Risk Factors for Bacterial Keratitis and Severe Disease in Hydrogel Contact Lens Users: A Multicenter Case-Control Study and Case-Only Analysis.

PURPOSE: To assess risk factors for contact lens (CL)-related bacterial keratitis, cases and high-risk controls were enrolled. Using high-risk controls can help elucidate whether certain CL types or modalities are attributable to disease burden if risky wear patterns are similar between the cases and controls. This analysis identified whether such CL factors were associated with the occurrence of bacterial keratitis. In addition, a case-only analysis determined CL factors associated with severe disease. METHODS: From 2018 to 2021, 158 controls were enrolled at University Hospitals of Cleveland Eye Institute, and 153 bacterial keratitis cases were enrolled across 14 sites in the United States. Cases were soft CL wearers with either culture-proven bacterial keratitis or a corneal infiltrate with an overlying epithelial defect within the central 4 mm of the cornea, uveitis, or significant pain. Fungal, protozoan, or nonsoft CL wear-related microbial keratitis cases were excluded. Controls were recruited from high-risk CL wearers with no history of disease. All participants completed a questionnaire related to demographics, type of CL used, wearing schedule, lens handling practices, and storage case handling. Cases with ulcer/infiltrate size ≥2 mm in size, presence of hypopyon, or had fortified antibiotics prescribed were classified as severe keratitis. Univariate and multivariable logistic regression was used to assess association of CL variables with the occurrence of bacterial keratitis as well as occurrence of severe disease among the cases only. RESULTS: Compared with the control cohort, cases were older (mean age 45.6 vs. 38.9 years), had more males (42.5% vs. 23.6%), and had more current or former smokers (41.7% vs. 12.9%). There were no significant associations between CL material (silicone hydrogel vs. not) or CL type (daily disposable vs. reusable) and occurrence of bacterial keratitis. More than two-thirds (67.3%) of cases were classified as severe. Among cases only, univariate analyses found current smokers to have increased risk of severe disease (OR=2.87; 95% CI 1.13-7.26, P=0.03). Adjusting for age, sex, and smoking among the cases only, daily disposable lenses were protective against severe disease (OR=0.32; 95% CI 0.11-0.89, P=0.03). Reusable lenses increased risk of severe microbial keratitis between 3.0- and 4.4-fold compared with compliant daily disposability. DISCUSSION/CONCLUSION: Compared with a high-risk control cohort, no specific lens factors were associated with occurrence of CL-associated bacterial keratitis. Among cases only, current smokers and patients wearing reusable lenses are at increased risk of severe keratitis. Daily disposable lenses were protective even when noncompliance to daily disposability was considered.

Outcomes and Readmission in Patients With Retinal Artery Occlusion (from the Nationwide Readmission Database).

Retinal artery occlusion (RAO) is an ophthalmologic emergency, leading to sudden vision loss. Understanding its risk factors and garnering information on the incidence of adverse events can provide helpful information on the cost-effective evaluation of patients and secondary prevention. In this retrospective cohort study, we used the Nationwide Readmission Database from 2016 to 2018 and queried the database to identify patients with RAO. The clinical outcomes were cumulative incidence of myocardial infarction (MI), stroke, death (in-hospital and 6 months after discharge), resource utilization, all-cause readmission at 6 months, and reasons for all-cause readmission. We identified a total of 14,527 patients with RAO. The mean age of patients with RAO was 69 ± 13 years. Hypertension (11,839, 82%), hyperlipidemia (8,868, 61%), ischemic cardiomyopathy (4,826, 33%), smoking (4,772, 33%), and diabetes (4,588, 32%) were common co-morbidities in patients with RAO. Of 14,527 patients with RAO, 308 patients (2.1%) died, 1,577 (10.9%) developed stroke, and 615 (4.2%) developed MI within 6 months. A total of 2,841 patients (24.9%) were readmitted within 6 months of discharge. Carotid artery stenosis (386, 10.8%) was the most common cause of readmission. History of stroke or transient ischemic attack and Elixhauser co-morbidity index ≥3 were predictors of stroke. Female gender, ischemic cardiomyopathy, carotid artery disease, heart failure, chronic kidney disease, and cancer were predictors of MI. Cancer, chronic kidney disease, Elixhauser co-morbidity index ≥3, Medicare/Medicaid payer status, nonelective index admission, atrial fibrillation, and carotid artery disease were predictors of 6-month all-cause readmission. In conclusion, patients with RAO have a significant burden of co-morbidities, death, stroke, MI, and readmission. RAO may be used as a clinical marker of future stroke and MI, and should trigger screening for acute vascular ischemic events.

