Abstract:AIM: To determine whether chronic smoking affects fundus blood flow density using optical coherence tomography angiography (OCTA) based on artificial intelligence (AI). METHODS: All participants underwent a comprehensive ophthalmological examination in this study. The subjects were categorized into two groups: control and smoker. Fundus data obtained through the novel OCTA device were compared. RESULTS: Utilizing deep learning denoising techniques removed background noise and smoothed vessel surfaces. OCTA showed a significant decrease in fundus blood flow density after AI-based denoising on the right eyes of 36 smokers (36 males, average age 44.17±9.85y) and age- and sex-matched participants who never smoked. The thickness of the retina in both control and smoker groups failed to show any statistically significant differences. Smoking was associated with decreased blood flow density in the macula and the optic disk. CONCLUSION: Utilizing AI-based denoising to improve the sensitivity of OCTA images can be highly beneficial.

Abstract:AIM: To propose a novel glaucoma surgery for rebalancing translaminar pressure difference. METHODS: Three non-human primates with normal eyes and two with laser-induced glaucoma underwent the novel surgical procedure. Cannulation of the subarachnoid space was performed after completion of routine vitrectomy steps. An XEN 45 implant was inserted into the created puncture to communicate between the vitreous body and subarachnoid space. Intraocular pressure (IOP), fundus photography, and spectral-domain optical coherence tomography were assessed at baseline and regular intervals during follow-up. RESULTS: All operated eyes showed IOP reduction in the first postoperative month. Two (2/3) normal eyes and one (1/2) glaucomatous eye maintained lower IOP until 18mo after operation. The XEN 45 implant remained positioned through the lamina cribrosa in all normal eyes but was not detected in two glaucomatous eyes. Complications observed in this study included retinal vascular bleeding in 1/3 normal eyes and XEN implant dislocation in all 2 glaucomatous eyes. CONCLUSION: Subarachnoid space cannulation and mini-shunt implantation may contribute to IOP reduction, possibly by rebalancing translaminar pressure difference and enhancing aqueous humor drainage. The development of a suitable mini-shunt requires further investigation.

Abstract:AIM: To investigate the role of RNA methylation in retinal pigment epithelial (RPE) cells in age-related macular degeneration (AMD). METHODS: RNA methylation-related gene expression profiles of AMD patient and normal control retinal pigment epithelium were evaluated by single-cell transcriptome from 34 samples (11 from normal donors and 23 from AMD patients). The causal relationship between RNA methylation dysfunction and AMD was analyzed by summary-data-based Mendelian randomization (SMR) using AMD GWAS data and multi-omics quantitative trait loci (QTL), including expression QTLs (eQTLs), protein QTLs (pQTLs), splicing QTLs (sQTLs), and m6A-QTLs (mQTLs). Additionally, machine learning models were applied to validate the causal association between RNA methylation dysfunction and AMD using Bulk RNA sequencing data from 31 normal donors and 37 AMD patients. RESULTS: The single-cell transcriptome data analysis revealed massive dysregulation of RNA methylation-related gene expression in the RPE of AMD patients. SMR revealed causal associations between key RNA methylation regulators (METTL3, NSUN6, and MRM1, etc.) and AMD onset. Machine learning models further validated these findings and demonstrated a high accuracy of AMD risk prediction by using the above-identified RNA methylation-related genes: METTL3, NSUN6, and MRM1. Furthermore, METTL3 and NSUN6 were found to have a protective effect, while MRM1 was associated with an increased risk of AMD. CONCLUSION: The results reveal the implication of dysregulation of RNA methylation-related gene expression in the RPE of AMD patients and further demonstrated a causal association between RNA methylation-related genes (METTL3, NSUN6, and MRM1) and AMD. These findings highlight the importance of RNA methylation in the pathogenesis of AMD and offer potential biomarkers and therapeutic targets for AMD management.

