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.

Postoperative Inflammation After Anterior Segment Surgery.

A 71-year-old woman had 2 months of worsening vision and pain in her right eye. Examination revealed retrocorneal plaque, peaking of the pupil, and temporal prominent scleral vessels with inferotemporal scleral thinning. What would you do next?

Repeatability assessment of anterior segment measurements in myopic patients using an anterior segment OCT with placido corneal topography and agreement with a swept-source OCT.

BACKGROUND: The precision of anterior segment biometric measurements in eyes has become increasingly important in refractive surgery. The purpose of this study is to assess the repeatability of the automatic measurements provided by a new spectral-domain optical coherence tomograph (SD-OCT)/Placido topographer (MS-39, CSO) and its agreement with a swept-source OCT (SS-OCT) biometer (CASIA SS-1000, Tomey) in patients with myopia. METHODS: The right eye of 235 subjects was scanned 3 times with both devices. The evaluated parameters included central corneal radius of the steep meridian, central corneal radius of the flat meridian, mean central corneal radius, thinnest corneal thickness, central corneal thickness, anterior chamber depth, corneal volume and diameter. The intraobserver repeatability of the MS-39 measurements was calculated using intraclass correlation coefficient (ICC), within subject standard deviation, coefficient of repeatability, coefficient of variation and repeated-measures analysis of variance of the 3 repeated measurements. The agreement between the two devices was evaluated by 95% limits of agreement (LoA). RESULTS: The majority of the parameters acquired from MS-39 showed high repeatability. The repeatability of corneal diameter was slightly lower than the other measurements, although the ICC remained high. Agreement with the CASIA SS-1000 was good, indicated by the Bland-Altman plots with narrow 95% LoA values for all parameters assessed. CONCLUSIONS: The high repeatability of automatic measurements by the new device supports its clinical application in eyes with myopia, and the good agreement between the two devices indicates they could be used interchangeably for the parameters evaluated.

Zonular instability-associated morphologic features in eyes with primary angle closure disease using the swept-source anterior segment - optical coherence tomography system.

BACKGROUND: This study aims to investigate the morphologic features of the crystalline lens in Primary Angle Closure Disease (PACD) patients with zonular instability during cataract surgery using the swept-source CASIA 2 Anterior Segment-Optical Coherence Tomography (AS-OCT) system. METHODS: A total of 398 eyes (125 PACD eyes with zonular instability, 133 PACD eyes with zonular stability, and 140 cataract patient controls) of 398 patients who underwent cataract surgery combined or not glaucoma surgery between January 2021 and January 2023 were enrolled. The crystalline lens parameters were measured by CASIA2 AS-OCT. Then, logistic regression was performed to evaluate the risk factors associated with zonular instability. RESULTS: The results revealed that PACD eyes had a more anterior lens equator position, a steeper anterior curvature of lens, shorter Axial Length (AL), shallower Anterior Chamber Distance (ACD), higher Lens Vault (LV) and thicker Lens Thickness (LT), when compared to eyes in the cataract control group. Furthermore, PACD eyes in the zonular instability group had steeper front R, front Rs and Front Rf, flatter back Rf, thicker lens anterior part thickness, higher lens anterior-to-posterior part thickness ratios, shallower ACD, and greater LV, when compared to PACD eyes with zonular stability. The logistic regression analysis, which was adjusted for age and gender, revealed that zonular instability was positively correlated with anterior part thickness, lens anterior-to-posterior part thickness ratio, and LV, but was negatively correlated with lens anterior radius and ACD. CONCLUSION: Steeper anterior curvature, increased lens anterior part thickness, higher anterior-to-posterior part thickness ratio, shallower ACD, and greater LV are the anatomic features of PACD eyes associated with zonular instability.

Estimation of angle parameters by ASOCT and biometric parameters by optical biometer in eyes with occludable angles and open angles.

