The Short-term Effects of Artificial Tears on the Tear Film Assessed by a Novel High-Resolution Tear Film Imager: A Pilot Study.

PURPOSE: The purpose of this study was to investigate the effects of artificial tears (AT) on the sublayers of the tear film assessed by a novel tear film imaging (TFI) device. METHODS: The mucoaqueous layer thickness (MALT) and lipid layer thickness (LLT) of 198 images from 11 healthy participants, 9 of whom had meibomian gland disease, were prospectively measured before and after exposure to 3 different AT preparations (Refresh Plus; Retaine [RTA]; Systane Complete PF [SYS]), using a novel nanometer resolution TFI device (AdOM, Israel). Participants were assessed at baseline and at 1, 5, 10, 30, and 60 minutes after instilling 1 drop of AT during 3 sessions on separate days. Repeated-measures analysis of variances were used for comparisons with P < 0.05 considered significant. RESULTS: For all ATs, the mean MALT was greatest 1 minute after drop instillation, with an increase of 67%, 55%, and 11% above the baseline for SYS, Refresh Plus, and RTA, respectively. The SYS formulation demonstrated the highest percentage increases in mean MALT and LLT at most postdrop time points. The MALT differences were significantly higher in the SYS than in the RTA (P = 0.014). After 60 minutes, no AT group demonstrated statistically significant changes in MALT or LLT compared with baseline. CONCLUSIONS: We report, for the first time, the effects of AT on MALT and LLT using a high-resolution TFI. A substantial acute mean MALT increase occurs 1 minute after AT instillation with all agents tested, but there were clear differences in response and durability, suggesting the benefits of choosing specific AT according to the needs of each patient.

"Persistence of Memory" - Multimodal imaging of delayed sympathetic ophthalmia.

Purpose: To describe a case of late post-surgical sympathetic ophthalmia documented with multimodal imaging. Observations: A 74-year-old male presented to the urgent care of the New York Eye and Ear Infirmary with blurry vision and discomfort in his left eye for three weeks. His vision was 20/50, with intraocular pressure of 13 mmHg, and slit lamp examination was significant for conjunctival congestion, 1+ anterior segment cell and flare, and diffuse keratic precipitates. His right eye was no light perception with a condensed hyphema, intraocular lens and inferonasal tube. His medical history included coronary artery bypass, prostate cancer, hyperlipidemia, and hypertension. His ocular history included blunt trauma to the right eye at age 11 with development of a traumatic macular hole and later rhegmatogenous retinal detachment at age 53, repaired with multiple vitreoretinal procedures. He developed glaucoma in the right eye and was treated with a tube shunt and ultimately transscleral cyclophotocoagulation (TSCPC) 7 years later, 13 years prior to his presentation of the left eye. Dilated fundus examination of his left eye revealed diffuse chorioretinal folds in the macula without any discrete chorioretinal lesions. Ultrasound of the right showed serous macular detachments with scleral thickening. Presumptive diagnosis of sympathetic ophthalmia was made and oral corticosteroid therapy was initiated. Subsequent SD-OCT and en-face OCT-A demonstrated Dalen-Fuchs nodules within the macula underlying areas of resolved serous detachment, after 6 weeks of oral steroids and initiation of immunomodulatory therapy (IMT). Conclusions: Sympathetic ophthalmia may rarely present with very delayed onset, and TSCPC is an uncommon inciting event. These patients may develop serous detachment, choroidal folds and inflammatory nodules identifiable on exam and multimodal imaging, which can resolve when treated appropriately. OCT-A may provide utility in monitoring response to immunosuppressive treatment in these patients.

Artificial corneas versus donor corneas for repeat corneal transplants.

