High myopia is protective against diabetic retinopathy in the participants of the National Health and Nutrition Examination Survey.

PURPOSE: To investigate the association of subjects with refractive error and diabetic retinopathy (DR) in the United States comparing results between different race groups. METHODS: All data were derived from National Health and Nutrition Examination Survey (NHANES) from 2005 to 2008. The data were divided into four groups (emmetropia, mild myopia, high myopia, hypertropia) according to the spherical equivalent (SE), and those who met the enrollment conditions were selected as the study subjects. Multivariable logistic regression analysis was used to evaluate the relationship between refractive error and diabetic retinopathy risk. RESULTS: A total of 1317 participants were included in the study, including 331 participants with diabetic retinopathy, and 986 without diabetic retinopathy. After adjustment for potential confounders, subjects with high myopia were associated with a lower risk of diabetic retinopathy. The odds ratio (OR) was 0.44, 95% confidence interval (CI): (0.20-0.96), P-value = 0.040 in the multivariate regression analysis. Subgroup analyses showed that subjects with high myopia in the non-Hispanic Black group were associated with decreased odds of diabetic retinopathy. (OR was 0.20, and 95% CI: 0.04-0.95, P-value = 0.042). CONCLUSION: The results show that high myopia is associated with diabetic retinopathy in diabetic patients.

The inhibiting effect of Aspirin Triggered-Resolvin D1 in non-canonical pyroptosis in rats with acute keratitis.

PURPOSE: To investigate the effect of Aspirin Triggered-Resolvin D1 (AT-RvD1) as an anti-pyroptosis and anti-inflammatory agent on lipopolysaccharide (LPS) induced acute keratitis in Wistar rats. METHODS: Acute keratitis in rats were induced by LPS stromal injection. Inflammatory reaction was measured by clinical score and histological observations. The non-canonical pyroptosis, the role of AT-RvD1 and Docosahexaenoic Acid (DHA) on non-canonical pyroptosis, were verified by quantification real-time PCR (qRT-PCR) and Western-blot. Besides, Human corneal epithelial cells (HCECs) primed with LPS, were stimulated with Nigericin, AT-RvD1 and necrosulfonamide (NSA), a Gasdermin-D (GSDMD) inhibitor separately. CCK-8 tests and flow cytometry were conducted to evaluate the cell viability and death ratio. And the marker of non-canonical pyroptosis were verified by Western blot. RESULTS: AT-RvD1 and DHA both alleviated the inflammation of rat cornea through inhibiting the expression of Caspase-11 and p30 which was triggered by LPS. Meanwhile, the activation of Caspase-4 and p30 were also significantly suppressed by AT-RvD1 in vitro, which is consistent with the results in rats. CONCLUSIONS: The non-canonical pyroptosis signaling pathways played an important role in rats with acute keratitis. In addition, AT-RvD1 can exert as an anti-inflammatory activity by inhibiting the non-canonical pyroptosis. Hence, it may be a promising and safe agent in treating acute keratitis.

Changes in Dimensions and Functions of Crystalline Lens in High Myopia Using CASIA2 Optical Coherence Tomography.

INTRODUCTION: Crystalline lens is the major dioptric component and varies with refractive status. In this study, we aim to evaluate the changes of dimensions and functions of crystalline lens in high myopia (HM) and its correlated variables using CASIA2 swept-source optical coherence tomography. METHODS: One hundred and thirty eligible eyes of myopic patients from 18 to 40 years old were enrolled and divided into low-to-moderate myopia (LMM) and HM groups according to spherical equivalent (SE). Anterior segment features, including lens thickness (LT), anterior radius of curvature (ARC), posterior radius of curvature (PRC), anterior chamber depth (ACD), and lens tilt were obtained by CASIA2. Lens power was calculated using Bennett's formula. Sixty-seven participants were imaged at the static state and the accommodative state induced by -3 diopter (D) stimulus. RESULTS: Compared to the LMM group, the HM group exhibited a significantly reduction in LT, ARC, and lens tilt (all p < 0.01). Each parameter correlated positively with SE (all p < 0.01). Lens power increased with LT and tilt (r = 0.42, 0.45) but decreased with ARC and axial length (AL) (r = -0.37, -0.62) among highly myopic eyes. Multivariate regression analysis revealed that lower lens power appeared to be independently associated with axial elongation in both groups (LMM: ß = -1.124, p = 0.002; HM: ß = -1.603, p < 0.001, respectively). Decreases in ARC and ACD were accompanied by accommodative response in each group, while PRC reduced during accommodation (p = 0.009) only in HM. CONCLUSIONS: Young adults with HM presented a thinner thickness, smaller tilt, less lens power, and higher accommodative response. Lens shape was closely associated with SE; however, AL was a meaningful indicator of lens power.

