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.

Study profile: the Genetics of Glaucoma Study.

PURPOSE: Glaucoma, a major cause of irreversible blindness, is a highly heritable human disease. Currently, the majority of the risk genes for glaucoma are unknown. We established the Genetics of Glaucoma Study (GOGS) to identify disease genes and improve genetic prediction of glaucoma risk and response to treatment. PARTICIPANTS: More than 5700 participants with glaucoma or a family history of glaucoma were recruited through a media campaign and the Australian Government healthcare service provider, Services Australia, making GOGS one of the largest genetic studies of glaucoma globally. The mean age of the participants was 65.30±9.36 years, and 62% were female. Participants completed a questionnaire obtaining information about their glaucoma-related medical history such as family history, glaucoma status and subtypes, surgical procedures, and prescriptions. The questionnaire also obtained information about other eye and systemic diseases. Approximately 80% of the participants provided a DNA sample and ~70% consented to data linkage to their Australian Government Medicare and Pharmaceutical Benefits Scheme schedules. FINDINGS TO DATE: 4336 GOGS participants reported that an optometrist or ophthalmologist has diagnosed them with glaucoma and 3639 participants reported having a family history of glaucoma. The vast majority of the participants (N=4393) had used at least one glaucoma-related medication; latanoprost was the most commonly prescribed drug (54% of the participants who had a glaucoma prescription). A subset of the participants reported a surgical treatment for glaucoma including a laser surgery in 2008 participants and a non-laser operation in 803 participants. Several comorbid eye and systemic diseases were also observed; the most common reports were ocular hypertension (53% of the participants), cataract (48%), hypertension (40%), nearsightedness (31%), astigmatism (22%), farsightedness (16%), diabetes (12%), sleep apnoea (11%) and migraines (10%). FUTURE PLANS: GOGS will contribute to the global gene-mapping efforts as one of the largest genetic studies for glaucoma. We will also use GOGS to develop or validate genetic risk prediction models to stratify glaucoma risk, particularly in individuals with a family history of glaucoma, and to predict clinical outcomes (eg, which medication works better for an individual and whether glaucoma surgery is required). GOGS will also help us answer various research questions about genetic overlap and causal relationships between glaucoma and its comorbidities.

Effect of alternate nostril breathing exercise on autonomic functions, ocular hypertension, and quality of life in elderly with systemic hypertension and high-tension primary open-angle glaucoma.

Investigating the response of ocular hypertension and quality of life to a 4-week alternate-nostril breathing exercise (ANBE) in older adults with systemic hypertension (SH) and high-tension form of primary open-angle glaucoma (HTF-POAG) was our aim. Sixty older adults with SH and HTF-POAG were randomly assigned to the ANBE group (n=30, received morning and evening 30 min sessions of daily ANBE) or the control (waitlist) group (n=30). Right-eye intraocular pressure (IOP), left-eye IOP, blood pressure, short-form-36 survey (SF36S), rates of respiration and radial-artery pulsation, hospital anxiety and depression scale (depression subscale abbreviated as HADS-D and anxiety subscale abbreviated as HADS-A), and glaucoma quality-of-life 15-item questionnaire (GQoL-15) were assessed. All measurements were improved in the ANBE group only. In conclusion, a 4-week ANBE could be an adjunctive modality to improve HADS-D, rates of respiration and radial-artery pulsation, HADS-A, blood pressure, IOP, GQol-15, and SF36S in older adults SH and HTF-POAG.

Glaucoma suspects referred by general ophthalmologists to a tertiary center in Brazil: outcomes of the glaucoma specialist assessment.

