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In health care, virtual reality (VR) and augmented reality (AR) have been applied extensively for many purposes. Similar to other technologies such as telemedicine and artificial intelligence, VR and AR may improve clinical diagnosis and screening services in ophthalmology by alleviating current problems, including workforce shortage, diagnostic error, and underdiagnosis. In the past decade a number of studies and products have used VR and AR concepts to build clinical tests for ophthalmology, but comprehensive reviews on these studies are limited. Therefore, we conducted a systematic review on the use of VR and AR as a diagnostic and screening tool in ophthalmology. We identified 26 studies that implemented a variety of VR and AR tests on different conditions, including VR cover tests for binocular vision disorder, VR perimetry for glaucoma, and AR slit lamp biomicroscopy for retinal diseases. In general, while VR and AR tools can become standardized, automated, and cost-effective tests with good user experience, several weaknesses, including unsatisfactory accuracy, weak validation, and hardware limitations, have prevented these VR and AR tools from having wider clinical application. Also, a comparison between VR and AR is made to explain why studies have predominantly used VR rather than AR.

This study aims to investigate the diagnostic accuracy of store-and-forward tele-ophthalmology consultations for non-diabetic patients, aged 40 and above, presenting with vision impairment of 3 months or more, in terms of cataracts, glaucoma, and age-related macular degeneration.This is a prospective comparative study. Enrolled subjects were independently assessed by both tele-ophthalmology and face-to-face assessment. Agreement level between the two modalities for diagnosis and severity were compared using kappa statistic. Diagnostic accuracy of tele-ophthalmology was determined using the face-to-face consultation serving as the gold standard. Costs were compared by calculating the downstream costs generated by each modality in terms of investigations and treatment.A total of 860 eyes of 430 patients were assessed during the study period. Tele-ophthalmology consultations had significantly high agreement with face-to-face consultations in the diagnosis and grading of all three ocular conditions; cataracts, glaucoma, and AMD. Diagnosis and grading of cataracts and AMD reached [Formula: see text] values of 0.8, while diagnosis and grading of glaucoma reached [Formula: see text] values between 0.61 and 0.8. In terms of diagnostic accuracy, tele-ophthalmology consultations were highly sensitive and specific for AMD with greater than 99% sensitivity and specificity achieved by tele-ophthalmology. There was high specificity when diagnosing cataracts, but lower sensitivity at 87.8%. Conversely, there was high sensitivity for diagnosing glaucoma, but lower specificity at 76.5%. Downstream costs were similar between groups.Store-and-forward tele-ophthalmology consultations are accurate and comparable to face-to-face consultations for diagnosis and grading of cataracts, glaucoma, and AMD.

Forming thin tissue constructs with minimal extracellular matrix surrounding them is important for tissue engineering applications. Here, we explore and optimize a strategy that enables rapid fabrication of scaffold-free corneal tissue constructs using the liquid-liquid interface of an aqueous two-phase system (ATPS) that is based on biocompatible polymers, dextran and polyethylene glycol. Intact tissue-like constructs, made of corneal epithelial or endothelial cells, can be formed on the interface between the two liquid phases of ATPS within hours and subsequently collected simply by removing the liquid phases. The formed corneal cell constructs express essential physiological markers and have preserved viability and proliferative ability

Thyroid Eye Disease (TED) is an autoimmune disease that affects the extraocular muscles and periorbital fat. It most commonly occurs with Graves' Disease (GD) as an extrathyroidal manifestation, hence, it is also sometimes used interchangeably with Graves' Ophthalmopathy (GO). Well-known autoimmune markers for GD include thyroid stimulating hormone (TSH) receptor antibodies (TSH-R-Ab) which contribute to hyperthyroidism and ocular signs. Currently, apart from radiological investigations, detection of TED is based on clinical signs and symptoms which is largely subjective, with no established biomarkers which could differentiate TED from merely GD. We evaluated a total of 28 studies on potential biomarkers for diagnosis of TED. Articles included were published in English, which investigated clinical markers in tear fluid, orbital adipose-connective tissues, orbital fibroblasts and extraocular muscles, serum, thyroid tissue, as well as imaging biomarkers. Results demonstrated that biomarkers with reported diagnostic power have high sensitivity and specificity for TED, including those using a combination of biomarkers to differentiate between TED and GD, as well as the use of magnetic resonance imaging (MRI). Other biomarkers which were upregulated include cytokines, proinflammatory markers, and acute phase reactants in subjects with TED, which are however, deemed less specific to TED. Further clinical investigations for these biomarkers, scrutinising their specificity and sensitivity on a larger sample of patients, may point towards selection of suitable biomarkers for aiding detection and prognosis of TED in the future.

The public specialty ophthalmic clinics in Hong Kong, under the Hospital Authority, receive tens of thousands of referrals each year. Triaging these referrals incurs a significant workload for practitioners and the other clinical duties. It is well-established that Hong Kong is currently facing a shortage of healthcare workers. Thus a more efficient system in triaging will not only free up resources for better use but also improve the satisfaction of both practitioners and patients. Machine learning (ML) has been shown to improve the efficiency of various medical workflows, including triaging, by both reducing the workload and increasing accuracy in some cases. Despite a myriad of studies on medical artificial intelligence, there is no specific framework for a triaging algorithm in ophthalmology clinics. This study proposes a general framework for developing, deploying and evaluating an ML-based triaging algorithm in a clinical setting. Through literature review, this study identifies good practices in various facets of developing such a network and protocols for maintenance and evaluation of the impact concerning clinical utility and external validity out of the laboratory. We hope this framework, albeit not exhaustive, can act as a foundation to accelerate future pilot studies and deployments.

