BACKGROUND/AIMS:To investigate the biomechanical mechanisms underlying the occurrence of optic disc haemorrhage (ODH) in glaucoma by analysing the stress at the lamina cribrosa (LC)-sclera interface using patient-specific finite element models based on clinical data. METHODS:This was a retrospective, single-centre, simulation-based, case-control study. Finite element simulations were conducted on individualised optic nerve head models under two gaze conditions: primary gaze and 10° ocular rotation (adduction). The von Mises stress was calculated at the anterior and posterior boundaries of the LC-sclera interface. Intergroup differences in stress and their association with clinical variables were evaluated using analysis of variance, correlation and regression analyses. RESULTS:A total of 111 eyes were included: 44 eyes with primary open-angle glaucoma (POAG) and ODH, 34 eyes with POAG without ODH and 33 control eyes. We found statistically significant differences in stress at both the anterior and posterior boundaries during adduction between the POAG with ODH group and the other groups (p<0.01). Age and axial length were positively associated with stress at the temporal LC-sclera interface during adduction. Logistic regression identified adduction-induced stress as significantly associated with ODH. The multivariate analysis identified age as the strongest contributor to stress during adduction. CONCLUSION:This study demonstrates that increased stress at the LC-sclera interface may contribute to the occurrence of ODH in glaucoma during adduction in the temporal region. We also found that ageing and longer axial lengths may increase stress, potentially leading to the disruption of small vessels at the optic nerve head.

To investigate the effect of preservative-containing and preservative-free latanoprost eyedrops on dry eye symptoms and matrix metalloproteinase 9 expression in untreated open-angle glaucoma patients. Prospective Treatment-naïve open-angle glaucoma patients were randomly assigned to either preservative-containing or preservative-free latanoprost groups. The ocular surface disease index score, Schirmer test, tear break up time, corneal staining score, and matrix metalloproteinase 9 expression in tears were prospectively compared before and at 1 and 3 months after drug instillation. Ocular surface disease index score, Schirmer’s test, tear break up time, corneal staining score, and matrix metalloproteinase 9 expression levels did not significantly differ between the two groups before drug instillation. After 3 months, the preservative-free latanoprost group exhibited a significantly longer tear break up time and improved corneal staining score. The proportion of patients with positive matrix metalloproteinase 9 in tears was lower in the preservative-free group, although this difference was not statistically significant (75.0

To investigate the impact of biomechanical changes in the optic nerve head on glaucoma progression during ocular rotation in highly myopic eyes with primary open-angle glaucoma. This study retrospectively enrolled 147 patients with primary open-angle glaucoma, including 57 with high myopia and 90 with non-high myopia. Personalized optic nerve head models were designed, and simulations were performed using finite element analysis to evaluate the effect of ocular rotation on the optic nerve head. Biomechanical changes in the optic nerve head were analyzed and compared between the groups. The mean strain on the lamina cribrosa was significantly higher in the high myopia group compared to the non-high myopia group during ocular rotation. The stress ratio, indicating asymmetric stress distribution, was higher in the high myopia group than in the non-high myopia group. The stress ratio increased significantly as axial length increased. Both stress ratio and mean lamina cribrosa strain were correlated with rate of retinal nerve fiber layer thickness reduction (stress ratio: partial coefficient = -0.171, P = 0.040; mean lamina cribrosa strain: partial coefficient = -0.196, P = 0.018). High myopia leads to increased lamina cribrosa strain and asymmetric stress distribution during ocular rotation. These findings underscore the importance of considering optic nerve head biomechanics in patients with high myopia. Additionally, the stress ratio may serve as a novel indicator for predicting glaucoma progression. What is known What is new

The management of patients with concurrent pseudoexfoliation glaucoma (PXG) and cataract is challenging given its worse prognosis compared to other glaucoma types and the increased risk associated with cataract surgery. In this retrospective study, we investigated the long-term outcomes of cataract surgery in patients with PXG. We enrolled patients with PXG who had undergone cataract surgery at least 2 years previously and compared them with mean deviation (MD) matched patients with phakic eyes. The results showed that both groups experienced a decrease in MD, with the group of pseudophakic eyes exhibiting a significantly higher rate of decline (−2.15 ± 2.66 dB/year vs. −0.86 ± 0.95 dB/year; P = 0.040). Similarly, there was a trend towards more rapid thinning of the retinal nerve fiber layer in the pseudophakic group (−2.92 ± 2.34 μm/year vs. −1.79 ± 1.71 μm/year; P = 0.074). No significant differences in the intraocular pressure parameters were observed between the two groups. Multivariate analysis revealed that pseudophakic lens status was significantly associated with a faster rate of MD decline in patients with PXG (regression coefficient, −1.391; P = 0.022). These findings underscore the importance of close monitoring of patients with pseudophakic PXG to effectively manage glaucoma progression.

