The Management of Ocular Surface Squamous Neoplasia (OSSN).

The rise of primary topical monotherapy with chemotherapeutic drugs and immunomodulatory agents represents an increasing recognition of the medical management of ocular surface squamous neoplasia (OSSN), which may replace surgery as the standard of care in the future. Currently, there is no consensus regarding the best way to manage OSSN with no existing guidelines to date. This paper seeks to evaluate evidence surrounding available treatment modalities and proposes an approach to management. The approach will guide ophthalmologists in selecting the most appropriate treatment regime based on patient and disease factors to minimize treatment related morbidity and improve OSSN control. Further work can be done to validate this algorithm and to develop formal guidelines to direct the management of OSSN.

Single B-Cell Genomic Analyses Differentiate Vitreoretinal Lymphoma from Chronic Inflammation.

PURPOSE: To test whether analyzing DEPArray (Menarini Silicon Biosystems) isolated single B cells from the vitreous fluid can reveal crucial genomic and clinicopathological features to distinguish patients with vitreoretinal lymphoma (VRL) from those with chronic inflammation using immunoglobulin heavy chain (IGH), disease biomarker myeloid differentiation primary response 88 (MYD88)L265P mutation, and copy number profiling. DESIGN: A single-center, retrospective study. PARTICIPANTS: Remnant vitreous biopsies from 7 patients with VRL and 4 patients with chronic inflammation were acquired for molecular analysis. METHODS: Vitreous fluid samples were prefixed in PreservCyt (Hologic) and underwent cytologic analysis and immunohistochemistry examination. Single cells were isolated using the DEPArray NxT system, followed by downstream genomic analysis. MAIN OUTCOME MEASURES: The frequencies of the dominant IGH and MYD88L265P mutation and the genome-wide copy number aberration (CNA) profiles of individual vitreous-isolated B cells were characterized. RESULTS: An average of 10 to 13 vitreous B cells were used in the single-cell IGH and MYD88 analyses. Higher frequencies of dominant IGH (88.8% ± 13.2%) and MYD88L265P mutations (35.0% ± 31.3%) were detected in patients with VRL than in patients with chronic inflammation (65.9% ± 13.4% and 1.5% ± 2.6% for IGH and MYD88L265P, respectively). In a cytology-proven VRL case, all 15 vitreous isolated B cells were derived from the same clone with 100% paired IGH: immunoglobulin light chain (IGK) sequences. Genome-wide copy number profiling revealed a high degree of similarity between B cells from the same patient with VRL, with extensive gains and losses at the same areas across the whole genome. In addition, 14 of 15 B cells showed a BCL2/JH t(14;18) translocation, confirming cellular malignancy with a clonal origin. Clustering analysis of the copy number profiles revealed that malignant B cells derived from different patients with VRL had no common genome-wide signatures. CONCLUSIONS: Single B-cell genomic characterization of the IGH, MYD88L265P mutation, and copy number profile enables VRL diagnosis. Because our study involved only a small cohort, these meaningful proof-of-concept data now warrant further investigation in a larger patient cohort.

Ethnic variation in medial orbital wall anatomy and its implications for decompression surgery.

BACKGROUND: To describe the inter-ethnic variation in medial orbital wall anatomy between Chinese, Malay, Indian and Caucasian subjects. METHODS: Single-centre, retrospective, Computed Tomography (CT)-based observational study. 20 subjects of each ethnicity, were matched for gender and laterality. We excluded subjects younger than 16 years and those with orbital pathology. OsiriX version 8.5.1 (Pixmeo., Switzerland) and DICOM image viewing software CARESTREAM Vue PACS (Carestream Health Inc., USA) were used to measure the ethmoidal sinus length, width and volume, medial orbital wall and floor angle and the relative position of the posterior ethmoid sinus to the posterior maxillary wall. Statistical analyses were performed using Statistical Package for Social Sciences version 25.0 (IBM, USA). RESULTS: There were 12 males (60 %) in each group, with no significant difference in age (p = 0.334-0.994). The mean ethmoid sinus length in Chinese, Malay, Indian and Caucasian subjects, using the Chinese as reference, were 37.2, 36.9, 38.0 and 37.4mm, the mean width was 11.6, 10.5, 11.4 and 10.0mm (p = 0.020) and the mean ethmoid sinus volume were 3362, 3652, 3349 and 3898mm3 respectively. The mean medial orbital wall and floor angle was 135.0, 131.4, 131.0 and 136.8 degrees and the mean relative position of posterior ethmoid sinus to posterior maxillary wall were - 2.0, -0.2, -1.5 and 1.6mm (p = 0.003) respectively. CONCLUSIONS: No inter-ethnic variation was found in decompressible ethmoid sinus volume. Caucasians had their posterior maxillary sinus wall anterior to their posterior ethmoidal walls unlike the Chinese, Malay and Indians. Awareness of ethnic variation is essential for safe orbital decompression.

