The Royal Victorian Eye & Ear Hospital

OBJECTIVE: To update a 15-year-old study of 800 postlinguistically deaf adult patients showing how duration of severe to profound hearing loss, age at cochlear implantation (CI), age at onset of severe to profound hearing loss, etiology and CI experience affected CI outcome. STUDY DESIGN: Retrospective multicenter study. METHODS: Data from 2251 adult patients implanted since 2003 in 15 international centers were collected and speech scores in quiet were converted to percentile ranks to remove differences between centers. RESULTS: The negative effect of long duration of severe to profound hearing loss was less important in the new data than in 1996; the effects of age at CI and age at onset of severe to profound hearing loss were delayed until older ages; etiology had a smaller effect, and the effect of CI experience was greater with a steeper learning curve. Patients with longer durations of severe to profound hearing loss were less likely to improve with CI experience than patients with shorter duration of severe to profound hearing loss. CONCLUSIONS: The factors that were relevant in 1996 were still relevant in 2011, although their relative importance had changed. Relaxed patient selection criteria, improved clinical management of hearing loss, modifications of surgical practice, and improved devices may explain the differences.

Shallowness of the anterior chamber received special attention after the demonstration by von Graefe (1857) that iridectomy could cure acute glaucoma. Bowman (I862) referred to the care required in performing iridectomies on eyes with shallow anterior chambers.

OBJECTIVE: To test the influence of multiple factors on cochlear implant (CI) speech performance in quiet and in noise for postlinguistically deaf adults, and to design a model of predicted auditory performance with a CI as a function of the significant factors. STUDY DESIGN: Retrospective multi-centre study. METHODS: Data from 2251 patients implanted since 2003 in 15 international centres were collected. Speech scores in quiet and in noise were converted into percentile ranks to remove differences between centres. The influence of 15 pre-, per- and postoperative factors, such as the duration of moderate hearing loss (mHL), the surgical approach (cochleostomy or round window approach), the angle of insertion, the percentage of active electrodes, and the brand of device were tested. The usual factors, duration of profound HL (pHL), age, etiology, duration of CI experience, that are already known to have an influence, were included in the statistical analyses. RESULTS: The significant factors were: the pure tone average threshold of the better ear, the brand of device, the percentage of active electrodes, the use of hearing aids (HAs) during the period of pHL, and the duration of mHL. CONCLUSIONS: A new model was designed showing a decrease of performance that started during the period of mHL, and became faster during the period of pHL. The use of bilateral HAs slowed down the related central reorganization that is the likely cause of the decreased performance.

Importance: Early diagnosis of retinoblastoma, the most common intraocular cancer, can save both a child's life and vision. However, anecdotal evidence suggests that many children across the world are diagnosed late. To our knowledge, the clinical presentation of retinoblastoma has never been assessed on a global scale. Objectives: To report the retinoblastoma stage at diagnosis in patients across the world during a single year, to investigate associations between clinical variables and national income level, and to investigate risk factors for advanced disease at diagnosis. Design, Setting, and Participants: A total of 278 retinoblastoma treatment centers were recruited from June 2017 through December 2018 to participate in a cross-sectional analysis of treatment-naive patients with retinoblastoma who were diagnosed in 2017. Main Outcomes and Measures: Age at presentation, proportion of familial history of retinoblastoma, and tumor stage and metastasis. Results: The cohort included 4351 new patients from 153 countries; the median age at diagnosis was 30.5 (interquartile range, 18.3-45.9) months, and 1976 patients (45.4%) were female. Most patients (n = 3685 [84.7%]) were from low- and middle-income countries (LMICs). Globally, the most common indication for referral was leukocoria (n = 2638 [62.8%]), followed by strabismus (n = 429 [10.2%]) and proptosis (n = 309 [7.4%]). Patients from high-income countries (HICs) were diagnosed at a median age of 14.1 months, with 656 of 666 (98.5%) patients having intraocular retinoblastoma and 2 (0.3%) having metastasis. Patients from low-income countries were diagnosed at a median age of 30.5 months, with 256 of 521 (49.1%) having extraocular retinoblastoma and 94 of 498 (18.9%) having metastasis. Lower national income level was associated with older presentation age, higher proportion of locally advanced disease and distant metastasis, and smaller proportion of familial history of retinoblastoma. Advanced disease at diagnosis was more common in LMICs even after adjusting for age (odds ratio for low-income countries vs upper-middle-income countries and HICs, 17.92 [95% CI, 12.94-24.80], and for lower-middle-income countries vs upper-middle-income countries and HICs, 5.74 [95% CI, 4.30-7.68]). Conclusions and Relevance: This study is estimated to have included more than half of all new retinoblastoma cases worldwide in 2017. Children from LMICs, where the main global retinoblastoma burden lies, presented at an older age with more advanced disease and demonstrated a smaller proportion of familial history of retinoblastoma, likely because many do not reach a childbearing age. Given that retinoblastoma is curable, these data are concerning and mandate intervention at national and international levels. Further studies are needed to investigate factors, other than age at presentation, that may be associated with advanced disease in LMICs.

