Glaucomatous Visual Field Loss Research Articles

Assessing the value of the water drinking test in glaucoma-a systematic review and meta-analysis.

This systematic review and meta-analysis examines the relationship between intraocular pressure (IOP) parameters derived from the water drinking test (WDT) and diurnal IOP monitoring, and evaluates the reproducibility of the WDT and its association with future glaucomatous visual field (VF) loss. A literature search was performed on PubMed, EMBASE, and Cochrane Library from inception to 31 March 2023. Cohort, cross-sectional and observational studies reporting WDT results in glaucoma patients were included. Meta analysis with random-effect model was performed using "metafor" package in R version 3.2.1. 641 studies were identified on initial literature search. 38 studies (2479 subjects) were included in final analysis. Meta-analytic estimates of 5 studies (310 subjects) found strong positive correlation in peak IOP between the WDT and diurnal IOP monitoring (r = 0.92, 95% CI = 0.75, 1.08, p < 0.0001). However, there was only weak positive correlation for IOP fluctuation between both methods (r = 0.26, 95% CI = 0.06,0.47, p < 0.0001). Meta-analytic estimates of 3 studies (189 subjects) suggested a trend of the diurnal peak IOP being lower than that derived from the WDT (MD = -2.37 mmHg, 95% Limit of Agreement (LOA) =-5.58,0.84, p = 0.147). Two studies found that a higher WDT peak IOP was associated with greater future VF progression. Two studies demonstrated good reproducibility in peak IOP measurements for WDTs conducted across different days. In conclusion, there was a strong positive correlation between IOP peak measurements from the WDT and diurnal IOP monitoring in glaucoma patients. The WDT peak IOP demonstrated good reproducibility and may be associated with greater future VF progression.

Development and evaluation of Order of Magnitude (OM): a virtual reality-based visual field analyzer for glaucoma detection.

This study introduces the Order of Magnitude (OM), a cost-effective, indigenous, virtual reality-based visual field analyzer designed for detecting glaucomatous visual field loss. The OM test employs a two-step supra-thresholding algorithm utilizing stimuli of 0.43°diameter (equivalent to Goldmann size III) at low and high thresholds. A comparative analysis was conducted against the Humphrey visual field (HVF) test, considered the gold standard in clinical practice. Participants, including those with glaucoma and normal individuals, underwent comprehensive eye examinations alongside the OM and HVF tests between April and October 2019. Diagnostic sensitivity and specificity of the OM test were assessed against clinical diagnoses made by specialists. We studied 157 eyes (74 glaucomatous, 83 control) of 152 participants. Results demonstrated a high level of reliability for both OM and HVF tests, with no significant difference observed (P = 0.19, Chi-square test). The sensitivity and specificity of the OM test were found to be 93% (95% CI 86-100%) and 83% (95% CI 72.4-93%), respectively, while the HVF test showed sensitivity and specificity of 98% (95% CI 93.9-100%) and 83% (95% CI 73.9-92.8%), respectively. These findings suggest that the OM test is non-inferior to the reference standard HVF test in identifying glaucomatous visual field loss.

Molecular genetics of inherited normal tension glaucoma.

Normal tension glaucoma (NTG) is a complex optic neuropathy characterized by progressive retinal ganglion cell death and glaucomatous visual field loss, despite normal intraocular pressure (IOP). This condition poses a unique clinical challenge due to the absence of elevated IOP, a major risk factor in typical glaucoma. Recent research indicates that up to 21% of NTG patients have a family history of glaucoma, suggesting a genetic predisposition. In this comprehensive review using PubMed studies from January 1990 to December 2023, our focus delves into the genetic basis of autosomal dominant NTG, the only known form of inheritance for glaucoma. Specifically exploring optineurin ( OPTN ), TANK binding kinase 1 ( TBK1 ), methyltransferase-like 23 ( METTL23 ), and myocilin ( MYOC ) mutations, we summarize their clinical manifestations, mutant protein behaviors, relevant animal models, and potential therapeutic pathways. This exploration aims to illuminate the intricate pathogenesis of NTG, unraveling the contribution of these genetic components to its complex development.

