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Purpose: We aimed to evaluate the morphological changes in meibomian glands in keratoconus patients using scleral contact lenses and compare them with keratoconus and healthy controls., Methods: The study included 34 eyes of 20 patients who were wearing scleral contact lenses due to keratoconus, as well as 31 age- and sex-matched keratoconus controls and 31 healthy controls. Slit-lamp biomicroscopy, non-invasive tear film break-up time assessment, Schirmer I test, meibography, and corneal staining with fluorescein were performed. Subjective symptoms were assessed using the Ocular Surface Disease Index., Results: In this study, the lower and upper percentage meibomian gland loss was statistically higher in the scleral contact lens group than in the keratoconus and healthy control groups (p < 0.001 and p = 0.013, respectively). There was a positive correlation between scleral contact lens wear duration and the lower eyelid percentage meibomian gland loss and upper eyelid gland curling scores (rho: 0.396; p = 0.021 and rho: 0.344; p = 0.047, respectively). The lower and upper eyelid percentage meibomian gland loss, and upper eyelid gland curling values were higher, and the Schirmer 1 values were found to be lower in patients who used scleral contact lenses for more than three years than those who wore them less than three years., Conclusion: In patients using scleral contact lenses for more than three years, meibomian gland curling values and percentages of meibomian gland loss in both eyelids are higher., (© 2024. The Author(s), under exclusive licence to Springer Nature B.V.)

Purpose: This study aims to investigate the effect of quercetin (QUE) on scleral remodeling by inhibiting the PERK-EIF2α signaling pathway and to evaluate its potential role in slowing myopia., Methods: Lens-induced myopia (LIM) guinea pigs were obtained and treated with QUE. After 4 and 6 weeks of treatments, ocular biological measurements were conducted. Hematoxylin and eosin (H&E) staining was used to observe the changes in scleral morphology and thickness, and Masson staining was used to examine scleral collagen fiber arrangement. Quantitative PCR (qPCR) and Western bolt were utilized to detect the mRNA and protein expression of PERK, EIF2α, MMP-2, TIMP-2, and collagen I in the scleral tissues. Calcium ion flow in each group was measured using noninvasive micro-test technology, and reactive oxygen species levels were detected by flow cytometry., Results: Compared with the LIM group, the ocular measurements showed that the refractive errors and axial length of the eyes were significantly reduced in the LIM + QUE group (P < 0.01). H&E and Masson staining showed that sclera in the LIM + QUE group was thickened, collagen was dense, and the fiber gap was reduced. In the LIM + QUE group, the expression levels of PERK, EIF2α, and MMP-2 were decreased, whereas the expression levels of TIMP-2 and collagen I were increased. Calcium release and reactive oxygen species (ROS) in the LIM + QUE group were decreased., Conclusions: Quercetin ameliorates scleral remodeling in myopic guinea pigs by inhibiting the PERK-EIF2α signaling pathway, thereby alleviating the progression of myopia. These findings provide new experimental evidence for the potential application of quercetin in myopia prevention and treatment.

Purpose: To investigate the anterior scleral thickness (AST) in patients with Marfan syndrome (MFS)., Methods: A prospective, cross-sectional study was conducted at the Department of Ophthalmology, Ghent University Hospital, Ghent, including patients with a genetically confirmed clinical diagnosis of MFS and age-, gender- and axial length-matched controls. Subjects with known corneal, conjunctival or scleral pathology and a history of ocular surgery, including pars plana vitrectomy, recent contact lens use or high-grade astigmatism were excluded. Subjects underwent non-cycloplegic autorefraction, Scheimpflug-based corneal tomography, axial length measurement and spectral-domain optical coherence tomography (OCT). AST was manually measured at 1 mm (AST1), 2 mm (AST2) and 3 mm (AST3) from the scleral spur, temporally and nasally., Results: A total of 56 subjects (28 subjects in the MFS group and 28 matched subjects in the control group) were included in this study. In patients with MFS, AST was significantly reduced compared to matched controls, both overall and at every analysed measuring point in the nasal and temporal areas (p < 0.001). Central corneal thickness (CCT) and mean keratometry (Kmean) values were significantly lower in patients with MFS (p < 0.05). A positive correlation was found between nasal AST and CCT in patients with MFS. No correlation was found between AST and Kmean or between AST and axial length. In patients with MFS with ectopia lentis, compared to those without, temporal AST3 was significantly lower (p < 0.05). AST was significantly lower in patients with MFS harbouring a variant predicted to cause haploinsufficiency compared to those with a variant expected to lead to a dominant negative effect for both nasal and temporal measurements., Conclusion: Based on anterior segment OCT measurements, AST of patients with MFS is significantly lower compared to matched controls., (© 2024 Acta Ophthalmologica Scandinavica Foundation. Published by John Wiley & Sons Ltd.)

Purpose: Surgical repair might be required in patients with uveal melanoma (UM) that develop advanced forms of radiation-induced scleral necrosis (RISN). In this monocentric long-term observational study, we aimed at analyzing the treatment outcome after RISN surgery., Methods: All consecutive cases with UM who underwent surgical intervention for RISN between 1999 and 2020 were included. Achievement of the tectonic stability and evaluation of incidence and the risk factors for a repetitive patch surgery (RPS) were the main endpoints., Results: The final analysis included 57 patients (mean age: 58.7 years; 63.2% female patients), where 55 individuals underwent a patch grafting, and 2 cases were treated with conjunctival reconstructive surgery. The mean follow-up time after grafting was 38.5 months (0.03-221.1 months). Tectonic stability was achieved in 56 (98.3%) patients. Scleral graft (38/55, 69.1%) was the most frequent patching material, followed by Tutopatch (7/55, 12.7%), corneal graft (7/55, 12.7%), dura graft (2/55, 3.6%), and fascia lata (FL) graft (1/55, 1.8%). Eleven patients (20%) underwent RPS after the mean time of 12.9 months (0.3-50.3 months). In the final multivariate Cox regression analysis, the use of Tutopatch (5/7; 71.4%, adjusted hazard ratio = 4.66, P = 0.044) and RISN progression after patch grafting (9/11; 81.8%, adjusted hazard ratio = 9.67, P = 0.008) were independent risk factors for RPS., Conclusions: RISN surgery maintains long-term tectonic stability in most of the cases underwent surgical repair for RISN after brachytherapy for UM. Depending on graft material and, particularly, further RISN progression, an RPS might be necessary in certain cases., Competing Interests: The authors have no funding or conflicts of interest to disclose., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Background: At present, the severity and grade of anterior scleritis are judged mainly based on the area and location of involvement, whether there is necrosis, etc. Quantitative measurement of sclera and surrounding tissues will help to accurately assess the severity of scleritis and provide quantitative indicators for the choice of treatment., Methods: We retrospectively analyzed the thickness of sclera and ciliary bodies detected by ultrasound biological microscopy (UBM) in noninfectious anterior scleritis patients who subsequently were treated with topical or systemic treatment, and visited our hospital from March 2014 to March 2021. Age- and sex-matched normal individuals were used as controls., Results: A total of 185 patients (50 males and 135 females) with noninfectious anterior scleritis and 84 (31 males and 53 females) controls were included. In patients with noninfectious scleritis, the thickness of sclera and the ciliary body were significantly greater than those in the control group ( p  < 0.05). Before treatment, the thickness of sclera and the ciliary body in systemic treatment group was significantly higher than that in topical treatment group ( p  < 0.05). After treatment, both thicknesses of sclera and the ciliary body decreased significantly ( p  < 0.05). The ratio of ciliary body thickness from the site of inflammation to the normal position was significantly higher in the systemic treatment group than in the topical treatment group., Conclusions: UBM quantitatively shows a decrease in AST/CBT in patients with anterior scleritis after treatment. The ratio of ciliary body thickness at the site of information to that at the normal position may be a reference for the choice of treatment.

This study aimed to investigate clinical characteristics and glaucoma progression in eyes with disc hemorrhage (DH) in the region of peripapillary atrophy (PPA) or DH in temporal region among glaucoma patients with myopia. One hundred ninety-six eyes of 196 glaucoma patients with myopia who were observed at least 4 years and had more than six visual field (VF) tests were included. Eyes with DHs located in the optic disc region at the superotemporal or inferotemporal locations were defined as typical DH. PPA area, disc ovality ratio, and disc torsion were measured. Length of γ-zone PPA, distance from disc edge to fovea, angle of scleral bending were measured using optical coherence tomography. Comparison of baseline characteristics between eyes with and without DH in PPA/DH in temporal region showed similar axial length (26.95 ± 1.60 mm; 26.82 ± 1.07 mm). γ-zone PPA was longer and angle of scleral bending was larger in eyes with DH in PPA/DH in temporal region (both p ≤ 0.001). Longer γ-zone PPA (β = 1.001; p = 0.018) and larger angle of scleral bending (β = 1.033; p = 0.008) were associated with presence of DH in PPA/DH in temporal region using logistic regression analysis. Eyes with DH in PPA/DH in temporal region had a smaller mean deviation slope of VF, a larger disc ovality ratio, a longer γ-zone PPA, and a larger PPA area when compared to those of eyes typical DH. VF progression was associated with absence of DH in PPA/DH in temporal region (p = 0.030) and larger angle of scleral bending (p = 0.019) using Cox proportional hazards model. DH in PPA/DH in temporal region was associated with stretching and deformation of sclera that may be result from myopic changes. Associated factors with VF progression was the degree of scleral deformation, not the presence of DH in PPA/DH in temporal region, showing that DH related to scleral deformation may possess clinical significance in glaucoma with myopia., (© 2024. The Author(s).)

