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BACKGROUND: Intraocular pressure (IOP) monitoring in glaucoma management is evolving with novel devices. We investigated the reproducibility of 24 hour profiles on two consecutive days and after 30 days of self-measurements via telemetric IOP monitoring. METHODS: Seven primary patients with open-angle glaucoma previously implanted with a telemetric IOP sensor in one eye underwent automatic measurements throughout 24 hours on two consecutive days (day 1 and day 2). Patients wore an antenna adjacent to the study eye connected to a reader device to record IOP every 5 min. Also, self-measurements in six of seven patients were collected for a period of 30 days. Analysis included calculation of hourly averages to correlate time-pairs of day 1 versus day 2 and the self-measurements vers day 2. RESULTS: The number of IOP measurements per patient ranged between 151 and 268 on day 1, 175 and 268 on day 2 and 19 and 1236 during 30 days of self-measurements. IOP time-pairs of automatic measurements on day 1 and day 2 were significantly correlated at the group level (R=0.83, p

BackgroundTo examine long-term retinal nerve fibre layer thickness (RNFLT) variability and associated clinical factors in African (AD) and European descent (ED) individuals with glaucoma.MethodsThis retrospective cohort study included glaucoma eyes of AD and ED from Diagnostic Innovations in Glaucoma Study/The African Descent and Glaucoma Evaluation Study with ≥4 visits/2 years of follow-up. We calculated optic nerve head RNFLT variability per-examination/visit as the absolute error of its residuals across follow-up. Full, baseline and parsimonious linear-mixed models were fit to evaluate the effects of clinical factors (demographics and ocular characteristics, prior/intervening glaucoma surgeries and cataract extraction (CE), RNFLT thinning rate, scan quality, visit/testing frequency, etc) on RNFLT variability in both races.ResultsThere were 376 and 625 eyes (226 and 349 participants) of AD and ED, and the mean (95% CI) RNFLT variability was 1.62 (1.52, 1.71) µm and 1.42 (1.34, 1.50) µm, respectively (p=0.002). AD and ED had some shared predictors of RNFLT variability, including intraocular pressure fluctuation and scan quality, although the effects varied (p

Background/aimsTo investigate the association between longitudinal changes of foveal avascular zone (FAZ) area and the rate of structural and functional progression in glaucoma.MethodsA longitudinal cohort included 115 eyes (46 glaucoma suspect and 66 primary open-angle glaucoma) of 81 patients having ≥2 year follow-up, and ≥4 visits with optical coherence tomography angiography and visual field (VF). Eyes in the longitudinal cohort with a slope greater than that found in 95 percentile of separate healthy test-retest series for FAZ area were categorised into FAZ progressors; all other eyes were defined as FAZ non-progressors. A generalised linear mixed-effect model was used to investigate the association of FAZ progressors with demographic and clinical characteristics.ResultsFaster ganglion cell complex (GCC) thinning and faster VF mean deviation (MD) loss were found in eyes with FAZ progressors compared with FAZ non-progressors (mean difference: -0.7 (95% CI, -1.4 to -0.1) µm/y; p=0.026, -0.3 (-0.5 to -0.1) dB/y; p=0.017, respectively), while whole image vessel density was not associated with FAZ progressors (p=0.929). SD of intraocular pressure (IOP) and IOP range were also associated with FAZ progressors in separate multivariable models (OR: 1.54 (1.02 to 2.32) per 1 mm Hg higher, p=0.041; OR: 1.20 (1.01 to 1.41) per 1 mm Hg higher; p=0.035, respectively).ConclusionsSignificant FAZ increase was weakly associated with moderately faster rates of both GCC thinning and VF MD loss, but not macular vessel density change in glaucoma eyes. Additional studies are needed to elucidate the pathophysiological associations between macula GCC thinning and FAZ area increases in glaucoma.

Mutations in myocilin (MYOC) are the leading known genetic cause of primary open-angle glaucoma, responsible for about 4% of all cases. Mutations in MYOC cause a gain-of-function phenotype in which mutant myocilin accumulates in the endoplasmic reticulum (ER) leading to ER stress and trabecular meshwork (TM) cell death. Therefore, knocking out myocilin at the genome level is an ideal strategy to permanently cure the disease. We have previously utilized CRISPR/Cas9 genome editing successfully to target MYOC using adenovirus 5 (Ad5). However, Ad5 is not a suitable vector for clinical use. Here, we sought to determine the efficacy of adeno-associated viruses (AAVs) and lentiviruses (LVs) to target the TM. First, we examined the TM tropism of single-stranded (ss) and self-complimentary (sc) AAV serotypes as well as LV expressing GFP via intravitreal (IVT) and intracameral (IC) injections. We observed that LV_GFP expression was more specific to the TM injected via the IVT route. IC injections of Trp-mutant scAAV2 showed a prominent expression of GFP in the TM. However, robust GFP expression was also observed in the ciliary body and retina. We next constructed lentiviral particles expressing Cas9 and guide RNA (gRNA) targeting MYOC (crMYOC) and transduction of TM cells stably expressing mutant myocilin with LV_crMYOC significantly reduced myocilin accumulation and its associated chronic ER stress. A single IVT injection of LV_crMYOC in Tg-MYOCY437H mice decreased myocilin accumulation in TM and reduced elevated IOP significantly. Together, our data indicates, LV_crMYOC targets MYOC gene editing in TM and rescues a mouse model of myocilin-associated glaucoma.

Purpose of reviewAssessing whether lifestyle related factors play a role in causing primary open-angle glaucoma (POAG) is of great value to clinicians, public health experts and policy makers. Smoking is a major global public health concern and contributes to ocular diseases such as cataracts, and age-related macular degeneration through ischemic and oxidative mechanisms. Recently, smoking has been investigated as a modifiable risk factor for glaucoma. In the presence of an association with glaucoma, provision of advice and information regarding smoking to patients may help reduce the burden of disease caused by POAG. Therefore, the aim of this review is to summarize the current evidence regarding the effect of smoking in the pathogenesis of glaucoma and its incidence, progression as well as the benefits of smoking cessation.Recent findingsWhile the association between glaucoma development and smoking history is controversial, in the last decade, several recent studies have helped to identify possible effects of smoking, especially heavy smoking, in regard to glaucomatous progression. Smoking cessation may possibly be protective against glaucoma progression.SummarySmoking may play a role in glaucoma progression and long-term smoking cessation may be associated with lower glaucoma progression. The dose-response relationship between smoking and glaucoma as well as therapeutic potential of smoking cessation needs to be further validated with both preclinical and rigorous clinical studies.

Glaucoma is a chronic optic neuropathy that leads to irreversible vision loss. Aging and family history are the two most important risk factors of glaucoma. One of the most studied genes involved in the onset of open-angle glaucoma is myocilin (MYOC). About 105 germline mutations within MYOC are known to be associated with glaucoma and result in endoplasmic reticulum (ER) stress, which leads to trabecular meshwork (TM) cell death and subsequent intraocular pressure (IOP) elevation. However, only about 4% of the population carry these mutations. An analysis of MYOC somatic cancer-associated mutations revealed a notable overlap with pathogenic glaucoma variants. Because TM cells have the potential to accumulate somatic mutations at a rapid rate due to ultraviolet (UV) light exposure, we propose that an accumulation of somatic mutations within MYOC is an important contributor to the onset of glaucoma.

