Photocrosslinkable Sericin Hydrogel Injected into the Anterior Chamber of Mice with Chronic Ocular Hypertension Efficacy, Medication Sensitivity, and Material Safety.

(1) Background: A rise in intraocular pressure (IOP) and decreased retinal ganglion cells are frequent indicators of effective modeling of chronic ocular hypertension in mice. In this study, the sensitivity of the mouse model to pharmaceutical therapy to reduce intraocular tension was assessed, the model's safety was confirmed using a cytotoxicity test, and the success rate of the mouse model of ocular hypertension was assessed by assessing alterations in IOP and neurons in the ganglion cell layer. (2) Methods: A mouse model of chronic ocular hypertension was produced in this study by employing photocrosslinkable sericin hydrogel injection and LED lamp irradiation. The eyes of 25 C57BL/6 male mice were subjected to 405 nm UV light from the front for 2 min after being injected with 5 µL of sericin hydrogel in the anterior chamber of the left eye. IOP in the mice was measured daily, and IOP rises greater than 5 mmHg were considered intraocular hypertension. When the IOP was lowered, the intervention was repeated once, but the interval between treatments was at least 2 weeks. The right eyes were not treated with anything as a normal control group. Mice eyeballs were stained with HE, Ni-type, and immunofluorescence to assess the model's efficacy. Two common drugs (tafluprost eye drops and timolol eye drops) were provided for one week after four weeks of stable IOP, and IOP changes were assessed to determine the drug sensitivity of the mouse model of chronic ocular hypertension. Furthermore, CellTiter 96® AQueous One Solution Cell Proliferation Assay (MTS) was utilized to investigate the safety of the ocular hypertension model by evaluating the deleterious effects of photocrosslinkable sericin hydrogel on cells. (3) Results: Before injection, the basal IOP was (9.42 ± 1.28) mmHg (1 kPa = 7.5 mmHg) in the experimental group and (9.08 ± 1.21) in the control group. After injection, cataract occurred in one eye, corneal edema in one eye, endophthalmitis in one eye, iris incarceration in one eye, and eyeball atrophy in one eye. Five mice with complications were excluded from the experiment, and twenty mice were left. Four weeks after injection, the IOP of the experimental group was maintained at (19.7 ± 4.52) mmHg, and that of the control group was maintained at (9.92 ± 1.55) mmHg, and the difference between the two groups was statistically significant (p < 0.05). Before the intervention, the IOP in the experimental group was (21.7 ± 3.31) mmHg in the high IOP control group, (20.33 ± 2.00) mmHg in the tafluprost eye drops group, and (20.67 ± 3.12) mmHg in the timolol maleate eye drops group. The IOP after the intervention was (23.2 ± 1.03) mmHg, (12.7 ± 2.11) mmHg, and (10.4 ± 1.43) mmHg, respectively. Before and after the intervention, there were no significant differences in the high-IOP control group (p > 0.05), there were statistically significant differences in the timolol eye drops group (p < 0.05), and there were statistically significant differences in the tafluprost eye drops group (p < 0.05). One week after drug withdrawal, there was no significant difference in IOP among the three groups (p > 0.05). In the high-IOP group, the protein (sericin hydrogel) showed a short strips or fragmented structure in the anterior chamber, accompanied by a large number of macrophages and a small number of plasma cells. The shape of the chamber angle was normal in the blank control group. The number of retinal ganglion cells decreased significantly 8 weeks after injection of sericin hydrogel into the anterior chamber, and the difference was statistically significant compared with the blank control group (p < 0.05). After the cells were treated with photocrosslinkable sericin hydrogel, there was no significant difference in the data of the CellTiter 96® assay kit of MTS compared with the blank control group (p > 0.05). (4) Conclusions: A mouse model of chronic intraocular hypertension can be established successfully by injecting sericin in the anterior chamber and irradiating with ultraviolet light. The model can simulate the structural and functional changes of glaucoma and can effectively reduce IOP after the action of most antihypertensive drugs, and it is highly sensitive to drugs. Sericin has no obvious toxic effect on cells and has high safety.

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.

A novel adjustable PHBV basement film for enhancing the efficacy of glaucoma surgery by inhibiting scar formation.