The purpose of this study was to assess the effect of ocular movements on the progression of glaucoma. A total of 118 primary open-angle glaucoma patients were enrolled, comprising 71 patients in the progression group and 47 patients in the non-progression group. Utilizing three geometric parameters—axial length, optic disc radius, and optic cup deepening—a personalized virtual optic nerve head (ONH) model was designed. ONH biomechanical changes during ocular movement were simulated using a finite element analysis. Simulation results were analyzed and compared between the progression and non-progression groups. In both progression and non-progression groups, ONH strains significantly increased with increasing rotation angle. When the eye rotated by 10°, the stress on the anterior surface of the lamina cribrosa on the temporal side was significantly higher in the progression group compared to the non-progression group (16.19 ± 0.90 kPa vs. 13.24 ± 3.00 kPa, P < 0.001). The stress ratio, indicating asymmetric stress distribution, was higher in the progression group than in the non-progression group (0.56 ± 0.13 vs. 0.49 ± 0.19, P = 0.018). Stress ratio significantly increased with increasing optic disc radius (standardized β = 0.303, P < 0.001) and optic cup deepening (standardized β = 0.538, P < 0.001). Asymmetric stress distribution with ocular movement was higher in the progression group. This asymmetry was associated with optic disc radius and optic cup deepening. Therefore, ocular movement may contribute to the progression of glaucoma, with ONH geometry playing a role.

Précis: Relative flow indices as novel optical coherence tomography angiography (OCTA) biomarkers demonstrated reduced optic nerve head and peripapillary large vessel and capillary perfusion in primary open angle glaucoma (POAG). Large vessel perfusion correlated with disease severity and progression. Purpose: To introduce relative flow indices as novel OCTA biomarkers and their pathologic insights in POAG. Materials and Methods: This is a retrospective case-control study where 57 POAG and 57 control eyes were included. OCTA 4.5×4.5 mm optic nerve head (ONH) were analyzed using ImageJ 1.53t to calculate global flow indices (GFIs) and relative flow indices (RFIs) for whole image optic nerve head, isolated radial peripapillary capillary plexus, and isolated large vessel angiograms. Results: Retinal nerve fiber layer thickness (RNFLT), ONH vascular density (VD), except inside disc and large vessel VD, GFIs, and RFIs were lower in POAG than control. There was a positive correlation between RNFLT and both VD and GFIs. Among RFIs, only large vessel RFI (ONHLVRFI) demonstrated a positive correlation with average RNFLT. Linear regression demonstrated a significant positive coefficient for ONHLVRFI with RNFLT as the dependent variable. The area under receiver operating characteristic curve showed diagnostic accuracy ranging fair, good, and excellent for all biomarkers. Inferior RNFLT had the highest area under the curve (0.922) while optic nerve head large vessel density had the lowest (0.523). Conclusions: POAG showed structural loss of RNFL neurovascular unit manifesting as positively correlated reduction of VD and RNFLT. Also, POAG had lower global perfusion of the optic nerve head and peripapillary area, resulting in the positively correlated reduction of GFIs and RNFLT. Although RFIs were lower in POAG, only ONHLVRFI demonstrated a positive correlation and regression with RNFLT, implying that large vessel hypoperfusion was associated with POAG severity and progression.