The Australian Patient Safety Foundation was formed in 1987; it was decided to set up and co-ordinate the Australian Incident Monitoring Study as a function of this Foundation; 90 hospitals and practices joined the study. Participating anaesthetists were invited to report, on an anonymous and voluntary basis, any unintended incident which reduced, or could have reduced, the safety margin for a patient. Any incident could be reported, not only those which were deemed "preventable" or were thought to involve human error. The Mark I AIMS form was developed which incorporated features and concepts from several other studies. All the incidents in this symposium were reported using this form, which contains general instructions to the reporter, key words and space for a narrative of the incident, structured sections for what happened (with subsections for circuitry incidents, circuitry involved, equipment involved, pharmacological incidents and airway incidents), why it happened (with subsections for factors contributing to the incident, factors minimising the incident and suggested corrective strategies), the type of anaesthesia and procedure, monitors in use, when and where the incident happened, the experience of the personnel involved, patient age and a classification of patient outcome. Enrollment, reporting and data-handling procedures are described. Data on patient outcome are presented; this is correlated with the stages at which the incident occurred and with the ASA status of the patients. The locations at which the incidents occurred and the types of procedures, the sets of incidents analysed in detail and a breakdown of the incidents due to drugs are also presented.(ABSTRACT TRUNCATED AT 250 WORDS)

BACKGROUND: This is an update of a Cochrane review first published in The Cochrane Library in Issue 1, 2006 and previously updated in 2009.Idiopathic sudden sensorineural hearing loss (ISSHL) is a clinical diagnosis characterised by a sudden deafness of cochlear or retrocochlear origin in the absence of a clear precipitating cause. Steroids are commonly prescribed to treat this condition. There is no consensus on their effectiveness. OBJECTIVES: To determine whether steroids in the treatment of ISSHL a) improve hearing (primary) and b) reduce tinnitus (secondary).To determine the incidence of significant side effects from the medication. SEARCH METHODS: We searched the Cochrane Ear, Nose and Throat Disorders Group Trials Register; the Cochrane Central Register of Controlled Trials (CENTRAL); PubMed; EMBASE; CINAHL; Web of Science; Cambridge Scientific Abstracts; ICTRP and additional sources for published and unpublished trials. The date of the most recent search was 22 April 2013. SELECTION CRITERIA: We identified all randomised controlled trials (with or without blinding) in which steroids were evaluated in comparison with either no treatment or a placebo. We considered trials including the use of steroids in combination with another treatment if the comparison control group also received the same other treatment. The two authors reviewed the full-text articles of all the retrieved trials of possible relevance and applied the inclusion criteria independently. DATA COLLECTION AND ANALYSIS: We graded trials for risk of bias using the Cochrane approach. The data extraction was performed in a standardised manner by one author and rechecked by the other author. Where necessary we contacted investigators to obtain the missing information. Meta-analysis was neither possible nor considered appropriate because of the heterogeneity of the populations studied and the differences in steroid formulations, dosages and duration of treatment. We analysed and reported the quality of the results of each study individually. A narrative overview of the results is presented. MAIN RESULTS: Only three trials, involving 267 participants, satisfied the inclusion criteria and all three studies were at high risk of bias. One trial showed a lack of effect of oral steroids in improving hearing compared with the placebo control group. The second trial showed a significant improvement of hearing in 61% of the patients receiving oral steroid and in only 32% of the patients from the control group (combination of placebo-treated group and untreated control group). The third trial also showed a lack of effect of oral steroids in improving hearing compared with the placebo control. However, this trial did not follow strict inclusion criteria for participant selection and analysis of data was limited by significant exclusion of participants from the final analysis and lack of participant compliance to the treatment protocol. No clear evidence was presented in two trials about any harmful side effects of the steroids. Only one study declared that no patients suffered from adverse effects of the steroid treatment. AUTHORS' CONCLUSIONS: The value of steroids in the treatment of idiopathic sudden sensorineural hearing loss remains unclear since the evidence obtained from randomised controlled trials is contradictory in outcome, in part because the studies are based upon too small a number of patients.