Comparative proteome analysis of form-deprivation myopia in sclera with iTRAQ-based quantitative proteomics.

Objective: Scleral remodeling plays a key role in axial elongation in myopia. The aim of the present study was to identify the proteomics changes and specific signaling networks to gain insight into the molecular basis of scleral remodeling in myopic eyes. Methods: Guinea pig form-deprivation myopia was induced with a translucent diffuser on a random eye for 4 weeks, while the other eye served as the contralateral control group. The axial length and refraction were measured at the beginning and end of the treatment. The proteins were extracted from the sclerae of each group and prepared for quantitative isobaric tags for relative and absolute quantification (iTRAQ) labeling combined with liquid chromatography-tandem mass spectrometry (LC-MS/MS) analysis. The coexpression networks and protein functions were analyzed using Gene Ontology (GO) and Ingenuity Pathway Analysis (IPA). Quantitative real-time PCR (qRT-PCR) and western blotting were performed to confirm the authenticity and accuracy of the iTRAQ results. Results: After 4 weeks, the form-deprivation eyes developed significant degrees of myopia, and the axial length increased statistically significantly (p<0.05). A total of 2,579 unique proteins with <1% false discovery rate (FDR) were identified. Furthermore, 56 proteins were found to be upregulated, and 84 proteins were found to be downregulated, with a threshold of a 1.2-fold change and p<0.05 in the myopia group, when compared to the control group. Further bioinformatics analysis indicated that 44 of 140 differentially expressed proteins were involved in cellular movement and cellular assembly and organization. The qRT-PCR or western blotting results confirmed that myosin IIB, ACTIN3, and cellular cytoskeletons were downregulated, while RhoA and RAP1A were upregulated in the sclera in myopic eyes. These results were consistent with the proteomics results. Conclusions: Proteomics and bioinformatics results can be helpful for identifying proteins and providing new insights for better understanding of the molecular mechanism underlying scleral remodeling. These results revealed that the proteins associated with cellular movement and cellular assembly and organization are altered during the development of myopia. Furthermore, RhoA plays a key role in the pathways involved in cellular movement and cellular assembly and organization.

Transient reduction in the retinal microvascular network following implantation surgery of implantable collamer lens: An OCT angiography study.

Purpose: To evaluate changes in the retinal microvascular network after posterior chamber phakic implantable collamer lens (ICL) surgery using optical coherence tomography angiography (OCTA) in patients with high myopia. Methods: Patients with high myopia who underwent ICL surgery were enrolled in this study. All patients underwent comprehensive ophthalmologic exams preoperatively and 1 week, 1 month, and 3 months postoperatively. The vascular densities (VDs) in the retina and the superficial and deep capillary plexuses of different annular and quadrantal areas were evaluated from OCTA images (Zeiss Cirrus 5000). Correlations between the variations in microvascular density and possible factors were further analyzed. Results: The study comprised 32 eyes of 32 patients. The mean age of the patients was 26.91±7.610 years (15 men and 17 women). A statistically significant reduction in microvascular density in the retina and the superficial plexus was found 1 week and 1 month postoperatively (p<0.05, repeated-measures ANOVA). Further fractal analysis found that the VD of the outer ring declined statistically significantly (p<0.05). A statistically significant decrease was also found in the inferior nasal sector 1 week postoperatively, with an overall decrease in all four quadrants 1 month postoperatively. The microvascular density recovered toward the baseline level 3 months postoperatively. No correlations were observed between the variation in microvascular density and the spherical equivalent (SE), axial length (AL), intraocular pressure (IOP), amplitude of accommodation (AA), or contrast sensitivity. Conclusions: Retinal microvascular density was decreased postoperatively and then recovered toward the baseline level after 3 months. ICL surgery may have a transient influence on the retinal microvascular network without affecting visual function.

Potential effects of angiogenesis-related factors on the severity of APAC and surgical outcomes of trabeculectomy.