Abstract:AIM: To investigate cuproptosis-related molecular and immune infiltration in age-related macular degeneration (AMD) development and establish a predictive model. METHODS: The expression profiles of cuproptosis-related genes and immune signature in AMD based on the microarray dataset GSE29801 were analyzed. A total of 142 AMD samples were used to identify the cuproptosis-related differentially expressed genes (Cu-DEGs), together with the immune cell infiltration. To further refine the list of potential genes for AMD diagnosis, three machine learning techniques were used, and an external dataset were applied for confirming the accuracy of the predictive performance. Reverse transcription polymerase chain reaction (RT-PCR) were also performed to examine the level of mRNA of hub genes. The activated immune responses and Cu-DEGs were assessed between AMD and controls. RESULTS: Six genes, including ATP7A, DBT, VEGFA, UBE2D3, CP, SLC31A1, were screened as cuproptosis-signature in AMD via three machine learning methods. Next, SLC31A1 and VEGFA was selected as hub genes by performance evaluation in an external dataset GSE160011, further analysis showed that SLC31A1 and VEGFA were associated with pathways related to immune signaling and immune function, which were then observed in relation to infiltrating immune cells. Finally, the mRNA expression levels of SLC31A1 and VEGFA were significantly higher in laser induced choroidal neovascularization (CNV) group than in control group detected by RT-PCR. CONCLUSION: In this study, the possible relationship between cuproptosis and AMD is expounded systematically. A predictive model is developed to assess the risk of cuproptosis-related genes and their clinical prognostic value in AMD patients.

Abstract:AIM: To examine carcinoma ex pleomorphic adenoma (CXPA) and its development to provide information for its clinical assessment and prognosis. METHODS: The clinical data of 26 patients with pathologically diagnosed CXPA were included for analysis. The patients’ medical histories and data (e.g., gender, age, eye laterality, clinical manifestations, pathologic and immunohistochemical indices, treatments, and prognosis) were recorded. RESULTS: The average age of the 26 patients was 59.6±15.7y. There was no significant difference in the gender distribution. The incidence of CXPA bone destruction was approximately 57.7%, and the incidence of optic nerve involvement and extraocular muscle involvement was approximately 15.4% and 19.2%, respectively. The most common pathological type was adenocarcinoma (34.6%), followed by ductal carcinoma (26.9%). Five patients had recurrence or metastasis (19.2%). The 5-year recurrence-free survival rate was 59.0%. There were no significant differences in survival rates among patients with different pathologic types and stages (P>0.05). Bone destruction, nerve invasion, and peripheral tissue invasion did not significantly affect survival rate (P>0.05). Surgery combined with 125I radiation therapy leads to a better survival prognosis (P<0.05). CONCLUSION: CXPA has a variety of pathologic classifications, with characteristics of bone destruction and peripheral tissue invasion. Surgery combined with 125I endoradiotherapy is a preferable treatment option. However, long-term follow-up and close observation for recurrence or metastasis should be performed.

Abstract:AIM: To assess whether the implantation of a posterior chamber phakic intraocular lens produces changes in optical coherence tomography (OCT) measurements of macular thickness (MT) and two parameters that define the structure of the optic nerve, the peripapillary nerve fiber layer (RNFL) and the Bruch’s membrane opening-minimum rim width (BMO-MRW). METHODS: This nonrandomized prospective pre-post study included 86 eyes of 48 patients (age, 20-47y; axial length: 23.10-28.95 mm) scheduled for myopia or myopic astigmatism correction with implantation of the implantable collamer lens (ICL). Eyes with glaucoma or any other ocular disease that could alter OCT results were excluded. RNFL, BMO-MRW and MT were measured preoperatively, and at 1 and 6mo after surgery using spectral-domain OCT. Changes between preoperative and postoperative values were evaluated. RESULTS: There was a significant increase in BMO-MRW at 1mo (mean change: 3.48±15.07 µm, P=0.041). No significant changes were found during the rest of follow-up (1-6mo postop., P=0.623). There was also a significant increase in RNFL thickness at 1mo after surgery (1.45±2.18 µm, P<0.001), but with a significant reduction from 1 to 6mo postoperatively (P=0.002). Regarding MT, it increased significantly at 1mo (2.46±3.76 µm, P<0.001), with a significant decrease afterwards (P=0.048). Measurements of the three parameters at 6mo were slightly superior to preoperative values (P<0.01). CONCLUSION: Minimal changes are induced in BMO-MRW, RNFL and MT after ICL implantation in healthy eyes, confirming the safety of the surgical procedure regarding the structure of the optic nerve head and the macula, and indicating that this phakic intraocular lens seems to have a slight impact on OCT measurements.

