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Tanner J Ferguson,1 Nathan M Radcliffe,2 Sarah H Van Tassel,3 Brandon J Baartman,4 Vance M Thompson,4 Richard L Lindstrom,4,5 Mitch J Ibach,4,5 John P Berdahl4 1Cole Eye Institute, Cleveland Clinic, Cleveland, OH, USA; 2New York Eye and Ear Infirmary of Mount Sinai, New York, NY, USA; 3Department of Ophthalmology, Weill Cornell Medicine, New York, NY, USA; 4Vance Thompson Vision, Sioux Falls, SD, USA; 5Minnesota Eye Consultants, Minnesota, MN, USACorrespondence: Tanner J Ferguson Email tannerferg@gmail.comPurpose: To investigate the safety and tolerability of the multi-pressure dial (MPD) worn overnight for seven consecutive days.Design: Prospective, open-label, randomized, single-site study.Subjects: Twenty eyes of 10 subjects with open-angle glaucoma were fitted with an MPD and randomized to negative pressure application of − 10 mmHg in one eye (study eye) worn overnight for 7 consecutive days.Methods: Safety measures included best-corrected visual acuity (BCVA), intraocular pressure (IOP) changes from baseline during and after negative pressure application, slit lamp and dilated fundus exam findings, and rate of adverse events. Subjective assessments were completed daily by the subjects during the 7-day study period and immediately following the study period.Results: Prior to the 7-day testing period, application of 10 mmHg negative pressure reduced mean IOP from 18.2 ± 3.8 mmHg to 14.0 ± 2.1 mmHg (p< 0.01), a 22% reduction. After 7 days of consecutive nightly wear, repeat IOP measurements with the application of negative pressure showed a decrease in mean IOP from 16.9 ± 4.3 mmHg to 13.5 ± 3.7 mmHg. The observed IOP reduction was in addition to the subjects’ current treatment regimen. There were no statistically significant changes in IOP, BCVA from baseline following the 7-day period of nightly wear with the application of negative pressure. The patient-reported outcomes were favorable.Conclusion: The MPD can safely and comfortably be worn overnight. The decrease in IOP of > 20% in addition to current therapy is both clinically and statistically significant. The MPD shows promise as a potential new treatment option for nocturnal IOP control.Keywords: multi-pressure dial, open-angle glaucoma, normal-tension glaucoma, nocturnal IOP, multi-pressure glaucoma management

Abstract Purpose The efficacy and safety of the trabecular micro-bypass stents (iStent and iStent inject) have been well documented in various open-angle glaucoma subtypes. However, their outcomes remain understudied in normal-tension glaucoma (NTG). The present study aimed to assess the 1-year outcomes related to the implantation of two second-generation trabecular micro-bypass stents (iStent inject) concomitant with cataract surgery (CE-TMS), exclusively in eyes with NTG. Methods This multi-center, consecutive case series included eyes with cataract and normal-tension glaucoma that underwent CE-TMS to reduce intraocular pressure or glaucoma medication use. The 12-month efficacy measures included change in average intraocular pressure (IOP) and medication burden. Safety included change in best-corrected visual acuity, cup-to-disc ratio, visual field mean-deviation and retinal nerve fiber layer thickness. Intra- or postoperative adverse events were noted. Results A total of 62 eyes with mild-to-severe NTG and average preoperative IOP of 15.82 ± 2.94 mmHg on 1.50 ± 1.28 glaucoma medications were included. Postoperatively, IOP declined by 22% from 15.82 ± 2.94 mmHg to 12.32 ± 2.58 (p

Koji Nitta,1,2 Shiro Shimamoto,3 Ryotaro Wajima,2 Gaku Tachibana,2 Yutaro Yamada,1,2 Miyuki Domoto,1 Ryuji Takeda,4,5 Yoshinari Takahashi,6 Kazuhisa Sugiyama2 1Fukui-ken Saiseikai Hospital, Fukui, Japan; 2Department of Ophthalmology, Kanazawa University Graduate School of Medical Science, Kanazawa, Japan; 3Shimamoto Ophthalmology Clinic, Fukui, Japan; 4Department of Nutritional Sciences for Well-Being, Faculty of Health Sciences for Welfare, Kansai University of Welfare Sciences, Osaka, Japan; 5Department of Applied Biological Chemistry, Faculty of Agriculture, Kindai University, Nara, Japan; 6Inary Co., Ltd., Tokyo, JapanCorrespondence: Koji NittaDepartment of Ophthalmology, Fukui-ken Saiseikai Hospital, 7-1 Funabashi, Wadanaka-cho, Fukui 918-8503, JapanTel +81 776 23 1111Fax +81 776 28 8515Email nitta.koji7001@fukui.saiseikai.or.jpBackground: This retrospective study evaluated the effect of adjunctive administration of brimonidine 0.1% on disc hemorrhage (DH) in patients with primary open-angle glaucoma or normal-tension glaucoma who were already treated with other anti-glaucoma drugs.Methods: Patients with DH, before adjunctive therapy with brimonidine, were enrolled. Subjects were excluded if their treatment regimen was changed within 1 year after initiation of adjunctive therapy with brimonidine. We investigated the frequency of DH and intraocular pressure (IOP). Both parameters were compared before and after adjunctive administration of brimonidine.Results: The frequency of DH before and after brimonidine administration was 0.67± 0.68 and 0.31± 0.72 times/year, respectively, with a significant decrease (P=0.01), and the mean IOP before and after brimonidine administration was 12.5± 1.9 and 11.2± 2.2 mmHg, respectively, (P=0.0006) with a significant reduction after adjunctive administration.Conclusion: The results of this study supported the hypothesis that the frequency of DH is reduced by brimonidine alongside lowering of IOP.Keywords: disc hemorrhage, intraocular pressure, brimonidine, primary open-angle glaucoma, normal-tension glaucoma

Growing evidence suggests that intracranial pressure (ICP) plays an important role in the pathophysiology of glaucoma, especially in normal-tension glaucoma (NTG) patients. Controversial results exist about ICP’s relationship to visual field (VF) changes. With the aim to assess the relationship between ICP and VF zones in NTG patients, 80 NTG patients (age 59.5 (11.6) years) with early-stage glaucoma were included in this prospective study. Intraocular pressure (IOP) (Goldmann), visual perimetry (Humphrey) and non-invasive ICP (via a two-depth Transcranial Doppler, Vittamed UAB, Lithuania) were evaluated. Translaminar pressure difference (TPD) was calculated according to the formula TPD = IOP − ICP. The VFs of each patient were divided into five zones: nasal, temporal, peripheral, central, and paracentral. The average pattern deviation (PD) scores were calculated in each zone. The level of significance p < 0.05 was considered significant. NTG patients had a mean ICP of 8.5 (2.4) mmHg. Higher TPD was related with lower mean deviation (MD) (p = 0.01) and higher pattern standard deviation (PSD) (p = 0.01). ICP was significantly associated with the lowest averaged PD scores in the nasal VF zone (p < 0.001). There were no significant correlations between ICP and other VF zones with the most negative mean PD value. (p > 0.05). Further studies are needed to analyze the involvement of ICP in NTG management.

Since glaucoma is a progressive and irreversible optic neuropathy, accurate screening and/or early diagnosis is critical in preventing permanent vision loss. Recently, optical coherence tomography (OCT) has become an accurate diagnostic tool to observe and extract the thickness of the retinal nerve fiber layer (RNFL), which closely reflects the nerve damage caused by glaucoma. However, OCT is less accessible than fundus photography due to higher cost and expertise required for operation. Though widely used, fundus photography is effective for early glaucoma detection only when used by experts with extensive training. Here, we introduce a deep learning-based approach to predict the RNFL thickness around optic disc regions in fundus photography for glaucoma screening. The proposed deep learning model is based on a convolutional neural network (CNN) and utilizes images taken with fundus photography and with RNFL thickness measured with OCT for model training and validation. Using a dataset acquired from normal tension glaucoma (NTG) patients, the trained model can estimate RNFL thicknesses in 12 optic disc regions from fundus photos. Using intuitive thickness labels to identify localized damage of the optic nerve head and then estimating regional RNFL thicknesses from fundus images, we determine that screening for glaucoma could achieve 92% sensitivity and 86.9% specificity. Receiver operating characteristic (ROC) analysis results for specificity of 80% demonstrate that use of the localized mean over superior and inferior regions reaches 90.7% sensitivity, whereas 71.2% sensitivity is reached using the global RNFL thicknesses for specificity at 80%. This demonstrates that the new approach of using regional RNFL thicknesses in fundus images holds good promise as a potential screening technique for early stage of glaucoma.