PURPOSE: To characterize patients with suspected glaucoma who were referred to the clinic for suspected glaucoma in a tertiary public hospital in southern Brazil and to evaluate differences in functional and structural damages between patients diagnosed with different types of glaucoma, those with normal eye examination results, and those who remained as glaucoma suspects. METHODS: This is a cohort study of patients referred by general ophthalmologists to the clinic for suspected glaucoma at Hospital Nossa Senhora da Conceição, Porto Alegre, Brazil, between March 2016 and December 2018. The patients were followed up until they had undergone reliable examinations (eye examination, visual field screening, and optic coherence tomography for classification as normal and having a suspected glaucoma, glaucoma with an elevated intraocular pressure, normotensive glaucoma, or ocular hypertension. RESULTS: A total of 135 patients were included in this study. Of the patients, 117 subjects completed all examinations and met the inclusion criteria. Most patients were normal (36.8%), followed by those with suspected glaucoma (25.64%), normal tension glaucoma (18.8%), glaucoma with elevated intraocular pressure (12%), and ocular hypertensive (6%). The main reason for referral was increased optic nerve head cupping. The patients with normal tension glaucoma were older than the other subjects on average (p=0.03). In addition, the normal tension glaucoma group had a significantly worse baseline visual field index and mean deviation of the visual field than the normal, glaucoma suspect, and ocular hypertensive groups. The circumpapillary retinal nerve fiber layer on OCT was thinner on average in the normal tension glaucoma group than in the normal and glaucoma suspect groups (p<0.002) but did not significantly differ between the glaucoma group with elevated intraocular pressure and the other groups. CONCLUSIONS: Patients with normal tension glaucoma tend to be diagnosed later because of their normal intraocular pressures; thus, the optic nerve cupping must be greater to raise the suspicion of glaucoma. In this study, we found that the patients with normal tension glaucoma had worse disease at the time of diagnosis.

A Case of Sterile Corneal Stromal Infiltration with Hypotonic Maculopathy Under Brimonidine Treatment.

INTRODUCTION: Brimonidine is a commonly used drug for glaucoma treatment, which has been linked to ocular autoimmune disorders like uveitis and conjunctivitis. Corneal pathology under brimonidine is generally less common. CASE DESCRIPTION: Here, we report a 78 -year-old male patient suffering from immune corneal stromal inflammation with hypotony and resulting hypotonic maculopathy after 6 weeks after introduction of brimonidine treatment. Systemic work-up for system autoimmune and infectious diseases was negative. We discontinued brimonidine and administered topical prednisolone under which inflammatory corneal signs and intraocular pressure normalized. Chorioretinal folds persisted after 9 months. CONCLUSION: Our case report suggests monitoring patients under brimonidine for sterile corneal infiltration.

Oral administration of a dual ETA/ETB receptor antagonist promotes neuroprotection in a rodent model of glaucoma.

Purpose: Glaucoma is a neurodegenerative disease associated with elevated intraocular pressure and characterized by optic nerve axonal degeneration, cupping of the optic disc, and loss of retinal ganglion cells (RGCs). The endothelin (ET) system of vasoactive peptides (ET-1, ET-2, ET-3) and their G-protein coupled receptors (ETA and ETB receptors) have been shown to contribute to the pathophysiology of glaucoma. The purpose of this study was to determine whether administration of the endothelin receptor antagonist macitentan was neuroprotective to RGCs and optic nerve axons when administered after the onset of intraocular pressure (IOP) elevation in ocular hypertensive rats. Methods: Male and female Brown Norway rats were subjected to the Morrison model of ocular hypertension by injection of hypertonic saline through the episcleral veins. Following IOP elevation, macitentan (5 mg/kg body wt) was administered orally 3 days per week, and rats with IOP elevation were maintained for 4 weeks. RGC function was determined by pattern electroretinography (PERG) at 2 and 4 weeks post-IOP elevation. Rats were euthanized by approved humane methods, and retinal flat mounts were generated and immunostained for the RGC-selective marker Brn3a. PPD-stained optic nerve sections were imaged by confocal microscopy. RGC and axon counts were conducted in a masked manner and compared between the treatment groups. Results: Significant protection against loss of RGCs and optic nerve axons was found following oral administration of macitentan in rats with elevated IOP. In addition, a protective trend for RGC function, as measured by pattern ERG analysis, was evident following macitentan treatment. Conclusions: Macitentan treatment had a neuroprotective effect on RGCs and their axons, independent of its IOP-lowering effect, suggesting that macitentan may complement existing treatments to prevent neurodegeneration during ocular hypertension. The findings presented have implications for the use of macitentan as an oral formulation to promote neuroprotection in glaucoma patients.

