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This study aimed to develop and evaluate a guinea pig model for glaucoma, comparing resultant eyeball enlargement with an existing myopia model. Thirty guinea pigs underwent intracameral injection of magnetic microspheres to induce chronic ocular hypertension (COH). Intraocular pressure (IOP) was systematically monitored, revealing a successful induction of COH in 73.33% of the guinea pigs. The mean IOP increased from a baseline of 18.04 ± 1.33 mmHg, reaching a peak at week 3 (36.31 ± 6.13 mmHg) and remaining elevated for at least 7 weeks. All data are presented as mean ± standard deviation of the mean. Subsequently, detailed assessments were conducted to validate the established glaucoma model. Immunofluorescent staining demonstrated a significant decrease in the density of retinal ganglion cells (RGC) in the glaucoma group. Optic disc excavation and notable thinning of the lamina cribrosa (LC) were observed. The quantity of optic nerve ax·ons in glaucoma group gradually decreased from baseline (44553 ± 3608/mm2) to week 4 (28687 ± 2071/mm2) and week 8 (17977 ± 3697/mm2). Moreover, regarding the global enlargement of eyeballs, both the transverse and longitudinal axis in glaucomatous eyes were found to be significantly larger than that in myopic eyes, particularly in the anterior chamber depth (1.758 ± 0.113 mm vs. 1.151 ± 0.046 mm). These findings indicate distinct patterns of structural changes associated with glaucoma and myopia in the guinea pig model. This guinea pig model holds promise for future research aimed at exploring biomechanical mechanisms, therapeutic interventions, and advancing our understanding of the relationship between glaucoma and myopia.
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Modelos Animais de Doenças , Glaucoma , Pressão Intraocular , Miopia , Células Ganglionares da Retina , Animais , Cobaias , Miopia/fisiopatologia , Miopia/patologia , Pressão Intraocular/fisiologia , Células Ganglionares da Retina/patologia , Glaucoma/fisiopatologia , Glaucoma/patologia , Disco Óptico/patologia , Masculino , Tomografia de Coerência Óptica , Tonometria OcularRESUMO
BACKGROUND: Circular RNAs (circRNAs) are implicated in retinal pathophysiology; however, their expression profiles and functions in photoreceptor apoptosis are largely unknown. We explored circRNA-expression profiles and circUvrag (host gene: Uvrag, ultraviolet radiation resistance associated gene) function in light-induced photoreceptor apoptosis. METHODS: Sprague-Dawley rats and 661 W photoreceptor cells were exposed to blue light to establish light-induced photoreceptor degeneration. Differentially expressed circRNAs were identified using microarrays. Potential functions of dysregulated circRNAs were analysed using Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analyses. CircUvrag expression and localization were evaluated using quantitative RT-PCR and fluorescence in situ hybridization, respectively. CircUvrag overexpression and knockdown were induced using a plasmid and a small interfering RNA, respectively, and retinal function and structure were assessed using scotopic electroretinography, haematoxylin-eosin staining, and TUNEL staining. Microglial migration was assessed using IBA1 immunostaining. The apoptosis ratio of photoreceptor cells in vitro was detected using flow cytometry. RESULTS: We identified 764 differentially expressed circRNAs, which were potentially related with the development of retinal structures, including neurons, dendrites, and synapses, and might participate in nervous-system pathophysiology. Light exposure enriched circUvrag in the cytoplasm of photoreceptors in the outer nuclear layer (ONL). CircUvrag knockdown decreased photoreceptor apoptosis and microglial migration to the ONL after light exposure, preserving ONL thickness and a-wave amplitude. In vitro, circUvrag knockdown inhibited photoreceptor apoptosis, although circUvrag overexpression slightly promoted photoreceptor apoptosis. CONCLUSIONS: CircUvrag knockdown attenuated light-induced photoreceptor apoptosis, and might be a potential target in retinal degeneration.
