Lacrimal Gland Hypoplasia and Corneal Anesthesia in MIRAGE Syndrome: A Case Report and Literature Review.

PURPOSE: The purpose of this report was to describe the ocular findings in Myelodysplasia, Infection, Restriction of growth, Adrenal hypoplasia, Genital problems, and Enteropathy (MIRAGE) syndrome, a multisystem congenital disorder. METHODS: This was a case report and literature review. RESULTS: An infant with MIRAGE syndrome (combined immunodeficiency with recurrent infections, growth restriction, adrenal insufficiency, 46,XY karyotype with hypovirilization, dysphagia, gastroesophageal reflux disease, and dysautonomia) underwent ophthalmological evaluation because of persistent conjunctivitis during his 8-month admission in the neonatal intensive care unit. His parents noted absence of tears when crying since birth. Bilateral broad corneal epithelial defects were noted, and treatment was initiated with frequent lubricating ointment. At 9 months, his vision was estimated at 20/380 in both eyes using Teller Acuity Cards. There were persistent bilateral epithelial defects, confluent punctate epithelial erosions, low Schirmer strip wetting (right eye 3 mm and left eye 2 mm), and decreased corneal sensation. Brain magnetic resonance imaging images demonstrated hypoplastic lacrimal glands bilaterally. More aggressive lubrication and installation of punctal plugs in all 4 lids were successful at preventing further epithelial defects. CONCLUSIONS: This case presents deficient lacrimation as a manifestation of MIRAGE syndrome and is the first to identify lacrimal gland hypoplasia and corneal anesthesia. Autonomic and neurologic dysfunction have been proposed to play a role in the pathophysiology of hypolacrimation in similar syndromes and likely contributed to the poor ocular surface in this case. Patients with MIRAGE should undergo ophthalmic assessment as soon as possible after birth because early intervention is essential to preventing irreversible corneal damage.

Limbal Stem Cell Dysfunction in Ichthyosis Follicularis, Alopecia, and Photophobia Syndrome.

PURPOSE: To describe the presentation and management of limbal stem cell dysfunction in ichthyosis follicularis, alopecia, and photophobia (IFAP) syndrome. METHODS: A retrospective case report. RESULTS: A 6-day-old male infant was diagnosed with IFAP syndrome based on family history and a mutation detected in the MBTPS2 gene. Initial examination showed hyperkeratotic eyelids, madarosis, and lagophthalmos, but otherwise clear corneas. He developed bilateral central corneal epithelial defects spontaneously 6 months later, which were managed with aggressive lubrication, prophylactic antibiotics, and bilateral permanent lateral tarsorrhaphies at 7 months of age. During the procedure, the patient was noted to have bilateral limbal thickening, peripheral corneal pannus with underlying stromal scarring, and late fluorescein staining of the corneal surface. Anterior segment optical coherence tomography demonstrated a significantly abnormal and hyperreflective epithelial surface overlying a thinned corneal stroma, suggestive of limbal stem cell dysfunction. The corneal surface was maintained with lubrication and tarsorrhaphy and has remained stable since. CONCLUSIONS: The progressive conjunctivalization, spontaneous epithelial defects, and anterior segment optical coherence tomography features are highly suggestive of limbal stem cell dysfunction in IFAP syndrome. Optimizing the ocular surface is of importance in the management of children with this rare disease.

Acute Unilateral Ptosis and Myositis Following the H1N1 Influenza Vaccine.

The authors present a rare case of sudden onset unilateral complete ptosis occurring hours after administration of the H1N1 influenza vaccine. A complete workup for autoimmune and neurological disease was negative. MRI of the orbits demonstrated unilateral orbital myositis involving the left superior rectus/levator complex, superior oblique, and medial rectus muscles. Ptosis resolved spontaneously over 2 months without intervention. An autoimmune mechanism may explain rare cases of orbital myositis following administration of the H1N1 influenza vaccination.A case of acute onset and spontaneous resolution of complete unilateral ptosis and orbital myositis post H1N1 influenza vaccination.

