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.

Causal association among glaucoma, cerebral cortical structures, and Alzheimer's disease: insights from genetic correlation and Mendelian randomization.

Glaucoma and Alzheimer's disease are critical degenerative neuropathies with global impact. Previous studies have indicated that glaucomatous damage could extend beyond ocular structures, leading to brain alterations potentially associated with Alzheimer's disease risk. This study aimed to explore the causal associations among glaucoma, brain alterations, and Alzheimer's disease. We conducted a comprehensive investigation into the genetic correlation and causality between glaucoma, glaucoma endophenotypes, cerebral cortical surficial area and thickness, and Alzheimer's disease (including late-onset Alzheimer's disease, cognitive performance, and reaction time) using linkage disequilibrium score regression and Mendelian randomization. This study showed suggestive genetic correlations between glaucoma, cortical structures, and Alzheimer's disease. The genetically predicted all-caused glaucoma was nominally associated with a decreased risk of Alzheimer's disease (OR = 0.96, 95% CI: 0.93-0.99, P = 0.013). We found evidence for suggestive causality between glaucoma (endophenotypes) and 20 cortical regions and between 29 cortical regions and Alzheimer's disease (endophenotypes). Four cortical regions were causally associated with cognitive performance or reaction time at a significant threshold (P < 6.2E-04). Thirteen shared cortical regions between glaucoma (endophenotypes) and Alzheimer's disease (endophenotypes) were identified. Our findings complex causal relationships among glaucoma, cerebral cortical structures, and Alzheimer's disease. More studies are required to clarify the mediation effect of cortical alterations in the relationship between glaucoma and Alzheimer's disease.

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.

Ocular dominance in cataract surgery: research status and progress.

Ocular dominance (OD), a commonly used concept in clinical practice, plays an important role in optometry and refractive surgery. With the development of refractive cataract surgery, the refractive function of the intraocular lens determines the achievement of the postoperative full range of vision based on the retinal defocus blur suppression and binocular monovision principle. Therefore, OD plays an important role in cataract surgery. OD is related to the visual formation of the cerebral cortex, and its plasticity suggests that visual experience can influence the visual system. Cataract surgery changes the visual experience and transforms the dominant eye, which confirms the plasticity of the visual system. Based on the concept and mechanism of OD, this review summarizes the application of OD in cataract surgery.

Non-penetrating filtration surgery versus trabeculectomy in postoperative astigmatism: a meta-analysis.

OBJECTIVE: Trabeculectomy and non-penetrating trabecular surgery are common operations for glaucoma. This meta-analysis aims to compare the effect of trabeculectomy and non-penetrating trabecular surgery in postoperative astigmatism of patients with glaucoma. METHODS: A systematic literature search was performed for studies comparing trabeculectomy and non-penetrating trabecular surgery in patients with glaucoma. The time frame for the search was from the time of construction to April 2024. There were no restrictions regarding study type or type of glaucoma. The endpoint was the surgically induced astigmatism assessed 6 months after operation. We conducted this meta-analysis following the PRISMA (Preferred Reporting Items for Systematic Review and Meta-Analysis). RESULTS: Five eligible studies were included in this meta-analysis and presented data for 359 eyes with various types of glaucoma at different stages. The results revealed an increase in astigmatism in patients with glaucoma after trabeculectomy and non-penetrating trabecular surgery. Trabeculectomy had a higher incidence of astigmatism than in the non-penetrating trabecular surgery group at or around 6 months postoperatively, and the difference was statistically significant. (SMD = 0.40, 95% CI = 0.19 to 0.61, P = 0.02). CONCLUSION: Our results demonstrated that both trabeculectomy and non-penetrating trabecular surgery could increase astigmatism until 6 months after operation. Moreover, non-penetrating trabecular surgery group seems to have less influence on astigmatism. TRIAL REGISTRATION NUMBER: CRD42024517708.

