Confronting Inequalities and Bridging the Divide: A Retrospective Study Assessment of Country-Level COVID-19 Vaccine Equality with a Cox Regression Model.

COVID-19 vaccination is vital in reducing illness, hospitalization, and mortality in the face of this global pandemic. However, COVID-19 vaccination rates worldwide remain below WHO public health targets, and persistent structural inequities reduce vaccine uptake likelihood among populations of low socioeconomic status. We conducted a cross-sectional study based on publicly available data from the Our World in Data project. We included all 124 countries with available open epidemic data and a population of more than 5 million. We used a Cox Regression Model, with population, population density, median age, human development index, GDP per capita, gender inequality index, healthcare access and quality index, hospital beds per thousand people, completion rate of primary education, infection cases of COVID-19 by the end of 2022, and death rate due to COVID-19 by the end of 2022 as predictors for model hazard rates of completion of 50% population vaccination. According to our study, countries with higher populations, higher population density, higher human development index, lower gender inequality index, and lower hospital beds per 1000 people had a higher hazard rate, which means they were more likely to achieve 50% population vaccination faster. By utilizing the time to achieve vaccination rate goals as our primary endpoint, we evaluated inequity from a dual perspective, considering both the differences in vaccination rates and the duration required to attain them. Consequently, this study employed survival analysis approaches to gain a comprehensive understanding of vaccine drivers and population-level trends nationally and inform all communities from a statistical perspective to prepare for health emergencies. Development-level standing modified the effects of equal access to COVID-19 vaccination on cumulative cases and mortality, for which countries of low or medium human development tended to fare worse in outcomes than high human development countries. As COVID-19 vaccination efforts evolve, healthcare professionals, scholars, and policymakers need to identify the structural impediments to equitable vaccination awareness, access, and uptake so that future vaccination campaigns are not impeded by these barriers to immunization. Recognizing the complex nature of this significant barrier, it is evident that no single statistical analysis method can comprehensively address all intricacies.

Visual supplementation is an effective tool in cataract surgery counselling by eye-care practitioners.

BACKGROUND: Informed consent constitutes an important aspect of eye care. However, patients often experience difficulties understanding and retaining information presented to them during consultations. This study investigates the efficacy of pictorial aids in supplementing preoperative counselling of patients undergoing cataract surgery. METHODS: Patients attending routine pre-cataract surgery counselling were randomized to receive either a standard verbal consultation (control) or a verbal consultation with a digitalized pictorial aid illustrating key surgical steps (intervention). Patients were assessed after the consultation on their knowledge, satisfaction, anxiety and preparedness using an anonymous questionnaire. RESULTS: Seventy-six patients were recruited and randomized into the control and intervention groups. The intervention group attained better Knowledge Scores (control: 5 [2-6] vs. intervention: 6 [6]), and more patients "strongly agreed" that they were more prepared (control: 78.9% vs. intervention: 97.4%, P=0.028). A higher proportion of patients in the control group either "disagreed" or "neither disagree nor agreed (neutral)" that they were less worried (control: 15.8% vs. intervention: 0.0%, Fisher's Exact Test P=0.025). Although the consultation duration was shorter in the intervention group (21±4mins vs. 27±6mins, P<0.001), the use of digital pictorial aids during consultation resulted in more effective counselling with increased patient knowledge, easier decision-making process and reduced patient anxiety. CONCLUSION: Pictorial aids add to the repository of tools available to eye-care practitioners and are low-cost, easy to implement, and can effectively augment existing preoperative counselling processes to ensure accurate and effective preoperative counselling of patients.

Systemic Involvement in Immunoglobulin G4-Related Ophthalmic Disease.