Herpes simplex keratitis (HSK) is a significant cause of vision impairment worldwide. Currently, there are no set diagnostic criteria, and popular diagnostic methods, including clinical examination of the eye via slit lamp examination, could lead to false-negatives and misdiagnoses. Molecular testing with polymerase chain reaction (PCR) may lack concordance with clinical findings, posing a great challenge to ophthalmologists. We evaluate recent studies on techniques for the diagnosis of HSK. We included a total of 23 studies published between 2010 and 2020 in English on diagnostic techniques, including in vivo confocal microscopy, polymerase PCR testing, protein detection in tear film with enzyme-linked immunosorbent assay, and various other protein assays. Although PCR has been widely used as one of the current diagnostic methods for HSK, most studies evaluated its efficacy after including alterations to its normal protocol. Tear sample analysis was performed using multiple tools, although corneal scrapings demonstrated a higher positive detection rate. Diagnostic tools identified were able to detect HSK with varying accuracy. Newer diagnostic techniques like multiplex dot hybridization assay and immunochromatographic assays may be considered as the point-of-care preliminary diagnostic tools. More reliable results may be generated by developing a standardized diagnostic protocol.

The study population contains 145 patients who were prospectively recruited for coronary CT angiography (CCTA) and fundoscopy. This study first examined the association between retinal vascular changes and the Coronary Artery Disease Reporting and Data System (CAD-RADS) as assessed on CCTA. Then, we developed a graph neural network (GNN) model for predicting the CAD-RADS as a proxy for coronary artery disease. The CCTA scans were stratified by CAD-RADS scores by expert readers, and the vascular biomarkers were extracted from their fundus images. Association analyses of CAD-RADS scores were performed with patient characteristics, retinal diseases, and quantitative vascular biomarkers. Finally, a GNN model was constructed for the task of predicting the CAD-RADS score compared to traditional machine learning (ML) models. The experimental results showed that a few retinal vascular biomarkers were significantly associated with adverse CAD-RADS scores, which were mainly pertaining to arterial width, arterial angle, venous angle, and fractal dimensions. Additionally, the GNN model achieved a sensitivity, specificity, accuracy and area under the curve of 0.711, 0.697, 0.704 and 0.739, respectively. This performance outperformed the same evaluation metrics obtained from the traditional ML models (p < 0.05). The data suggested that retinal vasculature could be a potential biomarker for atherosclerosis in the coronary artery and that the GNN model could be utilized for accurate prediction.

Immune checkpoint inhibitors (ICIs) have revolutionised the field of oncology. While most ICIs are well-tolerated, severe and fatal immune-related adverse events (irAEs) have been documented, likely related to the strengthened immunity harnessed by ICIs against tumours. Endocrinopathies are some of the most common irAEs, with both hypothyroidism and hyperthyroidism encountered after ICI use. As such, patients with pre-existing autoimmune conditions, such as Graves' disease (GD) with clinically active thyroid eye disease (TED), are excluded from most clinical trials studying ICIs due to concerns of exacerbating pre-existing autoimmune conditions or of increasing the potential for irAE development. The limited information currently available on the safety and efficacy of ICIs in this population poses a clinical challenge for oncologists. The objective of this commentary is to highlight these challenges and provide treatment recommendations pertaining to two specific cohorts of patients with GD, namely GD patients with minimal eye complications and GD patients with previous TED who underwent radiotherapy, surgery or pulse methylprednisolone and whose disease is now quiescent, and to patients with subclinical autoimmune thyroid disease.

Despite advances in ophthalmic diagnostics, the direct ophthalmoscope remains a key clinical skill taught to medical students and is the tool of choice for retina examination among non-ophthalmic physicians. However, in recent years viable alternatives have become available. The coronavirus disease 2019 (COVID-19) pandemic has forced a major re-thinking in medical education worldwide. In this commentary, we examined the current merits and limitations of the direct ophthalmoscope in both the clinical sense and in the context of infection control. Furthermore, we compared the direct ophthalmoscope with alternatives, including commercially available portable non-mydriatic fundus cameras, that would allow a change in focus during ophthalmic teaching. We concluded that the latter will better prepare our medical students for the age of telemedicine and deep-learning systems. While the COVID-19 pandemic will not be the sole reason for the ‘death’ of the direct ophthalmoscope, the global situation will inevitably serve to expedite long overdue changes in our teaching of ophthalmic skills to non-ophthalmic physicians.

Introduction: This review aims to summarise the role of different cells, genes, proteins and lipid in regulating cornea epithelial-stromal homeostasis. Methods: We performed an Entrez PubMed literature search using keywords “human,” “cornea,” “epithelial,” “stromal,” “homeostasis,” “fibrosis response,” and “pathogenesis” on 24th of September 2019, resulting in 35 papers, of which 18 were chosen after filtering for “English language” and “published within 10 years” as well as curation for relevance by the authors. Results: The 18 selected papers showed that corneal epithelial cells, fibroblasts and telocytes, together with genes such as Klf4, Pax6 and Id found in the cells, play important roles in achieving homeostasis to maintain corneal integrity and transparency. Proteins classified as pro-fibrotic ligands and anti-fibrotic ligands are responsible for regulating cornea stromal fibrosis and extracellular matrix deposition, thus regulators of scar formation during wound healing. Anti-inflammatory ligands and wound repairing ligands are critical in eliciting protective inflammation and promoting epithelial healing, respectively. Protein receptors located on cellular membrane play a role in maintaining intercellular connections as well as corneal hydration. Discussion/Conclusion: These studies prompt development of novel therapeutic strategies such as tear drops or ointments that target certain proteins to maintain corneal homeostasis. However, more in vitro and in vivo studies are required to prove the effectiveness of exogenous administration of molecules in improving healing outcome. Hence, future investigations of the molecular pathways highlighted in this review will reveal novel therapeutic tools such as gene or cell therapy to treat corneal diseases.