Case report: Topical pilocarpine ameliorated the accommodation loss and pupillary dilation after micropulse transscleral laser treatment.

BACKGROUND: The present study elucidates a common significant postoperative complication of micropulse transscleral laser treatment (mTLT) and explores its potential management strategies for younger patients with good central vision. CASE PRESENTATION: Three younger Chinese glaucoma patients with good central vision maintained high intraocular pressures (IOPs) (36, 25, and 30 mmHg) on maximally tolerated topical anti-glaucoma medications. All patients were treated with mTLT because of a higher risk of complications with filtering surgery. After the procedure, their best-corrected visual acuities were not significantly changed, IOPs were significantly decreased, and the number of topical anti-glaucoma medicines was gradually decreased. However, all patients complained about reduced near visual acuity (NVA) for 1-5 months. Slit-lamp examination revealed pupillary dilation, and binocular accommodative function examination indicated accommodation loss. After treatment with 2% topical pilocarpine, all patients reported an improvement in NVA. Among them, we could observe pupillary constriction, recovery of accommodation function, and improved NVA, even discontinuation of pilocarpine in Patient 2. CONCLUSION: In younger patients with good central vision, topical pilocarpine might ameliorate accommodation loss and pupillary dilation after mTLT.

Impact of peripapillary staphylomas on the vascular and structural characteristics in myopic eyes: a propensity score matching analysis.

PURPOSE: To apply propensity score matching to evaluate the impact of peripapillary staphylomas (PPS) on vascular and structural characteristics in the myopic eyes. METHODS: This was a prospective, cross-sectional study. Forty-one control eyes and 41 eyes with PPS were analyzed. The eyes were selected using propensity score matching analysis based on the age and axial length. All subjects underwent ophthalmologic examinations for assessing vessel and structure parameters using swept-source optical coherence tomography (SS-OCT), OCT angiography, color fundus photography, and ocular biometry. RESULTS: As compared with control eyes, the eyes with PPS had shallower anterior chamber depth (3.61 ± 0.24 mm vs 3.77 ± 0.24 mm, P = 0.004), higher intraocular pressure (IOP) (16.59 ± 2.88 mmHg vs 14.53 ± 2.45 mmHg, P = 0.002), and higher myopic spherical equivalent (- 11.52 ± 3.22D vs - 9.88 ± 2.20D, P = 0.009). while corneal curvature and lens thickness between the two groups were not statistically different. Compared with control eyes, increased macular deep vessel density, reduced macular choriocapillaris and radial peripapillary capillary, and thinning retinal layer, ganglion cell complex, choroidal layer as well as the superior and inferior peripapillary retinal nerve fiber layer were observed in eyes with PPS, apart from larger disc area, parapapillary atrophy area, and degree of disc rotation. Logistic regression analysis revealed that the IOP (P = 0.046), disc rotation (P = 0.003), and average peripapillary choroidal thickness (P = 0.009) were associated with the presence of PPS. CONCLUSION: Close association of PPS with exacerbation of myopia and anatomical alterations was observed which not only affected the eye posterior segment but also the anterior segments. We further identified significant reductions in the radial peripapillary capillary and macular choroidal perfusion with the increase in macular deep retinal flow blood of myopic eyes with PPS. Higher IOP, thinner peripapillary choroidal thickness, and rotated optic disc were risk factors for the presence of PPS.

The efficacy and safety of micropulse transscleral laser treatment in glaucoma: a systematic review and meta-analysis.