Comparison of Visual Field Fluctuation Between Myopic and Emmetropic Glaucoma Patients

Background: Conflicting epidemiologic studies suggest that myopia may both increase and decrease the risk of glaucomatous visual field loss. To provide appropriate treatment to glaucoma patients, it is important to detect meaningful changes in the visual field, which requires distinguishing between visual field fluctuation and progression. Visual field fluctuation is defined as the variability between two visual field tests performed on separate days or months on the same eye that cannot be attributed to a pathologic change. We hypothesize that glaucoma patients with myopia will demonstrate more visual field fluctuation compared to emmetropic patients.&#x0D; Methods: Four or more 24-2 or 30-2 Humphrey visual field tests over several visits will be analyzed per patient. Data including the VFI plot, mean deviation, and threshold sensitivity on the glaucoma progression analysis will be collected to measure fluctuation. The sample is divided into two groups: 1. emmetropic glaucoma patients with a spherical equivalent refraction between +2 to -2 diopters and 2. high myopic glaucoma patients with a spherical equivalent refraction over -5 diopters. Bland-Altman plots, Mann-Whitney U tests, Root Mean Square Error (RMSE), intraclass correlation coefficients, and generalized estimating equation models for ordinal data will be used to analyze the collected data.&#x0D; Results: Thus far, 2,979 charts have been reviewed with data collected from 27 emmetropes and myopes who met the inclusion criteria. The recruitment goal is 78 per group and 156 total. Preliminary results for RMSE found a statistically significant p-value for mean deviation (0.0320), and no statistically significant difference for threshold sensitivity (0.5179) and VFI (0.0904).&#x0D; Conclusion and Potential Impact: This ongoing study will help establish if glaucoma patients with high myopia demonstrate greater visual field fluctuation. It is important for clinicians to have this information so that these patients can be examined carefully to prevent misdiagnoses or delayed glaucoma treatment.

Detecting Established Glaucoma Using OCT Alone: Utilizing an OCT Reading Center in a Real-World Clinical Setting.

We evaluated the ability of an optical coherence tomography (OCT)-based reading center for glaucoma (ORG) to detect established glaucoma using OCT alone. This study included eyes from 70 consecutive patients with established glaucoma (i.e. moderate or severe glaucoma according to the International Classification of Diseases [ICD]-10 guidelines) and 20 consecutive healthy subjects, who had no evidence of glaucomatous optic neuropathy (GON) or visual field (VF) loss in either eye. Using a standardized ORG quality assessment, 33 eyes were excluded due to media opacity (12), poor image quality (13), or epiretinal membrane (8). Of the remaining 147 eyes, 86 had established glaucoma and 36 were from healthy controls (total n = 122). Based on the OCT report alone and applying a previously described evaluation method, the presence of GON in each eye was determined by two masked ORG graders. The main outcome measures were sensitivity and specificity for detection of eyes with established glaucoma. Of the 86 eyes with established glaucoma (average mean deviation [MD] = -10.9 ± 7.7dB, range = -0.5 to -31.5dB), only one eye (MD = -0.46) was missed (sensitivity = 98.8%). However, the other eye of this patient was correctly classified as GON. Therefore, at a patient level, sensitivity was 100%. None of the 36 healthy eyes was classified as GON by the ORG (specificity = 100%). An OCT-based reading center is able to identify eyes with established glaucoma using OCT alone with high sensitivity and specificity. Our study validates the use of a systematic OCT-based approach for glaucoma detection in a real-world setting.

Saccadic movements during an exploratory visual search task in patients with glaucomatous visual field loss.

To evaluate the saccadic movements of patients with visual field loss due to primary open-angle glaucoma. Thirteen patients with good visual acuity (0.2 logMAR or better) (seven patients with primary open-angle glaucoma 65 ± 13 years) and six controls (51 ± 6 years) yielded a comprehensive ophthalmological examination, including Humphrey Visual Field tests (SITA-Standard 24-2), and performed a monocular, exploratory digital visual search task that quantifies the duration for finding the number "4" on a random array of digits distributed on the screen. After individual adjustments of the angle and distance positioning, the screen was spatially matched with the 24-2 visual field, and divided into five areas for analysis. During the task, saccades were simultaneously recorded in the same eye with a video-based eye tracker. The patients with primary open-angle glaucoma showed a significantly higher number of saccades/screen (median ± interquartile range, 59.00 ± 29.00 vs. 32.50 ± 19.75 saccades (p=0.027) and visual search time per screen (38.50 ± 60.14 vs. 23.75 ± 8.90 seconds (p=0.035) than the controls did. Although the univariate analysis indicated a significant correlation with visual field mean deviation (coefficient=26.19 (p=0.02), only the visual search time/screen was significantly associated with the number of saccades/screen in the multivariate regression model (coefficient=0.55 (p<0.001). Overall, no significant correlation was observed between the sectorial number of saccades and the sensitivity of the five visual field areas. The patients with primary open-angle glaucoma show impaired search performance and showed a higher number of saccades needed to find stimuli when performing the exploratory visual task.