Background/aimsTo assess the long-term variability of macular optical coherence tomography (OCT)/OCT angiography (OCTA) and visual field (VF) parameters.MethodsHealthy and glaucoma eyes with ≥1-year follow-up were included. 24-2 VF and macular OCT/OCTA parameters, including VF mean deviation (MD), whole-image vessel density (wiVD) and ganglion cell complex thickness (wiGCC) were analysed. Intraclass correlation coefficient (ICC), root mean squared error (RMSE), within-subject test-retest SD (Sw) and test-retest variability were calculated for stable eye cohort (max follow-up=1.5 years). Rates of change and RMSE were evaluated in the extended cohort including all eyes (unlimited follow-up).ResultsFrom a total of 230 eyes (150 participants; age=67.7 years), 86 eyes (37%, 62 participants) were stable. In stable eyes, OCT parameters showed the highest mean (95%) ICC (wiGCC=0.99 (0.99, 0.99)), followed by VF (VF MD=0.91 (0.88, 0.93)) and OCTA (wiVD=0.82 (0.75, 0.87)). RMSE and Sw for VF MD were 0.92 dB and 0.81 dB, respectively, for wiVD were 1.64% and 1.48%, respectively, and for wiGCC, 0.91 µm and 0.78 µm, respectively. The long-term test-rest variability of VF MD, wiVD and wiGCC was 2.2 dB, 4.1% and 2.2 µm, respectively. In the extended cohort (mean follow-up=3.0 years), all parameters had significant rates of change (p

Background/aimsTo evaluate the relationship over time between intraocular pressure (IOP) and the rate of macula whole image vessel density (wiVD) loss and whole image ganglion cell complex (wiGCC) thinning in glaucoma METHODS: From 62 patients in the Diagnostic Innovations in Glaucoma Study, 59 Primary open-angle glaucoma and 27 glaucoma suspect eyes with mean follow-up of 3.2 years were followed. Optical coherence tomography angiography (OCT-A)-based vessel density and OCT-based structural thickness of the same 6×6 mm GCC scan slab were evaluated. Univariable and multivariable linear mixed models were performed for all eyes and also a subset of them in which peak IOP

Background: To evaluate the one-year safety and effectiveness of bio-interventional cyclodialysis and scleral reinforcement in open-angle glaucoma (OAG) patients undergoing cataract surgery. Methods: An ab-interno approach was used to create a sectoral cyclodialysis in OAG patients who were prospectively followed in a consecutive case series. Subsequent visco-cycloplasty with scleral reinforcement using homologous minimally modified allograft scaffold was completed to maintain patency of the cyclodialysis reservoir and increase uveoscleral outflow. Outcomes were mean medicated IOP and mean number of IOP-lowering medications. Safety outcomes were adverse events (AEs) and best-corrected visual acuity (BCVA) changes. Results: Successful cyclodialysis and allograft bio-scaffold reinforcement was achieved in 117 eyes. There was minimal intraoperatie bleeding and few post-operative adverse events. At baseline, mean BCVA was 0.48 (95% CI: 0.42‒0.54; 20/40 Snellen) and mean ± SD medicated IOP was 20.2 ± 6.0 mmHg on 1.4 ± 1.3 IOP-lowering medications. At 12 months, there was a 27.1% reduction from baseline mean medicated IOP. In eyes with medicated baseline IOP > 21 mmHg (n = 45), there was a 39.7% paired IOP reduction at 12 months with a concurrent reduction in the mean number of IOP lowering medications to 0.8 ± 0.9 which were statistically significant (p < 0.01). For all eyes, 81.9% achieved a medicated IOP ≤ 18 mmHg with no increase in medications at 12 months. To achieve target IOP control, secondary glaucoma surgery was performed in 3.2% of the cases. Conclusion: IOP lowering through uveoscleral outflow enhancement can be achieved by means of a bio-interventional cyclodialysis procedure with allograft scleral reinforcement. [ABSTRACT FROM AUTHOR]

BACKGROUND/AIMS: To report a first-in-human trial in open-angle glaucoma (OAG) subjects treated with a new microinterventional biostent-reinforced cyclodialysis technique to enhance supraciliary aqueous drainage. METHODS: Subjects (N=10; 74.1±7.9 years old) with OAG and cataracts underwent combined phacoemulsification cataract surgery with implantation of a permanent endoscleral supraciliary biostent to reinforce a controlled cyclodialysis cleft. The biostent comprised decellularised scleral allograft tissue microtrephined into a polymer tubular implant intraoperative/postoperative safety, intraocular pressure (IOP) and glaucoma medications were tracked through 12 months postimplantation. RESULTS: Baseline medicated IOP averaged 24.2±6.9 mm Hg with subjects using 1.3±0.8 IOP-lowering medications. Successful biostent implantation was achieved in all individuals without significant complications. Immediate IOP lowering was sustained through 1 year. Twelve-month mean IOP was reduced 40% from baseline to 14.6±3.2 mm Hg (p=0.004; paired two-tailed t-test), and 80% of patients achieved >20% IOP reduction. Biostenting reduced glaucoma medication use 62%, from a baseline mean of 1.3 required medications to 0.5 medications (p=0.037) at postoperative 12 months. The biotissue implant was well tolerated and demonstrated good endothelial safety with only 11% endothelial cell loss at 12 months after combined phaco-biostenting surgery, similar to that expected after phacoemulsification alone. Mean BCVA increased from baseline 20/130 Snellen to 20/36 at postoperative 12 months (p=0.001). CONCLUSION: Supraciliary biostenting in OAG patients is well tolerated, has a good safety profile and produces long-term IOP-lowering while reducing glaucoma medication requirements.

PurposeTo develop and evaluate a deep learning (DL) model to assess fundus photograph quality, and quantitatively measure its impact on automated POAG detection in independent study populations.MethodsImage quality ground truth was determined by manual review of 2815 fundus photographs of healthy and POAG eyes from the Diagnostic Innovations in Glaucoma Study and African Descent and Glaucoma Evaluation Study (DIGS/ADAGES), as well as 11,350 from the Ocular Hypertension Treatment Study (OHTS). Human experts assessed a photograph as high quality if of sufficient quality to determine POAG status and poor quality if not. A DL quality model was trained on photographs from DIGS/ADAGES and tested on OHTS. The effect of DL quality assessment on DL POAG detection was measured using area under the receiver operating characteristic (AUROC).ResultsThe DL quality model yielded an AUROC of 0.97 for differentiating between high- and low-quality photographs; qualitative human review affirmed high model performance. Diagnostic accuracy of the DL POAG model was significantly greater (P < 0.001) in good (AUROC, 0.87; 95% CI, 0.80-0.92) compared with poor quality photographs (AUROC, 0.77; 95% CI, 0.67-0.88).ConclusionsThe DL quality model was able to accurately assess fundus photograph quality. Using automated quality assessment to filter out low-quality photographs increased the accuracy of a DL POAG detection model.Translational relevanceIncorporating DL quality assessment into automated review of fundus photographs can help to decrease the burden of manual review and improve accuracy for automated DL POAG detection.

BACKGROUND: Which phenotypes are we able to recognize in the optic nerve of patients with primary open angle glaucoma? METHODS: Retrospective interventional case series. 885 eyes from 885 patients at an outpatient tertiary care centre who met specified criteria for POAG were included. Disc photographs were classified by three glaucoma specialists into the following phenotypes according to their predominant characteristics: (1) concentric rim thinning, (2) focal rim thinning, (3) acquired pit of the optic nerve (APON), (4) tilted, (5) extensive peripapillary atrophy (PPA), and (6) broad rim thinning. Demographic, medical, and ocular data were collected. Kruskal-Wallis was used as a non-parametric test and pairwise comparison was performed by using Wilcoxon rank sum test corrected. RESULTS: Phenotypic distribution was as follows: 398(45%) focal thinning, 153(18%) concentric thinning, 153(17%) broad thinning, 109(12%) tilted, 47(5%) extensive PPA and 25(3%) APON. Phenotypic traits of interest included a higher proportion of female patients with the focal thinning phenotype (p = 0.015); myopia (p = 0.000), Asian race (OR: 8.8, p = 0.000), and younger age (p = 0.000) were associated with the tilted phenotype; the concentric thinning patients had thicker RNFL (p = 0.000), higher MD (p = 0.008) and lower PSD (p = 0.043) than broad thinning, despite no difference in disc sizes (p = 0.849). The focal thinning group had a localized VF pattern with high PSD compared to concentric thinning (p = 0.005). CONCLUSION: We report six phenotypic classifications of POAG patients with demographic and ocular differences between phenotypes. Future refinement of phenotypes should allow enhanced identification of genetic associations and improved individualization of patient care.