Pediatric glaucoma suspects: characteristics and outcomes.

PURPOSE: To determine the characteristics of children diagnosed with glaucoma suspect (GS) status, their clinical outcomes, and risk factors for progression to a diagnosis of glaucoma. METHODS: This was a retrospective sequential cohort study of children <18 years diagnosed as GS between 2013 and 2019, based on clinical (C-GS) and CGRN (CGRN-GS) criteria. Children with penetrating ocular trauma, steroid-response, treated ocular hypertension, and glaucoma at presentation were excluded. Outcomes included glaucoma, treated ocular hypertension, nonglaucomatous cupping (pseudoglaucomatous or physiologic), or persistent GS. Secondary outcomes were characteristics of children who progressed to glaucoma. RESULTS: A total of 887 children (mean age, 9.3 ± 4.7 years) were diagnosed as C-GS, because of optic nerve appearance (83%), family history (25%), ocular hypertension (15%), periocular lesion (4% [eg, Sturge-Weber]), blunt-trauma history (3%), ocular anomaly (2%), and systemic/genetic syndrome (1.5%). Outcomes among 487 children with one or more follow-up visits (mean, 1.7 ± 1.6 years) included 14 (3%) with glaucoma, 98 (20%) with physiologic cupping, 50 (10%) with prematurity-associated cupping, and 1 (0.2%) with treated ocular hypertension; 324 (67%) remained GS. Of children lost to follow-up, 116 (29%) were suspected physiologic or pseudoglaucomatous. Glaucoma diagnosis occurred at a mean age of 8.4 ± 5.5 years, based on elevated intraocular pressure (IOP; 79%), optical coherence tomography changes (43%), disk changes (21%), or field defects (14%). Risk factors for glaucoma were baseline IOP of ≥24 (P = 0.01) and periocular lesion (P = 0.008). Results from 773 children who met CGRN-GS criteria were similar. CONCLUSIONS: Risk of conversion to glaucoma diagnosis among children with glaucoma suspect status appears low. Baseline cup:disk ratio and family history of glaucoma were not predictive of glaucoma diagnosis. Baseline IOP >24 and presence of a periocular lesion carry higher risk.

Efficacy of Nimodipine Combined with Latanoprost in Treating Open-Angle Glaucoma and Its Influence on Ocular Hemodynamics and Visual Field Defects.

Background: Open-angle glaucoma is a common ophthalmic disease, which has a great impact on the vision of middle-aged and elderly people. Medication plays an important role in the treatment of glaucoma, so finding effective drug treatment is of great significance to improve the quality of life of glaucoma patients. Objective: To explore the curative effect of nimodipine combined with latanoprost in the treatment of open-angle glaucoma and its effect on ocular hemodynamics and visual field defects. Methods: This study retrospectively analyzed the clinical data of 87 patients with open-angle glaucoma who came to the Shanxi Province Fenyang Hospital and The First Affiliated Hospital of Shanxi Datong University for treatment from January 2019 to January 2021. According to different treatment plans, the patients were divided into two groups: an observation group (n = 46) treated with nimodipine combined with latanoprost, and a control group (n = 41) treated by latanoprost monotherapy. Treatment efficacy, hemodynamics, visual field defects, 24-hour peak intraocular pressure, binocular optic disc parameters, adverse reactions and quality of life were recorded and compared between two groups of patients. Results: The overall therapeutic effect of the observation group was significantly better than that in the control group. After treatment, ocular hemodynamics, visual field defects, 24-hour peak intraocular pressure, binocular optic disc parameters and life quality of both groups were obviously improved compared to those before treatment, with more significant improvements in the observation group. In addition, there was no significant difference in the incidence of adverse reactions between the two groups. Conclusion: Nimodipine combined with latanoprost eye drops is effective in the treatment of primary open-angle glaucoma, which could effectively improve the ocular hemodynamics and visual field defects of patients with fewer adverse reactions and higher safety. Therefore, it can be further promoted and used in clinical practice.

