William Rojas Carabali

All Publications

• Complexities in the Terminology Used for Describing, Diagnosing, and Classifying Retinal Vasculitis: A Scoping Review from the International Uveitis Study Group (IUSG) Retinal Vasculitis Study (ReViSe)-Report 6 OCULAR IMMUNOLOGY AND INFLAMMATION Chua, C., Rojas-Carabali, W., Cifuentes-Gonzalez, C., Gangaputra, S., Smet, M. D., Yao, L., Okada, A. A., Biswas, J., McCluskey, P., Tugal-Tutkun, I., Bodaghi, B., Invernizzi, A., Chan, C., Sobrin, L., Sadda, S., Dick, A., Jabs, D., Edward, D., Thorne, J. E., De-la-Torre, A., Gupta, V., Rosenbaum, J. T., Agrawal, R., ReViSe-IUSG Study Grp 2025: 1-11

  Abstract

  Retinal vasculitis (RV) is a complex inflammatory condition that affects the retinal vessels, often presenting as perivascular sheathing, vascular leakage, and occlusion. Despite its well-documented clinical and angiographic features, the definition and classification of RV remain inconsistent across clinical and research settings. This lack of uniformity has led to challenges in diagnosis, management, and understanding of research findings. Thus, this scoping review aims to objectively identify any ambiguity in the terminology of RV and discuss possible reasons for it, laying the groundwork for a subsequent panel of experts to provide consensus definitions for RV through a Delphi process.This review included 97 studies. The authors extracted and summarised data on the definitions and diagnostic criteria used for RV, the definitions used for subtypes of RV (e.g. isolated, idiopathic, undifferentiated, primary RV), the imaging modalities used for RV diagnosis, and any references to existing guidelines.The results confirmed a significant degree of ambiguity in RV terminology. Among the 17 papers that explicitly defined RV in their methodology, four distinct definitions emerged. We also found that the terms' idiopathic,' 'primary,' and 'undifferentiated' RV were often used interchangeably, despite reflecting distinct aspects of the disease. Notably, all 52 studies that noted the diagnostic modalities used included fluorescein angiography, although the usage of other modalities was contentious.There are significant inconsistencies and ambiguities in defining and classifying RV, highlighting the need for a standardized, consensus-based framework to improve clarity and consistency in both research and clinical practice.

  View details for DOI 10.1080/09273948.2025.2566981

  View details for Web of Science ID 001613850900001

  View details for PubMedID 41231527

• Dynamic Prediction of Treatment Failure in Ocular Tuberculosis Using Machine Learning and Explainable AI. Translational vision science & technology Rojas-Carabali, W., Guérand, T., Cifuentes-González, C., Abisheganaden, J., Rk, P., Wei, Y. C., Mejía-Salgado, G., de-la-Torre, A., Smith, J. R., Kempen, J. H., Nguyen, Q. D., Pavesio, C., Lee, B., Gupta, V., Peyrin, T., Agrawal, R. 2025; 14 (10): 31

  Abstract

  Ocular tuberculosis (OTB) poses significant challenges in treatment because of its complex diagnostic and therapeutic landscapes. Predicting treatment failure effectively is crucial for timely intervention and improving patient outcomes. We report the application of machine learning (ML) approaches to (i) allow predictions using baseline data and (ii) dynamically update predictions based on patient history and new observations.The Collaborative Ocular Tuberculosis Study (COTS) was a multinational retrospective study encompassing data from 836 patients with tubercular uveitis across 27 international eye care centers. This study evaluated the performance of nine ML models to predict treatment failure at six, 12, and 24 months using baseline and longitudinal data. Metrics such as area under the curve (AUC), precision, accuracy, F1-score, and model complexity were reported. Top features and their importance were identified using XGBoost, with weight of evidence and information value calculated to enhance interpretability.Data were collected from 836, 769, and 418 patients at six, 12, and 24 months, respectively. XGBoost and Random Forest (RF) models consistently showed superior performance across all timepoints. At 6 months, XGBoost achieved an AUC of 0.915 ± 0.019 and accuracy of 0.879 ± 0.027. At 12 months, RF outperformed with an AUC of 0.921 ± 0.011 and accuracy of 0.944 ± 0.022. At 24 months, RF maintained high accuracy (0.960 ± 0.029) despite a slight drop in AUC (0.888 ± 0.099). Deep Neural Networks and TT-net models were underfitted.ML models like XGBoost and RF demonstrate promise for early and accurate prediction of treatment failure in OTB, with explainability tools enhancing clinical interpretability.This study bridges basic ML research and clinical care by offering explainable, performance-driven models that support real-time, data-informed treatment decisions in managing OTB, potentially improving long-term outcomes.

  View details for DOI 10.1167/tvst.14.10.31

  View details for PubMedID 41134278

• Characterisation of Ocular Manifestations in Patients with Multiple Sclerosis in Colombia: A Multicentric Study NEURO-OPHTHALMOLOGY Manrique-Samer, A., Cifuentes-Gonzalez, C., Alvarez-Martinez, J., Rojas-Carabali, W., Cortes-Albornoz, M., Velez Van-Meerbeke, A., Ortiz-Salas, P., Casallas-Vanegas, A., Guio-Sanchez, C. M., Cardona-Lopez, J., Mejia-Salgado, G., de-la-Torre, A. 2025

  View details for DOI 10.1080/01658107.2025.2563194

  View details for Web of Science ID 001596434300001

• Common data elements for observational studies in ocular toxoplasmosis: a Delphi consensus. Journal of ophthalmic inflammation and infection Rojas-Carabali, W., Cifuentes-González, C., Goetz, K., Cicinelli, M. V., Thng, Z. X., Baxter, S. L., Tsui, E., Mahendradas, P., Biswas, J., Androudi, S., Curi, A. L., Ho, S. L., Adán, A., La Distia Nora, R., Silveira, C., Nascimento, H., Furtado, J. M., Muccioli, C., Mejía-Salgado, G., Urzua, C. A., Garweg, J. G., Schlaen, A., Wei, X., Balamurugan, S., Kharel Sitaula, R., Putera, I., Rudzinski, M., Babu, K., Westcott, M., Belfort, R., Smith, J. R., Gomez-Marin, J., Nguyen, Q. D., Gupta, V., Agrawal, R., de-la-Torre, A. 2025; 15 (1): 68