BACKGROUND: Individuals who have failed one or more full thickness penetrating keratoplasties may be offered repeat corneal surgery using an artificial or donor cornea. An artificial or prosthetic cornea is known as a keratoprosthesis. Both donor and artificial corneal transplantations involve removal of the diseased and opaque recipient cornea (or the previously failed cornea) and replacement with another donor or prosthetic cornea. OBJECTIVES: To assess the effectiveness of artificial versus donor corneas in individuals who have had one or more failed donor corneal transplantations. SEARCH METHODS: We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (which contains the Cochrane Eyes and Vision Trials Register) (2019, Issue 11); Ovid MEDLINE; Ovid Embase; LILACS (Latin American and Caribbean Health Sciences Literature database); ClinicalTrials.gov; and the World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP). We did not use any date or language restrictions in the electronic search for trials. We last searched the electronic databases on 4 November 2019. SELECTION CRITERIA: Two review authors independently assessed reports from the electronic searches to identify randomized controlled trials or controlled clinical trials. Any discrepancies were resolved by discussion or consultation. DATA COLLECTION AND ANALYSIS: We used standard methodological procedures expected by Cochrane. For discussion purposes, we summarized findings from relevant comparative case series. We performed no data synthesis. MAIN RESULTS: We did not identify any randomized controlled trials or controlled clinical trials comparing artificial corneas with donor corneas for repeat corneal transplantations. AUTHORS' CONCLUSIONS: The optimal management for those individuals who have failed a conventional corneal transplantation is unknown. Currently, in some centers, artificial corneal devices are routinely recommended after just one graft failure, while in other centers, they are not recommended until after multiple graft failures, or not at all. To date, there have been no controlled trials comparing the visual outcomes and complications of artificial corneal devices (particularly the Boston type 1 keratoprosthesis, which is the most commonly implanted artificial corneal device) with repeat donor corneal transplantation, in order to guide surgeons and their patients. Such a trial is needed and would offer significant benefit to an ever-increasing pool of people with visual disability due to corneal opacification, most of whom are still in productive stages of their lives.

Impact of automated OCT in a high-volume eye urgent care setting.

BACKGROUND/AIMS: Optical coherence tomography (OCT) has become standard of care in the diagnosis and management of a myriad of retinal and optic nerve pathology. Access to diagnostic equipment and skilled imaging personnel in the after-hours setting is often limited. We examined the utility and diagnostic indications for automated OCT in a high-volume after-hours clinic within an eye institute. METHODS: OCT images obtained over a period of 15 months were reviewed in the context of electronic patient records. Residents and fellows were surveyed regarding their experience with the OCT and its value in emergency patient management. RESULTS: 202 patients and 359 eyes were examined. Complaints prompting imaging included flashes/floaters, metamorphopsia, decreased vision and scotomas. Diagnoses included vascular occlusion, retinal detachment, macular hole, cystoid macular oedema and central serous retinopathy. Of the 25 residents and fellows surveyed, most agreed that the OCT that facilitated delivery of optimal urgent management. OCT also aided in the triage of patients to specialty clinics. CONCLUSION: Expanded access to automated OCT in the urgent care setting shows promise for improving the accuracy and timeliness of diagnosis, which can be critical for optimising patient outcomes. OCT also provides clear, immediate documentation of pathology for substantiating medical decision-making.

Histone deacetylase inhibitors prevent the degradation and restore the activity of glucocerebrosidase in Gaucher disease.

Gaucher disease (GD) is caused by a spectrum of genetic mutations within the gene encoding the lysosomal enzyme glucocerebrosidase (GCase). These mutations often lead to misfolded proteins that are recognized by the unfolded protein response system and are degraded through the ubiquitin-proteasome pathway. Modulating this pathway with histone deacetylase inhibitors (HDACis) has been shown to improve protein stability in other disease settings. To identify the mechanisms involved in the regulation of GCase and determine the effects of HDACis on protein stability, we investigated the most prevalent mutations for nonneuronopathic (N370S) and neuronopathic (L444P) GD in cultured fibroblasts derived from GD patients and HeLa cells transfected with these mutations. The half-lives of mutant GCase proteins correspond to decreases in protein levels and enzymatic activity. GCase was found to bind to Hsp70, which directed the protein to TCP1 for proper folding, and to Hsp90, which directed the protein to the ubiquitin-proteasome pathway. Using a known HDACi (SAHA) and a unique small-molecule HDACi (LB-205), GCase levels increased rescuing enzymatic activity in mutant cells. The increase in the quantity of protein can be attributed to increases in protein half-life that correspond primarily with a decrease in degradation rather than an increase in chaperoned folding. HDACis reduce binding to Hsp90 and prevent subsequent ubiquitination and proteasomal degradation without affecting binding to Hsp70 or TCP1. These findings provide insight into the pathogenesis of GD and indicate a potent therapeutic potential of HDAC inhibitors for the treatment of GD and other human protein misfolding disorders.

