Benchmarking four large language models' performance of addressing Chinese patients' inquiries about dry eye disease: A two-phase study.

Purpose: To evaluate the performance of four large language models (LLMs)-GPT-4, PaLM 2, Qwen, and Baichuan 2-in generating responses to inquiries from Chinese patients about dry eye disease (DED). Design: Two-phase study, including a cross-sectional test in the first phase and a real-world clinical assessment in the second phase. Subjects: Eight board-certified ophthalmologists and 46 patients with DED. Methods: The chatbots' responses to Chinese patients' inquiries about DED were assessed by the evaluation. In the first phase, six senior ophthalmologists subjectively rated the chatbots' responses using a 5-point Likert scale across five domains: correctness, completeness, readability, helpfulness, and safety. Objective readability analysis was performed using a Chinese readability analysis platform. In the second phase, 46 representative patients with DED asked the two language models (GPT-4 and Baichuan 2) that performed best in the in the first phase questions and then rated the answers for satisfaction and readability. Two senior ophthalmologists then assessed the responses across the five domains. Main outcome measures: Subjective scores for the five domains and objective readability scores in the first phase. The patient satisfaction, readability scores, and subjective scores for the five-domains in the second phase. Results: In the first phase, GPT-4 exhibited superior performance across the five domains (correctness: 4.47; completeness: 4.39; readability: 4.47; helpfulness: 4.49; safety: 4.47, p < 0.05). However, the readability analysis revealed that GPT-4's responses were highly complex, with an average score of 12.86 (p < 0.05) compared to scores of 10.87, 11.53, and 11.26 for Qwen, Baichuan 2, and PaLM 2, respectively. In the second phase, as shown by the scores for the five domains, both GPT-4 and Baichuan 2 were adept in answering questions posed by patients with DED. However, the completeness of Baichuan 2's responses was relatively poor (4.04 vs. 4.48 for GPT-4, p < 0.05). Nevertheless, Baichuan 2's recommendations more comprehensible than those of GPT-4 (patient readability: 3.91 vs. 4.61, p < 0.05; ophthalmologist readability: 2.67 vs. 4.33). Conclusions: The findings underscore the potential of LLMs, particularly that of GPT-4 and Baichuan 2, in delivering accurate and comprehensive responses to questions from Chinese patients about DED.

Primary congenital glaucoma: We are always on the way.

Primary congenital glaucoma (PCG), a developmental glaucoma occurring due to angle anomaly, earns growing concerns among ophthalmologists for its vision-damaging attribute. The incidence of PCG varies among races and geographic regions and is mostly genetically associated. Theories have been posed in attempt to address the etiology of this congenital maldevelopment and in the meanwhile providing evidence for feasibility of PCG surgeries. In regard to the clinical aspects of this entity, both the clinical characteristics and general principals of management are introduced, with angle surgeries highlighted for clarifying details including their success rates, key points for a successful surgical intervention, postoperative management, and follow-up strategies. Taking patients' vision-associated quality of life into consideration, we stressed that further perceptual learning and low vision rehabilitation are momentous. However, much has yet to be elucidated in respect of the truly comprehensive pathogenesis underneath as well as means by which clinical outcomes of PCG can be further improved. We are now looking forward to innovative therapeutic approaches like gene therapy in specific genes in the future, with the hope of improving their life-long visual quality in those young patients.

MicroRNA-146a-5p protects retinal ganglion cells through reducing neuroinflammation in experimental glaucoma.

Neuroinflammation plays important roles in retinal ganglion cell (RGC) degeneration in glaucoma. MicroRNA-146 (miR-146) has been shown to regulate inflammatory response in neurodegenerative diseases. In this study, whether and how miR-146 could affect RGC injury in chronic ocular hypertension (COH) experimental glaucoma were investigated. We showed that in the members of miR-146 family only miR-146a-5p expression was upregulated in COH retinas. The upregulation of miR-146a-5p was observed in the activated microglia and Müller cells both in primary cultured conditions and in COH retinas, but mainly occurred in microglia. Overexpression of miR-146a-5p in COH retinas reduced the levels pro-inflammatory cytokines and upregulated the levels of anti-inflammatory cytokines, which were further confirmed in the activated primary cultured microglia. Transfection of miR-146a-5p mimic increased the percentage of anti-inflammatory phenotype in the activated BV2 microglia, while transfection of miR-146a-5p inhibitor resulted in the opposite effects. Transfection of miR-146a-5p mimic/agomir inhibited the levels of interleukin-1 receptor associated kinase (IRAK1) and TNF receptor associated factor 6 (TRAF6) and phosphorylated NF-κB subunit p65. Dual luciferase reporter gene assay confirmed that miR-146a-5p could directly target IRAK1 and TRAF6. Moreover, downregulation of IRAK1 and TRAF6 by siRNA techniques or blocking NF-κB by SN50 in cultured microglia reversed the miR-146a-5p inhibitor-induced changes of inflammatory cytokines. In COH retinas, overexpression of miR-146a-5p reduced RGC apoptosis, increased RGC survival, and partially rescued the amplitudes of photopic negative response. Our results demonstrate that overexpression of miR-146a-5p attenuates RGC injury in glaucoma by reducing neuroinflammation through downregulating IRAK1/TRAF6/NF-κB signaling pathway in microglia.

