in the TM region of mouse eyes. TGM2 KO significantly decreased IOP by itself and also in TGFβ2 induced ocular hypertensive mice. TGM2 KO also restores the outflow facility in TGFβ2 transduced eyes. Overall, TGM2 KO rescued the TGFβ2-induced ocular hypertensive phenotype. Thus, TGM2 may offer potential as a new therapeutic target for glaucoma., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

The acute and chronic effects of repeated intravitreal antivascular endothelial growth factor (VEGF) injections on intraocular pressure have not been fully characterized, and the development of sustained ocular hypertension could adversely affect patients who are at risk of glaucomatous optic neuropathy. As expected, volume-driven, acute ocular hypertension immediately follows intravitreal injection, but this pressure elevation is generally transient and well tolerated. Several medications have been investigated to limit acute ocular hypertension following anti-VEGF therapy, but the benefits of pretreatment are not conclusive. Chronic, sustained ocular hypertension, distinct from the short-term acute ocular hypertension after each injection, has also been associated with repeated intravitreal anti-VEGF injections. Risk factors for chronic ocular hypertension include the total number of injections, a greater frequency of injection, and preexisting glaucoma. Proposed mechanisms for chronic ocular hypertension include microparticle obstruction, toxic or inflammatory effects on trabecular meshwork, as well as alterations in outflow facility by anti-VEGF agents. Although limiting anti-VEGF therapy could minimize the risk of both acute and chronic ocular hypertension, foregoing anti-VEGF therapy risks progression of various macular diseases with resulting permanent central vision loss. While definitive evidence of damage to the retinal nerve fiber layer is lacking, patients receiving repeated injections should be monitored for ocular hypertension and patients in whom sustained ocular hypertension subsequently developed should be periodically monitored for glaucomatous changes with optic nerve optical coherence tomography and static visual fields., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Objective: To determine whether topical hypotensive medications prevent postoperative ocular hypertension (POH) after phacoemulsification., Animals Studied: 52 client-owned dogs (88 eyes)., Procedures: Diabetic and nondiabetic dogs having undergone phacoemulsification were included in this retrospective study. The control group received no ocular hypotensive medications. The treatment groups received latanoprost, dorzolamide, or dorzolamide/timolol, beginning immediately after surgery, for 2-week duration. IOPs were obtained at initial examination followed by 4 h, 24 h, 7 days, and 14 days postoperatively. POH was defined as an IOP above 20 mmHg (POH20) or 25 mmHg (POH25)., Results: POH20 occurred in 33 of 87 eyes (37.93%), including 11 of 21 eyes (52.38%) in the control group, three of 23 eyes (13.04%) in the latanoprost group, eight of 15 eyes (53.33%) in the dorzolamide group, and 11 of 28 eyes (39.29%) in the dorzolamide/timolol group. Active treatment groups were compared to the control group, and the overall group effect was not significant (P = 0.11). POH25 occurred in 22 of 86 eyes (25.58%), including seven of 21 eyes (33.33%) in the control group, two of 23 eyes (8.70%) in the latanoprost group, five of 15 eyes (33.33%) in the dorzolamide group, and eight of 27 eyes (29.63%) in the dorzolamide/timolol group. Active treatment groups were compared to the control group, and the overall group effect was not significant (P = 0.31). Intraoperative use of intracameral tissue plasminogen activator significantly decreased the chances of POH25 (P = 0.0063)., Conclusions and Clinical Relevance: The latanoprost group had a substantially lower percentage of POH 20 and POH25 compared to the control and other active treatment groups, although statistical significance was not achieved. Intraoperative intracameral tissue plasminogen activator decreased the incidence of POH25., (© 2017 American College of Veterinary Ophthalmologists.)

Purpose: To find out the rate of suture requirement and post-operative hypotony in a series of 23-gauge pars plana vitrectomy cases and analyze the factors affecting post-operative hypotony and leakage of sclerotomy leading to suture placement., Methods: This is a single-center retrospective interventional case series. Eighty-four eyes underwent 23-gauge vitrectomy. Primary endpoint measures were rate of leakage of 23-gauge sclerotomies requiring suture placement at the end of surgery and rate of early post-operative hypotony. Secondary endpoint measures were risk factors for early hypotony and leakage requiring suture placement at the end of surgery., Results: Suture placement in at least one sclerotomy because of sclerotomy leakage was required in 28.6 % (24 of 84) of eyes at the end of surgery. Early post-operative hypotony was seen in 14.3 % (12 of 84). Silicone oil endotamponade and single-step surgery were found as factors increasing the risk of sclerotomy leakage leading to suture placement. Suture placement was the only significant factor increasing the risk of early post-operative hypotony., Conclusion: Sclerotomy sutures may be required in 23-gauge surgery, more frequently in cases of single-step sclerotomy and/or silicone oil endotamponade. Meticulous suturation of leaking sclerotomies may decrease the rate of post-operative hypotony.