Decreased glucocerebrosidase activity in Gaucher disease parallels quantitative enzyme loss due to abnormal interaction with TCP1 and c-Cbl.

Gaucher disease (GD), the most common lysosomal storage disorder of humans, is caused by mutations in the gene coding for the enzyme glucocerebrosidase (GCase). Clinical manifestations vary among patients with the three types of GD, and phenotypic heterogeneity occurs even among patients with identical mutations. To gain insight into why phenotypic heterogeneity occurs in GD, we investigated mechanisms underlying the net loss of GCase catalytic activity in cultured skin fibroblasts derived from patients with the three types of GD. The findings indicate that the loss of catalytic activity of GCase correlates with its quantitative reduction, rather than a decrease in functional capacity of mutant enzyme. Use of a proteasome inhibitor, lactacystin, resulted in increased expression of GCase, suggesting a mechanism of protein degradation in GD. Furthermore, reduced binding of GCase to TCP1 ring complex (TRiC), a regulator of correct protein folding, may result in defective maturation of nascent GCase in GD cells. Additionally, increased interaction between GCase and c-Cbl, an E3 ubiquitin ligase, may be involved in the degradation and loss of GCase in GD. The findings suggest that specific molecular mediators involved in GCase maturation and degradation could be responsible for phenotypic variation among patients with the same genotypes and that these mediators could be therapeutically targeted to increase GCase activity in patients with GD.

Anti-tumor effects of mouse factor VII-Staphylococcus enterotoxin A (mfVII) chimeric protein in mice / 中华肿瘤杂志

<p><b>OBJECTIVE</b>Mouse factor VII (mfVII), ligand of tissue factor (TF) which is frequently over-expressed during neovascularization activated by tumor growth, was fused to staphylococcus enterotoxin A (SEA) that mediates greater intensity of T-cell activation against tumor cells. The anti-tumor effects of the mfVII-SEA chimeric protein were evaluated.</p><p><b>METHODS</b>Fusion of SEA and mfVII cDNA was constructed using adenovirus vector and produced in 293 packaging cell lines. The 293 cells containing the adenovirus were administered subcutaneously to mice. Fluorescence studies at the injection site and the liver were performed 3 days later. Mouse prostatic tumor RM-1 cells and mouse sarcoma MCA 205 H12 cell lines were then used in mice to create lung metastasis and subcutaneous tumor to carry out efficacy evaluation, respectively.</p><p><b>RESULTS</b>Adenovirus released from the injected 293 cells only infected the subcutaneous tissue at the injection site. The in vivo experiments in mice revealed that formation of lung metastasis was strongly inhibited by the mfVII-SEA (23 +/- 8) compared to the vacant vector control group (193 +/- 38) and PBS control group (211 +/- 42) (P < 0.01). The mfVII-SEA also strongly suppressed tumor growth at the subcutaneous injection site (342.6 +/- 107.1) mm(3) compared to that of vacant vector control (2244.3 +/- 350) mm(3) and SEA (1208.3 +/- 210) mm(3) by the 23rd day.</p><p><b>CONCLUSION</b>The chimeric protein mfVII-SEA significantly inhibits lung metastasis formation and local tumor growth.</p>