Journal of Ophthalmology最新文献

Inherited retinal dystrophies (IRDs) constitute a heterogeneous group of primarily monogenic orphan diseases caused by mutations in over 300 genes, collectively affecting millions of individuals worldwide with visual impairment. Despite significant advances, the development of gene replacement therapy for IRDs has predominantly focused on single-gene approaches, lacking a unified strategy driven by factors such as global prevalence, disease burden, and feasibility of therapeutic delivery. In this review, we propose a comprehensive protocol integrating multifaceted methodologies to refine the identification of suitable gene therapy candidates. We assessed gene prevalence, transcript size compatibility with vector packaging, and cell-type-specific expression, enabling the prioritization of promising therapeutic targets. Our approach focuses on assessing enzyme-coding genes as prime, more suitable candidates for therapeutic intervention due to their relatively similar replacement mechanism. Our findings provide a framework for identifying additional genes that may benefit from similar translational pipelines. This approach revealed a spectrum of potential candidates, including several underexplored genes with high therapeutic potential. Our findings underscore the necessity of adopting a strategic, data-driven framework to prioritize clinically impactful and scalable gene therapy targets, paving the way for broader and more effective therapeutic applications in the field of IRDs. Trial Registration: ClinicalTrials.gov identifier: NCT01482195, NCT03316560, NCT06333249, NCT06275620, NCT04850118, NCT05926583.

Purpose: High myopia is a feature of several inherited retinal diseases, including X-linked retinitis pigmentosa (XLRP) which is characterized by childhood onset, centripetal photoreceptor degeneration, and rapid progression to blindness by the fourth decade. Mutations in the retinitis pigmentosa GTPase regulator (RPGR) gene cause over 90% of XLRP cases. It presents with a varied clinical phenotype, categorized into the predominant rod-cone, cone-rod, and cone dystrophy. This case-series study examines the clinical characteristics of patients with RPGR-related retinal dystrophy to identify associations with refractive error. Methods: Data collected between October 2023 and April 2024 from retinal imaging, clinical ophthalmic examination, and genetic analysis were retrospectively analyzed. Results: Twenty-four male patients were identified, with a mean age of 30 years (range 7-57). The median (IQR) best-corrected visual acuity was 60 (55-66) letters in the cone-rod/cone phenotype and 65 (49-73) letters in the rod-cone phenotype. High axial myopia showed preponderance in cone-dominated degenerations. Estimated mean refractive error was -7.92DS (95% CI: [-11.39, -4.44]) in the cone-rod phenotype and -3.52DS (95% CI: [-5.87, -1.17]) in the rod-cone phenotype, adjusting for age and genetic mutation. This difference between phenotype was significant (p=0.041). In a subanalysis, no significant association was found between refractive error and nucleotide position. Evaluation of disease progression found that all patients with a fast-progressing, rod-cone phenotype had high myopia. Conversely, one patient who presented with a slow-progressing, cone-rod phenotype did not have high myopia. Conclusions: Refractive trends in this cohort suggest that cone photoreceptor degeneration occurring during early childhood is associated with high myopia. Image degradation primarily due to cone photoreceptor dysfunction may act as a stimulus to drive myopia development in early childhood. These observations advocate for the earlier treatment of myopia in cone-dominated RPGR-related retinal dystrophy to preserve retinal function and minimize the risks of retinal gene therapy surgery for patients enrolling in clinical trials. Trial Registration: ClinicalTrials.gov identifier: NCT03116113.

Patients with intellectual disabilities (IDs) have been associated with having a higher frequency of ocular pathologies, including glaucoma. However, despite this association, there is little guidance in the literature pertaining to patient management or outcomes after glaucoma surgery. Literature review of the management of surgical eye conditions in ID patients provides historical considerations in treatment of these patients and educates the community of providers caring for this population. Using these data, we propose a novel set of criteria for selecting which patients with ID and glaucoma should be offered glaucoma surgery.