Association of Rare CYP39A1 Variants With Exfoliation Syndrome Involving the Anterior Chamber of the Eye.

Importance: Exfoliation syndrome is a systemic disorder characterized by progressive accumulation of abnormal fibrillar protein aggregates manifesting clinically in the anterior chamber of the eye. This disorder is the most commonly known cause of glaucoma and a major cause of irreversible blindness. Objective: To determine if exfoliation syndrome is associated with rare, protein-changing variants predicted to impair protein function. Design, Setting, and Participants: A 2-stage, case-control, whole-exome sequencing association study with a discovery cohort and 2 independently ascertained validation cohorts. Study participants from 14 countries were enrolled between February 1999 and December 2019. The date of last clinical follow-up was December 2019. Affected individuals had exfoliation material on anterior segment structures of at least 1 eye as visualized by slit lamp examination. Unaffected individuals had no signs of exfoliation syndrome. Exposures: Rare, coding-sequence genetic variants predicted to be damaging by bioinformatic algorithms trained to recognize alterations that impair protein function. Main Outcomes and Measures: The primary outcome was the presence of exfoliation syndrome. Exome-wide significance for detected variants was defined as P < 2.5 × 10-6. The secondary outcomes included biochemical enzymatic assays and gene expression analyses. Results: The discovery cohort included 4028 participants with exfoliation syndrome (median age, 78 years [interquartile range, 73-83 years]; 2377 [59.0%] women) and 5638 participants without exfoliation syndrome (median age, 72 years [interquartile range, 65-78 years]; 3159 [56.0%] women). In the discovery cohort, persons with exfoliation syndrome, compared with those without exfoliation syndrome, were significantly more likely to carry damaging CYP39A1 variants (1.3% vs 0.30%, respectively; odds ratio, 3.55 [95% CI, 2.07-6.10]; P = 6.1 × 10-7). This outcome was validated in 2 independent cohorts. The first validation cohort included 2337 individuals with exfoliation syndrome (median age, 74 years; 1132 women; n = 1934 with demographic data) and 2813 individuals without exfoliation syndrome (median age, 72 years; 1287 women; n = 2421 with demographic data). The second validation cohort included 1663 individuals with exfoliation syndrome (median age, 75 years; 587 women; n = 1064 with demographic data) and 3962 individuals without exfoliation syndrome (median age, 74 years; 951 women; n = 1555 with demographic data). Of the individuals from both validation cohorts, 5.2% with exfoliation syndrome carried CYP39A1 damaging alleles vs 3.1% without exfoliation syndrome (odds ratio, 1.82 [95% CI, 1.47-2.26]; P < .001). Biochemical assays classified 34 of 42 damaging CYP39A1 alleles as functionally deficient (median reduction in enzymatic activity compared with wild-type CYP39A1, 94.4% [interquartile range, 78.7%-98.2%] for the 34 deficient variants). CYP39A1 transcript expression was 47% lower (95% CI, 30%-64% lower; P < .001) in ciliary body tissues from individuals with exfoliation syndrome compared with individuals without exfoliation syndrome. Conclusions and Relevance: In this whole-exome sequencing case-control study, presence of exfoliation syndrome was significantly associated with carriage of functionally deficient CYP39A1 sequence variants. Further research is needed to understand the clinical implications of these findings.

