A genome-wide association study identifies a functional ERAP2 haplotype associated with birdshot chorioretinopathy.

Birdshot chorioretinopathy (BSCR) is a rare form of autoimmune uveitis that can lead to severe visual impairment. Intriguingly, >95% of cases carry the HLA-A29 allele, which defines the strongest documented HLA association for a human disease. We have conducted a genome-wide association study in 96 Dutch and 27 Spanish cases, and 398 unrelated Dutch and 380 Spanish controls. Fine-mapping the primary MHC association through high-resolution imputation at classical HLA loci, identified HLA-A*29:02 as the principal MHC association (odds ratio (OR) = 157.5, 95% CI 91.6-272.6, P = 6.6 × 10(-74)). We also identified two novel susceptibility loci at 5q15 near ERAP2 (rs7705093; OR = 2.3, 95% CI 1.7-3.1, for the T allele, P = 8.6 × 10(-8)) and at 14q32.31 in the TECPR2 gene (rs150571175; OR = 6.1, 95% CI 3.2-11.7, for the A allele, P = 3.2 × 10(-8)). The association near ERAP2 was confirmed in an independent British case-control samples (combined meta-analysis P = 1.7 × 10(-9)). Functional analyses revealed that the risk allele of the polymorphism near ERAP2 is strongly associated with high mRNA and protein expression of ERAP2 in B cells. This study further defined an extremely strong MHC risk component in BSCR, and detected evidence for a novel disease mechanism that affects peptide processing in the endoplasmic reticulum.

Childhood uveitis not associated with juvenile idiopathic arthritis: a national survey of incidence, management and visual outcomes.

AIMS: To estimate the incidence of childhood uveitis not associated with juvenile idiopathic arthritis (JIA) in the United Kingdom. METHODS: Children under 16 years who presented with a new diagnosis of uveitis from November 2014 to October 2015 were identified prospectively through the British and Scottish Ophthalmological Surveillance Unit reporting card system. Incident questionnaires were sent to reporting ophthalmologists at presentation and 12 months. RESULTS: From 1st November 2014 to 31st October 2015, 119 cases were reported. Thirty-nine cases were excluded. The estimated minimum annual incidence of non-JIA uveitis in children younger than 16 years is 0.66 per 100,000 (95% CI 0.52-0.82). Median age at presentation was 10 years. 73% had bilateral uveitis. Median (IQR) BCVA in the worse eye was 0.3 (IQR 0.1-0.66) logMAR. The location of uveitis was: anterior 36%, intermediate 24%, posterior 6.8% and panuveitis 30%. 70% of cases were idiopathic. Most children were started on topical corticosteroids at presentation (86%, n = 51). At presentation, 31% (n = 19) were on started on systemic corticosteroids. At 1 year only 13% (n = 7) remained on corticosteroids, with the majority transitioned to steroid-sparing agents: methotrexate (30.8%, n = 16), mycophenolate (5.8%) and anti-TNF agents 5 (9.6%). At 1 year, 46% had ongoing intraocular inflammation despite treatment. The most common ocular adverse event was raised intraocular pressure (13.5%, n = 7). CONCLUSION: Our study provides the first national population-based data of non-JIA childhood uveitis. Most children remain on treatment at 1 year, but visual acuity improves and none were eligible for sight-impairment registration.

Investigation of the efficacy of an online tool for improving the diagnosis of macular lesions imaged by optical coherence tomography.

PURPOSE: Optical coherence tomography (OCT) is a non-invasive method for diagnosis and monitoring of retinal (typically, macular) conditions. The unfamiliar nature of OCT images can present considerable challenges for some community optometrists. The purpose of this research is to develop and assess the efficacy of a novel internet resource designed to assist optometrists in using OCT for diagnosis of macular disease and patient management. METHODS: An online tool (OCTAID) has been designed to assist practitioners in the diagnosis of macular lesions detected by OCT. The effectiveness of OCTAID was evaluated in a randomised controlled trial comparing two groups of practitioners who underwent an online assessment (using clinical vignettes) based on OCT images, before (exam 1) and after (exam 2) an educational intervention. Participants' answers were validated against experts' classifications (the reference standard). OCTAID was randomly allocated as the educational intervention for one group with the control group receiving an intervention of standard OCT educational material. The participants were community optometrists. RESULTS: Random allocation resulted in 53 optometrists receiving OCTAID and 65 receiving the control intervention. Both groups performed similarly at baseline with no significant difference in mean exam 1 scores (p = 0.21). The primary outcome measure was mean improvement in exam score between the two exam modules. Participants who received OCTAID improved their exam score significantly more than those who received conventional educational materials (p = 0.005). CONCLUSION: Use of OCTAID is associated with an improvement in the combined skill of OCT scan recognition and patient management decisions.

