Rejection of Acellular Porcine Corneal Stroma Transplantation During Coronavirus Disease 2019 Pandemic.

ABSTRACT: To report 2 successfully managed cases of graft rejection with acellular porcine corneal stroma (APCS) transplantation in patients with fungal corneal ulcer. Two patients were diagnosed with fungal corneal ulcer and received APCS transplantation. Graft rejection developed due to the lost follow-up during the period of coronavirus disease 2019 outbreak. Amniotic membranes transplantation and cauterization of neovascularization was performed, respectively. The graft failure resolved successfully after the procedure. To the best of our knowledge, amniotic membranes transplantation and cauterization of new vessels are the firstly reported in treating APCS graft failure. Amniotic membranes transplantation or cauterization of neovascularization appear to be a safe and costeffective method for treating graft failure.

Use of Intense Pulsed Light to Mitigate Meibomian Gland Dysfunction for Dry Eye Disease.

Dry Eye Disease (DED) is a common ocular condition that needs prompt diagnosis and careful treatment interventions. If left untreated, it can lead to numerous sight-threatening complications, including ulceration of the cornea, blepharitis, alterations of the tear film, conjunctivitis, and in severe cases, may lead to scarring, thinning, and even perforation of the cornea. Intense pulsed light (IPL) is a non-laser high-intensity light source that has shown to play a valuable role in dry eye disease. Recent evidence from various research works has shown that IPL modifies the mechanism of meibomian gland dysfunction (MGD), which helps to relieve the symptoms of DED. In this review, we demonstrated the mechanism of action of IPL, including its benefits on DED. The emerging evidence shows that the role of IPL in DED is novel and therapeutic. These results direct us to conclude that IPL is a potentially beneficial tool and essential future therapy for dry eye disease. Advances in the treatment of DED will lead to a better quality of life. However, tools to recognize potentially severe side effects of DED earlier in order to treat or prevent them must be developed.

Circular RNAs: Novel Promising Biomarkers in Ocular Diseases.

Circular RNAs (circRNAs) are a novel class of endogenous non-coding RNAs produced by back-splicing. They are found to be expressed in eukaryotic cells and play certain roles in various cellular functions, including fibrosis, cell proliferation, differentiation, apoptosis and angiogenesis. Dysregulated circRNAs are found in several human disorders including, malignancy, vascular, inflammatory as well as nervous diseases. Although, increasing evidence suggests that circRNAs may also contribute in different ocular diseases, the outline of circRNAs in ocular diseases remains obscure. In this review we consider the current state of knowledge regarding the potential role and underlying mechanism of circRNAs in ocular diseases including pterygium, age-related cataract, glaucoma, diabetic retinopathy, retinoblastoma, retinal vascular dysfunction and hyperhomocysteinemia induced ocular diseases, emphasizing that circRNAs could be promising biomarkers for the diagnosis and prognosis evaluation. Future circRNAs-targeted intervention may become a novel therapeutic tool for the treatment of ocular diseases.

NONRATT021972 long-noncoding RNA: A promising lncRNA in diabetes-related diseases.

Diabetes mellitus (DM) is a principal health problem with increasing incidence worldwide. It can be associated with various systemic diseases. Long non-coding RNA (lncRNA), a member of non-coding RNA has been newly linked with various human diseases. Recent evidence from animal experiments has shown that the incidence and development of type 2 diabetes are contributed by the atypical expression of lncRNA in which the biomarker with capable clinical potential was lncRNA NONRATT021972. In this review, we demonstrated the numerous functions of NONRATT021972 in different diabetes-related diseases including diabetic neuropathy, diabetic cardiac autonomic neuropathy, myocardial ischemia, and hepatic glucokinase dysfunction. The emerging evidence shows that the role of NONRATT021972 in diabetic-related disease is novel and therapeutic. These results direct us to conclude that NONRATT021972 is a potential diagnostic and future targeted therapy for diabetes-associated diseases.

MALAT1 as a Diagnostic and Therapeutic Target in Diabetes-Related Complications: A Promising Long-Noncoding RNA.

