QuestionIs manual marking-assisted capsulorhexis (MMAC) using a lens caliper (LC) noninferior to digital guidance-assisted capsulorhexis (DGAC) for the accuracy of capsulorhexis in phacoemulsification for age-related cataract?FindingsIn this noninferiority randomized clinical trial of 156 participants, MMAC was found to be noninferior to DGAC in terms of the accuracy of capsulorhexis, postoperative best-corrected visual acuity, and intraocular lens stability.MeaningThese findings support MMAC with an LC as a feasible auxiliary capsulorhexis technique, which does not require special equipment and is simple to operate and therefore might be appropriate if similar outcomes are obtained in other clinical practice settings. This randomized clinical trial evaluates the accuracy of manual marking-assisted capsulorhexis vs digital guidance-assisted capsulorhexis following phacoemulsification for age-related cataract. ImportanceAppropriately sized and well-centered capsulorhexis is key for high-quality phacoemulsification cataract surgery and can be achieved with digital-guidance devices. However, such devices are not readily available, warranting the need for a device-free manual auxiliary capsulorhexis technique.ObjectivesTo determine if manual marking-assisted capsulorhexis (MMAC) is noninferior to a digital guidance-assisted capsulorhexis (DGAC) in capsulorhexis accuracy following phacoemulsification for age-related cataract.Design, Setting, and ParticipantsThis noninferiority randomized clinical trial was conducted between July 2021 and December 2021 at Zhongshan Ophthalmic Center, China, with follow-up through 1 month after surgery. Of 204 adults screened, 156 were included who were aged 55 to 80 years and had pupil diameter >= 6.5 mm after pupil dilation and Lens Opacities Classification System III with nuclear opalescence grade of 3.0 to 4.0. Patients were excluded if they had previous intraocular surgery or a diagnosed eye disease that might affect functions of lens suspensory ligament. Data were analyzed from September to December 2024.InterventionsIn the MMAC group, a lens caliper was used to measure and locate capsulorhexis position, subsequently applying its blunt head to mark the anterior lens capsule for capsulotomy guidance. In the DGAC group, a ring with predefined target diameter was projected to guide capsulorhexis.Main Outcomes and MeasuresThe primary outcome was the median deviation of capsulorhexis diameter from the target diameter with a noninferiority margin of 0.2 mm. Secondary outcomes included ratio of ideal capsulorhexis, grades of capsulorhexis-intraocular lens (IOL) overlap, off-center distance of capsulorhexis, postoperative best-corrected visual acuity, IOL tilt, and decentration.ResultsAmong 156 participants randomized into the MMAC group (mean [SD] age, 71 [7] years; 47 [60%] female) or DGAC group (mean [SD] age, 72 [7]; 47 [60%] female), median deviations comparing the capsulorhexis and target diameters were 0.22 mm (95% CI, 0.11-0.37) in the MMAC group vs 0.27 mm (95% CI, 0.14-0.52) in the DGAC group (difference, -0.05 mm; 95% CI, -0.16 to 0.07) for horizontal diameter and 0.27 mm (95% CI, 0.12-0.40) vs 0.33 mm (95% CI, 0.20-0.51) (difference, -0.06 mm; 95% CI, -0.17 to 0.05), respectively, for vertical diameters, both within the noninferiority margin of 0.20 mm. The proportion of ideal capsulorhexis was 96.2% (75 of 78) in the MMAC group and 88.5% (69 of 78) in the DGAC group (difference, 7.7%; 95% CI, -0.6 to 16.0), also within the noninferiority margin of -5.0%.Conclusions and RelevanceThe findings in this trial indicate that accuracy of capsulorhexis with MMAC was noninferior to DGAC. Since the MMAC technique does not require special equipment, it might be considered routinely in clinical practice settings if similar outcomes are obtained elsewhere.Trial RegistrationClinicalTrials.gov Identifier: NCT04977115

