Neuropathic Corneal Pain: Approaches for Management.

Neuropathic pain is caused by a primary lesion or dysfunction of the nervous system and can occur in the cornea. However, neuropathic corneal pain (NCP) is currently an ill-defined disease. Patients with NCP are extremely challenging to manage, and evidence-based clinical recommendations for the management of patients with NCP are scarce. The objectives of this review are to provide guidelines for diagnosis and treatment of patients with NCP and to summarize current evidence-based literature in this area. We performed a systematic literature search of all relevant publications between 1966 and 2017. Treatment recommendations are, in part, based on methodologically sound randomized controlled trials (RCTs), demonstrating superiority to placebo or relevant control treatments, and on the consistency of evidence, degree of efficacy, and safety. In addition, the recommendations include our own extensive experience in the management of these patients over the past decade. A comprehensive algorithm, based on clinical evaluation and complementary tests, is presented for diagnosis and subcategorization of patients with NCP. Recommended first-line topical treatments include neuroregenerative and anti-inflammatory agents, and first-line systemic pharmacotherapy includes tricyclic antidepressants and an anticonvulsant. Second-line oral treatments recommended include an opioid-antagonist and opiate analgesics. Complementary and alternative treatments, such as cardiovascular exercise, acupuncture, omega-3 fatty acid supplementation, and gluten-free diet, may have additional benefits, as do potential noninvasive and invasive procedures in recalcitrant cases. Medication selection should be tailored on an individual basis, considering side effects, comorbidities, and levels of peripheral and centralized pain. Nevertheless, there is an urgent need for long-term studies and RCTs assessing the efficacy of treatments for NCP.

Fungal Keratitis Secondary to Trametes betulina: A Case Report and Review of Literature.

PURPOSE: We report the first case of human infection and keratitis secondary to Trametes betulina, a rare filamentous fungus. METHODS: Clinical examination including external and slit-lamp examination and corneal scrapings with microbiologic evaluation were performed on a patient with chronic allergic conjunctivitis, entropion and a long-standing corneal ulcer resistant to treatment. RESULTS: The culture from the corneal scraping revealed a basidiomycetous fungus which was submitted for identification. DNA extraction with sequencing and analysis of the ITS and D1/D2 regions were performed on the isolate and demonstrated 100% similarity to Lenzites betulina/Trametes betulina. Susceptibility testing demonstrated potent in vitro activity of voriconazole (MIC < 0.03 µg/ml). The patient was treated with voriconazole, and the corneal ulcer and infiltrate resolved. The infection resulted in corneal thinning and a dense central corneal scar. Penetrating keratoplasty was performed 5 months after diagnosis and treatment and revealed stromal scarring without fungal elements. CONCLUSION: This is the first reported case of keratitis caused by Trametes betulina. This organism should be considered in the differential diagnosis for rare filamentous fungal keratitis and its treatment with voriconazole also noted.

Effect of aspirin on models of retinal pigment epithelium pathology.

BACKGROUND: To characterize the effect of aspirin (ASA) in mouse models of choroidal neovascularization (CNV) and retinal degeneration. METHODS: In vivo: Male C57BL/6 mice were given ASA in food or regular rodent diet. CNV was induced by argon laser photocoagulation. Subretinal injections of polyethylene glycol 400 (PEG-400) were administered to induce retinal degeneration. CNV size, laser spot area and mean intensity of VEGF in the laser injured zones were measured. In the PEG injected eyes the thickness of retinal pigment epithelium (RPE) and choroid was measured. In vitro: Human ARPE-19 cells were treated with 0.5 or 2.0 mM/L of ASA for 72 h. ELISA was used to measure the concentration of VEGF and CCL-2 in the supernatants. Additionally, damaged RPE monolayer was treated with ASA (0.5 or 2.0 mM/L) and vehicle separately. Size of damaged area was measured. ELISA was used to measure secretion of VEGF-A and CCL-2 by damaged cells after 24 h. RESULTS: No statistically significant effect of ASA on CNV size, laser spot size or VEGF expression was noted in CNV model. In the PEG model, ASA did not have any effect on RPE and choroid thickness; however, a significant increase in RPE atrophy was observed (P = 0.02 + 38%). In addition, ASA had a significant effect on the ability of the RPE cells to regenerate and become confluent after mechanical damage. CONCLUSIONS: ASA at doses consumed clinically for various medical causes may not worsen CNV in human subjects. However, ASA may increase RPE atrophy when consumed over long periods of time.

Choroidal Ganglioneuroma and Orbital Plexiform Neurofibroma Presenting as Buphthalmos in an Infant With Neurofibromatosis Type 1.