BACKGROUND: Immunoglobulin G4-related ophthalmic disease (IgG4-ROD) poses clinical challenges due to its heterogeneous ocular and systemic manifestations. We aim to report the systemic involvement and the clinical, serological and radiological associations of a cohort of Chinese patients. METHODS: A territory-wide, biopsy-proven, Chinese cohort. A retrospective, masked chart review of medical records, orbital images, and histopathology reports. RESULTS: A total of 122 (65 male) patients with a follow-up of 81 ± 49 (24 to 84) months were reviewed. Ninety (74%) patients presented bilaterally. Subacute upper eyelid swelling was the commonest presentation (82/122, 67%). During follow-up, 91/122 patients (75%) underwent extra-orbital imaging including computer tomography (692 films), ultrasonography (182 films), magnetic resonance imaging (76 films) and whole body FDG-PET scan (33 films). Eighty-six (95%) of these 91 patients had extra-orbital involvement radiologically (2.7 ± 1.6 regions, range: 0 to 9). Lymph node was the most prevalent (N = 60,66%), followed by salivary gland (N = 51,56%), lung (N = 49,54%), kidney (N = 22, 24%), hepatobiliary tree (N = 18, 20%) and pancreas (N = 17, 19%). Other organs include thyroid, aorta, meninges/brain and skin. Twenty-eight (23%) patients had allergic diseases (19 asthma, 16 allergic rhinitis, and 6 eczemas). Fifty-seven (48%) patients had paranasal sinusitis. Serum eosinophilia was associated with a higher number (3.24 versus 2.52, P = 0.0304) of organ involvement. Patients with deep organ involvement was associated with a higher age of IgG4-ROD onset (70 ± 12 versus 56 ± 13, P < 0.0001). CONCLUSIONS: 95% of the patients who underwent systemic imaging in our cohort had systemic organ involvement. An early physicians' assessment and radiological imaging are recommended after the diagnosis of IgG4-ROD.

Ten-year territory-wide trends in the utilisation and clinical outcomes of extracorporeal membrane oxygenation in Hong Kong.

INTRODUCTION: The utilisation of extracorporeal membrane oxygenation (ECMO) has been rapidly increasing in Hong Kong. This study examined 10-year trends in the utilisation and clinical outcomes of ECMO in Hong Kong. METHODS: We retrospectively reviewed the records of all adult patients receiving ECMO who were admitted to the intensive care units (ICUs) of public hospitals in Hong Kong between 2010 and 2019. Temporal trends across years were assessed using the Mann-Kendall test. Observed hospital mortality was compared with the Acute Physiology and Chronic Health Evaluation (APACHE) IV-predicted mortality. RESULTS: The annual number of patients receiving ECMO increased from 18 to 171 over 10 years. In total, 911 patients received ECMO during the study period: 297 (32.6%) received veno-arterial ECMO, 450 (49.4%) received veno-venous ECMO, and 164 (18.0%) received extracorporeal cardiopulmonary resuscitation. The annual number of patients aged ≥65 years increased from 0 to 47 (27.5%) [P for trend=0.001]. The median (interquartile range) Charlson Comorbidity Index increased from 1 (0-1) to 2 (1-3) [P for trend<0.001] while the median (interquartile range) APACHE IV score increased from 90 (57-112) to 105 (77-137) [P for trend=0.003]. The overall standardised mortality ratio comparing hospital mortality with APACHE IV-predicted mortality was 1.11 (95% confidence interval=1.01-1.22). Hospital and ICU length of stay both significantly decreased (P for trend=0.011 and <0.001, respectively). CONCLUSION: As ECMO utilisation increased in Hong Kong, patients put on ECMO were older, more critically ill, and had more co-morbidities. It is important to combine service expansion with adequate resource allocation and training to maintain quality of care.

Droplet digital PCR is a cost-effective method for analyzing long cell-free DNA in maternal plasma: Application in preeclampsia.