Background/aimsTo evaluate the association of macular vessel density (VD) and ganglion cell complex (GCC) thickness with 10-2 central visual field (CVF) progression in glaucoma.MethodsIn this retrospective cohort study, patients with glaucoma from Diagnostic Innovation in Glaucoma Study with≥five 10-2 visual field (VF) tests and 3-year follow-up before optical coherence tomography (OCT) and OCT angiography (OCTA) imaging were included. Whole-image GCC thickness (wiGCC) and superficial VD (wiVD) were obtained from 6*6 macula scans. The association of wiVD and wiGCC with past rate of 10-2 VF mean deviation worsening, and with past CVF progression (defined using clustered linear regression criteria) was evaluated using linear mixed models after adjusting for confounders.ResultsFrom 238 eyes (141 patients), 25 eyes (11%) of 16 patients were CVF progressors. In the multivariable analysis of the association between OCT/OCTA parameters and past rate of 10-2 CVF worsening, lower wiVD (β=-0.04 (-0.05, -0.02); p

Background/aimsTo investigate the association of macular optical coherence tomography (OCT)/OCT angiography (OCTA) parameters with visual acuity (VA) in glaucoma.Methods144 pseudophakic primary open-angle glaucoma eyes were included. Foveal (fVD), parafoveal (pf), perifoveal (perifVD) and whole-image vessel densities (wiVD) of superficial and deep layers, and their corresponding ganglion cell complex (GCC) thicknesses were obtained from OCTA 6×6 mm2 macula scans. Foveal avascular zone (FAZ) area, FAZ circumference and foveal density-300 (FD300) were measured. Correlation between OCT/OCTA parameters and Logarithm of the Minimum Angle of Resolution VA (logMAR VA) in early and moderate-advanced glaucoma was evaluated with age and Signal Strength Index-adjusted mixed models. Area under receiver operating characteristic (AUC) was used to evaluate discriminative power of OCT/OCTA for decreased VA (

Heat shock proteins (HSP) or stress proteins are induced in cells. They protect the cell and increase cell survival. The aim of this research was to determine the plasma concentration of HSP 70 in patients with primary open-angle glaucoma with elevated intraocular pressure (POAGHTG) and patients with pseudoexfoliative open-angle glaucoma (XFG), and to investigate the relationship between this biomarker and the structural and functional characteristics of glaucoma. The study included 90 participants divided into three groups: 37 patients with primary open-angle glaucoma with increased intraocular pressure (hypertensive glaucoma, POAG-HTG), 24 patients with pseudoexfoliative open-angle glaucoma (XFG), and 29 participants without systemic diseases and glaucoma, matched by sex and age (control group of subjects, CONT). The concentration of circulating HSP 70 was measured in participants' plasma using the sandwich enzyme-linked immunosorbent assay (ELISA). Plasma levels of HSP 70 were very similar in all three groups of participants, without any significant differences among the examined patients. A significant negative correlation of the plasma concentration of HSP 70 and RNFL Savg (p < 0.05) was found in POAG-HTG patients, whereas the negative correlations of HSP 70 with MD (p = 0.0538) and with RNFL Iavg (p = 0.0584) were very close to statistical significance. There was no increase in the plasma concentration of HSP 70 in POAG-HTG and XFG patients. There was an interdependence between the plasma level of HSP 70 and the examined clinical parameters of POAG-HTG patients (MD, RNFL Avg, RNFL Savg and RNFL Iavg). HSP 70 can be a significant biomarker for glaucoma. [ABSTRACT FROM AUTHOR]

ObjectiveTo investigate the effect of smoking on choroidal microvasculature dropout (MvD) in glaucoma.DesignCross-sectional study.SettingTertiary glaucoma centre.Participants223 eyes of 163 patients with primary open-angle glaucoma who had undergone imaging with optical coherence tomography angiography and completed a questionnaire on smoking from the Diagnostic Innovations in Glaucoma Study.Primary outcome measuresLinear mixed-effects models were used to determine the effect of each parameter on MvD area and angular circumference. The sensitivity analysis was performed by categorising the glaucoma severity determined by visual field mean deviation (MD).ResultsMvD was found in 37 (51.4%) eyes with smoking history and in 67 (44.4%) eyes with non-smokers (p=0.389). Larger MvD area and wider angular circumference were found in smokers compared with non-smokers (p=0.068 and p=0.046, respectively). In a multivariable model, smoking intensity was significantly associated with MvD area (0.30(95% CI 0.01 to 0.60) each 0.01 mm2 per 10 pack-years; p=0.044). In eyes with moderate-severe glaucoma (MD

BACKGROUND: Patients with glaucoma on topical glaucoma medication are often affected by dry eye symptoms and thus likely to rub or squeeze their eyelids. Here, we telemetrically measure peak intraocular pressure (IOP) during eyelid manoeuvres and eyelid rubbing. METHODS: Eleven patients with primary open-angle glaucoma (POAG) previously implanted with a telemetric IOP sensor (Eyemate-IO) were instructed to look straight ahead for 1 min as a baseline measurement. Next, 6 repeats of blinking on instruction with 10 s intervals in between were performed. In addition, 5 repeats of eyelid closure (n=9), eyelid squeezing and eyelid rubbing (n=7) were performed with 15 s intervals in between. IOP was recorded via an external antenna placed around the study eye. Average peak IOP increases from baseline were analysed and tested against zero (no change) with one-sample t-tests. RESULTS: For eyelid rubbing, the average peak ∆ IOP increase (mean±SEM) was 59.1±9.6 mm Hg (p

ObjectivesTo investigate the associations of alcohol consumption and smoking with the development of perimetric glaucoma in patients with suspected glaucoma.DesignA retrospective cohort study of patients suspected to have glaucoma enrolled in the Diagnostic Innovations in Glaucoma Study (DIGS) and the African Descent and Glaucoma Evaluation Study (ADAGES).SettingThree tertiary glaucoma centres in the USA.Participants825 eyes of 610 patients with glaucoma suspect eyes with normal visual fields (VF) at baseline were followed over an average of 9 years from the DIGS and ADAGES studies.Outcome measuresDevelopment of glaucoma was defined as occurrence of three consecutive abnormal VF tests during follow-up. Univariable and multivariable Cox regression models were used to investigate lifestyle-related factors associated with development of VF loss over time.ResultsVF tests were abnormal three times in a row in 235 (28.5%) eyes. Alcohol consumption was associated with a higher risk of developing glaucoma (HR 1.57, 95% CI 1.03 to 2.38, p=0.037). In men, the risk of developing glaucoma in alcohol drinkers (HR 1.92, 95% CI 1.00 to 3.68, p=0.048) was greater than non-alcohol drinkers. In individuals of African descent, the risk of developing glaucoma in alcohol drinkers (HR 1.79, 95% CI 1.02 to 3.15, p=0.043) was greater than non-alcohol drinkers. Age was a modifier of the relationship between smoking and glaucomatous VF defects (p=0.048). The risk of developing glaucoma in smokers (HR 1.73, 95% CI 1.10 to 2.72, p=0.019) was greater than never smokers after adjustment for confounding factors in older patients (age >61 years).ConclusionAlcohol consumption was associated with an increased risk of developing glaucoma, particularly in men and individuals of African descent. The risk of developing glaucoma among smokers suspected of having glaucoma was influenced by age, with older individuals having a higher risk than younger people.Trial registration numberNCT00221897 and NCT00221923.

Background/aimsTo investigate the factors associated with choroidal microvasculature drop-out (MvD) enlargement detected by optical coherence tomography angiography (OCT-A) in glaucomatous eyes.MethodsNinety-one eyes of 68 primary open-angle glaucoma patients were enrolled. Only eyes with a minimum of four good quality OCT-A and OCT scans of the optic nerve head acquired at least and with a minimum of 2 years follow-up were included. Area and angular circumference of MvD were analysed on en face images. Univariable and multivariable mixed effects models were constructed to identify the factors contributing to MvD area and angular circumference change over time.ResultsPeripapillary MvD was detected in 53 (58.2%) eyes at baseline and in an additional 17 (18.6%) eyes during follow-up, whereas MvD was not detected in 21 (23.0 %) eyes during the entire follow-up period. In multivariable analysis, worse baseline visual field (VF) mean deviation (MD) (ß=0.27, 95% CI 0.10 to 0.44, p=0.002), greater intraocular pressure (IOP) fluctuations (ß=0.86, 95% CI 0.24 to 1.48, p=0.007), higher peak IOP (ß=0.17, 95% CI -0.01 to 0.35, p=0.067) and greater number of IOP lowering medications (ß=1.36, 95% CI 0.67 to 2.05, p

BACKGROUND/AIMS: To evaluate the electroretinographic (ERG) changes in the early postoperative period following glaucoma filtration surgery, and its relationship with choroidal detachment (CD). METHODS: This retrospective observational single-centre study included 57 consecutive patients with primary open-angle glaucoma who underwent unilateral glaucoma filtration surgery. The patients were divided into two groups according to the presence or absence of CD. ERG components, including the photopic negative response (PhNR), a-wave and b-wave were compared before and after surgery using skin electrodes. RESULTS: There were 46 patients in the non-CD group and 11 in the CD group. ERG was recorded within 5.1 (2.1 to 8.1) (mean (95% CI)) days after surgery. In the non-CD group, the PhNR amplitude, PhNR/b-wave amplitude ratio and PhNR implicit time improved significantly after surgery (p=0.008, 0.002 and 0.039, respectively). In the CD group, the amplitude of the PhNR, a-wave and b-wave were significantly deteriorated after surgery (p=0.002, 0.001 and 0.001, respectively). Postoperative intraocular pressure (IOP) (p=0.031) and postoperative CD (p