The association between airborne particulate matter (PM2.5) exposure level and primary open-angle glaucoma.

The eye is vulnerable to the adverse effects of air pollution. Previous experimental study found that fine particulate matter (PM2.5) had a direct toxic effect on intraocular tissues. However, clinical evidence for the impact of air pollutants exposure on functional and structural changes in glaucoma remains scarce. A total of 120 patients with primary open-angle glaucoma (POAG) who met the inclusion criteria were included in this retrospective study. The standardized ophthalmic examination, such as intraocular pressure (IOP), visual field, optical coherence tomography, and comprehensive physical examination, were performed. The air pollution data, including PM2.5 concentration and air quality index (AQI), were collected. PM2.5 and AQI for the day of the medical examination, as well as one month, and three months before the medical examination date, were investigated. In our results, higher average exposure levels for one-month and three-month, were associated with increased IOP (r=0.229, P=0.013; r=0.204, P=0.028, respectively) and decreased visual field mean sensitivity (MS) (r=-0.212, P=0.037; r=-0.305, P=0.002, respectively). PM2.5 concentrations for the day of the medical examination was not significantly associated with ocular parameters. In multiple linear regression analysis adjusted for demographic and clinical factors, higher PM2.5 exposure for one month was associated with elevated IOP (P=0.040, ß=0.173, 95 %CI=0.008-0.337). We also found an association between PM2.5 and MS (one-month exposure: ß=-0.160, P=0.029; three-month exposure: ß=-0.238, P=0.002). The logistic regression analysis found that three-month average PM2.5 exposure level was significantly associated with the disease severity (ß=0.043, P=0.025, 95 %CI=1.005-1.084). In conclusion, this study is the first to investigate the relationship between air pollution and detailed ocular parameters of POAG patients in Shanghai over a three-year period, and to explore the effects of different exposure times of PM2.5 on glaucoma. This study found that PM2.5 exposure was correlated with elevated IOP and decreased MS. The one-month PM2.5 exposure level had the most significant effects on IOP. The three-month PM2.5 exposure level was an independent risk factor for POAG severity. Current evidence suggests there may be an association between PM2.5 exposure and POAG.

Sustained release of brimonidine from conjunctival sac insert to reduce intraocular pressure for glaucoma treatment.

BACKGROUND: Glaucoma is one of the major irreversible blinding eye diseases in the world. Reducing intraocular pressure (IOP) is the primary treatment option, and taking eye drops daily is the common method. However, short drug duration and poor bioavailability of eye drops may lead to unsatisfied therapeutic effects and inadequate patient compliance. METHODS: A brimonidine-loaded silicone rubber insert (BRI@SR@PT) was prepared by loading brimonidine into a surface-modified silicone rubber ring, followed by polydopamine/thermoplastic polyurethane coatings. The physical properties, in vitro cytocompatibility and drug release of BRI@SR@PT were investigated. The BRI@SR@PT was administrated in the conjunctival sac of rabbit eyes, and its in vivo drug release, IOP-lowering efficacy and biosafety were assessed. RESULTS: The BRI@SR@PT presented great thermal stability and excellent elasticity. The BRI@SR@PT was able to release BRI sustainably for 28 days with little toxicity in vitro. Compared to BRI eye drops, the BRI@SR@PT effectively lowered IOP for 21 days based on the sustained BRI release with great biosafety when administrated in conjunctival sac of rabbit eyes in a noninvasive fashion. CONCLUSIONS: The conjunctival sac insert (BRI@SR@PT), as a promising drug-delivery platform, may provide a sustained IOP-lowering treatment for patients with ocular hypertension or glaucoma, without the need for invasive procedures.

Association of Long-Term Exposure to Ambient Air Pollution With the Risk of Acute Primary Angle Closure.