Diabetes mellitus is a global issue with increasing incidence rate worldwide. In an uncontrolled case, it can advance to various organ-related complications leading to an increase in morbidity and mortality. Long non-coding RNA (lncRNA) Metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) appears to be a fairly novel lncRNA that is relevant to diabetes and its role in diabetic-related diseases initiation and progression have long been a subject of attention to many scholars. The expression of MALAT1 is elevated in different diabetic-related diseases. In this review, we demonstrate the various functions of MALAT1 in the different diabetes-related complications including ischemic reperfusion injury, retinopathy, cataract, atherosclerosis, cardiomyopathy, non-alcoholic steatohepatitis, gastroparesis, kidney disease, and gestational diabetes. The emerging evidence showed that the role of MALAT1 in diabetic-related complications is both pro-inflammatory and apoptosis in different cell types. These results concluded that MALAT1 is a potential diagnostic and future targeted therapy for diabetes-associated complications.

Central retinal artery occlusion associated with persistent truncus arteriosus and single atrium: a case report.

BACKGROUND: Central retinal artery occlusion (CRAO) is an ocular emergency and most of the cases present with painless sudden persistent loss of vision in the range of counting fingers to perception of light. The presentation of CRAO is associated with a variety of medical conditions. We report a rare case of CRAO associated with persistent truncus arteriosus (PTA) and single atrium in a female patient. CASE PRESENTATION: A 23-year-old woman was admitted due to sudden painless visual loss in the left eye. On examination visual acuity of light-perception was noted in the left eye with a left relative afferent pupillary defect. Fundoscopic examination revealed retinal ischemic whitening, constriction of the arteriole and venule with segmentation and typical "cherry-red spot" suggesting CRAO. The patient was treated with ocular massage and anterior chamber paracentesis. She was commenced on 150 mg of aspirin and also received hyperbaric oxygen therapy. An echocardiogram revealed PTA and single atrium. A diagnosis of CRAO associated with PTA and single atrium was made. CONCLUSION: The ophthalmologist should enquire about congenital and acquired cardiac abnormalities in patients with CRAO and consider such abnormalities to be possible sources of emboli.

Misdiagnosed as Fungal Keratitis: Herpes Simplex Virus-1 Keratitis Confirmed by Next-Generation Sequencing.

Objective: The purpose of this study was to report a case of herpes simplex virus-1 (HSV-1) keratitis misdiagnosed as fungal keratitis due to its clinical presentation being similar to that of fungal keratitis, ultimately diagnosed by NGS. Patients and Methods: A 59-year-old male presented with reduced vision in the right eye, combined with a history of trauma with vegetative matter. The corneal ulcer was accompanied with feathery infiltration, satellite lesion, and endothelial plaques. In vivo confocal microscopy (IVCM) showed hyper-reflective linear, thin, and branching interlocking structures. Fungal keratitis was diagnosed. Voriconazole 100 mg orally daily, topical tobramycin and 1% voriconazole were initiated empirically right away. The condition was aggravated and penetrating keratoplasty was performed. Anterior segment optical coherence tomography (AS-OCT) demonstrated the presence of plaques with a clear boundary between plaques and endothelium, resembling the AS-OCT images observed in cases of viral keratitis. Next-generation sequencing (NGS) further detected HSV-1 deoxyribonucleic acid, and no fungal component was found. Antifungal agents were discontinued and antiviral treatments were added. Results: We successfully treated a patient with HSV-1 keratitis who was misdiagnosed due to clinical features and IVCM findings similar to fungal keratitis. The patient's infection was controlled. At 2 years after surgery, the cornea recovered well. Conclusions: HSV-1 keratitis with atypical clinical presentation can be easily misdiagnosed. This case report emphasizes the importance of NGS in diagnosing the pathogens of keratitis.

Impacts of air pollution and meteorological conditions on dry eye disease among residents in a northeastern Chinese metropolis: a six-year crossover study in a cold region.