Précis: In primary open angle glaucoma, the rate of retinal nerve fiber layer thickness decrease was negatively correlated with lamina cribrosa strain, which was associated with intraocular pressure and optic nerve head geometric factors. Purpose: We hypothesized that the biomechanical deformation of the optic nerve head (ONH) contributes to the progression of primary open angle glaucoma (POAG). This study investigated the biomechanical stress and strain on the ONH in patients with POAG using computer simulations based on finite element analysis and analyzed its association with disease progression. Methods: We conducted a retrospective analysis that included patients diagnosed with early-to-moderate stage POAG. The strains and stresses on the retinal nerve fiber layer (RNFL) surface, prelaminar region, and lamina cribrosa (LC) were calculated using computer simulations based on finite element analysis. The correlations between the rate of RNFL thickness decrease and biomechanical stress and strain were investigated in both the progression and nonprogression groups. Results: The study included 71 and 47 patients in the progression and nonprogression groups, respectively. In the progression group, the factors exhibiting negative correlations with the RNFL thickness decrease rate included the maximum and mean strain on the LC. In multivariate analysis, the mean strain on the LC was associated with optic disc radius, optic cup deepening, axial length, and mean intraocular pressure (IOP), whereas the maximum strain was only associated with mean IOP. Conclusions: In early-to-moderate stage POAG, the rate of RNFL thickness decrease was influenced by both the mean and maximum strain on the LC. Strains on the LC were associated with mean IOP, optic disc radius, axial length, and optic cup deepening. These results suggest that not only IOP but also ONH geometric factors are important in the progression of glaucoma.

Pigment epithelial detachment (PED) is common in eyes with central serous chorioretinopathy (CSC), and choroidal neovascularisation (CNV), which is almost always associated with PED, is found in a higher proportion than previously expected. Using en-face optical coherence tomography, this retrospective study aimed to investigate the PED location in relation to various geometric landmarks including the foveal centre (FC), greatest choroidal thickness (GCT) point and optic disc centre. In a total of 98 eyes, the distance from the FC to PED centroid was correlated with the ratio of GCT to subfoveal choroidal thickness (r = 0.278, P = 0.006) and the distance from the FC to GCT point (r = 0.371, P < 0.001). Eyes with CNV had a shorter distance between the PED centroid and FC (700 ± 439 μm) than those without (1191 ± 964 μm, P = 0.001). Analysis of covariance showed that the distance from the FC to the PED centroid was significantly correlated with the distance from the FC to the GCT point (P = 0.009) and the PED group with and without CNV (P = 0.020). This result suggests that the development of complicated PED with CNV can be related to both choroidal vascular abnormalities and retinal pigment epithelial insufficiency.

Choroidal changes have been suggested to be involved in the pathophysiology of both age-related macular degeneration (AMD) and pachychoroid spectrum diseases (PSD). To find out the choroidal characteristics of each disease groups, various groups of AMD and PSD were classified into several clusters according to choroidal profiles based on subfoveal choroidal thickness (CT), peripapillary CT, the ratio of subfoveal CT to peripapillary CT and age. We retrospectively analyzed 661 eyes, including 190 normal controls and 471 with AMD or PSDs. In the AMD groups, eyes with soft drusen or reticular pseudodrusen were belonged to the same cluster as those with classic exudative AMD (all p < 0.001). However, eyes with pachydrusen were not clustered with eyes from other AMD groups; instead, they were classified in the same cluster as eyes from the PSD group (all p < 0.001). In the PSD group, eyes with pachychoroid neovasculopathy were grouped in the same cluster of those with polypoidal choroidal vasculopathy (p < 0.001). The cluster analysis based on the CT profiles, including subfoveal CT, peripapillary CT, and their ratio, revealed a clustering pattern of eyes with AMD and PSDs. These findings support the suggestion that pachydrusen has the common pathogenesis as PSD.

Purpose: To identify the correlation between near work and the occurrence of delayed-onset consecutive esotropia after surgery for intermittent exotropia. Methods: A survey and retrospective review were conducted on patients in two groups. The study included patients who visited from January 2019 to January 2020. Patients who re-developed esodeviation after recovering orthophoria after the initial postoperative overcorrection for the surgical correction of intermittent exotropia were included in the delayed-onset esotropia group (Group 1), and patients with persistent orthotropia for at least 3 years after bilateral lateral rectus recession for intermittent exotropia were included in Group 2. We evaluated the daily frequency and hours of distance/near work in both groups. Results: A total of 42 patients were evaluated. Preoperative exodeviation at a distance was 28.5 +/- 4.4 prism diopters (PD) in group 1 and 30.5 +/- 5.2 PD in group 2, with no significant difference between the two groups. The percentages of patients who chose two or more extremely near-work activities a day were 47.8% and 15.8% for groups 1 and 2, respectively; these values were statistically significant (p = 0.02). Twelve patients in Group 2 answered "watching TV" (63.2%) as the most common activity, which was statistically significant compared to Group 1 (26.1% in Group 1, p = 0.02). The total numbers of hours of extremely near-work a day were 2.7 +/- 2.1 and 1.5 +/- 1.2 hours for groups 1 and 2, respectively, which was also statistically significant (p = 0.037). Conclusions: We found a significant correlation with occurrence of delayed-onset consecutive esotropia with the frequency and hours of extremely near-work after bilateral lateral rectus recession for intermittent exotropia. More attention to extremely near-work should be considered carefully after bilateral lateral rectus recession for intermittent exotropia.