OBJECTIVE: Micropulse transscleral laser treatment (mTLT) is the latest alternative intraocular pressure (IOP) lowering approach for glaucoma patients. This meta-analysis aims to evaluate the efficacy and safety of mTLT and continuous wave transscleral cyclophotocoagulation (CW-TSCPC) for the treatment of glaucoma. METHODS: We searched the PubMed, Embase, and Cochrane Library of Systematic Reviews databases from January 2000 to July 2022 to identify studies that, evaluated the efficacy and safety of mTLT in glaucoma. There were no restrictions regarding study type, patient age, or type of glaucoma. We analysed the reduction in IOP and the number of anti-glaucoma medications (NOAM), retreatment rates, and complications between mTLT and CW-TSCPC treatment. Publication bias was conducted for evaluating bias. This systematic review followed the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA 2020) reporting guideline. RESULTS: We identified 6 eligible studies of which only 2 RCTs and 386 participants with various types of glaucoma at different stages were ultimately included. The results revealed significant IOP decreases after mTLT up to 12 months and significant NOAM reductions at 1 month (WMD=-0.30, 95% CI -0.54 to 0.06), and 3 months (WMD=-0.39, 95% CI -0.64 to 0.14) in mTLT compared to CW-TSCPC. Moreover, the retreatment rates (Log OR=-1.00, 95% CI -1.71 to -0.28), hypotony (Log OR=-1.21, 95% CI -2.26 to -0.16), prolonged inflammation or uveitis (Log OR=-1.63, 95% CI -2.85 to -0.41), and worsening of visual acuity (Log OR=-1.13, 95% CI -2.19 to 0.06) occurred less frequently after mTLT. CONCLUSION: Our results demonstrated that mTLT could lower the IOP until 12 months after treatment. mTLT seems to have a lower risk of retreatment after the first procedure, and mTLT is superior to CW-TSCPC with respect to safety. Studies with longer follow-up durations and larger sample sizes are necessary in the future. TRIAL REGISTRATION NUMBER: INPLASY202290120.

Morphology and microcirculation changes of the optic nerve head between simple high myopia and pathologic myopia.

PURPOSE: To investigate morphological and microcirculation changes of optic nerve head (ONH) in simple high myopia (SHM) and pathologic myopia(PM) to evaluate and identify ONH changes in the development of PM. METHODS: A cross-sectional clinical study was used. Medical records from 193 right eyes of 193 patients with high myopia (HM) were included. Using the Topocon swept source optical coherence tomograph (SS-OCT) and fundus camera to detect the parameters, we have assessed the relative position and size of ONH, tilt and rotation of ONH, angle α (Defined as between retinal temporal arterial vascular arcades was measured from the centre of ONH with 250 pixels' radius), size and type of peripapillary atrophy (PPA), the thickness of peripapillary retinal nerve fiber layer (PRNFL), peripapillary choriodal thickness (PCT) and peripapillary scleral thickness (PST), and peripapillary vessel density (PVD). In addition, subjects were grouped as SHM and PM according to retinopathy, and the above parameters were compared between the two groups. RESULTS: Patients were divided into the SHM group (138 eyes) and the PM group (55 eyes). Paramters like older age, higher diopter and longer axial length (AL) of the PM were compared to SHM (t=-3.585, -8.808, -11.409, all P<0.05). There were no differences in the smallest diameter and area of ONH, rotation angle and ratio, or PST (all P>0.05). The angle α in PM was smaller than that in SHM (t = 2.728, P<0.01). The disc-fovea distance (DFD), the largest diameter, tilt index and ratio, PPA area and radian in PM were larger than in SHM (t=-3.962, Z=-2.525, t=-2.229, Z=-4.303, Z=-2.834, all P<0.05). The superior and inferior PRNFLs in PM were smaller than in SHM (t = 4.172, 4.263, all P<0.01). The temporoinferior PRNFL was the opposite (t=-2.421, P<0.01). The average PCT in PM (93.82 ± 29.96 µm) was smaller than in SHM (108.75 ± 30.70 µm) (P<0.05). The PVD in each direction of PM was smaller than that in SHM (t = 6.398, 4.196, 4.971, 3.267, 5.029, 5.653, 4.202, 5.146, 2.090, all P<0.05). CONCLUSION: Compared with SHM, the PM patients were older, with higher diopter. Their AL and DFD were longer, the angle α was smaller, the tilt index was more extensive, the PPA area and radian were larger, PCT was generally thinner, and PVD was lower. When the PPA area was bigger than the ONH area, this already indicated the presence of PM. Based on these results, we suggest ophthalmologists and myopia patients pay more attention to ONH's morphology and microcirculation changes as there is a possibility that microcirculatory changes precede morphologic changes.

