Circulating autoantibody profiling identifies LIMS1 as a potential target for pathogenic autoimmunity in pathologic myopia.

High myopia is a leading cause of blindness worldwide, among which pathologic myopia, characterized by typical myopic macular degeneration, is the most detrimental. However, its pathogenesis remains largely unknown. Here, using an HuProt array, we first initiated a serological autoantibody profiling of high myopia and identified 18 potential autoantibodies, of which anti-LIMS1 autoantibody was validated by a customized focused microarray. Further subgroup analysis revealed its actual relevance to pathologic myopia, rather than simple high myopia without myopic macular degeneration. Mechanistically, anti-LIMS1 autoantibody predominantly belonged to IgG1/IgG2/IgG3 subclasses. Serum IgG obtained from patients with pathologic myopia could disrupt the barrier function of retinal pigment epithelial cells via cytoskeleton disorganization and tight junction component reduction, and also trigger a pro-inflammatory mediator cascade in retinal pigment epithelial cells, which were all attenuated by depletion of anti-LIMS1 autoantibody. Together, these data uncover a previously unrecognized autoimmune etiology of myopic macular degeneration in pathologic myopia.

Outcomes of cataract surgery in eyes with axial length > 33 mm.

PURPOSE: To evaluate the visual outcomes and perioperative complications for cataract surgery in eyes with axial length (AL) > 33.0 mm. DESIGN: Prospective clinical cohort study. METHODS: One hundred and twenty-two eyes with moderate high myopia (26.0 mm ≤ AL<28.0 mm, control group), and 118 eyes with extreme high myopia (AL > 33.0 mm, EHM group) were followed up after cataract surgery (one week and one year post-op). Myopic maculopathy grading according to ATN system, best-corrected visual acuity (BCVA), and complications were compared. RESULTS: Postoperatively, BCVA in the EHM group improved significantly at both visits (both P < 0.001), despite being worse than that of the control group (both P < 0.05). The EHM group exhibited greater hyperopic refractive errors (P < 0.001), which were found to be associated with more severe T grade, longer AL, poorer second follow-up BCVA, and smaller anterior capsular opening (ACO) area. A higher incidence of retinal detachment and a more constricted ACO were observed in the EHM group (P = 0.030 and < 0.001, respectively), with the latter being significantly associated with longer AL and the absence of capsular tension ring (both P < 0.05). No difference in BCVA was found between the aphakic and pseudophakic eyes in the EHM group at both visits (both P > 0.05). CONCLUSION: Cataract surgery improves vision of eyes with AL > 33 mm, yet the increased risk of perioperative complications requires attention. Leaving these eyes aphakic might be effective and safe in the long term.

Fabrication of a 3D bioprinting model for posterior capsule opacification using GelMA and PLMA hydrogel-coated resin.

Posterior capsule opacification (PCO) remains the predominant complication following cataract surgery, significantly impairing visual function restoration. In this study, we developed a PCO model that closely mimics the anatomical structure of the crystalline lens capsule post-surgery. The model incorporated a threaded structure for accurate positioning and observation, allowing for opening and closing. Utilizing 3D printing technology, a stable external support system was created using resin material consisting of a rigid, hollow base and cover. To replicate the lens capsule structure, a thin hydrogel coating was applied to the resin scaffold. The biocompatibility and impact on cellular functionality of various hydrogel compositions were assessed through an array of staining techniques, including calcein-AM/PI staining, rhodamine staining, BODIPY-C11 staining and EdU staining in conjunction with transwell assays. Additionally, the PCO model was utilized to investigate the effects of eight drugs with anti-inflammatory and anti-proliferative properties, including 5-aminoimidazole-4-carboxamide ribonucleotide (AICAR), THZ1, sorbinil, 4-octyl itaconate (4-OI), xanthohumol, zebularine, rapamycin and caffeic acid phenethyl ester, on human lens epithelial cells (HLECs). Confocal microscopy facilitated comprehensive imaging of the PCO model. The results demonstrated that the GelMA 60 5% + PLMA 2% composite hydrogel exhibited superior biocompatibility and minimal lipid peroxidation levels among the tested hydrogels. Moreover, compared to using hydrogel as the material for 3D printing the entire model, applying surface hydrogel spin coating with parameters of 2000 rpm × 2 on the resin-based 3D printed base yielded a more uniform cell distribution and reduced apoptosis. Furthermore, rapamycin, 4-OI and AICAR demonstrated potent antiproliferative effects in the drug intervention study. Confocal microscopy imaging revealed a uniform distribution of HLECs along the anatomical structure of the crystalline lens capsule within the PCO model, showcasing robust cell viability and regular morphology. In conclusion, the PCO model provides a valuable experimental platform for studying PCO pathogenesis and exploring potential therapeutic interventions.