Background/purpose: To analyze the prognostic factors for ocular hypertension after posterior subtenon injection of triamcinolone acetonide (PSTA) for the treatment of diabetic macular edema (DME)., Methods: Patients who received PSTA for DME from January 2006 to December 2011 were enrolled retrospectively and were followed until December 2012 in one hospital. Modified Cox regression models were used to analyze the factors associated with ocular hypertension, which was defined as an intraocular pressure>21 mmHg after PSTA., Results: A total of 180 PSTA injections were given to 114 eyes from 73 adults with DME. During a mean follow-up of 50.4 weeks after each injection, ocular hypertension occurred in 20.6% of injections (28.1% of eyes). Treatment-naïve patients with proliferative diabetic retinopathy (PDR) had a higher risk of ocular hypertension after PSTA than those with nonproliferative diabetic retinopathy (NPDR) [hazard ratio (HR)=3.255, p=0.030]. Intravitreal injection of bevacizumab (IVB) before PSTA had a significant effect in lowering the risk of ocular hypertension after PSTA in patients with PDR who had received panretinal photocoagulation (PRP) (HR=0.107, p=0.035). Both prompt PRP and IVB following PSTA had a protective effect against ocular hypertension in treatment-naïve patients with PDR (HR=0.086, p=0.0002 and HR=0.155, p=0.049, respectively)., Conclusion: Treatment-naïve patients with PDR had a higher risk of ocular hypertension after PSTA than those with NPDR. Bevacizumab and prompt PRP both had a protective effect against ocular hypertension after PSTA in patients with PDR., (Copyright © 2016. Published by Elsevier B.V.)

Purpose: To confirm the prophylactic effect of oral acetazolamide against increased intraocular pressure (IOP) in the period immediately after cataract surgery in eyes with primary open-angle glaucoma (POAG) and to evaluate the appropriate administration time of oral acetazolamide to prevent IOP elevation., Design: Randomized clinical study., Participants: Ninety eyes of 90 patients with well-controlled POAG scheduled for phacoemulsification., Methods: Eyes were assigned randomly to 1 of 3 groups: (1) oral acetazolamide (500 mg) administration 1 hour preoperatively, (2) oral acetazolamide (500 mg) administration 3 hours postoperatively, or (3) no acetazolamide administration. Intraocular pressure was measured using a rebound tonometer 1 hour preoperatively, at the conclusion of surgery (adjusted in the range between 15 and 25 mmHg), and 1, 3, 5, 7, and 24 hours postoperatively. The incidence of eyes with IOP elevation more than 100% above the preoperative IOP was compared., Main Outcome Measures: Postoperative IOP and incidence of eyes with marked IOP elevation., Results: Mean IOP 1 hour preoperatively and that at the conclusion of surgery did not differ significantly among groups. In all groups, mean IOP was significantly elevated from 3 to 7 hours postoperatively, and then decreased at 24 hours. At 1 and 3 hours postoperatively, mean IOP was significantly lower in the group receiving oral acetazolamide preoperatively than in the other 2 groups (postoperative administration or no administration; P ≤ 0.0031). At 5, 7, and 24 hours postoperatively, the IOP was significantly lower in both the preoperative and postoperative administration groups than in the nonadministration group (P ≤ 0.0224). Intraocular pressure elevation of more than 100% occurred in 1 eye (3.3%) in the preoperative administration group, 7 eyes (23.3%) in the postoperative administration group, and 8 eyes (26.6%) in the nonadministration group; the incidence was significantly lower in the preoperative administration group (P = 0.0459)., Conclusions: Eyes with POAG experienced short-term IOP elevation from 3 to 7 hours after phacoemulsification. Oral acetazolamide administration 1 hour preoperatively significantly reduced the IOP elevation from 1 to 24 hours, while administration 3 hours postoperatively reduced the IOP elevation at 5 hours or more after surgery., (Copyright © 2017 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.)