Does the sampling frequency of an eye tracker affect the detection of glaucomatous visual field loss?

Evidence suggests that eye movements have potential as a tool for detecting glaucomatous visual field defects. This study evaluated the influence of sampling frequency on eye movement parameters in detecting glaucomatous visual field defects during a free-viewing task. We investigated eye movements in two sets of experiments: (a) young adults with and without simulated visual field defects and (b) glaucoma patients and age-matched controls. In Experiment 1, we recruited 30 healthy volunteers. Among these, 10 performed the task with a gaze-contingent superior arcuate (SARC) scotoma, 10 performed the task with a gaze-contingent biarcuate (BARC) scotoma and 10 performed the task without a simulated scotoma (NoSim). The experimental task involved participants freely exploring 100 images, each for 4 s. Eye movements were recorded using the LiveTrack Lightning eye-tracker (500 Hz). In Experiment 2, we recruited 20 glaucoma patients and 16 age-matched controls. All participants underwent similar experimental tasks as in Experiment 1, except only 37 images were shown for exploration. To analyse the effect of sampling frequency, data were downsampled to 250, 120 and 60 Hz. Eye movement parameters, such as the number of fixations, fixation duration, saccadic amplitude and bivariate contour ellipse area (BCEA), were computed across various sampling frequencies. Two-way ANOVA revealed no significant effects of sampling frequency on fixation duration (simulation, p = 0.37; glaucoma patients, p = 0.95) and BCEA (simulation, p = 0.84; glaucoma patients: p = 0.91). BCEA showed good distinguishability in differentiating groups across different sampling frequencies, whereas fixation duration failed to distinguish between glaucoma patients and controls. Number of fixations and saccade amplitude showed variations with sampling frequency in both simulations and glaucoma patients. In both simulations and glaucoma patients, BCEA consistently differentiated them from controls across various sampling frequencies.

Normative Percentiles of Retinal Nerve Fiber Layer Thickness and Glaucomatous Visual Field Loss.

Circumpapillary retinal nerve fiber layer thickness (RNFLT) measurement aids in the clinical diagnosis of glaucoma. Spectral domain optical coherence tomography (SD-OCT) machines measure RNFLT and provide normative color-coded plots. In this retrospective study, we investigate whether normative percentiles of RNFLT (pRNFLT) from Spectralis SD-OCT improve prediction of glaucomatous visual field loss over raw RNFLT. A longitudinal database containing OCT scans and visual fields from Massachusetts Eye & Ear glaucoma clinic patients was generated. Reliable OCT-visual field pairs were selected. Spectralis OCT normative distributions were extracted from machine printouts. Supervised machine learning models compared predictive performance between pRNFLT and raw RNFLT inputs. Regional structure-function associations were assessed with univariate regression to predict mean deviation (MD). Multivariable classification predicted MD, pattern standard deviation, MD change per year, and glaucoma hemifield test. There were 3016 OCT-visual field pairs that met the reliability criteria. Spectralis norms were found to be independent of age, sex, and ocular magnification. Regional analysis showed significant decrease in R2 from pRNFLT models compared to raw RNFLT models in inferotemporal sectors, across multiple regressors. In multivariable classification, there were no significant improvements in area under the curve of receiver operating characteristic curve (ROC-AUC) score with pRNFLT models compared to raw RNFLT models. Our results challenge the assumption that normative percentiles from OCT machines improve prediction of glaucomatous visual field loss. Raw RNFLT alone shows strong prediction, with no models presenting improvement by the manufacturer norms. This may result from insufficient patient stratification in tested norms. Understanding correlation of normative databases to visual function may improve clinical interpretation of OCT data.

NCX 470 Exerts Retinal Cell Protection and Enhances Ophthalmic Artery Blood Flow After Ischemia/Reperfusion Injury of Optic Nerve Head and Retina.