The efficacy of XEN gel stent implantation in glaucoma: a systematic review and meta-analysis.

BACKGROUND: Xen is a device for minimally invasive glaucoma surgery, and is used to treat POAG, pseudoexfoliative or pigmentary glaucoma, as well as refractory glaucoma. The efficacy of XEN in treating glaucoma remains to be confirmed and clarified. Hence, we conducted a systematic review and meta-analysis to examine the efficacy and associated complication of XEN implantations. METHODS: We conducted a literature search in PubMed, EMBASE, the Cochrane Library of Systematic Reviews, Web of Science, China National Knowledge Infrastructure, WanFang and SinoMed databases to identify studies, published before May 15, 2021, which evaluated XEN in glaucoma, and parameters for measurements included intra-ocular pressure (IOP), number of anti-glaucoma medications (NOAM), and bleb needling rate. We compared the measurements of XEN-only procedure between phaco-XEN and trabeculectomy, and we also did sub-analysis based on time points, glaucoma types, ethnics, etc. Sensitivity analyses and publication bias were conducted for evaluating bias.This study followed the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA 2020) reporting guideline. RESULTS: We identified 78 eligible studies, analysis revealed obvious IOP reduction after XEN stent implantation (SMD: 1.69, 95% CI 1.52 to 1.86, p value < 0.001) and NOAM reduction (SMD: 2.11, 95% CI 1.84 to 2.38, p value < 0.001). Sub-analysis showed no significant difference with respect to time points, ethnicities, and economic status. No significant difference was found between XEN treatment effect on POAG and PEXG eyes and between pseudo-phakic and phakic eyes. Also no significant difference was found between XEN and phaco-XEN surgery in terms of IOP after surgery (SMD: -0.01, 95% CI -0.09 to 0.08, p value 0.894). However, NOAM (after publication bias correction) and bleb needling rate (RR: 1.45, 95% CI 1.06to 1.99, p value 0.019) were lower in phaco-XEN group compared to XEN only group. Compared to trabeculectomy, XEN implantation had similar after-surgery IOP, however bleb needling rate (RR: 2.42, 95% CI 1.33 to 4.43, p value 0.004) was higher. CONCLUSION: Our results confirmed that XEN is effective in lowering both IOP and NOAM till 48 months after surgery. It is noteworthy that XEN implantation leads to higher needling rate, compared to phaco-XEN or trabeculectomy. Further research, studying complications of XEN on non-European ethnicities, especially on Asian, are in urgent need before XEN is widely applied.

Prevalence and diagnostic ability of ß-zone parapapillary atrophy in open-angle glaucoma: a systematic review and meta-analysis.