PURPOSE: To compare anterior chamber angle (ACA) parameters measured by Anterior Segment Optical Coherence Tomography (ASOCT) and biometric parameters measured by Swept-Source (SS) OCT-based biometry among patients with suspected occludable angles and open angles. METHODS: An analytical, cross-sectional study was performed on subjects attending our ophthalmology outpatient department with suspected occludable angles (van Herick grades 0, 1, and 2) in group 1, and with open angles (van Herick grades 3 and 4) in group 2. Each subject underwent a complete ophthalmic examination to exclude any intraocular pathology like cataract. We recruited 128 eyes of 64 subjects, 34 in group 1 and 30 in group 2. Each eye was henceforth subjected to ASOCT (Spectralis, Heidelberg Engineering, Heidelberg) and SS-OCT-based optical biometry (IOL Master 700, Carl Zeiss Meditec AG). Anatomical parameters were recorded and compared between the two groups. RESULTS: The main outcome measures of the study included nine ASOCT parameters (central corneal thickness [CCT], lens vault, AOD750, ACA, TISA750 [nasal and temporal], and ACW) and five optical biometric parameters (CCT, ACD, WTW, LT, and axial length). We found a significant difference (p < 0.05) among all the anatomical parameters between the two groups, except CCT which was not significantly different (p = 0.297). CONCLUSIONS: ASOCT and SSOCT biometry overcome the challenges of gonioscopy and allow screening for angle closure disease in otherwise normal subjects. ASOCT may serve as an alternative to gonioscopy as it clearly separates occludable angles from open angles in a non-invasive and objective manner.

Rat Model of Type 2 Diabetes Mellitus Recapitulates Human Disease in the Anterior Segment of the Eye.

Changes in the anterior segment of the eye due to type 2 diabetes mellitus (T2DM) are not well-characterized, in part due to the lack of a reliable animal model. This study evaluated changes in the anterior segment, including crystalline lens health, corneal endothelial cell density, aqueous humor metabolites, and ciliary body vasculature, in a rat model of T2DM compared with human eyes. Male Sprague-Dawley rats were fed a high-fat diet (45% fat) or normal diet, and rats fed the high-fat diet were injected with streptozotocin intraperitoneally to generate a model of T2DM. Cataract formation and corneal endothelial cell density were assessed using microscopic analysis. Diabetes-related rat aqueous humor alterations were assessed using metabolomics screening. Transmission electron microscopy was used to assess qualitative ultrastructural changes ciliary process microvessels at the site of aqueous formation in the eyes of diabetic rats and humans. Eyes from the diabetic rats demonstrated cataracts, lower corneal endothelial cell densities, altered aqueous metabolites, and ciliary body ultrastructural changes, including vascular endothelial cell activation, pericyte degeneration, perivascular edema, and basement membrane reduplication. These findings recapitulated diabetic changes in human eyes. These results support the use of this model for studying ocular manifestations of T2DM and support a hypothesis postulating blood-aqueous barrier breakdown and vascular leakage at the ciliary body as a mechanism for diabetic anterior segment pathology.

Direct observation and measurement of circumlental space and its relation to anterior chamber angle characteristics in iridotomized phakic eyes with primary angle closure disease.

Primary angle closure disease (PACD) is a major cause of blindness worldwide. It has a high prevalence in East Asia, especially in China, which leads to a higher incidence of blindness than open-angle glaucoma. The aim of this study was to directly observe the circumlental space (CLS) in laser peripheral iridotomized eyes with PACD and to determine whether this structure plays a role in the pathogenesis of PACD. Fifty eyes of 50 patients with PACD, who had received laser peripheral iridotomy performed with neodymium:yttrium-aluminum-garnet were recruited from glaucoma clinics from March 2021 to May 2022, including 17 primary angle closure suspect (PACS), 16 primary angle closure (PAC) and 17 primary angle closure glaucoma (PACG). They were classified into two groups based on whether the ciliary process and the crystalline lens equator were in contact using slit-lamp photograph: the attached group and the unattached group. The demographic, clinical characteristics and anterior segment parameters measured from ultrasound biomicroscopy were compared between the attached group and the unattached group. Thirty-three eyes were assigned to the attached group and 17 eyes belonged to the unattached group. In the unattached group, the mean CLS was 0.10 ± 0.07 mm. No significant differences were identified between the different diagnosis groups in age, sex, best-corrected visual acuity, intraocular pressure, white-to-white, axial length, central corneal thickness, anterior chamber depth, flat keratometry, steep keratometry or iridotomy diameter (p > 0.05). The unattached group had shorter trabecular-ciliary process distance (p = 0.021) and larger ciliary process area (p = 0.001) compared with the attached group. Small CLS and its potential effect (partial ciliary block) might be considered as one of the mechanisms of PACD.

Atypical presentation of bilateral iridoschisis with abnormal visibility of iris vessels: Role of anterior segment optical coherence tomography.

