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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. [ABSTRACT FROM AUTHOR]

Aims: Recently, chemically modified silicone oil has been demonstrated as a reservoir for sustained release of intraocular drugs, many of which might be amphiphilic in nature. In this work, we study the effect of amphiphilic additives in silicone oil on emulsification under eye‐like movements. Methods: Three silicone‐oil‐soluble surfactants, namely DC749, MQ1640 and FZ2233, were used as model amphiphilic additives. The change of viscosity was measured by a rheometer in the cone‐and‐plate geometry. The interfacial tension (IFT) between silicone oil and model aqueous phase was measured by pendant drop tensiometry. Emulsification of silicone oil was induced by simulated saccadic eye movements on a cell‐coated eye‐on‐a‐chip platform for 4 days. The number of emulsified silicone oil droplets observed in the aqueous phase was assessed daily by optical microscopy. Results: Significantly more emulsified droplets were formed in silicone oil with DC749 or MQ1640 (P < 0.05). However, such increase was not directly related to the change in IFT nor viscosity. Moreover, water droplets were also found in the silicone oil, but not in the control silicone oil without additive. Conclusions: The amphiphilic substances in silicone oil promoted emulsification. Besides typical oil‐in‐water drops that normally affect the eye, water‐in‐oil drops were also formed. Before silicone oil could be considered as a vehicle for drug delivery, the nature of the drug and its possible effect on emulsification and therefore on the pharmacokinetics needs to be investigated. An additional concern is that water‐in‐oil droplets in the eye would affect the optical clarity of silicone oil and might cause visual symptoms. [ABSTRACT FROM AUTHOR]

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, SiOHMW2000 and SiOHMW5000, 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 SiOHMW2000 (6.0 ± 4.5) and SiOHMW5000 (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. [ABSTRACT FROM AUTHOR]

The article discusses how the COVID-19 pandemic has changed the way clinical skill teaching is conceived and delivered. Topics covered include how medical education responded and adapted when routine bed-side teaching is impossible because of school suspension, lockdown and social distancing measures, the popularity of the incorporation of teleconference practice by means for routine ward teaching, and the limitations of videoconference-based teaching.

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., Competing Interests: The authors declare that there are no conflicts of interests of this paper., (Copyright: © 2019 Taiwan J Ophthalmol.)

Aim: To investigate the effect of microbead iridocorneal angle occlusion on intraocular pressure (IOP) diurnal fluctuation in rat eyes., Methods: Male Dark Agouti (DA) rats, 8-10 week old, were each given a single intracameral injection of microbeads, followed by injection of dispersive viscoelastic solution. The right eye served as the experimental eye, while the left eye served as the control. IOP was measured twice daily postoperatively for 3wk and compared between groups. At the end of 3wk, the rats were sacrificed and the eyes were harvested for histological analysis and retinal ganglion cell (RGC) counting., Results: After microbead injection, experimental eyes had significantly higher dark time IOP than controls from the second week to the third week [2 nd week: 22.92±1.631 mm Hg ( n =5) vs 17.35±0.751 mm Hg ( n =5); 3 rd week: 23.59±1.494 mm Hg vs 17.73±0.592 mm Hg ( n =5)], while light time IOP was comparable between groups. The fluctuation levels of IOP in the experimental eyes were 7.21±0.398 mm Hg ( n =5), 9.50±1.017 mm Hg ( n =5) and 10.66±0.894 mm Hg ( n =5) from the first week to the third week after injection. Comparatively, they were significantly lower in the control eyes, which were 4.69±0.323 mm Hg ( n =5), 2.84±1.122 mm Hg ( n =5) and 4.98±0.603 mm Hg ( n =5) respectively. However, at the end of 3wk, the larger fluctuations in IOP in the experimental eyes was not associated with a significant loss of RGCs., Conclusion: Microbead occlusion exacerbates diurnal IOP fluctuation in rats. This reported model may serve as a method of investigating the pathological effects of IOP fluctuation. A longer observation period, or repeated injections, may be needed to observe a significant change in RGC density.

Purpose: To investigate the effect of transcorneal electrical stimulation (TcES) on retinal ganglion cell (RGC) function and survival after acute ocular hypertension-related retinal injury in gerbil eyes., Methods: Gerbil eyes were subjected to acute ocular hypertensive injury (80 mm Hg for 60 minutes). In the treatment group, TcES was applied to the surgical eye immediately and then twice weekly for a total of 1 month. In the control group, sham TcES was given to the surgical eye at the same time points. Retinal function was assessed and compared between groups using flash electroretinography. For histological analysis, the number of RGC and microglial cells were counted by immunofluorescence staining after the gerbils were sacrificed on day 7 and day 28. Real-time polymerase chain reaction and western blot analysis were conducted to compare expression of interleukin (IL)-10, IL-6, COX-2, tumor necrosis factor (TNF)-α, and NF-κB phosphorylation among groups., Results: TcES-treated eyes had significantly higher RGC survival at 1 month compared to controls. This was associated with RGC function. Furthermore, TcES-treated eyes were shown to have increased IL-10 expression, with a corresponding reduction in IL-6 and COX-2 expression as well as reduction in NF-κB phosphorylation. This was associated with a suppression in microglial cell activation in TcES-treated eyes., Conclusions: Early treatment with TcES in gerbils protected the RGC from secondary damage and preserved retinal function in acute ocular hypertensive injury through modulation of the microglial-cell activated local inflammatory response., Translational Relevance: Our study strengthens the argument for translating TcES as a viable treatment in acute glaucoma.