OBJECTIVE: Long cell-free DNA (cfDNA) can be found in the plasma of pregnant women and cancer patients. We investigated if droplet digital PCR (ddPCR) can analyze such molecules for diagnostic purposes using preeclampsia as a model. METHOD: Plasma samples from ten preeclamptic and sixteen normal pregnancies were analyzed. Two ddPCR assays targeting a single-copy gene, VCP, and one ddPCR assay targeting LINE-1 repetitive regions were used to measure the percentages of long cfDNA >533, 1001, and 170 bp, respectively. The LINE-1 assay was developed as guided by in silico PCR analyses to better differentiate preeclamptic and normal pregnancies. RESULTS: Preeclamptic patients had a significantly lower median percentage of long cfDNA than healthy pregnant controls, as determined by the LINE-1 170 bp assay (28.9% vs. 35.1%, p < 0.0001) and the VCP 533 bp assay (6.6% vs. 8.7%, p = 0.014). The LINE-1 assay provided a better differentiation than the VCP 533 bp assay (area under ROC curves, 0.94 vs. 0.79). CONCLUSION: ddPCR is a cost-effective approach for unlocking diagnostic information carried by long cfDNA in plasma and may have applications for the detection of preeclampsia. Further longitudinal studies with larger cohorts are required to assess the clinical utility of this test.

Ocular Surface Evaluation in Immunoglobulin G4-Related Ophthalmic Disease.

PURPOSE: To evaluate the functional and structural changes of the meibomian glands and ocular surface in immunoglobulin G4-related ophthalmic disease (IgG4-ROD) patients. DESIGN: Cross-sectional, matched case-control comparison study. METHODS: This study included 64 patients with biopsy-proven IgG4-ROD (aged 63.4 ± 12.2 years, 39 male) and 64 sex- and age-matched healthy controls. Patients were managed by hospitals covering the publicly funded ophthalmology service in Hong Kong. Outcome measures included anterior segment examination and keratographic and meibographic imagings. RESULTS: A total of 64 worst-affected eyes of the 64 IgG4-ROD patients were analyzed. Corneal fluorescein staining (P = .0187), lid margin telangiectasia (P = .0360), lid-parallel conjunctival folds (P = .0112), papillae (P = .0393), meibomian gland plugging (P = .0001), meibomian gland expressibility (P = .0001), and meibum quality (P = .0001) were more significant in IgG4-ROD patients compared with healthy controls. Both upper and lower meibomian gland dropouts (P = .001 and .0003), and tear meniscus height (P = .0001) were higher in IgG4-ROD patients. Non-invasive tear break-up time (NITBUT) (P = .0166) and Schirmer test results (P = .0243) were lower in IgG4-ROD patients. Upper (r = 0.336, P = .0140) meibomian gland dropouts and NITBUT (r = -0.293, P = .0497) were positively and negatively correlated with the IgG4-ROD onset age, respectively. The number of extraocular organ involvement was negatively correlated with the Schirmer test(r = -0.341, P = .0167). Lower NITBUT was found in IgG4-ROD eyes with lacrimal gland enlargement than in IgG4-ROD eyes without lacrimal gland enlargement radiologically (P < .0001). CONCLUSIONS: IgG4-ROD patients showed features of both aqueous tear deficiency and evaporative dry eye disease. We recommend ocular surface evaluation to all patients newly diagnosed with IgG4-ROD. Further studies are warranted to clarify the mechanism of IgG4-related dry eye disease.

Reward System in Late-Life Depression: a Cross-Sectional Case-Control Study.

OBJECTIVE: Anhedonia, commonly defined as a reduced ability to feel pleasure, is a core clinical symptom of late-life depression (LLD). Deficits in reward processing are hypothesised to be associated with anhedonia. We examined differences in reward sensitivity between patients with LLD and healthy controls and explored the associations between LLD-related symptomatology, global cognition, and the reward system. METHODS: The reward responsiveness of 63 patients with LLD and 58 healthy controls aged ≥60 years was assessed using the probabilistic reward learning task with an asymmetric reward schedule. RESULTS: Compared with healthy controls, patients with LLD displayed lower response bias and reward learning. Global cognition of all participants was positively correlated with response bias. In patients with LLD, anhedonia severity explained impaired reward learning. CONCLUSION: A deficit in reward processing is implicated in patients with LLD. Our findings suggest that executive dysfunction and anhedonia contribute to lower sensitivity to reward learning in patients with LLD.