Abstract:AIM: To present a case series of rapid-onset neovascular glaucoma (NVG) accompanied by vitreous haemorrhage (VH) following cataract surgery in diabetic patients, and to evaluate the efficacy of pars plana vitrectomy (PPV) combined with Ahmed glaucoma valve (AGV) implantation. METHODS: This is a retrospective, single-center, consecutive case series. All patients underwent 23-gauge PPV with AGV implantation 2–3d after intravitreal ranibizumab injection (IVR). The minimum postoperative follow-up period lasted 12mo. The primary outcome measures included best-corrected visual acuity (BCVA), intraocular pressure (IOP), and topical hypotensive medications. RESULTS: Fifteen diabetic patients (age, 46–81y) with rapid-onset NVG and VH following uncomplicated phacoemulsification were included. The median time to the initial NVG diagnosis following cataract surgery was within 4wk. After PPV combined with AGV implantation, the mean BCVA (logMAR) improved from 1.9 (range: 1.0 to 2.6) preoperatively to 1.2 (range: 0.2 to 2.6) at the final follow-up. Baseline BCVA and the presence of diabetic nephropathy (DN) were significantly associated with the final BCVA in the multiple regression model. The mean postoperative IOP at all follow-up visits was significantly reduced compared to baseline. At the final follow-up, 9 patients required one or two topical ocular hypotensive medications, while the other 6 needed not. Success was achieved in 87%, and the reoperation rate was 20%. The majority of NVG cases (9/15) were primarily attributed to the rapid progression of proliferative diabetic retinopathy. However, a notable subset (6 eyes) was complicated retinal vein occlusion or carotid artery occlusion. CONCLUSION: PPV combined with AGV implantation after adjuvant IVR for rapid-onset NVG with VH following diabetic cataract surgery is one of the safe and effective treatments. Baseline BCVA and preexisting DN may be potential indicators for visual outcomes.

Abstract:AIM: To evaluate the one-year clinical outcomes of a novel canaloplasty device used in combination with cataract extraction (CE) in patients with mild to severe open angle glaucoma (OAG). METHODS: This study reviewed patients diagnosed with mild to severe OAG, who underwent canaloplasty with the STREAMLINE® Surgical System combined with CE. The primary outcome was surgical success, defined as achieving ≥20% intraocular pressure (IOP) reduction and/or a reduction of ≥1 glaucoma medication compared to baseline. Secondary outcomes included mean IOP, average number of glaucoma medications, and best-corrected distance visual acuity (BCDVA). Data was collected preoperatively and at multiple postoperative time points up to one year. RESULTS: A total of 68 eyes of 47 patients were included with mean age was 73.1±7.0y and 60% were females. Surgical success at one year was achieved in 68.8% of eyes, with 67.6% success in mild, 80.0% in moderate, and 66.7% in severe OAG cases. IOP was significantly reduced from a baseline of 16.1±0.5 to 14.7±0.4 mm Hg at one year (P=0.0004). The number of medications decreased significantly in all eyes from a baseline of 1.2±0.1 to 0.6±0.1 at one year (P<0.0001). When stratified by glaucoma severity, only the mild group experienced a statistically significant decrease from a baseline of 1.1±0.1 to 0.4±0.1 (P<0.0001). BCDVA improved significantly from baseline to one year. No sight-threatening complications were reported. CONCLUSION: Canaloplasty using the STREAMLINE® surgical system combined with CE effectively reduces IOP at one year in mild to severe OAG with minimal complications. IOP lowering efficacy, reduction in IOP lowering medications, and safety in moderate to severe OAG require further study.

