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Contains fulltext : 292919.pdf (Publisher’s version ) (Open Access) BACKGROUND: High myopia (HM), defined as a spherical equivalent refractive error (SER) ≤ -6.00 diopters (D), is a leading cause of sight impairment, through myopic macular degeneration (MMD). We aimed to derive an improved polygenic score (PGS) for predicting children at risk of HM and to test if a PGS is predictive of MMD after accounting for SER. METHODS: The PGS was derived from genome-wide association studies in participants of UK Biobank, CREAM Consortium, and Genetic Epidemiology Research on Adult Health and Aging. MMD severity was quantified by a deep learning algorithm. Prediction of HM was quantified as the area under the receiver operating curve (AUROC). Prediction of severe MMD was assessed by logistic regression. FINDINGS: In independent samples of European, African, South Asian and East Asian ancestry, the PGS explained 19% (95% confidence interval 17-21%), 2% (1-3%), 8% (7-10%) and 6% (3-9%) of the variation in SER, respectively. The AUROC for HM in these samples was 0.78 (0.75-0.81), 0.58 (0.53-0.64), 0.71 (0.69-0.74) and 0.67 (0.62-0.72), respectively. The PGS was not associated with the risk of MMD after accounting for SER: OR = 1.07 (0.92-1.24). INTERPRETATION: Performance of the PGS approached the level required for clinical utility in Europeans but not in other ancestries. A PGS for refractive error was not predictive of MMD risk once SER was accounted for. FUNDING: Supported by the Welsh Government and Fight for Sight (24WG201).

Purpose: Serum lipids are modifiable, routinely collected blood test features associated with cardiovascular health. We examined the association of commonly collected serum lipid measures (total cholesterol [TC], high-density lipoprotein cholesterol [HDL-C], low-density lipoprotein cholesterol [LDL-C], and triglycerides) with intraocular pressure (IOP). Design: Cross-sectional study in the UK Biobank and European Prospective Investigation into Cancer and Nutrition (EPIC)-Norfolk cohorts. Participants: We included 94 323 participants from the UK Biobank (mean age, 57 years) and 6230 participants from the EPIC-Norfolk (mean age, 68 years) cohorts with data on TC, HDL-C, LDL-C, and triglycerides collected between 2006 and 2009. Methods: Multivariate linear regression adjusting for demographic, lifestyle, anthropometric, medical, and ophthalmic covariables was used to examine the associations of serum lipids with corneal-compensated IOP (IOPcc). Main Outcome Measures: Corneal-compensated IOP. Results: Higher levels of TC, HDL-C, and LDL-C were associated independently with higher IOPcc in both cohorts after adjustment for key demographic, medical, and lifestyle factors. For each 1-standard deviation increase in TC, HDL-C, and LDL-C, IOPcc was higher by 0.09 mmHg (95% confidence interval [CI], 0.06–0.11 mmHg; P < 0.001), 0.11 mmHg (95% CI, 0.08–0.13 mmHg; P < 0.001), and 0.07 mmHg (95% CI, 0.05–0.09 mmHg; P < 0.001), respectively, in the UK Biobank cohort. In the EPIC-Norfolk cohort, each 1-standard deviation increase in TC, HDL-C, and LDL-C was associated with a higher IOPcc by 0.19 mmHg (95% CI, 0.07–0.31 mmHg; P = 0.001), 0.14 mmHg (95% CI, 0.03–0.25 mmHg; P = 0.016), and 0.17 mmHg (95% CI, 0.06–0.29 mmHg; P = 0.003). An inverse association between triglyceride levels and IOP in the UK Biobank (–0.05 mmHg; 95% CI, –0.08 to –0.03; P < 0.001) was not replicated in the EPIC-Norfolk cohort (P = 0.30). Conclusions: Our findings suggest that serum TC, HDL-C, and LDL-C are associated positively with IOP in 2 United Kingdom cohorts and that triglyceride levels may be associated negatively. Future research is required to assess whether these associations are causal in nature.

