Design and Development of Inexpensive Paper-Based Chemosensors for Detection of Divalent Copper.

Simple, portable, and low-cost paper-based sensors are alternative devices that have the potential to replace high-cost sensing technologies. The compatibility of the paper base biosensors for both chemical and biochemical accentuates its feasibility for application in clinical diagnosis, environmental monitoring, and food quality monitoring. High concentration of copper in blood serum and urine is associated with diseases like liver diseases, carcinomas, acute and chronic infections, rheumatoid arthritis, etc. Detection of copper concentration can give an early sign of Alzheimer disease. Apart from that genetic Wilson's disease can be detected by evaluating the concentration of copper in the urine. In view of the above advantages, a novel and the highly sensitive paper-based sensor has been designed for the selective detection of Cu2+ ions. The fast and highly sensitive chemiresistive multi-dye system sensor can detect Cu2+ ions selectively in as low as 2.23 ppm concentration. Least interference has been observed for counter ion in the detection of Cu2+. Copper chloride, nitrate, and acetate were used to validate the detection process. This assay provides a very high selectivity of Cu2+ ion over other metal cations such as Na+, Mg2+, Ca2+, etc. The easy preparation and high stability of dye solutions, easy functionalization of the paper-based sensors, high selectivity over other cations, low interference of counter anion, and significantly low detection limit of 2.23 ppm make it an effective Cu2+ ion sensor for real-time application in near future.

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.

Boston Type 1 Keratoprosthesis versus Repeat Donor Keratoplasty for Corneal Graft Failure: A Systematic Review and Meta-analysis.

PURPOSE: To compare repeat penetrating keratoplasty (PK) with Boston type I keratoprosthesis (KPro) implantation for full-thickness donor corneal graft failure. DESIGN: Previous donor graft failure is a common indication for both PK and KPro implantation. Selection of the surgical procedure is entirely dependent on the surgeon because there are no studies available for guidance. Therefore, a systematic review was undertaken to examine vision, device retention, graft clarity, and postoperative glaucoma and infection outcomes after repeat PK versus KPro implantation. METHODS: Articles with data regarding repeat PK published between 1990 and 2014 were identified in PubMed, EMBASE, the Latin American and Caribbean Health Sciences Literature Database, and the Cochrane Central Register of Controlled Trials and were reviewed. Results were compared with a retrospective review of consecutive, nonrandomized, longitudinal case series of KPro implantations performed at 5 tertiary care centers in the United States. Visual acuity at 2 years was the primary outcome measure. The proportion of clear grafts in the repeat PK group, device retention in the KPro group, and the development of postoperative glaucoma and infection were secondary outcome measures. RESULTS: The search strategy identified 17 128 articles in the PK analysis. After screening, 26 studies (21 case series and 5 cohort studies) were included in the review. Pooled analysis of the 26 unique studies demonstrated a 42% (95% confidence interval [CI], 30%-56%) likelihood of maintaining 20/200 or better at 2 years after repeat PK, compared with an 80% (95% CI, 68%-88%) probability with KPro implantation. The probability of maintaining a clear graft at 5 years was 47% (95% CI, 40%-54%) after repeat PK, whereas the probability of retention of the KPro at 5 years was 75% (95% CI, 64%-84%). The rate of progression of glaucoma at 3 years was 25% (95% CI, 10%-44%) after repeat PK and 30% in the KPro cohort. CONCLUSIONS: These results demonstrate favorable outcomes of KPro surgery for donor corneal graft failure with a greater likelihood of maintaining visual improvement without higher risk of postoperative glaucoma compared with repeat donor PK.

Demographic and Systemic Risk Factors for Persistent Corneal Edema Following Cataract Surgery in Patients With and Without Diabetes.