Purpose: The purpose of this study was to investigate the association between long-term exposure to ambient air pollutants and the risk of acute primary angle closure (APAC). Methods: Two hundred eighty-one (281) patients with APAC and 730 age- and sex-matched controls hospitalized between January 2017 and December 2019 were enrolled in this retrospective case-control study. Residential exposure to ambient air pollutants, including fine particulate matter (PM2.5), inhalable particulate (PM10), nitrogen dioxide (NO2), sulfur dioxide (SO2), and ozone were estimated by satellite-models or ground measurement. Multivariate regression analyses explored the association between annual air pollutants exposure and the risk of APAC. Results: Of the 1011 participants (31.1% were male subjects), the average age was 64.0 years. Long-term exposure to PM2.5, PM10, and SO2 were significantly associated with an increased risk of APAC. The adjusted odds ratios (aORs) for each interquartile range (IQR) increment of PM2.5, PM10, and SO2 were 1.28 (95% confidence interval [CI] = 1.06-1.57), 1.26 (95% CI = 1.06-1.50), and 1.30 (95% CI = 1.04-1.62) separately, after controlling for confounders. Robust associations were observed for a longer lag 2-year exposure. Conclusions: Long-term exposure to PM2.5, PM10, and SO2 was associated with an increased risk of APAC in a Chinese population. Our findings provide epidemiological implications on the adverse effects of air pollution on ocular diseases. Translational Relevance: Long-term exposure to ambient air pollutants increased the risk of APAC.

Eight Years and Beyond Longitudinal Changes of Peripapillary Structures on OCT in Adult Myopia.

PURPOSE: To investigate the long-term changes of peripapillary structures detected by enhanced depth imaging of optical coherence tomography (OCT) in adult myopia. DESIGN: Observational case series. METHODS: Myopic participants who had undergone a full baseline ophthalmologic examination and had been followed up for a minimum of 8 years were included. Using enhanced depth imaging of OCT, scans around the optic disc in the Spectralis software Follow-up mode, which enabled capturing of the same positions, were performed in 65 eyes. The peripapillary parameters including the size of border tissue, Bruch membrane opening (BMO), peripapillary choroidal thickness, and the angle between peripapillary Bruch membrane (BM) and anterior sclera were manually delineated and measured. RESULTS: The axial length showed a significant elongation after a mean follow-up of 9.46 ± 0.92 years. The rates of changes were 0.015 ± 0.011 mm/y in the medium myopia group and 0.057 ± 0.039 mm/y in the high myopia group. At the last visit, the average border tissue length and BMO diameter were increased. The angle between peripapillary BM did not show significant change, while the angle between the peripapillary sclera showed a significant rise. On multivariate analysis, the border tissue elongation, BMO enlargement, and increased sclera angle were all associated with a change in axial length. The development of a BM defect and inward protrusion of sclera in the temporal peripapillary region was observed on 8 eyes (34.8%) in the high myopia group, along with an extreme thinning or disappearing of the peripapillary choroid. CONCLUSION: Marked longitudinal changes in peripapillary structures including border tissue, BM, choroid, and sclera could be observed in adult myopic eyes, which may impact the biomechanical environment around the optic nerve head.

Metabolomics identifies and validates serum androstenedione as novel biomarker for diagnosing primary angle closure glaucoma and predicting the visual field progression.

Background: Primary angle closure glaucoma (PACG) is the leading cause of irreversible blindness in Asia, and no reliable, effective diagnostic, and predictive biomarkers are used in clinical routines. A growing body of evidence shows metabolic alterations in patients with glaucoma. We aimed to develop and validate potential metabolite biomarkers to diagnose and predict the visual field progression of PACG. Methods: Here, we used a five-phase (discovery phase, validation phase 1, validation phase 2, supplementary phase, and cohort phase) multicenter (EENT hospital, Shanghai Xuhui Central Hospital), cross-sectional, prospective cohort study designed to perform widely targeted metabolomics and chemiluminescence immunoassay to determine candidate biomarkers. Five machine learning (random forest, support vector machine, lasso, K-nearest neighbor, and GaussianNaive Bayes [NB]) approaches were used to identify an optimal algorithm. The discrimination ability was evaluated using the area under the receiver operating characteristic curve (AUC). Calibration was assessed by Hosmer-Lemeshow tests and calibration plots. Results: Studied serum samples were collected from 616 participants, and 1464 metabolites were identified. Machine learning algorithm determines that androstenedione exhibited excellent discrimination and acceptable calibration in discriminating PACG across the discovery phase (discovery set 1, AUCs=1.0 [95% CI, 1.00-1.00]; discovery set 2, AUCs = 0.85 [95% CI, 0.80-0.90]) and validation phases (internal validation, AUCs = 0.86 [95% CI, 0.81-0.91]; external validation, AUCs = 0.87 [95% CI, 0.80-0.95]). Androstenedione also exhibited a higher AUC (0.92-0.98) to discriminate the severity of PACG. In the supplemental phase, serum androstenedione levels were consistent with those in aqueous humor (r=0.82, p=0.038) and significantly (p=0.021) decreased after treatment. Further, cohort phase demonstrates that higher baseline androstenedione levels (hazard ratio = 2.71 [95% CI: 1.199-6.104], p=0.017) were associated with faster visual field progression. Conclusions: Our study identifies serum androstenedione as a potential biomarker for diagnosing PACG and indicating visual field progression. Funding: This work was supported by Youth Medical Talents - Clinical Laboratory Practitioner Program (2022-65), the National Natural Science Foundation of China (82302582), Shanghai Municipal Health Commission Project (20224Y0317), and Higher Education Industry-Academic-Research Innovation Fund of China (2023JQ006).