BACKGROUND: ß-Zone parapapillary atrophy (ß-PPA) is a common sign in patients with open-angle glaucoma (OAG). Some studies have suggested that ß-PPA can aid in the diagnosis of OAG. We performed a systematic review and meta-analysis of the prevalence and diagnostic ability of ß-PPA in OAG. METHODS: We performed a literature search in PubMed, Web of Science, Embase and Google Scholar from inception to 1st November, 2021. Both hospital-based and population-based studies that reported details of ß-PPA in OAG were included. RESULTS: We screened 1404 articles from these databases and ultimately included 24 articles in our meta-analysis. The prevalence of ß-PPA in OAG was 0.73 (95% CI 0.67 to 0.78). The results of subgroup analysis by country revealed prevalence rates of 0.83 (95% CI 0.78 to 0.88) in Japan, 0.85 (95% CI 0.64 to 0.97) in Korea, 0.64 (95% CI 0.55 to 0.73) in the USA, 0.61 (95% CI 0.58 to 0.63) in Germany and 0.57 (95% CI 0.39 to 0.74) in China. Fundus photography, Heidelberg retina tomography (HRT), Heidelberg retina angiography (HRA) + indocyanine green angiography (ICGA), Spectral domain optical coherence tomography (SD-OCT)and Swept source optical coherence tomography(SS-OCT) values were 0.65 (95% CI 0.58 to 0.71), 0.70 (95% CI 0.50 to 0.86), 0.78 (95% CI 0.61 to 0.91), 0.77 (95% CI 0.65 to 0.88) and 0.99(95% CI 0.87 to 1.00) respectively. The sensitivity and specificity of ß-PPA as a diagnostic marker were 0.78 (95% CI 0.68 to 0.85) and 0.63 (95% CI 0.51 to 0.73), respectively. CONCLUSIONS: ß-PPA is a potential diagnostic marker for OAG. However, a more detailed understanding of ß-PPA characteristics is needed to improve the ability to predict OAG.

Detection of a novel PAX6 variant in a Chinese family with multiple ocular abnormalities.

BACKGROUND: Aniridia is a congenital, panocular disease that can affect the cornea, anterior chamber angle, iris, lens, retina and optic nerve. PAX6 loss-of-function variants are the most common cause of aniridia, and variants throughout the gene have been linked to a range of ophthalmic abnormalities. Furthermore, particular variants at a given site in PAX6 lead to distinct phenotypes. This study aimed to characterize genetic variants associated with congenital aniridia in a Chinese family. METHODS: The proband and family underwent ophthalmologic examinations. DNA was sampled from the peripheral blood of all 6 individuals, and whole-exome sequencing was performed. Sanger sequencing was used to verify the variant in this family members. RESULTS: A novel variant (c.114_119delinsAATTTCC: p.Pro39llefsTer17) in the PAX6 gene was identified in subjects II-1, III-1 and III-2, who exhibited complete aniridia and cataracts. The proband and the proband's brother also had glaucoma, high myopia, and foveal hypoplasia. CONCLUSIONS: We identified that a novel PAX6 frameshift heterozygous deletion variant is the predominant cause of aniridia in this Chinese family. TRIAL REGISTRATION: We did not perform any health-related interventions for the participants.

Micropulse laser trabeculoplasty on Chinese patients with glaucoma or ocular hypertension: average 35 months follow-up results.

BACKGROUND: Glaucoma is a group of eye diseases that can damage the optic nerve and cause vision loss. A novel technology micropulse laser trabeculoplasty (MLT) can use duty-circle subvisible laser pulses to treat glaucoma. The aim of this study is to evaluate the efficacy of 360° MLT to alleviate intraocular pressure (IOP) in patients with glaucoma. METHODS: This was a single-center prospective study on patients treated with 360° MLT using a Diode True-Yellow 577-nm Laser with MicroPulse technology. All the patients were recruited from the Department of Ophthalmology. Follow-up visits were carried out at 1 day, 1 week, 1 month, 3 months, 6 months, 18 months, and 36 months after the procedure. Best-corrected visual acuity (BCVA), Intraocular pressure (IOP), and vertical cup-to-disc ratio (C/D ratio) were measured during the follow-up. Repeated-measures analysis of variance (ANOVA) and Kaplan-Meier analysis were performed to evaluate the outcomes. RESULTS: A total of 39 eyes from 25 patients were included in this study (10 men/15 women). The average age of patients was 41.47 ± 14.39 years old, and the baseline IOP was 21.13 ± 7.75 mmHg. MLT significantly reduced the IOP at 1 day (range 15.61-19.01, P = 0.0218), 3 months (range 16.47-19.22, P = 0.0390), and 6 months (range 15.38-18.56, P = 0.0332) compared with the baseline. However, by the end of the study, only 21.88% of patients demonstrated a ≥ 20% IOP reduction, while seven eyes needed further laser or surgical treatment. The IOP of glaucoma patients was significantly lower than the ocular hypertension patients at 1 month (P = 0.0124), 3 months (P = 0.0004), 18 months (P = 0.0061) and 36 months (P = 0.0119). CONCLUSIONS: Micropulse laser trabeculoplasty reduce IOP in patients with glaucoma or ocular hypertension for a short period, but its lowering efficiency is limited up to 6 months of the follow-up period.