OBJECTIVES:To investigate the impact of residual refraction within ±1.0 dioptre (D) on uncorrected distance visual acuity (UDVA) in pseudophakic eyes. DESIGN:Cross-sectional study. SETTING:This study was based on retrospectively collected electronic refraction records from a tertiary care academic ophthalmology centre in southern China between May 2022 and July 2025. PARTICIPANTS:Patients aged ≥40 years who underwent uneventful phacoemulsification cataract surgery with in-the-bag monofocal intraocular lens implantation and achieved a postoperative corrected distance visual acuity (CDVA) of ≤0.1 logarithm of the minimum angle of resolution were enrolled. They were stratified by astigmatism subtypes: minimal astigmatism (<0.50 D), with-the-rule (WTR) astigmatism, against-the-rule (ATR) astigmatism and oblique astigmatism. OUTCOMES MEASURES:Postoperative evaluation (≥1 month) included spherical equivalent (SE) refraction, UDVA and CDVA. UDVA was compared across eyes with SE intervals of 0.50 D within ±1.0 D. ORs were calculated to assess the relative risk of failing to achieve a UDVA of 0.1 or better for postoperative SE within ±1.0 D, using 0.00 D as the reference. RESULTS:The study included 1333 eyes from 1333 patients (mean (SD) age, 66.1 (8.96) years; 532 male (39.9%)). Overall, and particularly in the minimal astigmatism (<0.50 D), ATR astigmatism and oblique astigmatism subgroups, hyperopic eyes exhibited significantly better UDVA than their myopic counterparts. Slight myopia [-0.50 D, 0 D) significantly worsened UDVA versus 0 D in both the overall population and the minimal astigmatism subgroup. Slight hyperopia (0 D, +0.50 D] minimally affected UDVA, whereas an equivalent degree of myopia increased the odds of not achieving UDVA ≤0.1 by 1.55-fold (95% CI 1.08 to 2.21) overall and by 3.14-fold (95% CI 1.49 to 6.58) in the minimal astigmatism subgroup. Additionally, UDVA was optimal with minimal astigmatism and decreased progressively with each 0.50 D increment in residual astigmatism magnitude, a dose-dependent trend consistent across astigmatism subtypes. CONCLUSIONS:The impact of refractive errors (≤1.0 D) on UDVA was associated with the magnitude and type of astigmatism. Residual astigmatism of ≥0.50 D exerted a significant negative effect on UDVA. A plano SE (0 D) was optimal for minimum and WTR astigmatism, whereas slight hyperopia yielded superior UDVA in ATR and oblique astigmatism.

Purpose:To evaluate anisometropia at age 7 years after bilateral secondary intraocular lens (IOL) implantation in children with pediatric aphakia and to identify factors associated with long-term refractive symmetry. Design:A prospective observational cohort study. Participants:This study was conducted from 2014 to 2023 at a single center. Of 251 eligible children, 158 (316 eyes) who underwent lensectomy before age 2 and secondary IOL implantation between ages 2 and 6 were included. Methods:Participants were grouped by age at secondary IOL implantation: 2 to <3 years, 3 to <4 years, 4 to <5 years, and 5 to <6 years. Demographic and clinical data were collected, and refractive outcomes at postoperative 1 month and age 7 years were analyzed. All refractive outcomes were expressed as spherical equivalent (SE), calculated as the sphere plus half of the cylinder (SE = sphere + ½ cylinder). Main Outcome Measures:Interocular anisometropia at age 7 years, defined as the absolute interocular difference in SE. Results:At postoperative month 1, 77.2% of children had anisometropia <1.0 D. By age 7 years, this proportion decreased to 52.5%, and significant differences in anisometropia distribution were observed among age-at-implantation groups (P = 0.035). In multivariable analyses, earlier age at secondary IOL implantation (β = -0.260; 95% confidence interval [CI], -0.386 to -0.134; P < 0.001), greater interocular axial length difference at implantation (β = 0.330; 95% CI, 0.033-0.628; P = 0.030), and greater early postoperative anisometropia (β = 0.355; 95% CI, 0.079-0.631; P = 0.012) were independently associated with greater anisometropia at age 7 years. Conclusions:Interocular anisometropia tends to increase during childhood after bilateral secondary IOL implantation and is influenced by implantation timing, interocular axial length asymmetry, and early postoperative refractive status. Minimizing early postoperative anisometropia may be important for optimizing long-term refractive symmetry, and delayed secondary IOL implantation may be considered in children with marked interocular axial length asymmetry. Financial Disclosures:The authors have no proprietary or commercial interest in any materials discussed in this article.

Purpose To evaluate anisometropia at age 7 years following bilateral secondary intraocular lens (IOL) implantation in children with pediatric aphakia and to identify factors associated with long-term refractive symmetry. Design Prospective observational cohort study. Participants This study was conducted from 2014 to 2023 at a single center. Of 251 eligible children, 158 (316 eyes) who underwent lensectomy before age 2 and secondary IOL implantation between ages 2 and 6 were included. Methods Participants were grouped by age at secondary IOL implantation: 2 to <3 years, 3 to <4 years, 4 to <5 years, and 5 to <6 years. Demographic and clinical data were collected, and refractive outcomes at postoperative 1 month and age 7 years were analyzed. All refractive outcomes were expressed as spherical equivalent (SE), calculated as the sphere plus half of the cylinder (SE = sphere + ½ cylinder). Main Outcome Measures Interocular anisometropia at age 7 years, defined as the absolute interocular difference in SE. Results At postoperative month 1, 77.2% of children had anisometropia <1.0 D. By age 7 years, this proportion decreased to 52.5%, and significant differences in anisometropia distribution were observed among age-at-implantation groups (P = 0.035). In multivariable analyses, earlier age at secondary IOL implantation (β = –0.260; 95% confidence interval [CI], –0.386 to –0.134; P < 0.001), greater interocular axial length difference at implantation (β = 0.330; 95% CI, 0.033–0.628; P = 0.030), and greater early postoperative anisometropia (β = 0.355; 95% CI, 0.079–0.631; P = 0.012) were independently associated with greater anisometropia at age 7 years. Conclusions Interocular anisometropia tends to increase during childhood following bilateral secondary IOL implantation and is influenced by implantation timing, interocular axial length asymmetry, and early postoperative refractive status. Minimizing early postoperative anisometropia may be important for optimizing long-term refractive symmetry, and delayed secondary IOL implantation may be considered in children with marked interocular axial length asymmetry.