The purpose of this study is to explore the associations among dry eye disease (DED), air pollution, and meteorological conditions in the cold region of a northeastern Chinese metropolis (i.e., Changchun). Data on ambient air pollutants and meteorological parameters as well as diagnosed DED outpatients during 2015-2021 were collected. The associations between DED and environmental factors were analysed at multiple time scales using various statistical methods (i.e., correlation, regression and machine learning). Among the 10,809 DED patients (21,617 eyes) studied, 64.60% were female and 35.40% were male. A higher frequency of DED was observed in March and April, followed by January, August and October. Individual and multiple factor models showed the positive importance of particles with aerodynamic diameters <10 µm (PM10), carbon monoxide (CO), and ozone (O3) among normal air pollutants and air pressure (AP), air temperature (AT) and wind speed (WS) among normal meteorological parameters. Air pollutants (PM10, nitrogen dioxide: NO2) and meteorological parameters (AT, AP) have combined impacts on DED occurrence. For the first time, we further explored the associations of detailed components of atmospheric particles and DED, suggesting potential emission sources, including spring dust from bare soil and roads and precursor pollutants of summer O3 formation from vehicles and industry in Northeast China. Our results revealed the quantitative associations among air pollutants, meteorological conditions and DED outpatients in cold regions, highlighting the importance of coordinated policies in air pollution control and climate change mitigation.

Air pollution and meteorological conditions significantly contribute to the worsening of allergic conjunctivitis: a regional 20-city, 5-year study in Northeast China.

This study is the first to explore the potential associations among allergic conjunctivitis (AC), air pollution, and meteorological conditions in Northeast China. Data of meteorology, ambient atmospheric pollutants, and the incidence of allergic conjunctivitis (IAC) in prefecture-level cities between the years 2014 and 2018 are analyzed. The results show an increasing trend in the AC of average growth rate per annum 7.6%, with the highest incidence in the provincial capitals. The IAC is positively correlated with atmospheric pollutants (i.e., PM2.5, PM10, CO, SO2, NO2, and O3) and meteorological factors (i.e., air temperature and wind speed), but negatively correlated with relative humidity. These results suggest that the IAC is directly proportional to pollution level and climatic conditions, and also the precedence of air pollution. We have further obtained the threshold values of atmospheric pollutants concentration and meteorological factors, a turning point above which more AC may be induced. Compared with the air quality standard advised by China and the World Health Organization (WHO), both thresholds of PM10 (70 µg m-3) and PM2.5 (45 µg m-3) are higher than current standards and pose a less environmental risk for the IAC. SO2 threshold (23 µg m-3) is comparable to the WHO standard and significantly lower than that of China's, indicating greater environmental risks in China. Both thresholds of NO2 (27 µg m-3) and O3 (88 µg m-3) are below current standards, indicating that they are major environmental risk factors for the IAC. Our findings highlight the importance of atmospheric environmental protection and reference for health-based amendment.

Tectonic keratoplasty using femtosecond laser lenticule in pediatric patients with corneal perforation secondary to blepharokeratoconjunctivitis: a case report and literature review.

Blepharokeratoconjunctivitis secondary to ocular demodicosis in the pediatric population is often neglected and may result in a serious sight-threatening condition. In severe cases, it can lead to corneal perforation necessitating urgent corneal transplantation. However, the shortage and high cost of donor corneas is the foremost limitation of keratoplasty in developing countries. Small-incision lenticule extraction is an advanced flapless femtosecond laser refractive procedure in which an intrastromal corneal lenticule is detached and removed to correct myopia and myopic astigmatism. We herein describe a technique in which lenticules are used for the management of corneal perforation secondary to Demodex-induced blepharokeratoconjunctivitis. The lenticule was sutured over the site of the perforated cornea using 10-0 interrupted nylon sutures. The globe integrity was maintained with a good visual outcome. Thus, tectonic keratoplasty using small-incision lenticule extraction appears to be a safe, cost-effective, and reliable alternative method for the management of corneal perforation secondary to blepharokeratoconjunctivitis.

