A multi-cohort genome-wide association study in African ancestry individuals reveals risk loci for primary open-angle glaucoma.

Primary open-angle glaucoma (POAG), the leading cause of irreversible blindness worldwide, disproportionately affects individuals of African ancestry. We conducted a genome-wide association study (GWAS) for POAG in 11,275 individuals of African ancestry (6,003 cases; 5,272 controls). We detected 46 risk loci associated with POAG at genome-wide significance. Replication and post-GWAS analyses, including functionally informed fine-mapping, multiple trait co-localization, and in silico validation, implicated two previously undescribed variants (rs1666698 mapping to DBF4P2; rs34957764 mapping to ROCK1P1) and one previously associated variant (rs11824032 mapping to ARHGEF12) as likely causal. For individuals of African ancestry, a polygenic risk score (PRS) for POAG from our mega-analysis (African ancestry individuals) outperformed a PRS from summary statistics of a much larger GWAS derived from European ancestry individuals. This study quantifies the genetic architecture similarities and differences between African and non-African ancestry populations for this blinding disease.

DDX58 variant triggers IFN-ß-induced autophagy in trabecular meshwork and influences intraocular pressure.

Singleton-Merten syndrome (SMS) is a rare immunogenetic disorder affecting multiple systems, characterized by dental dysplasia, aortic calcification, glaucoma, skeletal abnormalities, and psoriasis. Glaucoma, a key feature of both classical and atypical SMS, remains poorly understood in terms of its molecular mechanism caused by DDX58 mutation. This study presented a novel DDX58 variant (c.1649A>C [p.Asp550Ala]) in a family with childhood glaucoma. Functional analysis showed that DDX58 variant caused an increase in IFN-stimulated gene expression and high IFN-ß-based type-I IFN. As the trabecular meshwork (TM) is responsible for controlling intraocular pressure (IOP), we examine the effect of IFN-ß on TM cells. Our study is the first to demonstrate that IFN-ß significantly reduced TM cell viability and function by activating autophagy. In addition, anterior chamber injection of IFN-ß remarkably increased IOP level in mice, which can be attenuated by treatments with autophagy inhibitor chloroquine. To uncover the specific mechanism underlying IFN-ß-induced autophagy in TM cells, we performed microarray analysis in IFN-ß-treated and DDX58 p.Asp550Ala TM cells. It showed that RSAD2 is necessary for IFN-ß-induced autophagy. Knockdown of RSAD2 by siRNA significantly decreased autophagy flux induced by IFN-ß. Our findings suggest that DDX58 mutation leads to the overproduction of IFN-ß, which elevates IOP by modulating autophagy through RSAD2 in TM cells.

Selective Laser Trabeculoplasty for the Treatment of Glaucoma: A Report by the American Academy of Ophthalmology.

PURPOSE: To review the current published literature for high-quality studies on the use of selective laser trabeculoplasty (SLT) for the treatment of glaucoma. This is an update of the Ophthalmic Technology Assessment titled, "Laser Trabeculoplasty for Open-Angle Glaucoma," published in November 2011. METHODS: Literature searches in the PubMed database in March 2020, September 2021, August 2022, and March 2023 yielded 110 articles. The abstracts of these articles were examined to include those written since November 2011 and to exclude reviews and non-English articles. The panel reviewed 47 articles in full text, and 30 were found to fit the inclusion criteria. The panel methodologist assigned a level I rating to 19 studies and a level II rating to 11 studies. RESULTS: Data in the level I studies support the long-term effectiveness of SLT as primary treatment or as a supplemental therapy to glaucoma medications for patients with open-angle glaucoma. Several level I studies also found that SLT and argon laser trabeculoplasty (ALT) are equivalent in terms of safety and long-term efficacy. Level I evidence indicates that perioperative corticosteroid and nonsteroidal anti-inflammatory drug eye drops do not hinder the intraocular pressure (IOP)-lowering effect of SLT treatment. The impact of these eye drops on lowering IOP differed in various studies. No level I or II studies exist that determine the ideal power settings for SLT. CONCLUSIONS: Based on level I evidence, SLT is an effective long-term option for the treatment of open-angle glaucoma and is equivalent to ALT. It can be used as either a primary intervention, a replacement for medication, or an additional therapy with glaucoma medications. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

Ab-Externo MicroShunt versus Trabeculectomy in Primary Open-Angle Glaucoma: Two-Year Results from a Randomized, Multicenter Study.