(1) Background: Topical antiglaucoma medications may alter the microcirculation in the optic nerve head. We aimed to evaluate the changes in retinal vessel density (VD) on optical coherence tomography angiography (OCTA) in patients with newly diagnosed normal-tension glaucoma (NTG) treated with a topical beta-blocker. (2) Methods: This study included 80 patients diagnosed with NTG not using systemic medication, who received topical carteolol treatment between December 2019 and November 2020. We studied the changes in the OCTA VD/signal strength index (SSI) after the 6-month treatment period and determined the predictive factors affecting the changes in VD/SSI. (3) Results: After the 6-month treatment period, the peripapillary VD increased in 40 patients but decreased in the other 40 patients. The univariate and multivariate analyses revealed that old age and hypertension were significant factors associated with a VD/SSI decrease after carteolol treatment. Moreover, high baseline peripapillary, superficial, and deep macular VDs were significantly associated with the VD decrease after carteolol treatment. (4) Conclusions: Carteolol treatment could increase or decrease the VD in patients with NTG. The baseline VD, age, and hypertension could affect these VD changes. Patients with NTG and higher baseline peripapillary or macular VD, older age, and hypertension are more likely to have a decreased VD after carteolol treatment. [ABSTRACT FROM AUTHOR]

Purpose: To investigate how the central visual field would be changed after fornix-based trabeculectomy with mitomycin C in Japanese normal-tension glaucoma (NTG) patients monitored for more than 10 years including before surgery. Methods: This is a retrospective cohort study. We identified twenty-eight eyes of 28 NTG cases regularly monitored for more than 5 years and examined static visual field (VF) tests for more than five times before and after fornix-based trabeculectomy (including combined surgery). Based on preoperative data for 6.3 years, we evaluated postoperative changes for 6.0 years in 10–2 VF and 30–2 VF. Results: Six patients were male and 22 females, the mean age was 57.9 years, and the mean deviation was − 13.7 decibels. After surgery, mean IOP decreased from 13.9 to 9.0 mmHg (P ≤ 0.01), and medication score also did. The rate of 10–2 VF deterioration was significantly suppressed from − 1.0 dB/year preoperatively to − 0.4 dB/year postoperatively (P ≤ 0.01). And when 30–2 VF was divided into six relevant sectors, the rate of deterioration at cecocentral and arcuate areas of the superior hemifield was suppressed postoperatively (P ≤ 0.01 and P = 0.042, respectively). Conclusion: Based on long-term preoperative data, a significant positive change in 10–2 VF was observed after fornix-based trabeculectomy with mitomycin C in Japanese NTG patients with a mean IOP of 13.9 mmHg. Central vision could be expected to be maintained for NTG patients even if its preoperative IOP is low after successful trabeculectomy. [ABSTRACT FROM AUTHOR]

Introduction: The purpose of this study was to investigate the short-term safety and feasibility of negative pressure application by the Multi-Pressure Dial (MPD) System to lower nocturnal intraocular pressure (IOP) in subjects with open-angle glaucoma (OAG). Methods: A prospective, controlled, intra-subject study of 22 eyes from 11 subjects at a single site was performed. All subjects had a history of OAG and were currently using a topical prostaglandin. For each subject, the eye with the highest IOP in the supine position was selected as the treatment eye (TE) and the contralateral eye served as the control eye (CE). The negative pressure for the TE was set to 60% of the baseline IOP value with no negative pressure in the CE. IOP measurements were collected at three prespecified time points overnight in the supine position with active negative pressure. The primary outcome measure was mean IOP with the application of negative pressure. Results: At the three overnight time points, the mean (± standard deviation) baseline IOP prior to negative pressure application was 22.2 ± 2.5 mmHg in the TE and 21.8 ± 2.5 mmHg in the CE. With the application of 60% negative pressure to the TE and no active negative pressure to the CE, the mean IOP was 14.2 ± 2.2 and 19.5 ± 2.4 mmHg, respectively. The mean percentage IOP reduction in the TE was 35% (p < 0.001). There were two minor adverse events, both unrelated to device wear, and there were no IOP spikes ≥ 10 mmHg. Conclusion: The MPD can safely and effectively lower nocturnal IOP in the supine position. The MPD holds promise as a potential new, non-invasive treatment option for the control of nocturnal IOP. [ABSTRACT FROM AUTHOR]

Glaucoma is the leading cause of irreversible blindness worldwide. As a chronic disease, glaucoma presents a significant burden to the individual, health‐care provider and the health‐care system. Currently, strategies for treating glaucoma are focused on lowering intraocular pressure, which is aimed at slowing or arresting disease progression over time. This is the only current accepted therapeutic strategy for glaucoma, and can be achieved using topical drugs, laser trabeculoplasty, filtration surgery or cyclodestructive techniques. The lowering of intraocular pressure has been well‐supported by numerous large‐scale seminal clinical trials in primary open‐angle glaucoma, in both its early and advanced stages. Although such guidance remains current, in the last 10-years, there has been a significant evolution in preferred first‐line therapies in the treatment of open‐angle glaucoma with a resultant shift in practice patterns, particularly early in the course of the disease. These changes reflect both from the perspective of the doctor – in titrating the most effective and least risky treatment modality – and the perspective of the patient, in consenting to a treatment that preserves vision and results in minimal negative impact on quality of life. In this review, the most recent evidence regarding treatment modalities for early primary open‐angle glaucoma is presented and an updated framework for management guidance is proposed. [ABSTRACT FROM AUTHOR]

Introduction: To evaluate the association of focal lamina cribrosa (LC) defect with asymmetric visual field (VF) loss in normal-tension glaucoma (NTG) through intereye comparisons. Methods: Paired eyes were divided into better and worse eyes according to the mean deviation (MD), and ocular parameters were compared between them. Furthermore, patients in the asymmetric group were classified as subgroup A (one eye with LC defect and the fellow one without), subgroup B (both eyes without LC defect), and subgroup C (both eyes with LC defect). Generalized estimation equation approach was used to evaluate the association between ocular parameters and asymmetric VF. Results: A total of 140 eyes of 70 NTG patients were included in the asymmetric group. LC defects were more common in better eyes than that in worse eyes (27/70 [38.57%] vs. 10/70 [14.29%], p = 0.001), and all eyes with LC defect had myopia. Multivariate analysis revealed that the presence of LC defect was significantly associated with better eyes in the asymmetric group (odds ratio, 0.27; p = 0.001). For subgroup A, eyes with LC defects exhibited lower peak IOP (p = 0.011) and lower mean IOP (p = 0.018) than the fellow eyes without. In addition, longer AL (p = 0.025) and larger tilt ratio (p = 0.032) were found in eyes with LC defects. For subgroup B without LC defects, larger tilt ratio was shown to be a risk factor for VF loss (odds ratio, 6.13; p = 0.001). There was no significant difference of binocular parameters except for MD (p < 0.001) in subgroup C. Conclusions: LC defects in myopia were suggested to be associated with better eyes in NTG with asymmetric VF loss. However, in patients without LC defect, larger tilt ratio was a risk factor for VF defect. There might be different pathological mechanisms in asymmetric VF loss for different NTG subtypes. [ABSTRACT FROM AUTHOR]

Purpose: To compare the therapeutic efficacy and safety of newly developed preservative-free (PF) brimonidine/timolol fixed-combination (BTFC) ophthalmic solutions and a preservative-containing (PC) BTFC ophthalmic solution in patients with open-angle glaucoma.Methods: This study was conducted as a multicenter, randomized, open-label, parallel-group clinical trial to evaluate the efficacy and safety of PF BTFC as compared with PC BTFC in adult patients (aged ≥ 19 years) with open-angle glaucoma (OAG) and ocular hypertension (OHT). A total of the 106 patients were enrolled, with 53 patients each randomized to the two treatment groups and included in the analysis of the safety set (SS).After a washout period, patients with an IOP below 35 mmHg at 9 a.m. were enrolled. After a full ophthalmic and glaucoma examination, a total of 106 OAG and OHT patients were randomized to the PF group or PC group.All subjects were examined 4 and 12 weeks after first administration. At each follow-up visit, IOP was measured at 9 a.m. and 11 a.m. and the efficacy, safety, and compliance were evaluated. Throughout the study, all adverse events were recorded and monitored by the investigators.Results The mean IOP changes from baseline to 12 weeks at 11:00 a.m. were -3.45 ± 2.53 mmHg in the PF group and -3.65 ± 2.76 mmHg in the PC group (p < .0001 for both). The difference in mean IOP change between the two groups was 0.20 ± 2.65 mmHg, which was not significantly different. The proportion of patients with IOP reductions of ≥ 15% and ≥ 20% and IOP at all-time points in the PF group were not significantly different when compared with in the PC group. There were no specific differences between the two groups regarding the incidence of adverse events.Conclusions PF BTFC ophthalmic solution shows a similar efficacy and safety profile to that of PC BTFC. [ABSTRACT FROM AUTHOR]

