NAION or not NAION? A literature review of pathogenesis and differential diagnosis of anterior ischaemic optic neuropathies.

PURPOSE: To offer a comprehensive review of the available data regarding non-arteritic anterior ischaemic optic neuropathy and its phenocopies, focusing on the current evidence to support the different existing aetiopathogenic hypotheses for the development of these conditions. CONCLUSIONS AND IMPORTANCE: Due to the limited array of responses of the neural tissue and other retinal structures, different aetiopathogenic mechanisms may result in a similar clinical picture. Moreover, when the insult occurs within a confined space, such as the optic nerve or the optic nerve head, in which different tissues (neural, glial, vascular) are highly interconnected and packed together, determining the primary noxa can be challenging and may lead to misdiagnosis. Anterior ischaemic optic neuropathy is a condition most clinicians will face during their everyday work, and it is important to correctly differentiate among resembling pathologies affecting the optic nerve to avoid unnecessary diagnostic procedures. Combining a good clinical history and multimodal imaging can assist diagnosis in most cases. The key remains to combine demographic data (e.g. age), with ophthalmic data (e.g. refractive error), systemic data (e.g. comorbidities and medication), imaging data (e.g. retinal OCT) with topographic signs (e.g. focal neurology). METHODOLOGY: Papers relevant for this work were obtained from the MEDLINE and Embase databases by using the PubMed search engine. One author (MPMG) performed the search and selected only publications with relevant information about the aetiology, pathogenic mechanisms, risk factors as well as clinical characteristics of phenocopies (such as vitreopapillary traction, intrapapillary haemorrhage with adjacent peripapillary subretinal haemorrhage or diabetic papillopathy) of non-arteritic anterior ischaemic optic neuropathy (NAION). The terms "non-arteritic ischaemic optic neuropathy/NAION", "vitreopapillary traction", "vitreopapillary traction AND non-arteritic ischaemic optic neuropathy/NAION", "posterior vitreous detachment AND non-arteritic ischaemic optic neuropathy/NAION", "central retinal vein occlusion AND non-arteritic ischaemic optic neuropathy/NAION", "disc oedema/disc oedema", "diabetes mellitus AND non-arteritic ischaemic optic neuropathy/NAION" and "diabetic papillopathy" were searched on PubMed. From each of these searches, publications were selected based on their title, obtaining a total of 115 papers. All papers not written in English were then excluded, and those whose abstracts were not deemed relevant for our review, according to the aforementioned criteria. Subsequent scrutiny of the main text of the remaining publications led us (MPMG, AP, ZS) to include references which had not been selected during our first search, as their titles did not contain the previously mentioned MeSH terms, due to their significantly relevant contents for our work. A total of 62 publications were finally consulted for our review. The literature review was last updated on 24-Aug-2022.

Choroidal macrovessels: multimodal imaging findings and review of the literature.

BACKGROUND/AIMS: To describe clinical and multimodal imaging features in a cohort of choroidal macrovessels. METHODS: Demographics and multimodal imaging features of 16 eyes of 13 patients with choroidal macrovessels were reviewed. The multimodal imaging included colour fundus photography, fundus autofluorescence (FAF), spectral domain enhanced depth imaging optical coherence tomography (OCT), en face OCT, OCT-angiography (OCT-A), B-scan ultrasonography (US), fluorescein angiography (FFA) and indocyanine green angiography (ICGA). RESULTS: Three patients had bilateral involvement. On colour fundus photography, three patterns were evident (a clearly visible orange-red vessel; a track of pigmentary changes; spots of mild pigmentary changes). Vessel orientation was horizontal (11 eyes), oblique (4 eyes) or vertical (1 eye). In 2 eyes, the vessel was extra-macular. OCT in all cases showed a hyporeflective choroidal area with posterior shadowing and elevation of the overlying retina. Subretinal fluid was present in 4 eyes. FAF (12 eyes) was normal (7 eyes) or showed a hypofluorescent/hyperfluorescent track (4 eyes) or linear hyperautofluorescence (1 eye). En-face OCT (2 eyes) revealed the course of the macrovessel at the level of choroid and choriocapillaris. On OCT-A (2 eyes) the vessel had a reflectivity similar to surrounding vessels but larger diameter. B-scan US (8 eyes) showed a nodular hypoechogenic lesion. FFA (5 eyes) showed early focal hyperfluorescence (4 eyes) not increasing in later phases, or was normal (1 eye). ICGA (6 eyes) showed early hyperfluorescence of the vessel. CONCLUSIONS: Choroidal macrovessels can mimic other entities, leading to underdiagnosis. Appreciating relevant features on different imaging modalities will aid a correct diagnosis.

