Nonviral Liver Disease Burden in People Living With HIV and Elevated Transaminases: A Cross-Sectional Study.

INTRODUCTION: Because of improved life expectancy in people living with HIV (PLWH), liver disease is increasingly being recognized. We assessed nonviral chronic liver disease burden in PLWH. METHODS: The HIV non-virAL liver disease study (2014-2021) prospectively recruited PLWH with elevated serum alanine aminotransferase levels and negative hepatitis serology. Clinically significant hepatic fibrosis (CSHF) was defined as liver stiffness measurement of >7.1 kPa and hazardous alcohol use as Alcohol Use Disorders Identification Test score ≥ 8. Primary outcome was prevalence/predictors of CSHF. RESULTS: Total recruited were n = 274, 92% male, median age 52 (45-59) years, and 96% having undetectable HIV viral load. Overall, n = 97 (35%) had hazardous alcohol use, n = 72 (26%) had metabolic syndrome, and 17%-27% had exposure to hepatotoxic antiretrovirals. Prevalence of CSHF was 20% (n = 54), prevalence of cirrhosis (liver stiffness measurement > 12.5 kPa) being 7% (19/274). Risk factors for CSHF were hazardous alcohol use in 44% (n = 24), metabolic syndrome in 46% (n = 25), and hepatotoxic antiretrovirals in 56% (n = 30), most having more than one risk factor. Independent predictors of CSHF were serum high-density lipoprotein (odds ratio [OR] 0.220; 95% confidence interval [CI]: 0.061 to 0.790, P = 0.020) (inverse relationship); serum aspartate aminotransferase (OR 1.033, 95% CI: 1.001 to 1.067, P = 0.045), and didanosine use (OR 2.878, 95% CI: 1.228 to 6.774, P = 0.015). Moderate-severe hepatic steatosis was identified in 52% (n = 142). FIB-4 and aspartate aminotransferase-to-platelet ratio index performed poorly in predicting CSHF (positive predictive value 27.3% and 30.6%, respectively) and advanced fibrosis (≥F3) (positive predictive value 17.6% and 5.9%, respectively). CONCLUSION: In this study, 20% of PLWH had CSHF associated with high prevalence of hazardous alcohol use/metabolic syndrome/potentially hepatotoxic antiretrovirals. These potentially modifiable risk factors need addressing.

Does regulating the sale of high-strength beer and cider impact hospital admissions with decompensated alcohol-related liver disease: A retrospective cohort study.

OBJECTIVE: 'Sensible on Strength' (SoS), a local public health initiative, is aimed at reducing high-strength beer and cider availability. The objective of this study was to assess its impact on local hospital admissions with alcohol-related liver disease (ALD) and on drinking behaviour. DESIGN: This was a retrospective cohort study in patients admitted with decompensated ALD, 3 years before and 3 years after the introduction of the SoS initiative.Hospital records of 143 index admissions with decompensated ALD were reviewed. Outcomes measures were the severity of liver disease on admission and mortality (inpatient and long-term), and change (if any) in alcohol drinking behaviour. RESULTS: Comparing patients admitted in both phases, there were no significant differences in liver prognostic scores, liver-related complications, length of stay and inpatient/long-term mortality (p>0.05). However, the SoS initiative was associated with a 33% move away from beer and cider consumption (36.3% vs 54.0%; p=0.034), but without a significant change in units of alcohol consumed. The Model for End-stage Liver Disease (MELD) score was the only independent predictor of inpatient mortality (odds ratio 1.25; p=0.025). CONCLUSION: Despite having no apparent impact on the clinical spectrum of local ALD admissions, it is conceivable that longer follow-up is needed to determine the true impact of this initiative.

Role of in vivo confocal microscopy in the diagnosis of infectious keratitis.

PURPOSE: To investigate the utility of in vivo confocal microscopy (IVCM) in the diagnosis of infectious keratitis (IK). METHODS: Retrospective chart review of 46 patients with a final diagnosis of IK were included in the study. All patients received IVCM corneal imaging using the Heidelberg Retinal Tomography III system. All available scans were randomized and analyzed in a masked fashion. Sensitivity and specificity of IVCM in diagnosing bacterial keratitis (BK), Acanthamoeba keratitis (AK), fungal keratitis (FK), and HSV viral keratitis (VK) were assessed. RESULTS: The pooled sensitivity and specificity of IVCM in identifying atypical IK (AK and FK cases combined) were 85.3% (95% CI 68.2-94.5%) and 100% (95% CI 74.7-100%), respectively. The sensitivity and specificity of IVCM in identifying BK were 66.7% (95% CI 35.4-88.7%) and 89.2% (95% CI 73.4-96.5%), respectively. The sensitivity and specificity of IVCM in identifying VK were 100% (95% CI 46.3-100%) and 93.2% (95% CI 80.3-98.2%). Additionally, IVCM was able to make the correct diagnosis in 8 out of the 11 atypical keratitis cases misdiagnosed clinically. In the AK subgroup, IVCM was more accurate than clinical assessment (16 vs. 11). In the FK subgroup, IVCM were as accurate as clinical assessment, but did correct one misdiagnosed cases by identfying fungal hyphae. CONCLUSION: IVCM is an non-invasive imaging modality that can rapidly and accurately diagnose IK even for experienced corneal specialists. In complex cases of polymicrobial infection, IVCM may guide the correct clinical diagnosis and initiation of the appropriate treatment.

