Repeat corneal transplantation in Southern China: Indications, surgical technique, outcomes, and risk factors for repeat keratoplasty failure.

PURPOSE: To report the indications, surgical techniques, and outcomes of repeat keratoplasty and evaluate the risk factors for graft failure in the Chinese population. METHODS: The medical records of 216 patients (243 cases) who underwent at least two keratoplasties at a leading eye hospital in southern China between 2011 and 2020 were retrospectively reviewed. Indications and surgical procedures for repeat corneal transplantation were analyzed. Kaplan-Meier survival analysis was used to determine the graft survival rate after repeat keratoplasty. A multivariable survival model was used to assess the risk factors. RESULTS: Repeated keratoplasties increased continuously from 2011 to 2020 (P = 0.002). The most common primary indication was infectious keratitis (38.7%), and the most common reason for repeat keratoplasty was graft rejection (30.04%). Regraft techniques included penetrating keratoplasty (PK) in 165 cases (67.9%), deep lamellar keratoplasty (DALK) in 52 cases (21.40%), and endothelial keratoplasty (EK) in 26 cases (10.7%). Median survival was 5.3, 6.8, and 6.4 years for PK, DALK, and EK, respectively. The 5-year survival rate was 53.5%, 66.6%, and 69.8% for PK, DALK, and EK, respectively. The median LogMAR visual acuity was 1.4 for PK, 0.75 for DALK, and 1.2 for EK at the end of the follow-up. Multivariate analysis revealed that graft rejection is a risk factor for repeat keratoplasty failure (P = 0.002). CONCLUSIONS: DALK and EK may provide better outcomes than PK in treating graft failure. Preventing and treating postoperative graft rejection may be key to improving regraft survival. These findings will aid in the management of failed corneal grafts.

U-NTCA: nnUNet and nested transformer with channel attention for corneal cell segmentation.

Background: Automatic segmentation of corneal stromal cells can assist ophthalmologists to detect abnormal morphology in confocal microscopy images, thereby assessing the virus infection or conical mutation of corneas, and avoiding irreversible pathological damage. However, the corneal stromal cells often suffer from uneven illumination and disordered vascular occlusion, resulting in inaccurate segmentation. Methods: In response to these challenges, this study proposes a novel approach: a nnUNet and nested Transformer-based network integrated with dual high-order channel attention, named U-NTCA. Unlike nnUNet, this architecture allows for the recursive transmission of crucial contextual features and direct interaction of features across layers to improve the accuracy of cell recognition in low-quality regions. The proposed methodology involves multiple steps. Firstly, three underlying features with the same channel number are sent into an attention channel named gnConv to facilitate higher-order interaction of local context. Secondly, we leverage different layers in U-Net to integrate Transformer nested with gnConv, and concatenate multiple Transformers to transmit multi-scale features in a bottom-up manner. We encode the downsampling features, corresponding upsampling features, and low-level feature information transmitted from lower layers to model potential correlations between features of varying sizes and resolutions. These multi-scale features play a pivotal role in refining the position information and morphological details of the current layer through recursive transmission. Results: Experimental results on a clinical dataset including 136 images show that the proposed method achieves competitive performance with a Dice score of 82.72% and an AUC (Area Under Curve) of 90.92%, which are higher than the performance of nnUNet. Conclusion: The experimental results indicate that our model provides a cost-effective and high-precision segmentation solution for corneal stromal cells, particularly in challenging image scenarios.

Engineering Matrix-Free Drug Protein Nanoparticles with Promising Penetration through Biobarriers for Treating Corneal Neovascularization.