Purpose: Keratoconus (KC) can lead to severe vision loss, impacting daily life. The etiology of KC is not yet clear, and early diagnosis and treatment are crucial for prognosis. This study aimed to explore basement membrane (BM)-related gene signatures for the diagnosis and therapy of KC and provide novel insights into its pathogenesis. Methods: Based on the public datasets GSE112155 and GSE151631 in the GEO database, we obtained the differentially expressed genes (DEGs) of KC and downloaded BM-related genes based on the GeneCards database. Through a combination of bioinformatics methods, primarily weighted gene coexpression network analysis (WGCNA) and machine learning such as random forest (RF) and support vector machine (SVM), BM-related genes were identified as biomarkers for KC diagnosis. Subsequently, we further validated these findings using unsupervised clustering analysis, nomogram, and ROC curve analysis. Results: Through the analysis of two KC-related datasets, 227 DEGs were screened out and intersected with BM-related genes to obtain 195 intersecting genes. By applying WGCNA and two machine learning algorithms, we identified four key genes, namely, CRY2, RNF19B, PPP1R18, and PFKFB3. These genes were significantly expressed in the normal control group. According to the ROC analysis, all four genes demonstrated excellent diagnostic performance in internal validation, with AUC values all exceeding 0.8. In external validation, CRY2, RNF19B, and PPP1R18 showed good predictive performance, each with AUC values greater than 0.6. Unsupervised clustering and nomogram also supported the good diagnostic capabilities of these genes. In addition, unsupervised clustering analysis also indicated that these four genes were mainly distributed in subtype A of KC. Immune infiltration analysis and functional enrichment analysis further suggested that immune inflammation, metabolism, and apoptosis were also involved in KC. Conclusion: Using bioinformatics analysis, we found three novel hub genes, CRY2, RNF19B, and PPP1R18, which are beneficial for the diagnosis and therapy of KC.

Background: Abnormalities in the retina have a profound impact on vision, and accurate diagnosis and monitoring are essential for effective clinical management. Retinal hyperreflective foci (HRF), lesions, or dots, identified using optical coherence tomography (OCT), are observed in both animals and humans and have been associated with several ocular conditions, including diabetic retinopathy (DR), age-related macular degeneration (AMD), and retinal vascular diseases. Methods: To evaluate the relevance of retinal HRF, we conducted a comprehensive scoping review of the literature published up to July 2024 including in the discussion key papers that emerged in 2025. Our search spanned electronic databases utilizing carefully identified search terms related to HRF and OCT within the last six years. We excluded publications on HRF outside the retina, treatments, non-peer-reviewed content, duplicates, studies older than 6 years, and those not focused on AMD, DR, or glaucoma. Results: A total of 141,085 records were initially identified from various databases and further refined based on keywords and content relevance. Finally, 42 reports meeting the criteria were retained for in-depth analysis. HRF were observed mainly in OCT scans of the AMD retina, as well as in DR and, to a lesser extent, in other retinopathies and interestingly in glaucoma. In AMD, HRF are described as a marker for disease progression, often associated with a compromised photoreceptor structure. In DR, HRF indicated issues such as abnormal blood vessels and cellular changes linked to microglia activation. In glaucoma, HRF may reflect microglia and macrophage activation. Most publications concur that the presence of HRF correlates with inflammatory processes and aging in the retina, with early appearance of small HRF serving as a biomarker for ocular disease. The size of HRF and their location were consistent with disease presentation. Conclusion: There is an agreement that HRF of less than 30 μm are biomarkers of inflammation in the retina despite having variable intraretinal locations. HRF resulting from the effect of aging can be discerned from AMD based on their quantity and appearance. The results show the importance of HRF as a biomarker of ocular disease and confirm that HRF are indicative of an inflammatory eye disorder.