Trends in low vision care provided by ophthalmologists in Ontario between 2009 and 2015.

OBJECTIVE: Little is known about how low vision services by ophthalmologists are being provided. Here, we analyze the patterns of provision and utilization of vision rehabilitation services in Ontario, Canada. DESIGN: Retrospective population-based study between 2009 and 2015. PARTICIPANTS: Ophthalmologists (n = 92) who billed for vision rehabilitation services through the Ontario Health Insurance Plan in Ontario and the patients (n = 8949) who received these services. METHODS: Billing data for low vision services (2009-2015) was received from Ontario Health Insurance Plan. Data were analyzed to describe patient demographics (age, sex, geographic distribution, number, and type of visits) and service provider information (geographic location, number of years providing services, and number of services per year). RESULTS: It is estimated that ≤ 5% of patients with low vision in Ontario accessed these vision rehabilitation services by ophthalmologists. The majority of these patients were females (61%) and > 60 years old (79%). While patient and provider geographic distributions overlapped in the areas with largest patient populations, many regions lacked services. The majority of patients (71%) made only one vision rehabilitation visit. Nine providers practiced low vision for 7 years, while 43 provided services for only 1 year. In 2015, the most common diagnostic service provided to low vision patients was Optical Coherence Tomography of the retina and the most common therapeutic service was intravitreal for wet age-related macular degeneration. CONCLUSION: Although low vision services increased between 2009 and 2015, there were differences in ability to access care based on age, sex, and geographic location.

Adherence to World Glaucoma Association Guidelines for Surgical Trials in the Era of Microinvasive Glaucoma Surgeries.

PURPOSE: To determine how well microinvasive glaucoma surgical (MIGS) trials conform to the World Glaucoma Association (WGA) guidelines. Lack of well-designed MIGS studies hinders meaningful evaluation of these technologies. DESIGN: Cross-sectional literature survey. METHODS: Using a predefined search strategy, the following databases were searched for comparative trials involving MIGS in the English peer-reviewed literature from January 1, 2000, through June 21, 2018: Medline, EMBASE, BIOSIS, Cochrane, and Web of Science. From the WGA guidelines, 53 outcomes were selected for evaluation: methodology (n = 31), definition of success (n = 7), ethics (n = 10), postoperative complications (n = 1), economic evaluation (n = 1), and statistical reporting (n = 3). Each article was assessed by 2 reviewers; differences were resolved by consensus. RESULTS: Twenty-five eligible publications were identified: 10 randomized controlled trials (RCTs) and 15 nonrandomized comparative trials (non-RCTs). The mean follow-up was 19.9±11.6 months (range, 6-48 months). The mean number of outcomes adhering to the WGA guidelines of the 53 evaluated was 24.2±6.1 (45.6% compliance): 28.0±6.2 (52.8%) and 21.6±4.7 (40.8%) for RCTs and non-RCTs, respectively (P = 0.01). Mean percent compliance for each subsection were: methodology, 48.8%; definition of success, 21.1%; ethics, 55.6%; postoperative complications, 88%; economic evaluation, 0%; and statistical reporting, 37.3%. In 16 studies (64%), at least 1 author reported an association with the industry. Thirty-two percent of studies reported an author being a shareholder. Twenty-four percent of studies had an industry employee author. The primary intraocular pressure (IOP) end point was defined as both an upper limit and percentage reduction in only 4 studies (16%; 1 RCT, 3 non-RCTs). An IOP-based survival curve was provided in 7 studies (28%; none of the RCTs). Two studies (8%) included an IOP scatterplot. Twelve studies (48%) reported 95% confidence intervals. Only 4 studies (16%) used the mean of 3 diurnal IOP readings as the baseline IOP. CONCLUSIONS: Published comparative MIGS trials show low adherence (45.6%) to the WGA guidelines. Development of standardized methodology and outcomes could enhance interpretation and transparency of study results and facilitate comparisons between trials. Authors and journals should be encouraged to follow the WGA guidelines.