BACKGROUND: EPO (erythropoietin) and PDGF (platelet derived growth factor) families are thought to be associated with angiogenesis under hypoxic condition. The sharp rise of intraocular pressure in acute primary angle closure (APAC) results in an inefficient supply of oxygen and nutrients. We aimed to measure the expression of EPO and PDGF family members in APAC eyes and demonstrate their associations with APAC's surgical success rate. METHODS: Concentrations of EPO, PDGF-AA, -BB, -CC and -DD collected in aqueous humor samples of 55 patients recruited were measured. Before operations, correlations between target proteins and IOP (intraocular pressure) were detected between APAC (acute primary angle closure) and cataract patients. Based on the post-operative follow-up, the effects of EPO and PDGF family members on the successful rate of trabeculectomy were tested. RESULTS: The levels of EPO, PDGF-CC and -DD were significantly elevated in the APAC group compared to the cataract group. During the post-operative follow-up, EPO, PDGF-CC and -DD showed significant differences between the success and failure groups. In multivariable linear regression analyses, failed filtration surgery was more likely in APAC eyes with higher EPO level. The Kaplan-Meier survival plot suggested that the success rate in eyes with low EPO level was significantly higher than that in eyes with high EPO level. CONCLUSION: The levels of EPO, PDGF-CC and -DD were significantly elevated in failure group. EPO level correlated with preoperative IOP and numbers of eyedrops, and higher EPO level in aqueous humor is a risk factor for trabeculectomy failure. It can be a biomarker to estimate the severity of APAC and the success rate of surgery. The investigation of mechanism of EPO in APAC a may have potential clinical applications for the surgical treatment of APAC.

Transient Alteration of Retinal Microvasculature after Refractive Surgery.

PURPOSE: The purpose of this study was to determine the retinal microvasculature in myopic patients after refractive surgery. METHODS: Thirty-six right eyes of 36 patients who undertook femtosecond laser-assisted laser in situ keratomileusis (FS-LASIK) were imaged using optical coherence tomography angiography preoperatively, 1-week, 1-month, and 3-month postoperation, respectively. Vessel density was analyzed after the correction of magnification, and results were correlated with clinical manifestations, including spherical equivalent (SE), amplitude of accommodation, intraocular pressure, and axial length. RESULTS: There was a significant decrease in microvascular density 1-week postoperation compared to preoperative measurement (p < 0.05), and it recovered 1-month postoperation. Microvascular densities in superficial vascular plexus (r = 0.528, p < 0.01), deep vascular plexus (r = 0.500, p < 0.01), and retinal vascular network (r = 0.390, p < 0.05) were all positively correlated with the decrease of the SE 1-week postoperation. CONCLUSION: The transient alteration of the retinal microvasculature after refractive surgery appeared to recover quickly, which may not impact the visual function after FS-LASIK.

Alternative Flicker Glass: A New Anti-Suppression Approach to the Treatment of Anisometropic Amblyopia.

INTRODUCTION: Amblyopia always presents with monocular and binocular dysfunction. In this study, we aim to investigate the efficacy of alternative occlusion using liquid crystal glasses versus continuous occlusion therapy using traditional patches for treating amblyopia. METHODS: Eligible subjects with anisometropic amblyopia were randomized into 2 groups: alternative flicker glass (AFG) or patching group. In the AFG group, subjects were instructed to wear the flicker glasses for 1 h a day. The AFG is a lightweight spectacle frame with liquid crystal lenses that provide direct square-wave alternating occlusion, which were preprogrammed at a temporal frequency of 7 Hz. In the patching group, the patients were prescribed to wear traditional patches for 2 h a day. The best-corrected visual acuity (BCVA), contrast sensitivity function (CSF), and stereoacuity were measured at the baseline and 3 and 12 weeks. RESULTS: In this pilot study, a total of 40 children were recruited, with 20 in the AFG group. Mean BCVA improved by 0.17 ± 0.14 logMAR (95% CI = 0.10-0.23) in the AFG group and 0.18 ± 0.18 logMAR (95% CI = 0.09-0.26) in the patching group from baseline to 12 weeks. The improvement in BCVA in both groups was significant (both p < 0.01), while there was no significant difference between the groups (p = 0.82). The CSF of both low and high spatial frequencies exhibited significant improvement at 12 weeks in the AFG group (p < 0.01, respectively) and just had a significant improvement at low spatial frequency in the patching group (p < 0.01). The stereoacuity significantly improved by 504.00 ± 848.00 (95% CI = 107.12 to 900.88) arc seconds in the AFG group (p < 0.05), while it was 263.50 ± 639.55 (95% CI = -35.82 to 562.82) arc seconds in the patching group (p > 0.05). CONCLUSION: Alternative flicker glass was effective in improving both monocular and binocular function, which was most likely achieved by reducing suppression and promoting binocular fusion. This therapy exhibited promise as an alternative method for amblyopia treatment.