  Abstract

  Ocular toxoplasmosis (OT) is the most common cause of posterior uveitis globally, with a significant risk of visual impairment. However, the lack of standardized data collection hinders meaningful comparisons across studies. This study aimed to develop a consensus-based set of Common Data Elements (CDEs) for observational studies in OT using a Delphi approach.A set of CDEs was developed through a combination of a comprehensive literature review, a hybrid workshop, and a Delphi consensus process. This effort was led by an international panel of experts in OT to define a standardized CDE set for research and clinical purposes.A multidisciplinary steering committee identified an initial list of candidate CDEs through a targeted literature review. A panel of 30 international experts participated in a structured, one-round Delphi process to evaluate and refine these CDEs. Consensus was determined based on predefined thresholds for inclusion, exclusion, and modification.A total of 139 CDEs were categorized across nine domains: Demographic and Background Information, Medical and Ocular History, Clinical Presentation, Clinical Findings, Lesion Characteristics, Diagnostics, Imaging Findings, Treatment and Interventions, and Outcomes. All 139 CDEs met the inclusion criteria, with 79.8% rated as "very important". The consensus underscores the importance of a comprehensive, standardized dataset for OT research.This study establishes the first expert-derived standardized dataset requested for reporting OT outcomes, providing a framework to standardize data collection for future observational studies. Adopting these CDEs will enhance data comparability, improve meta-analyses, and strengthen the evidence base for clinical decision-making in OT. Future work will focus on real-world validation and refinement of this dataset.

  View details for DOI 10.1186/s12348-025-00525-2

  View details for PubMedID 40993348

  View details for PubMedCentralID 11870091

• Clinical trials and quasi-experimental studies in the treatment of noninfectious retinal vasculitis: A Systematic Review from the International Uveitis Study Group (IUSG) Retinal Vasculitis Study (ReViSe) - Report 4. Survey of ophthalmology Saboya-Galindo, P., Cifuentes-González, C., Rojas-Carabali, W., Mejía-Salgado, G., Le Tong, Y., Putera, I., Song, X. Y., Walter, C. F., Shengjuan, Z., Chan, R., La Distia Nora, R., Biswas, J., Gangaputra, S., Pulido, J. S., Kempen, J. H., Nguyen, Q. D., de-la-Torre, A., Gupta, V., Rosenbaum, J. T., Agrawal, R. 2025

  Abstract

  This systematic review evaluates clinical trials and quasi-experimental studies reporting diagnostic criteria, disease activity scoring systems (including Disease Activity Index (DAI), Total Inflammatory Activity Index (TIAI), and Total Adjusted Disease Activity Index (TADAI), and others), and therapeutic strategies used in noninfectious retinal vasculitis (RV), aiming to consolidate current evidence on treatment response and effectiveness measures. Of 5,533 articles screened (PROSPERO: CRD42023489232), 15 studies met the inclusion criteria. Most were conducted in Asia (73.3%) and focused on Behçet disease (60%) or Eales disease (27%). RV was diagnosed clinically in all studies, while half incorporated fluorescein angiography to confirm vascular inflammation through leakage, staining, or occlusion; however, definitions of RV were highly variable, often inferred rather than explicitly stated, and lacked standardization. This diagnostic inconsistency, combined with limited imaging data, undermines comparability across studies. Disease activity was assessed using outdated composite indices such as the DAI, TIAI, and TADAI, which lack external validation and fail to capture key clinical features such as macular ischemia or capillary non-perfusion. Best corrected visual acuity, although frequently reported, was confounded by unrelated factors such as cataracts or macular scarring. Therapeutic strategies included systemic corticosteroids, immunosuppressants (e.g., methotrexate, azathioprine), and biologics (e.g., infliximab, interferon-alpha). Treatment selection was heterogeneous, and several regimens-such as cyclophosphamide-azathioprine combinations-do not align with current standards of care. Due to variability in study design and outcome reporting, no pooled effect estimates, or statistical comparisons were conducted. Treatment outcomes were synthesized descriptively based on individual study findings. Current evidence in RV clinical trials is outdated and lacks diagnostic and therapeutic standardization. There is a particular need for RV-specific definitions, validated disease activity and response indices, and contemporary therapeutic trials to guide clinical management and improve outcome comparability.

  View details for DOI 10.1016/j.survophthal.2025.09.013

  View details for PubMedID 40983164

• Work-up in patients with retinal vasculitis: A systematic review and meta-analysis: International Uveitis Study Group (IUSG) Retinal Vasculitis Study (ReViSe) Report 2. Survey of ophthalmology Cifuentes-González, C. G., Putera, I., Walter, C. F., Mejía-Salgado, M. S., Le Tong, Y., Chan, R., Rojas-Carabali, W., Song, X. Y., Mobasserian, A., Nora, R. L., Biswas, J., Gangaputra, S., Pulido, J. S., Kempen, J. H., Nguyen, Q. D., de la Torre, A., Gupta, V., Rosenbaum, J. T., Agrawal, R. 2025

  Abstract

  This systematic review and meta-analysis investigate global diagnostic approaches for retinal vasculitis (RV), with a focus on infectious and non-infectious causes. As in our prior report, systematic searches were conducted in five databased and registered in PROSPERO (CRD42023489232). Studies included articles on at least 10 patients with RV without publication date or language restrictions. RV was categorized as secondary RV if they were associated with systemic disease, syndromic if they were associated with a syndromic ocular disease, involvement without systemic disease, idiopathic RV without association to systemic or syndromic ocular diseases. This included 84 studies analyzing 3,480 patients with RV. Among infectious causes, tuberculosis tests were frequently reported, with TST/IGRA positivity observed in 31.4% (95% CI: 17.2-50.2%) of de novo RV cases, increasing to 64.7% (95% CI: 47.8-78.9%) in confirmed tubercular RV and 65.7% (95% CI: 39.0-85.1%) in Eales disease. Chest radiograph abnormalities were present in 21.8% (95% CI: 12.9-33.8%) of tubercular RV cases. Non-infectious causes showed notable regional variability. HLA-B51 positivity was 1% (95% CI: 0.03-3.1%) in de novo RV but rose to 61.4% (95% CI: 23.1-89.4%) in Behçet RV. Sarcoidosis RV revealed noncaseating granulomas in 80.5% (95% CI: 9.7-99.4%), with ACE elevation in 4.6% (95% CI: 2.3-9.1%). This study highlights significant geographic variability in RV etiologies. Tuberculosis remains a key infectious cause, while non-infectious causes vary regionally. Region-specific diagnostics and Bayesian testing protocols are critical to improving diagnostic accuracy and patient outcomes.