Purpose: To quantitatively characterize the posterior morphology of high myopia eyes with posterior staphyloma., Methods: Surface points of the eyeball were automatically extracted from magnetic resonance imaging scans using deep learning. Subsequently, the topography of posterior staphylomas was constructed to facilitate accurate visualization and quantification of their location and severity. In the three-dimensional Cartesian coordinate system established with surface points, measurements of distances (D) from each point to the hypothetical pre-elongation eye center within the eyeball and local curvatures (C) at each point on the posterior sclera were computed. Using this data, specific parameters were formulated. The concordance of these parameters with traditional staphyloma classification methods and their association with myopic traction maculopathy (MTM) grades based on the ATN classifications were investigated., Results: The study included 102 eyes from 52 participants. The measured parameters, particularly the variance of distance (Dvar) and the maximum value of the curvature and distance product (C · Dmax), demonstrated efficacy in differentiating various types of posterior staphyloma and exhibited strong correlations with the grades of MTM., Conclusions: The automated generation of the posterior scleral topography facilitated visualization and quantification of staphyloma location and severity. Simple geometric parameters can quantify staphyloma shape and correlate well with retinal complications. Future works on expanding these measures to more imaging modalities could improve their clinical use and deepen insights into the link between posterior staphyloma and related retinal diseases., Translational Relevance: This work has the potential to be translated into clinical practice, allowing for the accurate assessment of staphyloma severity and ultimately improving disease management.

Prcis: The relationship between anterior scleral thickness (AST) and scleral spur (SS) length was disrupted in eyes with pseudoexfoliation (PX), and SS length was shorter in eyes with pseudoexfoliative glaucoma (PXG)., Objectives: To evaluate AST in eyes with PX and to examine the relationship between AST and Schlemm canal (SC), trabecular meshwork (TM), and SS., Patients and Methods: Thirty-eight patients with PX syndrome (PXS), 38 patients with PXG, and 38 healthy patients were included in the study. Using sweep source anterior segment optical coherence tomography, AST (0, 1, 2, and 3 mm from the SS), SC, and TM were visualized in the nasal and temporal areas, and measurements were compared between groups. The relationships between corneal thickness, TM, SS, SC, and AST were then evaluated., Results: In all groups, the AST, SC, and TM measurements were similar ( P > 0.05). In the PXG group, SS lengths in the temporal area were shorter than those in the control and PXS groups ( P = 0.012). There were significant correlations between TM length and AST in the PXG group ( P < 0.05). The SS length exhibited moderately positive correlations with SC length and mean TM thickness in the PXG ( P < 0.05). There was a significant relationship between AST0 and SS in healthy eyes ( P < 0.05), but not in other eyes., Conclusions: The shorter SS length observed in eyes with PXG may be a sign of structural changes. In addition, disruption of the relationship between AST and SS may be an early sign of pathologic processes, especially in eyes with PXS, and may require closer follow-up of these eyes., Competing Interests: Disclosure: The authors declare no conflict of interest., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Osteogenesis imperfecta (OI), a rare genetic connective tissue disorder, primarily arises from pathogenic variants affecting the production or structure of collagen type I. In addition to skeletal fragility, individuals with OI may face an increased risk of developing ophthalmic diseases. This association is believed to stem from the widespread presence of collagen type I throughout various parts of the eye. However, the precise consequences of abnormal collagen type I on different ocular tissues remain unknown. Of particular significance is the sclera, where collagen type I is abundant and crucial for maintaining the structural integrity of the eye. Recent research on healthy individuals has uncovered a unique organizational pattern of collagen fibers within the sclera, characterized by fiber arrangement in both circular and radial layers around the optic nerve head. While the precise function of this organizational pattern remains unclear, it is hypothesized to play a role in providing mechanical support to the optic nerve. The objective of this study is to investigate the impact of abnormal collagen type I on the sclera by assessing the fiber organization near the optic nerve head in individuals with OI and comparing them to healthy individuals. Collagen fiber orientation of the sclera was measured using polarization-sensitive optical coherence tomography (PS-OCT), an extension of the conventional OCT that is sensitive to materials that exhibit birefringence (axial changes in light refraction). Birefringence was quantified and used as imaging contrast to extract collagen fiber orientation as well as the thickness of the radially oriented scleral layer. Three individuals with OI, exhibiting different degrees of disease severity, were assessed and analyzed, along with seventeen healthy individuals. Mean values obtained from individuals with OI were descriptively compared to those of the healthy participant group. PS-OCT revealed a similar orientation pattern of scleral collagen fibers around the optic nerve head between OI individuals and healthy individuals. However, two OI participants exhibited reduced mean birefringence of the radially oriented scleral layer compared to the healthy participant group (OI participant 1 oculus dexter et sinister (ODS): 0.34°/μm, OI participant 2: ODS 0.26°/μm, OI participant 3: OD: 0.29°/μm, OS: 0.28°/μm, healthy participants: ODS 0.38 ± 0.05°/μm). The radially oriented scleral layer was thinner in all OI participants although within ±2 standard deviations of the mean observed in healthy individuals (OI participant 1 OD: 101 μm, OS 104 μm, OI participant 2: OD 97 μm, OS 98 μm, OI participant 3: OD: 94 μm, OS 120 μm, healthy participants: OD 122.8 ± 13.6 μm, OS 120.8 ± 15.1 μm). These findings imply abnormalities in collagen organization or composition, underscoring the necessity for additional research to comprehend the ocular phenotype in OI., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Purpose: To investigate the changing patterns of corneal endothelial cells and the associated factors in children with congenital ectopia lentis (CEL) after scleral-fixated intraocular lens (SF IOL) surgery., Setting: Zhongshan Ophthalmic Center, Guangzhou, China., Design: Retrospective study., Methods: Patients were divided into the surgery group and the control group. Central endothelial cell density (ECD), coefficient of variation in cell size, the percentage of hexagonal cells (hexagonality), average cell size (AVG), and central corneal thickness were analyzed for both groups at baseline and each follow-up visit. Clinic characteristic, ocular parameters, IOL decentration, and IOL tilt of patients in the surgery group were collected. Multiple linear regression was performed to assess the potential associated factors for the postoperative changes in corneal endothelial cells in the surgery group., Results: After 2-year follow-up, the decline of ECD was 17.8% (95% CI, -21.8 to -13.9) in the surgery group and -3.1% (95% CI, -5.2 to -1.0) in the control group ( P < .001), while the increase of AVG was 24.3% (17.1-31.6) in the surgery group and 2.7% (1.0 to 4.5) in the control group ( P < .001). Multivariate analysis showed that axial length (AL) ≥24 mm and white-to-white (WTW) <12.2 mm were significantly associated with greater loss of ECD (β = -241.41, 95% CI, -457.91 to -24.91, P = .030 and β = 251.63, 95% CI, 42.10-461.17, P = .020, respectively) and AL ≥24 mm was significantly positively associated with the increase of AVG (β = 34.81, 95% CI, 0.90-68.71, P = .044)., Conclusions: The SF IOL had a significant impact on corneal endothelium in children with CEL. More attention should be paid to monitor postoperative corneal endothelium change during long-term follow-up in CEL children, especially for those with longer AL and smaller WTW., (Copyright © 2024 Published by Wolters Kluwer on behalf of ASCRS and ESCRS.)

Scleral hypoxia is considered a trigger in scleral remodeling-induced myopia. Identifying differentially expressed molecules within the sclera is essential for understanding the mechanism of myopia. We developed a scleral fibroblast hypoxia model and conducted RNA sequencing and bioinformatic analysis. RNA interference technology was then applied to knock down targeted genes with upregulated expression, followed by an analysis of COLLAGEN I protein level. Microarray data analysis showed that the expression of Adamts1 and Adamts5 were upregulated in fibroblasts under hypoxia (t-test, p < 0.05). Western blot analysis confirmed increased protein levels of ADAMTS1 and ADAMTS5, and a concurrent decrease in COLLAGEN I in hypoxic fibroblasts. The knockdown of either Adamts1 or Adamts5 in scleral fibroblasts under hypoxia resulted in an upregulation of COLLAGEN I. Moreover, a form-deprivation myopia (FDM) mouse model was established for validation. The sclera tissue from FDM mice exhibited increased levels of ADAMTS1 and ADAMTS5 protein and a decrease in COLLAGEN I, compared to controls. The study suggests that Adamts1 and Adamts5 may be involved in scleral remodeling induced by hypoxia and the development of myopia., Competing Interests: Declaration of competing interest The authors declare that they have no competing financial interests., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Purpose: Midday fogging (MDF) occurs when particulate material accumulates in the fluid reservoir (FR) beneath scleral lenses (SL), and its impact on epithelial cells is unknown. This study examines the in vitro pro-inflammatory effect of the FR on human corneal epithelial cells in varying degrees of MDF., Methods: Normal SL neophytes were recruited to wear SL 8 h daily for 4 days. Following 8 h on days 1 and 4, optical coherence tomography (OCT) images were acquired for MDF quantification using ImageJ, and the FR was collected. FR samples from the same eye were later pooled, diluted 2-fold and applied on human telomerase-immortalized corneal epithelial (hTCEpi) cells cultured on Terasaki microwell plates. Tumor necrosis factor (TNF)-α and culture media were used as positive and negative controls, respectively. After a 30-minute treatment, the nuclear factor-kappa B (NF-κB) pathway was measured by NF-κB-p65 immunofluorescence and images were analyzed with ImageJ. Pearson's correlation was conducted to determine the association between median nuclear fluorescence and MDF., Results: Fourteen FR samples with a mean volume of 22 ± 16 µl were tested. Mean MDF severity following 8 h of SL wear was 25 ± 17 units (range 7 - 64). The median nuclear fluorescence (NF-κB-p65 translocation) in cultured hTCEpi cells ranged from 31.43 to 45.16 while the negative and positive controls were 44.71 ± 1.72 and 108.77 ± 68.38, respectively. Although a potential positive trend between MDF and median nuclear fluorescence was observed, Pearson's correlation analysis revealed no significant association (r = +0.48, P = 0.09)., Conclusions: The results suggest that the FR can trigger NF-κB-p65 translocation in hTCEpi cells, which may be associated with MDF severity. This study introduces the use of Terasaki microwell plates for immunofluorescence studies of the FR. The technique is simple, minimizes sample usage, and does not require expensive instrumentation., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 British Contact Lens Association. Published by Elsevier Ltd. All rights reserved.)