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.

Purpose To describe and compare associations with macular retinal nerve fiber layer (mRNFL), ganglion cell complex (GCC), and ganglion cell–inner plexiform layer (GCIPL) thicknesses in a large cohort. Design Cross-sectional study. Participants We included 42 044 participants in the UK Biobank. The mean age was 56 years. Methods Spectral-domain OCT macular images were segmented and analyzed. Corneal-compensated intraocular pressure (IOPcc) was measured with the Ocular Response Analyzer (Reichert, Corp., Buffalo, NY). Multivariable linear regression was used to examine associations with mean mRNFL, GCC, and GCIPL thicknesses. Factors examined were age, sex, ethnicity, height, body mass index (BMI), smoking status, alcohol intake, Townsend deprivation index, education level, diabetes status, spherical equivalent, and IOPcc. Main Outcome Measures Thicknesses of mRNFL, GCC, and GCIPL. Results We identified several novel independent associations with thinner inner retinal thickness. Thinner inner retina was associated with alcohol intake (most significant for GCIPL: –0.46 μm for daily or almost daily intake compared with special occasion only or never [95% confidence interval (CI), 0.61–0.30]; P = 1.1×10–8), greater social deprivation (most significant for GCIPL: –0.28 μm for most deprived quartile compared with least deprived quartile [95% CI, –0.42 to –0.14]; P = 6.6×10–5), lower educational attainment (most significant for mRNFL: –0.36 μm for less than O level compared with degree level [95% CI, –0.45 to 0.26]; P = 2.3×10–14), and nonwhite ethnicity (most significant for mRNFL comparing blacks with whites: –1.65 μm [95% CI, –1.86 to –1.43]; P = 2.4×10–50). Corneal-compensated intraocular pressure was associated most significantly with GCIPL (–0.04 μm/mmHg [95% CI, –0.05 to –0.03]; P = 4.0×10–10) and was not associated significantly with mRNFL (0.00 μm/mmHg [95% CI, –0.01 to 0.01]; P = 0.77). The variables examined explained a greater proportion of the variance of GCIPL (11%) than GCC (6%) or mRNFL (7%). Conclusions The novel associations we identified may be important to consider when using inner retinal parameters as a diagnostic tool. Associations generally were strongest with GCIPL, particularly for IOP. This suggests that GCIPL may be the superior inner retinal biomarker for macular pathophysiologic processes and especially for glaucoma.

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.

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.]