  View details for DOI 10.1016/j.survophthal.2025.09.011

  View details for PubMedID 40972796

• Validation of the COTS Calculator for Tubercular Uveitis: Predictive Performance and Diagnostic Utility in an Indian Cohort OCULAR IMMUNOLOGY AND INFLAMMATION Palani, J., Cifuentes Gonzalez, C., Patnaik, G., Rojas-Carabali, W., Zhang, L., Thng, Z., Lee, B., Agrawal, R., Biswas, J. 2025; 33 (8): 1634-1642

  Abstract

  Diagnosing ocular tuberculosis (OTB) is clinically challenging due to its paucibacillary nature and lack of definitive diagnostic tests. The Collaborative Ocular Tuberculosis Study (COTS) Calculator was developed as a clinical decision-support tool to guide anti-tubercular therapy (ATT) initiation. This study externally validates the COTS Calculator in a high-burden Indian cohort and assesses the additive value of radiological and immunological testing.This retrospective cohort study included 196 OTB patients treated between 2015 and 2022 at a tertiary eye care center in South India. Inclusion required complete diagnostic workup, ≥6-month follow-up post-ATT, and at least one supportive test (TST, IGRA, CT, or CXR). Two thresholds were evaluated: M4I1 (median ≥ 4) and M4I2 (median ≥ 4, IQR ≤ 2). Treatment response and recurrence were primary outcomes. Diagnostic performance was measured using AUC, sensitivity, specificity, PPV, and NPV. Composite scores (CT+CXR and TST+IGRA) were also analyzed.The M4I2 threshold yielded higher sensitivity (83%) than M4I1 (60%) with comparable AUC (0.60 vs 0.58), though at lower specificity (38% vs 56%). Both thresholds achieved high PPV (94%) but poor NPV (11-17%). Composite testing showed similar high PPV (93%) and poor NPV (9-11%). Higher COTS scores and multiple positive tests correlated with favorable treatment response.The COTS Calculator, particularly the M4I2 model, provides a useful clinical tool to guide ATT decisions in OTB. While limited in ruling out TB, its integration with radiological and immunological testing supports early treatment decisions in TB-endemic settings. Prospective validation is warranted.

  View details for DOI 10.1080/09273948.2025.2517309

  View details for Web of Science ID 001510171400001

  View details for PubMedID 40521722

• A Survey of Diagnostic and Management Practices in Retinal Vasculitis: International Uveitis Study Group (IUSG) Retinal Vasculitis Study (ReViSe)-Report 5 OCULAR IMMUNOLOGY AND INFLAMMATION Liu, R., Cifuentes-Gonzalez, C., Gangaputra, S., Putera, I., Rojas-Carabali, W., La Distia Nora, R., de-la-Torre, A., Gupta, V., Rosenbaum, J. T., Agrawal, R., ReViSe IUSG Study Grp 2026; 34 (6): 1219-1227

  Abstract

  Retinal vasculitis (RV) is a complex inflammatory disorder of retinal blood vessels with variability in diagnosis, classification, and management. Despite efforts to standardize definitions, discrepancies persist regarding clinical features, systemic associations, and treatment approaches. This study aimed to assess clinical practices among uveitis specialists to identify areas requiring consensus.A cross-sectional, semi-structured survey was conducted among members of the International Uveitis Study Group (IUSG). Eligible participants were uveitis specialists with formal training in ocular inflammation. The survey included 120 questions on diagnosis, imaging, systemic associations, and management strategies. Responses were collected anonymously via REDCap (January to August 2024).Fifty-five specialists participated, mainly from Europe, Asia, and North America. Most rated their RV knowledge as "adequate" or "proficient." While 85.5% agreed on a definition involving retinal vascular abnormalities with intraocular inflammation, variability persisted in diagnostic and management practices. Diagnostic testing prioritized infectious and systemic causes. Wide-field imaging and fluorescein angiography were commonly used. Methotrexate, mycophenolate, and adalimumab were preferred treatments. Treatment success was primarily defined by improvements in vascular leakage and macular edema. Monitoring practices and referral patterns varied.Substantial variability exists in RV diagnosis and management, highlighting the need for standardized clinical guidelines.

  View details for DOI 10.1080/09273948.2025.2503337

  View details for Web of Science ID 001504245300001

  View details for PubMedID 40478525

• Systematic Review and meta-analysis: International Uveitis Study Group (IUSG) Retinal Vasculitis Study (ReViSe) Report 3. Survey of ophthalmology Cifuentes-González, C., Le Tong, Y., Rojas-Carabali, W., Mejía-Salgado, G., Putera, I., Song, X. Y., Walter, C. F., Shengjuan, Z., Chan, R., Mobasserian, A., Nora, R. L., Biswas, J., Gangaputra, S., Pulido, J. S., Kempen, J. H., Nguyen, Q. D., de la Torre, A., Gupta, V., Rosenbaum, J. T., Agrawal, R. 2025

  Abstract

  ThiWe investigate the clinical characteristics and complications of retinal vasculitis (RV), categorizing cases into Secondary RV (associated with systemic disease), Syndromic RV (linked to ocular syndromes without systemic disease), Idiopathic RV (without systemic disease or ocular syndrome diagnoses), and Multiple Etiology RV (cohorts of retinal vasculitis with more than one subcategories of the above). A systematic search conducted on June 14, 2023, across PubMed, Embase, Cochrane (Ovid), VHL, and ProQuest databases followed PRISMA guidelines (PROSPERO registration: CRD42023489232). Out of 5,533 screened articles, 97 studies involving 7,619 patients with RV met the eligibility criteria. Bilateral involvement (64%) and reduced vision (52%) were common across all RV categories, with Idiopathic RV showing the highest rates of bilateral involvement (80%) and vision loss (79%). Syndromic RV was characterized by retinal ischemia (76%) and vitreous hemorrhage (46%), while Secondary RV exhibited higher incidences of cystoid macular edema (32%) and neovascular glaucoma (24%). Geographic variations were evident in Multiple Etiology RV, with inflammation in more than 1 intraocular structure more prevalent in Asia (64%) than in Europe (29%). These findings highlight the heterogeneity in RV presentation and complications, illustrating the need for standardized diagnostic criteria and improved clinical reporting to enable better classification, treatment strategies, and patient outcomes.