Vasoactive Intestinal Peptide Promotes Corneal Allograft Survival.

Corneal transplantation is the most prevalent form of tissue transplantation. The success of corneal transplantation mainly relies on the integrity of corneal endothelial cells (CEnCs), which maintain graft transparency. CEnC density decreases significantly after corneal transplantation even in the absence of graft rejection. To date, different strategies have been used to enhance CEnC survival. The neuropeptide vasoactive intestinal peptide (VIP) improves CEnC integrity during donor cornea tissue storage and protects CEnCs against oxidative stress-induced apoptosis. However, little is known about the effect of exogenous administration of VIP on corneal transplant outcomes. We found that VIP significantly accelerates endothelial wound closure and suppresses interferon-γ- and tumor necrosis factor-α-induced CEnC apoptosis in vitro in a dose-dependent manner. In addition, we found that intracameral administration of VIP to mice undergoing syngeneic corneal transplantation with endothelial injury increases CEnC density and decreases graft opacity scores. Finally, using a mouse model of allogeneic corneal transplantation, we found for the first time that treatment with VIP significantly suppresses posttransplantation CEnC loss and improves corneal allograft survival.

Hepatocyte Growth Factor Suppresses Inflammation and Promotes Epithelium Repair in Corneal Injury.

Corneal injuries are among the major causes of ocular morbidity and vision impairment. Optimal epithelial wound healing is critical for the integrity and transparency of the cornea after injury. Hepatocyte growth factor (HGF) is a mitogen and motility factor that primarily regulates epithelial cell function. Herein, we investigate the effect of HGF on proliferation of corneal epithelial cells (CECs) in inflamed conditions both in vitro and in vivo. We demonstrate that HGF not only promotes CEC proliferation in homeostatic conditions but also reverses the anti-proliferative effect of the inflammatory environment on these cells. Furthermore, using a mouse model of ocular injury, we show that HGF treatment suppresses ocular inflammation and actively augments CEC proliferation, leading to improved and accelerated corneal epithelial repair. These findings have potential translational implications and could provide a framework for the development of novel HGF-based therapies for corneal epithelial defects.

Overview of Coronary Heart Disease Risk Initiatives in South Asia.

PURPOSE OF REVIEW: Cardiovascular disease (CVD) is now the leading cause of morbidity and mortality worldwide. Industrialization and economic growth have led to an unprecedented increment in the burden of CVD and their risk factors in less industrialized regions of the world. While there are abundant data on CVD and their risk factors from longitudinal cohort studies done in the West, good-quality data from South Asia are lacking. RECENT FINDINGS: Several multi-institutional, observational, prospective registries, and epidemiologic cohorts in South Asia have been established to systematically evaluate the burden of CVD and their risk factors. The PINNACLE (Practice Innovation and Clinical Excellence) India Quality Improvement Program (PIQIP), the Kerala Acute Coronary Syndrome (ACS), and Trivandrum Heart Failure registries have focused on secondary prevention of CVD and performance measurement in both outpatient and inpatient settings, respectively. The Prospective Urban and Rural Epidemiology (PURE), Centre for Cardiometabolic Risk Reduction in South Asia (CARRS), and other epidemiologic and genetic studies have focused on primary prevention of CVD and evaluated variables such as environment, smoking, physical activity, health systems, food and nutrition policy, dietary consumption patterns, socioeconomic factors, and healthy neighborhoods. The international cardiovascular community has been responsive to a burgeoning cardiovascular disease burden in South Asia. Several collaborations have formed between the West (North America in particular) and South Asia to catalyze evidence-based and data-driven changes in the federal health policy in this part of the world to promote cardiovascular health and mitigate cardiovascular risk.

