Effect of Glucosamine on Intraocular Pressure and Risk of Developing Glaucoma.

PRCIS: Glucosamine supplementation is common but can be associated with increased intraocular pressure (IOP) and could contribute to the pathogenesis of glaucoma. It may be prudent for ophthalmologists to elicit any history of glucosamine use from their patients and advise them accordingly. Further studies on the role of glucosamine in glaucoma are warranted. BACKGROUND: The most frequently recommended slow-acting medication for osteoarthritis symptoms is glucosamine, although its effectiveness is questionable. Widely used glucosamine sulfate supplements may increase IOP. METHODS: In the current study, we analyzed online databases such as UK Biobank, MedWatch, and FinnGen to evaluate the relationship between glucosamine and IOP and glaucoma. We included budesonide and fluticasone in the analysis for comparison since these drugs are associated with increased IOP. RESULTS: In UK Biobank subjects, glucosamine use was associated with increased corneal compensated IOP ( P =0.002, 2-tailed t test). This was also true in subjects without glaucoma ( P =0.002, 2-tailed t test). However, no significant association between glucosamine and IOP was detected in subjects with a diagnosis of glaucoma. In MedWatch, 0.21% of subjects taking glucosamine reported glaucoma, 0.29% of subjects using budesonide reported glaucoma, and 0.22% of subjects using fluticasone reported glaucoma. In contrast, 0.08% of subjects using any other drug reported glaucoma. This variability is significant ( P <0.001, 2-tailed Fisher exact test). Data from FinnGen on the risk of primary open angle glaucoma or glaucoma in subjects using glucosamine before the diagnosis of the disease revealed a significantly increased risk for both primary open angle glaucoma (hazard ratio: 2.35) and glaucoma (hazard ratio: 1.95). CONCLUSION: Glucosamine supplementation is common but can be associated with increased IOP and could contribute to the pathogenesis of glaucoma. It may be prudent for ophthalmologists to elicit any history of glucosamine use from their patients and advise them accordingly. Further studies on the role of glucosamine in glaucoma are warranted.

Artificial intelligence in glaucoma detection using color fundus photographs.

PURPOSE: To explore the potential of artificial intelligence (AI) for glaucoma detection using deep learning algorithm and evaluate its accuracy for image classification of glaucomatous optic neuropathy (GON) from color fundus photographs. METHODS: A total of 1375 color fundus photographs, 735 normal optic nerve head and 640 GON, were uploaded on the AI software for training, validation, and testing using deep learning model, which is based on Residual Network (Res Net) 50V2. For initial training and validation, 400 fundus images (200 normal and 200 GON) were uploaded and for the final training and testing 975 (535 normal and 440 GON) were uploaded later. Accuracy, sensitivity, and specificity were used to evaluate the image classification performance of the algorithm. Also, positive predictive value, negative predictive value, positive likelihood ratio, and negative likelihood ratio were calculated. RESULTS: The model used in the study showed an image classification accuracy of 81.3%, sensitivity of 83%, and specificity of 80% for the detection of GON. The false-negative grading was 17% and false-positive grading was 20% for the image classification of GON. Coexistence of glaucoma in patients with high myopia, early glaucoma in a small disc, and software misclassification of GON were the reasons for false-negative results. Physiological large cupping in a large disc, myopic or titled disc, and software misclassification of normal optic disc were the reasons for false-positive results. CONCLUSION: The model employed in this study achieved a good accuracy, and hence has a good potential in detection of GON using color fundus photographs.

Retinal vein occlusions associated or complicated with glaucoma. Aspects of prediction and paths of progression.