The potential role of long noncoding RNAs in primary open-angle glaucoma.

PURPOSE: To identify the potential genes in human trabecular meshwork (TM) related to primary open-angle glaucoma (POAG). METHODS: First, long noncoding RNA (LncRNA) and mRNA expression profiles in TM samples from 4 control subjects and 4 POAG patients were accessed by microarray analyses. Then, twenty lncRNAs were validated by real-time quantitative PCR in the same samples from microarray analyses. Finally, eight highly expressed lncRNAs were further tested by real-time quantitative PCR in TM from 8 normal controls and 19 POAG patients. Expression data were normalized and analyzed using the R software. Pathway analyses were performed by Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis. RESULTS: A total of 2179 lncRNAs and 923 mRNAs in the TM of POAG patients were significantly upregulated, and 3111 lncRNAs and 887 mRNAs were significantly downregulated. ENST00000552367, ENST00000582505, ENST00000609130, NR_029395, NR_038379, and ENST00000586949 expression levels were significantly higher in the TM from a different cohort of POAG patient than normal controls. CONCLUSION: ENST00000552367, ENST00000582505, ENST000006091- 30, NR_029395, NR_038379, and ENST00000586949 may play essential roles in the development of POAG.

Posterior staphyloma is associated with the microvasculature and microstructure of myopic eyes.

OBJECTIVE: To investigate the microvasculature and structural characteristics of the eyes of myopic patients and their association with posterior staphyloma (PS). METHODS: This was a retrospective, case-control study comprising of 106 eyes from 72 individuals. Using 1:1 matching of axial length (AL) of their eyes, patients were allocated into a PS group or no posterior staphyloma (NPS) group. All patients were examined using ultra-widefield fundus imaging, optical coherence tomography angiography, and ocular biometry to acquire microvasculature and microstructure parameters. RESULTS: The anterior chamber depth (ACD) of the PS group was significantly different from that of the NPS group (3.56 mm vs 3.76 mm, P < 0.001), as was 1ens thickness (3.72 mm vs 3.57 mm, P = 0.005) and spherical equivalent (SE)(-10.11D vs -8.80D, P = 0.014). The PS group had reduced choriocapillaris flow, subfoveal choroidal thickness (SFCT), and a thinner retinal layer compared with the NPS group. No difference in retinal blood flow between the two groups was observed. The PS group exhibited a smaller disc area (15082.89 vs 17,043.32, P = 0.003) and angle α between temporal retinal arterial vascular arcades (113.29°vs 128.39°, P = 0.003), a larger disc tilt ratio (1.41 vs 1.24, P < 0.001) and parapapillary atrophy (PPA) area (13840.98 vs 8753.86, P = 0.020), compared with the NPS group. Multivariate regression analysis indicated that disc tilt ratio (P = 0.031) and SFCT (P = 0.015) were significant predictors of PS. In addition, PS (P = 0.049), AL (P = 0.003), corneal refractive power (P < 0.001), ACD (P = 0.022), relative lens position (P = 0.045), and disc area (P = 0.011) were significant predictors of SE. CONCLUSIONS: PS was found to be closely linked to a reduction in choriocapillaris perfusion and anatomical abnormalities including posterior and anterior segments. Furthermore, PS exacerbated the progression of myopia.