Objectives To evaluate recent in vivo studies on emerging therapies for managing corneal epithelial injuries. Methods The search was conducted on PubMed for articles published between January 2015 and September 2019 and in English language. Results Thirty studies were identified for evaluation, including those on mesenchymal stem cells, amniotic membrane-derived therapies, endogenous peptides and their inhibitors, as well as hydrogel therapies. Intermediate to strong levels of evidence are presented regarding the use of these strategies on chemically injured cornea, including their effects on healing of corneal epithelial defect, anti-inflammatory properties, prevention of corneal neovascularization, as well as restoration of anatomy and functions of the anterior eye, although clinical trials are needed to determine the safety and efficacy of these strategies on humans. Conclusion Recent advances and understanding in various novel therapeutic methods for corneal epithelial chemical injuries should provide potential alternatives to current standard treatment regimens and help reduce risks of complications, hence improve patient outcomes.

To investigate the prevalence, associations, and causes of visual impairment and blindness in the adult population of Hong Kong.This cross-sectional population-based study included 2018 (870, 43% male) randomly selected adults with a mean age 52 ± 16 years (range 18-90 years) in Hong Kong. Each participant underwent comprehensive ophthalmic examinations. Presenting visual acuity (PVA) and best-corrected visual acuity (BCVA) of each eye was recorded. Prevalence of visual impairment and blindness was calculated using both World Health Organization (WHO) and United States (US) definitions, based on BCVA and PVA.Visual acuity measurements were available for 1952 (96.8%) participants. The prevalence of visual impairment, based on BCVA value, using WHO and US definition, was 1.0 ± 0.1% and 2.7 ± 0.4%, respectively. The prevalence of visual impairment, based on PVA value, was 5.1 ± 0.5% and 14.0 ± 0.8%, using WHO and US definition, respectively. Multivariate analysis demonstrated the presence of visual impairment (PVA, WHO definition) increased significantly with older age (odds ratio 1.039,The prevalence of visual impairment in Hong Kong increased significantly with older age and thinner central corneal thickness. The major causes for impairment were under-correction of refractive error, cataract, and age-related macular degeneration.

To evaluate recent studies on available therapies for meibomian gland dysfunction (MGD).A literature search on recent publications, within the last five years, concerning treatment options for MGD was performed.A total of 35 articles were reviewed after curation by the authors for relevance. In general, all modalities of treatments were shown to have clinical efficacy in alleviating dry eye signs and symptoms, although the extent of improvement and persistency of outcomes varied between the different treatments. Evidence from published studies demonstrate that thermal pulsation produces the longest lasting effect per treatment, but it also incurs the highest per-treatment cost. Reusable methods for warm compress with lipid/semi-fluorinated alkane-containing eye drops are recommended as first-line treatment for mild-to-moderate dry eye patients, because this option is most technically feasible and cost-effective in clinical practice. Intense pulsed light (IPL) therapy and thermal pulsation may be suitable as second line for patients unresponsive to warm compress therapy; however, their respective limitations need to be considered. For refractory MGD with features of periductal fibrosis or severe blepharitis, supplementary treatment with meibomian gland probing or oral antibiotics may be used.All eight forms of treatments, including self-applied eyelid warming, thermal pulsation, IPL, MG probing, antibiotics, lipid-containing eye drops, and perfluorohexyloctane, were effective against MGD, although with varying extent of clinical improvements. A better understanding on the mechanisms of actions may guide physicians to make better treatment decisions targeting the root causes.

Chemical injury of the cornea results in epithelial defect and subsequent stromal scarring and infection. Our study aims to evaluate the effectiveness of pre-treatment of Lycium barbarum polysaccharide (LBP) in promoting corneal re-epithelialization after alkaline burn. The corneas of C57BL/6J mice were pre-treated with topical phosphate-buffered saline or LBP (0.2/2/20 mg/mL) for 7 days, following by 0.1M sodium hydroxide injury for 30 s and washing with distilled water for another 30 s. Area of epithelial defect and thickness of cornea were evaluated. Inflammatory cytokines and water channel expression levels were assessed using immunohistochemistry and Western blot. Compared to the injury group, mice with 2 mg/mL LBP pre-treatment revealed a significant decrease in fluorescein stained area after injury (p = 0.025), with increased epithelial layer thickness (p = 0.004). The corneal opacity was significantly reduced in the group with 2 mg/mL LBP pre-treatment followed by injury (p = 0.02). The expression of matrix metalloproteinase 12 (p = 0.033), platelet derived growth factor-BB (p = 0.031), and aquaporin 5 (p = 0.022) resulted in a decrease in expression level in group with 2 mg/mL LBP pre-treatment. Our results showed that 2 mg/mL LBP, with no apoptotic effect on corneal cells, promoted corneal epithelial growth and minimized disruption of the collagen architecture after injury in vivo. We suggest that LBP, as a natural Traditional Chinese Medicine, may potentially be a novel topical pre-treatment option for patients highly susceptible to ocular injury.

Different pathophysiologic mechanisms are involved in the initiation, development, and outcome of dry eye disease (DED). Animal models have proven valuable and efficient in establishing ocular surface microenvironments that mimic humans, thus enabling better understanding of the pathogenesis. Several dry eye animal models, including lacrimal secretion insufficiency, evaporation, neuronal dysfunction, and environmental stress models, are related to different etiological factors. Other models may be categorized as having a multifactorial DED. In addition, there are variations in the methodological classification, including surgical lacrimal gland removal, drug-induced models, irradiation impairment, autoimmune antibody-induced models, and transgenic animals. The aforementioned models may manifest varying degrees of severity or specific pathophysiological mechanisms that contribute to the complexity of DED. This review aimed to summarize various dry eye animal models and evaluate their respective characteristics to improve our understanding of the underlying mechanism and identify therapeutic prospects for clinical purposes.