Thomas W Samuelson,1 Tanner J Ferguson,2 Nathan M Radcliffe,3 Richard Lewis,4 Justin Schweitzer,5 Russell Swan,5 John P Berdahl5 1Minnesota Eye Consultants, Minneapolis, MN, USA; 2Cole Eye Institute, Cleveland Clinic, Cleveland, OH, USA; 3Department of Ophthalmology, New York Eye and Ear Infirmary of Mount Sinai, New York, NY, USA; 4Sacramento Eye Consultants, Sacramento, CA, USA; 5Vance Thompson Vision, Sioux Falls, SD, USACorrespondence: Tanner J FergusonCole Eye Institute, Cleveland Clinic, Cleveland OH, USAEmail tannerferg@gmail.comPurpose: To investigate the safety and tolerability of the multi-pressure dial with a continuous 8-hr duration in subjects with open-angle glaucoma.Design: Prospective, controlled open-label, randomized, single site study.Subjects: Twenty eyes of 10 subjects with open-angle glaucoma were fitted with a multi-pressure dial and randomized to negative pressure application of −10 mmHg in one eye for 8 (continuous) hours and ambient atmospheric pressure in the contralateral eye.Methods: Main safety outcome measures include best-corrected visual acuity (BCVA), intraocular pressure (IOP) changes from baseline after negative pressure application, slit lamp and dilated fundus exam findings, and rate of adverse events. Subjective assessments were administered both hourly during the 8-hr study period and immediately following the study period.Results: There were no statistically significant changes in IOP, BCVA or TBUT immediately following the 8-hr study period or at the 1-week follow-up visit. Patient-reported tolerability was favorable with a mean response of 1.8 ± 0.4 (scale → 1=best, 10 = worst). Subjects also reported positive interest in the MPD as a glaucoma therapy with a mean response of 1.8 ± 0.5 (scale → 1=best, 10 = worst). One adverse event was reported (headache) and resolved at conclusion of the Day 0 visit.Conclusion: The MPD demonstrated favorable safety with key parameters remaining stable after an 8-hr wear with negative pressure. Negative pressure application through the MPD was well tolerated by subjects enrolled in the study. The favorable findings demonstrate the safety of sustained delivery of negative pressure over a continuous, uninterrupted 8-hr duration.Keywords: multi-pressure dial, normal-tension glaucoma, open-angle glaucoma, glaucoma treatment

Abstract Introduction Prospective, open-label, non-randomized, single site study to assess the safety and tolerability of a multi-pressure dial. Methods 30 healthy subjects received application of negative pressure (–15 mmHg) in one eye for 30 minutes and ambient atmospheric pressure in the contralateral eye. To evaluate safety, the primary outcome measures included best corrected visual acuity (BCVA), intraocular pressure (IOP) changes from baseline, slit-lamp and dilated fundus examination findings, and rate of adverse events. Exploratory analyses included in this study also evaluated changes from baseline measurement in tear break-up time (TBUT) and RNFL thickness measured by OCT. In addition to baseline screening, subjects underwent testing and negative pressure application on day 0 and returned 1 week after the initial visit for clinical testing. The follow-up visit did not include use of the multi-pressure dial (MPD) but repeated baseline testing and evaluated for adverse events. Results No adverse events were reported in the study. After short-term wear of the MPD on day 0, there was a minimal but statistically significant increase of half a line (LogMAR) in BCDVA for study eyes; this increase was not present at 1 week. There were no observed changes in cup-disk ratio and TBUT 1 week after the initial testing. There was a statistically significant pressure reduction in both study and fellow eyes at 1 week following the study, but clinical significance has yet to be determined. Conclusion The MPD, which consists of a pair of goggles connected to a handheld, programmable pump, was well tolerated by subjects enrolled in the study. Key safety parameters remained stable after short-term exposure. The favorable safety results of this study support the safety profile of the MPD and promote further investigation of the device as a potential treatment of glaucoma. Funding Equinox Ophthalmic, Inc. (Newport Beach, CA).

Background: The prevalence of open-angle glaucoma (OAG) varies from 0.5% to 7.0% among populations of diverse ancestry, suggesting the existence of genetic differences. The purposes of this study were to provide insights into genetic causes of OAG, which can result in prevalence and phenotype differences among populations of diverse ancestry for OAG, and to compare allele frequencies of intraocular pressure (IOP) elevation-related SNPs in OAG among Koreans and other ethnic groups. Methods: We collected the data on a total of 135 OAG-associated single nucleotide polymorphisms (SNPs) from a genome-wide association studies (GWAS) catalog. The population-level allele frequencies of these SNPs were derived based on the 1000 Genomes Project and Korean Reference Genome Database. We used Fisher's exact test to assess whether the effect allele at a given SNP was significantly enriched or depleted. Results: European, American, and South Asian populations showed similar heatmap patterns, while African, East Asian, and Korean populations had distinct patterns. Korean population presented different profiles compared to other groups; rs1579050 (FMNL2 gene), rs2024211 (CAV2;CAV1), and rs8141433 (GNB1L;TXNRD2 gene), which are known to be associated with IOP variation, were enriched in Americans, Europeans, and Africans, and depleted in Koreans. These can be the candidates for the causative genes of differences in the prevalence of IOP variation in OAG according to ethnic groups. Conclusions: Differences in allele frequencies associated with IOP related SNPs between Koreans and other ethnicities were observed, which may explain the high prevalence of OAG with normal IOP predominantly in Koreans and East Asians. [ABSTRACT FROM AUTHOR]

Background: We know little about the changes of brain activity in patients with normal-tension glaucoma (NTG). Purpose: To investigate the altered spontaneous brain activity in patients with NTG through the resting state functional magnetic resonance imaging-fractional amplitude of low-frequency fluctuation (rsfMRI-fALFF) technique, and to explore the relationship with optical coherence tomography (OCT) and field of vision. Material and Methods: Twenty patients with NTG and 20 healthy controls (HCs) (matched for sex, age, and level of education) were enrolled. Spontaneous cerebral activity variations were investigated using the rsfMRI-fALFF technique in all individuals. The average fALFF values of patients with NTG and HCs were compared. Results: Compared with HCs, patients with NTG had significantly lower fALFF values in the right angular gyrus and precuneus; however, higher fALFF values in the brain regions were not observed. The values showed statistically significant negative correlation with those of the retinal nerve fiber layer (right angular gyrus: r = -0.607, P = 0.010; right precuneus: r = -0.504, P = 0.020). There was no significant correlation between the fALFF value and cup-disc ratio (right angular gyrus: r = 0.158, P = 0.494; right precuneus: r = -0.087, P = 0.706), mean deviation (right angular gyrus: r = 0.096, P = 0.468; right precuneus: r = 0.026, P = 0.845), and pattern SD value (right angular gyrus: r = 0.064, P = 0.626; right precuneus: r =-0.145, P = 0.268). Conclusion: Abnormal spontaneous activities were detected in numerous brain regions of patients with NTG, which may provide useful information for understanding the dysfunction in NTG. These activity changes in brain regions may be used as effective clinical indicators for NTG. [ABSTRACT FROM AUTHOR]

Purpose: To report the occurrence probability of disc haemorrhage (DH) and risk factors for it in otherwise healthy Japanese normal‐tension glaucoma (NTG) patients who had lower normal intraocular pressure (IOP) and were followed without treatment for 5 years. Methods: A prospective observational study. Normal‐tension glaucoma (NTG) patients with IOP consistently ≤15 mmHg without treatment were enrolled. The presence or absence of DH was checked semi‐annually on the fundus photographs by three independent observers, while patients were followed without treatment. Cox proportional hazards model taking inter‐eye correlation into consideration was adopted to identify risk factors for DH occurrence. The main outcomes were DH occurrence probability during 5‐year period and its risk factors. Results: One hundred seventeen eyes of 90 patients with mean age of 54.1 years, mean deviation value of −3.6 decibels and mean IOP during follow‐up of 12.4 mmHg were included. Disc haemorrhage (DH) was observed at least once in 34 eyes and more than twice in 15 eyes during the follow‐up. The DH occurrence probability at 5 years was 31% (95% confidence interval: 21–40%), and lower myopic refraction (HR = 1.18; p = 0.018), higher IOP during follow‐up (HR = 1.35; p = 0.047) and presence of DH at baseline (HR = 4.19; p = 0.002) were its risk factors. Conclusion: Disc haemorrhage (DH) occurrence probability of Japanese healthy NTG patients with mean IOP of 12.4 mmHg and no systemic and/or topical treatment was 31% at 5 years. Lower myopic refraction, higher IOP and its existence at baseline were its risk factors. [ABSTRACT FROM AUTHOR]

Purpose: Anti-vascular endothelial growth factor (VEGF) injections, while used to effectively treat numerous retinal vascular conditions, can be associated with transient and prolonged ocular hypertension. There is minimal literature detailing the development of normal-tension glaucoma (NTG) following intravitreal anti-VEGF injections. Observations: A 38-year-old Caucasian male with no medical or ocular history was diagnosed with an inferior HRVO with macular edema in the left eye. The patient received a total of eleven monthly intravitreal aflibercept injections over one year, with maintenance of stable vision and intraocular pressure (IOP) throughout the treatment period and during follow-up. Nine months after the last aflibercept injection, cup-to-disc asymmetry, inferior thinning of retinal nerve fiber layer (RNFL), and reduced superior visual field was evident in the left eye. Clinically, the patient was consistent with normal tension glaucoma and thus, the patient was started on daily timolol drops; however, the role of the glaucomatous findings being secondary to repeated injection-related IOP elevations is possible. Conclusions and Importance: While the clinical features based on visual fields and RNFL thinning with unmedicated normotensive IOP may suggest NTG in a patient, this clinical presentation may be a masquerader of NTG with the etiology of the glaucoma optic neuropathy caused by cumulative impact of transient IOP elevations secondary to intravitreal injections.

