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Worldwide, myopia is the leading cause of visual impairment. It results from inappropriate extension of the ocular axis and concomitant declines in scleral strength and thickness caused by extracellular matrix (ECM) remodeling. However, the identities of the initiators and signaling pathways that induce scleral ECM remodeling in myopia are unknown. Here, we used single-cell RNA-sequencing to identify pathways activated in the sclera during myopia development. We found that the hypoxia-signaling, the eIF2-signaling, and mTOR-signaling pathways were activated in murine myopic sclera. Consistent with the role of hypoxic pathways in mouse model of myopia, nearly one third of human myopia risk genes from the genome-wide association study and linkage analyses interact with genes in the hypoxia-inducible factor-1α (HIF-1α)–signaling pathway. Furthermore, experimental myopia selectively induced HIF-1α up-regulation in the myopic sclera of both mice and guinea pigs. Additionally, hypoxia exposure (5% O₂) promoted myofibroblast transdifferentiation with down-regulation of type I collagen in human scleral fibroblasts. Importantly, the antihypoxia drugs salidroside and formononetin down-regulated HIF-1α expression as well as the phosphorylation levels of eIF2α and mTOR, slowing experimental myopia progression without affecting normal ocular growth in guinea pigs. Furthermore, eIF2α phosphorylation inhibition suppressed experimental myopia, whereas mTOR phosphorylation induced myopia in normal mice. Collectively, these findings defined an essential role of hypoxia in scleral ECM remodeling and myopia development, suggesting a therapeutic approach to control myopia by ameliorating hypoxia.

Purpose The purpose of this study was to compare 27-gauge (27G) with 25-gauge (25G) microincision vitrectomy in patients with epiretinal membrane (ERM). Participants Seventy-four eyes of 66 patients undergoing 3-port pars plana vitrectomy using 27G or 25G instrumentation. Methods Seventy-four eyes of 66 patients with ERM, who underwent 27G or 25G microincision vitrectomy were prospectively evaluated. Results The mean operation time for vitrectomy was significantly longer in the 27G group than in the 25G group (9.9±3.5 vs 6.2±2.7 min, respectively, P <0.0001). No statistically significant difference was found between the two groups in terms of the mean operation time for ERM–inner limiting membrane peeling (27G vs 25G: 20.2±9.9 vs 16.1±9.3 min, P =0.14), although the time for vitreous cutting was longer in the 27G group (9.9±3.5 vs 6.2±2.7 min, respectively, P <0.0001). The flare value, intraocular pressure (IOP), and rate of hypotony 1 day after surgery did not differ between the 27G and 25G groups (flare value: 18.7 vs 17.2; IOP: 8.8 vs 9.7 mm Hg; rate of hypotony: 30 vs 35%, respectively). There was no significant difference in the surgically induced astigmatism between the two groups in the follow-up period. The mean time required for wound closure did not show a significant difference between the 27G and 25G groups (7.7 vs 8.6 weeks, respectively). Conclusion The 27G system is as safe and useful for ERM vitrectomy as the 25G system. Based on its potential, further improvement of 27G instruments could result in greater efficiency.

Purpose To assess the efficacy of adding Ahmed’s sub-flap mattress suture to deep sclerectomy (DS). Methods Forty eyes with open angle glaucoma were assigned randomly into two groups: Group A : underwent DS with Ahmed’s sub-flap mattress suture. Group B : underwent conventional DS. Patients were followed up closely for 6 months with serial IOP measurements and ultrasound biomicroscopy (UBM) was used to assess the surgical site functionally and anatomically at the first and sixth month. Results Adding Ahmed’s sub-flap mattress suture improved the IOP lowering effect of DS significantly from 43% in group B to 53% in group A at 6-month ( p  = 0.027). IOP in group A was at 1 week, 1 month and 6-month visits (7.9 ± 1.3, 11.7 ± 2.2 and 13.3 ± 1.9 mmHg respectively) compared to group B (10.1 ± 4.6, 14.1 ± 5.2 and 16.8 ± 4.1 mmHg respectively) ( p  = 0.025, 0.041 and 0.001 respectively). UBM parameters were significantly larger in group A at 1 and 6 months. Strong statistically significant negative correlations were established between IOP and all the UBM parameters apart from intrascleral lake height at the first and sixth month ( p  < 0.01 in all of them). Finally, significant correlations were found between IOP at 6 months and whole bleb anteroposterior length and height at 1 month ( p  = 0.001). Conclusion Adding Ahmed’s sub-flap mattress suture to routine DS is an effective economical addition that will enhance the IOP lowering effect of DS. Also, assessment of the bleb by UBM is useful in predicting the success of deep sclerectomy surgery. Key messages What is known: Ahmed’s sub-flap mattress suture proved to be an effective economical addition to deep sclerectomy. What is new : UMB parameters are significantly larger in Ahmed’s sub-flap mattress suture deep sclerectomy than in conventional deep sclerectomy. UBM parameters in early postoperative period in deep sclerectomy can be used as indication for late success or failure.