Purpose: To observe postoperative histological changes in the anterior part of the posterior fixation suture after a Faden operation in an animal model., Methods: A posterior fixation suture was placed at two points 6 mm posterior to the insertion of the extraocular muscle on the superior rectus muscle of the right eye in eight rabbits. The superior rectus muscle of the left eye was used as a control. The eyes were enucleated and the anterior portion of the posterior fixation suture, including the myoscleral junction, was extracted 4 weeks after surgery. Postoperative adhesion was graded from 0 to 4 based on histologic findings (hematoxylin-eosin and Masson's trichrome staining)., Results: Histological evaluation revealed diffuse fibrosis at the myoscleral junction and the anterior part of the posterior fixation suture after the Faden operation. The graded scores for fibrosis, acute inflammation, chronic inflammation, and foreign body reactions in the Faden operation group were significantly higher than those in the control group ( P < .05). Postoperative diffuse fibrosis of the myoscleral junction and anterior-to-posterior fixation sutures were observed in an animal model., Conclusions: Histologic changes may affect ocular alignment and motility, making reoperation unpredictable after the Faden procedure. [ J Pediatr Ophthalmol Strabismus . 2024;61(5):371-375.] .

Central serous chorioretinopathy (CSC) is a common disorder characterized by serous retinal detachment. Several studies using indocyanine green angiography (ICGA) have revealed that choroidal filling delay, choroidal vascular dilation, and choroidal vascular hyperpermeability are the characteristic findings of CSC. These ICGA findings confirm that choroidal circulatory disturbances are the primary factors in the pathogenesis of CSC. With advancements in optical coherence tomography (OCT), choroidal thickness has been found to be significantly greater in eyes with CSC than in normal eyes. Dilated large choroidal vessels reportedly account for the thickened choroid in eyes with CSC. Although many possible mechanisms and risk factors have been suggested, the pathophysiologic features of choroidal circulatory disturbances and choroidal thickening in eyes with CSC have not yet been fully elucidated. Recently, using anterior segment OCT, we proposed that the sclera may induce choroidal circulatory disturbances since CSC eyes have significantly thicker sclera than do normal eyes. This review summarizes updated information on the close relationship between CSC pathogenesis and the sclera., (© 2024. The Author(s).)

Purpose: To describe the epidemiological and clinical features and course of patients with posterior scleritis (PS)., Methods: This retrospective, cross-sectional consecutive case series analyzed the medical records of 16 patients diagnosed with PS., Results: Female gender and unilateral involvement were dominant. Blurred vision (84.21%) and ocular pain (78.95%) were the most common presenting complaints. Serous retinal detachment was the most common ocular finding (84.21%), followed by optic disc swelling (42.11%). Increased scleral thickness was observed in all patients, although a T-sign was detected 8 of 19 eyes (42.1%). Recurrence occured in 5 of 19 eyes in mean 30.2 ± 34.7 months. Central macular thickness, choroidal thickness, and retinal nerve fiber layer thickness were reduced with treatment at final examination significantly ( p  = .005, .002, and .002, respectively)., Conclusions: PS should be considered in patients presenting with unilateral ocular pain and decreased vision. Not only USG findings but also OCT findings are very useful in the follow-up of treatment response.

Purpose: To explore the phenotype of sclera macrophages in form-deprivation (FD) myopia mice and the effects of M2 macrophage in FD myopia development., Methods: C57BL/6 mice were under 2 weeks of unilateral FD treatment. and they were separated into two groups, including an intraperitoneally injected(IP) vehicle group and Panobinostat (LBH589) (10 mg/kg per body weight) treatment group. All biometric parameters were measured before and after treatments, and the type and density of sclera macrophages were identified by immunofluorescence and RT-qPCR. In vitro, we analyzed the M2 macrophage and primary human sclera fibroblast (HSF) co-culture system by using the transcriptome sequencing method. Gene ontology (GO) and KEGG enrichment analyses were used to pinpoint the biological functions and pathways associated with the identified Differentially Expressed Genes (DEGs). The hub genes were investigated using the STRING database and Cytoscape software and were confirmed using RT-qPCR., Results: We found that the M2-type sclera macrophage density and expression increased in FD-treated eyes. The results showed that LBH589 inhibited the M2 macrophage polarization, and reduced FDM development. GO and KEGG analyses revealed that the DEGs were predominantly involved in the synthesis and breakdown of the extracellular matrix (ECM), as well as in pathways related to ECM-receptor interaction and the PI3K-Akt signaling pathway. Five hub genes (FN-1, MMP-2, COL1A1, CD44, and IL6) were identified, and RT-qPCR validated the variation in expression levels among these genes., Conclusion: M2 macrophage polarization occurred in the sclera in FDM mice. Panobinostat-mediated inhibition of M2 macrophage polarization may decrease FDM progression, as M2 macrophages are crucial in controlling ECM remodeling by HSFs., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

The purpose of this study was to assess whether growth and remodeling (G&R) theory could explain staphyloma formation from a local scleral weakening-as could occur from age-related elastin degradation, myopia progression, or other factors. A finite element model of a healthy eye was reconstructed, including the lamina cribrosa, the peripapillary sclera, and the peripheral sclera. The homogenized constrained mixture model was employed to simulate the adaptation of the sclera to alterations in its biomechanical environment over a duration of 13.7 years. G&R processes were triggered by reducing the shear stiffness of the ground matrix in the peripapillary sclera and lamina cribrosa by 85%. Three distinct G&R scenarios were investigated: (1) low mass turnover rate in combination with transmural volumetric growth; (2) high mass turnover rate in combination with transmural volumetric growth; and (3) high mass turnover rate in combination with mass density growth. In scenario 1, we observed a significant outpouching of the posterior pole, closely resembling the shape of a Type-III staphyloma. Additionally, we found a notable change in scleral curvature and a thinning of the peripapillary sclera by 84%. In contrast, scenario 2 and 3 exhibited less drastic deformations, with stable posterior staphylomas after approximately 7 years. Our proposed framework suggests that local scleral weakening is sufficient to trigger staphyloma formation under a normal level of intraocular pressure. Our model also reproduced characteristics of Type-III staphylomas. With patient-specific scleral geometries (as could be obtained with wide-field optical coherence tomography), our framework could be clinically translated to help us identify those at risks of developing posterior staphylomas., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

We characterized the tensile behavior of sclera, optic nerve (ON), and ON sheath in eyes from donors with glaucoma, for comparison with published data without glaucoma. Twelve freshly harvested eyes were obtained from donors with history of glaucoma, of average age 86 ± 7 (standard deviation) years. Rectangular samples were taken from anterior, equatorial, posterior, and peripapillary sclera, and ON sheath, while ON was in native form and measured using calipers. Under physiological temperature and humidity, tissues were preconditioned at 5% strain before loading at 0.1 mm/s. Force-displacement data were converted into engineering stress-strain curves fit by reduced polynomial hyperelastic models and analyzed by tangent moduli at 3% and 7% strain. Data were compared with an age-matched sample of 7 published control eyes. Optic atrophy was supported by significant reduction in ON cross section to 73% of normal in glaucomatous eyes. Glaucomatous was significantly stiffer than control in equatorial and peripapillary regions (P < 0.001). However, glaucomatous ON and sheath were significantly less stiff than control, particularly at low strain (P < 0.001). Hyperelastic models were well fit to stress-strain data (R 2  > 0.997). Tangent moduli had variability similar to control in most regions, but was abnormally large in peripapillary sclera. Tensile properties were varied independently among various regions of the same eyes. Glaucomatous sclera is abnormally stiff, but the ON and sheath are abnormally compliant. These abnormalities correspond to properties predicted by finite element analysis to transfer potentially pathologic stress to the vulnerable disk and lamina cribrosa region during adduction eye movement., Competing Interests: Declarations Conflict of interest The authors have no financial or proprietary interests in any material discussed in this article. Joseph L. Demer is an uncompensated Trustee of the Association for Research in Vision and Ophthalmology. Ethical approval This study conformed to the tenets of the Declaration of Helsinki., (© 2024. The Author(s).)

Extreme myopia (EM), defined as a spherical equivalent (SE) ≤ -10.00 diopters (D), is one of the leading causes of sight impairment. Known EM-associated variants only explain limited risk and are inadequate for clinical decision-making. To discover risk genes, we performed a whole-exome sequencing (WES) on 449 EM individuals and 9606 controls. We find a significant excess of rare protein-truncating variants (PTVs) in EM cases, enriched in the retrograde vesicle-mediated transport pathway. Employing single-cell RNA-sequencing (scRNA-seq) and a single-cell polygenic burden score (scPBS), we pinpointed PI16 + /SFRP4+ fibroblasts as the most relevant cell type. We observed that KDELR3 is highly expressed in scleral fibroblast and involved in scleral extracellular matrix (ECM) organization. The zebrafish model revealed that kdelr3 downregulation leads to elongated ocular axial length and increased lens diameter. Together, our study provides insight into the genetics of EM in humans and highlights KDELR3's role in EM pathogenesis., (© 2024. The Author(s).)