Substance P inhibits high urea-induced apoptosis through the AKT/GSK-3ß pathway in human corneal epithelial cells.

To investigate the effect of substance P (SP) on human corneal epithelial cells (HCECs) that have been stressed by a high urea environment and to determine the relationship between SP and the protein kinase B (AKT)/glycogen synthase kinase-3ß (GSK-3ß) signaling pathway. An in vitro model of chronic renal failure (CRF)-related dry eye was used to study HCECs that were treated with high urea concentrations. Cell proliferation was assayed using a cell counting kit-8 test. Besides, cell apoptosis was evaluated by flow cytometry. Furthermore, the effects of SP and the AKT inhibitor perifosine on the urea-treated HCECs were examined using immunofluorescence, quantitative real time polymerase chain reaction (qRT-PCR), and Western blot analysis. SP markedly reduced the number of apoptotic HCECs and decreased the cleaved caspase-3 expression levels while contributing to increased cellular proliferation (P < 0.05). The Western blot analysis and qRT-PCR experiments revealed that SP significantly increased the expression of p-AKT and p-GSK-3ß (P < 0.05); additionally, these increases were attenuated after the perifosine inhibition of the AKT signaling pathway (P < 0.05). These in vitro experiments demonstrated that SP may protect against the apoptotic damage of HCECs caused by the high urea condition. The underlying mechanism may be related to the activation of the AKT/GSK-3ß signaling pathway.

LY2109761, Transforming Growth Factor ß Receptor Type I and Type II Dual Inhibitor, is a Novel Approach to Suppress Endothelial Mesenchymal Transformation in Human Corneal Endothelial Cells.

BACKGROUND/AIMS: Preventing undesirable endothelial-mesenchymal transformation (EnMT) with repetitious in vitro expansion of human corneal endothelial cells (CECs) is a pivotal issue in cornea regeneration. Previous studies have shown that inhibition of the TGF-ß pathway reduces epithelial-mesenchymal transformation. However, its potential role in EnMT remains poorly understood. As such, the effect of LY2109761, a novel TGF-ß receptor type I and type II dual inhibitor, was investigated on EnMT. METHODS: CECs cultured with various concentrations of LY2109761 were evaluated for their growth rate and phenotype. Additionally, the expression of functional markers (sodium-potassium pump Na+/K+-ATPase and the tight junction protein ZO-1) and mesenchymal markers (CD73, fibronectin, and vimentin) was detected using immunostaining and western blot. The mRNA expressions were also assayed by real-time polymerase chain reaction analysis. RESULTS: At a 1 µM concentration, LY2109761 did not influence the proliferation of CECs and subsequent experiments were therefore performed using this concentration. Furthermore, CECs cultured in the presence of 1 µM LY2109761 maintained their ability to grow as a monolayer of hexagonal-shaped cells. The expression of functional markers increased in LY2109761-treated CECs, while the expression of mesenchymal markers decreased (both in protein and mRNA levels). CONCLUSION: Inhibition of TGF-ß receptor type I and type II by LY2109761 maintained the phenotype of CECs and inhibited the EnMT process. These results indicate the possible continuous in vitro expansion of CECs with normal function.

Slitlamp Photography and Videography With High Magnifications.

