Intraoperative challenges and outcomes of pediatric cataract surgery following glaucoma filtering surgery.

PURPOSE: To analyze the intraoperative challenges of cataract surgery in children, following glaucoma filtering surgery. METHODS: This was a retrospective study to analyze intra-op challenges and outcomes of pediatric cataract surgery in post-glaucoma filtration surgery eyes, between January 2007 and December 2019. RESULTS: We included 20 eyes of 16 children. The most common glaucoma surgery performed was trabeculectomy and trabeculotomy (14 eyes). The median age at the time of cataract surgery was 74.5 months. The most common cataract surgery performed was lens aspiration with posterior chamber intraocular lens implantation (LA + PCIOL) (9/20). The most common intraoperative challenge faced was difficulty in capsulorrhexis (ten eyes), followed by extension of primary posterior capsulotomy (six eyes). At the final follow up eight eyes had improvement in visual acuity, five eyes had stable visual acuity and five eyes had a drop in visual acuity. In 12/20 eyes IOL was implanted, nine eyes in-the-bag and three eyes had in ciliary sulcus. None of the IOLs in the bag had decentration of IOL. The median postoperative IOP (p = 0.12) and median number of postoperative AGM (p = 0.13) at 2 years remained stable compared to the preoperative values. The IOP remained well controlled in 4 eyes without anti-glaucoma medications and in 14 eyes with anti-glaucoma medications and none needed additional surgery for IOP control. Two eyes developed retinal detachment postoperatively. CONCLUSION: Cataract surgery in pediatric eyes with prior glaucoma surgeries, have challenges with capsulorrhexis and IOL stability. The visual outcomes were reasonably good so was the IOP control.

Assessing the Efficacy of Synthetic Optic Disc Images for Detecting Glaucomatous Optic Neuropathy Using Deep Learning.

Purpose: Deep learning architectures can automatically learn complex features and patterns associated with glaucomatous optic neuropathy (GON). However, developing robust algorithms requires a large number of data sets. We sought to train an adversarial model for generating high-quality optic disc images from a large, diverse data set and then assessed the performance of models on generated synthetic images for detecting GON. Methods: A total of 17,060 (6874 glaucomatous and 10,186 healthy) fundus images were used to train deep convolutional generative adversarial networks (DCGANs) for synthesizing disc images for both classes. We then trained two models to detect GON, one solely on these synthetic images and another on a mixed data set (synthetic and real clinical images). Both the models were externally validated on a data set not used for training. The multiple classification metrics were evaluated with 95% confidence intervals. Models' decision-making processes were assessed using gradient-weighted class activation mapping (Grad-CAM) techniques. Results: Following receiver operating characteristic curve analysis, an optimal cup-to-disc ratio threshold for detecting GON from the training data was found to be 0.619. DCGANs generated high-quality synthetic disc images for healthy and glaucomatous eyes. When trained on a mixed data set, the model's area under the receiver operating characteristic curve attained 99.85% on internal validation and 86.45% on external validation. Grad-CAM saliency maps were primarily centered on the optic nerve head, indicating a more precise and clinically relevant attention area of the fundus image. Conclusions: Although our model performed well on synthetic data, training on a mixed data set demonstrated better performance and generalization. Integrating synthetic and real clinical images can optimize the performance of a deep learning model in glaucoma detection. Translational Relevance: Optimizing deep learning models for glaucoma detection through integrating DCGAN-generated synthetic and real-world clinical data can be improved and generalized in clinical practice.

Multiple use of preservative-free single dose unit dexamethasone 0.1% eye drops is safe within 24 hours.