The Role of Autophagy in Chemical Proteasome Inhibition Model of Retinal Degeneration.

We recently demonstrated that chemical proteasome inhibition induced inner retinal degeneration, supporting the pivotal roles of the ubiquitin-proteasome system in retinal structural integrity maintenance. In this study, using beclin1-heterozygous (Becn1-Het) mice with autophagic dysfunction, we tested our hypothesis that autophagy could be a compensatory retinal protective mechanism for proteasomal impairment. Despite the reduced number of autophagosome, the ocular tissue morphology and intraocular pressure were normal. Surprisingly, Becn1-Het mice experienced the same extent of retinal degeneration as was observed in wild-type mice, following an intravitreal injection of a chemical proteasome inhibitor. Similarly, these mice equally responded to other chemical insults, including endoplasmic reticulum stress inducer, N-methyl-D-aspartate, and lipopolysaccharide. Interestingly, in cultured neuroblastoma cells, we found that the mammalian target of rapamycin-independent autophagy activators, lithium chloride and rilmenidine, rescued these cells against proteasome inhibition-induced death. These results suggest that Becn1-mediated autophagy is not an effective intrinsic protective mechanism for retinal damage induced by insults, including impaired proteasomal activity; furthermore, autophagic activation beyond normal levels is required to alleviate the cytotoxic effect of proteasomal inhibition. Further studies are underway to delineate the precise roles of different forms of autophagy, and investigate the effects of their activation in rescuing retinal neurons under various pathological conditions.

Enteric dysbiosis in liver and kidney transplant recipients: a systematic review.

Several factors mediate intestinal microbiome (IM) alterations in transplant recipients, including immunosuppressive (IS) and antimicrobial drugs. Studies on the structure and function of the IM in the post-transplant scenario and its role in the development of metabolic abnormalities, infection, and cancer are limited. We conducted a systematic review to study the taxonomic changes in liver (LT) and kidney (KT) transplantation, and their potential contribution to post-transplant complications. The review also includes pre-transplant taxa, which may play a critical role in microbial alterations post-transplant. Two reviewers independently screened articles, and assessed risk of bias. The review identified 13 clinical studies, which focused on adult kidney and liver transplant recipients. Patient characteristics and methodologies varied widely between studies. Ten studies reported increased an abundance of opportunistic pathogens (Enterobacteriaceae, Enterococcaceae, Fusobacteriaceae, and Streptococcaceae) followed by butyrate-producing bacteria (Lachnospiraceae and Ruminococcaceae) in nine studies in post-transplant conditions. The current evidence is mostly based on observational data and studies with no proof of causality. Therefore, further studies exploring the bacterial gene functions rather than taxonomic changes alone are in demand to better understand the potential contribution of the IM in post-transplant complications.

Rabbit Fungal Keratitis Model of Fusarium solani Tested Against Three Commercially Available Antifungal Drugs.

OBJECTIVES: The purpose of this study was to develop a reproducible preclinical Fusarium solani keratitis model, which would allow comparative testing of currently available antifungals (NATACYN [Alcon, Fort Worth, TX], voriconazole 1%, and amphotericin B 0.1%) as well as efficacy testing of new antifungals for translation into clinical practice in the future. METHODS: The rabbit F. solani keratitis model was developed in New Zealand white rabbits using local and systemic immunosuppression. Infection was introduced by intrastromal injection of F. solani spores into one of the immunosuppressed rabbit eyes while the contralateral eye was a control. Progress of the infection was assessed by the clinical features, histopathology, and viable fungal counts. In this study, the efficacy of currently available antifungals (NATACYN [Alcon], voriconazole 1%, and amphotericin B 0.1%) was compared. Rabbits were randomly divided (n=4 in each group), and the respective antifungal was instilled topically 5 times/day for 7 days. Treatment effects were analyzed by evaluating the anterior segment with the help of slit-lamp, histopathological findings and viable fungal culture at the end of the experiment. RESULTS: We report the development of a reproducible and progressive rabbit F. solani keratitis model as shown by the substantial viable fungal counts (3 log CFU), the presence of large patchy lesions and substantial hypopyon in the 12-day model correlated with specific histopathological analysis for fungus (extended F. solani hyphae from midcorneal stroma into the anterior chamber and traverse Descemet membrane with anterior chamber suppurative plaque). Voriconazole 1% and NATACYN revealed significant reduction of the fungal wound area (P=0.02 and 0.021), respectively, while amphotericin B 0.1% exhibited P value of 0.083 compared with their infected nontreated controls. Voriconazole 1% and amphotericin B 0.1% showed significant viable fungal count differences (P=0.004 and 0.01), respectively, whereas P value of NATACYN was 0.337 compared with control infected corneas. CONCLUSION: The reported rabbit fungal keratitis model can be used for screening new antifungals and evaluating currently available antifungals to facilitate better clinical outcomes. Voriconazole 1% showed the best efficacy among the three tested currently available antifungals by showing the significant differences in both wound size and viable fungal count comparisons in our F. solani rabbit keratitis model.