Importance:Appropriately sized and well-centered capsulorhexis is key for high-quality phacoemulsification cataract surgery and can be achieved with digital-guidance devices. However, such devices are not readily available, warranting the need for a device-free manual auxiliary capsulorhexis technique. Objectives:To determine if manual marking-assisted capsulorhexis (MMAC) is noninferior to a digital guidance-assisted capsulorhexis (DGAC) in capsulorhexis accuracy following phacoemulsification for age-related cataract. Design, Setting, and Participants:This noninferiority randomized clinical trial was conducted between July 2021 and December 2021 at Zhongshan Ophthalmic Center, China, with follow-up through 1 month after surgery. Of 204 adults screened, 156 were included who were aged 55 to 80 years and had pupil diameter ≥6.5 mm after pupil dilation and Lens Opacities Classification System III with nuclear opalescence grade of 3.0 to 4.0. Patients were excluded if they had previous intraocular surgery or a diagnosed eye disease that might affect functions of lens suspensory ligament. Data were analyzed from September to December 2024. Interventions:In the MMAC group, a lens caliper was used to measure and locate capsulorhexis position, subsequently applying its blunt head to mark the anterior lens capsule for capsulotomy guidance. In the DGAC group, a ring with predefined target diameter was projected to guide capsulorhexis. Main Outcomes and Measures:The primary outcome was the median deviation of capsulorhexis diameter from the target diameter with a noninferiority margin of 0.2 mm. Secondary outcomes included ratio of ideal capsulorhexis, grades of capsulorhexis-intraocular lens (IOL) overlap, off-center distance of capsulorhexis, postoperative best-corrected visual acuity, IOL tilt, and decentration. Results:Among 156 participants randomized into the MMAC group (mean [SD] age, 71 [7] years; 47 [60%] female) or DGAC group (mean [SD] age, 72 [7]; 47 [60%] female), median deviations comparing the capsulorhexis and target diameters were 0.22 mm (95% CI, 0.11-0.37) in the MMAC group vs 0.27 mm (95% CI, 0.14-0.52) in the DGAC group (difference, -0.05 mm; 95% CI, -0.16 to 0.07) for horizontal diameter and 0.27 mm (95% CI, 0.12-0.40) vs 0.33 mm (95% CI, 0.20-0.51) (difference, -0.06 mm; 95% CI, -0.17 to 0.05), respectively, for vertical diameters, both within the noninferiority margin of 0.20 mm. The proportion of ideal capsulorhexis was 96.2% (75 of 78) in the MMAC group and 88.5% (69 of 78) in the DGAC group (difference, 7.7%; 95% CI, -0.6 to 16.0), also within the noninferiority margin of -5.0%. Conclusions and Relevance:The findings in this trial indicate that accuracy of capsulorhexis with MMAC was noninferior to DGAC. Since the MMAC technique does not require special equipment, it might be considered routinely in clinical practice settings if similar outcomes are obtained elsewhere. Trial Registration:ClinicalTrials.gov Identifier: NCT04977115.

All cancers arise from the malignant transformation of normal cells, yet their cells-of-origin remain challenging to identify due to the inability to directly observe dynamic changes in human tumors. Retinoblastoma (Rb), a malignant intraocular cancer, serves as a well-established model for investigating the molecular and cellular mechanisms underlying tumorigenesis. While the maturing cone precursors (CPs) have been proposed as the cellular origin of human Rb, it is unclear whether other retinal cell types are similarly sensitive to RB1 inactivation. In this study, we developed RB1-deficient human retinal organoids (ROs) models using RB1−/− or RB1+/- human induced pluripotent stem cells (hiPSCs). RB1−/− hiPSCs generated tumor cells that recapitulated key features of human Rb and formed serial orthotopic xenografts. Importantly, RB1 loss induced overproliferation of ATOH7+ neurogenic retinal progenitor cells (nRPCs), which disrupted retinal development by generating ectopic dividing early-born retinal cells (retinal ganglion cells and CPs). Single-cell RNA sequencing analysis confirmed that ATOH7+/RXRγ+ nascent CPs survived and ultimately drove Rb tumorigenesis. In contrast, monoallelic RB1 inactivation resulting in low pRB expression did not induce proliferation of nascent CPs, but only triggered overproliferation of nRPCs, leading to a retinocytoma-like phenotype. Finally, a potential therapeutic target for Rb was identified from multi-omics data and validated through knockdown experiment and a small-molecule inhibitor. Our findings demonstrate, for the first time, that nRPCs are the most sensitive cells to RB1 loss inducing abnormal proliferation of nascent retinal cells, while ATOH7+ nascent CPs represent the earliest cellular origin of human Rb. These insights may facilitate the development of targeted therapies for Rb.