The optic nerve head (ONH) is a complex structure wherein the axons of the retinal ganglion cells extrude from the eyeball through three openings: 1) the Bruch's membrane opening (BMO) in the retinal layer, 2) the anterior scleral canal opening in the anterior scleral layer, and 3) the lamina cribrosa (LC). Eyeball expansion during growth induces an offset among openings, since the expansion affects the inner retinal and outer scleral layers differently: the posterior polar retinal structure is preserved by the preferential growth in the equatorial region, whereas no such regional difference is observed in the scleral layer. The various modes and extents of eyeball expansion result in diverse directionality and amount of offset among openings, which causes diverse ONH morphology in adults, especially in myopia. In this review, we summarize the ONH changes that occur during myopic axial elongation. These changes were observed prospectively in our previous studies, wherein LC shift and subsequent offset from the BMO center could be predicted by tracing the central retinal vascular trunk position. This offset induces the formation of γ-zone parapapillary atrophy or externally oblique border tissue. As a presumptive site of glaucomatous damage, the LC/BMO offset may render the LC pores in the opposite direction more vulnerable. To support such speculation, we also summarize the relationship between LC/BMO offset and glaucomatous damage. Indeed, LC/BMO offset is not only the cause of diverse ONH morphology in adults, but is also, potentially, an important clinical marker for assessment of glaucoma., Competing Interests: Declaration of competing interest None., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Purpose: To evaluate the efficacy of topical erythropoietin for chemical burn induced scleral necrosis., Methods: This study included 18 eyes of 16 patients with chemical burn induced scleral necrosis who presented within 6 weeks of the injury. In the prospective arm, 11 eyes received topical erythropoietin, 3000 IU/mL every 6 h, along with standard medical treatment. Retrospectively, we included 7 consecutive eyes of 7 patients who were managed with conventional treatment as historical control group. The main outcome measure was healing of avascular scleral lesions. The secondary outcome measure was complete re-epithelization of cornea., Results: Mean patient age was 39.8 ± 16.2 years in the erythropoietin group, and they presented 16.6 ± 15.2 days after acute chemical injury. Scleral necrosis improved in all eyes after 30.7 ± 23.2 days of treatment with topical erythropoietin. Corneal epithelial defects were completely healed in 10 eyes 61.9 ± 50.7 days after the start of the medication. In comparison, standard medical treatment alone did not improve scleral necrosis in the historical control group, necessitating ocular surface reconstruction including conjunctival advancement (1 eye) and tenonplasty (6 eyes)., Conclusion: The results of our study showed that topical erythropoietin was effective in the management of chemical burn induced scleral necrosis. This treatment could avoid ocular surface reconstruction procedures in inflamed eyes., Competing Interests: Declaration of Competing Interest The authors do not have competing interests to declare., (Copyright © 2024 Elsevier Ltd and International Society of Burns Injuries. All rights reserved.)

Purpose: To evaluate changes in scleral thickness in Vogt-Koyanagi-Harada (VKH) disease., Methods: This study included 34 eyes of 17 treatment-naïve patients with acute-phase VKH disease. Scleral thickness and the presence of ciliochoroidal effusion were examined using anterior segment optical coherence tomography at baseline and 1 week, 2 weeks, and 12 weeks after the start of corticosteroid treatment. Scleral thickness was measured 6 mm posterior to the scleral spur in four directions., Results: Twenty-eight eyes (82.4%) initially had ciliochoroidal effusion, but this rapidly decreased to nine eyes (26.5%) after 1 week. The sclera with ciliochoroidal effusion became thinner from baseline to 1 week at the superior (400.2 ± 46.9-353.5 ± 47.9 µm), temporal (428.4 ± 53.6-387.8 ± 56.1 µm), inferior (451.5 ± 71.0-400.5 ± 50.5 µm), and nasal (452.4 ± 78.0-407.6 ± 62.9 µm) points (P < 0.01 for all), and no further changes were observed. The sclera without ciliochoroidal effusion remained unchanged., Conclusion: In VKH disease, eyes with ciliochoroidal effusion exhibited the maximum scleral thickness during the acute phase. This thickening responded rapidly to treatment and became thinner within 1 week. Inflammation in VKH disease may affect not only the choroid but also the sclera.

Objective: To observe the morphological characteristics of posterior scleral staphyloma (PSS) with or without macular retinoschisis (MRS) using optical coherence tomography (OCT). Additionally, the incidence and severity of other pathologic myopic maculopathy associated with posterior scleral staphyloma was also evaluated., Methods: General information and OCT imaging data from 440 patients with posterior scleral staphyloma (PSS) and the PSS curvature > 20×10 -3 μm -1 were collected. These patients visited the Department of Ophthalmology at the First Affiliated Hospital of Harbin Medical University from January 2013 to June 2021. The obtained OCT images of PSS were analyzed using the Image J software to measure the curvature along the Bruch's membrane. The measured curvature was divided into four levels using the quartile method. The classification of macular retinoschisis (MRS) was based on the anatomical structure of the retina and the location of macular retinoschisis. Patients with PSS accompanied by MRS were assigned to the MRS group, while PSS patients without MRS were assigned to the non-MRS group. Additionally, typical OCT changes in other pathologic myopic maculopathy diseases, such as myopic choroidal neovascularization (mCNV), myopic traction maculopathy (MTM), and myopic foveoschisis (MF), were recorded and evaluated., Results: A total of 615 eyes (328 right eyes, 287 left eyes) from 440 patients (80 males and 360 females) were recruited in this study. The MRS group consisted of 159 patients (36.1%) with 190 eyes (30.9%), while the non-MRS group consisted of 281 patients (63.9%) with 425 eyes (69.1%). Both groups had a significantly higher proportion of female patients compared to male patients, and the right eye was more commonly affected than the left eye. In the MRS group, the prevalence of MRS increased progressively with the severity of PSS. Among the common posterior pole diseases, epiretinal membrane had the highest prevalence (33.2%), while lamellar macular hole had the lowest prevalence (5.3%). In the non-MRS group, the proportion of PSS in each group decreased progressively (except for an equal prevalence in the third and fourth levels) with increasing severity of PSS. Among the common posterior pole diseases, choroidal neovascularization had the highest prevalence (41.4%), while lamellar macular hole had the lowest prevalence (6.5%). When comparing the two groups, there were no significant differences in age, gender, and eye distribution. The MRS group had a higher prevalence of macular schisis, retinal detachment, and dome-shaped macula (17.9%, 14.2%, 14.8%) compared to the non-MRS group (11.3%, 9.2%, 9.6%). The non-MRS group had a significantly higher prevalence of choroidal neovascularization (41.4%) compared to the MRS group (12.6%), while there were no significant differences in the prevalence of epiretinal membrane and lamellar macular hole between the two groups., Conclusion: The prevalence of MRS increased progressively with the severity of PSS, and the MRS occurrence was positively correlated with PSS, which indicated that PSS may lead to MRS, while the proportion of PSS in each group decreases gradually with the severity of PSS in the non-MRS group decreased progressively (except for an equal prevalence in the third and fourth levels). In the MRS group, outer macular retinoschisiss were most relevant to posterior scleral staphyloma, and the prevalence of macular holes and retinal detachments was higher in the MRS group compared to the non-MRS group, indicating that MRS may further turn into complications such as macular holes and retinal detachments, which can significantly affect vision or lead to blindness. The prevalence of choroidal neovascularization (CNV) was significantly higher in the non-MRS group compared to the MRS group, suggesting that PSS with lower severity is more prone to develop into CNV. Dome-shaped macula (DSM) seems to play a protective role in the development of pathologic myopia, and abnormal changes in posterior scleral staphyloma curvature may be an important factor affecting the development and shape of DSM., Competing Interests: Declaration of competing interests This was not an industry supported study. The authors report no conflicts of interest in this work., (Copyright © 2024. Published by Elsevier B.V.)