The purpose of this study was to assess the retinal protective activity and ocular hemodynamics after NCX 470 (0.1%) compared to bimatoprost administered as the US Food and Drug Administration (FDA)-approved drug (Lumigan - 0.01% ophthalmic solution, LUM) and at an equimolar dose (0.072%, BIM) to that released by NCX 470. Endothelin-1 (ET-1) induced ischemia/reperfusion injury model in rabbits was used. ET-1 was injected nearby the optic nerve head (ONH) twice/week for 6 weeks. Starting on week 3, the animals received vehicle (VEH), NCX 470, LUM, or BIM (30 µL/eye, twice daily, 6days/week) until the end of ET-1 treatment. Intraocular pressure (IOP), ophthalmic artery resistive index (OA-RI), and electroretinogram (ERG) data were collected prior to dosing and at different time points postdosing. Reduced glutathione, 8-Hydroxy 2-deoxyguanosine, and Caspase-3 were determined in the retina of treated eyes. DNA fragmentation was determined by terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick-end labeling (TUNEL) staining. ET-1 increased IOP (VEHIOP_Baseline = 20.5 ± 0.8 and VEHIOP_Week6 = 24.8 ± 0.3mmHg) and OA-RI (VEHOA-RI_Baseline = 0.36 ± 0.02 and VEHOA-RI_Week6 = 0.55 ± 0.01) and reduced rod/cone responses over time. Oxidative stress, inflammation, and apoptotic markers increased in ET-1-treated eyes. NCX 470 prevented IOP (NCX 470IOP_Week6 = 18.1 ± 0.6mmHg) and OA-RI changes (NCX 470OA-RI_Week6 = 0.33 ± 0.01) and restored ERG amplitude leaving unaltered the respective latency; these effects were only partially demonstrated by LUM or BIM. Additionally, NCX 470 reduced oxidative stress, inflammation, and apoptosis in the retinas of treated eyes. BIM and LUM were numerically less effective on these parameters. NCX 470 repeated ocular dosing ameliorates ocular hemodynamics and retinal cell dysfunction caused by ischemia/reperfusion via nitric oxide- and bimatoprost-mediated mechanisms. If confirmed in clinical setting our data may open new therapeutic opportunities to reduce visual field loss in glaucoma.

Relationship between Optical Coherence Tomography Angiography Vessel Density and Severity of Visual Field Loss in Glaucoma

Relationship between Optical Coherence Tomography Angiography Vessel Density and Severity of Visual Field Loss in Glaucoma

Choroidal detachment and hypotony following selective laser trabeculoplasty: a case report

BackgroundSelective laser trabeculoplasty (SLT) is relatively safe and effective in lowering intraocular pressure (IOP). However, although rare, complications can occur after SLT. This report describes a patient with choroidal detachment due to hypotony following SLT without anterior chamber (AC) inflammation.Case presentationA 67-year-old man was referred for elevated IOP in his left eye with advanced glaucomatous visual field loss. He had previously been diagnosed with idiopathic uveitic glaucoma in the left eye, for which he underwent laser iridotomy, trabeculectomy, and cataract surgery. At the first visit, the IOP of his left eye measured by Goldmann tonometry was 28 mmHg despite maximally tolerated medical treatment. SLT was performed in his left eye, resulting in an IOP of 7 mmHg 7 days later. At 3 weeks post-procedure, the patient experienced ocular pain and decreased visual acuity in his left eye. Slit-lamp examination revealed deep anterior chamber depth and no inflammation reaction, but the IOP in his left eye was 4 mmHg, and both fundus and B-scan ultrasonography showed serous choroidal detachment. All anti-glaucoma agents were stopped, and the patient was started on treatment with oral prednisolone and cyclopentolate eye drops. Three weeks later, choroidal detachment had resolved and the IOP in his left eye had stabilized at 8 mmHg. Follow-up 3 months later showed that the IOP in his left eye remained stable.ConclusionsChoroidal detachment-related hypotony is a rare complication of SLT. This possible complication following SLT should be informed to the patients and considered when performing the procedure.