PURPOSE:To compare the prediction accuracy of new-generation and traditional intraocular lens (IOL) power calculation formulas in pediatric primary IOL implantation and identify factors influencing refractive prediction errors. SETTING:Zhongshan Ophthalmic Center, Guangzhou, China. DESIGN:Retrospective consecutive case-series study. METHODS:The prediction error (PE) was calculated for Holladay 1, SRK/T, Hoffer Q, Haigis, Barrett Universal II, Kane, Emmetropia Verifying Optical 2.0, and Ladas Super Formula (LSF) in pediatric primary IOL implantation. Subgroup analyses were conducted based on age, axial length (AL), average keratometry, surgical procedure, and IOL type. Multivariate regression analysis was used to identify factors associated with significant refractive surprise. RESULTS:83 patients (108 eyes) were included in the study. Significant differences in both PE and absolute PE were observed among formulas ( P < .001). The SRK/T and Kane formulas demonstrated lower mean predicted error (ME) and median absolute error (MedAE), whereas LSF and Haigis formulas showed higher ME and MedAE, respectively. Patients who were older age and had longer AL exhibited improved predictive accuracy. No significant differences in prediction accuracy were found between eyes with different surgical procedures or different IOL types. Multivariate regression analysis showed that younger age and shorter preoperative AL were predictors of significant refractive surprise across formulas. CONCLUSIONS:The predictive accuracy of IOL formulas in pediatric primary IOL implantation remains suboptimal, with the SRK/T and Kane formulas performing relatively better. Younger age and shorter AL remain major predictors of refractive surprise, while surgical procedure and IOL type show no significant association. Further development of pediatric-specific IOL power formulas is warranted.

PURPOSE:Whole eye transplantation (WET) is a promising approach for vision restoration in severe ocular damage. This study pioneers an allogeneic whole-eye transplantation model in non-human primates, designed to: (1) Establish standardized surgical protocols; (2) Overcome critical barriers to clinical translation-specifically immune rejection, functional visual restoration, and sustained graft viability; (3) Provide preclinical foundations for advancing human eye transplantation into clinical practice. DESIGN:Experimental animal study METHODS: Four cynomolgus macaques underwent unilateral whole-eye transplantation with distinct vascular anastomosis sequences using microsurgery, surgical navigation, and hypothermic perfusion: Strategy 1 (n = 2) implemented ``Artery then vein'' anastomosis, while Strategy 2 (n = 2) employed "Vein then artery" anastomosis. Recipients received perioperative standard triple immunosuppression (tacrolimus + mycophenolate mofetil + methylprednisolone). Transplanted eye structure and function were monitored via multimodal ophthalmic imaging and full-field electroretinography. Postoperative rejection was determined by ocular and dermal manifestations. RESULTS:The "Vein then artery" procedure achieved 19-day graft survival with intact circulation, normal intraocular pressure, and clear ocular media. Functional preservation was evidenced by detectable ERG signals and confirmed retinal perfusion. Rejection signs emerged on day 17, prompting termination on day 19. Histological analysis revealed reduced retinal ganglion cell density and inflammatory cell infiltration. The ``Artery then vein'' strategy caused acute intraocular pressure (IOP) elevation (49 mmHg), corneal edema, retinal disruption, and graft failure within 3 days. CONCLUSIONS:This research establishes the first proof-of-concept for allogeneic whole-eye transplantation in non-human primates, achieving 19-day graft survival with preserved structural integrity and partial retinal function. Overcoming postoperative immune rejection and functional reconstitution of retina-cortical connectivity remain pivotal challenges in WET. Given the profound anatomical homology of ocular structures between cynomolgus macaques and human, this model provides a translational foundation for addressing core barriers to clinical Whole eyeball transplantation.