Purpose: To investigate the long-term changes of peripapillary structures detected by enhanced depth imaging of optical coherence tomography (OCT) in adult myopia., Design: Observational case series., Methods: Myopic participants who had undergone a full baseline ophthalmologic examination and had been followed up for a minimum of 8 years were included. Using enhanced depth imaging of OCT, scans around the optic disc in the Spectralis software Follow-up mode, which enabled capturing of the same positions, were performed in 65 eyes. The peripapillary parameters including the size of border tissue, Bruch membrane opening (BMO), peripapillary choroidal thickness, and the angle between peripapillary Bruch membrane (BM) and anterior sclera were manually delineated and measured., Results: The axial length showed a significant elongation after a mean follow-up of 9.46 ± 0.92 years. The rates of changes were 0.015 ± 0.011 mm/y in the medium myopia group and 0.057 ± 0.039 mm/y in the high myopia group. At the last visit, the average border tissue length and BMO diameter were increased. The angle between peripapillary BM did not show significant change, while the angle between the peripapillary sclera showed a significant rise. On multivariate analysis, the border tissue elongation, BMO enlargement, and increased sclera angle were all associated with a change in axial length. The development of a BM defect and inward protrusion of sclera in the temporal peripapillary region was observed on 8 eyes (34.8%) in the high myopia group, along with an extreme thinning or disappearing of the peripapillary choroid., Conclusion: Marked longitudinal changes in peripapillary structures including border tissue, BM, choroid, and sclera could be observed in adult myopic eyes, which may impact the biomechanical environment around the optic nerve head., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background: Myopia is one of the most common eye diseases in children and adolescents worldwide, and scleral remodeling plays a role in myopia progression. However, the identity of the initiating factors and signaling pathways that induce myopia-associated scleral remodeling is still unclear. This study aimed to identify biomarkers of scleral remodeling to elucidate the pathogenesis of myopia., Methods: The gene expression omnibus (GEO) and comparative toxicogenomics database (CTD) mining were used to identify the miRNA-mRNA regulatory network related to scleral remodeling in myopia. Real-time quantitative PCR (RT-qPCR), Western blot, immunofluorescence, H&E staining, Masson staining, and flow cytometry were used to detect the changes in the FOXO signaling pathway, fibrosis, apoptosis, cell cycle, and other related factors in scleral remodeling., Results: miR-15b-5p/miR-379-3p can regulate the FOXO signaling pathway. Confirmatory studies confirmed that the axial length of the eye was significantly increased, the scleral thickness was thinner, the levels of miR-15b-5p, miR-379-3p, PTEN, p-PTEN, FOXO3a, cyclin-dependent kinase (CDK) inhibitor 1B (CDKN1B) were increased, and the levels of IGF1R were decreased in Len-induced myopia (LIM) group. CDK2, cyclin D1 (CCND1), and cell cycle block assessed by flow cytometry indicated G1/S cell cycle arrest in myopic sclera. The increase in BAX level and the decrease in BCL-2 level indicated enhanced apoptosis of the myopic sclera. In addition, we found that the levels of transforming growth factor-β1 (TGF-β1), collagen type 1 (COL-1), and α-smooth muscle actin (α-SMA) were decreased, suggesting scleral remodeling occurred in myopia., Conclusions: miR-15b-5p/miR-379-3p can regulate the scleral cell cycle and apoptosis through the IGF1R/PTEN/FOXO signaling pathway, thereby promoting scleral remodeling in myopia progression., (© 2024. The Author(s).)

Purpose: To report a case of a focal scleral nodule (FSN) that demonstrated growth over three years., Methods: Case report., Results: An asymptomatic emmetropic 15-year-old female patient was referred with an incidental finding of a left fundus lesion on routine examination. On examination, there was an isolated 1.9-mm (vertical) × 1.4-mm (horizontal) diameter-raised, circular, pale, yellow-white lesion with an orange halo located along the inferotemporal vascular arcade. Enhanced-depth imaging optical coherence tomography (EDI-OCT) demonstrated a focal protrusion of the sclera with thinning of the overlying choroid, consistent with focal scleral nodule (FSN). On EDI-OCT, the horizontal basal diameter measured 3138 μm, and its height was 528 μm. Three years later, the lesion had increased in size to 2.7-mm (vertical) × 2.1-mm (horizontal) diameter on color fundus photography and a horizontal basal diameter of 3991 μm and height of 647 μm on EDI-OCT. The patient remained systemically well without visual complaints., Conclusion: FSN can increase in size over time, suggesting that scleral remodeling within and around the lesion can occur. Longitudinal observation of FSN can help to inform its clinical course and shed insight into its pathogenesis., Competing Interests: The authors report no conflicts of interest. None of the authors have a financial or proprietary interest in any material or method. No funding was received for this work. The authors warrant that this article is original and has not been in part or in whole published in another journal.

Ocular melanocytosis is a well-established risk factor for choroidal melanomas but, despite its reported associations in the literature, it is infrequently discussed in relation to orbital melanomas. The authors describe a teenage patient with ocular melanocytosis who presented with an asymptomatic ipsilateral right orbital mass associated with the lateral rectus muscle. An exploratory orbitotomy revealed a lesion lightly adherent to the underlying sclera. Histopathology demonstrated a markedly atypical epithelioid melanocytic proliferation, bound by a thin rim of superficial sclera, implying an origin from intrascleral melanocytes, likely within an emissary canal. Next-generation sequencing identified GNAQ and NF1 mutations. The histopathology and molecular genetics designated the lesion as having a uveal melanoma-like profile, suggesting that it may behave as a choroidal melanoma. This case underscores the importance of the association between ocular melanocytosis and orbital melanoma and provides additional evidence for primary orbital melanoma etiopathogenesis., Competing Interests: The authors have no financial or conflicts of interest to disclose., (Copyright © 2024 The American Society of Ophthalmic Plastic and Reconstructive Surgery, Inc.)

Purpose: To evaluate the Schlemm's canal (SC) parameters obtained by swept-source optical coherence tomography (OCT) different in Graves' ophthalmopathy (GO) eyes compared to healthy eyes., Methods: This cross-sectional observational study evaluated 64 eyes of 32 GO cases and 56 eyes of 28 healthy controls. The study was conducted between October 2020 and June 2021. SC images were obtained from the temporal limbus of individuals using swept-source OCT. SC length (SCL) and SC area (SCA) were measured. The relationship between SC parameters in the patient group and intraocular pressure (IOP), retinal nerve fiber layer (RNFL) thickness, Graves' disease (GD) duration, and clinical activity score (CAS) was evaluated., Results: In the GO group, 64 eyes of 32 patients were evaluated, and in the age and gender-matched healthy control group, 56 eyes of 28 individuals were assessed. SC images from 4 eyes of 4 patients in the patient group and 1 eye of 1 patient in the control group were not clear, preventing SCL and SCA measurements for these eyes. SCL and SCA measurements were found to be lower, and IOP and Hertel values were higher in the GO group compared to the healthy controls. However, no significant correlation was observed between SCL and SCA with IOP, RNFL thickness, GD duration, GO duration, or CAS in the GO group. In the GO group, the mean value of SCA was found to be higher in eyes with glaucoma or OHT compared to those without., Conclusion: These findings indicate that SC in GO-affected eyes is shorter and has a smaller area than in healthy individuals. Additionally, higher IOP and Hertel values were observed in the GO group compared to healthy controls. This study suggests that assessing SC using anterior segment OCT could provide valuable insights into the regulation of IOP and the development of glaucoma in GO-affected eyes., (© 2024. The Author(s).)

Purpose: The purpose of this study was to investigate the effect of globe and optic nerve (ON) morphologies and tissue stiffnesses on gaze-induced optic nerve head deformations using parametric finite element modeling and a design of experiment (DOE) approach., Methods: A custom software was developed to generate finite element models of the eye using 10 morphological parameters: dural radius, scleral, choroidal, retinal, pial and peripapillary border tissue thicknesses, prelaminar tissue depth, lamina cribrosa (LC) depth, ON radius, and ON tortuosity. A central composite face-centered design (1045 models) was used to predict the effects of each morphological factor and their interactions on LC strains induced by 13 degrees of adduction. Subsequently, a further DOE analysis (1045 models) was conducted to study the effects and potential interactions between the top five morphological parameters identified from the initial DOE study and five critical tissue stiffnesses., Results: In the DOE analysis of 10 morphological parameters, the 5 most significant factors were ON tortuosity, dural radius, ON radius, scleral thickness, and LC depth. Further DOE analysis incorporating biomechanical parameters highlighted the importance of dural and LC stiffness. A larger dural radius and stiffer dura increased LC strains but the other main factors had the opposite effects. Notably, the significant interactions were found between dural radius with dural stiffness, ON radius, and ON tortuosity., Conclusions: This study highlights the significant impact of morphological factors on LC deformations during eye movements, with key morphological effects being more pronounced than tissue stiffnesses.

Purpose: The purpose of this study was to examine characteristics of lamina cribrosa (LC) configuration in highly myopic (HM) eyes., Methods: Participants from the Beijing Eye Study 2011, free of optic nerve or retinal diseases, were randomly selected to examine LC depth (LCD) and LC tilt (LCT) using three-dimensional optical coherent tomography images of the optic nerve head (ONH). LCD and LCT were measured as the distance and angle between the LC plane with two reference planes, including the Bruch's membrane opening (BMO) plane and the peripapillary sclera (PPS) plane, respectively. Each parameter was measured in both horizontal and vertical B-scans., Results: The study included 685 individuals (685 eyes) aged 59.6 ± 7.7 years, including 72 HM eyes and 613 non-HM eyes. LCD measurements showed no significant differences between HM eyes and non-HM eyes in both horizontal (LCD-BMO = 421.83 ± 107.86 µm for HM eyes vs. 447.24 ± 104.94 µm for non-HM eyes, P = 0.18; and LCD-PPS = 406.39 ± 127.69 µm vs. 394.00 ± 101.64 µm, P = 1.00) and vertical directions (LCD-BMO = 435.78 ± 101.29 µm vs. 450.97 ± 106.54 µm, P = 0.70; and LCD-PPS = 401.62 ± 109.9 µm vs. 379.85 ± 110.35 µm, P = 0.35). However, the LCT was significantly more negative (tilted) in HM eyes than in non-HM eyes horizontally (LCT-BMO = -4.38 ± 5.94 degrees vs. -0.04 ± 5.86 degrees, P < 0.001; and LCT-PPS = -3.16 ± 5.23 degrees vs. -0.94 ± 4.71 degrees, P = 0.003), but not vertically (P = 1.00)., Conclusions: Although LCD did not differ significantly between HM and non-HM eyes, LCT was more negative in HM eyes, suggesting that the temporal or inferior side of the LC was closer to the reference plane. These findings provide insights into morphological and structural changes in the LC and ONH between HM and non-HM eyes.