  View details for DOI 10.1016/j.survophthal.2025.04.001

  View details for PubMedID 40320076

• Real-world performance of the inflammadry test in dry eye diagnosis: an analysis of 1,515 patients GRAEFES ARCHIVE FOR CLINICAL AND EXPERIMENTAL OPHTHALMOLOGY Mejia-Salgado, G., Rojas-Carabali, W., Cifuentes-Gonzalez, C., Zarate-Pinzon, L., Rodriguez-Rodriguez, C., Marroquin-Gomez, G., Moreno-Pardo, M., Tirado-angel, J., de-la-Torre, A. 2025; 263 (6): 1623-1631

  Abstract

  To assess the diagnostic performance of the InflammaDry test in diagnosing dry eye disease (DED) using different diagnostic criteria and across varying severities.A retrospective study was conducted on 1,515 patients. Subjects were categorized into three groups: Group (1) DED based on Dry Eye Workshop-II (DEWS-II): Ocular Surface Disease Index (OSDI) ≥ 13 and at least one abnormal clinical sign (non-invasive tear break-up time [NIBUT] < 10 s, osmolarity > 308 mOsm/L, or corneal/conjunctival staining). Group (2) DED based on criteria used in prior clinical trials: OSDI > 13, Schirmer < 10 mm in 5 min, NIBUT < 10 s, and keratoconjunctival staining. Group (3) Healthy controls: OSDI ≤ 7, NIBUT ≥ 10 s, Schirmer ≥ 10 mm, and no keratoconjunctival staining. DED severity was classified using the ODISSEY European Consensus Group's definitions into severe and non-severe. Sensitivity, specificity, and predictive values were calculated for both criteria.1,363 patients were included in Group 1, 401 in Group 2, and 152 in Group 3. Sensitivity was 81.30% in the population diagnosed using previous clinical trial criteria but decreased to 69.99% when applying the DEWS-II criteria. Specificity was 38.16% in both groups, with 409/467 false negatives respectively.InflammaDry shows good sensitivity in detecting DED in highly symptomatic cases with multiple clinical signs, but its performance decreases when broader criteria like DEWS-II are used. While valuable for detecting inflammation, routine use for DED diagnosis may lead to false negatives, especially in milder cases.

  View details for DOI 10.1007/s00417-025-06760-6

  View details for Web of Science ID 001438323600001

  View details for PubMedID 40042683

  View details for PubMedCentralID PMC12238174

• Semaglutide and Nonarteritic Anterior Ischemic Optic Neuropathy. JAMA ophthalmology Cai, C. X., Hribar, M., Baxter, S., Goetz, K., Swaminathan, S. S., Flowers, A., Brown, E. N., Toy, B., Xu, B., Chen, J., Chen, A., Wang, S., Lee, C., Leng, T., Ehrlich, J. R., Barkmeier, A., Armbrust, K. R., Boland, M. V., Dorr, D., Boyce, D., Alshammari, T., Swerdel, J., Suchard, M. A., Schuemie, M., Bu, F., Sena, A. G., Hripcsak, G., Nishimura, A., Nagy, P., Falconer, T., DuVall, S. L., Matheny, M., Viernes, B., O'Brien, W., Zhang, L., Martin, B., Westlund, E., Mathioudakis, N., Fan, R., Wilcox, A., Lai, A., Stocking, J. C., Takkouche, S., Lee, L. H., Xie, Y., Humes, I., McCoy, D. B., Adibuzzaman, M., Areaux, R. G., Rojas-Carabali, W., Brash, J., Lee, D. A., Weiskopf, N. G., Mawn, L., Agrawal, R., Morgan-Cooper, H., Desai, P., Ryan, P. B. 2025

  Abstract

  Semaglutide, a glucagonlike peptide-1 receptor agonist (GLP-1RA), has recently been implicated in cases of nonarteritic anterior ischemic optic neuropathy (NAION), raising safety concerns in the treatment of type 2 diabetes (T2D).To investigate the potential association between semaglutide and NAION in the Observational Health Data Sciences and Informatics (OHDSI) network.This was a retrospective study across 14 databases (6 administrative claims and 8 electronic health records). Included were adults with T2D taking semaglutide, other GLP-1RA (dulaglutide, exenatide), or non-GLP-1RA medications (empagliflozin, sitagliptin, glipizide) from December 1, 2017, to December 31, 2023. The incidence proportion and rate of NAION were calculated. Association between semaglutide and NAION was assessed using 2 approaches: an active-comparator cohort design comparing new users of semaglutide with those taking other GLP-1RAs and non-GLP-1RA drugs, and a self-controlled case-series (SCCS) analysis to compare individuals' risks during exposure and nonexposure periods for each drug. The cohort design used propensity score-adjusted Cox proportional hazards models to estimate hazard ratios (HRs). The SCCS used conditional Poisson regression models to estimate incidence rate ratios (IRRs). Network-wide HR and IRR estimates were generated using a random-effects meta-analysis model.GLP-1RA and non-GLP-1RAs.NAION under 2 alternative definitions based on diagnosis codes: one more inclusive and sensitive, the other more restrictive and specific.The study included 37.1 million individuals with T2D, including 810 390 new semaglutide users. Of the 43 620 new users of semaglutide in the Optum's deidentified Clinformatics Data Mart Database, 24 473 (56%) were aged 50 to 69 years, and 26 699 (61%) were female. The incidence rate of NAION was 14.5 per 100 000 person-years among semaglutide users. The HR for NAION among new users of semaglutide was not different compared with that of the non-GLP-1RAs using the sensitive NAION definition-empagliflozin (HR, 1.44; 95% CI, 0.78-2.68; P = .12), sitagliptin (HR, 1.30; 95% CI, 0.56-3.01; P = .27), and glipizide (HR, 1.23; 95% CI, 0.66-2.28; P = .25). The risk was higher only compared with patients taking empagliflozin (HR, 2.27; 95% CI, 1.16-4.46; P = .02) using the specific definition. SCCS analysis of semaglutide exposure showed an increased risk of NAION (meta-analysis IRR, 1.32; 95% CI, 1.14-1.54; P < .001).Results of this study suggest a modest increase in the risk of NAION among individuals with T2D associated with semaglutide use, smaller than that previously reported, and warranting further investigation into the clinical implications of this association.