PurposeTo assess the clinical characteristics of focal temporal optic disc microvasculature dropout (MvD-D) in primary open-angle glaucoma (POAG) patients.MethodsOne hundred and eighty-seven eyes of 187 POAG patients having MvD-D on Swept-Source optical coherence tomography angiography (SS-OCTA) were enrolled. Three groups were categorized according to the presence of temporal MvD-D within the upper and lower 45° of the fovea-Bruch's membrane (BM) opening axis: focal temporal MvD-D (Group 1, isolated focal temporal MvD-D; 44 eyes), supero/inferotemporal MvD-D (Group 2, MvD-D only in superotemporal or inferotemporal sector; 78 eyes), and diffuse temporal MvD-D (Group 3, MvD-D spanning ≥ 2 consecutive sectors, at least one of which being temporal sector; 65 eyes).ResultsGroup 1 had a significantly longer axial length and β-zone parapapillary atrophy without BM. There also was a larger horizontal tilt angle and ovality index than the other two groups (P < 0.001). Group 1 had a significantly thinner retinal nerve fiber layer (RNFL) in the temporal sector than did Group 2 (P < 0.001), despite similar thicknesses in all other areas (P > 0.05). Group 3 had significantly worse visual field mean deviation and thinner RNFL than the other two groups in all areas other than the nasal, temporal, and superotemporal sectors (P < 0.05).ConclusionsFocal temporal MvD-D detected by SS-OCTA was associated with a longer axial length and related subsequent morphological changes of the optic disc and parapapillary area. This suggests that stretching of the optic disc consequent on axial elongation may lead to absence of temporal optic disc microvasculature.

This prospective, observer-masked, randomized clinical trial was conducted between December 2018 and June 2021 at Eye Hospital, China Academy of Chinese Medical Sciences. A total of 45 glaucoma patients from Beijing, China, were enrolled in this clinical trial to compare the short-term efficacy of primary single-selective laser trabeculoplasty (SLT) to 0.005% latanoprost eye drops for the treatment of 24-h intraocular pressure (IOP) in patients with newly diagnosed primary open angle glaucoma (POAG) and ocular hypertension (OHT). Both SLT and latanoprost significantly decreased mean 24-h IOP and peak IOP, although the latanoprost group effect was more potent when compared to the SLT group (both Ps

Background/aimsTo investigate the relationship between ganglion cell complex (GCC) thinning and baseline deep and superficial macular vessel density (VD) in glaucoma.Methods97 eyes of 69 primary open-angle glaucoma (POAG) and glaucoma suspect patients from the Diagnostics Innovations in Glaucoma Study with a minimum of 4 visits and 2 years of follow-up after baseline optical coherence tomography angiography (OCTA) examination were included. OCTA 3×3 mm2 macular scans were acquired at each visit and used to calculate superficial and deep parafoveal VD (pfVD) and OCT-based parafoveal GCC (pfGCC) thickness. Association of baseline superficial and deep pfVD with pfGCC thinning rate was evaluated using linear mixed model.ResultsThe included subjects had a baseline mean visual field mean deviation (95% CI) of -2.9 (-3.7 to -2.1) dB and a mean follow-up period of 3.6 years. In the univariable model, lower baseline superficial pfVD and higher mean intraocular pressure (IOP) during follow-up were significantly associated with a faster pfGCC thinning rate (p

Background/aimsTo investigate the rate of ganglion cell complex (GCC) thinning in primary open-angle glaucoma (POAG) patients with and without deep-layer microvasculature drop-out (MvD).MethodsPOAG patients who had at least 1.5 years of follow-up and a minimum of three visits were included from the Diagnostic Innovations in Glaucoma Study. MvD was detected at baseline by optical coherence tomography angiography (OCT-A). Area and angular circumference of MvD were evaluated on en face choroidal vessel density images and horizontal B-scans. Rates of global and hemisphere GCC thinning were compared in MvD and non-MvD eyes using linear mixed-effects models.ResultsThirty-six eyes with MvD and 37 eyes without MvD of 63 patients were followed for a mean of 3.3 years. In 30 out of 36 eyes, MvD was localised in the inferotemporal region. While mean baseline visual field mean deviation was similar between the two groups (p=0.128), global GCC thinning was significantly faster in eyes with MvD than in those without MvD (mean differences: -0.50 (95% CI -0.83 to -0.17) µm/year; p=0.003)). Presence of MvD, area and angular circumference of MvD were independently associated with a faster rate of thinning (p=0.002, p=0.031 and p=0.013, respectively).ConclusionIn POAG eyes, GCC thinning is faster in eyes with MvD. Detection of MvD in OCT-A images can assist clinicians to identify patients who are at higher risk for central macula thinning and glaucomatous progression and may require more intensive management.

BACKGROUND/OBJECTIVE: Management of concomitant cataract and glaucoma depends on the stage of glaucoma and the patients situation. There are different surgical options for handling visually significant cataract and mild-to-moderate open-angle glaucoma (OAG). We aimed to compare the one-year results of phacoemulsification alone versus phacoviscocanalostomy in these patients. SUBJECTS/METHODS: This was a parallel-arm, single-masked, randomized-controlled trial, conducted at Farabi Eye Hospital, Tehran, Iran between January 2016 and January 2018. We enrolled 89 eyes from 89 patients with mild-to-moderate primary OAG or pseudoexfoliative glaucoma (PEXG) with visually significant age-related cataract. They randomly underwent phacoemulsification alone (n = 44) or combined phaco-viscocanalostomy (n = 45). All patients had a 12-month follow-up period, and the mean intraocular pressure (IOP), the number of antiglaucoma medications, and complete and qualified success rates were compared. RESULTS: After the 1st and 3rd months, the mean IOP showed significantly decreased in the phaco-visco group compared to the phaco group (P

Background/aimsTo assess and compare long-term reproducibility of optic nerve head (ONH) and macula optical coherence tomography angiography (OCTA) vascular parameters and optical coherence tomography (OCT) thickness parameters in stable primary open-angle glaucoma (POAG), glaucoma suspect and healthy eyes.MethodsEighty-eight eyes (15 healthy, 38 glaucoma suspect and 35 non-progressing POAG) of 68 subjects who had at least three visits within 1-1.5 years with OCTA and OCT imaging (Angiovue; Optovue, Fremont, California, USA) on the same day were included. A series of vascular and thickness parameters were measured including macular parafoveal vessel density (pfVD), ONH circumpapillary capillary density (cpCD), macular parafoveal ganglion cell complex (pfGCC) and ONH circumpapillary retinal nerve fibre layer (cpRNFL). A random effects analysis of variance model was used to estimate intraclass correlation (ICC) coefficients and long-term variability estimates.ResultsICC was lower for OCTA (pfVD 0.823 (95% CI 0.736 to 0.888) and cpCD 0.871 (0.818 to 0.912)) compared with OCT (pfGCC 0.995 (0.993 to 0.997) and cpRNFL 0.975 (0.964 to 0.984)). Within-subject test-retest SD was 1.17% and 1.22% for pfVD and cpCD, and 0.57 and 1.22 µm for pfGCC and cpRNFL. Older age and lower signal strength index were associated with decreasing long-term variability of vessel densities.ConclusionsOCTA-measured macula and ONH vascular parameters have good long-term reproducibility, supporting the use of this instrument for longitudinal analysis. OCTA long-term reproducibility is less than OCT-measured thickness reproducibility. This needs to be taken into consideration when serial OCTA images are evaluated for change.Trial registration numberNCT00221897.

BACKGROUND/AIMS: To identify clinical characteristics and factors associated with microcystic macular edema (MME) in patients with primary open-angle glaucoma (POAG). METHODS: We included 315 POAG eyes between 2010 and 2019 with good-quality macular volume scans that had reliable visual fields (VF) available within 6 months in this observational retrospective cohort study. Eyes with retinal pathologies except for epiretinal membrane (ERM) were excluded. The inner nuclear layer was qualitatively assessed for the presence of MME. Global mean deviation (MD) and Visual Field Index (VFI) decay rates, superior and inferior MD rates and pointwise total deviation rates of change were estimated with linear regression. Logistic regression was performed to identify baseline factors associated with the presence of MME and to determine whether MME is associated with progressive VF loss. RESULTS: 25 out of 315 eyes (7.9%) demonstrated MME. The average (±SD) age and MD in eyes with and without MME was 57.2 (±8.7) versus 62.0 (±9.9) years (p=0.02) and -9.8 (±5.7) versus -4.9 (±5.3) dB (p0.49). CONCLUSIONS: More severe glaucoma and younger age were associated with MME. MME was not associated with faster global VF decay in this cohort. MME may confound monitoring of glaucoma with full macular thickness.