Aim: To estimate the overall drug compliance for local Chinese glaucoma patients on long-term topical treatment., Methods: This was a retrospective cross-sectional study. Fifty-seven primary glaucoma patients from the subspecialty clinic of a publicly-funded tertiary care hospital in Hong Kong completed a questionnaire on compliance with topical glaucoma medication, attitude towards glaucoma and therapy and vision related quality of life. Noncompliance was defined as reporting missing more than or equal to 10% of the prescribed topical glaucoma medication during the 2wk immediately prior to the consultation. Relationships between noncompliance and demographics, attitude, disease and treatment status was studied. Cost was estimated with quality of life and direct medical cost involved with noncompliance. Multivariable logistic regression on noncompliance was performed on selected factors., Results: Compliance was calculated as 75% (95% CI: 64%-87%) among 57 subjects (mean age 69y, female 51%). No statistical significant relationship was established between noncompliance and any single factors or outcomes. Age ( P =0.048) and forgetfulness ( P =0.064) were found to be marginally significant predictive factors on noncompliance in multivariable logistic regression. Noncompliance might be related ( P =0.130) to poorer self-rated vision-associated quality of life. The societal cost of noncompliance was estimated to be over 2510 life-years and US$ 3.7 million territory-wide., Conclusion: The compliance of Chinese glaucoma patients in Hong Kong is comparable to other parts in the world, and carries detrimental impacts on individual and societal levels. Age and forgetfulness are two possible independent predictors for noncompliance.

Aim: To describe and compare the differences in electroretinographic responses between two different age groups of adult Dark Agouti (DA) rats and to better understand the effect of age on retinal histology and function., Methods: The electroretinographic responses of two different age groups of adult DA rats were compared. Animals were divided into younger adult DA rats 10-12wk (n=8) and older adult DA rats 17-19wk (n=8). Full field electroretinography (ERG) was recorded simultaneously from both eyes after dark adaption and light adaption and parameters including the positive scotopic threshold response (pSTR), negative scotopic threshold response (nSTR), scotopic a-wave, b-wave, photopic a-wave, b-wave and photopic negative response (PhNR) were compared between groups., Results: The older adult rats displayed lower stimulation thresholds of the STRs (pSTR and nSTR) and higher amplitudes of pSTR, scotopic a-wave and b-wave, photopic b-wave and PhNR amplitudes, with shorter implicit times. Photopic a-wave amplitudes were however higher in the younger adult rats., Conclusion: In summary, for the rod system, photoreceptor, bipolar cell and RGC activity was enhanced in the older adult rats. For the cone system, RGC and bipolar cell activity was enhanced, while photoreceptor activity was depressed in the older adult rats. Such age-related selective modification of retinal cell function needs to be considered when conducting ophthalmic research in adult rats.

Objective: We aimed to explore the precise molecular mechanism of early and invasive tumor growth in a small-for-size graft after liver transplantation and to identify the distinct molecular signature linked to acute-phase injury and late-phase tumor invasiveness., Summary Background Data: Acute phase small-for-size liver graft injury plays an important role in tumor recurrence after liver transplantation. For prevention of such recurrence, understanding of its underlying mechanism will be important in developing novel therapeutic strategies., Methods: An orthotopic rat liver transplantation model was applied using whole grafts and small-for-size (50%) grafts. The recipients were injected with hepatoma cell lines via the portal vein to mimic tumor recurrence after liver transplantation. Tumor invasive properties were compared between the tumor developed from small and whole graft. Gene signatures of acute phase graft injury (days 1 and 3) and late phase tumor recurrence (days 14 and 21) were screened using cDNA microarray analysis and further confirmed by quantitative RT-PCR. The potential gene candidate CXCL10 was singled out for further functional studies to investigate its role in tumor progression., Results: A number of genes linked to inflammatory responses and tumor invasiveness were found over-expressed in small-for-size liver grafts and/or tumors developed in small liver grafts by cDNA microarray screening. Real-time RT-PCR also confirmed that the gene CXCL10 was over-expressed not only in small-for-size graft at the early phase, but also in tumor from small-for-size graft at the late phase after liver transplantation. In vitro functional studies further confirmed that CXCL10 promoted tumor-invasion-related properties and tumor-associated macrophage activation., Conclusion: CXCL10 over-expression, the distinct gene signature of acute-phase graft injury and tumor invasiveness in small-for-size liver grafts, may contribute to early tumor recurrence after liver transplantation. CXCL10 and its downstream signals may be potential therapeutic targets in the prevention of tumor recurrence after liver transplantation using small-for-size graft.