To use Optical Coherence Tomography (OCT) to measure scleral thickness (ST) and subfoveal choroid thickness (SFCT) in patients with Branch Retinal Vein Occlusion (BRVO) and to conduct a correlation analysis. A cross-sectional study was conducted. From May 2022 to December 2022, a total of 34 cases (68 eyes) of untreated unilateral Branch Retinal Vein Occlusion (BRVO) patients were recruited at the Affiliated Eye Hospital of Nanchang University. Among these cases, 31 were temporal branch vein occlusions, 2 were nasal branch occlusions, and 1 was a superior branch occlusion. Additionally, 39 cases (39 eyes) of gender- and age-matched control eyes were included in the study. Anterior Segment Optical Coherence Tomography (AS-OCT) was used to measure ST at 6 mm superior, inferior, nasal, and temporal to the limbus, while Enhanced Depth Imaging Optical Coherence Tomography (EDI-OCT) was used to measure SFCT. The differences in ST and SFCT between the affected eye, contralateral eye, and control eye of BRVO patients were compared and analyzed for correlation. The axial lengths of the BRVO-affected eye, contralateral eye, and control group were (22.92 ± 0.30) mm, (22.89 ± 0.32) mm and (22.90 ± 0.28) mm respectively, with no significant difference in axial length between the affected eye and contralateral eye (P > 0.05). The SFCT and ST measurements in different areas showed significant differences between the BRVO-affected eye, contralateral eye in BRVO patients (P < 0.05). The CRT of BRVO-affected eyes was significantly higher than that of the contralateral eyes and the control eyes (P < 0.001). In comparison between BRVO-affected eyes and control eyes, there were no statistically significant differences in age and axial length between the two groups (P > 0.05). However, significant differences were observed in SFCT and temporal, nasal, superior, and inferior ST between the two groups (P < 0.05). The difference in temporal ST between the contralateral eyes and the control eyes was not statistically significant (t = - 0.35, P = 0.73). However, the contralateral group showed statistically significant increases in SFCT, nasal, superior and inferior ST compared to control eyes (t = - 3.153, 3.27, 4.21, 4.79, P = 0.002, 0.002, < 0.001, < 0.001). However, the difference between the CRT of the contralateral and control eyes was not statistically significant (P = 0.421). When comparing SFCT and ST between BRVO-affected eyes with and without macular edema, no statistically significant differences were found (t = - 1.10, 0.45, - 1.30, - 0.30, 1.00; P = 0.28, 0.66, 0.21, 0.77, 0.33). The thickness of SFCT and temporal ST in major BRVO group is higher than the macular BRVO group and the difference was statistically significant (t = 6.39, 7.17, P < 0.001 for all). Pearson correlation analysis revealed that in BRVO patients, there was a significant positive correlation between SFCT/CRT and temporal ST (r = 0.288, 0.355, P = 0.049, 0.04). However, there was no correlation between SFCT/CRT and nasal ST, superior ST, and inferior ST (P > 0.05). In BRVO patients, both SFCT/CRT and ST increase, and there is a significant correlation between SFCT/CRT and the ST at the site of vascular occlusion., (© 2024. The Author(s).)

This study aims to correlate adaptive optics-transscleral flood illumination (AO-TFI) images of the retinal pigment epithelium (RPE) in central serous chorioretinopathy (CSCR) with standard clinical images and compare cell morphological features with those of healthy eyes. After stitching 125 AO-TFI images acquired in CSCR eyes (including 6 active CSCR, 15 resolved CSCR, and 3 from healthy contralateral), 24 montages were correlated with blue-autofluorescence, infrared and optical coherence tomography images. All 68 AO-TFI images acquired in pathological areas exhibited significant RPE contrast changes. Among the 52 healthy areas in clinical images, AO-TFI revealed a normal RPE mosaic in 62% of the images and an altered RPE pattern in 38% of the images. Morphological features of the RPE cells were quantified in 54 AO-TFI images depicting clinically normal areas (from 12 CSCR eyes). Comparison with data from 149 AO-TFI images acquired in 33 healthy eyes revealed significantly increased morphological heterogeneity. In CSCR, AO-TFI not only enabled high-resolution imaging of outer retinal alterations, but also revealed RPE abnormalities undetectable by all other imaging modalities. Further studies are required to estimate the prognosis value of these abnormalities. Imaging of the RPE using AO-TFI holds great promise for improving our understanding of the CSCR pathogenesis., (© 2024. The Author(s).)

Background: To compare the ocular features of highly myopic eyes with posterior staphyloma of wide macular type according to its morphological complexity., Methods: In this cross-sectional study, wide macular posterior staphyloma (WMPS) was classified into the primary (Curtin type I) and the compound (Curtin types VI to X) forms based on the configuration within the staphyloma. The grades of myopic maculopathy and the thicknesses of choroid and sclera were compared between the primary and compound forms of WMPS., Results: A total of 154 eyes (103 patients) with primary WMPS and 65 eyes (49 patients) with compound WMPS were included. Eyes with compound WMPS had worse visual acuity (P = 0.001) and greater axial length (P < 0.001) than those with primary WMPS. Compared to primary WMPS, compound WMPS had a higher grade of myopic macular degeneration (P < 0.001) and a higher frequency of lamellar or full-thickness macular hole associated with myopic traction (21.5% vs. 10.4%; P = 0.028) and active or scarred myopic choroidal neovascularization (33.8% vs. 20.1%; P = 0.030). On swept-source optical coherence tomography, eyes with compound WMPS had significantly thinner choroid and sclera., Conclusions: The compound form of WMPS had more severe myopic macular changes and worse visual prognosis compared to the primary form of WMPS, and these were associated with more structural deformation in the posterior eyeball. Compound WMPS should be considered as an advanced form of staphyloma., (© 2024. The Author(s).)

Purpose: To investigate the short-term effect of scleral lens (SL) on corneal curvature and corneal oedema in Pellucid Marginal Degeneration (PMD) eyes., Methods: Corneal anterior, posterior curvature and corneal thickness were measured in 14 eyes of 14 PMD participants with Schiempflug imaging at different corneal diameters and meridians at baseline and after 6 h of SL wear., Results: There was a significant flattening (up to 0.26 mm) of the anterior corneal curvature noted in the inferotemporal quadrant (from 210 to 255 degree at 2 mm, 8 mm and 10 mm corneal diameter), inferonasal quadrant (from 285 to 345 degree at 6 mm and 8 mm corneal diameter), and inferiorly at 2 mm and 10 mm corneal diameter (p < 0.05). Similarly, posterior corneal curvature showed statistically significant steepening mostly in inferotemporal quadrants (from 195 to 255 degree from 4 mm to 8 mm corneal diameter) and inferonasally at 2 mm and 4 mm corneal diameter (p < 0.05). A statistically significant increase in the corneal thickness noted in different corneal diameters with corneal oedema ranging from 2.10 % to 4.00 % after 6 h of SL wear. A gradual increase in corneal oedema was noted form centre to periphery. The baseline central fluid reservoir thickness (FRT) was 341.07 ± 139.8 which reduced to 276.71 ± 114.32 µm after 6 h of lens wear. No significant correlation was noted between corneal oedema with different parameters like initial and final FRT, change in anterior and posterior corneal curvature, and lens thickness (p > 0.05)., Conclusions: Short-term SL wear induced a clinically acceptable range of corneal oedema. A clinically significant flattening in anterior curvature and minimal steepening in posterior curvature were noted. Practitioners should be careful while measuring corneal parameters in PMD eyes wearing SL, as these alterations can provide false impression of disease progression., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 British Contact Lens Association. Published by Elsevier Ltd. All rights reserved.)

Objectives: To evaluate scleral thickness measurements of pterygium patients using anterior segment optical coherence tomography (AS-OCT) and to compare them with healthy individuals., Material and Methods: Scleral thickness was measured from 2, 4, 6 mm posterior to the scleral spur with AS-OCT (Swept Source OCT Triton, Topcon, Japan) in 4 quadrants (superior, inferior, nasal and temporal)., Results: Eyes with pterygium were determined as Group 1, and contralateral eyes without pterygium were determined as Group 2. Healthy controls were determined as Group 3. In the measurements made from 4 mm posterior, no significant difference was found between Group 1 and Group 2 in any quadrants (p > 0.05). In all measurements made from 4 mm posterior to the scleral spur, scleral thickness was found to be significantly higher in Group 1 compared to Group 3 (p < 0.05). Measurements made from 2 mm posterior to the scleral spur in Group 1 was found to be significantly higher in the superior and temporal quadrants compared to Group 3 (p = 0.05), while no significant difference was found in the nasal and inferior quadrants (p > 0.05). When Group 2 and Group 3 were compared, scleral thickness measurements made from 4 mm posterior to the scleral spur was significantly thicker in all quadrants in Group 2 (p > 0.05)., Conclusion: Scleral thickness was found to be higher in pterygium patients compared to healthy controls, especially when measured from 4 mm posterior to the scleral spur. It has been predicted that high scleral thickness may be associated with high fibroblast activity in subconjunctival structures, and this may predispose to pterygium., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 British Contact Lens Association. Published by Elsevier Ltd. All rights reserved.)