PURPOSE: To compare the effectiveness and safety of the MicroShunt (Santen Inc) versus trabeculectomy in patients with primary open-angle glaucoma (POAG). DESIGN: Prospective, randomized, multicenter trial conducted in the United States and Europe. PARTICIPANTS: Adult patients (aged 40-85 years) with mild to severe POAG inadequately controlled on maximum tolerated medical therapy and intraocular pressure (IOP) ≥ 15 mmHg and ≤ 40 mmHg. METHODS: Patients were randomized 3:1 to stand-alone MicroShunt implantation (n = 395) or trabeculectomy (n = 132), both augmented with mitomycin C (MMC) 0.2 mg/ml for 2 minutes. MAIN OUTCOME MEASURES: The primary effectiveness end point was surgical success, defined as ≥ 20% reduction in mean diurnal IOP from baseline with no increase in glaucoma medications. Secondary end points included changes in mean IOP and medication use from baseline and the need for postoperative interventions. RESULTS: At 2 years, the rate of surgical success was lower in the MicroShunt group than in the trabeculectomy group (50.6% vs. 64.4%, P = 0.005). Mean diurnal IOP was reduced from 21.1 ± 4.9 mmHg at baseline to 13.9 ± 3.9 mmHg at 24 months in the MicroShunt group and from 21.1 ± 5.0 mmHg at baseline to 10.7 ± 3.7 mmHg at 24 months in the trabeculectomy group (P < 0.001 compared with baseline in both groups). Mean medication use decreased from 3.1 to 0.9 in the MicroShunt group and from 2.9 to 0.4 in the trabeculectomy group (P < 0.001 compared with baseline in both groups). Adverse events at 2 years were generally similar in the 2 groups, except that hypotony was more common in eyes undergoing trabeculectomy (51.1% vs. 30.9%, P < 0.001). Repositioning or explantation of the implant occurred in 6.8% of MicroShunt patients. The majority of these patients had device removal at the time of subsequent glaucoma surgery. Vision-threatening complications were uncommon in both groups. CONCLUSION: At 2 years, both the MicroShunt and trabeculectomy provided significant reductions in IOP and medication use, with trabeculectomy continuing to have greater surgical success. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

Progressive Changes in the Neuroretinal Rim and Retinal Nerve Fiber Layer in Glaucoma: Impact of Baseline Values and Floor Effects.

PURPOSE: To determine whether more severe baseline damage impedes measurement of minimum rim width (MRW) and peripapillary retinal nerve fiber layer thickness (RNFLT) change in glaucoma patients because of a floor effect. DESIGN: Prospective, longitudinal cohort study in a hospital-based setting. PARTICIPANTS: The study included patients with open-angle glaucoma and healthy control subjects. Participants had at least 5 years of follow-up with OCT every 6 months. METHODS: Baseline global and sectorial MRW and RNFLT values were classified as within normal limits, borderline, or outside normal limits based on reference normative values. Regression analysis was used to determine the magnitude and significance of MRW and RNFLT change. Additionally, the follow-up period for each participant was divided into 2 equal halves (first and second periods) to determine whether there was attenuation of MRW and RNFLT change with follow-up time. MAIN OUTCOME MEASURES: Rates of global and sectoral MRW and RNFLT changes (slopes). RESULTS: A total of 97 patients with glaucoma (median age, 70.3 years) and 42 healthy subjects (median age, 64.8 years) were followed for a median of 6.9 years and 7.0 years, respectively. The median mean deviation of the visual field in glaucoma patients was -4.30 decibels (dB) (interquartile range, -7.81 to -2.06 dB; range, -20.68 to 1.37 dB). Statistically significant changes in global and sectoral MRW and RNFLT were detected across all baseline classifications; however, there was a tendency for less change with increasing baseline damage. In glaucoma patients, RNFLT slopes, but not MRW slopes, were significantly more positive (less change) in the second period compared with the first. There were also no differences in MRW or RNFLT slopes in the first and second periods in healthy subjects. CONCLUSIONS: Significant MRW and RNFLT changes were detected at all levels of baseline damage. However, an attenuation in the rate of RNFLT change compared with MRW indicates an earlier floor effect in RNFLT measurements globally and in equivalent sectors. Because the axonal component of these measurements should be equivalent, our results suggest important differences in tissue remodeling at the level of the optic nerve head and peripapillary retina. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found after the references.

Evaluating Primary Treatment for People with Advanced Glaucoma: Five-Year Results of the Treatment of Advanced Glaucoma Study.