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Apoptose , Luz , Células Fotorreceptoras de Vertebrados , RNA Circular , RNA , Ratos Sprague-Dawley , Degeneração Retiniana , Animais , RNA Circular/genética , Degeneração Retiniana/genética , Degeneração Retiniana/metabolismo , Degeneração Retiniana/etiologia , Degeneração Retiniana/fisiopatologia , Ratos , Células Fotorreceptoras de Vertebrados/patologia , Células Fotorreceptoras de Vertebrados/metabolismo , Luz/efeitos adversos , RNA/genética , Hibridização in Situ Fluorescente , Regulação da Expressão Gênica , Modelos Animais de Doenças , Eletrorretinografia , Lesões Experimentais por Radiação/genética , Lesões Experimentais por Radiação/metabolismo , Reação em Cadeia da Polimerase em Tempo Real , Perfilação da Expressão Gênica , Marcação In Situ das Extremidades Cortadas , Masculino , Citometria de FluxoRESUMO
PURPOSE: To develop and validate the performance of a high myopia (HM)-specific normative database of peripapillary retinal nerve fiber layer (pRNFL) thickness in differentiating HM from highly myopic glaucoma (HMG). DESIGN: Cross-sectional multicenter study. PARTICIPANTS: A total of 1367 Chinese participants (2325 eyes) with nonpathologic HM or HMG were included from 4 centers. After quality control, 1108 eyes from 694 participants with HM were included in the normative database; 459 eyes from 408 participants (323 eyes with HM and 136 eyes with HMG) and 322 eyes from 197 participants (131 eyes with HM and 191 eyes with HMG) were included in the internal and external validation sets, respectively. Only HMG eyes with an intraocular pressure > 21 mmHg were included. METHODS: The pRNFL thickness was measured with swept-source (SS) OCT. Four strategies of pRNFL-specified values were examined, including global and quadrantic pRNFL thickness below the lowest fifth or the lowest first percentile of the normative database. MAIN OUTCOMES MEASURES: The accuracy, sensitivity, and specificity of the HM-specific normative database for detecting HMG. RESULTS: Setting the fifth percentile of the global pRNFL thickness as the threshold, using the HM-specific normative database, we achieved an accuracy of 0.93 (95% confidence interval [CI], 0.90-0.95) and 0.85 (95% CI, 0.81-0.89), and, using the first percentile as the threshold, we acheived an accuracy of 0.85 (95% CI, 0.81-0.88) and 0.70 (95% CI, 0.65-0.75) in detecting HMG in the internal and external validation sets, respectively. The fifth percentile of the global pRNFL thickness achieved high sensitivities of 0.75 (95% CI, 0.67-0.82) and 0.75 (95% CI, 0.68-0.81) and specificities of 1.00 (95% CI, 0.99-1.00) and 1.00 (95% CI, 0.97-1.00) in the internal and external validation datasets, respectively. Compared with the built-in database of the OCT device, the HM-specific normative database showed a higher sensitivity and specificity than the corresponding pRNFL thickness below the fifth or first percentile (P < 0.001 for all). CONCLUSIONS: The HM-specific normative database is more capable of detecting HMG eyes than the SS OCT built-in database, which may be an effective tool for differential diagnosis between HMG and HM. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.