Transfer RNA derived fragment, tRF-Glu-CTC, aggravates the development of neovascular age-related macular degeneration.

Rationale: Angiogenesis expedites tissue impairment in many diseases, including age-related macular degeneration (AMD), a leading cause of irreversible blindness in elderly. A substantial proportion of neovascular AMD patients, characterized by aberrant choroidal neovascularization (CNV), exhibit poor responses or adverse reactions to anti-VEGF therapy. Herein, we aimed to unveil the function of newly identified transfer RNA-derived small RNA, tRF-Glu-CTC, in the pathology of CNV and determine its potential in inhibiting angiogenesis. Methods: Small non-coding RNA sequencing and quantitative polymerase chain reaction were conducted to detect expression pattern of tRF-Glu-CTC in CNV development. Immunofluorescence staining, fundus fluorescein angiography and ex vivo choroidal sprouting assays were employed for the evaluation of tRF-Glu-CTC's function in CNV development. The role of tRF-Glu-CTC in endothelial cells were determined by in vitro endothelial cell proliferation, migration and tube formation assays. Transcriptome sequencing, dual-luciferase reporter assay and in vitro experiments were conducted to investigate downstream mechanism of tRF-Glu-CTC mediated pathology. Results: tRF-Glu-CTC exhibited substantial up-regulation in AMD patients, laser-induced CNV model, and endothelial cells under hypoxia condition, which is a hallmark of CNV. Inhibiting tRF-Glu-CTC reduced angiogenesis and hypoxia stress in the neovascular region without neuroretina toxicity in laser-induced CNV model, showing an anti-angiogenic effect comparable to bevacizumab, while overexpression of tRF-Glu-CTC significantly augmented CNV. Mechanically, under hypoxia condition, angiogenin was involved in the production of tRF-Glu-CTC, which in turn triggered endothelial cell tubulogenesis, migration and promoted the secretion of inflammatory factors via the suppression of vasohibin 1 (VASH1). When downregulating VASH1 expression, the inhibition of tRF-Glu-CTC showed minimal suppression on angiogenesis. Conclusions: This study demonstrated the important role of tRF-Glu-CTC in the progression of angiogenesis. Targeting of tRF-Glu-CTC may be an alternative to current anti-VEGF therapy for CNV in AMD and other conditions with angiogenesis.

Influence of Lens Thickness on Accuracy of Kane, Hill-RBF 3.0, Barrett Universal II, Emmetropia Verifying Optical, and Pearl-DGS Formulas in Eyes with Nonhigh Myopia and High Myopia.

PURPOSE: To investigate the influence of lens thickness (LT) on accuracy of Kane, Hill-RBF 3.0 Barrett Universal II (BUII), Emmetropia Verifying Optical (EVO), and Pearl-DGS formulas in eyes with different axial lengths (AL). METHODS: The prospective cohort study was conducted at Eye and ENT Hospital of Fudan University. Patients who had uneventful cataract surgery between March 2021 and July 2023 were recruited. Manifest refraction was conducted two-month post-surgery. Eyes were divided into 4 groups based on AL: short (<22mm), medium (22-24.5 mm), medium long (24.5-26mm) and very long (≥26mm). In each AL group, eyes were then divided into 3 subgroups based on the LT measured with IOLmaster700: thin (<4.5 mm), medium (4.5-5.0 mm), and thick (≥ 5 mm). The influence of LT on accuracy of Kane, Hill-RBF 3.0, BUII, EVO, and Pearl-DGS formulas were investigated in each AL group. RESULTS: A total of 327 eyes from 327 patients were analyzed, with 64, 102, 73 and 88 eyes in each AL group, respectively. In eyes with AL < 24.5 mm, myopic PE was significantly associated with greater LT using all the 5 formulas (all p < 0.05). Backward stepwise multivariate regression analyses revealed that LT was an important influencing factor for PE in all 5 formulas, particularly in eyes with AL <24.5 mm. In eyes with AL <24.5 mm and LT > 5.0 mm, PE of all 5 formulas calculated with the optional parameter LT were more myopic than those calculated without LT. CONCLUSIONS: Thicker LT was associated with more myopic PE among eyes with AL <24.5 mm when using all 5 formulas. Further optimization of current formulas is necessary, especially for eyes with short AL and thick LT.