Topical Ganciclovir for Prophylaxis of Cytomegalovirus Endotheliitis in Endothelial Keratoplasty.

PURPOSE: To describe the presentation and management of 2 cases of Descemet stripping automated endothelial keratoplasty (DSAEK) with failure secondary to cytomegalovirus (CMV) infection and prophylaxis with topical ganciclovir to prevent repeat failure of Descemet membrane endothelial keratoplasty (DMEK) regrafts. METHODS: A retrospective chart review was conducted for 2 patients with DSAEK failure secondary to CMV infection. RESULTS: A 70-year-old immunocompetent man (case 1) and a 53-year-old immunocompromised man (case 2) received DSAEK for presumed pseudophakic bullous keratopathy and endothelial decompensation secondary to recurrent uveitis, respectively. Case 1 had first graft failure at 10 months and case 2 at 21 months with inferior edema and keratic precipitates. Both failed to respond to topical steroid drops, and case 1 had 3 subsequent failed DSAEKs. Anterior chamber paracentesis confirmed CMV DNA. Neither had a clinical response to 6 weeks of oral valganciclovir. They were then administered topical ganciclovir (0.15% ophthalmic gel), and repeat endothelial transplant (DMEK) was performed for both patients. They were again administered topical ganciclovir 4 times daily after surgery because aqueous samples remained positive for CMV. Both remain free of inflammation or failure on topical ganciclovir for 21 months (case 1) and 29 months (case 2) with uncorrected visual acuities of 20/40 and 20/25, respectively. CONCLUSIONS: Long-term topical ganciclovir use can prevent recurrence of CMV-associated graft failure even in immunocompromised hosts without side effects of systemic antivirals. DMEK may have advantages over DSEK in eyes with previous CMV infection and in eyes prone to inflammation.

The extent of intrauterine growth restriction determines the severity of cerebral injury and neurobehavioural deficits in rodents.

BACKGROUND: Cerebral Palsy (CP) is the most common physical pediatric neurodevelopmental disorder and spastic diplegic injury is its most frequent subtype. CP results in substantial neuromotor and cognitive impairments that have significant socioeconomic impact. Despite this, its underlying pathophysiological mechanisms and etiology remain incompletely understood. Furthermore, there is a need for clinically relevant injury models, which a) reflect the heterogeneity of the condition and b) can be used to evaluate new translational therapies. To address these key knowledge gaps, we characterized a chronic placental insufficiency (PI) model, using bilateral uterine artery ligation (BUAL) of dams. This injury model results in intrauterine growth restriction (IUGR) in pups, and animals recapitulate the human phenotype both in terms of neurobehavioural and anatomical deficits. METHODS: Effects of BUAL were studied using luxol fast blue (LFB)/hematoxylin & eosin (H&E) staining, immunohistochemistry, quantitative Magnetic Resonance Imaging (MRI), and Catwalk neurobehavioural tests. RESULTS: Neuroanatomical analysis revealed regional ventricular enlargement and corpus callosum thinning in IUGR animals, which was correlated with the extent of growth restriction. Olig2 staining revealed reductions in oligodendrocyte density in white and grey matter structures, including the corpus callosum, optic chiasm, and nucleus accumbens. The caudate nucleus, along with other brain structures such as the optic chiasm, internal capsule, septofimbrial and lateral septal nuclei, exhibited reduced size in animals with IUGR. The size of the pretectal nucleus was reduced only in moderately injured animals. MAG/NF200 staining demonstrated reduced myelination and axonal counts in the corpus callosum of IUGR animals. NeuN staining revealed changes in neuronal density in the hippocampus and in the thickness of hippocampal CA2 and CA3 regions. Diffusion weighted imaging (DWI) revealed regional white and grey matter changes at 3 weeks of age. Furthermore, neurobehavioural testing demonstrated neuromotor impairments in animals with IUGR in paw intensities, swing speed, relative print positions, and phase dispersions. CONCLUSIONS: We have characterized a rodent model of IUGR and have demonstrated that the neuroanatomical and neurobehavioural deficits mirror the severity of the IUGR injury. This model has the potential to be applied to examine the pathobiology of and potential therapeutic strategies for IUGR-related brain injury. Thus, this work has potential translational relevance for the study of CP.

