Topical losartan inhibits corneal scarring fibrosis and collagen type IV deposition after Descemet's membrane-endothelial excision in rabbits.

The purpose of this study was to examine the effect of topical and/or oral angiotensin converting enzyme II inhibitor and TGF-beta signaling blocker losartan on corneal stromal fibrosis that developed in rabbit corneas after Descemetorhexis removal of central Descemet's membrane and corneal endothelium. Twenty-eight New Zealand white rabbits were included and either had 8 mm central Descemetorhexis or sham control surgery without Descemetorhexis in one eye. Groups of 4 eyes without Descemetorhexis were treated for one month with no medications, topical losartan or oral losartan. Groups of 4 eyes with Descemetorhexis were treated with topical and oral vehicle, topical losartan, oral losartan, or both topical losartan and oral losartan for one month. Standardized slit lamp photos were obtained with central opacity intensity measured with ImageJ. The posterior fibrotic zone of corneas was measured on immunohistochemistry for alpha-smooth muscle actin (SMA) and keratocan using QuPath analysis. Collagen type IV expression in the posterior cornea was quantitated with ImageJ and duplex immunohistochemistry for collagen type IV and TGF beta-1. After Descemetorhexis, topical, but not oral, losartan decreased the intensity of central stromal opacity, reduced peripheral corneal scarring, and decreased alpha-smooth muscle actin myofibroblast fibrosis area compared to corneas that had Descemetorhexis and treatment with vehicles alone. Topical losartan decreased posterior stromal cellular, non-Descemet's membrane, collagen type IV production, that is likely stimulated by TGF beta as part of a negative regulatory feedback mechanism, compared to vehicle treatment at one month after Descemetorhexis. Topical losartan is likely to be effective in reducing corneal scarring fibrosis produced by traumatic injury, microbial infection, and some corneal diseases and surgeries.

Open-Source Automated Segmentation of Neuronal Structures in Corneal Confocal Microscopy Images of the Subbasal Nerve Plexus With Accuracy on Par With Human Segmentation.

PURPOSE: The aim of this study was to perform automated segmentation of corneal nerves and other structures in corneal confocal microscopy (CCM) images of the subbasal nerve plexus (SNP) in eyes with ocular surface diseases (OSDs). METHODS: A deep learning-based 2-stage algorithm was designed to perform segmentation of SNP features. In the first stage, to address applanation artifacts, a generative adversarial network-enabled deep network was constructed to identify 3 neighboring corneal layers on each CCM image: epithelium, SNP, and stroma. This network was trained/validated on 470 images of each layer from 73 individuals. The segmented SNP regions were further classified in the second stage by another deep network as follows: background, nerve, neuroma, and immune cells. Twenty-one-fold cross-validation was used to assess the performance of the overall algorithm on a separate data set of 207 manually segmented SNP images from 43 patients with OSD. RESULTS: For the background, nerve, neuroma, and immune cell classes, the Dice similarity coefficients of the proposed automatic method were 0.992, 0.814, 0.748, and 0.736, respectively. The performance metrics for automatic segmentations were statistically better or equal as compared to human segmentation. In addition, the resulting clinical metrics had good to excellent intraclass correlation coefficients between automatic and human segmentations. CONCLUSIONS: The proposed automatic method can reliably segment potential CCM biomarkers of OSD onset and progression with accuracy on par with human gradings in real clinical data, which frequently exhibited image acquisition artifacts. To facilitate future studies on OSD, we made our data set and algorithms freely available online as an open-source software package.

Acute corneal edema decades after penetrating keratoplasty for keratoconus in eyes wearing scleral contact lenses.

PURPOSE: To report three cases of acute corneal edema occurring decades after penetrating keratoplasty (PK) for keratoconus in eyes wearing scleral contact lenses (ScCLs) with previously clear corneal grafts. METHODS: Retrospective chart review of three ScCL wearers presenting for sudden onset pain and blurred vision. Data extracted included clinical presentation, year and reason for PK, ocular medications and comorbidities, contact lens wearing history, results of any ancillary testing available including corneal topography, anterior segment optical coherence tomography (OCT), and specular microscopy surrounding the event, treatment and outcomes of intervention. The number of PK eyes fit with ScCLs in the author's practice was determined to estimate the prevalence of this event. RESULTS: The three patients each had a longstanding PK for keratoconus performed between 33-35 years prior to presentation and recurrent ectasia. Each patient presented with an acute, painful eye and reduced vision either 3 days, 4 months or 9 years after refitting into ScCLs. Each eye had well demarcated focal microcystic epithelial and stromal edema within the graft and crossing the wound margin onto the host cornea. Although a definitive break or detachment of Descemet's membrane was not visualized, the presentations suggest these were episodes of acute hydrops. CONCLUSIONS: Longstanding PKs with recurrent ectasia and acute focal edema suggestive of corneal hydrops is demonstrated in this case series of ScCL wearers. Although similar events have occurred as part of the natural history of post-PK corneas for keratoconus, the proximity of ScCL refitting to two of the events suggests some association.