BACKGROUND: Unpreserved single-dose unit (SDU) eye drops are commonly used to avoid benzalkonium chloride-related toxicity. Although intended for single use, many patients report off-label repeated use of SDUs over a prolonged period. We investigated whether repeated use of dexamethasone 0.1% SDUs in the same patient increases the bacterial contamination rate. METHODS: We prospectively enrolled patients scheduled for inpatient corneal and glaucoma surgery receiving dexamethasone 0.1% SDU four times per day from the same vial. To assess contamination rates, one drop from the vial was cultured immediately after opening the SDU (t0), 10 hours later after four drop applications (t10) and 24 hours after opening without further drop applications (t24). Conjunctival swabs were taken before and after drop application. Contamination rate was assessed with a standard clinical culturing protocol without introducing a positive control. RESULTS: 110 eyes of 109 patients were evaluated. Drops collected immediately after opening the SDU (t0) were contaminated in 9/110 cultures (8.1%). At t10, 13/110 cultures were contaminated (11.8%; p=0.267) and 11/110 at t24 (10.0%; t24 vs t0; p=1.00). In 5 of 21 cases of contaminated drops at t10 and/or t24, the same isolates were cultured from the initial conjunctival swab and the SDU. In three cases, the same bacterial species was found in consecutive samples. CONCLUSION: The contamination rate of the SDU did not increase after multiple use within 24 hours. Contamination from fingertip flora was more likely than from ocular surface flora. Reuse of dexamethasone 0.1% SDU in the same patient within 24 hours appears to be safe.

The effect of cumulative energy in repeated subliminal transscleral cyclophotocoagulation: a retrospective study.

BACKGROUND: The long-term safety and efficacy of repeated applications of subliminal transscleral cyclophotocoagulation (SL-TSCPC) with a focus on cumulative energy was evaluated in glaucoma patients. METHODS: In this retrospective, multicentric study the data of a total of 82 eyes with various causes of glaucoma that were treated with a single or multiple applications of SL-TSCPC were collected. Treatments were performed under general or local anesthesia with an 810 nm diode laser. Power was 2000 mW; duty cycle, 31.3%; total treatment duration, 80-320 s; equaling a total energy of 50-200 J per treatment session. Fifty-five eyes (55 patients) presented for all follow-ups, and these eyes were selected for further statistical analysis. The mean age was 60.0 ± 17.1 years, and 22 (40%) of the patients were female. Intraocular pressure (IOP) and dependence on further glaucoma medication were evaluated at 12 months following the initial treatment. RESULTS: Eyes underwent 1 or 2 consecutive SL-TSCPC treatments. Median (min-max) baseline IOP of 34 (13-69) decreased to 21.5 (7-61), 22 (8-68), 20 (9-68), and 19.5 (3-60) mmHg at the 1, 3, 6, and 12-month postoperative timepoints respectively. The mean (± SD) IOP decrease at 12 months was 26 ± 27%, 39 ± 32%, and 49 ± 33% in the low (below 120 J, n = 18), medium (120-200 J, n = 24), and high (above 200 J, n = 13) cumulative energy groups respectively. At the 12-month timepoint, oral carbonic anhydrase use was discontinued in ¾ of the cases. CONCLUSIONS: It was found that the repeated application of SL-TSCPC safely and efficiently decreases IOP in a Caucasian population with heterogenous causes of glaucoma, eyes with silicone oil responded to a greater extent. Inclusion of cumulative energy scales may contribute to better addressing repeated procedures in a standardized fashion.

cFLIP in the molecular regulation of astroglia-driven neuroinflammation in experimental glaucoma.