Recent studies have highlighted the association between ocular diseases and microbiota profiles of the host intestinal tract and oral cavity. There is mounting evidence supporting the existence of a ‘gut–eye axis’, whereby changes in gut microbiome alter host immunity, with consequential implications for ocular health and disease. In this review, we examined recent published findings on the association between gut microbiome and ocular morbidity, based on 25 original articles published between 2011 to 2020. The review included both clinical and in vivo animal studies, with particular focus on the influence of the microbiome on host immunity and metabolism. Significant associations between altered intestinal microbiome and specific ocular diseases and pathological processes, including Behçet’s syndrome, autoimmune uveitis, age-related macular degeneration, choroidal neovascularization, bacterial keratitis, and Sjögren-like lacrimal keratoconjunctivitis have been demonstrated. Furthermore, alterations in the gut microbiome resulted in quantifiable changes in the host immune response, suggesting immunopathogenesis as the basis for the link between intestinal dysbiosis and ocular disease. We also examined and compared different techniques used in the identification and quantification of gut microorganisms. With our enhanced understanding of the potential role of gut commensals in ophthalmic disease, the stage is set for further studies on the underlying mechanisms linking the gut microbiome, the host immune response, and the pathogenesis of ophthalmic disease.

We systematically reviewed published research on dry eye disease and its association with higher order aberrations (HOAs). The purpose of this review was to first determine if an association between tear film metrics and HOAs exists and second to determine if the treatment of dry eyes can improve tear film metrics and HOAs together. A search was conducted in Entrez PubMed on 25 April 2021 using the keywords “higher order aberrations” and “dry eye”. The initial search yielded 61 articles. After publications were restricted to only original articles measuring HOA outcomes in patients with dry eye, the final yield was 27 relevant articles. Of these 27 papers, 12 directly looked at associations and correlations between dry eyes and HOA parameters. The remaining 15 studies looked at dry eye interventions and HOA outcomes and parameters. There is clear evidence demonstrating that dry eyes and HOAs have an association, and that the tear film is one of the most important factors in this relationship. There is also a direct correlation between tear film metrics and HOAs. Improvements in HOAs with dry eye interventions provide further evidence to support the intricate relationship between the two. Despite the clear association between HOAs and dry eye disease, further research is still required in the realm of clinical application as dry eye interventions vary depending on many factors, including patient severity and eye drop viscosity.

Retinal ganglion cell (RGC) death is the central and irreversible endpoint of optic neuropathies. Current management of optic neuropathies and glaucoma focuses on intraocular pressure-lowering treatment which is insufficient. As such, patients are effectively condemned to irreversible visual impairment. This review summarizes experimental treatments targeting RGCs over the last decade. In particular, we examine the various treatment modalities and determine their viability and limitations in translation to clinical practice. Experimental RGC treatment can be divided into (1) cell replacement therapy, (2) neuroprotection, and (3) gene therapy. For cell replacement therapy, difficulties remain in successfully integrating transplanted RGCs from various sources into the complex neural network of the human retina. However, there is significant potential for achieving full visual restoration with this technique. Neuroprotective strategies, in the form of pharmacological agents, nutritional supplementation, and neurotrophic factors, are viable strategies with encouraging results from preliminary noncomparative interventional case series. It is important to note, however, that most published studies are focused on glaucoma, with few treating optic neuropathies of other etiologies. Gene therapy, through the use of viral vectors, has shown promising results in clinical trials, particularly for diseases with specific genetic mutations like Leber’s hereditary optic neuropathy. This treatment technique can be further extended to nonhereditary diseases, through transfer of genes promoting cell survival and neuroprotection. Crucially though, for gene therapy, teratogenicity remains a significant issue in translation to clinical practice.

To evaluate recent studies on available and experimental therapies in preventing or minimizing corneal stromal scarring after injury.We performed an Entrez PubMed literature search using keywords "cornea," "scarring," "haze," "opacity," "ulcer," "treatments," "therapies," "treatment complications," and "pathophysiology" resulting in 390 articles of which 12 were analyzed after filtering, based on English language and publication within 8 years, and curation for relevance by the authors.The 12 articles selected included four randomized control trials (RCTs) (two were double-blinded placebo-controlled RCTs, one was a prospective partially masked RCT, and one was an open-label RCT), two retrospective observational studies, and six laboratory-based studies including two studies having in vivo and in vitro experiments, one was in vivo study, one was ex vivo study, and the last two were in vitro studies. The current mainstay for preventing or minimizing corneal scarring involves the use of topical corticosteroids and local application of mitomycin C. However, supportive evidence for their use in clinical practice from well-designed RCTs is lacking. Laboratory studies on topical rosiglitazone therapy, vitamin C prophylaxis, gene therapy, and stem cell therapy have shown promising results but have yet to be translated to clinical research.There is a need for more robust randomized controlled trials to support treatments using topical corticosteroids and mitomycin C. Furthermore, their clinical efficacy and safety profile should be compared with new treatments that have shown promising results in the laboratory setting. Ultimately, the goal should be to personalize cornea scarring treatment according to the most effective treatment for the specific underlying pathology.