Clinical analysis of infectious endophthalmitis following glaucoma filtration surgery.

BACKGROUND: This study aimed to evaluate the clinical correlative factors and outcomes of treatment of bleb-associated endophthalmitis (BAE) following glaucoma filtration surgery in a Chinese population from the year 2012 to 2022, and to compare them with the clinical course during the coronavirus disease (COVID-19) pandemic period. METHODS: This was a retrospective analysis of consecutive cases of BAE treated at the Eye & ENT Hospital of Fudan University, Shanghai, China, between January 1, 2012, and December 31, 2022. The clinical presentation, treatment modality, microbiological data, clinical course, and outcomes of visual acuity (VA) and intraocular pressure (IOP) in all BAE cases were collected and analyzed. RESULTS: A total of 28 eyes with BAE were examined, predominantly in male patients (71.4%, p = 0.023). Most patients underwent trabeculectomy (89.3%, p ≤ 0.001), while a smaller proportion underwent Ex-PRESS implantation (10.7%). Primary open-angle glaucoma (POAG) was the most common type of glaucoma (39.3%, p ≤ 0.001). Most patients (96.4%) presented with poor visual acuity, worse than 20/400, and IOP ranged from 3-60 mmHg. Treatment, including initial tap-and-inject procedure of antibiotics (Ceftazidime and Norvancomycin) or initial pars plana vitrectomy (PPV), was initiated 5.0 ± 7.1 days after BAE onset. Streptococcus was the most common causative organism (53.6% of cases, p ≤ 0.001). The visual acuity significantly improved from 2.58 ± 0.27 to 2.14 ± 0.85 (reported in logMAR) after treatment (p ≤ 0.001), and most patients maintained normal tension during follow-up. Poisson regression model analysis showed the annual incidence of BAE during the COVID-19 pandemic period was significantly twice greater than that of previous years. CONCLUSIONS: BAE may cause irreversible visual impairment. POAG filtering surgery with male sex and the COVID-19 pandemic period might be potentially relevant factors for BAE. Culture positivity was closely related to BAE prognosis, with Streptococcus species being the leading pathogenic organisms. Online outpatient services, early diagnosis, and timely treatment may rescue vision and maintain IOP control in the presence of BAE.

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

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

Three-dimensional choroidal vascularity index and choroidal thickness in fellow eyes of acute and chronic primary angle-closure using swept-source optical coherence tomography.