Human error is a pervasive and normal part of everyday life and is of interest to the anaesthetist because errors may lead to accidents. Definitions of, and the relationships between, errors, incidents and accidents are provided as the basis to this introduction to the psychology of human error in the context of the work of the anaesthetist. Examples are drawn from the Australian Incident Monitoring Study (AIMS). An argument is put forward for the use of contemporaneous incident reporting (eliciting relevant contextual information as well as details of use to cognitive psychologists), rather than the use of accident investigation after the event (with the inherent problems of scant information, altered perception and outcome bias). A classification of errors is provided. "Active" errors may be classified into knowledge-based, rule-based, skill-based and technical errors. Different strategies are required for the prevention of each type and it may now be useful to place more emphasis in anaesthetic practice on categories to which little attention has been directed in the past. "Latent" errors make an enormous contribution to problems in anaesthesia and several categories are discussed (e.g. environment, physiological state, equipment, work practices, personnel training, social and cultural factors). An approach is provided for the prevention and management of errors, incidents and accidents which allows clinical problems to be categorized, the relative importance of various contributing factors to be established, and appropriate preventative strategies to be devised and implemented on the basis of priorities determined from the AIMS data. Accidents cannot be abolished; however, an understanding of the factors underlying them can lead to the rational direction of resources and effort to prevent them and minimise their effects.

OBJECTIVE: Examine the influence of age at implant on speech perception, language, and speech production outcomes in a large unselected paediatric cohort. STUDY DESIGN: This study pools available assessment data (collected prospectively and entered into respective databases from 1990 to 2014) from three Australian centers. PATIENTS: Children (n = 403) with congenital bilateral severe to profound hearing loss who received cochlear implants under 6 years of age (excluding those with acquired onset of profound hearing loss after 12 mo, those with progressive hearing loss and those with mild/moderate/severe additional cognitive delay/disability). MAIN OUTCOME MEASURE(S): Speech perception; open-set words (scored for words and phonemes correct) and sentence understanding at school entry and late primary school time points. Language; PLS and PPVT standard score equivalents at school entry, CELF standard scores. Speech Production; DEAP percentage accuracy of vowels, consonants, phonemes-total and clusters, and percentage word-intelligibility at school entry. RESULTS: Regression analysis indicated a significant effect for age-at-implant for all outcome measures. Cognitive skills also accounted for significant variance in all outcome measures except open-set phoneme scores. ANOVA with Tukey pairwise comparisons examined group differences for children implanted younger than 12 months (Group 1), between 13 and 18 months (Group 2), between 19 and 24 months (Group 3), between 25 and 42 months (Group 4), and between 43 and 72 months (Group 5). Open-set speech perception scores for Groups 1, 2, and 3 were significantly higher than Groups 4 and 5. Language standard scores for Group 1 were significantly higher than Groups 2, 3, 4, and 5. Speech production outcomes for Group 1 were significantly higher than scores obtained for Groups 2, 3, and 4 combined. Cross tabulation and χ2 tests supported the hypothesis that a greater percentage of Group 1 children (than Groups 2, 3, 4, or 5) demonstrated language performance within the normative range by school entry. CONCLUSIONS: Results support provision of cochlear implants younger than 12 months of age for children with severe to profound hearing loss to optimize speech perception and subsequent language acquisition and speech production accuracy.