Background: Glaucoma is the international leading cause of irreversible blindness. Intraocular pressure (IOP) is the only currently known modifiable risk factor; it can be reduced by medications, incisional surgery, or laser trabeculoplasty (LTP). LTP reduces IOP by 25% to 30% from baseline, but early acute IOP elevation after LTP is a common adverse effect. Most of these IOP elevations are transient, but temporarily elevated IOP may cause further optic nerve damage, worsening of glaucoma requiring additional therapy, and permanent vision loss. Antihypertensive prophylaxis with medications such as acetazolamide, apraclonidine, brimonidine, dipivefrin, pilocarpine, and timolol have been recommended to blunt and treat the postoperative IOP spike and associated pain and discomfort. Conversely, other researchers have observed that early postoperative IOP rise happens regardless of whether people receive perioperative glaucoma medications. It is unclear whether perioperative administration of antiglaucoma medications may be helpful in preventing or reducing the occurrence of postoperative IOP elevation., Objectives: To assess the effectiveness of medications administered perioperatively to prevent temporarily increased intraocular pressure (IOP) after laser trabeculoplasty (LTP) in people with open-angle glaucoma (OAG)., Search Methods: We searched CENTRAL (which contains the Cochrane Eyes and Vision Trials Register) (2016, Issue 11), MEDLINE Ovid (1946 to 18 November 2016), Embase.com (1947 to 18 November 2016), PubMed (1948 to 18 November 2016), LILACS (Latin American and Caribbean Health Sciences Literature Database) (1982 to 18 November 2016), the metaRegister of Controlled Trials (mRCT) (www.controlled-trials.com); last searched 17 September 2013, ClinicalTrials.gov (www.clinicaltrials.gov); searched 18 November 2016 and the WHO International Clinical Trials Registry Platform (ICTRP) (www.who.int/ictrp/search/en); searched 18 November 2016. We did not use any date or language restrictions., Selection Criteria: We included randomized controlled trials (RCTs) in which participants with OAG received LTP. We included trials which compared any antiglaucoma medication with no medication, one type of antiglaucoma medication compared with another type of antiglaucoma medication, or different timings of medication., Data Collection and Analysis: Two review authors independently screened records retrieved by the database searches, assessed the risk of bias, and abstracted data. We graded the certainty of the evidence using GRADE., Main Results: We included 22 trials that analyzed 2112 participants and identified no ongoing trials. We performed several comparisons of outcomes: one comparison of any antiglaucoma medication versus no medication or placebo, three comparisons of one antiglaucoma medication versus a different antiglaucoma mediation, and one comparison of antiglaucoma medication given before LTP to the same antiglaucoma medication given after LTP. Only one of the included trials used selective laser trabeculoplasty (SLT); the remaining trials used argon laser trabeculoplasty (ALT). Risk of bias issues were primarily in detection bias, reporting bias, and other potential bias due to studies funded by industry. Two potentially relevant studies are awaiting classification due to needing translation.In the comparison of any medication versus no medication/placebo, there was moderate-certainty evidence that the medication group had a lower risk of IOP increase of 10 mmHg or greater within two hours compared with the no medication/placebo group (risk ratio (RR) 0.05, 95% confidence interval (CI) 0.01 to 0.20). This trend favoring medication continued between two and 24 hours, but the evidence was of low and very low-certainty for an IOP increase of 5 mmHg or greater (RR 0.17, 95% CI 0.09 to 0.31) and 10 mmHg or greater (RR 0.22, 95% CI 0.11 to 0.42). Medication was favored over placebo/no medication with moderate-certainty in reducing IOP from the pre-LTP measurements for both within two hours and between two and 24 hours. At two hours, the mean difference (MD) in IOP between the medication group and the placebo/no medication group was -7.43 mmHg (95% CI -10.60 to -4.27); at between two and 24 hours, the medication group had a mean reduction in IOP of 5.32 mmHg more than the mean change in the placebo/no medication group (95% CI -7.37 to -3.28). Conjunctival blanching was an ocular adverse effect that was more common when brimonidine was given perioperatively compared with placebo in three studies.In our comparison of brimonidine versus apraclonidine, neither medication resulted in a lower risk of increased IOP of 5 mmHg or greater two hours of surgery; however, we were very uncertain about the estimate. There may be a greater mean decrease in IOP within two hours after LTP. We were unable to perform any meta-analyses for other review outcomes for this comparison.In our comparison of apraclonidine versus pilocarpine, we had insufficient data to perform meta-analyses to estimate effects on either of the primary outcomes. There was moderate-certainty evidence that neither medication was favored based on the mean change in IOP measurements from pre-LTP to two hours after surgery.In the comparison of medication given before LTP versus the same medication given after LTP, we had insufficient data for meta-analysis of IOP increase within two hours. For the risk of IOP increase of 5 mmHg or greater and 10 mmHg or greater at time points between two and 24 hours, there was no advantage of medication administration before or after LTP regarding the proportion of participants with an IOP spike (5 mmHg or greater: RR 0.82, 95% CI 0.25 to 2.63; 10 mmHg or greater: RR 1.55, 95% CI 0.19 to 12.43). For an IOP increase of 10 mmHg or greater, we had very low-certainty in the estimate, it would likely change with data from new studies., Authors' Conclusions: Perioperative medications are superior to no medication or placebo to prevent IOP spikes during the first two hours and up to 24 hours after LTP, but some medications can cause temporary conjunctival blanching, a short-term cosmetic effect. Overall, perioperative treatment was well tolerated and safe. Alpha-2 agonists are useful in helping to prevent IOP increases after LTP, but it is unclear whether one medication in this class of drugs is better than another. There was no notable difference between apraclonidine and pilocarpine in the outcomes we were able to assess. Future research should include participants who have been using these antiglaucoma medications for daily treatment of glaucoma before LTP was performed.