  View details for DOI 10.1001/jamaophthalmol.2024.6555

  View details for PubMedID 39976940

• Geographical differences in ophthalmic trauma outcomes and risk factors: the International Globe and Adnexal Trauma Epidemiological Eye Study (IGATES). Eye (London, England) Hoskin, A. K., Sheng, S. N., Blanch, R. J., Giridhar, A., Pauly, M., Shah, M., Sen, A., Irawati, Y., Pradhan, E., Romero, J., Agarwal, M., Soleimani, M., Grover, A. K., Mishra, C., Ocampo, H. H., Khatri, A., Bhalerao, S. A., Bhasin, P., Ayachit, A., Subramanian, P. S., Khandelwal, R., Natarajan, S., Sindal, M. D., Singh, S., Fredrick T, N., Zvornicanin, J., Sundar, G., Dalma-Weiszhausz, J., Awan, A., Ratra, D., Bhatacharjee, K., Choovuthayakorn, J., Sharma, S., Tawdekar, Y., Jayadev, C., Boesoirie, S. F., Rousselot, A. M., Rojas-Carabali, W., Watson, S. L., Lee, B., Agrawal, R. 2025

  Abstract

  Characterise the international variation in ophthalmic trauma and determine risk factors associated with visual and anatomical outcomes for low-, middle- and high-income countries.Observational multi-centre cohort study using data from the International Globe and Adnexal Trauma Epidemiological Eye Study (IGATES) from April 2014 to August 2023. Data on acute presentations of ophthalmic injury including open/closed globe injury, and/or Adnexal/orbital involvement, and/or intraocular/ intraorbital foreign body were collected and Ocular Trauma Score (OTS) was calculated. A total of 5350 patients (5557 eyes) from 31 centres in 12 countries were included. The main outcome measures included demographics, mechanism and setting of injury, and presenting and final visual outcomes. Descriptive statistics, Kruskal-Wallis tests and multinomial logistic regression (MLR) analysis are presented, with correction performed using the Hochberg method. P values less than 0.005 were significant.Age, gender, presenting and final best-corrected visual acuity were all strongly associated with country (p < 0.005). Poor final visual outcomes were strongly associated with OTS predictions, type of injury (p < 0.005) and delayed presentation as well as firework injuries. High-income countries (HIC) showing reduced duration to presentation (HIC 5 h) and increased improvement in visual acuity (HIC -0.40) compared to low to middle-income countries (LMICs) (28 h) (-0.19). MLR analysis identified a significant association between countries' income classification and BCVA worse than 6/60, presence of scleral, iris, limbus injury and surgery being undertaken (p < 0.005).Data from 31 centres internationally identified differences in demographic trends for each country. Age was identified as a risk factor for eye injuries. Low- and middle-income countries were associated with longer delays to presentation, smaller gains in BCVA and poorer visual outcomes. IGATES provides an opportunity to collect global data on ophthalmic trauma to facilitate improved management and prevention strategies.

  View details for DOI 10.1038/s41433-024-03581-5

  View details for PubMedID 39972204

  View details for PubMedCentralID 8342302

• Global demographic and etiological variations of retinal vasculitis: A systematic review and meta-analysis: International Uveitis Study Group (IUSG) Retinal Vasculitis Study (ReViSe) Report 1. Survey of ophthalmology Cifuentes-González, C., Le Tong, Y., Mejía-Salgado, G., Chan, R., Walter, C. F., Rojas-Carabali, W., Putera, I., Mobasserian, A., Nora, R. L., Biswas, J., Gangaputra, S., Pulido, J. S., Kempen, J. H., Nguyen, Q. D., de la Torre, A., Gupta, V., Rosenbaum, J. T., Agrawal, R. 2025

  Abstract

  This systematic review with meta-analysis explores the global demographic and etiological variations of retinal vasculitis (RV), focusing on differences in frequency, age, sex, and etiology across diverse geographic populations. RV is an inflammatory condition that can lead to visual impairment, making understanding its variations essential for targeted screening and management. Systematic searches were conducted in multiple databases up to February, 2023, following PRISMA guidelines. We included studies with at least 10 RV, such that a frequency measurement can be estimated, without restrictions on publication date or language. RV was categorized as Idiopathic RV in the absence of additional ocular or systemic disease, Syndromic RV for ocular involvement without systemic disease, and Secondary RV with systemic disease. The risk of bias was evaluated using standardized tools. A total of 95 studies, including 23,180 patients, were analyzed. The overall RV frequency among uveitis cohorts was 17%, with European populations showing the highest frequency at 25%. Idiopathic RV accounted for 1% of uveitis cohorts and 38% of RV cohorts, with significant differences across continents. Behçet disease had the highest RV frequency at 56%. The median age of diagnosis was 33.5 years, and RV was more frequent in males (57%). The overall RV frequency among uveitis cohorts was 17%, while Idiopathic RV represented 1% of uveitis cohorts and 38% of RV cohorts. Our findings underscore the considerable geographic and demographic variability in RV, particularly in Idiopathic RV, tuberculosis-related RV, and Behçet disease, highlighting the need for tailored, region-specific, and gender-specific approaches to RV diagnosis and treatment.

  View details for DOI 10.1016/j.survophthal.2025.01.012

  View details for PubMedID 39921003

• Half a Century's Quest for Seasonal Hyperacute Panuveitis (SHAPU): From Academic Curiosity to Public Health Concern OCULAR IMMUNOLOGY AND INFLAMMATION Goh, Y., Sitaula, R., Rojas-Carabali, W., Agrawal, R., Karki, P., Gurung, H., Shrestha, E., Joshi, P., Khatri, A., Sharma, A., Joshi, S., Ram Bhusal, D., Prasad Upadhyay, M. 2025: 819-826

  Abstract

  For the past 50 years, significant progress has been made in understanding Seasonal Hyperacute Panuveitis (SHAPU), a mysterious blinding disease first reported in Nepal in 1975. Predominantly affecting Nepalese children, SHAPU occurs cyclically every odd year from September to December. While initially misclassified as endophthalmitis, SHAPU is set apart by its lack of trauma or surgery, failure to grow organisms in most intraocular fluid cultures, and its hallmark presentation of a "white pupil in red eye" with an association with moth exposure. Recent findings have expanded SHAPU's geographical scope beyond Nepal, with cases reported in Bhutan. Moreover, sporadic summer outbreaks have emerged, showing worse clinical outcomes than the typical cases. Recent studies suggest that the Gazalina moth may play a role, although the exact cause of SHAPU remains undetermined. Despite the increased understanding of SHAPU's geographic distribution and cyclical patterns, it is possible that some cases remain misdiagnosed or underreported. Continued research is critical to further exploring the aetiology of SHAPU, which will lead to better diagnostic tools, targeted treatments, and improved outcomes. The inclusion of SHAPU under more general categories such as endophthalmitis underscores the need for a clearer distinction of this condition to prevent blindness in at-risk populations.