Dry eyes is one of the most common complications after laser vision correction. Small incision lenticule extraction (SMILE) is a flapless procedure with a smaller corneal incision, less corneal nerves are transected during, making it theoretically less prone to dry eyes. Both SMILE and femtosecond-laser-assisted in situ keratomileusis (FS-LASIK) induce a transient worsening in dry eye parameters, but there is evidence showing that SMILE holds promises to have fewer negative impacts on the ocular surface parameters and allow an earlier recovery. SMILE-treated eyes may also have shown less corneal denervation and better corneal sensitivity compared with FS-LASIK eyes. This review summarizes the mechanisms of dry eyes after laser vision correction, the short-term (≤6 months) and long-term (>6 months) results in changes to dry eyes signs and symptoms, and corneal sensitivity of SMILE, as compared with FS-LASIK. Limitation of the studies and reasons accounting for their discrepancies will be discussed. Future randomized controlled trials with standardized postoperative regime are needed for better evaluation of dry eyes after SMILE.

Background To investigate the occurrence of ciliochoroidal detachment (CCD), its risk factors and its impact on the success rate after Ahmed glaucoma valve (AGV) implantation. Methods This is a retrospective observational study carried out at Eye Hospital of Wenzhou Medical University, Zhejiang, China. Patients with uncontrolled glaucoma who underwent AGV implantation alone or combined with phacoemulsification (AGV-Phaco) in the hospital from April 1, 2013 to July 31, 2016 were included. The preoperative and postoperative CCD was defined when the detachment between ciliary body and choroid was detected by the ultrasound biomicroscopy (UBM) and anterior segment optical coherence tomography (AS-OCT) respectively. The main outcomes included the incidence of CCD and the success rate at 6 months after surgery. Results In total, 97 male and 56 female patients were included. CCD was observed in 92 (57.8%) eyes. The glaucoma diagnosis in the Non-CCD and CCD group included primary open angle glaucoma (21(31.3%) vs 33(35.9%)), primary angle closure glaucoma (10(14.9%) vs 13(14.1%)), secondary glaucoma (25(37.3%) vs (28(30.4%)) and so on. The preoperative median IOP (interquartile range) were 21.7(16.0,32.0) mmHg and 23.0(16.0,33.0) mmHg in the Non-CCD group and CCD group. Previous surgical history (95% confidence interval (CI), 1.24 to 13.34; odds ratio (OR) 4.06; p = 0.02) and shorter axial length (95% CI, 0.62 to 0.97 OR 0.78; p = 0.02) were the two risk factors of CCD. The success rate between the CCD and Non-CCD group was not significantly different (64.3% vs 62.5%, p = 0.86) at 6 months. Conclusions The incidence of CCD is 57.8% after AGV surgery. Eyes with previous surgical procedure was prone to CCD occurrence and longer axial length was protective against CCD. But at 6 months postoperatively, CCD did not reduce the success rate of AGV surgery and may not be a worrisome complication.

In recent years, there has been increasing scientific interest in the use of tear film biomarkers in the diagnosis and management of dry eye disease (DED), owing to their potential important roles in the pathogenesis of ocular surface damage, as well as the technical feasibility of tear sample collection techniques. An Entrez PubMed search was conducted on March 2, 2019, to include papers investigating the use of tear film biomarkers in DED, and the results were classified according to whether the DED is associated with systemic inflammatory disease or not and further classified within each section according to the molecular nature of the biomarker for further discussion. A total of 58 relevant articles were reviewed. Certain cytokines, including interleukin-6 (IL-6), tumor necrosis factor-alpha, IL-17, and IL-8, were found by a number of studies to consistently reflect disease severity well and had strong correlations with tear film metrics and tests for ocular surface damage in dry eye without systemic inflammatory disease. For dry eye with systemic inflammatory disease, IL-17, IL-8, and IL-1 receptor antagonists were shown to be consistently higher in affected eyes and correlated well with ocular surface disease severity in more than one type of inflammatory disease. With the advancement in technology and lowered costs in the future, tear film biomarker counts would allow better diagnosis and monitoring of DED, as well as facilitate personalized treatment strategies.

This systematic review aimed to determine the comorbid dry eye (DE) and allergic conjunctivitis (AC) prevalence. We searched PubMed and EMBASE for articles published until 22 March 2022, combining the terms “(dry eye OR keratoconjunctivitis sicca) AND allergic conjunctivitis.” Study-specific estimates (DE and AC incidence rates among patients with AC and DE, respectively) were combined using the one-group meta-analysis in a random-effects model. The initial search yielded 700 studies. Five articles reporting AC incidence among individuals with DE and six articles reporting DE incidence among individuals with AC were included in the qualitative synthesis. In these nine articles, the total sample size was 7254 patients. The DE incidence among individuals with AC was 0.9–97.5%; the AC incidence among individuals with DE was 6.2–38.0%. One-group meta-analysis using a random-effects model showed that 47.2% (95% confidence interval: 0.165–0.779; 320/1932 cases) of patients with AC had comorbid DE and 17.8% (95% confidence interval: 0.120–0.236; 793/4855 cases) of patients with DE had comorbid AC, as defined by each article. Complimentary screening and treatment for patients with DE and AC may improve long-term outcomes and prevent chronic ocular damage in highly susceptible populations.

Background Limbic encephalitis is characterized by rapid onset of working memory deficit, mood changes, and often seizures. The condition has a strong paraneoplastic association, but not all cases are invariably due to tumors. Case presentation We present a case of limbic encephalitis in a Chinese patient who initially presented to our hospital with optic neuritis and no other neurological symptoms. The diagnosis was made radiologically, and cognitive and neurological symptoms did not occur until 5 months later. Extensive investigations for autoimmune, infective, and neoplastic causes were all negative. A working diagnosis of paraneoplastic neurological syndrome was made, and the patient is being managed with high-dose steroid therapy according to the Optic Neuritis Treatment Trial protocol during relapses, as well as with tumor surveillance. Conclusions This case highlights ocular symptoms as important clues for diagnosing neurological diseases, as well as autoimmune encephalitis as an important differential diagnosis in the management of “idiopathic” optic neuritis in the Chinese population.