Trabeculectomy is the primary surgical approach used to treat glaucoma, but scarring of the filtering passage (filtering bleb) after surgery often leads to treatment failure. To address this issue, we have developed a drug release system called RSG/Pd@ZIF-8 PHBV film. This system enables the sustained release of an anti-fibrosis drug, aiming to prevent scarring. In vitro, the film has the function of continuous Rosiglitazone (RSG) release, with accelerated release after laser irradiation. The antibacterial experiments revealed that the film exhibited antibacterial rates of 87.0 % against E.coli and 97.1 % against S.aureus, respectively. Moreover, we confirmed its efficacy in a rabbit eye model undergoing trabeculectomy. After implantation of the film, we observed a prolonged postoperative period for reducing intraocular pressure (IOP), increased survival rate of filtering blebs, and improved long-term surgical outcomes in vivo. Additionally, the film exhibited excellent biosafety. In summary, the designed sustained-release film in this study possesses the aforementioned functionalities, allowing for the regulation of anti-scarring drug release without causing harm post-surgery. This personalized and precise anti-scarring strategy represents a significant advancement.

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.

MiR-29b Downregulation by p53/Sp1 Complex Plays a Critical Role in Bleb Scar Formation After Glaucoma Filtration Surgery.

Purpose: To investigate the function and mechanism of tumor protein p53 in pathological scarring after glaucoma filtration surgery (GFS) using human Tenon's fibroblasts (HTFs) and a rabbit GFS model. Methods: The expression of p53 in bleb scarring after GFS and transforming growth factor-ß (TGF-ß)-induced HTFs (myofibroblasts [MFs]) was examined by western blot and immunochemical analysis. The interaction between p53 and specificity protein 1 (Sp1) was investigated by immunoprecipitation. The role of p53 and Sp1 in the accumulation of collagen type I alpha 1 chain (COL1A1) and the migration of MFs was evaluated by western blot, quantitative real-time polymerase chain reaction (qRT-PCR), wound healing, and Transwell assay. The regulatory mechanisms among p53/Sp1 and miR-29b were detected via qRT-PCR, western blot, luciferase reporter assay, and chromatin immunoprecipitation assay. The therapeutic effect of mithramycin A, a specific inhibitor of Sp1, on scarring formation was evaluated in a rabbit GFS model. Results: p53 was upregulated in bleb scar tissue and MFs. p53 and Sp1 form a transcription factor complex that induces the accumulation of COL1A1 and promotes the migration of MFs through downregulation of miR-29b, a known suppressor of COL1A1. The p53/Sp1 axis inhibits miR-29b expression by the direct binding promoter of the miR-29b gene. Mithramycin A treatment attenuated bleb scar formation in vivo. Conclusions: The p53/Sp1/miR-29b signaling pathway plays a critical role in bleb scar formation after GFS. This pathway could be targeted for therapeutic intervention of pathological scarring after GFS. Translational Relevance: Our research indicates that inhibition of p53/Sp1/miR-29b is a promising therapeutic strategy for preventing post-GFS pathological scarring.

Construction of miRNA-mRNA regulatory network indicates potential biomarkers for primary open-angle glaucoma.

BACKGROUND: Trabecular meshwork (TM) dysfunction-induced elevation of intraocular pressure has been identified as the main risk factor of irreversible optic nerve injury in Primary open­angle glaucoma (POAG). Increasing evidences suggest that microRNA (miRNA) plays a vital role in the pathogenesis of POAG. This study aims to construct a miRNA-mRNA regulatory network and identify biomarkers for POAG. METHODS: miRNAs and mRNAs expression profiling of TM samples from controls and POAG patients were assessed through microarray analysis. Target genes of differentially expressed miRNAs (DEmiRNAs) were predicted by miEAA and miRNet. Then GO and KEGG pathway analysis of differentially expressed mRNAs (DEmRNAs) were performed. PPI of top 30 hub genes was identified and miRNA-mRNA network was established by STRING database and Cytoscape software. GSE27276 and GSE105269 datasets were used to verify the expression of hub genes and to predict potential biomarkers in TM and aqueous humor (AH) for POAG, respectively. Finally, GSEA analysis was conducted to estimate the main signaling pathway of POAG pathogenesis. RESULTS: A total of 29 up-regulated and 7 down-regulated miRNAs, 923 up-regulated and 887 down-regulated mRNAs were identified in TM of POAG compared with controls. Target genes and DEmRNAs were mainly enriched in nitric oxide biosynthetic process, vasopressin-regulated water reabsorption, and so on. Through miRNA-mRNA network construction, top 30 hub genes were regulated by 24 DEmiRNAs. 8 genes were aberrantly expressed in dataset GSE27276. 3 genes (CREB1, CAPZA2, SLC2A3) and 2 miRNAs (miR-106b-5p, miR-15a-5p) were identified as potential biomarkers for POAG in TM and AH, respectively. GSEA analysis revealed that these 3 genes modulated POAG through different pathways. CONCLUSION: In this study, construction of miRNA-mRNA network and identification of biomarkers provide a novel insight into the pathogenesis, early diagnosis and treatment for POAG.