Effect of Mindfulness-Based Stress Reduction on Intraocular Pressure in Patients With Ocular Hypertension: A Randomized Control Trial.

PURPOSE: To evaluate the effect of mindfulness-based stress reduction (MBSR) on intraocular pressure (IOP) in patients with ocular hypertension (OHT). DESIGN: Parallel arm, single masked, randomized controlled trial. METHODS: Sixty patients with ocular hypertension and IOP > 21 and < 30 mmHg were recruited at a tertiary eye care centre in India. Thirty patients (group 1) underwent six weeks of one hour daily MBSR sessions, while the other 30 patients (group 2) were waitlisted and kept on follow-up. The primary outcome was change in IOP (ΔIOP) after six weeks of MBSR. Secondary outcomes were effect on serum cortisol level, diurnal variation of IOP, vessel perfusion and vessel density on optical coherence tomography angiography (OCTA), and quality of life (QOL). RESULTS: At six weeks, a significant decrease in IOP was noted in group 1 (23.05 ± 1.17 to 19.15 ± 1.45 mmHg; P = .001) compared with group 2 (22.55 ± 0.98 mmHg to 22.37 ± 1.07 mmHg; P = .107). The ΔIOP was significantly greater in group 1 (3.93 ± 1.47) than group 2 (0.17 ± 0.58; P = .001). The diurnal fluctuation of IOP decreased in group 1 (4.87 ± 1.13 mmHg to 2.73 ± 0.98 mmHg; P = .001) as compared with group 2 (4.50 ± 0.86 mmHg to 4.30 ± 0.83 mmHg; P = .227). Significant improvement in vessel perfusion, vessel density, and flux index was noted on OCTA in group 1 compared with group 2. Group 1 showed a significant decrease (P ≤ .001) in serum cortisol level and an improved QOL (P = .001). CONCLUSION: Mindfulness-based stress reduction was associated with a significant decrease in IOP and serum cortisol, along with an improvement in optic nerve head perfusion and QOL. Mindfulness-based stress reduction can be considered as a potential treatment option in the management of OHT.

Clinical Study of the IOPTx™ System - an Electroceutical Wearable to Lower Intraocular Pressure.

Purpose: To investigate the safety and efficacy of the IOPTx™ system - a novel wearable, electroceutical treatment to lower intraocular pressure. Methods: Patients wear the customized contact lens and spectacles of the IOPTx™ system and undergo three 15-minute randomized stimulation trials at different stimulus amplitudes with 15 minutes of rest in between. The parameters for the stimulation trials include a frequency of 50 Hz, a pulse width of 100 µs, and current amplitudes between 90-150 µA. The optometrist measures the intraocular pressure (IOP) before, immediately after, and 15 minutes after the trial, and performs topography, a slit eye examination, and specular microscopy before and after the entire study to check the health of the eye and confirm the safety of the system. Results: The IOPTx™ system successfully modulates a patient's IOP. By testing various currents, we create individual tuning curves examining the effect of the stimulation amplitude on the change in IOP. Each patient may have an optimal dose-response curve and by normalizing to this value, the IOPTx™ system decreased IOP by an average of 17.7% with fifteen minutes of therapy. No Adverse Events or Adverse Device Effects occurred.Conclusions: The results of this clinical case series provide preliminary evidence of efficacy and safety of the IOPTx™ system and its potential usefulness to lower IOP in glaucoma and ocular hypertension.

Efficacy, Drug Sensitivity, and Safety of a Chronic Ocular Hypertension Rat Model Established Using a Single Intracameral Injection of Hydrogel into the Anterior Chamber.