AN ASSOCIATION BETWEEN STELLATE NONHEREDITARY IDIOPATHIC FOVEOMACULAR RETINOSCHISIS, PERIPHERAL RETINOSCHISIS, AND POSTERIOR HYALOID ATTACHMENT.

PURPOSE: Stellate nonhereditary idiopathic foveomacular retinoschisis is a disorder characterized by splitting of the retina at the macula, without a known underlying mechanical or inherited cause. This study investigates demographic, anatomical, and functional characteristics of subjects with stellate nonhereditary idiopathic foveomacular retinoschisis, to explore potential underlying mechanisms. METHODS: In this single-site, retrospective, and cross-sectional, observational study, data were collected from 28 eyes from 24 subjects with stellate nonhereditary idiopathic foveomacular retinoschisis. Descriptive statistics were reported, based on the observed anatomico-functional features. RESULTS: The visual acuity remained stable (median 20/20) in all subjects over a median follow-up of 17 months. All cases demonstrated foveomacular retinoschisis within Henle's fiber layer, at the junction of the outer plexiform and outer nuclear layers. This schisis cavity extended beyond the limits of the macular OCT temporally in all eyes. In most affected eyes, there were documented features of peripheral retinoschisis and broad attachment of the posterior hyaloid at the macula. Functional testing in a cross-sectional subset demonstrated normal retinal sensitivity centrally but an absolute scotoma peripherally. CONCLUSION: Stellate nonhereditary idiopathic foveomacular retinoschisis seems to be associated with peripheral retinoschisis and anomalous or incomplete posterior hyaloid detachment. Despite chronic manifestation, this does not significantly affect central visual function but can manifest with profound loss of peripheral visual function.

Comparative Analysis of Anterior Chamber Flare Grading between Clinicians with Different Levels of Experience and Semi-automated Laser Flare Photometry.

PURPOSE: To assess correlation for anterior chamber flare grading between clinicians with different levels of experience and with semi-automated flare reading in a cohort of patients with heterogeneous uveitic entities. METHODS: Fifty-nine observations from 36 patients were recorded and analyzed for statistical association. In each patient, flare was assessed objectively using the Kowa FM-700 laser flare photometer, and subjective masked grading by two clinicians was performed. RESULTS: The study demonstrated disparity in flare readings between clinical graders with one step disagreement in clinical grading in 26 (44.06%) eyes (p < 0.001) and concordance between the flare readings by experienced grader and flare photometry. After review of semi-automated flare readings, management was changed in 11% of the patients. CONCLUSION: Laser flare photometry can be a valuable tool to remove the observer bias in grading flare for selected cohort of uveitis patients. It can be further applied to titrate therapy in intraocular inflammation.

Classification of semi-automated flare readings using the Kowa FM 700 laser cell flare meter in patients with uveitis.