AimTo investigate the safety and performance of a telemetric suprachoroidal intraocular pressure (IOP) sensor (EYEMATE-SC) and the accuracy of its IOP measurements in open angle glaucoma (OAG) patients undergoing simultaneous non-penetrating glaucoma surgery (NPGS).MethodsProspective, multicentre, open-label, single-arm, interventional clinical trial. Twenty-four eyes of 24 patients with OAG regularly scheduled for NPGS (canaloplasty or deep sclerectomy) were simultaneously implanted with an EYEMATE-SC sensor. Six-month follow-up on the sensor's safety and performance as well as on the level of agreement between the EYEMATE-SC measurements and IOP measurements with Goldmann applanation tonometry (GAT).ResultsThe eyes underwent canaloplasty (n=15) or deep sclerectomy (n=9) and achieved successful implantation of the sensor. No device migration, dislocation or serious device-related complications occurred. A total of 367 comparisons were included in the IOP agreement analysis. The overall mean difference between GAT and EYEMATE-SC measurements was 1.31 mm Hg (lower limit of agreement (LoA) 7.55 mm Hg; upper LoA -4.92 mm Hg). The maximum difference of 2.5 mm Hg ±3.96 (LoA 0.30-2.29) was reached on day 10 and continuously improved to an agreement of -0.15 mm Hg ±2.28 (LoA -1.24 to 0.89) after 6 months. Accordingly, the percentage of eyes within an IOP difference of ±5 mm Hg improved from 78% (day 3) to 100% (6 months).ConclusionsAfter 6 months, the EYEMATE-SC sensor was safe and well tolerated, and allowed continual IOP monitoring.Trial registration numberNCT03756662.

PurposeTo perform a phase Ⅰ/Ⅱ evaluation of an H-1337 ophthalmic solution in subjects with primary open-angle glaucoma (POAG) or ocular hypertension (OHT).DesignThis was a phase I/II, randomized, double-masked, vehicle-controlled, dose-response study conducted at 6 private practice sites in the United States. The study was registered with clinicaltrials.gov as NCT03452033.ParticipantsEighty-seven subjects with bilateral POAG or OHT were enrolled.MethodsAfter washout of ocular hypotensive medications as required, the subjects were randomized to receive either the H-1337 ophthalmic solution at 0.06%, 0.2%, and 0.6% or its vehicle twice daily unilaterally in the study eye for the first 3 days and then twice daily in both eyes from day 4 to 28.Main outcome measuresThe primary efficacy end point was the mean change in intraocular pressure from baseline (day 0) for each group on day 28 at hour 4 compared with the vehicle.ResultsIn the primary efficacy end point, i.e., mean change from the baseline on day 28 at hour 4, the mean change from the baseline was - 4.45 ± 3.801, - 5.16 ± 3.114, - 4.93 ± 3.110, and - 0.39 ± 2.355 in the 0.06%, 0.2%, and 0.6% H-1337 and vehicle groups, respectively. The difference between each active group and the vehicle group was statistically significant (P < 0.0001). Treatment-emergent adverse events (TEAEs) occurred in 49% of subjects who received H-1337 (range, 41% [0.2% arm]-64% [0.6% arm] across the H-1337 arms) and 18% of subjects who received the vehicle. The majority of TEAEs were mild in severity; 3 subjects who received H-1337 had a TEAE of moderate intensity (instillation site erythema, blurred vision, and muscle strain).ConclusionsThe H-1337 ophthalmic solution showed clinically and statistically significant ocular hypotensive activity and was well tolerated, with a relatively low incidence of hyperemia.Financial disclosure(s)Proprietary or commercial disclosure may be found after the references.

PURPOSE: To demonstrate the utility of operating on the temporal trabecular meshwork with in vivo - aqueous angiography demonstrating new aqueous outflow channels. METHOD: In a patient with primary open angle glaucoma, nuclear sclerosis, and medically uncontrolled intraocular pressure, Indocyanine green aqueous angiography (0.5%) was performed to visualize baseline functional aqueous outflow channels. This was followed by 30 degrees bent needle ab-interno goniectomy in the temporal quadrant, where no aqueous outflow channels were initially visualized. Aqueous angiography was repeated using 2% fluorescein to visualize aqueous outflow channels after bent needle ab-interno goniectomy. RESULTS: Prebent needle ab-interno goniectomy, aqueous angiography revealed functional outflow channels in the nasal quadrant although none were visible in the temporal quadrant. Postbent needle ab-interno goniectomy in temporal quadrant aqueous angiography demonstrated 2 new aqueous outflow channels. CONCLUSION: In a patient with open angle glaucoma, following temporal quadrant ab-interno goniectomy, the recruitment of aqueous outflow channels was demonstrated using aqueous angiography.

Background/aimsTo investigate the relationship between the foveal avascular zone (FAZ) parameters assessed by optical coherence tomography angiography (OCTA) and central visual field parameters in glaucoma and healthy subjects.MethodsOne hundred and eighty-eight subjects (248 eyes), including 24 healthy (38 eyes), 37 glaucoma suspect (42 eyes, and 127 primary open angle glaucoma (POAG) patients (168 eyes), underwent imaging using OCTA and standard automated perimetry using the 24-2 and 10-2 Swedish Interactive Thresholding Algorithm. OCTA-based and OCT-based FAZ parameters (superficial FAZ area, FAZ circumference), foveal vessel density (FD300) and foveal thickness were measured. The correlation between FAZ parameters and visual field parameters was assessed using linear mixed model.ResultsAxial length adjusted-FAZ area was not different among the three groups (mean (95% CI)): in healthy 0.31 (0.27 to 0.36) mm2, glaucoma suspect 0.29 (0.26 to 0.31) mm2 and POAG eyes 0.28 (0.27 to 0.30) mm2 (p=0.578). FD300 was lower in glaucoma suspect 49.1% (47.9% to 50.4%) and POAG eyes 48.7% (48.1% to 49.4%) than healthy eyes 50.5% (49.3% to 51.7%) though the difference was not statistically significant (p=0.071). Lower FD300 was associated with worse 24-2 and 10-2 visual field mean deviation and foveal threshold in multivariable linear mixed models (all p

Purpose: To evaluate the time course of biodegradation of an intracameral, biodegradable, sustained-release bimatoprost implant that lowers intraocular pressure without the need for daily eye drops. Methods: In 2 identically designed, randomized, phase 3 clinical trials, adults with open-angle glaucoma or ocular hypertension and open iridocorneal angles inferiorly in the study eye were administered 10- or 15-μg bimatoprost implant (day 1 and weeks 16 and 32) or twice-daily topical timolol 0.5%. Implants were assessed on gonioscopy throughout the studies. Investigators reported whether implants were visible, estimated the size of visible implants relative to their initial size at implantation, and reported the implant location. Data for 10-μg implant placed on day 1 were pooled from both studies for analysis. Results: A total of 372 patients received the 10-μg bimatoprost implant. The degree of implant biodegradation at each follow-up time point was variable among patients. The implant frequently swelled during the initial phase of biodegradation from 6 to 28 weeks. Accelerated biodegradation occurred between 31 and 52 weeks, resulting in 82% of implants absent or ≤25% of initial size by 52 weeks. By month 20, 95% of implants had biodegraded to absent or ≤25% of initial size. The implant was predominantly located inferiorly in the iridocorneal angle. Conclusions: Bimatoprost implant biodegradation in phase 3 studies showed some degree of variability among patients. Clinically significant implant biodegradation was observed in the majority of patients by 12 months. Clinical studies are in progress to further understand implant biodegradation and the ideal timing for implant re-administration. ClinicalTrials.gov NCT02247804; ClinicalTrials.gov NCT02250651.