Purpose: To evaluate whether defects in cervical lymphatic drainage influence the intraocular pressure (IOP)-lowering effect of latanoprost in patients with primary open-angle glaucoma (POAG) who have undergone unilateral radical neck dissection (uRND)., Methods: We enrolled (1) bilateral POAG patients who had started (bilateral) latanoprost (0.005%) monotherapy prior to their uRND and (2) treatment-naïve, bilateral glaucoma suspects (GSs) who had undergone the same surgery. We compared the eyes ipsilateral to the uRND with their fellow eyes in terms of the changes in IOP between the baseline (prior to the uRND) and the follow-up visits (1, 3, and 6 months after the uRND)., Results: The study involved 22 eyes of 11 POAG patients and 14 eyes of 7 GSs. In the POAG patients, IOP had increased significantly after surgery in the eyes ipsilateral to the uRND (from 14.7±1.4mmHg to 17.1±2.2mmHg; P = 0.007). Interestingly, in the eyes contralateral to the uRND, IOP had not changed significantly after surgery (from 14.2±1.8mmHg to 14.4±2.0mmHg; P = 0.826). In GSs, the eyes ipsilateral to the uRND did not differ significantly from their fellow eyes in terms of post-operative IOP change (ipsilateral value: 0.3±0.5mmHg, fellow eyes: -0.1±0.7mmHg; P = 0.242)., Conclusion: In the POAG patients, IOP had increased significantly in the eyes ipsilateral to the uRND. However, it had not changed significantly in the eyes contralateral to the surgery or in the eyes of the GSs. These findings suggest that, latanoprost works, at least in part, by enhancing outflow from the aqueous humor via the uveolymphatic pathway., Competing Interests: The authors have declared that no competing interests exist.

OBJECTIVE To assess the effects of topically applied 2% dorzolamide hydrochloride-0.5% timolol maleate ophthalmic solution (DHTM) on incidence and severity of postoperative ocular hypertension (POH; ie, intraocular pressure [IOP] > 25 mm Hg) in dogs undergoing cataract extraction by phacoemulsification. DESIGN Randomized, masked, controlled study. ANIMALS 103 dogs (180 eyes). PROCEDURES Pertinent history, signalment, and ophthalmic examination findings were recorded. Dogs received 1 drop of DHTM or sham treatment solution (sterile, buffered, isotonic eye drops) in both eyes 14 hours and 2 hours before anesthetic induction and at the time of corneal incision closure (ie, end of surgery); IOPs were assessed by rebound tonometry 2, 4, 6, and 8 hours after surgery and between 7:30 and 8:00 am on the following day. Dogs with IOPs of 26 to 45 mm Hg received 1 drop of 0.005% latanoprost solution topically; the surgeon's treatment of choice was used for dogs with IOPs > 45 mm Hg. Incidence of POH and postoperative IOPs were compared between treatment groups. RESULTS DHTM treatment resulted in significantly lower incidence of POH than did sham treatment at the level of the dog (18/53 [34%] vs 31/50 [62%]) and the eye (24/94 [26%] vs 42/86 [48%]). Mean IOP did not differ between groups at the time of POH detection. The DHTM-treated eyes that developed POH were significantly more likely to have a 1-hour follow-up IOP < 25 mm Hg after latanoprost administration than were sham-treated eyes (19/25 [76%] vs 18/35 [51%]; OR, 3.87). CONCLUSIONS AND CLINICAL RELEVANCE Multidose perioperative administration of DHTM in dogs undergoing phacoemulsification reduced the incidence of POH and improved responsiveness of POH to latanoprost treatment.

Purpose: To observe the effect of prophylactic intraocular pressure (IOP)-lowering medication (brinzolamide) on IOP after ranibizumab intravitreal injections (IVIs)., Materials and Methods: This prospective case-control study included 352 eyes from 352 patients (1 eye per patient) who were treated with ranibizumab intravitreal injection and divided randomly into two groups. Two hundred and three patients in control group only received the ranibizumab IVI, but 149 patients in case group received one drop of prophylactic intraocular brinzolamide preinjection. The IOP was measured by noncontact tonometer before injection, at 10, 30, 120 min and 1 day after injection in a sitting position., Results: The mean IOP measured before injection, at 10, 30, 120 min and 1 day after injection individually were 15.79 ± 2.21 mmHg, 19.33 ± 4.86 mmHg, 16.64 ± 2.93 mmHg, 16.17 ± 3.13 mmHg, and 15.07 ± 2.55 mmHg in case group and were 15.82 ± 2.57 mmHg, 21.34 ± 5.88 mmHg, 18.17 ± 4.06 mmHg, 17.59 ± 4.42 mmHg, and15.48 ± 2.92 mmHg in control group. Comparing two groups, the mean increase on IOP was statistically significant at 10, 30, 120 min postinjection (P < 0.05)., Conclusions: IVI of ranibizumab causes a considerable short-term transient rise on IOP in most patients. The effect of prophylactic IOP-lowering medication on IOP after IVIs can be statistically significant from 10 min to 2 h after IVIs., Competing Interests: There are no conflicts of interest.