Neurofibromatosis type 1 (NF-1) is an autosomal dominant familial tumor predisposition syndrome characterized by the growth of benign and malignant tumors involving the peripheral and central nervous system. In the following report, the authors describe a case of a 1-year-old child with NF-1, who underwent enucleation for a blind, proptotic, painful eye with subsequent histopathological examination revealing choroidal ganglioneuroma, a very rare entity.

Extubation failure in infants with shunt-dependent pulmonary blood flow and univentricular physiology.

OBJECTIVE: The objective of the study was to identify incidence, aetiology, and outcomes of extubation failure in infants with shunt-dependent pulmonary blood flow at a single tertiary care, academic children's hospital. The second objective of this study was to determine the haemodynamic effects of transition of positive pressure ventilation to spontaneous breathing in infants with extubation failure. PATIENTS AND METHODS: Extubation failure for our study was defined as the need for positive pressure ventilation within 96 hours after extubation. We collected demographics, pre-operative, intra-operative, post-operative, and peri-extubation data in a retrospective, observational format in patients who underwent a modified Blalock-Taussig shunt between January, 2005 and March, 2011. Infants undergoing Norwood operation or Damus-Kaye-Stansel with modified Blalock-Taussig shunt were excluded from the study. The cardiorespiratory variables collected before extubation and immediately after extubation included heart rate, respiratory rate, mean arterial blood pressure, central venous pressures, near infrared spectroscopy, oxygen saturations, and lactate levels. Clinical outcomes evaluated included the success or failure of extubation, cardiovascular intensive care unit length of stay, hospital length of stay, and mortality. Descriptive and univariate statistics were utilised to compare groups with extubation failure and extubation success. RESULTS: Of the 55 eligible patients during the study period, extubation failure occurred in 27% (15/55) of the patients. Of the 15 patients with extubation failure, 10 patients needed reintubation and five patients received continuous positive pressure ventilation without getting reintubated. There were three patients who had extubation failure in the first 2 hours after extubation, nine patients in the 2-24-hour period, and three patients in the 24-96-hour period. In all, eight patients were extubated in the second attempt after the first extubation failure, with a median duration of mechanical ventilation of 2 days (1 day, 6 days). The median age of patients at extubation was 19 days (12 days, 22 days) and median weight of patients was 3.6 kg (3.02 kg, 4.26 kg). In all, 38% (21/55) of the patients were intubated before surgery. The most common risk factors for failed extubation were lung disease in 46% (7/15), cardiac dysfunction in 26% (4/15), diaphragmatic paralysis in 13% (2/15), airway oedema in 6% (1/15), and vocal cord paralysis in 6% (1/15). The median duration of mechanical ventilation was 4 days (1 day, 10.5 days), median cardiovascular intensive care unit length of stay was 11 days (6.5 days, 23.5 days), and the median hospital length of stay was 30 days (14 days, 48 days). The overall mortality at the time of hospital discharge was 7%. CONCLUSIONS: Extubation failure in infants with shunt-dependent pulmonary blood flow and univentricular physiology is high and aetiology is diverse. Cardiopulmonary effects of removal of positive pressure ventilation are more pronounced in children with extubation failure and include escalation in the need for oxygen requirement and increase in mean arterial blood pressure. The majority of extubation failures in this select patient population occurs in the first 24 hours. Extubation failure in these patients is not associated with increased hospital length of stay or mortality.

A novel pro-lymphangiogenic function for Th17/IL-17.

Th17 cells, in addition to their proinflammatory functions, have been recognized as potent inducers of angiogenesis in autoimmune diseases and malignancies. In the present study, we demonstrate distinct mechanisms by which IL-17 induces lymphangiogenesis. Using the mouse cornea micropocket and cell culture assays, our data demonstrate that IL-17 directly promotes growth of lymphatic vessels by inducing increased expression of prolymphangiogenic VEGF-D and proliferation of lymphatic endothelial cells. However, IL-17-induced growth of blood vessels is primarily mediated through IL-1ß secretion by IL-17-responsive cells. Furthermore, in vivo blockade of IL-17 in a preclinical model of Th17-dominant autoimmune ocular disease demonstrates a significant reduction in the corneal lymphangiogenesis and in the progression of clinical disease. Taken together, our findings demonstrate a novel prolymphangiogenic function for Th17/IL-17, indicating that IL-17 can promote the progression and amplification of immunity in part through its induction of lymphangiogenesis.

Impact of 22q11.2 deletion on the postoperative course of children after cardiac surgery.