BACKGROUND: Recent experimental studies of neuroinflammation in glaucoma pointed to cFLIP as a molecular switch for cell fate decisions, mainly regulating cell type-specific caspase-8 functions in cell death and inflammation. This study aimed to determine the importance of cFLIP for regulating astroglia-driven neuroinflammation in experimental glaucoma by analyzing the outcomes of astroglia-targeted transgenic deletion of cFLIP or cFLIPL. METHODS: Glaucoma was modeled by anterior chamber microbead injections to induce ocular hypertension in mouse lines with or without conditional deletion of cFLIP or cFLIPL in astroglia. Morphological analysis of astroglia responses assessed quantitative parameters in retinal whole mounts immunolabeled for GFAP and inflammatory molecules or assayed for TUNEL. The molecular analysis included 36-plexed immunoassays of the retina and optic nerve cytokines and chemokines, NanoString-based profiling of inflammation-related gene expression, and Western blot analysis of selected proteins in freshly isolated samples of astroglia. RESULTS: Immunoassays and immunolabeling of retina and optic nerve tissues presented reduced production of various proinflammatory cytokines, including TNFα, in GFAP/cFLIP and GFAP/cFLIPL relative to controls at 12 weeks of ocular hypertension with no detectable alteration in TUNEL. Besides presenting a similar trend of the proinflammatory versus anti-inflammatory molecules displayed by immunoassays, NanoString-based molecular profiling detected downregulated NF-κB/RelA and upregulated RelB expression of astroglia in ocular hypertensive samples of GFAP/cFLIP compared to ocular hypertensive controls. Analysis of protein expression also revealed decreased phospho-RelA and increased phospho-RelB in parallel with an increase in caspase-8 cleavage products. CONCLUSIONS: A prominent response limiting neuroinflammation in ocular hypertensive eyes with cFLIP-deletion in astroglia values the role of cFLIP in the molecular regulation of glia-driven neuroinflammation during glaucomatous neurodegeneration. The molecular responses accompanying the lessening of neurodegenerative inflammation also seem to maintain astroglia survival despite increased caspase-8 cleavage with cFLIP deletion. A transcriptional autoregulatory response, dampening RelA but boosting RelB for selective expression of NF-κB target genes, might reinforce cell survival in cFLIP-deleted astroglia.

The influence of the tear film on the intraocular pressure and the corneal biomechanical properties analyzed with the Ocular Response Analyzer / La influencia de la película lagrimal sobre la presión intraocular y las propiedades biomecánicas corneales analizadas con el Analizador de Respuesta Ocular

Purpose: As ocular dryness and glaucoma are more prevalent with increasing age, understanding how the tear film affects tonometry is important. The present study aims to understand the impact that changes in the tear film have on intraocular pressure (IOP), corneal hysteresis, and corneal resistance factor measurements. Methods: Cross-sectional research was conducted and 37 patients were assessed. The tear film lipid layer and the non-invasive break-up time (NIBUT) were evaluated using the Tearscope Plus (Keeler, Windsor, UK). Dry eye symptoms were evaluated using the Ocular Surface Disease Index (OSDI) questionnaire. IOP was measured using rebound tonometry and the Ocular Response Analyzer (ORA, Reichert). Corneal biomechanical properties were measured using ORA. Results: It was found that an increase in the IOP measured with the iCare was directly correlated with the subclass that evaluated symptomatology associated with environmental factors (r = 0.414, p<0.05, Spearman). Goldmann-correlated IOP (IOPg) and Corneal-compensated IOP (IOPcc) values were statistically significantly different between the various interferometric patterns (p<0.05). It was also found that an increase in the corneal biomechanical properties measured with ORA was directly correlated with the overall scores obtained when using the OSDI and some of its subclasses. Conclusions: Tear film interferometric patterns were shown to have some impact on the IOP measured using ORA. The IOP measured with iCare seems to be related to the symptomatology obtained from OSDI. Corneal biomechanical properties were related to the OSDI total score and some of its subclasses. An increase in symptomatology was associated with an increase in the measured biomechanical properties of the cornea.(AU)

Acute Glaucoma Following Internal Carotid Artery Stenting: A Rare But Serious Complication of Ocular Ischemic Syndrome.

Acute glaucoma following carotid artery recanalization is a rare but severe complication of underlying ocular ischemic syndrome. We present a case of a 71-year-old woman with ocular ischemic syndrome and severe stenosis of the right internal and external carotid artery undergoing carotid artery stenting. Immediate postprocedural angiography showed pronounced reperfusion of the ophthalmic artery. Subsequently, the patient developed vision-threatening acute glaucoma despite treatment with acetazolamide. Monitoring of intraocular pressure is important in patients who are at risk of developing ocular ischemic syndrome because of internal carotid artery stenosis. Interventionalists should also assess the degree of vascular collateralization from the external carotid artery.