Background and Objectives: The aim of the study is to evaluate prediction factors and progression paths when retinal vein occlusions are associated with preexisting glaucoma or complicated with neovascular glaucoma. Materials and Methods: The study included 111 patients diagnosed with retinal vein occlusions, of whom 21 with preexisting open angle glaucoma and 12 with neovascular glaucoma as complication. The study was conducted from September 2020 to September 2022 in Timisoara, Romania. We assessed intraocular pressure, cup-disc ratio and retinal nerve fiber layer from the moment of retinal vein occlusion diagnosis until at least one year of follow-up, considering these aspects as values of prediction concerning the paths of progression when glaucoma and retinal vein occlusions come together. Results: The mean initial IOP for the affected eyes was higher (15.89 ± 2.73) than for fellow eyes (15.20 ± 3.11), with an increase of the IOP after one year, but with no statistically significant differences for the affected eyes (p=0.116) or for the other eyes (p=0.684), neither for the affected eyes associated with glaucoma in comparison with affected eyes without glaucoma association. The mean cup-disc ratio was higher for the affected eyes in comparison with the fellow eyes (0.4812 ± 0.219 for the affected eyes and 0.4738 ± 0.229 for the fellow ones in cases without associated glaucoma and 0.681 ± 0.157 for the affected eyes and 0.600 ± 0.241 for the fellow eyes in cases with associated glaucoma), with statistical significant differences in the evolution for both groups in comparison with the unaffected eyes (p=0.0056 for the first group and p=0.0003 for the second group). Comparing the evolution of the affected eyes with the preexisting glaucoma and the affected eyes without preexisting glaucoma, no statistical difference has been found (p=0.1104). The mean retinal nerve fiber layer decreased significantly in affected eyes without glaucoma (from 96 ± 14.71 to 89.16 ± 13.07) and in affected eyes with associated glaucoma (from 78.50 ± 4.23 to 75.50 ± 5.83), but with no significant differences (p=0.182). The level of decreasing was significantly more consistent in association with a venous occlusion (p= 0.0001). Conclusions: The findings of the current study fortify the correlation between glaucoma as a risk factor for retinal venous occlusion development, the intraocular pressure and optic nerve cupping as prediction factors in retinal venous occlusions, the association of a well-controlled preexisting glaucoma with no effect on the progression of the retinal venous occlusions and the development of a neovascular glaucoma with a much aggressive and different path of disease progression.

Thinning of the Lamina Cribrosa and Deep Layer Microvascular Dropout in Patients With Open Angle Glaucoma and High Myopia.

PRCIS: Lamina cribrosa (LC) thinning (thickness of ≤128.00 µm) helps to distinguish open angle glaucoma from high myopia, which was associated with the presence of microvasculature dropout and elevated intraocular pressure. PURPOSE: The purpose of this study was to analyze the factors associated with LC thickness in highly myopic eyes with and without open angle glaucoma. METHODS: In total, 240 highly myopic eyes with γ-zones (194 eyes without and 46 eyes with open angle glaucoma) were examined, and the LC center, externally oblique border, an abrupt change of scleral curvature (scleral step), deep layer microvasculature dropout and global retinal nerve fiber layer thickness were investigated on optical coherence tomography and optical coherence tomography angiography. RESULTS: LC were thinner in highly myopic open angle glaucoma compared with high myopia alone (107.76±9.86 vs. 137.07±18.51 µm, P <0.001), which was associated with deep layer microvasculature dropout and elevated intraocular pressure. The areas under the receiver operating characteristic curve for detecting open angle glaucoma from the LC thickness was 0.964, which was statistically higher ( P <0.05) than from the global retinal nerve fiber layer thickness (0.921) and vertical cup-to-disc ratio (0.902). A LC thickness cutoff value of 128 µm provided 100% sensitivity for detecting open angle glaucoma with 84% specificity. CONCLUSIONS: Highly myopic eyes with open angle glaucoma appear to have a thinner LC, which was associated with elevated intraocular pressure and deep layer microvasculature dropout. LC thinning (≤128.00 µm) helps distinguish open angle glaucoma from high myopia with an abnormal retinal nerve fiber layer thickness distribution and unclear shallow disc cupping.

Effects of Myopia and Glaucoma on the Neural Canal and Lamina Cribrosa Using Optical Coherence Tomography.