Purpose: To compare the regional differences in the choroidal thickness (CT) between patients with pachychoroid neovasculopathy (PNV) and classic exudative age-related macular degeneration (ceAMD). Materials and Methods: We included both eyes of patients with unilateral macular neovascularization (MNV) due to ceAMD or PNV. Unilateral eyes of normal subjects were also included as a normal control group. The regional difference in CT was defined as a difference between the macular and extramacular areas, and calculated as the ratio of subfoveal CT (SFCT) to nasal peripapillary CT (PCT). Results: In normal subjects, the choroid was 2.25 +/- 0.10 times thicker at the macula than at the extramacular area. The SFCT and PCT were significantly affected by age (P P < .001, respectively), whereas the regional difference in CT were independent of age (P = .076). Analysis of covariance including age, sex, and MNV group showed that regional difference in CT were significantly affected by sex, nasal peripapillary CT, and MNV group (P = .023, P < .001, and P < .001, respectively). The estimated marginal mean of the regional difference in CT was significantly smaller in the ceAMD group (1.671 +/- 0.103) than in the normal control (2.250 +/- 0.095, P = .003) and PNV groups (2.0880 +/- 0.086, P < .001). Conclusions: Regional differences in CT were consistent with aging. However, the difference varied with the presence of PNV or ceAMD. Measurement of regional differences in CT provides additional information for characterizing the choroid in patients with MNV.

To investigate the relationship between choroidal thickness (CT) profile and clinical outcomes after anti-vascular endothelial growth factor (VEGF) treatment in polypoidal choroidal vasculopathy (PCV). Medical records of patients diagnosed with PCV who received anti-VEGF treatment over 12 months were reviewed. Subfoveal CT (SFCT) and peripapillary CT (PCT) were measured on swept-source optical coherence tomography images. Patients were divided into various groups based on choroidal profiles including SFCT, nasal PCT (nPCT) and ratio of SFCT to nPCT (SFCT/nPCT). Clinical outcomes were compared between the thin and thick CT groups. A total of 65 patients with PCV patients were included. After ant-VEGF treatment, SFCT was significantly decreased after anti-VEGF treatment (P = 0.001), but nasal PCT (nPCT) was not. Clinical outcomes were not different between the thin and thick SFCT groups. Total number of injections during the 12 months was significantly fewer in the thin nPCT group (3.4 ± 1.3) than in the thick nPCT group (4.5 ± 1.8) (P = 0.020). Complete resolution after loading injections was more frequently observed in the high SFCT/nPCT ratio (> 1.9) group (87.9%) than in the low SFCT/nPCT ratio (≤ 1.90) group (59.4%) (P = 0.009). The ratio of SFCT/nPCT showed the best predictive ability for poor responders (area under curve = 0.771). These results suggest that baseline nPCT and SFCT/nPCT ratio could be a good biomarker that reflects clinical outcomes after anti-VEGF treatment in PCV.