  View details for DOI 10.1080/09273948.2024.2444510

  View details for Web of Science ID 001539468900001

  View details for PubMedID 39804087

• Validation of the Online Collaborative Ocular Tuberculosis Study Calculator for Tubercular Uveitis. JAMA ophthalmology Zhang, L., Rojas-Carabali, W., Choo, S. S., Thng, Z. X., Lim, Y. H., Lee, B., Jun, S. W., Patnaik, G., Biswas, J., Agarwal, A., Testi, I., Mahajan, S., Kempen, J. H., Smith, J. R., McCluskey, P., Kon, O. M., Nguyen, Q. D., Pavesio, C., Gupta, V., Agrawal, R., Collaborative Ocular Tuberculosis Study (COTS) Group, Agrawal, R., Testi, I., Mahajan, S., Yuen, Y. S., Agarwal, A., Rousselot, A., Raje, D., Gunasekeran, D. V., Kon, O. M., Barisani-Asenbauer, T., Kempen, J. H., Gupta, A., Jabs, D. A., Smith, J. R., Bodaghi, B., Zierhut, M., DeSmet, M., McCluskey, P., Agarwal, M., Agarwal, M., Aggarwal, K., Agrawal, M., Al-Dhibi, H., Androudi, S., Asyari, F., Balasundaram, M. B., Murthy, K. B., Baglivo, E., Banker, A., Bansal, R., Basu, S., Behera, D., Biswas, J., Carreno, E., Caspers, L., Chee, S., Chhabra, R., Cimino, L., Concha Del Rio, L. E., Cunningham, E. T., Curi, A. L., Das, D., Denisova, E., Denniston, A. K., Errera, M., Fonollosa, A., George, A., Goldstein, D. A., Crosier, Y. G., Gurbaxani, A., Invernizzi, A., Isa, H. M., Islam, S. M., Jones, N., Katoch, D., Khairallah, M., Khosla, A., Kramer, M., Kumar, A., Kumar, A., La Distia Nora, R., Lee, R., Lowder, C., Luthra, S., Mahendradas, P., Makhoul, D., Mazumdar, S., Mehta, S., Miserocchi, E., Mochizuki, M., Mohamed, O. S., Muccioli, C., Munk, M. R., Murthy, S., Narain, S., Nascimento, H., Neri, P., Nguyen, M., Okada, A. A., Ozdal, P., Palestine, A., Pichi, F., Rathinam, S. R., Schlaen, A., Sehgal, S., Sen, H. N., Sharma, A., Sharma, K., Shoughy, S. S., Singh, N., Singh, R., Soheilian, M., Sridharan, S., Thorne, J. E., Tappeiner, C., Teoh, S., Tognon, M. S., Tugal-Tutkun, I., Tyagi, M., Uy, H., Vasconcelos-Santos, D. V., Vidovic Valentincic, N., Westcott, M., Yanai, R., Yanez Alvarez, B., Zahedur, R., Nguyen, Q. D., Pavesio, C., Gupta, V. 2024

  Abstract

  Importance: This was the first study, to the authors' knowledge, to statistically evaluate the predictive accuracy of Collaborative Ocular Tuberculosis Study (COTS) calculator in guiding initiation of antitubercular therapy (ATT) in patients with clinically suspicious tubercular uveitis (TBU) in an international cohort.Objective: To evaluate the accuracy of a score of 4 or greater on the online COTS calculator in recommending ATT initiation.Design, Setting, and Participants: This study was an evaluation of a diagnostic test or technology. Data input required for the COTS calculator were extracted from the COTS-1 study dataset, which comprised retrospective, observational records of patients with TBU who were monitored for 12 months after treatment. Patients were recruited from international ophthalmic centers. In the absence of a traditional criterion standard, the 12-month treatment response to ATT was used to classify patients as disease positive or negative. The accuracy of clinicians at the ATT decision-making stage in the COTS-1 study was set against COTS calculator scores of 4 or greater. Diagnostic accuracy metrics, including sensitivity, specificity, positive predictive value (PPV), precision, recall, and F1 score, were computed. Data collected from January 2004 to December 2014 were analyzed.Exposures: COTS calculator to guide initiation of ATT in patients with TBU.Main Outcomes and Measures: Comparison of accuracy between clinician judgment and the COTS calculator, analyzed at varying scores and further stratified by tuberculosis endemicity.Results: Of the 492 participants (mean [SD] age, 42.3 [19.0] years; 233 male [47.3%]), application of the COTS calculator identified 225 (45.7%) with high or very high probability to start ATT (score=4 or 5) and 111 (22.5%) with very high probability alone (score=5). COTS-5 exhibited the highest specificity (88.7%; 95% CI, 81.4%-93.8%) compared with clinician judgment (29.6%; 95% CI, 21.4%-38.8%), and clinician judgment led in sensitivity (95.5%; 95% CI, 92.9%-97.4%) compared with COTS-5 (26%; 95% CI, 21.6%-30.7%). COTS-4 and COTS-5 balanced specificity (64.3%; 95% CI, 54.9%-73.1%) and sensitivity (48.8%; 95% CI, 43.7%-54%). PPV and sensitivity were consistently higher in the endemic group for all 3 tests.Conclusions and Relevance: Results of this diagnostic study suggest that the COTS calculator (score ≥4) was more specific than clinician judgment for ATT initiation. Although clinician judgment is a good first step to identify all potential true positives (with high sensitivity), a second consultation with COTS-5 (with high PPV) may lead to less false positives. This tool, apt for high-prevalence, low-resource settings, recommends ATT more selectively for genuine TBU cases. Large prospective studies are essential to explore potential improvements in the calculator's sensitivity.