PURPOSE: To determine whether primary trabeculectomy or medical treatment produces better outcomes in terms of quality of life (QoL), clinical effectiveness, and safety in patients with advanced glaucoma. DESIGN: Multicenter randomized controlled trial. PARTICIPANTS: Between June 3, 2014, and May 31, 2017, 453 adults with newly diagnosed advanced open-angle glaucoma in at least 1 eye (Hodapp classification) were recruited from 27 secondary care glaucoma departments in the United Kingdom. Two hundred twenty-seven were allocated to trabeculectomy, and 226 were allocated medical management. METHODS: Participants were randomized on a 1:1 basis to have either mitomycin C-augmented trabeculectomy or escalating medical management with intraocular pressure (IOP)-reducing drops as the primary intervention and were followed up for 5 years. MAIN OUTCOME MEASURES: The primary outcome was vision-specific QoL measured with the 25-item Visual Function Questionnaire (VFQ-25) at 5 years. Secondary outcomes were general health status, glaucoma-related QoL, clinical effectiveness (IOP, visual field, and visual acuity), and safety. RESULTS: At 5 years, the mean ± standard deviation VFQ-25 scores in the trabeculectomy and medication arms were 83.3 ± 15.5 and 81.3 ± 17.5, respectively, and the mean difference was 1.01 (95% confidence interval [CI], -1.99 to 4.00; P = 0.51). The mean IOPs were 12.07 ± 5.18 mmHg and 14.76 ± 4.14 mmHg, respectively, and the mean difference was -2.56 (95% CI, -3.80 to -1.32; P < 0.001). Glaucoma severity measured with visual field mean deviation were -14.30 ± 7.14 dB and -16.74 ± 6.78 dB, respectively, with a mean difference of 1.87 (95% CI, 0.87-2.87 dB; P < 0.001). Safety events occurred in 115 (52.2%) of patients in the trabeculectomy arm and 124 (57.9%) of patients in the medication arm (relative risk, 0.92; 95% CI, 0.72-1.19; P = 0.54). Serious adverse events were rare. CONCLUSIONS: At 5 years, the Treatment of Advanced Glaucoma Study demonstrated that primary trabeculectomy surgery is more effective in lowering IOP and preventing disease progression than primary medical treatment in patients with advanced disease and has a similar safety profile. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

Causal relationships between Gut microbiota and primary open-angle Glaucoma: A Mendelian randomization and mediation analysis of Glaucoma endophenotypes.

Primary open-angle glaucoma (POAG) is a widespread condition responsible for irreversible blindness, and its prevalence is expected to increase substantially in the coming decades. Despite its significance, the exact cause of POAG remains elusive, necessitating a comprehensive exploration of its pathogenesis. Emerging research suggests a potential link between alterations in gut microbiota composition and POAG. However, establishing causality in these associations remains a challenge. In this study, we employed Mendelian randomization (MR) analysis to investigate the potential causal relationships between gut microbiota (GM) and POAG. Significant bacteria taxa were further analyzed with POAG endophenotypes. We utilized data from genome-wide association studies (GWAS) for GM and POAG, as well as for glaucoma endophenotypes, including intraocular pressure (IOP), retinal nerve fiber layer (RNFL) thickness, vertical cup-to-disc ratio (VCDR), and central corneal thickness (CCT). Univariable, multivariable MR and mediation effect analysis were conducted. Our analysis revealed that certain taxa, including phylum Euryarchaeota, genus Odoribacter, Rumnicoccaceae UCG009, Ruminiclostridium9, unknown genus id.2071, and Eubacterium rectale group, were associated with an increased risk of POAG. On the other hand, family Victivallaceae, Lacchnospiraceae, genus Lachnoclostridium, Oscillospira, Ruminococcaceae UCG011, Alloprevotella, and Faecalibacterium were found to be associated with a decreased risk of POAG. Furthermore, some of these taxa were found to be connected to glaucoma endophenotypes. Through further multivariable MR analysis, it was determined that IOP, VCDR, and CCT might played mediating roles between GM and POAG. In conclusion, this study utilizes MR analysis to elucidate potential causal associations between GM and POAG, providing insights into specific GM taxa that influence POAG risk and related endophenotypes. These findings emphasize the potential role of the gut microbiota in the pathogenesis of POAG and pave the way for future research and therapeutic interventions.

Genetic association of IL1B gene variants with primary glaucoma in a North Indian Punjabi cohort: An original study and meta-analysis.