A PITX2 splice-site mutation in a family with Axenfeld-Rieger syndrome leads to decreased expression of nuclear PITX2 protein.

PURPOSE: Axenfeld-Rieger syndrome (ARS) is an autosomal dominant disorder characterized by ocular anterior segment abnormalities. In the current study, we describe clinical and genetic findings in a Chinese ARS pedigree. METHODS: An ARS pedigree was recruited and patients were given comprehensive ophthalmic examinations and general physical examinations. DNA from the proband II:2 was used for exome sequencing. Sanger sequencing was utilized to identify and validate PITX2 variations. qPCR and western blotting were performed to detect PITX2 expression in immortalized peripheral blood lymphocytes. RESULTS: All affected family members showed typical ocular abnormalities, including iris atrophy, corectopia, shallow anterior chamber, complete or partial angle closure, and advanced glaucoma. They also exhibited systemic anomalies, such as microdontia, hypodontia, and redundant periumbilical skin. A heterozygous splice-site variation c.390 + 1G > A in PITX2, which might lead to a truncated PITX2 protein (p.Val131IlefsX127), was found in the proband. Sanger sequencing validated that the variation completely co-segregated with the ARS phenotype within this family and was absent in 100 unrelated controls. Western blotting revealed that the nuclear PITX2 protein was significantly decreased in patients compared with controls. Nonetheless, there was no significant difference in the total PITX2 protein level, consistent with qPCR results showing no alteration in PITX2 mRNA levels in the patient group. CONCLUSIONS: PITX2 c.390 + 1G > A (p.Val131IlefsX127) was a novel genetic etiology of the ARS pedigree. The mutation leads to decreased nuclear PITX2, indicating lower transcriptional activity.

Potential Biomarkers for Primary Open-Angle Glaucoma Identified by Long Noncoding RNA Profiling in the Aqueous Humor.

This study aimed to identify potential biomarkers for primary open-angle glaucoma (POAG) diagnosis. First, long noncoding RNA (lncRNA) and mRNA expression profiles in the aqueous humor (AH) from 10 POAG and 10 control patients were accessed by microarray analyses. Coding-noncoding gene coexpression networks were drawn to predict potential lncRNA functions. lncRNA T267384, ENST00000607393, and T342877 expression levels were further tested by real-time quantitative PCR in AH from 29 POAG and 30 cataract patients, in iris tissues from 16 POAG patients and 10 controls, and in plasma from 49 POAG patients and 55 healthy controls. Finally, ENST00000607393 function was characterized in an in vitro model of cell calcification. A total of 3627 lncRNAs and 2228 mRNAs in the AH of POAG patients were significantly up-regulated, and 1520 lncRNAs and 820 mRNAs were significantly down-regulated. Seven lncRNAs showed positive correlation with glaucoma-associated gene, bone morphogenetic protein 2. Moreover, real-time quantitative RT-PCR confirmed that T267384, ENST00000607393, and T342877 expression levels were significantly higher in the AH from a different cohort of POAG patients. ENST00000607393 was also significantly higher in the iris and plasma of POAG patients. Last, ENST00000607393 knockdown alleviated calcification of primary human trabecular meshwork cells in vitro. Therefore, lncRNAs T267384, ENST00000607393, and T342877 may be potential biomarkers for POAG diagnosis. ENST00000607393 might be a new therapeutic target for trabecular meshwork calcification.

A novel glaucomatous representation method based on Radon and wavelet transform.