Purpose:Epithelial-mesenchymal transition (EMT) of lens epithelial cells (LECs) is a predominant pathological driver for fibrotic cataracts. This study explores the role and mechanism of peroxisome proliferator-activated receptor γ coactivator 1-α (PGC1A), a key mitochondrial regulator, in EMT of LECs. Methods:RNA-sequencing analysis was applied to reveal biological changes during human lens epithelial fibrosis. Primary rabbit LECs were treated with TGFβ2 to induce EMT. Mitochondrial alterations were evaluated by MitoTracker staining, transmission electron microscopy, mitochondrial membrane potential assay, ATP content assay, and reactive oxygen species (ROS) assay. Loss- and gain-of-function studies were performed to uncover roles and mechanisms of PGC1A in EMT of LECs. Changes of PGC1A, EMT markers, and mitochondrial regulators were analyzed by Western blot, immunofluorescence staining, and RT-qPCR. Cell migration was assessed using the cell scratch assay. Ex vivo whole rat lenses were treated with TGFβ2 to induce fibrotic cataract to evaluate the potential therapeutic effect of PGC1A on lens fibrosis. Lens epithelial fibrosis was examined by hematoxylin and eosin (H&E) and immunofluorescence staining. Results:PGC1A was decreased with significant mitochondrial dysfunction during TGFβ2-induced EMT of LECs. PGC1A silencing promoted EMT by enhancing TGFβ2-Smad2/3 signaling, accelerating subcapsular fibrotic plaque formation. PGC1A upregulation protected LECs from TGFβ2-induced EMT by restoring mitochondrial health and energy metabolism. Mechanistically, PGC1A inhibition decreased mitochondrial transcription factor (TFAM), which mediated protective effects of PGC1A on mitochondria and LECs. Further, ZLN005, a PGC1A agonist, attenuated fibrotic lens opacity via preventing LECs from EMT. Conclusions:PGC1A safeguards LECs against EMT by restoring TFAM-mediated mitochondrial energy metabolism under TGFβ2 stress, offering potential targets for the treatment of lens epithelial fibrosis.

AIM:To evaluate the accuracy of intraocular lens (IOL) power calculation formulas with/without preoperative aphakic anterior chamber depth (aph-ACD) in pediatric aphakia. METHODS:A total of 102 pediatric patients (150 eyes) undergoing secondary IOL implantation were divided into two groups (in-the-bag or ciliary sulcus). Prediction error was calculated for 9 IOL power calculation formulas, including: 1) not requiring ACD: Hoffer Q, Holladay 1, SRK/T; 2) usable without or with entering ACD: Barrett Universal II (BUII), Emmetropia Verifying Optical (EVO) 2.0, and Ladas Artificial Intelligence Super (Ladas AI); 3) requiring ACD: Haigis, Kane, and Pearl-DGS. Mean prediction error (ME), mean absolute error (MAE), median absolute error (MedAE) and the percentage of eyes within ±0.25, ±0.50, ±0.75, and ±1.00 D were calculated. RESULTS:For the BUII, EVO 2.0, and Ladas AI, with aph-ACD demonstrated a higher MedAE compared to without aph-ACD (BUII: 1.27 vs 1.13 D, EVO 2.0: 1.26 vs 1.06 D, Ladas AI: 1.30 vs 1.10 D; all P<0.05). Formulas requiring ACD (Haigis, Kane, and Pearl-DGS) exhibited larger MedAE than those not requiring aph-ACD (Hoffer Q, Holladay 1, and SRK/T; P<0.05). In the capsular group, the percentage of eyes within ±1.00 D ranged from 44.83% to 74.14%, and it was 19.57% to 32.61% in the sulcus group. CONCLUSION:The introduction of aph-ACD does not improve the accuracy of IOL calculation for pediatric aphakia, regardless of in-the-bag or sulcus IOL secondary implantation. The relationship between aph-ACD and effective lens position in pediatric aphakia warrants further study.

DNA methyltransferase 1 (DNMT1) is an enzyme known for DNA methylation maintenance. Point mutations in its replication focus targeting sequence (RFTS) domain lead to late-onset neurodegeneration, such as autosomal dominant cerebellar ataxia-deafness and narcolepsy (ADCA-DN) disorder. Here, we demonstrated that DNMT1 has the capability to bind to mRNA transcripts and facilitate 5-methylcytosine (m5C) RNA methylation by recruiting NOP2/Sun RNA methyltransferase 2 (NSUN2). RNA m5C methylation, in turn, promotes RNA stability for those genes modulating mitochondrial function. When the DNMT1 RFTS domain is mutated in mice, it triggers aberrant DNMT1-RNA interaction and significantly elevated m5C RNA methylation and RNA stability for a portion of metabolic genes. Consequently, increased levels of metabolic RNA transcripts contribute to cumulative oxidative stress, mitochondrial dysfunction, and neurological symptoms. Collectively, our results reveal a dual role of DNMT1 in regulating both DNA and RNA methylation, which further modulates mitochondrial function, shedding light on the pathogenic mechanism of DNMT1 mutation-induced neurodegeneration.