AIM: To compare the three-dimensional choroidal vascularity index (CVI) and choroidal thickness between fellow eyes of acute primary angle-closure (F-APAC) and chronic primary angle-closure glaucoma (F-CPACG) and the eyes of normal controls. METHODS: This study included 37 patients with unilateral APAC, 37 with asymmetric CPACG without prior treatment, and 36 healthy participants. Using swept-source optical coherence tomography (SS-OCT), the macular and peripapillary choroidal thickness and three-dimensional CVI were measured and compared globally and sectorally. Pearson's correlation analysis and multivariate regression models were used to evaluate choroidal thickness or CVI with related factors. RESULTS: The mean subfoveal CVIs were 0.35±0.10, 0.33±0.09, and 0.29±0.04, and the mean subfoveal choroidal thickness were 315.62±52.92, 306.22±59.29, and 262.69±45.55 µm in the F-APAC, F-CPACG, and normal groups, respectively. All macular sectors showed significantly higher CVIs and choroidal thickness in the F-APAC and F-CPACG eyes than in the normal eyes (P<0.05), while there were no significant differences between the F-APAC and F-CPACG eyes. In the peripapillary region, the mean overall CVIs were 0.21±0.08, 0.20±0.08, and 0.19±0.05, and the mean overall choroidal thickness were 180.45±54.18, 174.82±50.67, and 176.18±37.94 µm in the F-APAC, F-CPACG, and normal groups, respectively. There were no significant differences between any of the two groups in all peripapillary sectors. Younger age, shorter axial length, and the F-APAC or F-CPACG diagnosis were significantly associated with higher subfoveal CVI and thicker subfoveal choroidal thickness (P<0.05). CONCLUSION: The fellow eyes of unilateral APAC or asymmetric CPACG have higher macular CVI and choroidal thickness than those of the normal controls. Neither CVI nor choroidal thickness can distinguish between eyes predisposed to APAC or CPACG. A thicker choroid with a higher vascular volume may play a role in the pathogenesis of primary angle-closure glaucoma.

Adult-onset neuronal intranuclear inclusion disease related retinal degeneration: a Chinese case series.

Purpose: To evaluate adult-onset neuronal intranuclear inclusion disease (NIID)-related retinopathy with guanine-guanine-cytosine repeat expansions in NOTCH2NLC. Materials and methods: Neuro-ophthalmic evaluations, including best-corrected visual acuity, slit-lamp biomicroscopy, intraocular pressure (IOP), ultrasound biomicroscopy, pupillometry, fundus photography, fundus autofluorescence (FAF), optical coherence tomography (OCT), Humphrey visual field, full-field electroretinography (ERG), and multifocal ERG (mf-ERG) were performed in patients with gene-proven NIID. Results: Nine patients (18 eyes) were evaluated, with a median age of 62 years (55-68) and only one man was included in our study. Six patients presented with decreased visual acuity or night blindness, whereas the other three were asymptomatic. The visual acuity was measured from 20/200 to 20/20. Miosis was present in eight patients, four of whom had ciliary process hypertrophy and pronation, and three of whom had shallow anterior chambers. Fundus photography, FAF, and OCT showed consistent structural abnormalities mainly started from peripapillary areas and localized in the outer layer of photoreceptors and inner ganglion cell layer. ERG and mf-ERG also revealed retinal dysfunction in the corresponding regions. Conclusion: Patients with NIID showed both structural and functional retinopathies which were unique and different from common cone-rod dystrophy or retinitis pigmentosa. Patients with miosis may have a potential risk of an angle-closure glaucoma attack. Neuro-ophthalmic evaluations is essential for evaluating patients with NIID, even without visual symptom.

The Outbreak of Acute Primary Angle-Closure Cases During the COVID-19 Omicron Variant Pandemic at a Tertiary Eye Center in Shanghai.

Purpose: This study aimed to investigate the outbreak of acute primary angle-closure (APAC) during the COVID-19 Omicron variant pandemic in Shanghai. Methods: This single-center retrospective observational study included all newly diagnosed patients with APAC in Eye, Ear, Nose, and Throat Hospital of Fudan University from December 15, 2022, to January 14, 2023 (pandemic group) during the COVID-19 pandemic of Omicron Variant, and from November 15, 2021, to February 14, 2022 (control group) when the infection rate of COVID-19 is very low in Shanghai. Demographic features, intraocular pressure, axial length, anterior chamber depth, lens thickness and pupil diameter were compared between the two groups. Results: A total of 223 patients (261 eyes) were included in the pandemic group and 75 patients (82 eyes) in the control group. The number of APAC patients and eyes in the pandemic group is 8.92-fold and 9.55-fold of the monthly average number in the control group. The onset dates of acute angle-closure were mainly between December 17 and December 31, 2022. In the pandemic group, 72.65% of patients with APAC had a recent COVID-19 infection. Among the COVID-19-positive patients, 72% suffered APAC attacks within 24h of the occurrence of COVID-19 symptoms and 92% within 3 days. The pandemic group showed a longer time from symptoms to treatment and larger pupil diameter than the control group (7.92 ± 6.14 vs 3.63 ± 2.93 days, p = 0.006; 4.53 ± 1.17 vs 3.78 ± 1.24 mm, p = 0.003, respectively). Conclusion: An outbreak of APAC attack was observed in our eye center during the COVID-19 Omicron variant pandemic in Shanghai. There may be a correlation between the onset of APAC and new COVID-19 Omicron variant infection, but the exact reason needs to be investigated further.