Interleukin (IL) 1B is an important candidate gene in glaucoma pathogenesis as it affects the survival of retinal ganglion cells (RGCs). In the present study, -511T/C and +3953C/T polymorphisms in the IL1B were assessed as genetic risk factors for primary open angle (POAG) and angle closure glaucoma (PACG) in a North Indian Punjabi cohort comprising 867 samples (POAG cases = 307; PACG cases = 133 and controls = 427). Genetic association, diplotype and linkage disequilibrium (LD) analyses were performed. Corrections for confounding variables and multiple testing were applied. An updated meta-analysis was also performed. Pooled OR with 95% CI was calculated for dominant, over dominant, and recessive models. Level of heterozygosity among studies was tested using I2 statistic with fixed or random effect model based on the extent of heterogeneity. For -511T > C polymorphism, a positive association was observed with PACG under dominant (p = 0.038; OR = 0.65; pcorr = 0.011; OR = 0.55) and over dominant models (p = 0.010; OR = 0.59; pcorr = 0.001; OR = 0.46). Significant association of +3953C > T was also observed with POAG under dominant (p = 0.011; OR = 1.46; pcorr = 0.018; OR = 1.48) and PACG under recessive models (p < 0.0001; OR = 4.47; pcorr<0.0001; OR = 4.06). While C-C diplotype provided protection against primary glaucoma (0.67-fold; p = 0.0004), T-T and T-C diplotypes predisposed individuals to higher risk (1.31-fold; p = 0.030 and 1.36-fold; p = 0.022 respectively). In meta-analysis, a significant association between +3453 C>T and POAG was observed under dominant (pooled OR = 1.33, p = 0.0046) and over dominant (pooled OR = 1.25; p = 0.0269) models with overall heterogeneity of 15% and 0% respectively. The study provides strong evidence of IL1B variants in modifying genetic susceptibility to primary glaucoma in the targeted North Indian Punjabi population. Replication of the present findings in other populations, and functional studies are warranted to further assess the relevance of IL1B variants in the pathogenesis of primary glaucoma.

Development and characterization of a chronic high intraocular pressure model in New Zealand white rabbits for glaucoma research.

Glaucoma is a neurodegenerative disease characterized by visual field loss associated with optic nerve damage and ocular hypertension. The biological basis for the elevated intraocular pressure (IOP) is largely unknown, such that lowering the IOP is currently the only established treatment. Several animal models have been developed to elucidate the mechanism underlying the increased IOP and for use in drug discovery research, but their utility is often limited by the occurrence of severe intraocular inflammation and by technical challenges. In this study, we developed a rabbit glaucoma model that does not require experimental disease induction. Rabbits were chosen as the model because their eyeballs are similar in size to those of humans, and they are easy to breed. By crossing rabbit strains with inherited glaucoma, as indicated by obvious buphthalmos, we produced a strain that exhibits ocular hypertension. The IOP of the Ocular Hypertension (OH) rabbits was significantly higher than that of the wild type (WT; normal New Zealand white rabbits) from the age of 3 weeks to at least 22 weeks. The significantly larger corneal diameter of the OH rabbits indicated ocular enlargement, whereas there was no significant difference in corneal thickness compared with WT rabbits. Anterior segment ocular coherence tomography and gonioscopic observations revealed an open angle in the OH rabbits. Hematoxylin and eosin (HE) staining together with Masson's trichrome staining showed abnormal collagen accumulation in the angle of the OH rabbit's eyes. Furthermore, aqueous humor (AH) outflow imaging following an intravitreal injection of a fluorescent probe into the anterior chamber for tissue-section analysis revealed retention of the probe in the area of collagen deposition in the OH eyes. The OH rabbits also had a time-dependent increase in the cup/disc ratio. In conclusion, investigations using our newly developed rabbit model of open-angle ocular hypertension showed that abnormal accumulation of extracellular matrix at the angle increased AH outflow resistance in the conventional outflow pathway, leading to a high IOP. Furthermore, the OH rabbits exhibited glaucomatous optic disc cupping over time. These findings suggest the utility of the OH rabbits as a model for open-angle glaucoma (OAG).

Prescription of glucagon-like peptide 1 agonists and risk of subsequent open-angle glaucoma in individuals with type 2 diabetes mellitus.

