[Topical application of hypotensive drugs for the prevention of intraocular pressure elevation after intravitreal injections of anti-VEGF drugs]. / Mestnoe primenenie gipotenzivnykh preparatov s tsel'yu profilaktiki povysheniya urovnya vnutriglaznogo davleniya posle intravitreal'nykh in"ektsii anti-VEGF-preparatov.

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.

Prophylaxis against intraocular pressure spikes following uncomplicated phacoemulsification: a systematic-review and meta-analysis.

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.

Exploring the Potential of Wild Olive (Acebuche) Oil as a Pharm-Food to Prevent Ocular Hypertension and Fibrotic Events in the Retina of Hypertensive Mice.

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.

Prophylactic intraocular pressure lowering measures in anti-vascular endothelial growth factor therapy: A systematic review and meta-analysis.

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.

A Novel Postoperative Drop Regimen Reduces Risk of Ocular Hypertension Following Pars Plana Vitrectomy.

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%.

[Prevention of intraocular pressure elevation following intravitreal injections]. / Profilaktika povysheniya urovnya vnutriglaznogo davleniya posle intravitreal'nykh in"ektsii.

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.

Prophylactic efficacy of intravenous paracetamol administration to reduce the incidence of post-operative ocular hypertension in dogs undergoing phacoemulsification: A pilot study.

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.

Intravitreally Injected Methylene Blue Protects Retina against Acute Ocular Hypertension in Rats.

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.

The prophylactic effect of betaxolol 0.5% versus brimonidine 0.2% on IOP elevation after Nd:YAG laser posterior capsulotomy.

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.

Randomized, Double-Masked Trial of Netarsudil 0.02% Ophthalmic Solution for Prevention of Corticosteroid-Induced Ocular Hypertension.

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.

Brinzolamide-brimonidine fixed combination for the prevention of intraocular pressure elevation after phacoemulsification.

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.

Prophylactic treatment of intraocular pressure elevation after uncomplicated cataract surgery in nonglaucomatous eyes - a systematic review.

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.

Effect of Topical Hypotensive Medications for Preventing Intraocular Pressure Increase after Cataract Surgery in Eyes with Glaucoma.

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 F2α analog (travoprost), 2) ß-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.

Effect of immediate postoperative intracameral tissue plasminogen activator (tPA) on anterior chamber fibrin formation in dogs undergoing phacoemulsification.

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.

Are you seeing this: the impact of steep Trendelenburg position during robot-assisted laparoscopic radical prostatectomy on intraocular pressure: a brief review of the literature.

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.

Hypotensive efficacy of topical brimonidine for intraocular pressure spikes following intravitreal injections of antivascular endothelial growth factor agents: a randomised crossover trial.

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.

Mesenchymal Stem Cell-Derived Small Extracellular Vesicles Promote Neuroprotection in a Genetic DBA/2J Mouse Model of Glaucoma.

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.

Etidronate protects chronic ocular hypertension induced retinal oxidative stress and promotes retinal ganglion cells growth through IGF-1 signaling pathway.

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.

Non-Self-Sealing (Leaky) Anterior Chamber Paracentesis: A New Technique in Managing Postphacoemulsification Intraocular Pressure Rise in Glaucoma and Normal Eyes.

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.

Preoperative Brimonidine Tartrate 0.2% Does not Prevent an Intraocular Pressure Rise During Prostatectomy in Steep Trendelenburg Position.

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.