OBJECTIVES: This study aimed to provide a descriptive analysis of recent evidence available in the literature in relation to the efficacy of unilateral cochlear implantation in adults, the general findings of these studies, and the populations to which these findings apply. It also aimed to appraise the individual success rate and the magnitude of benefit following implantation. DESIGN: A scoping review was conducted to identify English-language, peer-reviewed journal articles published between 2000 and 2018 assessing the outcomes of cochlear implantation in adults who received their first cochlear implant from 2000 onwards. To be included, studies had to report speech perception or self-reported measures of listening or quality of life at least three months after implantation. Systematic searches were conducted in Medline, Embase, Web of Science and Google Scholar. A two-stage screening approach was used, with seven reviewers independently screening titles and abstracts against inclusion criteria and three from this group further reviewing full-texts. A data charting form was developed and trialled, with 10% of the study data extracted in duplicate to compare results and further refine the form. Data relevant for efficacy analyses were extracted from studies with sample sizes of at least 10 participants. RESULTS: A total of 4182 abstracts were screened against inclusion criteria, and of these, 603 full-texts were further screened. After exclusion of non-eligible articles, 201 articles were included in the first part of this scoping review. The majority of these articles were case series or comparative studies without a concurrent group, and had small sample sizes. Data synthesis conducted with the 102 articles with more than 10 participants highlighted that the average word perception ability improved from 8.2% to 53.9% after implantation. Self-reported benefit improved by 21.5 percentage points. At the individual level, 82.0% of adults with postlingual hearing loss and 53.4% of adults with prelingual hearing loss improved their speech perception ability by 15 percentage points or more. A small proportion had poorer ability after implantation or had stopped using the cochlear implant. CONCLUSIONS: Despite broad inconsistencies in measurement, research design, and reporting across articles, it is evident that cochlear implantation is beneficial to the majority of adults of any age who have limited aided speech perception abilities. While many adults with severe-to-profound hearing loss may also have poor speech perception abilities with hearing aids, the validity of using hearing loss severity as a criterion for cochlear implantation has not been demonstrated. Clinical and research recommendations derived from this review are provided.

Primary congenital glaucoma (PCG) is a devastating eye disease and an important cause of childhood blindness worldwide. In PCG, defects in the anterior chamber aqueous humor outflow structures of the eye result in elevated intraocular pressure (IOP); however, the genes and molecular mechanisms involved in the etiology of these defects have not been fully characterized. Previously, we observed PCG-like phenotypes in transgenic mice that lack functional angiopoietin-TEK signaling. Herein, we identified rare TEK variants in 10 of 189 unrelated PCG families and demonstrated that each mutation results in haploinsufficiency due to protein loss of function. Multiple cellular mechanisms were responsible for the loss of protein function resulting from individual TEK variants, including an absence of normal protein production, protein aggregate formation, enhanced proteasomal degradation, altered subcellular localization, and reduced responsiveness to ligand stimulation. Further, in mice, hemizygosity for Tek led to the formation of severely hypomorphic Schlemm's canal and trabecular meshwork, as well as elevated IOP, demonstrating that anterior chamber vascular development is sensitive to Tek gene dosage and the resulting decrease in angiopoietin-TEK signaling. Collectively, these results identify TEK mutations in patients with PCG that likely underlie disease and are transmitted in an autosomal dominant pattern with variable expressivity.

short tandem repeat. Genetic analyses confirmed the pathogenic expansion in 18 of 22 CANVAS-affected families and identified a core ancestral haplotype, estimated to have arisen in Europe more than twenty-five thousand years ago. WGS of the four RFC1-negative CANVAS-affected families identified plausible variants in three, with genomic re-diagnosis of SCA3, spastic ataxia of the Charlevoix-Saguenay type, and SCA45. This study identified the genetic basis of CANVAS and demonstrated that these improved bioinformatics tools increase the diagnostic utility of WGS to determine the genetic basis of a heterogeneous group of clinically overlapping neurogenetic disorders.

BACKGROUND: Identifying mechanisms of diseases with complex inheritance patterns, such as macular telangiectasia type 2, is challenging. A link between macular telangiectasia type 2 and altered serine metabolism has been established previously. METHODS: encoding a subunit of serine palmitoyltransferase (SPT). Because mutations affecting SPT are known to cause hereditary sensory and autonomic neuropathy type 1 (HSAN1), we examined 10 additional persons with HSAN1 for ophthalmologic disease. We assayed serum amino acid and sphingoid base levels, including levels of deoxysphingolipids, in patients who had macular telangiectasia type 2 but did not have HSAN1 or pathogenic variants affecting SPT. We characterized mice with low serine levels and tested the effects of deoxysphingolipids on human retinal organoids. RESULTS: Two variants known to cause HSAN1 were identified as causal for macular telangiectasia type 2: of 11 patients with HSAN1, 9 also had macular telangiectasia type 2. Circulating deoxysphingolipid levels were 84.2% higher among 125 patients with macular telangiectasia type 2 who did not have pathogenic variants affecting SPT than among 94 unaffected controls. Deoxysphingolipid levels were negatively correlated with serine levels, which were 20.6% lower than among controls. Reduction of serine levels in mice led to increases in levels of retinal deoxysphingolipids and compromised visual function. Deoxysphingolipids caused photoreceptor-cell death in retinal organoids, but not in the presence of regulators of lipid metabolism. CONCLUSIONS: or by low serine levels, were risk factors for macular telangiectasia type 2, as well as for peripheral neuropathy. (Funded by the Lowy Medical Research Institute and others.).