Background Paediatric sarcoidosis represents a spectrum of disease. Early onset sarcoidosis & Blau syndrome associated with NOD2 mutations are characterized by fever, rash, arthritis & organomegaly. Later onset sarcoidosis has wider organ involvement (lungs, kidneys, lachrymal & extra-ocular glands). Both presentations may lead to long term complications due to end-stage organ damage. Ocular sarcoidosis has a well described uveitis phenotype. We aim to describe a retrospective cohort of children with sarcoid-like uveitis & their systemic manifestations at time of study; compare cohort of patients fulfilling IWOS criteria for ocular sarcoidosis versus who did not; and describe their management in retrospective cohort. Methods We performed a retrospective case review of all children currently followed at GOSH with ocular sarcoidosis phenotype with uveitis (ophthalmologist definition based on IWOS, or diagnosis of idiopathic uveitis with raised ACE level at least once. We collected demographics & all extra-ocular involvement described in sarcoidosis. Results n = 52; 27/52 males. Median age at onset of uveitis 4.20 years (1.41-15.16). 49/52 bilateral uveitis. 27/52 (50%) 1:80) in 15/47 (32%). Systemic involvement (n = 52): arthritis 29%, liver 29%, lymphadenopathy 19%, renal 16%, lungs 15.3%, skin 17.3%, spleen 7.7%, glands 1.9%. Patients as per adult IWOS criteria: Definite 12/52, Presumed 6/52, Probable7/52 and Not fulfilling – 27/52. Systemic involvement in patients not fulfilling IWOS criteria (27/52) – renal 14.8%, arthritis 22.2%, hilar or peripheral lymphadenopathy 0 %, skin involvement 7.4%, lung 18.5%, splenomegaly 3.7%. Comparing IWOS fulfilling (25) with the ones who did not (27) – systemic involvement consistently less common in the ones NOT fulfilling but only reaches statistical significance difference for involvement. Lymphadenopathy and skin (p < 0.001 and p < 0.050 respectively). Suggesting that paediatric age group cannot be classified as per the adult IWOS ocular sarcoidosis criteria and needs early systemic screening. Medications used to treat uveitis and/or extra-ocular manifestations: methotrexate alone 25%, methotrexate + adalimumab 21.1%, mycophenolate mofetil 9.61%, only systemic steroids 3.8%. 9 patients- no systemic medications at any time during their disease. Conclusion Most sarcoid-like uveitis patients had at least one systemic involvement. 51.9% patients did not fulfil the IWOS ocular sarcoidosis criteria, still had systemic involvement. Hilar lymphadenopathy criteria cannot be applied to the paediatric population, peripheral more common. ACE not a sensitive biomarker to predict sarcoidosis. 17.3 % had mild phenotype & required no treatment. This study demonstrates the importance of close monitoring for systemic manifestations & highlights good clinical response to steroids, MTX, MMF and anti-TNF. Conflicts of Interest The authors declare no conflicts of interest.

Background Paediatric sarcoidosis may represent a spectrum of disease. Early onset sarcoidosis & its genetically defined counterpart Blau syndrome associated with NOD2 mutations are characterized by fever, rash, arthritis and organomegaly. Later onset sarcoidosis has wider organ involvement including lungs, kidneys, lachrymal and extra-ocular glands. Both presentations may lead to long term complications due to end-stage organ damage. Although similar disease manifestations can be seen in adults and children, some entities are essentially pediatric at onset, namely Blau syndrome and most forms of immunodeficiency associated granulomatous diseases. Ocular sarcoidosis has a well described uveitis phenotype (1). We created a retrospective cohort of patients currently followed at GOSH with likely ocular manifestation of sarcoidosis (1) Objectives To describe a retrospective cohort of children with sarcoid-like uveitis, To describe their extra-ocular manifestations at the time of the study,To describe their management Methods: retrospective case review of children currently followed at GOSH with a phenotype of ocular sarcoidosis with uveitis (ophthalmologist defn (5, 6)), or a diagnosis of idiopathic uveitis (anterior, posterior, intermediate or panuveitis) with raised ACE level at least once. We collected demographics and all extra-ocular involvement described in sarcoidosis Results 52 patients. 27/52 males. Median age onset of uveitis 4.20 yrs (1.41-15.16). 30/52had onset Ethnicity: black 13, asian 10, caucasian 13, unknown 16/52. 49/52 patients had bilateral uveitis. Uveitis anterior 17/52, intermediate 5/52, posterior 2/52, panuveitis 25/52, unknown 1/52. ANA+15/47(32%). Extra-ocular (n=52): Lymphadenopathy: 15 (29%) clinically Liver: 16 (31%) - transaminitis 9, ultrasound(USS) abnormality (hepatomegaly, calcification, increased echogenicity) 5 & both abnormal USS & blood 2 Arthritis: 15 (29%) large joints of lower limbs & joints hands. Tenosynovitis 4 (7.7%) Renal: 15 (29%) (USS or Blood/urine tests – raised serum creatinine, raised urinary ca creat ratio, raised urinary NAG/RBP) — 4/15 on USS and 9/15 in blood/urine tests, 2/15 on both USS and blood/urine tests. Lungs: 7 (13.5%): 6 abnormal lung function test, 1abnormal CXR, lung function& CT chest - severe interstitial lung disease & presented- progressive shortness of breath. Skin: 10(19.2%), eczema-like/non-specific skin Parotid/glandular: 1 (1.9%) on USS Splenomegaly: 4 (7.7%) on USS Sensorineural hearing loss: 2 (3.8%) Medications to treat uveitis and/or extra-ocular manifestations were: Methotrexate 13 (25%), Methotrexate + Adalimumab 11 (21.2%), MMF 6 (11.5%), topical steroids 8 (15.4%), systemic steroids 2 (3.8%). 10 patients no medication Conclusion Most of the sarcoid-like uveitis patients had at least one extra-ocular involvement. ACE does not appear to be a sensitive biomarker. Some patients (19.2%) have a mild phenotype and require no treatment. Our data demonstrate the importance of close monitoring for extra-ocular manifestations and highlight good clinical response to steroids, MTX, MMF and anti-TNF. Reference [1] Acharya NR et al International Ocular Sarcoidosis Working Group. Distinguishing Features of Ocular Sarcoidosis in an International Cohort of Uveitis Patients. Ophthalmology. 2018 Jan;125(1):119-126. Disclosure of Interests Abhay Shivpuri: None declared, Emily Kalms: None declared, Ameenat Lola Solebo: None declared, Harry Petrushkin: None declared, Dhanes Thomas: None declared, Elizabeth Graham: None declared, Clive Edelsten: None declared, Sandrine Compeyrot-Lacassagne Grant/research support from: Abbvie