PURPOSE: Primary open-angle glaucoma (POAG) is a degenerative eye disease for which early treatment is critical to mitigate visual impairment and irreversible blindness. POAG-associated loci individually confer incremental risk. Genetic risk score(s) (GRS) could enable POAG risk stratification. Despite significantly higher POAG burden among individuals of African ancestry (AFR), GRS are limited in this population. A recent large-scale, multi-ancestry meta-analysis identified 127 POAG-associated loci and calculated cross-ancestry and ancestry-specific effect estimates, including in European ancestry (EUR) and AFR individuals. We assessed the utility of the 127-variant GRS for POAG risk stratification in EUR and AFR Veterans in the Million Veteran Program (MVP). We also explored the association between GRS and documented invasive glaucoma surgery (IGS). DESIGN: Cross-sectional study. PARTICIPANTS: MVP Veterans with imputed genetic data, including 5830 POAG cases (445 with IGS documented in the electronic health record) and 64 476 controls. METHODS: We tested unweighted and weighted GRS of 127 published risk variants in EUR (3382 cases and 58 811 controls) and AFR (2448 cases and 5665 controls) Veterans in the MVP. Weighted GRS were calculated using effect estimates from the most recently published report of cross-ancestry and ancestry-specific meta-analyses. We also evaluated GRS in POAG cases with documented IGS. MAIN OUTCOME MEASURES: Performance of 127-variant GRS in EUR and AFR Veterans for POAG risk stratification and association with documented IGS. RESULTS: GRS were significantly associated with POAG (P < 5 × 10-5) in both groups; a higher proportion of EUR compared with AFR were consistently categorized in the top GRS decile (21.9%-23.6% and 12.9%-14.5%, respectively). Only GRS weighted by ancestry-specific effect estimates were associated with IGS documentation in AFR cases; all GRS types were associated with IGS in EUR cases. CONCLUSIONS: Varied performance of the GRS for POAG risk stratification and documented IGS association in EUR and AFR Veterans highlights (1) the complex risk architecture of POAG, (2) the importance of diverse representation in genomics studies that inform GRS construction and evaluation, and (3) the necessity of expanding diverse POAG-related genomic data so that GRS can equitably aid in screening individuals at high risk of POAG and who may require more aggressive treatment.

PurposeTo evaluate the effects of pressure changes induced by a multipressure dial (MPD) on circumpapillary retinal nerve fiber layer (RNFL) and capillary density (CD) measurements in patients with glaucoma using OCT angiography (OCTA).DesignProspective interventional study.ParticipantsTwenty-four patients with primary open-angle glaucoma.MethodsOne eye of each patient underwent negative pressure application with the MPD. The MPD alters intraocular pressure (IOP) relative to atmospheric pressure by generating a negative pressure vacuum within a goggle chamber that is placed over the eye. Each participant underwent serial high density OCTA imaging (AngioVue) of the optic nerve head at different negative pressure increments of -5 mmHg, starting from 0 mmHg, ending at -20 mmHg, and then returning to baseline. Images were acquired after 2 minutes of sustained negative pressure at each target pressure to allow for stabilization of the retinal structures and microvasculature. The RNFL thickness and CD measurements were automatically calculated using the native AngioVue software, and then exported for analysis.Main outcome measuresThe influence of different levels of negative pressure on circumpapillary RNFL thickness and CD measurements, assessed by a linear mixed-effects model with repeated measures.ResultsThe mean (± SD) age was 71.0 years (± 7.8 years), the baseline IOP was 17.5 mmHg (± 3.6 mmHg), and there was a mean 24-2 mean deviation of -2.80 dB (± 2.55 dB). Serial circumpapillary CD measurements showed a statistically significant dose-dependent increase from baseline, without negative pressure application, to the maximum negative pressure application of -20 mmHg (difference, 2.27%; P = 0.010). Capillary density measurements then decreased symmetrically when lowering the negative pressure to baseline. Circumpapillary CD measurements at target negative pressures of -10 mmHg, -15 mmHg, and -20 mmHg were significantly higher than the baseline measurements (all P values < 0.05). Circumpapillary RNFL thickness remained the same throughout different levels of negative pressure.ConclusionsCircumpapillary CD measurements showed a dose-dependent increase with the induction of negative pressure, while RNFL thickness measurements remained unchanged.

PurposeTo investigate the relationship of longitudinal changes in macular vessel density (VD) from OCT angiography and in ganglion cell complex (GCC) from OCT with central visual field (VF) in eyes with early glaucoma.DesignObservational cohort.ParticipantsA total of 95 eyes, 37 preperimetric and 58 with early glaucoma (24-2 VF mean deviation [MD] ≥ -6 decibels), with an average follow-up of 3.8 years and 5.3 visits, were included.MethodsWhole-image VD (wiVD) and whole-image GCC (wiGCC) and parafoveal scans, as well as localized regions of interest (LROIs), hemiretinae of whole images, and superior, inferior, temporal, and nasal sectors of parafoveal maps, were matched with central VF locations. Age-adjusted rates of change of VD, GCC, mean sensitivity of VF locations, and 10-2 VF MD were calculated using linear mixed-effect models. Normalized rates of change were calculated for comparison of change rates in wiVD and wiGCC.Main outcome measuresStructure-function (SF) correlations of VD and GCC with central VF measurement change rates and comparison of different correlations of SF relationships after bootstrapping the difference of the correlation coefficients.ResultsVessel density loss and GCC thinning demonstrated significant correlations with central VF damage, globally and with most LROIs. The SF correlation (r, 95% confidence interval [CI]) between wiVD and 10-2 VF MD change rates was 0.42 [0.24, 0.58], whereas it was 0.27 [0.08, 0.45] between wiGCC and 10-2 VF MD changes rates (all P < 0.05). In contrast to GCC thinning, VD loss in the parafoveal sectors demonstrated significant correlations with central VF damage in inferior and temporal sectors. Differences in the relationship of SF with central VF damage were not significant between VD loss and GCC thinning. The mean (95% CI) normalized change rates of wiVD (-7.40 [-7.71 to 7.09] %/year) was faster than that of wiGCC (-2.39 [-2.94 to 1.84] %/year) (P < 0.05).ConclusionsRates of VD loss and GCC thinning are associated with central VF loss over time. Assessment of both macular VD and GCC thickness should be considered for evaluation of glaucoma progression.

PurposeTo investigate the effect of smoking on rates of progressive visual field (VF) damage over time in glaucoma.DesignRetrospective cohort study.ParticipantsFive hundred eleven eyes of 354 patients with glaucoma followed up from multicenter glaucoma registries.MethodsIn this longitudinal study, 354 patients with primary open-angle glaucoma with a minimum of 3 years of follow-up and 5 VF tests were enrolled from the Diagnostic Innovations in Glaucoma Study and the African Descent and Glaucoma Evaluation Study. Univariate and multivariate linear mixed models were used to investigate the effects of smoking on rates of 24-2 VF mean deviation loss. Visual field progression was defined using pointwise linear and significant negative VF mean deviation loss. Logistic regression was used to identify baseline factors and whether different levels of smoking intensity were associated with VF progression. Kaplan-Meier survival analysis and the log-rank test were used to compare the cumulative risk ratio of progression between smoker and never smoker groups.Main outcome measuresVisual field progression.ResultsFive hundred eleven eyes of 354 patients were included over the median follow-up of 12.5 years. Median baseline age was 64.8 years. Of the 354 patients, 124 (35%) were Black, and 149 (42.1%) and 168 (59.8%) had reported a history of smoking or alcohol consumption, respectively. In a multivariate model, higher smoking intensity was associated with faster VF loss (coefficient, -0.05 decibels (dB)/year per 10 pack-years; 95% confidence interval [CI], -0.08 to -0.01 dB/year per 10 pack-years; P = 0.010). Developing VF progression in eyes of heavy smokers (≥ 20 pack-years) was 2.2 times more than in eyes of patients without smoking history (odds ratio, 2.21; 95% CI, 1.02-4.76; P = 0.044). Statistically significant differences were found between heavy smokers (≥ 20 pack-years) and never smokers by Kaplan-Meier analysis (P = 0.011, log-rank test).ConclusionsHeavy smokers are more likely to sustain VF loss in eyes with glaucoma. The prospective longitudinal design of this study supports the hypothesis that levels of smoking may be a significant predictor for glaucoma progression. Additionally, this information can be used for clinically relevant tobacco prevention and intervention messages.