A retrospective study on risk assessment and management of forensic psychiatric inpatients in Hong Kong.

The Department of Forensic Psychiatry of Castle Peak Hospital is the only facility in Hong Kong that provides territory-wide forensic psychiatric services for patients with criminal involvement. This retrospective study aimed to explore whether the rehabilitation programs provided by the department could significantly reduce the risks of forensic psychiatric inpatients as measured by the Short-Term Assessment of Risk and Treatability (START). START ratings of inpatients who were hospitalized in the department for more than 3 months and were discharged to the community during the period from 11 April 2015 to 31 March 2019 were analyzed. A total of 79 patients were assessed, of whom 61 (77.2%) were males. Fifty-four (68.4%) patients suffered from schizophrenia. START scores upon admission (strength score = 5.67; vulnerability score = 17.43) and upon discharge (strength score = 6.87, vulnerability score = 11.18) indicated significant reduction of risks among inpatients (p < 0.05).

Primary angle closure glaucoma (PACG) susceptibility gene PLEKHA7 encodes a novel Rac1/Cdc42 GAP that modulates cell migration and blood-aqueous barrier function.

PLEKHA7, a gene recently associated with primary angle closure glaucoma (PACG), encodes an apical junctional protein expressed in components of the blood aqueous barrier (BAB). We found that PLEKHA7 is down-regulated in lens epithelial cells and in iris tissue of PACG patients. PLEKHA7 expression also correlated with the C risk allele of the sentinel SNP rs11024102 with the risk allele carrier groups having significantly reduced PLEKHA7 levels compared to non-risk allele carriers. Silencing of PLEKHA7 in human immortalized non-pigmented ciliary epithelium (h-iNPCE) and primary trabecular meshwork cells, which are intimately linked to BAB and aqueous humor outflow respectively, affected actin cytoskeleton organization. PLEKHA7 specifically interacts with GTP-bound Rac1 and Cdc42, but not RhoA, and the activation status of the two small GTPases is linked to PLEKHA7 expression levels. PLEKHA7 stimulates Rac1 and Cdc42 GTP hydrolysis, without affecting nucleotide exchange, identifying PLEKHA7 as a novel Rac1/Cdc42 GAP. Consistent with the regulatory role of Rac1 and Cdc42 in maintaining the tight junction permeability, silencing of PLEKHA7 compromises the paracellular barrier between h-iNPCE cells. Thus, downregulation of PLEKHA7 in PACG may affect BAB integrity and aqueous humor outflow via its Rac1/Cdc42 GAP activity, thereby contributing to disease etiology.

Permeability of the porcine iris stroma.