A hybrid framework for glaucoma detection through federated machine learning and deep learning models.

BACKGROUND: Glaucoma, the second leading cause of global blindness, demands timely detection due to its asymptomatic progression. This paper introduces an advanced computerized system, integrates Machine Learning (ML), convolutional neural networks (CNNs), and image processing for accurate glaucoma detection using medical imaging data, surpassing prior research efforts. METHOD: Developing a hybrid glaucoma detection framework using CNNs (ResNet50, VGG-16) and Random Forest. Models analyze pre-processed retinal images independently, and post-processing rules combine predictions for an overall glaucoma impact assessment. RESULT: The hybrid framework achieves a significant 95.41% accuracy, with precision and recall at 99.37% and 88.37%, respectively. The F1 score, balancing precision and recall, reaches a commendable 93.52%. These results highlight the robustness and effectiveness of the hybrid framework in accurate glaucoma diagnosis. CONCLUSION: In summary, our research presents an innovative hybrid framework combining CNNs and traditional ML models for glaucoma detection. Using ResNet50, VGG-16, and Random Forest in an ensemble approach yields remarkable accuracy, precision, recall, and F1 score. These results showcase the methodology's potential to enhance glaucoma diagnosis, emphasizing its promising role in early detection and preventing irreversible vision loss. The integration of ML and DNNs in medical imaging analysis suggests a valuable path for future advancements in ophthalmic healthcare.

[To discuss the minimally invasive glaucoma surgery related to trabeculotomy from the perspective of physiological function of trabecular meshwork drainage pathway].

The advent of minimally invasive glaucoma surgery (MIGS) has broadened the therapeutic options for managing glaucoma. In recent years, MIGS procedures targeting the trabecular meshwork-Schlemm's canal aqueous outflow resistance site have garnered significant attention. This focus has extended to the pathophysiological changes occurring within the aqueous outflow pathway. However, questions persist regarding the efficacy of near-peripheral or peripheral trabeculotomy in achieving the anticipated reduction of outflow resistance and the suitability of MIGS surgery for patients with primary open-angle glaucoma. By integrating clinical experience with pertinent clinical research, this paper advocates for a reevaluation of MIGS procedures to aid clinicians in making informed decisions regarding various glaucoma surgical interventions.

[Clinical characteristics and surgical management outcomes of glaucoma secondary to congenital ectropion uveae: a preliminary analysis of penetrating Schlemm's canaloplasty].

Objective: To investigate the clinical characteristics and treatment outcomes of glaucoma secondary to congenital ectropion uveae (CEU) using penetrating Schlemm's canaloplasty. Methods: This was a retrospective case series study. Medical records of patients diagnosed with glaucoma secondary to CEU and undergoing penetrating Schlemm's canaloplasty at the Eye Hospital of Wenzhou Medical University between August 2020 and December 2021 were collected. Clinical characteristics including the extent and location of iris ectropion, type of glaucoma, were analyzed. Follow-up visits were conducted at 1, 3, 6 months, and 1 year postoperatively. Visual acuity, intraocular pressure (IOP), anterior segment and fundus condition, filtering bleb morphology, use of IOP-lowering medications, ultrasound biomicroscopy results, and other indicators were analyzed to summarize surgical outcomes. Results: Six cases (6 eyes) of glaucoma secondary to CEU were included, all unilateral, with 3 left eyes and 3 right eyes; median age was 10.0 (5.3, 28.8) years; including 3 males and 3 females. Preoperative IOP was (31.7±10.0) mmHg (1 mmHg=0.133 kPa), and the preoperative number of IOP-lowering medications used was 2.0 (2.0, 3.2). The extent of iris ectropion in the 6 cases ranged from 270 ° to 360 °, with peripheral anterior synechiae corresponding to the location of iris ectropion, and angle closure with the degree of synechiae extending beyond Schwalbe's line. No surgical complications occurred in any of the 6 cases postoperatively. At 1 month postoperatively, the IOP was (16.4±3.2) mmHg, with a median of 0.0 (0.0, 1.5) medications used. At 3 months postoperatively, the IOP was (14.8±6.0) mmHg, with a median of 0.0 (0.0, 2.2) medications used. At 6 months postoperatively, the IOP was (18.1±6.1) mmHg, with a median of 0.0 (0.0, 0.5) medications used. Among them, 5 patients had a follow-up period of 1 year postoperatively, all achieving controlled IOP without the use of IOP-lowering medications, with an average IOP of (15.5±3.1) mmHg. No obvious filtering bleb formation was observed at the surgical site in all patients. Conclusions: Glaucoma secondary to CEU manifests primarily as closed-angle glaucoma, with a correspondence between the closure range of anterior iris adhesions in the angle and the extent of iris ectropion. Penetrating Schlemm's canaloplasty demonstrates favorable and stable efficacy for its treatment.