PURPOSE: To identify risk factors associated with the development of corneal edema (CE) and the need for corneal transplantation following cataract surgery. DESIGN: Retrospective cohort study. METHODS SETTING: Nation-wide sample of Medicare beneficiaries from 2011-2015. STUDY POPULATION: Medicare beneficiaries aged over 65 years who received cataract surgery between 2011-2014 with at least 1 year of continuous follow-up. Data was retrieved from the Denominator and Physician Supplier Part B file from the Center for Medicare and Medicaid Services. MAIN OUTCOME(S) AND MEASURE(S): The main outcome was the association between demographic characteristics (e.g., age, sex, race/ethnicity) and systemic factors including diabetes status, hypertension, and tobacco use on the incidence of CE and the subsequent need for corneal transplantation following cataract surgery. RESULTS: Among 187,746 beneficiaries, 67,734 had diabetes and 120,012 did not. Beneficiaries with diabetes were more likely to develop CE compared to those without (Odds ratio [OR] 1.19, 95% Confidence Interval [CI] [1.02-1.40]). Compared to those aged 65-74, beneficiaries aged 75-84 and over 85 were more likely to develop CE (OR 1.29 [1.09-1.52]) and OR 1.96 [1.55-2.46], respectively). Asian (OR 2.42 [1.66-3.40]), Hispanic (OR 2.60 [1.73-3.74]), and North American Native (OR 3.59 [1.78-6.39]) race was associated with increased likelihood of developing CE. North American Native beneficiaries had higher risk of requiring corneal transplantation compared to White beneficiaries (OR 9.30 [2.26-25.31]). Female sex decreased likelihood of requiring corneal transplantation post-operatively (OR 0.56 [0.36-0.87]). Amongst those with diabetes, the presence of proliferative diabetic retinopathy increased the likelihood of developing CE (OR 1.94 [1.05-3.39]). CONCLUSION: Older age, diabetes, and non-White race elevate the risk of CE following cataract surgery, with race incurring the highest risk. Further research is needed to understand the factors underlying the significantly increased risk of CE in racial and ethnic minorities within the United States.

Ocular toxicities of fibroblast growth factor receptor inhibitors: A review.

Fibroblast growth factor receptor (FGFR) inhibitors are an emerging class of small molecule targeted cancer drugs with promising therapeutic possibilities for a wide variety of malignancies. While ocular adverse events from FGFR inhibitors are reported in clinical trials, subsequent case studies continue to reveal new toxicities. Disease pathology affecting multiple parts of the eye has been reported, but the ocular surface and the retina are the most commonly encountered areas affected by FGFR inhibitors, manifesting as dry eye and FGFR inhibitor-associated retinopathy, respectively. Corneal thinning and melt is a rare but serious and potentially vision-threatening complication of FGFR inhibitor toxicity. Similarities between toxicities observed from other targeted cancer therapy drugs and FGFR inhibitors may help us understand underlying pathophysiological changes. The management of these adverse events requires close ophthalmologic follow-up and may require discontinuation of the offending agents in some cases.

Demographic and Psychiatric Associations With Dry Eye in a Medicare Population.

PURPOSE: The purpose of this study was to investigate the impact of demographic characteristics and psychiatric comorbidity on the prevalence of dry eye disease in the American geriatric population. METHODS: Data were collected from a 2011 nationwide sample of Medicare beneficiaries aged 65 years and older (N = 1,321,000). Age, sex, race/ethnicity, residential area, climate region, and income, along with psychiatric comorbidities including depression and anxiety, were collected. Multivariable logistic regression models were used to assess the relationship between demographic and psychiatric factors and the prevalence of dry eye disease. RESULTS: Among 21,059 patients with clinically significant dry eye, women had higher odds of having dry eye compared with men [odds ratio (OR) 2.03, 95% confidence interval (1.97-2.10)]. Asian and Native American patients had increased odds of having dry eye compared with White patients [OR 1.85 (1.69-2.02) and OR 1.51 (1.19-1.93)], while Black patients were less likely to have dry eye [OR 0.83 (0.79-0.87)]. Patients aged 75 to 84 years and 85+ were more likely to have dry eye compared with those aged 65 to 74 years [OR 1.49 (0.45-1.53) and OR 1.54 (1.48-1.60)]. Having both depression and anxiety were associated with higher odds of having dry eye [OR 2.38 (2.22-2.55)] compared with having depression alone [OR 1.95 (1.86-2.04)] or anxiety alone [OR 2.22 (2.10-2.35)]. CONCLUSIONS: Significant racial and regional disparities in dry eye prevalence were found. Psychiatric association with dry eye varied with age, sex, race, and residence region. Further research is needed to comprehend the underlying mechanisms, implications, and to address disparities in the diagnosis and management of dry eye.

Association Between Serum Vitamin D Levels and Myopia in the National Health and Nutrition Examination Survey (2001-2006).

PURPOSE: To assess the relationship between serum vitamin D levels and myopia in people aged 12-50 years using the National Health and Nutrition Examination Survey (NHANES) database. METHODS: Demographics, vision, and serum vitamin D levels from NHANES (2001-2006) were analyzed. Multivariate analyses were performed to examine the relationship between serum vitamin D levels and myopia while controlling for sex, age, ethnicity, education level, serum vitamin A, and poverty status. The main outcome was presence or absence of myopia, defined as a spherical equivalent of -1 diopters or more. RESULTS: Of the 11669 participants, 5,310 (45.5%) had myopia. The average serum vitamin D concentration was 61.6 ± 0.9 nmol/L for the myopic group and 63.1 ± 0.8 nmol/L for the non-myopic group (p = .01). After adjusting for all covariates, having higher serum vitamin D was associated with lower odds of having myopia (odds ratio 0.82 [0.74-0.92], p = .0007). In linear regression modeling that excluded hyperopes (spherical equivalent > +1 diopters), there was a positive relationship between spherical equivalent and serum vitamin D levels. Specifically, as serum vitamin D doubled, spherical equivalent increased by 0.17 (p = .02) indicating a positive dose-response relationship between vitamin D and myopia. CONCLUSIONS: Participants with myopia, on average, had lower serum concentrations of vitamin D compared to those without myopia. While further studies are needed to determine the mechanism, this study suggests that higher vitamin D levels are associated with lower incidence of myopia.