Current literature has not considered or provided any data on the permeability of the iris stroma. In this study, we aimed to determine the hydraulic permeability of porcine irides from the isolated stroma. Fifteen enucleated porcine eyes were acquired from the local abattoir. The iris pigment epithelium was scraped off using a pair of forceps and the dilator muscles were pinched off using a pair of colibri toothed forceps. We designed an experimental setup, based on Darcy's law, and consisting of a custom 3D-printed pressure column using acrylonitrile butadiene styrene (ABS) plastic. PBS solution was passed through the iris stroma in a 180° arc shape, with a column height of approximately 204 mm (2000 Pa). Measurements of iris stromal thickness were conducted using optical coherence tomography (OCT). To measure flow rate, we measured the mass (volume) of PBS solution using a mass balance in approximately 1 min. Histology was performed using hematoxylin and eosin (H&E) and anti-smooth muscle antibody (anti-α-SMA) for validation. The permeability experiments demonstrated that the iris stroma is a biphasic tissue that allows fluid flow. Our image processing results determined the area of flow to be 7.55 mm2 and the tissue thickness to be between 180 and 430 µm. The hydraulic permeability of the porcine stroma, calculated using Darcy's law, was 5.13 ±â€¯2.39 × 10-5 mm2/Pa•s. Histological and immunochemical studies confirmed that the tissues used for this permeability study were solely iris stroma. Additionally, anti-α-SMA staining revealed staining specific for stromal blood vessels, with the notable absence of dilator and sphincter muscle staining. Our study combined experimental microscopic data with the theory of biphasic materials to investigate the hydraulic permeability of the iris stroma. This work will serve as a basis on which to validate future biomechanical studies of human irides with which may ultimately aid disease diagnosis and inform the design of novel treatments.

A common variant near TGFBR3 is associated with primary open angle glaucoma.

Primary open angle glaucoma (POAG), a major cause of blindness worldwide, is a complex disease with a significant genetic contribution. We performed Exome Array (Illumina) analysis on 3504 POAG cases and 9746 controls with replication of the most significant findings in 9173 POAG cases and 26 780 controls across 18 collections of Asian, African and European descent. Apart from confirming strong evidence of association at CDKN2B-AS1 (rs2157719 [G], odds ratio [OR] = 0.71, P = 2.81 × 10(-33)), we observed one SNP showing significant association to POAG (CDC7-TGFBR3 rs1192415, ORG-allele = 1.13, Pmeta = 1.60 × 10(-8)). This particular SNP has previously been shown to be strongly associated with optic disc area and vertical cup-to-disc ratio, which are regarded as glaucoma-related quantitative traits. Our study now extends this by directly implicating it in POAG disease pathogenesis.

Clinical Features and Treatment Outcomes of Orbital Inflammatory Disease in Singapore: A 10-Year Clinicopathologic Review.

PURPOSE: 1) To assess the clinical profile and treatment outcomes of orbital inflammatory disease in the local population, and 2) classify patients using current histopathological criteria. METHODS: Ten-year retrospective clinicopathologic review of patients diagnosed with orbital inflammatory disease who underwent tissue biopsy from January 2001 to December 2011 at a tertiary referral centre in Singapore. Data collection included patient demographics, clinical presentation, investigations, systemic disease, histopathology review, clinical classification, medical and surgical management, response to treatment and recurrence rates. RESULTS: The study comprised 70 patients. Thirty-seven (52.9%) had nonspecific inflammation distributed as follows: lacrimal (n = 23), diffuse (n = 5), anterior (n = 5), myositic (n = 4). Thirty-three (47.1%) had specific inflammation of the following subtypes: idiopathic sclerosing inflammation (n = 9), granulomatous disorders (n = 8), transitional lesions (n = 5), vasculitis (n = 4), and others (n = 7). A total of 76.8% of patients received oral prednisolone, with a median duration of three months. Response to treatment was good in 71.9% of patients. Recurrence occurred in 22 (32.8%) patients at a mean interval of 20 months after completion of treatment, and was higher in myositic and vasculitic subtypes. There was no significant correlation between duration of treatment and recurrence. CONCLUSIONS: This study has re-emphasized the importance and utility of orbital biopsy and histopathologic typing for optimal management of orbital inflammatory disease. It has also improved the knowledge of the rate and response to treatment of its various subtypes.

Sectoral variations of iridocorneal angle width and iris volume in Chinese Singaporeans: a swept-source optical coherence tomography study.