Associations of severe liver diseases with cataract using data from UK Biobank: a prospective cohort study.

Background: Liver disease is linked to series of extrahepatic multisystem manifestations. However, little is known about the associations between liver and eye diseases, especially cataract, the global leading cause of blindness. We aimed to investigate whether severe liver diseases, including non-alcoholic fatty liver disease (NAFLD), alcoholic liver disease (ALD), viral hepatitis, and liver fibrosis and cirrhosis, were associated with an increased risk of the cataract. Methods: A total of 326,558 participants without cataract at baseline enrolled in the UK Biobank between 2006 and 2010 were included in this prospective study. The exposures of interest were severe liver diseases (defined as hospital admission), including NAFLD, ALD, viral hepatitis and liver fibrosis and cirrhosis. The outcome was incident cataract. Cox proportional hazards models were used to estimate the hazard ratios (HRs) and 95% confidence intervals (CIs). Each liver disease was first treated as a binary time-varying variable to investigate its association with cataract, and then was treated as a ternary time-varying variable to examine the recent (liver disease within 0-5 years) vs. long-term (liver disease > 5 years) state associations with the risk of cataract. Findings: After a median follow-up of 13.3 years (interquartile range, 12.5-14.0 years), 37,064 individuals were documented as developing cataract. Higher risk of cataract was found in those with severe NAFLD (HR, 1.47; 95% CI, 1.33-1.61), ALD (HR, 1.57; 95% CI, 1.28-1.94) and liver fibrosis and cirrhosis (HR, 1.58; 95% CI, 1.35-1.85), but not in individuals with viral hepatitis when exposure was treated as a binary time-varying variable (P = 0.13). When treating exposure as a ternary time-varying variable, an association between recently diagnosed viral hepatitis and cataract was also observed (HR, 1.55; 95% CI, 1.07-2.23). Results from the combined model suggested they were independent risk factors for incident cataract. No substantial changes were found in further sensitivity analyses. Interpretation: Severe liver diseases, including NAFLD, ALD, liver fibrosis and cirrhosis and recently diagnosed viral hepatitis, were associated with cataract. The revelation of liver-eye connection suggests the importance of ophthalmic care in the management of liver disease, and the intervention precedence of patients with liver disease in the early screening and diagnosis of cataract. Funding: National Natural Science Foundation of China, Science and Technology Innovation Action Plan of Shanghai Science and Technology Commission, Clinical Research Plan of Shanghai Shenkang Hospital Development Center, Shanghai Municipal Key Clinical Specialty Program, the Guangdong Basic and Applied Basic Research Foundation and Shenzhen Science and Technology Program.

COMBINED APPLICATION OF B-SCAN ULTRASONOGRAPHY AND EYE-STEERING ULTRAWIDE FIELD IMAGING TO IMPROVE THE DETECTION OF RETINAL TEARS BEFORE CATARACT SURGERY.

PURPOSE: To investigate the efficacy of combined application of B-scan ultrasonography (US) and ultrawide field imaging (UWFI) in detecting retinal tears before cataract surgery. METHODS: Of 1,277 cataract patients, 2,552 eyes were enrolled and received both B-scan US and UWFI examinations preoperatively. Three types of combination were applied: type 1 (union, B-scan US or centered UWFI), type 2 (intersection, B-scan US and centered UWFI), and type 3 (B-scan US and eye-steering UWFI). Sensitivity and specificity of detecting retinal tears by different methods were assessed. RESULTS: Totally 4.55% (116/2,552) of eyes were presented with retinal tears. The sensitivity of B-scan US and UWFI was 87.93% and 84.48%, and specificity was 95.16% and 99.79%, respectively. By applying type 1 and type 2 combination, the sensitivity was 98.28% and 74.14%, and specificity was 95.03% and 99.92%, respectively. By type 3 combination, the sensitivity increased to 95.69% and specificity to 99.88%, both of which were comparable to indirect ophthalmoscopy regardless of the number, type, and location of tears ( P > 0.05). In eyes with any cataract type or axial length, type 3 combination also gained comparable performance to indirect ophthalmoscopy. CONCLUSION: Combined application of B-scan US and eye-steering UWFI presented satisfactory performance in detecting retinal tears before cataract surgery.