PRCIS: Glaucoma was associated with axial bowing and rotation of Bruchs membrane opening (BMO) and anterior laminar insertion (ALI), skewed neural canal, and deeper anterior lamina cribrosa surface (ALCS). Longer axial length was associated with wider, longer, and more skewed neural canal and flatter ALCS. PURPOSE: Investigate the effects of myopia and glaucoma in the prelaminar neural canal and anterior lamina cribrosa using 1060-nm swept-source optical coherence tomography. PATIENTS: 19 control (38 eyes) and 38 glaucomatous subjects (63 eyes). MATERIALS AND METHODS: Participants were imaged with swept-source optical coherence tomography, and the images were analyzed for the BMO and ALI dimensions, prelaminar neural canal dimensions, and ALCS depth. RESULTS: Glaucomatous eyes had more bowed and nasally rotated BMO and ALI, more horizontally skewed prelaminar neural canal, and deeper ALCS than the control eyes. Increased axial length was associated with a wider, longer, and more horizontally skewed neural canal and a decrease in the ALCS depth and curvature. CONCLUSION: Our findings suggest that glaucomatous posterior bowing or cupping of lamina cribrosa can be significantly confounded by the myopic expansion of the neural canal. This may be related to higher glaucoma risk associated with myopia from decreased compliance and increased susceptibility to IOP-related damage of LC being pulled taut.

Yield of investigations in patients with questionable nonglaucomatous optic neuropathy.

OBJECTIVE: Nonglaucomatous optic neuropathy (NGON) may often be mistaken for normal-tension glaucoma. The distinction between these two entities is important in determining treatment, prognosis, and need for further investigations. We report characteristics of a cohort of patients referred for neuro-ophthalmologic consultation to distinguish between glaucomatous (GON) and NGON. METHODS: Retrospective chart review of patients presenting to a tertiary neuro-ophthalmology practice investigated for GON versus NGON between 2018 and 2020. Patients were classified as GON or NGON based on presence of optic disc pallor, degree of cupping, central visual acuity, and/or when investigations yielded a cause of NGON. RESULTS: Eighty-three patients were enrolled. Seventy-one patients (86%) were deemed to have possible NGON after initial evaluation and having undergone neuroimaging. Of these, 14 patients (19.7%) were determined to have NGON and 7 patients (9.9%) both GON and NGON. The most common causes of NGON were undetermined (8), previous optic neuritis (4), and neurovascular conflict (2). The yield of neuroimaging was low, with abnormalities seen in only 4 of 71 patients (5.6%). No patients with bilateral cupping and no relative afferent pupillary defect (RAPD) had abnormalities on imaging, and no patients with positive imaging required intervention. Patients with NGON had lower intraocular pressure and cup-to-disc ratio and usually had optic disc pallor (86%). Nerve fibre bundle defects were most common in both GON and NGON, with more nasal defects seen in GON. CONCLUSIONS: When NGON resembles GON, the underlying cause is often undetermined, and the yield of neuroimaging is low. The yield of investigating patients with bilateral cupping and no RAPD for NGON is especially low.

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.

Unilateral advanced glaucoma in isolated congenital ectropion uveae with ipsilateral ptosis: A pictorial description of five children.

Aim: To report the cases of five children with unilateral advanced glaucoma in isolated congenital ectropion uveae (CEU) with ipsilateral ptosis and myopia. Methods: This is an ambispective observational case series. After diagnosing one patient with CEU and glaucoma, consecutive patients presenting with unilateral ptosis, congenital iris anomaly, and glaucoma between 2014 to 2020, and had completed a minimum one-year postoperative follow-up, were analyzed. Results: Of the 1421 newly registered pediatric glaucoma patients in the period under review, five children were diagnosed with CEU. All patients presented with gradual painless diminution of vision in the left eye in early adolescence. The left eye of all patients had peculiar clinical features: mild congenital ptosis, high iris insertion, crypt-less smooth iris surface, congenital ectropion uveae, pigments over anterior lens capsule, high myopia, advanced glaucomatous optic disc cupping, and very high intraocular pressure (IOP), which was > 45 mmHg in all cases. The right eye showed signs of angle dysgenesis with mild anterior iris insertion and numerous fine iris processes. Antiglaucoma medications and angle surgery failed to control the IOP, and all children required glaucoma filtration surgery, resulting in reasonable IOP control. Despite the older age, postoperative strict amblyopia treatment resulted in significant improvement in vision. Conclusions: Although ectropion uveae and ptosis have been present since birth, unilaterality, and the asymptomatic nature of the disease led to the late presentation with irreversible damage. Early surgical management and amblyopia therapy are the cornerstones of management. Abbreviations: CEU = Congenital ectropion uvea, CIES = Congenital Iris Ectropion Syndrome, ASD = Anterior segment dysgenesis syndrome, BCVA = Best-corrected visual acuity, IOP = Intraocular pressure.