Abstract:AIM: To report the 24mo outcomes of vascular endothelial growth factor (VEGF) inhibitors for myopic choroidal neovascularization (mCNV) in routine clinical practice and simultaneously evaluated the real-world safety. METHODS: The patients who received intravitreal injections of VEGF inhibitors of either ranibizumab (0.5 mg) or conbercept (0.5 mg) for mCNV were analyzed from 1 January 2017 to 1 January 2022. The primary outcome variables were mean change in best-corrected visual acuity (BCVA) and central macular thickness (CMT) changes. The secondary outcome variables included IOP changes, the period of mCNV re-treatment, and ocular adverse events. RESULTS: Totally 83 patients aged 56.40±15.36y with axial length 29.67±2.09 mm were included. In visual acuity, the mean logMAR BCVA at baseline was 0.81±0.43. After the initial improvement at 1, 3, and 6mo (P<0.05), from month 12 onwards, no statistical difference compared to baseline was found. The mean CMT from 1mo onwards had a statistically significant decrease compared with baseline CMT (P<0.05). The regression model showed better baseline BCVA and thicker baseline CMT, significantly associated with the final outcomes. In univariate analysis, choosing 3+pro re nata (PRN) as the initial injection treatment regimen was associated with better BCVA at 24mo [hazard ratio (HR)=-0.65, 95%CI: -1.23, -0.07, P=0.048]. However, the difference was not significant in multivariate analysis (HR=-0.59, 95%CI: -1.21, 0.03, P=0.089). Regarding mCNV recurrence, the mean period (P=0.725) and the proportion of mCNV reactivation (P=1.00) were similar between ranibizumab and conbercept. Kaplan-Meier plot also analyzed that the median time of re-injection was not significantly different among gender, drug, and initial injection treatment regimen. No systemic adverse events related to the therapy were observed. CONCLUSION: BCVA gains achieved by the end of our study maintain generally sustained at the 24-mo follow-up. The findings also indicate that ranibizumab and conbercept demonstrate comparable efficacy and safety profiles. Additionally, intravitreal anti-VEGF therapy using 1+PRN regimen, offers certain advantages in both efficacy and cost-effectiveness.

Abstract:AIM: To investigate the outcomes and prognosis of macular epiretinal membrane (ERM) after pars plana vitrectomy (PPV) in patients with high myopia (HM), focusing on the optimal timing of surgery and its impact on prognosis. METHODS: The clinical data of 50 eyes from 49 patients diagnosed with ERM, who were highly myopic and underwent PPV were retrospectively analyzed. The patients with ERM were classified into five groups based on the characteristics associated with different levels of myopic traction maculopathy. Group 1: Simple ERM without complex vertical and tangential direction traction on retina on optical coherence tomography (OCT) image; Group 2: ERM with obvious macular foveal schisis, without macular hole (MH); Group 3: ERM with inner lamellar MH, with or without macular foveal schisis; Group 4: ERM with outer lamellar MH, with or without foveal retinal detachment (RD); Group 5: ERM with full-thickness MH. Baseline characteristics, changes in best corrected visual acuity (BCVA) before and after surgery, and anatomical characteristics through spectral domain OCT were compared. RESULTS: The 50 eyes were followed for 6mo, with an average age of 58.66y and an average axial length (AL) of 28.69 mm. Among the five groups, postoperative logMAR BCVA improved (P<0.05). Group 1 had better mean BCVA at baseline (0.59±0.36) and at 6mo postoperatively (0.16±0.22) compared to the other groups, while Group 5 had worse mean BCVA at baseline (1.68±0.45) and at 6mo postoperatively (1.27±0.64). There were no statistically significant differences in sex, age or AL between the groups (P>0.05). OCT showed that Groups 4 and 5 exhibited poorer macular anatomy compared to the other three groups, as evidenced by lower rates of central retinal reattachment (64.3% in Group 4, 86.7% in Group 5) and integrity of the inner segment/outer segment of photoreceptor junction (28.6% in Group 4, 26.7% in Group 5). CONCLUSION: PPV is an effective treatment for ERM in patients with HM. All groups showed postoperative improvement in BCVA compared to preoperative levels, demonstrating the necessity of surgical intervention. Early intervention, particularly before the fourth stage of the disease, may lead to better visual outcomes.