Re-examine the transfusion transmitted risk of SARS-CoV-2 virus during a major COVID-19 outbreak in 2022.

INTRODUCTION: Although no case of COVID-19 transmission through transfusion has been reported, blood transfusion service (BTS) continues to implement pre-donation and post-donation measures to minimise the risk. In year 2022, when local healthcare system was badly impacted by a major outbreak, it opened an opportunity to re-examine the viraemia risk in these asymptomatic donors. MATERIALS AND METHODS: Records were retrieved from blood donors who reported COVID-19 after donation and follow-up was also made for recipients who received their blood. Blood samples at donation were tested for SARS-CoV-2 viraemia by single-tube nested real-time RT-PCR assay designed to detect most SARS-CoV-2 variants including the prevailing delta and omicron variants. RESULTS: From 1 January to 15 August 2022, the city with 7.4 M inhabitants recorded 1 187 844 COVID-19 positive cases and 125 936 successful blood donations were received. 781 donors reported to the BTS after donation with 701 being COVID-19 related (including close contact and symptoms respiratory tract infection). 525 COVID-19 were positive at the time of call back or follow-up. Of the 701 donations, they were processed into 1480 components with 1073 discarded upon donors' call back. For remaining 407 components, no recipient was found to have adverse event or COVID-19 positive. 510 samples from the above 525 COVID-19 positive donors were available and all tested negative for SARS-CoV-2 RNA. DISCUSSION: With the negative SARS-CoV-2 RNA in blood donation samples and follow up data in transfusion recipients, the risk of transfusion transmitted COVID-19 appears negligible. However, current measures remains important in securing blood safety with ongoing surveillance of their effectiveness.

The effectiveness of an ultrafast breast MRI protocol in the differentiation of benign and malignant breast lesions.

AIM: To evaluate the effectiveness of an ultrafast breast magnetic resonance imaging (MRI) protocol in differentiating benign and malignant breast lesions. MATERIALS AND METHODS: Fifty-four patients with Breast Imaging Reporting and Data System (BI-RADS) 4 or 5 lesions were recruited between July 2020 to May 2021. A standard breast MRI was performed with the inclusion of the ultrafast protocol between the unenhanced sequence and the first contrast-enhanced sequence. Three radiologists performed image interpretation in consensus. Ultrafast kinetic parameters analysed included the maximum slope (MS), time to enhancement (TTE), and arteriovenous index (AVI). These parameters were compared using receiver operating characteristics with p-values of <0.05 considered to indicate statistical significance. RESULTS: Eighty-three histopathological proven lesions from 54 patients (mean age 53.87 years, SD 12.34, range 26-78 years) were analysed. Forty-one per cent (n=34) were benign and 59% (n=49) were malignant. All malignant and 38.2% (n=13) benign lesions were visualised on the ultrafast protocol. Of the malignant lesions, 77.6% (n=53) were invasive ductal carcinoma (IDC) and 18.4% (n=9) were ductal carcinoma in situ (DCIS). The MS for malignant lesions (13.27%/s) were significantly larger than for benign (5.45%/s; p<0.0001). No significant differences were seen for TTE and AVI. The area under the ROC curve (AUC) for the MS, TTE, and AVI were 0.836, 0.647, and 0.684, respectively. Different types of invasive carcinoma had similar MS and TTE. The MS of high-grade DCIS was also similar to that of IDC. Lower MS values were observed for low-grade (5.3%/s) compared to high-grade DCIS (14.8%/s) but the results were not significant statistically. CONCLUSION: The ultrafast protocol showed potential to discriminate between malignant and benign breast lesions with high accuracy using MS.

DNA methylation age in paired tumor and adjacent normal breast tissue in Chinese women with breast cancer.