PURPOSE: To assess variations in the iridocorneal angle width and iris volume in Chinese subjects using swept-source optical coherence tomography (SS-OCT). METHODS: Consecutive subjects, aged 40-80 years, with no previous ophthalmic problems were recruited from a population-based study of Chinese Singaporeans. All subjects underwent 360° SS-OCT (SS-1000 CASIA, Tomey Corporation, Nagoya, Japan) angle imaging and gonioscopy in one randomly selected eye in the dark. For each eye, 16 frames (11.25° apart) were selected for analysis from 128 cross-sectional images, and measurements of the trabecular iris space area 750 µm from the scleral spur (TISA750) and iris volume were made for each image. The measurements from four consecutive frames were further averaged as a sector of 45°. Sector-wise angle width and quadrant-wise iris volume were analyzed. RESULTS: Two hundred and twelve subjects (90 with closed-angles) were examined. The majority of the subjects were female (70.7 %) with mean age 61 (±8.9) years. The TISA750 (mm(2)) of superior [0.101 (0.09)], inferior [0.105 (0.09)], superior-nasal [0.111 (0.09)] and superior-temporal [0.117 (0.09)] sectors were smaller compared with other sectors (P < 0.05). The nasal iris volume (mm(3)) was the smallest compared with other quadrants for the entire cohort [nasal 8.18 (1.2) < inferior 9.13 (1.3) < temporal 9.16 (1.2) < superior 9.33 (1.3), P < 0.001], as well as for open- and closed-angle groups. CONCLUSIONS: The irido-corneal angle was narrower in the superior, inferior, superior-nasal and superior-temporal sectors compared with other sectors. Iris volume in the nasal quadrant was the smallest compared with the other quadrants.

Rodent genetically modified models of glaucoma.

Glaucoma, one of the leading causes of irreversible blindness worldwide, is a complex and heterogenous disease. While environmental factors are important, it is well-recognized that the disease has a strong heritable component. With the advent of large-cohort genome wide association studies, a myriad of genetic risk loci has been linked to different forms of glaucoma. Animal models have been an indispensable tool in characterizing these loci, especially if they lie within coding regions in the genome. Not only do these models connect genotype to phenotype, advancing our understanding of glaucoma pathogenesis in the process, they also have valuable utility as a platform for the pre-clinical testing of potential therapies. In this review, we will outline genetic models used for studying the major forms of glaucoma, including primary open angle glaucoma, normal tension glaucoma, primary angle closure glaucoma, pigmentary glaucoma, pseudoexfoliation glaucoma, and early onset glaucoma, including congenital and developmental glaucoma, and how studying these models have helped shed light on human glaucoma.

Assessment of trabecular meshwork width using swept source optical coherence tomography.

PURPOSE: Measurements of the angle width by ultrasound biomicroscopy or anterior segment optical coherence tomography are usually performed 500 µm from the scleral spur, as the anterior part of trabecular meshwork (TM) is assumed to lie within this distance. The aim of this study was to measure TM width using swept source optical coherence tomography (SS-OCT, CASIA SS-1000, Tomey Corporation, Nagoya, Japan), and to investigate factors influencing this measurement. METHODS: Participants underwent gonioscopy and SS-OCT imaging in the dark. High-definition SS-OCT images were corrected for refractive distortion; and customized software (ImageJ; National Institutes of Health, Bethesda, MD, USA) was utilized to measure TM width (distance between the scleral spur and Schwalbe's line). Linear regression analysis was performed to assess the relationship between TM width with demographic and angle parameters. RESULTS: One hundred and forty eight Chinese subjects were analyzed. The majority was female (62.4 %); the mean age was 59.2 ± 8.68 years. Identification of the scleral spur and Schwalbe's line with SS-OCT was possible in 590 (99.7 %) and 585 angle quadrants (98.8 %) respectively. TM width was wider in the inferior and superior quadrants (mean 889 [SD 138] and 793 [136] µm), compared to the nasal and temporal quadrants (712 [137] and 724 [115] µm, P<0.001). There was a difference in average TM width between open (789 [100]) and closed angle eyes (753 [86]) (P=0.048). There was no significant association between TM width and angle parameters, laterality, or demographic factors. CONCLUSIONS: In SS-OCT HD images, the mean TM width varied from 710 to 890 µm in the different quadrants of the eye, and the inferior quadrant TM was the widest compared to other quadrants.