PURPOSE: To propose a classification system to grade semi-automated flare readings and assess its correlation with clinical flare grading and also to explore the utility of an additional step in clinical flare assessment between grades 0 and 1. METHODS: Semi-automated flare readings from 103 eyes with uveitis were taken using the Kowa FM 700 laser flare meter and classified into two models (LFCM and LFCM_1), and introduction of a 0.5 step in flare grading was explored. RESULTS: Good correlation was present between the conventional SUN clinical flare and the proposed clinical classification for flare (weighted kappa (WK) = 89.64%, p < 0.001). Semi-automated flare grading (LFCM and LFCM_1) had WK agreement of 82.52% and 79.85% (p < 0.001) with conventional SUN clinical flare grading. CONCLUSIONS: The proposed classification system for semi-automated laser flare readings (LFCM) allows stratification of measurements into grades analogous to clinical flare grades and correlates well with conventional clinical flare grading.

A prospective randomised controlled clinical trial comparing a combination of repeated intravitreal Ozurdex and macular laser therapy versus macular laser only in centre-involving diabetic macular oedema (OZLASE study).

BACKGROUND/AIMS: To evaluate the clinical efficacy and safety of combined repeated Ozurdex and macular laser therapy (MLT) compared with MLT monotherapy in participants with visual impairment due to centre-involving diabetic macular oedema (DMO). METHODS: 80 patients with best corrected visual acuity (BCVA) between 54 and 78 ETDRS letters due to centre-involving DMO were randomised to combination therapy with Ozurdex and MLT or MLT only. The combination arm received mandated Ozurdex injections at baseline and 16 weeks followed by retreatment criteria-guided pro-re-nata therapy at 32 and 48 weeks. Patients randomised to MLT only were treated every 16 weeks if clinically significant macular oedema was present. The primary outcome was the mean change from baseline in BCVA between arms at 56 weeks. RESULTS: The mean change in BCVA at 56 weeks was -0.3 (SD 11.4) ETDRS letters in the combination arm versus +0.4 (SD 9.6) ETDRS (Early Treatment Diabetic Retinopathy study) letters in the MLT arm (effect estimate 1.15 (95% CI -3.32 to 5.61)). However, at 56 weeks, a post hoc comparison of central subfield thickness (CST) showed a decrease of -113 µm (IQR -218, -64) (combination) versus -17 µm (-128, 12) (MLT arm) (p<0.001). Elevated intraocular pressure requiring topical therapy was observed in 8 (20%) eyes in the combination versus 1 (2.5%) in the MLT arm. 33% (9/27) of phakic patients in the combination arm underwent cataract surgery. CONCLUSIONS: Visual outcome following combination therapy did not differ from MLT alone in the centre-involving DMO despite a significant decrease in CST likely due to an entry visual acuity-related ceiling effect and cataract development. TRIAL REGISTRATION NUMBER: EudraCT 2011-003339-74.

A detailed clinical and molecular survey of subjects with nonsyndromic USH2A retinopathy reveals an allelic hierarchy of disease-causing variants.

Defects in USH2A cause both isolated retinal disease and Usher syndrome (ie, retinal disease and deafness). To gain insights into isolated/nonsyndromic USH2A retinopathy, we screened USH2A in 186 probands with recessive retinal disease and no hearing complaint in childhood (discovery cohort) and in 84 probands with recessive retinal disease (replication cohort). Detailed phenotyping, including retinal imaging and audiological assessment, was performed in individuals with two likely disease-causing USH2A variants. Further genetic testing, including screening for a deep-intronic disease-causing variant and large deletions/duplications, was performed in those with one likely disease-causing change. Overall, 23 of 186 probands (discovery cohort) were found to harbour two likely disease-causing variants in USH2A. Some of these variants were predominantly associated with nonsyndromic retinal degeneration ('retinal disease-specific'); these included the common c.2276 G>T, p.(Cys759Phe) mutation and five additional variants: c.2802 T>G, p.(Cys934Trp); c.10073 G>A, p.(Cys3358Tyr); c.11156 G>A, p.(Arg3719His); c.12295-3 T>A; and c.12575 G>A, p.(Arg4192His). An allelic hierarchy was observed in the discovery cohort and confirmed in the replication cohort. In nonsyndromic USH2A disease, retinopathy was consistent with retinitis pigmentosa and the audiological phenotype was variable. USH2A retinopathy is a common cause of nonsyndromic recessive retinal degeneration and has a different mutational spectrum to that observed in Usher syndrome. The following model is proposed: the presence of at least one 'retinal disease-specific' USH2A allele in a patient with USH2A-related disease results in the preservation of normal hearing. Careful genotype-phenotype studies such as this will become increasingly important, especially now that high-throughput sequencing is widely used in the clinical setting.