PURPOSE: To describe clinical and anterior segment optical coherence tomography (AS-OCT) findings in a patient with bilateral iridoschisis and unilateral angle closure glaucoma (ACG) associated with abnormal visibility of iris vessels. CASE PRESENTATION: A 67-year-old male patient with a history of red and painful left eye (LE) one year earlier, presented to our ophthalmology department for a routine examination.Ophthalmic examination of the right eye revealed narrow anterior chamber with sectorial iris atrophy associated to abnormal visibility of an iris vessel. Intraocular pressure (IOP) was 12 mmHg with normal optic disc appearance. LE anterior chamber was narrow with diffuse iris atrophy and abnormal vessels visibility. IOP was 28 mmHg with an important optic disc excavation. On gonioscopy, angle was narrow without neovessels nor synechiae. AS-OCT of both eyes revealed shallow angles, iris splitting with material release in the anterior chamber, while pigmented epithelium was preservedAnti-glaucoma eye drops were prescribed and peripheral laser iridotomy was performed in both eyes with decreased IOP at 14 mmHg in the LE. CONCLUSION: Iridoschisis is a rare ocular condition characterized by a separation between the anterior and posterior layers of iris stroma with several clinical presentations, and may be associated with abnormal visibility of iris vessels in some cases. The diagnosis of iridoschisis may be challenging and AS-OCT can be a very useful tool to confirm the diagnosis in atypical presentations and to detect associated angle closure.

Toxic anterior segment syndrome (TASS): A review and update.

Toxic anterior segment syndrome (TASS) is an acute, sterile, postoperative inflammatory reaction of the anterior segment without vitreous involvement, following an uncomplicated and uneventful ocular surgery, having broad and multiple etiologies. The symptoms of decreased visual acuity and ocular discomfort generally occur within the first 12-48 h after intraocular surgery. The clinical signs include prominent limbus-to-limbus corneal edema, anterior chamber cells, aqueous flare, fibrinous inflammation, and/or keratic precipitates. There can be sight-threatening complications of TASS, such as permanent corneal decompensation, intractable glaucoma, and cystoid macular edema. The causes of TASS are emerging and being reported, so are the newer treatment options for managing the inflammation and its complications. Prevention guidelines for TASS are being updated, and a traceability system for surgical instruments and intraocular fluids used during the surgery is being perpetually developed. It is important to recognize TASS and start treatment on an immediate effect. Hereby, we review the literature on TASS, emphasizing its etiology, pathophysiology, management, prognosis, complications, and the importance of prevention as well as prompt recognition.

Portable Anterior Eye Segment Imaging System for Teleophthalmology.

Objective: This study aims to compare a new prototype for a portable anterior eye segment imaging system with the standard method for ophthalmology examination. Methods: The new imaging system consisted of two IMX219 Arducam autofocus sensors (Arducam, China, Nanjing) for Raspberry Pi V2 camera module connected to a Raspberry Pi Zero W (Raspberry Pi Foundation, UK, Cambridge) that clips to a wearable headset. The 2D videos of the anterior eye segment were recorded with the new system and a 720p FaceTime HD camera (Apple, Cupertino, CA). Afterward, ophthalmologists evaluated the videos using a standard clinical eye examination form. These evaluations were compared with the standard slit-lamp clinical assessment performed during the patient's visit. Results: Thirty-five eyes were evaluated. The sensitivity and specificity percentages were statistically significant between the two imaging modalities (P ≤ 0.001). The evaluations performed from videos obtained with the new imaging system had better sensitivity and specificity percentages overall. However, statistically significant differences were only observed in cornea, anterior chamber, iris, and lens. Conclusions: Specificity percentages were higher than sensitivity percentages in both imaging modalities, indicating that video evaluations are less accurate for pathological screening. Nevertheless, the new system evaluations were significantly better than the webcam evaluations. Translational Relevance: This study presented an alternative system to assess eye conditions for telemedicine, one that provides more details than the current standard and uses new wearable headsets technologies.

Cardiac anomalies in Axenfeld-Rieger syndrome.

Axenfeld-Rieger syndrome is a rare multi-system disorder associated with cardiac anomalies. All patients with a diagnosis of Axenfeld-Rieger syndrome were identified from our electronic medical record. Chart review was performed to document the presence and types of CHD. Out of 58 patients, 14 (24.1%) had CHD and a wide variety of cardiac lesions were identified.

Tissue-engineered anterior segment eye cultures demonstrate hallmarks of conventional organ culture.