The primary objective of this study was to describe the impact of 22q11.2 deletion (del22q11) on the clinical characteristics, postoperative course, and short-term outcomes of children undergoing surgery for congenital heart disease. The charts of all children ages 1 day-18 years who received cardiac surgery for interrupted aortic arch (IAA), tetralogy of Fallot (TOF), or truncus arteriosus (TA) repair from 1 January 2001 to 31 December 2011 were retrospectively reviewed. The patients were divided into two groups: the 22q11 group including children with del22q11 undergoing surgery for TOF, IAA, or TA and the non-22q11 or control group including children with no chromosomal or genetic abnormality undergoing surgery for TOF, IAA, or TA. Demographic information, cardiac diagnoses, noncardiac abnormalities, preoperative factors, intraoperative details, surgical procedures performed, postoperative complications, and in-hospital deaths were collected. The outcome data collected included days of inotrope use, need for dialysis, length of mechanical ventilation, intensive care unit (ICU) length of stay (LOS), hospital LOS, and mortality. The study enrolled 173 patients: 65 patients in the 22q11 group and 108 patients in the control group. Of the 65 patients in the 22q11 group, 36 (55 %) underwent repair for TOF, 13 (20 %) for IAA, and 16 (25 %) for TA. The two groups did not differ in terms of age or weight. The preexisting conditions were similar in the two groups. Unplanned noncardiac operations were more common in the children with del22q11, but delayed chest closure was similar in the two groups. The incidence of postoperative noncardiac complications such as reintubation, vocal cord paralysis, and diaphragmatic paralysis was similar in the two groups. However, increasing numbers of patients in del22q11 group needed dialysis in one form or the other during the immediate postoperative stay. The incidence of fungal infection and wound infection was higher in the del22q11 group than in the control group. Duration of mechanical ventilation, ICU LOS, and hospital LOS were similar in the two groups, except in certain subgroups. Mortality did not differ significantly between the two groups. In conclusion, children with del22q11 have a higher risk of postoperative complications after cardiac surgery, with no difference in length of mechanical ventilation, ICU LOS, hospital LOS, or mortality. However, short-term outcomes may differ in certain subgroups.

A tale of two Purtscher's retinopathy.

PURPOSE: To characterize the outcome in two cases of unilateral traumatic Purtscher's retinopathy that developed after blunt head trauma. METHODS: Observational case series of two patients diagnosed at the University of Arkansas for Medical Sciences with Purtscher's retinopathy following blunt head trauma. All patients underwent a comprehensive ophthalmic examination, which included best corrected visual acuity, slit lamp biomicroscopy, dilated fundus exam, and retinal imaging fundus photography and high-definition Spectral domain optical coherence tomography (HD-SDOCT). RESULTS: Two cases of Purtscher's retinopathy after blunt head trauma were diagnosed between July 2011 and December 2011. Case 1 was involved in a motor vehicle accident and underwent observational management with no change in initial baseline vision (20/400) after follow-up of 4 months. Case 2 fell from a 16-foot high deer-stand and managed with systemic steroids, wherein vision improved after one month from 20/60 (initial presentation) to 20/25; vision remained stable after follow-up of 4 months. CONCLUSION: Purtscher's retinopathy can have different visual outcomes depending on the initial and final degree of injury to the retinal architecture. Steroids may help limit damage and improve the overall outcome in patients with Purtscher's retinopathy.

Autoimmunity in dry eye is due to resistance of Th17 to Treg suppression.

Dry eye disease (DED), an inflammatory autoimmune disorder affecting the ocular surface, degrades visual performance and the quality of life of >10 million people in the United States alone. The primary limitation in the effective treatment of DED is an incomplete understanding of its specific cellular and molecular pathogenic elements. Using a validated mouse model of DED, herein we functionally characterize the different T cell subsets, including regulatory T cells (Tregs) and pathogenic effector T cells, and determine their contribution to the pathogenesis of DED. Our data demonstrate the presence of dysfunctional Tregs and the resistance of pathogenic T cells, particularly Th17 cells, to Treg suppression in DED. In addition, we clearly show that in vivo blockade of IL-17 significantly reduces the severity and progression of disease, which is paralleled by a reduction in the expansion of Th17 cells and restoration of Treg function. Our findings elucidate involvement of a previously unknown pathogenic T cell subset (Th17) in DED that is associated specifically with Treg dysfunction and disease pathogenesis and suggest a new target for dry eye therapy.

Prolonged mechanical support in children with severe adenoviral infections: a case series and review of the literature.