Cornea epithelial-stromal scarring is related to the differentiation of fibroblasts into opaque myofibroblasts. Our study aims to assess the effectiveness of Lycium barbarum polysaccharide (LBP) solution as a pre-treatment in minimizing corneal scarring.Human corneal fibroblasts were cultured in a three-dimensional collagen type I-based hydrogel in an eye-on-a-chip model. Fibroblasts were pre-treated with 2 mg/mL LBP for 24 h, followed by another 24-h incubation with 10 ng/mL transforming growth factor-beta 1 (TGF-β1) to induce relevant physiological events after stromal injury. Intracellular pro-fibrotic proteins, extracellular matrix proteins, and pro-inflammatory cytokines that involved in fibrosis, were assessed using immunocytochemistry and enzyme-linked immunosorbent assays.Compared to the positive control TGF-β1 group, LBP pre-treated cells had a significantly lower expression of alpha-smooth muscle actin, marker of myofibroblasts, vimentin (p 0.05), and also extracellular matrix proteins both collagen type II and type III (p 0.05) that can be found in scar tissues. Moreover, LBP pre-treated cells had a significantly lower secretion of pro-inflammatory cytokines interleukin-6 and interleukin-8 (p 0.05). The cell-laden hydrogel contraction and stiffness showed no significant difference between LBP pre-treatment and control groups. Fibroblasts pretreated with LBP as well had reduced angiogenic factors expression and suppression of undesired proliferation (p 0.05).Our results showed that LBP reduced both pro-fibrotic proteins and pro-inflammatory cytokines on corneal injury in vitro. We suggest that LBP, as a natural Traditional Chinese Medicine, may potentially be a novel topical pre-treatment option prior to corneal refractive surgeries with an improved prognosis.

In 2020, the COVID-19 pandemic led to an almost overnight adoption of online learning across medical schools worldwide. The initial experience proved jarring and challenging for students and medical educators alike, with neither side familiar with the new tools thrusted upon them. Over time, it became apparent that the adaptations made catalysed a long overdue systemic re-examination of the way medical education has been, and should be, delivered.So far, COVID-19 has served as a strong impetus for education institutes to incorporate commercially available and widely accessible communication platforms, including Zoom, to effectively deliver didactic lectures and interactive tutorials in the digital space. At our institution,the University of Hong Kong Li Ka Shing Faculty of Medicine (HKUMed), one such example is the problem-based learning (PBL) tutorial, the format of which has largely remained unchanged since its introduction two decades ago. By closely examining our offline-to-online transition, we have been able to identify certain pitfalls when attempting to translate traditional tutorials to the digital space; key considerations concerning the online facilitator-learner experience, and enhancements for more effective learning. In this article, we present twelve tips rooted in our experience as learners and teachers that should make PBL sessions more fruitful for everyone involved. &nbsp

Jasper Ka Wai Wong,1 Jeremy Sze Wai John Kwok,1 Jonathan Cheuk Hung Chan,1 Kendrick Co Shih,1 ‪Renyuan Qin,2 Denvid Lau,2 Jimmy Shiu Ming Lai1 1Department of Ophthalmology, Li Ka Shing Faculty of Medicine, University of Hong Kong, Hong Kong; 2Department of Architecture and Civil Engineering, College of Engineering, City University of Hong Kong, Hong KongCorrespondence: Jimmy Shiu Ming LaiDepartment of Ophthalmology, Li Ka Shing Faculty of Medicine, University of Hong Kong, Room 301, Block B, Cyberport 4, 100 Cyberport Road, Hong KongTel +852 39621405Email smjlai@netvigator.comBackground: Concerns had been raised for the potential hazard of SARS-CoV-2 transmissions via aerosols and fluid droplets during cataract surgeries amid the COVID-19 pandemic. This study aims to evaluate the rate of visible aerosol generation and fluid spillage from surgical wounds during phacoemulsification in human subjects.Methods: This is a prospective consecutive interventional case series. High-resolution video captures of 30 consecutive uncomplicated phacoemulsification surgeries, performed by 3 board-certified specialists in ophthalmology, were assessed by 2 independent and masked investigators for intraoperative aerosolization and fluid spillage. Water-contact indicator tape was mounted on the base of the operating microscope, around the objective lens, to detect any fluid contact.Results: No visible intraoperative aerosolization was detected in any of the cases, irrespective of different surgical practices among the surgeons with regard to wound size and position, lens fragmentation technique, power settings and means of ocular lubrication, or the different densities of cataract encountered. Large droplets spillage was noted from the paracentesis wounds in 70% of the cases. For all cases where fluid spill was detected on video, there was no fluid contact detected on the water-contact indicator tape.Conclusion: Visible aerosolization was not detected during phacoemulsification in our case series. Although the rate of fluid spillage was high, the lack of detectable contact with the indicator tape suggested that these large droplets posed no significant infectious risks to members of the surgical team.Keywords: phacoemulsification, aerosols, aerosolization, droplets, COVID

(1) Objective: To study the anti-fibrotic effects of Lycium barbarum polysaccharides (LBP) on corneal stromal fibroblasts and assess LBP&rsquo, s effect on cell viability. (2) Methods: Primary human corneal keratocytes of passage 3 to 6 were used for all experiments. Cells are pretreated with LBP solution for 24 h and then transforming growth factor beta 1 (TGF&beta, 1) for 48 h and collected for experiments. Fibrotic protein analysis was performed using immunofluorescence and Western blot. The effect of LBP on cell viability was assessed using the MTS assay. (3) Results: LBP significantly reduced the expression of fibrotic proteins, including &alpha, SMA and extracellular matrix proteins (collagen type I and III). LBP significantly decreased the viability of myofibroblasts but not the fibroblasts. Conclusions: In this study, LBP was effective in the prevention of fibrosis gene expression. Further studies to assess the underlying mechanism and pharmacological properties will facilitate the formation of a topical LBP solution for in vivo studies.