Orbital changes in thyroid orbitopathy (TO) result from de novo adipogenesis, hyaluronan synthesis, interstitial oedema and enlargement of extraocular muscles. Cellular immunity, with predominantly CD4+ T cells expressing Th1 cytokines, and overexpression of macrophage-derived cytokines, perpetuate orbital inflammation. Orbital fibroblasts appear to be the major effector cells. Orbital fibroblasts express both thyrotropin receptor (TSHR) and insulin-like growth factor-1 receptor (IGF-1R) at higher levels than normal fibroblasts. TSHR expression increases in adipogenesis; TSHR agonism enhances hyaluronan production. IGF-1R stimulation leads to adipogenesis, hyaluronan synthesis and production of the chemokines, interleukin (IL)-16 and Regulated on Activation, Normal T Cell Expression and Secreted, which facilitate lymphocyte trafficking into the orbit. Immune activation uses a specific CD40:CD154 molecular bridge to activate orbital fibroblasts, which secrete pro-inflammatory cytokines including IL-1β, IL-1α, IL-6, IL-8, macrophage chemoattractant protein-1 and transforming growth factor-β, to perpetuate orbital inflammation. Molecular pathways including adenylyl cyclase/cyclic adenosine monophosphate, phophoinositide 3 kinase/AKT/mammalian target of rapamycin, mitogen-activated protein kinase are involved in TO. The emergence of a TO animal model and a new generation of TSHR antibody assays increasingly point towards TSHR as the primary autoantigen for extrathyroidal orbital involvement. Oxidative stress in TO resulting from imbalances of the oxidation-reduction state provides a framework of understanding for smoking prevention, achieving euthyroidism and the use of antioxidants such as selenium. Progress has been made in the understanding of the pathogenesis of TO, which should advance development of novel therapies targeting cellular immunity, specifically the CD40:CD40 ligand interaction, antibody-producing B cells, cytokines, TSHR and IGF-1R and its signalling pathways. Further studies in signalling networks and molecular triggers leading to burnout of TO will further our understanding of TO.

OBJECTIVE: To compare the accuracy of a new intraocular lens (IOL) power formula (Kane formula) with existing formulas using IOLMaster, predominantly model 3, biometry (measures variables axial length, keratometry and anterior chamber depth) and optimised lens constants. To compare the accuracy of three new or updated IOL power formulas (Kane, Hill-RBF V.2.0 and Holladay 2 with new axial length adjustment) compared with existing formulas (Olsen, Barrett Universal 2, Haigis, Holladay 1, Hoffer Q, SRK/T). METHODS AND ANALYSIS: A single surgeon retrospective case review was performed from patients having uneventful cataract surgery with Acrysof IQ SN60WF IOL implantation over 11 years in a Melbourne private practice. Using optimised lens constants, the predicted refractive outcome for each formula was calculated for each patient. This was compared with the actual refractive outcome to give the prediction error. Eyes were separated into subgroups based on axial length as follows: short (≤22.0 mm), medium (>22.0 to <26.0 mm) and long (≥26.0 mm). RESULTS: The study included 846 patients. Over the entire axial length range, the Kane formula had the lowest mean absolute prediction error (p<0.001, all formulas). The mean postoperative difference from intended outcome for the Kane formula was -0.14+0.27×1 (95% LCL -1.52+0.93×43; 95% UCL +0.54+1.03×149). The formula demonstrated the lowest absolute error in the medium axial length range (p<0.001). In the short and long axial length groups, no formula demonstrated a significantly lower absolute mean prediction error. CONCLUSION: Using three variables (AL, K, ACD), the Kane formula was a more accurate predictor of actual postoperative refraction than the other formulae under investigation. There were not enough eyes of short or long axial length to adequately power statistical comparisons within axial length subgroups.