Glaucomatous optic nerve damage in the contralateral eye of a patient with peripapillary retinoschisis: a case report

BackgroundPeripapillary retinoschisis (PPRS) is often associated with glaucomatous eyes. It usually occurs in eyes with a more advanced stage of glaucoma with obvious optic nerve damage. We report a patient who was found to have PPRS in one eye during a routine physical examination without obvious glaucoma symptoms. Further examination revealed glaucomatous visual field loss and retinal nerve fiber layer defects in the contralateral eye.Case presentationA 55-year-old man presented for a routine physical examination. The anterior segment was normal in both eyes. Fundus examination revealed an elevated and red optic disc in the right eye. In addition, scattered patchy red lesions were seen on the retina on the temporal side of the optic disc. The color and boundary of the left optic disc were normal, and the cup-to-disc ratio was 0.6. Optical coherence tomography showed retinoschisis on the optic nerve head of the right eye throughout the entire circumference, extending to the retina on the temporal side of the optic disc. The intraocular pressure was 18 mmHg OD and 19 mmHg OS. The patient was diagnosed with PPRS (OD). However, no optic disc pit or optic disc coloboma was found. Further examination showed that the visual field of the patient’s right eye was generally normal, while a glaucomatous visual field defect was found in the left eye, which manifested as a nasal step visual field defect. Moreover, stereophotography and a red-free fundus image revealed two retinal nerve fiber layer defects in the supratemporal and infratemporal regions of the retina of the left eye. Continuous intraocular pressure measurement found that the intraocular pressure fluctuated between 18 and 22 mmHg OD and 19–26 mmHg OS during the daytime. Primary open-angle glaucoma was then diagnosed.ConclusionsIn this case, we found that PPRS was associated with glaucomatous optic nerve changes and visual field defects in the fellow eye.

Iridotomy to slow progression of visual field loss in angle-closure glaucoma.

Primary angle-closure glaucoma is a type of glaucoma associated with a physically obstructed anterior chamber angle. For example, contact between the iris and lens at the pupillary margin creates a pupillary block that increases resistance to aqueous outflow. Obstruction of the anterior chamber angle blocks drainage of fluids (aqueous humor) within the eye and may raise intraocular pressure (IOP). Elevated IOP is associated with glaucomatous optic nerve damage and visual field loss. Laser peripheral iridotomy ('iridotomy') is a procedure to eliminate pupillary block by allowing aqueous humor to pass directly from the posterior to anterior chamber, which is achieved by creating a hole in the iris using laser. Iridotomy is used to treat patients with primary angle-closure glaucoma, patients with primary angle-closure (narrow angles and no signs of glaucomatous optic neuropathy), and patients who are primary angle-closure suspects (patients with reversible obstruction). However, the effectiveness of iridotomy on slowing progression of visual field loss is uncertain. To assess the effects of iridotomy compared with no iridotomy for primary angle-closure glaucoma, primary angle-closure, and primary angle-closure suspect. We searched the Cochrane Central Register of Controlled Trials (CENTRAL; 2021, Issue 10), which contains the Cochrane Eyes and Vision Trials Register; MEDLINE Ovid; Embase Ovid; PubMed; LILACS; ClinicalTrials.gov; and the WHO ICTRP. The date of the most recent search was 10 October 2021. Randomized or quasi-randomized controlled trials that compared iridotomy with no iridotomy in primary angle-closure suspects, people with primary angle-closure, or people with primary angle-closure glaucoma in one or both eyes were eligible. We used standard Cochrane methodology and assessed the certainty of the body of evidence for prespecified outcomes using the GRADE approach. We identified four studies (3086 eyes of 1543 participants) that compared iridotomy with no iridotomy in participants (range of mean age 59.6 to 62.9 years) who were primary angle-closure suspects from China, Singapore, or the UK. Study investigators randomized one eye of each participant to iridotomy and the other to no iridotomy. Two studies provided long-term (five or more years) results. We judged the certainty of the evidence as moderate to low across the prespecified outcomes, downgrading for high risk of bias (e.g. performance and detection biases) and imprecision of results. Meta-analyses of data from two studies suggest that iridotomy probably results in little to no difference in IOP compared with no iridotomy at one year (mean difference (MD) 0.04 mm Hg, 95% confidence interval (CI) -0.17 to 0.24; I2 = 65%; 2598 eyes of 1299 participants; moderate certainty evidence) and five years (MD 0.12 mm Hg, 95% CI -0.11 to 0.35; I2 = 0%; 2016 eyes of 1008 participants), and in best-corrected visual acuity measured as logMAR at one year (MD 0.00, 95% CI -0.01 to 0.01; I2 = 69%; 2596 eyes of 1298 participants; moderate certainty evidence) and five years (MD 0.01, 95% CI -0.01 to 0.03; I2 = 0%; 2002 eyes of 1001 participants). In terms of gonioscopic findings, eyes treated with iridotomy likely had wider angles in Shaffer grading scale (MD 4.93 units, 95% CI 4.73 to 5.12; I2 = 59%; 2598 eyes of 1299 participants at one year; MD 5.07, 95% CI 4.78 to 5.36; I2 = 97%; 2016 eyes of 1008 participants at five years; moderate certainty evidence) and experienced fewer peripheral anterior synechiae (PAS) than eyes that received no iridotomy at five years (risk ratio (RR) 0.41, 95% CI 0.24 to 0.67; I2 = 28%; 2 studies, 2738 eyes of 1369 participants), but the evidence was less conclusive at one year (RR 0.62, 95% CI 0.25 to 1.54; I2 = 57%; 3 studies, 2896 eyes of 1448 participants; low certainty evidence). No studies reported data on the proportion of participants with progressive visual field loss during follow-up (the primary outcome of this review), mean number of medications to control IOP, or quality of life outcomes. Low certainty evidence suggests that iridotomy may result in little to no difference in the incidence of acute angle-closure (RR 0.29, 95% CI 0.07 to 1.20; I2 = 0%; 3 studies, 3006 eyes of 1503 participants). Other ocular adverse events (e.g. eye pain, dry eye, redness of eyes, and ocular discomfort), although rare, were more common in eyes treated with iridotomy than in eyes in the control group. AUTHORS' CONCLUSIONS: We did not find sufficient evidence to draw any meaningful conclusions on the use of iridotomy for the purpose of slowing progression of visual field loss. No study reported on progressive visual field loss, the primary outcome of this review. Although there is moderate certainty evidence that iridotomy results in improved gonioscopic findings, in is unclear if these findings translate to clinically meaningful benefits.