Background: The glucagon-like peptide 1 receptor agonist (GLP-1RA) is an antidiabetic medication with vascular protection and anti-inflammatory properties. Theoretically, the use of GLP-1RA should inhibit the development of open-angle glaucoma (OAG) as both vascular damage and inflammation are associated with OAG. Therefore, our objective was to investigate the association between the application of GLP-1RA and the subsequent OAG in individuals with type 2 diabetes mellitus (T2DM). Methods: We conducted a retrospective cohort study by using data from the National Health Insurance Research Database (NHIRD) of Taiwan. Participants with T2DM were divided into those who used GLP-1RA and those who did not, forming the GLP-1RA and control groups. The primary outcome was the occurrence of OAG based on diagnostic codes. Cox proportional hazard regression was employed to calculate the adjusted hazard ratio (aHR) and 95% confidence interval (CI) for OAG. Results: 91 patients in the control group developed OAG, and 40 patients in the GLP-1RA group developed OAG. After adjustment for all covariates, the GLP-1RA group exhibited a significantly lower incidence of OAG compared with the control group (aHR: 0.712, 95% CI: 0.533-0.936. P = 0.0025). In the subgroup analyses, the association between GLP-1RA use and OAG incidence was more pronounced in patients with T2DM using GLP-1RA and aged younger than 60 years (P = 0.0438). Conclusion: The prescription of GLP-1RA is associated with a lower incidence of subsequent OAG in individuals with T2DM, and this association was more significant in patients with T2DM under the age of 60 years.

Combined versus standalone XEN45 Gel Stent implantation in either phakic or pseudophakic patients: a case-matched study.

PURPOSE: To determine differing outcomes among either phakic or pseudophakic patients who received standalone XEN45 Gel Stent (Allergan, an AbbVie Company, CA, USA) implantation and patients who underwent combined surgery with phacoemulsification. METHODS: This retrospective single-center study involved 180 eyes of 180 participants who underwent XEN45 Gel Stent implantation, of which 60 eyes received combined surgery with phacoemulsification (combined group). Standalone stent implantation was performed on 60 phakic (phakic group) and on 60 pseudophakic eyes (pseudophakic group). The groups were matched in a ratio of 1:1:1 based on multiple criteria. Successful surgery was defined by three scores: IOP at the longest follow-up of < 21 mmHg (Score A) or < 18 mmHg (Score B) and an IOP reduction > 20% or IOP ≤ 15 mmHg and an IOP reduction ≥ 40% (Score C). In all scores, one open conjunctival revision was allowed, and additional repeat surgery was considered a failure. RESULTS: After an average follow-up time interval of 20.6 ± 12.6 months, there was a mean IOP-reduction by 37% among the entire cohort. Comparative analysis between the three groups did not show significant differences regarding postoperative IOP, postoperative medication score, side effects, revision rate, repeat surgery rate or success rate. A dysfunctional stent was detected in eight eyes (4%) during open conjunctival revision in 76 eyes. CONCLUSION: The clinical endpoints investigated did not differ significantly among either phakic or pseudophakic patients who received standalone stent implantation and patients who underwent combined surgery. However mean latency between primary stent implantation and first revision surgery after combined surgery was markedly shorter.

Contributing factors for intraocular pressure control in patients with mostly normal-tension glaucoma after initial Ex-PRESS drainage device implantation.

PURPOSE: To investigate the postoperative intraocular pressure (IOP) control and identify the factors associated with failure of initial Ex-PRESS surgery in patients with open-angle glaucoma for 3 years. METHODS: A total of 79 patients with medically uncontrolled open-angle glaucoma (55 normal-tension glaucoma and 24 primary open-angle glaucoma) were enrolled. All patients underwent Ex-PRESS implantation (including combined cataract surgery). The outcome measure was the survival rate using life table analysis, the failure was defined as IOP of > 18 mmHg (criterion A), > 15 mmHg (criterion B) or > 12 mmHg (criterion C) and/or IOP reduction of < 20% from baseline (each criterion) without any glaucoma medications. The Cox proportional hazards model was used to identify risk factors for IOP management defined as the above criterion.  RESULTS: The mean preoperative IOP was 19.3 ± 5.8 mmHg. At 36 months, the mean IOP was 11.8 ± 3.6 mmHg with a mean IOP change of 7.5 mmHg (reduction rate 39.0%). The cumulative probability of success was 58% (95%CI: 42-64%) (criterion A), 48% (95%CI: 37-59%) (criterion B) and 30% (95%CI: 20-40%) (criterion C). In multivariate analyses, factors that predicted poor IOP control included the intervention of bleb needling after 6 months after the surgery (HR: 2.43; 95%CI: 1.35-4.37; P = 0.032). Transient hypotony was observed in 4 patients. CONCLUSION: The implementation of bleb needling after Ex-PRESS surgery in the late postoperative period was suggested to be the main risk factor for achieving lower IOP.

An eternal hunt for glaucoma.