Purpose: Brn3b is a class IV POU domain transcription factor that plays an important role in the development of retinal ganglion cells (RGCs), RGC survival, and particularly axon growth and pathfinding. Our previous study demonstrated that recombinant adenoassociated virus serotype 2 (rAAV-2)-mediated overexpression of Brn3b in RGCs promoted neuroprotection in a rodent model of glaucoma. However, the mechanisms underlying neuroprotection of RGCs in rats overexpressing Brn3b in animal models of glaucoma remain largely unknown. The goal of this study was to understand some of the mechanisms underlying the neuroprotection of RGCs overexpressing Brn3b during intraocular pressure (IOP) elevation in Brown Norway rats., Methods: One eye of Brown Norway rats (Rattus norvegicus) was injected with an AAV construct encoding either green fluorescent protein (GFP; recombinant adenoassociated virus-green fluorescent protein, rAAV-hSyn-GFP) or Brn3b (rAAV-hSyn-Brn3b). Expression of antiapoptotic proteins, including B cell lymphoma/leukemia-2 (Bcl-2) family proteins (Bcl-2 and Bcl-xL), and p-AKT, was observed following immunostaining of rat retinas that overexpress Brn3b. In a different set of experiments, intraocular pressure was elevated in one eye of Brown Norway rats, which was followed by intravitreal injection with AAV constructs encoding either GFP (rAAV-CMV-GFP) or Brn3b (rAAV-CMV-Brn3b). Retinal sections were stained for prosurvival factors, including Bcl-2, Bcl-XL, and p-AKT., Results: AAV-mediated expression of transcription factor Brn3b promoted statistically significant upregulation of the Bcl-2 protein and increased expression of p-AKT in RGCs of Brown Norway rats. In addition, following IOP elevation, AAV-mediated Brn3b expression also statistically significantly increased levels of Bcl-2 in the RGC layer in Brown Norway rats., Conclusions: Adenoassociated virus-mediated Brn3b protein overexpression may promote neuroprotection by upregulating key antiapoptotic proteins, including Bcl-2, Bcl-xL, and p-AKT, in animal models of glaucoma.

The study purpose was to evaluate preventive use of dorzolamide-timolol ophthalmic solution (Cosopt) during laparoscopic surgery with the patient in steep Trendelenburg (ST) position. Periorbital swelling, venous congestion, and elevated intraocular pressure (IOP) may produce low ocular perfusion. Prompt IOP reduction is important because 30- to 40-minute episodes of acute IOP elevations can result in retinal ganglion cell dysfunction. Dorzolamide-timolol ophthalmic drops reduce IOP and may ameliorate this effect. A double-blind randomized experimental study was conducted to test the effect of dorzolamide-timolol on IOP elevation during laparoscopic surgeries in ST position. Patients were randomly assigned to receive dorzolamide-timolol treatment or balanced salt solution following anesthesia induction. The IOP levels were measured at baseline and 30-minutes intervals throughout surgery. The generalized estimating equations model was used to analyze treatment and time effects and treatment by time interactions. Ninety patients were recruited, with 46 receiving dorzolamide-timolol treatment and 44 receiving balanced salt solution. Statistical analysis revealed significant treatment and time effects and treatment-time interactions on IOP. Patients' IOP was significantly lower in the treatment group than controls (P < .05 to P < .001). Treatment effects were medium to strong. Prophylactic therapy with dorzolamide-timolol significantly reduced IOP of surgical patients during ST positioning.

Corticosteroids are a mainstay therapeutic option for the treatment of ocular inflammation. However, safety remains a concern for clinicians, particularly with long-term use. Though highly effective at suppressing inflammatory and allergic responses, topical ophthalmic corticosteroids carry an inherent risk of side effects, including elevated intraocular pressure (IOP), a risk factor for the development of glaucoma. The corticosteroid loteprednol etabonate (LE) contains an ester rather than a ketone at the C-20 position, minimizing the potential for side effects, including IOP elevation. In early pivotal clinical trials of LE ophthalmic suspension for conjunctivitis (allergic, giant papillary), anterior uveitis, and post-operative inflammation, LE had minimal impact on IOP over short-term (<28 days) and long-term (≥28 days) use. Since then, new LE formulations-including a gel, an ointment, and a suspension of LE in combination with tobramycin-have become commercially available. Multiple studies evaluating the safety and efficacy of LE for inflammatory conditions have been reported, including those requiring longer-term treatment such as photorefractive keratectomy, corneal transplantation, and dry eye disease. We review the available published data on the effect of LE on IOP and report on the cumulative incidence of clinically significant IOP elevations (≥10 mm Hg from baseline) with short-term and long-term LE use. In all studies, LE consistently demonstrated a low propensity to elevate IOP, regardless of formulation, dosage regimen, or treatment duration, including in known steroid responders. The cumulative proportion of patients exhibiting clinically significant IOP increases was 0.8% (14/1725 subjects) in studies evaluating short-term LE treatment and 1.5% (21/1386 subjects) in long-term studies. Furthermore, use of LE was associated with significantly lower rates of IOP elevation ≥10 mm Hg as compared to prednisolone acetate or dexamethasone (when used in combination with tobramycin). The cumulative data to date substantiates a favorable IOP-safety profile for LE with both short-term and long-term use.