PURPOSE. Lens development requires tight regulation of cell proliferation and differentiation processes, the disruption of which might lead to congenital cataract formation. N6-methyladenosine (m6A) is the most prevalent mRNA internal modification and has been shown to play important roles in regulating the development, physiology, and pathology of various organs and tissues. However, the function of m6A during lens development remains unknown. The purpose of this study was to investigate the function of Mettl3, the core catalytic component of the m6A-writer complex, during lens development. METHODS. Lens-specific Mettl3 conditional knockout (Mettl3-CKO) mice were used as a model to investigate the function of Mettl3 during lens development. Hematoxylin and eosin staining was used to examine lens histology. Immunofluorescence (IF) staining was used to examine the expression of genes in the lenses. RNA sequencing (RNA-seq) was used to characterize the transcriptome of the lenses. Modified m6A sequencing was used to characterize the m6A epitranscriptome of the lenses. RESULTS. Mettl3-CKO mice developed cataracts; histologic and IF examination revealed that Mettl3-CKO lenses presented defects in several secondary fiber differentiation processes, including delayed cell cycle exit, mislocalization, and failed cell body elongation. RNA-seq revealed that the expression of genes regulating actin-cytoskeleton dynamics and cell cycle progression was altered in Mettl3-CKO lenses. m6A-seq characterized the lens m6A epitranscriptome and suggested its potential role in regulating fiber cell differentiation processes. CONCLUSIONS. Mettl3 regulates lens development by promoting the cell cycle exit and cell morphological changes during secondary lens fiber differentiation.

Capsular tension ring (CTR) implantation has been shown to reduce intraocular lens (IOL) decentration and tilt in high myopia. However, the effect of CTR implantation in highly myopic eyes on IOL power calculation remains unclear, particularly in new-generation formulas. To evaluate the influence of CTR implantation on IOL power calculation in highly myopic eyes. This is a prespecified secondary analysis of outcomes of a randomized clinical trial conducted between November 2021 and September 2023 at the Zhongshan Ophthalmic Center in Guangzhou, China. Cataract patients with an axial length (AL) of 26 mm or longer were enrolled and stratified into 3 strata based on AL (stratum 1: AL 26-<28 mm; stratum 2: AL 28-<30 mm; stratum 3: AL ≥30 mm). Participants were stratified based on AL and randomized to the CTR group (a C-loop IOL combined with a CTR) or the control group (only a C-loop IOL) within each stratum. Predictive outcomes of 6 new-generation formulas and 4 traditional formulas were evaluated. The arithmetic and absolute prediction error (PE) and the percentages of eyes within ±0.25 diopter (D), ±0.50 D, ±0.75 D, and ±1.00 D of PE were analyzed. A total of 186 eyes of 186 participants were randomized into the CTR group (93 eyes [50%]) or control group (93 eyes [50%]). Excluding a withdrawal case and 24 eyes with best-corrected visual acuity less than 20/40, 80 eyes in the CTR group (86.0%) and 81 eyes in the control group (87.1%) were analyzed. Of 161 participants analyzed, overall mean (SD) participant age was 56.7 (10.5) years, and 100 participants (62.1%) were female. No differences were observed in arithmetic PE between the CTR and control groups in any strata. The CTR group showed smaller absolute PE in all new-generation formulas and higher percentage of PE within ±0.50 D in the Emmetropia Verifying Optical 2.0, Hoffer QST, LISA, and Pearl-DGS formulas only for eyes with an AL of 30 mm or longer compared with the control group. In traditional formulas, no differences were observed between the 2 groups in any strata. In this secondary analysis, CTR implantation in highly myopic eyes did not affect the target refraction and can improve the prediction accuracy of new-generation IOL calculation formulas in eyes with AL of 30 mm or longer. These findings support use of CTR implantation in eyes with an AL of 30 mm or longer. ClinicalTrials.gov Identifier: NCT05161520

The evolution of surgical techniques aims to augment surgeons' capabilities through digital guidance and robotization for higher precision and consistency. Currently, surgeries heavily rely on surgeon's experience and visual judgment, causing operation variations. Artificial intelligence (AI) offers a solution by extracting and digitizing surgical trajectories and features from videos to provide digital guidance. In this study, we collected 17,538 videos of capsulorhexis, a crucial step in cataract surgery, to create an AI-driven system named Meta Surgery (MetaS). MetaS evaluates and identifies ideal cases, extracts their digital characteristics, and fits an optimal capsulorhexis path in real-time during surgery. Surgeons performed capsulorhexis benefited from MetaS's guidance and a lens caliper, which increased the rate of ideal capsulorhexis by ~40%. Additionally, these digital features enabled a surgical robot to perform precise capsulorhexis autonomously in porcine eyes. This approach augments surgeons' surgical skills and paves the way for the autonomous operation of surgical robots.