BACKGROUND: Glaucoma is a blinding disease largely caused by dysregulation of outflow through the trabecular meshwork (TM), resulting in elevated intraocular pressure (IOP). We hypothesized that transplanting TM cells into a decellularized, tissue-engineered anterior segment eye culture could restore the outflow structure and function. METHODS: Porcine eyes were decellularized with freeze-thaw cycles and perfusion of surfactant. We seeded control scaffolds with CrFK cells transduced with lentiviral vectors to stably express eGFP and compared them to scaffolds seeded with primary TM cells as well as to normal, unaltered eyes. We tracked the repopulation behavior, performed IOP maintenance challenges, and analyzed the histology. RESULTS: Transplanted cells localized to the TM and progressively infiltrated the extracellular matrix, reaching a distribution comparable to normal, unaltered eyes. After a perfusion rate challenge to mimic a glaucomatous pressure elevation, transplanted and normal eyes reestablished a normal intraocular pressure (transplanted = 16.5 ± 0.9 mmHg, normal = 16.9 ± 0.9). However, eyes reseeded with eGFP-expressing CrFK cells could not regulate IOP, remaining high and unstable (27.0 ± 6.2 mmHg) instead. CONCLUSION: Tissue-engineered anterior segment scaffolds can serve as readily available, scalable ocular perfusion cultures. This could reduce dependency on scarce donor globes in outflow research and may allow engineering perfusion cultures with specific geno- and phenotypes.

When the savior becomes a demon: Silicon oil synechia-induced glaucoma.

Background: Silicon oil is an important adjunct for achieving internal tamponade in the treatment of retinal detachment. Silicone oil tamponade often leads to narrowing of the angle and development of adhesions between the iris and anterior chamber angle structures, with consequential elevation of the intraocular pressure. The video showcases the management of these challenging scenarios. Purpose: To highlight the management of early synechial closures due to silicon oil tamponade. Synopsis: The video highlights the management of early synechial closure following silicon oil tamponade. Surgical pupilloplasty has been demonstrated to break the peripheral anterior synechias on intraoperative gonioscopy as well as on anterior segment optical coherence tomography (AS-OCT). Performing pupilloplasty in the early phase of development of peripheral anterior synechias (PAS) helps to break the existing synechias and prevent angle closure and sequential deterioration of vision. Highlights: Surgical pupilloplasty helps to relieve the post silicon oil-induced secondary angle closure glaucoma by breaking the peripheral anterior synechias and significantly opening the anterior chamber angles. Online Video Link: https://youtu.be/xe2NGlhPBF4.

Predicting demographic characteristics from anterior segment OCT images with deep learning: A study protocol.

INTRODUCTION: Anterior segment optical coherence tomography (AS-OCT) is a non-contact, rapid, and high-resolution in vivo modality for imaging of the eyeball's anterior segment structures. Because progressive anterior segment deformation is a hallmark of certain eye diseases such as angle-closure glaucoma, identification of AS-OCT structural changes over time is fundamental to their diagnosis and monitoring. Detection of pathologic damage, however, relies on the ability to differentiate it from normal, age-related structural changes. METHODS AND ANALYSIS: This proposed large-scale, retrospective cross-sectional study will determine whether demographic characteristics including age can be predicted from deep learning analysis of AS-OCT images; it will also assess the importance of specific anterior segment areas of the eyeball to the prediction. We plan to extract, from SUPREME®, a clinical data warehouse (CDW) of Seoul National University Hospital (SNUH; Seoul, South Korea), a list of patients (at least 2,000) who underwent AS-OCT imaging between 2008 and 2020. AS-OCT images as well as demographic characteristics including age, gender, height, weight and body mass index (BMI) will be collected from electronic medical records (EMRs). The dataset of horizontal AS-OCT images will be split into training (80%), validation (10%), and test (10%) datasets, and a Vision Transformer (ViT) model will be built to predict demographics. Gradient-weighted Class Activation Mapping (Grad-CAM) will be used to visualize the regions of AS-OCT images that contributed to the model's decisions. The accuracy, sensitivity, specificity, and area under the receiver operating characteristic (ROC) curve (AUC) will be applied to evaluate the model performance. CONCLUSION: This paper presents a study protocol for prediction of demographic characteristics from AS-OCT images of the eyeball using a deep learning model. The results of this study will aid clinicians in understanding and identifying age-related structural changes and other demographics-based structural differences. TRIAL REGISTRATION: Registration ID with open science framework: 10.17605/OSF.IO/FQ46X.

[Primary anterior chamber angle closure: progression from suspect to glaucoma. Part 2. Predictors of primary angle closure]. / Pervichnyi zakrytyi ugol perednei kamery: progressirovanie ot podozreniya do glaukomy. Chast' 2. Prediktory pervichnogo zakrytogo ugla.