Background Childhood uveitis is a group of heterogenous, potentially blinding inflammatory disorders. Management is complex. There is growing recognition of the importance of actively involving affected children and their families in their own care. Co-designed interventions, developed through active involvement of staff and patients, can provide effective solutions to problems identified by those affected. Objectives To use findings from a patient and family discussion group to inform the co-designed development of health care processes and interventions. Methods Five children/young people with uveitis (age ranges 8 to 17), seven parent/carers of children with uveitis and four health care professionals attended a 90 minute discussion group. Main discussion topic was the identification of areas in need of interventions or support structures. Sub-topics were determined a priori using previous PPI and existent research (REFS). They comprised: Direct health care; Impact on families; School, education and peers. Responses were collated. Consent was taken for use of direct quotes from participants. Results We outline the areas identified by children and families: Direct health care Four interconnected areas were identified: (1) Transitioning to adult services, (2) peer support (health care services being a valuable site for identifying peers), (3) communication between care structures, and (4) education for families. With regards to family education, there was identification of the need for specific services or interventions around the communication of (4a) diagnosis, (4b) treatment, (4c) likely long term outcomes/prognosis, (4d) and the child’s progress. There was also discussion on (4e) the formats used to communicate with families. Impact on families Participants discussed support around (1) family relationships, (2) the impact of systemic medication. They also discussed (3) a need for recognition of the changing nature of their lived experience as affected families over the disease course and the need for on-going psychologic support especially at presentation to help with acceptance. School, education and peers Participants discussed the need for support around: (1) the impact of treatment on school life, (2) communication with school professionals and peers, (3) impact of visual impairments, (4) managing the visibility/invisibility paradox (ie being made to feel different but also having a disorder which was not externally apparent), and (5) managing adolescence. Conclusion Through the above approach, we have identified a range of issues affecting our patients and their families. Our findings are similar to those of other groups (1, 2) These lived experiences will be used to inform the co-design of supportive services (patient leaflets, videos, website, psychology intervention) and research on the effectiveness of these interventions in improving the management of affected children and their families. References [1] Parker DM, Angeles-Han ST, Stanton AL, Holland GN. Chronic Anterior Uveitis in Children: Psychosocial Challenges for Patients and Their Families. Am J Ophthalmol. 2018 Jul; 191:xvi-xxiv [2] Silva LMP, Arantes TE, Casaroli-Marano R, Vaz T, Belfort R Jr, Muccioli C. Quality of Life and Psychological Aspects in Patients with Visual Impairment Secondary to Uveitis: A Clinical Study in a Tertiary Care Hospital in Brazil. Ocul Immunol Inflamm. 2017 Oct 11:1-9. Disclosure of Interests Sandrine Compeyrot-Lacassagne Grant/research support from: Abbvie, Christine Twoney: None declared, Harry Petrushkin: None declared, Dhanes Thomas: None declared, Emily Robinson: None declared, Lucia Kossarova: None declared, Ameenat Lola Solebo: None declared