Visual Acuity Outcomes in Diseases Associated with Reduced Visual Acuity: An Analysis of the National Health Insurance Service Database in Korea.

Visual acuity declines with age, and disease-related visual acuity changes vary. We evaluated factors affecting visual acuity and age-related visual acuity in diseases associated with reduced visual acuity such as hypertension, diabetes mellitus (DM), glaucoma, and diabetic retinopathy (DR). The Korean National Health Insurance Service 2015-2016 data were analyzed for age-related visual acuity changes and prevalence of diseases associated with reduced visual acuity. Among 993,062 participants, the prevalence rates of hypertension, DM, glaucoma, and DR were 27.0%, 15.1%, 13.8%, and 2.7%, respectively. Despite having the lowest prevalence, DR alone or DR with hypertension and glaucoma resulted in low visual acuity. Correlation analysis between disease frequency and mean age-related visual acuity revealed higher positive correlations in DR and hypertension than in DM and glaucoma, indicating lower visual acuity. Odds ratios for low visual acuity in cases including one disease such as hypertension, DM, glaucoma, and DR were 1.73, 1.23, 1.04, and 1.52, respectively. The prevalence and number of diseases associated with reduced visual acuity increased with age, and visual acuity decreased. The leading causes of vision loss were DR as a single disease and hypertension as a concomitant disease. Therefore, age-related vision management, through periodic eye examination and correction with age, should be performed along with management of diabetes and hypertension.

The Role of NAD+ and Nicotinamide (Vitamin B3) in Glaucoma: A Literature Review.

Glaucoma is a collection of irreversible optic neuropathies which, if left untreated, lead to severe visual field loss. These diseases are a leading cause of blindness across the globe and are estimated to affect approximately 80 million people, particularly women and people of Asian descent (Quigley HA, Broman AT. 2006. Br J Ophthalmol 90: 262-267). This represents a major burden on healthcare systems worldwide. Recently, there has been increasing interest in the potential of nicotinamide (vitamin B3) as a novel option in the management of glaucoma. This review aims to analyse the currently available literature to determine whether there is evidence of an association between nicotinamide adenine dinucleotide (NAD+) and glaucomatous optic neuropathy, and whether nicotinamide has the potential to prevent or reverse these effects. The literature showed a strong connection between reduced NAD+ levels and retinal ganglion cell dysfunction through multiple different studies. There is also evidence of the positive effect of nicotinamide supplementation on retinal ganglion cell function in models of mouse glaucoma and in a study involving humans. Based on the literature findings, a recommendation has been made that more research into the efficacy, appropriate dosing, and potential side effects of nicotinamide supplementation is needed before it can be definitively determined whether it is appropriate for widespread prophylactic and therapeutic use against glaucoma in humans.

Differential effects of obstructive sleep apnea on the corneal subbasal nerve plexus and retinal nerve fiber layer.

PURPOSE: Obstructive sleep apnea (OSA) is an established independent risk factor for peripheral neuropathy. Macro and microvascular changes have been documented in OSA, including high levels of potent vasoconstrictors. In diabetes, vasoconstriction has been identified as an underlying risk factor for corneal neuropathy. This study sought to establish a potential relationship between OSA and corneal nerve morphology and sensitivity, and to determine whether changes in corneal nerves may be reflective of OSA severity. DESIGN: Single center cross-sectional study. METHODS: Sixty-seven patients were stratified into two groups: those with OSA and healthy controls. Groups were matched for age, sex, race, smoking, and dry eye status. Outcome measures included serologies, a dilated fundus exam, dry eye testing, anthropometric parameters, corneal sensitivity, subbasal nerve plexus morphology, retinal nerve fiber layer (RNFL) thickness, and the use of questionnaires to assess symptoms of dry eye disease, risk of OSA, and continuous positive airway pressure (CPAP) compliance. RESULTS: No significant differences were observed in corneal nerve morphology, sensitivity, or the number of dendritic cells. In the OSA test group, RNFL thinning was noted in the superior and inferior regions of the optic disc and peripapillary region. A greater proportion of participants in the OSA group required a subsequent evaluation for glaucoma than in the control. In those with OSA, an increase in the apnea hypopnea index was associated with an increase in optic nerve cupping. CONCLUSIONS: OSA does not exert a robust effect on corneal nerves. OSA is however, associated with thinning of the RNFL. Participants with glaucomatous optic nerve changes and risk factors for OSA should be examined as uncontrolled OSA may exacerbate glaucoma progression.