A framework for Frizzled-G protein coupling and implications to the PCP signaling pathways.

The ten Frizzled receptors (FZDs) are essential in Wnt signaling and play important roles in embryonic development and tumorigenesis. Among these, FZD6 is closely associated with lens development. Understanding FZD activation mechanism is key to unlock these emerging targets. Here we present the cryo-EM structures of FZD6 and FZD3 which are known to relay non-canonical planar cell polarity (PCP) signaling pathways as well as FZD1 in their G protein-coupled states and in the apo inactive states, respectively. Comparison of the three inactive/active pairs unveiled a shared activation framework among all ten FZDs. Mutagenesis along with imaging and functional analysis on the human lens epithelial tissues suggested potential crosstalk between the G-protein coupling of FZD6 and the PCP signaling pathways. Together, this study provides an integrated understanding of FZD structure and function, and lays the foundation for developing therapeutic modulators to activate or inhibit FZD signaling for a range of disorders including cancers and cataracts.

Challenges of refractive cataract surgery in the era of myopia epidemic: a mini-review.

Myopia is the leading cause of visual impairment in the world. With ever-increasing prevalence in these years, it creates an alarming global epidemic. In addition to the difficulty in seeing distant objects, myopia also increases the risk of cataract and advances its onset, greatly affecting the productivity of myopes of working age. Cataract management in myopic eyes, especially highly myopic eyes is originally more complicated than that in normal eyes, whereas the growing population of cataract with myopia, increasing popularity of corneal and lens based refractive surgery, and rising demand for spectacle independence after cataract surgery all further pose unprecedented challenges to ophthalmologists. Previous history of corneal refractive surgery and existence of implantable collamer lens will both affect the accuracy of biometry including measurement of corneal curvature and axial length before cataract surgery, which may result in larger intraocular lens (IOL) power prediction errors and a compromise in the surgical outcome especially in a refractive cataract surgery. A prudent choice of formula for cataract patients with different characteristics is essential in improving this condition. Besides, the characteristics of myopic eyes might affect the long-term stability of IOL, which is important for the maintenance of visual outcomes especially after the implantation of premium IOLs, thus a proper selection of IOL accordingly is crucial. In this mini-review, we provide an overview of the impact of myopia epidemic on treatment for cataract and to discuss new challenges that surgeons may encounter in the foreseeable future when planning refractive cataract surgery for myopic patients.

Single-cell RNA sequencing of retina revealed novel transcriptional landscape in high myopia and underlying cell-type-specific mechanisms.

High myopia is a leading cause of blindness worldwide with increasing prevalence. Retina percepts visual information and triggers myopia development, but the underlying etiology is not fully understood because of cellular heterogeneity. In this study, single-cell RNA sequencing analysis was performed on retinas of mouse highly myopic and control eyes to dissect the involvement of each cell type during high myopia progression. For highly myopic photoreceptors, Hk2 inhibition underlying metabolic remodeling from aerobic glycolysis toward oxidative phosphorylation and excessive oxidative stress was identified. Importantly, a novel Apoe + rod subpopulation was specifically identified in highly myopic retina. In retinal neurons of highly myopic eyes, neurodegeneration was generally discovered, and the imbalanced ON/OFF signaling driven by cone-bipolar cells and the downregulated dopamine receptors in amacrine cells were among the most predominant findings, indicating the aberrant light processing in highly myopic eyes. Besides, microglia exhibited elevated expression of cytokines and TGF-ß receptors, suggesting enhanced responses to inflammation and the growth-promoting states involved in high myopia progression. Furthermore, cell-cell communication network revealed attenuated neuronal interactions and increased glial/vascular interactions in highly myopic retinas. In conclusion, this study outlines the transcriptional landscape of highly myopic retina, providing novel insights into high myopia development and prevention.

CCL2-mediated inflammatory pathogenesis underlies high myopia-related anxiety.