Protein drugs have been widely used in treating various clinical diseases because of their high specificity, fewer side effects, and favorable therapeutic effect, but they greatly suffer from their weak permeability through tissue barriers, high sensitivity to microenvironments, degradation by proteases, and rapid clearance by the immune system. Herein, we disrupted the standard protocol where protein drugs must be delivered as the cargo via a delivery system and innovatively developed a free entrapping matrix strategy by simply mixing bevacizumab (Beva) with zinc ions to generate Beva-NPs (Beva-Zn2+), where Beva is coordinatively cross-linked by zinc ions with a loading efficiency as high as 99.2% ± 0.41%. This strategy was universal to generating various protein NPs, with different metal ions (Cu2+, Fe3+, Mg2+, Sr2+). The synthetic conditions of Beva-NPs were optimized, and the generated mechanism was investigated in detail. The entrapment, releasing profile, and the bioactivities of released Beva were thoroughly studied. By using in situ doping of the fourth-generation polyamindoamine dendrimer (G4), the Beva-G4-NPs exhibited extended ocular retention and penetration through biobarriers in the anterior segment through transcellular and paracellular pathways, effectively inhibiting corneal neovascularization (CNV) from 91.6 ± 2.03% to 13.5 ± 1.87% in a rat model of CNV. This study contributes to engineering of protein NPs by using a facile strategy for overcoming the weaknesses of protein drugs and protein NPs, such as weak tissue barrier permeability, low encapsulation efficiency, poor loading capacity, and susceptibility to inactivation.

CorNet: Autonomous feature learning in raw Corvis ST data for keratoconus diagnosis via residual CNN approach.

PURPOSE: To ascertain whether the integration of raw Corvis ST data with an end-to-end CNN can enhance the diagnosis of keratoconus (KC). METHOD: The Corvis ST is a non-contact device for in vivo measurement of corneal biomechanics. The CorNet was trained and validated on a dataset consisting of 1786 Corvis ST raw data from 1112 normal eyes and 674 KC eyes. Each raw data consists of the anterior and posterior corneal surface elevation during air-puff induced dynamic deformation. The architecture of CorNet utilizes four ResNet-inspired convolutional structures that employ 1 × 1 convolution in identity mapping. Gradient-weighted Class Activation Mapping (Grad-CAM) was adopted to visualize the attention allocation to diagnostic areas. Discriminative performance was assessed using metrics including the AUC of ROC curve, sensitivity, specificity, precision, accuracy, and F1 score. RESULTS: CorNet demonstrated outstanding performance in distinguishing KC from normal eyes, achieving an AUC of 0.971 (sensitivity: 92.49%, specificity: 91.54%) in the validation set, outperforming the best existing Corvis ST parameters, namely the Corvis Biomechanical Index (CBI) with an AUC of 0.947, and its updated version for Chinese populations (cCBI) with an AUC of 0.963. Though the ROC curve analysis showed no significant difference between CorNet and cCBI (p = 0.295), it indicated a notable difference between CorNet and CBI (p = 0.011). The Grad-CAM visualizations highlighted the significance of corneal deformation data during the loading phase rather than the unloading phase for KC diagnosis. CONCLUSION: This study proposed an end-to-end CNN approach utilizing raw biomechanical data by Corvis ST for KC detection, showing effectiveness comparable to or surpassing existing parameters provided by Corvis ST. The CorNet, autonomously learning comprehensive temporal and spatial features, demonstrated a promising performance for advancing KC diagnosis in ophthalmology.

Comparison of deep learning-assisted blinking analysis system and Lipiview interferometer in dry eye patients: a cross-sectional study.

BACKGROUND: Abnormal blinking pattern is associated with ocular surface diseases. However, blink is difficult to analyze due to the rapid movement of eyelids. Deep learning machine (DLM) has been proposed as an optional tool for blinking analysis, but its clinical practicability still needs to be proven. Therefore, the study aims to compare the DLM-assisted Keratograph 5M (K5M) as a novel method with the currently available Lipiview in the clinic and assess whether blinking parameters can be applied in the diagnosis of dry eye disease (DED). METHODS: Thirty-five DED participants and 35 normal subjects were recruited in this cross-sectional study. DED questionnaire and ocular surface signs were evaluated. Blinking parameters including number of blinks, number of incomplete blinking (IB), and IB rate were collected from the blinking videos recorded by the K5M and Lipiview. Blinking parameters were individually collected from the DLM analyzed K5M videos and Lipiview generated results. The agreement and consistency of blinking parameters were compared between the two devices. The association of blinking parameters to DED symptoms and signs were evaluated via heatmap. RESULTS: In total, 140 eyes of 70 participants were included in this study. Lipiview presented a higher number of IB and IB rate than those from DLM-assisted K5M (P ≤ 0.006). DLM-assisted K5M captured significant differences in number of blinks, number of IB and IB rate between DED and normal subjects (P ≤ 0.035). In all three parameters, DLM-assisted K5M also showed a better consistency in repeated measurements than Lipiview with higher intraclass correlation coefficients (number of blinks: 0.841 versus 0.665; number of IB: 0.750 versus 0.564; IB rate: 0.633 versus 0.589). More correlations between blinking parameters and DED symptoms and signs were found by DLM-assisted K5M. Moreover, the receiver operating characteristic analysis showed the number of IB from K5M exhibiting the highest area under curve of 0.773. CONCLUSIONS: DLM-assisted K5M is a useful tool to analyze blinking videos and detect abnormal blinking patterns, especially in distinguishing DED patients from normal subjects. Large sample investigations are therefore warranted to assess its clinical utility before implementation.