PURPOSE: To demonstrate the use of the slitlamp photography and videography with extremely high magnifications for visualizing structures of the anterior segment of the eye. METHODS: A Canon 60D digital camera with Movie Crop Function was adapted into a Nikon FS-2 slitlamp to capture still images and video clips of the structures of the anterior segment of the eye. Images obtained using the slitlamp were tested for spatial resolution. The cornea of human eyes was imaged with the slitlamp, and the structures were compared with the pictures captured using the ultra-high-resolution optical coherence tomography (UHR-OCT). The central thickness of the corneal epithelium and total cornea was obtained using the slitlamp, and the results were compared with the thickness obtained using UHR-OCT. RESULTS: High-quality ocular images and higher spatial resolutions were obtained using the slitlamp with extremely high magnifications and Movie Crop Function, rather than the traditional slitlamp. The structures and characteristics of the cornea, such as the normal epithelium, abnormal epithelium of corneal intraepithelial neoplasia, laser in situ keratomileusis interface, and contact lenses, were clearly visualized using this device. These features were confirmed by comparing the obtained images with those acquired using UHR-OCT. Moreover, the tear film debris on the ocular surface and the corneal nerve in the anterior corneal stroma were also visualized. The thicknesses of the corneal epithelium and total cornea were similar to that measured using UHR-OCT (P<0.05). CONCLUSIONS: We demonstrated that the slitlamp photography and videography with extremely high magnifications allow better visualization of the anterior segment structures of the eye, especially of the epithelium, when compared with the traditional slitlamp.

Prediction of Myopia Eye Axial Elongation With Orthokeratology Treatment via Dense I2I Based Corneal Topography Change Analysis.

While orthokeratology (OK) has shown effective to slow the progression of myopia, it remains unknown how spatially distributed structural stress/tension applying to different regions affects the change of corneal geometry, and consecutive the outcome of myopia control, at fine-grained detail. Acknowledging that the underlying working mechanism of OK lens is essentially mechanics induced refractive parameter reshaping, in this study, we develop a novel mechanics rule guided deep image-to-image learning framework, which densely predicts patient's corneal topography change according to treatment parameters (lens geometry, wearing time, physiological parameters, etc.), and consecutively predicts the influence on eye axial length change after OK treatment. Encapsulated in a U-shaped multi-resolution map-to-map architecture, the proposed model features two major components. First, geometric and wearing parameters of OK lens are spatially encoded with convolutions to form a multi-channel input volume/tensor for latent encodings of external stress/tension applied to different regions of cornea. Second, these external latent force maps are progressively down-sampled and injected into this multi-scale architecture for predicting the change of corneal topography map. At each feature learning layer, we formally derive a mathematic framework that simulates the physical process of corneal deformation induced by lens-to-cornea interaction and corneal internal tension, which is reformulated into parameter learnable cross-attention/self-attention modules in the context of transformer architecture. A total of 1854 eyes of myopia patients are included in the study and the results show that the proposed model precisely predicts corneal topography change with a high PSNR as 28.45dB, as well as a significant accuracy gain for axial elongation prediction (i.e., 0.0276 in MSE). It is also demonstrated that our method provides interpretable associations between various OK treatment parameters and the final control effect. Our project code package is available at https://github.com/Rongdingyi/PhyIntNet.

Change in three-dimensional choroidal vessel network after AR device assisted 1-hour visual task in 2D/3D mode in young healthy subjects.

PURPOSE: The purpose of the study was to investigate the changes of choroidal blood perfusion in different layers and quadrants and its possible related factors after 1 h visual task by augmented reality (AR) device in two-dimensional (2D) and three-dimensional (3D) mode, respectively. METHODS: Thirty healthy subjects aged 22-37 years watched the same video source in 2D and 3D mode separately using AR glasses for 1 h with a one-week interval. Swept-source optical coherence tomography angiography (SS-OCTA) was performed before and immediately after watching to acquire choroidal thickness (ChT), three-dimensional choroidal vascularity index (CVI) of large- and middle-sized choroidal vessels and choriocapillaris flow voids (FV%) at macular and peripapillary area. Near point of accommodation (NPA) and accommodative facility (AF) were examined to evaluate the accommodative ability. Pupil diameters by infrared-automated pupillometer under scotopic, mesopic and photopic condition were also obtained. RESULTS: Compared with pre-visual task, the subfoveal CVI decreased from 0.406 ± 0.097 to 0.360 ± 0.102 after 2D watching (p < 0.001) and to 0.368 ± 0.102 after 3D watching (p = 0.002). Pupil sizes under different illuminance conditions became smaller after both 2D and 3D watching (all p < 0.001). AF increased after both 2D and 3D watching (both p < 0.05). NPA receded in post-3D watching (p = 0.017) while a not significant tendency was observed in post-2D. CONCLUSION: A reduction in subfoveal choroidal blood flow accompanied with pupil constriction was observed immediately after 1 h visual task using AR glasses in 2D and 3D mode. Accommodative facility improved after 2D and 3D watching with AR glasses, whereas decrease in the maximum accommodation power was only found in 3D mode.