[Preliminary clinical observation and analysis of structural changes of optic nerve head in glaucoma patients after visual training].

Objective: To investigate the effect of virtual reality visual training on remodeling optic nerve structures of glaucoma patients and analyze the influencing factors of visual training effect. Methods: A prospective non-randomized controlled trial was conducted. Glaucoma patients who presented to the Department of Ophthalmology, Beijing Shijitan Hospital between October 2021 and October 2022 were collected and divided into the training group or the control group according to their intentions. The training group accepted 3 months of visual training, while the control group did not. Optical coherence tomography was used to examine the disc edge area, cup volume, disc area, cup-to-disc ratio, and other parameters of the optic disc of both eyes of the patients at enrollment and after 3 months, and the changes of each parameter in the two groups were analyzed. Multivariate analysis was performed in the training group to investigate the effects of sex, age, visual field index, and mean defect on visual disc structure changes during visual training. Results: A total of 53 glaucoma patients (101 eyes) were included in the final analysis, among which the training group consisted of 27 cases (51 eyes), with 19 males and 8 females, and the age range was 48.0 (40.0, 61.0) years old. The control group comprised 26 cases (50 eyes), with 26 males and 11 females, and the age range was 54.0 (38.0, 63.0) years old. Compared with the control group, the deviation of cup volume was -0.006(-0.050, 0.015)mm3 (P<0.05), and the deviation of disc edge area was 0.00(-0.04, 0.05)mm2 (P<0. 05)in the visual training group after 3 months of visual training. The gender (OR=4.217, 95%CI=1.188-14.966) may be the influence factor of rim area. While,the mean defect (OR=1.526, 95%CI=0.245-9.491) was not that influential on rim area change. Conclusions: Visual training can increase the disc area and decrease the optic cup volume of the optic nerve in glaucoma patients. The rim area may be increased more easily after visual training in male glaucoma patients.

[Clinical study on the efficacy and safety of glaucoma drainage implants in the treatment of different types of glaucoma].