BACKGROUND Chronic ocular hypertension (COH) models mostly focus on changes in intraocular pressure (IOP) and loss of retinal ganglion cells (RGCs). The present study evaluated important glaucoma-related changes in visual function, response to common ocular hypotensive drugs, and safety for our previously developed rat model. MATERIAL AND METHODS The model was established through a single injection of hydrogel into the anterior chambers. Efficacy was assessed through F-VEP by measuring latency and amplitude of P1. We evenly divided 112 rats into 4 groups: control and COH at 2, 4, and 8 weeks. Response to 5 common drugs (brimonidine, timolol, benzamide, pilocarpine, and bimatoprost) were each tested on 6 rats and assessed using difference in IOP. Safety assessment was conducted through histological analysis of 24 rats evenly divided into 4 groups of control and COH at 2, 4, and 8 weeks. Corneal endothelial cells (CECs) of 24 additional rats were used to determine toxic effects through TUNEL and CCK-8 assays. RESULTS P1 latency and amplitude of VEP demonstrated the model is effective in inducing optic nerve function impairment. Only the drug pilocarpine failed to have an obvious hypotensive effect, while the other 4 were effective. CECs at 2, 4, and 8 weeks showed no significant differences from control groups in results of histological analysis, TUNEL, and CCK-8 assays. CONCLUSIONS A single injection of hydrogel into the anterior chamber is effective for modeling COH, can respond to most commonly used hypotensive drugs, and is non-toxic to the eyes.

Longitudinal assessment of optic nerve head changes using optical coherence tomography in a primate microbead model of ocular hypertension.

In humans, the longitudinal characterisation of early optic nerve head (ONH) damage in ocular hypertension (OHT) is difficult as patients with glaucoma usually have structural ONH damage at the time of diagnosis. Previous studies assessed glaucomatous ONH cupping by measuring the anterior lamina cribrosa depth (LCD) and minimal rim width (MRW) using optical coherence tomography (OCT). In this study, we induced OHT by repeated intracameral microbead injections in 16 cynomolgus primates (10 unilateral; 6 bilateral) and assessed the structural changes of the ONH longitudinally to observe early changes. Elevated intraocular pressure (IOP) in OHT eyes was maintained for 7 months and serial OCT measurements were performed during this period. The mean IOP was significantly elevated in OHT eyes when compared to baseline and compared to the control eyes. Thinner MRW and deeper LCD values from baseline were observed in OHT eyes with the greatest changes seen between month 1 and month 2 of OHT. Both the mean and maximum IOP values were significant predictors of MRW and LCD changes, although the maximum IOP was a slightly better predictor. We believe that this model could be useful to study IOP-induced early ONH structural damage which is important for understanding glaucoma pathogenesis.

Effect of Intravenous Dexmedetomidine on Intraocular Pressure in Patients Undergoing Glaucoma Surgery Under Local Anesthesia: A Pilot Study.

PRECIS: Preoperative intravenous (IV) dexmedetomidine produced a 33% reduction in intraocular pressure (IOP) within 15 minutes of administration in patients with glaucoma. PURPOSE: To evaluate the effect of preoperative IV dexmedetomidine on IOP in adult patients undergoing glaucoma surgery under local anesthesia. METHODS: In a prospective interventional case series, 12 patients with uncontrolled IOP (IOP>24 mm Hg in both the eyes) with the systemic status of American Society of Anesthesiologists (ASA) classification I-II, received IV dexmedetomidine 0.6 µg/kg 30 minutes preoperatively. The IOP of the nonsurgical eye (measured with Perkins tonometer), the heart rate (HR), and blood pressure (BP) were recorded 5 minutes prior, 15 minutes and 2 hours after IV dexmedetomidine administration, and were compared using analysis of variance and Tukey honestly significant difference tests. RESULTS: There were 4 women and 8 men with a mean age (±SD) of 60.6±10.4 years. The mean number of antiglaucoma medications was 4.3±1.3. The mean pre-dexmedetomidine IOP was 31.5±5.6 mm Hg. At 15 minutes post-dexmedetomidine administration, the mean and percentage drop in IOP were 10.2±3.2 mm Hg (P=0.001) and 33%±11%, respectively. The mean and percentage drop in systolic BP were 18±20 mm Hg (P=0.01) and 12%±14%, and drop in diastolic BP were 6.5±10 mm Hg (P=0.05) and 7%±11%, respectively. The mean and percentage drop in HR were 2±0.6 bpm (P=0.48) and 2%±13%, respectively. None of the subjects experienced any medication-related adverse effects. At 2 hours, the mean and percentage drop in IOP were 5.3±3 mm Hg and 17%±11%, respectively. CONCLUSION: In the small sample of (ASA I-II) patients studied, preoperative dexmedetomidine produced a significant drop in IOP (33%) within 15 minutes of IV administration in patients with glaucoma that was reversing at 2 hours, with a good safety profile.