Purpose: To investigate choroidal vascularity outside the macula in central serous chorioretinopathy (CSC). Methods: Fifty normal controls and 103 patients with a history of CSC (31 with acute CSC, 32 with chronic CSC, and 40 with resolved CSC) were included. Using swept-source optical coherence tomography, we measured choroidal thickness (CT) and choroidal vascularity index (CVI) at the subfoveal and nasal peripapillary areas. Results: Subfoveal CT in the acute CSC group was greater than that in all other groups (all P < 0.05). Peripapillary CT in the acute and chronic CSC groups was significantly greater than that in controls (all P ≤ 0.005). However, subfoveal and peripapillary CT in the resolved CSC group was not different from controls. Subfoveal CVI in the acute group (64.71% ± 2.68%) was higher than that in controls (61.68% ± 5.68%) (P = 0.015). Peripapillary CVIs in the acute (67.35% ± 6.04%) and chronic groups (64.90% ± 5.31%) were higher than controls (54.57% ± 7.02%) (all P < 0.001). Subfoveal CVI in the resolved CSC group was not different from controls (P = 0.252), whereas peripapillary CVI (62.61% ± 6.03%) was higher (P < 0.001). Conclusions: Unlike CT, CVI outside the macula was increased in all eyes with both current and past history of CSC. These findings suggest that the choroidal vascularity outside the macula may represent choroidal characteristics in addition to the subfoveal area. Translational Relevance: Peripapillary CVI outside the macula may provide additional information beyond what is known through subfoveal choroid studies.

We demonstrate the first commercial production–ready white light-emitting diodes (LEDs) for the general illumination market with red colloidal quantum dots (QDs) applied in an on–chip configuration. We show the red QDs with tunable peak emission and narrow full width at half-maximum in combination with a conventional phosphor material can lead to LED conversion efficiency improvements of 5% to 15% over commercial phosphor based LEDs at correlated color temperatures (CCTs) ranging from 5000 to 2700 K. Furthermore, the challenges associated with reliability under high temperature, high blue flux intensity, and high humidity operation have been overcome to meet consumer market requirements. Finally, a demonstrator lamp at 3000 K color temperature and 90 color rendering index (CRI) with QD based LEDs show a larger efficiency gain up to 17%, attributed to the reduced blue LED droop from the lower drive current and the lower heat sink temperature when compared to a standard phosphor based LED lamp output.

Microfluidic technologies have recently been shown to hold significant potential as novel tools for producing micro- and nano-scale structures for a variety of applications in tissue engineering and cell biology. Over the last decade, microfluidic spinning has emerged as an advanced method for fabricating fibers with diverse shapes and sizes without the use of complicated devices or facilities. In this critical review, we describe the current development of microfluidic-based spinning techniques for producing micro- and nano-scale fibers based on different solidification methods, platforms, geometries, or biomaterials. We also highlight the emerging applications of fibers as bottom-up scaffolds such as cell encapsulation or guidance for use in tissue engineering research and clinical practice.

This paper provides a method for microscale fiber spinning and the in situ construction of a 3D fibrous scaffold on a single microfluidic platform. This platform was also used to fabricate a variety of fibrous scaffolds with diverse compositions without the use of complicated devices. We explored the potential utility of the fibrous scaffolds for tissue engineering applications by constructing a fibrous scaffold encapsulating primary hepatocytes. The cells in scaffold were cultured over seven days and maintained higher viability comparing with 3D alginate non-fibrous block. The main advantage of this platform is that the fibrous structure used to form a scaffold can be generated without damaging the mechanically weak alginate fibers or encapsulated cells because all procedures are performed in a single platform without the intervention of the operator. In addition, the proposed fibrous scaffold permitted high diffusion capability of molecules, which enabled better viability of encapsulated cells than non-fibrous scaffold even in massive cell culture.

We have developed a three-dimensional (3D) liver-on-a-chip to investigate the interaction of hepatocytes and hepatic stellate cells (HSCs) in which primary 3D hepatocyte spheroids and HSCs are co-cultured without direct cell-cell contact. Here, we show that the 3D liver chip offers substantial advantages for the formation and harvesting of spheroids. The most important feature of this liver chip is that it enables continuous flow of medium to the cells through osmotic pumping, and thus requires only minimal handling and no external power source. We also demonstrate that flow assists the formation and long-term maintenance of spheroids. Additionally, we quantitatively and qualitatively investigated the paracrine effects of HSCs, demonstrating that HSCs assist in the maintenance of hepatocyte spheroids and play an important role in the formation of tight cell-cell contacts, thereby improving liver-specific function. Spheroids derived from co-cultures exhibited improved albumin and urea secretion rates compared to mono-cultured spheroids after 9 days. Immunostaining for cytochrome P450 revealed that the enzymatic activity of spheroids co-cultured for 8 days was greater than that of mono-cultured spheroids. These results indicate that this system has the potential for further development as a unique model for studying cellular interactions or as a tool that can be incorporated into other models aimed at creating hepatic structure and prolonging hepatocyte function in culture.