BACKGROUND: Few studies have examined epigenetic age acceleration (AA), the difference between DNA methylation (DNAm) predicted age and chronological age, in relation to somatic genomic features in paired cancer and normal tissue, with less work done in non-European populations. In this study, we aimed to examine DNAm age and its associations with breast cancer risk factors, subtypes, somatic genomic profiles including mutation and copy number alterations and other aging markers in breast tissue of Chinese breast cancer (BC) patients from Hong Kong. METHODS: We performed genome-wide DNA methylation profiling of 196 tumor and 188 paired adjacent normal tissue collected from Chinese BC patients in Hong Kong (HKBC) using Illumina MethylationEPIC array. The DNAm age was calculated using Horvath's pan-tissue clock model. Somatic genomic features were based on data from RNA sequencing (RNASeq), whole-exome sequencing (WES), and whole-genome sequencing (WGS). Pearson's correlation (r), Kruskal-Wallis test, and regression models were used to estimate associations of DNAm AA with somatic features and breast cancer risk factors. RESULTS: DNAm age showed a stronger correlation with chronological age in normal (Pearson r = 0.78, P < 2.2e-16) than in tumor tissue (Pearson r = 0.31, P = 7.8e-06). Although overall DNAm age or AA did not vary significantly by tissue within the same individual, luminal A tumors exhibited increased DNAm AA (P = 0.004) while HER2-enriched/basal-like tumors exhibited markedly lower DNAm AA (P = < .0001) compared with paired normal tissue. Consistent with the subtype association, tumor DNAm AA was positively correlated with ESR1 (Pearson r = 0.39, P = 6.3e-06) and PGR (Pearson r = 0.36, P = 2.4e-05) gene expression. In line with this, we found that increasing DNAm AA was associated with higher body mass index (P = 0.039) and earlier age at menarche (P = 0.035), factors that are related to cumulative exposure to estrogen. In contrast, variables indicating extensive genomic instability, such as TP53 somatic mutations, high tumor mutation/copy number alteration burden, and homologous repair deficiency were associated with lower DNAm AA. CONCLUSIONS: Our findings provide additional insights into the complexity of breast tissue aging that is associated with the interaction of hormonal, genomic, and epigenetic mechanisms in an East Asian population.

Osteoarthritis year in review 2022: Genetics, genomics and epigenetics.

This "year in review" provides a summary of the research findings on the topic of genetics, genomics and epigenetics for osteoarthritis (OA) between Mar 2021-Apr 2022. A search routine of the literature in PubMed for the keyword, osteoarthritis, together with topics on genetics, genomics, epigenetics, polymorphism, Deoxyribonucleic acid (DNA) methylation, noncoding RNA, lncRNA, proteomics, and single cell RNA sequencing, returned key research articles and relevant reviews. Following filtering of duplicates across search routines, 695 unique research articles and 112 reviews were identified. We manually curated these articles and selected 90 as references for this review. However, we were unable to refer to all these articles, and only used selected articles to highlight key outcomes and trends. The trend in genetics is on the meta-analysis of existing cohorts with comparable genetic and phenotype characterization of OA; in particular, clear definition of sub phenotypes to enhance the genetic power. Further, many researchers are realizing the power of big data and multi-omics approaches to gain molecular insights for OA, and this has opened innovative approaches to include transcriptomics and epigenetics data as quantitative trait loci (QTLs). Given that most of the genetic loci for OA are not located within coding regions of genes, implying the impact is likely to be on gene regulation, epigenetics is a hot topic, and there is a surge in studies relating to the role of miRNA and long non-coding RNA on cartilage biology and pathology. The findings are exciting and new insights are provided in this review to summarize a year of research and the road map to capture all new innovations to achieve the desired goal in OA prevention and treatment.

Towards data-driven tele-medicine intelligence: community-based mental healthcare paradigm shift for smart aging amid COVID-19 pandemic.