The Effect of Dietary Vitamin K1 Supplementation on Trabecular Meshwork and Retina in a Chronic Ocular Hypertensive Rat Model.

Purpose: The pathophysiologic relationship between vitamin K and glaucoma remains largely unknown. The aim of the study was to explore the effect of dietary vitamin K supplementation in a rat glaucoma model. Methods: Rats were randomly divided into two groups: standard diet and high vitamin K1 (VitK1) diet (300 mg VitK1/kg diet). Induction of chronic ocular hypertension by episcleral vein cauterization was performed on the right eye. The left eye with sham operation served as controls. Rats received standard or high VitK1 diets for 5 weeks after surgery until the end of experiment. Immunohistochemistry analyses of the retina and trabecular meshwork were performed. The change in coagulation function and IOP were evaluated. Results: We observed a significant declined IOP at 2 weeks after surgery in the high VitK1 group compared with the control group. High VitK1 showed no significant effect on the body weight, rat phenotypes, or coagulation function. High VitK1 significantly inhibited the loss of retinal ganglion cells in the retina and increased the expression of matrix gla protein. High VitK1 also ameliorated the collapsed trabecular meshwork structure and increased collagen staining in the trabecular meshwork. Conclusions: High VitK1 intake inhibited the loss of retinal ganglion cells during glaucomatous injury, probably by increasing the expression of matrix gla protein. A transient decrease in the IOP was observed in the high VitK1 group, implying a potential effect of VitK1 on aqueous outflow. Retinal ganglion cells protection by high VitK1 supplementation may be due to the IOP-lowering effects as well as neuroprotective effect. Further research is required to delineate these processes.

A Dietary Combination of Forskolin with Homotaurine, Spearmint and B Vitamins Protects Injured Retinal Ganglion Cells in a Rodent Model of Hypertensive Glaucoma.

There is indication that nutritional supplements protect retinal cells from degeneration. In a previous study, we demonstrated that dietary supplementation with an association of forskolin, homotaurine, spearmint extract and B vitamins efficiently counteracts retinal dysfunction associated with retinal ganglion cell (RGC) death caused by optic nerve crush. We extended our investigation on the efficacy of dietary supplementation with the use of a mouse model in which RGC degeneration depends as closely as possible on intraocular pressure (IOP) elevation. In this model, injecting the anterior chamber of the eye with methylcellulose (MCE) causes IOP elevation leading to RGC dysfunction. The MCE model was characterized in terms of IOP elevation, retinal dysfunction as determined by electrophysiological recordings, RGC loss as determined by brain-specific homeobox/POU domain protein 3A immunoreactivity and dysregulated levels of inflammatory and apoptotic markers. Except for IOP elevation, dysfunctional retinal parameters were all recovered by dietary supplementation indicating the involvement of non-IOP-related neuroprotective mechanisms of action. Our hypothesis is that the diet supplement may be used to counteract the inflammatory processes triggered by glial cell activation, thus leading to spared RGC loss and the preservation of visual dysfunction. In this respect, the present compound may be viewed as a potential remedy to be added to the currently approved drug therapies for improving RGC protection.

Protection of the Retinal Ganglion Cells: Intravitreal Injection of Resveratrol in Mouse Model of Ocular Hypertension.