In Vivo Confocal Microscopy in Dry Eye Disease Associated With Chronic Graft-Versus-Host Disease.

PURPOSE: To compare densities of corneal epithelial dendritic cells (DCs), corneal subbasal nerves, and conjunctival epithelial immune cells (EICs) between patients with dry eye disease (DED) with and without graft-versus-host disease (GVHD) using in vivo confocal microscopy (IVCM). METHODS: This study included 54 patients who had moderate to severe DED either associated with (n = 33) or without (n = 21) chronic GVHD. In addition to evaluating clinical parameters of DED, images obtained by laser-scanning IVCM of the central cornea and superior tarsal conjunctiva were analyzed to measure densities of corneal epithelial DCs, corneal subbasal nerves, and conjunctival EICs. RESULTS: Although there were no significant differences between GVHD and non-GVHD groups in symptom scores, the GVHD group had significantly worse corneal fluorescein staining, tear break-up time, and Schirmer's scores than the non-GVHD group. Corneal epithelial DC density, corneal subbasal nerve density, and conjunctival EIC density were 148 ± 135 cells/mm2, 16.3 ± 6.1 mm/mm2, and 670 ± 267 cells/mm2, respectively, in the GVHD group; and 122 ± 99 cells/mm2, 18.3 ± 5.1 mm/mm2, and 572 ± 271 cells/mm2, respectively, in the non-GVHD group. After adjusting for clinical parameters, including the DED severity, none of the IVCM parameters was significantly different between the GVHD versus non-GVHD groups (P = 0.82, P = 0.21, and P = 0.60, respectively). CONCLUSIONS: In GVHD-associated DED, cellular changes in the cornea and conjunctiva observed by IVCM were similar to those seen in patients who have non-GVHD dry eye with the same level of disease severity. Therefore, corneal and conjunctival IVCM findings in GVHD-associated DED are possibly reflective of the local disease (DED) severity rather than the underlying systemic disease process.

Human Platelet Lysate as a Replacement for Fetal Bovine Serum in Limbal Stem Cell Therapy.

PURPOSE: To evaluate the use of human platelet lysate (HPL) as an alternative supplement for limbal explant culture. METHODS: Culture media were prepared using either 10% pooled HPL (PHPL), single donor HPL, or fetal bovine serum (FBS). Limbal tissues, obtained from the Minnesota Lions Eye Bank, were cultured in each medium on plastic plates or on denuded amniotic membrane (AM). Immunofluorescence staining was performed for ABCG2, tumor protein p63α, and cytokeratin 3 (K3). Quantitative reverse transcriptase polymerase chain reaction (qRT-PCR) was used to evaluate the expression of ABCG2 and p63. Limbal explants grown in each medium were labeled with bromodeoxyuridine (BrdU) to assess the proliferative capacity in each medium. Concentration of growth factors including epidermal growth factor (EGF), vascular endothelial growth factor (VEGF), transforming growth factor-ß (TGF-ß), and platelet derived growth factor (PDGF) in HPL and PHPL was compared to that in human serum (HS). RESULTS: Immunofluorescence staining on AM showed prominent expression of ABCG2, p63α but sparse expression of K3 in HPL and PHPL supplemented medium. Real time-PCR showed 1.7 fold higher expression of ABCG2 in PHPL supplemented medium (p = 0.03), and similar expression of p63 in HPL and PHPL supplemented medium compared to FBS medium. The proliferation assay showed that LSCs retained their proliferative potential in HPL supplemented medium. Higher concentration of growth factors were found in HPL, compared to HS. CONCLUSIONS: Human platelet lysate has higher concentration of grown factors and is effective in maintaining growth and stem cell phenotype of corneal limbal explant cultures.

Collagen cross-linking in keratoconus in Asian eyes: visual, refractive and confocal microscopy outcomes in a prospective randomized controlled trial.