High myopia is a leading cause of blindness worldwide. It may lead to emotional defects that rely closely on the link between visual sensation and the central nervous system. However, the extent of the defects and its underlying mechanism remain unknown. Here, we report that highly myopic patients exhibit greater anxiety, accompanied by higher CC chemokine ligand 2 (CCL2) and monocyte levels in the blood. Similar findings are found in the mouse model of high myopia. Mechanistic evaluations using GFP-positive bone marrow chimeric mice, parabiotic mouse model, enhanced magnetic resonance imaging, etc., show that highly myopic visual stimulation increases CCL2 expression in eyes, aggravates monocyte/macrophage infiltration into eyes and brains, and disrupts blood-ocular barrier and blood-brain barrier of mice. Conversely, Ccl2-deficient highly myopic mice exhibit attenuated ocular and brain infiltration of monocytes/macrophages, reduced disruption of the blood-ocular barrier and blood-brain barrier, and less anxiety. Substantial alleviation of high myopia-related anxiety can also be achieved with the administration of CCL2-neutralizing antibodies. Our results establish the association between high myopia and anxiety, and implicate the CCL2-mediated inflammatory pathogenesis as an underlying mechanism.

Tear inflammatory cytokines as potential biomarkers for myopic macular degeneration.

Previous studies have reported that inflammatory cytokine levels increase in the intraocular fluids (aqueous humor and vitreous) of highly myopic eyes, However, there has been currently no study revealing the levels of inflammatory cytokines in tear. Therefore, this study aimed to determine tear cytokine levels of highly myopic eyes, and their relationships with myopic macular degeneration (MMD). This case-control study screened inflammatory cytokines of tear samples from 132 highly myopic and 105 emmetropic eyes using a multiplex cytokine antibody array, and cytokines showing significant intergroup differences were further validated using ProQuantum immunoassays in tear samples from another 60 highly myopic and 60 emmetropic eyes. Ultra-widefield fundus photographs of eyes were classified according to the meta-analyses of the Pathologic Myopia Classification. Associations between tear cytokine levels and MMD category were investigated. As a result, tear levels of interleukin (IL)-6, IL-13 and monocyte chemoattractant protein (MCP)-1 were screened significantly higher in highly myopic eyes than in emmetropic controls (IL-6: 11.70 ± 16.81 versus 8.22 ± 10.76 pg/mL; MCP-1: 63.60 ± 54.40 versus 33.87 ± 43.82 pg/mL; both P < 0.05). Validation assays further demonstrated the elevated concentrations of IL-6 and MCP-1 (IL-6: 13.97 ± 8.41 versus 8.06 ± 7.94 pg/mL, P < 0.001; MCP-1: 32.69 ± 8.41 versus 18.07 ± 8.41 pg/mL, P = 0.003). Tear levels of IL-6 and MCP-1 differed significantly among MMD categories (both P < 0.05). The area under receiver operating characteristic curve were 0.783 and 0.682 respectively (both P < 0.05), when using tear IL-6 and MCP-1 levels to predict the presence of MMD (category ≥2). The ordered logistic regression model also indicated that longer axial length, and higher IL-6 and MCP-1 tear levels were independent predictors of higher MMD category. In our study, highly myopic eyes presented significantly higher levels of tear IL-6 and MCP-1, which may also serve as potential biomarkers for MMD.

A Genome-Wide Association Study for Susceptibility to Axial Length in Highly Myopic Eyes.

High myopia has long been highly prevalent worldwide with a largely yet unexplained genetic contribution. To identify novel susceptibility genes for axial length (AL) in highly myopic eyes, a genome-wide association study (GWAS) was performed using the genomic dataset of 350 deep whole-genome sequencing data from highly myopic patients. Top single nucleotide polymorphisms (SNPs) were functionally annotated. Immunofluorescence staining, quantitative polymerase chain reaction, and western blot were performed using neural retina of form-deprived myopic mice. Enrichment analyses were further performed. We identified the four top SNPs and found that ADAM Metallopeptidase With Thrombospondin Type 1 Motif 16 (ADAMTS16) and Phosphatidylinositol Glycan Anchor Biosynthesis Class Z (PIGZ) had the potential of clinical significance. Animal experiments confirmed that PIGZ expression could be observed and showed higher expression level in form-deprived mice, especially in the ganglion cell layer. The messenger RNA (mRNA) levels of both ADAMTS16 and PIGZ were significantly higher in the neural retina of form-deprived eyes (p = 0.005 and 0.007 respectively), and both proteins showed significantly upregulated expression in the neural retina of deprived eyes (p = 0.004 and 0.042, respectively). Enrichment analysis revealed a significant role of cellular adhesion and signal transduction in AL, and also several AL-related pathways including circadian entrainment and inflammatory mediator regulation of transient receptor potential channels were proposed. In conclusion, the current study identified four novel SNPs associated with AL in highly myopic eyes and confirmed that the expression of ADAMTS16 and PIGZ was significantly upregulated in neural retina of deprived eyes. Enrichment analyses provided novel insight into the etiology of high myopia and opened avenues for future research interest. Supplementary Information: The online version contains supplementary material available at 10.1007/s43657-022-00082-x.