Optic neuropathy secondary to Linezolid for multidrug-resistant mycobacterial spinal tuberculosis.

AIM: To report a case of optic neuropathy secondary to Linezolid, second line anti tuberculosis agent. CASE REPORT: 22 year Indian male with multidrug resistant spinal tuberculosis and TB meningitis was started on second line anti tuberculosis drugs. Within one month of onset of second line anti TB drug, he was noted to have optic neuropathy in both eyes. Visual field and electro diagnostics suggested optic neuropathy. DISCUSSION: Linezolid is a synthetic oxazolidinone broad spectrum antibiotic and has been in off label use for multidrug resistant tuberculosis (MDR-TB). There are very scattered case reports of optic neuropathy secondary to use of this off label drug. In our case, the optic neuropathy was however reversible on stoppage of the drug. CONCLUSION: It seems prudent that baseline ophthalmological evaluation to be done for all patients to be subjected for treatment with this drug for any short term or long term therapy.

The effect of the common c.2299delG mutation in USH2A on RNA splicing.

Recessive variants in the USH2A gene are an important cause of both Usher syndrome and nonsyndromic retinitis pigmentosa. A single base-pair deletion in exon 13 (c.2299delG, p.Glu767Serfs*21) is considered the most frequent mutation of USH2A. It is predicted to generate a premature termination codon and is presumed to lead to nonsense mediated decay. However the effect of this variant on RNA has not been formally investigated. It is not uncommon for exonic sequence alterations to cause aberrant splicing and the aim of the present report is to evaluate the effect of c.2299delG on USH2A transcripts. Nasal cells represent the simplest available tissue to study splicing defects in USH2A. Nasal brushing, RNA extraction from nasal epithelial cells and reverse transcription PCR were performed in five Usher syndrome patients who were homozygous for c.2299delG, two unaffected c.2299delG heterozygotes and seven control individuals. Primers to amplify between exons 12 and 15 and exons 10 and 14 were utilised. Significant variability was observed between different RT-PCR experiments. Importantly, in controls, PCR product of the expected size were amplified on all occasions (13/13 experiments); for patients this was true in only 4/14 experiments (Fisher exact test p = 0.0002). Bioinformatics tools predict the c.2299delG change to disrupt an exonic splicing enhancer and to create an exonic splicing silencer within exon 13. Here, we report an effect of the common c.2299delG mutation on splicing of exons 12 and 13 of USH2A. Future studies are expected to provide important insights into the contribution of this effect on the phenotype.

Natural history and retinal structure in patients with Usher syndrome type 1 owing to MYO7A mutation.