PurposeTo investigate the optic disc and peripapillary vessel density, as well as its ocular and systemic associations, in healthy eyes among adult Chinese population.MethodsA population-based cross-sectional eye survey was conducted on Chinese adults residing in Hong Kong. 1891 eyes from 1891 participants who completed 4.5×4.5 mm optical coherence tomography angiography scans were recruited. Among the 1891 eyes, 404 were excluded due to low scan quality, optic disc or retinal disorders and non-Chinese ethnicity. The vessel densities (VDs) at nerve fibre layer plexus (NFLP) at both optic disc and peripapillary were collected for analysis. Multiple linear regression analysis was performed to determine the ocular and systemic associations of NFLP VD.ResultsThe study included 1487 participants (men: 41.2%) with a mean age of 48.8±15.4 years. The mean NFLP VD of the whole en face image, inside disc and peripapillary region was 53.8%, 42.7% and 60.3%, respectively. In the multivariable model, decreased NFLP VDs were significantly associated with older age, male gender, longer axial length (AL) and lower Signal Strength Index.ConclusionsThis large population-based cross-sectional study provided quantitative data of optic disc and peripapillary NFLP VD which may serve as a normative reference for clinical use. Apart from age, gender and AL, the scan signal strength also should be taken into consideration during the assessment of NFLP VD.

Background The last visual survey of older adults in Hong Kong was a district-level study in 2002, with no assessment of behavioral and medical risk factors for visual impairment (VI). Our objectives were to determine the latest VI prevalence among older adults, significance of any spatial and temporal differences on the prevalence, and any associations of sociodemographic, behavioral and medical risk factors with VI from a multi-perspective analysis. Methods Community-based pilot survey of residents from a suburb of Hong Kong, aged ≥50, using a standardized questionnaire, was conducted in 2016. Results Of the 222 subjects, crude rates of bilateral and unilateral VI were 9.46 and 32.88%, respectively, or corresponding age-and-gender-adjusted rates of 6.89 and 30.5%. Older age and lower educational were associated with higher risk for unilateral VI, while older age, temporary housing, obesity and hyperlipidemia were associated with higher risk for bilateral VI. Smoking and alcohol-drinking status were not associated with unilateral or bilateral VI. Relative changes in ORs of hypertension or educational level on unilateral or bilateral VI were > 10% after adjusting for age. Interaction term between hyperlipidemia and gender or obesity was significant for unilateral VI. Gender, hypertension and cataract were not associated with unilateral or bilateral VI in general population of pooled analysis but were identified as risk factors in specific subgroups of stratified analysis. Refractive error (myopia or hyperopia) was significantly associated with VI in the eye-level analysis after adjusting the inter-eye correlation. Conclusions Sociodemographic and medical risk factors contributed to VI, but behavioral risk factors did not. Sociodemographic disparities of visual health existed. Age was the confounders of the VI-hypertension or VI-educational level relationships. Gender and obesity were more likely to have multiplicative effect on unilateral VI when combined with hyperlipidemia. Stratified analysis should be conducted to provide further insight into the risk factors for VI in specific populations. Uncorrected refractive error remains a significant cause of impaired vision. The spatial and temporal differences in bilateral VI prevalence from the previous local study indicates a territory-wide survey is needed to assess regional differences and overall prevalence of VI in Hong Kong.

Summary Background Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) emerged in December 2019, causing a respiratory disease (coronavirus disease 2019, COVID-19) of varying severity in Wuhan, China, and subsequently leading to a pandemic. The transmissibility and pathogenesis of SARS-CoV-2 remain poorly understood. We evaluate its tissue and cellular tropism in human respiratory tract, conjunctiva, and innate immune responses in comparison with other coronavirus and influenza virus to provide insights into COVID-19 pathogenesis. Methods We isolated SARS-CoV-2 from a patient with confirmed COVID-19, and compared virus tropism and replication competence with SARS-CoV, Middle East respiratory syndrome-associated coronavirus (MERS-CoV), and 2009 pandemic influenza H1N1 (H1N1pdm) in ex-vivo cultures of human bronchus (n=5) and lung (n=4). We assessed extrapulmonary infection using ex-vivo cultures of human conjunctiva (n=3) and in-vitro cultures of human colorectal adenocarcinoma cell lines. Innate immune responses and angiotensin-converting enzyme 2 expression were investigated in human alveolar epithelial cells and macrophages. In-vitro studies included the highly pathogenic avian influenza H5N1 virus (H5N1) and mock-infected cells as controls. Findings SARS-CoV-2 infected ciliated, mucus-secreting, and club cells of bronchial epithelium, type 1 pneumocytes in the lung, and the conjunctival mucosa. In the bronchus, SARS-CoV-2 replication competence was similar to MERS-CoV, and higher than SARS-CoV, but lower than H1N1pdm. In the lung, SARS-CoV-2 replication was similar to SARS-CoV and H1N1pdm, but was lower than MERS-CoV. In conjunctiva, SARS-CoV-2 replication was greater than SARS-CoV. SARS-CoV-2 was a less potent inducer of proinflammatory cytokines than H5N1, H1N1pdm, or MERS-CoV. Interpretation The conjunctival epithelium and conducting airways appear to be potential portals of infection for SARS-CoV-2. Both SARS-CoV and SARS-CoV-2 replicated similarly in the alveolar epithelium; SARS-CoV-2 replicated more extensively in the bronchus than SARS-CoV. These findings provide important insights into the transmissibility and pathogenesis of SARS-CoV-2 infection and differences with other respiratory pathogens. Funding US National Institute of Allergy and Infectious Diseases, University Grants Committee of Hong Kong Special Administrative Region, China; Health and Medical Research Fund, Food and Health Bureau, Government of Hong Kong Special Administrative Region, China.