To evaluate the safety and efficacy of collagen cross-linking (CXL) in the treatment of keratoconus. A prospective randomized sham-controlled clinical trial was undertaken and 43 eyes with moderate to severe keratoconus were randomized into two groups that is the treatment (n = 23) and the sham (n = 20) group. CXL was performed with riboflavin (0.1 in 20 % dextran) followed by UVA radiation (365 nm, 3 mW/cm(2), 30 min). In the sham group, only riboflavin was administered without UVA radiation. Uncorrected distance visual acuity (UDVA), corrected distance visual acuity, intraocular pressure, corneal thickness, keratometry, endothelial count, confocal microscopy were evaluated at baseline and at 1 week, 1, 3, and 6 months. In cases where CXL was done, UDVA improved by mean 0.11 ± 0.06 logMAR units at 6 months (P = 0.01). The refractive cylinder and spherical equivalent decreased by mean of 0.62 D (P = 0.01) and 0.5 D (P = 0.19), respectively. Ultrasonic central corneal thickness decreased by mean 22.7 ± 10.3 µm (P = 0.01). The maximum and minimum keratometry decreased by mean of 1.2 ± 0.8 D (P = 0.01) and 0.83 ± 1.2 D (P = 0.39), respectively. The specular count and intraocular pressure did not show any significant change. In the sham group, no significant change was observed in any parameter. Confocal analysis showed that the epithelial healing was complete at 1 week after crosslinking. The sub-epithelial plexus showed loss of nerve plexus at 1 month, regeneration of nerve fibers which started at 3 months and was complete at 6 months. The anterior stroma showed loss of keratocytes with honeycomb oedema and apoptotic bodies till 3 months. The regeneration of keratocytes started at 3 months and was complete at 6 months of follow-up. Collagen cross-linking is an effective procedure to halt progression in keratoconus. The confocal microscopic changes correlate with the outcomes in the treatment and the sham groups.

Primary intraventricular central nervous system lymphoma in an immunocompetent patient.

We report a young 15-year-old boy with 6 months history of headache, vomiting, and seizure. He underwent septostomy followed by right ventriculoperitoneal shunt for obstructive hydrocephalus and was managed with empirical antituberculosis treatment. Magnetic resonance imaging (MRI) revealed solid, nodular, enhancing masses in bilateral lateral ventricles and 4(th) ventricle. Surgical biopsy from 4(th) ventricular lesion confirmed a B-cell lymphoma. Staging evaluation with MRI positron emission tomography and bone marrow biopsy were normal suggesting an intraventricular primary central nervous system lymphoma.

Comparative evaluation of dual Scheimpflug imaging parameters in keratoconus, early keratoconus, and normal eyes.

PURPOSE: To determine the efficacy of various parameters measured by dual Scheimpflug imaging technology in differentiating eyes with keratoconus or early keratoconus from normal eyes. SETTING: Cornea Service, Wills Eye Institute, Philadelphia, Pennsylvania, USA. DESIGN: Comparative case series. METHODS: A retrospective evaluation was performed of the parameters provided by the Galilei dual Scheimpflug analyzer in keratoconus, early keratoconus, and normal eyes. Logistic regression and receiver operating characteristic curve analysis were used to compare the mean values and to calculate the sensitivity and specificity of these parameters. RESULTS: Many parameters were statistically significantly different between keratoconus and normal eyes compared with early keratoconus eyes (P<.05). Total cornea power-steep and posterior curvature-steep keratometry had the highest area under the curve (AUC) score (0.99) for differentiating keratoconus eyes from normal eyes. All anterior curvature parameters were statistically significant in differentiating keratoconus eyes from normal eyes, whereas only the anterior curvature-steep was statistically significant in differentiating early keratoconus eyes from normal eyes. The central pachymetry and thinnest pachymetry were statistically significant in differentiating keratoconus and early keratoconus eyes from normal eyes. Third-order root mean square (RMS) and total RMS had the highest AUC scores (0.83 and 0.82, respectively) for differentiating early keratoconus eyes from normal eyes. CONCLUSION: Total corneal power, anterior curvature, posterior curvature, pachymetry, and corneal aberration data generated from the dual Scheimpflug analyzer showed promising results in differentiating keratoconus and early keratoconus eyes from normal eyes. FINANCIAL DISCLOSURE: No author has a financial or proprietary interest in any material or method mentioned.