In the first issue of Graefe's Archive from 1854, Albrecht von Graefe wrote about glaucoma. Glaucoma comes from the Greek word "glaukos," gleaming, which was first used by Homer around 800 BCE. Since then, glaukos and glaucoma have taken on many different meanings. The terms blindness, cataract and glaucoma were used interchangeably and twisted together in incomprehensible contexts. Over 2500 years of glaucoma theories were upset by the discovery of the ophthalmoscope in 1851. The first reports of increased intraocular pressure appeared in the mid-seventeenth century, but it took over 200 years for this elevated pressure to be accepted by the ophthalmological community. The discovery of glaucoma simplex in 1861 was an important step forward. What did doctors know about glaucoma before 1850 and why did it take so long to classify glaucoma in its various categories? And why is it that we still do not know what the cause is for primary open angle glaucoma? I will try to answer some of these questions after a historical overview.

Choroidal thickness in juvenile open angle glaucoma: insights from a south asian case-control study.

PURPOSE: The purpose of this study is to compare choroidal thickness in juvenile open angle glaucoma (JOAG) and healthy controls using spectral domain optical coherence tomography (SD-OCT) and study its correlations. METHODS: In this case-control study, 56 eyes of 28 JOAG patients and an equal number of controls were recruited. SD-OCT was used to measure the choroidal thickness (ChT), in the macular region at 5 locations: subfoveal, 1500 µm and 3000 µm nasal and temporal to the foveal center, and in the peripapillary region at 6 locations: up to 1500 µm, nasal and temporal to the disc, respectively. The ChT and its correlations with age, intraocular pressure, cup-to-disc ratio, central corneal thickness, mean deviation, and axial length were studied. RESULTS: The average macular ChT in JOAG was 306.30 ± 56.49 µm vs. 277.12 ± 64.68 µm in controls. The average peripapillary ChT in JOAG was 197.79 ± 44.05 µm vs. 187.24 ± 38.89 µm in controls. The average total ChT (p = 0.042), the average macular ChT (p = 0.022), the subfoveal ChT (p = 0.022), the ChT 1500 µm (p < 0.001), and 3000 µm temporal to the fovea (p = 0.002) were significantly thicker in the JOAG group. In the JOAG group, the average macular ChT had a significant negative correlation with age, whereas axial length was positively correlated with the average peripapillary ChT. CONCLUSIONS: In this South Asian cohort of JOAG, the average total ChT, average macular ChT, subfoveal ChT, and ChT at 1500 µm, and 3000 µm temporal to the fovea were significantly thicker when compared to healthy controls.

Intermediate-term impact on corneal endothelial cells and efficacy of Preserflo MicroShunt implantation in patients with open-angle glaucoma - a prospective study over two years.

INTRODUCTION: Preserflo MicroShunt is a novel microinvasive bleb forming device for the treatment of primary open-angle glaucoma. The intermediate- and long-term success and the impact of this procedure on corneal endothelial cell density remain to be investigated. METHODS: In this prospective observational study, 62 eyes of 55 glaucoma patients (mean age ± SD: 67.0 ± 15.0 years) receiving a Preserflo MicroShunt were included. Corneal endothelial cell density, intraocular pressure and best corrected visual acuity were assessed preoperatively and at 3, 6, 9, 12, 18 and 24 months postoperatively. Success rates, bleb revision rates and complications were analysed. Complete success was defined as an intraocular pressure reduction of ≥ 20% and achieving a target pressure of ≤ 18, ≤ 15 or ≤ 12 mmHg without antiglaucoma medication. Qualified success indicated that the criteria were reached with or without medication. RESULTS: Corneal endothelial cells showed no significant decline over 24 months (p > 0.05). Intraocular pressure showed a substantial reduction postoperatively (p < 0.001), decreasing from 29.6 ± 8,3 mmHg to 13.0 ± 4.3 mmHg after 24 months (p < 0.001). Complete and qualified success with a target pressure ≤ 15 mmHg was achieved in 52.9% and 54.6% of cases after 24 months, respectively. Best corrected visual acuity did not change after 24 months. CONCLUSION: Preserflo MicroShunt had no negative side effects on corneal endothelial cells and showed favourable success rates after 2 years in patients with open-angle glaucoma.

Evaluation of inner retinal function at different stages of primary open angle glaucoma using the photopic negative response (PhNR) measured by RETeval electroretinography.