Purpose: Histological evidence indicates that the earliest structural changes to the optic nerve head (ONH) in glaucoma occur in the lamina cribrosa (LC) and its interface with the sclera. However, clinical imaging of these structures remains challenging. We compared the visibility of deep ONH structures with newer iterations of spectral-domain (SD) and swept-source (SS) optical coherence tomography (OCT)., Methods: Twelve patients with open-angle glaucoma were imaged with SD-OCT with 24 radial B-scans centred on Bruch's membrane opening (BMO) and SS-OCT with a horizontal and vertical raster scan pattern containing five lines each, centred on the ONH. Single best-matched horizontal and vertical scans from the two modalities were selected and exported. Three independent observers masked to modality determined if BMO, posterior choroid surface, anterior scleral canal opening and anterior and posterior LC insertions into the sclera were detectable in the matched B-scan images. We determined the interobserver agreement and concordance in detecting each structure with the two OCT imaging modalities., Results: There was a high interobserver agreement with both SS-OCT and SD-OCT (inter-item correlations: 0.81-0.93 and 0.77-0.82, respectively). There was a consistent tendency for higher overall detection rates with SS-OCT, however, the differences failed to reach statistical significance. With respect to individual structures, only the posterior LC insertion in the nasal quadrant was statistically different, with a detection rate of 13 and 6 (pooled out of a total of 36 across the three observers) with SS-OCT and SD-OCT, respectively (p=0.04)., Conclusion: Overall, both SS-OCT and SD-OCT showed statistically equivalent visualisation of ONH structures, however, SS-OCT tended to have higher visualisation rates., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

Aim: To perform an independent validation of deep learning (DL) algorithms for automated scleral spur detection and measurement of scleral spur-based biometric parameters in anterior segment optical coherence tomography (AS-OCT) images., Methods: Patients receiving routine eye care underwent AS-OCT imaging using the ANTERION OCT system (Heidelberg Engineering, Heidelberg, Germany). Scleral spur locations were marked by three human graders (reference, expert and novice) and predicted using DL algorithms developed by Heidelberg Engineering that prioritise a false positive rate <4% (FPR4) or true positive rate >95% (TPR95). Performance of human graders and DL algorithms were evaluated based on agreement of scleral spur locations and biometric measurements with the reference grader., Results: 1308 AS-OCT images were obtained from 117 participants. Median differences in scleral spur locations from reference locations were significantly smaller (p<0.001) for the FPR4 (52.6±48.6 µm) and TPR95 (55.5±50.6 µm) algorithms compared with the expert (61.1±65.7 µm) and novice (79.4±74.9 µm) graders. Intergrader reproducibility of biometric measurements was excellent overall for all four (intraclass correlation coefficient range 0.918-0.997). Intergrader reproducibility of the expert grader (0.567-0.965) and DL algorithms (0.746-0.979) exceeded that of the novice grader (0.146-0.929) for images with narrow angles defined by OCT measurement of angle opening distance 500 µm anterior to the scleral spur (AOD500)<150 µm., Conclusions: DL algorithms on the ANTERION approximate expert-level measurement of scleral spur-based biometric parameters in an independent patient population. These algorithms could enhance clinical utility of AS-OCT imaging, especially for evaluating patients with angle closure and performing intraocular lens calculations., Competing Interests: Competing interests: BYX and ASH receive research support from Heidelberg Engineering. MS is employed by Heidelberg Engineering., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

The annual increase in myopia prevalence poses a significant economic and health challenge. Our study investigated the effect of calcitriol role in myopia by inducing the condition in guinea pigs through form deprivation for four weeks. Untargeted metabolomics methods were used to analyze the differences in metabolites in the vitreous body, and the expression of vitamin D receptor (VDR) in the retina was detected. Following form deprivation, the guinea pigs received intraperitoneal injections of calcitriol at different concentrations. We assessed myopia progression using diopter measurements and biometric analysis after four weeks. Results indicated that form deprivation led to a pronounced shift towards myopia, characterized by reduced choroidal and scleral thickness, disorganized collagen fibers, and decreased scleral collagen fiber diameter. Notably, a reduction in calcitriol expression in vitreous body, diminished vitamin D and calcitriol levels in the blood, and decreased VDR protein expression in retinal tissues were observed in myopic guinea pigs. Calcitriol administration effectively slowed myopia progression, preserved choroidal and scleral thickness, and prevented the reduction of scleral collagen fiber diameter. Our findings highlight a significant decrease in calcitriol and VDR expressions in myopic guinea pigs and demonstrate that exogenous calcitriol supplementation can halt myopia development, enhancing choroidal and scleral thickness and scleral collagen fiber diameter., (© 2024. The Author(s).)

Purpose: Blue sclera is a characteristic and common clinical sign of Osteogenesis Imperfecta (OI). However, there is currently no widely accepted, objective method for assessing and grading blue sclera in individuals with OI. To address this medical need, this study is aimed to design and validate a new method called 'BLUES' (BLUe Eye Sclera) to objectively identify and quantify the blue color in the sclera of patients affected by OI., Methods: Sixty-two patients affected by OI and 35 healthy controls were enrolled in the present prospective study, for a total of 194 eyes analyzed. In the 'BLUES' procedure, eye images from patients with OI and control subjects were analyzed to assess and grade the blue level of the sclera using Adobe Photoshop Software. The validation process then involved comparing the results obtained with the 'BLUES' procedure to the judgement of experienced ophthalmologists (JEO). A receiver-operating characteristic (ROC) curve analysis was used to examine the overall discriminatory power. The sensitivity and specificity levels and the Cohen's Kappa (K) indexes of 'BLUES' and 'JEO' were estimated versus the standard OI diagnosis. The K indexes of 'BLUES' versus 'JEO' were also evaluated., Results: The optimal cut-off point of the scleral blue peak was calculated at 17%. Our findings demonstrated a sensitivity of 89% (CI95%: 0.835-0.945) and specificity of 87% (CI95%: 0.791-0.949) for the 'BLUES' procedure with an agreement versus the diagnosis of OI of 0.747. In comparison, the sensitivity and specificity of 'JEO' ranged from 89 to 94% and 77% to 100%, respectively, with an agreement ranging from 0.663 to 0.871 with the diagnosis of OI. The agreement between 'BLUES 'and 'JEO' evaluations ranged from 0.613 to 0.734., Conclusions: Our findings demonstrated an 89% sensitivity and an impressive 87% specificity of our method to analyze the blue sclera in OI. The results indicated high agreement with disease diagnosis and were consistent with evaluations by experienced ophthalmologists. The 'BLUES' procedure appears to be a simple, reliable and objective method for effectively identify and quantify the blue color of the sclera in OI., (© 2024. The Author(s).)

Background: Ciliary body tumor is extremely rare and treatment is challenging. The aim of this study is to present our experience in treating this rare entity, especially large tumors with more than 5 clock hours of involvement, and to evaluate the surgical outcomes and complications of local resection via partial lamellar sclerouvectomy in four cases of ciliary body tumors in China., Methods: Four patients with ciliary body tumors underwent partial lamellar sclerouvectomy between October 2019 and April 2023 in Shanghai General Hospital, China. Tumor features, histopathologic findings, complications, visual acuity, and surgical outcomes were reviewed at a mean follow-up of 20.8 months., Results: Four patients with a mean age of 31.8 years were included in this study. The histopathological diagnosis was adenoma of non-pigmented ciliary epithelium (ANPCE), schwannoma, and multiple ciliary body pigment epithelial cysts. The mean largest tumor base diameter was 6.00 mm (range: 2.00-10.00) and the mean tumor thickness was 3.50 mm (range: 2.00-5.00). Preoperative complications included cataract in 3 (75%) eyes, lens dislocation in 2 (50%), and secondary glaucoma in 1 (25%). Temporary ocular hypotonia was observed in one case and no other postoperative complications were observed. At a mean follow-up of 20.8 months, the best corrected visual acuity increased in 3 eyes and was stable in 1 eye. Tumor recurrence was absent in all eyes. All patients were alive at the end of follow-up., Conclusions: Local tumor resection via PLSU is useful in the treatment of ciliary body tumors, including large tumors occupying more than five clock hours of pars plicata. Surgery-related complications were manageable with adequate preoperative assessment and careful operation during surgery., (© 2024. The Author(s).)

Purpose: To investigate the differences in anterior scleral thickness (AST) among the refractive statuses of Chinese adults aged 18-35., Methods: This study recruited 170 Chinese participants (mean age, 24.06 ± 2.78 years), including myopes (spherical equivalent refraction [SER] -1.00 to -12.75 diopters [D]; n = 134), emmetropes (SER ± 0.75 D; n = 36), and AST (superior, inferior, nasal, and temporal), which were investigated via swept-source optical coherence tomography. Semiautomated custom-designed software measured the scleral thickness from the scleral spur to 5 mm along four meridians., Results: The mean axial length and spherical equivalent refractive error were 25.12 ± 1.44 mm and -3.93 ± 3.09 D, respectively. The anterior sclera was thickest in the inferior region and thinnest in the superior region (753.9 ± 88.7 μm versus 613.6 ± 58.4; p < 0.001). The AST in the temporal meridian was significantly thicker than that in the nasal meridian (727.5 ± 60.8, 690.9 ± 55 μm; p < 0.001). There were no significant variations in AST in the myopes and emmetropes along the five latitude lines. AST along the inferior meridian at the 4-mm (r 2 = 0.0992; p < 0.001) and 5-mm (r 2 = 0.0888; p < 0.001) locations decreased significantly with increasing myopia., Conclusion: With increased myopia, AST at the 4-mm and 5-mm locations showed significant thinning in the inferior meridian. The results indicate that AST, especially along the inferior meridian, may act as a biologic marker to monitor the progression of myopia., (Copyright © 2024 Molecular Vision.)