Comparison of sutureless intrascleral fixation and sutured scleral fixation for the treatment of dislocated intraocular lenses.

BACKGROUND: To compare the outcomes of sutured transscleral fixation and sutureless intrascleral fixation for the treatment of a dislocated intraocular lens (IOL). METHODS: Thirty-five eyes of 35 patients who required IOL repositioning surgery due to IOL dislocation were included in this retrospective study. Sixteen eyes underwent two-point sutured transscleral fixation, eight eyes underwent one-point sutured transscleral fixation, and 11 eyes underwent sutureless intrascleral IOL fixation. The patients were followed for ≥ 12 months after repositioning surgery, and their postoperative outcomes were recorded and analyzed. RESULTS: The major cause of IOL dislocation was ocular blunt trauma (19/35, 54.3%). The mean corrected distance visual acuity (CDVA) improved significantly after IOL repositioning (P = 0.022). The mean postoperative change in endothelial cell density (ECD) was - 4.5%. There were no significant differences in the changes in CDVA or ECD among the three groups with different repositioning techniques (both P > 0.1). The mean vertical tilt of the IOLs in all enrolled patients was significantly greater than the horizontal value (P = 0.001). The vertical tilt was greater in the two-point scleral fixation group than that in the sutureless intrascleral fixation group (P = 0.048). The mean decentration values in the one-point scleral fixation group in the horizontal and vertical directions were greater than those in the other two groups (all P < 0.01). CONCLUSION: All three IOL repositioning techniques resulted in favorable ocular prognosis.

Role of Optic Nerve Head Characteristics in Predicting Intraocular Pressure Spikes after Cataract Surgery in Highly Myopic Eyes.

INTRODUCTION: To evaluate the characteristics of optic nerve head (ONH) in highly myopic eyes and its role in predicting intraocular pressure (IOP) spikes after cataract surgery. METHODS: Patients who are highly myopic and were scheduled for cataract surgery were enrolled in this prospective case series study. IOP was measured preoperatively and at 1 day and 3 days postoperatively. ONH characteristics including area, tilt ratio, lamina cribrosa (LC) thickness, and depth, and the presence of LC defects were evaluated with enhanced depth imaging optical coherence tomography. Factors influencing LC defects and early IOP spike were investigated using multivariate stepwise logistic regression. RESULTS: In total, 200 highly myopic eyes of 200 patients were analyzed: 35.00% had small ONH, 53.00% had ONH tilt, and 14.00% had LC defects. Multivariate analysis demonstrated female patients with larger ONH area and deeper LC tended to have LC defects (all P < 0.05). As to postoperative IOP, IOP change, and incidence of IOP spikes, eyes with small ONH, ONH tilt, and LC defects had similar (all P > 0.05), higher (all P < 0.05), and lower (all P < 0.05) outcomes compared with those without the corresponding characteristic, respectively. Multivariate analysis showed that presence of LC defects and thicker LC were protective factors for early IOP spikes, and axial length > 28 mm was a risk factor (all P < 0.05). CONCLUSION: Female patients with larger ONH area and deeper LC tend to have LC defects, which, together with thicker LC, was correlated with less IOP spikes in highly myopic eyes. TRIAL REGISTRATION: This study was conducted as part of a larger project, the Shanghai High Myopia Study, registered at www. CLINICALTRIALS: gov (accession number NCT03062085).

Preclinical biocompatibility and biosafety evaluation of a new foldable brown diaphragm intraocular lens: An in vitro and in vivo study.