PURPOSE: To investigate the objective function of the inner retinal layer in each stage of primary open angle glaucoma (POAG) using the photopic negative response (PhNR) measured by RETeval full-field electroretinography (ERG), and to identify which PhNR parameter is the most useful. METHODS: Ninety eyes of 90 patients with POAG (30 with mild POAG (mean deviation (MD) ≥ -6 dB) and 60 with moderate-to-advanced POAG (MD < -6 dB)) and 76 eyes of 76 control cases were examined. We investigated six PhNR parameters and their relationships with the results of the Humphrey 30-2 visual field test and the thickness of the circumpapillary retinal nerve fiber layer (cpRNFL) obtained from optical coherence tomography. The following PhNR parameters were assessed: base-to-trough (BT), peak-to-trough (PT), 72msPhNR, the W-ratio, P-ratio, implicit time (IT), and a-wave and b-wave amplitudes on ERG. RESULTS: All PhNR parameters other than IT significantly differed between the all POAG (all stages) and control groups and between the moderate-to-advanced POAG and control groups. BT and 72msPhNR in the mild POAG group, significantly differed from those in the control group. Regarding the relationships between PhNR parameters and the visual field and between these parameters and cpRNFL thickness, correlations were observed between all PhNR parameters, except PT and IT, and both the visual field and cpRNFL thickness in the all and moderate-to-advanced POAG groups. 72msPhNR correlated with cpRNFL thickness in the mild POAG group. The area under the receiver operating characteristic curve was greater for BT than for the other PhNR parameters in both the mild and moderate-to-advanced POAG groups. The discriminant linear function for examining the presence or absence of POAG and the threshold for diagnosis were quantitatively obtained as follows. Regarding BT: discriminant = 0.505 × BT + 2.017; threshold = positive for POAG, negative for no POAG; correct answer rate = 80.7%. Concerning 72msPhNR: discriminant = 0.533 × 72msPhNR + 1.553; threshold = positive for POAG and negative for no POAG; correct answer rate = 77.1%. CONCLUSION: RETeval-measured PhNR parameters were useful for an objective evaluation of visual function in moderate-to-advanced POAG. BT appeared to be the most diagnostically useful parameter.

Comparison of bleb morphologies between phacoemulsification combined with Ex-PRESS mini shunt implantation, phacotrabeculectomy and trabeculectomy alone: a two-year retrospective in vivo confocal microscopy study.

BACKGROUND: To compare the bleb morphologies of phacoemulsification combined with Ex-PRESS implantation (Phaco-ExPRESS), phaco trabeculectomy (Phaco-Trab), and trabeculectomy (Trab) in postoperative two years. METHODS: Patients with primary open-angle glaucoma (POAG) with or without cataracts were included in this study. All patients underwent surgeries of either Phaco-ExPRESS, Phaco-Trab, or Trab. The morphologic structures of the filtering bleb, including microcysts area, hyperreflective dot density, and stromal connective tissue under in vivo confocal microscope (IVCM), were compared between the three groups. The data were collected preoperatively and postoperatively at 2 weeks, 1 month, 3 months, 6 months, 12 months, 18 months, and 24 months. RESULTS: Eighty-nine eyes from 89 patients were enrolled, including 32 in the Phaco-ExPRESS group, 25 in the Phaco-Trab group, and 32 in the Trab group. In a 24-month follow-up, bleb morphologies in Phaco-ExPRESS were similar to the Trab group. The area of epithelial microcysts was significantly increased in Phaco-ExPRESS and Trab groups while significantly decreased in Phaco-Trab. At postoperative 24 months, the complete success rate was 65.1% in Phaco-ExPRESS, 32.0% in Phaco-Trab, and 59.4% in the Trab group (P = 0.03). The phaco-Trab group had more postoperative anti-glaucoma medications than the other two groups (P < 0.05). CONCLUSIONS: Phaco-ExPRESS group and Trab group had similar blebs morphologies in IVCM, with larger microcyst area, looser connective tissue, and less inflammation than Phaco-Trab, indicating that the function of blebs in the Phaco-ExPRESS and Trab group, was more potent than that of Phaco-Trab. All these surgical methods provided adequate IOP control, but Phaco-Trab required more anti-glaucoma medications.

Risk Factors for Progression of Primary Open-Angle Glaucoma with Lower Normal Intraocular Pressure.