Purpose: Telemedicine are experiencing an unprecedented boom globally since the beginning of the COVID-19 pandemic. As the most vulnerable groups amid COVID-19, the digital delivery of healthcare poses great challenges to the elderly population, caregiver, health service providers, and health policy makers. To bridge the service delivery gaps between the telemedicine demand side and supply side, explore evidence-based approach for integrated care, address challenges for aging policy, and build foundation for the development of data-driven and community-based telemedicine, our R&D team applied translational research to design and develop telemedicine "SMART" for enhancing elderly mental health wellbeing amid COVID-19. Our aim is to investigate the preparedness mechanisms of mental health disease including response, intervention, and connection these three healthcare delivery pipelines with the collection, consolidation, and synergy of heath parameters and social determinants, using data analytics approach to achieve Evidence-Based Medicine (EBM). Methods: A mix of quantitative and qualitative research design for scientifically rigorous consultation and analysis was conducted from Jan 2020 to June 2021 in Hong Kong. An exploratory and descriptive qualitative design was used in this study. The data were collected through focus group discussions conducted from elderly and their caregivers living in 10 main districts of Hong Kong. Our research pilot tested "SMART" targeting for elderly with mental health improvement needs. Baseline questionnaire with 110 tele-medicine product users includes questions on demographic information, self-rated mental health digital adoption. The follow-up five focus group discussions with 57 users (elderly and their caregivers) further explore the social determinants of telemedicine transformation and help propose the integrated telemedicine paradigm shift framework establishment, development, and enhancement. Results: Grounded on the baseline needs assessment and feedbacks collected, it is evident that multi-dimensional health information from the four various streams (community, clinic, home, remote) and customized digital health solutions are playing a key role in addressing elderly mental health digital service needs and bridging digital divide. The designed tele-medicine product lines up health service provider (supplier side) and elderly specific needs (demand side) with our three-level design, enables elderly and their families to follow and control their own health management and connect with the service provider, community of practice (CoP), and health policy makers. Conclusion: It's beneficial to involve elderly and gerontechnology stakeholders as part of Community-Based Participatory Research (CBPR) before and throughout the developing and delivery phases an integrated and age-friendly digital intervention. The challenges in applying and disseminating telemedicine reflected by the elderly and caregivers can be used as important input for further development and indicators for the sustainable and integrated elderly primary care framework. Supplementary Information: The online version contains supplementary material available at 10.1007/s13755-022-00198-4.

A prospective study on serum citrate levels and clinical correlations in patients receiving regional citrate anticoagulation.

Background: Current ways to diagnose citrate accumulation (CA) in patients receiving regional citrate anticoagulation (RCA) continuous renal replacement therapy (CRRT) are confounded by various clinical factors. Serum citrate measurement emerges as a more direct way to diagnose CA, but its clinical utility and optimal cut-off values remain undefined. This study examined serum citrate kinetics and its diagnostic performance for CA in patients receiving RCA CRRT. Methods: A multicentre prospective study was carried out in two tertiary referral centre intensive care units in Hong Kong with serum citrate levels measured at baseline and 2, 6, 12, 24, 36, 48 and 72 h after initiation of RCA CRRT and their relationships with the development of CA. Results: Among the 133 patients analysed, 18 patients (13.5%) developed CA. The serum citrate levels at baseline and 2, 6 and 12 h after initiation of RCA CRRT in patients who had CA were significantly higher than the non-CA group (P < .001 for all). The CA group also had higher serum citrate levels than the non-CA group {median 0.93 mmol/L [interquartile range (IQR) 0.81-1.16) versus 0.37 mmol/L (IQR 0.26-0.57), P < .001}. Using a cut-off of 0.85 mmol/L, the serum citrate level had a sensitivity of 0.77 and a specificity 0.96 for the diagnosis of CA [area under the receiver operating characteristics curve (AUROC) 0.90, P < .001]. The 2-h and 6-h serum citrate levels had good discriminatory abilities for predicting subsequent development of CA (AUROC 0.86 and 0.83 for 2-h and 6-h citrate levels using cut-off values of 0.34 and 0.63 mmol/L, respectively; P < .001). Conclusion: Serum citrate levels were significantly higher in patients with CA compared with patients without CA. Serum citrate levels showed good performance in diagnosing and predicting the development of CA.