Trends in Health Service Use for Dry Eye Disease From 2017 to 2021: A Real-World Analysis of 369,755 Outpatient Visits.

Purpose: We aimed to analyze the trends and patterns in outpatient health service treatment of dry eye disease (DED) using real-world data from Yinzhou District in China. Methods: The Yinzhou Health Information System is a comprehensive database including electronic medical records from 277 medical institutions representing over 1.64 million residents. We extracted outpatient records from January 1, 2017, to December 31, 2021, that included the first diagnosis of DED according to the International Classification of Diseases, 10th Revision (H04.101, H04.103, H11.104, H16.202, or H18.803). We analyzed the trends and patterns of DED outpatient visits using the Mann-Kendall trend test and Cochran-Armitage trend test. Results: We identified a total of 369,755 outpatient visits from 145,712 patients with DED of all ages (60.37% female; 54.10% 50 years or older). Primary medical institutions had the largest number of DED outpatient visits (42%), followed by tertiary medical institutions (35%). Over the 5-year period, the number of DED outpatient visits increased from 59,260 to 90,807 (53.23%). We observed significant consecutive annual proportion increases in females (from 61.09% to 62.01%; P = 0.001), patients 50 years or older (from 55.10% to 60.08%; P < 0.001), and outpatient visits in primary medical institutions (from 33.19% to 48.75%; P < 0.001). Conclusions: Our study found an increase in outpatient health service use for DED in Yinzhou from 2017 to 2021, with higher proportions and increases among females, patients 50 years or older, and primary medical institutions. Translational Relevance: The rapid growth in the prevalence of DED indicates high eye healthcare needs in patients.

Road dust exposure and human corneal damage in a plateau high geological background provincial capital city: Spatial distribution, sources, bioaccessibility, and cytotoxicity of dust heavy metals.

Ocular surface diseases are common in the plateau city, Kunming China, the continued daily exposure to heavy metals in dust may be an important inducement. In this study, the 150 road dust samples from five functional areas in Kunming were collected. The concentrations, distribution, possible sources, and bioaccessibility of heavy metals were analyzed. The adverse effects of dust extracts on human corneal epithelial cells and the underlying mechanisms were also assessed. The concentrations (mg·kg-1) of As (19.1), Cd (2.67), Cr (90.5), Cu (123), Pb (78.4), and Zn (389) in road dust were higher than the soil background, with commercial and residential areas showing the highest pollution. Their bioaccessibility in artificial tears was As (6.59 %) > Cu (5.11 %) > Ni (1.47 %) > Cr (1.17 %) > Mn (0.84 %) > Cd (0.76 %) > Zn (0.50 %) > Pb (0.31 %). The two main sources of heavy metals included tire and mechanical abrasion (24.5 %) and traffic exhaust (21.6 %). All dust extracts induced cytotoxicity, evidenced by stronger inhibition of cell viability, higher production of ROS, and altered mRNA expression of antioxidant enzymes and cell cycle-related genes, with commercial- areas-2 (CA2)-dust extract showing the greatest oxidative damage and cell cycle arrest. Our data may provide new evidence that dust exposure in high geological background cities could trigger human cornea damage.