Purpose: To provide the first report of effective use of bilateral XEN Gel Stent implantation using an ab externo open-conjunctival approach designed to improve bleb function and meet the uniquely low intraocular pressure requirements of a Japanese patient with normal-tension glaucoma refractory to topical medical therapy. Observations: A 54-year-old phakic Japanese woman with severe normal-tension glaucoma on maximally tolerated medical therapy of four topical agents presented with above-goal intraocular pressures and new medication intolerances. She underwent bilateral ab externo open-conjunctival XEN Gel Stent implantation with tenectomy and sub-Tenon's injection of 40μg of mitomycin-C, which resulted in reduction of intraocular pressures by 41.2 and 28.6% to 10 and 10 mmHg in the right and left eyes, respectively at the most recent visit. Postoperatively, a diffuse filtering bleb with good morphology developed in both eyes. The procedure has so far allowed for complete cessation of all four topical medications for up to eight months following surgery without any serious complications. Conclusions: This case illustrates the potential of Xen Gel Stent implantation through an ab externo, open-conjunctival approach to be an effective, simple alternative to trabeculectomy to meet the unique low-pressure requirements of normal-tension glaucoma patients with practical and safety benefits of a micro-invasive approach.

Background: Open-angle glaucoma (OAG) and Alzheimer's disease (AD) are two age-related neurodegenerative diseases of significant public health importance. Epidemiological studies have indicated that there might be an association between the disorders. Methods: Predictors of AD, including mixed and unspecified dementia, were analysed in a cohort of 712 residents aged 65-74 years, examined in a population survey in the rural district of Tierp, Sweden, from 1984 to 1986. To expand the sample size, 821 people were recruited by means of glaucoma case records established at the Eye Department in Tierp from 1978 to 2007. In this way, the cohort comprised 1,533 people, representing more than 21,000 person-years at risk. Medical records were reviewed to identify subjects diagnosed with dementia. Those with a follow-up duration shorter than 2 years were excluded. Results: By the conclusion of the study, in August 2020, 307 subjects had received a diagnosis of AD, including mixed and unspecified dementia. Of these cases, 55 were affected with definite OAG at baseline. Higher age and ischemic heart disease were the only predictors of AD identified. In multivariate analysis, adjusting for age, participation in the population survey and competing events, no association was found between OAG and AD (hazard ratio 1.08; 95% confidence interval: 0.80-1.47). Conclusion: In this long-term follow-up study of subjects aged 65-74 years old in Sweden, OAG was not associated with AD. [ABSTRACT FROM AUTHOR]

Purpose: To determine the trans-lamina cribrosa pressure difference (TLCPD) in a cohort of normal community-based patients and the relationship to primary open-angle glaucoma (POAG) and normal-tension glaucoma (NTG)., Design: Retrospective cohort study of the Mayo Clinic Study of Aging., Participants: The Mayo Clinic Study of Aging is a prospective study evaluating the normal aging population., Methods: Mayo Clinic Study of Aging patients who underwent routine lumbar puncture (LP) studies with eye examinations were reviewed. The trans-lamina cribrosa pressure difference was calculated in 2 contexts of intraocular pressure (IOP): (1) maximum IOP at eye visit closest in time to the LP (closest-in-time TLCPD); and (2) IOP before IOP-lowering treatment (pretreatment IOP and pretreatment TLCPD) in POAG and NTG patients. Glaucoma patients without POAG or NTG were excluded. Regression analyses were performed to determine the relationship with glaucoma., Main Outcome Measures: IOP, intracranial pressure, TLCPD, POAG, normal-tension glaucoma (NTG) diagnosis, glaucoma parameters., Results: Five hundred forty-eight patients were analyzed. Of these, there were 38 treated glaucoma patients (14 POAG and 24 NTG) and 510 nonglaucomatous patients. Cerebral spinal fluid (CSF) opening pressure was 155.0 ± 42.2 mmH 2 O in nonglaucomatous patients, 144.0 ± 34.0 mmH 2 O in POAG (P = 0.15 vs. nonglaucomatous patients), and 136.6 ± 29.3 mmH 2 O in NTG (P = 0.017 vs. nonglaucomatous patients). Intraocular pressure was 15.47 ± 2.9 mmHg in nonglaucomatous patients, 26.6 ± 3.7 mmHg in POAG, and 17.4 ± 3.4 mmHg in NTG. The closest-in-time TLCPD in the nonglaucomatous cohort was 4.07 ± 4.22 mmHg, which was lower than both the POAG cohort (7.19 ± 3.6 mmHg) and the NTG cohort (5.79 ± 4.5 mmHg, P = 0.04). Pretreatment TLCPD for the overall glaucoma cohort was 10.57 ± 6.1 mmHg. The POAG cohort had a higher pretreatment TLCPD (16.05 ± 5.2 mmHg) than the NTG cohort (7.37 ± 4.1 mmHg; P < 0.0001). Closest-in-time TLCPD for the nonglaucoma cohort (4.07± 4.2 mmHg) was significantly lower than pretreatment TLCPDs for both POAG (16.05 ± 5.2 mmHg; P < 0.0001) and NTG (7.37 ± 4.1 mmHg; P < 0.0001) cohorts., Conclusions: This study establishes the baseline TLCPD in a large cohort of normal, community-based patients. The differences in regression analysis between TLCPD and IOP suggests NTG pathophysiology is partially driven by TLCPD, but is also likely multifactorial., Financial Disclosure(s): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article., (Copyright © 2023 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.)

Purpose: A new glaucoma treatment device, known as the multi-pressure dial (MPD), has been introduced, which offers a novel approach to IOP reduction by delivering negative pressure to the periocular region. Clinical studies have demonstrated the IOP-lowering effect of the MPD via direct measurements using pneumatonometry. It remains unclear whether the eyelids, when closed, affect the transmission of negative pressure and subsequently affect IOP reduction. This study aimed to evaluate whether the transfer of negative pressure and subsequent decrease in IOP are altered by the presence of synthetic eyelid tissue. Methods: A model with 13 different configurations controlling for eyelid material type, presence of slit/opening, and eyelid–cornea contact was employed. The slit modification was employed to mimic the physiologic separation that exists between the eyelids. Baseline IOP within an eye model was set at various levels ranging from 10 to 30 mmHg with applied negative pressure settings of 10, 15, and 20 mmHg utilized at each baseline IOP. The percentage of vacuum transfer was calculated by comparing baseline IOP to resultant IOP measurements following application of vacuum to the system. Results: In the open configuration (without eyelid tissue), the mean % vacuum transfer was 98.7%. The sealed, full-contact configurations exhibited values of 97.4%, 98.8%, and 97.2%. The slit configurations, which closely mimic the physiologic eyelid, demonstrated a mean % vacuum transfer of 98.7% across all settings. Conclusions: The impact of eyelid tissue on transfer of negative pressure can be isolated and evaluated. The presence of eyelid tissue has an insignificant impact on the transfer of negative pressure, and the IOP reduction achievable with the MPD would not be altered with the eyelids closed. [ABSTRACT FROM AUTHOR]

Peter Wostyn Department of Psychiatry, PC Sint-Amandus, Beernem, BelgiumCorrespondence: Peter WostynDepartment of Psychiatry, PC Sint-Amandus, Reigerlostraat 10, Beernem, 8730, BelgiumTel + 32-472713719Fax + 32-50-819720Email wostyn.peter@skynet.be View the original paper by Pircher and colleagues