Purpose: To create a standardized method for evaluating the video recordings of patients self-instilling eye drops and to determine the level of agreement of eye drop instillation efficacy, safety and efficiency ratings by three masked graders., Design: Prospective cross-sectional study., Participants: 78 patients with open-angle glaucoma or ocular hypertension who had at least 6 months of experience with the use of eye drop medications., Methods: Participants were video recorded while self-instilling artificial tears sequentially to both eyes. Three masked observers graded these video recordings on three criteria: efficacy (the determination of whether an eye drop was instilled on the ocular surface), safety (assessment of whether the tip of the medication bottle made contact with the ocular surface or eyelids), and efficiency (the number of eye drops expressed from the bottle)., Main Outcome Measures: After grading the video recordings based on efficacy, safety, and efficiency, kappa statistics were used to estimate inter-rater agreement., Results: The mean kappa level of agreement for efficacy, safety, and efficiency was 0.64 (95% confidence interval (CI), 0.42-0.87), 0.73 (95% CI, 0.58-0.88), and 0.62 (95% CI, 0.42-0.81), respectively., Conclusions: We demonstrated good inter-rater reproducibility of the masked analysis of video recordings of patients self-instilling eye drops based on three criteria: efficiency, safety, and efficacy.

Aim: To determine the effect of alpha-2-agonist (AA) premedication (PM) on intraocular pressure (IOP) following selective laser trabeculoplasty (SLT)., Methods: Retrospective cohort study of all patients undergoing 360° SLT at an institution with two prevalent practice patterns consisting of SLT performed with PM and without premedication (NPM) with AA. The association between pre- and post-operative IOP was evaluated using a linear regression model in 49 (59%) PM and 34 (41%) NPM eyes., Results: The prevalence of IOP elevations up to 5 mmHg 1 h postoperatively was similar in both groups, occurring in 18% of PM and in 15% of NPM. Elevations above 5 mmHg were seen in 4% of PM and 8% of NPM (P = 0.732). After correcting for age, gender, diagnosis, number of medications, and preoperative IOP, the presence or absence of AA PM had no significant association with any postoperative IOP (P > 0.5)., Conclusion: The practice of using AAs before SLT and measuring IOP at 1 h has not been validated yet adds to expenses and workflow burden. Our retrospective study showed no significant correlation between PM and postoperative or longer-term IOP. IOP at 1 h should be measured in patients who cannot tolerate transient pressure elevations. Further studies are needed to elucidate this relationship.

Background: Lamellar keratoplasties, e.g. Descemet's stripping automated endothelial keratoplasty (DSAEK) and Descemet membrane endothelial keratoplasty (DMEK) are considered the procedures of choice for corneal endothelial diseases. In comparison to penetrating keratoplasty (PK) they are associated with faster visual rehabilitation, a lower risk of complications and a decreased necessity for follow-up visits, which reduces the burden on quality of life in elderly patients. In order to advise patients regarding the indications for surgery and to facilitate the follow-up management, it is important to know the most important complications associated with these keratoplasty techniques., Results and Discussion: The most important preoperative complication is a delayed indication for the operation. In contrast to PK, DSAEK and DMEK surgery should be provided at an earlier stage of disease as chronic edema alters the stroma and reduces the speed of visual recovery. The most important complications during or early after surgery are detached lamellae, pupillary blocks with increased pressure or air bubbles in the vitreous cavity in patients with previous vitrectomy. The main long-term complications include chronic increased intraocular pressure and immune-mediated graft rejections in DSAEK patients after reducing or stopping topical corticosteroid therapy. This article describes the potential complications of endothelial keratoplasty and provides a detailed explanation of strategies to avoid these complications.

Descemet's membrane endothelial keratoplasty (DMEK) is a relatively new, but now established surgical procedure to cure corneal endothelial disorders. However, there are donor- and recipient-associated sources of potential complications, some of which can be identified and addressed prior to the procedure and others that may lead to intra- or postoperative problems. Preoperatively, risk factors for a limited visual outcome (ocular comorbidities, previous ocular surgery, subepithelial/stromal scars) and the specific indication for DMEK should be discussed with the patient. Intraoperatively, young donor age can be associated with a particularly elastic graft, which may be difficult to unfold. Such transplants are not appropriate for particularly difficult recipient situations (very opaque cornea, history of vitreoretinal surgery). Postoperatively, transplant dehiscence is the most common complication, which in many cases can be managed by reinjection of air (or a 20 % SF6 gas/air mix) into the anterior chamber. An elevation of the intraocular pressure after DMEK is often caused by a reaction to topical steroid therapy. Although immune rejections after DMEK are less likely than after Descemet's stripping automated endothelial keratoplasty (DSAEK) and perforating keratoplasty, adequate treatment with topical steroidal drugs is recommended. These common and several rare complications are discussed in this review.