Purpose: Objective: We aimed to investigate the attitudes of ophthalmologists toward the excessive amount of waste generated during modern cataract surgery practices. Methods: Survey study and a prospective, cross-sectional, descriptive study. An online questionnaire consisting of 23 questions was directed to ophthalmologists practicing in Erzurum Province and its surroundings. Duplicate responses were prevented by allowing only one submission to the survey. Participants were asked to complete the questionnaire only if they performed cataract surgery. Results: The study included 102 ophthalmologists through an online survey. Approximately 43% of the participants performed between 200-500 cataract surgeries per year. 90% of the respondents believed that operating room waste was excessive and should be reduced. Among the drivers of waste/garbage generation in the study, the most common response (78%) was the widely recognized safety benefits of disposables. Again, when asked about the main drivers for using disposable instruments in ophthalmic surgery, the most common response was reduced liability (77%). 80% of respondents said that device and supply manufacturers should consider the environmental/carbon footprint in product design. When asked to what extent it reduces your willingness to use a material or medication in more than one patient, the highest preferred answer was the risk of endophthalmitis, while the least preferred answer was decreased efficiency. Conclusion: In conclusion, most ophthalmologists agree that a lot of waste is generated during surgery and that more widespread use of sterilizable materials rather than disposables could reduce waste.

Purpose: In clinical practice, some eyes preoperatively diagnosed with "idiopathic epiretinal membranes (iERM)" will be amended to "secondary epiretinal membranes (sERM)" once peripheral retinal hole is detected. This study utilized optical coherence tomography (OCT) images to compare the characteristics between the iERM and sERM due to peripheral retinal hole (PRH). Methods: In this retrospective, cross-sectional study, 635 eyes that had undergone pars plana vitrectomy with membrane peeling were enrolled. A total of 115 eyes (18.1%) detected with peripheral retinal holes were allocated to the sERM-PRH group while the other 520 eyes were to the iERM group. The demographic data and OCT characteristics were compared between the two groups. Besides, all the eyes were evaluated by a double-grading scheme: severity grading of ERM progression into four stages plus anatomical classification into three kinds of part-thickness macular holes associated with ERMs. Results: No significant difference was found in age, gender, symptom duration, axial length, or best-corrected visual acuity between the two groups. There was also no difference concerning the features based on OCT, ranging from central macular thickness, the ratios of the photoreceptor inner/outer segment junction line defect, intraretinal fluid, cotton ball sign, to epiretinal proliferation. However, the native difference in parafoveal thickness between the temporal and nasal quadrants was observed in the iERM group, yet disappeared in the sERM-PRH group. Moreover, eyes between the two groups were distributionally similar in both grading scales. Conclusion: Our results demonstrated that even OCT images could hardly provide effective clues for early differentiating sERM from iERM, which highlighted the necessity of a thorough pre- and intro-operative fundus examination of the peripheral retina for clinicians.

Objective: A bibliometric analysis was performed in the domain of ranibizumab and age-related macular degeneration (AMD) to delineate current trends in international research dynamics and to provide a visual representation of research hotspots and challenges associated with ophthalmic drugs over the past 15 years. This study also evaluates the sustainability of ranibizumab therapy through reduced injection burden, cost-effectiveness compared to alternative treatments, and long-term outcomes that minimize healthcare resource utilization. Method: In this cross-sectional study, bibliometrics analyzed data retrieved and extracted from the Web of Science Core Collection (WOSCC) database to analyze the evolution and thematic trends in the delivery of studies from January 1, 2008, to September 2, 2023, for ranibizumab and AMD studies. A total of 2691 articles on the field were assessed for specific characteristics such as the year of publication, journal, author, institution, country/region, citation, and keywords. Co-authorship analysis, co-occurrence analysis, co-citation analysis, and network visualization were constructed using VOSviewer. Some important subtopics identified by bibliometric characterization were further discussed and reviewed. Results: From 2008 to 2023, the cumulative number of articles published globally increased from 1 to 2,691, with the highest number of articles published in 2020 (255 papers). RETINA THE JOURNAL OF RETINAL AND VITREOUS DISEASES published the most manuscripts (285 papers) and was cited (6496 citations), followed by OPHTHALMOLOGY (193 papers) and GRAEFES ARCHIVE FOR CLINICAL AND EXPERIMENTAL OPHTHALMOLOGY (163 papers). OPHTHALMOLOGY was the most cited (20,865 citations), with the United States (786 papers, 38,014 citations), Univ Sydney (98 papers, 5245 citations), and Kim, Jong Woo (56 papers, 550 citations) being the most productive and influential institutions, countries, and authors, respectively. Five clusters were formed by summarizing the top 100 keywords, which marked the emerging frontier of ranibizumab and AMD-related research. Further discussion of the five clusters of research is to assist the researcher in determining the scope of the research topic and planning the direction of the research. Conclusion: Over the past two decades, there has been a notable increase in the number of publications and citations pertaining to ranibizumab and AMD across various countries, institutions, and authors. This study elucidates current trends, global collaboration patterns, foundational knowledge, research hotspots, and developmental trajectories within the realm of ranibizumab-related AMD research. Key advancements in AMD treatment with ranibizumab over the last 15 years have centered on less frequent injection schedules, extended drug efficacy, and enhanced safety profiles.