Background: A novel human coronavirus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) emerged in December 2019, to cause a respiratory disease (COVID-19) of varying severity in Wuhan China, subsequently spreading to other parts of China and beyond. Methods: We infected ex vivo explant cultures of the human conjunctiva, bronchus and lung, and in vitro cultures of primary human alveolar epithelial cells and macrophages with SARS-CoV-2, and assessed viral tropism, replication competence and innate immune responses, in comparison with SARS-CoV, MERS-CoV, and the 2009 pandemic influenza H1N1 (pdmH1N1) virus. Findings: SARS-CoV-2 infected ciliated, mucus secreting and club cells of bronchial epithelium, spindled morphologically type I pneumocytes in the lung, and the conjunctival mucosa. Virus replication competence of SARS-CoV-2 in the bronchus was higher than that of SARS-CoV but lower than pdmH1N1. SARS-CoV-2 replication was comparable with SARS-CoV and pdmH1N1 in the lung but was lower than MERS-CoV. SARS-CoV-2 virus was a less potent inducer of pro-inflammatory cytokines compared with H5N1 and MERS-CoV. Influenza virus infection of alveolar epithelial cells increased ACE2 expression. Interpretation: The conjunctival epithelium and the conducting airways appear to be potential portals of infection of SARS-CoV-2. Both SARS-CoV and SARS-CoV-2 replicated comparably in the alveolar epithelium explaining the progression of infection to a primary viral pneumonia. Funding Statement: US National Institute of Allergy and Infectious Diseases (NIAID) under Centers of Excellence for Influenza Research and Surveillance (CEIRS) contract no. HHSN272201400006C and the Theme Based Research Scheme (Ref: T11-705/14N), Hong Kong Special Administrative Region. Declaration of Interests: There is no conflict of interest for all authors. Ethics Approval Statement: All experiments were carried out in a Bio-safety level 3 (BSL-3) facility. Informed consent was obtained from all subjects and approval was granted by the Institutional Review Board (IRB) of the University of Hong Kong and the Hospital Authority (Hong Kong West) (approval no: UW 20-167).

Purpose Silicone oil (SiO) with additives of high-molecular-weight (HMW) SiO molecules, eases both the injection and removal. When used inside an eye, it remains unclear how increasing extensional viscosity of SiO might reduce emulsification. Using cell-lined models, this study aims to understand the reason why SiO with HMW is less prone to emulsification. Methods The adhesion of SiO was studied and recorded in a cell-coated microchannel by optical microscopy. The resistance of SiO against emulsification was tested on another cell-coated eye-on-a-chip platform, which was subject to simulated saccadic eye movements, for 4 days. Silicone oil (SiO) candidates with HMW, SiOHMW 2000 and SiOHMW 5000 , and their counterparts SiO2000 and SiO5000 without HMW, were tested. The quantity of the SiO emulsified droplets formed was assessed daily by optical microscopy. Results When flowing in the microchannel, SiO adheres on the cell-coated substrate. The number of droplets is generally lower in SiO with HMW than their counterparts. At the end of the experiment, the average numbers of droplets in SiO2000 (29.1 ± 41.0) and SiO5000 (9.1 ± 19.5) are higher than those in SiOHMW 2000 (6.0 ± 4.5) and SiOHMW 5000 (5.6 ± 4.1). Conclusion A new mechanism of emulsification of SiO is proposed: SiO adheres to ocular tissue to form emulsified droplets. The presence of HMW, which increases the extensional viscosity, may resist the break-up of SiO from the substrate to form emulsified droplets. When tested in a physiologically representative platform, the use of HMW in SiO generally reduces the number of droplets formed in vitro.

Importance Diabetes mellitus is known to be associated with dry eye syndrome (DES), but the effects of long-term glycaemic control on tear film metrics and dry eye symptoms are not known in the Chinese population. Background To evaluate tear film stability and dry eye symptoms and their associations with systemic risk factors in Chinese patients with type 2 diabetes mellitus (T2DM). Design Cross-sectional study set at the Lo Fong Siu Po Eye Centre (Grantham Hospital), Hong Kong. Participants A total of 80 Chinese participants, aged 18 or above, with T2DM recruited from the specialist outpatient setting were included. Methods The Oculus Keratograph 5M (Oculus Inc., Wetzlar, Germany) was used to measure the non-invasive tear break-up time (NITBUT). Ocular symptoms were evaluated using the Ocular Surface Disease Index (OSDI). The association between OSDI, NITBUT and metabolic parameters relating to diabetes were evaluated using multiple linear regression. Main outcome measures The associations between long-term glycaemic control and NITBUT and OSDI scores. Results Stepwise multiple linear regression analysis revealed glycated haemoglobin to be the only significant independent variable for NITBUT (R2 = 0.099, P = 0.014) and OSDI (R2 = 0.062, P = 0.044) after controlling for potential confounders. The age-adjusted prevalence of DES was 20% (95% confidence interval: 11-30%) in the Chinese T2DM population. The odds of DES for increasing percentage of glycated haemoglobin was 1.49 (95% confidence interval: 1.03-2.17, P = 0.04). Conclusions and relevance Our findings highlight the importance of good glycaemic control as a modifiable risk factor for both dry eye symptoms and tear film instability in patients with T2DM.