[A Case Series of Elderly Patients with Aortic Stenosis (AS) Undergoing Conscious Glaucoma Surgery in Sub-Tenon's or Subconjunctival Anaesthesia]. / Eine Fallserie wacher Glaukomoperationen mittels Sub-Tenon- oder subkonjunktivaler Anästhesie bei älteren PatientInnen mit Aortenklappenstenose.

With the current demographic changes, an increasing number of patients scheduled for glaucoma surgery presents with aortic sclerosis (AS) as part of their list of systemic diseases. This presents a definite challenge for anaesthesiologists and eye surgeons alike. We illustrate 6 cases of patients with aortic sclerosis undergoing glaucoma surgery in subconjunctival local anaesthesia or sub-Tenon block (STB). In one patient, due to discomfort, local anaesthesia had to be given repeatedly. Her blood pressure rose permanently to hypertensive values. During surgery, localised, temporal choroidal bleeding was noticed. The follow-up was complicated by exorbitant intraocular pressure swings and secondary localised choroidal bleeding. Anaesthesiologist and ophthalmic surgeon must harmonise their strategy to provide optimal transmural pressure across choroidal vessels and stenotic aortic valve outlet. Clinicians are often not aware of the core principals of each other's speciality. Our discussion considers different approaches for both disciplines to safely reduce the risk of suprachoroidal bleeding for this high-risk patient population with aortic stenosis.

Enhanced depth imaging optical coherence tomography of the optic nerve head improves correct diagnosis in glaucoma suspects without glaucomatous optic disc morphology.

An 83-year-old woman with a long history of glaucoma and optic disc drusen (ODD) was referred for neuro-ophthalmological second opinion. The patient had been treated for decades with bilateral intraocular pressure (IOP)-lowering eye drops, laser trabeculoplasty and trabeculectomy and had severe, bilateral loss of visual fields and retinal nerve fibre layer (RNFL) thinning on optical coherence tomography (OCT) despite IOP that never exceeded 24 mm Hg. On ophthalmoscopy, only a single ODD was visible in the left eye and no optic disc cupping was apparent in either eye. Enhanced depth imaging OCT (EDI-OCT) of the optic nerve head revealed bilateral multiple, large, deep ODD, which in itself could easily explain the visual field loss and RNFL thinning of this patient. Optic nerve head examination using EDI-OCT is highly recommended for patients with a history of glaucoma but without optic nerve head cupping to avoid a potential misdiagnosis with consequent unnecessary treatment.

Epiretinal Membrane Surgery in Eyes with Glaucoma: Visual Outcomes and Clinical Significance of Inner Microcystoid Changes.

OBJECTIVE: To investigate visual acuity (VA) outcomes and OCT-based biomarkers of vision outcomes in eyes with glaucoma undergoing pars plana vitrectomy (PPV) for idiopathic epiretinal membrane (ERM). DESIGN: Retrospective, consecutive case-control series. A previously described ERM grading scale was utilized for OCT analysis. SUBJECTS: Eyes with glaucoma undergoing PPV for idiopathic ERM. INTERVENTION: PPV with membrane peel (MP) surgery. MAIN OUTCOME MEASURES: The primary outcome was VA at postoperative month 6. Outcomes were compared to a contemporary, matched control group of eyes without concurrent glaucoma undergoing PPV for idiopathic ERM. RESULTS: A total of 103 eyes from 103 patients with ERM and glaucoma were followed for a mean (± standard deviation) of 656 (± 421) days after PPV with MP surgery. Glaucoma was classified as open angle in 98 (95.1%) eyes and closed angle in 5 (4.9%) eyes. Visual acuity improved from 0.72 ± 0.48 (20/105) to 0.55 ± 0.51 (20/71) at 6 months and to 0.50 ± 0.56 (20/63) at final follow-up (P < 0.001 for both the time points). Eyes with preoperative inner microcystoid changes (n = 59; 57.3%) had significantly worse preoperative VA, postoperative VA at month 6, and final VA compared to eyes without inner microcystoid changes (P = 0.028, 0.004, and 0.007, respectively). Eyes were then compared to a matched control group of 139 eyes without glaucoma. Eyes with ERM and glaucoma had a higher rate of microcystic changes both before surgery (P < 0.001) and at postoperative month 6 (P < 0.001), and had a worse VA at 6 months (P = 0.03) and final follow-up (P = 0.04) compared to control eyes without glaucoma. Advanced disc cupping was the only factor independently correlated with worse 6-month (P = 0.01) and final (P = 0.007) VA in multivariate analysis. CONCLUSIONS: Preoperative inner microcystoid changes on OCT were present in over half of eyes with ERM and concurrent glaucoma, and may be a poor prognostic OCT biomarker. Eyes with ERM and concurrent glaucoma experienced worse vision outcomes compared to eyes with ERM alone, particularly those with advanced disc cupping.