Importance: The relevance of visualizing scleral fiber orientation may offer insights into the pathogenesis of pathologic myopia, including dome-shaped maculopathy (DSM)., Objective: To investigate the orientation and density of scleral collagen fibers in highly myopic eyes with and without DSM by polarization-sensitive optical coherence tomography (PS-OCT)., Design, Setting, and Participants: This case series included patients with highly myopic eyes (defined as a refractive error ≥6 diopters or an axial length ≥26.5 mm) with and without a DSM examined at a single site in May and June 2019. Analysis was performed from September 2019 to October 2023., Exposures: The PS-OCT was used to study the birefringence and optic axis of the scleral collagen fibers., Main Outcomes and Measures: The orientation and optic axis of scleral fibers in inner and outer layers of highly myopic eyes were assessed, and the results were compared between eyes with and without a DSM., Results: A total of 72 patients (51 [70.8%] female; mean [SD] age, 61.5 [12.8] years) were included, and 89 highly myopic eyes were examined (mean [SD] axial length, 30.4 [1.7] mm); 52 (58.4%) did not have a DSM and 37 (41.6%) had a DSM (10 bidirectional [27.0%] and 27 horizontal [73.0%]). Among the 52 eyes without DSM, the 13 eyes with simple high myopia had primarily inner sclera visible, displaying radially oriented fibers in optic axis images. In contrast, the entire thickness of the sclera was visible in 39 eyes with pathologic myopia. In these eyes, the optic axis images showed vertically oriented fibers within the outer sclera. Eyes presenting with both horizontal and bidirectional DSMs had clusters of fibers with low birefringence at the site of the DSM. In the optic axis images, horizontally or obliquely oriented scleral fibers were aggregated in the inner layer at the DSM. The vertical fibers located posterior to the inner fiber aggregation were not thickened and appeared thin compared with the surrounding areas., Conclusions and Relevance: This study using PS-OCT revealed inner scleral fiber aggregation without outer scleral thickening at the site of the DSM in highly myopic eyes. Given the common occurrence of scleral pathologies, such as DSM, and staphylomas in eyes with pathologic myopia, recognizing these fiber patterns could be important. These insights may be relevant to developing targeted therapies to address scleral abnormalities early and, thus, mitigate potential damage to the overlying neural tissue.

Scleritis is a severe and painful ophthalmic disorder, in which a pathogenic role for collagen-directed autoimmunity was repeatedly suggested. We evaluated the presence of sclera-specific antibodies in a large cohort of patients with non-infectious scleritis. Therefore, we prospectively collected serum samples from 121 patients with non-infectious scleritis in a multicenter cohort study in the Netherlands. In addition, healthy (n = 39) and uveitis controls (n = 48) were included. Serum samples were tested for anti-native human type II collagen antibodies using a validated enzyme-linked immunosorbent assay (ELISA). Further, sclera-specific antibodies were determined using indirect immunofluorescence (IIF) on primate retinal/scleral cryosections. Lastly, human leukocyte antigen (HLA) typing was performed in 111 patients with scleritis. Anti-type II collagen antibodies were found in 13% of scleritis patients, in 10% of healthy controls and in 11% of uveitis controls (p = 0.91). A specific reaction to scleral nerve tissue on IIF was observed in 33% of patients with scleritis, which was higher than in healthy controls (11%; p = 0.01), but similar to uveitis controls (25%; p = 0.36). Reactivity to the scleral nerve tissue was significantly associated with earlier onset of scleritis (48 versus 56 years; p < 0.001), bilateral involvement (65% versus 42%; p = 0.01), and less frequent development of scleral necrosis (5% versus 22%; p = 0.02). HLA-B27 was found to be twice as prevalent in patients with scleritis (15.3%) compared to a healthy population (7.2%). In conclusion, scleral nerve autoantibody reactivity was more common in scleritis and uveitis patients in contrast to healthy controls. Further research is needed to characterize these scleral-nerve directed antibodies and assess their clinical value., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Pathologic myopia has seriously jeopardized the visual health of adolescents in the past decades. The progression of high myopia is associated with a decrease in collagen aggregation and thinning of the sclera, which ultimately leads to longer eye axis length and image formation in front of the retina. Herein, we report a fibroblast-loaded hydrogel as a posterior scleral reinforcement (PSR) surgery implant for the prevention of myopia progression. The fibroblast-loaded gelatin methacrylate (GelMA)-poly(ethylene glycol) diacrylate (PEGDA) hydrogel was prepared through bioprinting with digital light processing (DLP). The introduction of the PEGDA component endowed the GelMA-PEGDA hydrogel with a high compression modulus for PRS surgery. The encapsulated fibroblasts could consistently maintain a high survival rate during 7 days of in vitro incubation, and could normally secrete collagen type I. Eventually, both the hydrogel and fibroblast-loaded hydrogel demonstrated an effective shortening of the myopic eye axis length in a guinea pig model of visual deprivation over three weeks after implantation, and the sclera thickness of myopic guinea pigs became significantly thicker after 4 weeks, verifying the success of sclera remodeling and showing that myopic progression was effectively controlled. In particular, the fibroblast-loaded hydrogel demonstrated the best therapeutic effect through the synergistic effect of cell therapy and PSR surgery.

The role of extracellular matrix (ECM) remodeling in the axial elongation associated with myopia has not been fully elucidated, although it is considered a significant factor. EFEMP1, a regulator of ECM, has been associated with various pathological conditions. This study aimed to examine the involvement of EFEMP1 in scleral remodeling during form deprivation myopia. The results indicate a progressive increase in EFEMP1 expression following prolonged form deprivation treatment, followed by a subsequent decrease upon recovery. To gain a deeper understanding of the mechanism of EFEMP1, we conducted transcriptome sequencing on primary scleral fibroblasts that were subjected to lentivirus-mediated overexpression of EFEMP1. Validation was performed using lentivirus-induced overexpression and shRNA targeting EFEMP1 in combination with LY294002, a PI3K inhibitor. Our findings suggest that EFEMP1 may be involved in the development of FDM by regulating the expression of the PI3K/AKT/MMP2 axis. The AAV-mediated injection of shEFEMP1 under Tenon's capsule in guinea pigs was observed to effectively delay the progression of myopia and posterior scleral remodeling. In contrast, the AAV-mediated overexpression of EFEMP1 exacerbated the development of myopia and resulted in further thinning of collagen fibers in the posterior sclera. In summary, adjusting EFEMP1 concentrations could potentially serve as a viable approach to prevent and treat myopia by influencing the remodeling process of the posterior sclera., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023. Published by Elsevier B.V.)

Transient receptor potential vanilloid (TRPV) channels are members of the TRP channel superfamily, which are ion channels that sense mechanical and osmotic stimuli and participate in Ca 2+ signalling across the cell membrane. TRPV channels play important roles in maintaining the normal functions of an organism, and defects or abnormalities in TRPV channel function cause a range of diseases, including cardiovascular, neurological and urological disorders. Glaucoma is a group of chronic progressive optic nerve diseases with pathological changes that can occur in the tissues of the anterior and posterior segments of the eye, including the ciliary body, trabecular meshwork, Schlemm's canal, and retina. TRPV channels are expressed in these tissues and play various roles in glaucoma. In this article, we review various aspects of the pathogenesis of glaucoma, the structure and function of TRPV channels, the relationship between TRPV channels and systemic diseases, and the relationship between TRPV channels and ocular diseases, especially glaucoma, and we suggest future research directions. This information will help to further our understanding of TRPV channels and provide new ideas and targets for the treatment of glaucoma and optic nerve damage., Competing Interests: Declaration of competing interest The authors declare that they have no competing interests., (Copyright © 2024. Published by Elsevier Ltd.)

The optic nerve head (ONH) region at the posterior pole of the eye is supported by a fibrous structure of collagen fiber bundles. Discerning how the fibrous structure determines the region biomechanics is crucial to understand normal physiology, and the roles of biomechanics on vision loss. The fiber bundles within the ONH structure exhibit complex three-dimensional (3D) organization and continuity across the various tissue components. Computational models of the ONH, however, usually represent collagen fibers in a homogenized fashion without accounting for their continuity across tissues, fibers interacting with each other and other fiber-specific effects in a fibrous structure. We present a fibrous finite element (FFE) model of the ONH that incorporates discrete collagen fiber bundles and their histology-based 3D organization to study ONH biomechanics as a fibrous structure. The FFE model was constructed using polarized light microscopy data of porcine ONH cryosections, representing individual fiber bundles in the sclera, dura and pia maters with beam elements and canal tissues as continuum structures. The FFE model mimics the histological in-plane orientation and width distributions of collagen bundles as well as their continuity across different tissues. Modeling the fiber bundles as linear materials, the FFE model predicts the nonlinear ONH response observed in an inflation experiment from the literature. The model also captures important microstructural mechanisms including fiber interactions and long-range strain transmission among bundles that have not been considered before. The FFE model presented here advances our understanding of the role of fibrous collagen structure in the ONH biomechanics. STATEMENT OF SIGNIFICANCE: The microstructure and mechanics of the optic nerve head (ONH) are central to ocular physiology. Histologically, the ONH region exhibits a complex continuous fibrous structure of collagen bundles. Understanding the role of the fibrous collagen structure on ONH biomechanics requires high-fidelity computational models previously unavailable. We present a computational model of the ONH that incorporates histology-based fibrous collagen structure derived from polarized light microscopy images. The model predictions agree with experiments in the literature, and provide insight into important microstructural mechanisms of fibrous tissue biomechanics, such as long-range strain transmission along fiber bundles. Our model can be used to study the microstructural basis of biomechanical damage and the effects of collagen remodeling in glaucoma., Competing Interests: Declaration of Competing Interest The authors declare there is no conflict of interests., (Copyright © 2023 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.)