Analysis of Falls Efficacy Scale and Vulnerable Elders Survey as Predictors of Falls.

Introduction Falls are the leading cause of injury-related death among older adults according to the Centers for Disease Control and Prevention (CDC). The Falls Efficacy Scale (FES) and Vulnerable Elder Survey (VES-13) are validated screening tools used to assess concern of falling, health deterioration and functional decline. We set out to determine if the FES or VES-13 could serve as a predictor of falls among older adults in the Emergency Department (ED) setting. Methods This prospective pilot cohort study was conducted at a Level 1 Trauma Center. ED patients aged ≥65 were eligible for the study if they had a mechanical fall risk defined by CDC criteria. After consent and enrollment, FES and the VES surveys were completed. Participants were followed by phone quarterly, and results of the one-year follow-up self-report of fall history described.  Results There were 200 subjects enrolled and after excluding those that were withdrawn, deceased, or lost to follow-up, 184 were available for analysis of their follow-up visit at 12 months. A greater proportion of the participants were women (108 (58.7%) vs 76 (41.3%); P=0.88). The average age of the study participants was 74.2±7.3 years. There was no significant difference in age between men and women (median: 73 vs 73; p=0.47).  At the follow-up visit, 33 (17.9%) had a reported fall. The mean age did not significantly differ when comparing those with versus without a fall (75.6 vs 73.9; p=0.24). There was no significant difference in the proportion with a VES-13 ≥ 3 when comparing those with and without a reported fall (45.5% vs 37.8%; p = 0.41). The median FES score did not differ among those with as compared to without a fall (11 vs 10; p=0.12). Conclusions Subjects who had a VES-13 score of ≥3 were statistically no more likely to have fallen than those with a score of <3. Additionally, the FES score did not statistically differ when comparing those who had fallen to those who had not. Further research into alternative screening methods in the ED setting for fall risk is recommended.

The Efficacy of Topical HGF on Corneal Fibrosis and Epithelial Healing after Scar-Producing PRK Injury in Rabbits.

Purpose: To determine the effect of topical hepatocyte growth factor (HGF) on myofibroblast development and corneal opacity after fibrosis-producing photorefractive keratectomy (PRK). Methods: Twelve New Zealand rabbits had transepithelial PRK. Six rabbits received topical recombinant human HGF (rhHGF) (50 µL of 0.1 mg/mL) 3 times a day for 1 week beginning 6 hours prior surgery and until full closure of the epithelium, and 6 control rabbits received vehicle by the same schedule. Slit lamp photos were taken immediately and at 43 to 45 hours after surgery to determine the rate of epithelial healing. Slit lamp photographs and immunohistochemistry for α-smooth muscle actin were analyzed at 1 month in masked fashion. Results: The rhHGF group tended to have slower re-epithelization when compared with the controls, but no statistically significant difference was noted (P = 0.62). There was no significant difference in the density of myofibroblasts in the central stroma (P = 0.49) or corneal opacity (P = 0.84) between the HGF and control groups at 1 month after PRK. Conclusions: Topical rhHGF applied three times a day during the early postoperative period prior to epithelial closure did not significantly change the corneal epithelial healing rate, myofibroblast density, or opacity compared with vehicle after transepithelial -9.0 D PRK injury of the central cornea in rabbits. Translational Relevance: HGF has been reported to decrease myofibroblast generation and fibrosis in many organs, but topical HGF applied to the cornea until epithelial healing had no effect on scarring fibrosis in rabbit corneas.

Clinical and Demographic Parameters of Patients Treated Using a Sepsis Protocol.

PURPOSE: The purpose of this study was to investigate potential differences by sex in the demographic and clinical characteristics of patients treated utilizing a sepsis electronic bundle order set. Risk factors for in-hospital mortality were also assessed. METHODS: Data on patients in whom the sepsis order set was initiated in the emergency department over a 16-month period were entered into the hospital database. Data were analyzed for differences by sex in demographic and clinical factors, treatment modalities, and in-hospital mortality. The Bonferroni correction was applied to account for multiple comparisons; α was set at 0.006 for sex differences. FINDINGS: A total of 2204 patients were included. Male and female cohorts were similar with regard to a variety of demographic and clinical factors, including age, Emergency Severity Index (ESI) levels 1 and 2, time to disposition, appropriateness of antibiotics, and total fluids given by weight. The ESI is an assessment score ranging from 1 to 5 (1 is emergent). There were modest differences in the source of infection (genitourinary was 4% more common in women; P = 0.03) and mode of arrival (men were 4% more likely to arrive by ambulance; P = 0.03). These differences did not achieve our predefined α of 0.006 when the Bonferroni correction was applied. Factors associated with in-hospital mortality were advanced age, arrival by ambulance, and an ESI level of 1 or 2 (all, P < 0.01). IMPLICATIONS: Women were more likely to have a genitourinary cause of sepsis and less likely to arrive by ambulance. Risk factors of in-hospital mortality were older age, arrival by ambulance, and an ESI level of 1 or 2, but not sex.