Yasutaka Takagi,1 Kazunori Santo,1 Masayo Hashimoto,1 Takeo Fukuchi2 1Japan Medical Affairs Group, Santen Pharmaceutical Co., Ltd., Osaka, Japan; 2Division of Ophthalmology and Visual Science, Graduate School of Medical and Dental Sciences, Niigata University, Niigata, Japan Purpose: This paper aimed to evaluate the intraocular pressure (IOP)-lowering effects of prostaglandin analogs (PGAs) in Japanese patients with normal-tension glaucoma (NTG) by reviewing the current literature. Methods: In February 2018, database searches were performed in PubMed, Embase, ProQuest, and the Japanese databases JAPICDOC and JMEDPlus. Studies were sorted into two categories: Category 1 consisted of studies of patients with NTG who reported reduced IOP values and Category 2 consisted of studies of patients with NTG who had IOP values at predosing and a final evaluation point. Search terms included ([unoprostone or latanoprost or travoprost or bimatoprost or tafluprost] and [glaucoma] and [Japan or Japanese]). The weighted ocular hypotensive efficacy was calculated. A scatter plot analysis was performed and a regression equation was calculated for each medication. The fitting of each regression equation was evaluated by the least squares method. Results: Eleven articles were eligible for Category 1 and 25 articles for Category 2. In the rank order of IOP-lowering efficacy of PGAs, bimatoprost was the strongest and latanoprost the weakest. Travoprost and tafluprost had almost the same level of ocular hypotensive effect, and both were stronger than latanoprost. The scatter plot analysis showed that all PGAs reduced IOP by 15%–20%. At higher IOP (17–18 mmHg), the ocular hypotensive effect was almost the same with latanoprost, travoprost, and tafluprost. In contrast, at lower IOP (12–15 mmHg), the IOP reduction with latanoprost was weaker than with travoprost or tafluprost. Conclusion: This literature review of the ocular hypotensive effects of PGAs in Japanese patients with NTG highlighted that PGAs had different ocular hypotensive effects. Ophthalmologists should understand the IOP-lowering profiles of various PGAs and apply them to patients with NTG on a case-by-case basis. Trial registration: UMIN Clinical Trials Registry UMIN000032344. Keywords: Japanese, normal-tension glaucoma, ocular hypotensive effects, prostaglandin analogs

Normal-tension glaucoma (NTG) that occurs despite normal intraocular pressure has genetic predisposition. Since retinal ganglion cells (RGCs) are a key node in pathogenesis of glaucoma, neurodegeneration of RGCs is thought to be the main cause increasing the risk of NTG development. Here, we aimed to investigate the association of polymorphisms in RGC development genes with NTG development. We performed a case–control association study of 435 patients with NTG and 419 normal controls. We genotyped four single nucleotide polymorphisms (SNPs) in genes responsible for RGC development, namely POU4F2 (rs13152799 and rs1504360), POU4F1 (rs9601092), and ISL1 (rs2288468), by either real-time PCR or PCR-RFLP, and evaluated its association with the risk of NTG development. No significant association was observed between the candidate SNPs and NTG development. To the best of our knowledge, this is the first report exploring the association between genes regulating RGC development and NTG susceptibility. Our data could provide a reference for further researches that focus on finding additional potential SNPs of POU4F2, POU4F1, ISL1 or other RGC development genes for NTG. [ABSTRACT FROM AUTHOR]

Purpose: The efficacy and safety of the trabecular micro-bypass stents (iStent and iStent inject) have been well documented in various open-angle glaucoma subtypes. However, their outcomes remain understudied in normal-tension glaucoma (NTG). The present study aimed to assess the 1-year outcomes related to the implantation of two second-generation trabecular micro-bypass stents (iStent inject) concomitant with cataract surgery (CE-TMS), exclusively in eyes with NTG. Methods: This multi-center, consecutive case series included eyes with cataract and normal-tension glaucoma that underwent CE-TMS to reduce intraocular pressure or glaucoma medication use. The 12-month efficacy measures included change in average intraocular pressure (IOP) and medication burden. Safety included change in best-corrected visual acuity, cup-to-disc ratio, visual field mean-deviation and retinal nerve fiber layer thickness. Intra- or postoperative adverse events were noted. Results: A total of 62 eyes with mild-to-severe NTG and average preoperative IOP of 15.82 ± 2.94 mmHg on 1.50 ± 1.28 glaucoma medications were included. Postoperatively, IOP declined by 22% from 15.82 ± 2.94 mmHg to 12.32 ± 2.58 (p < 0.001), all eyes had IOP ≤ 18 mmHg (versus 74% preoperatively), and half had IOP ≤ 12 mmHg (versus 15% preoperatively). Medication burden decreased by 70% from 1.50 ± 1.28 to 0.45 ± 0.86 (p < 0.001), and 73% of the eyes were medication-free (versus 23% preoperatively). Safety was favorable, with no evidence of sight-threatening adverse events. Conclusion: Implantation of iStent inject (two second-generation trabecular micro-bypass stents) combined with cataract surgery is efficacious in reducing IOP and medication burden with a favorable safety profile in eyes with mild-to-severe NTG. [ABSTRACT FROM AUTHOR]

Assessing the papillomacular nerve fiber bundle (PMB) can identify glaucoma patients with decreased visual acuity. In this study, we explore efficient methods for evaluating PMB thickness in glaucoma patients, based on swept source-optical coherence tomography (SS-OCT). This study included 347 eyes of 205 open-angle glaucoma (OAG) patients. Patients were excluded if they had best-corrected decimal visual acuity < 0.3, axial length >28 mm, non-glaucoma ocular disease, or systemic disease affecting the visual field. We obtained vertical 12.0 × 9.0 mm 3D volume scans covering both the macular and optic disc regions with SS-OCT (DRI OCT Triton, Topcon), and measured the thickness of the PMB, as well as average macular retinal nerve fiber layer thickness (mRNFLT) and macular ganglion cell complex thickness (mGCCT) in the macular map and temporal-quadrant circumpapillary RNFL thickness (tcpRNFLT). We also measured central-strip RNFLT (csRNFLT) and GCC (csGCCT) in a 1.5 × 6.6 mm area of the scan centered between the fovea and optic nerve head. CsRNFLT and csGCCT were divided lengthwise into three 1.5 × 2.2 mm sections. We then calculated Spearman's rank correlation coefficient between these OCT measurements and visual acuity. Logistic regression analysis was used to find the cutoff value for the OCT measurements to predict logMAR < 0. The correlation coefficients with logMAR were 0.38 for mRNFLT, 0.44 for mGCCT, 0.37 for middle csRNFLT, 0.50 for middle csGCCT, and 0.33 for tcpRNFLT (all P <.0001). For middle csGCCT, the area under the curve indicating decreased visual acuity was 0.80, with a cutoff value of 88.6 μm (P <.001). We found strong associations between OCT parameters in the PMB, especially middle csGCCT, and visual acuity in patients with OAG. The thickness of the PMB may therefore be valuable information for glaucoma care and may help prevent visual acuity disturbance. [ABSTRACT FROM AUTHOR]

Purpose: To quantitatively analyze the topographic features of localized retinal nerve fiber layer (RNFL) defects according to baseline intraocular pressure (IOP) level in cases of early primary open-angle glaucoma (POAG). Study design: Retrospective comparative study. Methods: POAG patients meeting the following conditions were consecutively included: (1) baseline office-hour diurnal IOP ≤ 21 mmHg, (2) 1 localized RNFL defect as observed on red-free fundus photography, and (3) corresponding visual field defect. Defects' approximations to the macula (angle α) and width (angle ß) as well as the angle between the disc long axis and the vertical meridian line (angle Ɣ) were measured on red-free fundus photography. The corrected angle α was calculated as the difference between angles α and Ɣ. The defect area's RNFL thickness was calculated by means of optical coherence tomography's Advanced Extraction analysis utility. Results: Comparative analysis was performed between 2 groups: 45 eyes of 45 patients with low-teen IOP (group A: highest IOP ≤ 15 mmHg) and 49 eyes of 49 patients with high-teen IOP (group B: lowest IOP > 15 mmHg). In group A, the mean baseline IOP was lower (12.9 ± 1.3 vs 17.1 ± 1.0 mmHg; P <.001), the corrected angle α was smaller (32.4 ± 15.1 vs 39.5 ± 13.1 degrees; P =.017), and the defect area's RNFL thickness was thinner (66.3 ± 16.8 vs 76.3 ± 14.9 μm; P =.003) than in group B; angle ß showed no intergroup difference (P =.230). Conclusions: In POAG patients with low-teen IOP relative to those with high-teen IOP, localized RNFL defects were closer to the macula. In addition, the RNFL thickness of the defect area was markedly thinner. [ABSTRACT FROM AUTHOR]