Adenovirus infections occur primarily in infants and children less than 5 years of age, accounting for 2% to 5% of respiratory illnesses in the pediatric population and 4% to 10% of childhood pneumonias. Although the majority of children with adenovirus disease develop mild upper respiratory tract disease, more severe disease may occur with involvement of the lower respiratory tract characterized by pneumonitis and/or small airways disease. The authors present a case series of 3 high-risk children with severe lower respiratory tract adenoviral infections. These cases demonstrate the potential for the development of severe respiratory involvement from adenovirus in infants and children with comorbid conditions and illustrate that there may be a rapid progression of the disease as well as the need, in selected circumstances, for prolonged mechanical support. We review the role of adenovirus in lower respiratory tract infections in infants and children, its potential to result in life-threatening complications in pediatric patients with comorbid conditions, and the potential life-saving role of mechanical ventilation and extracorporeal life support (ECLS) in these children.

Meta-analysis and review on the effect of bevacizumab in diabetic macular edema.

BACKGROUND: Systematic review and meta-analysis to evaluate the effect of bevacizumab (Avastin) in diabetic macular edema (DME) METHODS: Pertinent publications were identified through systematic searches of PUBMED and Cochrane Central Register of Controlled Trials. Change in central subfield macular thickness (CSMT) in µm and best-corrected visual acuity (BCVA) in log MAR equivalents were extracted at 6, 12 and 24 weeks, and results compared between groups receiving intravitreal bevacizumab (IVB), a combination of IVB and intravitreal triamcinolone acetonide (IVT), and macular laser photocoagulation or sham control groups. RESULTS: The summary mean difference indicated a statistically significant reduction in CSMT at 6 weeks when treated with bevacizumab compared to control. IVB treatment, however, lost significance at 12 weeks and 24 weeks. The summary mean difference in BCVA for IVB group compared to control reached significance only at 6 and 24 weeks. Combination therapy of IVB and IVT did not result in any significant reduction in CSMT or gain in vision compared to treatment with IVB alone at any point in time. CONCLUSIONS: Current data suggests that IVB is an effective short-term treatment for diabetic macular edema, and that its efficacy wanes after 6 weeks. More trials exploring the therapeutic role of intravitreal bevacizumab in DME need to be conducted to define the role of bevacizumab.

Risk factors associated with hospital admission among healthy children with adenovirus infection.

Adenovirus infections mimic bacterial infections on initial presentation in healthy children, leading to higher likelihood of hospital admission. The objective of this study was to identify risk factors associated with hospital admission in previously healthy children with adenovirus infection. This is a retrospective study of 125 previously healthy children, who tested positive with direct immunofluorescence assay (DFA) for adenoviral infection at our center between January 2001 and October 2007. The primary outcome of the study was the need for hospital admission. The relationship between clinical variables at initial emergency room (ER) presentation and need for hospital admission were explored using univariate and multivariate logistic regression models. The model's predictive value was investigated by calculating the area under the receiver operating characteristic (ROC) curve and Hosmer-Lemeshow test. On stepwise multivariate logistic regression analysis, the presence of respiratory distress (odds ratio [OR]: 5.6; p = 0.014), acute gastroenteritis (OR: 3.8; p = 0.019) and wheezes at initial presentation (OR: 6.5; p = 0.003) at the time of initial presentation in the ER were associated with need for hospital admission. For this model, the area under the ROC curve was 0.79, and there was no evidence of lack of fit on Hosmer-Lemeshow goodness-of-fit test (p = 0.56). Our study identifies three risk factors, namely, respiratory distress, wheezing and acute gastroenteritis, associated with hospital admission for healthy children with adenoviral infections.

Factors associated with motor vehicle-related eye injuries presenting to the US emergency departments.

OBJECTIVES: To evaluate risk factors associated with eye injuries related to motor vehicle accidents (MVA) using a multicentre national database from the US emergency departments. PATIENTS AND METHODS: A post hoc analysis from the Nationwide Emergency Department Sample database (2006-2013) was performed. Patients presenting to the emergency department (ED) with MVA-related trauma were included. We then evaluated patient- and centre-level risk factors associated with the presence of ocular trauma using a multivariable logistic regression model. RESULTS: A total of 2,745,152 patients from 2080 ED were identified for inclusion. Of these, 31,493 patients (1.14%) were associated with ocular trauma. The most common ocular injuries reported in our study were injury to ocular adnexa, orbital fractures, subconjunctival haemorrhage, foreign body on eye, and open wound of the eyeball. In univariate analysis, the other patient factors associated with ocular trauma included male gender, >1 chronic condition, admission during weekend, >1 bodily injury, higher injury severity score (ISS), presence of skull fractures and other bodily fractures, seizures, and initiation of mechanical ventilation after MVA. The hospital characteristics associated with highest incidence of ocular trauma included ED visit to a level I trauma centre and metropolitan teaching hospital. The independent factors associated with ocular trauma included younger age groups, male gender, weekend injury, presence of chronic conditions, >1 bodily injury, higher ISS, presence of skull fractures, ED admission to level-1 trauma centre, and ED admission to a teaching hospital. CONCLUSIONS: This multicentre study establishes that both patient- and centre-level factors are associated with MVA-related eye injuries.