Single-cell landscape reveals the epithelial cell-centric pro-inflammatory immune microenvironment in dry eye development.

Dry eye disease (DED) is a prevalent chronic eye disease characterized by an aberrant inflammatory response in ocular surface mucosa. The immunological alterations underlying DED remain largely unknown. In this study, we employed single-cell transcriptome sequencing of conjunctival tissue from environment-induced DED mice to investigate multicellular ecosystem and functional changes at different DED stages. Our results revealed an epithelial subtype with fibroblastic characteristics and pro-inflammatory effects emerging in the acute phase of DED. We also found that T helper (Th)1, Th17, and regulatory T cells (Treg) were the dominant clusters of differentiation (CD)4+ T-cell types involved in regulating immune responses and identified three distinct macrophage subtypes, with the CD72+CD11c+ subtype enhancing chronic inflammation. Furthermore, bulk transcriptome analysis of video display terminal-induced DED consistently suggested the presence of the pro-inflammatory epithelial subtype in human conjunctiva. Our findings have uncovered a DED-associated pro-inflammatory microenvironment in the conjunctiva, centered around epithelial cells, involving interactions with macrophages and CD4+ T cells, which deepens our understanding of ocular surface mucosal immune responses during DED progression.

Deep learning for detecting visually impaired cataracts using fundus images.

Purpose: To develop a visual function-based deep learning system (DLS) using fundus images to screen for visually impaired cataracts. Materials and methods: A total of 8,395 fundus images (5,245 subjects) with corresponding visual function parameters collected from three clinical centers were used to develop and evaluate a DLS for classifying non-cataracts, mild cataracts, and visually impaired cataracts. Three deep learning algorithms (DenseNet121, Inception V3, and ResNet50) were leveraged to train models to obtain the best one for the system. The performance of the system was evaluated using the area under the receiver operating characteristic curve (AUC), sensitivity, and specificity. Results: The AUC of the best algorithm (DenseNet121) on the internal test dataset and the two external test datasets were 0.998 (95% CI, 0.996-0.999) to 0.999 (95% CI, 0.998-1.000),0.938 (95% CI, 0.924-0.951) to 0.966 (95% CI, 0.946-0.983) and 0.937 (95% CI, 0.918-0.953) to 0.977 (95% CI, 0.962-0.989), respectively. In the comparison between the system and cataract specialists, better performance was observed in the system for detecting visually impaired cataracts (p < 0.05). Conclusion: Our study shows the potential of a function-focused screening tool to identify visually impaired cataracts from fundus images, enabling timely patient referral to tertiary eye hospitals.

Impacts of gender and age on meibomian gland in aged people using artificial intelligence.

Purpose: To evaluate the effects of age and gender on meibomian gland (MG) parameters and the associations among MG parameters in aged people using a deep-learning based artificial intelligence (AI). Methods: A total of 119 subjects aged ≥60 were enrolled. Subjects completed an ocular surface disease index (OSDI) questionnaire, received ocular surface examinations including Meibography images captured by Keratograph 5M, diagnosis of meibomian gland dysfunction (MGD) and assessment of lid margin and meibum. Images were analyzed using an AI system to evaluate the MG area, density, number, height, width and tortuosity. Results: The mean age of the subjects was 71.61 ± 7.36 years. The prevalence of severe MGD and meibomian gland loss (MGL) increased with age, as well as the lid margin abnormities. Gender differences of MG morphological parameters were most significant in subjects less than 70 years old. The MG morphological parameters detected by AI system had strong relationship with the traditional manual evaluation of MGL and lid margin parameters. Lid margin abnormities were significantly correlated with MG height and MGL. OSDI was related to MGL, MG area, MG height, plugging and lipid extrusion test (LET). Male subjects, especially the ones who smoke or drink, had severe lid margin abnormities, and significantly decreased MG number, height, and area than the females. Conclusion: The AI system is a reliable and high-efficient method for evaluating MG morphology and function. MG morphological abnormities developed with age and were worse in the aging males, and smoking and drinking were risk factors.