INTRODUCTION: This study aimed to investigate intraocular pressure (IOP)-independent factors associated with the progression of primary open-angle glaucoma (POAG) with IOP ≤15 mm Hg. METHODS: POAG patients with maximum IOP ≤15 mm Hg at the Kyoto University Hospital between January 2011 and August 2021 were retrospectively enrolled. We evaluated effects of various factors on the rate of mean deviation (MD) changes in the visual field (VF) examinations using a linear mixed model. These factors included hypertension, diabetes mellitus (DM), hyperlipidemia (HL), cardiovascular disease, arrhythmia, disc hemorrhage, sleep apnea syndrome, orthopedic diseases, and malignant tumors. RESULTS: In total, 98 eyes from 68 patients were included. The baseline MD was -9.74 ± 7.85 dB. The mean rate of MD change and IOP during the observation period were -0.28 ± 0.04 dB/year and 11.8 ± 1.0 mm Hg, respectively. Comorbidity of DM or HL showed a significant positive association with the rate of MD change (ß = 0.35, p = 0.0006 and ß = 0.18, p = 0.036, respectively) in the model adjusted for age, sex, axial length, mean IOP, and standard deviation of IOP during the observation period. However, no significant association of DM or HL was found after adjusting for central corneal thickness. CONCLUSION: This study suggests that DM or HL is associated with VF deterioration in glaucoma with lower IOP, but the association may be due to differences in IOP characteristics.

Clinical Characteristics of Microcystic Macular Edema in Chronic Primary Angle-Closure Glaucoma and Primary Open-Angle Glaucoma Patients.

INTRODUCTION: This study investigated the clinical characteristics of and risk factors for microcystic macular edema (MME) in patients with chronic primary angle-closure glaucoma (CPACG) and primary open-angle glaucoma (POAG). METHODS: This retrospective observational study included 1,588 eyes from 926 glaucoma inpatients and analyzed the patients' basic demographic information, visual field parameters, macular scans, and peripapillary retinal nerve fiber layer thickness. RESULTS: Our findings were that the incidence rate of MME was 3.97% (34/857) in CPACG and 5.88% (43/731) in POAG. MME was predominantly diagnosed at an advanced stage in CPACG (almost 100%) compared to POAG (93.02%). MME was most frequently involved in the inferior (83.12%) quadrant of the peri-macular region in both CPACG and POAG. Risk factors for MME occurrence in CPACG and POAG included lower visual field mean deviation (OR = 1.14, 95%: CI 1.05-1.24, p = 0.003; OR = 1.14, 95% CI: 1.06-1.21, p < 0.001) and younger age (OR = 0.92, 95% CI: 0.88-0.96, p < 0.001; OR = 0.96, 95% CI: 0.93-0.99, p = 0.003), while female sex (OR = 0.30, 95% CI: 0.11-0.84, p = 0.022) reduced the MME occurrence in POAG. CONCLUSION: MME could develop in both CPACG and POAG patients, occurring earlier in POAG. The inferior peri-macular region is commonly affected. Younger age and poorer visual field are risk factors for MME in glaucoma patients.

Evaluation of Optic Nerve Head Microcirculation in Open-Angle Glaucoma Patients with Unilateral Visual Field Defect.

INTRODUCTION: Microcirculation of optic nerve head (ONH) in open-angle glaucoma (OAG) patients with unilateral visual field (VF) loss has yet to be fully investigated, especially the perimetrically unaffected fellow eyes. METHODS: Thirty-eight OAG patients with VF defect in one eye and normal VF in the other eye, and thirty-one healthy participants were analyzed. All participants underwent laser speckle flowgraphy (LSFG), spectral-domain optical coherence tomography (SD-OCT) imaging, and VF test for further analyses. LSFG measurements included mean blur rate in all area of ONH (MA), big vessel area of ONH (MV), and tissue area of ONH (MT). SD-OCT parameters included circumpapillary retinal nerve fiber layer (cpRNFL) thickness and macula thicknesses. The difference of LSFG and SD-OCT indices between glaucoma patients and healthy controls were compared. The diagnostic accuracy was analyzed with the areas under the receiver operating characteristic curves (AROCs). RESULTS: Global cpRNFL thickness and macular thickness in unaffected eyes of OAG patients were higher than their fellow eyes and lower than healthy eyes. MA and MV in healthy eyes and unaffected eyes were significantly higher than in affected eyes. MT in unaffected eyes of OAG patients was higher than in their fellow affected eyes but lower than in healthy eyes. The AROCs were highest for cpRNFL (0.925), followed by macular thickness (0.838), and MT (0.834). CONCLUSIONS: ONH microcirculation in perimetrically unaffected fellow eyes was decreased in OAG patients with unilateral VF loss. LSFG can detect changes of ONH in high-risk eyes before detectable VF damage, which may reflect the vascular pathophysiology for glaucoma.