PURPOSE: To evaluate the phenotypic variability and natural history of ocular disease in a cohort of 28 individuals with MYO7A-related disease. Mutations in the MYO7A gene are the most common cause of Usher syndrome type 1, characterized by profound congenital deafness, vestibular arreflexia, and progressive retinal degeneration. DESIGN: Retrospective case series. PARTICIPANTS: Twenty-eight patients from 26 families (age range, 3-65 years; median, 32) with 2 likely disease-causing variants in MYO7A. METHODS: Clinical investigations included fundus photography, optical coherence tomography, fundus autofluorescence (FAF) imaging, and audiologic and vestibular assessments. Longitudinal visual acuity and FAF data (over a 3-year period) were available for 20 and 10 study subjects, respectively. MAIN OUTCOME MEASURES: Clinical, structural, and functional characteristics. RESULTS: All patients with MYO7A mutations presented with features consistent with Usher type 1. The median visual acuity for the cohort was 0.39 logarithm of the minimum angle of resolution (logMAR; range, 0.0-2.7) and visual acuity in logMAR correlated with age (Spearman's rank correlation coefficient, r = 0.71; P<0.0001). Survival analysis revealed that acuity ≤ 0.22 logMAR was maintained in 50% of studied subjects until age 33.9; legal blindness based on loss of acuity (≥ 1.00 logMAR) or loss of field (≤ 20°) was reached at a median age of 40.6 years. Three distinct patterns were observed on FAF imaging: 13 of 22 patients tested had relatively preserved foveal autofluorescence surrounded by a ring of high density, 4 of 22 had increased signal in the fovea with no obvious hyperautofluorescent ring, and 5 of 22 had widespread hypoautofluorescence corresponding to retinal pigment epithelial atrophy. Despite a number of cases presenting with a milder phenotype, there seemed to be no obvious genotype-phenotype correlation. CONCLUSIONS: MYO7A-related ocular disease is variable. Central vision typically remains preserved at least until the third decade of life, with 50% of affected individuals reaching legal blindness by 40 years of age. Distinct phenotypic subsets were identified on FAF imaging. A specific allele, previously reported in nonsyndromic deafness, may be associated with a mild retinopathy.

Comparison of fundus autofluorescence with photopic and scotopic fine matrix mapping in patients with retinitis pigmentosa: 4- to 8-year follow-up.

PURPOSE: To assess the significance and evolution of parafoveal rings of high-density fundus autofluorescence (AF) in 12 patients with retinitis pigmentosa (RP). METHODS: Twelve patients with autosomal recessive RP or Usher syndrome type 2 were ascertained who had a parafoveal ring of high-density AF and a visual acuity of 20/30 or better at baseline. Photopic and scotopic fine matrix mapping (FMM) were performed to test sensitivity across the macula. AF imaging and FMM were repeated after 4 to 8 years and optical coherence tomography (OCT) performed. RESULTS: The size of the AF ring reduced over time and disappeared in one subject. Photopic thresholds were normal over the fovea; thresholds were elevated by 0.6 log units over the ring and by 1.2 log units external to the ring at baseline and differed by less than 0.1 log unit at follow-up. Mild photopic losses close to the internal edge of the ring were detected at baseline or follow-up in all. Mean scotopic thresholds over parafoveal areas within the ring were markedly elevated in 8 of 10 at baseline and were severely elevated in 9 of 11 at follow-up. The eccentricity of the inner edge of the AF ring corresponded closely with the lateral extent of the inner segment ellipsoid band in the OCT image. CONCLUSIONS: Ring constriction was largely coincident with progressive centripetal photopic threshold elevation led by worsening of rod photoreceptor function. The rate of constriction differed across patients, and a ring may reach a critical minimum before disappearing, at which stage central visual loss occurs. The structural and functional changes associated with rings of increased autofluorescence confirm that they provide an objective index of macular involvement and may aid the management of RP patients and the monitoring of future treatment efficacy.

Comprehensive sequence analysis of nine Usher syndrome genes in the UK National Collaborative Usher Study.