Publication rate of abstracts presented at the 2010 Canadian Ophthalmological Society Annual Meeting.

OBJECTIVE: To evaluate the publication rate of submitted abstracts accepted for presentation at the 2010 Canadian Ophthalmological Society (COS) Annual Meeting in peer-reviewed journals. DESIGN: A retrospective analysis and literature search of abstracts presented at the 2010 COS Annual Meeting. METHODS: Abstracts accepted as an oral presentation or poster from the 2010 COS Annual Meeting were tabulated by type of presentation (oral vs poster), subspecialty, study design, number of authors, and principal investigator's institution. A PubMed search was conducted for each abstract by key word, first author, and last author. The year of publication, journal, and impact factor were recorded for identified publications. Publication rate was calculated by type of presentation, subspecialty, study design, number of authors, and institution. RESULTS: A total of 175 abstracts were presented at the 2010 COS Annual Meeting. There were 105 oral (60%) and 70 poster (40%) presentations. The overall publication rate was 45.7%; 49.5% for oral presentations and 40.0% for posters. Cornea (57.6%) and public health (54.5%) had the highest publication rates of all subspecialties. Randomized control trials (71.4%) and cohort studies (70.0%) had higher publication rates than other study designs. Overall, 28.8% of abstracts were published in the Canadian Journal of Ophthalmology. The average impact factor of all publications was 2.73. CONCLUSION: Of abstracts presented at the 2010 COS Annual Meeting, 45.7% were published within 5 years after the conference. This publication rate is within the upper end of previously reported meeting publication rates for medical societies.

Comparison of glaucoma knowledge and referral practices among family physicians with ophthalmologists' expectations.

OBJECTIVE: To compare family physicians' glaucoma knowledge and clinical skills with ophthalmologists' expectations. DESIGN: An electronic cross-sectional survey of family physicians and ophthalmologists. PARTICIPANTS: Participants included members of the Canadian Ophthalmological Society, Canadian Glaucoma Society, and the American Glaucoma Society, as well as family physicians in the Canadian Medical Directory and the Society of Rural Physicians of Canada listserv. METHODS: Two complementary surveys were developed to evaluate family physicians' glaucoma knowledge and basic examination skills, and ophthalmologists' expected level of family physician clinical knowledge and skills. χ(2) tests identified differences between family physician and ophthalmologist responses. Differences in family physician knowledge based on practice location and frequency of patient visits with a diagnosis of glaucoma were also evaluated. RESULTS: A total of 142 ophthalmologists and 110 family physicians completed the survey. The majority (82%) of family physicians reported seeing patients with diagnosed glaucoma weekly, monthly, or semiannually. Significantly fewer family physicians than expected (p < 0.001) identified African descent (46%) and corticosteroid use (84%) as glaucoma risk factors. Family physicians were significantly less likely to refer based on risk factors (72%) than expected by ophthalmologists (91%; p < 0.001). Only 28% of family physicians were comfortable performing direct ophthalmoscopy, and 37% were comfortable checking for a relative afferent pupillary defect. A significant percentage of family physicians lacked knowledge of glaucoma medications (30%) and side effects (57%). CONCLUSIONS: This study revealed significant disparities in family physician glaucoma knowledge, clinical examination skills, and referral practices. Educational materials should target these knowledge gaps.

Neurological outcomes of animal models of uterine artery ligation and relevance to human intrauterine growth restriction: a systematic review.