Purpose: To investigate the efficacy of intravitreal administration of resveratrol (RSV) in a microbead-induced high intraocular pressure (IOP) murine model for glaucoma. Methods: Experiments were performed using adult C57BL/6JJcl mice. Polystyrene microbeads were injected into the anterior chamber to induce IOP elevation. Retinal flat-mounts and sections were assessed by immunohistochemistry to detect the expression of reactive oxygen species and acetyl-p53 in retinal ganglion cells (RGCs), brain-derived neurotrophic factor (BDNF) in Müller glial cells (MGCs), and the receptor tropomyosin receptor kinase B (TrkB) in RGCs. Light cycler real-time PCR was also used for confirming gene expression of BDNF in primary cultured MGCs exposed to RSV. Results: Microbeads induced high IOP followed by RGC death and axon loss. Administration of RSV rescued RGCs via decreased reactive oxygen species generation and acetyl-p53 expression in RGCs and upregulated BDNF in MGCs and TrkB expression in RGCs, which exhibited a strong cytoprotective action against cell death through multiple pathways under high IOP. Conclusions: Our data suggest that administration of RSV may delay the progress of visual dysfunction during glaucoma and may therefore have therapeutic potential.

Effect of Apraclonidine and Diclofenac on Early Changes in Intraocular Pressure After Selective Laser Trabeculoplasty.

PRéCIS:: Adjuvant diclofenac and apraclonidine eye drop given in conjunction with selective laser trabeculoplasty (SLT) do not significantly impact medium-term intraocular pressure (IOP) reduction compared with placebo, but apraclonidine can be used to blunt immediate postlaser pressure spikes. PURPOSE: There is limited high-grade evidence guiding the choice of eye drops given before and after SLT. The authors chose to measure IOP during the first 24 hours, at 1 week, 6 weeks, and 6 months after SLT, and compare the effect of apraclonidine before SLT and diclofenac after SLT, with placebo. MATERIALS AND METHODS: In this double-blind, randomized, placebo-controlled trial, patients with open-angle glaucoma or ocular hypertension referred for SLT were recruited between 2016 and 2018. Patients were randomized to receive either apraclonidine pre-SLT with placebo post-SLT, placebo pre-SLT with diclofenac post-SLT, or placebo before and after SLT. RESULTS: Sixty eyes from 35 patients were treated with 360-degree SLT. Twenty-four-hour IOP measurements with patient self-monitoring after SLT demonstrated a moderate IOP spike at 1 hour and 2 hours post-SLT in the placebo and diclofenac study arms (mean=+4.05±0.58 mm Hg and +4.47±0.73, respectively, P<0.001 vs. pre-SLT IOP), which was prevented by apraclonidine (mean=-2.41±0.88 mm Hg, P<0.0001 vs. other study arms post-SLT). There were no significant differences between the 3 arms of the study on the long-term IOP reduction achieved by SLT (6 wk: P=0.51, 6 mo: P=0.42). CONCLUSIONS: Neither the use of apraclonidine before SLT nor diclofenac after SLT significantly influenced the IOP reduction induced by SLT. Except for a slight and transient reduction in intraocular inflammation, there was no beneficial effect of diclofenac on early IOP changes or the degree of patient discomfort relative to placebo.

Effect of nutritional supplement based on melatonin on the intraocular pressure in normotensive subjects.