PurposeTo evaluate the diagnostic accuracy of a novel optical coherence tomography texture-based en face image analysis (SALSA-Texture) that requires segmentation of only 1 retinal layer for glaucoma detection in eyes with axial high myopia, and to compare SALSA-Texture with standard macular ganglion cell-inner plexiform layer (GCIPL) thickness, macular retinal nerve fiber layer (mRNFL) thickness, and ganglion cell complex (GCC) thickness maps.DesignComparison of diagnostic approaches.MethodsCross-sectional data were collected from 92 eyes with primary open-angle glaucoma (POAG) and 44 healthy control eyes with axial high myopia (axial length >26 mm). Optical coherence tomography texture en face images, developed using SALSA-Texture to model the spatial arrangement patterns of the pixel intensities in a region, were generated from 70-μm slabs just below the vitreal border of the inner limiting membrane. Areas under the receiver operating characteristic curves (AUROCs) and areas under the precision recall curves (AUPRCs) adjusted for both eyes, axial length, age, disc area, and image quality were used to compare different approaches.ResultsThe best parameter-adjusted AUROCs (95% confidence intervals) for differentiating between healthy and glaucoma high myopic eyes were 0.92 (0.88-0.94) for texture en face images, 0.88 (0.86-0.91) for macular RNFL thickness, 0.87 (0.83-0.89) for macula GCIPL thickness, and 0.87 (0.84-0.89) for GCC thickness. A subset analysis of highly advanced myopic eyes (axial length ≥27 mm; 38 glaucomatous eyes and 22 healthy eyes) showed the best AUROC was 0.92 (0.89-0.94) for texture en face images compared with 0.86 (0.84-0.88) for macular GCIPL, 0.86 (0.84-0.88) for GCC, and 0.84 (0.81-0.87) for RNFL thickness (P ≤ .02 compared with texture for all comparisons).ConclusionThe current results suggest that our novel en face texture-based analysis method can improve on most investigated macular tissue thickness measurements for discriminating between highly myopic glaucomatous and highly myopic healthy eyes. While further investigation is needed, texture en face images show promise for improving the detection of glaucoma in eyes with high myopia where traditional retinal layer segmentation often is challenging.

PrcisThe earlier a person quits smoking the more likely is the optic nerve be spared from damage.PurposeTo investigate the effect of smoking cessation on visual field (VF) progression in glaucoma.MethodsPrimary open angle glaucoma patients with a minimum of 3 years follow-up and 5 VFs were included. Linear mixed models were used to investigate the effects of smoking on the rates of 24-2 VF mean deviation loss after adjusting for confounding factors. Cox proportional hazard regression was used to identify whether different levels of smoking intensity were associated with VF progression with respect to different duration of quitting.ResultsFive hundred eleven eyes of 354 patients were included over the mean follow-up of 12.4 years. Mean baseline age (95% confidence interval) was 62.3 (61.2, 63.4) years. One hundred forty nine (42.1%) patients were smokers. In a multivariable model, smoking intensity was associated with faster VF loss (-0.06, 95% confidence interval (-0.10, -0.01) dB/year per 10 pack-years, P =0.01) among smokers. Heavy smokers (≥20 pack-years) who had quit ˂25 years prior had significantly greater odds of VF progression compared with never smokers (odds ratio=2.49 (1.01, 6.08); P =0.046). There was no significant difference in odds of VF progression in heavy smokers who had quit smoking more than 25 years compared with never smokers ( P =0.43). A significantly higher proportion of VF progression was found in heavy smokers who quit < 25 years compared with heavy smokers who quit ≥25 years by Kaplan-Meier analysis ( P =

PrcisBoth macular superficial vessel density and ganglion cell complex (GCC) thickness measurement are significantly associated with regional and global 10-degree central visual field (VF) sensitivity in advanced glaucoma.PurposeThe purpose of this study was to evaluate the regional and global structure-function relationships between macular vessel density (MVD) assessed by optical coherence tomography angiography (OCTA) and 10-2 VF sensitivity in advanced open angle glaucoma eyes.MethodsMacular OCTA and 10-2 VF sensitivity of 44 patients [mean deviation (MD)

OBJECTIVES: To evaluate the association between serum retinol concentration and normal-tension glaucoma (NTG). METHODS: A total of 345 study subjects were recruited in a prospective cross-sectional study: 101 patients with NTG, 106 patients with high-pressure primary open-angle glaucoma (POAG) and 138 healthy control subjects. Serum retinol concentration in fasting blood samples was determined by ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS). All study subjects were given complete ophthalmic examinations and diagnosed by two glaucoma sub-specialists. RESULTS: Serum retinol concentrations in NTG, POAG, and controls were 338.90 ± 103.23 ng/mL, 405.22 ± 114.12 ng/mL, and 408.84 ± 122.36 ng/mL respectively. NTG patients had lower serum retinol concentrations than POAG (p

PrcisDecreased superficial whole image capillary density was observed in open angle glaucoma (OAG) patients with high smoking intensity.PurposeTo investigate the effects of smoking on optic nerve head capillary density measured by optical coherence tomography angiography in patients with OAG.MethodsIn this retrospective cross-sectional study, perimetric and preperimetric glaucoma patients enrolled in the Diagnostic Innovations in Glaucoma Study (DIGS) with optical coherence tomography angiography follow-up were included. Univariable and multivariable linear mixed analysis were performed to determine the effects of different variables on the superficial whole image capillary density.ResultsA total of 432 eyes of 271 glaucoma patients comprising 63 preperimetric (106 eyes) and 208 perimetric OAG (326 eyes) were included. A history of tobacco consumption was reported in 105 (38.8%). Among smokers, mean (95% confidence interval) smoking intensity was 12.8 (10.2, 15.5) pack-years. After adjusting for age, glaucoma severity and other confounders, each 10 pack-year increase in smoking intensity (95% confidence interval) was associated with -0.54 (-1.06, -0.02) % lower whole image capillary density ( P =0.041).ConclusionsSmoking intensity is associated with reduced optic nerve vessel density in glaucoma.

PurposeTo evaluate the association between rates of choroidal microvasculature dropout (MvD) change and rates of circumpapillary retinal nerve fiber layer (cpRNFL) loss in primary open-angle glaucoma (POAG) eyes.DesignCohort study from clinical trial data.MethodsA total of 91 eyes of 68 POAG patients with and without localized MvD at baseline with at least 4 visits and 2 years of follow-up with optical coherence tomography angiography (OCT-A) and OCT scans were included. Area and angular circumference of MvD were evaluated on OCT-A en face and B-scan choroidal vessel density images during the follow-up period. Joint longitudinal mixed effects models were used to estimate the rates of change in MvD area or angular circumference and RNFL thickness. Univariable and multivariable regressions were completed to identify the factors contributing to cpRNFL thinning.ResultsMvD was identified in 53 eyes (58.2%) at baseline. Seventeen eyes (18.6%) that did not show MvD at baseline developed it over the follow-up period. Over a mean follow-up of 4.0 years, the mean rates of change in MvD area and angular circumference (95% CI) were 0.05 (0.04, 0.06) mm2 per year and 13.2° (10.7°, 15.8°) per year, respectively. In multivariable models, the rate of cpRNFL thinning was significantly associated with the rates of change in MvD area and angular circumference (P = .008 and P = .009, respectively).ConclusionsRates of MvD area and angular circumference change over time were associated with concurrent rates of cpRNFL loss in POAG eyes.

PurposeTo compare the differences in retinal vessel density (VD) between topical administration of latanoprostene bunod (LBN) ophthalmic solution 0.024% and timolol maleate 0.5% in patients with open-angle glaucoma (OAG) or ocular hypertension (OHT) and normal subjects.DesignRandomized, single center, crossover clinical trial.MethodsEligible subjects were examined during 6 study visits over 12 weeks. All subjects were randomized in a 1:1 ratio to LBN dosed once daily or timolol dosed twice daily in both eyes (OU) for a duration of 4 weeks each, separated by a 2-week washout period. A comprehensive eye examination OU was performed at each visit. Testing was performed with optical coherence tomography and optical coherence tomography angiography (optic nerve and macula), as well as visual field examination, on the study eye at baseline and before and after each treatment.ResultsOne eye from each of 50 patients was enrolled (10 healthy patients, 26 patients with OHT, and 14 patients with OAG). After administration of LBN there was significantly increased macular VD (0.76% [0.20%-1.33%], P = 0.009) and a trend in increasing peripapillary VD in patients with OAG and patients with OHT. In contrast, after administration of timolol, there were no differences in macular VD, and a decrease in peripapillary VD only was observed in the nasal inferior sector (-0.56% [-1.08% to -0.03%], P = .04) in patients with OAG and patients with OHT. No change in peripapillary or macular VD was observed in the normal subjects (P > .05 for all).ConclusionsTopical administration of LBN enhanced macular VD in patients with OAG or patients with OHT. In contrast, timolol administration did not have any effect on VD.