AIM: This review explores the molecular, neurological, and behavioural outcomes in animal models of uterine artery ligation. We analyse the relevance of this type of model to the pathological and functional phenotypes that are consistent with cerebral palsy and its developmental comorbidities in humans. METHOD: A literature search of the PubMed database was conducted for research using the uterine artery ligation model published between 1990 and 2013. From the studies included, any relevant neuroanatomical and behavioural deficits were then summarized from each document and used for further analysis. RESULTS: There were 25 papers that met the criteria included for review, and several outcomes were summarized from the results of these papers. Fetuses with growth restriction demonstrated a gradient of reduced body weight with a relative sparing of brain mass. There was a significant reduction in the size of the somatosensory cortex, hippocampus, and corpus callosum. The motor cortex appeared to be spared of identifiable deficits. Apoptotic proteins were upregulated, while those important to neuronal survival, growth, and differentiation were downregulated. Neuronal apoptosis and astrogliosis occurred diffusely throughout the brain regions. White matter injury involved oligodendrocyte precursor maturation arrest, hypomyelination, and an aberrant organization of existing myelin. Animals with growth restriction demonstrated deficits in gait, memory, object recognition, and spatial processing. INTERPRETATION: This review concludes that neuronal death, white matter injury, motor abnormalities, and cognitive deficits are important outcomes of uterine artery ligation in animal models. Therefore, this is a clinically relevant type of model, as these findings resemble deficits in human cerebral palsy.

The neuroanatomical organization of projection neurons associated with different olfactory bulb pathways in the sea lamprey, Petromyzon marinus.

Although there is abundant evidence for segregated processing in the olfactory system across vertebrate taxa, the spatial relationship between the second order projection neurons (PNs) of olfactory subsystems connecting sensory input to higher brain structures is less clear. In the sea lamprey, there is tight coupling between olfaction and locomotion via PNs extending to the posterior tuberculum from the medial region of the olfactory bulb. This medial region receives peripheral input predominantly from the accessory olfactory organ. However, the axons from olfactory sensory neurons residing in the main olfactory epithelium extend to non-medial regions of the olfactory bulb, and the non-medial bulbar PNs extend their axons to the lateral pallium. It is not known if the receptive fields of the PNs in the two output pathways overlap; nor has the morphology of these PNs been investigated. In this study, retrograde labelling was utilized to investigate the PNs belonging to medial and non-medial projections. The dendrites and somata of the medial PNs were confined to medial glomerular neuropil, and dendrites of non-medial PNs did not enter this territory. The cell bodies and dendrites of the non-medial PNs were predominantly located below the glomeruli (frequently deeper in the olfactory bulb). While PNs in both locations contained single or multiple primary dendrites, the somal size was greater for medial than for non-medial PNs. When considered with the evidence-to-date, this study shows different neuroanatomical organization for medial olfactory bulb PNs extending to locomotor control centers and non-medial PNs extending to the lateral pallium in this vertebrate.

Nutritional management of Eosinophilic Gastroenteropathies: Case series from the community.

Eosinophilic gastroenteropathies, such as eosinophilic esophagitis and eosinophilic colitis, have classically been treated with swallowed inhaled corticosteroids or oral corticosteroids. More recent studies have found elimination and elemental diets to be effective treatment alternatives to steroids. In this case series we describe the treatment of three children using nutritional management in a community setting. Elimination diets and elemental diets based on patch testing and skin prick tests reduced the eosinophil counts to normal levels in all three children. Food items which tested positive were then reintroduced while symptoms and eosinophil counts were monitored. Nutritional management of eosinophilic esophagitis and eosinophilic colitis was found to be effective in reducing symptoms. However, obstacles facing patients who choose this type of therapy include limitations due to the cost of repeated endoscopies, palatability of elimination/elemental diets and the availability of subspecialists trained in management (e.g. Allergy, Gastroenterology, and Pathology). It may be a worthwhile endeavour to overcome these obstacles as nutritional management minimizes the potential long-term effects of chronic steroid therapy.