Semi-supervised OCT lesion segmentation via transformation-consistent with uncertainty and self-deep supervision.

Optical coherence tomography (OCT) is a non-invasive, high-resolution ocular imaging technique with important implications for the diagnosis and management of retinal diseases. Automatic segmentation of lesions in OCT images is critical for assessing disease progression and treatment outcomes. However, existing methods for lesion segmentation require numerous pixel-wise annotations, which are difficult and time-consuming to obtain. To address this challenge, we propose a novel framework for semi-supervised OCT lesion segmentation, termed transformation-consistent with uncertainty and self-deep supervision (TCUS). To address the issue of lesion area blurring in OCT images and unreliable predictions from the teacher network for unlabeled images, an uncertainty-guided transformation-consistent strategy is proposed. Transformation-consistent is used to enhance the unsupervised regularization effect. The student network gradually learns from meaningful and reliable targets by utilizing the uncertainty information from the teacher network, to alleviate the performance degradation caused by potential errors in the teacher network's prediction results. Additionally, self-deep supervision is used to acquire multi-scale information from labeled and unlabeled OCT images, enabling accurate segmentation of lesions of various sizes and shapes. Self-deep supervision significantly improves the accuracy of lesion segmentation in terms of the Dice coefficient. Experimental results on two OCT datasets demonstrate that the proposed TCUS outperforms state-of-the-art semi-supervised segmentation methods.

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.

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.

Distribution of the Retinal Microcirculation Based on the Morphology of the Optic Nerve Head in High Myopia.

PURPOSE: To explore the retinal microvasculature of the optic nerve head and macula and their associations with the optic nerve head deformation in high myopia. METHODS: One hundred sixty-seven eyes from patients with high myopia (HM) were enrolled in a cross-sectional study. We have evaluated and measured characteristics like the tilt ratio of the optic disc, interpupillary vascular density (IVD), peripapillary vascular density (PVD), macular vascular density (MVD), subfoveal choroidal thickness (SFCT) and foveal avascular zone (FAZ). The subjects were classified as a non-tilt group (control group) and a tilt group based on the tilt index. The above parameters were utilized to compare the two groups. In addition, we collected the data from the subjects' right eyes to analyze variance, the Kruskal-Wallis test, and the least significant difference. RESULTS: The patients were divided into the non-tilt group of ninety-one eyes and the tilt group of seventy-six eyes. We found that the IVD in the tilt group was more significant than in the non-tilt group (t = -2.794, P = .006). On the other hand, the PVD was less in the tilt group than in the non-tilt, especially in the NS, NI and IN directions (tNS = 3.782; tNI = 3.07; tIN = 2.086; P < .05). Interestingly, the values of PVD were the highest in temporal, second in superior and inferior and lowest in nasal. Concerning the fovea-DMVD (including fovea, parafovea and perifovea), we characterized them as more minor in the tilt group when compared to those in the non-tilt group (P < .05). CONCLUSION: Herein, we discovered that the retinal microvasculature differed significantly in patients with HM according to the ONH morphology. In this population, lower PVD and thinner SFCT were associated with higher odds of the tilted optic disc. In addition, the other two characteristics, the IVD and DMVD, were affected by the ONH deformation. Finally, we showed that PVD demonstrated better predictability of rapid myopic progression than MVD.

Changes of optic nerve head microcirculation in high myopia.