Percutaneous Endoscopic Gastrostomy Tube Timing in Head and Neck Cancer Surgery.

OBJECTIVE: To examine outcomes and complications in patients receiving a percutaneous endoscopic gastrostomy (PEG) tube on the same day of head and neck cancer (HNC) surgery versus later in hospitalization. METHODS: The 2003-2014 Nationwide Inpatient Sample was queried for patients undergoing ablative HNC procedures who had a PEG tube placed. Cases were stratified by PEG tube timing into an early (on the same day as ablative procedure) and late (later in hospitalization) group. Demographics and outcomes were compared using univariate analysis and multivariate regression modeling. RESULTS: A total of 4,068 cases were included, of which 2,206 (54.23%) underwent early PEG and 1,862 (45.77%) received a late PEG tube. Late PEG tube patients were more likely to have a diagnosis of malnutrition (18.0% vs. 15.3%, p = 0.018) or renal failure (4.7% vs. 3.0%, p = 0.006). On multivariate regression analysis, patients receiving late PEG tubes were more likely to experience aspiration pneumonia, acute pulmonary disease, infectious pneumonia, sepsis, hematoma, wound disruption, surgical site infection, and fistula formation (all p < 0.05). The mean length of stay and hospital charges in the late PEG group were significantly greater (17.1 vs. 12.6 days, p < 0.001) and ($159,993 vs. $125,705, p < 0.001), respectively. CONCLUSIONS: Patients undergoing HNC surgery who received a PEG tube on the day of ablative surgery had lower complication rates, shorter length of stay, and decreased hospital costs compared to those who had a PEG tube placed later during hospitalization. Further research is needed to determine the causal relationships behind these findings. LEVEL OF EVIDENCE: 3 Laryngoscope, 133:109-115, 2023.

Malignancies in Immunoglobulin G4-related ophthalmic disease.

PURPOSE: Clinical phenotypes in Immunoglobulin G4-related disease (IgG4-RD) according to the patterns of affecting organs have different risks of malignancies. We attempt to determine the association of malignancies with IgG4-related ophthalmic disease (IgG4-ROD). DESIGN: Retrospective cohort study. METHODS: Review of medical records, orbital images and histopathology reports in a territory-wide cohort of biopsy proven IgG4-ROD patients from 2005-2019. FINDINGS: Among 122 patients who had biopsies taken from adnexal lesions including lacrimal glands (n = 108), orbital mass (n = 30), infiltrated orbital fat (n = 10), conjunctiva (n = 2) or extraocular muscles (n = 3), 13% (16/122) developed malignancies over 73 ± 48months' follow-up. There were 9 cases of ocular adnexal lymphoma (OAL) and 7 extra-orbital malignancies. Compared with the general population, the incidence of OAL was significantly higher (standardized incidence ratios, SIRs = 10.0, 95%CI = 4.5-17.6) while that of extra-orbital malignancies was similar. The SIRs was highest within the first year (SIR = 46.7, 95%CI = 18.5-87.6) when 7 OAL were concomitantly diagnosed. Patients who developed OAL or extra-orbital malignancies were older than other patients at IgG4-ROD diagnosis (64.9 ± 7.1, 68.3 ± 8.5 versus 55.2 ± 15.0 years, P < 0.05). Asymmetric lacrimal gland enlargement (78% versus 13%), lack of frontal (0% versus 12%) or infraorbital nerve enlargement (0% versus 36%) were associated with OAL (all P < 0.05). Pre-treatment serum IgG4 level or extra-orbital IgG4-RD involvement was similar among patients with or without malignancies. CONCLUSION: In this biopsy-proven IgG4-ROD cohort, 7% developed OAL which was 10 times higher than the general population. Patients with asymmetric lacrimal gland enlargement or without trigeminal nerves involvement radiologically were associated with OAL.