Subacute idiopathic retinal vasculitis, aneurysms and neuroretinitis (IRVAN) in a child and review of paediatric cases of IRVAN revealing preserved capillary perfusion as a more common feature

Item does not contain fulltext 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 x 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 x 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 x 10(-8)). The association near ERAP2 was confirmed in an independent British case-control samples (combined meta-analysis P = 1.7 x 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.

e recently reported that 73.8%of subjects diagnosed withVogt–Koyanaga–Harada (VKH) dis-ease experienced recurrences (Erreraet al. 2011). Based on our experience,we believed that finding an exudativeretinal detachment (ERD) thatresponded to corticosteroids or othermedical treatment more than 1 yearafter onset is low. To better evaluatelate posterior recurrences, we reviewedthe records of a large series of 45patients with VKH disease from fourtertiary centres. The median follow-upduration was 34 months since initialpresentation.Late posterior segment relapses weredefined as posterior segment manifes-tations of inflammation occurring laterthan 52 weeks after first presentationof VKH (Garcia-Valenzuela et al.2000; Sachdev et al. 2008; Dolz-Marcoet al. 2011). The study adhered to thetenets of the Declaration of Helsinki.Relapsing ERDs were noted within10 months after presentation in 16(84%) of 19 subjects who experiencedsuch reactivation, with only four expe-riencing late ERDs, one of whom alsohad early relapses. Report of foursubjects with late ERDs relapses at amedian of 19 months (16–25 months).By examination and optical coher-ence tomography (OCT), subretinalfluid was limited localized areas ofsubmacular ERDs in all late posteriorsegment relapses (Fig. 1).Intravenous pulse therapy was usedwithin the first month for three of thefour subjects who experienced a lateposterior reactivation. In the fourthsubject, the diagnosis of VKH diseasewas made 3 months after the firstinflammatory signs, which caused adelay in the initiation of the correcttreatment. This latter subject had treat-ment with corticosteroids for only1 month, while the other three subjectsreceived an initial duration of systemiccorticosteroids for at least 6 months.In all four subjects, immunosuppres-sive therapy (infliximab, cyclosporin orinterferon) was initiated after the firstrelapse because response to therapywith corticosteroid at acceptable long-term doses was insufficient.All four subjects had been on immu-nomodulatory agents (cyclophospha-mide, infliximab and azathioprine),but these agents had been stopped 5to 13 months prior to the relapse.In one subject, the relapse occurredwhile he was taking 25 mg/day ofprednisone. He had responded to rein-troduction of high-dose corticotherapyfor an episode 6 months previously,and he was on tapering of therapy. Thesecond subject was receiving bothprednisone and cyclophosphamide.The third was on infliximab and low-dose oral corticosteroids at the time ofrelapse.In the experience at our institutionsthere were 4 late relapses (ERDs) of 45subjects with an incidence rate of 12cases per 1000 VKH affected person-years. Late relapses as ERDs occurredin patients receiving early intravenouspulse corticosteroids, and all four hadbeen on other corticosteroid-sparingimmunomodulatory therapy at somepoint. One possible explanation is thatthe need for more aggressive treatmentin our patients with late relapses ofVKH may be a marker of more severedisease. Early corticosteroid-sparingimmunomodulatory therapy might beuseful as first-line therapy to reduce thedevelopment of complications (AbuEl-Asrar et al. 2013). Although it is

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.