Assessment of OCT-Based Macular Curvature and Its Relationship with Macular Microvasculature in Children with Anisomyopia.

INTRODUCTION: To evaluate the intraocular differences in optical coherence tomography (OCT)-based macular curvature index (MCI) among children with anisomyopia and to investigate the relationship between MCI and the macular microvasculature. METHODS: Fifty-two schoolchildren with anisometropia > 2.00 D were enrolled and underwent comprehensive examinations including cycloplegic refraction, axial length (AL), and swept source OCT/OCT angiography. OCT-based MCIs were determined from horizontal and vertical B-scans by a customized curve fitting model in MATLAB R2022 at 1-mm-, 3-mm-, and 6-mm-diameter circles at fovea. Characteristics and topographic variation of MCI was analyzed, and the relationships with microvascularity and its associated factors were investigated. RESULTS: MCI achieved high reliability and repeatability. There were overall larger MCIs in the more myopic eyes than the less myopic eyes in 1-mm-, 3-mm-, and 6-mm-diameter circles at fovea (all p < 0.001). For the topographic variation, horizontal MCI was significantly greater than vertical MCI (all p < 0.001), and was the largest in 6-mm circle, followed by 3-mm and 1-mm circles. Stronger correlation of horizontal MCI with myopic severity than vertical MCI was found. Partial Pearson's correlation found MCI was negatively associated with deep capillary plexus (DCP) vessel density (p = 0.016). Eyes with a higher MCI in a 6-mm circle were more likely to have longer AL (p < 0.001), lower DCP vessel density (p = 0.037), and thinner choroidal thickness (ChT) (p = 0.045). CONCLUSION: Larger MCI was found in the more myopic eyes of children with anisomyopia and was significantly associated with smaller DCP density, suggesting that MCI was an important indicator of myopia-related retinal microvascularity change, and it could be a valuable metric for myopia assessment in children.

MedMNIST v2 - A large-scale lightweight benchmark for 2D and 3D biomedical image classification.

We introduce MedMNIST v2, a large-scale MNIST-like dataset collection of standardized biomedical images, including 12 datasets for 2D and 6 datasets for 3D. All images are pre-processed into a small size of 28 × 28 (2D) or 28 × 28 × 28 (3D) with the corresponding classification labels so that no background knowledge is required for users. Covering primary data modalities in biomedical images, MedMNIST v2 is designed to perform classification on lightweight 2D and 3D images with various dataset scales (from 100 to 100,000) and diverse tasks (binary/multi-class, ordinal regression, and multi-label). The resulting dataset, consisting of 708,069 2D images and 9,998 3D images in total, could support numerous research/educational purposes in biomedical image analysis, computer vision, and machine learning. We benchmark several baseline methods on MedMNIST v2, including 2D/3D neural networks and open-source/commercial AutoML tools. The data and code are publicly available at https://medmnist.com/ .

The Impact of Corneal Epithelial Thickening and Inhomogeneity on Corneal Aberrations After Small Incision Lenticule Extraction.

PURPOSE: To investigate the corneal epithelial remodeling profile after small incision lenticule extraction (SMILE), the correlated explanatory variables, and its potential impact on corneal higher order aberrations (HOAs). METHODS: This single-center study prospectively evaluated 75 right eyes of 75 patients scheduled for SMILE. An anterior segment optical coherence tomography device was used to automatically obtain central 6-mm corneal epithelial thickness (ET), total corneal HOAs, and individual Zernike components before and after surgery. The ET inhomogeneity over the central 3- and 6-mm cornea was quantified with coefficient of variance (CV). RESULTS: Both ET and CV significantly increased 1 month postoperatively (all P < .05). The stepwise multiple regression analysis showed that ET and CV were significantly correlated with preoperative ET and CV, respectively (all P < .01). The corrected spherical equivalent also significantly influenced ET and CV (all P < .01). Over the central 6-mm zone, the alterations of total corneal HOAs and individual Zernike components such as vertical coma (Z7) and spherical aberration (Z12, Z24) were significantly correlated with ET and CV (all P < .05). CONCLUSIONS: The SMILE-induced epithelial remodeling involved both ET and ET inhomogeneity. The modulation was associated with preoperative and treatment parameters, and exerted a significant impact on corneal HOA alterations especially over the central 6-mm cornea. Together with the amount of correction and corneal curvature gradient change, preoperative assessment of ET and ET inhomogeneity might help predict postoperative epithelial remodeling. [J Refract Surg. 2023;39(1):23-32.].