Abstract:AIM: To investigate the prevalence and clinical implications of hyperreflective walls (HRW) in foveal cystoid spaces in patients with cystoid macular edema (CME) caused by retinal diseases and noninfectious uveitis (NIU). METHODS: This retrospective cross-sectional study included 443 eyes with CME secondary to diabetic macular edema (DME), retinal vein occlusion (RVO), retinitis pigmentosa (RP), neovascular age-related macular degeneration (nAMD), and NIU. Demographic data, HRW features, and other spectral domain optical coherence tomography (SD-OCT) biomarkers were analyzed. RESULTS: HRW was observed in 40.9% of DME eyes (present, n=77, 38 males, 58.30±12.04y; absent, n=111, 50 males, 55.95±10.56y), 32.5% of RVO eyes (present, n=49, 22 males, 64.53±11.90y; absent, n=102, 42 males, 60.67±11.73y), 31.4% of nAMD eyes (present, n=16, 8 males, 70.13±7.75y; absent, n=35, 13 males, 73.91±9.11y), 57.1% of RP eyes (present, n=12, 4 males, 40.50±12.06y; absent, n=9, 4 males, 44.11±14.32y), and 18.8% of uveitic macular edema (UME) eyes (present, n=6, 3 males, 30.83±16.23y; absent, n=26, 12 males, 43.46±17.58y). HRW was significantly associated with vitreoretinal abnormalities [odds ratio (OR), 2.202; 95% confidence interval (95%CI), 1.342–3.613; P=0.002], hyperreflective foci (OR, 3.33; 95%CI, 1.884–5.883; P<0.001), inner retinal layer disorganization (OR, 1.816; 95%CI, 1.087–3.035; P=0.023), external limiting membrane disruptions (OR, 3.476; 95%CI, 1.839–6.574; P<0.001), and disrupted ellipsoid zone length (OR, 1.001; 95%CI, 1.000–1.002; P=0.04), and a high HRW height in the foveal cystoid spaces (OR, 1.003; 95%CI, 1.001–1.006; P=0.003). CONCLUSION: HRW in foveal cystoid spaces is a common OCT finding in CME and is associated with more severe retinal structural damage and worse visual acuity. HRW may be utilized as a prognostic OCT biomarker for disease severity and treatment response in patients with CME. This study suggests that early detection of HRW and optimization of treatment strategies may improve patient prognosis.

Abstract:AIM: To detect and segregate causative mutations in congenital families with optic nerve hypoplasia (ONH). METHODS: Two unrelated consanguineous Pakistani families with severe ONH, showing features of micropthalmia, nystagmus, corneal opacity, and keratopathy were included. Genetic analysis was carried out by Target Panel Sequencing, and the nucleotide variant was confirmed by Sanger sequencing. In silico analyses were carried out to study the protein order-disorder functions and their effects on messenger ribonucleic acid (mRNA). RESULTS: Target panel sequencing revealed that the afflicted family members carried a novel frameshift mutation (NM_145178.4; c.91del G; p.Gly31Glyfs*55) that ensued in the conservation of an amino acid residue in the bHLH domain of ATOH7 protein. In silico studies predicted that the activity of the ATOH7 gene is probably affected by this mutation, which results in a shortened and non-functional protein. Three-dimensional structural analysis shows that DNA binding may be impacted by amino acid changes from non-polar to positively charged and vice versa (Arg42Pro and Pro18Arg), as well as from positively charged (Arg) to a small polar amino acid (Gly). CONCLUSION: A novel ATOH7 mutation is harmful. This study also emphasizes the potential effects of modified ATOH7 configurations on the stability and functionality of proteins.

Abstract:AIM: To measure abducens nerve palsy patients’ visual angle using real time video-based gaze tracking system. METHODS: This research was a cross-sectional study. The subjects were taken by convenience sampling technique in the Neuro-ophthalmology department at Sardjito General Hospital Yogyakarta, Indonesia, and had met the inclusion and exclusion criteria. The visual angle measurements were performed using an eye tracker with a computer webcam (GENICULA system/Gaze Tracking Artificial Intelligence for Ocular Motor Palsy). The analytical method used was the Mann-Whitney test to compare the visual angle between the abducens nerve palsy group and the healthy eye group. The Wilcoxon test was used to see the significance of differences in visual angle improvement in abducens nerve palsy patients. RESULTS: A total of 39 subjects participated, with a mean age of 46.54±15.67y; 17 were male and 22 were female. The visual angle was 20.88±3.76 in the abducens nerve palsy group (n=39 eyes) and 23.10±2.91 in the normal group (n=39 eyes, P=0.011). The visual angle improvement of abducens nerve palsy before and after cured was statistically significant (P=0.039). CONCLUSION: The real time video-based gaze tracking system is easy to use, efficient, and accurate. A slight decrease in visual angle measurement can be detected using this GENICULA system and therefore it is important for diagnosis slight deviation in abducens nerve palsy.