Assessment of Corneal Changes Associated with Topical Antiglaucoma Therapy Using in vivo Confocal Microscopy.

PURPOSE: Ocular surface disease (OSD) is highly prevalent in eyes treated with chronic, topical antiglaucoma (A/G) therapy. The purpose of this study was to utilize in vivo confocal microscopy (IVCM) to evaluate the corneal morphology, including characteristics of corneal epithelial cells, presence of epithelial dendritic cells (DCs), and characteristics of subbasal nerve plexus, of eyes under topical A/G therapy versus normal eyes. METHODS: Central corneal images were prospectively captured from 30 eyes of 16 patients under topical A/G therapy (>6 months) and 20 normal control eyes, using IVCM (HRT 3 RCM, Heidelberg, Germany). Demographic data were collected, as well as information on the types and duration of A/G therapy. In addition, OSD index (OSDI) score, tear film breakup time, Schirmer 1 test results, density of epithelial wing cells (WCs) and basal cells (BCs), subbasal nerve features (density, tortuosity, and reflectivity), and presence of DCs were all assessed and recorded by trained Doheny Image Reading Center graders. RESULTS: IVCM findings of 30 glaucomatous eyes and 20 normal control eyes were analyzed. The mean OSDI score was 8.72 in controls and 32.06 in patients under A/G therapy (p = 0.002). Nerve fiber density, nerve fiber reflectivity, and BC density were all decreased in the A/G group (1,789.07 ± 785.70 µm/frame, 2.79 ± 0.83, 6,457.67 ± 692.55 cells/mm2, respectively) as compared to controls (2,815.981 ± 563.77 µm/frame, 3.52 ± 0.50, 7,854.13 ± 1,073.69 cells/mm2, respectively) (p < 0.05), whereas the decrease in WC density was statistically nonsignificant (p = 0.5). Nerve tortuosity and DC density were both significantly greater in the A/G eyes (3.00 ± 0.57, 71.24 ± 61.74 cells/mm2, respectively) compared to controls (2.10 ± 0.42, 34.08 ± 11.70 cells/mm2, respectively) (p < 0.05). Tear film breakup time and Schirmer 1 test results were significantly lower in the A/G group as compared to controls (p < 0.001). CONCLUSIONS: Using IVCM, our study identified significant microstructural alterations in the corneas of eyes treated with topical A/G therapy. In addition, our study also revealed that glaucoma patients treated with topical A/G therapy report significantly higher OSDI scores compared to controls. Thus, IVCM may be a useful tool in providing structural parameters to correlate with the functional OSDI assessments in the evaluation of ocular surface toxicity associated with topical A/G therapy.

A Phenotype of Primary Open-angle Glaucoma With Systemic Vasospasm.

PURPOSE: Primary open-angle glaucoma (POAG) patients constitute a heterogenous group. Identification of phenotypic subtypes among these patients may provide a deeper understanding of the disease and aid associations with genotypes. We describe a phenotype of POAG patients associated with a constellation of systemic disorders; patients with this phenotype seem to be vulnerable to optic nerve damage at low intraocular pressures. MATERIALS AND METHODS: In this retrospective study, we evaluated the medical records of active Jules Stein Eye Institute glaucoma patients from January 1996 to 2017 and included subjects with POAG, acquired pits of the optic nerve (APON), and at least one of the following: systolic blood pressure persistently ≤100 mm Hg, history of migraine headaches or migraine variant, and the Raynaud syndrome. RESULTS: Of 87 patients (125 eyes) with APON, 37 patients (55 eyes) met the study criteria. In total, 34 patients were female (92%). The median age at the time of diagnosis was 55 years. Nineteen patients (73%) had low systolic blood pressures, same number had Raynaud syndrome, and 25 (68%) had a history of migraine. CONCLUSIONS: We describe a POAG subtype with APON and systemic vascular instability, predominantly female in their sixth decade of life who demonstrate progressive glaucomatous visual field damage at low intraocular pressure. We suggest that this clinical picture represents an important phenotype of POAG, and that identification and further study of it will help guide diagnosis and development of individualized treatments.

