Emerging treatments for corneal endothelium decompensation - a systematic review.

PURPOSE: Endothelial keratoplasty (EK) is the conventional treatment to improve visual acuity of corneal endothelium decompensation (CED) patients, with other therapies mainly for symptomatic relief. However, the shortage of corneal grafts and other limitations to EK urge the development of novel alternative treatments. In the last decade, novel options have been proposed, yet only a limited number of reviews have systematically reported on outcomes. Therefore, this systematic review evaluates the existing clinical evidence of novel surgical approaches for CED. METHOD: We identified 24 studies that illustrated the clinical observations of the surgical approaches in interest. We included Descemet stripping only (DSO), Descemet membrane transplantation (DMT) where Descement membrane alone instead of corneal endothelium with cells is transplanted, and cell-based therapy. RESULTS: In general, these therapies may provide visual outcomes comparable with EK under specific conditions. DSO and DMT target CED with relatively healthy peripheral corneal endothelium like Fuchs' corneal endothelial dystrophy, while cell-based therapy offers more versatile applications. Side effects of DSO would decrease with modifications to surgical techniques. Moreover, Rho-associated protein kinase inhibitor adjuvant therapy could enhance clinical results in DSO and cell-based therapy. CONCLUSION: Long-term controlled clinical trials with larger sample size on the therapies are needed. The simplicity of DSO and the high translational potential of cell-based therapy to treat CED of most etiologies made these two treatment strategies promising.

A systematic review of multimodal clinical biomarkers in the management of thyroid eye disease.

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.

A Systematic Review on Cornea Epithelial-Stromal Homeostasis.

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.

A Systematic Review of Emerging Therapeutic Strategies in the Management of Chemical Injuries of the Ocular Surface.

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.

Ocular manifestations and diagnosis of tuberculosis involving the uvea: a case series.

BACKGROUND: Ocular tuberculosis (TB) affects 1-2% of patients with TB, with TB uveitis being the most common. This series aims to look at different manifestations of tuberculosis associated uveitis and the different tests used to make a presumptive or definitive diagnosis. METHODS: Patients diagnosed with TB related uveitis in Hong Kong SAR between 2017 and 2020 were reviewed. Demographics, clinical features, investigations and treatments of patients were collected. RESULTS: Fifteen eyes in 10 patients with a mean age 57.30 ± 10.17 years were included. The ocular manifestations on presentation included anterior uveitis (50%), posterior uveitis (40%) and panuveitis (10%), where 70% of them were unilateral and 30% were bilaterally infected; on subsequent visits the manifestations further developed into posterior uveitis (40%), panuveitis (40%) and anterior uveitis (20%), where 50% of them were unilateral and 50% bilateral infected. Tuberculosis tests were positive in 5 out of 7 Mantoux tests, 4 out of 4 T-SPOT TB tests, 3 out of 4 QuantiFERON-TB gold tests, 1 out of 1 lymph node biopsy, 0 out of 9 chest x-rays, and no aqueous fluid polymerase chain reaction (PCR) was tested. Vision impairing complications were seen in 6 patients where retinal vasculitis was most commonly seen. With anti-TB treatment prescribed in 9 patients, side effects occurred in 5 patients, including ocular hypertension, disc swelling, and hepatitis. CONCLUSIONS: Ocular TB infections may manifest in various forms, and can involve different parts of the eye. Bilateral involvement of TB is commonly presented, and both eyes should be evaluated at every follow up. When TB is suspected in a patient, diagnostic confirmation requires multimodal investigations where a negative chest x-ray is not useful in ruling out ocular TB infections, especially in an endemic region like Hong Kong. In these patients, it is crucial to have a high index of suspicion for TB, even when they do not demonstrate classical respiratory signs and symptoms of TB.

Virtual reality and augmented reality- emerging screening and diagnostic techniques in ophthalmology: A systematic review.

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.

Scaffold-Free Strategy Using a PEG-Dextran Aqueous Two-Phase-System for Corneal Tissue Repair.

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 in vitro. The corneal epithelial cell constructs are also able to re-epithelialize the corneal epithelial wound in vitro. The results suggest the promise of our reported strategy in corneal repair.

A Review of the Impact of Alterations in Gut Microbiome on the Immunopathogenesis of Ocular Diseases.

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.

A systematic review on advances in diagnostics for herpes simplex keratitis.

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.