Depression in Individuals With Diabetic Retinopathy in the US National Health and Nutrition Examination Survey, 2005-2008.

PURPOSE: To examine the relationship between diabetic retinopathy (DR) and depression in the United States. DESIGN: Retrospective, cross-sectional study. METHODS: National Health and Nutrition Examination Survey (NHANES) participants between 2005 and 2008 (ages 40-85 years) were included. Prevalence of major depression among DR stages as determined by retinal imaging was estimated. Multivariable models assessed associations between depression and DR. RESULTS: Depression was more common in those with moderate to severe DR (16%) than in those with no DR (7%), mild nonproliferative diabetic retinopathy (NPDR, 6%), or proliferative DR (5%). In a model with DR stages that adjusted for demographic factors, there was an association between moderate to severe DR and depression (odds ratio [OR], 2.46, 95% CI, 1.03-5.85). CONCLUSIONS: Depression was more prevalent in those with moderate to severe NPDR than in those with no DR, mild NPDR, or proliferative DR. This relationship is statistically significant after adjustment for demographic factors.

Anthropometric Measures and Their Relationship to Steep Cornea in the United States Population.

PURPOSE: The aim of this study was to determine the relationship between anthropometric measures and steep cornea. METHODS: Participants from the 1999 to 2008 US National Health and Nutrition Examination Survey visual examination were included (20,165 subjects). Cases had a mean dioptric power, averaged across the meridians, ≥ 48.0 diopters (n = 171). Separate multivariable models assessed body mass index, height, and weight in relation to steep cornea. Analyses included both overall and sex-stratified populations. RESULTS: A relationship between BMI and steep cornea in the overall population was not detected ( P for trend = 0.78). There was a strong inverse relationship between height (adjusted for weight) and steep cornea in the overall population ( P for trend <0.0001) and in women ( P for trend <0.0001). For every 1-inch increase in height, there was a 16% reduced odds of steep cornea in the overall population (OR, 0.84; 95% CI: 0.77-0.92). A relationship between weight and steep cornea was not detected in the overall population (P for trend = 0.79). CONCLUSIONS: Greater height was associated with a lower risk of steep cornea.

National trends in surgical subspecialisation in ophthalmology in the USA.

BACKGROUND/AIMS: To assess surgical patterns in ophthalmology by subspecialty in the USA. METHODS: Ophthalmic surgeons were categorised as comprehensive/subspecialist based on billed procedures in the 2017-2018 Medicare Provider Utilization and Payment Data. Poisson regression models assessed factors associated with physicians performing surgeries in the core domain (eg, cataract extractions) and subspecialty domain. Models were adjusted for provider gender, time since graduation, geographical region, practice setting and hospital affiliation. RESULTS: There were 10 346 ophthalmic surgeons, 74.7% comprehensive and 25.3% subspecialists. Cataract extractions were performed by 6.0%, 9.9%, 21.0%, 88.1% and 95.3% of specialists in surgical retina, neuro-ophthalmology/paediatrics, oculoplastics, glaucoma and cornea, respectively. Retina specialists were more likely to perform cataract surgery if they were 20-30 or>30 years in practice (relative risk: 2.20 (95% CI: 1.17 to 4.12) and 3.74 (95% CI: 1.80 to 7.76), respectively) or in a non-metropolitan setting (3.78 (95% CI: 1.71 to 8.38)). Among oculoplastics specialists, male surgeons (2.71 (95% CI: 1.36 to 5.42)), those in practice 10-20 years or 20-30 years (1.93 (95% CI: 1.15 to 3.26) and 1.91 (95% CI: 1.11 to 3.27), respectively) and in non-metropolitan settings (3.07 (95% CI: 1.88 to 5.02)) were more likely to perform cataract surgery. Only 26 of the 2620 subspecialists performed surgeries in two or more subspecialty domains. CONCLUSIONS: There is a trend towards surgical subspecialisation in ophthalmology in the USA whereby some surgeons focus their surgical practice on subspecialty procedures and rarely perform surgeries in the core domain.