BACKGROUND: A new foldable brown diaphragm intraocular lens (IOL) was preclinically evaluated in vitro and in vivo by comparing its biocompatibility and biosafety with those of a commercially available IOL. METHODS: The new foldable iris-diaphragm IOL is composed of hydrophobic acrylic material, with a transparent optical zone and surrounding brown diaphragm. Cellular experiments evaluating lens epithelial cell morphology, adhesion, and migration were conducted to exclude cytotoxic effects. Twelve New Zealand rabbits underwent implantation of a brown diaphragm IOL in one eye, whilst an additional 12 had a commercially available foldable IOL implanted, followed by slit-lamp evaluations of inflammatory reactions and capsular opacification. Corneal endothelial cells density was measured before and after implantation. Aqueous humour samples were obtained weekly for liquid chromatography-tandem mass spectrometry (LC-MS/MS) analysis to investigate dye leakage from the brown-diaphragm IOL. Following 12 weeks of observation, haematoxylin and eosin staining of ocular tissue and scanning electron microscopy (SEM) of the IOL surface were performed. RESULTS: Results from in vivo experiments found no statistically significant differences between the two groups in terms of postoperative inflammation and capsular biocompatibility. No significant changes in corneal endothelial cell density were observed in either group before and after surgery. LC-MS/MS analysis showed that the target dye was not detected in aqueous humour samples. Histopathology of ocular sections and SEM imaging of IOL surfaces showed similar changes in both groups. CONCLUSIONS: The newly invented IOL showed good biocompatibility and biosafety. Combined with its foldability and peripheral shading, it could be a new choice for patients with iris defects.

Long-Term Outcomes of Posterior Capsular Opacification in Highly Myopic Eyes and Its Influencing Factors.

INTRODUCTION: The purpose of this study was to evaluate the long-term outcomes of posterior capsular opacification (PCO) in highly myopic eyes and its influencing factors. METHODS: Patients undergoing phacoemulsification with intraocular lens implantation and followed up for 1-5 years were included in this prospective cohort study. The severity of PCO was evaluated using EPCO2000 software system, with the area of central 3.0 mm (PCO-3 mm) and within the capsulorhexis (PCO-C) both being analyzed. Percentage of eyes after Nd:YAG capsulotomy, as well as clinically significant PCO (defined as eyes with visual-impairing PCO or after capsulotomy), were also included as outcome variables. RESULTS: A total of 673 highly myopic eyes [axial length (AL) ≥ 26 mm] and 224 control eyes (AL < 26 mm) were analyzed. The mean follow-up time was 34.0 ± 9.0 months. PCO was more severe in highly myopic eyes compared with controls with regard to higher EPCO scores (P < 0.001 for both PCO-3 mm and PCO-C), higher capsulotomy rate (P = 0.001), higher clinically significant PCO rate (P < 0.001) and shorter PCO-free survival time (P < 0.001). Extreme myopia (AL ≥ 28 mm) would further aggravate PCO in terms of higher EPCO scores (PCO-3 mm: P = 0.017; PCO-C: P = 0.013) and higher clinically significant PCO rate (P = 0.024) compared with other myopic eyes. In highly myopic eyes, AL [odds ratio (OR) 1.124, P = 0.004] and follow-up duration (OR 1.082, P < 0.001) were independent risk factors for clinically significant PCO after cataract surgery. CONCLUSION: Highly myopic eyes had more severe PCO in the long term. Longer AL and follow-up duration were associated with higher risk of PCO. CLINICAL TRIAL REGISTRATION: The study was registered at ClinicalTrials.gov (NCT03062085).

The Zhu-Lu formula: a machine learning-based intraocular lens power calculation formula for highly myopic eyes.

BACKGROUND: To develop a novel machine learning-based intraocular lens (IOL) power calculation formula for highly myopic eyes. METHODS: A total of 1828 eyes (from 1828 highly myopic patients) undergoing cataract surgery in our hospital were used as the internal dataset, and 151 eyes from 151 highly myopic patients from two other hospitals were used as external test dataset. The Zhu-Lu formula was developed based on the eXtreme Gradient Boosting and the support vector regression algorithms. Its accuracy was compared in the internal and external test datasets with the Barrett Universal II (BUII), Emmetropia Verifying Optical (EVO) 2.0, Kane, Pearl-DGS and Radial Basis Function (RBF) 3.0 formulas. RESULTS: In the internal test dataset, the Zhu-Lu, RBF 3.0 and BUII ranked top three from low to high taking into account standard deviations (SDs) of prediction errors (PEs). The Zhu-Lu and RBF 3.0 showed significantly lower median absolute errors (MedAEs) than the other formulas (all P < 0.05). In the external test dataset, the Zhu-Lu, Kane and EVO 2.0 ranked top three from low to high considering SDs of PEs. The Zhu-Lu formula showed a comparable MedAE with BUII and EVO 2.0 but significantly lower than Kane, Pearl-DGS and RBF 3.0 (all P < 0.05). The Zhu-Lu formula ranked first regarding the percentages of eyes within ± 0.50 D of the PE in both test datasets (internal: 80.61%; external: 72.85%). In the axial length subgroup analysis, the PE of the Zhu-Lu stayed stably close to zero in all subgroups. CONCLUSIONS: The novel IOL power calculation formula for highly myopic eyes demonstrated improved and stable predictive accuracy compared with other artificial intelligence-based formulas.