Causal effects of serum lipid biomarkers on early age-related macular degeneration using Mendelian randomization.

BACKGROUND: Age-related macular degeneration (AMD) is one of the major causes of vision loss. Early AMD needs to be taken seriously, but the causal effects of lipid biomarkers on early AMD remain unclear. METHODS: In this study, two-sample Mendelian randomization (MR) analysis was performed to systematically assess the causal relationships between seven serum lipid biomarkers (apolipoprotein A (ApoA), apolipoprotein B (ApoB), total cholesterol (CHOL), high-density lipoprotein cholesterol (HDL-C), direct low-density lipoprotein cholesterol (LDL-C), lipoprotein A [Lp(a)], and triglycerides (TG)) and risk of early AMD. In total, 14,034 cases and 91,214 controls of European ancestry were included in the analysis (number of SNPs = 11,304,110). RESULTS: MR estimates revealed that a higher HDL-C level is strongly associated with increased risk of early AMD (OR = 1.25, 95% CI: 1.15-1.35, P = 2.61 × 10-8). In addition, level of ApoA is also positively associated with risk of early AMD (OR = 2.04, 95% CI: 1.50-2.77, P = 6.27 × 10-6). Conversely, higher levels of TG significantly decrease the risk of early AMD (OR = 0.77, 95% CI: 0.71-0.84, P = 5.02 × 10-10). Sensitivity analyses further supported these associations. Moreover, multivariable MR analyses, adjusted for the effects of correlated lipid biomarkers, yielded similar results. CONCLUSION: This study identifies causal relationships between elevated circulating HDL-C/ApoA levels and increased risk of early AMD, in addition to finding that TG specifically reduces the risk of early AMD. These findings contribute to a better understanding of the role of lipid metabolism in drusen formation, particularly in early AMD development.

Effects of TCPP and TCEP exposure on human corneal epithelial cells: Oxidative damage, cell cycle arrest, and pyroptosis.

Tris(2-chloroisopropyl) phosphate (TCPP) and Tris(2-chloroethyl) phosphate (TCEP) are the widely used organophosphorus flame retardants indoors and easily accessible to the eyes as the common adhesive components of dust and particle matter, however, hardly any evidence has demonstrated their corneal toxicity. In this study, the adverse effects of TCPP, TCEP, and TCPP + TCEP exposure on human corneal epithelial cells (HCECs) were investigated. The cell viability and morphology, intracellular reactive oxygen species (ROS), cell cycle, and the expressions of cell cycle and pyroptosis-related genes were assessed to explain the underlying mechanisms. Compared to individual exposure, co-exposure to TCPP20+TCEP20 showed higher cytotoxicity with a sharp decrease of >30% in viability and more serious oxidative damage by increasing ROS production to 110.92% compared to the control group. Furthermore, the cell cycle arrested at the S phase (36.20%) was observed after combined treatment, evidenced by the upregulation of cyclin D1, CDK2, CDK4, CDK6, p21, and p27. Interestingly, pyroptosis-related genes GSDMD, Caspase-1, NLRP3, IL-1ß, IL-18, NLRP1, and NLRC4 expressions were promoted with cell swelling and glowing morphology. Oxidative stress and cell cycle arrest probably acted as a key role in TCPP20+TCEP20-induced cytotoxicity and pyroptosis in HCECs. Our results suggested that TCPP20+TCEP20 co-exposure induced severer corneal damage, further illustrating its significance in estimating indoor health hazards to humans.

Tunneling nanotubes-based intercellular mitochondrial trafficking as a novel therapeutic target in dry eye.