PurposeTo evaluate the role of corneal hysteresis (CH) as a risk factor of central visual field (VF) progression in a cohort of glaucoma suspect and glaucoma patients.DesignProspective cohort study.MethodsTwo hundred forty-eight eyes of 143 subjects who were followed for an average of 4.8 years with a minimum of 5 visits with 10-2 and 24-2 VF tests were included. Univariable and multivariable linear mixed-effects models were used to identify characteristics associated with the rate of change over time in 10-2 and 24-2 mean deviation (MD). Mixed-effects logistic regression was used to evaluate characteristics associated with an increased likelihood of event-based 10-2 VF progression based on the clustered pointwise linear regression criterion.ResultsCH was significantly associated with 10-2 and 24-2 VF progression in the univariable trend-based analysis. In multivariable trend-based analyses, lower CH was associated with a faster rate of decline in 10-2 MD (0.07 dB/y per 1 mm Hg, P < .001) but not with 24-2 MD (P = .490). In multivariable event-based analysis, lower CH was associated with an increased likelihood of 10-2 VF progression (odds ratio = 1.35 per 1 mm Hg lower, P = .025). Similar results were found in eyes with early glaucomatous damage at the baseline (baseline: 24-2 MD ≥ -6 dB).ConclusionsLower CH was associated with a statistically significant, but relatively small, increased risk of central VF progression on the 10-2 test grid. Given the substantial influence of central VF impairment on the quality of life, clinicians should consider using CH to assess the risk of progression in patients with primary open-angle glaucoma including those with early disease.

PrcisIn the Thessaloniki Eye Study (TES) incidence phase population, frequent dietary salt intake was potentially associated with increased risk of open angle glaucoma in antihypertensive users.PurposeThe aim was to examine the association between dietary salt intake and glaucoma by antihypertensive use in the TES population.Materials and methodsThe study population included TES incidence phase participants. Dietary salt intake frequency was assessed by self-report. Outcomes included prevalence of any open angle glaucoma (OAG), primary open angle glaucoma (POAG), and pseudoexfoliation (PEX). Covariates included demographics, cardiovascular disease, migraines, diabetes, steroid use, smoking, history of cataract surgery, central corneal thickness, intraocular pressure, blood pressure, and antihypertensive use. Logistic regression was used to examine associations between frequency of salt intake and glaucoma, controlling for covariates and stratified by antihypertensive use.ResultsThe study included 1076 participants 80.5±4.4 years old, of whom 518 were female. There were 89/1076 (8.3%) participants with any OAG, 46/789 (5.8%) with POAG, and 287/1030 (27.9%) with PEX. In participants with antihypertensive use, frequent versus never salt intake was associated with increased risk of any OAG [adjusted odds ratio (aOR)=2.65, 95% confidence interval (CI)=1.12, 6.28; n=784] and POAG (aOR=3.59, 95% CI=1.16, 11.11; n=578) overall, and additionally in participants with diastolic blood pressure

PurposeTo compare the rates of visual field (VF) progression between individuals of Black and White race and to investigate whether treatment effects may help explain differences previously reported between racial groups.DesignMulticenter prospective observational cohort study.MethodsParticipants were patients in referral tertiary care glaucoma clinics with open angle glaucoma. Eyes were excluded who had

PurposeTo evaluate the association between optical microangiography (OMAG) measurements and progressive ganglion cell-inner plexiform layer (GCIPL) loss in patients with primary open-angle glaucoma (POAG).DesignProspective case series.MethodsSixty-three eyes of 38 patients with POAG were studied for ≥2 years and with ≥ 3 optical coherence tomography examinations. Only those hemifields with mild to moderate functional damage at baseline (106 hemifields) were included in the analysis. OMAG imaging was performed at the baseline visit. The effects of clinical parameters (age, gender, central corneal thickness, presence of disc hemorrhage, and mean and fluctuation of intraocular pressure), baseline mean deviation, retinal nerve fiber layer, and GCIPL thickness and baseline OMAG measurements (peripapillary and macular perfusion density [PD] and vessel density [VD]) on the rate of change of GCIPL thickness were evaluated using linear mixed models.ResultsAverage (± standard deviation) mean deviation, quadrant retinal nerve fiber layer, and sector GCIPL thickness of the analyzed hemifields respectively at baseline were -5.2 ± 2.8 dB, 94.5 ± 20.0 µm, and 72.4 ± 8.7 µm, respectively. Peripapillary PD and VD in the quadrant were 43.1% ± 7.0% and 17.0 ± 2.6 mm/mm2, respectively. Macular PD and VD in the quadrant were 37.2% ± 6.9% and 15.1 ± 2.6 mm/mm2, respectively. Rate of sector GCIPL change was -0.97 ± 0.15 µm per year. Multivariate mixed models showed that lower peripapillary PD (coefficient 0.04, P = .01) and VD (coefficient 0.09, P = .05) were significantly associated with a faster rate of GCIPL loss.ConclusionsLower baseline peripapillary OMAG measurements were significantly associated with a faster rate of GCIPL loss in patients with mild to moderate POAG.

PurposeTo compare measurements of global and regional circumpapillary capillary density (cpCD) with retinal nerve fiber layer (RNFL) thickness and characterize their relationship with visual function in early primary open-angle glaucoma (POAG).DesignCross-sectional study.ParticipantsEighty healthy eyes, 64 preperimetric eyes, and 184 mild POAG eyes from the Diagnostic Innovations in Glaucoma Study.MethodsGlobal and regional RNFL thickness and cpCD measurements were obtained using OCT and OCT angiography (OCTA). For direct comparison at the individual and diagnostic group level, RNFL thickness and capillary density values were converted to a normalized relative loss scale.Main outcome measuresRetinal nerve fiber layer thickness and cpCD normalized loss at the individual level and diagnostic group. Global and regional areas under the receiver operating characteristic curve (AUROC) for RNFL thickness and cpCD to detect preperimetric glaucoma and glaucoma, R2 for the strength of associations between RNFL thickness function and capillary density function in diagnostic groups.ResultsBoth global and regional RNFL thickness and cpCD decreased progressively with increasing glaucoma severity (P < 0.05, except for temporal RNFL thickness). Global and regional cpCD relative loss values were higher than those of RNFL thickness (P < 0.05) in preperimetric glaucoma (except for the superonasal region) and glaucoma (except for the inferonasal and superonasal regions) eyes. Race, intraocular pressure (IOP), and cpCD were associated with greater cpCD than RNFL thickness loss in early glaucoma at the individual level (P < 0.05). Global measurements of capillary density (whole image capillary density and cpCD) had higher diagnostic accuracies than RNFL thickness in detecting preperimetric glaucoma and glaucoma (P < 0.05; except for cpCD/RNFL thickness comparison in glaucoma [P = 0.059]). Visual function was significantly associated with RNFL thickness and cpCD globally and in all regions (P < 0.05, except for temporal RNFL thickness-function association [P = 0.070]).ConclusionsAssociations between capillary density and visual function were found in the regions known to be at highest risk for damage in preperimetric glaucoma eyes and all regions of mild glaucoma eyes. In early glaucoma, capillary density loss was more pronounced than RNFL thickness loss. Individual characteristics influence the relative magnitudes of capillary density loss compared with RNFL thickness loss. Retinal nerve fiber layer thickness and microvascular assessments are complementary and yield valuable information for the detection of early damages seen in POAG.

PurposeTo evaluate the association of macular superficial vessel density (SVD) and projection-resolved deep vessel density (DVD) with past visual field (VF) progression in patients with primary open-angle glaucoma.DesignRetrospective cohort.MethodsIn this longitudinal study, 208 eyes of 147 patients with glaucoma from the Diagnostics Innovations in Glaucoma Study were included. Eligible participants were required to have at least five 24-2 VF tests over a minimum follow-up period of 3 years before macular optical coherence tomography angiography imaging. VF progression was defined based on both event-based pointwise linear regression and trend-based methods. The association of macular SVD and DVD with the probability and rate of past VF progression was evaluated using a linear mixed effects model.ResultsFifty-two (25%) eyes had VF progression based on the pointwise linear regression based criterion at the end of a mean ± standard deviation follow-up duration of 6.9 ± 1.2 years. In the event-based multivariable analysis, a lower baseline SVD was associated with a higher likelihood of past VF progression (odds ratio per 1% lower. 1.28; 95% confidence interval, 1.02-1.59). Similarly, in the trend-based multivariable analysis, lower macular SVD was associated with a faster past rate of mean deviation decline (coefficient = -0.03 dB/year; 95% confidence interval, -0.04 to -0.01). Event-based and trend-based analyses found no significant associations for macular DVD with the likelihood/rate of past VF progression (P > .05).ConclusionsLower macular SVD, and not DVD, was associated with a higher probability of past VF progression. Macular optical coherence tomography angiography imaging shows promise for identifying eyes at risk of VF progression in patients with glaucoma.