Cohort profile: design and methods in the eye and vision consortium of UK Biobank.

PURPOSE: To describe the rationale, methods and research potential of eye and vision measures available in UK Biobank. PARTICIPANTS: UK Biobank is a large, multisite, prospective cohort study. Extensive lifestyle and health questionnaires, a range of physical measures and collection of biological specimens are collected. The scope of UK Biobank was extended midway through data collection to include assessments of other measures of health, including eyes and vision. The eye assessment at baseline included questionnaires detailing past ophthalmic and family history, measurement of visual acuity, refractive error and keratometry, intraocular pressure (IOP), corneal biomechanics, spectral domain optical coherence tomography (OCT) of the macula and a disc-macula fundus photograph. Since recruitment, UK Biobank has collected accelerometer data and begun multimodal imaging data (including brain, heart and abdominal MRI) in 100 000 participants. Dense genotypic data and a panel of 20 biochemistry measures are available, and linkage to medical health records for the full cohort has begun. FINDINGS TO DATE: A total of 502 665 people aged between 40 and 69 were recruited to participate in UK Biobank. Of these, 117 175 took part in baseline assessment of vision, IOP, refraction and keratometry. A subgroup of 67 321 underwent OCT and retinal photography. The introduction of eye and vision measures in UK Biobank was accompanied by intensive training, support and a data monitoring quality control process. FUTURE PLANS: UK Biobank is one of the largest prospective cohorts worldwide with extensive data on ophthalmic diseases and conditions. Data collection is an ongoing process and a repeat of the baseline assessment including the questionnaires, measurements and sample collection will be performed in subsets of 25 000 participants every 2-3 years. The depth and breadth of this dataset, coupled with its open-access policy, will create a powerful resource for all researchers to investigate the eye diseases in later life.

Unilateral Pigmented Paravenous Retinochoroidal Atrophy Associated With Presumed Ocular Tuberculosis.

This report describes a case of unilateral pigmented paravenous retinochoroidal atrophy (PPRCA) in a patient with low-grade unilateral intermediate uveitis. A 31-year-old woman, previously diagnosed with intermediate uveitis in the right eye (OD) presented to the clinic. Best-corrected visual acuity was 20/20 OD. Fundus examination, fluorescein angiography, autofluorescence, and optical coherence tomography OD were in keeping with a phenotypic diagnosis of PPRCA. Electrophysiology showed severe photoreceptor dysfunction of both the rod and the cone systems OD. Systemic workup revealed QuantiFERON-gold positive. This is the first report of unilateral PPRCA secondary to presumed ocular tuberculosis. [Ophthalmic Surg Lasers Imaging Retina. 2017;48:345-349.].

Optical Coherence Tomography in the UK Biobank Study - Rapid Automated Analysis of Retinal Thickness for Large Population-Based Studies.

PURPOSE: To describe an approach to the use of optical coherence tomography (OCT) imaging in large, population-based studies, including methods for OCT image acquisition, storage, and the remote, rapid, automated analysis of retinal thickness. METHODS: In UK Biobank, OCT images were acquired between 2009 and 2010 using a commercially available "spectral domain" OCT device (3D OCT-1000, Topcon). Images were obtained using a raster scan protocol, 6 mm x 6 mm in area, and consisting of 128 B-scans. OCT image sets were stored on UK Biobank servers in a central repository, adjacent to high performance computers. Rapid, automated analysis of retinal thickness was performed using custom image segmentation software developed by the Topcon Advanced Biomedical Imaging Laboratory (TABIL). This software employs dual-scale gradient information to allow for automated segmentation of nine intraretinal boundaries in a rapid fashion. RESULTS: 67,321 participants (134,642 eyes) in UK Biobank underwent OCT imaging of both eyes as part of the ocular module. 134,611 images were successfully processed with 31 images failing segmentation analysis due to corrupted OCT files or withdrawal of subject consent for UKBB study participation. Average time taken to call up an image from the database and complete segmentation analysis was approximately 120 seconds per data set per login, and analysis of the entire dataset was completed in approximately 28 days. CONCLUSIONS: We report an approach to the rapid, automated measurement of retinal thickness from nearly 140,000 OCT image sets from the UK Biobank. In the near future, these measurements will be publically available for utilization by researchers around the world, and thus for correlation with the wealth of other data collected in UK Biobank. The automated analysis approaches we describe may be of utility for future large population-based epidemiological studies, clinical trials, and screening programs that employ OCT imaging.