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Glaucoma , Miopia , Humanos , Estudos Transversais , População do Leste Asiático , Miopia/diagnóstico , Retina , Glaucoma/diagnóstico , Fibras NervosasRESUMO
INTRODUCTION: This retrospective study investigated the clinical characteristics of multiple subretinal fluid blebs (MSFBs) after successful surgery for rhegmatogenous retinal detachment (RRD), and explored the association between MSFB with best-corrected visual acuity (BCVA) and metamorphopsia. METHODS: The study comprised 206 patients after successful surgery for RRD, with 58 and 148 eyes undergoing, respectively, scleral buckling (SB) and pars plana vitrectomy (PPV). The clinical characteristics of MSFBs were analyzed by optical coherence tomography (OCT). The choroidal vessels in some cases were evaluated with OCT angiography. M-charts were used to determine the metamorphopsia. RESULTS: MSFBs occurred in 17 (29.3%) and 8 (5.4%) eyes given SB and PPV, respectively. MSFBs appeared 5.6 ± 5.5 weeks after surgery and required 34.9 ± 13.8 weeks to disappear. Disrupted external limiting membrane and ellipsoid zone could still be seen in 83.3% and 66.7% of the patients 12 months after surgery; these rates were significantly higher than those of patients without MSFBs (P = 0.047, 0.022, respectively). Twelve months post-surgery, BCVA and metamorphopsia scores of the patients with MSFBs were statistically comparable to those of the controls. CONCLUSIONS: MSFBs occur more commonly after SB than PPV. MSFBs may delay the recovery of the outer retina structure, but do not affect postoperative BCVA and metamorphopsia.
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Due to the increasing prevalence of high myopia around the world, structural and functional damages to the optic nerve in high myopia has recently attracted much attention. Evidence has shown that high myopia is related to the development of glaucomatous or glaucoma-like optic neuropathy, and that both have many common features. These similarities often pose a diagnostic challenge that will affect the future management of glaucoma suspects in high myopia. In this review, we summarize similarities and differences in optic neuropathy arising from non-pathologic high myopia and glaucoma by considering their respective structural and functional characteristics on fundus photography, optical coherence tomography scanning, and visual field tests. These features may also help to distinguish the underlying mechanisms of the optic neuropathies and to determine management strategies for patients with high myopia and glaucoma.
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Glaucoma , Miopia , Disco Óptico , Doenças do Nervo Óptico , Humanos , Disco Óptico/patologia , Pressão Intraocular , Glaucoma/diagnóstico , Doenças do Nervo Óptico/patologia , Miopia/complicações , Miopia/diagnóstico , Tomografia de Coerência Óptica/métodosRESUMO
The carbonic anhydrase 2 (Car2) gene encodes the primary isoenzyme responsible for aqueous humor (AH) production and plays a major role in the regulation of intraocular pressure (IOP). The CRISPR-Cas9 system, based on the ShH10 adenovirus-associated virus, can efficiently disrupt the Car2 gene in the ciliary body. With a single intravitreal injection, Car2 knockout can significantly and sustainably reduce IOP in both normal mice and glaucoma models by inhibiting AH production. Furthermore, it effectively delays and even halts glaucomatous damage induced by prolonged high IOP in a chronic ocular hypertension model, surpassing the efficacy of clinically available carbonic anhydrase inhibitors such as brinzolamide. The clinical application of CRISPR-Cas9 based disruption of Car2 is an attractive therapeutic strategy that could bring additional benefits to patients with glaucoma.
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Sistemas CRISPR-Cas , Anidrase Carbônica II , Corpo Ciliar , Glaucoma , Pressão Intraocular , Animais , Glaucoma/genética , Glaucoma/patologia , Glaucoma/metabolismo , Sistemas CRISPR-Cas/genética , Corpo Ciliar/metabolismo , Corpo Ciliar/patologia , Anidrase Carbônica II/genética , Anidrase Carbônica II/metabolismo , Camundongos , Humor Aquoso/metabolismo , Humanos , Modelos Animais de Doenças , Inibidores da Anidrase Carbônica/farmacologia , Inibidores da Anidrase Carbônica/uso terapêutico , Deleção de Genes , Camundongos Endogâmicos C57BL , Hipertensão Ocular/genética , Hipertensão Ocular/patologiaRESUMO