AIM: To analyze the correlation of age, spherical equivalent (SE), and axial length (AL) with the microcirculation of optic nerve head (ONH) in high myopia (HM). METHODS: In this cross-sectional clinical study, 164 right eyes were included. Optical coherence tomography angiography (OCTA) was used to detect ONH vessel density. Eyes were classified based on age, SE, and AL. Groups of Age1, Age2, and Age3 were denoted for age classification (Age1<20y, 20y≤Age2<30y, Age3≥30y); Groups SE1, SE2, and SE3 for the SE classification (-9≤SE1<-6 D, -12≤SE2<-9 D, SE3<-12 D); Groups AL1, AL2, AL3, and AL4 for the AL classification (AL1<26 mm, 26≤AL2<27 mm, 27≤AL3<28 mm, AL4≥28 mm). RESULTS: No significant difference was observed in vessel density among the Age1, Age2, and Age3 groups (all P>0.05) and the SE1, SE2, and SE3 groups (all P>0.05). No significant difference was observed in the intrapapillary vascular density (IVD) among AL1, AL2, AL3, and AL4 groups (P>0.05). However, a significant decrease was found in the peripapillary vascular density (PVD) in the AL1, AL2, AL3, and AL4 groups (F=3.605, P=0.015), especially in the inferotemporal (IT; F=6.25, P<0.001), temporoinferior (TI; F=2.865, P=0.038), and temporosuperior (TS; F=6.812, P<0.001) sectors. The IVD was correlated with age (r=-0.190, P<0.05) but not with SE or AL (P>0.05). The PVD was correlated with AL (r=-0.236, P<0.01) but not with age or SE (P>0.05). CONCLUSION: With the increase of AL, the IVD remains stable while the PVD decreases, especially in the three directions of temporal (IT, TI, and TS). The main cause of microcirculation reduction may be related to AL elongation rather than an increase in age or SE.

Safety of Fixed-Combination Bimatoprost 0.03%/Timolol 0.5% Ophthalmic Solution at 6 Months in Chinese Patients with Open-Angle Glaucoma or Ocular Hypertension.

INTRODUCTION: Fixed-combination bimatoprost 0.03%/timolol 0.5% ophthalmic solution (FCBT; Ganfort®, Allergan, an AbbVie company) effectively reduces intraocular pressure (IOP) via complementary mechanisms of action of the agents, but long-term (> 12 weeks) safety evaluations of FCBT remain limited. FCBT safety is evaluated herein, with particular focus on hyperemia and eyelash growth, at 24 weeks in Chinese patients with open-angle glaucoma (OAG) or ocular hypertension (OHT). METHODS: In this multicenter, open-label, noncomparative, phase 4 study conducted in China, patients diagnosed with OAG or OHT having insufficient response to ß-blocker- or prostaglandin analogue/prostamide (PGA)-based IOP-lowering monotherapy in one or both eyes were switched from their current IOP-lowering treatment to FCBT (one drop per eye every evening) without prior washout. Assessment visits were scheduled at baseline and weeks 4, 12, and 24 (or study exit). The primary outcome measure was adverse event (AE) incidence through 24 weeks. RESULTS: Of 725 patients enrolled, 632 (87.2%) completed the study; 93 (12.8%) patients discontinued, including 29 (4.0%) due to AEs. Of 1326 FCBT-treated eyes (total), 594 (44.8%) experienced ≥ 1 ocular treatment-related AE during the study. Conjunctival hyperemia (the most common AE overall) and eyelash growth were reported in 269 (20.3%) and 54 (4.1%) FCBT-treated eyes, respectively. The incidence of other known PGA-related AEs (including blepharal pigmentation and erythema of eyelid) was < 10% each. Most conjunctival hyperemia reports were mild in severity (214/259; 82.6%) and only 1/259 (0.4%) was severe. Similarly, most cases of eyelash growth were mild (46/52; 88.5%); none were severe. One (< 0.1%) FCBT-treated eye had a serious ocular AE (OAG) considered FCBT-related. CONCLUSIONS: The frequency and severity of FCBT-related AEs, including conjunctival hyperemia and eyelash growth, are consistent with previously published findings. No new safety concerns were raised. This prospective study reaffirms that once-daily FCBT is a safe and well-tolerated therapy for OAG and OHT. GOV IDENTIFIER: NCT02571712.

Elevated IOP Alters the Material Properties of Sclera and Lamina Cribrosa in Monkeys.

Objective: Elevated intraocular pressure (IOP) has significant impacts on different stages in the progression of chronic glaucoma. In this study, we investigated changes in the material properties of sclera and lamina cribrosa (LC) in a nonhuman primate model with elevated IOP. Methods: Normal adult Tibetan macaques were selected for the construction of elevated IOP model. After 40 days of stable maintenance on the ocular hypertension, the binocular eyeballs were obtained for the measurement of macroscopic parameters of the eyeballs. Posterior scleral tissue strips were obtained in circumferential and axial directions, and thickness was measured, respectively. Biomechanical parameters were obtained with stress relaxation, creep, and tensile test. The nanoindentation test was performed on the LC and scleral tissue around optic nerve head (ONH) to obtain compressive modulus. Results: In the presence of elevated IOP, variations of the axial diameter of the eyeball were greater than those of the transverse diameter, and the mean scleral thickness around ONH was smaller in the experimental group than control group. The elastic modulus and stress relaxation modulus of sclera were larger, and the creep rate was lower in the experimental group than control group. In the control group, the elastic modulus and stress relaxation modulus of the circumferential sclera were larger in the axial direction, and creep rate was smaller. In the experimental group, there was no significant difference in biomechanical characteristics between the two directions. Compared to the control group, the compression modulus of the LC was smaller, and the compression modulus of sclera around ONH was larger in the experimental group. Conclusion: Elevated IOP alters the viscoelasticity and anisotropy of sclera and LC. These may contribute to reduction of the organizational resistance to external forces and decline in the ability of self-recovery.