Objective: To evaluate the efficacy and safety of glaucoma drainage implants(XEN-45 Gel Stent) for glaucoma treatment. Methods: A prospective study was conducted to continuously collect the clinical data of patients who were diagnosed with glaucoma and underwent XEN-45 Gel Stent implantation in the Ophthalmology Department of Peking University People's Hospital from January 2022 to August 2023. The visual acuity, intraocular pressure, number of glaucoma medications, and success rate of the patients were analyzed before and after surgery at 1 day, 1 week, 1 month, 3 months, 6 months, 12 months, and 18 months. The differences in intraocular pressure and number of glaucoma medications among primary open-angle glaucoma, primary angle closure glaucoma, secondary glaucoma, and different implantation methods of XEN-45 Gel Stent among patients with primary open-angle glaucoma were compared. The intraoperative and postoperative complications were observed, and the risk factors for needling and surgical complete success were analyzed. Results: A total of 48 eyes from 48 patients were included in this study, comprising 27 males and 21 females, with a mean age of (54.4±18.0) years and the disease duration was 36.0(7.3, 81.0) months.There were 28 cases of primary open-angle glaucoma, 4 cases of primary angle closure glaucoma, and 16 cases of secondary glaucoma.The follow-up period was 8.0 (3.0, 12.0) months. At 12 months after surgery, the intraocular pressure decreased from 20.5 (17.0, 26.0) mmHg to (13.5±3.3) mmHg (P<0.05), and the number of glaucoma medications decreased from 3.0 (3.0, 4.0) to 0.0 (0.0, 0.0) (P<0.05). The complete success rate and qualified success rate were 73.9% (17/23) and 91.3% (21/23), respectively. The most common postoperative complications were shallow anterior chamber in 6 cases (12.5%), hypotony in 3 cases (6.3%), and blocked stent in 3 cases (6.3%). The most common postoperative treatment was needling in 27 cases (56.3%). There was no significant difference in intraocular pressure among different types of glaucoma. In the comparison of postoperative effects of different surgical implantation methods for primary open-angle glaucoma, there were no statistically significant differences in intraocular pressure and the number of glaucoma medications at other follow-up time points except 1 month after surgery (P<0.05). Univariate logistic regression analysis did not find any risk factors associated with needling and surgical complete success. Conclusions: XEN-45 Gel Stent implantation is an effective and safe surgical option for different types of glaucoma patients in China, which can significantly reduce intraocular pressure and the use of glaucoma medications and has a high success rate. However, some patients may need needling or other treatments after surgery.

Glaucoma detection using non-perfused areas in OCTA.

Multiple ophthalmic diseases lead to decreased capillary perfusion that can be visualized using optical coherence tomography angiography images. To quantify the decrease in perfusion, past studies have often used the vessel density, which is the percentage of vessel pixels in the image. However, this method is often not sensitive enough to detect subtle changes in early pathology. More recent methods are based on quantifying non-perfused or intercapillary areas between the vessels. These methods rely upon the accuracy of vessel segmentation, which is a challenging task and therefore a limiting factor for reliability. Intercapillary areas computed from perfusion-distance measures are less sensitive to errors in the vessel segmentation since the distance to the next vessel is only slightly changing if gaps are present in the segmentation. We present a novel method for distinguishing between glaucoma patients and healthy controls based on features computed from the probability density function of these perfusion-distance areas. The proposed approach is evaluated on different capillary plexuses and outperforms previously proposed methods that use handcrafted features for classification. Moreover the results of the proposed method are in the same range as the ones of convolutional neural networks trained on the raw input images and is therefore a computationally efficient, simple to implement and explainable alternative to deep learning-based approaches.

[Transscleral ciliary surgery in glaucoma:from destructive surgery to minimally invasive surgery].

Over the years, there has been significant advancement in the safety and effectiveness of external cyclosurgery for glaucoma. This progress ranges from the initial "cyclodestructive surgery" to modern cycloplasty techniques, expanding beyond end-stage glaucoma treatment. Notably, innovative approaches like micropulse transscleral cycloplasty and ultrasonic cycloplasty are now being employed in earlier stages of glaucoma with better visual acuity, qualifying as minimally invasive procedures. Through a comprehensive review of the historical evolution of external cyclosurgery, elucidation of the mechanisms, clinical outcomes, and potential complications associated with novel cycloplasty techniques, and integration of practical clinical insights, this article aims to furnish clinicians with a profound comprehension of external cyclosurgery for glaucoma.

[Research progress in the diagnosis and treatment of childhood glaucoma].

Childhood glaucoma is a disease that seriously endangers children's visual health. It will accompany the patients throughout their lives and bring a heavy burden to families and society. Most childhood blindness caused by glaucoma is preventable or treatable. Relevant research has made progress in recent years. Based on the new consensus reached by the World Glaucoma Association and the latest medical evidence at home and abroad, this article summarizes the definition, classification, diagnosis, molecular genetics, pathogenesis and comprehensive treatments including drugs and surgery of childhood glaucoma, with a focus on the application of various surgical methods, so as to provide reference for clinical and scientific research and improve the clinical diagnosis and treatment of childhood glaucoma.

Epidemiological analysis of congenital glaucoma: a national scenario.