Using an Image Fusion Methodology to Improve Efficiency and Traceability of Posterior Pole Vessel Analysis by ROPtool.

BACKGROUND: The diagnosis of plus disease in retinopathy of prematurity (ROP) largely determines the need for treatment; however, this diagnosis is subjective. To make the diagnosis of plus disease more objective, semi-automated computer programs (e.g. ROPtool) have been created to quantify vascular dilation and tortuosity. ROPtool can accurately analyze blood vessels only in images with very good quality, but many still images captured by indirect ophthalmoscopy have insufficient image quality for ROPtool analysis. PURPOSE: To evaluate the ability of an image fusion methodology (robust mosaicing) to increase the efficiency and traceability of posterior pole vessel analysis by ROPtool. MATERIALS AND METHODOLOGY: We retrospectively reviewed video indirect ophthalmoscopy images acquired during routine ROP examinations and selected the best unenhanced still image from the video for each infant. Robust mosaicing was used to create an enhanced mosaic image from the same video for each eye. We evaluated the time required for ROPtool analysis as well as ROPtool's ability to analyze vessels in enhanced vs. unenhanced images. RESULTS: We included 39 eyes of 39 infants. ROPtool analysis was faster (125 vs. 152 seconds; p=0.02) in enhanced vs. unenhanced images, respectively. ROPtool was able to trace retinal vessels in more quadrants (143/156, 92% vs 115/156, 74%; p=0.16) in enhanced mosaic vs. unenhanced still images, respectively and in more overall (38/39, 97% vs. 34/39, 87%; p=0.07) enhanced mosaic vs. unenhanced still images, respectively. CONCLUSION: Retinal image enhancement using robust mosaicing advances efforts to automate grading of posterior pole disease in ROP.

Quantitative Analysis of Depth, Distribution, and Density of Cysts in Acanthamoeba Keratitis Using Confocal Microscopy.

PURPOSE: To quantify the density, distribution, and depth of invasion of cysts in the corneas of eyes with acanthamoeba keratitis (AK) by in vivo confocal microscopy (IVCM) with a novel scanning pattern. METHODS: The medical records of patients with AK evaluated at the Doheny Eye Center UCLA between September 2014 and July 2016 were reviewed retrospectively. Patients with clinically diagnosed AK underwent IVCM at various time points during their clinical course. Five corneal locations were scanned at each time point: the central area and 4 standard points on the peripheral cornea corresponding to temporal, nasal, inferior, and superior locations. The IVCM scans were manually graded to quantify the maximum depth of invasion and density of cysts. RESULTS: Twenty-one eyes of 18 patients with visible cysts on IVCM were included. Mean cyst density at presentation was 214.1 ± 120.2/mm (range: 64-484 cells/mm), and the average cyst depth was 164.3 ± 81.2 µm (range: 17-290 µm). In 17 eyes, the average cyst depth was 139.4 ± 68.6 µm (range: 17-245 µm), mean cyst density was 177.9 ± 99.6/mm, and an average of 1.4 ± 1.3 quadrants was infiltrated at presentation, and reached clinical resolution with medical treatment without surgical intervention. Four eyes that ultimately underwent therapeutic penetrating keratoplasty had cysts in all 4 quadrants and deeper cyst infiltration; the average cyst depth in these corneas was 270.5 ± 17.5 µm (range: 252-290). CONCLUSIONS: Eyes with AK requiring therapeutic keratoplasty were more likely to have a deeper and more diffuse penetration of cysts in the cornea compared with those resolving with medical treatment.

Deficit irrigation reduces postharvest rib pinking in wholehead Iceberg lettuce, but at the expense of head fresh weight.

BACKGROUND: Postharvest pinking is a serious issue affecting lettuce quality. Previous studies suggested the possibility of using deficit irrigation to control discolouration; however, this approach may also affect yield. This study investigated the effect of varying irrigation deficits on iceberg lettuce (Lactuca sativa L.) to determine the relationship between irrigation deficit, pinking and fresh weight. RESULTS: The deficit imposed and head fresh weight obtained depended on both the duration and timing of withholding irrigation. Withholding irrigation for a period of 2 or 3 weeks in the middle or end of the growth period significantly reduced rib pinking compared to well-watered controls. Withholding irrigation for 2 weeks at the start of the growth period or 1 week at the end did not significantly reduce pinking. Withholding irrigation also reduced head fresh weight such that minimising pinking would be predicted to incur a loss of 40% relative to well-watered controls. However, smaller benefits to pinking reduction were achieved with less effect on head fresh weight. CONCLUSION: Deficit irrigation could be used to provide smaller but higher quality heads which are less likely to be rejected. The balance of these factors will determine the degree of adoption of this approach to growers. © 2016 Society of Chemical Industry.