Objectives: Elevated optic nerve sheath diameter on sonography is known to correlate with increased intracranial pressure and is observed in acute mountain sickness. This study aimed to determine whether optic nerve sheath diameter changes on ascent to high altitude are associated with acute mountain sickness incidence., Methods: Eighty-six healthy adults enrolled at 1240 m (4100 ft), drove to 3545 m (11,700 ft) and then hiked to and slept at 3810 m (12,500 ft). Lake Louise Questionnaire scores and optic nerve sheath diameter measurements were taken before, the evening of, and the morning after ascent., Results: The incidence of acute mountain sickness was 55.8%, with a mean Lake Louise Questionnaire score ± SD of 3.81 ± 2.5. The mean maximum optic nerve sheath diameter increased on ascent from 5.58 ± 0.79 to 6.13 ± 0.73 mm, a difference of 0.91 ± 0.55 mm (P = .09). Optic nerve sheath diameter increased at high altitude regardless of acute mountain sickness diagnosis; however, compared to baseline values, we observed a significant increase in diameter only in those with a diagnosis of acute mountain sickness (0.57 ± 0.77 versus 0.21 ± 0.76 mm; P = .04). This change from baseline, or Δ optic nerve sheath diameter, was associated with twice the odds of developing acute mountain sickness (95% confidence interval, 1.08-3.93)., Conclusions: The mean optic nerve sheath diameter increased on ascent to high altitude compared to baseline values, but not to a statistically significant degree. The magnitude of the observed Δ optic nerve sheath diameter was positively associated with acute mountain sickness diagnosis. No such significant association was found between acute mountain sickness and diameter elevation above standard cutoff values, limiting the utility of sonography as a diagnostic tool., (© 2015 by the American Institute of Ultrasound in Medicine.)

Diabetic retinopathy remains as a leading cause of blindness in developed countries. Current treatments target late stages of DR when vision has already been significantly affected. A better understanding of the pathogenesis of DR would permit the development of more efficient preventional/interventional strategies against early stages of DR. In this article a critical review of the state of the art of this issue is provided along with a discussion of problems which have yet to be overcome. Neuroprotection as a new approach for the treatment of the early stages of DR has been particularly emphasized. The development and progression of DR is not homogeneous and, apart from blood glucose levels and blood pressure, it depends on genetic factors which remain to be elucidated. In addition, the role of the pathogenic pathways is not the same in all patients. All these factors should be taken into account in the near future when an individualized oriented treatment for DR could become feasible. The new techniques in retinal imaging acquisition, the identification of useful circulating biomarkers and the individualized analysis of biological samples could facilitate the development of early and personalized therapy in the setting of DR. Finally, it should be noted that only a coordinated action among ophthalmologists, diabetologists, basic researchers, experts in pharmaco-economics and health care providers addressed to the design of rational strategies targeting prevention and the early stages of DR will be effective in reducing the burden and improving the clinical outcome of this devastating complication of diabetes., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

Intravitreal injections are a therapeutic delivery method best suited to the treatment of retinal diseases. Recent years have been marked by the use of anti-VEGF agents as well as the arrival of sustained-release corticosteroid implants in France, replacing triamcinolone acetonide. A common complication of IVT steroids is secondary ocular hypertension (OHT) resulting from increased outflow resistance. This article summarizes current understanding. OHT induced by topical steroids has been described for 60 years. Intravitreal use also shows a temporary effect if the exposure is short, dose dependence, and varying incidence depending on the drug used. Sustained release formulations and discontinuing treatment have reduced the risk of induced OHT. Risk factors that induce OHT must be clearly identified prior to an injection. Most cases of OHT can be controlled medically, although differences exist between different drugs. In cases where it cannot be controlled, removal of the implant, selective laser trabeculoplasty, and filtration surgery can be discussed., (Copyright © 2015 Elsevier Masson SAS. All rights reserved.)

Purpose: This study aimed to compare the effects of remifentanil and esmolol on the elevation of intraocular pressure (IOP) and hemodynamic response., Methods: After approval of the institutional Ethics Committee and obtaining informed consent, 60 adult patients with American Society of Anesthesiologists I-II status undergoing elective, nonophthalmic surgery were included in the study. Exclusion criteria were preexisting eye disease, neuromuscular disease, esophageal reflux, hiatus hernia, allergy to any of the study drugs, and the use of β-blockers, diuretics, or other antihypertensive agents. The patients were randomized into 2 groups by using the sealed-envelope method, as follows: group E (esmolol) and group R (remifentanil). A single intravenous dose of esmolol (0.5 mg/kg) or remifentanil (1 μg/kg) just before induction agents were given to patients in groups E and R, respectively. IOP, heart rate (HR), and mean arterial pressure (MAP) values were recorded before intubation and at 1, 3, 5, and 10 minutes after intubation., Results: The IOP decrease in group R was statistically significant compared with group E (P<0.01). HR values at 10 minutes after intubation were significantly decreased in group E compared with group R (P<0.05). There was no significant difference in MAP values between the groups., Conclusions: It was concluded that remifentanil is more effective than esmolol in preventing IOP elevation related to laryngoscopy and tracheal intubation, while there is no significant difference between the 2 agents in terms of HR and MAP.