Effects of Tafluprost on Ocular Blood Flow.

Increasing evidence indicates that improving ocular blood flow (OBF) can be a therapeutic direction for glaucoma therapy. Tafluprost, a prostaglandin analogue which lowers the intraocular pressure (IOP), has been shown to improve OBF in animals and humans. Several animal experiments showed that topical tafluprost significantly increased optic nerve head and retinal blood flow. Clinical trials also showed a beneficial effect of tafluprost on optic nerve head and macula blood flow, and a good ocular pulse amplitude-lowering effect. But, there are still a few conflicting results. Overall, tafluprost seems to have a beneficial effect on OBF, and the positive effect is probably independent from its IOP-lowering effect, which also is expected to improve OBF. Moreover, reducing the intracellular free Ca2+ concentration may be a possible mechanism of tafluprost's effect on OBF. More well-designed studies are required to reveal the truth.

A naringin-derived bioink enhances the shape fidelity of 3D bioprinting and efficiency of cartilage defect repair.

3D bioprinting is a major area of interest in health sciences for customized manufacturing, but lacks specific bioinks to enhance the shape fidelity of 3D bioprinting and efficiency of tissue repair for particular clinical purposes. A naringin derived bioink, which contains 1.5 mM methylacryloyl naringin and 0.15 mM methylacryloyl gelatin, improves the fidelity of 3D bioprinting due to 405 nm light absorption of methylacryloyl naringin. The naringin derived bioink promotes the growth of chondrocytes due to preserving bioactivities of naringin and functions as a medical ingredient from which it has been described as a medical bioink in this study. It facilitates cartilage regeneration by upregulating the transcription of chondrogenesis-related genes like SOX9 and genes against oxidative stress like SOD1 and SOD2 and maintains chondrocytes active resulting from the significantly enhanced COL II/COL I ratio. According to a rabbit cartilage defect model, the proposed naringin derived medical bioink significantly improves the efficiency and quality of cartilage defect repair, suggesting that the bioink is suitable for cartilage defect repair applications and a feasible strategy is provided for the formulation of medical bioinks for specific clinical purposes.

A Narrative Review of Ocular Surface Disease Related to Anti-Glaucomatous Medications.

Topical anti-glaucomatous medications are still the most important measure to lower intraocular pressure. Large number of studies have confirmed that long-term use of anti-glaucomatous eye drops, especially containing benzalkonium chloride, a preservative, can cause or aggravate ocular surface injury. Ocular surface diseases damage the ocular microenvironmental health status, reduce the patients' compliance with the treatment, and finally affect the treatment result. Therefore, the ocular surface management of patients with glaucoma is very important. This includes the selection of drugs that are better tolerated according to individual conditions, preservative-free formulations, drugs that protect against ocular surface disease, or selecting surgery and laser treatment, to prevent the damage to the ocular surface by topical anti-glaucomatous drugs.

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.

Dual-consistency semi-supervision combined with self-supervision for vessel segmentation in retinal OCTA images.

Optical coherence tomography angiography(OCTA) is an advanced noninvasive vascular imaging technique that has important implications in many vision-related diseases. The automatic segmentation of retinal vessels in OCTA is understudied, and the existing segmentation methods require large-scale pixel-level annotated images. However, manually annotating labels is time-consuming and labor-intensive. Therefore, we propose a dual-consistency semi-supervised segmentation network incorporating multi-scale self-supervised puzzle subtasks(DCSS-Net) to tackle the challenge of limited annotations. First, we adopt a novel self-supervised task in assisting semi-supervised networks in training to learn better feature representations. Second, we propose a dual-consistency regularization strategy that imposed data-based and feature-based perturbation to effectively utilize a large number of unlabeled data, alleviate the overfitting of the model, and generate more accurate segmentation predictions. Experimental results on two OCTA retina datasets validate the effectiveness of our DCSS-Net. With very little labeled data, the performance of our method is comparable with fully supervised methods trained on the entire labeled dataset.