Cell-to-cell mitochondria transfer via tunneling nanotubes (TNTs) has recently been revealed as a spontaneous way to protect damaged cells. Previously, we have reported mesenchymal stem cells (MSCs) can rescue retinal ganglion cell and corneal epithelium through intercellular mitochondrial trafficking. Mitochondrial damage and oxidative stress in corneal epithelial cells are vital in dry eye disease (DED). However, whether intercellular mitochondrial transfer is involved in the pathological and repair process of DED is currently unknown. Therefore, in this study, we designed a coculture system to evaluate the role of intercellular mitochondrial transfer between human corneal epithelial cells (CEC) in DED. In addition, we successfully discovered the ROCK inhibitor, Y-27632 as an intensifier to improve the efficiency of intercellular mitochondrial transport. As expected, the enhanced mitochondrial transfer promotes the regeneration of CECs. Moreover, through further exploration of mechanisms, it was demonstrated that F-actin-mediated cell morphological changes and cytoskeletal remodeling may be potential mechanisms for Y-27632 to induce mitochondrial metastasis. In conclusion, we established a new method for cell repair in DED that healthy CEC offered mitochondria to damaged CEC, providing a new insight into the cellular mechanism of corneal epithelium homeostatic regenerative therapeutics in DED.

Epigenetic Activation of Circadian Clock Genes Elicits Inflammation in Experimental Murine Dry Eye.

PURPOSE: To explore whether circadian clock genes contribute to elicit inflammation in experimental dry eye (EDE). METHODS: RNA sequencing analyzed mRNA expression patterns in EDE model. RT-qPCR and/or Western blot determined the expression of inflammatory factors and circadian genes during EDE. MethylTarget™ assays determined the promoter methylation levels of Per genes in vivo. Per2 or Per3 knockdown assessed their effects on inflammatory factors in vitro. RESULTS: We utilized an intelligently controlled environmental system (ICES) to establish a mouse EDE model. The significant upregulated genes were enriched for circadian rhythms. Therein lied oscillatory and time-dependent upregulation of PER2 and PER3, as well as their promoter hypomethylation during EDE. Silencing PER2 or PER3 significantly decreased inflammatory factor expression and also reversed such increased inflammatory response in azacitidine (AZA) treatment in vitro model. CONCLUSIONS: Our findings suggest that DNA methylation mediated the upregulation of PER2 and PER3, leading to inflammatory response in EDE.

Elliptical deep anterior lamellar keratoplasty in severe Acanthamoeba keratitis.

Acanthamoeba keratitis (AK) is an intractable infection of the cornea. Penetrating keratoplasty is widely used for the management of severe AK but suffers from complications like graft rejection, endophthalmitis, and glaucoma. Herein, we aimed to describe the surgical technique and the results of elliptical deep anterior lamellar keratoplasty (eDALK) for the management of severe AK. In this retrospective case series, records of consecutive patients with AK poorly responsive to medical treatment who underwent eDALK from January 2012 to May 2020 were reviewed. The largest diameter of infiltration was ≥8 mm and did not involve the endothelium. The recipient bed was made by an elliptical trephine, and big bubble or wet-peeling technique was performed. Postoperative best spectacle-corrected visual acuity, endothelial cell density, corneal topographic data, and complications were evaluated. Thirteen eyes of thirteen patients (eight men and five women, 45.54 ± 11.78 years old) were included in this study. The mean follow-up interval was 21.31 ± 19.59 months (range, 12-82 months). At the last follow-up, the mean best spectacle-corrected visual acuity was 0.35 ± 0.27 logarithm of the minimum angle of resolution. The mean refractive and topographic astigmatism were - 3.21 ± 1.77 and 3.08 ± 1.14 D, respectively. Intraoperative perforation was encountered in one case and double anterior chambers occurred in two cases. One graft developed stromal rejection and one eye developed amoebic recurrence. eDALK can serve as the first-line surgical management of severe AK poorly responsive to medical treatment.

SIRT1 Inhibits High Glucose-Induced TXNIP/NLRP3 Inflammasome Activation and Cataract Formation.