Diabetes mellitus is a known risk factor for corneal epithelial defects (CEDs) after pars plana vitrectomy (PPV), but it is unclear if diabetes severity or specific diabetic risk factors are associated with an increased risk of CED. The purpose of this retrospective cohort study was to identify factors associated with CED and healing time in association with diabetes severity in diabetic patients following PPV. The electronic health record database at University of Florida in Gainesville was queried to identify patients who underwent PPV for retinal detachment (RD) between April 2016 and April 2022. Patient charts were reviewed for clinical data including type of diabetes (if present), diabetes duration and severity, and associated diabetic comorbidities. The main outcome measures included presence of a CED within one month postoperatively, treatment of CED if present, and CED healing time. A total of 637 patients were analyzed, with a total of 243 eyes (26.5%) that belonged to diabetic patients. The diabetic patients were further separated into a proliferative diabetic retinopathy (PDR) group and a nonproliferative diabetic retinopathy (NPDR) group. Diabetes was associated with the development of an initial CED (p=0.040), consistent with existing literature. There was not a significant difference in CED risk when comparing NPDR and PDR patients, although PDR patients tended to have more severe long-term outcomes with persistent corneal epithelial defects (PCEDs). This suggests that PDR patients may still require closer monitoring and earlier intervention for postoperative CED following PPV, as compared to the NPDR patient population.

Background: To elucidate the epidemiologic and clinical characteristics of pediatric traumatic canalicular lacerations treated at a tertiary hospital and analyze the prognostic factors of influencing functional outcomes. Methods: This retrospective review included all pediatric patients who sustained a primary canalicular laceration at Hebei Eye Hospital between January 1, 2013, and December 31, 2022. Data on patient demographics, mode of injury, and surgical outcomes were collected through detailed chart review. The prognostic factors of affecting functional outcomes were assessed using Fisher's exact test for categorical variables. Results: The study included 89 pediatric patients (66 males and 23 females) with a mean age of 7.26 years. There were 65 patients with lower canalicular lacerations, 19 patients with upper lacerations, and 5 patients with concurrent lacerations. Right eye damage was observed in 51 patients and 38 with damage to the left eye. The most common cause of injury was scratches caused by sharp objects (52.8%), followed by electric bicycle accidents (18.0%), falls (18.0%), and dog bites (7.9%). Statistically significant prognostic factors for functional outcomes included the location of the laceration (p=0.009), mode of injury (p=0.045), and the time interval from injury to surgical repair (p=0.032). Conclusions: In this study, key prognostic factors for pediatric canalicular lacerations included laceration location, injury mechanism, and delay in surgical repair. Variables such as age, gender, affected side, stent type, and removal timing did not significantly impact outcomes. Increasing hazard awareness of the caregiver, enhancing public education, and implementing preventive measures to reduce injury incidence are crucial for prevention.