Genetic Correlations Among Corneal Biophysical Parameters and Anthropometric Traits.

Purpose: The genetic architecture of corneal dysfunction remains poorly understood. Epidemiological and clinical evidence suggests a relationship between corneal structural features and anthropometric measures. We used global and local genetic similarity analysis to identify genomic features that may underlie structural corneal dysfunction. Methods: We assembled genome-wide association study summary statistics for corneal features (central corneal thickness, corneal hysteresis [CH], corneal resistance factor [CRF], and the 3 mm index of keratometry) and anthropometric traits (body mass index, weight, and height) in Europeans. We calculated global genetic correlations (rg) between traits using linkage disequilibrium (LD) score regression and local genetic covariance using ρ-HESS, which partitions the genome and performs regression with LD regions. Finally, we identified genes located within regions of significant genetic covariance and analyzed patterns of tissue expression and pathway enrichment. Results: Global LD score regression revealed significant negative correlations between height and both CH (rg = -0.12; P = 2.0 × 10-7) and CRF (rg = -0.11; P = 6.9 × 10-7). Local analysis revealed 68 genomic regions exhibiting significant local genetic covariance between CRF and height, containing 2874 unique genes. Pathway analysis of genes in regions with significant local rg revealed enrichment among signaling pathways with known keratoconus associations, including cadherin and Wnt signaling, as well as enrichment of genes modulated by copper and zinc ions. Conclusions: Corneal biophysical parameters and height share a common genomic architecture, which may facilitate identification of disease-associated genes and therapies for corneal ectasias. Translational Relevance: Local genetic covariance analysis enables the identification of associated genes and therapeutic targets for corneal ectatic disease.

TFOS Lifestyle: Impact of nutrition on the ocular surface.

Nutrients, required by human bodies to perform life-sustaining functions, are obtained from the diet. They are broadly classified into macronutrients (carbohydrates, lipids, and proteins), micronutrients (vitamins and minerals) and water. All nutrients serve as a source of energy, provide structural support to the body and/or regulate the chemical processes of the body. Food and drinks also consist of non-nutrients that may be beneficial (e.g., antioxidants) or harmful (e.g., dyes or preservatives added to processed foods) to the body and the ocular surface. There is also a complex interplay between systemic disorders and an individual's nutritional status. Changes in the gut microbiome may lead to alterations at the ocular surface. Poor nutrition may exacerbate select systemic conditions. Similarly, certain systemic conditions may affect the uptake, processing and distribution of nutrients by the body. These disorders may lead to deficiencies in micro- and macro-nutrients that are important in maintaining ocular surface health. Medications used to treat these conditions may also cause ocular surface changes. The prevalence of nutrition-related chronic diseases is climbing worldwide. This report sought to review the evidence supporting the impact of nutrition on the ocular surface, either directly or as a consequence of the chronic diseases that result. To address a key question, a systematic review investigated the effects of intentional food restriction on ocular surface health; of the 25 included studies, most investigated Ramadan fasting (56%), followed by bariatric surgery (16%), anorexia nervosa (16%), but none were judged to be of high quality, with no randomized-controlled trials.

Outcome Measures to Assess Dry Eye Severity: A Review.

Outcome measures used to assess efficacy of dry eye therapeutics have not been consistently applied in clinical settings, nor have they been shown to correlate with functional outcomes. We propose that corneal staining, a clinically meaningful dry eye parameter, should be used as a standard objective outcome measure across all clinical trials evaluating dry eye treatments. We justify this based on evidence regarding its relationship to vision and vision related quality-of-life. In addition, corneal staining has been shown to correlate with ocular surface inflammation, a well elucidated aspect of dry eye pathophysiology and an active area in therapeutics research. No one outcome measure explored herein correlates perfectly to this heterogenous disease. However, there is mounting evidence showing the correlation between corneal staining and functional visual indices. We hope that future clinical trials will standardize corneal staining as a measure to determine the efficacy of interventions and justify their clinical utility.

Glaucoma and Ocular Surface Disease: More than Meets the Eye.

Understanding the association between ocular surface disease and glaucoma is important for improving adherence to treatment and introducing practical solutions. While topical antihypertensive medications for glaucoma are well tolerated according to short-term studies, there is little evidence on their long-term effects. Since they are often required for many years, the effects of these drops on the ocular surface become important in regard to quality of life and adherence. In this nonsystematic review performed in April 2022, we summarize what is known about the relationship between glaucoma and ocular surface disease. Specifically, we examine how each class of topical glaucoma drops affects the ocular surface. We then review the treatment of ocular surface disease for patients on topical glaucoma therapy. Finally, we discuss treatments that may reduce or eliminate the burden of topical medications.