BACKGROUND: Usher syndrome (USH) is an autosomal recessive disorder comprising retinitis pigmentosa, hearing loss and, in some cases, vestibular dysfunction. It is clinically and genetically heterogeneous with three distinctive clinical types (I-III) and nine Usher genes identified. This study is a comprehensive clinical and genetic analysis of 172 Usher patients and evaluates the contribution of digenic inheritance. METHODS: The genes MYO7A, USH1C, CDH23, PCDH15, USH1G, USH2A, GPR98, WHRN, CLRN1 and the candidate gene SLC4A7 were sequenced in 172 UK Usher patients, regardless of clinical type. RESULTS: No subject had definite mutations (nonsense, frameshift or consensus splice site mutations) in two different USH genes. Novel missense variants were classified UV1-4 (unclassified variant): UV4 is 'probably pathogenic', based on control frequency <0.23%, identification in trans to a pathogenic/probably pathogenic mutation and segregation with USH in only one family; and UV3 ('likely pathogenic') as above, but no information on phase. Overall 79% of identified pathogenic/UV4/UV3 variants were truncating and 21% were missense changes. MYO7A accounted for 53.2%, and USH1C for 14.9% of USH1 families (USH1C:c.496+1G>A being the most common USH1 mutation in the cohort). USH2A was responsible for 79.3% of USH2 families and GPR98 for only 6.6%. No mutations were found in USH1G, WHRN or SLC4A7. CONCLUSIONS: One or two pathogenic/likely pathogenic variants were identified in 86% of cases. No convincing cases of digenic inheritance were found. It is concluded that digenic inheritance does not make a significant contribution to Usher syndrome; the observation of multiple variants in different genes is likely to reflect polymorphic variation, rather than digenic effects.

Mutations in the USH1C gene associated with sector retinitis pigmentosa and hearing loss.

PURPOSE: To determine the molecular cause of sector retinitis pigmentosa and hearing loss in two affected siblings. METHODS: Direct DNA sequencing of the USH1C gene was performed in two affected siblings. Putative pathogenic sequence changes were assayed in their parent's chromosomes and in control chromosomes. Clinical examination included visual acuity measurement, visual field measurement, electrophysiologic assessment, and fine matrix mapping. Retinal imaging with fundus photography, scanning laser ophthalmoscope (fundus autofluorescence), and optical coherence tomography was performed. Hearing and vestibular function was also assessed. RESULTS: The siblings were aged 42 years and 40 years, and both were compound heterozygotes for the p.R103H missense change and the novel splice site change c.2227-1G>A in the USH1C gene. Both alleles were found to be in trans. Neither allele was identified in a panel of 866 control chromosomes, and both were considered pathogenic. Both siblings had sector retinitis pigmentosa restricted to the inferior and nasal retina. Fundus autofluorescence imaging showed a clear demarcation between normal and abnormal areas of retina, which corresponded to areas of reduced sensitivity on fine matrix mapping and loss of visual field. Both siblings had severe hearing loss but were able to develop language. CONCLUSION: We report a novel molecular cause of sector retinitis pigmentosa associated with hearing loss representing a new phenotype associated with mutations in the USH1C gene.

Update on Usher syndrome.

PURPOSE OF REVIEW: The present review addresses the mechanisms, genetics and pathogenesis of Usher syndrome. RECENT FINDINGS: Recent molecular findings have provided more information regarding the pathogenesis of this disorder and the wide phenotypic variation in both audiovestibular and/or visual systems. Evidence has begun to emerge supporting a theory of a protein interactome involving the Usher proteins in both the inner ear and the retina. This interactome appears to be important for hair cell development in the ear but its role in the retina remains unclear. SUMMARY: Understanding clinical disease progression and molecular pathways is important in the progress towards developing gene therapy to prevent blindness due to Usher syndrome as well as delivering prognostic information to affected individuals.

Functional characteristics of patients with retinal dystrophy that manifest abnormal parafoveal annuli of high density fundus autofluorescence; a review and update.