AimsTo evaluate, using anterior segment optical coherence tomography (AS-OCT) and in vivo confocal microscopy (IVCM), the uveo-scleral aqueous humour (AH) outflow pathways after ultrasonic circular cyclocoagulation (UCCC).MethodsForty-four patients with refractory glaucoma underwent 4 or 6 s UCCC (group 1, 24 eyes; group 2, 20 eyes). UCCC was successful when the preoperative intraocular pressure (IOP) reduced by one-third. AS-OCT and IVCM were performed at baseline and at month 1 to evaluate the sclera and conjunctiva. The main outcomes were mean intra-scleral hyporeflective spaces area (MIHSA: mm2) at AS-OCT, mean density and area of conjunctival microcysts (MMD: cysts/mm2; MMA: µm2) at IVCM. The relations between MIHSA, MMA and MMD with IOP were analysed.ResultsMean baseline IOP was 26.9±2.8 mm Hg in group 1 and 27.5±4.0 in group 2. Intra-scleral hyporeflective spaces and microcysts were observed in both groups, without significant differences in MIHSA, MMA and MMD. At month 1, UCCC was successful in 63.6% of patients (41.6% in group 1, 80% in group 2), and IOP reduced to 18.8±3.2 (30.1%) and 17.1±2.7 mm Hg (38.7%), respectively (p<0.001). MIHSA showed a twofold and threefold increase in group 1 and 2 (p<0.05), with a significant difference between groups (p<0.05). MMA and MMD increased in both groups (p<0.05), with values higher in group 2 (p<0.05). Significant relations were found between MIHSA and IOP in both groups (p<0.01).ConclusionsUCCC induced anatomical modifications of sclera and conjunctiva, which suggested that the trans-scleral AH outflow enhancement is one of the possible mechanisms exploited by ultrasounds to reduce IOP.

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.

Background Myopia presents a noteworthy global health concern, urging exploration of innovative treatments. The role of intraocular pressure (IOP) in regulating the progression of myopia has been controversial. Methods To investigate the impact of reducing IOP to varying extents on myopia progression, three groups receiving distinct IOP-lowering medications (Brinzolamide, Latanoprost, and a combination of Brinzolamide and Latanoprost) were designed in a form-deprived myopic guinea pig model. Additionally, proteomics analyses were conducted to identify differentially expressed proteins in the sclera. Results Based on 24-h and 4-week IOP monitoring, the group receiving both Brinzolamide and Latanoprost exhibited the greatest magnitude of IOP reduction and the most significant inhibition of axial length (AL) growth. Moreover, the administration of IOP-lowering medications increased choroidal thickness and induced alterations in the structure of scleral collagen fibrils. Notably, scleral proteomics revealed remodeling processes associated with key mechanisms, including proteolysis, fibrinolysis, and metal ion binding. Conclusions Our findings highlight that pressure-dependent scleral remodeling contributes to the deceleration of AL elongation. These results underscore the efficacy of IOP reduction in mitigating the progression of myopia, providing a promising alternative strategy for myopia management.

AimTo 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.MethodsPatients 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.Results1308 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.ConclusionsDL 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.

The mechanical properties of the sclera play a critical role in supporting the ocular structure and maintaining its shape. However, non-invasive measurements to quantify scleral biomechanics remain challenging. Recently introduced multi-directional optical coherence elastography (OCE) combined with an air-coupled ultrasound transducer for excitation of elastic surface waves was used to estimate phase speed and shear modulus in ex vivo rabbit globes (n = 7). The scleral phase speed (12.1 ± 3.2 m/s) was directional-dependent and higher than for corneal tissue (5.9 ± 1.4 m/s). In the tested locations, the sclera proved to be more anisotropic than the cornea by a factor of 11 in the maximum of modified planar anisotropy coefficient. The scleral shear moduli, estimated using a modified Rayleigh-Lamb wave model, showed significantly higher values in the circumferential direction (65.4 ± 31.9 kPa) than in meridional (22.5 ± 7.2 kPa); and in the anterior zone (27.3 ± 9.3 kPa) than in the posterior zone (17.8 ± 7.4 kPa). The multi-directional scanning approach allowed both quantification and radial mapping of estimated parameters within a single measurement. The results indicate that multi-directional OCE provides a valuable non-invasive assessment of scleral tissue properties that may be useful in the development of improved ocular models, the evaluation of potential myopia treatment strategies, and disease characterization and monitoring.

The biomechanical behavior of the sclera determines the level of mechanical insult from intraocular pressure to the axons and tissues of the optic nerve head, as is of interest in glaucoma. In this study, we measure the collagen fiber structure and the strain response, and estimate the material properties of glaucomatous and normal human donor scleras. Twenty-two posterior scleras from normal and diagnosed glaucoma donors were obtained from an eyebank. Optic nerve cross-sections were graded to determine the presence of axon loss. The specimens were subjected to pressure-controlled inflation testing. Full-field displacement maps were measured by digital image correlation (DIC) and spatially differentiated to compute surface strains. Maps of the collagen fiber structure across the posterior sclera of each inflated specimen were obtained using synchrotron wide-angle X-ray scattering (WAXS). Finite element (FE) models of the posterior scleras, incorporating a specimen-specific representation of the collagen structure, were constructed from the DIC-measured geometry. An inverse finite element analysis was developed to estimate the stiffness of the collagen fiber and inter-fiber matrix. The differences between glaucoma and non-glaucoma eyes were small in magnitude. Sectorial variations of degree of fiber alignment and peripapillary scleral strain significantly differed between normal and diagnosed glaucoma specimens. Meridional strains were on average larger in diagnosed glaucoma eyes compared with normal specimens. Non-glaucoma specimens had on average the lowest matrix and fiber stiffness, followed by undamaged glaucoma eyes, and damaged glaucoma eyes but the differences in stiffness were not significant. The observed biomechanical and microstructural changes could be the result of tissue remodeling occuring in glaucoma and are likely to alter the mechanical environment of the optic nerve head and contribute to axonal damage.

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.