BACKGROUND: In adult patients with high myopia (HM), progressive axial elongation poses a significant risk for the development of subsequent ocular complications that may lead to visual impairment. Effective strategies to reduce or prevent further axial elongation in highly myopic adult patients have not been available so far. Recent studies suggested that medically lowering intraocular pressure (IOP) may reduce axial elongation. OBJECTIVE: This clinical randomised controlled trial (RCT) aims to evaluate the efficacy of medical IOP reduction in adult patients with progressive HM (PHM). TRIAL DESIGN: Single-centre, open-label, prospective RCT. METHODS: This RCT will recruit 152 participants with PHM at the Zhongshan Ophthalmic Center (ZOC). Randomised in a ratio of 1:1, participants will receive IOP-lowering eyedrops (intervention group) or will be followed without treatment (control group) for 12 months. Follow-up visits will be conducted at 1, 6 and 12 months after baseline. Only one eye per eligible participant will be included for analysis. The primary outcome is the change in axial length (AL) within the study period of 12 months. Secondary outcomes include the incidence and progression of visual field (VF) defects, changes in optic disc morphology and incidence and progression of myopic maculopathy. Difference in AL changes between the two groups will be analysed using linear regression analysis. For the secondary outcomes, a multifactor Poisson regression within a generalised linear model will be used to estimate the relative risk of progression in VF defects and myopic maculopathy, and the rate of thinning in retinal nerve fibre layer and ganglion cell-inner plexiform will be assessed through Kaplan-Meier curves and log-rank tests. ETHICS AND DISSEMINATION: Full ethics approval for this trial has been obtained from the Ethics Committee of ZOC, Sun Yat-sen University, China (ID: 2023KYPJ110). Results of this trial will be disseminated through peer-reviewed journals and conference presentations. TRIAL REGISTRATION NUMBER: NCT05850936.
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Pressão Intraocular , Miopia Degenerativa , Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Comprimento Axial do Olho , Progressão da Doença , Soluções Oftálmicas , Estudos Prospectivos , Ensaios Clínicos Controlados Aleatórios como Assunto , Campos VisuaisRESUMO
PURPOSE: To investigate the progression patterns and risk factors of axial elongation in young adults with non-pathologic high myopia. DESIGN: Prospective, clinical observational cohort study with 2- to 4-year follow-up. METHODS: A total of 1043 eyes of 563 participants (3515 medical records) aged 18 to 50 years with non-pathologic high myopia (axial length [AL] ≥ 26 mm; myopic maculopathy < diffuse chorioretinal atrophy; without posterior staphyloma) were included from 1546 participants (6318 medical records). Annual axial elongation was calculated via linear mixed-effect models. The associated risk factors of axial elongation were determined by ordinal logistic regression analysis, with generalized estimate equations for eliminating an interocular correlation bias. RESULTS: Based on 5359 times of AL measurements, the annual axial elongation of participants (mean [SD] age 31.39 [9.22] years) was 0.03 mm/year (95% confidence interval [CI], 0.03-0.04, P < 0.001) during a 30.23 (6.06) months' follow-up. Severe (> 0.1 mm/year), moderate (0.05-0.09 mm/year), mild (0-0.049 mm/year), and nil (≤ 0 mm/year) elongation was observed in 122 (11.7%), 211 (20.2%), 417 (40.0%), and 293 (28.1%) eyes. The following risk factors were significantly associated with axial elongation: baseline AL≥ 28 mm (odds ratio [OR], 4.23; 95%CI, 2.95-6.06; P < 0.001); age < 40 years (OR, 1.64; 95%CI, 1.18-2.28; Pâ¯=â¯0.003); axial asymmetry (OR, 2.04; 95%CI, 1.26-3.29; Pâ¯=â¯0.003), and women (OR, 1.52; 95%CI, 1.13-2.2.05; Pâ¯=â¯0.006). Using anti-glaucoma medications was a protective factor (OR, 0.46; 95%CI, 0.27-0.79; Pâ¯=â¯0.005), which slowed 75% of axial elongation from 0.04 (0.06) to 0.01 (0.06) mm/y (P < 0.001). CONCLUSIONS: Axial elongation continued in young adults with non-pathologic myopia. Risk factors included longer baseline AL and axial asymmetry, younger age, and woman. Topical use of anti-glaucoma medications may be useful to reduce ongoing axial elongation.