Peripapillary and macular retinoschisis - A vision-threatening sequelae of advanced glaucomatous cupping.

PURPOSE: To present a selected case series of advanced glaucoma-associated peripapillary and macular retinoschisis and response to various treatment strategies with a comprehensive literature review. METHODS: Retrospective observational case series. Retrospective review of five selected cases of advanced glaucoma with peripapillary and macular retinoschisis. RESULTS: All five patients had advanced glaucomatous damage with macular and peripapillary retinoschisis, three (patients 2, 3, and 5) had a neurosensory detachment of the macula. Increased intraocular pressure was managed with maximal antiglaucoma medications and G6 micropulse diode laser treatment in the first patient, transscleral diode laser in the second patient, mitomycin-C augmented trabeculectomy in the third patient, maximal antiglaucoma medications alone in the fourth patient, pars plana vitrectomy followed by trabeculectomy in the fifth patient. CONCLUSION: We speculate that peripapillary and macular retinoschisis may indicate a vision-threatening sequelae of advanced glaucoma. The probable inciting factor for this vision-threatening pathology being elevated intraocular pressure, fluctuations in intraocular pressure, and chronic glaucoma with advanced cupping. We emphasize that meticulous examination of the macula in patients with advanced glaucoma is mandatory. It is imperative to do OCT macula in patients with advanced glaucoma to diagnose this distinct entity at an earlier stage and preserve the existing visual potential.

Effects of non-pharmacological interventions on anxiety, depression, and sleep quality in patients with postoperative glaucoma: A protocol for systematic review and network meta-analysis.

BACKGROUND: Glaucoma is the second most-common blinding ophthalmic disease in the world, and its incidence has been rising year by year in recent years. Currently, the main treatment of glaucoma still relies on surgery. Glaucoma patients often suffer from various psychological problems like anxiety and depression not only because of the lack of understanding of the surgical treatment of glaucoma, but also the long-term stress and the poor prognosis. As alternative therapies, non-pharmacological interventions can greatly alleviate psychological burdens and improve sleep quality in surgically treated glaucoma patients. Randomized controlled trials of non-pharmacologic interventions for glaucoma have been reported, although the results remain conflicting. Evidences for determining the efficacy of non-pharmacologic interventions for glaucoma are scant. This study aims to assess the effects of non-pharmacological interventions on anxiety, depression, and sleep quality in patients with postoperative glaucoma through a network meta-analysis. METHODS: A systematic search of relevant literatures published before August 2021 about the effects of non-pharmacological interventions on anxiety, depression, and sleep quality in patients with postoperative glaucoma will be performed in Wanfang, VP Information Chinese Journal Service Platform, China National Knowledge Infrastructure, Chinese BioMedicine Literature Database, Pubmed, Embase, Cochrane, and Web of science. Two reviewers will be independently responsible for literature screening and selection, quality assessment, and data extraction. WinBUGS 1.4 will be used for the network meta-analysis. RESULTS: This meta-analysis will provide additional and stronger evidences for non-pharmacological interventions on anxiety, depression, and sleep quality in patients with postoperative glaucoma, which will help clinicians and decision makers to make an optimal therapeutic strategy. CONCLUSION: This study will provide a reliable evidence-based basis for the clinical application of non-pharmacological interventions on anxiety, depression, and sleep quality in patients with postoperative glaucoma. ETHICS AND DISSEMINATION: Ethical approval was not required for this study. The systematic review will be published in a peer-reviewed journal, presented at conferences, and shared on social media platforms. This review would be disseminated in a peer-reviewed journal or conference presentations. OSF REGISTRATION NUMBER: DOI 10.17605/OSF.IO/TYJPK.