Neuroprotective effects of overexpressed microRNA-200a on activation of glaucoma-related retinal glial cells and apoptosis of ganglion cells via downregulating FGF7-mediated MAPK signaling pathway.

Glaucoma is a progressive optic neuropathy and is one of the leading causes of blindness in the industrialized countries. The involvement of microRNAs (miRs) has been implicated in regulating the complex biological responses to changes in intraocular pressure. However, the therapeutic role of miR-200a on glaucoma has not been well studied yet. In this study, we confirmed the role of miR-200a in glaucoma progression and identified the related mechanism. Microarray expression profiles were used to screen the glaucoma-related genes. The relationship between miR-200a and FGF7 was validated by bioinformatics analysis and dual-luciferase reporter gene assay. Glaucoma-related parameters including the expression of CD11b and iNOS, activation of Muller cells, and apoptosis of retinal ganglion cells (RGCs) in the mouse model were measured by immunohistochemistry, MTT assay and TUNEL assay, respectively. miR-200a was reduced in glaucoma, whereas FGF7 was robustly induced. Thereby, we speculated that FGF7 was negatively regulated by miR-200a. Downregulated miR-200a could activate the MAPK signaling pathway following elevations in ERK, JNK, p38 and Bax expression and reduction in Bcl-2 expression. In the mouse model, downregulated miR-200a increased the expression of CD11b and iNOS and the apoptosis of RGCs, but stimulated the inactivation of Muller cells. However, the above-mentioned alternations induced by downregulated miR-200a were reversed after FGF7 repression. miR-200a can inhibit the FGF7-mediated MAPK signaling pathway and play a protective role on improving the glaucoma-induced optical nerve injury.

Lamellar keratoplasty using femtosecond laser intrastromal lenticule for limbal dermoid: case report and literature review.

Small incision refractive lenticule extraction (SMILE) is a femtosecond laser technique to correct myopia and myopic astigmatism. Herein, we report a technique where intrastromal lenticule obtained from the SMILE procedure served as a graft for lamellar keratoplasty in the management of a limbal dermoid. An 18-year-old woman presented to the clinic with a corneal-limbal mass in the right eye. Slit-lamp examination revealed a vascularized circular mass of approximately 6 mm × 5 mm, which was attached at 7 o'clock in the inferotemporal region of the corneal limbus; this suggested limbal dermoid. Anterior segment optical coherence tomography revealed superficial involvement of the cornea. The patient was treated with excision and lamellar keratoplasty by using femtosecond intrastromal lenticule. The lenticule was sutured over the cornea with 10-0 interrupted nylon sutures. On postoperative follow-up, best-corrected visual acuity was 20/20; there was no corneal neovascularization and no sign of rejection. This case of limbal dermoid was managed by simple surgical excision and lamellar keratoplasty with a SMILE-extracted lenticule. This method may serve as an alternative surgical approach for management of limbal dermoid.

A novel case using femtosecond laser-acquired lenticule for recurrent pterygium: case report and literature review.

Small incision lenticule extraction (SMILE) is a minimally invasive, safe and flapless femtosecond laser technique used mainly to correct myopia through extraction of a corneal lenticule. Lenticules obtained in this way are transparent and of high quality, and thus, can be used to treat other corneal diseases. A 65-year-old male patient presented with recurrent pterygium complicated by thin cornea. The patient was treated surgically using a SMILE-extracted lenticule to avoid further complications and to maintain eyeball integrity. The lenticule was sutured over the thin section of cornea using 10-0 interrupted nylon sutures and enclosed by a single layer of amniotic membrane. The patient was evaluated using slit-lamp biomicroscopy and anterior-segment optical-coherence tomography. During an 8-month follow-up, the graft remained intact with no sign of rejection and corneal thickness was maintained. Tectonic keratoplasty using a SMILE-extracted lenticule appears to be a safe, cost-effective and reliable method for treating thin cornea due to repeated surgeries for recurrent pterygium. This is the first case of recurrent pterygium complicated by thin cornea managed surgically using a SMILE-extracted lenticule.

The Nrf2 Signaling in Retinal Ganglion Cells under Oxidative Stress in Ocular Neurodegenerative Diseases.