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Large language models (LLMs), a natural language processing technology based on deep learning, are currently in the spotlight. These models closely mimic natural language comprehension and generation. Their evolution has undergone several waves of innovation similar to convolutional neural networks. The transformer architecture advancement in generative artificial intelligence marks a monumental leap beyond early-stage pattern recognition via supervised learning. With the expansion of parameters and training data (terabytes), LLMs unveil remarkable human interactivity, encompassing capabilities such as memory retention and comprehension. These advances make LLMs particularly well-suited for roles in healthcare communication between medical practitioners and patients. In this comprehensive review, we discuss the trajectory of LLMs and their potential implications for clinicians and patients. For clinicians, LLMs can be used for automated medical documentation, and given better inputs and extensive validation, LLMs may be able to autonomously diagnose and treat in the future. For patient care, LLMs can be used for triage suggestions, summarization of medical documents, explanation of a patient's condition, and customizing patient education materials tailored to their comprehension level. The limitations of LLMs and possible solutions for real-world use are also presented. Given the rapid advancements in this area, this review attempts to briefly cover many roles that LLMs may play in the ophthalmic space, with a focus on improving the quality of healthcare delivery.
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PURPOSE: To describe the optic nerve head (ONH) abnormalities in nonpathologic highly myopic eyes based on swept-source optical coherence tomography (OCT) and the relationship with visual field (VF). DESIGN: Secondary analysis from a longitudinal cohort study. METHODS: Highly myopic patients without myopic maculopathy of category 2 or higher were enrolled. All participants underwent a swept-source OCT examination focused on ONH. We differentiated between 3 major types (optic disc morphologic abnormality, papillary/peripapillary tissue defect, and papillary/peripapillary schisis) and 12 subtypes of ONH abnormalities. The prevalence and characteristics of ONH abnormalities and the relationship with VF were analyzed. RESULTS: A total of 857 participants (1389 eyes) were included. Among the 1389 eyes, 91.86%, 68.61%, and 34.92% of them had at least 1, 2, or 3 ONH abnormalities, respectively, which corresponded to 29.55%, 31.79%, and 35.67% of VF defects, respectively. Among the 12 subtypes of the 3 major types, peripapillary hyperreflective ovoid mass-like structure, visible retrobulbar subarachnoid space, and prelaminar schisis were the most common, respectively. Perimetric defects corresponding to OCT abnormalities were more commonly found in eyes with peripapillary retinal detachment, peripapillary retinoschisis, and peripapillary hyperreflective ovoid mass-like structure. Glaucoma-like VF defects were more common in eyes with deep optic cups (28.17%) and with optic disc pit/pit-like change (18.92%). CONCLUSIONS: We observed and clarified the ONH structural abnormalities in eyes with nonpathologic high myopia. These descriptions may be helpful to differentiate changes in pathologic high myopia or glaucoma.
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Anormalidades do Olho , Glaucoma , Miopia , Disco Óptico , Humanos , Disco Óptico/diagnóstico por imagem , Disco Óptico/patologia , Campos Visuais , Estudos Longitudinais , Miopia/complicações , Miopia/diagnóstico , Anormalidades do Olho/complicações , Anormalidades do Olho/diagnóstico , Tomografia de Coerência Óptica/métodos , Transtornos da Visão/diagnósticoRESUMO
Mice have emerged as a widely employed model for investigating various retinal diseases. However, the availability of comprehensive datasets capturing the entire developmental and aging stages of the mouse retina, particularly during the elderly period, encompassing integrated lncRNA and mRNA expression profiles, is limited. In this study, we assembled a total of 18 retina samples from mice across 6 distinct stages of development and aging (5 days, 3 weeks, 6 weeks, 10 weeks, 6 months, and 15 months) to conduct integrated lncRNA and mRNA sequencing analysis. This invaluable dataset offers a comprehensive transcriptomic resource of mRNA and lncRNA expression profiles during the natural progression of retinal development and aging. The discoveries stemming from this investigation will significantly contribute to the elucidation of the underlying molecular mechanisms associated with various retinal diseases, such as congenital retinal dysplasia and retinal degenerative diseases.