Abstract:AIM: To investigate the causal relationship between dietary intake and myopia using Mendelian randomization (MR) analysis. METHODS: Genome-wide association study (GWAS) data from the IEU Open GWAS database were utilized to examine associations between myopia and various dietary factors. MR analysis, incorporating both univariable and multivariable approaches, assessed the impact of food intake on myopia risk through five analytical methods, with inverse variance weighted (IVW) serving as the primary reference. Sensitivity analyses, including heterogeneity assessment, horizontal pleiotropy evaluation, and leave-one-out analysis, were conducted to validate the MR findings. RESULTS: Univariable MR analysis identified a causal link between food intake and myopia. Consumption of breaded fish, canned soup, sweet biscuits, and certain fruits correlated with a lower risk of myopia, whereas intake of low-calorie hot chocolate and cereal was associated with an increased risk. Multivariable MR analysis further confirmed that breaded fish consumption exerted a direct protective effect against myopia, particularly when consumed alongside other dietary components. These findings highlight the intricate interplay between specific dietary factors and myopia development, offering valuable insights for further research. CONCLUSION: MR analysis provides evidence supporting a potential causal relationship between breaded fish intake and myopia, underscoring its relevance in targeted myopia prevention strategies.

Abstract:AIM: To assess and rank the efficacy of various non-steroidal anti-inflammatory drugs (NSAIDs) in preventing postoperative macular edema (PME) after cataract surgery. METHODS: A comprehensive search was conducted across PubMed, Embase, Cochrane Library, and Web of Science databases. Randomized controlled trials (RCTs) comparing different NSAIDs and control treatments for the prevention of PME were included. Data from the studies were synthesized using the “gemtc” package in R. Risk of bias was assessed with the Cochrane RoB 2 tool, and heterogeneity was evaluated using the global I2 statistic. Surface under the cumulative ranking curve (SUCRA) values were calculated for each treatment. RESULTS: Of 132 identified records, 9 RCTs met the inclusion criteria. The Network Meta-analysis indicated that nepafenac had the highest efficacy in preventing PME, followed by artificial tear substitute, ketorolac, diclofenac, and bromfenac. The league table comparisons and rankograms corroborated these findings, with nepafenac consistently ranking highest. Heterogeneity analysis yielded high I2 values, indicating substantial variability across studies. CONCLUSION: This Network Meta-analysis suggests that nepafenac is the most effective NSAID for preventing PME following cataract surgery. Given the substantial heterogeneity observed, further high-quality RCTs are required to confirm these findings and explore the sources of variability. Clinicians should consider these results when selecting NSAIDs for PME prophylaxis in cataract surgery patients.