The aim of this study was to explore the immune protective mechanism of rMOMP protein vaccine in intraocular hypertension and retinal optic nerve injury in rats. The rMOMP protein ophthalmic vaccine was prepared and quality-controlled. Sixty normal adult SD rats were randomly divided into two groups to establish a chronic ocular hypertension model and an optic nerve injury model. The model rats were vaccinated with rMOMP-CS ophthalmic vaccine. Fluorogold retrograde tracing was used to observe retinal ganglion cells, and an immunofluorescence method to determine the expression of retinal GAP43, CD3, BDNF, and GDNF. rMOMP protein ophthalmic vaccine met the requirements for medicinal use. The number of retinal ganglion cells (RGCs) of the rMOMP-CS group in the chronic ocular hypertension model was significantly higher than that of the CS group (P < 0.05). The count of RGCs of the rMOMP-CS group in the optic nerve clamping injury model was significantly higher than that of the CS group (P < 0.01). Thus, rMOMP protein ophthalmic vaccine can induce an increase in the expression of retinal neurotrophic factors, thereby exerting a protective effect on damaged retinal optic nerve.

Glaucoma or ocular hypertension can be caused by the presence of pseudoexfoliation (PEX) material and/or pigmented cells in the trabecular meshwork (TM) and/or in the irido-corneal angle (ICA). Accumulation of this material can be highlighted by slit-lamp (SL), gonioscopy, and ultrasound biomicroscopy (UBM). Such material prevents aqueous humor from flowing out and thus induces intraocular pressure (IOP) elevation. A new technique using a special cannula for washing the TM and ICA, combined with cataract surgery, can lower IOP and reduce the number of hypotensive drugs needed. This study analyzed 11 patients (13 eyes) presenting a pseudoexfoliation glaucoma with cataract. They all had cataract surgery combined with the special washing technique. Visual acuity and IOP were noted before surgery, just after surgery and during follow-up. The number of hypotensive drugs needed was also recorded. Mean follow-up time was 34.4 months (range 21.8-59.2). The first case underwent surgery in 2007 and has a 5-year follow-up time. Local status was controlled by SL, gonioscopy, and UBM. Mean age was 79 years (range 71.6-86.0). Mean visual acuity was 0.37 pre-op (range 0.05-0.6) and 0.89 post-op (range 0.05-1.0). Mean IOP before and after surgery was 32.8 ± 8.7 mmHg (range 20-53) and 15.1 ± 3.5 mmHg (range 10-20), respectively. The amount of hypotensive drugs needed was 87 % lower after surgery. No PEX material recurrence was seen with SL, gonioscopy, and UBM during the mean follow-up of 3 years. No complication was recorded in this study. Cataract surgery combined with the new washout technique of the TM and ICA to remove PEX material or pigmented cells significantly lowers IOP and the amount of drugs needed. Long-term follow-up gives good results with no complication or recurrence. Eye status after surgery remains physiological and further glaucoma surgery can be performed if necessary. More research with a higher number of patients should be initiated to confirm this technique.

The present study aimed to study the effects of exercise training (ET) performed by rats on a 10-week high-fructose diet on metabolic, hemodynamic, and autonomic changes, as well as intraocular pressure (IOP). Male Wistar rats receiving fructose overload in drinking water (100 g/L) were concomitantly trained on a treadmill for 10 weeks (FT group) or kept sedentary (F group), and a control group (C) was kept in normal laboratory conditions. The metabolic evaluation comprised the Lee index, glycemia, and insulin tolerance test (KITT). Arterial pressure (AP) was measured directly, and systolic AP variability was performed to determine peripheral autonomic modulation. ET attenuated impaired metabolic parameters, AP, IOP, and ocular perfusion pressure (OPP) induced by fructose overload (FT vs F). The increase in peripheral sympathetic modulation in F rats, demonstrated by systolic AP variance and low frequency (LF) band (F: 37±2, 6.6±0.3 vs C: 26±3, 3.6±0.5 mmHg2), was prevented by ET (FT: 29±3, 3.4±0.7 mmHg2). Positive correlations were found between the LF band and right IOP (r=0.57, P=0.01) and left IOP (r=0.64, P=0.003). Negative correlations were noted between KITT values and right IOP (r=-0.55, P=0.01) and left IOP (r=-0.62, P=0.005). ET in rats effectively prevented metabolic abnormalities and AP and IOP increases promoted by a high-fructose diet. In addition, ocular benefits triggered by exercise training were associated with peripheral autonomic improvement.