Characteristics and Fate of Abstracts Presented at American Academy of Ophthalmology Meetings.

PURPOSE: The purpose of this study is to evaluate the characteristics and publication outcomes of abstracts presented in American Academy of Ophthalmology (AAO) meetings. SUBJECT AND METHODS: Abstracts from AAO meetings for the years 2012 and 2013 were evaluated from the meeting archives. The study characteristics were recorded for each abstract. Each abstract was assessed for publication in a peer-reviewed scientific journal using three search engines (PubMed, Medline, and Google Scholar). Time to publication was also calculated. RESULTS: A total of 929 abstracts presented to 2 AAO meetings were analyzed. Among subspecialty areas, retina represented the largest percentage of accepted meeting abstracts (33.3%) followed by cornea (21.9%), cataract (14.9%), and glaucoma (14.4%). A total of 304 abstracts (32.7%) were published in peer-reviewed journals as full-length articles. The median time to publication was 40 months, and the median impact factor of the journal for the published manuscript was 1.9. In multivariable models, topics related to glaucoma were most likely to be published followed by retina. The odds for publication were higher if the first author was affiliated with a residency program, and if the first author originated from South Korea and the United States. CONCLUSIONS: Our study presents the landscape of publication outcomes for abstracts presented in national AAO meetings with ~1/3 of presented abstracts culminated in publication in a peer-reviewed journal.

Patient characteristics and outcomes of retained lens fragments in the anterior chamber after uneventful phacoemulsification.

PURPOSE: To determine patient characteristics and outcomes for developing retained nuclear fragments in the anterior chamber after phacoemulsification in at-risk populations. SETTING: University of Arkansas for Medical Sciences, Jones Eye Institute, Little Rock, Arkansas, USA. DESIGN: Retrospective case series. METHODS: Using Current Procedural Terminology codes 2006 to 2018, patients with a diagnosis of retained nuclear fragment in the anterior chamber after uncomplicated phacoemulsification cataract extraction were identified. Patient demographics, ocular biometrics, treatments, and clinical management were recorded. Main outcome measures were visual outcomes and visual acuity at regular follow-up appointments. RESULTS: Nineteen patients (13 with myopia) were identified. Most patients (n = 15) presented with corneal edema and anterior chamber inflammation, and the fragments were diagnosed on slitlamp examination in most patients (n = 18). Seventeen retained fragments were found in the inferior angle. The mean axial length, keratometry, and anterior chamber depth (ACD) values were 23.58 mm, 44.93 diopters, and 2.97 mm, respectively. The mean time from cataract extraction to fragment removal was 34.7 days. The final corrected distance visual acuity ranged from 20/20 to 20/400. Three patients developed cystoid macular edema, and 2 patients had corneal complications after fragment removal. CONCLUSIONS: A comparison between the patients in this study and cited cases indicates that long eyes, steep corneas, and a shallow ACD might be risk factors for retained nuclear fragments in patients having cataract extraction. Prompt identification and surgical removal provided the best visual outcomes because most cases proved refractory to steroid treatment.

Comparison of the Effect of Cycloplegia on Astigmatism Measurements in a Pediatric Amblyopic Population: A Prospective Study.

PURPOSE: To study the effect of cycloplegia on astigmatism measurements in pediatric patients with amblyopia. METHODS: This was a prospective comparative clinical study. Participants 4 to 17 years old were recruited from the patient population at the Arkansas Children's Hospital eye clinic after informed consent was obtained. Autorefractor measurements were used to obtain values of refractive error in amblyopic and non-amblyopic patients before and after cycloplegia. The groups were subdivided into myopia and hyperopia and with and without underlying amblyopia. The refractive error was expressed as sphere, cylinder, axis of astigmatism, and spherical equivalent. The treatment effect was summarized as the mean difference (95% confidence interval) for each outcome. RESULTS: No statistically significant difference was found on the axis and power of astigmatism before and after cycloplegia in the patients with amblyopia (P = .28 and .99, respectively). CONCLUSIONS: Non-cycloplegic autorefraction measurements may be considered safe for refining astigmatism power and axis in pediatric patients with amblyopia. [J Pediatr Ophthalmol Strabismus. 2018;55(5):293-298.].