Perfluorohexyloctane Eye Drops for Dry Eye Disease Associated With Meibomian Gland Dysfunction in Chinese Patients: A Randomized Clinical Trial.

Importance: Meibomian gland dysfunction (MGD) is a leading cause of evaporative dry eye disease (DED). Medical and surgical management for DED is limited; therefore, new treatment options are sought. Objective: To evaluate the efficacy and safety of SHR8058 (perfluorohexyloctane) eye drops in Chinese patients with DED associated with MGD through 57 days. Design, Setting, and Participants: This was a randomized, multicenter, double-masked, saline-controlled, phase 3 clinical trial conducted from February 4, 2021, to September 7, 2022. Patients were recruited from the departments of ophthalmology in 15 hospitals in China. Patients with DED associated with MGD were enrolled between February 4 and July 1, 2021. The diagnosis was based on patient complaint of DED symptoms, an ocular surface disease index of 25 or higher, tear film break-up time of 5 seconds or less, Schirmer I test without anesthesia results of 5 mm or more at 5 minutes, total corneal fluorescein staining (tCFS) score of 4 to 11, and an MGD score of 3 or higher. Interventions: Eligible participants were randomly assigned 1:1 to receive perfluorohexyloctane eye drops or 0.6% sodium chloride [NaCl]) 4 times per day. Main Outcomes and Measures: The primary end points were the changes from baseline in tCFS and eye dryness scores at day 57. Results: A total of 312 participants were included in the analysis: 156 (mean [SD] age, 45.4 [15.2] years; 118 female [75.6%]) in the perfluorohexyloctane group and 156 (mean [SD] age, 43.7 [15.1] years; 127 female [81.4%]) in the NaCl group. Both primary end points were achieved, ie, changes from baseline at day 57 of tCFS score (mean [SD], -3.8 [2.7] vs -2.7 [2.8]) and eye dryness score (mean [SD], -38.6 [21.9] vs -28.3 [20.8]) in the perfluorohexyloctane group were superior to the control group, with estimated mean differences of -1.14 (95% CI, -1.70 to -0.57; P < .001) and -12.74 (95% CI, -17.20 to -8.28, P < .001), respectively. Improvements on both end points appeared to be noted on day 29 and day 15, respectively, and maintained through day 57. Compared with the control, perfluorohexyloctane eye drops also alleviated symptoms including pain (mean [SD] tCFS score, 26.7 [23.7] vs -18.7 [22.5]; P = .003), awareness of DED symptoms (mean [SD] tCFS score, -38.1 [25.1] vs -23.7 [27.6]; P < .001), and frequency of dryness (mean [SD] tCFS score, -43.3 [23.8] vs -29.1 [24.8]; P < .001). Treatment-emergent adverse events occurred in 34 participants (21.8%) and 40 participants (25.6%) in the perfluorohexyloctane and control groups, respectively. Conclusions and Relevance: Results of this randomized clinical trial demonstrate that perfluorohexyloctane eye drops significantly ameliorated the signs and symptoms of DED associated with MGD with a rapid efficacy as well as satisfactory tolerability and safety through 57 days. Findings support the use of these eye drops if results can be confirmed independently and over longer time periods. Trial Registration: ClinicalTrials.gov Identifier: NCT05515471.

Three-Dimensional Choroidal Vascularity Index in High Myopia Using Swept-Source Optical Coherence Tomography.