Young girl with abnormal behavior: Anti-N-Methyl-D-Aspartate receptor immune encephalitis.

Anti N Methyl D Aspartate receptor immune encephalitis (Anti NMDARE) is a recently defined, under-recognized and often misdiagnosed disease, which typically occurs in young females and may be associated with an underlying tumor, usually ovarian teratoma. If diagnosed early, initiation of immunotherapy and tumor removal (if present) may result in recovery. We report a case of a 17 years old girl with Anti NMDARE who was initially misdiagnosed as Functional psychosis, Neuroleptic Malignant Syndrome and Sepsis syndrome. To the best of our knowledge, this is only the second case of anti NMDARE being reported from India. This case report underscores the need for a greater awareness of this entity across multiple specialties, e.g., general medicine, psychiatry and neurology, to ensure a heightened diagnostic suspicion, which can lead to timely diagnosis and adequate therapy of this treatable disease.

Indications and outcomes of corneal transplantation in geriatric patients.

PURPOSE: To identify the most common corneal transplant procedures, indications, coexisting ocular diseases, and outcomes in elderly patients, and to compare younger geriatric patients with super-geriatric patients. DESIGN: Retrospective case series. METHODS: Data of all patients 65 years old and older who underwent corneal transplantation at Wills Eye Institute from April 2007 to January 2013, and were followed up for at least 1 year, were collected. Two hundred seventy-one eyes of 253 patients were divided into 2 groups according to the age of the patient. RESULTS: Group I (65-79 years old) included 181 eyes and Group II (80 years and older) included 90 eyes. The most common indication was Fuchs endothelial dystrophy, with 78 eyes (43%) in Group I and 34 eyes (38%) in Group II. In Group I, 93 Descemet stripping endothelial keratoplasty (DSEK) (51%), 84 penetrating keratoplasty (PK) (46%), and 4 keratoprosthesis procedures(2%) were performed; in Group II, 37 DSEK (41%), 51 PK (57%), and 2 keratoprosthesis procedures (2%) were performed. Graft survival rate at last visit was 90% for Group I and 88% for Group II. Rejection occurred in 18 Group I eyes (10%) and 7 Group II eyes (8%) (P = .562). CONCLUSION: Endothelial abnormalities were more common indications and keratoconus was a less common indication for surgery in the elderly. Fuchs dystrophy was the leading indication for surgery in both super-geriatric and younger geriatric patients. Graft survival rate was slightly higher in the younger geriatric age group but was not statistically significant. In the elderly, there is an increased prevalence of both glaucoma and retinal diseases that can affect the visual outcomes after corneal transplantation.

Corneal collagen cross-linking: ectasia and beyond.

PURPOSE OF REVIEW: Corneal collagen cross-linking has recently emerged as a novel approach for management of ectasia. This article reviews the literature published in the past 3 years about the expanding spectrum of cross-linking as a therapeutic modality and its complications. RECENT FINDINGS: Recent studies have confirmed the beneficial effects of cross-linking in stabilization and to a lesser extent, regression of keratoconus and postrefractive surgery ectasia. Other applications include cross-linking as a combined procedure with intracorneal ring segments, and photorefractive keratectomy for ectasia, corneal edema, and infectious keratitis. Animal studies of chemical cross-linking of sclera as a potential treatment for progressive myopia have also been performed. Various modifications of the technique to increase the safety profile of cross-linking have been reported, including the use of hypoosmolar riboflavin, transepithelial cross-linking, customized epithelial debridement, and higher fluence shorter duration ultraviolet A light exposure. Reported complications include keratitis, corneal haze, endothelial cell loss and failure of treatment. SUMMARY: Cross-linking has been shown to be an effective modality for corneal ectasia, the regression being less in patients with postrefractive ectasia than keratoconus. In a few studies, it has been found to be effective in symptomatic improvement of bullous keratopathy, and infectious keratitis but further studies are required. Cross-linking with epithelial debridement is found to be most effective but various modifications are being investigated for an improved, and better safety outcome.