Purpose: To seek the threshold value of Bruch's membrane opening-minimum rim width (BMO-MRW) where visual field (VF) damage occurs in open-angle glaucoma (OAG) and explore whether there are structural differences between primary open-angle glaucoma (POAG) and normal-tension glaucoma (NTG). Methods: We recruited 83 healthy and 106 glaucoma (49 with POAG and 57 with NTG) subjects for this study. All subjects underwent optical coherence tomography (OCT), BMO-MRW scans, and Humphrey visual field (VF) analyzer examination. Global and sectoral BMO-MRW was correlated with the corresponding VF according to the Garway-Heath map. Using a broken-stick statistical model, the structure–function relationship of VF values and BMO-MRW, the tipping point where VF defects were associated with a reduction in BMO-MRW and the slopes above and below the tipping point were determined and compared between POAG and NTG. Results: The tipping point of global BMO-MRW for VF impairment was 234.38 μm, 228.09 μm, and 249.68 μm in the OAG, POAG, and NTG groups, respectively. The slope below the tipping point was significantly steeper than the slope above it in all quadrants of each group (p < 0.001). The tipping point in NTG in the inferotemporal and nasal quadrants was smaller than that of POAG, especially in the inferotemporal quadrant. Conclusion: In OAG, BMO-MRW loss seems to occur before the onset of perimetric impairment. Compared with POAG, NTG appears to have more severe rim damage, especially in the inferotemporal quadrant at the onset of detectable VF defects. [ABSTRACT FROM AUTHOR]

Glaucoma is a chronic, debilitating disease and a leading cause of global blindness. Despite treatment efforts, 10% of patients demonstrate loss of vision. In the US, > 80% of glaucoma cases are classified as open-angle glaucoma (OAG), with primary open-angle (POAG) being the most common. Although there has been tremendous innovation in the surgical treatment of glaucoma as of late, two clinical variants of OAG, normal-tension glaucoma (NTG) and severe POAG, are especially challenging for providers because patients with access to care and excellent treatment options may progress despite achieving a "target" intraocular pressure value. Additionally, recent research has highlighted the importance of nocturnal IOP control in avoiding glaucomatous disease progression. There remains an unmet need for new treatment options that can effectively treat NTG and severe POAG patients, irrespective of baseline IOP, while overcoming adherence limitations of current pharmacotherapies, demonstrating a robust safety profile, and more effectively controlling nocturnal IOP. Funding The Rapid Service Fees were funded by the corresponding author, Tanner J. Ferguson, MD. [ABSTRACT FROM AUTHOR]

Purpose: To assess the performance of machine learning classifiers for prediction of progression of normal-tension glaucoma (NTG) in young myopic patients. Study design: Cross-sectional study. Methods: One hundred and fifty-five eyes of 155 myopic NTG patients (axial length [AL] ≥ 24.00 mm and refractive error ≤ − 3.0 D) between the ages of 20 and 40 were enrolled and divided into training (110) and test (45) sets. Sixty-five eyes showed glaucoma progression as defined by standard automated perimetry, while 91 eyes (nonprogressors) had been stable over the course of a follow-up period of at least 3 years. Two machine learning classifiers were built using the random forest and extremely randomized trees (extra-trees) models. Baseline clinical measurements obtained only at the initial visit were used as input features. The area under the receiver operating characteristic curve (AUC) was calculated to evaluate the accuracy of prediction. Results: Mean age and AL did not significantly differ between the 2 groups on either the training or the test set. The extra-trees model achieved an AUC of 0.881 [95% CI 0.814–0.945], higher than that of the random forest model (0.811 [0.731–0.888]; P = 0.010). The extra-trees model also outperformed all the clinical measurements for prediction of NTG progression, including average macular ganglion cell-inner plexiform layer thickness (0.735 [0.639–0.831]) and average circumpapillary retinal nerve fiber layer thickness (0.691 [0.590–0.792]; both P < 0.001). Conclusions: In young myopic patients, the machine learning classifier with the extra-trees model can predict glaucomatous progression more effectively than clinical diagnostic parameters. [ABSTRACT FROM AUTHOR]

Background: Previous studies have reported the association of HK2 and NCK2 genes with normal-tension glaucoma (NTG) in Japan, but there has been no follow-up study in other countries, so the relevance of these genes to NTG appears uncertain at present. Thus, we investigated the relationship between the HK2 and NCK2 genes and NTG in a Korean NTG cohort. Methods: In total, 154 unrelated Korean patients with NTG and 101 normal Korean controls were recruited. Thus, a total of 255 participants were analyzed for NCK2 (rs2033008) and HK2 (rs678350) gene polymorphisms. Results: The minor allele frequency (MAF) of rs678350 was significantly higher in NTG patients (MAF = 0.32) than in controls (MAF = 0.23) (OR, 1.586; 95% CI, 1.058 to 2.375; P = 0.028). This trend was more significant in the dominant model (OR, 1.908; 95% CI, 1.144 to 3.180; P = 0.015). When we performed logistic regression analysis to adjust for age, both the allelic and dominant models were still statistically significant. No significant difference was observed in rs2033008 allele or genotype frequencies between the NTG patients and control subjects. Conclusions: The current study suggested that HK2 gene polymorphism may contribute to the genetic susceptibility to NTG. [ABSTRACT FROM AUTHOR]

Daisuke Takemoto, Tomomi Higashide, Yoshiaki Saito, Shinji Ohkubo, Sachiko Udagawa, Hisashi Takeda, Kazuhisa Sugiyama Department of Ophthalmology, Kanazawa University Graduate School of Medical Science, Kanazawa, Japan Purpose: We conducted a prospective study in patients with normal-tension glaucoma (NTG) who received either isopropyl unoprostone or latanoprost. We compared the drugs in terms of their effects on intraocular pressure (IOP) and visual field loss progression over a 3-year period. Study design: Prospective, randomized controlled study. Methods: We enrolled 48 patients with newly diagnosed NTG at Kanazawa University Hospital. Eligible patients were randomly allocated (1:1) to receive either unoprostone or latanoprost ophthalmic solutions. The primary outcomes were IOP changes and visual field deterioration within 36 months. Visual field changes were analyzed: the cumulative survival rates were calculated in terms of mean deviation, pattern standard deviation, and total deviation of the upper or lower hemi-visual field, each visual field sector, and guided progression analysis. In addition, we evaluated the progression of glaucomatous optic disc changes using fundus photography and confocal scanning laser ophthalmoscopy. Results: The mean pretreatment IOP was 15.0±2.4 mmHg in the Unoprostone group and 15.2±1.9 mmHg in the Latanoprost group. The mean IOP during the treatment period was 13.7±2.3 mmHg in the Unoprostone group and 13.0±1.8 mmHg in the Latanoprost group. In both groups, the IOP decreased significantly (p

AIM: To investigate the change of anterior chamber angle morphology and intraocular pressure (IOP) reduction after cataract surgery in patients with normal-tension glaucoma (NTG) using swept-source optical coherence tomography (SS-OCT). METHODS: This prospective, comparative, observational study recruited patients into two groups. Group 1 was the control group including normal subjects except those with cataracts (cataract group, n=67 eyes of 67 patients), and group 2 was NTG group including patients who were diagnosed with NTG and cataracts (n=43 eyes of 43 patients), which were treated with phacoemulsification and intraocular lens implantation. Before surgery, and at postoperative 1 and 6mo, anterior chamber angles were evaluated by SS-OCT under dark conditions using three-dimensional angle analysis scan protocol. Angle opening distance (AOD), angle recess area (ARA), and trabecular-iris surface area (TISA) at four quadrants (temporal, nasal, superior, and inferior) were calculated automatically by SS-OCT, after the observer marked scleral spurs. RESULTS: A total of 106 patients (54 males and 52 females) were enrolled in the study. Angle parameters, AOD, ARA, and TISA were increased after surgery in both groups. However, changes of angle parameters were only significant in group 2. In group 2, preoperative IOP was 13.2±2.9 mm Hg, and postoperative IOP at 1 and 6mo were 10.5±3.0 and 10.7±2.8 mm Hg, respectively. In group 1, preoperative IOP was 12.4±2.8 mm Hg, and postoperative IOP at 1 and 6mo were 11.6±2.5 and 12.0±2.8 mm Hg, respectively. After cataract surgery, angle parameters changed significantly while IOP significantly reduced and was maintained in group 2 (P