Investigation of the efficacy of an online tool for improving the diagnosis of macular lesions imaged by optical coherence tomography

Purpose: Optical coherence tomography (OCT) is a non-invasive method for diagnosis and monitoring of retinal (typically, macular) conditions. The unfamiliar nature of OCT images can present considerable challenges for some community optometrists.The purpose of this research is to develop and assess the efficacy of a novel internet resource designed to assist optometrists in using OCT for diagnosis of macular disease and patient management.MethodsAn online tool (OCTAID) has been designed to assist practitioners in the diagnosis of macular lesions detected by OCT. The effectiveness of OCTAID was evaluated in a randomised controlled trial comparing two groups of practitioners who underwent an online assessment (using clinical vignettes) based on OCT images, before (exam 1) and after (exam 2) an educational intervention. Participants’ answers were validated against experts’ classifications (the reference standard). OCTAID was randomly allocated as the educational intervention for one group with the control group receiving an intervention of standard OCT educational material. The participants were community optometrists.ResultsRandom allocation resulted in 53 optometrists receiving OCTAID and 65 receiving the control intervention. Both groups performed similarly at baseline with no significant difference in mean exam 1 scores (p = 0.21). The primary outcome measure was mean improvement in exam score between the two exam modules. Participants who received OCTAID improved their exam score significantly more than those who received conventional educational materials (p = 0.005).ConclusionUse of OCTAID is associated with an improvement in the combined skill of OCT scan recognition and patient management decisions. (AU)

Safety testing of indocyanine green and trypan blue using retinal pigment epithelium and glial cell cultures.

PURPOSE: Indocyanine green (ICG) and trypan blue have been advocated as vital stains for use during macular surgery. The safety of these agents was tested using a cell culture model. METHODS: Human retinal pigment epithelium (RPE) and Müller cell lines were exposed to ICG over a range of concentrations up to 0.5%, and trypan blue up to 0.2%. Cells were exposed to each dye for 5, 15, or 30 minutes, rinsed, and incubated 24 hours. Cell viability was measured using a mitochondrial dehydrogenase-assay and fluorescent live-dead probe. Experiments were repeated using 0.5% and 1% ICG and 0.06% and 0.12% trypan blue, with follow-up at 0, 1, 5, and 15 days. ICG experiments were repeated in the presence of illumination from a xenon light-source channeled through a surgical endolight, and using reduced osmolarity solutions of 0.1%, 0.5%, and 1% (185 vs. 275 mOsM). RESULTS: There was no clear relationship between cell viability and the concentration of the agent or duration of follow-up, except in RPE cells exposed to 1% ICG. These showed a linear (R(2) 0.9952) decline in viability with time, with a significant reduction by day 15 (P = 0.016). RPE cells exposed to ICG and illumination were not significantly different from the negative control, but when illumination was combined with low osmolarity, viability was reduced (P = 0.0016). ICG and illumination reduced Müller cell viability (P < 0.0001 for both 185 and 275 mOsM). Müller cells incubated with 185 mOsM 1% ICG showed a significant reduction in viability (P < 0.0001) not seen with the 185 mOsM 0.5% or 0.1% solutions or in the low-osmolarity RPE groups. CONCLUSIONS: The combination of exposure to 0.5% ICG and the newer endoillumination light-sources can damage cultured Müller cells. Although the preparations of ICG most commonly used clinically did not produce significant damage, relatively small changes in ICG osmolarity and concentration did. This suggests that safety margins are not large. Trypan blue is safe in a cell culture model.

Flashes, floaters and fuzz.

Flashing lights (photopsia) and floaters are common visual phenomena and patients frequently present to hospital with these symptoms. This article provides a guide for the non-specialist to the different pathologies that may result in photopsia and floaters.

Frequency and associations of a taut thickened posterior hyaloid, partial vitreomacular separation, and subretinal fluid in patients with diabetic macular edema.

PURPOSE: To determine prospectively among patients with diabetic macular edema (DME) the frequency of a clinically evident taut thickened posterior hyaloid (TTPH), optical coherence tomography (OCT) signs suggestive of partial vitreomacular separation (PVMS), and OCT evidence of subretinal fluid (SRF) and to investigate for associations between these findings. METHODS: In a prospective case series, patients with DME despite previous laser treatment were examined for the presence of a TTPH. OCT was performed to investigate for PVMS and SRF. RESULTS: One hundred forty patients and eyes were included in the study. A TTPH was present in six patients (4%). PVMS was present in 14 (10%) of 140 patients with DME, of whom 5 also had a TTPH. SRF was present in 15 (11%) of 140 patients, of whom 4 had TTPH. OCT showed that 66% of patients with SRF and DME had neither a clinical TTPH nor partial posterior hyaloid separation. CONCLUSION: A TTPH was found in 4% of subjects with DME. Partial posterior hyaloid separation and SRF may be found in patients who do not have a TTPH. SRF in patients with DME may not be tractional.