DNA methylation is an essential mechanism controlling gene expression during differentiation and development. We investigated the epigenetic regulation of the nuclear-encoded, mitochondrial DNA (mtDNA) polymerase γ catalytic subunit (PolgA) by examining the methylation status of a CpG island within exon 2 of PolgA. Bisulphite sequencing identified low methylation levels (<10%) within exon 2 of mouse oocytes, blastocysts and embryonic stem cells (ESCs), while somatic tissues contained significantly higher levels (>40%). In contrast, induced pluripotent stem (iPS) cells and somatic nuclear transfer ESCs were hypermethylated (>20%), indicating abnormal epigenetic reprogramming. Real time PCR analysis of 5-methylcytosine (5mC) and 5-hydroxymethylcytosine (5hmC) immunoprecipitated DNA suggests active DNA methylation and demethylation within exon 2 of PolgA. Moreover, neural differentiation of ESCs promoted de novo methylation and demethylation at the exon 2 locus. Regression analysis demonstrates that cell-specific PolgA expression levels were negatively correlated with DNA methylation within exon 2 and mtDNA copy number. Finally, using chromatin immunoprecipitation (ChIP) against RNA polymerase II (RNApII) phosphorylated on serine 2, we show increased DNA methylation levels are associated with reduced RNApII transcriptional elongation. This is the first study linking nuclear DNA epigenetic regulation with mtDNA regulation during differentiation and cell specialization.

PURPOSE: To review the clinical features, treatment, outcome and survival of metastatic tumors of the orbit. MATERIALS AND METHODS: Retrospective, non-comparative, chart review of 80 patients with orbital metastasis treated in four tertiary orbital centres in Australia. RESULTS: The study included 80 patients of which, 44 were male with a mean age of 60 years. Orbital involvement commonly presented late in a multisystemic disease; however, the orbit was the first presentation in 15% of the cases. Diplopia (48%), pain (42%), and visual loss (30%) were the commonest symptoms at presentation; whereas proptosis (63%), strabismus (62%), and visual loss (41%) were the most frequent clinical signs. Computed tomography commonly showed a solid enhancing mass (42 cases) located within the orbital fat (43%), or enlarging an extraocular muscle (28%). Breast carcinoma (29%), melanoma (20%), and prostatic cancer (13%) were the most frequent histological types. Treatment was often multi-disciplinary and modalities included radiotherapy, chemotherapy, hormone therapy, surgery, and immunotherapy. Survival was limited to 1.5 years after diagnosis independent of the histological type, with 29% of patients alive after 17 months follow-up. CONCLUSIONS: A high index of suspicion and appropriate intervention with histological diagnosis can help in the management and quality of life in patients with metastatic orbital disease. Overall survival is limited and we encountered statistical limitations proving differences in the survival based on the sub-type of primary tumour involved. Metastatic orbital melanoma presented a higher incidence when compared with previous studies, probably due to the increase frequency of skin found in the Australian population.

Primary open-angle glaucoma (POAG) is the leading cause of irreversible blindness worldwide for which 15 disease-associated loci had been discovered. Among them, only 5 loci have been associated with POAG in Asians. We carried out a genome-wide association study and a replication study that included a total of 7378 POAG cases and 36 385 controls from a Japanese population. After combining the genome-wide association study and the two replication sets, we identified 11 POAG-associated loci, including 4 known (CDKN2B-AS1, ABCA1, SIX6 and AFAP1) and 7 novel loci (FNDC3B, ANKRD55-MAP3K1, LMX1B, LHPP, HMGA2, MEIS2 and LOXL1) at a genome-wide significance level (P < 5.0×10-8), bringing the total number of POAG-susceptibility loci to 22. The 7 novel variants were subsequently evaluated in a multiethnic population comprising non-Japanese East Asians (1008 cases, 591 controls), Europeans (5008 cases, 35 472 controls) and Africans (2341 cases, 2037 controls). The candidate genes located within the new loci were related to ocular development (LMX1B, HMGA2 and MAP3K1) and glaucoma-related phenotypes (FNDC3B, LMX1B and LOXL1). Pathway analysis suggested epidermal growth factor receptor signaling might be involved in POAG pathogenesis. Genetic correlation analysis revealed the relationships between POAG and systemic diseases, including type 2 diabetes and cardiovascular diseases. These results improve our understanding of the genetic factors that affect the risk of developing POAG and provide new insight into the genetic architecture of POAG in Asians.