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RNA Longo não Codificante , Retina , Animais , Camundongos , Envelhecimento/genética , Perfilação da Expressão Gênica , Retina/crescimento & desenvolvimento , Degeneração Retiniana/genética , RNA Longo não Codificante/genética , RNA Mensageiro/genética , Displasia Retiniana/genética , HumanosRESUMO
This article describes a patient who developed Harada disease-like uveitis after quadrivalent human papillomavirus (HPV4) vaccination and experienced resolution without any systemic treatment. To achieve this aim, a case report and a review of related literature on HPV vaccination causing uveitis were conducted. The results of this study show a diagnosis of Harada disease-like uveitis after HPV4 vaccination based on the vaccination history, clinical symptoms, and multimodal imaging. Resolution without any systemic corticosteroid treatment was observed. According to these findings, patients may develop uveitis with Harada-like features, which can be a mild and self-limiting process, after HPV4 vaccination.
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Alphapapillomavirus , Infecções por Papillomavirus , Vacinas contra Papillomavirus , Uveíte , Humanos , Infecções por Papillomavirus/prevenção & controle , Vacinas contra Papillomavirus/efeitos adversos , Vacinação/efeitos adversosRESUMO
PURPOSE: To observe the changes in metamorphopsia after scleral buckling (SB) surgery for macula-off rhegmatogenous retinal detachment (RRD) and its association with morphological changes in the macula. METHODS: This prospective study included 20 eyes of 20 patients. Before surgery and 1, 3, 6, and 12 months after surgery, metamorphopsia measured by M-charts and best-corrected visual acuity (BCVA) and macular microstructures assessed using optical coherence tomography were recorded. RESULTS: Both the vertical and horizontal M-scores improved significantly after SB surgery. BCVA also improved gradually. The mean M-score in the eyes with a continuous external limiting membrane (ELM) was smaller than that in the eyes with a disrupted ELM (P=0.008). Preoperative and postoperative BCVA did not correlate with the mean M-score at any time point. The other studied parameters, namely, the duration of RRD, the height of retinal detachment, central foveal thickness, inner nuclear layer thickness, and continuation of the ellipsoid zone, were also not relevant. CONCLUSIONS: The continuation of the ELM may be a critical factor in determining the severity of metamorphopsia after SB surgery for macula-off RRD.
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Purpose: This retrospective study investigated the patterns and risk factors of progression of myopic traction maculopathy (MTM) of fellow eyes after pars plana vitrectomy (PPV) of primary eyes. Methods: The study population comprised 153 patients with MTM in both myopic eyes who sequentially underwent PPV (2006-2021). Observation periods were from PPV of the primary eye (baseline) to PPV of the fellow (end). MTM was graded based on optical coherence tomography (OCT) images and the ATN (atrophy [A], traction [T], and neovascularization [N]) system. An increase in T grade was considered MTM progression. Results: MTM progressed in 43.8% of fellow eyes during 34.57 ± 34.08 months. The progression of fellow eyes correlated with T grade of primary eyes (P < 0.001). Risk factors for the progression of MTM in fellow eyes were primary eyes in T4-T5, age at baseline <60 years, and fellow eyes with partial posterior vitreous detachment (PVD; P < 0.001, P = 0.042, and P = 0.002, respectively). Fellow eyes in T1/T2 at baseline progressed faster compared with those in T0 (P < 0.001); the annual rate of progression to T3-T5 of the T0 (T1-T2) groups was 9.98% (24.59%). Conclusions: Risk factors for the progression of MTM in fellow eyes included PPV when relatively young, primary eye at high T grade, and partial PVD of the fellow eye. Personalized follow-up for fellow eyes should be based on the severity of MTM of both eyes.