BACKGROUND: Glaucoma is an irreversible eye disease caused by the optic nerve injury. Therefore, it usually changes the structure of the optic nerve head (ONH). Clinically, ONH assessment based on fundus image is one of the most useful way for glaucoma detection. However, the effective representation for ONH assessment is a challenging task because its structural changes result in the complex and mixed visual patterns. METHOD: We proposed a novel feature representation based on Radon and Wavelet transform to capture these visual patterns. Firstly, Radon transform (RT) is used to map the fundus image into Radon domain, in which the spatial radial variations of ONH are converted to a discrete signal for the description of image structural features. Secondly, the discrete wavelet transform (DWT) is utilized to capture differences and get quantitative representation. Finally, principal component analysis (PCA) and support vector machine (SVM) are used for dimensionality reduction and glaucoma detection. RESULTS: The proposed method achieves the state-of-the-art detection performance on RIMONE-r2 dataset with the accuracy and area under the curve (AUC) at 0.861 and 0.906, respectively. CONCLUSION: In conclusion, we showed that the proposed method has the capacity as an effective tool for large-scale glaucoma screening, and it can provide a reference for the clinical diagnosis on glaucoma.

A novel frameshift mutation in the PITX2 gene in a family with Axenfeld-Rieger syndrome using targeted exome sequencing.

BACKGROUND: Axenfeld-Rieger syndrome (ARS) is an autosomal dominant genetic disorder that is characterized by specific abnormalities of the anterior segment of the eye. Heterozygous mutations in two developmental transcription factor genes PITX2 and FOXC1 have been identified within ARS patients, accounting for 40 to 70% of cases. Our purpose is to describe clinical and genetic findings in a Chinese family with ARS. METHODS: An ARS family with three affected members was recruited. The patients underwent a series of complete ophthalmologic examinations, general physical examination and dental radiography. DNA samples of proband II-1 were used for targeted exome sequencing of the FOXC1 and PITX2 genes. Sanger sequencing was used to validate the variation in PITX2. Quantitative real-time PCR was carried out to detect the expression of PITX2 in patients and normal controls. RESULTS: All affected members showed iris atrophy, corectopia, shallow anterior chamber, complete or partial angle closure, and advanced glaucoma. In addition, they revealed systemic anomalies, including microdontia, hypodontia, and redundant periumbilical skin. A novel heterozygous frameshift variation, c.515delA, in PITX2 was found in the proband, which might lead to a truncated PITX2 protein (p.Gln172ArgfsX36). Sanger sequencing validated that the variation completely cosegregated with the ARS phenotype among this family, but was absent in 100 unrelated controls. Quantitative real-time PCR analysis revealed that the mRNA expression of PITX2 was significantly decreased in patients compared with that in unrelated normal controls. CONCLUSIONS: PITX2 c.515delA (p.Gln172ArgfsX36) was the genetic etiology of our pedigree. The mutation led to decreased PITX2 gene expression and a truncated mRNA transcript.

Roles of CYP2C19 Gene Polymorphisms in Susceptibility to POAG and Individual Differences in Drug Treatment Response.

BACKGROUND: The aim of this study was to investigate the roles of cytochrome P450 2C19 (CYP2C19) polymorphisms in primary open-angle glaucoma (POAG) susceptibility and individual responses to drug treatment. MATERIAL/METHODS: This case-control study consisted of 93 cases with POAG and 125 controls. Polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) was used to analyze CYP2C19 single-nucleotide polymorphisms (SNPs). After timolol treatment, patients were classified into side effect (SE) group and non-side effect (NSE) group. According to drug treatment responses, patients were divided into 3 groups: excellent group (Ex) (IOP ≥8 mm Hg); utility group (Ut) (5 0.05). Frequencies of extensive metabolizer phenotype and poor metabolizer phenotype or poor metabolizer phenotype and intermediate metabolizer phenotype were significantly different between the SE group and NSE group (both P<0.05). The distribution of intermediate metabolizer phenotype and extensive metabolizer phenotype were significantly different among Ex group, Ut group, and In group (all P<0.05). CONCLUSIONS: We found no evidence that CYP2C19 polymorphisms are associated with susceptibility to POAG. However, different CYP2C19 metabolizer phenotypes were identified and observed to have important effects on the individual differences in drug treatment response.