Genetic variants associated with glaucomatous visual field loss in primary open-angle glaucoma

Primary open-angle glaucoma (POAG) is characterized by a progressive optic neuropathy with visual field loss. To investigate the genetic variants associated with visual field loss in POAG, Japanese POAG patients (n = 426) and control subjects (n = 246) were genotyped for 22 genetic variants predisposing to POAG that can be classified into those associated with intraocular pressure (IOP) elevation (IOP-related genetic variants) and optic nerve vulnerability independent of IOP (optic nerve-related genetic variants). The genetic risk score (GRS) of the 17 IOP-related and five optic nerve-related genetic variants was calculated, and the associations between the GRS and the mean deviation (MD) of automated static perimetry as an indicator of the severity of visual field loss and pattern standard deviation (PSD) as an indicator of the focal disturbance were evaluated. There was a significant association (Beta = − 0.51, P = 0.0012) between the IOP-related GRS and MD. The severity of visual field loss may depend on the magnitude of IOP elevation induced by additive effects of IOP-related genetic variants. A significant association (n = 135, Beta = 0.65, P = 0.0097) was found between the optic nerve-related, but not IOP-related, GRS and PSD. The optic nerve-related (optic nerve vulnerability) and IOP-related (IOP elevation) genetic variants may play an important role in the focal and diffuse visual field loss respectively. To our knowledge, this is the first report to show an association between additive effects of genetic variants predisposing to POAG and glaucomatous visual field loss, including severity and focal/diffuse disturbance of visual field loss, in POAG.

Association of baseline optical coherence tomography angiography with the development of glaucomatous visual field defects in preperimetric glaucoma eyes

AimsTo evaluate whether baseline vessel density (VD) parameters derived from optical coherence tomography angiography (OCT-A) is associated with the development of glaucomatous visual field (VF) defects in preperimetric glaucoma (PPG)...

Regulatory mechanisms of retinal ganglion cell death in normal tension glaucoma and potential therapies.

Normal tension glaucoma (NTG) is a multifactorial optic neuropathy characterized by normal intraocular pressure, progressive retinal ganglion cell (RGC) death, and glaucomatous visual field loss. Recent studies have described the mechanisms underlying the pathogenesis of NTG. In addition to controlling intraocular pressure, neuroprotection and reduction of RGC degeneration may be beneficial therapies for NTG. In this review, we summarized the main regulatory mechanisms of RGC death in NTG, including autophagy, glutamate neurotoxicity, oxidative stress, neuroinflammation, immunity, and vasoconstriction. Autophagy can be induced by retinal hypoxia and axonal damage. In this process, ischemia can cause mutations of optineurin and activate the nuclear factor-kappa B pathway. Glutamate neurotoxicity is induced by the over-stimulation of N-methyl-D-aspartate membrane receptors by glutamate, which occurs in RGCs and induces progressive glaucomatous optic neuropathy. Oxidative stress also participates in NTG-related glaucomatous optic neuropathy. It impairs the mitochondrial and DNA function of RGCs through the apoptosis signal-regulating kinase-JUN N-terminal kinase pathway. Moreover, it increases inflammation and the immune response of RGCs. Endothelin 1 causes endothelial dysfunction and impairment of ocular blood flow, promoting vasospasm and glaucomatous optic neuropathy, as a result of NTG. In conclusion, we discussed research progress on potential options for the protection of RGCs, including TANK binding kinase 1 inhibitors regulating autophagy, N-methyl-D-aspartate receptor antagonists inhibiting glutamate toxicity, ASK1 inhibitors regulating mitochondrial function, and antioxidants inhibiting oxidative stress. In NTG, RGC death is regulated by a network of mechanisms, while various potential targets protect RGCs. Collectively, these findings provide insight into the pathogenesis of NTG and potential therapeutic strategies.