PURPOSE: To evaluate the effect of a new nutritional supplement based on melatonin on the intraocular pressure (IOP) in normotensive subjects. PATIENTS AND METHODS: A short-term prospective study was designed. Sixty-seven normotensive subjects were recruited. Patients were divided into two groups. The daily group (DG) (n = 18) was instructed to take the supplement between 22:00 and 23:00 (before sleeping) for 3 consecutive days. IOP was measured from 10.00 to 11.00 am the day before treatment and during the 3 days of experiment. The acute group (AG) (n = 49) was instructed to take the supplement after the second measure (11.00) of the second day. IOP was measured 1 h and just before the intake of the supplement and 1 and 2 h after. All measurements in this group were taken 1 day before without any supplement (control) and the day of experiment. RESULTS: The DG group showed a significant decrease in IOP after supplement intake in all days of experiment, from 14.9 ± 3.4 mm Hg to 13.8 ± 2.9 mm Hg after 3 days of experiment (p value < 0.001). For AG, IOP did not change during the control day; however, a reduction of 1 mm Hg was found 2 and 3 h after supplement intake, from 15.7 ± 2.5 mm Hg to 14.7 ± 2.5 mm Hg and 15.1 ± 2.7 mm Hg, respectively, being statistically significant (p value < 0.001). CONCLUSION: The supplement based on melatonin was able to reduce the IOP in normotensive subjects after 2 h of intake. Moreover, the daily intake showed a reduction in IOP during the 3 days of experiment.

Posttreatment Intervention With Lycium Barbarum Polysaccharides is Neuroprotective in a Rat Model of Chronic Ocular Hypertension.

Purpose: To investigate the neuroprotective effects of Lycium barbarum polysaccharides (LBP) against chronic ocular hypertension (OHT) in rats and to consider if effects differed when treatment was applied before (pretreatment) or during (posttreatment) chronic IOP elevation. Methods: Sprague-Dawley rats (10-weeks old) underwent suture implantation around the limbus for 15 weeks (OHT) or 1 day (sham). Four experimental groups were studied, three OHT groups (n = 8 each) treated either with vehicle (PBS), LBP pretreatment or posttreatment, and a sham control (n = 5) received no treatment. LBP (1 mg/kg) pre- and posttreatment were commenced at 1 week before and 4 weeks after OHT induction, respectively. Treatments continued up through week 15. IOP was monitored twice weekly for 15 weeks. Optical coherence tomography and ERG were measured at baseline, week 4, 8, 12, and 15. Eyes were collected for ganglion cell layer (GCL) histologic analysis at week 15. Results: Suture implantation successfully induced approximately 50% IOP elevation and the cumulative IOP was similar between the three OHT groups. When compared with vehicle control (week 4: -23 ± 5%, P = 0.03), LBP pretreatment delayed the onset of retinal nerve fiber layer (RNFL) thinning (week 4, 8: -2 ± 7%, -11 ± 3%, P > 0.05) and arrested further reduction up through week 15 (-10 ± 4%, P > 0.05). LBP posttreatment intervention showed no significant change in rate of loss (week 4, 15: -25 ± 4.1%, -28 ± 3%). However, both LBP treatments preserved the retinal ganglion cells (RGC) and retinal functions up to week 15, which were significantly reduced in vehicle control. Conclusions: LBP posttreatment arrested the subsequent neuronal degeneration after treatment commencement and preserved RGC density and retinal functions in a chronic OHT model, which was comparable with pretreatment outcomes.

Development of a Novel Intraocular-Pressure-Lowering Therapy Targeting ATX.

Elevated intraocular pressure (IOP) is the major cause of glaucoma, which is the second leading cause of blindness. However, current glaucoma treatments cannot completely regulate IOP and progression of glaucoma. Our group recently found that autotaxin (ATX) activity in human aqueous humor (AH) was positively correlated with increased IOP in various subtypes of glaucoma. To develop new IOP-lowering treatments, we generated a novel ATX inhibitor as an ophthalmic drug by high-throughput screening, followed by inhibitor optimization. Administration of the optimized ATX inhibitor (Aiprenon) reduced IOP in laser-treated mice exhibiting elevated IOP and higher level of ATX activity in AH and normal mice in vivo. The stimulation of ATX induced outflow resistance in the trabecular pathway; however, administration of Aiprenon recovered the outflow resistance in vitro. The in vitro experiments implied that the IOP-lowering effect of Aiprenon could be correlated with the altered cellular behavior of trabecular meshwork (TM) and Schlemm's canal endothelial (SC) cells. Overall, our findings showed that ATX had major impact in regulating IOP as a target molecule, and potent ATX inhibitors such as Aiprenon could be a promising therapeutic approach for lowering IOP.