Objective: To compare peripapillary vessel density using optical coherence tomography angiography (OCT-A) in eyes of healthy people, primary open-angle glaucoma (POAG), and normal-tension glaucoma (NTG)., Methods: Thirty patients with POAG, 27 patients with NTG, and 29 healthy individuals in the control group were assessed. Capillary vessels in peripapillary retinal nerve fiber layer (RNFL) represented by whole image RPC (radial peripapillary capillary) density in an AngioDisc scan 4.5 × 4.5 mm centered on the optic disc, and ONH morphological variables (disc area, rim area, cup to disc area ratio (CDR)), and average peripapillary RNFL thickness were measured., Results: Differences in mean RPC, RNFL, disc area, rim area, and CDR between the groups were statistically significant (P < 0.05). The difference in RNFL thickness and rim area was not significant between NTG and healthy groups, while RPC and CDR showed a statistically significant difference between all pairs. The vessel density in the POAG group was 8.25% and 11.7% lower compared to the NTG and healthy groups, respectively; while the mean difference was less (2.97%) for the NTG and healthy group. In the POAG group, 67.2% of the variation in RPC can be explained by a model containing CDR and RNFL thickness, and in normal eyes 38.8% of the changes using a model containing RNFL., Conclusion: The peripapillary vessel density is reduced in both types of glaucoma. The vessel density in NTG was significantly lower than in the healthy eyes, despite the lack of significant difference in RNFL thickness and neuroretinal rim area between them., Competing Interests: Declaration of conflicting interestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Glaucoma is a neurodegenerative disease that affects the retinal ganglion cells (RGCs). The main risk factor is elevated intraocular pressure (IOP), but the actual cause of the disease remains unknown. Emerging evidence indicates that metabolic dysfunction plays a central role. The aim of the current study was to determine and compare the effect of universal hypoxia on the metabolomic signature in plasma samples from healthy controls ( n = 10), patients with normal-tension glaucoma (NTG, n = 10), and ocular hypertension (OHT, n = 10). By subjecting humans to universal hypoxia, we aim to mimic a state in which the mitochondria in the body are universally stressed. Participants were exposed to normobaric hypoxia for two hours, followed by a 30 min recovery period in normobaric normoxia. Blood samples were collected at baseline, during hypoxia, and in recovery. Plasma samples were analyzed using a non-targeted metabolomics approach based on liquid chromatography coupled with high-resolution mass spectrometry (LC-HRMS). Multivariate analyses were conducted using principal component analysis (PCA) and orthogonal partial least squares-discriminant analysis (OPLS-DA), and univariate analysis using the Wilcoxon signed-rank test and false discovery rate (FDR) correction. Unique metabolites involved in fatty acid biosynthesis and ketone body metabolism were upregulated, while metabolites of the kynurenine pathway were downregulated in OHT patients exposed to universal hypoxia. Differential affection of metabolic pathways may explain why patients with OHT initially do not suffer or are more resilient from optic nerve degeneration. The metabolomes of NTG and OHT patients are regulated differently from control subjects and show dysregulation of metabolites important for energy production. These dysregulated processes may potentially contribute to the elevation of IOP and, ultimately, cell death of the RGCs.

Ventriculoperitoneal shunt placement is the most commonly used treatment of normal-pressure hydrocephalus (NPH). It has been hypothesized that normal-tension glaucoma (NTG) is caused by the treatment of NPH by using the shunt to reduce intracranial pressure (ICP). The aim of this study is to review the literature published regarding this hypothesis and to emphasize the need for neuro-ophthalmic follow-up for the concerned patients. The source literature was selected from the results of an online PubMed search, using the keywords “hydrocephalus glaucoma” and “normal-tension glaucoma shunt”. One prospective study on adults, one prospective study on children, two retrospective studies on adults and children, two case reports, three review papers including medical hypotheses, and one prospective study on monkeys were identified. Hypothesis about the association between the treatment of NPH using the shunt to reduce ICP and the development of NTG were supported in all reviewed papers. This suggests that a safe lower limit of ICP for neurological patients, especially shunt-treated NPH patients, should be kept. Thus, we proposed to modify the paradigm of safe upper ICP threshold recommended in neurosurgery and neurology into the paradigm of safe ICP corridor applicable in neurology and ophthalmology, especially for shunt-treated hydrocephalic and glaucoma patients.

Purpose: To assess the efficacy and safety of filtration surgery using the EX-PRESS glaucoma filtration device in patients with normal-tension glaucoma (NTG). Study design: Prospective, single-arm, multicenter interventional case series. Methods: Eyes with NTG underwent EX-PRESS implantation with or without cataract surgery. The efficacy and safety were assessed at 1 day; 1 and 2 weeks; and 1, 3, 6, and 12 months after surgery. The main outcome measure was reduction in intraocular pressure (IOP) from baseline at 3, 6, and 12 months after surgery. Safety assessments included adverse event incidence, postoperative inflammation, and corneal endothelial cell density. Results: Thirty-two Japanese patients (37 eyes) with NTG were enrolled. The mean IOP decreased from 14.8 ± 2.3 mmHg at baseline to 10.0 ± 3.1 mmHg at 12 months after surgery (mean reduction 4.9 ± 4.2 mmHg [31.1%]; P <.0001). IOP-lowering medication use decreased from a mean of 3.3 medications per eye before surgery to 0.1 medications per eye at 12 months after surgery. IOP reductions > 20% were achieved by 61.5% of the eyes at 12 months. Adverse events were typical for filtration procedures, and none was deemed device-related. Postoperative inflammation was mild and self-limiting. The mean corneal endothelial cell density had decreased by 3.3% at 12 months after surgery. Conclusion: The EX-PRESS glaucoma filtration device is safe and effective for filtration surgery in patients with NTG, providing mean IOP reduction consistent with recommendations based on the Collaborative NTG Study. [ABSTRACT FROM AUTHOR]

The patient performed a 30-2 glaucoma tendency-oriented perimetry visual field and optic nerve head imaging with optical coherence tomography. Glaucoma treatment in patients diagnosed with sleep apnoea has been thoroughly studied. The hazard ratio of developing glaucoma in those patients left untreated was 2:15;[10] patients undergoing a combination of treatments - either nasal or pharyngeal surgery with continuous positive airway pressure - significantly reduced the hazard ratio to levels not statistically different from controls. [Extracted from the article]

Purpose: In order to clarify the association between peripapillary vascular changes and disc hemorrhage (DH) occurrences over time, we analyzed the density of radial peripapillary capillary (RPC) and clinical parameters during follow-up periods in patients with normal-tension glaucoma (NTG). Methods: Seventy-seven eyes of 77 NTG patients were subjected to analysis. We selected patients who had an initial optical coherence tomography angiography (OCTA) scan in 2015 and who had another OCTA scan in 2018 with both OCTA scans showing good-quality images. We investigated the relationships between DH occurrence and each of the following parameters: RPC density, circumpapillary retinal nerve fiber layer (cpRNFL) thickness slope and total deviation (TD) slope. Results: In the period between the initial and final OCTA, we categorized the patients into 53 sides with DH (DH group) and 101 sides without DH (non-DH group). The ΔRPC density of sides with DH was significantly greater than that of sides without DH (DH, − 4.42 ± 6.43%; without DH, − 2.48 ± 5.29%; p = 0.0469). The cpRNFL thickness slope of sides with DH was significantly faster than that of sides without DH (DH, − 2.85 ± 3.17; without DH, − 0.74 ± 2.46 μm/y; p < 0.0001). The TD slope of sides with DH was significantly faster than that of sides without DH (DH, − 0.50 ± 0.77; without DH, − 0.22 ± 0.53 dB/y; p = 0.0163). As DH occurrence increased, the RPC density significantly decreased (r = −0.255, p = 0.0014). Stepwise multiple regression analysis to identify factors influencing RPC changes showed that frequency of DH (β = − 0.224, p = 0.008) and central corneal thickness (β = − 0.220, p = 0.009) were significantly associated with RPC changes. Conclusions: DH occurrence may prompt the structural and vascular deterioration of NTG. [ABSTRACT FROM AUTHOR]

Objectives: Evaluate the correlation between basal macular circulation and late structural damage in progressed high-tension glaucoma (HTG) and normal-tension glaucoma (NTG) via optical coherence tomography angiography (OCTA). Methods: Patients who received an OCTA examination were divided into progressed HTG, progressed NTG, and well-controlled HTG (control) groups. Superficial macular vessel density (SmVD), deep macular vessel density (DmVD), foveal avascular zone (FAZ), and flow area of the outer retina and choriocapillaris were obtained by one OCTA device. Associations between macular angiography and glaucoma parameters, including the visual field, retinal nerve fiber layer, and ganglion cell complex, were analyzed. Results: A total of 60 eyes from 60 patients were enrolled. The progressed HTG and NTG groups had lower SmVD than the control group, while the progressed NTG group had lower DmVD and a larger FAZ than the control group. The flow area of the outer retina in the progressed HTG group was lower than that of the control. A significant correlation between SmVD and glaucoma parameters was found in the progressed HTG group, while a similar correlation between SmVD and DmVD to glaucoma parameters was observed in the progressed NTG group. Conclusion: The progressed HTG and NTG patients showed an impaired vascular intake before significant disease development compared to well-controlled cases. [ABSTRACT FROM AUTHOR]