INTRODUCTION: Congenital glaucoma is a disease that involves increased intraocular pressure and can result in irreversible visual deterioration. The study of epidemiology allows the delineation of the characteristics associated with patients and specific risk factors. OBJECTIVE: The objective of this study was to examine epidemiological trends, place of residence, duration of gestation, sex, and race of the newborn diagnosed with congenital glaucoma in Brazil. METHODS: Data from SINASC (National Live Birth System) were used to analyze the period from 2017 to 2021 in Brazil. Linear regression and analysis of variance tests were employed to assess significance. The statistical significance was determined by p<0.05. RESULTS: A total of 47 cases of congenital glaucoma were identified in Brazil during the study period, with the highest incidence between the years of 2018 and 2021. The analysis of the distribution indicated that the states with the highest incidence were São Paulo, followed by Rio Grande do Sul and Pernambuco. Approximately 60% of cases occurred in male individuals, compared with 19 female cases. The ethnic analysis showed the highest incidence among whites and mixed. Regarding the length of pregnancy, statistical differences were observed between newborns of different periods of gestation. Infants born from pregnancies lasting between 28 and 31 weeks and 32 and 36 weeks were significant when analyzed with the group between 37 and 41 weeks. CONCLUSION: Studies on the mechanisms of congenital glaucoma seek to improve knowledge about the disease. Epidemiological evaluation is essential for identifying demographic and clinical patterns of the disease.

[INTERVENTIONAL GLAUCOMA - A SHIFT IN THE TREATMENT PARADIGM].

INTRODUCTION: Glaucoma is a progressive optic neuropathy and is the leading cause of preventable irreversible blindness worldwide. Glaucoma causes progressive visual field loss and can have significant implications on the patient's quality of life. Lowering intraocular pressure (IOP) is the only treatment proven to prevent vision loss from glaucoma. It is achieved using medication, laser treatment and surgery. The treatment paradigm of glaucoma has been one whereby surgical intervention has been left for advanced cases due to a variety of reasons, mainly concerning safety and long term success. The past two decades have seen a paradigm shift towards earlier IOP lowering interventions using a wide array of different technologies in the laser and surgical spaces. This review aims to understand the background to this paradigm shift, its necessity, and its potential impact on the vision and life of glaucoma patients.

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.

TGFß Signaling Dysregulation May Contribute to COL4A1-Related Glaucomatous Optic Nerve Damage.

Purpose: Mutations in the genes encoding type IV collagen alpha 1 (COL4A1) and alpha 2 (COL4A2) cause a multisystem disorder that includes ocular anterior segment dysgenesis (ASD) and glaucoma. We previously showed that transforming growth factor beta (TGFß) signaling was elevated in developing anterior segments from Col4a1 mutant mice and that reducing TGFß signaling ameliorated ASD, supporting a role for the TGFß pathway in disease pathogenesis. Here, we tested whether altered TGFß signaling also contributes to glaucoma-related phenotypes in Col4a1 mutant mice. Methods: To test the role of TGFß signaling in glaucoma-relevant phenotypes, we genetically reduced TGFß signaling using mice with mutated Tgfbr2, which encodes the common receptor for all TGFß ligands in Col4a1+/G1344D mice. We performed slit-lamp biomicroscopy and optical coherence tomography for qualitative and quantitative analyses of anterior and posterior ocular segments, histological analyses of ocular tissues and optic nerves, and intraocular pressure assessments using rebound tonometry. Results: Col4a1+/G1344D mice showed defects of the ocular drainage structures, including iridocorneal adhesions, and phenotypes consistent with glaucomatous neurodegeneration, including thinning of the nerve fiber layer, retinal ganglion cell loss, optic nerve head excavation, and optic nerve degeneration. We found that reducing TGFß receptor 2 (TGFBR2) was protective for ASD, ameliorated ocular drainage structure defects, and protected against glaucomatous neurodegeneration in Col4a1+/G1344D mice. Conclusions: Our results suggest that elevated TGFß signaling contributes to glaucomatous neurodegeneration in Col4a1 mutant mice.