OBJECTIVE: To review the literature devoted to the search of predictors of primary angle closure (PAC) progression as an important link in the pathogenesis of primary angle-closure glaucoma. This part presents a cluster analysis, describes the mechanisms of PAC development, and considers the studies aimed at discovering the risk factors for the progression of primary angle closure suspect into true angle closure. The results of the analyzed literature are ambiguous, indicating the need for further research that would involve strict inclusion criteria, and a standard approach to defining the primary angle closure disease and expanding the diagnostic parameters, in which a key role belongs to anterior segment optical coherence tomography (AS-OCT).

Anterior segment dysgenesis: Insights into the genetics and pathogenesis.

Childhood glaucoma is a treatable cause of blindness, provided it is recognized, diagnosed, and treated in time. WHO has estimated that it is responsible for Blind Years second only to cataracts. The fundamental pathophysiology of all childhood glaucoma is impaired outflow through the trabecular meshwork. Anterior segment Dysgeneses (ASD) are a group of non-acquired ocular anomalies associated with glaucoma, characterized by developmental abnormalities of the tissues of the anterior segment. The cause is multifactorial, and many genes are involved in the development of the anterior segment. Over the last decade, molecular and developmental genetic research has transformed our understanding of the molecular basis of ASD and the developmental mechanisms underlying these conditions. Identifying the genetic changes underlying ASD has gradually led to the recognition that some of these conditions may be parts of a disease spectrum. The characterization of genes responsible for glaucoma is the critical first step toward developing diagnostic and screening tests, which could identify individuals at risk for disease before irreversible optic nerve damage occurs. It is also crucial for genetic counseling and risk stratification of later pregnancies. It also aids pre-natal testing by various methods allowing for effective genetic counseling. This review will summarize the known genetic variants associated with phenotypes of ASD and the possible significance and utility of genetic testing in the clinic.

Anterior segment optical coherence tomography (AS-OCT) image analysis methods and applications: A systematic review.

BACKGROUND: Anterior segment optical coherence tomography (AS-OCT) constitutes an important imaging modality to examine the anterior eye, which is commonly used in research and clinical practice. Since its introduction, a range of image analysis methods have been developed to quantify these images using different analysis techniques for various applications. This systematic review aims to provide an in-depth summary and to classify image analysis techniques found in the literature applied to AS-OCT images. METHODS: Scopus and Engineering Village databases were searched to retrieve relevant studies up to and including January 2022. Customized search statements were used along with cross reference and hand search techniques to ensure a complete coverage. Performance metrics were extracted, analyzed, and compared (when possible). RESULTS: Three main application categories were identified: glaucoma assessment, corneal segmentation, and anterior segment biometry. These three categories constitute 66% of the total studies reported in this review. Studies were also analyzed by year of publication, and since 2019 deep learning methods were favored over traditional programming or machine learning methodologies. Overall, the AS-OCT image analysis field is less developed compared to posterior segment OCT imaging. CONCLUSION: This review presents the state of the art in the field of AS-OCT image analysis. It highlights the opportunities for future areas of research, such as the expansion of DL methods and the extension to specific clinical areas that have received limited attention including surgical monitoring, contact lenses, and specific clinical conditions such as keratoconus and corneal lesions.

Bilateral anterior segment dysgenesis in a 7-week-old domestic shorthaired cat.

A 7-week-old, intact, female domestic shorthaired cat was presented to the Atlantic Veterinary College (AVC) Ophthalmology service for a 1-week history of buphthalmia in the left eye and bilateral elevated intraocular pressures. Ocular examination revealed bilateral non-visual glaucomatous eyes. Bilateral enucleations were performed without complications and histopathology revealed anterior segment dysgenesis of varying degrees in both eyes. Key clinical message: Anterior segment dysgenesis is a developmental condition that can result in primary congenital glaucoma for which the best course of treatment is enucleation.

Dysgénésie bilatérale du segment antérieur chez un chat domestique à poils courts de 7 semaines. Une chatte domestique à poil court femelle intacte âgée de 7 semaines a été présentée au service d'ophtalmologie du Atlantic Veterinary College pour une histoire d'une semaine de buphtalmie dans l'æil gauche et de pressions intraoculaires bilatérales élevées. L'examen oculaire a révélé des yeux glaucomateux non visuels bilatéraux. Les énucléations bilatérales ont été réalisées sans complications et l'histopathologie a révélé une dysgénésie du segment antérieur à des degrés divers dans les deux yeux.Message clinique clé :La dysgénésie du segment antérieur est une affection du développement qui peut entraîner un glaucome congénital primaire pour lequel le meilleur traitement est l'énucléation.(Traduit par Dr Serge Messier).