  View details for DOI 10.1001/jamaophthalmol.2024.4567

  View details for PubMedID 39480402

• Biological and Therapeutic Role of Interleukin-6 in Non-Infectious Uveitis: A Narrative Review OCULAR IMMUNOLOGY AND INFLAMMATION Cifuentes-Gonzalez, C., Mejia-Salgado, G., Rojas-Carabali, W., Diez-Bahamon, L. A., Garzon-Dangond, J., Janela, B., de-la-Torre, A., Agrawal, R. 2026; 34 (5): 1093-1107

  Abstract

  Biologic agents targeting interleukin-6 (IL-6) have gained attention as a promising treatment option for non-infectious uveitis (NIU) cases resistant to first-line therapies. IL-6 plays a pivotal role in the pathogenesis of uveitic conditions and its complications (i.e. macular edema and neovscularization). This review aims to assess the therapeutic potential of IL-6 inhibitors in managing NIU, especially focused in clinical outcomes, such as visual acuity and macular edema.Narrative review of studies evaluating the efficacy of IL-6 inhibitors in patients with NIU. Parameters assessed include control of inflammation, corticosteroid-sparing effects, visual acuity improvement, and reduction of macular edema.IL-6 inhibitors have demonstrated efficacy in controlling inflammation in 34% to 88% of cases and reducing corticosteroid dependence in approximately 55% of patients. Complete remission rates have been reported between 60% and 70%, with improvement in macular edema observed in 35.8% to 100% of cases. These results suggest that IL-6 inhibitors could be a therapeutic alternative for managing difficult cases of NIU.IL-6 inhibitors, including Tocilizumab and Sarilumab, have shown efficacy in controlling inflammation, improving visual outcomes, and reducing corticosteroid dependence in NIU. However, despite these promising results, further studies are needed to establish their long-term efficacy and safety. These therapies hold great potential for the future management of patients with uveitis.

  View details for DOI 10.1080/09273948.2024.2408401

  View details for Web of Science ID 001331868800001

  View details for PubMedID 39404707

• Managing A Patient with Uveitis in The Era of Artificial Intelligence: Current Approaches, Emerging Trends, And Future Perspectives. Asia-Pacific journal of ophthalmology (Philadelphia, Pa.) Rojas-Carabali, W., Cifuentes-González, C., Gutierrez-Sinisterra, L., Heng, L. Y., Tsui, E., Gangaputra, S., Sadda, S., Nguyen, Q. D., Kempen, J. H., Pavesio, C. E., Gupta, V., Raman, R., Yan, M. C., Lee, B., de-la-Torre, A., Agrawal, R. 2024: 100082

  Abstract

  The integration of artificial intelligence (AI) with healthcare has opened new avenues for diagnosing, treating, and managing medical conditions with remarkable precision. Uveitis, a diverse group of rare eye conditions characterized by inflammation of the uveal tract, exemplifies the complexities in ophthalmology due to its varied causes, clinical presentations, and responses to treatments. Uveitis, if not managed promptly and effectively, can lead to significant visual impairment. However, its management requires specialized knowledge, which is often lacking, particularly in regions with limited access to care. AI's capabilities in pattern recognition, data analysis, and predictive modelling offer significant potential to revolutionize uveitis management. AI can classify disease outcomes, analyze multimodal imaging data, and identify new therapeutic targets. However, transforming these AI models into clinical applications and meeting patient expectations involves overcoming challenges like acquiring extensive, annotated datasets, ensuring algorithmic transparency, and validating these models in real-world settings. This review delves into the complexities of uveitis and the current AI landscape, discussing the development, opportunities, and challenges of AI from theoretical models to bedside application. It also examines the epidemiology of uveitis, the global shortage of uveitis specialists, and the disease's socioeconomic impacts, underlining the critical need for AI-driven approaches. Furthermore, it explores the integration of AI in diagnostic imaging and future directions in ophthalmology, aiming to highlight emerging trends that could transform management of a patient with uveitis and suggesting collaborative efforts to enhance AI applications in clinical practice.

  View details for DOI 10.1016/j.apjo.2024.100082

  View details for PubMedID 39019261

• Colombian Ocular Diseases Epidemiology Study (CODES): Prevalence and Sociodemographic Characterization of Refractive Errors in Colombian Eye Care Consultations OPHTHALMIC EPIDEMIOLOGY Mejia-Salgado, G., Cifuentes-Gonzalez, C., Zarate-Pinzon, L., Pena-Pulgar, L., Rojas-Carabali, W., Valdes-Arias, D., Cruz, D., de-la-Torre, A. 2025; 32 (1): 52-60

  Abstract

  To estimate the prevalence and demographic characteristics of uncorrected refractive errors (URE) in people who attended eye care consultations in Colombia between 2015 and 2019, using the National Health Registry data.We identified ICD codes for myopia (H-52.1), degenerative myopia (H-44.2), hyperopia (H-52.0), and astigmatism (H-52.2) from the Integrated Social Protection Information System. Crude prevalence rates by age and sex were calculated for the population attending eye care services during these years. Additionally, we developed a standardized morbidity map across county departments.In Colombia, the prevalence of URE among eye care consultations was 30.26%, increasing from 30.39% in 2015 to 35.14% in 2019. Of the 1,579,778 cases analyzed, 60.9% were females. Astigmatism emerged as the most prevalent URE, predominantly seen in individuals under 40 years old. Myopia showed the highest prevalence in the 10-30 age group, whereas hyperopia was most prevalent in the first decade of life. Geographically, the Andean region recorded most of URE cases, while more remote areas have seen a rising morbidity risk in recent years.The rising trend of URE in Colombia and its demographic and geographical variations underscores the urgent need for health professionals and government authorities to acknowledge and address this issue. This study provides crucial insights into the refractive error landscape across the country, highlighting the necessity for prevention programs specifically designed to cater to the country's unique needs.