Importance:The optimal timing for secondary intraocular lens (IOL) implantation in children with bilateral aphakia remains uncertain, with important implications for long-term visual outcomes and the risk of complications such as glaucoma. Determining when to implant to achieve the best visual outcomes while minimizing complications is critical for improving clinical decision-making in pediatric cataract management. Objective:To report the visual acuity (VA) and complications in children with bilateral aphakia after lensectomy for pediatric cataracts, undergoing secondary IOL implantation at different ages. Design, Setting, and Participants:This single-center prospective observational cohort study, conducted from 2014 to 2023, is a 7-year follow-up study. A total of 251 children met the inclusion criteria. After exclusion, 158 children were enrolled in this study. These 158 children (316 eyes) underwent lensectomy before the age of 2 years, followed by secondary IOL implantation between the ages of 2 and younger than 6 years in bilateral pediatric cataracts. Exposure:Study participants were categorized into 4 groups based on the timing of secondary IOL implantation (2 to <3 years, 3 to <4 years, 4 to <5 years, and 5 to <6 years). Main Outcome and Measure:Best-corrected VA (BCVA) outcomes at age 7 years after secondary IOL implantation in children with bilateral pediatric cataracts. Results:Among the 158 children included in the study, 103 (65.2%) were male. At age 7 years, the mean (SD) BCVA for children who underwent secondary IOL implantation was 0.49 (0.35) logMAR (Snellen equivalent, 20/62) at 2 to younger than 3 years, 0.59 (0.36) logMAR (Snellen equivalent, 20/78) at 3 to younger than 4 years, 0.60 (0.30) logMAR (Snellen equivalent, 20/80) at 4 to younger than 5 years, and 0.65 (0.34) logMAR (Snellen equivalent, 20/89) at 5 to younger than 6 years (P = .20). Glaucoma-related adverse events occurred in 47 eyes in total: 6 eyes (8.8%), 7 eyes (9.0%), 10 eyes (15.6%), and 24 eyes (22.6%) across the groups, respectively, with a statistical difference among the groups (P = .03). Conclusions and Relevance:These findings suggest that secondary IOL implantation performed between the ages of 2 and younger than 6 years following bilateral pediatric cataract lensectomy can achieve comparable visual outcomes; however, the risk of glaucoma increases with older implantation age.

All cancers develop from malignant transformation of normal cells, while it is challenging to identify these cells-of-origin since it is impossible to witness the dynamic changes in human cancers. Retinoblastoma (Rb), an intraocular malignant cancer, is a typical model for study the molecular and cellular mechanisms of cancers. Although the maturing cone precursors (CPs) are proposed as the cellular origin of human Rb, it is unknow whether other retinal cells are also sensitive to RB1 inactivation. Here we developed RB1-deficient human retinal organoids (ROs) models from RB1-/- or RB1+/- human induced pluripotent stem cells (hiPSCs). RB1-/- hiPSCs developed into Rb tumors which recapitulated the features of human native Rb and had the ability to form consecutive orthotopic xenografts in mice. Importantly, RB1 loss induced the overproliferation of ATOH7+ neurogenic retinal progenitor cells (nRPCs), which disrupted the retinal development by generating proliferative, nascent retinal cells including retinal ganglion cells and CPs. scRNA-seq analysis verified the ATOH7+/RXRγ+ nascent CPs survived and finally drove Rb development. In contrast, monoallelic RB1 inactivation with low pRB expression did not induce nascent CPs proliferation, but only induced nRPCs overproliferation which caused retinocytoma-like phenotype. Finally, a potential therapeutic agent for Rb was identified from multi-omics data. Our findings firstly indicate that nRPCs are the most sensitive cells to RB1 loss inducing nascent retinal cells abnormal proliferation, and ATOH7+ nascent CPs are the earliest cellular origin of human Rb, facilitating drug development for Rb. ### Competing Interest Statement The authors have declared no competing interest.

Importance:There is currently no consensus regarding the association of capsular tension ring (CTR) on intraocular lens (IOL) position or the indications for its implantation. Objective:To evaluate the association of CTR implantation on IOL position. Data Sources:PubMed, Embase, and Cochrane Library were searched from their inception to October 18, 2024. Study Selection:Randomized clinical trials (RCTs) or prospective cohorts reporting the effect or association of CTR on postoperative anterior chamber depth (ACD), IOL decentration, tilt, or rotation. Data Extraction and Synthesis:Data extraction was conducted by 2 reviewers and verified by another for accuracy. Mean difference (MD) was used to synthesize the effect measures, and subgroup analyses were conducted according to IOL haptic design (C-loop and plate haptic) and whether the patient had high myopia. Main Outcome and Measures:Postoperative ACD and IOL decentration, tilt, and rotation. Results:A total of 11 RCTs and 7 cohort studies, involving 809 eyes with CTR and 822 eyes without CTR, were included in this meta-analysis. The analysis revealed that IOL tilt (MD, -1.04°; 95% CI, -2.05° to -0.03°; P = .04) and rotation (MD, -0.82°; 95% CI, -1.27° to -0.37°; P < .001) were smaller in the CTR group compared with the control group. The subgroup analysis of ACD (I2 = 70.7%; P = .03), decentration (I2 = 66.5%, P = .08), and tilt (I2 = 76.7%, P = .01) revealed a heterogeneity between the subgroups stratified according to IOL haptic design. Additionally, subgroup analysis demonstrated that CTR group showed a deeper ACD in eyes implanted with plate haptic IOLs (MD, 0.11 mm; 95% CI, 0.02 to 0.20 mm; P = .01), and a smaller IOL tilt in highly myopic eyes (MD, -1.43°; 95% CI, -2.59° to -0.26°; P = .02) compared with the control group. Conclusions and Relevance:CTR implantation was associated with enhanced stability of IOL rotation in this meta-analysis, while only reducing IOL tilt in high myopia. While the direct clinical relevance of these results could not be determined from this investigation, these findings provide evidence supporting use of CTR implantation when toric IOLs have been implanted or with high myopia, although a hyperopic refractive shift after implantation of plate haptic IOLs may require target refraction adjustment.