Oxidative discolouration in whole-head and cut lettuce: biochemical and environmental influences on a complex phenotype and potential breeding strategies to improve shelf-life.

Lettuce discolouration is a key post-harvest trait. The major enzyme controlling oxidative discolouration has long been considered to be polyphenol oxidase (PPO) however, levels of PPO and subsequent development of discolouration symptoms have not always correlated. The predominance of a latent state of the enzyme in plant tissues combined with substrate activation and contemporaneous suicide inactivation mechanisms are considered as potential explanations for this phenomenon. Leaf tissue physical properties have been associated with subsequent discolouration and these may be influenced by variation in nutrient availability, especially excess nitrogen and head maturity at harvest. Mild calcium and irrigation stress has also been associated with a reduction in subsequent discolouration, although excess irrigation has been linked to increased discolouration potentially through leaf physical properties. These environmental factors, including high temperature and UV light intensities, often have impacts on levels of phenolic compounds linking the environmental responses to the biochemistry of the PPO pathway. Breeding strategies targeting the PAL and PPO pathway biochemistry and environmental response genes are discussed as a more cost-effective method of mitigating oxidative discolouration then either modified atmosphere packaging or post-harvest treatments, although current understanding of the biochemistry means that such programs are likely to be limited in nature and it is likely that they will need to be deployed alongside other methods for the foreseeable future.

Femtosecond laser-assisted keratotomy.

PURPOSE OF REVIEW: To review the recent literature on femtosecond laser-assisted astigmatic keratotomy and its applications to naturally occurring as well as postoperative astigmatism in multiple settings. RECENT FINDINGS: Femtosecond laser technology has improved the safety and efficacy of astigmatic keratotomy in the treatment of astigmatism. Intrastromal femtosecond astigmatic keratotomy (ISAK) may have even lower complication rates, though long-term results are still being established. Femtosecond laser-assisted keratotomy (FSAK) in the surgical setting, such as at the time of or after cataract surgery, keratoplasty, and glaucoma surgery, has been investigated with overall good results. There have been some reports of overcorrection and undercorrection of astigmatism, particularly in the setting of high and nonorthogonal astigmatism. Further refinement of nomograms in these settings is indicated. Complications such as full thickness FSAK and ISAK incisions are rare but have been reported, and may be mitigated by the integration of dynamic optical coherence tomography (OCT) into femtosecond laser systems. SUMMARY: FSAK is an effective and safe way to correct astigmatism. These procedures have some advantages over manual astigmatic keratotomy, including increased accuracy of incision depth and placement. As nomograms are refined and technologies such as dynamic OCT are further incorporated into femtosecond systems, results are likely to continue improving.

ROPtool analysis of images acquired using a noncontact handheld fundus camera (Pictor)--a pilot study.

The presence of plus disease is the primary indication for treatment of retinopathy of prematurity (ROP), but its diagnosis is subjective and prone to error. ROPtool is a semiautomated computer program that quantifies vascular tortuosity and dilation. Pictor is an FDA-approved, noncontact, handheld digital fundus camera. This pilot study evaluated ROPtool's ability to analyze high-quality Pictor images of premature infants and its accuracy in diagnosing plus disease compared to clinical examination. In our small sample of images, ROPtool could trace and identify the presence of plus disease with high accuracy.

The Future of Dry Eye Treatment: A Glance into the Therapeutic Pipeline.

Dry eye syndrome is both a primary disease and a secondary result of many pathological states of the eye. The symptoms range from mild to severe itching, burning, irritation, eye fatigue, and even vision loss that can lead to disability. Dry eye affects approximately 60 million people worldwide; as a result, medications to treat dry eye comprise approximately 15% of the ophthalmic pharmaceutical market. While doctors and patients eagerly await new treatments, pharmaceuticals in the pipeline are moving through the approval process with several promising drugs having completed phase 3 clinical testing. This review summarizes the findings of studies of the most promising, upcoming dry eye treatments in phase 2 and 3 clinical trials in the USA.

More 'crop per drop': constraints and opportunities for precision irrigation in European agriculture.

Dwindling water supplies, increasing drought frequency and uncertainties associated with a changing climate mean Europe's irrigated agriculture sector needs to improve water efficiency and produce more 'crop per drop'. This paper summarizes the drivers for change, and the constraints and opportunities for improving agricultural water management through uptake of precision irrigation technologies. A multi-disciplinary and integrated approach involving irrigation engineers, soil scientists, agronomists and plant physiologists will be needed if the potential for precision irrigation within the field crop sector is to be realized.