Abstract:AIM: To provide a comprehensive review of the advances in research on diabetes-associated dry eye (DADE), highlighting its pathophysiological mechanisms, risk factors, and demographic characteristics, laying the foundation for further investigation into its pathogenesis and treatment strategies. METHODS: A systemic review of the documents related to DADE had been performed based on the Web of Science database prior to achieving the plain text files of authors, titles, journals, and abstracts which afterwards had been imported into Citespace and VOSviewer software for data cleansing. The visual analysis was implemented from the following aspects: journals’ publications, author and national cooperation, keyword co-occurrence, timeline analysis, and burst detection. RESULTS: The 318 documents in 167 journals had been incorporated with the overall annual citations and annual publications respectively growing significantly since 2014 and 2016. The keyword co-occurrence networks formed 4 clusters, with the representative keywords being dry eye, diabetes mellitus, prevalence, and diabetic retinopathy. Both the timeline map and the burst detection demonstrated that in the exploration of the pathogenesis of DADE, initial research was dedicated to Sjögren’s syndrome, followed by cross-sectional statistical analysis of the pertinent contributing factors of DADE using online databases. Precisely the oxidative stress seemed to surge into the research spotlight presently. The key pathogenic mechanisms of DADE include inflammation, oxidative stress and corneal neuropathy, contributing to the development of dry eye symptoms. CONCLUSION: Age, gender, diabetes duration, and diabetic retinopathy are strongly associated with the development of DADE, but the impact of other systemic factors require further investigation. With high prevalence of dry eye in Asia, valuable resources like the Korea National Health and Nutrition Examination Survey (KNHANES) database offer crucial data for developing risk prediction models for DADE. Building risk prediction models using machine learning algorithms is a promising future research direction, enabling physicians to identify high-risk individuals and implement early interventions.

Abstract:AIM: To comprehensively investigate the current state of research on the application of neurotrophic factors in glaucoma therapy and identify potential research hotspots. METHODS: On September 30, 2023, a literature search was conducted on Scopus using specific keywords related to neurotrophic factors and glaucoma. Of the 918 articles retrieved, 780 met the inclusion criteria. These articles were subsequently analyzed and visualized using Google Sheets, Biblioshiny 3.1, and VosViewer 1.6.18. RESULTS: A total of 780 studies published between 1989 and 2023 were included, and the global publication count showed an upward trend through 2023 (projected to continue rising by 2030). The United States, China, Japan, Italy, and Australia were the most significant contributors to the publication output. Research in this field had been published in 313 journals, spanning categories such as pharmacology and drug development, ophthalmology, genetics and gene therapy, and neuroscience. A total of 2622 authors had contributed to these studies, with the most prolific author publishing 14 articles. The focus of research in this field had evolved sequentially from “glutamate” to “CNTF” and “GDNF”, and finally to “optic nerve injury”. Co-occurrence analysis identified five clusters: glaucoma and ocular health, neuroinflammation in ophthalmology, neuroprotection in ophthalmology, ocular drug delivery, and stem cell therapy. Several areas in this field require further exploration, including the neurophysiological mechanisms underlying glaucoma, ocular drug delivery systems, and the clinical value of specific neurotrophic factors. CONCLUSION: This study systematically reviews global research trends on neurotrophic factors in glaucoma therapy, clarifying the current research status and future directions.

Abstract:AIM: To analyse the research status and explore global trends in retinal vein occlusion (RVO) studies. METHODS: Publications related to RVO from 2004 to 2023 were extracted from the Web of Science Core Collection (WoSCC). Variables including the number of publications, as well as countries, organizations, authors, journals, references and keywords were analysed using Bibliometrix-BilioShiny. Data visualization was performed using VOSviewer and CiteSpace. RESULTS: A total of 4848 publications were retrieved, and generally, the number of publications showed an overall increasing trend with slight fluctuations over the past 20y. The country with the most publications was the United States. The journal with the most publications was Retina, and the most cited journal was Ophthalmology. The most prolific organization was the University of California, Los Angeles. The most productive author was Noma H, and the most cited author was Campochiaro PA. The top co-cited references mainly focused on the prevalence of RVO and the therapies used in clinical trials. According to the co-occurrence analysis, the keywords formed 3 clusters: 1) risk factors and pathogenesis of RVO, 2) treatments of RVO, and 3) imaging diagnosis of RVO. Anti-vascular endothelial growth factor (VEGF) treatments and artificial intelligence have recently become popular research topics. CONCLUSION: Bibliometric analysis of the research status and trends of RVO could provide researchers and clinicians with valuable insights for further collaboration, future research directions, and clinical practice.