There is currently no consensus regarding the association of capsular tension ring (CTR) on intraocular lens (IOL) position or the indications for its implantation. To evaluate the association of CTR implantation on IOL position. PubMed, Embase, and Cochrane Library were searched from their inception to October 18, 2024. Randomized clinical trials (RCTs) or prospective cohorts reporting the effect or association of CTR on postoperative anterior chamber depth (ACD), IOL decentration, tilt, or rotation. Data extraction was conducted by 2 reviewers and verified by another for accuracy. Mean difference (MD) was used to synthesize the effect measures, and subgroup analyses were conducted according to IOL haptic design (C-loop and plate haptic) and whether the patient had high myopia. Postoperative ACD and IOL decentration, tilt, and rotation. A total of 11 RCTs and 7 cohort studies, involving 809 eyes with CTR and 822 eyes without CTR, were included in this meta-analysis. The analysis revealed that IOL tilt (MD, −1.04°; 95% CI, −2.05° to −0.03°; P = .04) and rotation (MD, −0.82°; 95% CI, −1.27° to −0.37°; P < .001) were smaller in the CTR group compared with the control group. The subgroup analysis of ACD (I2 = 70.7%; P = .03), decentration (I2 = 66.5%, P = .08), and tilt (I2 = 76.7%, P = .01) revealed a heterogeneity between the subgroups stratified according to IOL haptic design. Additionally, subgroup analysis demonstrated that CTR group showed a deeper ACD in eyes implanted with plate haptic IOLs (MD, 0.11 mm; 95% CI, 0.02 to 0.20 mm; P = .01), and a smaller IOL tilt in highly myopic eyes (MD, −1.43°; 95% CI, −2.59° to −0.26°; P = .02) compared with the control group. CTR implantation was associated with enhanced stability of IOL rotation in this meta-analysis, while only reducing IOL tilt in high myopia. While the direct clinical relevance of these results could not be determined from this investigation, these findings provide evidence supporting use of CTR implantation when toric IOLs have been implanted or with high myopia, although a hyperopic refractive shift after implantation of plate haptic IOLs may require target refraction adjustment.

Importance:Capsular tension ring (CTR) implantation has been shown to reduce intraocular lens (IOL) decentration and tilt in high myopia. However, the effect of CTR implantation in highly myopic eyes on IOL power calculation remains unclear, particularly in new-generation formulas. Objective:To evaluate the influence of CTR implantation on IOL power calculation in highly myopic eyes. Design, Setting, and Participants:This is a prespecified secondary analysis of outcomes of a randomized clinical trial conducted between November 2021 and September 2023 at the Zhongshan Ophthalmic Center in Guangzhou, China. Cataract patients with an axial length (AL) of 26 mm or longer were enrolled and stratified into 3 strata based on AL (stratum 1: AL 26-<28 mm; stratum 2: AL 28-<30 mm; stratum 3: AL ≥30 mm). Interventions:Participants were stratified based on AL and randomized to the CTR group (a C-loop IOL combined with a CTR) or the control group (only a C-loop IOL) within each stratum. Main Outcomes and Measures:Predictive outcomes of 6 new-generation formulas and 4 traditional formulas were evaluated. The arithmetic and absolute prediction error (PE) and the percentages of eyes within ±0.25 diopter (D), ±0.50 D, ±0.75 D, and ±1.00 D of PE were analyzed. Results:A total of 186 eyes of 186 participants were randomized into the CTR group (93 eyes [50%]) or control group (93 eyes [50%]). Excluding a withdrawal case and 24 eyes with best-corrected visual acuity less than 20/40, 80 eyes in the CTR group (86.0%) and 81 eyes in the control group (87.1%) were analyzed. Of 161 participants analyzed, overall mean (SD) participant age was 56.7 (10.5) years, and 100 participants (62.1%) were female. No differences were observed in arithmetic PE between the CTR and control groups in any strata. The CTR group showed smaller absolute PE in all new-generation formulas and higher percentage of PE within ±0.50 D in the Emmetropia Verifying Optical 2.0, Hoffer QST, LISA, and Pearl-DGS formulas only for eyes with an AL of 30 mm or longer compared with the control group. In traditional formulas, no differences were observed between the 2 groups in any strata. Conclusions and Relevance:In this secondary analysis, CTR implantation in highly myopic eyes did not affect the target refraction and can improve the prediction accuracy of new-generation IOL calculation formulas in eyes with AL of 30 mm or longer. These findings support use of CTR implantation in eyes with an AL of 30 mm or longer. Trial Registration:ClinicalTrials.gov Identifier: NCT05161520.