Association of Initial Optical Coherence Tomography Angiography Vessel Density Loss With Faster Visual Field Loss in Glaucoma

Rapid vessel density loss during an initial follow-up period may be associated with the rates of visual field loss over time. To evaluate the association between the rate of vessel density loss during initial follow-up and the rate of visual field loss during an extended follow-up period in patients suspected of having glaucoma and patients with primary open-angle glaucoma. This retrospective cohort study assessed 124 eyes (86 with primary open-angle glaucoma and 38 suspected of having glaucoma) of 82 patients who were followed up at a tertiary glaucoma center for a mean of 4.0 years (95% CI, 3.9-4.1 years) from January 1, 2015, to February 29, 2020. Data analysis for the current study was undertaken in March 2021. The rate of vessel density loss was derived from macular whole-image vessel density values from 3 optical coherence tomography angiography scans early during the study. The rate of visual field loss was calculated from visual field mean deviation during the entire follow-up period after the first optical coherence tomography angiography visit. Linear mixed-effects models were used to estimate rates of change. A total of 124 eyes from 82 patients (mean [SD] age, 69.2 [10.9] years; 41 female [50.0%] and 41 male [50.0%]; and 20 African American [24.4%], 10 Asian [12.2%], 50 White [61.0%], and 2 other race or ethnicity [2.4%]) were assessed. The annual rate of vessel density change was -0.80% (95% CI, -0.88% to -0.72%) during a mean initial follow-up of 2.1 years (95% CI, 1.9-2.3 years). Eyes with annual rates of vessel density loss of -0.75% or greater (n = 62) were categorized as fast progressors, and eyes with annual rates of less than -0.75% (n = 62) were categorized as slow progressors. The annual rate of visual field loss was -0.15 dB (95% CI, -0.29 to -0.01 dB) for the slow optical coherence tomography angiography progressors and -0.43 dB (95% CI, -0.58 to -0.29 dB) for the fast optical coherence tomography angiography progressors (difference, -0.28 dB; 95% CI, -0.48 to -0.08 dB; P = .006). The fast optical coherence tomography angiography progressor group was associated with the faster overall rate of visual field loss in a multivariable model after adjusting to include concurrent visual field mean deviation rate (-0.17 dB; 95% CI, -0.33 to -0.01 dB; P = .04). The findings of this cohort study suggest that faster vessel density loss during an initial follow-up period was associated with faster concurrent and subsequent rates of visual field loss during an extended period.

Rates of Glaucoma Progression Derived from Linear Mixed Models Using Varied Random Effect Distributions.

PurposeTo compare the ability of linear mixed models with different random effect distributions to estimate rates of visual field loss in glaucoma patients.MethodsEyes with five or more reliable standard automated perimetry (SAP) tests were identified from the Duke Glaucoma Registry. Mean deviation (MD) values from each visual field and associated timepoints were collected. These data were modeled using ordinary least square (OLS) regression and linear mixed models using the Gaussian, Student's t, or log-gamma (LG) distributions as the prior distribution for random effects. Model fit was compared using the Watanabe–Akaike information criterion (WAIC). Simulated eyes of varying initial disease severity and rates of progression were created to assess the accuracy of each model in predicting the rate of change and likelihood of declaring progression.ResultsA total of 52,900 visual fields from 6558 eyes of 3981 subjects were included. Mean follow-up period was 8.7 ± 4.0 years, with an average of 8.1 ± 3.7 visual fields per eye. The LG model produced the lowest WAIC, demonstrating optimal model fit. In simulations, the LG model declared progression earlier than OLS (P < 0.001) and had the greatest accuracy in predicted slopes (P < 0.001). The Gaussian model significantly underestimated rates of progression among fast and catastrophic progressors.ConclusionsLinear mixed models using the LG distribution outperformed conventional approaches for estimating rates of SAP MD loss in a population with glaucoma.Translational RelevanceUse of the LG distribution in models estimating rates of change among glaucoma patients may improve their accuracy in rapidly identifying progressors at high risk for vision loss.