The International Society for Clinical Electrophysiology of Vision (ISCEV) Standard for full-field electroretinography (ERG) describes a minimum procedure, but encourages more extensive testing. This ISCEV extended protocol describes an extension to the ERG Standard, namely the photopic negative response (PhNR) of the light-adapted flash ERG, as a well-established technique that is broadly accepted by experts in the field. The PhNR is a slow negative-going wave after the b-wave that provides information about the function of retinal ganglion cells and their axons. The PhNR can be reduced in disorders that affect the innermost retina, including glaucoma and other forms of optic neuropathy. This document, based on existing literature, provides a protocol for recording and analyzing the PhNR in response to a brief flash. The protocol includes full-field stimulation, a frequency bandwidth of the recording in which the lower limit does not exceed 0.3 Hz, and a spectrally narrowband stimulus, specifically, a red flash on a rod saturating blue background. Suggested flash strengths cover a range up to and including the minimum required to elicit a maximum amplitude PhNR. This extended protocol for recording the PhNR provides a simple test of generalized retinal ganglion cell function that could be added to standard ERG testing.

This study reviews the cochlear histology from four hearing preservation cochlear implantation experiments conducted on 73 guinea pigs from our institution, and relates histopathological findings to residual hearing. All guinea pigs had normal hearing prior to surgery and underwent cochlear implantation via a cochleostomy with a silastic-platinum dummy electrode. Pure tone auditory brainstem response (ABR) thresholds from 2 to 32 kHz were recorded prior to surgery, and at one and four weeks postoperatively. The cochleae were then fixed in paraformaldehyde, decalcified, paraffin embedded, and mid-modiolar sections were prepared. The treatment groups were as follows: 1) Systemic dexamethasone, 0.2 mg/kg administered 1 h before implantation, 2) Local dexamethasone, 2% applied topically to the round window for 30 min prior to cochlear implantation, 3) Local n-acetyl cysteine, 200 μg applied topically to the round window for 30 min prior to implantation, 4) inoculation to keyhole-limpet hemocyanin (KLH) prior to implantation, and 5) untreated controls. There was a significant correlation between the extent of the tissue reaction in the cochlea and the presence of foreign body giant cells (FBGCs), new bone formation and injury to the osseous spiral lamina (OSL). The extent of the tissue response, as a percentage of the area of the scala tympani, limited the best hearing that was observed four weeks after cochlear implantation. Poorer hearing at four weeks correlated with a more extensive tissue response, lower outer hair cell (OHC) counts and OSL injury in the basal turn. Progressive hearing loss was also correlated with the extent of tissue response. Hearing at 2 kHz, which corresponds to the region of the second cochlear turn, did not correspond with loco-regional inner hair cell (IHC), OHC or SGC counts. We conclude that cochlear injury is associated with poorer hearing early after implantation. The tissue response is related to indices of cochlear inflammation and injury. An extensive tissue response limits hearing at four weeks, and correlates with progressive hearing loss. These latter effects may be due to inflammation, but would also be consistent with interference of cochlear mechanics.

BACKGROUND: Bacterial orbital cellulitis is an uncommon condition previously associated with severe complications. The purpose of this paper is to describe current investigations and treatment in orbital cellulitis, establish their effectiveness and to describe the incidence of complications and surgical intervention. METHODS: A chart review of all patients admitted to the Royal Victorian Eye and Ear Hospital and the Royal Children's Hospital, Melbourne with a diagnosis of orbital cellulitis for the period July 1993 to July 1997. RESULTS: A total of 52 patients fulfilling the diagnostic criteria for orbital cellulitis were identified. Paranasal sinus disease was the commonest predisposing cause, especially in the paediatric age group. Diagnosis was made clinically with radiological confirmation in all cases. Microbiological investigation and results varied. The commonest species isolated were Staphylococci and Streptococci. Three cases of mixed anaerobes and one of Clostridium were seen. Cultures from abscess cavities and infected sinuses gave the highest positive yield (50-100%). Blood cultures were taken in 26% of adults and in 56% of children; none was positive. Treatment was either by intravenous broad-spectrum antibiotics alone or with surgery to drain orbital abscesses, usually n conjunction with sinus surgery. No patient suffered permanent visual impairment other than one case of enucleation for endophthalmitis that had caused orbital cellulitis. There was one case of permanent ocular motility impairment, and one of meningitis. CONCLUSIONS: Despite its past history of severe morbidity and even mortality, adequately treated orbital cellulitis rarely has significant morbidity today. Paranasal sinus disease remains the commonest cause. Culture of infected paranasal sinuses or pus from abscesses is most likely to yield significantly positive results in this study. Blood cultures were not helpful.