Retinal ganglion cells (RGCs) are one of the important cell types affected in many ocular neurodegenerative diseases. Oxidative stress is considered to be involved in retinal RGCs death in ocular neurodegenerative diseases. More and more attention has been focused on studying the agents that may have neuroprotective effects. Nuclear factor (erythroid-derived 2)-like 2 (Nrf2) is a key nuclear transcription factor for the systemic antioxidant defense system. This review elucidates the underlying mechanism of the Nrf2-mediated neuroprotective effects on RGCs in ocular neurodegenerative diseases, such as diabetic retinopathy and retinal ischemia-reperfusion injury. Several Nrf2 inducers that shield RGCs from oxidative stress-induced neurodegeneration via regulating Nrf2 signaling are discussed.

The BRAF activated non-coding RNA: A pivotal long non-coding RNA in human malignancies.

Long non-coding RNAs (lncRNAs) participate in the complex network of cancer and play an important role in tumourigenesis and progression. BRAF activated non-coding RNA (BANCR), a 4-exon transcript of 693-bp, was first discovered as an oncogenic long non-coding RNA in BRAFV600E melanomas cells in 2012 and was related to melanoma cell migration. Besides melanoma, increasing evidence has explored the potential role of BANCR in the development and progression of multiple other human malignancies, such as retinoblastoma, lung cancer, gastric cancer etc. since its discovery. The expression pattern of BANCR varies in different types of cancers, either as a tumour suppressor or as an accelerator. Functional BANCR may serve as a promising biomarker for cancer diagnosis as well as prognosis evaluation. BANCR-targeted intervention may also become a valuable novel therapeutic tool against human malignancies. This review summarized the advanced research progresses concerning the expression and role of BANCR in different human malignancies.

HOXA11 antisense long noncoding RNA (HOXA11-AS): A promising lncRNA in human cancers.

The cancers are the leading cause of disease-related deaths worldwide with a high risk of morbidity and mortality. Long noncoding RNAs (lncRNAs) play a critical role in a wide range of biological processes, including tumorigenesis. HOXA11-AS (NCRNA00076), the antisense strands of HOXA11 gene, was initially revealed in a mouse embryonic cDNA library in 2009 and it was a fairly novel lncRNA. This review summarized the advanced research progression concerning the expression and role of HOXA11-AS in different human malignancies. The expression of HOXA11-AS is aberrantly altered in many cancers, either as a tumor suppressor or as a tumor accelerator. The different underlying mechanism of HOXA11-AS in different cancers (including, nonsmall cell lung cancers, osteosarcoma, uveal melanoma, glioma, hepatocellular carcinoma, gastric cancer, breast cancer, cervical cancer, ovarian cancer, colorectal cancer, ovarian cancer, and glioblastoma) was also detailed. These findings lead us to conclude that HOXA11-AS participate in the complex network of cancers and plays an important role in the tumorigenesis and progression. Functional HOXA11-AS could be a promising biomarker for early detection as well as prognosis evaluation in cancer patients. Future HOXA11-AS-targeted intervention may become a valuable novel therapeutic tool, improving the clinical management of cancers.

Efficacy of curcumin in inducing apoptosis and inhibiting the expression of VEGF in human pterygium fibroblasts.

Pterygium is an inflammatory and degenerative ocular surface disease, in which the conjunctiva on the cornea grows to form a fibrous tissue in the shape of a triangle. Although pterygium surgery is used broadly in clinical practice, its high recurrence rate poses a great concern for patients and doctors. In the present study, we examined the effects of curcumin on the apoptosis and proliferation of human pterygium fibroblasts (HPFs) in an in vitro culture system. HPFs were incubated with curcumin for 24 to 72 h (5, 20, 80 or 200 µmol/l). The proliferation-inhibiting effects of curcumin were assayed by MTT assay at different time points and at various concentrations. The expression of vascular endothelial growth factor (VEGF) in each group was detected by RT-qPCR and ELISA. The apoptotic effects of curcumin were detected by flow cytometry (FCM). Treatment with curcumin at 80 µmol/l for 48 h significantly inhibited HPF proliferation. Curcumin significant induced the apoptosis of HPFs. Our findings thus suggest that curcumin suppress cell proliferation in the pterygium by inducing HPF apoptosis and inhibiting VEGF expression. Thus, curcumin has potential for use as a novel agent for the treatment of pterygium in the near future.