Introduction: Prospective, open-label, non-randomized, single site study to assess the safety and tolerability of a multi-pressure dial. Methods: 30 healthy subjects received application of negative pressure (–15 mmHg) in one eye for 30 minutes and ambient atmospheric pressure in the contralateral eye. To evaluate safety, the primary outcome measures included best corrected visual acuity (BCVA), intraocular pressure (IOP) changes from baseline, slit-lamp and dilated fundus examination findings, and rate of adverse events. Exploratory analyses included in this study also evaluated changes from baseline measurement in tear break-up time (TBUT) and RNFL thickness measured by OCT. In addition to baseline screening, subjects underwent testing and negative pressure application on day 0 and returned 1 week after the initial visit for clinical testing. The follow-up visit did not include use of the multi-pressure dial (MPD) but repeated baseline testing and evaluated for adverse events. Results: No adverse events were reported in the study. After short-term wear of the MPD on day 0, there was a minimal but statistically significant increase of half a line (LogMAR) in BCDVA for study eyes; this increase was not present at 1 week. There were no observed changes in cup-disk ratio and TBUT 1 week after the initial testing. There was a statistically significant pressure reduction in both study and fellow eyes at 1 week following the study, but clinical significance has yet to be determined. Conclusion: The MPD, which consists of a pair of goggles connected to a handheld, programmable pump, was well tolerated by subjects enrolled in the study. Key safety parameters remained stable after short-term exposure. The favorable safety results of this study support the safety profile of the MPD and promote further investigation of the device as a potential treatment of glaucoma. Funding: Equinox Ophthalmic, Inc. (Newport Beach, CA). [ABSTRACT FROM AUTHOR]

Purpose: Vascular factors have been suggested to influence the development and progression of glaucoma. They are thought to be especially relevant for normal‐tension glaucoma (NTG) patients. We aim to investigate which vascular factors, including advanced vascular examinations, better describe patients with NTG comparing to those with primary open‐angle glaucoma (POAG). Methods: The Leuven Eye Study database (182 NTG and 202 POAG patients; similar structural and functional damage) was used to compute three multivariate logistic regression models: a conventional model (conventional parameters only, including vascular‐related self‐reported phenomena, such as migraine or peripheral vasospasm); an advanced vascular model (advanced vascular parameters only: colour Doppler imaging (CDI), retinal oximetry, ocular pulse amplitude and choroidal thickness); and a global model, in which both types of parameters were allowed. Receiver operating characteristic (ROC) curves and corresponding areas under the curve (AUC) were calculated and compared between models. Results: Patients with NTG had a higher resistive index and lower early systolic acceleration (ESA) in their retrobulbar vessels and a smaller arteriovenous retinal oxygen saturation difference. The global model (AUC 0.743) showed a significantly better discriminative ability when compared to either the conventional (AUC 0.687, p = 0.049) or the advanced vascular (AUC 0.677, p = 0.005) models. Also, the conventional and the advanced vascular models showed a similar discriminative ability (p = 0.823). Conclusion: Patients with NTG have more signs of vascular dysfunction. Clinical conventional parameters, such as asking simple vascular‐related questions, combined with advanced vascular examinations provide information to better understand the value that non‐IOP‐related factors play in NTG. [ABSTRACT FROM AUTHOR]

Despite the importance of the early detection of glaucoma, most patients with progressive glaucoma show minimal symptoms. We aimed to evaluate biomarkers for glaucoma diagnosis in Korea. Forty-two volunteers with/without open-angle glaucoma were enrolled from January through October 2015—divided into a control or open-angle glaucoma group, which was further divided into normal-tension glaucoma (NTG) and high-tension glaucoma (HTG) groups—and underwent assessments for myelin basic protein (MBP), heat shock protein 60, anti-Sjögren’s-syndrome-related antigen A (SSA) and antigen B (SSB), anti-α-fodrin, and anti-nucleic acid. The glaucoma group showed a higher serum MBP level and lower serum anti-α-fodrin antibody level than the control group (p < 0.05). The NTG group showed higher serum anti-SSA and anti-SSB levels and lower anti-α-fodrin IgG/IgA levels than the HTG group. In the receiver operating characteristic curve analysis, the area under the curve (AUC) for serum MBP level was 0.917 in discriminating between controls and patients with glaucoma. Between the NTG and HTG groups, anti-SSA, anti-SSB, and anti-α-fodrin IgG/IgA levels showed an AUC above 0.8. Thus, these biomarkers were useful for diagnosing glaucoma and discriminating between controls and patients with glaucoma, and patients with NTG and HTG.

Background and Objective: Glaucoma is a progressive optic neuropathy in which the optic nerve is damaged. The optic nerve is exposed not only to intraocular pressure (IOP) in the eye, but also to intracranial pressure (ICP), as it is surrounded by cerebrospinal fluid in the subarachnoid space. Here, we analyse ICP differences between patients with glaucoma and healthy subjects (HSs). Materials and Methods: Ninety-five patients with normal-tension glaucoma (NTG), 60 patients with high-tension glaucoma (HTG), and 62 HSs were included in the prospective clinical study, and ICP was measured non-invasively by two-depth transcranial Doppler (TCD). Results: The mean ICP of NTG patients (9.42 ± 2.83 mmHg) was significantly lower than that of HSs (10.73 ± 2.16 mmHg) (p = 0.007). The mean ICP of HTG patients (8.11 ± 2.68 mmHg) was significantly lower than that of NTG patients (9.42 ± 2.83 mmHg) (p = 0.008) and significantly lower than that of HSs (10.73 ± 2.16 mmHg) (p < 0.001). Conclusions: An abnormal ICP value could be one of the many influential factors in the optic nerve degeneration of NTG patients and should be considered as such instead of just being regarded as a “low ICP”.

Tomoko Naito,1 Keiji Yoshikawa,2 Shiro Mizoue,3 Mami Nanno,4 Tairo Kimura,5 Hirotaka Suzumura,6 Yuzo Umeda,7 Fumio Shiraga1 1Department of Ophthalmology, Okayama University Graduate School of Medicine, Okayama, Japan; 2Yoshikawa Eye Clinic, Tokyo, Japan; 3Department of Ophthalmology, Ehime University Graduate School of Medicine, Ehime, Japan; 4Kagurazaka Minamino Eye Clinic, 5Ueno Eye Clinic, 6Suzumura Eye Clinic, Tokyo, Japan; 7Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Okayama, Japan Purpose: To analyze the relationship between visual field (VF) progression and baseline refraction in Japanese patients with primary open-angle glaucoma (POAG) including normal-tension glaucoma.Patients and methods: In this retrospective study, the subjects were patients with POAG who had undergone VF tests at least ten times with a Humphrey Field Analyzer (Swedish interactive thresholding algorithm standard, Central 30-2 program). VF progression was defined as a significantly negative value of mean deviation (MD) slope at the final VF test. Multivariate logistic regression models were applied to detect an association between MD slope deterioration and baseline refraction.Results: A total of 156 eyes of 156 patients were included in this analysis. Significant deterioration of MD slope was observed in 70 eyes of 70 patients (44.9%), whereas no significant deterioration was evident in 86 eyes of 86 patients (55.1%). The eyes with VF progression had significantly higher baseline refraction compared to those without apparent VF progression (-1.9±3.8 diopter [D] vs -3.5±3.4 D, P=0.0048) (mean ± standard deviation). When subject eyes were classified into four groups by the level of baseline refraction applying spherical equivalent (SE): no myopia (SE > -1D), mild myopia (-1D ≥ SE > -3D), moderate myopia (-3D ≥ SE > -6D), and severe myopia (-6D ≥ SE), the Cochran–Armitage trend analysis showed a decreasing trend in the proportion of MD slope deterioration with increasing severity of myopia (P=0.0002). The multivariate analysis revealed that baseline refraction (P=0.0108, odds ratio [OR]: 1.13, 95% confidence interval [CI]: 1.03–1.25) and intraocular pressure reduction rate (P=0.0150, OR: 0.97, 95% CI: 0.94–0.99) had a significant association with MD slope deterioration.Conclusion: In the current analysis of Japanese patients with POAG, baseline refraction was a factor significantly associated with MD slope deterioration as well as intraocular pressure reduction rate. When baseline refraction was classified into four groups, MD slope in myopia groups was less deteriorated as compared to those in the emmetropic/hyperopic group.Keywords: primary open-angle glaucoma, normal-tension glaucoma, myopia, refraction, visual field progression, MD slope, intraocular pressure reduction rate