Abstract:The phenotypes of the adenine-to-guanine transition at position 3243 of mitochondrial DNA (m.3243A>G) are highly variable, with different symptoms observed in different patients. These include mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes (MELAS); maternally inherited diabetes and deafness syndrome (MIDD); other syndromic conditions; or non-syndromic mitochondrial disorders. Renal involvement associated with this mutation generally manifests as subnephrotic proteinuria, progressive deterioration of kidney function, and increased morbidity. The retinopathies linked to the m.3243A>G mutation have heterogeneous presentations, characterized by variable degrees of retinal pigment epithelium (RPE) atrophy and hyperpigmentation at the posterior pole. As a severe phenotype of the m.3243A>G mutation, MELAS combined with focal and segmental glomerulosclerosis (FSGS) is rare. We herein firstly reported in detail the ophthalmic manifestations of a patient with this condition. Additionally, we reviewed the literature on fundus, ophthalmic electrophysiology, and optical coherence tomography (OCT) findings related to the m.3243A>G mutation.

Abstract:Multiple evanescent white dot syndrome (MEWDS) is an inflammatory fundus disease primarily affecting the outer retina. It is characterized by transient yellow-white dots on the outer retina. Although the exact pathogenesis remains unclear, the progress in multimodal imaging (MMI) has enhanced our understanding of MEWDS. Most cases of MEWDS are idiopathic, lacking a definite cause, and can spontaneously recover; these are what we term classic MEWDS. Consequently, MEWDS is often referred to as the “common cold of the retina”. Simultaneously, patients with other disorders may present with varying degrees of manifestations similar to MEWDS. The resemblance in clinical or imaging findings can lead to misdiagnosis and inappropriate treatment. These MEWDS - like presentations are actually caused by other systemic or ocular disorders with diverse mechanisms. Thus, they differ from classic MEWDS in certain aspects. Using the keywords “MEWDS-like” and “Secondary MEWDS”, we searched for all relevant studies published in the PubMed database from January 2021 to January 2024. Subsequently, we retrospectively summarized the clinical and imaging characteristics of MEWDS, along with the manifestations in other diseases that resembled those of MEWDS, and compared classic MEWDS with these similar presentations. Based on our review, we classified such similar presentations under other conditions into two categories and summarized their features for differential diagnosis. We recommend paying close attention to patients suspected of having MEWDS, as there may be more serious systemic or ocular disorders that require prompt treatment.

Abstract:ChatGPT technology based on large language models (LLM) shows great potential in improving the quality of medical care, assisting clinical decision making and optimizing patient communication. The role of ChatGPT in ophthalmology is still in its infancy. This review aims to explore the application prospect of ChatGPT in ophthalmology. Relevant literature was reviewed and analyzed, and the application prospects of LLM represented by ChatGPT in ophthalmology were summarized, including clinical assisted diagnosis, patient education and communication, history collection and text writing, clinical research, and medical education, etc. At the same time, the challenges and solutions faced by ChatGPT in ophthalmology were pointed out. Its safety, efficacy and ethics remain controversial in practical applications. Therefore, it is necessary to strengthen the supervision and research on its application to ensure safety and effectiveness. In the future, with the development of technology, ChatGPT is expected to play a greater role in ophthalmology and enhance the medical experience.

Abstract:AIM: To evaluate visual outcomes of pars plana vitrectomy (PPV) combined with tissue plasminogen activator (tPA)-induced clot lysis and pneumatic displacement for submacular hemorrhage (SMH) in a cohort of closed-globe trauma patients. METHODS: A retrospective, multicenter interventional case series involving 7 eyes of 7 patients who underwent PPV with subretinal tPA administration for SMH secondary to closed-globe injury were conducted. The primary outcome measure was the change in Snellen visual acuity. RESULTS: The mean age of patients was 32y (range: 21-51y), with a mean follow-up duration of 4.6mo (range: 1.1-14.9mo). The average best-corrected visual acuity (BCVA) was 20/1020 at baseline and 20/114 at the final visit, respectively (P=0.025). Preoperative BCVA was not a significant predictor of final BCVA (r=0.102, P=0.827). Final BCVA did not differ significantly between patients who underwent PPV within 14d of symptom onset and those who underwent surgery after 14d (P=0.57). All eyes received SF6 or C3F8 gas tamponade. CONCLUSION: Surgical intervention involving tPA-mediated clot lysis and pneumatic displacement may yield visual benefits in trauma-induced SMH without underlying retinal vascular disease; however, larger prospective studies are warranted to confirm these findings.

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