Intravitreal Neuroglobin Mitigates Primate Experimental Glaucomatous Structural Damage in Association with Reduced Optic Nerve Microglial and Complement 3-Astrocyte Activation.

Current management of glaucomatous optic neuropathy is limited to intraocular pressure control. Neuroglobin (Ngb) is an endogenous neuroprotectant expressed in neurons and astrocytes. We recently showed that exogenous intravitreal Ngb reduced inflammatory cytokines and microglial activation in a rodent model of hypoxia. We thus hypothesised that IVT-Ngb may also be neuroprotective in experimental glaucoma (EG) by mitigating optic nerve (ON) astrogliosis and microgliosis as well as structural damage. In this study using a microbead-induced model of EG in six Cynomolgus primates, optical coherence imaging showed that Ngb-treated EG eyes had significantly less thinning of the peripapillary minimum rim width, retinal nerve fibre layer thickness, and ON head cupping than untreated EG eyes. Immunohistochemistry confirmed that ON astrocytes overexpressed Ngb following Ngb treatment. A reduction in complement 3 and cleaved-caspase 3 activated microglia and astrocytes was also noted. Our findings in higher-order primates recapitulate the effects of neuroprotection by Ngb treatment in rodent EG studies and suggest that Ngb may be a potential candidate for glaucoma neuroprotection in humans.

The Structural Layers of the Porcine Iris Exhibit Inherently Different Biomechanical Properties.

Purpose: The purpose of this study was to isolate the structural components of the ex vivo porcine iris tissue and to determine their biomechanical properties. Methods: The porcine stroma and dilator tissues were separated, and their dimensions were assessed using optical coherence tomography (OCT). The stroma underwent flow test (n = 32) to evaluate for permeability using Darcy's Law (ΔP = 2000 Pa, A = 0.0391 mm2), and both tissues underwent stress relaxation experiments (ε = 0.5 with initial ramp of δε = 0.1) to evaluate for their viscoelastic behaviours (n = 28). Viscoelasticity was characterized by the parameters ß (half width of the Gaussian distribution), τm (mean relaxation time constant), E0 (instantaneous modulus), and E∞ (equilibrium modulus). Results: For the stroma, the hydraulic permeability was 9.49 ± 3.05 × 10-6 mm2/Pa · s, and the viscoelastic parameters were ß = 2.50 ± 1.40, and τm = 7.43 ± 4.96 s, with the 2 moduli calculated to be E0 = 14.14 ± 6.44 kPa and E∞ = 6.08 ± 2.74 kPa. For the dilator tissue, the viscoelastic parameters were ß = 2.06 ± 1.33 and τm = 1.28 ± 1.27 seconds, with the 2 moduli calculated to be E0 = 9.16 ± 3.03 kPa and E∞ = 5.54 ± 1.98 kPa. Conclusions: We have established a new protocol to evaluate the biomechanical properties of the structural layers of the iris. Overall, the stroma was permeable and exhibited smaller moduli than those of the dilator muscle. An improved characterization of iris biomechanics may form the basis to further our understanding of angle closure glaucoma.

Propranolol Ameliorates the Antifungal Activity of Azoles in Invasive Candidiasis.

The effectiveness of current antifungal therapies is hampered by the emergence of drug resistance strains, highlighting an urgent need for new alternatives such as adjuvant antifungal treatments. This study aims to examine the synergism between propranolol and antifungal drugs, based on the premise that propranolol is known to inhibit fungal hyphae. In vitro studies demonstrate that propranolol potentiates the antifungal activity of azoles and that the effect is more pronounced for propranolol-itraconazole combination. Using an in vivo murine systemic candidemia model, we show that propranolol-itraconazole combination treatment resulted in a lower rate of body weight loss, decreased kidney fungal bioburden and renal inflammation when compared to propranolol and azole treatment alone or untreated control. Altogether, our findings suggest that propranolol increases the efficacy of azoles against C. albicans, offering a new therapeutic strategy against invasive fungal infections.