PURPOSE: To examine the presence and functional significance of annular fundus autofluorescence abnormalities in patients with different retinal dystrophies. METHODS: Eighty one patients were ascertained who had a parafoveal ring of high density on fundus autofluorescence imaging. Sixty two had had a clinical diagnosis of retinitis pigmentosa (RP) or Usher syndrome with normal visual acuity. Others included a case of Leber congenital amaurosis and genetically confirmed cases of cone or cone-rod dystrophy (GUCA1A, RPGR, RIMS1), "cone dystrophy with supernormal rod ERG" (KCNV2) and X-linked retinoschisis (RS1). International-standard full-field and pattern electroretinography (ERG; PERG) were performed. Some patients with rod-cone or cone-rod dystrophy underwent multifocal ERG (mfERG) testing and photopic and scotopic fine matrix mapping (FMM). RESULTS: In patients with RP, the radius of the parafoveal ring of high density correlated with PERG P50 (R = 0.83, P < 0.0005, N = 62) and encircled areas of preserved photopic function. In the other patients, AF rings either resembled those seen in RP or encircled an area of central atrophy. Ring radius was inversely related to the PERG P50 component in 4 of 18 cases with a detectable response. FMM showed that arcs of high density were associated with a gradient of sensitivity change. CONCLUSIONS: Parafoveal rings of high density autofluorescence are a non-specific manifestation of retinal dysfunction that can occur in different retinal dystrophies. Electrophysiology remains essential for accurate diagnosis. The high correlation of autofluorescence with PERG, mfERG and FMM demonstrates that AF abnormalities have functional significance and may help identify suitable patients and retinal areas amenable to future therapeutic intervention.

Development of a genotyping microarray for Usher syndrome.

BACKGROUND: Usher syndrome, a combination of retinitis pigmentosa (RP) and sensorineural hearing loss with or without vestibular dysfunction, displays a high degree of clinical and genetic heterogeneity. Three clinical subtypes can be distinguished, based on the age of onset and severity of the hearing impairment, and the presence or absence of vestibular abnormalities. Thus far, eight genes have been implicated in the syndrome, together comprising 347 protein-coding exons. METHODS: To improve DNA diagnostics for patients with Usher syndrome, we developed a genotyping microarray based on the arrayed primer extension (APEX) method. Allele-specific oligonucleotides corresponding to all 298 Usher syndrome-associated sequence variants known to date, 76 of which are novel, were arrayed. RESULTS: Approximately half of these variants were validated using original patient DNAs, which yielded an accuracy of >98%. The efficiency of the Usher genotyping microarray was tested using DNAs from 370 unrelated European and American patients with Usher syndrome. Sequence variants were identified in 64/140 (46%) patients with Usher syndrome type I, 45/189 (24%) patients with Usher syndrome type II, 6/21 (29%) patients with Usher syndrome type III and 6/20 (30%) patients with atypical Usher syndrome. The chip also identified two novel sequence variants, c.400C>T (p.R134X) in PCDH15 and c.1606T>C (p.C536S) in USH2A. CONCLUSION: The Usher genotyping microarray is a versatile and affordable screening tool for Usher syndrome. Its efficiency will improve with the addition of novel sequence variants with minimal extra costs, making it a very useful first-pass screening tool.

Nurse triage, diagnosis and treatment of eye casualty patients: a study of quality and utility.

INTRODUCTION: Patients presenting to the Accident and Emergency department of a district general hospital with an eye problem are referred directly to a dedicated eye casualty service. They are then triaged by a staff nurse from the eye department. This eye casualty sees around 8000 patients per annum. This study assesses whether the nurse triage of eye casualty patients forms an effective filter of problems which do not require the attention of the doctor on duty. The incidence of cases of misdiagnosis and inappropriate discharge of patients resulting in a delay in diagnosis and treatment was also assessed. METHODS: All patients presenting in a 3-month period managed solely by the triage nurse, were identified from the casualty register, and the hospital records retrieved and examined. RESULTS: Four hundred and forty of a total 1976 patients (22%) were seen exclusively by triage nurses; eight (2.5%) of these 440 patients returned unplanned to the eye department. In all cases it was considered that the return of the patient would not have been preventable by initial attention of the ophthalmologist on duty. DISCUSSION: With appropriate threshold for referral, nurses trained in slit lamp examination can offer a successful service to safely diagnose and treat common eye casualty presentations.