  View details for DOI 10.1080/09286586.2024.2330386

  View details for Web of Science ID 001190610400001

  View details for PubMedID 38527903

• Response to the Comment on "Evaluating the Diagnostic Accuracy and Management Recommendations of ChatGpt in Uveitis". Ocular immunology and inflammation Rojas-Carabali, W., Cifuentes-González, C., Wei, X., Putera, I., Sen, A., Thng, Z. X., Agrawal, R., Elze, T., Sobrin, L., Kempen, J. H., Lee, B., Biswas, J., Nguyen, Q. D., Gupta, V., de-la-Torre, A., Agrawal, R. 2023: 1-2

  View details for DOI 10.1080/09273948.2023.2293924

  View details for PubMedID 38133945

• Chatbots Vs. Human Experts: Evaluating Diagnostic Performance of Chatbots in Uveitis and the Perspectives on AI Adoption in Ophthalmology. Ocular immunology and inflammation Rojas-Carabali, W., Sen, A., Agarwal, A., Tan, G., Cheung, C. Y., Rousselot, A., Agrawal, R., Liu, R., Cifuentes-González, C., Elze, T., Kempen, J. H., Sobrin, L., Nguyen, Q. D., de-la-Torre, A., Lee, B., Gupta, V., Agrawal, R. 2023: 1-8

  Abstract

  To assess the diagnostic performance of two chatbots, ChatGPT and Glass, in uveitis diagnosis compared to renowned uveitis specialists, and evaluate clinicians' perception about utilizing artificial intelligence (AI) in ophthalmology practice.Six cases were presented to uveitis experts, ChatGPT (version 3.5 and 4.0) and Glass 1.0, and diagnostic accuracy was analyzed. Additionally, a survey about the emotions, confidence in utilizing AI-based tools, and the likelihood of incorporating such tools in clinical practice was done.Uveitis experts accurately diagnosed all cases (100%), while ChatGPT achieved a diagnostic success rate of 66% and Glass 1.0 achieved 33%. Most attendees felt excited or optimistic about utilizing AI in ophthalmology practice. Older age and high level of education were positively correlated with increased inclination to adopt AI-based tools.ChatGPT demonstrated promising diagnostic capabilities in uveitis cases and ophthalmologist showed enthusiasm for the integration of AI into clinical practice.

  View details for DOI 10.1080/09273948.2023.2266730

  View details for PubMedID 37831553

• Evaluating the Diagnostic Accuracy and Management Recommendations of ChatGPT in Uveitis. Ocular immunology and inflammation Rojas-Carabali, W., Cifuentes-González, C., Wei, X., Putera, I., Sen, A., Thng, Z. X., Agrawal, R., Elze, T., Sobrin, L., Kempen, J. H., Lee, B., Biswas, J., Nguyen, Q. D., Gupta, V., de-la-Torre, A., Agrawal, R. 2023: 1-6

  Abstract

  Accurate diagnosis and timely management are vital for favorable uveitis outcomes. Artificial Intelligence (AI) holds promise in medical decision-making, particularly in ophthalmology. Yet, the diagnostic precision and management advice from AI-based uveitis chatbots lack assessment.We appraised diagnostic accuracy and management suggestions of an AI-based chatbot, ChatGPT, versus five uveitis-trained ophthalmologists, using 25 standard cases aligned with new Uveitis Nomenclature guidelines. Participants predicted likely diagnoses, two differentials, and next management steps. Comparative success rates were computed.Ophthalmologists excelled (60-92%) in likely diagnosis, exceeding AI (60%). Considering fully and partially accurate diagnoses, ophthalmologists achieved 76-100% success; AI attained 72%. Despite an 8% AI improvement, its overall performance lagged. Ophthalmologists and AI agreed on diagnosis in 48% cases, with 91.6% exhibiting concurrence in management plans.The study underscores AI chatbots' potential in uveitis diagnosis and management, indicating their value in reducing diagnostic errors. Further research is essential to enhance AI chatbot precision in diagnosis and recommendations.

  View details for DOI 10.1080/09273948.2023.2253471

  View details for PubMedID 37722842

• The Potential Role of Large Language Models in Uveitis Care: Perspectives After ChatGPT and Bard Launch. Ocular immunology and inflammation Tan Yip Ming, C., Rojas-Carabali, W., Cifuentes-Gonzalez, C., Agrawal, R., Thorne, J. E., Tugal-Tutkun, I., Nguyen, Q. D., Gupta, V., de-la-Torre, A., Agrawal, R. 2023: 1-5

  View details for DOI 10.1080/09273948.2023.2242462

  View details for PubMedID 37562028

• Ocular Manifestations Related to Antibodies Positivity and Inflammatory Biomarkers in a Rheumatological Cohort CLINICAL OPHTHALMOLOGY Cifuentes-Gonzalez, C., Uribe-Reina, P., Reyes-Guanes, J., Munoz-Ortiz, J., Tatiana Munoz-Vargas, P., Rojas-Carabali, W., Victoria Nova-Florian, D., Sofia De-los-Rios, A., Dario Mantilla-Hernandez, R., De-la-Torre, A. 2022; 16: 2477-2490

  Abstract

  Ocular involvement is frequent in autoimmune diseases and even can be the first manifestation. There are multiple descriptions in the literature around the world regarding this topic. However, we evidenced a lack of studies analyzing the relationship between the ocular manifestations and systemic biomarkers, especially in Latinamerica. Therefore, this study aimed to examine the relationship between the positivity of inflammatory biomarkers and the ocular manifestations in a Colombian cohort of rheumatological patients.We conducted an observational, descriptive, non-comparative cross-sectional study in a rheumatology center, in Bogotá, Colombia, from 2013 to 2019. We calculated a sample size of 797 patients to assess the prevalence of ocular manifestations and inflammatory biomarkers. We performed univariate analyses for categorical and continuous variables and bivariate analyses using the Chi-square and Fisher's exact test for categorical variables.Women represented 84% of the population, and the mean age was 54.61± 15.64 years. Of 797 patients, 21.45% reported one or more ophthalmological diagnoses, being keratoconjunctivitis sicca (KCS) the most common (15.93%), followed by uveitis, and cataract (1.38%, each one). Regarding ophthalmological symptoms, 35% presented at least one, being dry eye sensation (DE) the most common (30.86%), followed by ocular pain (2.76%), red eye, and decreased visual acuity (2.63%, each one). The antibodies or inflammatory biomarkers most frequently found were antinuclear antibodies (ANAs) (35.3%), C-reactive protein (28.7%), and rheumatoid factor (27.9%). We found statistical associations between consumption of complement 3, anti-CCP, anti-RO, and anti-LA antibodies with ocular manifestations such as photophobia, DE, conjunctivitis, KCS, uveitis, retinal vasculitis, and maculopathy.Ocular manifestations are frequently found in patients with positive antibodies and inflammatory biomarkers. Our results suggest antibodies and inflammatory molecules could be biomarkers for ocular manifestations in patients with rheumatological diseases. This study provides the basis for future longitudinal studies.

  View details for DOI 10.2147/OPTH.S361243

  View details for Web of Science ID 000844634200001

  View details for PubMedID 35971506

  View details for PubMedCentralID PMC9375558