Visual and patient-reported outcomes of a diffractive trifocal intraocular lens in highly myopic eyes: a prospective multicenter study.

BACKGROUND: To investigate the visual and patient-reported outcomes of a diffractive trifocal intraocular lens (IOL) in highly myopic eyes. METHODS: Patients with planned cataract removal by phacoemulsification and implantation of a trifocal IOL (AT LISA tri 839MP) were enrolled in the prospective, multicenter cohort study. Patients were allocated into three groups according to their axial length (AL): control group, AL < 26 mm; high myopia group, AL 26-28 mm; extreme myopia group, AL ≥ 28 mm. At 3 months post-surgery, data for 456 eyes of 456 patients were collected, including visual acuity, defocus curve, contrast sensitivity (CS), visual quality, spectacle independence, and overall satisfaction. RESULTS: After surgery, the uncorrected distance visual acuity improved from 0.59 ± 0.41 to 0.06 ± 0.12 logMAR (P < 0.001). In all three groups, about 60% of eyes achieved uncorrected near and intermediate visual acuity of 0.10 logMAR or better, but significantly fewer eyes in the extreme myopia group achieved uncorrected distance visual acuity of 0.10 logMAR or better (P < 0.05). Defocus curves revealed that the visual acuity was significantly worse in the extreme myopia group than others at 0.00, - 0.50, and - 2.00 diopters (P < 0.05). CS did not differ between the control and high myopia groups but was significantly lower in the extreme myopia group at 3 cycles per degree. The extreme myopia group also had greater higher-order aberrations and coma, lower modulation transfer functions and VF-14 scores, more glare and halos, worse spectacle independence at far distance, and consequently lower patient satisfaction than others (all P < 0.05). CONCLUSIONS: In eyes with a high degree of myopia (AL < 28 mm), trifocal IOLs have been shown to provide similar visual outcomes to those in non-myopic eyes. However, in extremely myopic eyes, acceptable results may be obtained with trifocal IOLs, but a reduced level of uncorrected distance vision is expected.

Correction of Asymmetric Bowtie Corneal Astigmatism with a Toric Intraocular Lens: Outcomes and Accuracy of Measurement Modes.

The outcomes of toric intraocular lens (IOL) implantation in correcting asymmetric bowtie corneal astigmatism remain uncertain. The accurate measurement of corneal astigmatism is essential for surgical planning. In this prospective cohort study, patients with asymmetric or symmetric bowtie corneal astigmatism who underwent toric IOL implantation were recruited. Preoperative corneal astigmatism was measured with an IOLMaster and Pentacam (including the simulated keratometry (SimK), total corneal refractive power (TCRP), and wavefront aberration (WFA) modes). At 3 months after surgery, the refractive outcomes and residual astigmatic refractive errors were compared with patients with symmetric bowtie astigmatism. The prediction errors (the differences between the calculated actual corneal astigmatism and the measured corneal astigmatism) were compared among the different measurement modes in the asymmetric group. There were no differences in residual astigmatism between the asymmetric and symmetric groups. However, the mean absolute residual astigmatic refractive error was greater in the asymmetric group than in the symmetric group (0.72 ± 0.42 D vs. 0.53 ± 0.24 D, p = 0.043). In the asymmetric group, the mean absolute prediction errors for the IOLMaster, SimK, TCRP and WFA modes were 0.53 ± 0.40, 0.56 ± 0.47, 0.68 ± 0.52, and 0.43 ± 0.40 D, respectively. The Pentacam WFA mode was the most accurate mode (p < 0.05). The absolute prediction error of the WFA mode was positively correlated with the total corneal irregular astigmatism higher-order aberrations and coma (r = 0.416 and r = 0.473, respectively; both p < 0.05). Our study suggests toric IOL implantation effectively corrected asymmetric bowtie corneal astigmatism. The Pentacam WFA mode may be the most accurate measurement mode, although its accuracy decreased as asymmetry increased.