Protective Efficacy of a Dietary Supplement Based on Forskolin, Homotaurine, Spearmint Extract, and Group B Vitamins in a Mouse Model of Optic Nerve Injury.

Glaucoma is a multifactorial blinding disease with a major inflammatory component ultimately leading to apoptotic retinal ganglion cell (RGC) death. Pharmacological treatments lowering intraocular pressure can help slow or prevent vision loss although the damage caused by glaucoma cannot be reversed. Recently, nutritional approaches have been evaluated for their efficacy in preventing degenerative events in the retina although mechanisms underlying their effectiveness remain to be elucidated. Here, we evaluated the efficacy of a diet supplement consisting of forskolin, homotaurine, spearmint extract, and vitamins of the B group in counteracting retinal dysfunction in a mouse model of optic nerve crush (ONC) used as an in vivo model of glaucoma. After demonstrating that ONC did not affect retinal vasculature by fluorescein angiography, we determined the effect of the diet supplement on the photopic negative response (PhNR) whose amplitude is strictly related to RGC integrity and is therefore drastically reduced in concomitance with RGC death. We found that the diet supplementation prevents the reduction of PhNR amplitude (p < 0.001) and concomitantly counteracts RGC death, as in supplemented mice, RGC number assessed immunohistochemically is significantly higher than that in non-supplemented animals (p < 0.01). Major determinants of the protective efficacy of the compound are due to a reduction of ONC-associated cytokine secretion leading to decreased levels of apoptotic markers that in supplemented mice are significantly lower than in non-supplemented animals (p < 0.001), ultimately causing RGC survival and ameliorated visual dysfunction. Overall, our data suggest that the above association of compounds plays a neuroprotective role in this mouse model of glaucoma thus offering a new perspective in inflammation-associated neurodegenerative diseases of the inner retina.

Optic disk hemorrhage and vitreous hemorrhage after phacoemulsification in a normal tension glaucoma patient: A case report.

RATIONALE: Optic disk hemorrhage has been closely correlated with glaucoma for its development and progression. Phacoemulsification surgery results in large intraocular pressure (IOP) fluctuation. We report a case of optic disk hemorrhage and consequently progressive vitreous hemorrhage after an unsuccessful phacoemulsification surgery in an advanced normal tension glaucoma (NTG) patient. PATIENT CONCERNS: An advanced NTG patient of 82 years old with chronic hypertension underwent an unsuccessful phacoemulsification surgery complicated by posterior capsule rupture. During the postoperative 2 weeks, recurrent episodes of fresh hyphema occurred and B ultrasonography scan revealed the progressive vitreous hemorrhage. The IOP went out of control under the maximum tolerable IOP-lowering medications. DIAGNOSIS: Vitreous hemorrhage after phacoemulsification in an advanced NTG patient. INTERVENTIONS: Vitrectomy was performed to search for the cause of the progressive vitreous hemorrhage. After removal of the thick vitreous hemorrhage, a fresh spot of optic disk hemorrhage was detected at the nasal margin of the significantly-cupping disk. OUTCOMES: Postoperatively, the hemorrhagic vitreous opacity gradually resolved and the IOP remained stable at 10 ∼13 mmHg with topical prostaglandin analogue drops. Fundus examination revealed the dilated disk vessel with localized angiomatous change at the nasal disk margin. LESSONS: Severe optic disk hemorrhage may occur after phacoemulsification in advanced glaucoma patients. Systemic vascular factors, such as chronic hypertension and old age, and surgical complications, such as posterior capsule rupture and postoperative IOP elevation, would further increase the risk. For phacoemulsification in advanced glaucoma cases, extra care should be taken to control intraoperative IOP fluctuations and monitor postoperative IOP.