Evaluation of depth perception and association of severity in Glaucoma patients and suspects

BackgroundTo evaluate depth perception in Primary open angle glaucoma (POAG), glaucoma suspects compared to controls and to determine the association between depth perception and severity of glaucoma.MethodsThis was a hospital based, comparative, cross-sectional study. The ethical clearance was taken from institutional review committee of Institute of Medicine [Reference no.399 (6–11) E2 077-078]. Agematched, equal number of participants in each group (N=20) were evaluated with both Titmus and Frisby stereoacuity tests to measure depth perception as stereopsis threshold in seconds of arc. The participants were selected using the purposive sampling technique.ResultsThere was no differences in age, sex, or best corrected visual acuity, intraocular pressure, central corneal thickness (CCT), found among the three groups (POAG, Glaucoma Suspects and Control) respectively. However, there was significant difference in cup disc ratio (CDR) between the groups. Equal number of male and female were there in each group, while in POAG group male to female ratio was 3:2. The mean stereoacuity threshold in control group was 53.5±23.23 seconds of arc with Titmus test and 38.75±18.83 seconds of arc with Frisby stereoacuity test. The difference in threshold was significant between control and glaucoma suspect with Titmus (t=1.991, p=0.05) and with Frisby (t=2.114, p=0.04). The difference was also significant in POAG group by Titmus (t=3.135, p=0.0033) and by Frisby (t=3.014, p=0.004). More so, with increasing severity of glaucoma, the mean threshold of stereopsis increased as seen with both Titmus and Frisby Tests (ANOVA, p < 0.001)ConclusionPrimary open angle glaucoma patients and glaucoma suspects, showed significant reduction in depth perception. Decreased stereoacuity was associated with greater glaucomatous visual field loss.

Charles Bonnet Syndrome in Patients with Open-Angle Glaucoma: Prevalence and Correlation to Visual Field Loss

To determine the prevalence and characteristics of Charles Bonnet Syndrome (CBS) and its relation to visual field loss (VFL) in patients with open-angle glaucoma (OAG). Prospective, cross-sectional study. Adult patients (n= 337) with manifest OAG with verified VFL and without significant macular disease or extraocular conditions known to cause visual hallucinations. Patients attending the glaucoma outpatient department of the Skåne University hospital, Malmö, Sweden, between April 1, 2018, and December 31, 2018, were consecutively evaluated for inclusion. Potentially eligible patients admitting to having complex visual hallucinations were interviewed to explore the characteristics of their hallucinatory experiences. Recent automated visual field examinations were available for all participants, and swept-source OCT was performed in participants with CBS to rule out previously undiagnosed macular pathology. The correlation between potential risk factors and CBS was evaluated with logistic regression analysis. Prevalence of CBS in patients with OAG. Charles Bonnet Syndrome was found in 7.1% (95% confidence interval [CI], 4.7-10.6) of patients with OAG. Participants with CBS were more likely to have at least 1 eye with a visual field index (VFI) of ≤30% compared with those without CBS (71% vs. 34.2%; P= 0.001). Although the best-corrected visual acuity (BCVA) in the worse eye was significantly lower in participants with CBS (decimal equivalent of Snellen BCVA: 0.25 vs. 0.6, P= 0.003), 33% of these participants had a BCVA of ≥0.5 in the worse eye. In multivariable analysis, CBS was correlated to the VFI of the better eye (odds ratio, 0.984; 95% CI, 0.969-0.998, P= 0.030) and the BCVA of the worse-seeing eye (odds ratio, 0.210; 95% CI, 0.046-0.952, P= 0.043). Charles Bonnet Syndrome was not a rare condition in patients with glaucoma. Patients with a combination of advanced VFL and low BCVA had the highest risk of CBS; however, 1 of 3 patients with CBS hada BCVA of ≥0.5 in both eyes. These findings emphasize the importance of being attentive to symptoms ofCBS in patients with glaucomatous VFL even when visual acuity is preserved.