PURPOSE: To characterize the choroidal vasculature in high myopic eyes by three-dimensional choroidal vascularity index (CVI) using swept-source optical coherence tomography (SS-OCT). SUBJECTS AND METHODS: A cross-sectional observational study of 98 right eyes from 98 consecutive nonpathological myopic patients, including 46 high myopes (HM) and 52 low to moderate myopes (LMM). OCT and OCT angiography covering an area of 6 × 6 mm2 centered on the fovea was conducted with a commercially available SS-OCT device. Three-dimensional CVI was defined as the ratio of choroidal vessel volume (CVV) to total choroidal volume. With the built-in automated quantification software, we assessed choroidal vascular and stromal features: three-dimensional CVI; CVV; choriocapillaris flow density and choroidal stroma volume (CSV) apart from choroidal thickness (CT). RESULTS: Compared to LMM, there was a significant reduction in three-dimensional CVI, CVV and CSV along with choroidal thinning in HM at both subfoveal and macular regions (all P < .01). The nasal quadrant had both the lowest CVI and the thinnest choroid. The greatest CVI was at the subfovea, while the choroid at the subfovea was thinner than that at the superior, temporal, and inferior quadrants. Multiple linear regression indicated that choroidal characteristics (CVI, CVV, CSV, CT) were mainly negatively correlated with axial length (all P < .01) instead of myopic spherical equivalent (all P > .05). CONCLUSIONS: Besides two-dimensional choroidal thinning, we also found the axial length-related reduction of three-dimensional choroidal vessel and stroma components in high myopic eyes without myopic maculopathy. The quadrantal distribution characteristics of three-dimensional CVI indicate the subfovea and the nasal quadrant to be the essential quadrants for monitoring the choroidal vasculature alteration in the progression of myopia. The novel quantitative analyses of the choroidal vasculature by three-dimensional CVI may help to characterize the underlying pathophysiology of nonpathological high myopia.

Combination Therapy of 0.1% Fluorometholone and 0.05% Azelastine in Eyes with Severe Allergic Conjunctival Diseases: A Randomized Controlled Trial.

This study sought to evaluate the efficacy of the isolated use of fluorometholone compared with the combined use of azelastine and fluorometholone for the treatment of severe allergic conjunctival disease (ACD). One hundred and eleven patients with severe ACD were randomized into two groups: one treated with topical 0.1% fluorometholone combined with 0.05% azelastine and the other with 0.1% fluorometholone alone. The Ocular Surface Disease Index (OSDI) and the signs of keratopathy, palpebral conjunctiva papillae and conjunctival congestion were scored before and at one, two and six weeks after treatment and compared between the groups. The intra-ocular pressure (IOP) was also monitored. There were no significant differences between the groups in the baseline mean scores of signs and OSDI scores, which gradually improved at all visits after therapy in both groups. Although the time effect was significant for all the parameters (all p < 0.001), the reduction in corneal involvement scores from week 2 to week 6 was insignificant in both groups (p = 0.460 for the steroids group and p = 0.074 for the combination group). All signs and symptoms were significantly more improved in the combination group than in the isolated group at each control visit. IOP remained stable at all visits (all p < 0.001), except one patient in each group had elevated IOP over 21 mmHg. While both the isolated use of fluorometholone and combined use of azelastine and fluorometholone are effective in alleviating the signs and symptoms of severe ACD, optimal response can be achieved with adjunctive treatment including azelastine.

Fibroblast growth factor 10 upregulates the expression of mucins in rat conjunctival epithelial cells.

PURPOSE: This in vitro study aimed to gain insight into the function of fibroblast growth factor 10 (FGF10) on the ocular surface, especially its effect on mRNA expression of the mucins Muc1, Muc4, and Muc5ac, and mucin protein synthesis. METHODS: We isolated primary cultured rat conjunctival epithelial cells (Cj-ECs) and treated them with FGF10 (1 ng/ml, 10 ng/ml, 100 ng/ml, and 200 ng/ml) and basic fibroblast growth factor 2 (FGF2; 10 ng/ml) for 24 h or 48 h. The proliferation of Cj-ECs was evaluated by 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium (MTS). mRNA levels of Muc1, Muc4, and Muc5ac were determined by real-time PCR. Synthesis levels of MUC1 and MUC4 were measured by western blot. Flow cytometry and Annexin V/PI double staining revealed degrees of apoptosis. RESULTS: In primary culture, the epithelial cells were compact and cobblestone pavement in shape. Most of the cells were positive for cytokeratin (CK). FGF10 and FGF2 significantly stimulated Muc1, Muc4, and Muc5ac mRNA expression, cell proliferation, and synthesis of MUC1 and MUC4 proteins. FGF10 was more potent than FGF2 in these regards. FGF10 did not restrain the apoptosis of Cj-ECs. CONCLUSIONS: The results of this study demonstrated that FGF10 is associated with the promotion of Cj-EC proliferation and mucin production. The effects of FGF10 on Cj-ECs support a rationale to investigate its therapeutic potential for ocular surface diseases.