Pseudomonas aeruginosa endophthalmitis caused by accidental iatrogenic ocular injury with a hypodermic needle.

Iatrogenic traumatic endophthalmitis is a rare but serious ocular infection that can lead to severe vision loss. A 44-year-old man presented with pain and decreased vision in the right eye 4 hours after injury with a hypodermic needle during irrigation of his eye. Slit-lamp examination revealed a penetrating corneal puncture and iris hole in the right eye. Twenty hours later, his visual acuity had decreased to hand motion, and severe fibrinoid uveitis was noted. He immediately underwent irrigation of the anterior chamber and intravitreal antibiotic injection. The right eye became painful again, and emergent vitrectomy combined with lensectomy was performed along with intravitreal antibiotic administration. The patient remained stable during the 2-month follow-up. Standard practice should be adopted when irrigating the eye to prevent this type of injury, and emergent surgical intervention is very important to preserve visual function.

Clinical efficacy of conjunctival flap surgery in the treatment of refractory fungal keratitis.

The aim of the present study was to investigate the use and effectiveness of a selective, partial, pedunculated (tongue-shaped) conjunctival flap (CF) for the treatment of refractory fungal keratitis (FK) with or without perforation. A total of 31 cases of corneal diseases treated by CF surgery between April 2014 and October 2015 were evaluated. Among the 31 cases, 16 cases (male:female, 11:5) with FK were selected. Logistic regression analysis was used to investigate factors associated with complications of CF surgery. A higher prevalence of FK was identified among male farmers compared with female farmers, in which plant trauma was the most prevalent cause of the disease. Only 4 patients had experienced corneal perforation prior to CF surgery. Patients aged 61-80 years had a higher prevalence of FK (50%) compared with other age groups; however, there was no statistically significant correlation between the prevalence of FK and sex or age. It was also demonstrated that age, sex, combined surgery and surgery duration were not significantly associated with post-surgical complications. All CF surgeries were performed following corneal ulcer scraping; however, 4 patients (12.5%) required additional surgery. The visual acuity of participants post-surgery decreased in 4 cases and remained unchanged in 12 cases. A total of 3 study patients experienced post-surgical complications of corneal perforation (1 patient) and purulent exudate spreading (2 patients). The post-surgical outcome was good for all study participants as the surgeries were able to control infection and preserve the eyeball, with the potential of future corneal transplant. These results suggest that CF surgery may be a useful alternative treatment for refractory FK in countries such as China where there is lack of cornea donors.

Curcumin, A Potential Therapeutic Candidate for Anterior Segment Eye Diseases: A Review.

Curcumin, the major curcuminoid of the turmeric, has been extensively used in many countries since ancient time for preventing and/or treating a multitude of diseases. This review is to illustrate the researches on the properties of curcumin and its potential therapeutic efficacy in major anterior segment eye diseases. The bio-medical potential of curcumin is restricted because of its low solubility and digestive bioavailability. This review will discuss promising research in improving curcumin bioavailability through structural modification. In vitro and in vivo research made progress in studying the beneficial effects of curcumin on major anterior segment eye diseases, including anti-angiogenesis effect in corneal diseases; anti-inflammation or anti-allergy effects in dry eye disease, conjunctivitis, anterior uveitis; anti-proliferation and pro-apoptosis effects in pterygium; anti-oxidative stress, anti-osmotic stress, anti-lipid peroxidation, pro-apoptosis, regulating calcium homeostasis, sequestrating free radicals, protein modification and degradation effects in cataracts; neuroprotective effects in glaucoma. Curcumin exhibited to be a potent therapeutic candidate for treating those anterior segment eye diseases.