Purpose: To determine whether SIRT1 regulates high glucose (HG)-induced inflammation and cataract formation through modulating TXNIP/NLRP3 inflammasome activation in human lens epithelial cells (HLECs) and rat lenses. Methods: HG stress from 25 to 150 mM was imposed on HLECs, with treatments using small interfering RNAs (siRNAs) targeting NLRP3, TXNIP, and SIRT1, as well as a lentiviral vector (LV) for SIRT1. Rat lenses were cultivated with HG media, with or without the addition of NLRP3 inhibitor MCC950 or SIRT1 agonist SRT1720. High mannitol groups were applied as the osmotic controls. Real-time PCR, Western blots, and immunofluorescent staining evaluated the mRNA and protein levels of SIRT1, TXNIP, NLRP3, ASC, and IL-1ß. Reactive oxygen species (ROS) generation, cell viability, and death were also assessed. Results: HG stress induced a decline in SIRT1 expression and caused TXNIP/NLRP3 inflammasome activation in a concentration-dependent manner in HLECs, which was not observed in the high mannitol-treated groups. Knocking down NLRP3 or TXNIP inhibited NLRP3 inflammasome-induced IL-1ß p17 secretion under HG stress. Transfections of si-SIRT1 and LV-SIRT1 exerted inverse effects on NLRP3 inflammasome activation, suggesting that SIRT1 acts as an upstream regulator of TXNIP/NLRP3 activity. HG stress induced lens opacity and cataract formation in cultivated rat lenses, which was prevented by MCC950 or SRT1720 treatment, with concomitant reductions in ROS production and TXNIP/NLRP3/IL-1ß expression levels. Conclusions: The TXNIP/NLRP3 inflammasome pathway promotes HG-induced inflammation and HLEC pyroptosis, which is negatively regulated by SIRT1. This suggests viable strategies for treating diabetic cataract.

Short-Term Outcomes of Modified Boston Type-II Keratoprosthesis Implantation With Autologous Auricular Cartilage Reinforcement.

PURPOSE: To report the short-term visual outcomes and complications of a modified Boston Type-II keratoprosthesis (Kpro) procedure. DESIGN: Retrospective case series. METHODS: Thirty-seven eyes of 37 patients who had an implantation of autologous auricular cartilage-reinforced (AACR) Boston Type-II Kpro (BK2) were included in the current study. Preoperative and postoperative data were recorded and analyzed for each eye. Main outcome measures included best-corrected visual acuity, symptoms as assessed by questionnaires, complications associated with implantation, and retention of the implanted BK2 device. RESULTS: A total of 37 eyes, consisting of 19 with severe autoimmune dry eye (ADE) and 18 with burn injury, completed ≥12 months of follow-up. The median (interquartile range) best-corrected visual acuity at baseline, 1 month, 3 months, 6 months, 1 year, and 2 years of follow-up was hand motion (HM) 20/60 (20/100-20/40), 20/60 (20/200-20/40), 20/60 (20/200-20/40), 20/100 (20/200-20/40), and 20/100 (20/400-20/40), respectively. All eyes retained the initial device (37/37, 100%). Common postoperative complications included retroprosthetic membrane (n = 21), de novo glaucoma (n = 7), endophthalmitis (n = 1), and conjunctival erosion (n = 4). No ear complications were discovered during follow-up assessments. The ocular surface disease index score improved from baseline to a 2-year follow-up (median 57.5 vs 21.43). CONCLUSION: The modified AACR-BK2 procedure could be considered to restore vision in patients with end-stage corneal blindness.

Entropy-Mediated High-Entropy MXenes Nanotherapeutics: NIR-II-Enhanced Intrinsic Oxidase Mimic Activity to Combat Methicillin-Resistant Staphylococcus Aureus Infection.

Bacterial infections, such as bacterial keratitis (BK) and subcutaneous abscess, pose significant challenges to global healthcare. Innovative and new antibacterial agents and antibacterial strategies are in demand to control infections in this era of high drug resistance. Nanotechnology is gradually emerging as an economically feasible and effective anti-infection treatment. High-entropy MXenes (HE MXenes) are used to confer desirable properties with exposed active sites to high-entropy atomic layers, whose potential application in the field of biomedicine remains to be explored. Herein, monolayer HE MXenes are fabricated by implementing transition metals with high entropy and low Gibbs free energy to fill the gap in the biocatalytic performance of non-high-entropy MXenes. HE MXenes are endowed with extremely strong oxidase mimic activity (Km = 0.227 mm) and photothermal conversion efficiency (65.8%) in the second near-infrared (NIR-II) biowindow as entropy increases. Subsequently, HE MXenes realize NIR-II-enhanced intrinsic oxidase mimic activity for killing methicillin-resistant Staphylococcus aureus and rapidly removing the biofilm. Furthermore, HE MXenes can effectively treat BK and subcutaneous abscess infection induced by methicillin-resistant Staphylococcus aureus as nanotherapeutic agents with minuscule side effects. Overall, monolayer HE MXenes demonstrate promising clinical application potential in the treatment of drug-resistant bacterial infections and promote the healing of infected tissues.

Clinical Outcomes of the Intraocular Lens Injector and Busin Glide for Descemet Stripping Automated Endothelial Keratoplasty in Patients with Iridocorneal Endothelial Syndrome.

Purpose: To report the outcomes of Descemet stripping automated endothelial keratoplasty (DSAEK) performed in iridocorneal endothelial (ICE) syndrome patients using the intraocular lens injector (injector), in comparison with those using the Busin glide. Methods: In this retrospective, interventional comparative study, we evaluated the outcomes of DSAEK performed using the injector (n = 12) or the Busin glide (n = 12) for patients with ICE syndrome. Their graft position and postoperative complications were recorded. Their best-corrected visual acuity (BCVA) and endothelial cell loss (ECL) were monitored over a 12-month follow-up period. Results: DSAEK was conducted successfully in the 24 cases. The BCVA improved from the preoperative 0.99 ± 0.61 to 0.36 ± 0.35 at 12 months after operation (p < 0.001), with no significant difference between the two groups (the injector group and the Busin group) (p = 0.933). ECL at 1 month after DSAEK was 21.80 ± 15.01% in the injector group, which was significantly lower than 33.69 ± 9.75% of the Busin group (p = 0.031). No surgery-related complications were observed in the 24 cases intraoperatively or postoperatively except that one case suffered from postoperative graft dislocation, without statistical difference between the two groups. Conclusions: At 1 month after surgery, the use of graft injector for delivering DSAEK-based endothelial graft may cause significantly less endothelial cell damage than the pull-through technique used in the application of Busin glide. The injector allows safe endothelial graft delivery without the need of anterior chamber irrigation, which increases the ratio of successful graft attachment.

Development and multi-center validation of machine learning model for early detection of fungal keratitis.

BACKGROUND: Fungal keratitis (FK) is a leading cause of corneal blindness in developing countries due to poor clinical recognition and laboratory identification. Here, we aimed to identify the distinct clinical signature of FK and develop a diagnostic model to differentiate FK from other types of infectious keratitis. METHODS: We reviewed the electronic health records (EHRs) of all patients with suspected infectious keratitis in Beijing Tongren Hospital from January 2011 to December 2021. Twelve clinical signs of slit-lamp images were assessed by Lasso regression analysis and collinear variables were excluded. Three models based on binary logistic regression, random forest classification, and decision tree classification were trained for FK diagnosis and employed for internal validation. Independent external validation of the models was performed in a cohort of 420 patients from seven different ophthalmic centers to evaluate the accuracy, specificity, and sensitivity in real world. FINDINGS: Three diagnostic models of FK based on binary logistic regression, random forest classification, and decision tree classification were established and internal validation were achieved with the mean AUC of 0.916, 0.920, and 0.859, respectively. The models were well-calibrated by external validation using a prospective cohort including 210 FK and 210 non-FK patients from seven eye centers across China. The diagnostic model with the binary logistic regression algorithm classified the external validation dataset with a sensitivity of 0.907 (0.774, 1.000), specificity 0.899 (0.750, 1.000), accuracy 0.905 (0.805, 1.000), and AUC 0.903 (0.808, 0.998). INTERPRETATION: Our model enables rapid identification of FK, which will help ophthalmologists to establish a preliminary diagnosis and to improve the diagnostic accuracy in clinic. FUNDING: The Open Research Fund from the National Key Research and Development Program of China (2021YFC2301000) and the Open Research Fund from Beijing Advanced Innovation Center for Big Data-Based Precision Medicine, Beijing Tongren Hospital, Beihang University &Capital Medical University (BHTR-KFJJ-202001) supported this study.